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The available evidence on the connection between excessive alcohol consumption and diabetes is controversial. Therefore, the primary objective of this investigation was to examine the connection between excessive alcohol consumption and incident diabetes in a Japanese population through the utilization of propensity score matching (PSM) analysis. Our retrospective cohort study encompassed a sample of 15,464 Japanese individuals who were initially free of diabetes between the years 2004 and 2015. The study utilized comprehensive medical records of individuals who underwent a physical examination. Employing a one:one PSM analysis, the current research included 2298 individuals with and without excessive alcohol consumption. Furthermore, a doubly robust estimation method was employed to ascertain the connection between excessive alcohol consumption and diabetes. The findings revealed that individuals with excessive alcohol consumption exhibited a 73% higher likelihood of developing diabetes (HR = 1.73, 95% CI 1.08–2.77). Furthermore, upon adjusting for variables, the PSM cohort demonstrated that individuals with excessive alcohol consumption had a 78% increased risk of developing diabetes in comparison to those with non-excessive alcohol consumption (HR = 1.78, 95% CI 1.08–2.93). Individuals with excessive alcohol consumption were found to have a 73% higher risk of developing diabetes compared to those with non-excessive alcohol consumption, even after controlling for propensity score (HR = 1.73, 95% CI 1.08–2.78). Participants in the PSM cohort with excessive alcohol consumption had a 73% higher risk of developing diabetes than those with non-excessive alcohol consumption after controlling for confounding factors. These findings underscore the importance of alcohol consumption guidelines aimed at reducing excessive drinking. Clinicians should be vigilant in screening for alcohol use in patients, particularly those at risk for diabetes, and provide appropriate counseling and resources to support alcohol reduction. [ABSTRACT FROM AUTHOR]

Introduction: The escalating global surge in Rifampicin-resistant strains poses a formidable challenge to the worldwide campaign against tuberculosis (TB), particularly in developing countries. The frequent reports of suboptimal treatment outcomes, complications, and the absence of definitive treatment guidelines for Rifampicin-resistant spinal TB (DSTB) contribute significantly to the obstacles in its effective management. Consequently, there is an urgent need for innovative and efficacious drugs to address Rifampicin-resistant spinal tuberculosis, minimizing the duration of therapy sessions. This study aims to investigate potential targets for DSTB through comprehensive proteomic and pharmaco-transcriptomic analyses. Methods: Mass spectrometry-based proteomics analysis was employed to validate potential DSTB-related targets. PPI analysis confirmed by Immunohistochemistry (IHC) and Western blot analysis. Results: The proteomics analysis revealed 373 differentially expressed proteins (DEPs), with 137 upregulated and 236 downregulated proteins. Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses delved into the DSTB-related pathways associated with these DEPs. In the context of network pharmacology analysis, five key targets--human leukocyte antigen A chain (HLAA), human leukocyte antigen C chain (HLA-C), HLA Class II Histocompatibility Antigen, DRB1 Beta Chain (HLA-DRB1), metalloproteinase 9 (MMP9), and Phospholipase C-like 1 (PLCL1)--were identified as pivotal players in pathways such as "Antigen processing and presentation" and "Phagosome," which are crucially enriched in DSTB. Moreover, pharmaco-transcriptomic analysis can confirm that 58 drug compounds can regulate the expression of the key targets. Discussion: This research confirms the presence of protein alterations during the Rifampicin-resistant process in DSTB patients, offering novel insights into the molecular mechanisms underpinning DSTB. The findings suggest a promising avenue for the development of targeted drugs to enhance the management of Rifampicin-resistant spinal tuberculosis. [ABSTRACT FROM AUTHOR]

Objective: The connection between total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) ratio and stroke risk is controversial. This study aims to examine the connection between the TC/HDL-C ratio and stroke in middle-aged and older individuals who are part of the China Health and Retirement Longitudinal Study (CHARLS). Methods: This study conducted a retrospective cohort analysis, enrolling a total of 10,184 participants who met the designated criteria from CHARLS between 2011 and 2012. We then used the Cox proportional-hazards regression model to analyze the relationship between the TC/HDL-C ratio and stroke risk. Using a Cox proportional hazards regression model with cubic spline functions and smooth curve fitting, we were able to identify the non-linear relationship between the TC/HDL-C ratio and stroke occurrence. The sensitivity and subgroup analyses were also performed to investigate the connection between TC/HDL-C ratio and stroke. Results: This study revealed a statistically significant association between the TC/HDL-C ratio and stroke risk in subjects aged 45 years or older after adjusting for risk factors (HR: 1.05, 95%CI 1.00–1.10, P = 0.0410). Furthermore, a non-linear connection between the TC/HDL-C ratio and stroke risk was detected, with a TC/HDL-C ratio inflection point of 3.71. We identified a significant positive connection between the TC/HDL-C ratio and stroke risk, when the TC/HDL-C ratio was less than 3.71 (HR: 1.25, 95%CI 1.07–1.45, P = 0.0039). However, their connection was not significant when the TC/HDL-C ratio exceeded 3.71 (HR: 1.00, 95%CI 0.94–1.06, P = 0.9232). The sensitivity analysis and subgroup analyses revealed that our findings were well-robust. Conclusion: Our study demonstrated a positive, non-linear connection between the TC/HDL-C ratio and stroke risk in middle-aged and older individuals. There was a significant positive connection between the TC/HDL-C ratio and stroke risk, when the TC/HDL-C ratio was less than 3.71. The current research can be used as a guideline to support clinician consultation and optimize stroke prevention measures for middle-aged and older adults. [ABSTRACT FROM AUTHOR]

Background and Aims Anti-inflammatory trials have shown considerable benefits for cardiovascular disease. High neutrophil counts, an easily accessible inflammation biomarker, are associated with atherosclerosis in experimental studies. This study aimed to investigate the associations between neutrophil counts and risk of nine cardiovascular endpoints using observational and genetic approaches. Methods Observational studies were conducted in the Copenhagen General Population Study (n = 101 730). Genetic studies were firstly performed using one-sample Mendelian randomization (MR) with individual-level data from the UK Biobank (n = 365 913); secondly, two-sample MR analyses were performed using summary-level data from the Blood Cell Consortium (n = 563 085). Outcomes included ischaemic heart disease, myocardial infarction, peripheral arterial disease, ischaemic cerebrovascular disease, ischaemic stroke, vascular-related dementia, vascular dementia, heart failure, and atrial fibrillation. Results Observational analyses showed associations between high neutrophil counts with high risks of all outcomes. In the UK Biobank, odds ratios (95% confidence intervals) per 1-SD higher genetically predicted neutrophil counts were 1.15 (1.08, 1.21) for ischaemic heart disease, 1.22 (1.12, 1.34) for myocardial infarction, and 1.19 (1.04, 1.36) for peripheral arterial disease; similar results were observed in men and women separately. In two-sample MR, corresponding estimates were 1.14 (1.05, 1.23) for ischaemic heart disease and 1.11 (1.02, 1.20) for myocardial infarction; multiple sensitivity analyses showed consistent results. No robust associations in two-sample MR analyses were found for other types of leucocytes. Conclusions Observational and genetically determined high neutrophil counts were associated with atherosclerotic cardiovascular disease, supporting that high blood neutrophil counts is a causal risk factor for atherosclerotic cardiovascular disease. [ABSTRACT FROM AUTHOR]

Over the past decade, scholarly work has surged around grand societal challenges, such as climate change, public health, and poverty, often framed by the UN's Sustainable Development Goals (SDGs). These complex and global issues demand innovative organization design solutions. The "Organizing for Good" campaign, launched by the United Nations Refugee Agency (UNHCR) and the Organizational Design Community (ODC), aims to spotlight, curate, and stimulate research and practices contributing to the SDGs. This introductory essay serves as a prologue to a special issue in the Journal of Organization Design, which closely aligned with the campaign's objectives. It delves into the concept of organization design as a tool for addressing these challenges, viewing organization designs as problem-solving systems for collective action. Furthermore, it provides an overview of how the SDGs intersect with the scholarly community focusing on organization design, previews the content of articles featured in this special issue, and raises questions for future research. [ABSTRACT FROM AUTHOR]

Objective: The evidence on the relationship between remnant cholesterol (RC) and stroke remains controversial. Therefore, this study aimed to explore the relationship between RC and stroke risk in a Chinese population of middle-aged and elderly individuals. Methods: The present study included 10067 Chinese subjects of middle-aged and elderly individuals. The connection between RC and incident stroke was investigated using the multivariate Cox proportional hazards regression model, several sensitivity analyses, generalized additive models, and smoothed curve fitting. Results: A total of 1180 participants with stroke were recorded during the follow-up period. The multivariate Cox proportional hazards regression model identified a positive connection between RC and stroke risk (hazard ratio (HR) = 1.087, 95% confidence interval (CI): 1.001–1.180). In addition, the current study discovered a nonlinear connection between RC and incident stroke, and the point of inflection for RC was 1.78 mmol/L. The risk of stroke increased by 25.1% with each unit increase in RC level when RC was < 1.78 mmol/L (HR:1.251, 95%CI: 1.089–1.437, P = 0.0015). The results were not affected by sensitivity tests. Conclusion: The current study showed a positive and nonlinear connection between RC and stroke risk in a middle-aged and elderly Chinese population. These findings provided new information to help researchers better understand the relationship between RC levels and incident stroke. [ABSTRACT FROM AUTHOR]

Background: Studies have established the association between blood β-amyloid (Aβ) levels and Alzheimer's disease, but population-based studies concerning the association between selenium (Se) and Aβ levels in blood samples are very limited. Therefore, we explored the association in an elderly population with Se status and serum Aβ measures. Methods: A cross-sectional study on 469 elderly individuals from four rural counties with diverse soil Se levels was carried out. Fasting blood Se, serum selenoprotein P (SELENOP), and glutathione peroxidase (GPX), serum Aβ42, and Aβ40 were measured. Quantile regression models were used to determine the associations of blood Se, serum GPX, and SELENOP with Aβ levels. Results: Significant negative associations were observed between blood Se and serum Aβ42 and Aβ40 levels at all percentiles (P < 0.05). The associations were generally stronger at higher Aβ42 and Aβ40 percentiles than lower Aβ42 and Aβ40 percentiles. Blood Se was positively associated with serum Aβ42/Aβ40 ratio at 25th, 50th, and 75th percentiles. Significant positive associations were observed between serum GPX and Aβ42 and Aβ40 levels at all percentiles (P < 0.05). The positive associations were generally stronger at higher Aβ42 and Aβ40 percentiles than at lower percentiles. Serum GPX was negatively associated with Aβ42/Aβ40 ratio at 25th, 50th, 75th, and 95th percentiles. No associations with serum SELENOP and Aβ levels were observed. Conclusions: Our results suggest that higher Se levels are associated with lower serum Aβ42 and Aβ40 levels and with higher Aβ42/Aβ40 ratio, and the results are specific for different selenoproteins. [ABSTRACT FROM AUTHOR]

In order to improve the high added values and solve the environmental pollution problems of the waste edible oil (EO) and discarded cigarette butt (CB), the CB-derived activated carbons (ACs) were prepared by H3PO4, KOH, and CO2 activation methods and used as an adsorbent for the decolorization of waste EO. The CB-AC@H3PO4 prepared by H3PO4 activation method had the high surface area of 1423 m2/g, oxygen contents of 11.24%, and yield of 14.11%, and exhibited better decolorization performance for EO than the CB-AC@KOH and CB-AC@CO2. The optimal decolorization process parameters of CB-AC@H3PO4 based on the orthogonal experimental results were the AC contents of 8%, the decolorization temperature of 90 °C, and the decolorization time of 30 min, which resulted in the corresponding decolorization rate of 83%. Therefore, these provided one application case for turning waste into wealth, energy conservation, and emission reduction. [ABSTRACT FROM AUTHOR]

Background: Endothelial-mesenchymal transition (EndoMT) is an emerging adaptive process that modulates lymphatic endothelial function to drive aberrant lymphatic vascularization in the tumour microenvironment (TME); however, the molecular determinants that govern the functional role of EndoMT remain unclear. Here, we show that cancer-associated fibroblast (CAF)-derived PAI-1 promoted the EndoMT of lymphatic endothelial cells (LECs) in cervical squamous cell carcinoma (CSCC). Methods: Immunofluorescent staining of α-SMA, LYVE-1 and DAPI were examined in primary tumour samples obtained from 57 CSCC patients. Assessment of cytokines secreted by CAFs and normal fibroblasts (NFs) was performed using human cytokine antibody arrays. The phenotype of EndoMT in lymphatic endothelial cells (LECs), gene expression levels, protein secretion and activity of signaling pathways were measured by real-time RT-PCR, ELISA or western blotting. The function of lymphatic endothelial monolayers was examined by transwell, tube formation assay, transendothelial migration assay in vitro. Lymphatic metastasis was measured using popliteal lymph node metastasis model. Furthermore, association between PAI-1 expression and EndoMT in CSCC was analyzed by immunohistochemistry. The Cancer Genome Atlas (TCGA) databases was used to assess the association of PAI-1 with survival rate in CSCC. Results: CAF-derived PAI-1 promoted the EndoMT of LECs in CSCC. LECs undergoing EndoMT could initiate tumour neolymphangiogenesis that facilitated cancer cell intravasation/extravasation, which in turn promoted lymphatic metastasis in CSCC. Mechanistically, PAI-1 activated the AKT/ERK1/2 pathways by directly interacting with low-density lipoprotein receptor-related protein (LRP1), thereby leading to elevated EndoMT activity in LECs. Blockade of PAI-1 or inhibition of LRP1/AKT/ERK1/2 abrogated EndoMT and consequently attenuated CAF-induced tumour neolymphangiogenesis. Furthermore, clinical data revealed that increased PAI-1 levels positively correlated with EndoMT activity and poor prognosis in CSCC patients. Conclusion: Our data indicate that CAF-derived PAI-1 acts as an important neolymphangiogenesis-initiating molecular during CSCC progression through modulating the EndoMT of LECs, resulting in promotion of metastasis ability in primary site. PAI-1 could serve as an effective prognostic biomarker and therapeutic target for CSCC metastasis. [ABSTRACT FROM AUTHOR]

We explore transposition—bringing ideas from one context to a distant other context—as a mechanism for institutional change, and we study the conditions under which institutional actors successfully undertake it. Prior work on transposition has emphasized the paradox of embedded agency: actors embedded in a context may struggle to effect change because they lack exposure to fresh ideas. We complement this work by arguing that transposition is also subject to a paradox of peripheral influence: actors not embedded in a context, who may be a source of fresh ideas, can struggle to effect change because of their peripheral or outsider status. We suggest that these dual paradoxes can be overcome by actors who simultaneously have exposure to alternative institutional environments and are sufficiently embedded in the focal field to gain trust and buy-in from other decision makers. Such actors can both see the potential of new ideas and navigate their implementation successfully. We identify returnees from abroad, who have studied or worked elsewhere and then emigrated back to their home country, as one such type of actor. Using data on publicly listed Chinese companies from 2000 to 2012, we show that the presence on firms' boards of directors of returnees with relevant exposure abroad significantly raises firms' participation in corporate social responsibility, specifically in the form of making corporate donations. Supporting our theorizing about the two paradoxes, the effect of returnees is stronger when they or their board allies have greater exposure to foreign experience and greater embeddedness in the local context. The effect is also stronger when field conditions, such as insufficient economic development, present greater need for change. [ABSTRACT FROM AUTHOR]

Aim Mitochondrial DNA dysfunction has been implicated in the pathogenesis of cardiovascular diseases. We aimed to investigate the associations between leukocyte mitochondrial DNA (mtDNA) abundance, as a proxy of mitochondrial function, and coronary artery disease (CAD) and heart failure (HF) in a cohort study and approximate the causal nature of these relationships using Mendelian randomization (MR) in genetic studies. Methods and results Multivariable-adjusted Cox regression analyses were conducted in 273 619 unrelated participants of European ancestry from the UK Biobank (UKB). For genetic studies, we first performed MR analyses with individual-level data from the UKB using a weighted genetic risk score (GRS); two-sample MR analyses were subsequently performed using summary-level data from the publicly available three consortia/biobank for CAD and two for HF. MR analyses were performed per database separately and results were subsequently meta-analysed using fixed-effects models. During a median follow-up of 11.8 years, restricted cubic spline Cox regression analyses showed associations between lower mtDNA abundance and higher risk of CAD and HF. Hazard ratios for participants in the lowest quintile of mtDNA abundance compared with those in the highest quintile were 1.08 (95% confidence interval: 1.03, 1.14) and 1.15 (1.05, 1.24) for CAD and HF. Genetically, no evidence was observed for a possible non-linear causal effect using individual-level weighted genetic risk scores calculated in the UKB on the study outcomes; the pooled odds ratios (95% confidence interval) from two-sample MR of genetically predicted per one-SD decrease in mtDNA abundance were 1.09 (1.03, 1.16) for CAD and 0.99 (0.92, 1.08) for HF, respectively. Conclusion Our findings support a possible causal role of lower leukocyte mtDNA abundance in higher CAD risk, but not in HF. [ABSTRACT FROM AUTHOR]

Background: Systemic Sclerosis (SSc) is an autoimmune disease that is characterized by vasculopathy, digital ulcers, Raynaud's phenomenon, renal failure, pulmonary arterial hypertension, and fibrosis. Regulatory T (Treg) cell subsets have recently been found to play crucial roles in SSc with interstitial lung disease (ILD) pathogenesis. This study investigates the molecular mechanism of Treg-related genes in SSc patients through bioinformatic analyses. Methods: The GSE181228 dataset of SSc was used in this study. CIBERSORT was used for assessing the category and proportions of immune cells in SSc. Random forest and least absolute shrinkage and selection operator (LASSO) regression analysis were used to select the hub Treg-related genes. Results: Through bioinformatic analyses, LIPN and CLEC4D were selected as hub Treg-regulated genes. The diagnostic power of the two genes separately for SSc was 0.824 and 0.826. LIPN was associated with the pathway of aminoacyl−tRNA biosynthesis, Primary immunodeficiency, DNA replication, etc. The expression of CLEC4D was associated with the pathway of Neutrophil extracellular trap formation, PPAR signaling pathway, Staphylococcus aureus infection, Systemic lupus erythematosus, TNF signaling pathway, and Toll−like receptor signaling pathway. Conclusion: Through bioinformatic analyses, we identified two Treg-related hub genes (LIPN, CLEC4D) that are mainly involved in the immune response and metabolism of Tregs in SSc with ILD. Moreover, our findings may provide the potential for studying the molecular mechanism of SSc with ILD. [ABSTRACT FROM AUTHOR]

In this paper, the hot tensile deformation of a GH3230 superalloy double-sheet was conducted under deformation temperatures ranging from 1123~1273 K and strain rates ranging from 0.001~0.2 s−1. The flow behavior of the GH3230 superalloy double-sheet was analyzed in detail. The hot tensile deformation process of the GH3230 superalloy double-sheet includes four stages of elastic deformation, strain hardening, steady state and fracture. The true stress decreases with the increasing deformation temperature and decreasing strain rate. The variation of the strain rate sensitivity index and strain hardening index with processing parameters were discussed. The average apparent activation energy for hot tensile deformation is 408.53 ± 46.96 kJ·mol−1. A combined Johnson-Cook and Hensel-Spittle model considering the couple effect of strain hardening, strain rate hardening and thermal softening was established to describe the hot tensile behavior of the GH3230 alloy double-sheet. Compared to Johnson-Cook model and Hensel-Spittle model, this model has the highest predicting accuracy. The average absolute relative error of true stress between the experimental and the predicted is only 2.35%. [ABSTRACT FROM AUTHOR]

Oxidative stress has been proposed as a key contributor to lifestyle- and age-related diseases. Because free radicals play an important role in various processes such as immune responses and cellular signaling, the body possesses an arsenal of different enzymatic and non-enzymatic antioxidant defense mechanisms. Oxidative stress is, among others, the result of an imbalance between the production of various reactive oxygen species (ROS) and antioxidant defense mechanisms including vitamin E (α-tocopherol) as a non-enzymatic antioxidant. Dietary vitamins, such as vitamin C and E, can also be taken in as supplements. It has been postulated that increasing antioxidant levels through supplementation may delay and/or ameliorate outcomes of lifestyle- and age-related diseases that have been linked to oxidative stress. Although supported by many animal experiments and observational studies, randomized clinical trials in humans have failed to demonstrate any clinical benefit from antioxidant supplementation. Nevertheless, possible explanations for this discrepancy remain underreported. This review aims to provide an overview of recent developments and novel research techniques used to clarify the existing controversy on the benefits of antioxidant supplementation in health and disease, focusing on α-tocopherol as antioxidant. Based on the currently available literature, we propose that examining the difference between antioxidant activity and capacity, by considering the catabolism of antioxidants, will provide crucial knowledge on the preventative and therapeutical use of antioxidant supplementation in oxidative stress-related diseases. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Mitochondrial dysfunction, which can be approximated by blood mitochondrial DNA copy number (mtDNA-CN), has been implicated in the pathogenesis of type 2 diabetes mellitus. Thus far, however, insights from prospective cohort studies and Mendelian randomisation (MR) analyses on this relationship are limited. We assessed the association between blood mtDNA-CN and incident type 2 diabetes using multivariable-adjusted regression analyses, and the associations between blood mtDNA-CN and type 2 diabetes and BMI using bi-directional MR. Methods: Multivariable-adjusted Cox proportional hazard models were used to estimate the association between blood mtDNA-CN and incident type 2 diabetes in 285,967 unrelated European individuals from UK Biobank free of type 2 diabetes at baseline. Additionally, a cross-sectional analysis was performed to investigate the association between blood mtDNA-CN and BMI. We also assessed the potentially causal relationship between blood mtDNA-CN and type 2 diabetes (N=898,130 from DIAGRAM, N=215,654 from FinnGen) and BMI (N=681,275 from GIANT) using bi-directional two-sample MR. Results: During a median follow-up of 11.87 years, 15,111 participants developed type 2 diabetes. Participants with a higher level of blood mtDNA-CN are at lower risk of developing type 2 diabetes (HR 0.90 [95% CI 0.89, 0.92]). After additional adjustment for BMI and other confounders, these results attenuated moderately and remained present. The multivariable-adjusted cross-sectional analyses showed that higher blood mtDNA-CN was associated with lower BMI (−0.12 [95% CI −0.14, −0.10]) kg/m2. In the bi-directional MR analyses, we found no evidence for causal associations between blood mtDNA-CN and type 2 diabetes, and blood mtDNA-CN and BMI in either direction. Conclusions/interpretation: The results from the present study indicate that the observed association between low blood mtDNA-CN and higher risk of type 2 diabetes is likely not causal. [ABSTRACT FROM AUTHOR]

Observational studies have implied associations between multiple cytokines and cognitive decline, anti-inflammatory drugs however did not yield any protective effects on cognitive decline. We aimed to assess the associations of systemic inflammation, as measured by multiple cytokine and growth factor, with cognitive performance and brain atrophy using two-sample Mendelian randomization (MR). Independent genetic instruments (p < 5e − 8 and p < 5e − 6) for 41 systemic inflammatory markers were retrieved from a genome-wide association study conducted in 8293 Finnish participants. Summary statistics for gene-outcome associations were obtained for cognitive performance (N = 257,841) and for brain atrophy measures of cerebral cortical surface area and thickness (N = 51,665) and hippocampal volume (N = 33,536). To rule out the heterogeneity in the cognitive performance, we additionally included three domains: the fluid intelligence score (N = 108,818), prospective memory result (N = 111,099), and reaction time (N = 330,069). Main results were computed by inverse-variance weighting; sensitivity analyses taking pleiotropy and invalid instruments into account were performed by using weighted-median estimator, MR-Egger, and MR PRESSO. After correcting for multiple testing using false discovery rate, only genetically predicted (with p < 5e − 6 threshold) per-SD (standard deviation) higher IL-8 was associated with − 0.103 (− 0.155, − 0.051, padjusted = 0.004) mm3 smaller hippocampal volume and higher intelligence fluid score [β: 0.103 SD (95% CI: 0.042, 0.165), padjusted = 0.041]. Sensitivity analyses generally showed similar results, and no pleiotropic effect, heterogeneity, or possible reverse causation was detected. Our results suggested a possible causal association of high IL-8 levels with better cognitive performance but smaller hippocampal volume among the general healthy population, highlighting the complex role of inflammation in dementia-related phenotypes. Further research is needed to elucidate mechanisms underlying these associations. [ABSTRACT FROM AUTHOR]

Purpose: Currently, the most commonly applied method for the determination of breast cancer subtypes is to test estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 by immunohistochemistry (IHC). However, the IHC method has substantial intraobserver and interobserver variability. ESR1, PGR, ERBB2, and MKi67 mRNA tests by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay may improve the diagnostic objectivity and efficiency. Here, we compared the concordance between RT-qPCR and IHC for assessment of the same biomarkers and evaluated the subtypes. Methods: A total of 265 eligible cases were divided into a training cohort and a validation cohort, and the expressions of ER/ESR1, PR/PGR, HER2/ERBB2, and Ki67/MKI67 were tested by IHC and RT-qPCR. Then, the appropriate cutoff of RT-qPCR was calculated in the training cohort. The concordance between RT-qPCR and IHC was calculated for individual marker. In addition, we investigated the subtypes based on the RT-qPCR results. Results: The Spearman correlation coefficients between ER/ESR1, PR/PGR, HER2/ERBB2, and Ki67/MKI67 by IHC and RT-qPCR were 0.768, 0.699, 0.762, and 0.387, respectively. The cutoff values for the RT-qPCR assay of ESR1 (1%), PGR (1%), ERBB2, and MKi67 (14%) were 35.539, 32.139, 36.398, and 29.176, respectively. The overall percent agreement (OPA) between ER/ESR1, PR/PGR, HER2/ERBB2, and Ki67/MKI67 by IHC and RT-qPCR was 92.48%, 73.68%, 92.80%, and 74.44%, respectively. A total of 224 (84.53%) specimens were concordant for the breast cancer subtypes (IHC-based type) by RT-qPCR. Conclusion: Evaluation of breast cancer biomarker status by RT-qPCR was highly concordant with IHC. RT-qPCR can be used as a supplementary method to detect molecular markers of breast cancer. [ABSTRACT FROM AUTHOR]

Obesity and overweight have posed a severe threat to humanity, needing urgent efforts for the development of safe and effective therapeutic interventions. In this research work, we have developed two polyherbal formulations A and B basically consisting of Helianthus tuberosus root powder (also called inulin of synanthrin) along with other herbs for the treatment of obesity. Evaluation of the antioxidant activity of both formulations using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2 ′ -azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical scavenging assays showed good antioxidant potentials. Both formulations A and B showed good antiobesity activity on a diet-induced obesity (DIO) model of mice by effectively lowering the body weight of mice compared to the high-fat diet (HFD) control mice, mainly by reducing the food efficiency ratio (FER). Furthermore, both formulations ameliorated lipoprotein misbalances induced by obesity and thus decreased the atherogenic index. Treatment with both formulations significantly decreased the liver and epididymal white adipose tissue (WAT) weight. This was supported by the improvement in steatosis of the liver and reduced hypertrophy in WAT on histological examination. In addition, formulations A and B have been seen as effective in controlling fasting blood glucose levels probably by alleviating HFD-induced insulin resistance. All of these results collectively suggest that formulations A and B serve as potentially safe and effective herbal interventions to control obesity and its comorbidities. [ABSTRACT FROM AUTHOR]

Whether photosynthesis has improved with increasing yield in major crops remains controversial. Research in this area has often neglected to account for differences in light intensity experienced by cultivars released in different years. Light intensity is expected to be positively associated with photosynthetic capacity and the resistance of the photosynthetic apparatus to high light but negatively associated with light-utilization efficiency under low light. Here, we analyzed the light environment, photosynthetic activity, and protein components of leaves of 26 winter wheat cultivars released during the past 60 years in China. Over time, light levels on flag leaves significantly decreased due to architectural changes, but photosynthetic rates under high or low light and the resistance of the photosynthetic apparatus to high light remained steady, contrary to expectations. We propose that the difference between the actual and expected trends is due to breeding. Specifically, breeding has optimized photosynthetic performance under high light rather than low light. Moreover, breeding selectivity altered the stoichiometry of several proteins related to dynamic photosynthesis, canopy light distribution, and photoprotection. These results indicate that breeding has significantly altered the photosynthetic mechanism in wheat and its response to the light environment. These changes likely have helped increase wheat yields. [ABSTRACT FROM AUTHOR]

Crop production requires large areas of land and makes an important contribution to greenhouse gas emissions. Cleaner production of all crop types could be of great significance to realizing carbon neutrality as soon as possible. The present study adopted life cycle assessment (LCA) combined with the profit accounting method of input-output to compare the differences in greenhouse gas emissions in the entire life cycle of apple (Malus pumila Mill.), grain maize (Zea mays L.), wheat (Triticum aestivum L.), silage maize (Zea mays L.), and alfalfa (Medicago sativa Linn.) production in eastern Gansu Province with three functional units, including per ha of land, per ton of product, and per 10,000 yuan of output value. The results showed that apple had the largest carbon footprint per ha. Wheat had the largest carbon footprint per ton of product and per 10,000 yuan output. The results of LCA inventory sensitivity analysis showed that the main sources of greenhouse gas emissions for all crops were the production process of agricultural materials such as chemical fertilizer, machinery, and agricultural film. In particular, the excessive input of chemical fertilizer was the driving factor resulting in greenhouse gas emissions. Based on the study results, this paper also puts forward certain suggestions on the future land use of the cropping systems in the study area. [ABSTRACT FROM AUTHOR]

Obesity and overweight have posed a severe threat to humanity, needing urgent efforts for the development of safe and effective therapeutic interventions. In this research work, we have developed two polyherbal formulations A and B basically consisting of Helianthus tuberosus root powder (also called inulin of synanthrin) along with other herbs for the treatment of obesity. Evaluation of the antioxidant activity of both formulations using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2 ′ -azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical scavenging assays showed good antioxidant potentials. Both formulations A and B showed good antiobesity activity on a diet-induced obesity (DIO) model of mice by effectively lowering the body weight of mice compared to the high-fat diet (HFD) control mice, mainly by reducing the food efficiency ratio (FER). Furthermore, both formulations ameliorated lipoprotein misbalances induced by obesity and thus decreased the atherogenic index. Treatment with both formulations significantly decreased the liver and epididymal white adipose tissue (WAT) weight. This was supported by the improvement in steatosis of the liver and reduced hypertrophy in WAT on histological examination. In addition, formulations A and B have been seen as effective in controlling fasting blood glucose levels probably by alleviating HFD-induced insulin resistance. All of these results collectively suggest that formulations A and B serve as potentially safe and effective herbal interventions to control obesity and its comorbidities. [ABSTRACT FROM AUTHOR]

In order to analyze the distribution characteristics of pharyngeal bacteria in patients with chronic pharyngitis (CP) by 16SrDNA-based detection technology, a prospective study is conducted to collect pharyngeal secretion samples from patients diagnosed with CP who are admitted to the Otorhinolaryngology Department of The Third People's Hospital of Shenzhen from May 2021 to September 2021. Among them, 11 cases are chronic simple pharyngitis (CSP), 11 cases are chronic hypertrophic pharyngitis (CHP), and 8 cases are healthy subjects. All samples are detected by the 16SrDNA technique and analyzed by bioinformatics. 55724.64 ± 1772.80, 53697.73 ± 2252.19, and 55177.5 ± 1661.80 optimized sequences are obtained by 16SrDNA sequencing. The α diversity analysis of pharyngeal microflora showed that the abundance index SOBS of pharyngeal microflora is upregulated in patients with CHP compared with normal controls (NC), but the diversity index of pharyngeal bacteria in the three groups is not significantly changed, indicating that the abundance of pharyngeal bacteria in the CHP group is increased. The β diversity analysis of pharyngeal microflora showed that the three groups are similar in structure and composition, and there is no significant statistical difference. The structural difference analysis of pharyngeal flora combined with LEfSe difference analysis showed that at the phylum level, the relative abundance of Spirochaetes and Synergistetes in the CHP group is significantly higher than that in the CSP group. At the genus level, the relative abundance of opportunistic pathogens such as Selenomonas and Campylobacter increased significantly in the CSP group. The relative abundance of Escherichia, Mycoplasma, and Porphyromonas are significantly increased in the CHP group. The abundance of beneficial symbiotic bacteria decreased significantly in patients with CP. The pharyngitis of patients with CP is characterized by an increase in the abundance of pharyngitis, changes in the structure of pharyngitis, a decline in the symbiotic beneficial bacteria, and an increase in the content of opportunistic pathogens, which may be closely related to the onset and development of CP. [ABSTRACT FROM AUTHOR]

The composition of a magnetorheological fluid (MRF) usually includes magnetic particles, a carrier fluid, and additives. Among them, the magnetic particles and carrier fluid are the main sources of the mechanical properties of the MRF. The changes of the related properties of the two will affect the mechanical properties of the MRF directly or indirectly. Herein, first, the temperature–magnetic field characteristics are analyzed during the MRF working process. Then, the influence mechanism of temperature and magnetic field changes on the properties of the magnetic particles and carrier liquid are analyzed. On this basis, the traditional Bingham model is improved and optimized, in which the temperature variable is introduced to represent the effect of temperature–magnetic field coupling on the shear stress of the MRF. Finally, parameter fitting and simulation are carried out for the optimized model, and the self‐made shear stress of the MRF measuring device with temperature‐control function is used to experimentally verify the accuracy of the optimized model. The comparison and verification of the results show that the optimized model can better represent the variation of shear stress of an MRF with temperature and magnetic field than the traditional Bingham model. [ABSTRACT FROM AUTHOR]

Background Serum phospholipase A2 receptor (PLA2R) antibody (SAb) and glomerular deposits of PLA2R antigen (GAg) have been tested widely in idiopathic membranous nephropathy (MN). Recently, we noticed a special form of PLA2R-associated MN with positive circulating PLA2R antibody but negative PLA2R deposits in the glomeruli by immunofluorescence on frozen tissue (IF-F). The significance of this form of PLA2R-associated MN is yet to be elucidated. This study aimed to explore the clinicopathological features of these PLA2R-associated MN patients. Methods This study enrolled 229 biopsy-proven PLA2R-associated MN patients with SAb+. SAb was measured by enzyme-linked immunosorbent assay, and GAg was detected by IF-F. These patients were divided into SAb+/GAg+ and SAb+/GAg− groups. Clinicopathological characteristics of SAb+/GAg+ and SAb+/GAg− PLA2R-associated MN patients were compared. PLA2R antigens of 19 SAb+/GAg− PLA2R-associated MN patients were verified by immunohistochemistry on paraffin tissue (IHC-P). Results Among 229 SAb+ PLA2R-associated MN patients, 210 (91.70%) were GAg+ and 19 (8.3%) were GAg−. These 19 SAb+/GAg− PLA2R-associated MN patients presented positive PLA2R deposits by IHC-P. Compared with SAb+/GAg+ PLA2R-associated MN patients, SAb+/GAg- PLA2R-associated MN patients had higher levels of serum PLA2R antibody (P = 0.004), increased proteinuria (P = 0.008), lower serum albumin (P = 0.019), more prominent chronic pathological lesions in terms of glomerulosclerosis score (P = 0.025), interstitial fibrosis score (P = 0.016), tubular atrophy score (P = 0.010) and total renal chronicity score (P = 0.010), and were more likely to be accompanied by focal segmental glomerulosclerosis (P = 0.014). Higher SAb level was associated with the total renal chronicity score (odds ratio per 100 RU/mL, 1.16; 95% confidence interval 1.01–1.33; P = 0.033). Conclusions PLA2R-associated MN patients with seropositive PLA2R antibody but negative PLA2R deposits in the glomeruli by IF-F have higher levels of SAb and worse clinicopathological manifestations compared with their double-positive counterparts. IHC-P can be an alternative technique to reveal PLA2R glomerular deposits. [ABSTRACT FROM AUTHOR]

The sedimentation stability of Magnetorheological fluid (MRF) is one of the research hotspots in the academic field of magnetorheological science. Excellent sedimentation stability is of great significance for the preservation and application of MRF. Given many traditional methods of characterization of sedimentation stability, this paper proposes a new method to characterize the sedimentation stability of MRF based on the change of shear yield stress during the sedimentation process of MRF. Then, the key components of the self-made MRF shear yield stress test device were introduced in detail, and three different surfactants containing dodecyl benzoate, polyethylene glycol and oleic acid were prepared. And then used the device to test their effects on the sedimentation stability of MRF. The results showed that oleic acid has the best effect on improving the sedimentation stability. Finally, the change law of shear yield stress of MRF in the next 90 days was predicted successfully by fitting experimental data based on the least square method. By comparing the test value and fitting value of 60–75 days, the error of the best fitting result were within 3%, this showed the reliability of the predicted results. [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus (S.) aureus (MRSA) is a representative pathogen that produces numerous virulence factors involving manifold cytotoxins and exotoxins. The present study was designed to investigate the influence of Eleutheroside K (ETSK), a single compound isolated from the leaves of Acanthopanax (A.) henryi (Oliv.) Harms, on the exotoxins secreted by MRSA. The transcription and translation of the exotoxins (α-hemolysin and staphylococcal enterotoxins) related to virulence in S. aureus were determined via quantitative RT-PCR and western blot analysis. The effect of ETSK on the production of tumor necrosis factor (TNF)-α was evaluated using enzyme-linked immunosorbent assay. As a result, ETSK at sub-MIC concentrations could reduce the protein expression of α-hemolysin and enterotoxin, and the expression of genes that regulate virulence factors was also inhibited. In addition, the TNF-inducing activity of S. aureus was attenuated by ETSK in a dose-dependent manner. These results revealed that ETSK not only reduced the protein and gene expression levels of related exotoxins but also suppressed the ability of S. aureus to induce macrophages to release cytokines. This study indicated that the inhibition of MRSA infection by ETSK may be achieved by reducing the virulence of S. aureus and highlighted the potential of ETSK as an innovative strategy for the prevention and treatment of MRSA infections. [ABSTRACT FROM AUTHOR]

Nerve growth factor (NGF) plays an important role in regulating the hypothalamus-pituitary-gonadal (HPG) axis. However, the effects of NGF on spermatogenesis remain unclear. This study aimed to assess the potential application of NGF with nasal delivery on spermatogenesis in azoospermic mice. We established a model with azoospermia induced by a single intraperitoneal (i.p.) injection of busulfan. NGF pre-encapsulated with liposomes (25, 50, and 100 μg/kg) was delivered via internasal administration. Three weeks after busulfan injection, NGF treatments were performed twice a week for 8 weeks; the change of sperm quality, testis and epididymis histopathology, and androgenic hormone were analyzed to evaluate sperm regeneration. Furthermore, 30 mg/kg busulfan injection caused severe testicular atrophy of the seminiferous tubules, characterized by a loss of spermatogenic elements and sperms. NGF with nasal administration could significantly upregulate the markers expressing meiotic spermatogonia (Stra8) and spermatocytes (SYCP3), restore spermatogenesis, and improve sperm quality in busulfan-treated mice by increasing the secretion of sexual hormones. The convenient and noninvasive nasal delivery of NGF may be a new potential therapy for spermatogenesis via activating the HPG axis and elevating androgenic hormones. This study opened a new horizon for NGF application in reproductive endocrine. [ABSTRACT FROM AUTHOR]

Objective  The delivery mode is considered to be a significant influencing factor in the early gut microbiota composition, which is associated with the long-term health of the host. In this study, we tried to explore the effects of probiotics on the intestinal microbiota of C-section neonates. Study Design  Twenty-six Chinese neonates were enrolled in this study. The neonates were divided into four groups: VD (natural delivery neonates, n  = 3), CD (cesarean-born neonates, n  = 9), CDL (cesarean-born neonates supplemented with probiotic at a lower dosage, n  = 7), and CDH (cesarean-born neonates supplemented with probiotic at a higher dosage, n  = 7). Fecal samples were collected on the 3rd, 7th, and 28th day since birth. The V3–V4 region of the 16S ribosomal ribonucleic acid gene was sequenced by next-generation sequencing technology. Results  The α-diversity of the intestinal microbiota of cesarean delivery neonates was significantly lower than that of the naturally delivered neonates on the 28th day (p  = 0.005). After supplementation with probiotics for 28 days, the α-diversity and the β-diversity of the gut flora in the cesarean-born infants (CDL28 and CDH28) was similar to that in the vaginally delivery infants. Meanwhile, the abundances of Lactobacillus and Bifidobacterium were significantly increased since the 3rd day of probiotic supplementation. Besides, the sustained supplementation of probiotics to neonates would help improve the abundance of the operational taxonomic units in several different Clusters of Orthologous Groups of proteins. Conclusion  This study showed that probiotics supplementation to cesarean-born neonates since birth might impact the diversity and function of gut microbiota. Key Points Cesarean-born neonates Probiotic supplementation impact gut flora Bifidobacterium and Lactobacillus [ABSTRACT FROM AUTHOR]

Research Summary: We examine the returns to specialization versus variety in corporate philanthropy. Acknowledging the theoretical rationale for both a specialist and a generalist approach to philanthropy, we took a question‐driven, abductive approach, and found a robust positive association between philanthropic variety and firm profitability for donations by large US public corporations from 2003 to 2011. This association held for variety across causes but not within causes, for nonlocal giving and for giving by diversified firms, and was weaker for firms whose donations faced greater scrutiny. These findings are consistent with a moral hazard explanation whereby firms take advantage of the relatively inelastic support for philanthropy within a cause area by strategically spreading their donations across a wide range of supporter interests, thus maximizing profits. Managerial Summary: Do firms earn higher profits if they spread their philanthropic donations across many different causes, or if they concentrate them among a few? Examining donations by large US public corporations we found that firms earned higher returns when they gave to many different causes, holding the total amount of donations constant; that this relationship was primarily true for nonlocal giving and giving by multinational and multi‐business firms, and was weaker for firms under shareholder scrutiny or those that gave inconsistently over time. Our best explanation for these results is that supporters of corporate philanthropy care more about whether a firm gives to a cause than how much it gives, making it optimal for firms to give minimal amounts to a large variety of causes. [ABSTRACT FROM AUTHOR]

Lymphatic remodelling in the hypoxic tumour microenvironment (TME) is critically involved in the metastasis of cervical squamous cell carcinoma (CSCC); however, its underlying mechanisms remain unclear. Here, we uncovered a novel lymphatic pattern in the hypoxic TME, wherein lymphatic vessels (LVs) are encapsulated by tumour-associated macrophages (TAMs) to form an interconnected network. We describe these aggregates as LVEM (LVs encapsulated by TAMs) considering their advantageous metastatic capacity and active involvement in early lymph node metastasis (LNM). Mechanistic investigations revealed that interleukin-10 (IL-10) derived from hypoxic TAMs adjacent to LVs was a prerequisite for lymphangiogenesis and LVEM formation through its induction of Sp1 upregulation in lymphatic endothelial cells (LECs). Interestingly, Sp1high LECs promoted the transactivation of C–C motif chemokine ligand 1 (CCL1) to facilitate TAM and tumour cell recruitment, thereby forming a positive feedback loop to strengthen the LVEM formation. Knockdown of Sp1 or blockage of CCL1 abrogated LVEM and consequently attenuated LNM. Notably, CSCCnon-LNM is largely devoid of hypoxic TAMs and the resultant LVEM, which might explain its metastatic delay. These findings identify a novel and efficient metastasis-promoting lymphatic pattern in the hypoxic TME, which might provide new targets for anti-metastasis therapy and prognostic assessment. [ABSTRACT FROM AUTHOR]

Introduction: Little attention has been paid to the interacting effect of specific intensities of physical activities (PAs) and sedentary lifestyle, like television watching, and genetic predisposition on body composition indices among Chinese adults. Herein, we aimed to examine whether specific types of PAs and sedentary behaviors (SBs) were associated with body composition indices among Chinese adults and to further explore whether these associations interacted with the genetic predisposition to high BMI. Methods: Cross-sectional data regarding PAs and time spent on SBs and dietary intake of 3,976 Chinese adults (54.9% women) aged 25–65 years in Southwest China were obtained via questionnaires in 2013–2015. Weight, height, and waist circumference (WC) were measured, and BMI, percentage of body fat (%BF), fat mass index (FMI), and fat-free mass index (FFMI) of the participants were calculated. Genetic risk score (GRS) was calculated on 9 established BMI-associated SNPs among Chinese adults. Results: When the participants were stratified by GRS for BMI, significant associations were only found for adults with high GRS for BMI: moderate-to-vigorous physical activity (MVPA) was negatively associated with WC and %BF and positively related to FFMI. The adjusted positive relationship of time spent watching television with BMI, WC, %BF, and FMI were also just found between adults with high weighted GRS for high BMI: for every 1 h increment in television watching, the BMI, WC, %BF, and FMI of the participants increased by 0.2 kg/m2, 0.9 cm, 0.3%, and 0.1 kg/m2, respectively (p < 0.02). Conclusion: MVPA may be a protective factor against obesity, and prolonged television watching may accentuate adiposity. These putative effects may be more pronounced among individuals with a high genetic risk of a high BMI. [ABSTRACT FROM AUTHOR]

Objectives Functional IgG autoantibodies against diverse G protein-coupled receptors, i.e. antibodies with agonistic or antagonistic activity at these receptors, are abundant in human serum. Their levels are altered in patients with SSc, and autoantibodies against angiotensin II receptor 1 (ATR1) and endothelin receptor A (ETA) have been suggested to drive SSc by inducing the chemokines CXCL8 and CCL18 in the blood. The objective of our study is to profile the effect of IgG in SSc (SSc-IgG) on the production of soluble mediators in monocytic cells. Methods Monocyte-like THP-1 cells were stimulated with SSc-IgG and their secretome was analysed. Furthermore, the significance of major pro-inflammatory pathways for the induction of CXCL8 and CCL18 in response to SSc-IgG was assessed by a pharmacological approach. Results Stimulation with SSc-IgG significantly alters the secretome of THP-1 cells towards a general pro-inflammatory and profibrotic phenotype, which includes an increase of CCL18 and CXCL8. The consequent expression profiles vary depending on the individual donor of the SSc-IgG. CCL18 and CXCL8 expression is thus regulated differentially, with AP-1 driving the induction of both CCL18 and CXCL8 and the TAK/IKK-β/NF-κB pathway and ERK1/2 driving that of CXCL8. Conclusions Our results suggest that SSc-IgG contributes to the generation of the pro-inflammatory/profibrotic tissue milieu characteristic of SSc by its induction of a respective phenotype in monocytes. Furthermore, our results highlight AP-1 as a critical regulator of gene transcription of CCL18 in monocytic cells and as a promising pharmacological therapeutic target for the treatment of SSc. [ABSTRACT FROM AUTHOR]

Chlorogenic acid (CGA) exhibits substantial biological function in antioxidant, antibacterial, anti‐lipogenesis and anti‐inflammatory activities. Increased sebum production and inflammation are considered important for the development of acne. However, the therapeutic effects of CGA on acne vulgaris remain unexplored. In this study, to assess the effects and underlying mechanisms of CGA on acne, a model of skin inflammation in ears of ICR mouse induced by living Propionibacterium acnes was used. 24 hours after 1.0 × 107 CFU, P. acnes were intradermally injected into the ears of the ICR mouse. 1, 5 and 10 mg of CGA mixed with vaseline were applied to the surface of the skin every 12 hours for 3 days. Then, skin inflammation in the ears was assessed and the change of SREBP1 and TNF‐α expression was analysed after CGA treatment. The mechanisms of CGA in anti‐inflammatory activity and lipogenesis were also studied in primary sebocytes and HaCaT cells. We found that CGA treatment effectively rescued ear swelling, redness and erythema skin in ears of ICR mouse induced by P. acnes and significantly downregulated the expression of inflammatory cytokines by reducing the activity of the NF‐κB signalling pathway. Furthermore, CGA could inhibit lipogenesis at the protein secretion and transcription level by decreasing the AKT/mTOR/SREBP signalling pathway. Our findings suggest that CGA could become a potential alternative drug for the treatment of acne vulgaris. [ABSTRACT FROM AUTHOR]

We connect two distinct streams of research on categories to study the role of within-category typicality in the context of legitimacy shocks. We argue that, following a legitimacy shock, member organizations of the tainted, focal category suffer equally, irrespective of their typicality. However, only the typical members of the newly favored, oppositional category benefit. Therefore, the effects of legitimacy shocks are asymmetrically influenced by typicality. We argue this pattern is the result of a two-stage process of categorization by audiences, whereby audiences prioritize distinctions between organizations in a newly favored category and spend limited efforts considering distinctions in the tainted, focal category. We examine our theory in the context of the U.S. financial services industry, where four different kinds of organizations engage in competition: traditional commercial banks, community banks, single-bond credit unions, and multibond credit unions. Consistent with our theory, we show that both traditional commercial banks and community banks suffer in terms of deposit market share following the legitimacy shock of the 2007 financial crisis, but the relative gains to credit unions are strongest for single-bond credit unions. [ABSTRACT FROM AUTHOR]

Self‐renewal and differentiation of spermatogonial stem cell (SSC) are critical for male fertility and reproduction, both of which are highly regulated by testicular microenvironment. Exosomal miRNAs have emerged as new components in intercellular communication. However, their roles in the differentiation of SSC remain unclear. Here, we observed miR‐486‐5p enriched in Sertoli cell and Sertoli cell‐derived exosomes. The exosomes mediate the transfer of miR‐486‐5p from Sertoli cells to SSCs. Exosomes release miR‐486‐5p, thus up‐regulate expression of Stra8 (stimulated by retinoic acid 8) and promote differentiation of SSC. And PTEN was identified as a target of miR‐486‐5p. Overexpression of miR‐486‐5p in SSCs down‐regulates PTEN expression, which up‐regulates the expression of STRA8 and SYCP3, promotes SSCs differentiation. In addition, blocking the exosome‐mediated transfer of miR‐486‐5p inhibits differentiation of SSC. Our findings demonstrate that miR‐486‐5p acts as a communication molecule between Sertoli cells and SSCs in modulating differentiation of SSCs. This provides a new insight on molecular mechanisms that regulates SSC differentiation and a basis for the diagnosis, treatment, and prevention of male infertility. [ABSTRACT FROM AUTHOR]