Since the interplay between myelin lipids and axons is strictly coordinated by the extracellular matrix (ECM), we also discuss the role of different ECM components, and report the last findings on new ECM-modifiers able to foster endogenous remyelination.BACKGROUND Two single nucleotide polymorphisms (SNPs) of the VEGF gene, rs699947 and rs2010963, are responsible for differentiated gene expression. A mutual dependence between VEGF and leptin serum level has been observed. This study investigated the associations between the rs699947 and rs2010963 SNPs of VEGF gene, VEGF-A, and leptin serum concentrations, and cardiometabolic risk of body mass excess. METHODS In this case-control study, 212 subjects with excess body mass and 145 normal-weight controls gave blood samples and underwent anthropometric and pulse wave analysis. Genotyping of VEGF gene was carried out to analyze the rs699947 (-2578 C/A) and rs2010963 (-634 G/C) SNPs. (ClinicalTrials.gov ID NCT04077554). RESULTS This study showed a significant positive correlation between serum levels of VEGF-A and leptin in individuals with excess body mass possessing the CC genotype of the rs699947 variant of the VEGF gene. It has been registered that an increase in VEGF-A serum level correlates with an increase in arterial stiffness in excess body mass patients harboring AA genotype of the rs699947 (-2578 C/A) variant of the VEGF gene. No differences in VEGF-A and leptin serum concentrations were noted between particular genotypes. CONCLUSIONS The CC genotype of the rs699947 variant of the VEGF gene promotes a positive interdependency between leptin and VEGF-A serum levels in subjects with excess body mass.Secreted phospholipase A2-IIA (sPLA2-IIA) is a pro-inflammatory protein associated with cardiovascular disorders, whose functions and underlying mechanisms in cardiac remodelling are still under investigation. We herein study the role of sPLA2-IIA in cardiac fibroblast (CFs)-to-myofibroblast differentiation and fibrosis, two major features involved in cardiac remodelling, and also explore potential mechanisms involved. In a mice model of dilated cardiomyopathy (DCM) after autoimmune myocarditis, serum and cardiac sPLA2-IIA protein expression were found to be increased, together with elevated cardiac levels of the cross-linking enzyme lysyl oxidase (LOX) and reactive oxygen species (ROS) accumulation. Exogenous sPLA2-IIA treatment induced proliferation and differentiation of adult rat CFs. Molecular studies demonstrated that sPLA2-IIA promoted Src phosphorylation, shedding of the membrane-anchored heparin-binding EGF-like growth factor (HB-EGF) ectodomain and EGFR phosphorylation, which triggered phosphorylation of ERK, P70S6K and rS6. This was also accompanied by an up-regulated expression of the bone morphogenic protein (BMP)-1, LOX and collagen I. ROS accumulation were also found to be increased in sPLA2-IIA-treated CFs. The presence of inhibitors of the Src/ADAMs-dependent HB-EGF shedding/EGFR pathway abolished the CF phenotype induced by sPLA2-IIA. In conclusion, sPLA2-IIA may promote myofibroblast differentiation through its ability to modulate EGFR transactivation and signalling as key mechanisms that underlie its biological and pro-fibrotic effects.Sexting consists of sending, receiving, and distributing images of sexually suggestive content through electronic devices. This practice is one of the new ways of linking sex affectively through virtual environments, especially in adolescence. However, not all young people have the same relationship with the practice of sexting. This study of a sample of 603 Spanish and Moroccan adolescents residing in Andalusia analyzes beliefs towards sexting as part of a virtual sexuality and the perception of those who carry it out, defining profiles of affinity to sexting. The cluster analysis reveals the existence of three predominant profiles adolescents who show a sexting-philia, perceiving it as a fun, flirty, and daring practice; sexting-phobes, who consider sexting to be characteristic of people, or attitudes, who are desperate, impolite, and conflicting; and a third ambivalent profile of people who appreciate the practice as something fun but conflicting. The majority discourse is one that presents a positive view of this phenomenon. Young people also recognize that sexting has some characteristics of virtual sexuality, such as a loss of privacy and a distance between virtual and real behavior. These findings allow us to deepen our understanding of the new practices of relationships and offer measures for the prevention of the associated risks.Human bocavirus (HBoV) is a causative agent of respiratory and gastrointestinal diseases worldwide. Four HBoV species (HBoV1-4) have been identified so far. Although a previous report has documented the HBoV association with acute gastroenteritis (AGE) in Taiwan, their epidemiology, genetic diversity, and phylogenetic relationships remain unclear. In this study, we focused on an investigation of these unsolved issues, which will help to reveal molecular epidemiology and phylogeny of the circulating HBoV2 in Taiwan. A total of 176 stool samples were collected from children with AGE for this study. PCR amplification and sequencing on the VP1 gene region were used to identify species. Phylogenetic analysis was conducted by maximum-likelihood and neighbor-joining methods. https://www.selleckchem.com/products/incb084550.html Selection pressure was also estimated to obtain HBoV evolutionary information. Our results showed the prevalence of HBoV in AGE children was 8.5%, of which HBoV1 was the predominant species (6.3%), followed by HBoV2 (2.3%). Phylogenetic analysis showed those Taiwanese HBoV2 strains have significant genetic variability and can be divided into two clusters. One belongs to HBoV2 genotype A and the other forms an independent unclassified cluster. The nucleotide distance between that independent cluster and the known HBoV2 genotypes was more than 5%, suggesting a new HBoV2 genotype. No positive selection site was found and the virus was under purifying selection. This is the first report to reveal HBoV2 genetic diversity and phylogenetic relationships among AGE children in Taiwan. We find that HBoV2 may have been introduced into the country by multiple origins, and a potential new HBoV2 genotype is proposed.

Purpose To determine whether unilateral acute anterior uveitis (AAU) induces ipsilateral changes in the tear fluid proteome. Methods Five patients (25-77 years old) with unilateral AAU were included. Tear fluid samples were obtained using Schirmer's test strips. The healthy eye served as control. Proteins were identified by liquid chromatography tandem mass spectrometry. Results Two hundred forty-two tear fluid sample proteins were identified, of which 75 were present in at least three patients. Nine proteins were at least 1.5-fold increased, whereas eight were at least 1.5-fold decreased in tears from the diseased eye compared with the healthy eye. APOBEC3A was significantly increased (1.43-fold; P = 0.04), whereas TGM2 was significantly decreased (- 1.21-fold; P = 0.03) in tears from the diseased eye relative to the healthy eye. Ingenuity Pathway Analysis identified LXR/RXR (P less then 1.02E-4) as a top canonical pathway. Conclusion Unilateral AAU induced detectable changes in the ipsilateral tear fluid proteome and involvement of the inflammation-associated LXR/RXR pathway.Purpose Multiple intracranial aneurysms (MIA) occur in one-third of patients with intracranial aneurysms (IA), and have been previously associated with an overall worse prognosis. Risk factors for IA formation and rupture in patients with a single IA are well-known. However, risk factors associated with rupture in patients with MIA have been less studied. Methods We performed a retrospective search of patients with MIA identified by computed tomography angiography (CTA) within a 10-year period. Patients with > 1 saccular aneurysm with size ≥ 2.0 mm were included. The location, size, number, and rupture status of the aneurysms were recorded. Patient demographics and cerebrovascular risk factors were obtained from electronic medical records. The primary endpoint of this study was to determine the association of these factors with aneurysmal rupture. The case-fatality rate was evaluated as a secondary outcome. Results Of the 2957 patients with IA in our CTA database, 425 patients were diagnosed with MIA and were therefore included in our study. A total of 1082 aneurysms were identified. Predictors of increased risk of aneurysmal rupture were age (OR 0.98, 95% CI, 0.96-0.99), size ≥ 5 mm (OR 4.4, 95% CI 2.76-7.0); and location in the anterior communicating artery complex (AcomC) (OR 2.62, 95% CI, 1.46-4.72) or posterior communicating artery (PCOM) (OR 2.66, 95% CI, 1.45-4.87). Conclusions Younger age, aneurysm size ≥ 5 mm, and location in the AcomC and PCOM were independently associated with aneurysmal rupture in patients with MIA. Identifying these features could help recognize patients who might benefit from early intervention.Purpose Laugier's hernia is a rare clinical entity compared with a typical femoral hernia. Therefore, the clinical features, radiological findings, and appropriate treatment strategies remain largely unclear. In this study, we present 15 Laugier's hernia cases. Additionally, we review the relevant literature and discuss the clinical features, radiological findings, and appropriate treatment strategies pertaining to Laugier's hernia compared with a typical femoral hernia. Methods Among 1260 hernia patients, we retrospectively enrolled 15 Laugier's hernia patients (1.19%) and 89 femoral hernia patients (7.06%) who underwent herniorrhaphy and compared the demographic characteristics and radiological findings between the two groups. Results Regarding the patient characteristics, a significant difference was observed in the presence of pain (p less then 0.001) and ileus symptoms (p = 0.001). Regarding the hernia characteristics, significant differences were observed in the size of the hernial sac (p = 0.001), contents of the hernial sac (p = 0.003), repositioning of the hernial sac (p less then 0.001), and repair with polypropylene mesh (p less then 0.001). The characteristic multi-detector computed tomography (MDCT) findings enabled the preoperative diagnosis of Laugier's hernia versus conventional femoral hernia. Conclusion Surgeons should be alert to the possibility of atypical femoral hernias while examining femoral hernia or inguinal hernia patients. If Laugier's hernia is suspected, preoperative MDCT is recommended.Purpose Only a small fraction of resectable gallbladder cancer (GBC) patients receive a thorough lymphadenectomy. The aim of this systematic review and meta-analysis was to investigate the effect of lymphadenectomy on survival in GBC surgery. Methods On May 19, 2019, MEDLINE, EMBASE, and the Cochrane Library were searched for English or German articles published since 2002. Studies assessing the effect of lymphadenectomy on survival in GBC surgery were included. Fixed effect and random effects models were used to summarise the hazard ratio (HR). Results Of the 530 identified articles, 18 observational studies (27,570 patients, 10 population-based, 8 cohort studies) were reviewed. In the meta-analysis, lymphadenectomy did not show a significant benefit for T1a tumours (n = 495; HR, 1.37; 95%CI, 0.65-2.86; P = 0.41). Lymphadenectomy showed a significant survival benefit in T1b (n = 1618; HR, 0.69; 95%CI, 0.50-0.94; P = 0.02) and T2 (n = 6204; HR, 0.68; 95%CI, 0.56-0.83; P less then 0.01) tumours. Lymphadenectomy improved survival in the 2 studies assessing T3 tumours (n = 1961). A conclusive analysis was not possible for T4 tumours due to a low case load. Among patients undergoing lymphadenectomy, improved survival was observed in patients with a higher number of resected lymph nodes (HR, 0.57; 95%CI, 0.45-0.71; P less then 0.01). Conclusions Regional lymphadenectomy improves survival in T1b to T3 GBC. A minimum of 6 retrieved lymph nodes are necessary for adequate staging, indicating a thorough lymphadenectomy. Patients with T1a tumours should be evaluated for lymphadenectomy, especially if lymph node metastases are suspected.Purpose Intraoperative detection of intrahepatic lesions can be demanding. The use of preoperative contrast-enhanced magnetic resonance imaging (MRI) or computer tomography (CT) combined with intraoperative ultrasound of the liver is state of the art. Near totally regressed colorectal liver metastases (CRLM) after neoadjuvant chemotherapy or nodules in severely altered liver tissue as steatosis or cirrhosis are often hard to detect during the operative procedure. Especially differentiation between benign atypical nodules and malignant tumors can be very difficult. The intraoperative use of contrast-enhanced ultrasound or intraoperative navigation are helpful tools. However, both methods show relevant limitations. https://www.selleckchem.com/products/gm6001.html The use of intraoperative MRI (ioMRI) can overcome this problem. Relevant structures can be marked within the operative site or immediate control of complete tumor resection can be achieved. This might allow immediate surgical optimization in case of failure. Methods We report the intraoperative application of ioMRI in a case of a 61-year-old male patient suffering from rectal cancer with 10 synchronous bilobar CRLM who was treated stepwise by multimodal treatment and staged hepatectomy.

Larvae from embryos reared under 24-h light had lower wet body mass and LT50 values upon starvation compared to those reared under 14-h light. Coupled with the lowest metabolic rates under normoxic pO2 levels, this indicates the presence of negative latent effects. We discuss the findings in relation to the effect of the symbiotic relationship on hypoxia tolerance and larval fitness with respect to the presence of compensatory growth and negative latent effects. Optical polarimetry has been used to characterize muscle tissue samples of chicken, beef and mutton, exhibiting statistically significant (p  less then   0.01) differences in total depolarization and retardance of three tissue groups. Herein, the total depolarization and retardance were utilized to differentiate and classify the three tissue groups. Specifically, the Bagging classification algorithm was employed for this multi-class differentiation. The performance of the optical polarimetry in tandem with the Bagging model for machine-assisted classification of the three tissue groups was assessed in terms of a comprehensive set of evaluation metrics. The Bagging model correctly classified 47/48, 19/20 and 15/18, whereas the sensitivity (Sn = 97.9%, 82.6%, 100%), specificity (Sp = 97.4%, 98.4%, 95.8%), positive predictive values (PPV = 0.97, 0.95, 0.83) and negative predictive values (NPV = 0.97, 0.94, 1.0) were calculated for the chicken, beef and mutton tissue samples, respectively. This automatic classification of the three tissue samples indicates a novel application of the optical polarimetry in the meat industry. BACKGROUND Immune checkpoint inhibitors (ICIs) have been shown to be beneficial for some patients with advanced non-small cell lung cancer (NSCLC). However, the underlying mechanisms mediating the limited response to ICIs remain unclear. PATIENTS AND METHODS We performed whole-exome sequencing on 198 advanced NSCLC tumors that had been sampled prior to anti-PD-1/PD-L1 therapy. https://www.selleckchem.com/products/gm6001.html Detailed clinical characteristics were collected on these patients. We designed a new method to estimate HLA-corrected tumor mutation burden (TMB), a modification which considers the loss of heterozygosity of human leukocyte antigen (HLA-LOH) from conventional TMB. We performed external validation of our findings utilizing 89 NSCLC samples and 110 melanoma samples from two independent cohorts of immunotherapy-treated patients. RESULTS Homology-dependent recombination deficiency was identified in 37 patients (18.7%) and was associated with longer progression-free survival (PFS P = 0.049). Using the HLA-corrected TMB, non-responders to ICIs were identified, despite having a high TMB (top 25%). Ten patients (21.3% of the high TMB group) were reclassified from the high TMB group into the low TMB group. The objective response rate (ORR), PFS, and overall survival (OS) were all lower in these patients compared with those of the high TMB group (ORR 20% versus 59%, P = 0.0363, PFS hazard ratio = 2.91, P = 0.007, OS hazard ratio=3.43, P = 0.004). Multivariate analyses showed that high HLA-corrected TMB was associated with a significant survival advantage (hazard ratio = 0.44, P = 0.015), whereas high conventional TMB was not associated with a survival advantage (hazard ratio = 0.63, P = 0.118). Applying this approach to the independent cohorts of 89 NSCLC patients and 110 melanoma patients, TMB-based survival prediction was significantly improved. CONCLUSION HLA-corrected TMB can reconcile the observed disparity in relationships between TMB and ICI responses, and is of predictive and prognostic value for ICI therapies. Shoulder injuries and sports-related shoulder pain are substantial burdens for athletes performing a shoulder loading sport. The burden of shoulder problems in the athletic population highlights the need for prevention strategies, effective rehabilitation programs, and a individually based return-to-play (RTP) decision. The purpose of this clinical commentary is to discuss each of these 3 challenges in the sporting shoulder, to assist the professional in (1) preventing injury; (2) providing evidence-based practice rehabilitation and; (3) to guide the athlete toward RTP. The challenges for injury prevention may be found in the search for (the interaction between) relevant risk factors, develop valid screening tests, and implement feasible injury prevention programmes with maximal adherence from the athletes. Combined analytical and functional testing seems mandatory screening an athlete's performance. Many questions arise when rehabilitating the overhead athlete, from exercise selection, over the value of stretching, toward kinetic chain implementation and progression to high performance training. Evidence-based practice should be driven by the available research, clinical expertise and the patient's expectations. Deciding when to return to sport after a shoulder injury is complex and multifactorial. The main concern in the RTP decision is to minimize the risk of re-injury. In the absence of a "gold standard", clinicians may rely on general guidelines, based on expert opinion, regarding cutoff values for normal range of motion, strength and function, with attention to risk tolerance and load management. Mixed-lineage leukemia (MLL) fuses with a variety of partners to produce a functionally altered MLL complex that is not expressed in normal cells, which transforms normal hematopoietic progenitors into leukemia cells. Because more than 80 fusion partners have been identified to date, the molecular functions of MLL fusion protein complexes appear diverse. However, over the past decade, the common functions utilized for leukemic transformation have begun to be elucidated. It appears that most (if not all) MLL fusion protein complexes utilize the AF4/ENL/P-TEFb and DOT1L complexes to some extent. Based on an understanding of the underlying molecular mechanisms, several molecular targeting drugs are being developed, opening paths to novel therapies. Here, we review the recent progress made in identifying the molecular functions of various MLL fusions and categorize the numerous fusion partners into several functionally-distinct groups to help discern commonalities and differences among various MLL fusion protein complexes.

We confirm the effectiveness of this approach with a variety of calculations on LinHn clusters.In this work, cobalamins with different upper axial substituents and a cobalamin derivative with a ring modification were studied using chiroptical spectroscopies, in particular resonance Raman optical activity (RROA), to shed light on the influence of structural modifications on RROA spectra in these strongly chiral systems in resonance with multiple excited states at 532 nm excitation. We have demonstrated that for these unique systems RROA possesses augmented structural specificity, surpassing resonance Raman spectroscopy and enabling at the same time measurement of cobalamins at fairy low concentrations of ∼10-5 mol dm-3. The enhanced structural specificity of RROA is a result of bisignate spectra due to resonance via more than one electronic state. The observation of increased structural capability of RROA for cobalamins opens a new perspective for studying chiral properties of other biological systems incorporating d-metal ions.The complex phosphorylation pattern of natural and modified pentaphosphorylated magic spot nucleotides is generated in a highly efficient way. A cyclic pyrophosphoryl phosphoramidite (cPyPA) reagent is used to introduce four phosphates on nucleosides regioselectively in a one-flask key transformation. The obtained magic spot nucleotides are used to develop a capillary electrophoresis UV detection method, enabling nucleotide assignment in complex bacterial extracts.In continuous flow biocatalysis, chemical transformations can occur under milder, greener, more scalable, and safer conditions than conventional organic synthesis. However, the method typically involves extensive screening to optimize each enzyme's immobilization on its solid support material. The task of weighing solids for large numbers of experiments poses a bottleneck for screening enzyme immobilization conditions. For example, screening conditions often require multiple replicates exploring different support chemistries, buffer compositions, and temperatures. Thus, we report 3D-printed labware designed to measure and handle solids in multichannel format and expedite screening of enzyme immobilization conditions. To demonstrate the generality of these advances, alkaline phosphatase, glucose dehydrogenase, and laccase were screened for immobilization efficiency on seven resins. The results illustrate the requirements for optimization of each enzyme's loading and resin choice for optimal catalytic performance. Here, 3D-printed labware can decrease the requirements for an experimentalist's time by >95%. The approach to rapid optimization of enzyme immobilization is applicable to any enzyme and many solid support resins. Furthermore, the reported devices deliver precise and accurate aliquots of essentially any granular solid material.Rheumatoid arthritis (RA) is a chronic autoimmune disease that results in severe inflammatory microenvironments in the joint tissues. In clinics, disease-modifying antirheumatic drugs (DMARDs) are generally prescribed to patients with RA, but their long-term use often shows toxicity in some organs such as the gastrointestinal system, skin, and kidneys and immunosuppression-mediated infection. Nanomedicine has emerged as a new therapeutic strategy to efficiently localize the drugs in inflamed joints for the treatment of RA. In this Review, we introduce recent research in the area of nanomedicine for the treatment of RA and discuss how the nanomedicine can be used to deliver therapeutic agents to the inflamed joints and manage the progression of RA, particularly focusing on targeted delivery, controlled drug release, and immune modulation.De novo gene synthesis is the state-of-the-art method used to obtain genetic material adapted to the requirements of the host organism and a cornerstone for modern synthetic biology. Yet, little progress has been made regarding downstream processes of protein production from synthetic genetic material. The production of recombinant proteins traditionally requires extensive preparatory work including gene amplification, cloning, sequencing, transformation or transfection of the expression host, cultivation of living cells, and purification of the overexpressed protein. In this work we describe a fast and automated workflow for cell-free production of proteins starting from an electronic protein sequence or accession number. https://www.selleckchem.com/products/muramyl-dipeptide.html PRESTO (protein expression starting from oligonucleotides) seamlessly combines a tailored in silico sequence optimization with the assembly of short oligonucleotides into synthetic linear DNA expression cassettes, mammalian in vitro transcription/translation, and protein purification thereof. Integrated on a small liquid handling system it provides a hands-free high throughput source for functional synthetic proteins within 1 day.Protein glycosylation is a prevalent post-translational modification that mediates a variety of cellular processes. For membrane proteins, glycosylation at their terminal motif is usually more functional. Among the various glycosylation types found in membrane proteins, O-glycosylation is the most common and is closely correlated with a variety of cancer types, including breast cancer. Slightly aberrant expression of certain O-glycans can significantly affect cancer progression, especially at the cancer-related membrane protein level. To collect biological information on protein-specific glycosylation and further explore clinical applications, quantitative detection of glycosylation is essential. However, few assays have been reported for the in situ detection of protein-specific glycosylation to date. Herein, we developed a dual-probe approach for mass spectrometric quantification of protein-specific glycosylation using the terminal galactose/N-acetylgalactosamine (Gal/GalNAc) of MUC1 as a model. The dual-prer diagnosis/prognosis was also assessed.Genetic depletion of cyclin-dependent kinase 12 (CDK12) or selective inhibition of an analog-sensitive CDK12 reduces DNA damage repair gene expression, but selective inhibition of endogenous CDK12 is difficult. Here, we report the development of MFH290, a novel cysteine (Cys)-directed covalent inhibitor of CDK12/13. MFH290 forms a covalent bond with Cys-1039 of CDK12, exhibits excellent kinome selectivity, inhibits the phosphorylation of serine-2 in the C-terminal domain (CTD) of RNA-polymerase II (Pol II), and reduces the expression of key DNA damage repair genes. Importantly, these effects were demonstrated to be CDK12-dependent as mutation of Cys-1039 rendered the kinase refractory to MFH290 and restored Pol II CTD phosphorylation and DNA damage repair gene expression. Consistent with its effect on DNA damage repair gene expression, MFH290 augments the antiproliferative effect of the PARP inhibitor olaparib.

Herein, a fluorescence "turn ON-OFF" switch model PB@EuW10/SiO2 core@shell composite is designed and fabricated by coating EuW10-containing silica layer on Prussian blue (PB) nanoparticles via a facile method. It is found that the presence of PB can quench the photoluminescence of the composite which arises from EuW10. When hydrazine is mixed with the composite dispersion, PB can be reduced to Prussian white (PW), resulting in the decrease of UV absorption and the appearance of photoluminescence (turn ON). In addition, PW can also be converted back to PB, which is achieved by adding hydrogen peroxide, and the photoluminescence of the composite is quenched again (turn OFF). Thus, the composite is applied for N2H4 and H2O2 detection by fluorescence spectroscopy and UV-vis absorption spectroscopy. Wide linear ranges for N2H4 and H2O2 detection with low detection limits are found for both detection methods on the PB@EuW10/SiO2 core@shell composite. Besides, the color from light blue to colorless of the detection dispersion can also indicate the turn ON-OFF switch for fluorescence. Furthermore, the proposed model can also be extended to other composites.The highly efficient CO2 electrolysis system could be accomplished by introducing biomass oxidation as an alternative anodic reaction to the sluggish oxygen evolution reaction (OER) in CO2-saturated and near-neutral electrolyte. Here, we successfully demonstrate anodic biomass oxidation by synthesizing 5 nm-sized nickel oxide nanoparticles (NiO NPs). NiO NPs show a unique electrocatalytic activity for 5-hydroxymethylfurfural (HMF) oxidation under near-neutral condition, exhibiting an anodic current onset (1 mA cm-2) at 1.524 V vs RHE and total Faradaic efficiency up to 70%. Electrokinetic and in situ UV-Vis spectroscopic analyses suggest that redox active nickel hydroxide species is formed on the surface of NiO electrocatalysts during HMF oxidation, and this Ni(II) hydroxide oxidation to Ni(III) oxyhydroxide step could be the rate determining step (RDS). This mechanistic study for biomass oxidation in CO2-saturated electrolyte provides insight into constructing a highly efficient system for the paired electrolysis of CO2 reduction and biomass oxidation.The three-component reactions of α-amino acids, p-quinone monoacetals (or p-quinol ethers), and diarylphosphine oxides have been developed for the synthesis of 3-(diarylphosphinyl) anilides and N-aryl-2-diarylphosphinylpyrrolidines. The transformations may involve the in situ generation of conjugated azomethine ylides or 2-azaallyl anion species from the reaction of α-amino acids and p-quinone monoacetals, which are further trapped by diarylphosphine oxides.The spatial magnetic properties, through-space NMR shieldings (TSNMRS), of bent allene 1, the corresponding C-extended 1,3-butadiene derivative 2, and a number of related compounds 3-20 have been calculated using the gauge-independent atomic orbital perturbation method, employing the nucleus-independent chemical shift concept and visualized as isochemical shielding surfaces of various sizes and directions. https://www.selleckchem.com/products/nedisertib.html Prior to that, both structures and 13C chemical shifts were calculated and compared with available experimental bond lengths and δ(13C)/ppm values (also, as a quality criterion for the computed structures). Bond lengths, the δ(13C)/ppm, and the TSNMRS values are employed to qualify and quantify the electronic structure of the studied compounds in terms of dative or classical electron-sharing bonds.During the decompression of plastically deformed glasses at room temperature, some aspects of irreversible densification may be preserved. This densification has been attributed primarily to topological changes in the glass networks. The changes in short-range structures like cation coordination numbers are often assumed to be relaxed upon decompression. Here, the NMR results for aluminosilicate glass upon permanent densification up to 24 GPa reveal the noticeable changes in the Al coordination number at pressure conditions as low as ~6 GPa. A drastic increase in highly coordinated Al fraction is evident over only a relatively narrow pressure range of up to ~12 GPa, above which the coordination change becomes negligible up to 24 GPa. In contrast, Si coordination environments do not change, highlighting preferential coordination transformation during deformation. The observed trend in the coordination environment shows a remarkable similarity with the pressure-induced changes in the residual glass density, yielding the predictive relationship between the irreversible densification and the detailed structures under extreme compression. The results open a way to access the nature of plastic deformation in complex glasses at room temperature.Determination of ground-state spins of open-shell transition-metal complexes is critical to understanding catalytic and materials properties but also challenging with approximate electronic structure methods. As an alternative approach, we demonstrate how structure alone can be used to guide assignment of ground-state spin from experimentally determined crystal structures of transition-metal complexes. We first identify the limits of distance-based heuristics from distributions of metal-ligand bond lengths of over 2000 unique mononuclear Fe(II)/Fe(III) transition-metal complexes. To overcome these limits, we employ artificial neural networks (ANNs) to predict spin-state-dependent metal-ligand bond lengths and classify experimental ground-state spins based on agreement of experimental structures with the ANN predictions. Although the ANN is trained on hybrid density functional theory data, we exploit the method-insensitivity of geometric properties to enable assignment of ground states for the majority (ca. 80-90%) of structures. We demonstrate the utility of the ANN by data-mining the literature for spin-crossover (SCO) complexes, which have experimentally observed temperature-dependent geometric structure changes, by correctly assigning almost all (>95%) spin states in the 46 Fe(II) SCO complex set. This approach represents a promising complement to more conventional energy-based spin-state assignment from electronic structure theory at the low cost of a machine learning model.

Lymphatic filariasis (LF) is a neglected tropical disease targeted for elimination as public health problem through morbidity management and preventive annual mass drug administration (MDA). This cross-sectional community-based surveillance assessed the prevalence and correlates of LF infection in Mkinga district, Tanga-region, Tanzania. A total of 4115 individuals (49.7% males, 35.2% children) were screened for circulating filarial antigens (CFA), microfilaremia (mf) and disease manifestations in 15 villages between November 2018 and January 2019. MDA uptake in the previous year was assessed. Overall prevalence of CFA-positivity was 5.8% (239/4115; 95% CI 5.1-6.6), with significant heterogeneity between villages (range 1.2% to 13.5%). CFA-positivity was higher in males (8.8%) than females (3.3%), and correlated with increasing age (p less then 0.001). Prevalence of mf among CFA-positives was 5.2%. Only 60% of eligible inhabitants in the study area took MDA in the previous year, and CFA-positivity was 2-fold higher in those who missed MDA (p less then 0.0001). Prevalence of scrotal enlargement, hydrocele, arms or legs swelling, lymphoedema and lymphadenopathy was 6.4%, 3.7%, 1.35%, 1.2% and 0.32%, respectively. Compared to baseline data, 16 years of MDA intervention significantly reduced LF transmission and morbidity, although the intended elimination target of less then 1% mf and less then 2% antigenemia to level where recrudescence is unlikely to occur by the year 2020 may not be attained. The finding of hotspots with ongoing transmission calls for intensified control measures.The incidence of hypertension in diabetic patients has been increasing and contributing to the high mortality of diabetic patients. Recently, verapamil use was found to lower fasting blood glucose levels in diabetic patients, which led to a new indication of verapamil as combination treatment with anti-diabetic agents such as metformin. As pharmacokinetic (PK) interaction can affect drug efficacy and safety in drug combination, their PK-based interaction is recommended to be evaluated in preclinical levels as well as clinical levels. In case of metformin and verapamil, organic cation transporter (OCT) 1 and 2 primarily mediate metformin distribution to the liver and its elimination into urine, whereas cytochrome P450 is responsible for the hepatic metabolism of verapamil. Verapamil is also known as a potential OCT2 inhibitor. Thus, PK interaction between metformin (30 mg/kg) and verapamil (20 mg/kg) were investigated after their simultaneous administration to rats. In our results, verapamil inhibited the OCT2-mediated renal excretion of metformin, subsequently leading to increase of the systemic exposure of metformin. In contrast, metformin did not influence the pharmacokinetic pattern of verapamil. Although the further clinical investigation is required, our finding suggests a possibility of OCT2-mediated interaction of metformin and verapamil.The pyridinium oximes are known esterolytic agents, usually classified in the literature as catalysts, which mimic the catalytic mode of hydrolases. Herein, we combined kinetic and computational studies of the pyridinium-4-oxime-mediated acetylthiocholine (AcSCh+) hydrolysis to provide novel insights into their potential catalytic activity. The N-methyl- and N-benzylpyridinium-4-oximes have been tested as oximolytic agents toward the AcSCh+, while the newly synthesized O-acetyl-N-methylpyridinium-4-oxime iodide was employed for studying the consecutive hydrolytic reaction. The relevance of the AcSCh+ hydrolysis as a competitive reaction to AcSCh+ oximolysis was also investigated. The reactions were independently studied spectrophotometrically and rate constants, koxime, kw and kOH, were evaluated over a convenient pH-range at I = 0.1 M and 25 °C. The catalytic action of pyridinium-4-oximes comprises two successive stages, acetylation (oximolysis) and deacetylation stage (pyridinium-4-oxime-ester hydrolysis), the latter being crucial for understanding the whole catalytic cycle. The complete mechanism is presented by the free energy reaction profiles obtained with (CPCM)/M06-2X/6-311++G(2df,2pd)//(CPCM)/M06-2X/6-31+G(d) computational model. The comparison of the observed rates of AcSCh+ oximolytic cleavage and both competitive AcSCh+ and consecutive pyridinium-4-oxime-ester hydrolytic cleavage revealed that the pyridinium-4-oximes cannot be classified as non-enzyme catalyst of the AcSCh+ hydrolysis but as the very effective esterolytic agents.The chemical composition of standard Inconel 740 superalloy was modified by changes in the Al/Ti ratio (0.7, 1.5, 3.4) and addition of Ta (2.0, 3.0, 4.0%). https://www.selleckchem.com/products/GDC-0449.html Remelted Inconel 740 (A0) and nine variants with various chemical compositions were fabricated by lost-wax casting. The microstructure, microsegregation, phase transformation temperatures, thermal expansion coefficients and hardness of the superalloys were investigated by scanning electron microscopy, energy dispersive X-ray spectroscopy, differential scanning calorimetry, dilatometry and Vickers measurements. Typical dendritic microstructure was revealed with microsegregation of the alloying elements. Segregation coefficient ki for Ti, Nb and Ta did not exceed unity, and so precipitates enriched mainly in these elements were found in interdendritic spaces. The Nb-rich blocky precipitates, MC carbides, MN nitrides, oxides, and fine γ' was in all modified castings. Presence of other microstructural features, such as Ti-rich needles, eutectic γ-γ' islands, small Al-rich and Cr-rich precipitates depended on the casting composition. The lowest solidus and liquidus temperatures were observed in superalloys with a high Al/Ti ratio. Consequently, in A7-A9 variants, the solidification range did not exceed 100 °C. In the A0 variant the difference between liquidus and solidus temperature was 138 °C. Hardness of all modified superalloys was at least 50% higher than for the remelted Inconel 740 (209 HV10).In order to find a consistent, simple and time-efficient method of assessing mammographic breast density (MBD), different methods of assessing density comparing subjective, quantitative, semi-subjective and semi-quantitative methods were investigated. Subjective MBD of anonymized mammographic cases (n = 250) from a national breast-screening programme was rated by 49 radiologists from two countries (UK and USA) who were voluntarily recruited. Quantitatively, three measurement methods, namely VOLPARA, Hand Delineation (HD) and ImageJ (IJ) were used to calculate breast density using the same set of cases, however, for VOLPARA only mammographic cases (n = 122) with full raw digital data were included. The agreement level between methods was analysed using weighted kappa test. Agreement between UK and USA radiologists and VOLPARA varied from moderate (κw = 0.589) to substantial (κw = 0.639), respectively. The levels of agreement between USA, UK radiologists, VOLPARA with IJ were substantial (κw = 0.752, 0.768, 0.603), and with HD the levels of agreement varied from moderate to substantial (κw = 0.

This article critically examines the role of employment training programs in the personal recovery of adults living with mental illness in community settings. Using Cameron Duff's (2014) notion of 'assemblages of recovery,' we explore how, and to what extent, employment training programs provide the supportive resources linked to personal recovery. Using an ethnographic case study, we describe the ambivalent atmospheres associated with one program. This ambivalence expresses the fundamental tension between the genuine aspirations of personal recovery and the realities of the capitalist labor process.This article extends theorising on how spaces act therapeutically by using the lens of sensory and embodied ethnography to explore refugee place-making within an urban allotment located in the North West, UK. Findings suggest being physically present when allotment tending has potential to be therapeutic without the need for verbal communication. Physical activity distracted participants from internal stress. Sensory nostalgia provided continuity with past and present selves and the anthropomorphism of plants acted as a reminder to nurture the self and allowed for cathartic telling of stories. Findings are important if places of restoration and healing are to be sought out for refugees.The outer membrane protein A (OmpATb) of Mycobacterium tuberculosis is a virulence factor that neutralizes the host pH to impede the uptake of hydrophilic antitubercular drugs. Identifying natural compounds with the potential to inhibit OmpATb could allow circumvention of the porin-like activities of OmpATb. Four potential leads comprising ZINC000003958185, ZINC000000157405, ZINC000000001392 and ZINC000034268676 were obtained by virtual screening of 6394 diverse natural products. Characterization of the binding interactions of the potential leads with OmpATb revealed nine critical residues comprising ARG86, LEU110, LEU113, LEU114, ALA115, PHE142, SER145, VAL146, and PHE151. Molecular dynamics simulations also revealed very stable protein-lead complexes. Most residues contributed lower binding energies to the overall molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) binding free energies of the interactions between the molecules and OmpATb protein. Induced Fit Docking (IFD) of the compounds regenerated poses of the molecular docking using AutoDock Vina. These molecules could be starting templates for designing inhibitors to bypass the pore mediating activities of OmpATb. Based on structural similarity, ZINC000034268676 was suggested as a potential scaffold for designing efflux pump inhibitors of the gate mediating activities of OmpATb and may enhance the uptake of hydrophilic drugs to reduce the duration time of tuberculosis treatment. Furthermore, structurally similar compounds available in the DrugBank database with a similarity threshold of 0.7 have been reported to exhibit antitubercular and anti-mycobacterial activities. These biomolecules can be further characterized experimentally to corroborate their antitubercular activity. Also, the skeletons of the molecules can be adopted as sub-structures for the design of future anti-mycobacterial drugs.Many experimental studies focus on the physical damage mechanisms of short-term exposure to laser radiation. In the nanosecond (ns) pulse range, damage in the Retinal Pigment Epithelium (RPE) will most likely occur at threshold levels due to bubble formation at the surface of the absorbing melanosome. The energy uptake of the melanosomes is one key aspect in modeling the bubble formation and damage thresholds. This work presents a thermal finite volume model for the investigation of rising temperatures and the temperature distribution of irradiated melanosomes. The model takes the different geometries and thermal properties of melanosomes into account, such as the heat capacity and thermal conductivity of the heterogeneous absorbing melanosomes and the surrounding tissue. This is the first time the size and shape variations on the melanosomes' thermal behavior are considered. The calculations illustrate the effect of the geometry on the maximum surface temperature of the irradiated melanosome and the impact on the bubble formation threshold. A comparison between the calculated bubble formation thresholds and the RPE cell damage thresholds within a pulse range of 3 to 5000 ns leads to a mean deviation of μ=22mJ/cm2 with a standard deviation of σ=21mJ/cm2. The best results are achieved between the simulation and RPE cell damage thresholds for pulse durations close to the thermal confinement time of individual melanosomes.The similarity measure is an essential part of medical image retrieval systems for assisting in radiological diagnosis. https://www.selleckchem.com/products/nec-1s-7-cl-o-nec1.html Attempts have been made to use distance metric learning approaches to improve the retrieval performance while decreasing the semantic gap. However, existing approaches did not resolve the problem of dependency between images (e.g. normal and abnormal images are compared with the same distance). This affects the semantic and the visual similarity. Thus, this work aims at learning a distance metric which preserves both visual resemblance and semantic similarity and modeling this distance in order to treat each query independently. The proposed method is described in three stages (1) low-level image feature extraction, (2) offline distance metric modeling, and (3) online retrieval. The first stage exploits transform-domain texture descriptors based on local binary pattern histogram Fourier, shearlet, and curvelet transforms. The second stage is carried out using low-level features and machine learning. Given a query image, the online retrieval is based on the evaluation of the similarity between this image and each image within the dataset, while using a distance that is dynamically defined according to the query image. Realized experiments on the challenging Mammographic Image Analysis Society (MIAS) and Digital Database for Screening Mammography (DDSM) datasets prove the effectiveness of the proposed method in determining dynamically the adequate distance and retrieving the most semantically similar images, while investigating single low-level features as well as fused ones.

The shuttling of lithium polysulfides (LiPSs) in lithium-sulfur (Li-S) batteries results in low sulfur utilization and fast capacity decay, hindering their practical applications. Constructing an interlayer is an efficient way to block the LiPS shuttling, but maintaining a low Li ion diffusion resistance with such an interlayer is hard to achieve. Herein, a thin porous carbon nanosheet embedded with TiO2 nanoparticles (denoted PCNS-TiO2) was used to fabricate an interlayer on the separator, which effectively solves the above problem. The PCNS-TiO2 was prepared by using the Ti3C2Tx MXene as the two-dimensional (2D) template directing the porous carbon sheet formation, and the Ti3C2Tx transformed into TiO2 nanoparticles embedded in the PCNS. The decomposition of the MXene eliminates the ion blocking effect by the 2D nanosheet structure. The thin and hierarchical porous structure allows fast Li ion diffusion across the interlayer, and at the same time, the porous structure and the strong adsorption ability of TiO2 effectively block the polysulfide diffusion. https://www.selleckchem.com/products/ganetespib-sta-9090.html Thus, the Li-S battery with this interlayer shows good rate performance with a high capacity of 627 mA h g-1 at 2 C. Meanwhile, stable cycling performance is also achieved, showing a low capacity decay of 0.063% per cycle after 300 cycles at 0.5 C.Background Preeclampsia is a hypertensive disorder of pregnancy affecting about 2-10% pregnancies worldwide. mRNA expression of tumor necrosis factor alpha (TNF- α ), Fas, and FasL have been reported to be altered in placental bed in preeclamptic pregnancies. We hypothesized that the expression of these genes is also altered in peripheral blood mononuclear cells (PBMCs) in preeclampsia. Objective To compare the expression of Fas receptor and related genes in PBMCs of preeclamptic and normotensive pregnant women. Materials and methods A cross-sectional comparative study comprising of 18 cases and 18 controls was designed. 5 ml of venous blood was drawn and collected considering aseptic measures. Buffy coat was separated by centrifugation and stored at -20°C. Favor Prep total RNA Isolation Kit (Favorgen, Taiwan) was used for RNA extraction. The mRNA expression of TNF- α , Fas, and FasL was measured by real-time polymerase chain reaction in PBMCs in preeclamptic and normal pregnancies. Results A significant increase in mRNA expression of TNF- α , Fas, and FasL (p ≤ 0.001) was observed in PBMCs of preeclamptic pregnancies compared to the control group (p ≤ 0.001). Moreover, a significant positive correlation was found between the TNF- α mRNA expression and Fas and FasL (p ≤ 0.001). Conclusion The results lead to the conclusion that mRNA expression of TNF- α , Fas, and FasL in the maternal PBMCs is altered in preeclamptic pregnancies and might contribute to the pathogenesis of the disease.Shock waves are gaining interests in biological and medical applications. In this work, we investigated the mechanical characteristics of shock waves that affect cell viability. In vitro testing was conducted using the metastatic breast epithelial cell line MDA-MB-231. Shock waves were generated using a high-power pulse laser. Two different coating materials and different laser energy levels were used to vary the peak pressure, decay time, and the strength of subsequent peaks of the shock waves. Within the testing capability of the current study, it is shown that shock waves with a higher impulse led to lower cell viability, a higher detached cell ratio, and a higher cell death ratio, while shock waves with the same peak pressure could lead to different levels of cell damage. The results also showed that the detached cells had a higher cell death ratio compared to the attached cells. Moreover, a critical shock impulse of 5 Pa·s was found to cause the cell death ratio of the detached cells to exceed 50%. This work has demonstrated that, within the testing range shown here, the impulse, rather than the peak pressure, is the governing shock wave parameter for the damage of MDA-MB-231 breast cancer cells. The result suggests that a lower-pressure shock wave with a longer duration, or multiple sequential low amplitude shock waves can be applied over a duration shorter than the fundamental response period of the cells to achieve the same impact as shock waves with a high peak pressure but a short duration. The finding that cell viability is better correlated with shock impulse rather than peak pressure has potential significant implications on how shock waves should be tailored for cancer treatments, enhanced drug delivery, and diagnostic techniques to maximize efficacy while minimizing potential side effects.Background Sleep is a natural, restorative, physiological process that is characterized by perceptual disengagement from and unresponsiveness to whatever going around, which is reversible. Sleep quality refers to a sense of being rested and refreshed after waking up from sleep. People living with HIV/AIDS (PLWHA) are vulnerable to poor sleep quality as they suffer from social stigma and Anti-Retroviral drug side effects. The study aimed to examine the quality of sleep and its associated factors among people living with HIV/AIDS attending Anti-Retroviral Therapy (ART) clinic at Hawassa University comprehensive specialized hospital. Method Institutional based cross-sectional study was conducted among PLWHA attending ART clinic at Hawassa University comprehensive specialized hospital from May 1-30, 2019. A systematic random sampling technique was used to select an estimated 422 study participants and data was collected using interviewer-administered technique. Sleep Quality was assessed using the Pittsburgh SleeConclusion The prevalence of poor quality of sleep among PLWHA was significantly high. Average monthly income, age, anxiety, depression, and social support were found to be significantly associated with poor sleep quality. Health care professionals working at the ART clinic need to assess the sleep pattern of ART clients, give psychoeducation on the prevention and management of sleep pattern problems.The aim of this study was to determine the effect of rotenone stress on Aphis glycines Matsumura (Hemiptera Aphididae) populations in different habitats of Northeast China. The changes in kinase expression activity of endogenous substances (proteins, total sugars, trehalose, cholesterol, and free amino acids), detoxifying enzymes (cytochrome P450 and glutathione S-transferase), and metabolic enzymes (proteases and phosphofructokinases) in specimens from three populations were compared before and after stress with rotenone at median lethal concentration (LC50) and their response mechanisms were analyzed. Following a 24 h treatment with rotenone, the average LC50 rotenone values in A. glycines specimens from field populations A and B, and a laboratory population were 4.39, 4.61, and 4.03 mg/L, respectively. The degree of changes in the kinase expression activity of endogenous substances also differed, which indicated a difference in the response of A. glycines specimens from varying habitats to LC50 rotenone stress.

STUDY DESIGN Cross sectional. OBJECTIVES To determine the inter-rater and intra-rater reliability of the Spanish version of the Berg Balance Scale with incomplete spinal cord injured subjects. SETTING CINER Rehabilitation Center. METHODS We administered and video recorded the Spanish version of the Berg Balance Scale to 20 incomplete SCI patients. Two raters scored the videos on two different occasions at least three weeks apart. We used intraclass correlation coefficient (ICC) and a confidence interval (CI) of 95% to evaluate the inter-rater and intra-rater (test-retest) reliability of the BBS total scores. RESULTS ICC values for inter-rater reliability at first and second observation were 0.99 (95% CI 0.97-1.00) and 0.99 (95% CI 0.99-1.00), respectively. Intra-rater ICC for rater 1 was 1.00 (95% CI 1.00-1.00) and for rater 2 was 1.00 (95% CI 0.99-1.00). All of them were excellent. CONCLUSIONS The results indicate that the Spanish version of the Berg Balance Scale is a reliable tool to evaluate spinal cord injured patients' balance.Considering multi-body systems of monodisperse hard Brownian particles, it remains challenging to predict the forms of order that can emerge in their dense assembled structures. Surprisingly, here, using Monte Carlo simulations, we show that tetratic-ordered phases emerge in a dense two-dimensional system of hard kites that are rotationally asymmetric and have opposite 72° and α ≈ 90° internal angles. We observe a new tetragonal rectangular crystal (TRX) phase possessing (quasi-)long-range fourfold molecular-orientational order. We propose a method based on local polymorphic configurations of neighboring particle pairs (LPC-NPPs) to understand this emergent tetratic order and show that LPC-NPPs can be useful for predicting orientational order in such systems. To examine the dependence of the tetratic order on α, we apply LPC-NPP analysis to other hard kites for 54° ≤ α ≤ 144°. Our work provides insight into the creation of novel ordered materials by rationally designing particle shape based on anticipated LPC-NPPs.Papillary thyroid cancer (PTC) is the most common type of endocrine malignancy. By RNA-seq analysis, we identify a RET rearrangement in the tumour material of a patient who does not harbour any known RAS or BRAF mutations. This new gene fusion involves exons 1-4 from the 5' end of the Trk fused Gene (TFG) fused to the 3' end of RET tyrosine kinase leading to a TFG-RET fusion which transforms immortalized human thyroid cells in a kinase-dependent manner. TFG-RET oligomerises in a PB1 domain-dependent manner and oligomerisation of TFG-RET is required for oncogenic transformation. Quantitative proteomic analysis reveals the upregulation of E3 Ubiquitin ligase HUWE1 and DUBs like USP9X and UBP7 in both tumor and metastatic lesions, which is further confirmed in additional patients. Expression of TFG-RET leads to the upregulation of HUWE1 and inhibition of HUWE1 significantly reduces RET-mediated oncogenesis.Breast cancer susceptibility gene II (BRCA2) is central in homologous recombination (HR). In meiosis, BRCA2 binds to MEILB2 to localize to DNA double-strand breaks (DSBs). Here, we identify BRCA2 and MEILB2-associating protein 1 (BRME1), which functions as a stabilizer of MEILB2 by binding to an α-helical N-terminus of MEILB2 and preventing MEILB2 self-association. BRCA2 binds to the C-terminus of MEILB2, resulting in the formation of the BRCA2-MEILB2-BRME1 ternary complex. In Brme1 knockout (Brme1-/-) mice, the BRCA2-MEILB2 complex is destabilized, leading to defects in DSB repair, homolog synapsis, and crossover formation. Persistent DSBs in Brme1-/- reactivate the somatic-like DNA-damage response, which repairs DSBs but cannot complement the crossover formation defects. Further, MEILB2-BRME1 is activated in many human cancers, and somatically expressed MEILB2-BRME1 impairs mitotic HR. Thus, the meiotic BRCA2 complex is central in meiotic HR, and its misregulation is implicated in cancer development.Despite having common overlapping immunophenotypic and morphological features, T-cell lymphoblastic leukemia (T-ALL) and lymphoma (T-LBL) have distinct clinical manifestations, which may represent separate diseases. https://www.selleckchem.com/products/VX-770.html We investigated and compared the epigenetic and genetic landscape of adult and pediatric T-ALL (n = 77) and T-LBL (n = 15) patient samples by high-resolution genome-wide DNA methylation and Copy Number Variation (CNV) BeadChip arrays. DNA methylation profiling identified the presence of CpG island methylator phenotype (CIMP) subgroups within both pediatric and adult T-LBL and T-ALL. An epigenetic signature of 128 differentially methylated CpG sites was identified, that clustered T-LBL and T-ALL separately. The most significant differentially methylated gene loci included the SGCE/PEG10 shared promoter region, previously implicated in lymphoid malignancies. CNV analysis confirmed overlapping recurrent aberrations between T-ALL and T-LBL, including 9p21.3 (CDKN2A/CDKN2B) deletions. A significantly higher frequency of chromosome 13q14.2 deletions was identified in T-LBL samples (36% in T-LBL vs. 0% in T-ALL). This deletion, encompassing the RB1, MIR15A and MIR16-1 gene loci, has been reported as a recurrent deletion in B-cell malignancies. Our study reveals epigenetic and genetic markers that can distinguish between T-LBL and T-ALL, and deepen the understanding of the biology underlying the diverse disease localization.Previous studies by us and others demonstrated that activation of Wnt/β-catenin signaling plays a pathogenic role in chronic kidney diseases (CKD). Wnt co-receptor LRP5 variants are reported to associate with autosomal dominant polycystic kidney disease; but their exact roles in this disease and renal fibrosis have not been explored. Here, we observed the upregulation of LRP5 in the renal tubules of both type 1 and type 2 diabetic models and of an obstructive nephropathy model. In the obstructed kidneys, Lrp5 knockout significantly ameliorated tubulointerstitial fibrosis and tubular injury without changing Wnt/β-catenin signaling. Instead, decreased levels of TGF-β1 and TGF-β receptors (TβRs) were detected in Lrp5 knockout kidneys, followed by attenuated activation and nuclear translocation of Smad2/3 in the renal tubules, suggesting a regulatory effect of LRP5 on TGF-β/Smad signaling. In consistent with this hypothesis, LRP5 overexpression resulted in enhanced TGF-β/Smad signaling activation in renal tubule epithelial cells.