A Characterization and Functional Analysis of Peroxisome Proliferator-Activated Receptor Gamma Splicing Variants in the Buffalo Mammary Gland.

Peroxisome proliferator-activated receptor γ (PPARG) has various splicing variants and plays essential roles in the regulation of adipocyte differentiation and lipogenesis. However, little is known about the expression pattern and effect of the PPARG on milk fat synthesis in the buffalo mammary gland. In this study, we found that only PPARG-X17 and PPARG-X21 of the splicing variant were expressed in the buffalo mammary gland. Amino acid sequence characterization showed that the proteins encoded by PPARG-X17 and PPARG-X21 are endonuclear non-secreted hydrophilic proteins. Protein domain prediction found that only the PPARG-X21-encoded protein had PPAR ligand-binding domains (NR_LBD_PPAR), which may lead to functional differences between the two splices. RNA interference (RNAi) and the overexpression of PPARG-X17 and PPARG-X21 in buffalo mammary epithelial cells (BMECs) were performed. Results showed that the expression of fatty acid synthesis-related genes (ACACA, CD36, ACSL1, GPAT, AGPAT6, DGAT1) was significantly modified (p < 0.05) by the RNAi and overexpression of PPARG-X17 and PPARG-X21. All kinds of FAs detected in this study were significantly decreased (p < 0.05) after RNAi of PPARG-X17 or PPARG-X21. Overexpression of PPARG-X17 or PPARG-X21 significantly decreased (p < 0.05) the SFA content, while significantly increased (p < 0.05) the UFA, especially the MUFA in the BMECs. In conclusion, there are two PPARG splicing variants expressed in the BMECs that can regulate FA synthesis by altering the expression of diverse fatty acid synthesis-related genes. This study revealed the expression characteristics and functions of the PPARG gene in buffalo mammary glands and provided a reference for further understanding of fat synthesis in buffalo milk.

Multi-omics reveals the mechanism of rumen microbiome and its metabolome together with host metabolome participating in the regulation of milk production traits in dairy buffaloes.

Recently, it has been discovered that certain dairy buffaloes can produce higher milk yield and milk fat yield under the same feeding management conditions, which is a potential new trait. It is unknown to what extent, the rumen microbiome and its metabolites, as well as the host metabolism, contribute to milk yield and milk fat yield. Therefore, we will analyze the rumen microbiome and host-level potential regulatory mechanisms on milk yield and milk fat yield through rumen metagenomics, rumen metabolomics, and serum metabolomics experiments. Microbial metagenomics analysis revealed a significantly higher abundance of several species in the rumen of high-yield dairy buffaloes, which mainly belonged to genera, such as Prevotella, Butyrivibrio, Barnesiella, Lachnospiraceae, Ruminococcus, and Bacteroides. These species contribute to the degradation of diets and improve functions related to fatty acid biosynthesis and lipid metabolism. Furthermore, the rumen of high-yield dairy buffaloes exhibited a lower abundance of methanogenic bacteria and functions, which may produce less methane. Rumen metabolome analysis showed that high-yield dairy buffaloes had significantly higher concentrations of metabolites, including lipids, carbohydrates, and organic acids, as well as volatile fatty acids (VFAs), such as acetic acid and butyric acid. Meanwhile, several Prevotella, Butyrivibrio, Barnesiella, and Bacteroides species were significantly positively correlated with these metabolites. Serum metabolome analysis showed that high-yield dairy buffaloes had significantly higher concentrations of metabolites, mainly lipids and organic acids. Meanwhile, several Prevotella, Bacteroides, Barnesiella, Ruminococcus, and Butyrivibrio species were significantly positively correlated with these metabolites. The combined analysis showed that several species were present, including Prevotella.sp.CAG1031, Prevotella.sp.HUN102, Prevotella.sp.KHD1, Prevotella.phocaeensis, Butyrivibrio.sp.AE3009, Barnesiella.sp.An22, Bacteroides.sp.CAG927, and Bacteroidales.bacterium.52-46, which may play a crucial role in rumen and host lipid metabolism, contributing to milk yield and milk fat yield. The "omics-explainability" analysis revealed that the rumen microbial composition, functions, metabolites, and serum metabolites contributed 34.04, 47.13, 39.09, and 50.14%, respectively, to milk yield and milk fat yield. These findings demonstrate how the rumen microbiota and host jointly affect milk production traits in dairy buffaloes. This information is essential for developing targeted feeding management strategies to improve the quality and yield of buffalo milk.

Role of Different Members of the AGPAT Gene Family in Milk Fat Synthesis in Bubalus bubalis.

During triacylglycerol synthesis, the acylglycerol-3-phosphate acyltransferase (AGPAT) family catalyzes the conversion of lysophosphatidic acid to phosphatidic acid and the acylation of sn-2 fatty acids. However, the catalytic activity of different AGPAT members is different. Therefore, this study aimed to investigate the mechanism through which different AGPATs affect the efficiency of TAG synthesis and fatty acid composition. The conservation of amino acid sequences and protein domains of the AGPAT family was analyzed, and the functions of AGPAT1, AGPAT3, and AGPAT4 genes in buffalo mammary epithelial cells (BMECs) were studied using RNA interference and gene overexpression. Prediction of the protein tertiary structure of the AGPAT family demonstrated that four conservative motifs (motif1, motif2, motif3, and motif6) formed a hydrophobic pocket in AGPAT proteins, except AGPAT6. According to cytological studies, AGPAT1, AGPAT3, and AGPAT4 were found to promote the synthesis and fatty acid compositions of triacylglycerol, especially UFA compositions of triacylglycerol, by regulating ACSL1, FASN, GPAM, DGAT2, and PPARG gene expression. This study provides new insights into the role of different AGPAT gene family members involved in TAG synthesis, and a reference for improving the fatty acid composition of milk.

Lactobacillus-derived indole-3-lactic acid ameliorates colitis in cesarean-born offspring via activation of aryl hydrocarbon receptor.

Cesarean section (CS) delivery is known to disrupt the transmission of maternal microbiota to offspring, leading to an increased risk of inflammatory bowel disease (IBD). However, the underlying mechanisms remain poorly characterized. Here, we demonstrate that CS birth renders mice susceptible to dextran sulfate sodium (DSS)-induced colitis and impairs group 3 innate lymphoid cell (ILC3) development. Additionally, CS induces a sustained decrease in Lactobacillus abundance, which subsequently contributes to the colitis progression and ILC3 deficiency. Supplementation with a probiotic strain, L. acidophilus, or its metabolite, indole-3-lactic acid (ILA), can attenuate intestinal inflammation and restore ILC3 frequency and interleukin (IL)-22 level in CS offspring. Mechanistically, we indicate that ILA activates ILC3 through the aryl hydrocarbon receptor (AhR) signaling. Overall, our findings uncover a detrimental role of CS-induced gut dysbiosis in the pathogenesis of colitis and suggest L. acidophilus and ILA as potential targets to re-establish intestinal homeostasis in CS offspring.

Association between residential greenspace and mental health among cancer survivors in Shanghai, China.

BACKGROUND: Living near and enjoying visually green landscapes is associated with better mental health, but evidence focusing on vulnerable populations (such as cancer survivors) is sparse. The purpose of this study was to explore the association between residential greenspace and anxiety and depressive symptoms among cancer survivors in Shanghai, China. METHODS: In total, 4195 cancer survivors participated in this study from the 2022 Shanghai Cancer Patient Needs Survey. The estimation of residential greenspaces was based on Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI). The presence and severity of depressive and anxiety symptoms were assessed by using the Patient Health Questionnaire-2 (PHQ-2) and Generalized Anxiety Disorder-2 (GAD-2). The relation between mental health and green space was assessed using the Generalized Additive Model (GAM) after controlling for relevant individual covariates and contextual characteristics. RESULTS: The prevalence of anxiety and depression in cancer survivors was 36.2% and 28.3% respectively. After multivariate adjustment, each increase in inter-quartile range (IQR) for NDVI in the 250 m buffer (NDVI-250m) was associated with a decrease in PHQ-2 score (△score (95%CI): 0.018 (-0.034, -0.002)) and GAD-2 score (△score (95%CI): 0.018 (-0.034, -0.002)), respectively. We observed that an increase in IQR for NDVI-250m was associated with a 3.3% (Odds ratio (OR) (95%CI):0.967 (0.943, 0.991)) reduction in anxiety symptoms. More pronounced greenspace-mental health effects were found among young adults (18-65 years) and participants living in suburban areas, compared to young people over 65 and those living in urban areas (P-interaction < 0.05). CONCLUSIONS: Higher levels of residential green space are associated with lower risk of depression and anxiety disorders. Our findings will fill the gap in the relationship between green space and mental health among cancer survivors in urban China, and provide new evidence for garden afforestation, community planning and policy-making. To better understand this association, more longitudinal studies are necessary to investigate the mechanisms involved.

Current status of and future perspectives on care for cancer survivors in China.

Cancer is currently a major public health issue faced by countries around the world. With the progress of medical science and technology, the survival rate of cancer patients has increased significantly and the survival time has been effectively prolonged. How to provide quality and efficient care for the increasingly large group of cancer survivors with limited medical resources will be a key concern in the field of global public health in the future. Compared to developed countries, China's theoretical research and practical experience in care for cancer survivors are relatively limited and cannot meet the multi-faceted and diverse care needs of cancer patients. Based on the existing models of care worldwide, the current work reviews care for cancer survivors in China, it proposes considerations and suggestions for the creation of models of cancer care with Chinese characteristics in terms of optimizing top-level system design, enhancing institutional mechanisms, accelerating human resource development, and enhancing self-management and social support for patients.

The BAP31/miR-181a-5p/RECK axis promotes angiogenesis in colorectal cancer via fibroblast activation.

Background: B-cell receptor-associated protein 31 (BAP31) has been recognized as a tumor-associated protein and has largely been shown to promote metastasis in a variety of cancers. Cancer metastasis arises through multistep pathways, and the induction of angiogenesis is shown to be a rate-limiting step in the process of tumor metastasis. Methods and results: This study explored the effect of BAP31 on colorectal cancer (CRC) angiogenesis by regulating the tumor microenvironment. First, exosomes from BAP31-regulated CRCs affected the transition of normal fibroblasts to proangiogenic cancer-associated fibroblasts (CAFs) in vivo and in vitro. Next, microRNA sequencing was performed to analyze the microRNA expression profile of exosomes secreted from BAP31- overexpressing CRCs. The results indicated that the expression of BAP31 in CRCs significantly altered the levels of exosomal microRNAs, such as miR-181a- 5p. Meanwhile, an in vitro tube formation assay showed that fibroblasts with high levels of miR-181a-5p significantly promoted endothelial cell angiogenesis. Critically, we first identified that miR-181a-5p directly targeted the 3'-untranslated region (3'UTR) of reversion-inducing cysteine-rich protein with kazal motifs (RECK) using the dual-luciferase activity assay, which drove fibroblast transformation into proangiogenic CAFs by upregulating matrix metalloproteinase-9 (MMP-9) and phosphorylation of mothers against decapentaplegic homolog 2/Mothers against decapentaplegic homolog 3 (Smad2/3). Conclusion: Exosomes from BAP31-overexpressing/BAP31-knockdown CRCs are found to manipulate the transition of fibroblasts into proangiogenic CAFs by the miR-181a-5p/RECK axis.

Comparative evolutionary and molecular genetics based study of Buffalo lysozyme gene family to elucidate their antibacterial function.

Lysozyme is used as a food preservative, biological medicine, and infant food additive as a natural anti-infective chemical having bactericidal activity and abundantly secreted in mammals' milk, saliva, etc. We systematically analyzed the 16 coding LYZ genes (C and G-type) in buffalo and cattle to elucidate their evolutionary perspective thoroughly by evaluating an evolutionary relationship, motif patterning, physicochemical attributes, gene, and protein structure, as well as the functional role of the mammary gland-specific expressed buffalo and cattle LYZ genes precisely while considering expression levels difference and the interaction sites variation with bacteria envisaged the potential ability of buffalo LYZ protein with enhanced antibacterial effect. Thus, we speculated that the buffalo mammary glands expressed lysozyme has good antibacterial activity. This study on the buffalo lysozyme gene family not only provides comprehensive insights into the genetic architecture and their antibacterial effect but also offers a theoretical basis for the development of new veterinary drugs and animal health care for mastitis, as well as a new molecular genetic basis to study food or medical lysozyme.

Circ-ERBB2 knockdown sensitized colorectal cancer cells to 5-FU via miR-181a-5p/PTEN/Akt pathway.

Colorectal cancer (CRC) is the fourth most deadly cancer worldwide, drug resistance impedes treatment of CRC. It is still urgent to find new molecular targets to improve the sensitivity of chemotherapeutic drugs. In this study, circ-ERBB2 was upregulated in CRC cells. Upregulation of circ-ERBB2 promoted CRC cells proliferation and clone formation, but inhibited apoptosis. We identified miR-181a-5p as circ-ERBB2's target. The effect of miR-181a-5p on CRC cells was contrary to circ-ERBB2, miR-181a-5p downregulation abolished the function of circ-ERBB2 silencing in CRC cells. In addition, phosphatase and tensin homolog (PTEN) was verified as miR-181a-5p's downstream target, circ-ERBB2 activates the Akt pathway and inhibits cell apoptosis through modulating miR-181a-5p/PTEN. Circ-ERBB2 silencing significantly reduced CRC cell resistance to 5-FU. miR-181a-5p downregulation abolished the role of circ-ERBB2 knockdown in CRC cell resistance to 5-FU. In conclusion, upregulation of circ-ERBB2 promoted the malignancy of CRC and reduced CRC cell resistance to 5-FU. Besides, additional mechanism study provided a novel regulatory pathways that circ-ERBB2 knockdown promoted CRC cell sensitivity to 5-FU by regulating miR-181a-5p/PTEN/Akt pathway. This research indicated that circ-ERBB2 may be a valuable biomarker for the diagnosis and treatment of CRC.

Unmet supportive care needs and associated factors: Evidence from 4195 cancer survivors in Shanghai, China.

Background: Cancer survivors at different stages of life often have different needs that make it challenging for services to provide satisfactory care. Few studies have considered whether services are truly meeting the needs of cancer patients by exploring and identifying their perspectives on unmet needs. Objective: The aim of this study was to identify the unmet needs of cancer survivors and to further determine the potential impact of socio-demographic factors. Methods: A cross-sectional study that included 4195 cancer patients was conducted in Shanghai, China. Using Maslow's hierarchy of needs theory as a conceptual framework, the questionnaire included five dimensions: information, life and finances, continuing care, emotions, and self-actualization. Correlation analysis and ordered logistic regression analysis was used to explore the relationship between demographic sociological factors and unmet needs for supportive care. Results: The most common unmet supportive care needs include information needs (2.91 ± 1.32), self-actualization needs (2.69 ± 1.32) and continuing care needs (2.59 ± 1.30). Unmet needs for life and finances were more pronounced among cancer participants in the 45-69 age group. After adjusting for confounders, we found that each 6-month increase in the time since diagnosis was associated with a 0.8% (OR: 0.992, 95% CI: 0.985-0.998) reduction in high need for continuing care and a 0.9% (OR:0.991, 95% CI: 0.983-0.999) reduction in high need for self-actualization, respectively. Conclusions: Information needs are the most important concern among the diverse unmet needs of cancer survivors. Time since diagnosis is associated with unmet supportive care needs of cancer survivors. The findings highlight the large gap between actual health services and patients' unmet need for supportive care, which will provide the basis for a patient-centered supportive care system for cancer survivors.

Needs of cancer patients during the SARS-CoV-2 Omicron lockdown: A population-based survey in Shanghai, China.

The aim of this study was to investigate the medical and healthcare needs of cancer patients during the Shanghai lockdown due to the SARS-CoV-2 Omicron pandemic. From April 15 to April 21, 2022, 4,195 cancer patients from every district in Shanghai were surveyed using quota sampling via an online platform. The questionnaire consisted of three main parts: demographic and sociological data, disease diagnosis, and different dimensions of patients' needs. Correlation analysis was used to examine the relationship between participants' need scores in each dimension, and generalized linear regression models were used to analyze the factors influencing patients' need scores. The mean age of participants was 63.23 years (SD: 7.43 years), with more female than male participants (80.38% vs. 19.62%). Among participants, the three leading groups of patients were those with breast cancer (39.02%), colorectal cancer (12.82%), or tracheal and bronchial lung cancer (10.23%). Social support, dietary/nutritional support, and psychological counselling ranked as the top three needs of cancer patients. In addition, vaccination against SARS-CoV-2 may reduce psychological anxiety in cancer patients. Compared to participants who had never received the SARS-CoV-2 vaccine, participants who had received one, two, or three doses of the vaccine were respectively 36% (odds ratio (OR): 0.64, 95% confidence interval (CI): 0.56-0.73), 38% (OR: 0.62, 95% CI: 0.59-0.54), and 37% (OR: 0.63, 95% CI: 0.60-0.66) less likely to have an increased need for psychological counseling. In light of constraints on offline medical resources for cancer patients during the lockdown, the current authors have begun to re-examine the universal accessibility and spread of telemedicine in the future. In addition, immune barriers can be established for cancer patients and vaccination guidelines for different disease stages, tumor types, and treatment regimens can be explored in detail.

Rare Variant Analysis and Molecular Dynamics Simulation in Alzheimer's Disease Identifies Exonic Variants in FLG.

BACKGROUND: Although an increasing number of common variants contributing to Alzheimer's disease (AD) are uncovered by genome-wide association studies, they can only explain less than half of the heritability of AD. Rare variant association studies (RVAS) has become an increasingly important area to explain the risk or trait variability of AD. METHOD: To investigate the potential rare variants that cause AD, we screened 70,209 rare variants from two cohorts of a 175 AD cohort and a 214 cognitively normal cohort from the Alzheimer's Disease Neuroimaging Initiative database. MIRARE, a novel RVAS method, was performed on 232 non-synonymous variants selected by ANNOVAR annotation. Molecular docking and molecular dynamics (MD) simulation were adopted to verify the interaction between the chosen functional variants and BACE1. RESULTS: MIRAGE analysis revealed significant associations between AD and six potential pathogenic genes, including PREX2, FLG, DHX16, NID2, ZnF585B and ZnF875. Only interactions between FLG (including wild type and rs3120654(SER742TYR)) and BACE1 were verified by molecular docking and MD simulation. The interaction of FLG(SER742TYR) with BACE1 was greater than that of wildtype FLG with BACE1. CONCLUSIONS: According to the literature search, bio-informatics analysis, and molecular docking and MD simulation, we find non-synonymous rare variants in six genes, especially FLG(rs3120654), that may play key roles in AD.

Long noncoding RNA SNHG6 promotes oesophageal squamous cell carcinoma by downregulating the miR-101-3p/EZH2 pathway.

Long noncoding RNAs (LncRNAs) have been reported to play a vital role in the development of oesophageal squamous cell carcinoma (OSCC). Our previous study revealed that the significant upregulation of the LncRNA small nucleolar RNA host gene 6 (SNHG6) in OSCC promotes OSCC tumourigenesis. However, the mechanisms underlying the dynamics of SNHG6 expression in OSCC have rarely been studied. In this study, we verified the tumour-promoting effect of SNHG6 through sponging miR-101-3p, and their levels were negatively correlated in human samples of OSCC. In addition, miR-101-3p overexpression reversed the effect of SNHG6. Moreover, we confirmed that SNHG6/miR-101-3p affects OSCC by regulating the expression of the enhancer of zeste 2 (EZH2). The effect of EZH2 silencing resembled closely that of SNHG6 knockdown. EZH2 silencing inhibited the expression of protein cyclin D1 and ß-catenin, but in contrast, it enhanced the expression of E-cadherin. These findings demonstrated the oncogenic role of SNHG6, which promotes OSCC progression by regulating the expression of EZH2 through its interaction with miR-101-3p. These findings may help in improving the diagnosis and treatment methods of OSCC.

[Effects of Gui pi tang on myocardial ischemia in rats].

Objective: To investigate the effects of Guipitang (GPT) on myocardial ischemic (MI) injury of rats. Methods: Forty male SD rats were randomly divided into five groups as control, model, GPT low-dose and high-dose groups (7.52, 15.04 g/kg), and positive-drug trimetazidine group (2 mg/kg). Rat myocardial ischemia model was induced by feeding high fat forage and intraperitoneal injection of isoprenaline (ISO). After 15 days intragastric administration, rats were injected with ISO once a day for 3 days again. Subsequently, Electrocardiograph (ECG) was examined, serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and glucose (GLU) were detected using an automatic biochemical analyzer. The histopathological alterations of heart were assessed using HE and Masson staining. The protein expressions of Collagen I and Collagen III in heart were evaluated by Western blot. Results: Compared with control group, the electrocardiogram S-T segment of model rats moved down, the serum levels of TC, AST, CK, LDH and GLU in model group were increased significantly (P＜0.05), the expressions of collagen I and collagen III in heart were increased (P＜0.05), and the hearts were damaged severely. However, no significant changes of TG, HDL-C, LDL-C and ALT were observed (P＞0.05). Compared with the model group, the high and low dose groups of GPT and trimetazidine could inhibit the descent of S-T segment, reduced serum TC, AST, CK, LDH and GLU levels (P＜0.05), and decreased collagen III expression in heart (P＜0.05), and alleviated myocardial pathological damage as well. The high dose group of GPT could decrease the protein expression of collagen I. Conclusion: GPT could improve heart function and alleviate the injury of myocardial ischemia, especially the high lose.

Knockdown of circNRIP1 sensitizes colorectal cancer to 5­FU via sponging miR­532­3p.

The present study aimed to investigate the influence of circular RNA nuclear receptor­interacting protein 1 (circNRIP1) on the chemotherapeutic effect of 5­fluorouracil (5­FU) in colorectal cancer (CRC) and reveal its potential molecular mechanisms. The effects of circNRIP1 on cell proliferation, migration and invasion, and apoptosis were evaluated using Cell Counting Kit­8, Transwell and flow cytometric assays, respectively. A dual­luciferase reporter assay was performed to verify the potential interaction between circNRIP1 and microRNA (miR)­532­3p. The results of the present study indicated that circNRIP1 was upregulated in CRC and its increased expression was associated with CRC progression. Furthermore, overexpression of circNRIP1 promoted CRC cell proliferation, invasion and migration, while it inhibited apoptosis. Knockdown of circNRIP1 significantly enhanced the 5­FU­induced inhibition of the viability of HCT116 and SW480 cells. Bioinformatics analysis predicted that miR­532­3p was a direct target of circNRIP1, which was further confirmed by a dual­luciferase reporter assay. miR­532­3p silencing reversed the effects of circNRIP1 knockdown on the sensitivity of 5­FU in the chemotherapy of CRC. The results suggested that circNRIP1 and miR­532­3p may be utilized to improve the diagnosis of CRC and serve as diagnostic markers. In conclusion, overexpression of circNRIP1 promoted the progression of CRC, while circNRIP1 silencing sensitized CRC cells to 5­FU via sponging miR­532­3p.

Trend dynamics of thyroid cancer incidence among China and the U.S. adult population from 1990 to 2017: a joinpoint and age-period-cohort analysis.

BACKGROUND: Thyroid cancer (TC) is the most common malignant disease of the endocrine system. Based on the previously published reports, the incidence of TC has been increasing in the past 25 years, and the reason for the increase is not yet clear. The present study aims to reveal the long-term trends and age-period-cohort effects for the incidence of TC in China and the U.S. from 1990 to 2017. METHODS: We examined the trends of TC incidence and the average annual percentage change (AAPC) of rate using the Joinpoint regression analysis in the two countries, for the different genders (men/women) in the Global Burden of Disease (GBD 2017). We further used an age-period-cohort model to analyze age-period-cohort effects on TC incidence. RESULTS: The ASIR of China increased markedly with AAPC of 4.5% (95% confidence interval (CI): 4.0, 5.0%) and 1.8% (1.6, 2.0%) for men and women during 1990-2017. The ASIR of the U. S increased by 1.4% (1.0, 1.8%) and 1.3% (0.9, 1.7%) for men and women from 1990 to 2017.TC increased with the age and period. Aging was one of the most influential factors of TC in China. The age effect increased markedly in the U.S. compared with China. The period effect showed an increase in China while that tended to grow steadily during 1990-2017 in the U.S. The cohort effect peaked in 1963-1967 birth cohorts for men and women in China and declined consistently in the birth cohort in the U.S. CONCLUSION: From 1990 to 2017, due to ionizing radiation and over-diagnosis, age-standardized TC incidence rates in both genders rose in China and the U.S. The standardized incidence rate of women is higher than that of men. It is necessary to provide women with reasonable prevention and protection measures for TC. We need to apply for health services and screening to reduce ionizing radiation.

Melatonin sensitizes esophageal cancer cells to 5­fluorouracil via promotion of apoptosis by regulating EZH2 expression.

The present study aimed to investigate the effects of melatonin (MLT) and 5­fluorouracil (5­FU) combination on the chemotherapeutic effect of 5­FU in esophageal cancer, and determine the potential molecular mechanisms. The effects of MLT and 5­FU combination on cell proliferation, cell migration and invasion, and cell apoptosis were detected by Cell Counting Kit­8, Transwell assays and flow cytometric analysis, respectively. Quantitative PCR and western blotting were performed for mRNA and protein quantification, respectively. The present study revealed that MLT significantly inhibited cell activity in a dose­dependent manner and MLT significantly enhanced 5­FU­mediated inhibition of cell proliferation in esophageal cancer cells. Compared with the 5­FU group, the MLT and 5­FU combination group significantly inhibited the invasion and migration of EC­9706 and EC­109 cells. The present study also revealed that MLT and 5­FU synergistically promoted apoptosis via activation of the caspase­dependent apoptosis pathway. Histone-lysine N­methyltransferase EZH2 (EZH2) was highly expressed in esophageal cancer tissues and cells and its high expression promoted esophageal cancer progression. MLT and 5­FU combination inhibited cell proliferation and promoted apoptosis by regulating EZH2 expression. In conclusion, MLT enhanced 5­FU­mediated inhibition of cell proliferation via promotion of apoptosis by regulating EZH2 expression in esophageal cancer.

Residential Green and Blue Spaces and Type 2 Diabetes Mellitus: A Population-Based Health Study in China.

Evidence on the health benefits of green space in residential environments is still limited, and few studies have investigated the potential association between blue space and type 2 diabetes mellitus (T2DM) prevalence. This study included 39,019 participants who had completed the baseline survey from the Henan Rural Cohort Study, 2015-2017. The Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI) were employed to characterize the residential green space, and the distance from the participant's residential address to the nearest water body was considered to represent the residential blue space. Mixed effect models were applied to evaluate the associations of the residential environment with T2DM and fasting blood glucose (FBG) levels. An interquartile range (IQR) increase in NDVI and EVI was significantly associated with a 13.4% (odds ratio (OR): 0.866, 95% Confidence interval (CI): 0.830,0.903) and 14.2% (OR: 0.858, 95% CI: 0.817,0.901) decreased risk of T2DM, respectively. The residential green space was associated with lower fasting blood glucose levels in men (%change, -2.060 in men vs. -0.972 in women) and the elderly (%change, -1.696 in elderly vs. -1.268 in young people). Additionally, people who lived more than 5 km from the water body had a 15.7% lower risk of T2DM (OR: 0.843, 95% CI: 0.770,0.923) and 1.829% lower fasting blood glucose levels (95% CI: -2.335%,-1.320%) than those who lived closer to the blue space. Our findings suggest that residential green space was beneficially associated with T2DM and fasting blood glucose levels. However, further research is needed to explore more comprehensively the relationship between residential blue space and public health.

LncRNA SNHG6 Inhibits Apoptosis by Regulating EZH2 Expression via the Sponging of MiR-101-3p in Esophageal Squamous-Cell Carcinoma.

BACKGROUND: The long non-coding RNA (lncRNA) SNHG6 was significantly upregulated in esophageal squamous-cell carcinoma (ESCC), and it promoted ESCC cell proliferation, invasion, and migration. However, the effects of SNHG6 on cell apoptosis and the corresponding underlying mechanisms have not yet reported. METHODS: Apoptosis was detected by flow cytometric analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used for mRNA and protein quantification, respectively. A luciferase reporter assay was performed to verify downstream target genes for SNHG6 and miR-101-3p. RESULTS: Dysregulation of SNHG6 inhibited apoptosis in ESCC cells and regulated the expression of apoptosis-related proteins such as Bcl-2, Mcl-1, Bax and Caspase-3. Functionally, miR-101-3p could compete binding with 3'-untranslated region of SNHG6 and downregulation of miR-101-3p reversed its effect on cell apoptosis in SNHG6 knockdown cells. EZH2 was confirmed as a downstream target gene of miR-101-3p, silencing EZH2 expression had the same effect on apoptosis and protein expression as knocking down SNHG6. Overexpression of EZH2 reversed the effects of miR-101-3p overexpression on cell apoptosis in ESCC cells. CONCLUSION: In this study, we found that upregulation of the lncRNA SNHG6 inhibited apoptosis via miR-101-3p/EZH2 axis in ESCC. These findings may contribute to the diagnosis and treatment of ESCC.

Deletion of pancreatic ß-cell adenosine kinase improves glucose homeostasis in young mice and ameliorates streptozotocin-induced hyperglycaemia.

Severe reduction in the ß-cell number (collectively known as the ß-cell mass) contributes to the development of both type 1 and type 2 diabetes. Recent pharmacological studies have suggested that increased pancreatic ß-cell proliferation could be due to specific inhibition of adenosine kinase (ADK). However, genetic evidence for the function of pancreatic ß-cell ADK under physiological conditions or in a pathological context is still lacking. In this study, we crossed mice carrying LoxP-flanked Adk gene with Ins2-Cre mice to acquire pancreatic ß -cell ADK deficiency (Ins2-Cre± Adkfl/fl ) mice. Our results revealed that Ins2-Cre+/- Adkfl/fl mice showed improved glucose metabolism and ß-cell mass in younger mice, but showed normal activity in adult mice. Moreover, Ins2-Cre± Adkfl/fl mice were more resistant to streptozotocin (STZ) induced hyperglycaemia and pancreatic ß-cell damage in adult mice. In conclusion, we found that ADK negatively regulates ß-cell replication in young mice as well as under pathological conditions, such as STZ induced pancreatic ß-cell damage. Our study provided genetic evidence that specific inhibition of pancreatic ß-cell ADK has potential for anti-diabetic therapy.