From Physiology to Pathology of Astrocytes: Highlighting Their Potential as Therapeutic Targets for CNS Injury.

In the mammalian central nervous system (CNS), astrocytes are the ubiquitous glial cells that have complex morphological and molecular characteristics. These fascinating cells play essential neurosupportive and homeostatic roles in the healthy CNS and undergo morphological, molecular, and functional changes to adopt so-called 'reactive' states in response to CNS injury or disease. In recent years, interest in astrocyte research has increased dramatically and some new biological features and roles of astrocytes in physiological and pathological conditions have been discovered thanks to technological advances.

USP39 promotes hepatocellular carcinogenesis through regulating alternative splicing in cooperation with SRSF6/HNRNPC.

Abnormal alternative splicing (AS) caused by alterations in spliceosomal factors is implicated in cancers. Standard models posit that splice site selection is mainly determined by early spliceosomal U1 and U2 snRNPs. Whether and how other mid/late-acting spliceosome components such as USP39 modulate tumorigenic splice site choice remains largely elusive.

Coupling of co-transcriptional splicing and 3' end Pol II pausing during termination in Arabidopsis.

Background: In Arabidopsis, RNA Polymerase II (Pol II) often pauses within a few hundred base pairs downstream of the polyadenylation site, reflecting efficient transcriptional termination, but how such pausing is regulated remains largely elusive.

Result: Here, we analyze Pol II dynamics at 3' ends by combining comprehensive experiments with mathematical modelling. We generate high-resolution serine 2 phosphorylated (Ser2P) Pol II positioning data specifically enriched at 3' ends and define a 3' end pause index (3'PI).

Amino acid variability, tradeoffs and optimality in human diet.

Studies at the molecular level demonstrate that dietary amino acid intake produces substantial effects on health and disease by modulating metabolism. However, how these effects may manifest in human food consumption and dietary patterns is unknown. Here, we develop a series of algorithms to map, characterize and model the landscape of amino acid content in human food, dietary patterns, and individual consumption including relations to health status, covering over 2,000 foods, ten dietary patterns, and over 30,000 dietary profiles.

MCIBox: a toolkit for single-molecule multi-way chromatin interaction visualization and micro-domains identification.

The emerging ligation-free three-dimensional (3D) genome mapping technologies can identify multiplex chromatin interactions with single-molecule precision. These technologies not only offer new insight into high-dimensional chromatin organization and gene regulation, but also introduce new challenges in data visualization and analysis. To overcome these challenges, we developed MCIBox, a toolkit for multi-way chromatin interaction (MCI) analysis, including a visualization tool and a platform for identifying micro-domains with clustered single-molecule chromatin complexes.

Edaravone Ameliorates Cerebral Ischemia-Reperfusion Injury by Downregulating Ferroptosis via the Nrf2/FPN Pathway in Rats.

Edaravone, an antioxidant protective agent, has anti-cerebral ischemic reperfusion injury (CIRI) effects, but its anti-CIRI mechanism is unclear. The aim of this study is to investigate the anti-CIRI mechanism of edaravone based on the nuclear factor-E2-related factor 2 (Nrf2)/ferroportin (FPN) pathway that regulates ferroptosis-mediated cerebral ischemia-reperfusion injury. We evaluated the brain injury by constructing a middle cerebral artery occlusion and reperfusion (MCAO/R) model in rats.

Pinpointing Cancer Sub-Type Specific Metabolic Tasks Facilitates Identification of Anti-cancer Targets.

Metabolic reprogramming is one of the hallmarks of tumorigenesis. Understanding the metabolic changes in cancer cells may provide attractive therapeutic targets and new strategies for cancer therapy. The metabolic states are not the same in different cancer types or subtypes, even within the same sample of solid tumors.

Effects of Interleukin-10 -1082G/A and -592C/A Gene Polymorphisms on the Risk of Human Immunodeficiency Virus-1 Infection: An Updated Meta-analysis.

This paper has aimed to review the available evidence on the association between Interleukin (IL) -10 -1082G/A, -592C/A gene polymorphisms and the risk of human immunodeficiency virus-1(HIV-1) infection. The data of PubMed updated in May 2021 were retrieved. The HIV infection risks were estimated in allelic, recessive, dominant, homozygous, heterozygous, over-dominant models of IL-10-1082G/A and-592C/A gene locus as odds ratio (OR) with the corresponding 95% confidence interval (95% CI).

Astragaloside IV Alleviates Cerebral Ischemia-Reperfusion Injury through NLRP3 Inflammasome-Mediated Pyroptosis Inhibition via Activating Nrf2.

As one of the fundamental components of , astragaloside IV (AST IV) exerts protective effects against cerebral ischemia-reperfusion injury (CIRI). Nevertheless, the underlying mechanisms have not yet been conclusively elucidated. To do so, here, we report on the regulatory effects of Nrf2 on NLRP3 inflammasome-mediated pyroptosis.

Jiangzhi Ligan Decoction Inhibits GSDMD-Mediated Canonical/Noncanonical Pyroptosis Pathways and Alleviates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease.

Increasing evidence suggests that gasdermin D (GSDMD) mediated pyroptosis signaling pathways play a vital role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Jiangzhi Ligan Decoction (JZLGD) has been verified to prevent NAFLD, but its specific mechanism has not been determined. In this study, an NAFLD model was established in Sprague-Dawley rats by a high-fat diet (HFD).

Cellular stress signaling activates type-I IFN response through FOXO3-regulated lamin posttranslational modification.

Neural stem/progenitor cells (NSPCs) persist over the lifespan while encountering constant challenges from age or injury related brain environmental changes like elevated oxidative stress. But how oxidative stress regulates NSPC and its neurogenic differentiation is less clear. Here we report that acutely elevated cellular oxidative stress in NSPCs modulates neurogenic differentiation through induction of Forkhead box protein O3 (FOXO3)-mediated cGAS/STING and type I interferon (IFN-I) responses.

Erratum: Dynamic C Flux Analysis Captures the Reorganization of Adipocyte Glucose Metabolism in Response to Insulin.

[This corrects the article DOI: 10.1016/j.isci.

Author Correction: The evolving metabolic landscape of chromatin biology and epigenetics.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Serum 14-3-3η is a Marker that Complements Current Biomarkers for the Diagnosis of RA: Evidence from a Meta-analysis.

Objective: To systematically evaluate the diagnostic value of 14-3-3η protein for rheumatoid arthritis (RA).

Method: Searched PubMed, Web of Science, Embase and China Biology Medicine (CBM) databases comprehensively from inception to May 2020. The evaluation index were the pooled sensitivity, specificity, diagnosis odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), as well as the area under the summary receiver operating characteristic (SROC) curves.

Quantitative Analysis of the Physiological Contributions of Glucose to the TCA Cycle.

The nutritional source for catabolism in the tricarboxylic acid (TCA) cycle is a fundamental question in metabolic physiology. Limited by data and mathematical analysis, controversy exists. Using isotope-labeling data in vivo across several experimental conditions, we construct multiple models of central carbon metabolism and develop methods based on metabolic flux analysis (MFA) to solve for the preferences of glucose, lactate, and other nutrients used in the TCA cycle.

The evolving metabolic landscape of chromatin biology and epigenetics.

Molecular inputs to chromatin via cellular metabolism are modifiers of the epigenome. These inputs - which include both nutrient availability as a result of diet and growth factor signalling - are implicated in linking the environment to the maintenance of cellular homeostasis and cell identity. Recent studies have demonstrated that these inputs are much broader than had previously been known, encompassing metabolism from a wide variety of sources, including alcohol and microbiotal metabolism.

Cooperative virus propagation in COVID-19 transmission.

The global pandemic due to the emergence of a novel coronavirus (COVID-19) is a threat to humanity. There remains an urgent need to understand its transmission characteristics and design effective interventions to mitigate its spread. In this study, we define a non-linear (known in biochemistry models as allosteric or cooperative) relationship between viral shedding, viral dose and COVID-19 infection propagation.

Metabolism in the tumor microenvironment: insights from single-cell analysis.

The metabolism of both cancer and immune cells in the tumor microenvironment (TME) is poorly understood since most studies have focused on analysis in bulk samples and cell culture models. Our recent analyses of single-cell RNA sequencing data suggest that the metabolic features of single cells within TME differ greatly from those of the bulk measurements. Here, we discuss some key findings about metabolism in cancer and immune cells and discuss possible relevance to immunotherapy.

Dynamic C Flux Analysis Captures the Reorganization of Adipocyte Glucose Metabolism in Response to Insulin.

Cellular metabolism is dynamic, but quantifying non-steady metabolic fluxes by stable isotope tracers presents unique computational challenges. Here, we developed an efficient C-tracer dynamic metabolic flux analysis (13C-DMFA) framework for modeling central carbon fluxes that vary over time. We used B-splines to generalize the flux parameterization system and to improve the stability of the optimization algorithm.

Urinary Tumor Necrosis Factor-Like Weak Inducer of Apoptosis as a Biomarker for Diagnosis and Evaluating Activity in Lupus Nephritis: A Meta-analysis.

Objective: Urinary tumor necrosis factor-like weak inducer of apoptosis (uTWEAK) has been identified as a candidate biomarker for lupus nephritis (LN). However, its diagnostic value remains unclear. This meta-analysis was conducted to comprehensively evaluate the value of uTWEAK for diagnosis and evaluating activity in LN.

Preeclampsia in systemic lupus erythematosus pregnancy: a systematic review and meta-analysis.

Objectives: The impact of systemic lupus erythematosus (SLE) on preeclampsia is still obscure. This study was performed to systematically assess the association between preeclampsia and SLE.

Method: According to the PRISMA statement, designed literature research was performed in PubMed, Web of Science, and Cochrane Library from inception to June 30, 2018.

Evolved resistance to partial GAPDH inhibition results in loss of the Warburg effect and in a different state of glycolysis.

Aerobic glycolysis or the Warburg effect (WE) is characterized by increased glucose uptake and incomplete oxidation to lactate. Although the WE is ubiquitous, its biological role remains controversial, and whether glucose metabolism is functionally different during fully oxidative glycolysis or during the WE is unknown. To investigate this question, here we evolved resistance to koningic acid (KA), a natural product that specifically inhibits glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a rate-controlling glycolytic enzyme, during the WE.

Identification of Cancer-associated metabolic vulnerabilities by modeling multi-objective optimality in metabolism.

Background: Cancer cells undergo global reprogramming of cellular metabolism to satisfy demands of energy and biomass during proliferation and metastasis. Computational modeling of genome-scale metabolic models is an effective approach for designing new therapeutics targeting dysregulated cancer metabolism by identifying metabolic enzymes crucial for satisfying metabolic goals of cancer cells, but nearly all previous studies neglect the existence of metabolic demands other than biomass synthesis and trade-offs between these contradicting metabolic demands. It is thus necessary to develop computational models covering multiple metabolic objectives to study cancer metabolism and identify novel metabolic targets.

Increased circulating CXCL13 levels in systemic lupus erythematosus and rheumatoid arthritis: a meta-analysis.

Objectives: CXC ligand 13 (CXCL13) is known as B cell chemotactic factor (BLC), promoting the migration of B lymphocytes by communicating with its receptor CXCR5, which can be regarded as part of pathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). This meta-analysis was to evaluate the circulating CXCL13 levels in SLE and RA.

Methods: All articles were respectively gathered from PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) (by the end of 10 April 2019).