TGF-β isoforms inhibit hepatitis C virus propagation in transforming growth factor beta/SMAD protein signalling pathway dependent and independent manners

Transforming growth factor beta (TGF-β) plays an important role in the viral liver disease progression via controlling viral propagation and mediating inflammation-associated responses. However, the antiviral activities and mechanisms of TGF-β isoforms, including TGF-β1, TGF-β2 and TGF-β3, remain unclear. Here, we demonstrated that all of the three TGF-β isoforms were increased in Huh7.5 cells infected by hepatitis C virus (HCV), but in turn, the elevated TGF-β isoforms could inhibit HCV propagation with different potency in infectious HCV cell culture system. TGF-β isoforms suppressed HCV propagation through interrupting several different stages in the whole HCV life cycle, including virus entry and intracellular replication, in TGF-β/SMAD signalling pathway–dependent and TGF-β/SMAD signalling pathway–independent manners. TGF-β isoforms showed additional anti-HCV activities when combined with each other. However, the elevated TGF-β1 and TGF-β2, not TGF-β3, could also induce liver fibrosis with a high expression of type I collagen alpha-1 and α-smooth muscle actin in LX-2 cells. Our results showed a new insight into TGF-β isoforms in the HCV-related liver disease progression.     

Poly(ADP-ribose) polymerase inhibitor PJ34 protects against UVA-induced oxidative damage in corneal endothelium

Apoptosis - Fuchs endothelial corneal dystrophy (FECD) is one of the main causes for corneal endothelial blindness, which is characterized by the progressive decline of corneal endothelial cells....     

PRPF6 promotes androgen receptor/androgen receptor-variant 7 actions in castration-resistant prostate cancer cells

Androgen receptor (AR) and its variants play vital roles in development and progression of prostate cancer. To clarify the mechanisms involved in the enhancement of their actions would be crucial for understanding the process in prostate cancer and castration-resistant prostate cancer transformation. Here, we provided the evidence to show that pre-mRNA processing factor 6 (PRPF6) acts as a key regulator for action of both AR full length (AR-FL) and AR variant 7 (AR-V7), thereby participating in the enhancement of AR-FL and AR-V7-induced transactivation in prostate cancer. In addition, PRPF6 is recruited to cis-regulatory elements in AR target genes and associates with JMJD1A to enhance AR-induced transactivation. PRPF6 also promotes expression of AR-FL and AR-V7. Moreover, PRPF6 depletion reduces tumor growth in prostate cancer-derived cell lines and results in significant suppression of xenograft tumors even under castration condition in mouse model. Furthermore, PRPF6 is obviously highly expressed in human prostate cancer samples. Collectively, our results suggest PRPF6 is involved in enhancement of oncogenic AR signaling, which support a previously unknown role of PRPF6 during progression of prostate cancer and castration-resistant prostate cancers.     

ITGB1 enhances the Radioresistance of human Non-small Cell Lung Cancer Cells by modulating the DNA damage response and YAP1-induced Epithelial-mesenchymal Transition

Objectives: Radiotherapy has played a limited role in the treatment of non-small cell lung cancer (NSCLC) due to the risk of tumour radioresistance. We previously established the radioresistant non-small cell lung cancer (NSCLC) cell line H460R. In this study, we identified differentially expressed genes between these radioresistant H460R cells and their radiosensitive parent line. We further evaluated the role of a differentially expressed gene, ITGB1, in NSCLC cell radioresistance and as a potential target for improving radiosensitivity.Materials and Methods: The radiosensitivity of NSCLC cells was evaluated by flow cytometry, colony formation assays, immunofluorescence, and Western blotting. Bioinformatics assay was used to identify the effect of ITGB1 and YAP1 expression in NSCLC tissues.Results: ITGB1 mRNA and protein expression levels were higher in H460R than in the parental H460 cells. We observed lower clonogenic survival and cell viability and a higher rate of apoptosis of ITGB1-knockdown A549 and H460R cells than of wild type cells post-irradiation. Transfection with an ITGB1 short hairpin (sh) RNA enhanced radiation-induced DNA damage and G2/M phase arrest. Moreover, ITGB1 induced epithelial-mesenchymal transition (EMT) of NSCLC cells. Silencing ITGB1 suppressed the expression and intracellular translocation of Yes-associated protein 1 (YAP1), a downstream effector of ITGB1.Conclusions: ITGB1 may induce radioresistance via affecting DNA repair and YAP1-induced EMT. Taken together, our data suggest that ITGB1 is an attractive therapeutic target to overcome NSCLC cell radioresistance.     

贵州花溪大学城破碎化林地鸟类多样性与嵌套分布格局

为揭示城镇化进程中生境破碎化对鸟类多样性及分布格局的影响, 本研究于2017-2019年每年的4-8月使用样线法对贵州花溪大学城26块破碎化林地(面积介于0.3-290.4 ha)中的鸟类群落进行了10次调查。共记录到鸟类78种, 隶属于11目37科。其中, 东洋界物种数占56.4%, 古北界物种数占32.1%, 广布种占11.5%; 有中国特有种1种。剔除高空飞行、非森林鸟类及偶然出现物种后, 不同斑块中的鸟类物种数介于12-55之间, 平均每个斑块有23.2 ± 10.5种。线性回归分析显示, 鸟类物种丰富度与林地斑块的面积有显著相关性, 斑块面积越小, 鸟类物种丰富度越低; 斑块隔离度对物种丰富度没有显著影响。基于物种多度分布矩阵的WNODF (weighted nestedness metric based on overlap and decreasing fill)嵌套分析显示, 不同斑块中鸟类群落呈现出反嵌套结构。小斑块中鸟类物种丰富度较低可能与植物丰富度较低、食物资源稀缺和繁育条件不足有关, 但短距离的隔离对鸟类迁入或扩散影响有限。环境过滤效应、种间竞争或优先效应可能导致不同斑块间存在较大的物种组成差异, 从而导致反嵌套格局。因此, 本研究建议在城市规划建设中应注重维持栖息地的完整性, 对不同面积大小的破碎化斑块都应加以保护。     

Expression of Insulin-Like Growth Factor System Genes in Liver Tissue During Embryonic and Early Post-Hatch Development in Duck (Anas platyrhynchos Domestica)

The IGF system is one of the most important endocrine and paracrine growth factor systems that regulate fetal and placental growth, whereas the liver is the principal source of circulation IGF-I. In the present study, expression of IGF-I, IGF type-I receptor (IGF-IR), and IGF binding protein (IGFBP)-3 genes was quantified by RT-PCR in the liver tissue on days 13, 17, 21, 25, and 27 of embryonic development, as well as at 7 days post-hatching (PH) in meat-type Gaoyou ducks and egg-type Jinding ducks. The results showed that IGF-I mRNA could be detected as early as on E 13d, but the expression level was low throughout embryonic development before increasing dramatically by E 27d and 7 days PH in both duck breeds. However, Gaoyou ducks exhibited higher IGF-I mRNA level than Jinding ducks, and the differences were significant on E 13d, E 21d, and at 7 days PH. Expression of IGF-IR in liver increased gradually in the former stages of the embryonic development, reaching its highest point on E 21d, and then declined up until 7 days PH. The expression pattern of IGFBP-3 gene was similar to that of IGF-IR gene, increasing significantly from E 17d. The expression peak appeared on E 25d, then declined significantly just prior to hatching (day 27) and was followed by an increase at 7 days PH. In general, the expression level of IGF-IR and IGFBP-3 genes in Jinding ducks was higher than that in Gaoyou ducks. Inverse relationships were observed for the expression of IGF-I and IGF-IR, and IGF-I and IGFBP-3, whereas a positive relationship was observed for the expression of IGF-IR and IGFBP-3. Our data indicate a differential expression of selected genes that comprise the IGF system in the duck liver tissue during embryonic and early PH growth and development.     

The differential contributions of herkogamy and dichogamy as mechanisms of avoiding self‐interference in four self‐incompatible Epimedium species

Self‐interference is one of the most important selective forces in shaping floral evolution. Herkogamy and dichogamy both can achieve reductions in the extent of self‐interference, but they may have different roles in minimizing self‐interference in a single species. We used four self‐incompatible Epimedium species to explore the roles of herkogamy and dichogamy in avoiding self‐interference and to test the hypothesis that herkogamy and dichogamy may be separated and become selected preferentially in the taxa. Two species (E. franchetii and E. mikinorii) expressed strong herkogamy and weak protogyny (adichogamy), whereas another two species (E. sutchuenense and E. leptorrhizum) expressed slight herkogamy and partial protandry. Field investigations indicated that there was no physical self‐interference between male function and female function regarding pollen removal and pollen deposition in all species. Self‐pollination (autonomous or facilitated) was greater in species with slight herkogamy than in those with strong herkogamy. Artificial pollination treatments revealed that self‐pollination could reduce outcrossed female fertility in all species, and we found evidence that self‐interference reduced seed set in E. sutchuenense and E. leptorrhizum in the field, but not in E. franchetii and E. mikinorii. These results indicate that well‐developed herkogamy is more effective compared with dichogamy in avoiding self‐interference in the four species. In genus Epimedium, herkogamy instead of dichogamy should be selected preferentially and evolved as an effective mechanism for avoiding self‐interference and might not need to evolve linked with dichogamy.