Microscale grooves regulate maturation development of hPSC-CMs by the transient receptor potential channels (TRP channels)

The use of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is limited in drug discovery and cardiac disease mechanism studies due to cell immaturity. Micro-scaled grooves can promote the maturation of cardiomyocytes by aligning them in order, but the mechanism of cardiomyocytes alignment has not been studied. From the level of calcium activity, gene expression and cell morphology, we verified that the W20H5 grooves can effectively promote the maturation of cardiomyocytes. The transient receptor potential channels (TRP channels) also play an important role in the maturation and development of cardiomyocytes. These findings support the engineered hPSC-CMs as a powerful model to study cardiac disease mechanism and partly mimic the myocardial morphological development. The important role of the TRP channels in the maturation and development of myocardium is first revealed.     

Identification and expression analysis of lncRNA in seven organs of Rhinopithecus roxellana

Long non-coding RNA (lncRNA) represents a new direction to identify expression profiles and regulatory mechanisms in various organisms. Here, we report the first dataset of lncRNAs of the golden snub-nosed monkey (GSM), including 12,557 putative lncRNAs identified from seven organs. Compared with mRNA, GSM lncRNA had fewer exons and isoforms, and longer length. LncRNA showed more obvious tissue-specific expression than mRNA. However, for the top ten most abundant genes in each organ, mRNAs expression was more tissue-specific than lncRNAs. By identification of specifically expressed lncRNAs and mRNAs in each organ, it indicates that the expression of SEG-lncRNA (specifically expressed lncRNA) and SEG-mRNA (specifically expressed mRNA) had high correlation. In particular, combined our lncRNA and mRNA data, we identified 92 heart SEG-lncRNAs targeted ten mRNA genes in the oxidative phosphorylation pathway and upregulated the expression of these target genes such as ND4, ATP6, and ATP8. These may contribute to GSM adaption to its high-elevation environment. We also identified 171 liver SEG-lncRNAs, which targeted 27 genes associated with the metabolism of xenobiotics and leaded to high expression of these target genes in liver. These lncRNAs may play important roles in GSM adaptation to a folivory diet.

     

格氏栲天然林林窗植物物种多样性与系统发育多样性

林窗环境异质性导致群落物种多样性与系统发育多样性(phylogenetic diversity, PD)存在差异, 研究不同大小的林窗中群落的物种多样性与系统发育多样性有助于揭示林下生物多样性的形成及维持机制。本文以格氏栲(Castanopsis kawakamii)天然林为研究对象, 通过Pearson相关性分析与广义线性模型探讨了林窗内物种多样性与系统发育多样性间的相互关系及其环境影响因素。结果表明: (1)大林窗(面积 > 200 m²)植物种类及多度均高于中林窗(50 m² ≤ 面积 < 100 m²)、小林窗(30 m² ≤ 面积 < 50 m²)和非林窗(面积 = 100 m²)。大林窗群落系统发育结构趋于发散, 中、小林窗和非林窗群落系统发育结构受到生境过滤和竞争排斥综合作用。(2)群落系统发育多样性指数与物种丰富度(species richness, SR)、Margalef丰富度指数和Shannon-Wiener指数均呈显著正相关, 这与林窗内稀有种种类组成多于优势种有关。(3)林窗面积对物种多样性存在显著正效应; 土壤全氮含量对系统发育多样性和系统发育结构存在显著正效应。林窗形成提高了格氏栲天然林群落物种多样性和系统发育多样性, 林窗面积与土壤全氮共同驱动了格氏栲天然林林窗物种多样性和系统发育多样性的变化。     

支气管镜肺泡灌洗联合抗生素对小儿重症肺炎的疗效及对痰细菌清除率等指标的影响

目的探讨支气管镜肺泡灌洗联合抗生素对小儿重症肺炎的疗效及对痰细菌清除率和其他指标的影响。方法选取我科收治的重症肺炎患儿126例,分为研究组及对照组,各63例。其中研究组在常规治疗基础上联合支气管镜肺泡灌洗及局部应用抗生素治疗,对照组采用常规治疗,比较2组患者的临床治疗效果。结果治疗后,研究组的临床有效率为90.5%,高于对照组的76.2%(χ~2=4.629,P=0.031);治疗后研究组患者的痰液中病菌清除率为77.7%,显著高于对照组的57.2%(χ~2=6.110,P=0.013);治疗后研究组患者的相关炎性指标(高敏C反应蛋白、肿瘤坏死因子α及白介素-6)均较对照组显著降低(t=3.522、4.912、4.183,P=0.033、0.032、0.033);治疗后研究组患者的相关血气指标(动脉血氧分压及氧合指数)均较对照组显著升高,而二氧化碳分压较对照组显著降低(t=3.612、3.312、6.162,P=0.039、0.040、0.028)。结论 BAL联合抗生素对小儿重症肺炎的疗效更为显著,值得临床推广应用。     

Exosomal miR-21-5p derived from cisplatin-resistant SKOV3 ovarian cancer cells promotes glycolysis and inhibits chemosensitivity of its progenitor SKOV3 cells by targeting PDHA1

Ovarian cancer (OC) is a common reason for gynecologic cancer death. Standard treatments of OC consist of surgery and chemotherapy. However, chemoresistance should be considered. Exosomal miR-21-5p has been shown to regulate the chemosensitivity of cancer cells through regulating pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1). However, the role of miR-21-5p/PDHA1 in OC is unclear. The levels of miR-21-5p and PDHA1 in clinical samples and cells were investigated. Exosomes derived from SKOV3/cisplatin (SKOV3/DDP) cells (DDP-Exos) were isolated and used to treat SKOV3 cells to test DDP-Exos effects on SKOV3 cells. Extracellular acidification rate and oxygen consumption rate were tested with a Seahorse analyzer. Cell apoptosis was analyzed by a flow cytometer. PDHA1 was overexpressed and miR-21-5p was silenced in SKOV3 cells to study the underlying mechanism of miR-21-5p in OC. Quantitative real-time PCR and immunoblots were applied to measure gene expression at mRNA and protein levels. The levels of PDHA1 in DDP-resistant SKOV3 or tumor tissues were significantly decreased while the levels of miR-21-5p were remarkably upregulated. miR-21-5p in DDP-Exos was sharply increased compared to that of Exos. Data also indicated that DDP-Exos treatment suppressed the sensitivity of SKOV3 cells to DDP and promoted cell viability and glycolysis of SKOV3 cells through inhibiting PDHA1 by exosomal miR-21-5p. miR-21-5p derived from DDP-resistant SKOV3 OC cells promotes glycolysis and inhibits chemosensitivity of its progenitor SKOV3 cells by targeting PDHA1. Our data highlights the important role of miR-21-5p/PDHA1 axis in OC and sheds light on new therapeutic development.     

承气活血通腑汤联合穴位贴敷治疗粘连性肠梗阻的疗效及对胃肠功能和血清炎性因子的影响

目的:探讨承气活血通腑汤联合穴位贴敷治疗粘连性肠梗阻的疗效及对胃肠功能和血清炎性因子的影响。方法:选取2018年2月到2020年7月期间于我院接受诊治的粘连性肠梗阻患者60例。分组方法采用随机数字表法,将入选患者分为对照组(n=30,常规治疗)、研究组(n=30,对照组的基础上给予承气活血通腑汤联合穴位贴敷治疗),对比两组疗效、胃肠功能、炎性因子、住院时间、住院费用、临床症状评分。结果:研究组的临床总有效率较对照组高(P<0.05)。两组治疗12d后血清降钙素原(PCT)、C反应蛋白(CRP)水平较治疗前降低,且研究组较对照组低(P<0.05)。两组治疗12d后腹部胀痛、排便排气、恶心呕吐、口苦口干评分较治疗前降低,且研究组较对照组低(P<0.05)。研究组胃管拔除时间、恢复正常饮食时间均短于对照组(P<0.05)。研究组住院时间短于对照组,住院费用少于对照组(P<0.05)。结论:承气活血通腑汤联合穴位贴敷治疗粘连性肠梗阻的疗效确切,可改善患者临床症状和胃肠功能,促进患者早日恢复,减少住院费用,降低机体炎性因子水平。     

An efficient pipeline for ancient DNA mapping and recovery of endogenous ancient DNA from whole‐genome sequencing data

Ancient DNA research has developed rapidly over the past few decades due to improvements in PCR and next‐generation sequencing (NGS) technologies, but challenges still exist. One major challenge in relation to ancient DNA research is to recover genuine endogenous ancient DNA sequences from raw sequencing data. This is often difficult due to degradation of ancient DNA and high levels of contamination, especially homologous contamination that has extremely similar genetic background with that of the real ancient DNA. In this study, we collected whole‐genome sequencing (WGS) data from 6 ancient samples to compare different mapping algorithms. To further explore more effective methods to separate endogenous DNA from homologous contaminations, we attempted to recover reads based on ancient DNA specific characteristics of deamination, depurination, and DNA fragmentation with different parameters. We propose a quick and improved pipeline for separating endogenous ancient DNA while simultaneously decreasing homologous contaminations to very low proportions. Our goal in this research was to develop useful recommendations for ancient DNA mapping and for separation of endogenous DNA to facilitate future studies of ancient DNA.     

TWEAK signals through JAK–STAT to induce tumor cell apoptosis

The TWEAK receptor Fn14 (TNFRSF12), a member of the TNF Receptor superfamily, can mediate many processes, including apoptosis. Fn14 agonists have therefore been the subject of interest as potential cancer therapeutics. In cell culture experiments, interferon gamma (IFNγ) is typically required for induction of apoptotic activity by either TWEAK or Fn14 agonistic antibodies in most cell lines. We have investigated the mechanism of IFNγ signaling and the role of JAK–STAT signaling in TWEAK/Fn14-mediated tumor cell killing. We found that IFNγ-mediated enhancement of tumor cell killing is JAK–STAT dependent, as JAK inhibitors block IFNγ?dependent TWEAK induced apoptosis. Exposure of tumor cells to IFNγ results in an increase in Fn14 expression on the cell surface, which may be a mechanism by which IFNγ induces sensitivity to TWEAK. In a reciprocal fashion, we observed that IFNγ receptor levels increase in response to TWEAK treatment in WiDr cells. Significantly, we found that TWEAK alone can induce STAT1 phosphorylation in WiDr tumor cells. Moreover, TWEAK induction of tumor cell apoptosis in WiDr cells in the absence of IFNγ is mediated by the JAK–STAT pathway. Correspondingly, we show that treatment of tumor bearing mice with mBIIB036, an Fn14 agonistic antibody, results in STAT1 phosphorylation in the tumors. Notably, the level of STAT1 phosphorylation appears to correlate with the degree of tumor growth inhibition by BIIB036 in vivo. Additionally, in WiDr cells, TWEAK induces a soluble factor, which we have identified as IFNβ, capable of independently inducing STAT1 phosphorylation when transferred to naïve cells. Finally, either IFNα or IFNβ can partially substitute for IFNγ in sensitizing tumor cells to Fn14 agonists. In summary, we show that TWEAK/Fn14 can signal through the JAK–STAT pathway to induce IFNβ, and that the ability of TWEAK to induce tumor cell apoptosis is mediated by JAK-STAT signaling. We also demonstrate that IFNγ enhancement of TWEAK/FN14-mediated tumor cell death is JAK-dependent and may occur by IFNγ-dependent upregulation of Fn14 on tumor cells. These findings may have implications for the appropriately targeted clinical development of Fn14 agonists as anti-cancer therapy.     

Morphogenesis and Molecular Phylogeny of a New Freshwater Ciliate,Notohymena apoaustralis n. sp. (Ciliophora,Oxytrichidae)

The live morphology, infraciliature, and morphogenesis of a new oxytrichid ciliate, Notohymena apoaustralis n. sp. collected from a freshwater pond in Qingdao (Tsingtao), China, were studied in vivo and after protargol impregnation. Notohymena apoaustralis n. sp. is characterized as follows: undulating membranes in Notohymena‐pattern; cortical granules yellow‐green, grouped around the marginal cirri and dorsal bristles, and in short irregular rows elsewhere in the cell; single contractile vacuole positioned at anterior 1/3 of the body length; two macronuclear nodules and one micronucleus; about 39 adoral membranelles; 18 frontoventral transverse cirri in typical Oxytricha‐pattern; one right and one left marginal row, almost confluent posteriorly; dorsal ciliature in typical Oxytricha‐pattern; 8–10 caudal cirri arranged in three rows, one each at the posterior end of dorsal kineties 1, 2, and 4, indistinguishable from marginal cirri in life. The morphogenetic process in N. apoaustralis n. sp. is consistent with that of the type species, Notohymena rubescens Blatterer and Foissner, 1988. Phylogenetic analyses based on small subunit rDNA sequence data suggest a sister relationship between N. apoaustralis n. sp. and Paraurostyla weissei, which cluster in a clade with Rubrioxytricha ferruginea.