microRNA-10b confers cisplatin resistance by activating AKT/mTOR/P70S6K signaling via targeting PPARγ in esophageal cancer

It is well known that the acquisition of chemoresistance is a major obstacle for the effective treatment of human cancers. It is reported that microRNAs (miRNAs) are implicated in chemotherapy resistance of various malignancies. miR-10b was previously proved as an oncogene in multiple malignancies, including esophageal cancer. However, its biological significance in regulating cisplatin (DDP) resistance in esophageal cancer is still elusive. Here, we observed that miR-10b expression was upregulated and peroxisome proliferator-activated receptor-γ (PPARγ) expression was downregulated in esophageal cancer tumor tissues and cells. PPARγ was proved as a functional target of miR-10b. Moreover, suppression of miR-10b enhanced the chemosensitivity of esophageal cancer cells to DDP in vitro and in vivo. In addition, PPARγ-mediated DDP sensitivity was weakened by miR-10b overexpression. Furthermore, miR-10b-activated AKT/mTOR/p70S6K signaling pathway through targeting PPARγ. Inactivation of AKT/mTOR/p70S6K by AKT inhibitor (GSK690693) attenuated miR-10b-induced DDP resistance in esophageal cancer cells. Taken together these observation, miRNA-10b-mediated PPARγ inhibition enhanced DDP resistance by activating the AKT/mTOR/P70S6K signaling in esophageal cancer, suggesting a potential target to improve therapeutic response of patients with esophageal cancer to DDP.     

Gli1 interacts with YAP1 to promote tumorigenesis in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is the predominant esophageal cancer type in China. The aberrant activation of glioma-associated oncogene homolog1 (Gli1), a key factor in Hedgehog (Hh) signaling pathway, has been found in esophageal carcinoma. Moreover, Yes-associated protein 1 (YAP1), the major mediator of Hippo signaling pathway, has been linked to esophageal carcinoma progression. However, the precise roles and the underlying mechanism of both Gli1 and YAP1 in ESCC are unclear. Here, we found that Gli1 and YAP1 are overexpressed in ESCC and are associated with poor prognosis. In addition, we confirmed that knockdown of Gli1 or YAP1 suppresses ESCC cell growth, migration, and invasion in ESCC TE1 and EC109 cells. Significantly, Gli1 interacts with YAP1 in ESCC cells. Both Gli1 and YAP1 proteins are closely correlated with each other in human ESCC samples. Mechanistically, Gli1 upregulates YAP1 in a LATS1-independent manner. Conversely, YAP1 induces Gli1 by regulating phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. Most importantly, we demonstrated that the interaction between Gli1 and YAP1 promotes ESCC tumor growth in vitro and in vivo. Our findings established a novel signaling mechanism by which the interaction between Gli1 and YAP1 promotes ESCC cell growth. This signaling regulation of the tumorigenesis provides a new therapeutic strategy for highly lethal ESCC.     

L. plantarum,L. fermentum,and B. breve Beads Modified the Intestinal Microbiota and Alleviated the Inflammatory Response in High-Fat Diet–Fed Mice

Probiotics and Antimicrobial Proteins - This paper aims to study the effects of compound microbe-based beads on changes in the intestinal microbiota and alleviation of high-fat (HF)...     

物种分布模型在大型真菌红色名录评估及保护中的应用: 以冬虫夏草为例

我国大型真菌资源丰富, 由于受气候变化和人类活动等的影响, 近年来很多物种受到不同程度的威胁, 亟待保护。红色名录评估是物种保护的第一步, 为有效保护我国大型真菌多样性, 2016年生态环境部和中国科学院联合启动中国大型真菌红色名录评估项目。合理的评估依赖于完善的物种地理分布、种群数量规模及其动态变化信息。大型真菌评估信息较少, 需要引入新的方法解决评估信息不足的问题。冬虫夏草(Ophiocordyceps sinensis)是一种重要的食药用菌, 具有较高的经济价值, 受到全世界的广泛关注, 评估信息相对充足, 此次被评为易危物种。利用物种分布模型对冬虫夏草未来分布区变化的预测在评估过程中发挥了重要作用。为了将物种分布模型分析方法引入大型真菌的受威胁等级评估, 本文以此前我们利用物种分布模型预测冬虫夏草的潜在分布区及其对气候变化响应的研究为例, 介绍了应用物种分布模型预测大型真菌的潜在分布区、未来气候变化情景下分布区变化趋势的方法和流程, 以及在应用中可能存在的问题和解决方案。通过本文的分析, 我们认为物种分布模型在大型真菌的红色名录评估和保护中具有重要的应用潜力, 值得推广应用。     

Identification of Avramr1 from Phytophthora infestans using long read and cDNA pathogen-enrichment sequencing (PenSeq)

Potato late blight, caused by the oomycete pathogen Phytophthora infestans, significantly hampers potato production. Recently, a new Resistance to Phytophthora infestans (Rpi) gene, Rpi-amr1, was cloned from a wild Solanum species, Solanum americanum. Identification of the corresponding recognized effector (Avirulence or Avr) genes from P. infestans is key to elucidating their naturally occurring sequence variation, which in turn informs the potential durability of the cognate late blight resistance. To identify the P. infestans effector recognized by Rpi-amr1, we screened available RXLR effector libraries and used long read and cDNA pathogen-enrichment sequencing (PenSeq) on four P. infestans isolates to explore the untested effectors. Using single-molecule real-time sequencing (SMRT) and cDNA PenSeq, we identified 47 highly expressed effectors from P. infestans, including PITG_07569, which triggers a highly specific cell death response when transiently coexpressed with Rpi-amr1 in Nicotiana benthamiana, suggesting that PITG_07569 is Avramr1. Here we demonstrate that long read and cDNA PenSeq enables the identification of full-length RXLR effector families and their expression profile. This study has revealed key insights into the evolution and polymorphism of a complex RXLR effector family that is associated with the recognition by Rpi-amr1.     

A cross-talk between epithelium and endothelium mediates human alveolar–capillary injury during SARS-CoV-2 infection

COVID-19, caused by SARS-CoV-2, is an acute and rapidly developing pandemic, which leads to a global health crisis. SARS-CoV-2 primarily attacks human alveoli and causes severe lung infection and damage. To better understand the molecular basis of this disease, we sought to characterize the responses of alveolar epithelium and its adjacent microvascular endothelium to viral infection under a co-culture system. SARS-CoV-2 infection caused massive virus replication and dramatic organelles remodeling in alveolar epithelial cells, alone. While, viral infection affected endothelial cells in an indirect manner, which was mediated by infected alveolar epithelium. Proteomics analysis and TEM examinations showed viral infection caused global proteomic modulations and marked ultrastructural changes in both epithelial cells and endothelial cells under the co-culture system. In particular, viral infection elicited global protein changes and structural reorganizations across many sub-cellular compartments in epithelial cells. Among the affected organelles, mitochondrion seems to be a primary target organelle. Besides, according to EM and proteomic results, we identified Daurisoline, a potent autophagy inhibitor, could inhibit virus replication effectively in host cells. Collectively, our study revealed an unrecognized cross-talk between epithelium and endothelium, which contributed to alveolar–capillary injury during SARS-CoV-2 infection. These new findings will expand our understanding of COVID-19 and may also be helpful for targeted drug development.Subject terms: Mechanisms of disease, Viral infection     

Interaction between the α-barrel tip of Vibrio vulnificus TolC homologs and AcrA implies the adapter bridging model

The AcrAB-TolC multidrug efflux pump confers resistance to Escherichia coli against many antibiotics and toxic compounds. The TolC protein is an outer membrane factor that participates in the formation of type I secretion systems. The genome of Vibrio vulnificus encodes two proteins homologous to the E. coli TolC, designated TolCV1 and TolCV2. Here, we show that both TolCV1 and TolCV2 partially complement the E. coli TolC function and physically interact with the membrane fusion protein AcrA, a component of the E. coli AcrAB-TolC efflux pump. Using site-directed mutational analyses and an in vivo cross-linking assay, we demonstrated that the α-barrel tip region of TolC homologs plays a critical role in the formation of functional AcrAB-TolC efflux pumps. Our findings suggest the adapter bridging model as a general assembly mechanism for tripartite drug efflux pumps in Gram-negative bacteria.     

马尾松与乡土阔叶树种凋落叶混合分解过程中全碳释放的动态变化

为了调整低山丘陵区低效林林分结构,探明马尾松（Pinus massoniana Lamb.）与乡土阔叶树种凋落叶混合分解过程中的全碳（C）释放规律。本研究以华南广泛分布的马尾松、檫木（Sassafras tzumu（Hemsl.） Hemsl）、香樟（Cinnamomum camphora（Linn） Presl）以及香椿（Toona sinensis（A. Juss.） Roem.）凋落叶为研究对象,将这4个树种凋落叶按照不同树种搭配以及混合比例组合为35个处理后进行野外分解实验,探讨C释放最佳的凋落叶树种组合以及混合比例。研究发现：4个单一树种凋落叶之间,香椿凋落叶的C释放最快,檫木和香樟凋落叶次之,马尾松凋落叶最慢。31个混合凋落叶中,C释放的非加和效应随着分解时间的延长表现出先升增强后减弱的趋势,且相对于其他季节,凋落叶在秋季的非加和效应有所减弱。一针一阔树种组合中,香樟凋落叶占比≥30%的处理：PC73和PC64的协同效应较强;一针两阔和一针三阔组合中,阔叶占比≥30%且含有香椿凋落叶的处理：PST613和712、PCT631和613、PSCT7111和6121的协同效应较强。     

Delphinidin induces antiproliferation and apoptosis of endometrial cells by regulating cytosolic calcium levels and mitochondrial membrane potential depolarization

Endometriosis is a benign gynecological disease of women of reproductive ages, wherein endometrial cells grow ectopically, decreasing their quality of life due to chronic pelvic pain and severe dysmenorrhea. Although surgery and hormone therapies are gold standards for treating endometriosis, side effects are common and the recurrence rate is nearly 50%. Recent studies are exploring phytochemicals as pharmacological adjuvants for treating endometriosis. Delphinidin is an anthocyanin with anti-inflammatory, antioxidative, and anticancerous properties. In this study, delphinidin showed antiproliferative and apoptotic effects on human endometrial cells. Additionally, treatment with delphinidin decreased the mitochondrial membrane potential and increased cytosolic calcium levels in VK2/E6E7 and End1/E6E7 cells. Delphinidin decreased the phosphorylation of proliferative signaling molecules, including ERK1/2, AKT, P70S6K, and S6, while increasing the phosphorylation of P38 MAPK and P90RSK. These results imply that delphinidin is a novel therapeutic agent for treating and managing endometriosis, and has fewer side effects.