Correlations between glycolysis with clinical traits and immune function in bladder urothelial carcinoma

Background: Glycolysis was a representative hallmark in the tumor microenvironment (TME), and we aimed to explore the correlations between glycolysis with immune activity and clinical traits in bladder urothelial carcinoma (BLCA).Methods: Our study obtained glycolysis scores for each BLCA samples from TCGA by a single-sample gene set enrichment analysis (ssGSEA) algorithm, based on a glycolytic gene set. The relationship between glycolysis with prognosis, clinical characteristics, and immune function were investigated subsequently.Results: We found that enhanced glycolysis was associated with poor prognosis and metastasis in BLCA. Moreover, glycolysis had a close correlation with immune function, and enhanced glycolysis increased immune activities. In other words, glycolysis had a positive correlation with immune activities. Immune checkpoints such as IDO1, CD274, were up-regulated in high-glycolysis group as well.Conclusion: We speculated that in BLCA, elevated glycolysis enhanced immune function, which caused tumor cells to overexpress immune checkpoints to evade immune surveillance. Inhibition of glycolysis might be a promising assistant for immunotherapy in bladder cancer.     

Combined gene family characterization and RNA-Seq to study the response of β-ketoacyl-CoA synthase to abiotic stress in rice (Oryza sativa L.)

Plant Growth Regulation - β-ketoacyl-CoA synthase is a key enzyme in the biosynthesis of over-long-chain fattty acids; thus, it plays a crucial role in plant resistance to stress. Herein, 33...     

溶藻弧菌群体基因组学研究

溶藻弧菌(Vibrio alginolyticus)是一种能够对人类以及鱼、虾、贝类等水产品致病的弧菌,给人类健康带来威胁,也给水产养殖业造成巨大的经济损失。目前该物种基于全基因组的遗传多样性和重要遗传元件研究报道较少。本研究对采集自全国4个省份的68株溶藻弧菌进行高通量测序,获得全基因组序列,并结合113株公开发表的全球序列数据,利用fineSTRUCTURE软件、VFDB毒力因子库和CARD、ResFinder耐药数据库,对溶藻弧菌的种群结构和毒力、耐药因子分别进行解析。结果表明:溶藻弧菌可分为谱系1和谱系2。两个谱系在美洲和亚洲均有分布,但欧洲仅分离到谱系1菌株;共鉴定发现12个克隆群,其中一个克隆群内菌株存在跨洋传播现象。该物种携带tlh、OmpU、IlpA等多种不同功能的毒力因子;毒力因子在两个谱系间的分布无特异性,但存在地域间差异:其中欧洲菌株携带VP1611、vcrD、vopD和fleR/flrC的比率低于其他地区,而基因IlpA的携带率则明显高于其他地区,我国广西菌株中fleR/flrC基因携带率低于其他省份,且不携带IlpA。多个基因组携带blaCARB-42、tet(34)、tet(35)、parE、CRP、rsmA、TxR和fos等与多种抗生素耐受相关的基因,其中TxR和fos基因在谱系2中的出现频率远高于谱系1;此外,TxR基因在亚洲菌株中的携带率高于美洲和欧洲地区,而在我国四川菌株中的携带率则低于其他省份。在5个基因组中(VA24、VA28、2014V-1011、ZJ-T和Vb1833)观察到质粒或ICE等携带多种耐药基因的大片段。本研究通过群体基因组学的研究方法,揭示了溶藻弧菌的种群结构组成和毒力、耐药相关元件的分布,为进一步了解溶藻弧菌的遗传特征和致病机制提供必要基础,为该病原的监测、预防和控制工作提供科学支撑。     

LncRNA MALAT1 mediates doxorubicin resistance of hepatocellular carcinoma by regulating miR-3129-5p/Nova1 axis

Molecular and Cellular Biochemistry - Drug resistance is one of the major challenges for cancer therapies. In recent years, research on disease-related molecular signaling pathways has become the...     

Post-translational modification of RNA m6A demethylase ALKBH5 regulates ROS-induced DNA damage response

Faithful genome integrity maintenance plays an essential role in cell survival. Here, we identify the RNA demethylase ALKBH5 as a key regulator that protects cells from DNA damage and apoptosis during reactive oxygen species (ROS)-induced stress. We find that ROS significantly induces global mRNA N⁶-methyladenosine (m⁶A) levels by modulating ALKBH5 post-translational modifications (PTMs), leading to the rapid and efficient induction of thousands of genes involved in a variety of biological processes including DNA damage repair. Mechanistically, ROS promotes ALKBH5 SUMOylation through activating ERK/JNK signaling, leading to inhibition of ALKBH5 m⁶A demethylase activity by blocking substrate accessibility. Moreover, ERK/JNK/ALKBH5-PTMs/m⁶A axis is activated by ROS in hematopoietic stem/progenitor cells (HSPCs) in vivo in mice, suggesting a physiological role of this molecular pathway in the maintenance of genome stability in HSPCs. Together, our study uncovers a molecular mechanism involving ALKBH5 PTMs and increased mRNA m⁶A levels that protect genomic integrity of cells in response to ROS.     

SARS-CoV-2 nucleocapsid and Nsp3 binding: an in silico study

Archives of Microbiology - Severe acute respiratory syndrome virus 2 (SARS-CoV-2) belongs to the single-stranded positive-sense RNA family. The virus contains a large genome that encodes four...     

代谢工程发展30年

代谢工程学科建立30年以来先后与分子生物学、系统生物学和合成生物学发生深度的交叉融合,并在此基础上获得了飞速发展,极大地促进了生物技术产业的进步和升级。文中首先基于SCI论文发表情况对30年来代谢工程学术研究现状和我国在该领域的地位和影响力进行了分析,随后总结了近10年来系统生物学方法和合成生物学的主要使能技术在代谢工程中的应用。最后讨论了目前代谢工程发展中存在的主要问题和今后的发展趋势。     

Length of mucin-like domains enhances cell-Ebola virus adhesion by increasing binding probability

The Ebola virus (EBOV) hijacks normal physiological processes by apoptotic mimicry to be taken up by the cell it infects. The initial adhesion of the virus to the cell is based on the interaction between T cell immunoglobulin and mucin domain protein, TIM, on the cell surface and phosphatidylserine (PS) on the viral outer surface. Therefore, it is important to understand the interaction between EBOV and PS and TIM, with selective blocking of the interaction as a potential therapy. Recent experimental studies have shown that for TIM-dependent EBOV entry, a mucin-like domain with a length of at least 120 amino acids is required, possibly because of the increase of area of the PS-coated surface sampled. We examine this hypothesis by modeling the process of TIM-PS adhesion using a coarse-grained molecular model. We find that the strength of individual bound PS-TIM pairs is essentially independent of TIM length. TIMs with longer mucin-like domains collectively have higher average binding strengths because of an increase in the probability of binding between EBOV and TIM proteins. Similarly, we find that for larger persistence length (less flexible), the average binding force decreases, again because of a reduction in the probability of binding.