An exploration of the role of Sertoli cells on fetal testis development using cell ablation strategy

Sertoli cells (SCs) are presumed to be the center of testis differentiation because they provide both structural support and biological regulation for spermatogenesis. Previous studies suggest that SCs control germ cell (GC) count and Leydig cell (LC) development in mouse testes. However, the regulatory role of SCs on peritubular myoid (PTM) cell fate in fetal testis has not been clearly reported. Here, we employed Amh‐Cre; diphtheria toxin fragment A (DTA) mouse model to selectively ablate SCs from embryonic day (E) 14.5. Results found that SC ablation in the fetal stage caused the disruption of testis cords and the massive loss of GCs. Furthermore, the number of α‐smooth muscle actin‐labeled PTM cells was gradually decreased from E14.5 and almost lost at E18.5 in SC ablation testis. Interestingly, some Ki67 and 3β‐HSD double‐positive fetal LCs could be observed in Amh‐Cre; DTA testes at E16.5 and E18.5. Consistent with this phenomenon, the messenger RNA levels of Hsd3b1, Cyp11a1, Lhr, Star and the protein levels of 3β‐HSD and P450Scc were significantly elevated by SC ablation. SC ablation appears to induce ectopic proliferation of fetal LCs although the total LC number appeared reduced. Together, these findings bring us a better understanding of SCs’ central role in fetal testis development.     

LncRNA SNHG1 exerts a protective role in cardiomyocytes hypertrophy via targeting miR‐15a‐5p/HMGA1 axis

Heart failure preceded by pathological cardiac hypertrophy is a leading cause of death. Long noncoding RNA small nucleolar RNA host gene 1 (SNHG1) was reported to inhibit cardiomyocytes apoptosis, but the role and underlying mechanism of SNHG1 in pathological cardiac hypertrophy have not yet been understood. This study was designed to investigate the role and molecular mechanism of SNHG1 in regulating cardiac hypertrophy. We found that SNHG1 was upregulated during cardiac hypertrophy both in vivo (transverse aortic constriction treatment) and in vitro (phenylephrine [PE] treatment). SNHG1 overexpression attenuated the cardiomyocytes hypertrophy induced by PE, while SNHG1 inhibition promoted hypertrophic response of cardiomyocytes. Furthermore, SNHG1 and high‐mobility group AT‐hook 1 (HMGA1) were confirmed to be targets of miR‐15a‐5p. SNHG1 promoted HMGA1 expression by sponging miR‐15a‐5p, eventually attenuating cardiomyocytes hypertrophy. There data revealed a novel protective mechanism of SNHG1 in cardiomyocytes hypertrophy. Thus, targeting of SNHG1‐related pathway may be therapeutically harnessed to treat cardiac hypertrophy.     

Tripartite motif protein 52 (TRIM52) promoted fibrosis in LX‐2 cells through PPM1A‐mediated Smad2/3 pathway

To investigate the roles of tripartite motif containing 52 (TRIM52) in human hepatic fibrosis in vitro, human hepatic stellate cell line LX‐2 cells were transfected with hepatitis B virus (HBV) replicon to establish HBV‐induced fibrosis in LX‐2 cells, and then treated with small interfering RNA‐mediated knockdown of TRIM52 (siTRIM52). LX‐2 cells without HBV replicon transfection were treated with lentiviruses‐mediated overexpression of TRIM52 and phosphatase magnesium dependent 1A (PPM1A). Fibrosis response of LX‐2 cells were assessed by the production of hydroxyproline (Hyp) and collagen I/III, as well as protein levels of α‐smooth muscle actin (α‐SMA). PPM1A and phosphorylated (p)‐Smad2/3 were measured to assess the mechanism. The correlation between TRIM52 and PPM1A was determined using co‐immunoprecipitation, and whether and how TRIM52 regulated the degradation of PPM1A were determined by ubiquitination assay. Our data confirmed HBV‐induced fibrogenesis of LX‐2 cells, as evidenced by significant increase in Hyp and collagen I/III and α‐SMA, which was associated with reduction of PPM1A and elevation of transforming growth factor‐β (TGF‐β), p‐Smad2/3, and p‐Smad3L. However, those changes induced by HBV were significantly attenuated with additional siTRIM52 treatment. Similar to HBV, overexpression of TRIM52 exerted promoted effect in the fibrosis of LX‐2 cells. Interestingly, TRIM52 induced the fibrogenesis of LX‐2 cells and the activation of TGF‐β/Smad pathway were significantly reversed by PPM1A overexpression. Furthermore, our data confirmed TRIM52 as a deubiquitinase that influenced the accumulation of PPM1A protein, and subsequently regulated the fibrogenesis of LX‐2 cells. TRIM52 was a fibrosis promoter in hepatic fibrosis in vitro, likely through PPM1A‐mediated TGF‐β/Smad pathway.     

The protective effects of grape seed procyanidin B2 against asporin mediates glycated low‐density lipoprotein induced‐cardiomyocyte apoptosis and fibrosis

The progression of diabetic cardiomyopathy is related to cardiomyocyte dysfunction and apoptosis. Our previous studies showed that asporin (ASPN) was significantly increased in the myocardium of db/db mice through proteomics, and grape seed procyanidin B2 (GSPB2) significantly inhibited the expression of ASPN in the heart of db/db mice. We report here that ASPN played a critical role in glycated low‐density lipoproteins (gly‐LDL) induced‐cardiomyocyte apoptosis. We found that gly‐LDL upregulated ASPN expression. ASPN increased H9C2 cardiomyocyte apoptosis with down‐regulation of Bcl‐2, upregulation of transforming growth factor‐β1, Bax, collagen III, fibronectin, and phosphorylation of smad2 and smad3. However, GSPB2 treatment reversed ASPN‐induced impairments in H9C2 cardiomyocytes. These results provide evidence for the cardioprotective action of GSPB2 against ASPN injury, and thus suggest a new target for fighting against diabetic cardiomyopathy.     

基于景观尺度下的鄱阳湖湿地浅层土有机碳的空间特征

湿地土壤有机碳研究是全球碳循环研究的基础性工作, 对于准确评估湿地固碳增汇和全球温室气体减排都具有重要意义。以鄱阳湖国家自然保护区为研究区域, 选择六种景观类型(湿地洲滩景观包括受人工控制的碟形湖泊常湖池、半人工控制的碟形湖泊蚌湖、不受人工控制的洲滩前缘泗洲头以及岗地景观包括林地、田地和菜地), 湿地洲滩景观在各1 m高程(泗洲头和蚌湖采样高程10-17 m, 常湖池采样高程12-17 m)内的浅土壤采取3个土壤样品, 岗地景观浅层土壤各采取3个土壤样品, 分析浅层土壤有机碳含量。结果表明, 鄱阳湖不同景观类型的浅层土壤有机碳含量差异性显著。湿地洲滩浅层土壤(特别是0-10 cm土层)的有机碳随高程梯度变化呈现倒U型变化, 即低海拔与高海拔土壤有机碳的含量较中海拔土壤有机碳的含量低, 泗洲头洲滩土层0-10 cm的有机碳含量最高值出现在13-14 m高程, 其中0-10 cm土层的土壤有机碳含量变化值为1.56-12.29 g·kg-1, 10-20 cm土层的土壤有机碳含量变化值为0.96-8.19 g·kg-1; 蚌湖洲滩土层0-10 cm的有机碳含量最高值出现在14-15 m高程, 其中0-10 cm土层的土壤有机碳含量变化值为6.36-23.32 g·kg-1, 10-20 cm土层的土壤有机碳含量变化值为4.14-8.88 g·kg-1; 常湖池洲滩土层0-10 cm的有机碳含量最高值出现在16-17 m高程, 其中0-10 cm土层的土壤有机碳含量变化值为6.51-18.91 g·kg-1, 10-20 cm土层的土壤有机碳含量变化值为3.83-10.05 g·kg-1。岗地浅层土壤有机碳(特别是0-10 cm土层)田地的土壤有机碳含量最高, 菜地土壤有机碳含量最低。比较六种景观类型的浅层土壤有机碳含量, 泗洲头洲滩浅层土壤有机碳含量最低, 蚌湖洲滩浅层土壤有机碳含量最高。六种景观类型的浅层土壤有机碳含量呈现一致的现象是土层0-10 cm的机碳含量明显高于土层10-20 cm的有机碳含量, 说明鄱阳湖国家自然保护区内土壤有机碳含量主要富集在土壤浅层的特征。土壤pH值对湿地土壤有机碳呈显著负相关性, 而土壤含水量、地上部分生物量与土壤有机碳呈显著正相关性。     

Tripartite motif protein 25 is associated with epirubicin resistance in hepatocellular carcinoma cells via regulating PTEN/AKT pathway

Tripartite motif protein 25 (TRIM25) expression was altered in various human cancers. Herein, we found that the expression of TRIM25 was elevated in hepatocellular carcinoma (HCC) tissues and cell lines. Knockdown of TRIM25 increased the sensitivity of HCC HepG2 cells to epirubicin (EPI), as indicated by reduced cell viability, enhanced cell apoptosis, and downregulated P‐glycoprotein (P‐gp) and multiple drug‐resistance protein 1 (MRP1). Moreover, TRIM25 knockdown strengthened the effects of EPI on phosphatase and tensin homolog (PTEN) and phosphorylated (p)‐AKT. However, overexpression of TRIM25 exerted an opposite effect, weakening the sensitivity of Huh7 to EPI, and obviously increasing PTEN and reducing p‐AKT. Most important, all the changes induced by TRIM25 overexpression in Huh7 were reversed with additional treatment of LY294002 (an AKT pathway inhibitor). Notably, coimmunoprecipitation experiments confirmed the interaction between TRIM25 and PTEN. Knockdown of TRIM25 resulted in reduced ubiquitination of PTEN protein. Collectively, our data suggested that TRIM25 enhanced EPI resistance via modulating PTEN/AKT pathway, and targeting TRIM25 may enhance the sensitivity of HCC cells toward chemotherapy drugs.     

Source identification and risk assessment of heavy metals in road dust of steel industrial city (Anshan), Liaoning,Northeast China

Abstract

The purpose of the study was to acquire the source and evaluate the risk posed by heavy metals in road dust of steel industrial city (Anshan), Liaoning, Northeast China. Potential ecological risk index (RI), pollution index (PI) and geo-accumulation index (Igeo) were applied to evaluate the heavy metal pollution level, and the carcinogenic risk (RI) and hazard index (HI) were calculated to estimate the human health risk. The geographic information system maps clearly reveal the hot spots of heavy metal spatial distribution. Principle component analysis (PCA) and cluster analysis (CA) classified heavy metals into three groups. The metal Zn and Pb originate from the traffic emission, while Cd, Cr, Fe, Mn, Ni and Sb primarily come from industrial activities. These two pathways were the major source of heavy metals pollution by positive matrix factorization (PMF). The Igeo and PI values of heavy metals were decreased in the following order: Cd?>?Sb?>?Zn?>?Fe?>?Pb?>?Cu?>?Cr?>?Sn?>?Mn?>?Ni. The RI index showed the heavy metals were moderate to very high potential ecological risk. The HI values for children and adults presented a decreasing order of Cr?>?Pb?>?Ni?>?Cu?>?Cd?>?Zn. The HI also predicted a possibility of non-carcinogenic risk for children living in urban areas in comparison with adults.     

Distinct genomic traits of acral and mucosal melanomas revealed by targeted mutational profiling

The incidence of melanoma is rising globally including China. Comparing to Caucasians, the incidence of non‐cutaneous melanomas is significantly higher in Chinese. Herein, we performed genomic profiling of 89 Chinese surgically resected primary melanomas, including acral (n = 54), cutaneous (n = 22), and mucosal (n = 13), by hybrid capture‐based next‐generation sequencing. We show that mucosal melanomas tended to harbor more pathogenic mutations than other types of melanoma, though the biological significance of this finding remains uncertain. Chromosomal arm‐level alterations including 6q, 9p, and 10p/q loss were highly recurrent in all subtypes, but mucosal melanoma was significantly associated with increased genomic instability. Importantly, 7p gain significantly correlated with unfavorable clinical outcomes in non‐cutaneous melanomas, representing an intriguing prognostic biomarker of those subtypes. Furthermore, focal amplification of 4q12 (KIT, KDR, and PDGFRα) and RAD51 deletion were more abundant in mucosal melanoma, while NOTCH2 amplification was enriched in acral melanoma. Additionally, cutaneous melanomas had higher mutation load than acral melanomas, while mucosal melanomas did not differ from other subtypes in mutation burden. Together, our data revealed important features of acral and mucosal melanomas in Chinese including distinctive driver mutation pattern and increased genomic instability. These findings highlight the possibilities of combination therapies in the clinical management of melanoma.