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Blood vessel dysfunction causes several retinal diseases, including diabetic retinopathy, familial exudative vitreoretinopathy, macular degeneration and choroidal neovascularization in pathological myopia. Vascular endothelial growth factor (VEGF)-neutralizing proteins provide benefits in most of those diseases, yet unsolved haemorrhage and frequent intraocular injections still bothered patients. Here, we identified endothelial CD146 as a new target for retinal diseases. CD146 expression was activated in two ocular pathological angiogenesis models, a laser-induced choroid neovascularization model and an oxygen-induced retinopathy model. The absence of CD146 impaired hypoxia-induced cell migration and angiogenesis both in cell lines and animal model. Preventive or therapeutic treatment with anti-CD146 antibody AA98 significantly inhibited hypoxia-induced aberrant retinal angiogenesis in two retinal disease models. Mechanistically, under hypoxia condition, CD146 was involved in the activation of NFκB, Erk and Akt signalling pathways, which are partially independent of VEGF. Consistently, anti-CD146 therapy combined with anti-VEGF therapy showed enhanced impairment effect of hypoxia-induced angiogenesis in vitro and in vivo. Given the critical role of abnormal angiogenesis in retinal and choroidal diseases, our results provide novel insights into combinatorial therapy for neovascular fundus diseases.

Since coronavirus disease 2019 (COVID-19) has been a new disease, very less is known about the disease, and guidance for the treatment are often being made on the basis of an experiences or expert opinions. Now it is known that COVID-19 is caused by a new Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) virus which elicit infection to the cells by binding of the spike protein to angiotensin converting enzyme 2 (ACE2). Given the high transmissibility rate of the SARS-Cov-2 virus and known to have cytokine dysregulation by inducing an immune-mediated systemic inflammation, patients with underlying liver disease might be at an increased risk of severe infection and death. Here we report different mechanisms based on the organ cross-talk and other causes that how COVID-19 patients are prone to have liver injury.

The objective of this experiment was to investigate the potential benefits of active dry yeast (ADY) on the growth performance, rumen fermentation, nutrient digestibility, and serum parameters of weaned beef calves. Thirty Simmental crossbred male calves (body weight = 86.47 ± 4.41 kg and 70 ± 4 d of age) were randomly divided into 2 groups: control (CON) (fed basal ration) and ADY (fed basal ration and 5 g/d ADY per calf). The dietary concentrate-to-roughage ratio was 35:65. All the calves were regularly provided rations 3 times a day at 07:00, 13:00, and 19:00 and had free access to water. The experiment lasted for 60 d. The average daily gain of ADY group was higher (P = 0.007) than that of the CON group, and the ratio of feed intake to average daily gain in the ADY group was reduced (P = 0.022) as compared to the CON group. The concentration of ruminal ammonia-N was higher (P = 0.023) in the CON group than that in the ADY group, but an opposite trend of microbial protein was found between the 2 groups. Also, the ruminal concentrations of propionate and butyrate were higher (P

Recent evidence has shown that methionine (Met) supplementation can improve milk protein synthesis under hyperthermia (which reduces milk production). To explore the mechanism by which milk protein synthesis is affected by Met supplementation under hyperthermia, mammary alveolar (MAC-T) cells were incubated at a hyperthermic temperature of 42°C for 6 h in media with different concentrations of Met. While the control group (CON) contained a normal amino acid concentration profile (60 μg/mL of Met), the three treatment groups were supplemented with Met at concentrations of 10 μg/mL (MET70, 70 μg/mL of Met), 20 μg/mL (MET80, 80 μg/mL of Met), and 30 μg/mL (MET90,90 μg/mL of Met). Our results show that additional Met supplementation increases the mRNA and protein levels of BCL2 (B-cell lymphoma-2, an anti-apoptosis agent), and decreases the mRNA and protein levels of BAX (Bcl-2-associated X protein, a pro-apoptosis agent), especially at an additional supplementary concentration of 20 μg/mL (group Met80). Supplementation with higher concentrations of Met decreased the mRNA levels of Caspase-3 and Caspase-9, and increased protein levels of heat shock protein (HSP70). The total protein levels of the mechanistic target of rapamycin (mTOR) and the mTOR signalling pathway-related proteins, AKT, ribosomal protein S6 kinase B1 (RPS6KB1), and ribosomal protein S6 (RPS6), increased with increasing Met supplementation, and peaked at 80 μg/mL Met (group Met80). In addition, we also found that additional Met supplementation upregulated the gene expression of αS1-casein (CSN1S1), β-casein (CSN2), and the amino acid transporter genes SLC38A2, SLC38A3 which are known to be mTOR targets. Additional Met supplementation, however, had no effect on the gene expression of κ-casein (CSN3) and solute carrier family 34 member 2 (SLC34A2). Our results suggest that additional Met supplementation with 20 μg/mL may promote the synthesis of milk proteins in bovine mammary epithelial cells under hyperthermia by inhibiting apoptosis, activating the AKT-mTOR-RPS6KB1 signalling pathway, and regulating the entry of amino acids into these cells.

This study was conducted to examine the influence of uni and bilateral castration on growth performance and lipid metabolism in yellow cattle. Eighteen 9-month-old healthy yellow cattle (average body weight 184.03 ± 4.09 kg) were selected and divided into three groups: The uncastrated cattle (C), half castrated cattle (HC) and full castrated cattle (FC). The results showed that the growth rate of FC group was significantly reduced as compared to HC and C group, while the feed to gain ratio exhibited an opposite trend. The concentrations of triglycerides (TG), low-density lipoprotein cholesterol (LDL) and high-density lipoprotein (HDL) were increased significantly in FC group from day 60 to the end of the trial compared to HC and control groups. Serum testosterone concentration of FC group cattle was decreased from day 60 to 120 d of the trial compared to HC and control groups. The concentration of the lauric acid in FC cattle was significantly increased from the HC and control groups. In the FC group, the acetyl-CoA carboxylase alpha (ACACA), ACC and fatty acid synthase (FAS) gene expression levels were significantly higher compared to control and HC groups. Our results of this study suggest that bilateral castration increased the lipid metabolism and fatty acid composition compared to unilateral castrated and un-castrated cattle.HighlightsBilateral castration alters the growth performance in yellow cattle.Bilateral castration alters hormones levels and lipid metabolites levels in serum.Bilateral castration improves the lipid metabolism and fatty acid profile.

Background Ovarian cancer (OC) is a gynecological malignancy with the highest mortality rate. Cisplatin (DDP) based chemotherapy is a standard strategy for ovarian cancer. Despite good response rates for initial chemotherapy, almost 80% of the patients treated with DDP based chemotherapy will experience recurrence due to drug-resistant, which will ultimately result in fatality. The aim of the present study was to examine the pathogenesis and potential molecular markers of cisplatin-resistant OC by studying the differential expression of mRNAs and miRNAs between cisplatin resistant OC cell lines and normal cell lines. Methods Two mRNA datasets (GSE58470 and GSE45553) and two miRNA sequence datasets (GSE58469 and GSE148251) were downloaded from the Gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were screened by the NetworkAnalyst. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to analyze the biological functions of DEGs. The protein-protein interaction network was constructed using STRING and Cytoscape software to identify the molecular mechanisms of key signaling pathways and cellular activities. FunRich and MiRNATip databases were used to identify the target genes of the DEMs. Results A total of 380 DEGs, and 5 DEMs were identified. Protein–protein interaction (PPI) network of DEGs containing 379 nodes and 1049 edges was constructed, and 4 key modules and 24 hub genes related to cisplatin-resistant OC were screened. Two hundred ninety-nine target genes of the 5 DEMs were found out. Subsequently, one of these 299 target genes (UBB) belonging to the hub genes of GSE58470 and GSE45553 was identified by MCODE and CytoHubba,which was regulated by one miRNA (mir-454). Conclusions One miRNA–mRNA regulatory pairs (mir-454-UBB) was established. Taken together, our study provided evidence concerning the alteration genes involved in cisplatin-resistant OC, which will help to unravel the mechanisms underlying drug resistant.

It is increasingly recognized that the cellular microenvironment plays critical roles in regulating the fate and physiology of cells. Despite recent advancements in single-cell analysis technologies, engineering and integration of the microenvironment for single-cell analysis platforms remain limited. Here, we report a single-cell cytokine secretion analysis platform that integrated both the three-dimensional cell culture and the primary oral squamous cell carcinoma tumor cell co-culture to provide both physical and physiological cues for single cells to be analyzed. We apply the platform to investigate the immune responses of human macrophages stimulated with the ligand of toll-like receptor 4 lipopolysaccharide. Notably, we observe the differential modulation effect in cytokine secretions by the tumor microenvironment, in which antitumor cytokine TNF-a secretion was attenuated, and protumor cytokine IL-6 would increase. The differential modulation effect is conserved from cell line-derived macrophages to primary macrophages derived from healthy donors. Immunofluorescence staining further reveals that ∼50% of macrophage cells could be polarized from M1 to the M2 phenotype within 12 h in the engineered tumor microenvironment. This work demonstrates the significance of the cell microenvironment toward single-cell analysis, which could help to evaluate how immune cells will respond in the complex microenvironment more accurately.

Vogt-Koyanagi-Harada disease (VKH) is a rare multisystemic inflammatory autoimmune disorder. Glaucoma secondary to VKH frequently occurs during the recurrent phase of anterior uveitis; however, acute angle-closure glaucoma (ACG) secondary to both VKH and human immunodeficiency virus (HIV) infection has rarely been reported. We describe a case of secondary acute ACG involving VKH, characterized by sudden vision loss, moderately elevated intraocular pressure (IOP), shallow anterior chamber, and fully or partially closed angle, in an HIV-infected patient. Both VKH and HIV infection contributed to the occurrence of ACG due to the leakage and forward rotation of the ciliary body, as well as choroidal effusion. The deterioration of IOP and serous macular detachment were observed after initial corticosteroid therapy. Visual acuity and IOP were improved with subretinal fluid absorption after continued corticosteroid therapy. Understanding the response of IOP and serous macular detachment after corticosteroid therapy is important for clinical practice.

Investigation of the compositional and functional characteristics of the gastrointestinal bacterial community in beef cattle breeds can improve our understanding of the influence of gastrointestinal tract (GIT) regions and host breeds on the bacterial community. In this study, 16S ribosomal RNA (16S rRNA) gene amplicon sequencing was used to characterize the bacterial communities in the rumen, duodenum, jejunum, ileum, caecum, and colon of Xuanhan yellow cattle (XHC) and Simmental crossbred cattle (SXC). The results showed that the diversity of the bacterial population was different in GIT regions of XHC and SXC (P0.05). In total, ten bacterial phyla, sixteen bacterial genera, and nine metabolic pathways were identified in the core bacteria. The phyla Firmicutes, Bacteroidetes, and Proteobacteria were predominant, but their proportions were different in GIT regions (P0.05). The diversity, structure, and composition of the bacteria in the rumen were similar between the breeds (P0.05), and the indices in the intestine showed significant differences (P0.05). Moreover, the composition and structure of the bacterial communities in the rumen, small intestine, and large intestine were different regardless of the breed. Thus, the bacterial communities were different among the gastrointestinal regions in each breed, and the bacterial community in the rumen had more stable characteristics than that in the intestine between two breeds. Further studies may focus on the minor microbial communities and the functions of GIT bacteria to better understand gut-microbe interactions. KEY POINTS: • Differences in bacteria among gastrointestinal regions differ in cattle breeds. • Differences between the breeds in the ruminal bacteria are less pronounced than differences in the intestinal bacteria.

The chronicle backdrop of liver transplantation (LT) is an intricate story to reveal- it is an adventure of extraordinary achievement and catastrophic disappointments. Historically, controversies and LT seems to be synonymous. Despite the improvements in results, LT is still facing lots of challenges and controversies, whereby demand is high but the resources, primarily concerned to donor, are very limited. We have focused our perspective on LT for HCV-related cirrhosis and nutritional support for cachectic patients awaiting LT.

PurposePyroptosis is an inflammatory form of cell death associated with tumorigenesis and progression. However, the prognostic value of pyroptosis-related genes (PRGs) in hepatocellular carcinoma (HCC) have not been elucidated.MethodsWe downloaded mRNA expression profiles and clinical information from TCGA and ICGC database. Then, differently expressed PRGs were screened to construct a multigene prognostic signature by least absolute contraction and selection operator (LASSO) Cox regression method in TCGA cohort. Date from ICGC was used to validate the robustness of this signature. Kaplan-Meier analysis was used to compare overall survival (OS) between high- and low-risk group. Univariate and multivariate Cox analysis were performed to identify the independent prognostic value of the signature. Gene set enrichment analysis (GSEA) was utilized to conduct GO and KEGG analysis. Single-sample gene set enrichment analysis was implemented to assess the immune cell infiltration and immune-related function. TIDE algorithm evaluated the significance of this signature in predicting immunotherapeutic sensitivity. ResultsAn 8-PRGs prognostic model was established. The OS of low-risk group was significantly increased compared to high-risk group. Receiver operating characteristic curve showed the model had a good prognostic predictive accuracy. Cox regression analysis proved the model an independent predictor for OS in HCC. GSEA indicated that the risk score was associated with immune response. Furthermore, different subgroups exhibited different immunoinfiltration patterns, different immune-checkpoint levels and different potential responses for immune-checkpoint blockade therapy.ConclusionAn 8-PRGs signature can predict the prognosis of HCC patients and may act as an immunotherapeutic potential target for HCC.

The molecular epidemiology and biological characteristics of Escherichia coli associated with hemorrhagic pneumonia (HP) mink from five Chinese Provinces were determined. From 2017 to 2019, 85 E. coli strains were identified from 115 lung samples of mink suffering from HP. These samples were subjected to serotyping, antimicrobial susceptibility, detection of virulence genes, phylogenetic grouping, whole-genome sequencing, drug resistant gene, multilocus sequence typing (MLST) and biofilm-forming assays. E. coli strains were divided into 18 serotypes. Thirty-nine E. coli strains belonged to the O11 serotype. Eighty-five E. coli strains were classified into seven phylogenetic groups: E (45.9%, 39/85), A (27.1%, 23/85), B1 (14.1%, 12/85), B2 (3.7%, 3/85), D (3.7%, 3/85), F (2.4%, 2/85) and clade I (1.2%, 1/85). MLST showed that the main sequence types (STs) were ST457 (27/66), All E. coli strains had ≥4 virulence genes. The prevalence of virulence was 98.8% for yijp and fimC, 96.5% for iucD, 95.3% for ompA, 91.8% for cnf-Ⅰ, 89.4% for mat, 82.3% for hlyF, and 81.2% for ibeB. The prevalence of virulence genes iss, cva/cvi, aatA, ibeA, vat, hlyF, and STa was 3.5–57.6%. All E. coli strains were sensitive to sulfamethoxazole, but high resistance was shown to tetracycline (76.5%), chloramphenicol (71.8%), ciprofloxacin (63.5%) and florfenicol (52.9%), resistance to other antibiotics was 35.3–16.5%. The types and ratios of drug-resistance genes were tet(A), strA, strB, sul2, oqxA, blaTEM-1B, floR, and catA1 had the highest frequency from 34%-65%, which were consistent with our drug resistance phenotype tetracycline, florfenicol, quinolones, chloramphenicol, the bla-NDM-I and mcr-I were presented in ST457 strains. Out of 85 E. coli strains, six (7.1%) possessed a strong ability, 12 (14.1%) possessed a moderate ability, and 64 (75.3%) showed a weak ability to form biofilm. Our data will aid understanding of the epidemiological background and provide a clinical basis for HP treatment in mink caused by E. coli.

Single-cell EV (extracellular vesicle) secretion analysis is emerging for a better understanding of non-genetic cellular heterogeneity regulating human health and diseases through intercellular mediators. However, the requirements of expensive and bulky instrumentations hinder its widespread use. Herein, by combining gold nanoparticle-enhanced silver staining and the Poisson distribution, we reported the use of a home-use scanner to realize high-throughput single-cell EV secretion analysis without cell counting. We applied the platform to analyze the secretions of different EV phenotypes with the human oral squamous cell carcinoma cell line and primary cells from patients, which generated single-cell results comparable with those of the immunofluorescence approach. Notably, we also realized the quantification of the number of EVs secreted from every single cell using their respective titration curves obtained from population samples, making it possible to directly compare different EV phonotypes in regard to their secretion number, secretion rate, and so forth. The technology introduced here is simple, easy to operate, and of low cost, which make it a potential, easily accessible, and affordable tool for widespread use in both basic and clinical research.

Anaplastic thyroid carcinoma (ATC), as one of the most aggressive human malignancies, cannot be cured by 131iodine (131I) internal radiotherapy (RT) because the tumor cells cannot effectively take up 131I and are resistant to radiotherapy. In this study, a facile and simple method was proposed to synthesize mesoporous polydopamine nanoparticles (MPDA) and tailor their morphologies by component-adjusting Pluronic micelle-guided polymerization. Then, MPDA were used not only as nanocarriers to radiolabel 131I, but also as photothermal conversion agents for photothermal therapy (PTT) to promote RT. The iodine-labeling capacity and photothermal conversion efficiency of MPDA can be enhanced by optimizing their morphologies. It was found that MPDA NPs with a cerebroid pore channel structure (CPDA) showed the highest iodine-carrying capacity and a higher photothermal conversion efficiency as a result of their maximum specific surface area and unique morphology. In subsequent experiments in vitro and in vivo, our ATC animal models showed impressive therapeutic responses to CPDA-131I NPs because of the synergistic effect of PTT and RT. Additionally, CPDA-125I NPs can be utilized to obtain high-quality SPETC/CT images of tumors, which can guide clinical therapy for ATC. Considering their great biosafety, these radioiodine-labeled CPDA NPs may serve as a promising tool in combined therapy and diagnosis in ATC.

This study evaluated the effects of glutamine supplementation on nutrient digestibility, immunity, digestive enzyme activity, gut bacterial community and fermentation of growth-retarded yaks. A total of 16 growth-retarded yaks were randomly allocated to two groups: negative control (GRY) and glutamine supplementation group (GLN). Another eight growth-normal yaks were used as a positive control (GNY). Compared with GRY group, the crude protein digestibility was higher in GLN and GNY animals and the neutral detergent fiber digestibility was increased in GLN yaks. The concentrations of serum IgA, IgG, IgM and IL-10, as well as butyrate concentration and cellulase activity in the rumen and cecum were higher in GLN yaks compared to those in GRY animals. Supplementation with glutamine enhanced the chymotrypsin activity and increased the relative abundances of unclassified Peptostreptococcaceae and Romboutsia while decreased the relative abundances of unclassified Chitinophagaceae and Bacteroides in the jejunum and ileum of growth-retarded yaks. In the cecum, the relative abundance of unclassified Muribaculaceae was higher in GLN group than that in GRY group. The findings in this study suggest that the improved nutrient digestibility and immunity of growth-retarded yaks with glutamine supplementation may be through its potential impact on the lower gut host and microbial functions.

Cross-sectional studies have supported the association among depression, obesity, and type 2 diabetes, but the causality remains controversial in Chinese adults. In this longitudinal study, we evaluated the synergistic effect of depression and obesity on the risk of type 2 diabetes.This study included 2809 participants randomly selected from the Qingdao Diabetes Prevention Program, and their type 2 diabetes incidence was determined over a follow-up period of 3 years. The WHO 2006 criteria and the Zung Self-Rating Depression Scale score were employed to identify type 2 diabetes and depression at baseline, respectively. Multivariable-adjusted logistic regression was used to evaluate the synergistic effects of depression and obesity indicators on type 2 diabetes, with adjustment for age, sex, family history of diabetes, and other potential risk factors.During 3-year follow-up, 316 new incident cases were identified. The relative risk and 95% confidence interval of depression for diabetes incidence was 1.52 (1.05-2.21), after controlling for potential confounders. Sensitivity analysis showed that depression was significantly associated with diabetes incidence in women, younger people, and obese people (1.82 [1.14-2.92], 1.94 [1.25-3.02], and 4.29 [1.44-12.78], respectively]. The synergistic effects of positive depression and body mass index ≥30 kg/mDepression was associated with a 52% increased risk of type 2 diabetes incidence and exerts synergistic effects with obesity on diabetes incidence in Chinese adults. Early identification and intervention for depression and obesity can reduce the risk of diabetes.背景: 横断面研究证实抑郁、肥胖和糖尿病的相关性, 而它们之间的因果关系在中国人群中还未确定。在这项纵向性研究, 我们评估了抑郁和肥胖的交互作用对糖尿病发生风险的影响。 方法: 本研究纳入了青岛糖尿病预防项目的2809名随机调查者, 随访时间为3年, 并统计糖尿病的发生率。根据2006年世界卫生组织糖尿病诊断标准和Zung氏抑郁自评量表, 分别判定调查者基线的糖尿病和抑郁情况。借助多因素校正logistic回归模型评估抑郁和肥胖交互作用对糖尿病发病的影响, 校正因素包括年龄、性别、糖尿病家族史和其它潜在危险因素。 结果: 3年随访期间发现316名新诊糖尿病患者。校正可能的混杂因素后, 抑郁阳性者发生糖尿病的相对风险为1.52(1.05-2.21)。敏感性分析显示, 抑郁与糖尿病发病的相关性在女性、年轻人以及肥胖人群中有显著统计学意义, 相对风险分别为1.82(1.14-2.92)、1.94(1.25-3.02)和4.29(1.44-12.78)。抑郁阳性和体重指数≥ 30 kg/m

Severe uterine injuries may lead to infertility or pregnancy complications. There is a lack of effective methods to restore the structure and function of seriously injured uteri. Leukemia inhibitory factor (LIF), which plays a crucial role in blastocyst implantation, promotes the process of regeneration after injury in several different tissues. In this study, we explored the effect of LIF on the regeneration of rat uterine horns following full-thickness injury. One hundred and twenty four female Sprague-Dawley rats were assigned to three groups, including a sham-operated group (n = 34 uterine horns), a PBS/collagen group (n = 90 uterine horns), and a LIF/collagen group (n = 124 uterine horns). The regenerated uterine horns were collected at 1, 2, 4, 8, or 12 weeks after the surgery. The results showed that LIF/collagen scaffolds increased the number of endometrial cells and neovascularization 2 weeks after uterine full-thickness defect in excision sites (p < 0.001 vs PBS/collagen). Eight weeks after the surgery, the number of endometrial glands was dramatically higher in the LIF/collagen scaffolds group (35.2 ± 4.1/field) than in the PBS/collagen scaffolds (15.1 ± 1.4/field). The percentage of a-smooth muscle actin (a-SMA)-positive areas in the LIF/collagen scaffolds (88.8% ± 9.8%) was also significantly higher than that in the PBS/collagen group (52.9% ± 3.7%). Moreover, LIF improved the pregnancy rate and fetus number. We also found that LIF inhibited the infiltration of inflammatory cells and down-regulated the pro-inflammatory cytokine IL-12 expression while up-regulating the anti-inflammatory cytokine IL-10 expression in the injured part of the uterine horns. Our results indicate that LIF promotes regeneration of the uterus after injury, and this is at least partially due to its immunomodulatory properties. In addition, it is worth to explore further the possibility for LIF/collagen to be an alternative therapeutic approach for uterine damage in the clinic in near future.

Despite recent advances in single-cell analysis technologies, lacking simple methods to keep the live single-cells traceable for longitudinal detection reliably poses a significant obstacle in single-cell secretion analysis. Here we reported the high-density NOMA (narrow-opening microwell array) microchip that realized the retention of ≥97% of trapped single cells in dedicated spatial locations during repetitive detection procedures, verified with both adherent and suspension cells by two researchers independently. We applied it in monitoring single-cell protein secretions sequentially from the same single cells, and we found the digital protein secretion patterns dominate the protein secretion. We also demonstrated the microchip for longitudinally tracking IL-8 and the CD81+EV secretions from the same single-cells over days, which revealed the presence of “super secretors” within the cell population be more persistent to secrete protein or extracellular vesicle for an extended period. The NOMA platform reported here is simple, robust, and easy to operate for tracking sequential measurements from the same single cells, representing a novel and informative tool to inspire new observations in biomedical research.Table of Contents Graphic

PurposeThe prognostic value of caveolin-1 in prostate cancer remains uncertain. Hence, this meta-analysis was performed to evaluate the prognostic value of caveolin-1 in prostate cancer, as well as ascertain the relationship between caveolin-1 expression and clinicopathological characteristics of prostate cancer patients.MethodsThe PubMed, Embase, Chinese National Knowledge Infrastructure and Chinese Biology Medicine databases were electronically searched to retrieve published studies on caveolin-1 expression in prostate cancer. After study selection and data extraction, the meta-analysis was conducted using Review manager 5.3 software. Odds ratio (OR) with 95% confidence interval (CI) was used to estimate the pooled effect. Funnel plot was used to assess publication bias.ResultsA total of ten studies were enrolled, which included 3976 cases of prostate cancer, 72 cases of high-grade intraepithelial neoplasia (HGPIN), and 157 normal controls. Results of the meta-analysis showed that the positive rate of caveolin-1 expression in prostate cancer was 18.28 times higher than that in normal control (OR= 18.28, 95% CI: 9.02–37.04, p10 vs. ≤ 10 (OR=2.09, 95% CI: 1.35–3.22, pConclusionCaveolin-1 is overexpressed in prostate cancer, which can serve as a risk factor and adverse clinicopathological feature of prostate cancer. Caveolin-1 can also predict poor survival in prostate cancer patients after radical prostatectomy.

Background Age at natural menopause (ANM) is an important index for women’s health. Either early or late ANM is associated with a series of adverse outcomes later in life. Despite being an inheritable trait, its genetic determinant has not yet been fully understood. Methods Aiming to better characterize the genetic architecture of ANM, we conducted genome-wide association study (GWAS) meta-analyses in European-specific as well as trans-ancestry samples by using GWAS summary statistics from the following 3 large studies: the Reproductive Genetics Consortium (ReproGen; N = 69 626), the UK Biobank cohort (UKBB; N = 111 593) and the BioBank Japan Project (BBJ; N = 43 861), followed by a series of bioinformatical assessments and functional annotations. Results By integrating the summary statistics from the 3 GWAS of up to 225 200 participants, this largest meta-analysis identified 49 novel loci and 3 secondary signals that were associated with ANM at the genome-wide significance level (P < 5 × 10−8). No population specificity or heterogeneity was observed at most of the associated loci. Functional annotations prioritized 90 candidate genes at the newly identified loci. Among the 26 traits that were genetically correlated with ANM, hormone replacement therapy (HRT) exerted a causal relationship, implying a causal pattern by which HRT was determined by ANM. Conclusion Our findings improved our understanding of the etiology of female menopause, as well as shed light on potential new therapies for abnormal menopause.

In ruminants, the bacterial community in the gastrointestinal tract (GIT) has an essential role in healthy growth. Examining the bacterial composition in the GIT between growth-retarded and normal yaks could improve our understanding of the role of microorganisms in yaks with growth retardation. In this study, eight male yaks with growth retardation were used as the growth-retarded yak (GRY) group, and another eight male growth normal yaks (GNYs) with the same breed and age were used as the GNY group. We compared the bacterial community in the rumen, duodenum, jejunum, ileum, cecum, and colon between GRY and GNY groups based on the 16S ribosomal RNA gene sequencing. Alpha-diversity revealed that the Shannon index in the duodenum and ileum of the GNY group was higher (P < 0.05) than that of the GRY group. However, the opposite trend was found in the jejunum and cecum. The principal coordinates analysis (PCoA) showed that the bacterial structure in all segments of GIT differed from each other between two groups. In the rumen, the relative abundances of Ruminococcaceae NK4A214 group, Ruminococcaceae UCG-014, and Treponema 2 were higher (P < 0.05) in the GNY group as compared with the GRY group. However, the Christensenellaceae R-7 group exhibited an opposite trend. In the jejunum, compared with the GNY group, the unclassified Chitinophagaceae was enriched significantly (P < 0.05) in the GRY group. However, the unclassified Peptostreptococcaceae, Christensenellaceae R-7 group, and Lachnospiraceae NK3A20 group were enriched (P < 0.05) in the GNY group. In the ileum, the relative abundances of the Rikenellaceae RC9 gut group and Prevotellaceae UCG-004 were higher (P < 0.05) in the GNY group than those in the GRY group. In the cecum, the GNY group showed a higher (P < 0.05) relative abundance of Prevotellaceae UCG-003 as compared with the GRY group. In the colon, the relative abundances of Treponema 2 and unclassified Lachnospiraceae were slightly higher (0.05 < P < 0.10) in the GNY group than those in the GRY group. Overall, these results improve our knowledge about the bacterial composition in the GIT of growth-retarded and normal yaks, and regulating the bacterial community may be an effective solution to promote the compensatory growth of GRYs.

Early diagnosis is essential for the control and prevention of tuberculosis (TB). The objective of this study was to investigate the feasibility and performance of loop-mediated isothermal amplification (LAMP) in the diagnosis of pulmonary TB in county-level microscopy centers in Qingdao, Eastern China. A total of 523 presumptive TB patients were consecutively recruited between July 2017 and April 2018, and 22 patients were excluded from the analysis. Of 102 culture-positive cases, TB-LAMP identified 91 cases, demonstrating a sensitivity of 89.2%. In comparison, the sensitivity of routine smear microscopy was 69.6% (71/102), which was significantly lower than that of TB-LAMP (P=0.001). In addition, TB-LAMP sensitivities in smear-positive and smear-negative samples were 98.6% and 67.7%, respectively. In conclusion, our data demonstrate that TB-LAMP outperforms conventional smear microscopy in TB diagnosis, which could be used as an alternative method for smear microscopy in resource-limited settings in China.

Three ruminally fistulated Xuanhan steers weighting 312.5 (±23.85) kg were used to determine the kinetics of ruminal degradation of nutrients using in situ nylon bag technique, and a modified 3-step in vitro procedure was adopted to estimate intestinal digestibility of 16-h rumen undegradable protein (RUP) of maize cob (MC), distillers grains (DG), spent mushroom substrate (SMS), starch residue of sweet potato (SRSP), citrus pulp (CPP), and rice straw (RS). Samples were incubated for 0, 2, 6, 16, 24, 36, 48 and 72 h. Additional samples were incubated for 16 h in the rumen, and the residues from these bags were transferred to the nitrogen-free polyester bags for determination of intestinal digestibility in vitro. The highest DM disappearance at 6-h incubation was in SRSP (P 0.07) on CP disappearance between DG and MC at all the time points except for 16 and 24 h. NDF and ADF disappearance for SRSP was significantly higher (P < 0.01) than other roughages at all the time points except for ADF at 72 h. The lowest NDF and ADF disappearance was in DG at all the time points (P < 0.01) except 2 and 6 h. The effective degradability (ED) of DM was the highest in CPP (P < 0.01) and the lowest in MC and RS (P < 0.01). The highest and lowest ED of CP was in DG and in RS (P < 0.01), respectively. The ED of NDF was the highest in SRSP (P < 0.01), followed by CPP and RS, and the lowest in DG (P < 0.01). The ED of ADF was the highest in SRSP and CPP (P < 0.05), and the lowest in DG (P < 0.01). For MC, DG SMS, SRSP, CPP, and RS, the intestinal digestibility of RUP was 95.28%, 37.23%, 38.72%, 48.06%, 54.49%, and 37.88%, respectively, and the content of intestinal digestible crude protein (IDCP) was 23.65, 83.63, 35.63, 15.03, 25.60, and 12.03 g/kg, respectively. Distillers grain was considered to be of good quality for the greatest content of IDCP. Although not readily degraded in rumen, CP in MC may be digested well in small intestine.

BACKGROUND The study compared the growth performance, carcass characteristics and meat quality of steers of Xuanhan yellow cattle, Simmental crossbreed cattle (Simmental × Xuanhan yellow cattle) and cattle-yak (Jersey × yak). All steers were feed with the same diet from 6 months until slaughter at 30 months. The longissimus dorsi muscle was used to compare the meat quality traits. RESULTS By comparison, Simmental crossbreed cattle had higher growth performance (P

Background Hyperandrogenism (HA), inflammation, and oxidative damage play key roles in the pathophysiology of polycystic ovary syndrome (PCOS). Whether vitamin D adjuvant therapy improves hormonal, inflammation, and oxidative damage in PCOS patients has aroused widespread interest, but the results are controversial. To evaluate the effect of vitamin D supplementation on hormonal, oxidative stress, and inflammatory parameters in patients with PCOS. Methods A literature search was conducted in Medline, the Cochrane Library, EMBASE, and Web of Science for studies related to PCOS and vitamin D supplementation. All reports of randomized controlled trials (RCTs) published before December 2019 were identified. The fixed-effects model or random-effects model was used to calculate pooled estimates of standardized differences in means (SMD) with 95% confidence intervals (CI). Results A total of 956 identified studies were retrieved, and eighteen RCTs involving 1,060 participants were ultimately included in the current meta-analysis. The pooled results demonstrated that vitamin D supplementation in patients with PCOS resulted in a significant improvement in serum total testosterone (TT), high sensitivity C-reactive protein (hs-CRP), total antioxidant capacity (TAC), and malondialdehyde (MDA). No significant effect on free testosterone (FT), dehydroepiandrosterone sulfate (DHEA-S), sex hormone-binding globulin (SHBG), free androgen index (FAI), nitric oxide (NO), and total glutathione (GSH) levels was found. Subgroup analysis showed that vitamin D supplementation reduced hs-CRP and MDA irrespective of the treatment course, type of vitamin D intervention, supplementation frequency, and dosage. Twelve weeks of vitamin D supplementation improved TT and TAC while low-dose vitamin D supplementation (≤1,000 IU/day) improved TT and DHEA-S. Vitamin D co-supplementation reduced TT, FT, and DHEA-S, while a daily supplementation regime improved TT, DHEA-S, and TAC in patients with PCOS. Conclusions The current meta-analysis demonstrates that vitamin D supplementation in patients with PCOS resulted in an improvement in the levels of TT, hs-CRP, TAC, and MDA, but did not affect FT, DHEA-S, SHBG, FAI, NO, and GSH levels. Vitamin D co-supplementation, low-dose vitamin D supplementation (≤1,000 IU/day), and daily supplementation frequency appeared to be more conducive to improving hormones, inflammation, and oxidative stress in PCOS patients.

Background Yak (Bos grunniens) is an ancient bovine species on the Qinghai-Tibetan Plateau. Due to extremely harsh condition in the plateau, the growth retardation of yaks commonly exist, which can reduce the incomes of herdsman. The gastrointestinal barrier function plays a vital role in the absorption of nutrients and healthy growth. Functional deficiencies of the gastrointestinal barrier may be one of the contributors for yaks with growth retardation. Methods To this end, we compared the growth performance and gastrointestinal barrier function of growth-retarded (GRY) and normal yaks (GNY) based on average daily gain (ADG), serum parameters, tissue slice, real-time PCR, and western blotting, with eight yaks in each group. Results GRY exhibited lower (P P P = 0.004). In jejunum, with the exception of higher villus height, width, and surface area in GNY, numerical difference (P = 0.61) was detected between two groups for crypt depth. Both in rumen and jejunum, the mRNA expression of interleukin-1beta in GRY was markedly higher (P P P Conclusion The results indicated that the ruminal and jejunal barrier functions of GRY are disrupted as compared to GNY. In addition, our study provides a potential solution for promoting the growth of GRY by enhancing the gastrointestinal barrier function.

The ocean harbors a variety of bacteria that contain huge protease resources and offer a great potential for industrial and biotechnological applications. Here, we isolated a protease-secreting bacterium Vibrio pomeroyi strain 12613 from Atlantic seawater and purified a protease VP9 from strain 12613. VP9 was identified as a metalloprotease of the M4 family. VP9 could hydrolyze casein and gelatin but not elastin and collagen. With gelatin as the substrate, VP9 showed the highest activity at 40°C and pH 6.0–8.0. It was stable at temperatures of 50°C and less and in the range of pH 5.0–11.0. VP9 also had good tolerance to NaCl, non-ionic detergents, and organic solvent methanol. Unlike other M4 metalloproteases, VP9 has distinct collagen-swelling ability, and its collagen-swelling effect was concentration dependent. The relative expansion volume of collagen increased by approximately eightfold after treatment with 10 μM VP9 at 37°C for 12 h. The collagen-swelling mechanism of VP9 on bovine-insoluble type I collagen was further studied. Atomic force microscopy observation and biochemical analyses showed that VP9 can degrade proteoglycans in collagen fibers, resulting in the release of collagen fibrils from collagen fibers and the swelling of the latter. In addition, VP9 can degrade glycoproteins, a non-collagenous constituent interacting with collagen in the skin. The characteristics of VP9, such as sufficient specificity toward proteoglycans and glycoproteins but no activity toward collagen, suggest its promising potential in the unhairing and fiber-opening processing in leather industry.

A one-dimensional analytical model is proposed to analyze contaminant diffusion through a composite geomembrane cut-off wall (CGCW) composed of a geomembrane (GMB) and a bentonite cut-off wall (BCW). The model considers degradation process of contaminant and time-dependent inlet boundary condition which are common in engineering practices. Moreover, two limiting scenarios of the exit boundary condition (EBC) of CGCW for field conditions are taken into account, including the flushing and non-advective semi-infinite aquifer EBCs. The influence of boundary conditions and performance of CGCW are comprehensively investigated. The results show that the upper and lower limits of the mass flux of the exit face of CGCW can be obtained by the models with flushing EBC and the model with non-advective semi-infinite aquifer EBC, respectively. In addition, degradation has substantial influence on the contaminant migration, and smaller half-life in BCW results in smaller contaminant leakage . The performance of CGCW can be improved by embedding GMB at a proper location which is related to the type of contaminant and EBC. Furthermore, thickening HDPE GMB or adopting a coextruded EVOH GMB is efficient to improve the performance of CGCW. The present model can be used as an applicable tool for rational design of CGCW.

Simple Summary The specific enzymes secreted by microorganisms in the gastrointestinal tract (GIT) of ruminants, such as phytase, can catalyze the decomposition of calcium compounds (e.g., phytic acid) and release bound calcium for the absorption of animals. Therefore, we speculate that gastrointestinal microbes could be a factor affecting digestion and absorption of dietary calcium. However, little related research has been reported. In the present study, we found that the true digestibility of calcium (TDC) in goats is related to gastrointestinal bacteria. Some gastro-intestinal bacteria, such as ruminal Prevotella, were beneficial for true host digestibility of dietary calcium. Abstract The current study was performed to examine the relationship between the true digestibility of calcium (TDC) in the diet and bacterial community structure in the gastrointestinal tract (GIT) of goats. Twenty-six Nubian healthy female goats were selected as experimental animals, and their TDC was determined using metabolic experiments. Eight goats were grouped into the high digestibility of Calcium (HC) phenotype, and another eight were grouped into the low digestibility of Calcium (LC) phenotype. Their bacterial 16S rRNA gene amplicons from the rumen, abomasum, jejunum, cecum, and colon contents were sequenced using next-generation high-throughput sequencing technology. In the rumen, 239 genera belonging to 23 phyla, 319 genera belonging to 30 phyla in the abomasum, 248 genera belonging to 36 phyla in the jejunum, 248 genera belonging to 25 phyla in the colon and 246 genera belonging to 23 phyla in the cecum were detected. In addition, there was a significant correlation between the TDC and the relative abundance of Candidatus_Saccharimonas, Christensenellaceae_R-7_group, Mogibacterium, Prevotella_1, Prevotella_UCG_004, Ruminococcus_2, Saccharibacteria in the rumen, Eubacterium_coprostanoligens_group, Lachnospiraceae_ND3007_group, Lachnospiraceae_NK3A20_group, p-1088-a5_gut_group, and Planctomycetes in the abomasum, Butyrivibrio in the cecum, and Fibrobacter in the cecum were observed. This study suggests an association of GIT microbial communities as a factor influencing TDC in goats.

Lipid is the chief energy source for starved animals. &beta, hydroxybutyrate (BHBA) is the main ketone body produced by lipid decomposition. In Chinese hamster ovary (CHO) cell experiment, it was found that BHBA could be used not only as an energy substance, but also as a ligand of GPR109A for regulating lipid metabolism. However, whether BHBA can regulate lipid metabolism of yaks, and its effective concentration and signal pathway are not clear. This study investigated the effects and mechanism of starvation and BHBA on the lipid metabolism of yak. Eighteen male Jiulong yaks were selected and then randomly divided into three groups: normal feeding group (NG), starvation group (SG), and starvation with BHBA infusion group (SBG). The yaks in the NG group were freely fed during the trial, while the yaks in the SG and SBG groups fasted, from 7th to 9th days of the experiment, the NG and SG were infused continuous with 0.9% normal saline and SBG was infused 1.7 mmol/L BHBA solution respectively. The blood samples were collected on the 0th, 1st, 3rd, 5th, 7th, and 9th day of experiment. The subcutaneous adipose tissue of all the yaks in this study were taken from live bodies after infusion. Serum glucose, lipid metabolites, hormone concentrations, and mRNA and protein expressions of key factors of lipid metabolism and signaling pathway in subcutaneous adipose tissue were measured. The results showed that, as compared with NG, starvation significantly reduced the body weight of yak in SG, and significantly increased the concentration of BHBA in serum and the mRNA expression of PKA and CREB1 in subcutaneous adipose tissue, while the mRNA expression of MEK, PKC, ERK1/2, the area of adipocytes, and the proportion of saturated fatty acid were decreased. Whereas, further increase of BHBA concentration through infusion promoted the mRNA expression of GPR109A receptor in the subcutaneous adipose tissue of SBG, inhibited the mRNA expression of AC and PKA, and decreased the phosphorylation protein abundance of CREB1, and significantly increased the diameter and area of adipocytes. These findings suggest that starvation led to enhanced lipid catabolism in yaks. An increasing BHBA concentration could increase the mRNA expression of GPR109A receptor in subcutaneous adipose tissue and inhibit the cAMP/PKA/CREB signaling pathway and lipid decomposition.

BACKGROUND Caveolin-1 (CAV1) is an essential structural component of caveolae, regulates cellular processes through complex cellular signaling pathways, and influences tumorigenicity. However, the role of the CAV1 (rs7804372) polymorphism in digestive cancers remains inconclusive. The meta-analysis was performed to evaluate the effect of CAV1 polymorphism on digestive cancer susceptibility and to provide a basis for precise treatment. METHODS The databases of PubMed, EMBASE, Google Scholar and CNKI were used to retrieve the published studies on CAV1 (rs7804372) polymorphism and susceptibility to digestive cancers up to June 2020. Two researchers conducted study screening, data extraction, and methodological quality evaluation separately according to inclusion and exclusion criteria. Review Manager 5.3 software was used to conduct the meta-analysis. RESULTS Six case-control studies were enrolled, including 2477 patients with digestive cancers and 2477 healthy controls. The pooled results showed that the CAV1 rs7804372 (T29107A) polymorphism increased the risk of digestive cancer occurrence in the allele (T vs. A: odds ratio (OR) 1.33, 95% confidence interval (CI): 1.15-1.53, P

The present research was conducted to evaluate the connection between the true digestibility of Phosphorus (TDP) in diet and bacterial community structure in the gastrointestinal tract (GIT) of goats. Twenty-eight Nubian goats were chosen and metabolic experiment was conducted to analyze TDP of research animals. Eight goats were grouped into the high digestibility of phosphorus (HP) phenotype, and another 8 were grouped into the low digestibility of phosphorus (LP) phenotype. And from the rumen, abomasum, jejunim, cecum and colon content of the goats, bacterial 16S rRNA gene amplicons were sequenced. In the rumen 239 genera belonging to 23 phyla, in abomasum 319 genera belonging to 30 phyla, in jejunum 248 genera belonging to 36,in colon 248 genera belonging to 25 phyla and in cecum 246 genera belonging to 23 phyla were noticed. In addition, there was a significant correlation between the TDP and the abundance of Ruminococcaceae_UCG-010, Ruminococcus_2, Ruminococcaceae_UCG-014, Selenomonas_1 and Prevotella in the rumen, Lachnospiraceae_ND3007_group, Saccharofermentans, Ruminococcus_1, Ruminococcaceae_UCG-014, Lachnospiraceae_XPB1014_group and Desulfovibrio in the abomasum, Prevotella, Clostridium_sensu_stricto_1, Fibrobacter, Desulfovibrio and Ruminococcus_2 in the jejunum, Ruminococcaceae_UCG-014 in the colon, and Desulfovibrio in the cecum. Present research trial recommended that the community of gastrointestinal microbiota is a factor affecting TDP in goats.

Parkinson's disease (PD) is well known as a neurodegenerative disorder with progressive loss of dopaminergic (DA) neurons. Nei-like 1 (NEIL1) is one of four mammalian DNA glycosylases involved in the progression of various diseases, including neuroinflammation. However, it is still unknown if the expression changes of NEIL1 could contribute to PD progression. In the present study, we established mouse model with PD using 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to explore the effects of NEIL1 on PD development. Here, we found that NEIL1 deletion significantly promoted the motor dysfunction in the wild type mice treated with 6-OHDA. Furthermore, DA neuronal loss was further accelerated by NEIL1 deletion in 6-OHDA-injected mice, as evidenced by the significantly reduced expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT). Furthermore, in PD mice induced by MPTP, remarkably reduced expression of NEIL1 was observed in nigra and striatum of mice. A strong positive correlation was detected in the expression of NEIL1 and the survival rate of DA neurons. Also, NEIL1 ablation further elevated the DA neuronal loss in MPTP-treated mice, accompanied with higher glial activation, as evidenced by the obvious up-regulation of glial fibrillary acidic protein (GFAP) and Ionized calcium-Binding Adapter molecule 1 (Iba1). Moreover, MPTP-triggered inflammation was highly aggravated by the loss of NEIL1 through inducing the expression of pro-inflammatory cytokines and chemokines. In contrast, promoting NEIL1 expression effectively reversedPD progression induced by MPTP in mice. Together, these results demonstrated that NEIL1 insufficiency might be a contributing factor for the progression of PD, which therefore could be considered as a novel candidate to develop effective treatments against PD progression.

Yak suffers severe starvation and body weight reduction in the cold season and recovers relatively rapid growth in the warm season every year. Herein, we investigated the effects of starvation and refeeding on the growth, feed efficiency, blood biochemistry and rumen microbial community as well as functions of yaks. The results showed that starvation significantly reduced the body weight of yaks. Serum glucose and triglyceride concentrations significantly decreased, and &beta, hydroxybutyric acid and non-esterified fatty acid levels were significantly increased during the starvation period. Starvation also dramatically inhibited rumen microbial fermentations. Whereas, refeeding with the same diet significantly increased the feed efficiency, nutrient digestibility together with rumen acetate, propionate and microbial protein productions compared with those before starvation. The 16S rDNA sequencing results showed that starvation mainly decreased the ruminal protein-degrading bacteria Prevotella and propionate-producing bacteria Succiniclasticum populations and dramatically increased the denitrifying bacteria Thauera populations. Refeeding reduced the Euryarchaeota population and increased propionate-producing bacteria Succinivibrionaceae UCG-002 and starch-degrading bacteria Ruminobacter populations when compared with those before starvation. The predicted microbial metabolic pathways, related to amino acid and starch metabolisms, were also significantly altered during the starvation and refeeding. The results indicated that the rumen microorganisms and their metabolism pathways changed with feed supply, and these alterations in part contributed to yak adaption to starvation and re-alimentation. This study is helpful for enhancing the understanding and utilization of this natural character of yaks to explore and improve their growth potential.

Objective This study evaluated the effects of different levels of protein concentrate supplementation on the growth performance of yak calves, and correlated the growth rate to changes occurring in the plasma- amino acids, -insulin profile, and signaling activity of mammalian target of rapamycin (mTOR) cascade to characterize the mechanism through which the protein synthesis can be improved in early weaned yaks. Methods For this study, 48 early (3 months old) weaned yak calves were selected, and assigned into four dietary treatments according to randomized complete block design. The four blocks were balanced for body weight and sex. The yaks were either grazed on natural pasture (control diet) in a single herd or the grazing yaks was supplemented with one of the three protein rich supplements containing low (17%; LP), medium (19%; MP), or high (21%; HP) levels of crude proteins for a period of 30 days. Results Results showed that the average daily gain of calves increased (0.14 vs 0.23–0.26 kg; p0.05) when the grazing calves were supplemented with protein concentrates. Compared to control diet, the insulin level of calves increased (p

Objective As the main component of traditional Chinese medicine realgar, arsenic disulfide (As 2 S 2 ) is widely used in treating myelodysplastic syndromes (MDS). The goal of the current study is to assess the effects of As 2 S 2 on bone marrow mononuclear cells (BMMNC) of MDS. Methods BMMNCs were obtained from 10 lower risk MDS patients, 5 higher risk MDS patients, and 3 healthy controls. Then, the cells were treated with As 2 S 2 for 48 h, using vorinostat (also known as SAHA) as control. Cell proliferation and apoptosis were detected. mRNA and protein levels of histone deacetylase-1 (HDAC1), Toll-like receptor 2 (TLR2), and erythroid transcription factor (GATA-1) were detected by quantitative real-time PCR and western blot analysis. Results After As 2 S 2 treatment in concentrations ranging from 3.125 to 100 μmol/L, cell proliferation was inhibited in both lower risk and higher risk MDS. Fifty percent inhibitory concentrations were 24.4 μmol/L and 23.6 μmol/L, respectively, for lower and higher risk MDS. Apoptotic cells significantly increased in both types of MDS. mRNA and protein levels of HDAC1 and TLR2 were reduced, whereas GATA-1 was increased in both types of MDS. Conclusions As 2 S 2 could inhibit cell proliferation and induce apoptosis through histone acetylation modulation in MDS. Similar to SAHA, As 2 S 2 could reduce TLR2 activation and increase GATA-1 expression. Current data suggest epigenetic and immunological alternations are involved in therapeutic mechanisms of realgar in the treatment of MDS.