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  • Psychological stress has become a major concern, potentially leading to diverse health problems including psychopathology such as depression and anxiety. Transactional Model of Stress and Coping is an established model, conceptualizing stressful experiences via person-environment relationship. This cross-sectional study aimed to explore the pathway from stress to depression/anxiety, with a focus on self-criticism (inadequate-self and hated-self) and self-reassurance (reassured-self) in Czech students who suffered from high prevalence of mental health problems. Convenience sample of 119 undergraduates completed the Depression Anxiety and Stress Scale-21 and the Forms of the Self-Criticizing/Attacking & Self-Reassuring Scale. Correlation and path analyses were conducted. The Strengthening the Reporting of Observational Studies in Epidemiology guidelines were used to aid an accurate and complete report of the study. Depression, anxiety, and stress were positively associated with inadequate-self and hated-self while negatively associated with reassured-self. Both inadequate-self and hated-self partially mediated the stress-depression and stress-anxiety relationships, whereas reassured-self only partially mediated the stress-depression relationship. Inadequate-self had greater impact on the stress-depression/anxiety pathways than hated-self and reassured-self. Findings indicate that clinical treatment may benefit from targeting the feelings of inadequacy to prevent stress progressing to psychopathology. This is particularly relevant as stress levels are rising globally. Our findings offer developments to the Transactional Model, and help practitioners and educators identify solutions to protect mental health of Czech university students.Telehealth is a growing valuable strategy to assist patients accessing needed care when unable to get to a health care setting for one of several reasons. During the coronavirus disease 2019 (COVID-19) pandemic of 2020, many health care practices were forced to implement telehealth services to meet patient and practice needs. In 2020, several temporary waivers, exceptions, and telehealth policy changes emerged across the nation. Many telehealth policies are state or federal specific. This report provides a general overview of essential telehealth policies and legislative updates along with resources and websites to guide and support nurse practitioners with contemporary regulations regarding telehealth billing.Coronavirus disease 2019 (COVID-19) is a deadly global pandemic, with scientific efforts improving our understanding of this novel coronavirus. No proven disease-specific therapies exist, although 2 vaccines have been recently approved by the United States Food and Drug Administration under emergency use authorization, and several others are in development or phase III clinical trial testing. COVID-19 presents in greater severity in the medically fragile, obese, elderly, and socially disadvantaged, and children in general are less affected. All children are at risk, but those with comorbidities and neonates are more susceptible. The multisystem inflammatory syndrome is a severe version which can present in any child with a recent COVID-19 infection. https://www.selleckchem.com/products/PLX-4720.html The face of the pandemic has been changing in the last few months, with recent increasing cases, virus mutations, and onset of vaccination. This article provides COVID-19 management for children and adolescents and implications for nursing and advanced practice providers.We investigate the role of endowment inequality in a local and global public goods setting with multiple group membership and examine the effect of temporal role reversal on cooperation decisions. Subjects can contribute to a global public good which benefits all subjects and two local public goods which benefit only subjects of either their own group or the group of the other endowment type. Endowment inequality per-se decreases contributions of subjects with a high endowment to the global public good, but increases cooperation of subjects with a low endowment on their local public good, thereby aggravating income disparities. Exogenously induced role reversal for several periods affects cooperation behavior of subjects with a high endowment positively and induces them to contribute more to the global good. Cooperation in unequal environments thus appears to be more stable when all parties have experienced the public goods game from the disadvantageous perspective.
    The online version contains supplementary material available at 10.1007/s10683-021-09705-y.
    The online version contains supplementary material available at 10.1007/s10683-021-09705-y.Online teaching transition during COVID-19 school lockdown elicited challenges for teachers and schools across the globe. The existing literature on the impact of COVID-19 in the education sector is predominantly descriptive and focused on the difficulties faced by teachers during the process of transferring into online teaching, mainly in the higher education sector. This study adopted a mixed-method design to examine online teaching self-efficacy (TSE) during COVID-19, its associated factors and moderators. A sample of 351 Chinese school teachers retrospectively reported their online TSE at the beginning and end of COVID-19 school lockdown, out of which six were followed up for an in-depth interview. TSE for online instruction did not significantly increase (β = .014, p > 0.05) whereas that for technology application increased significantly (β = .231, p 
    The online version contains supplementary material available at 10.1007/s10639-021-10486-3.
    The online version contains supplementary material available at 10.1007/s10639-021-10486-3.Surveillance practices, both state and non-state in origin, are deployed increasingly to solve social problems beyond the traditional domains of criminal justice and national security, including public health concerns. Although such "protective" forms of surveillance are proffered by the state as beneficial for those under surveillance, they nonetheless retain coercive dimensions in practice and require the labeling of a group as "risky" in order to justify their use. Following Shelley Bielefeld's (2018) observations about protective state surveillance as a form of paternalism, and Jennifer Musto's (2016) notion of "carceral protectionism," this article uses a case study of the electronic monitoring of people with cognitive impairments to identify the carceral features of paternalistic surveillance and to explore how this practice is justified. I make the argument that, specifically through targeted vulnerability and distortions of risk, paternalistic surveillance practices can operate as a mode of carceral expansion.
    Psychological stress has become a major concern, potentially leading to diverse health problems including psychopathology such as depression and anxiety. Transactional Model of Stress and Coping is an established model, conceptualizing stressful experiences via person-environment relationship. This cross-sectional study aimed to explore the pathway from stress to depression/anxiety, with a focus on self-criticism (inadequate-self and hated-self) and self-reassurance (reassured-self) in Czech students who suffered from high prevalence of mental health problems. Convenience sample of 119 undergraduates completed the Depression Anxiety and Stress Scale-21 and the Forms of the Self-Criticizing/Attacking & Self-Reassuring Scale. Correlation and path analyses were conducted. The Strengthening the Reporting of Observational Studies in Epidemiology guidelines were used to aid an accurate and complete report of the study. Depression, anxiety, and stress were positively associated with inadequate-self and hated-self while negatively associated with reassured-self. Both inadequate-self and hated-self partially mediated the stress-depression and stress-anxiety relationships, whereas reassured-self only partially mediated the stress-depression relationship. Inadequate-self had greater impact on the stress-depression/anxiety pathways than hated-self and reassured-self. Findings indicate that clinical treatment may benefit from targeting the feelings of inadequacy to prevent stress progressing to psychopathology. This is particularly relevant as stress levels are rising globally. Our findings offer developments to the Transactional Model, and help practitioners and educators identify solutions to protect mental health of Czech university students.Telehealth is a growing valuable strategy to assist patients accessing needed care when unable to get to a health care setting for one of several reasons. During the coronavirus disease 2019 (COVID-19) pandemic of 2020, many health care practices were forced to implement telehealth services to meet patient and practice needs. In 2020, several temporary waivers, exceptions, and telehealth policy changes emerged across the nation. Many telehealth policies are state or federal specific. This report provides a general overview of essential telehealth policies and legislative updates along with resources and websites to guide and support nurse practitioners with contemporary regulations regarding telehealth billing.Coronavirus disease 2019 (COVID-19) is a deadly global pandemic, with scientific efforts improving our understanding of this novel coronavirus. No proven disease-specific therapies exist, although 2 vaccines have been recently approved by the United States Food and Drug Administration under emergency use authorization, and several others are in development or phase III clinical trial testing. COVID-19 presents in greater severity in the medically fragile, obese, elderly, and socially disadvantaged, and children in general are less affected. All children are at risk, but those with comorbidities and neonates are more susceptible. The multisystem inflammatory syndrome is a severe version which can present in any child with a recent COVID-19 infection. https://www.selleckchem.com/products/PLX-4720.html The face of the pandemic has been changing in the last few months, with recent increasing cases, virus mutations, and onset of vaccination. This article provides COVID-19 management for children and adolescents and implications for nursing and advanced practice providers.We investigate the role of endowment inequality in a local and global public goods setting with multiple group membership and examine the effect of temporal role reversal on cooperation decisions. Subjects can contribute to a global public good which benefits all subjects and two local public goods which benefit only subjects of either their own group or the group of the other endowment type. Endowment inequality per-se decreases contributions of subjects with a high endowment to the global public good, but increases cooperation of subjects with a low endowment on their local public good, thereby aggravating income disparities. Exogenously induced role reversal for several periods affects cooperation behavior of subjects with a high endowment positively and induces them to contribute more to the global good. Cooperation in unequal environments thus appears to be more stable when all parties have experienced the public goods game from the disadvantageous perspective. The online version contains supplementary material available at 10.1007/s10683-021-09705-y. The online version contains supplementary material available at 10.1007/s10683-021-09705-y.Online teaching transition during COVID-19 school lockdown elicited challenges for teachers and schools across the globe. The existing literature on the impact of COVID-19 in the education sector is predominantly descriptive and focused on the difficulties faced by teachers during the process of transferring into online teaching, mainly in the higher education sector. This study adopted a mixed-method design to examine online teaching self-efficacy (TSE) during COVID-19, its associated factors and moderators. A sample of 351 Chinese school teachers retrospectively reported their online TSE at the beginning and end of COVID-19 school lockdown, out of which six were followed up for an in-depth interview. TSE for online instruction did not significantly increase (β = .014, p > 0.05) whereas that for technology application increased significantly (β = .231, p  The online version contains supplementary material available at 10.1007/s10639-021-10486-3. The online version contains supplementary material available at 10.1007/s10639-021-10486-3.Surveillance practices, both state and non-state in origin, are deployed increasingly to solve social problems beyond the traditional domains of criminal justice and national security, including public health concerns. Although such "protective" forms of surveillance are proffered by the state as beneficial for those under surveillance, they nonetheless retain coercive dimensions in practice and require the labeling of a group as "risky" in order to justify their use. Following Shelley Bielefeld's (2018) observations about protective state surveillance as a form of paternalism, and Jennifer Musto's (2016) notion of "carceral protectionism," this article uses a case study of the electronic monitoring of people with cognitive impairments to identify the carceral features of paternalistic surveillance and to explore how this practice is justified. I make the argument that, specifically through targeted vulnerability and distortions of risk, paternalistic surveillance practices can operate as a mode of carceral expansion.
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  • These findings suggest that miR-33 targeting may decrease cholesterol deposition and ameliorate AMD initiation and progression.MicroRNAs (miRNAs) regulate gene expression by post-transcriptional inhibition of target genes. Proangiogenic small extracellular vesicles (sEVs; popularly identified with the name "exosomes") with a composite cargo of miRNAs are secreted by cultured stem cells and present in human biological fluids. Lipid nanoparticles (LNPs) represent an advanced platform for clinically approved delivery of RNA therapeutics. In this study, we aimed to (1) identify the miRNAs responsible for sEV-induced angiogenesis; (2) develop the prototype of bioinspired "artificial exosomes" (AEs) combining LNPs with a proangiogenic miRNA, and (3) validate the angiogenic potential of the bioinspired AEs. We previously reported that human sEVs from bone marrow (BM)-CD34+ cells and pericardial fluid (PF) are proangiogenic. Here, we have shown that sEVs secreted from saphenous vein pericytes and BM mesenchymal stem cells also promote angiogenesis. Analysis of miRNA datasets available in-house or datamined from GEO identified the let-7 family as common miRNA signature of the proangiogenic sEVs. LNPs with either hsa-let-7b-5p or cyanine 5 (Cy5)-conjugated Caenorhabditis elegans miR-39 (Cy5-cel-miR-39; control miRNA) were prepared using microfluidic micromixing. let-7b-5p-AEs did not cause toxicity and transferred functionally active let-7b-5p to recipient endothelial cells (ECs). let-7b-AEs also improved EC survival under hypoxia and angiogenesis in vitro and in vivo. Bioinspired proangiogenic AEs could be further developed into innovative nanomedicine products targeting ischemic diseases.Tumor cells increase glutamate release through the cystine/glutamate transporter cystine-glutamate exchange (xCT) to balance oxidative homeostasis in tumor cells and promote tumor progression. Although clinical studies have shown the potential of targeting programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) signaling in melanoma, response rates are low. However, it remains unclear how glutamate metabolism affects anti-PD-1/PD-L1 treatment efficacy in melanoma. Here, we demonstrated that although inhibition of xCT either by pharmacological inhibitor (sulfasalazine [SAS]), approved by US Food and Drug Administration (FDA) for inflammatory diseases, or genetic knockdown induced reactive oxygen species (ROS)-related death in melanoma cells, inhibition of xCT significantly reduced the efficacy of anti-PD-1/PD-L1 immune checkpoint blockade through upregulating PD-L1 expression via the transcription factors IRF4/EGR1, as a consequence, exosomes carrying relatively large amounts of PD-L1 secreted from melanoma cells resulted in M2 macrophage polarization and reduced the efficacy of anti-PD-1/PD-L1 therapy in melanoma. https://www.selleckchem.com/products/pf-04929113.html Taken together, our results reveal that inhibition of xCT by SAS is a promising therapeutic strategy for melanoma; on the other hand, SAS treatment blunted the efficacy of anti-PD-1/PD-L1 via exosomal PD-L1-induced macrophage M2 polarization and eventually induced anti-PD-1/PD-L1 therapy resistance.NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome activation has emerged as a central mediator of kidney inflammation in diabetic kidney disease (DKD). However, the mechanism underlying this activation in DKD remains poorly defined. In this study, we found that kidney-enriched microRNA-10a and -10b (miR-10a/b), predominantly expressed in podocytes and tubular epithelial cells, were downregulated in kidney from diabetic **** and patients with DKD. High glucose decreased miR-10a/b expression in vitro in an osmolarity-independent manner. miR-10a/b functioned as negative regulators of the NLRP3 inflammasome through targeting the 3'untranslated region of NLRP3 mRNA, inhibiting assembly of the NLRP3 inflammasome and decreasing caspase-1-dependent release of pro-inflammatory cytokines. Delivery of miR-10a/b into kidney prevented NLRP3 inflammasome activation and renal inflammation, and it reduced albuminuria in streptozotocin (STZ)-treated ****, whereas knocking down miR-10a/b increased NLRP3 inflammasome activation. Restoration of miR-10a/b expression in established DKD ameliorated kidney inflammation and mitigated albuminuria in both db/db and STZ-treated ****. These results suggest a novel intervention strategy for inhibiting kidney inflammation in DKD by targeting the NLRP3 inflammasome.Yinchen Wuling Powder (YCWLP) is a classic Chinese medicine prescription with a long history and has been commonly used for treating jaundice hepatitis, liver fibrosis, hyperlipidemia and early diabetes in clinical applications. However, the chemical composition of YCWLP is still unclear. In order to obtain the chemical profile of YCWLP, a systematic ultra-performance liquid chromatography coupled with fourier transform ion cyclotron resonance mass spectrometry (UPLC-FT-ICR-MS) method was developed in this study. As a result, a total of 138 compounds including terpenoid acids, organic acids, flavonoids, sesquiterpenes, coumarins and anthraquinones were identified by comparing the retention time, molecular ions and fragmentation behaviors with the reference compounds or the in-house database. This study comprehensively elucidated the chemical basis of YCWLP and provided a scientific basis for further quality control and pharmacology research.Metabolomics is widely used as a powerful technique for identifying metabolic patterns and functions of organs and biological systems. Normally, there are multiple groups/targets involved in data processed by discriminant analysis. This is more common in cerebral studies, as there are always several brain regions involved in neuronal studies or brain metabolic dysfunctions. Furthermore, neuronal activity is highly correlated with cerebral energy metabolism, such as oxidation of glucose, especially for glutamatergic (excitatory) and GABAergic (inhibitory) neuronal activities. Thus, regional cerebral energy metabolism recognition is essential for understanding brain functions. In the current study, ten different brain regions were considered for discrimination analysis. The metabolic kinetics were investigated with 13C enrichments in metabolic products of glucose and measured using the nuclear magnetic spectroscopic method. Multiple discriminative methods were used to construct classification models in order to screen out the best method.
    These findings suggest that miR-33 targeting may decrease cholesterol deposition and ameliorate AMD initiation and progression.MicroRNAs (miRNAs) regulate gene expression by post-transcriptional inhibition of target genes. Proangiogenic small extracellular vesicles (sEVs; popularly identified with the name "exosomes") with a composite cargo of miRNAs are secreted by cultured stem cells and present in human biological fluids. Lipid nanoparticles (LNPs) represent an advanced platform for clinically approved delivery of RNA therapeutics. In this study, we aimed to (1) identify the miRNAs responsible for sEV-induced angiogenesis; (2) develop the prototype of bioinspired "artificial exosomes" (AEs) combining LNPs with a proangiogenic miRNA, and (3) validate the angiogenic potential of the bioinspired AEs. We previously reported that human sEVs from bone marrow (BM)-CD34+ cells and pericardial fluid (PF) are proangiogenic. Here, we have shown that sEVs secreted from saphenous vein pericytes and BM mesenchymal stem cells also promote angiogenesis. Analysis of miRNA datasets available in-house or datamined from GEO identified the let-7 family as common miRNA signature of the proangiogenic sEVs. LNPs with either hsa-let-7b-5p or cyanine 5 (Cy5)-conjugated Caenorhabditis elegans miR-39 (Cy5-cel-miR-39; control miRNA) were prepared using microfluidic micromixing. let-7b-5p-AEs did not cause toxicity and transferred functionally active let-7b-5p to recipient endothelial cells (ECs). let-7b-AEs also improved EC survival under hypoxia and angiogenesis in vitro and in vivo. Bioinspired proangiogenic AEs could be further developed into innovative nanomedicine products targeting ischemic diseases.Tumor cells increase glutamate release through the cystine/glutamate transporter cystine-glutamate exchange (xCT) to balance oxidative homeostasis in tumor cells and promote tumor progression. Although clinical studies have shown the potential of targeting programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) signaling in melanoma, response rates are low. However, it remains unclear how glutamate metabolism affects anti-PD-1/PD-L1 treatment efficacy in melanoma. Here, we demonstrated that although inhibition of xCT either by pharmacological inhibitor (sulfasalazine [SAS]), approved by US Food and Drug Administration (FDA) for inflammatory diseases, or genetic knockdown induced reactive oxygen species (ROS)-related death in melanoma cells, inhibition of xCT significantly reduced the efficacy of anti-PD-1/PD-L1 immune checkpoint blockade through upregulating PD-L1 expression via the transcription factors IRF4/EGR1, as a consequence, exosomes carrying relatively large amounts of PD-L1 secreted from melanoma cells resulted in M2 macrophage polarization and reduced the efficacy of anti-PD-1/PD-L1 therapy in melanoma. https://www.selleckchem.com/products/pf-04929113.html Taken together, our results reveal that inhibition of xCT by SAS is a promising therapeutic strategy for melanoma; on the other hand, SAS treatment blunted the efficacy of anti-PD-1/PD-L1 via exosomal PD-L1-induced macrophage M2 polarization and eventually induced anti-PD-1/PD-L1 therapy resistance.NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome activation has emerged as a central mediator of kidney inflammation in diabetic kidney disease (DKD). However, the mechanism underlying this activation in DKD remains poorly defined. In this study, we found that kidney-enriched microRNA-10a and -10b (miR-10a/b), predominantly expressed in podocytes and tubular epithelial cells, were downregulated in kidney from diabetic mice and patients with DKD. High glucose decreased miR-10a/b expression in vitro in an osmolarity-independent manner. miR-10a/b functioned as negative regulators of the NLRP3 inflammasome through targeting the 3'untranslated region of NLRP3 mRNA, inhibiting assembly of the NLRP3 inflammasome and decreasing caspase-1-dependent release of pro-inflammatory cytokines. Delivery of miR-10a/b into kidney prevented NLRP3 inflammasome activation and renal inflammation, and it reduced albuminuria in streptozotocin (STZ)-treated mice, whereas knocking down miR-10a/b increased NLRP3 inflammasome activation. Restoration of miR-10a/b expression in established DKD ameliorated kidney inflammation and mitigated albuminuria in both db/db and STZ-treated mice. These results suggest a novel intervention strategy for inhibiting kidney inflammation in DKD by targeting the NLRP3 inflammasome.Yinchen Wuling Powder (YCWLP) is a classic Chinese medicine prescription with a long history and has been commonly used for treating jaundice hepatitis, liver fibrosis, hyperlipidemia and early diabetes in clinical applications. However, the chemical composition of YCWLP is still unclear. In order to obtain the chemical profile of YCWLP, a systematic ultra-performance liquid chromatography coupled with fourier transform ion cyclotron resonance mass spectrometry (UPLC-FT-ICR-MS) method was developed in this study. As a result, a total of 138 compounds including terpenoid acids, organic acids, flavonoids, sesquiterpenes, coumarins and anthraquinones were identified by comparing the retention time, molecular ions and fragmentation behaviors with the reference compounds or the in-house database. This study comprehensively elucidated the chemical basis of YCWLP and provided a scientific basis for further quality control and pharmacology research.Metabolomics is widely used as a powerful technique for identifying metabolic patterns and functions of organs and biological systems. Normally, there are multiple groups/targets involved in data processed by discriminant analysis. This is more common in cerebral studies, as there are always several brain regions involved in neuronal studies or brain metabolic dysfunctions. Furthermore, neuronal activity is highly correlated with cerebral energy metabolism, such as oxidation of glucose, especially for glutamatergic (excitatory) and GABAergic (inhibitory) neuronal activities. Thus, regional cerebral energy metabolism recognition is essential for understanding brain functions. In the current study, ten different brain regions were considered for discrimination analysis. The metabolic kinetics were investigated with 13C enrichments in metabolic products of glucose and measured using the nuclear magnetic spectroscopic method. Multiple discriminative methods were used to construct classification models in order to screen out the best method.
    0 Комментарии 0 Поделились 44 Просмотры 0 предпросмотр

  • TET2 is a dioxygenase dependent on Fe2+ and α-ketoglutarate which oxidizes 5-methylcytosine (5meC) to 5-hydroxymethylcytosine (5hmeC). TET proteins successively oxidize 5mC to yield 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Among these oxidized methylcytosines, 5fC and 5caC are directly excised by thymine DNA glycosylase (TDG) and ultimately replaced with unmethylated cytosine. Mutations in TET2 have been shown to lead to a hypermethylated state of the genome and to be responsible for the initiation of the oncogenetic process, especially in myeloid and lymphoid malignancies. Nonetheless, this was also shown to be the case in other cancers. In AML, TET2 mutations have been observed to be mutually exclusive with IDH1, IDH2, and WT1 mutations, all of them showing a similar impact on the transcription profile of the affected cell. Because of this, it is possible that TET2/IDH1/2/WT1 mutated AML could be considered as having similar characteristics between each other. Nonetheless, other genes also interact with TET2 and influence its effect, thus making it possible that other signatures exist that would mimic the effect of TET2 mutations. Thus, in this review, we searched the literature for the genes that were observed to interact with TET2 and classified them in the following manner transcription alteration, miRs, direct interaction, posttranslational changes, and substrate reduction. What we propose in the present review is the potential extension of the TET2/IDH1/2/WT1 entity with the addition of certain expression signatures that would be able to induce a similar phenotype with that induced by TET2 mutations. Nonetheless, we recommend that this approach be taken on a disease by disease basis.The mechanisms and clinical significance of the cellular senescence of tumor cells are a matter of ongoing debate. Recently, the triggers and molecular events underlying spontaneous, replicative senescence of primary epithelial ovarian cancer cells were characterized. In this study, we reanalyzed tumors obtained from ovarian cancer patients with respect to the expression of the senescence biomarkers SA-β-Gal and γ-H2A.X and the proliferative antigen Ki67. The results showed that the tumors displayed strong heterogeneity with respect to the expression of analyzed markers. The expression of SA-β-Gal and γ-H2A.X in the oldest patients (61-85 y.o.) was significantly higher than in the younger age groups. Conversely, the area of Ki67-positive cancer cells was greater in younger individuals. At the same time, there was a positive correlation between SA-β-Gal expression and calendar age in FIGO III-IV and malignant ascites-positive patients. The γ-H2A.X positively correlated with age in the whole group, FIGO III-IV, and ascites-positive patients. Ki67 levels correlated negatively with the age of patients among those same groups. Collectively, our study indicated that organismal aging may determine the development of the senescence phenotype in ovarian tumors, particularly in patients with advanced disease and those accumulating malignant ascites.Influenza virus, a highly mutable respiratory pathogen, causes significant disease nearly every year. Current vaccines are designed to protect against circulating influenza strains of a given season. However, mismatches between vaccine strains and circulating strains, as well as inferior vaccine effectiveness in immunodeficient populations, represent major obstacles. In an effort to expand the breadth of protection elicited by influenza vaccination, one of the major surface glycoproteins, hemagglutinin (HA), has been modified to develop immunogens that display conserved regions from multiple viruses or elicit a highly polyclonal antibody response to broaden protection. These approaches, which target either the head or the stalk domain of HA, or both domains, have shown promise in recent preclinical and clinical studies. Furthermore, the role of adjuvants in bolstering the robustness of the humoral response has been studied, and their effects on the vaccine-elicited antibody repertoire are currently being investigated. This review will discuss the progress made in the universal influenza vaccine field with respect to influenza A viruses from the perspectives of both antigen and adjuvant, with a focus on the elicitation of broadly neutralizing antibodies.Membranes play a crucial role in efficiency and longevity of flow batteries. Vanadium flow batteries suffer self-discharge and capacity fading due to crossover of electrolyte components through the membrane from one battery half-cell to the other. We consider the impact of vanadium species crossing ion exchange membranes on state of charge of the battery and we present a simple method to determine crossoverll open circuit potential measurements. State of s. State of charge for the negative and positive half-cell is simulated based on assumptions and simplifications for cation and anion exchange membranes and different crossover parameters. We introduce a crossover index "IndXovr" which enables the determination of crossover direction from state of charge data for the negative and positive half-cell and therewith identification of the half-cell in which predominant self-discharge occurs. Furthermore IndXovr allows statements on crossover amount in dependence on state of operation. Simulated case studies are compared to experimental state of charge values estimated from half-cell potential measurements. Our results reveal that half-cell potential monitoring respectively half-cell SOC estimation, is a simple and suitable tool for the identification of crossover direction and relative amount of crossover in VFB.Hydrogen sulfide (H2S)-mediated signaling pathways regulate many physiological and pathophysiological processes in mammalian and plant systems. The molecular mechanism by which hydrogen sulfide exerts its action involves the posttranslational modification of cysteine residues to form a persulfidated thiol motif. We developed a comparative and label-free quantitative proteomic analysis approach for the detection of endogenous persulfidated proteins in N-starved Arabidopsis thaliana roots by using the tag-switch method. In this work, we identified 5214 unique proteins from root tissue that were persulfidated, 1674 of which were quantitatively analyzed and found to show altered persulfidation levels in vivo under N deprivation. https://www.selleckchem.com/products/NPI-2358.html These proteins represented almost 13% of the entire annotated proteome in Arabidopsis. Bioinformatic analysis revealed that persulfidated proteins were involved in a wide range of biological functions, regulating important processes such as primary metabolism, plant responses to stresses, growth and development, RNA translation and protein degradation.
    TET2 is a dioxygenase dependent on Fe2+ and α-ketoglutarate which oxidizes 5-methylcytosine (5meC) to 5-hydroxymethylcytosine (5hmeC). TET proteins successively oxidize 5mC to yield 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Among these oxidized methylcytosines, 5fC and 5caC are directly excised by thymine DNA glycosylase (TDG) and ultimately replaced with unmethylated cytosine. Mutations in TET2 have been shown to lead to a hypermethylated state of the genome and to be responsible for the initiation of the oncogenetic process, especially in myeloid and lymphoid malignancies. Nonetheless, this was also shown to be the case in other cancers. In AML, TET2 mutations have been observed to be mutually exclusive with IDH1, IDH2, and WT1 mutations, all of them showing a similar impact on the transcription profile of the affected cell. Because of this, it is possible that TET2/IDH1/2/WT1 mutated AML could be considered as having similar characteristics between each other. Nonetheless, other genes also interact with TET2 and influence its effect, thus making it possible that other signatures exist that would mimic the effect of TET2 mutations. Thus, in this review, we searched the literature for the genes that were observed to interact with TET2 and classified them in the following manner transcription alteration, miRs, direct interaction, posttranslational changes, and substrate reduction. What we propose in the present review is the potential extension of the TET2/IDH1/2/WT1 entity with the addition of certain expression signatures that would be able to induce a similar phenotype with that induced by TET2 mutations. Nonetheless, we recommend that this approach be taken on a disease by disease basis.The mechanisms and clinical significance of the cellular senescence of tumor cells are a matter of ongoing debate. Recently, the triggers and molecular events underlying spontaneous, replicative senescence of primary epithelial ovarian cancer cells were characterized. In this study, we reanalyzed tumors obtained from ovarian cancer patients with respect to the expression of the senescence biomarkers SA-β-Gal and γ-H2A.X and the proliferative antigen Ki67. The results showed that the tumors displayed strong heterogeneity with respect to the expression of analyzed markers. The expression of SA-β-Gal and γ-H2A.X in the oldest patients (61-85 y.o.) was significantly higher than in the younger age groups. Conversely, the area of Ki67-positive cancer cells was greater in younger individuals. At the same time, there was a positive correlation between SA-β-Gal expression and calendar age in FIGO III-IV and malignant ascites-positive patients. The γ-H2A.X positively correlated with age in the whole group, FIGO III-IV, and ascites-positive patients. Ki67 levels correlated negatively with the age of patients among those same groups. Collectively, our study indicated that organismal aging may determine the development of the senescence phenotype in ovarian tumors, particularly in patients with advanced disease and those accumulating malignant ascites.Influenza virus, a highly mutable respiratory pathogen, causes significant disease nearly every year. Current vaccines are designed to protect against circulating influenza strains of a given season. However, mismatches between vaccine strains and circulating strains, as well as inferior vaccine effectiveness in immunodeficient populations, represent major obstacles. In an effort to expand the breadth of protection elicited by influenza vaccination, one of the major surface glycoproteins, hemagglutinin (HA), has been modified to develop immunogens that display conserved regions from multiple viruses or elicit a highly polyclonal antibody response to broaden protection. These approaches, which target either the head or the stalk domain of HA, or both domains, have shown promise in recent preclinical and clinical studies. Furthermore, the role of adjuvants in bolstering the robustness of the humoral response has been studied, and their effects on the vaccine-elicited antibody repertoire are currently being investigated. This review will discuss the progress made in the universal influenza vaccine field with respect to influenza A viruses from the perspectives of both antigen and adjuvant, with a focus on the elicitation of broadly neutralizing antibodies.Membranes play a crucial role in efficiency and longevity of flow batteries. Vanadium flow batteries suffer self-discharge and capacity fading due to crossover of electrolyte components through the membrane from one battery half-cell to the other. We consider the impact of vanadium species crossing ion exchange membranes on state of charge of the battery and we present a simple method to determine crossoverll open circuit potential measurements. State of s. State of charge for the negative and positive half-cell is simulated based on assumptions and simplifications for cation and anion exchange membranes and different crossover parameters. We introduce a crossover index "IndXovr" which enables the determination of crossover direction from state of charge data for the negative and positive half-cell and therewith identification of the half-cell in which predominant self-discharge occurs. Furthermore IndXovr allows statements on crossover amount in dependence on state of operation. Simulated case studies are compared to experimental state of charge values estimated from half-cell potential measurements. Our results reveal that half-cell potential monitoring respectively half-cell SOC estimation, is a simple and suitable tool for the identification of crossover direction and relative amount of crossover in VFB.Hydrogen sulfide (H2S)-mediated signaling pathways regulate many physiological and pathophysiological processes in mammalian and plant systems. The molecular mechanism by which hydrogen sulfide exerts its action involves the posttranslational modification of cysteine residues to form a persulfidated thiol motif. We developed a comparative and label-free quantitative proteomic analysis approach for the detection of endogenous persulfidated proteins in N-starved Arabidopsis thaliana roots by using the tag-switch method. In this work, we identified 5214 unique proteins from root tissue that were persulfidated, 1674 of which were quantitatively analyzed and found to show altered persulfidation levels in vivo under N deprivation. https://www.selleckchem.com/products/NPI-2358.html These proteins represented almost 13% of the entire annotated proteome in Arabidopsis. Bioinformatic analysis revealed that persulfidated proteins were involved in a wide range of biological functions, regulating important processes such as primary metabolism, plant responses to stresses, growth and development, RNA translation and protein degradation.
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  • 050, CI 1.010-1.093,
     = 0.015 and OR 1.063, CI 1.026-1.101,
     = 0.001, respectively) and higher BMI was associated with major polypharmacy (OR 1.186, CI 1.18-1.29,
     = 0.001). The rates of discontinuation of first DMT were similar among the three groups (50.7% for no-Poly RRMS, 50.8% for minor-Poly RRMS, and 53.3% for major-Poly RRMS,
     = 0.264). At log-Rank test, there were no differences among the three groups (
     = 0.834).

    Polypharmacy was more common in older RRMS patients with high BMI.
    Polypharmacy was more common in older RRMS patients with high BMI.Omniligase-1 is a broadly applicable enzyme for peptide bond formation between an activated acyl donor peptide and a non-protected acyl acceptor peptide. The enzyme is derived from an earlier subtilisin variant called peptiligase by several rounds of protein engineering aimed at increasing synthetic yields and substrate range. To examine the contribution of individual mutations on S/H ratio and substrate scope in peptide synthesis, we selected peptiligase variant M222P/L217H as a starting enzyme and introduced successive mutations. Mutation A225N in the S1' pocket and F189W of the S2' pocket increased the synthesis to hydrolysis (S/H) ratio and overall coupling efficiency, whereas the I107V mutation was added to S4 pocket to increase the reaction rate. The final omniligase variants appeared to have a very broad substrate range, coupling more than 250 peptides in a 400-member library of acyl acceptors, as indicated by a high-throughput FRET assay. Crystal structures and computational modelling could rationalize the exceptional properties of omniligase-1 in peptide synthesis.Immunotherapy has become a promising therapeutic option for Head and neck squamous cell carcinoma (HNSC). However, only a small percentage of patients could benefit from it, and the overall prognosis was far from satisfactory. https://www.selleckchem.com/products/SU11274.html In this study, by comprehensively computational analyses of hundreds of HNSC samples, a prognostic signature composed of 13 immune-related genes (IRGs) was constructed. The results of the analyses in multiple datasets indicated that our signature had high predictive accuracy and could serve as an independent prognostic predictor. Based on this signature and multiple clinical variables, we also established a prognostic nomogram to quantitatively predict the survival risk of individual patients. Moreover, this signature could accurately predict survival, reflect the immune microenvironment, and predict immunotherapy efficacy among HNSC patients. Two potential drugs (doxorubicin and daunorubicin) were also identified via Connectivity Map and molecular docking, which could be used for HNSC combination therapy. Taken together, we developed and validated a robust IRG-based prognostic signature to monitor the prognosis of HNSC, which could provide a solid foundation for individualized cancer immunotherapy.The properties of biological networks, such as those found in the ocular lens capsule, are difficult to study without simplified models. Model polymers are developed, inspired by "worm-like" curve models, that are shown to spontaneously self assemble to form networks similar to those observed experimentally in biological systems. These highly simplified coarse-grained models allow the self assembly process to be studied on near-realistic time-scales. Metrics are developed (using a polygon-based framework) which are useful for describing simulated networks and can also be applied to images of real networks. These metrics are used to show the range of control that the computational polymer model has over the networks, including the polygon structure and short range order. The structure of the simulated networks are compared to previous simulation work and microscope images of real networks. The network structure is shown to be a function of the interaction strengths, cooling rates and external pressure. In addition, "pre-tangled" network structures are introduced and shown to significantly influence the subsequent network structure. The network structures obtained fit into a region of the network landscape effectively inaccessible to random (entropically-driven) networks but which are occupied by experimentally-derived configurations.3D multicellular spheroids quickly emerged as in vitro models because they represent the in vivo tumor environment better than standard 2D cell cultures. However, with current microscopy technologies, it is difficult to visualize individual cells in the deeper layers of 3D samples mainly because of limited light penetration and scattering. To overcome this problem several optical clearing methods have been proposed but defining the most appropriate clearing approach is an open issue due to the lack of a gold standard metric. Here, we propose a guideline for 3D light microscopy imaging to achieve single-cell resolution. The guideline includes a validation experiment focusing on five optical clearing protocols. We review and compare seven quality metrics which quantitatively characterize the imaging quality of spheroids. As a test environment, we have created and shared a large 3D dataset including approximately hundred fluorescently stained and optically cleared spheroids. Based on the results we introduce the use of a novel quality metric as a promising method to serve as a gold standard, applicable to compare optical clearing protocols, and decide on the most suitable one for a particular experiment.The significance and ability for receptor targeted nanoliposomes (tNLs) to bind to their molecular targets in solid tumors in vivo has been questioned, particularly as the efficiency of their tumor accumulation and selectivity is not always predictive of their efficacy or molecular specificity. This study presents, for the first time, in situ NIR molecular imaging-based quantitation of the in vivo specificity of tNLs for their target receptors, as opposed to tumor selectivity, which includes influences of enhanced tumor permeability and retention. Results show that neither tumor delivery nor selectivity (tumor-to-normal ratio) of cetuximab and IRDye conjugated tNLs correlate with EGFR expression in U251, U87 and 9L tumors, and in fact underrepresent their imaging-derived molecular specificity by up to 94.2%. Conversely, their in vivo specificity, which we quantify as the concentration of tNL-reported tumor EGFR provided by NIR molecular imaging, correlates positively with EGFR expression levels in vitro and ex vivo (Pearson's r= 0.
    050, CI 1.010-1.093,  = 0.015 and OR 1.063, CI 1.026-1.101,  = 0.001, respectively) and higher BMI was associated with major polypharmacy (OR 1.186, CI 1.18-1.29,  = 0.001). The rates of discontinuation of first DMT were similar among the three groups (50.7% for no-Poly RRMS, 50.8% for minor-Poly RRMS, and 53.3% for major-Poly RRMS,  = 0.264). At log-Rank test, there were no differences among the three groups (  = 0.834). Polypharmacy was more common in older RRMS patients with high BMI. Polypharmacy was more common in older RRMS patients with high BMI.Omniligase-1 is a broadly applicable enzyme for peptide bond formation between an activated acyl donor peptide and a non-protected acyl acceptor peptide. The enzyme is derived from an earlier subtilisin variant called peptiligase by several rounds of protein engineering aimed at increasing synthetic yields and substrate range. To examine the contribution of individual mutations on S/H ratio and substrate scope in peptide synthesis, we selected peptiligase variant M222P/L217H as a starting enzyme and introduced successive mutations. Mutation A225N in the S1' pocket and F189W of the S2' pocket increased the synthesis to hydrolysis (S/H) ratio and overall coupling efficiency, whereas the I107V mutation was added to S4 pocket to increase the reaction rate. The final omniligase variants appeared to have a very broad substrate range, coupling more than 250 peptides in a 400-member library of acyl acceptors, as indicated by a high-throughput FRET assay. Crystal structures and computational modelling could rationalize the exceptional properties of omniligase-1 in peptide synthesis.Immunotherapy has become a promising therapeutic option for Head and neck squamous cell carcinoma (HNSC). However, only a small percentage of patients could benefit from it, and the overall prognosis was far from satisfactory. https://www.selleckchem.com/products/SU11274.html In this study, by comprehensively computational analyses of hundreds of HNSC samples, a prognostic signature composed of 13 immune-related genes (IRGs) was constructed. The results of the analyses in multiple datasets indicated that our signature had high predictive accuracy and could serve as an independent prognostic predictor. Based on this signature and multiple clinical variables, we also established a prognostic nomogram to quantitatively predict the survival risk of individual patients. Moreover, this signature could accurately predict survival, reflect the immune microenvironment, and predict immunotherapy efficacy among HNSC patients. Two potential drugs (doxorubicin and daunorubicin) were also identified via Connectivity Map and molecular docking, which could be used for HNSC combination therapy. Taken together, we developed and validated a robust IRG-based prognostic signature to monitor the prognosis of HNSC, which could provide a solid foundation for individualized cancer immunotherapy.The properties of biological networks, such as those found in the ocular lens capsule, are difficult to study without simplified models. Model polymers are developed, inspired by "worm-like" curve models, that are shown to spontaneously self assemble to form networks similar to those observed experimentally in biological systems. These highly simplified coarse-grained models allow the self assembly process to be studied on near-realistic time-scales. Metrics are developed (using a polygon-based framework) which are useful for describing simulated networks and can also be applied to images of real networks. These metrics are used to show the range of control that the computational polymer model has over the networks, including the polygon structure and short range order. The structure of the simulated networks are compared to previous simulation work and microscope images of real networks. The network structure is shown to be a function of the interaction strengths, cooling rates and external pressure. In addition, "pre-tangled" network structures are introduced and shown to significantly influence the subsequent network structure. The network structures obtained fit into a region of the network landscape effectively inaccessible to random (entropically-driven) networks but which are occupied by experimentally-derived configurations.3D multicellular spheroids quickly emerged as in vitro models because they represent the in vivo tumor environment better than standard 2D cell cultures. However, with current microscopy technologies, it is difficult to visualize individual cells in the deeper layers of 3D samples mainly because of limited light penetration and scattering. To overcome this problem several optical clearing methods have been proposed but defining the most appropriate clearing approach is an open issue due to the lack of a gold standard metric. Here, we propose a guideline for 3D light microscopy imaging to achieve single-cell resolution. The guideline includes a validation experiment focusing on five optical clearing protocols. We review and compare seven quality metrics which quantitatively characterize the imaging quality of spheroids. As a test environment, we have created and shared a large 3D dataset including approximately hundred fluorescently stained and optically cleared spheroids. Based on the results we introduce the use of a novel quality metric as a promising method to serve as a gold standard, applicable to compare optical clearing protocols, and decide on the most suitable one for a particular experiment.The significance and ability for receptor targeted nanoliposomes (tNLs) to bind to their molecular targets in solid tumors in vivo has been questioned, particularly as the efficiency of their tumor accumulation and selectivity is not always predictive of their efficacy or molecular specificity. This study presents, for the first time, in situ NIR molecular imaging-based quantitation of the in vivo specificity of tNLs for their target receptors, as opposed to tumor selectivity, which includes influences of enhanced tumor permeability and retention. Results show that neither tumor delivery nor selectivity (tumor-to-normal ratio) of cetuximab and IRDye conjugated tNLs correlate with EGFR expression in U251, U87 and 9L tumors, and in fact underrepresent their imaging-derived molecular specificity by up to 94.2%. Conversely, their in vivo specificity, which we quantify as the concentration of tNL-reported tumor EGFR provided by NIR molecular imaging, correlates positively with EGFR expression levels in vitro and ex vivo (Pearson's r= 0.
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  • Potassium level is measured for patients with high risk of hyperkalemia in the emergency department (ED) using both blood gas analyser (BGA) and biochemistry analyser (BCA). The study was conducted to evaluate the correlation and agreement of potassium measurement between BGA and BCA.

    This is a prospective cross-sectional study on the data obtained from Hospital Universiti Sains Malaysia (Hospital USM) from Jun 2018 until May 2019. Blood samples were taken via a single ***** from venous blood and sent separately using 1ml heparinised syringe and were analysed immediately in ED using BGA (Radiometer, ABL800 FLEX, Denmark) and another sample was sent to the central laboratory of Hospital USM and analysed by BCA (Architect, C8000, USA). Only patients who had potassium levels ≥5.0mmol/L on blood gas results were included. A total of 173 sample pairs were included. The correlation and agreement were evaluated using Passing and Bablok regression, Linear Regression and Bland-Altman test.

    Of the 173 sample pairs, the median of potassium level based on BGA and BCA were 5.50mmol/L (IQR 1.00) and 5.90mmol/L (IQR 0.95) respectively. There was significant correlation between two measurements (p<0.001, r 0.36). https://www.selleckchem.com/products/salinosporamide-a-npi-0052-marizomib.html The agreement between the two measurements showed within acceptable mean difference which was 0.27 mmol/L with 95% limit of agreement were 1.21mmol/L to 1.73mmol/L.

    The result of blood gas can be used as a guide for initial treatment of hyperkalaemia in critical cases where time is of the essence. However, BCA result is still the definitive value.
    The result of blood gas can be used as a guide for initial treatment of hyperkalaemia in critical cases where time is of the essence. However, BCA result is still the definitive value.
    Hepatocellular carcinoma (HCC) is among the common death-causing cancers worldwide. This liver malignancy is primarily diagnosed using radiological imaging techniques. Most of the patients in Malaysia present late and were diagnosed at an intermediate or advanced stage of Barcelona Clinic of Liver Cancer (BCLC). This causes a limitation on the treatment options for the patients.

    We performed a retrospective crosssectional study of HCC cases within a five-year period in our center with data collected from Hospital Canselor Tunku Mukhriz (HCTM). This study examines the HCC risk factors, the pattern of diagnosis, treatment options and overall survival.

    The findings from this study showed that viral hepatitis was the highest risk factor in which most of the patients were elderly males who presented with abdominal distension. In addition, given the high prevalence of metabolic diseases Malaysia, it is predicted that the number of non-alcoholic steatohepatosis (NASH)-related HCC cases might increase. Alpha-fetoprotein (AFP) proved to have no significant role in the detection of the disease. The number of patients detected at early BCLC was minimal, resulting in limited options of treatment. Overall survival of our HCC patients was poor at 17 months.

    We conclude that HCC patients in HCTM mostly presented at late stage to hospital, hence limiting the treatment options and resulted in poor survival rate. Disease awareness should be implemented at primary care level to detect HCC at its early stage. Subsequently, a multidisciplinary hospital team is required to manage the disease at its different stages of presentation.
    We conclude that HCC patients in HCTM mostly presented at late stage to hospital, hence limiting the treatment options and resulted in poor survival rate. Disease awareness should be implemented at primary care level to detect HCC at its early stage. Subsequently, a multidisciplinary hospital team is required to manage the disease at its different stages of presentation.
    Influenza outbreak causes high economic burden to Malaysia and other countries in South East Asia. Scientists have found a relatively new way to detect influenza outbreaks early thus reducing the burden of disease by early intervention. This new technology is a social network information system which uses Facebook or Twitter data to detect potential influenza cases. Such system is good to be developed by the Malaysian government as it can detect influenza outbreaks three weeks earlier than the normal pathway. However, to implement this we require good evidence that the development will be accepted by potential users.

    This study was looking at the acceptance towards using social network information system among public health workers.

    This study was done on 205 Malaysian One Health University Network (MyOHUN) members through email and physical survey.

    Results show that 62.4% public health workers accepted the use technology. The acceptance was shown to be associated with performance expectancy (p<0.0ory of Acceptance and Use of Technology (UTAUT) model, the acceptance of social network information system was not associated with effort expectancy, social factors, facilitating conditions and socio-demographic factors. Therefore, it is suggested that social network information system be developed by the authorities in Malaysia, and be developed in a way that the system could strongly increase performance in detection of outbreak earlier than the current normal pathways. As such the system to be accepted and used, it must be sensitive, specific and be able to detect influenza outbreak early CONCLUSION The development of social network information system is feasible as it is highly accepted and it's potential to improve early detection of influenza outbreak.
    Healthcare workers serve as the frontliners against the coronavirus 2019 disease (COVID-19) and this puts them most at risk of infection as they attend to numerous patients with unknown status. This study aimed to examine stress, anxiety, and depression among healthcare workers caring for COVID-19 patients in Sarawak General Hospital (SGH), Malaysia.

    This cross-sectional observational study conducted in SGH during the pandemic with an online self-administered questionnaire composed of two parts, the socio-demographic characteristics, and the Depression Anxiety Stress Scale (DASS).

    A total of 105 healthcare workers responded to this study. A questionnaire in both Bahasa Melayu and English was used. The findings showed that all healthcare workers had mild anxiety, with the majority experiencing mild stress (57.1%), and almost half of the respondents experiencing mild depression (41%). Female subjects had a significant higher mean score in anxiety level and stress level compared to male subjects (10.0±3.20 vs.
    Potassium level is measured for patients with high risk of hyperkalemia in the emergency department (ED) using both blood gas analyser (BGA) and biochemistry analyser (BCA). The study was conducted to evaluate the correlation and agreement of potassium measurement between BGA and BCA. This is a prospective cross-sectional study on the data obtained from Hospital Universiti Sains Malaysia (Hospital USM) from Jun 2018 until May 2019. Blood samples were taken via a single prick from venous blood and sent separately using 1ml heparinised syringe and were analysed immediately in ED using BGA (Radiometer, ABL800 FLEX, Denmark) and another sample was sent to the central laboratory of Hospital USM and analysed by BCA (Architect, C8000, USA). Only patients who had potassium levels ≥5.0mmol/L on blood gas results were included. A total of 173 sample pairs were included. The correlation and agreement were evaluated using Passing and Bablok regression, Linear Regression and Bland-Altman test. Of the 173 sample pairs, the median of potassium level based on BGA and BCA were 5.50mmol/L (IQR 1.00) and 5.90mmol/L (IQR 0.95) respectively. There was significant correlation between two measurements (p<0.001, r 0.36). https://www.selleckchem.com/products/salinosporamide-a-npi-0052-marizomib.html The agreement between the two measurements showed within acceptable mean difference which was 0.27 mmol/L with 95% limit of agreement were 1.21mmol/L to 1.73mmol/L. The result of blood gas can be used as a guide for initial treatment of hyperkalaemia in critical cases where time is of the essence. However, BCA result is still the definitive value. The result of blood gas can be used as a guide for initial treatment of hyperkalaemia in critical cases where time is of the essence. However, BCA result is still the definitive value. Hepatocellular carcinoma (HCC) is among the common death-causing cancers worldwide. This liver malignancy is primarily diagnosed using radiological imaging techniques. Most of the patients in Malaysia present late and were diagnosed at an intermediate or advanced stage of Barcelona Clinic of Liver Cancer (BCLC). This causes a limitation on the treatment options for the patients. We performed a retrospective crosssectional study of HCC cases within a five-year period in our center with data collected from Hospital Canselor Tunku Mukhriz (HCTM). This study examines the HCC risk factors, the pattern of diagnosis, treatment options and overall survival. The findings from this study showed that viral hepatitis was the highest risk factor in which most of the patients were elderly males who presented with abdominal distension. In addition, given the high prevalence of metabolic diseases Malaysia, it is predicted that the number of non-alcoholic steatohepatosis (NASH)-related HCC cases might increase. Alpha-fetoprotein (AFP) proved to have no significant role in the detection of the disease. The number of patients detected at early BCLC was minimal, resulting in limited options of treatment. Overall survival of our HCC patients was poor at 17 months. We conclude that HCC patients in HCTM mostly presented at late stage to hospital, hence limiting the treatment options and resulted in poor survival rate. Disease awareness should be implemented at primary care level to detect HCC at its early stage. Subsequently, a multidisciplinary hospital team is required to manage the disease at its different stages of presentation. We conclude that HCC patients in HCTM mostly presented at late stage to hospital, hence limiting the treatment options and resulted in poor survival rate. Disease awareness should be implemented at primary care level to detect HCC at its early stage. Subsequently, a multidisciplinary hospital team is required to manage the disease at its different stages of presentation. Influenza outbreak causes high economic burden to Malaysia and other countries in South East Asia. Scientists have found a relatively new way to detect influenza outbreaks early thus reducing the burden of disease by early intervention. This new technology is a social network information system which uses Facebook or Twitter data to detect potential influenza cases. Such system is good to be developed by the Malaysian government as it can detect influenza outbreaks three weeks earlier than the normal pathway. However, to implement this we require good evidence that the development will be accepted by potential users. This study was looking at the acceptance towards using social network information system among public health workers. This study was done on 205 Malaysian One Health University Network (MyOHUN) members through email and physical survey. Results show that 62.4% public health workers accepted the use technology. The acceptance was shown to be associated with performance expectancy (p<0.0ory of Acceptance and Use of Technology (UTAUT) model, the acceptance of social network information system was not associated with effort expectancy, social factors, facilitating conditions and socio-demographic factors. Therefore, it is suggested that social network information system be developed by the authorities in Malaysia, and be developed in a way that the system could strongly increase performance in detection of outbreak earlier than the current normal pathways. As such the system to be accepted and used, it must be sensitive, specific and be able to detect influenza outbreak early CONCLUSION The development of social network information system is feasible as it is highly accepted and it's potential to improve early detection of influenza outbreak. Healthcare workers serve as the frontliners against the coronavirus 2019 disease (COVID-19) and this puts them most at risk of infection as they attend to numerous patients with unknown status. This study aimed to examine stress, anxiety, and depression among healthcare workers caring for COVID-19 patients in Sarawak General Hospital (SGH), Malaysia. This cross-sectional observational study conducted in SGH during the pandemic with an online self-administered questionnaire composed of two parts, the socio-demographic characteristics, and the Depression Anxiety Stress Scale (DASS). A total of 105 healthcare workers responded to this study. A questionnaire in both Bahasa Melayu and English was used. The findings showed that all healthcare workers had mild anxiety, with the majority experiencing mild stress (57.1%), and almost half of the respondents experiencing mild depression (41%). Female subjects had a significant higher mean score in anxiety level and stress level compared to male subjects (10.0±3.20 vs.
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  • 01-0.06, 0.11-1.15 and 0.09-0.79 corresponding to Cd, Pb and Zn respectively). Therefore, miscanthus could be considered a TE-excluder, hence a potential candidate crop for coupling phytostabilization and biomass production on the studied Metaleurop TE-contaminated soils.Rice cultivation under cadmium (Cd) contaminated soil often results in reduced growth with excess grain Cd concentrations. A pot experiment was conducted to assess the potential of ultrasonic seed treatment to alleviate Cd stress in rice. Seeds of two aromatic rice cultivars i.e., Xiangyaxiangzhan and Meixiangzhan 2 and two non-aromatic rice cultivars i.e., Huahang 31 and Guangyan 1 were exposed to ultrasonic waves for 1.5 min in 20-40 KHz mixing frequency. The experimental treatments were comprised of untreated seeds (U0) and ultrasonic treated seeds (U1) transplanted in un-contaminated soil (H0) and Cd-contaminated soil (H1). Results revealed that Cd contents and Cd accumulation in grain in U1 were 33.33-42.31% and 12.86-57.58% lower than U0 for fragrant rice cultivars under H1. Meanwhile, biomass production was higher in U1 than U0 under H0 and better yield was assessed in U1 for all cultivars under H1. The activity of peroxidase (POD) in flag leaves was increased by 8.28-115.65% for all cultivars while malondialdehyde (MDA) contents were significantly decreased in U1 compared with U0 under H0. Conclusively, ultrasonic treatment modulated Cd distribution and accumulation in different parts while improved physiological performance as well as yield and grain quality of rice under Cd contaminated conditions.Nuclear factor erythroid 2-related factor 2 (Nrf2) is a nuclear transcription factor of great concern which is widely involved in physiological and pathological processes of the organism, but the role and regulatory mechanism of Nrf2 in kidney exposed to cadmium (Cd) remain largely unknown. Here we demonstrated that Cd exposure induced injury in primary rat proximal tubular (rPT) cells and NRK-52E cell line, which was accompanied by autophagic flux blockade and subsequent accumulation of p62. Cd-activated nucleus translocation of Nrf2 depended on p62, which promoted antioxidant genes transcription, but it failed to against Cd-induced cell injury and ultimately succumbed to Cd toxicity. CDDO Methyl Ester (CDDO-ME) or ML385 treatment aggravated or alleviated rPT cells injury induced by Cd respectively, indicating that Nrf2 nucleus translocation played a negative role during Cd-induced rPT cells injury. Phosphorylation of 5' AMP-activated protein kinase (AMPK) decreased together with enhanced Nrf2 nucleus translocation in rPT cells exposed to Cd. Dephosphorylation of AMPK induced by Cd were facilitated or restored by CDDO-ME or ML385 treatment, which confirmed AMPK is a downstream factor of Nrf2. Simultaneously, CDDO-ME further enhanced Phosphorylation of mTOR and AKT which increased during Cd exposure. While, Cd-induced phosphorylation of mTOR and AKT were reversed by ML385 treatment. These results illustrated that Cd mediated Nrf2 nucleus translocation depends on p62 accumulation which results from autophagic flux inhibition. The enhanced nucleus translocation of Nrf2 suppresses phosphorylation of AMPK to inactivate AKT/mTOR signaling, and results in rPT cells injury finally.
    The aim of the study is to develop a valid and reliable tool to assess sociobehavioural changes due to COVID among the general population.

    This mixed method study has two phases. Phase I for questionnaire development (literature review, focus group discussion, expert evaluation and pilot testing). Phase II for establishing construct validity via factor analysis and internal consistency via Cronbach's ɑ by administering the questionnaire on 179 participants.

    A questionnaire comprising 33 questions and five domains was developed having Cronbach's α of 0·82.

    The developed questionnaire is a concise, easy to administer and valid tool to assess socio-behavioural changes.
    The developed questionnaire is a concise, easy to administer and valid tool to assess socio-behavioural changes.
    The government of India recently planned to start the process of the mass vaccination program to end the COVID-19 crises. However, the process of vaccination was not made mandatory, and there are a lot of aspects that arise skepticism in the minds of common people regarding COVID-19 vaccines. This study using machine learning techniques analyzes the major concerns Indian citizens voice out about COVID-19 vaccines in social media.

    For this study, we have used social media posts as data. Using Python, we have scrapped the social media posts of Indian citizens discussing about the COVID- 19 vaccine. In Study 1, we performed a sentimental analysis to determine how the general perception of Indian citizens regarding the COVID-19 vaccine changes over different months of COVID-19 crises. In Study 2, we have performed topic modeling to understand the major issues that concern the general public regarding the COVID- 19 vaccine.

    Our results have indicated that 47% of social media posts discussing vaccines were in a neutral tone, and nearly 17% of the social media posts discussing the COVID-19 vaccine were in a negative tone. Fear of health and allergic reactions towards the vaccine are the two prominent issues that concern Indian citizens regarding the COVID-19 vaccine.

    With the positive sentiments regarding vaccine is just over 35%, the Indian government needs to focus especially on addressing the fear of vaccines before implementing the process of mass vaccination.
    With the positive sentiments regarding vaccine is just over 35%, the Indian government needs to focus especially on addressing the fear of vaccines before implementing the process of mass vaccination.
    Previous studies have reported the beneficial roles of the activation of calmodulin-dependent protein kinase (CaMK)II to many cellular functions associated with human health. This review aims at discussing its activation by exercise as well as its roles in the regulation of unsaturated, saturated, omega 3 fatty acids, and lipid metabolism.

    A wide literature search was conducted using online database such as 'PubMed', 'Google Scholar', 'Researcher', 'Scopus' and the website of World Health Organization (WHO) as well as Control Disease and Prevention (CDC). https://www.selleckchem.com/products/cpi-203.html The criteria for the search were mainly lipid and fatty acid metabolism, diabetes, and metabolic syndrome (MetS). A total of ninety-seven articles were included in the review.

    Calmodulin-dependent protein kinase activation by exercise is helpful in controlling membrane lipids related with type 2 diabetes and obesity. CaMKII regulates many health beneficial cellular functions in individuals who exercise compared with those who do not exercise. Regulation of lipid metabolism and fatty acids are crucial in the improvement of metabolic syndrome.
    01-0.06, 0.11-1.15 and 0.09-0.79 corresponding to Cd, Pb and Zn respectively). Therefore, miscanthus could be considered a TE-excluder, hence a potential candidate crop for coupling phytostabilization and biomass production on the studied Metaleurop TE-contaminated soils.Rice cultivation under cadmium (Cd) contaminated soil often results in reduced growth with excess grain Cd concentrations. A pot experiment was conducted to assess the potential of ultrasonic seed treatment to alleviate Cd stress in rice. Seeds of two aromatic rice cultivars i.e., Xiangyaxiangzhan and Meixiangzhan 2 and two non-aromatic rice cultivars i.e., Huahang 31 and Guangyan 1 were exposed to ultrasonic waves for 1.5 min in 20-40 KHz mixing frequency. The experimental treatments were comprised of untreated seeds (U0) and ultrasonic treated seeds (U1) transplanted in un-contaminated soil (H0) and Cd-contaminated soil (H1). Results revealed that Cd contents and Cd accumulation in grain in U1 were 33.33-42.31% and 12.86-57.58% lower than U0 for fragrant rice cultivars under H1. Meanwhile, biomass production was higher in U1 than U0 under H0 and better yield was assessed in U1 for all cultivars under H1. The activity of peroxidase (POD) in flag leaves was increased by 8.28-115.65% for all cultivars while malondialdehyde (MDA) contents were significantly decreased in U1 compared with U0 under H0. Conclusively, ultrasonic treatment modulated Cd distribution and accumulation in different parts while improved physiological performance as well as yield and grain quality of rice under Cd contaminated conditions.Nuclear factor erythroid 2-related factor 2 (Nrf2) is a nuclear transcription factor of great concern which is widely involved in physiological and pathological processes of the organism, but the role and regulatory mechanism of Nrf2 in kidney exposed to cadmium (Cd) remain largely unknown. Here we demonstrated that Cd exposure induced injury in primary rat proximal tubular (rPT) cells and NRK-52E cell line, which was accompanied by autophagic flux blockade and subsequent accumulation of p62. Cd-activated nucleus translocation of Nrf2 depended on p62, which promoted antioxidant genes transcription, but it failed to against Cd-induced cell injury and ultimately succumbed to Cd toxicity. CDDO Methyl Ester (CDDO-ME) or ML385 treatment aggravated or alleviated rPT cells injury induced by Cd respectively, indicating that Nrf2 nucleus translocation played a negative role during Cd-induced rPT cells injury. Phosphorylation of 5' AMP-activated protein kinase (AMPK) decreased together with enhanced Nrf2 nucleus translocation in rPT cells exposed to Cd. Dephosphorylation of AMPK induced by Cd were facilitated or restored by CDDO-ME or ML385 treatment, which confirmed AMPK is a downstream factor of Nrf2. Simultaneously, CDDO-ME further enhanced Phosphorylation of mTOR and AKT which increased during Cd exposure. While, Cd-induced phosphorylation of mTOR and AKT were reversed by ML385 treatment. These results illustrated that Cd mediated Nrf2 nucleus translocation depends on p62 accumulation which results from autophagic flux inhibition. The enhanced nucleus translocation of Nrf2 suppresses phosphorylation of AMPK to inactivate AKT/mTOR signaling, and results in rPT cells injury finally. The aim of the study is to develop a valid and reliable tool to assess sociobehavioural changes due to COVID among the general population. This mixed method study has two phases. Phase I for questionnaire development (literature review, focus group discussion, expert evaluation and pilot testing). Phase II for establishing construct validity via factor analysis and internal consistency via Cronbach's ɑ by administering the questionnaire on 179 participants. A questionnaire comprising 33 questions and five domains was developed having Cronbach's α of 0·82. The developed questionnaire is a concise, easy to administer and valid tool to assess socio-behavioural changes. The developed questionnaire is a concise, easy to administer and valid tool to assess socio-behavioural changes. The government of India recently planned to start the process of the mass vaccination program to end the COVID-19 crises. However, the process of vaccination was not made mandatory, and there are a lot of aspects that arise skepticism in the minds of common people regarding COVID-19 vaccines. This study using machine learning techniques analyzes the major concerns Indian citizens voice out about COVID-19 vaccines in social media. For this study, we have used social media posts as data. Using Python, we have scrapped the social media posts of Indian citizens discussing about the COVID- 19 vaccine. In Study 1, we performed a sentimental analysis to determine how the general perception of Indian citizens regarding the COVID-19 vaccine changes over different months of COVID-19 crises. In Study 2, we have performed topic modeling to understand the major issues that concern the general public regarding the COVID- 19 vaccine. Our results have indicated that 47% of social media posts discussing vaccines were in a neutral tone, and nearly 17% of the social media posts discussing the COVID-19 vaccine were in a negative tone. Fear of health and allergic reactions towards the vaccine are the two prominent issues that concern Indian citizens regarding the COVID-19 vaccine. With the positive sentiments regarding vaccine is just over 35%, the Indian government needs to focus especially on addressing the fear of vaccines before implementing the process of mass vaccination. With the positive sentiments regarding vaccine is just over 35%, the Indian government needs to focus especially on addressing the fear of vaccines before implementing the process of mass vaccination. Previous studies have reported the beneficial roles of the activation of calmodulin-dependent protein kinase (CaMK)II to many cellular functions associated with human health. This review aims at discussing its activation by exercise as well as its roles in the regulation of unsaturated, saturated, omega 3 fatty acids, and lipid metabolism. A wide literature search was conducted using online database such as 'PubMed', 'Google Scholar', 'Researcher', 'Scopus' and the website of World Health Organization (WHO) as well as Control Disease and Prevention (CDC). https://www.selleckchem.com/products/cpi-203.html The criteria for the search were mainly lipid and fatty acid metabolism, diabetes, and metabolic syndrome (MetS). A total of ninety-seven articles were included in the review. Calmodulin-dependent protein kinase activation by exercise is helpful in controlling membrane lipids related with type 2 diabetes and obesity. CaMKII regulates many health beneficial cellular functions in individuals who exercise compared with those who do not exercise. Regulation of lipid metabolism and fatty acids are crucial in the improvement of metabolic syndrome.
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  • Finally, a rescue assay was performed. The results suggested that lncRNA FOXD2-AS1 was upregulated in ovarian cancer tissues and cell lines. si-FOXD2-AS1 was able to inhibit the proliferation, migration and invasion of ovarian cancer cells. lncRNA FOXD2-AS1 was confirmed to directly target miR-4492. The expression of lncRNA FOXD2-AS1 and miR-4492 exhibited a negative correlation. In a rescue experiment, miR-4492 inhibitor abrogated the effect of siFOXD2-AS1 in SKOV3 and OVCAR3 cell lines. In conclusion, lncRNA FOXD2-AS1 promotes the proliferation and invasion of ovarian cancer cells via regulating the expression of miR-4492. It may be a novel potential diagnostic biomarker and therapeutic target for ovarian cancer.Infertility is defined as the inability to procreate, or carry or deliver a baby naturally. The majority of specialists describe infertility as being unable to get pregnant after having tried for at least one year. The relationship between infertility and psychological stress is complex. On the one hand, infertile couples are subject to greater stress and have a greater risk of developing psychological disorders compared with normal, healthy couples. https://www.selleckchem.com/products/onx-0914-pr-957.html On the other hand, high levels of psychological distress have been indicated to increase infertility. Therefore, in the present review, the main factors that may lead to increased stress in couples who try to conceive, psychological stress as the reason for infertility, and the therapies that can help decrease psychological distress and increase chances of pregnancy are underlined. In addition to the psychological side effects that may occur from infertility itself, a range of other side effects can be caused by hormones and drugs used to treat infertility. Additionally, problem during erection and ejaculation can cause of psychological distress, which can lead to infertility among men. Psychotherapy is the main intervention recommended for couples who suffer from any form of infertility. Ideally, counselling should begin before patients start any medical intervention to help with their infertility.Although keratin 15 (KRT15) has been indicated to be overexpressed in several types of tumor, its role in breast invasive carcinoma (****) has so far remained elusive. The aim of the present study was to explore KRT15 expression in **** based on data obtained from The Cancer Genome Atlas and The Genotype-Tissue Expression. KRT15 expression was compared using a Wilcoxon rank-sum test. Functional enrichment analysis was performed to reveal the biological roles and pathways of KRT15. The association between KRT15 expression and immune-cell infiltration was evaluated via single-sample gene set enrichment analysis (ssGSEA). To investigate the relationship between clinicopathological features and KRT15 expression, the prognostic value of KRT15 and other clinical factors was evaluated using Cox regression analysis and Kaplan-Meier (KM) plots. Subgroup prognostic analysis was also performed using forest plots and KM curves. Finally, a tissue microarray was used to assess KRT15 expression in **** tissues. KRT15 expresr in normal tissues compared with those in the **** tissues. In conclusion, low KRT15 expression was significantly associated with poor prognosis in patients with ****. Thus, KRT15 may serve an important role in **** progression and may be used as a promising prognostic marker for diagnostic and prognostic analyses in patients with ****.Distal trisomy or duplication of 15q is a very rare chromosomal disorder; most of the previously reported cases were derived from unbalanced translocations involving chromosome 15 and another chromosome, whereas other mechanisms (e.g. duplication) have rarely been reported. We herein report a very rare prenatal case of a partial 15q trisomy, a 42.64-Mb duplication of 15q22.2-q26.3, arising from a maternal pericentric inversion of chromosome 15 (p11q22) that was not the result of an unbalanced translocation or duplication, and was not associated with concomitant partial monosomy. Fetal ultrasound revealed isolated thickened nuchal translucency at 12 weeks and multiple abnormalities in the second trimester, including early growth restriction, unilateral ventriculomegaly, narrow cavum septi pellucidi with hypoplasia of the corpus callosum, unilateral postaxial polydactyly, clenched hands and clubfoot with clawing of the toes, and a particular general dysplastic and hypotrophic aspect of the heart. The distinctive aspects of the present case may help to refine the phenotype associated with distal duplication 15q. To the best of our knowledge, this is the first report of a prenatal diagnosis with a 15q22.2-q26.3 duplication that did not result from an unbalanced translocation and did not have a concomitant monosomic component.The aim of the present study was to investigate the effects of diammonium glycyrrhizinate lipid ligand (DGLL) treatment on acute lung injury (ALI) and pulmonary edema induced by lipopolysaccharide (LPS) in Sprague-Dawley rats. Rats orally received 30, 60 and 120 mg/kg DGLL. After 1 h, the rat ALI model was established by LPS (10 mg/kg) intraperitoneal injection. After 6 h, lung injury was evaluated using hematoxylin and eosin staining techniques. Pulmonary edema was evaluated using lung wet-dry weight ratio, protein concentrations in the bronchoalveolar lavage fluid (BALF) and Evans blue (EB) extravasation in lung tissue. The expression levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in lung tissues were measured using ELISA. Myeloperoxidase (MPO) expression levels were detected by immunohistochemical staining. Western blotting was used to measure the expression level changes of intercellular adhesion molecule (ICAM)-1, as well as adherent and tight junction proteins, including vascular endothelial (VE)-cadherin, zonula occludens (ZO)-1, occludin and junctional adhesion molecule (JAM)-1 that were associated with pulmonary inflammation and microvascular permeability. DGLL treatment significantly alleviated ALI induced by LPS, which was demonstrated by reduction of MPO-positive cells and expression levels of TNF-α, IL-1β and ICAM-1 in rat lung tissues. In addition, DGLL abrogated LPS-induced pulmonary edema, decreased the protein concentration in BALF and reduced EB extravasation. DGLL also reversed the reduced expression of VE-cadherin and tight junction proteins, including ZO-1, occludin and JAM-1 in the lung tissues caused by LPS. In conclusion, DGLL exhibits a protective effect on LPS-induced rat ALI, which is associated with the inhibition of inflammatory cell infiltration and microvascular barrier disruption. The present results provide a theoretical basis for the application of DGLL for the potential clinical treatment of ALI.
    Finally, a rescue assay was performed. The results suggested that lncRNA FOXD2-AS1 was upregulated in ovarian cancer tissues and cell lines. si-FOXD2-AS1 was able to inhibit the proliferation, migration and invasion of ovarian cancer cells. lncRNA FOXD2-AS1 was confirmed to directly target miR-4492. The expression of lncRNA FOXD2-AS1 and miR-4492 exhibited a negative correlation. In a rescue experiment, miR-4492 inhibitor abrogated the effect of siFOXD2-AS1 in SKOV3 and OVCAR3 cell lines. In conclusion, lncRNA FOXD2-AS1 promotes the proliferation and invasion of ovarian cancer cells via regulating the expression of miR-4492. It may be a novel potential diagnostic biomarker and therapeutic target for ovarian cancer.Infertility is defined as the inability to procreate, or carry or deliver a baby naturally. The majority of specialists describe infertility as being unable to get pregnant after having tried for at least one year. The relationship between infertility and psychological stress is complex. On the one hand, infertile couples are subject to greater stress and have a greater risk of developing psychological disorders compared with normal, healthy couples. https://www.selleckchem.com/products/onx-0914-pr-957.html On the other hand, high levels of psychological distress have been indicated to increase infertility. Therefore, in the present review, the main factors that may lead to increased stress in couples who try to conceive, psychological stress as the reason for infertility, and the therapies that can help decrease psychological distress and increase chances of pregnancy are underlined. In addition to the psychological side effects that may occur from infertility itself, a range of other side effects can be caused by hormones and drugs used to treat infertility. Additionally, problem during erection and ejaculation can cause of psychological distress, which can lead to infertility among men. Psychotherapy is the main intervention recommended for couples who suffer from any form of infertility. Ideally, counselling should begin before patients start any medical intervention to help with their infertility.Although keratin 15 (KRT15) has been indicated to be overexpressed in several types of tumor, its role in breast invasive carcinoma (BRCA) has so far remained elusive. The aim of the present study was to explore KRT15 expression in BRCA based on data obtained from The Cancer Genome Atlas and The Genotype-Tissue Expression. KRT15 expression was compared using a Wilcoxon rank-sum test. Functional enrichment analysis was performed to reveal the biological roles and pathways of KRT15. The association between KRT15 expression and immune-cell infiltration was evaluated via single-sample gene set enrichment analysis (ssGSEA). To investigate the relationship between clinicopathological features and KRT15 expression, the prognostic value of KRT15 and other clinical factors was evaluated using Cox regression analysis and Kaplan-Meier (KM) plots. Subgroup prognostic analysis was also performed using forest plots and KM curves. Finally, a tissue microarray was used to assess KRT15 expression in BRCA tissues. KRT15 expresr in normal tissues compared with those in the BRCA tissues. In conclusion, low KRT15 expression was significantly associated with poor prognosis in patients with BRCA. Thus, KRT15 may serve an important role in BRCA progression and may be used as a promising prognostic marker for diagnostic and prognostic analyses in patients with BRCA.Distal trisomy or duplication of 15q is a very rare chromosomal disorder; most of the previously reported cases were derived from unbalanced translocations involving chromosome 15 and another chromosome, whereas other mechanisms (e.g. duplication) have rarely been reported. We herein report a very rare prenatal case of a partial 15q trisomy, a 42.64-Mb duplication of 15q22.2-q26.3, arising from a maternal pericentric inversion of chromosome 15 (p11q22) that was not the result of an unbalanced translocation or duplication, and was not associated with concomitant partial monosomy. Fetal ultrasound revealed isolated thickened nuchal translucency at 12 weeks and multiple abnormalities in the second trimester, including early growth restriction, unilateral ventriculomegaly, narrow cavum septi pellucidi with hypoplasia of the corpus callosum, unilateral postaxial polydactyly, clenched hands and clubfoot with clawing of the toes, and a particular general dysplastic and hypotrophic aspect of the heart. The distinctive aspects of the present case may help to refine the phenotype associated with distal duplication 15q. To the best of our knowledge, this is the first report of a prenatal diagnosis with a 15q22.2-q26.3 duplication that did not result from an unbalanced translocation and did not have a concomitant monosomic component.The aim of the present study was to investigate the effects of diammonium glycyrrhizinate lipid ligand (DGLL) treatment on acute lung injury (ALI) and pulmonary edema induced by lipopolysaccharide (LPS) in Sprague-Dawley rats. Rats orally received 30, 60 and 120 mg/kg DGLL. After 1 h, the rat ALI model was established by LPS (10 mg/kg) intraperitoneal injection. After 6 h, lung injury was evaluated using hematoxylin and eosin staining techniques. Pulmonary edema was evaluated using lung wet-dry weight ratio, protein concentrations in the bronchoalveolar lavage fluid (BALF) and Evans blue (EB) extravasation in lung tissue. The expression levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in lung tissues were measured using ELISA. Myeloperoxidase (MPO) expression levels were detected by immunohistochemical staining. Western blotting was used to measure the expression level changes of intercellular adhesion molecule (ICAM)-1, as well as adherent and tight junction proteins, including vascular endothelial (VE)-cadherin, zonula occludens (ZO)-1, occludin and junctional adhesion molecule (JAM)-1 that were associated with pulmonary inflammation and microvascular permeability. DGLL treatment significantly alleviated ALI induced by LPS, which was demonstrated by reduction of MPO-positive cells and expression levels of TNF-α, IL-1β and ICAM-1 in rat lung tissues. In addition, DGLL abrogated LPS-induced pulmonary edema, decreased the protein concentration in BALF and reduced EB extravasation. DGLL also reversed the reduced expression of VE-cadherin and tight junction proteins, including ZO-1, occludin and JAM-1 in the lung tissues caused by LPS. In conclusion, DGLL exhibits a protective effect on LPS-induced rat ALI, which is associated with the inhibition of inflammatory cell infiltration and microvascular barrier disruption. The present results provide a theoretical basis for the application of DGLL for the potential clinical treatment of ALI.
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  • In an era of constrained and depleted natural resources, perennial grains could provide sustainable food production along with beneficial ecosystem services like reduced erosion and increased atmospheric carbon capture. Intermediate wheatgrass (IWG) [Thinopyrum intermedium (Host) Barkworth & D. R. Dewey subsp. intermedium] has been undergoing continuous breeding for domestication to develop a perennial grain crop since the 1980s. As a perennial, IWG has required 2-5 yr per selection generation, but starting in 2017, genomic selection (GS) was initiated in the breeding program at The Land Institute, Salina, KS (TLI), enabling one complete cycle per year. For each cycle, ∼4,000 seedlings were profiled using genotyping-by-sequencing (GBS) and genomic estimated breeding values (GEBVs) were calculated. Selection based on GEBVs identified ∼100 individuals to advance as parents each generation, while validation populations of 1,000-1,200 genets for GS model training were also selected using the genomic relationship matrix to represent genetic diversity in each cycle. The selected parents were randomly intermated in a greenhouse crossing block to form the subsequent cycle, while the validation populations were transplanted to irrigated and nonirrigated field sites for phenotypic evaluations in the following years. https://www.selleckchem.com/products/blz945.html For priority breeding traits of seed mass, free threshing, and nonshattering, correlations between predicted values and observed data were >.5. The realized selection differential ranged from 11-23% for selected traits, and the expected genetic gains for these traits, including spike yield, ranged from 6 to 14% per year. Genomic selection is a powerful tool to speed the domestication and development of IWG and other perennial crops with extended breeding timelines.Chronic rhinosinusitis with nasal polyps (CRSwNP) represents a challenging disease entity with significant rates of recurrence following appropriate medical and surgical therapy. Recent approval of targeted biologics in CRSwNP compels deeper understanding of underlying disease pathophysiology. Both of the approved biologics for CRSwNP modulate the type 2 inflammatory pathway, and the majority of drugs in the clinical trials pathway are similarly targeted. However, there remain multiple other pathogenic mechanisms relevant to CRSwNP for which targeted therapeutics already exist in other inflammatory diseases that have not been studied directly. In this article we summarize pathogenic mechanisms of interest in CRSwNP and discuss the results of ongoing clinical studies of targeted therapeutics in CRSwNP and other related human inflammatory diseases.
    Oral and oropharyngeal cancer are significant health problems. They are both life-threatening conditions usually diagnosed at an advanced stage causing survival rates to decline.

    To assess and compare practices, knowledge and attitude regarding oral and oropharyngeal cancer between dental and medical practitioners.

    A cross-sectional study was conducted to assess knowledge, attitude and practices of oral and oropharyngeal cancer among dental and medical practitioners at King Abdulaziz Medical City, Riyadh, Saudi Arabia. 360 participants were included in the study using a convenient sampling technique. Participants were approached in their clinics and printed self-administered questionnaire were handed over to them after signing a written consent form. Frequency distribution and Chi-Square test were used for the statistical analysis and the level of significance was set at P value of .05 or less.

    A total of 174 participants responded. Assessment of oral and oropharyngeal cancer knowledge between dental practitioners and medical practitioners showed comparable results. Regarding practices, a significant difference was seen between medical practitioners and dental practitioners in determining the duration of intra-oral ulcer to consider urgent referral (P= .006) and in number of referrals made in relation to suspicious oral lesions (P= .002). Moreover, a significant difference (P= .006) was seen between medical practitioners and dental practitioners in determining the duration of intra-oral ulcer to consider urgent referral.

    Medical and dental practitioners showed areas of differences in practice, attitude and knowledge of oral and oropharyngeal cancer that when addressed would lead to improved survival rates.
    Medical and dental practitioners showed areas of differences in practice, attitude and knowledge of oral and oropharyngeal cancer that when addressed would lead to improved survival rates.
    Understanding the daily health experiences of people with intellectual disability is necessary to illuminate factors that may be influencing health and health disparities. The objective of this study is to understand how people with intellectual disability participate in and access health promotion.

    Ten adults with intellectual disability engaged in an adapted photovoice study.

    Four themes emerged Health Is Who We Are; Health is What We Do; Health Is Our Body, Mind, and Place; and Barriers and Facilitators. Participants communicated an understanding of health, a strong identity of themselves as being healthy, and diverse participation in health promotion. Additionally, participants identified specific resources and support necessary to pursue health. Participants' broad description of health aligns with understandings of the social determinants of health.

    Participant's holistic view of health and experienced factors of health promotion should inform the development and implementation of inclusive health programming for people with intellectual disability.
    Participant's holistic view of health and experienced factors of health promotion should inform the development and implementation of inclusive health programming for people with intellectual disability.The present study reported the antimicrobial susceptibility trends, virulence genes, and drug resistance genes of Vibrio cholerae O1 strains isolated from outbreaks and epidemics over two and half decades (1995-2019) from Odisha, India. Antimicrobial susceptibility testing was performed by disc diffusion method. Virulence and drug resistance genes were detected by multiplex PCR assays. All V. cholerae O1 strains were sensitive to gentamicin, chloramphenicol, norfloxacin and ciprofloxacin while resistant to one or more antibiotics used. About 90% of the isolates of V. cholerae O1 carried antibiotic drug resistant genes (SulII, dfrA1 and strB) and SXT elements and the results correlated with the phenotypic antibiotic data obtained through disc diffusion assay. The tcpA Haitian variant V. cholerae O1 first appeared in 1999, gradually showing its increasing number upto 2019. TcpA El Tor strains only prevailed from 1995 to 2006; whereas the tcpA classical strains of V.choleraeO1 were found in less number from 1995 to 2016.
    In an era of constrained and depleted natural resources, perennial grains could provide sustainable food production along with beneficial ecosystem services like reduced erosion and increased atmospheric carbon capture. Intermediate wheatgrass (IWG) [Thinopyrum intermedium (Host) Barkworth & D. R. Dewey subsp. intermedium] has been undergoing continuous breeding for domestication to develop a perennial grain crop since the 1980s. As a perennial, IWG has required 2-5 yr per selection generation, but starting in 2017, genomic selection (GS) was initiated in the breeding program at The Land Institute, Salina, KS (TLI), enabling one complete cycle per year. For each cycle, ∼4,000 seedlings were profiled using genotyping-by-sequencing (GBS) and genomic estimated breeding values (GEBVs) were calculated. Selection based on GEBVs identified ∼100 individuals to advance as parents each generation, while validation populations of 1,000-1,200 genets for GS model training were also selected using the genomic relationship matrix to represent genetic diversity in each cycle. The selected parents were randomly intermated in a greenhouse crossing block to form the subsequent cycle, while the validation populations were transplanted to irrigated and nonirrigated field sites for phenotypic evaluations in the following years. https://www.selleckchem.com/products/blz945.html For priority breeding traits of seed mass, free threshing, and nonshattering, correlations between predicted values and observed data were >.5. The realized selection differential ranged from 11-23% for selected traits, and the expected genetic gains for these traits, including spike yield, ranged from 6 to 14% per year. Genomic selection is a powerful tool to speed the domestication and development of IWG and other perennial crops with extended breeding timelines.Chronic rhinosinusitis with nasal polyps (CRSwNP) represents a challenging disease entity with significant rates of recurrence following appropriate medical and surgical therapy. Recent approval of targeted biologics in CRSwNP compels deeper understanding of underlying disease pathophysiology. Both of the approved biologics for CRSwNP modulate the type 2 inflammatory pathway, and the majority of drugs in the clinical trials pathway are similarly targeted. However, there remain multiple other pathogenic mechanisms relevant to CRSwNP for which targeted therapeutics already exist in other inflammatory diseases that have not been studied directly. In this article we summarize pathogenic mechanisms of interest in CRSwNP and discuss the results of ongoing clinical studies of targeted therapeutics in CRSwNP and other related human inflammatory diseases. Oral and oropharyngeal cancer are significant health problems. They are both life-threatening conditions usually diagnosed at an advanced stage causing survival rates to decline. To assess and compare practices, knowledge and attitude regarding oral and oropharyngeal cancer between dental and medical practitioners. A cross-sectional study was conducted to assess knowledge, attitude and practices of oral and oropharyngeal cancer among dental and medical practitioners at King Abdulaziz Medical City, Riyadh, Saudi Arabia. 360 participants were included in the study using a convenient sampling technique. Participants were approached in their clinics and printed self-administered questionnaire were handed over to them after signing a written consent form. Frequency distribution and Chi-Square test were used for the statistical analysis and the level of significance was set at P value of .05 or less. A total of 174 participants responded. Assessment of oral and oropharyngeal cancer knowledge between dental practitioners and medical practitioners showed comparable results. Regarding practices, a significant difference was seen between medical practitioners and dental practitioners in determining the duration of intra-oral ulcer to consider urgent referral (P= .006) and in number of referrals made in relation to suspicious oral lesions (P= .002). Moreover, a significant difference (P= .006) was seen between medical practitioners and dental practitioners in determining the duration of intra-oral ulcer to consider urgent referral. Medical and dental practitioners showed areas of differences in practice, attitude and knowledge of oral and oropharyngeal cancer that when addressed would lead to improved survival rates. Medical and dental practitioners showed areas of differences in practice, attitude and knowledge of oral and oropharyngeal cancer that when addressed would lead to improved survival rates. Understanding the daily health experiences of people with intellectual disability is necessary to illuminate factors that may be influencing health and health disparities. The objective of this study is to understand how people with intellectual disability participate in and access health promotion. Ten adults with intellectual disability engaged in an adapted photovoice study. Four themes emerged Health Is Who We Are; Health is What We Do; Health Is Our Body, Mind, and Place; and Barriers and Facilitators. Participants communicated an understanding of health, a strong identity of themselves as being healthy, and diverse participation in health promotion. Additionally, participants identified specific resources and support necessary to pursue health. Participants' broad description of health aligns with understandings of the social determinants of health. Participant's holistic view of health and experienced factors of health promotion should inform the development and implementation of inclusive health programming for people with intellectual disability. Participant's holistic view of health and experienced factors of health promotion should inform the development and implementation of inclusive health programming for people with intellectual disability.The present study reported the antimicrobial susceptibility trends, virulence genes, and drug resistance genes of Vibrio cholerae O1 strains isolated from outbreaks and epidemics over two and half decades (1995-2019) from Odisha, India. Antimicrobial susceptibility testing was performed by disc diffusion method. Virulence and drug resistance genes were detected by multiplex PCR assays. All V. cholerae O1 strains were sensitive to gentamicin, chloramphenicol, norfloxacin and ciprofloxacin while resistant to one or more antibiotics used. About 90% of the isolates of V. cholerae O1 carried antibiotic drug resistant genes (SulII, dfrA1 and strB) and SXT elements and the results correlated with the phenotypic antibiotic data obtained through disc diffusion assay. The tcpA Haitian variant V. cholerae O1 first appeared in 1999, gradually showing its increasing number upto 2019. TcpA El Tor strains only prevailed from 1995 to 2006; whereas the tcpA classical strains of V.choleraeO1 were found in less number from 1995 to 2016.
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  • The reflex zone stimulation technique (RST) activates complex motor responses and has a positive impact on the locomotor system. This technique may also indirectly affect breathing; however, the use of this technique as adjunct of the treatment of cystic fibrosis (CF) has not yet been characterised.

    We performed a randomised controlled single-centre interventional trial to evaluate the short-term effects of RST on lung function in 21 paediatric CF patients with normal baseline spirometry. The effect of 30 min of RST was compared to that of sham therapy in a crossover design. The interventions were performed in random order and planned 6 months apart. The primary outcome was a change in global ventilation inhomogeneity after intervention, assessed by lung clearance index (LCI
    ) derived from a nitrogen multiple breath washout test. Secondary outcomes included changes in regional ventilation inhomogeneity (indices of acinar [Sacin*Vt] and conductive airway [Scond*Vt] inhomogeneity) and spirometry parameters (inspiratory capacity, forced vital capacity, and forced expiratory volume in 1 s). Trunk deformity was assessed by physiotherapists at study entry.

    After the RST intervention, the LCI
    (p = .004) and Scond*Vt (p = .009) decreased significantly, while inspiratory capacity increased (p = .012). In the sham-therapy group, none of the parameters changed significantly. Trunk deformity was seen in 76.5% of all patients, and 92.9% of those with trunk deformity showed a decrease in LCI
    after RST.

    RST has multiple positive short-term effects on lung function, especially in CF patients with trunk deformities.
    RST has multiple positive short-term effects on lung function, especially in CF patients with trunk deformities.Organoselenium compounds constitute an important class of substances with applications in the biological, medicinal and material sciences as well as in modern organic synthesis, attracting considerable attention from the scientific community. Therefore, the construction of the C-Se bond via facile, efficient and sustainable strategies to access complex scaffolds from simple substrates are an appealing and hot topic. Visible light can be regarded as an alternative source of energy and is associated with environmentally-friendly processes. Recently, the use of visible-light mediated seleno-functionalization has emerged as an ideal and powerful route to obtain high-value selenylated products, with diminished cost and waste. This approach, involving photo-excited substrates/catalyst and single-electron transfer (SET) between substrates in the presence of visible light has been successfully used in the versatile and direct insertion of organoselenium moieties in activated and unactivated C(sp3 )-H, C(sp2 )-H, C(sp)-H bonds as well as C-heteroatom bonds. In most cases, ease of operation and accessibility of the light source (LEDs or commercial CFL bulbs) makes this approach more attractive and sustainable than the traditional strategies.The pyrrhotite Fe7 S8 with mixed Fe-valence possesses high theoretical capacity, high conductivity, low discharge/charge voltage plateaus, and superior redox reversibility but suffers from structural degradation upon (de)potassiation process due to severe volume variations. Herein, to conquer this issue, a novel hierarchical architecture of confining nano-Fe7 S8 in carbon nanotubes covalently bonded onto 3D few-layer graphene (Fe7 S8 @CNT@3DFG) is designed for potassium storage. https://www.selleckchem.com/products/azd0364.html Notably, CNTs could successfully grow on the surface of 3DFG via a tip-growth model under the catalytic effect of Fe3 C. Such structure enables the hierarchical confinement of 0D nano-Fe7 S8 to 1D CNTs and further 1D CNTs to 3DFG, effectively buffering the volume variations, prohibiting the agglomeration of Fe7 S8 nanograins, and boosting the ionic/electronic transportation through the stable and conductive CNTs-grafted 3DFG framework. The as-prepared Fe7 S8 @CNT@3DFG electrode delivers an exceptional rate capability (502 mAh g-1 at 50 mA g-1 with 277 mAh g-1 at 1000 mA g-1 ) and an excellent long-term cyclic stability up to 1300 cycles. Besides, the in-situ XRD and ex-situ XPS/HRTEM results first elucidate the highly reversible potassium-storage mechanism of Fe7 S8 . Furthermore, the designed potassium full-cell employing Fe7 S8 @CNT@3DFG anode and potassium Prussian blue (KPB) cathode delivers a promising energy density of ≈120 Wh kg-1 , demonstrating great application prospects.Crystallographic facets in a crystal carry interior properties and proffer rich functionalities in a wide range of application areas. However, rational prediction, on-demand customization, and accurate synthesis of facets and facet junctions of a crystal are enormously desirable but still challenging. Herein, a framework of machine learning (ML)-aided crystal facet design with ionic liquid controllable synthesis is developed and then demonstrated with the star-material anatase TiO2 . Aided by employing ML to acquire surface energies from facet junction datasource, the relationships between surface energy and growth conditions based on the Langmuir adsorption isotherm are unveiled, enabling to develop controllable facet synthetic strategies. These strategies are successfully verified after applied for synthesizing TiO2 crystals with custom crystal facets and facet junctions under tuning ionic liquid [bmim][BF4 ] experimental conditions. Therefore, this innovative framework integrates data-intensive rational design and experimental controllable synthesis to develop and customize crystallographic facets and facet junctions. This proves the feasibility of an intelligent chemistry future to accelerate the discovery of facet-governed functional material candidates.The alternative splicing of select genes is an important mechanism to regulate responses to endogenous and environmental signals in plants. However, the role of alternative splicing in regulating fruit ripening remains unclear. Here, we discovered that MaMYB16L, an R1-type MYB transcription factor, undergoes alternative splicing and generates two transcripts, the full-length isoform MaMYB16L and a truncated form MaMYB16S, in banana fruit. During banana fruit ripening, the alternative splicing process intensifies with downregulated MaMYB16L and upregulated MaMYB16S. Moreover, MaMYB16L is a transcriptional repressor that directly binds with the promoters of many genes associated with starch degradation and MaDREB2, a positive ripening regulator, and represses their expression. In contrast, MaMBY16S lacks a DNA-binding domain but competitively combines and forms non-functional heterodimers with functional MaMYB16L. MaMYB16L-MaMYB16S heterodimers decrease the binding capacity and transrepression activity of MaMYB16L.
    The reflex zone stimulation technique (RST) activates complex motor responses and has a positive impact on the locomotor system. This technique may also indirectly affect breathing; however, the use of this technique as adjunct of the treatment of cystic fibrosis (CF) has not yet been characterised. We performed a randomised controlled single-centre interventional trial to evaluate the short-term effects of RST on lung function in 21 paediatric CF patients with normal baseline spirometry. The effect of 30 min of RST was compared to that of sham therapy in a crossover design. The interventions were performed in random order and planned 6 months apart. The primary outcome was a change in global ventilation inhomogeneity after intervention, assessed by lung clearance index (LCI ) derived from a nitrogen multiple breath washout test. Secondary outcomes included changes in regional ventilation inhomogeneity (indices of acinar [Sacin*Vt] and conductive airway [Scond*Vt] inhomogeneity) and spirometry parameters (inspiratory capacity, forced vital capacity, and forced expiratory volume in 1 s). Trunk deformity was assessed by physiotherapists at study entry. After the RST intervention, the LCI (p = .004) and Scond*Vt (p = .009) decreased significantly, while inspiratory capacity increased (p = .012). In the sham-therapy group, none of the parameters changed significantly. Trunk deformity was seen in 76.5% of all patients, and 92.9% of those with trunk deformity showed a decrease in LCI after RST. RST has multiple positive short-term effects on lung function, especially in CF patients with trunk deformities. RST has multiple positive short-term effects on lung function, especially in CF patients with trunk deformities.Organoselenium compounds constitute an important class of substances with applications in the biological, medicinal and material sciences as well as in modern organic synthesis, attracting considerable attention from the scientific community. Therefore, the construction of the C-Se bond via facile, efficient and sustainable strategies to access complex scaffolds from simple substrates are an appealing and hot topic. Visible light can be regarded as an alternative source of energy and is associated with environmentally-friendly processes. Recently, the use of visible-light mediated seleno-functionalization has emerged as an ideal and powerful route to obtain high-value selenylated products, with diminished cost and waste. This approach, involving photo-excited substrates/catalyst and single-electron transfer (SET) between substrates in the presence of visible light has been successfully used in the versatile and direct insertion of organoselenium moieties in activated and unactivated C(sp3 )-H, C(sp2 )-H, C(sp)-H bonds as well as C-heteroatom bonds. In most cases, ease of operation and accessibility of the light source (LEDs or commercial CFL bulbs) makes this approach more attractive and sustainable than the traditional strategies.The pyrrhotite Fe7 S8 with mixed Fe-valence possesses high theoretical capacity, high conductivity, low discharge/charge voltage plateaus, and superior redox reversibility but suffers from structural degradation upon (de)potassiation process due to severe volume variations. Herein, to conquer this issue, a novel hierarchical architecture of confining nano-Fe7 S8 in carbon nanotubes covalently bonded onto 3D few-layer graphene (Fe7 S8 @CNT@3DFG) is designed for potassium storage. https://www.selleckchem.com/products/azd0364.html Notably, CNTs could successfully grow on the surface of 3DFG via a tip-growth model under the catalytic effect of Fe3 C. Such structure enables the hierarchical confinement of 0D nano-Fe7 S8 to 1D CNTs and further 1D CNTs to 3DFG, effectively buffering the volume variations, prohibiting the agglomeration of Fe7 S8 nanograins, and boosting the ionic/electronic transportation through the stable and conductive CNTs-grafted 3DFG framework. The as-prepared Fe7 S8 @CNT@3DFG electrode delivers an exceptional rate capability (502 mAh g-1 at 50 mA g-1 with 277 mAh g-1 at 1000 mA g-1 ) and an excellent long-term cyclic stability up to 1300 cycles. Besides, the in-situ XRD and ex-situ XPS/HRTEM results first elucidate the highly reversible potassium-storage mechanism of Fe7 S8 . Furthermore, the designed potassium full-cell employing Fe7 S8 @CNT@3DFG anode and potassium Prussian blue (KPB) cathode delivers a promising energy density of ≈120 Wh kg-1 , demonstrating great application prospects.Crystallographic facets in a crystal carry interior properties and proffer rich functionalities in a wide range of application areas. However, rational prediction, on-demand customization, and accurate synthesis of facets and facet junctions of a crystal are enormously desirable but still challenging. Herein, a framework of machine learning (ML)-aided crystal facet design with ionic liquid controllable synthesis is developed and then demonstrated with the star-material anatase TiO2 . Aided by employing ML to acquire surface energies from facet junction datasource, the relationships between surface energy and growth conditions based on the Langmuir adsorption isotherm are unveiled, enabling to develop controllable facet synthetic strategies. These strategies are successfully verified after applied for synthesizing TiO2 crystals with custom crystal facets and facet junctions under tuning ionic liquid [bmim][BF4 ] experimental conditions. Therefore, this innovative framework integrates data-intensive rational design and experimental controllable synthesis to develop and customize crystallographic facets and facet junctions. This proves the feasibility of an intelligent chemistry future to accelerate the discovery of facet-governed functional material candidates.The alternative splicing of select genes is an important mechanism to regulate responses to endogenous and environmental signals in plants. However, the role of alternative splicing in regulating fruit ripening remains unclear. Here, we discovered that MaMYB16L, an R1-type MYB transcription factor, undergoes alternative splicing and generates two transcripts, the full-length isoform MaMYB16L and a truncated form MaMYB16S, in banana fruit. During banana fruit ripening, the alternative splicing process intensifies with downregulated MaMYB16L and upregulated MaMYB16S. Moreover, MaMYB16L is a transcriptional repressor that directly binds with the promoters of many genes associated with starch degradation and MaDREB2, a positive ripening regulator, and represses their expression. In contrast, MaMBY16S lacks a DNA-binding domain but competitively combines and forms non-functional heterodimers with functional MaMYB16L. MaMYB16L-MaMYB16S heterodimers decrease the binding capacity and transrepression activity of MaMYB16L.
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