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...     

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...     

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.     

Development of High‐Level Omega‐3 Eicosapentaenoic Acid (EPA) Production from Phaeodactylum tricornutum

Phaeodactylum tricornutum is a lipid‐rich marine diatom that contains a high level of omega‐3 polyunsaturated fatty acids, especially eicosapentaenoic acid (EPA). In an effort to reduce costs for large‐scale cultivation of this microalga, this study first established a New BBM medium (0.3 x strength BBM with only 3% of the initial phosphate level) to replace the traditional F/2 medium. Phaeodactylum tricornutum could grow in extremely low phosphate concentrations (25 µM), without compromising the EPA content. In the presence of sea salts, silicate addition was not necessary for high rate growth, high EPA content, or lipid accumulation in this species. Using urea as the sole nitrogen source tended to increase EPA contents per dry biomass (by 24.7%) while not affecting growth performance. The use of sea salts, rather than just sodium chloride, led to significantly improved biomass yields (20% increase) and EPA contents of total fatty acid (46–52% increase), most likely because it supplied sufficient essential elements such as magnesium. A salinity level of 35 led to significantly higher biomass yields compared with 20, but salinity had no significant influence on EPA content. EPA became the dominant fatty acid with average levels of 51.8% of total fatty acids during the exponential growth phase at 20 ppt in New BBM medium with sea salts.