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  • Cervical cancer is the fourth-ranked cancer in the world and is associated with a large number of deaths annually. Chemotherapy and radiotherapy are known as the common therapeutic approaches in the treatment of cervical cancer, but because of their side effects and toxicity, researchers are trying to discovery alternative therapies. Beta-glucans, a group of glucose polymers that are derived from the cell wall of fungi, bacteria, and etc. it has been showed that beta-glucans have some anti-cancer properties which due to their impacts on adaptive and innate immunity. Along to these impacts, these molecules could be used as drug carriers. In this regard, the application of beta-glucans is a promising therapeutic option for the cancer prevention and treatment especially for cervical cancer. Herein, we have summarized the therapeutic potential of beta-glucans alone or as adjuvant therapy in the treatment of cervical cancer. Moreover, we highlighted beta-glucans as drug carriers for preventive and therapeutic purposes.BACKGROUND Maternal smoking of traditional or electronic cigarettes during pregnancy, which constitutes developmental nicotine exposure (DNE), heightens the risk of neurodevelopmental disorders including ADHD, autism, and schizophrenia in children. Modeling the intergenerationally transmissible impacts of smoking during pregnancy, we previously demonstrated that both the first- and second-generation adolescent offspring of nicotine-exposed female **** exhibit enhanced nicotine preference, hyperactivity and risk-taking behaviors, aberrant rhythmicity of home cage activity, nicotinic acetylcholine receptor and dopamine transporter dysfunction, impaired furin-mediated proBDNF proteolysis, hypocorticosteronemia-related glucocorticoid receptor hypoactivity, and global DNA hypomethylation in the frontal cortices and striata. This ensemble of multigenerational DNE-induced behavioral, neuropharmacological, neurotrophic, neuroendocrine, and DNA methylomic anomalies recapitulates the pathosymptomatology of neurodevelopoth first- and second-generation DNE **** suggest that epigenetic perturbations may constitute a mechanistic hub for the intergenerational transmission of DNE-induced neurodevelopmental disorder-like phenotypes.BACKGROUND Mutations in PINK1 and parkin cause autosomal recessive Parkinson's disease (PD). Evidence placing PINK1 and parkin in common pathways regulating multiple aspects of mitochondrial quality control is burgeoning. However, compelling evidence to causatively link specific PINK1/parkin dependent mitochondrial pathways to dopamine neuron degeneration in PD is lacking. https://www.selleckchem.com/products/wp1066.html Although PINK1 and parkin are known to regulate mitophagy, emerging data suggest that defects in mitophagy are unlikely to be of pathological relevance. Mitochondrial functions of PINK1 and parkin are also tied to their proteasomal regulation of specific substrates. In this study, we examined how PINK1/parkin mediated regulation of the pathogenic substrate PARIS impacts dopaminergic mitochondrial network homeostasis and neuronal survival in Drosophila. METHODS The UAS-Gal4 system was employed for cell-type specific expression of the various transgenes. Effects on dopamine neuronal survival and function were assessed by anti-TH immunostaininpression in vivo. To our knowledge, PARIS is the only co-substrate of PINK1 and parkin to specifically accumulate in the DA neurons and cause neurodegeneration and locomotor defects stemming from disrupted dopamine signaling. CONCLUSIONS Our findings identify a highly conserved role for PINK1 and parkin in regulating mitochondrial biogenesis and promoting mitochondrial health via the PARIS/ PGC-1α axis. The Drosophila models described here effectively recapitulate the cardinal PD phenotypes and thus will facilitate identification of novel regulators of mitochondrial biogenesis for physiologically relevant therapeutic interventions.PURPOSE To quantify tumor anatomic change of non-small cell lung cancer (NSCLC) patients given passive-scattering proton therapy (PSPT) and intensity-modulated radiation therapy (IMRT) through 6-7 weeks of treatment, and analyze the correlation between anatomic change and the need to adopt adaptive radiotherapy (ART). MATERIALS AND METHODS Weekly 4D CT sets of 32 patients (8/8 IMRT with/without ART, 8/8 PSPT with/without ART) acquired during treatment, were registered to the planning CT using an in-house developed deformable registration algorithm. The anatomic change was quantified as the mean variation of the region of interest (ROI) relative to the planning CT by averaging the magnitude of deformation vectors of all voxels within the ROI contour. Mean variations of GTV and CTV were compared between subgroups classified by ART status and treatment modality using the independent t-test. Logistic regression analysis was performed to clarify the effect of anatomic change on the probability of ART adoption. RESULTS There was no significant difference (p = 0.679) for the time-averaged mean CTV variations from the planning CT between IMRT (7.61 ± 2.80 mm) and PSPT (7.21 ± 2.67 mm) patients. However, a significant difference (p = 0.001) was observed between ART (8.93 ± 2.19 mm) and non-ART (5.90 ± 2.33 mm) patients, when treatment modality was not considered. Mean CTV variation from the planning CT in all patients increases significantly (p  less then  0.001), with a changing rate of 1.77 mm per week. Findings for the GTV change was similar. The logistic regression model correctly predicted 71.9% of cases in ART adoption. The correlation is stronger in the PSPT group with a pseudo R2 value of 0.782, compared to that in the IMRT group (pseudo R2 = 0.182). CONCLUSION The magnitude of target volume variation over time could be greater than the usual treatment margin. Mean target volume variation from the planning position can be used to identify lung cancer patients that may need ART.The spatiotemporal control of 3D genome is fundamental for gene regulation, yet it remains challenging to profile high-resolution chromatin structure at cis-regulatory elements (CREs). Using C-terminally biotinylated dCas9, endogenous biotin ligases, and pooled sgRNAs, we describe the dCas9-based CAPTURE method for multiplexed analysis of locus-specific chromatin interactions. The redesigned system allows for quantitative analysis of the spatial configuration of a few to hundreds of enhancers or promoters in a single experiment, enabling comparisons across CREs within and between gene clusters. Multiplexed analyses of the spatiotemporal configuration of erythroid super-enhancers and promoter-centric interactions reveal organizational principles of genome structure and function.
    Cervical cancer is the fourth-ranked cancer in the world and is associated with a large number of deaths annually. Chemotherapy and radiotherapy are known as the common therapeutic approaches in the treatment of cervical cancer, but because of their side effects and toxicity, researchers are trying to discovery alternative therapies. Beta-glucans, a group of glucose polymers that are derived from the cell wall of fungi, bacteria, and etc. it has been showed that beta-glucans have some anti-cancer properties which due to their impacts on adaptive and innate immunity. Along to these impacts, these molecules could be used as drug carriers. In this regard, the application of beta-glucans is a promising therapeutic option for the cancer prevention and treatment especially for cervical cancer. Herein, we have summarized the therapeutic potential of beta-glucans alone or as adjuvant therapy in the treatment of cervical cancer. Moreover, we highlighted beta-glucans as drug carriers for preventive and therapeutic purposes.BACKGROUND Maternal smoking of traditional or electronic cigarettes during pregnancy, which constitutes developmental nicotine exposure (DNE), heightens the risk of neurodevelopmental disorders including ADHD, autism, and schizophrenia in children. Modeling the intergenerationally transmissible impacts of smoking during pregnancy, we previously demonstrated that both the first- and second-generation adolescent offspring of nicotine-exposed female mice exhibit enhanced nicotine preference, hyperactivity and risk-taking behaviors, aberrant rhythmicity of home cage activity, nicotinic acetylcholine receptor and dopamine transporter dysfunction, impaired furin-mediated proBDNF proteolysis, hypocorticosteronemia-related glucocorticoid receptor hypoactivity, and global DNA hypomethylation in the frontal cortices and striata. This ensemble of multigenerational DNE-induced behavioral, neuropharmacological, neurotrophic, neuroendocrine, and DNA methylomic anomalies recapitulates the pathosymptomatology of neurodevelopoth first- and second-generation DNE mice suggest that epigenetic perturbations may constitute a mechanistic hub for the intergenerational transmission of DNE-induced neurodevelopmental disorder-like phenotypes.BACKGROUND Mutations in PINK1 and parkin cause autosomal recessive Parkinson's disease (PD). Evidence placing PINK1 and parkin in common pathways regulating multiple aspects of mitochondrial quality control is burgeoning. However, compelling evidence to causatively link specific PINK1/parkin dependent mitochondrial pathways to dopamine neuron degeneration in PD is lacking. https://www.selleckchem.com/products/wp1066.html Although PINK1 and parkin are known to regulate mitophagy, emerging data suggest that defects in mitophagy are unlikely to be of pathological relevance. Mitochondrial functions of PINK1 and parkin are also tied to their proteasomal regulation of specific substrates. In this study, we examined how PINK1/parkin mediated regulation of the pathogenic substrate PARIS impacts dopaminergic mitochondrial network homeostasis and neuronal survival in Drosophila. METHODS The UAS-Gal4 system was employed for cell-type specific expression of the various transgenes. Effects on dopamine neuronal survival and function were assessed by anti-TH immunostaininpression in vivo. To our knowledge, PARIS is the only co-substrate of PINK1 and parkin to specifically accumulate in the DA neurons and cause neurodegeneration and locomotor defects stemming from disrupted dopamine signaling. CONCLUSIONS Our findings identify a highly conserved role for PINK1 and parkin in regulating mitochondrial biogenesis and promoting mitochondrial health via the PARIS/ PGC-1α axis. The Drosophila models described here effectively recapitulate the cardinal PD phenotypes and thus will facilitate identification of novel regulators of mitochondrial biogenesis for physiologically relevant therapeutic interventions.PURPOSE To quantify tumor anatomic change of non-small cell lung cancer (NSCLC) patients given passive-scattering proton therapy (PSPT) and intensity-modulated radiation therapy (IMRT) through 6-7 weeks of treatment, and analyze the correlation between anatomic change and the need to adopt adaptive radiotherapy (ART). MATERIALS AND METHODS Weekly 4D CT sets of 32 patients (8/8 IMRT with/without ART, 8/8 PSPT with/without ART) acquired during treatment, were registered to the planning CT using an in-house developed deformable registration algorithm. The anatomic change was quantified as the mean variation of the region of interest (ROI) relative to the planning CT by averaging the magnitude of deformation vectors of all voxels within the ROI contour. Mean variations of GTV and CTV were compared between subgroups classified by ART status and treatment modality using the independent t-test. Logistic regression analysis was performed to clarify the effect of anatomic change on the probability of ART adoption. RESULTS There was no significant difference (p = 0.679) for the time-averaged mean CTV variations from the planning CT between IMRT (7.61 ± 2.80 mm) and PSPT (7.21 ± 2.67 mm) patients. However, a significant difference (p = 0.001) was observed between ART (8.93 ± 2.19 mm) and non-ART (5.90 ± 2.33 mm) patients, when treatment modality was not considered. Mean CTV variation from the planning CT in all patients increases significantly (p  less then  0.001), with a changing rate of 1.77 mm per week. Findings for the GTV change was similar. The logistic regression model correctly predicted 71.9% of cases in ART adoption. The correlation is stronger in the PSPT group with a pseudo R2 value of 0.782, compared to that in the IMRT group (pseudo R2 = 0.182). CONCLUSION The magnitude of target volume variation over time could be greater than the usual treatment margin. Mean target volume variation from the planning position can be used to identify lung cancer patients that may need ART.The spatiotemporal control of 3D genome is fundamental for gene regulation, yet it remains challenging to profile high-resolution chromatin structure at cis-regulatory elements (CREs). Using C-terminally biotinylated dCas9, endogenous biotin ligases, and pooled sgRNAs, we describe the dCas9-based CAPTURE method for multiplexed analysis of locus-specific chromatin interactions. The redesigned system allows for quantitative analysis of the spatial configuration of a few to hundreds of enhancers or promoters in a single experiment, enabling comparisons across CREs within and between gene clusters. Multiplexed analyses of the spatiotemporal configuration of erythroid super-enhancers and promoter-centric interactions reveal organizational principles of genome structure and function.
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  • This study concludes that in soils with low Pb sorption ability, some of the Pb retained as DOM-Pb is water soluble and possibly re-released despite the presence of hydroxyapatite, although most Pb in DOM-Pb is stably sorbed as Pb ions. Indium and gallium are used widely in modern industry, mostly for the production of semiconductors. They are considered as Technology-Critical Elements and have therefore received growing attention in the past few years. We investigated the influence of different types of humic substances on the transport of indium and gallium in laboratory-scale, saturated column experiments, to gain understanding of their mobility in natural environments. We evaluated the effect of different humic substances on the transport of indium and gallium in quartz sand a commercial humic acid (Aldrich Humic Acid, AHA), a fulvic acid (Suwannee River Fulvic Acid, SRFA) and an aquatic natural organic matter (Suwannee River Natural Organic Matter, SRNOM). The impact of the flow rate and the influence of different concentrations of organic matter were also investigated. Indium was shown to be more mobile than gallium in the presence of humic substances. The mobility of indium in sand was highest for SRNOM, followed by SRFA and then AHA, while for gallium the order was SRFA > SRNOM > AHA. These results can be significant in understanding the mobility of indium and gallium in soils with various compositions of organic matter. Air pollution events occurred frequently in China, and tremendous efforts were devoted to the reduction of air pollution in recent years. Here, analysis of ambient monitoring data of six criteria air pollutants from 367 Chinese cities during 2015-2018, showed that PM2.5, PM10, SO2 and CO were reduced significantly by 22.1%, 13.5%, 46.4% and 21.5%, respectively, NO2 reduction was less significant (6.3%) while O3 level instead increased over China (13.7%). Spatial distribution, seasonal, monthly and diurnal variations of the air pollutants during 2018, implicated of effective control measures, were discussed in details, especially for the five key densely populated regions of Jing-Jin-Ji (JJJ), Fen Wei Plains (FWP), Yangtze River Delta (YRD), Sichuan Basin (SCB) and Pearl River Delta (PRD). Moreover, excess health risks (ERs) of the six pollutants were estimated for 2018, and such risks was two times higher if the World Health Organization (WHO) air quality guideline rather than Chinese guideline was adopted. Ptic product (GDP). The findings here demonstrate in great details the current characteristics of air pollution and its associated health risks in China, therefore providing important implications for effective air pollution control strategies in near future for different regions of China. BACKGROUND Preterm birth is a leading cause of infant morbidity and mortality. Identifying potentially modifiable triggers toward the end of gestation, such as extreme heat, can improve understanding of the role of acute stress on early deliveries and inform warning systems. In this study we examined the association between extreme heat, variously defined during the last week of gestation, and risk of preterm birth among mothers in California. METHODS We created a population-based cohort comprised of 1,967,300 mothers who had live, singleton births in California, from May through September 2005-2013. Daily temperature data estimated at the maternal zip code of residence was used to create 12 definitions of extreme heat with varying relative temperatures (75th, 90th, 95th, and 98th percentiles) and durations (at least 2, 3, or 4 consecutive days). We estimated risk of preterm birth ( less then 37 gestational weeks) in relation to exposure to extreme heat during the last week of gestation with multi-level Cox proportional hazard regression models, adjusting for maternal characteristics, sex of neonate, and seasonality. We also included randomly generated data, SAS code, and estimates for reproducibility purposes. RESULTS Approximately 7% of the cohort had a preterm birth. For all definitions of extreme heat, the risk of preterm birth was consistently higher among mothers who experienced an extreme heat episode during their last week of gestation. https://www.selleckchem.com/products/uc2288.html Hazard ratios ranged from 1.008 (95% CI 0.997, 1.021) to 1.128 (95% CI 1.052, 1.210), with increasing associations as the relative temperature and duration of extreme heat episode increased. CONCLUSION This study adds to the previous literature by considering multiple definitions of extreme heat and applying a time-to-event framework. Findings suggest that acute exposure to extreme heat during the last week of gestation may trigger an earlier delivery. Implementing heat warning systems targeted toward pregnant women may improve birth outcomes. Published by Elsevier Ltd.OBJECTIVE The different incidence of colorectal cancer between the sexes suggests that sex hormones may be involved in the susceptibility to colorectal cancer. The association between sex hormones and genetic variants in hormone metabolic pathways and the colorectal cancer risk remains unclear. METHODS We detected sex hormone levels in plasma from colorectal cancer patients and controls in males by ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). We evaluated the clinical significance of sex hormones on colorectal cancer diagnosis with the area under the receiver operating characteristic curve (AUC). The role of genetic variants in hormone metabolic pathways in the colorectal cancer risk was assessed by a logistic regression model. The biological functions were detected by luciferase reporter assays and cell behavior experiments. RESULTS We found that 2-methoxyestrone (2-MeO-E1) was highly expressed in cases (PFDR = 3.48 × 10-19). The expression of 2-MeO-E1 in plasma showed improved accuracy for predicting colorectal cancer (AUC = 0.88). In the 2-MeO-E1 metabolic pathway, rs165599 in COMT was significantly associated with an increased risk of colorectal cancer (P = 0.009). Mechanistically, we found that the rs165599 G allele could decrease the binding ability of miR-22-3p to the COMT 3'-UTR. Furthermore, knockdown of COMT inhibited cell proliferation, induced cell apoptosis and arrested the cell cycle in the G1 phase. CONCLUSION This is the first study to show that 2-MeO-E1 and a genetic variant in COMT contribute to the susceptibility to colorectal cancer. These results shed light on the different incidence of colorectal cancer between the sexes.
    This study concludes that in soils with low Pb sorption ability, some of the Pb retained as DOM-Pb is water soluble and possibly re-released despite the presence of hydroxyapatite, although most Pb in DOM-Pb is stably sorbed as Pb ions. Indium and gallium are used widely in modern industry, mostly for the production of semiconductors. They are considered as Technology-Critical Elements and have therefore received growing attention in the past few years. We investigated the influence of different types of humic substances on the transport of indium and gallium in laboratory-scale, saturated column experiments, to gain understanding of their mobility in natural environments. We evaluated the effect of different humic substances on the transport of indium and gallium in quartz sand a commercial humic acid (Aldrich Humic Acid, AHA), a fulvic acid (Suwannee River Fulvic Acid, SRFA) and an aquatic natural organic matter (Suwannee River Natural Organic Matter, SRNOM). The impact of the flow rate and the influence of different concentrations of organic matter were also investigated. Indium was shown to be more mobile than gallium in the presence of humic substances. The mobility of indium in sand was highest for SRNOM, followed by SRFA and then AHA, while for gallium the order was SRFA > SRNOM > AHA. These results can be significant in understanding the mobility of indium and gallium in soils with various compositions of organic matter. Air pollution events occurred frequently in China, and tremendous efforts were devoted to the reduction of air pollution in recent years. Here, analysis of ambient monitoring data of six criteria air pollutants from 367 Chinese cities during 2015-2018, showed that PM2.5, PM10, SO2 and CO were reduced significantly by 22.1%, 13.5%, 46.4% and 21.5%, respectively, NO2 reduction was less significant (6.3%) while O3 level instead increased over China (13.7%). Spatial distribution, seasonal, monthly and diurnal variations of the air pollutants during 2018, implicated of effective control measures, were discussed in details, especially for the five key densely populated regions of Jing-Jin-Ji (JJJ), Fen Wei Plains (FWP), Yangtze River Delta (YRD), Sichuan Basin (SCB) and Pearl River Delta (PRD). Moreover, excess health risks (ERs) of the six pollutants were estimated for 2018, and such risks was two times higher if the World Health Organization (WHO) air quality guideline rather than Chinese guideline was adopted. Ptic product (GDP). The findings here demonstrate in great details the current characteristics of air pollution and its associated health risks in China, therefore providing important implications for effective air pollution control strategies in near future for different regions of China. BACKGROUND Preterm birth is a leading cause of infant morbidity and mortality. Identifying potentially modifiable triggers toward the end of gestation, such as extreme heat, can improve understanding of the role of acute stress on early deliveries and inform warning systems. In this study we examined the association between extreme heat, variously defined during the last week of gestation, and risk of preterm birth among mothers in California. METHODS We created a population-based cohort comprised of 1,967,300 mothers who had live, singleton births in California, from May through September 2005-2013. Daily temperature data estimated at the maternal zip code of residence was used to create 12 definitions of extreme heat with varying relative temperatures (75th, 90th, 95th, and 98th percentiles) and durations (at least 2, 3, or 4 consecutive days). We estimated risk of preterm birth ( less then 37 gestational weeks) in relation to exposure to extreme heat during the last week of gestation with multi-level Cox proportional hazard regression models, adjusting for maternal characteristics, sex of neonate, and seasonality. We also included randomly generated data, SAS code, and estimates for reproducibility purposes. RESULTS Approximately 7% of the cohort had a preterm birth. For all definitions of extreme heat, the risk of preterm birth was consistently higher among mothers who experienced an extreme heat episode during their last week of gestation. https://www.selleckchem.com/products/uc2288.html Hazard ratios ranged from 1.008 (95% CI 0.997, 1.021) to 1.128 (95% CI 1.052, 1.210), with increasing associations as the relative temperature and duration of extreme heat episode increased. CONCLUSION This study adds to the previous literature by considering multiple definitions of extreme heat and applying a time-to-event framework. Findings suggest that acute exposure to extreme heat during the last week of gestation may trigger an earlier delivery. Implementing heat warning systems targeted toward pregnant women may improve birth outcomes. Published by Elsevier Ltd.OBJECTIVE The different incidence of colorectal cancer between the sexes suggests that sex hormones may be involved in the susceptibility to colorectal cancer. The association between sex hormones and genetic variants in hormone metabolic pathways and the colorectal cancer risk remains unclear. METHODS We detected sex hormone levels in plasma from colorectal cancer patients and controls in males by ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). We evaluated the clinical significance of sex hormones on colorectal cancer diagnosis with the area under the receiver operating characteristic curve (AUC). The role of genetic variants in hormone metabolic pathways in the colorectal cancer risk was assessed by a logistic regression model. The biological functions were detected by luciferase reporter assays and cell behavior experiments. RESULTS We found that 2-methoxyestrone (2-MeO-E1) was highly expressed in cases (PFDR = 3.48 × 10-19). The expression of 2-MeO-E1 in plasma showed improved accuracy for predicting colorectal cancer (AUC = 0.88). In the 2-MeO-E1 metabolic pathway, rs165599 in COMT was significantly associated with an increased risk of colorectal cancer (P = 0.009). Mechanistically, we found that the rs165599 G allele could decrease the binding ability of miR-22-3p to the COMT 3'-UTR. Furthermore, knockdown of COMT inhibited cell proliferation, induced cell apoptosis and arrested the cell cycle in the G1 phase. CONCLUSION This is the first study to show that 2-MeO-E1 and a genetic variant in COMT contribute to the susceptibility to colorectal cancer. These results shed light on the different incidence of colorectal cancer between the sexes.
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