Risk prediction of diabetic retinopathy based on visit-to-visit fasting blood glucose indices.

Objective: The long-term glucose monitoring is essential to the risk assessment of diabetic retinopathy (DR), the aim of this study was to investigate the predictive ability of visit-to-visit fasting blood glucose (FBG) indices on the risk of DR.

Methods: This was a community-based, cohort study conducted from 2013 to 2021. DR was diagnosed by digital fundus photography.

A machine learning enhanced EMS mutagenesis probability map for efficient identification of causal mutations in Caenorhabditis elegans.

Chemical mutagenesis-driven forward genetic screens are pivotal in unveiling gene functions, yet identifying causal mutations behind phenotypes remains laborious, hindering their high-throughput application. Here, we reveal a non-uniform mutation rate caused by Ethyl Methane Sulfonate (EMS) mutagenesis in the C. elegans genome, indicating that mutation frequency is influenced by proximate sequence context and chromatin status.

AlphaFold2-guided engineering of split-GFP technology enables labeling of endogenous tubulins across species while preserving function.

Dynamic properties are essential for microtubule (MT) physiology. Current techniques for in vivo imaging of MTs present intrinsic limitations in elucidating the isotype-specific nuances of tubulins, which contribute to their versatile functions. Harnessing the power of the AlphaFold2 pipeline, we engineered a strategy for the minimally invasive fluorescence labeling of endogenous tubulin isotypes or those harboring missense mutations.

COVID-19: from immune response to clinical intervention.

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has highlighted the pivotal role of the immune response in determining the progression and severity of viral infections. In this paper, we review the most recent studies on the complicated dynamics between SARS-CoV-2 and the host immune system, highlight the importance of understanding these dynamics in developing effective treatments and formulate potent management strategies for COVID-19. We describe the activation of the host's innate immunity and the subsequent adaptive immune response following infection with SARS-CoV-2.

Regulation of neuronal plasticity associated with neuropsychiatric disorders by the orexinergic system.

Orexins are a family of neuropeptides secreted by neurons in the lateral hypothalamus (LH). These peptides act widespreadly across the body by interacting with specific orexin receptors on target cells, which comprise the orexinergic system. Emerging evidence has revealed that the orexinergic system is tightly associated with neuropsychiatric disorders; however, the underlying mechanisms require further exploration.

Vacuolar H-ATPase determines daughter cell fates through asymmetric segregation of the nucleosome remodeling and deacetylase complex.

Asymmetric cell divisions (ACDs) generate two daughter cells with identical genetic information but distinct cell fates through epigenetic mechanisms. However, the process of partitioning different epigenetic information into daughter cells remains unclear. Here, we demonstrate that the nucleosome remodeling and deacetylase (NuRD) complex is asymmetrically segregated into the surviving daughter cell rather than the apoptotic one during ACDs in .

Transposase-assisted tagmentation: an economical and scalable strategy for single-worm whole-genome sequencing.

AlphaMissense identifies 23 million human missense variants as likely pathogenic, but only 0.1% have been clinically classified. To experimentally validate these predictions, chemical mutagenesis presents a rapid, cost-effective method to produce billions of mutations in model organisms.

Administration of Atosiban, an oxytocin receptor antagonist, ameliorates autistic-like behaviors in a female rat model of valproic acid-induced autism.

Autism spectrum disorder (ASD) is a pervasive developmental disorder with gender differences. Oxytocin (OXT) is currently an important candidate drug for autism, but the lack of data on female autism is a big issue. It has been reported that the effect of OXT is likely to be different between male and female ASD patients.

EZH2 Inhibition Enhances PD-L1 Protein Stability Through USP22-Mediated Deubiquitination in Colorectal Cancer.

The regulation of PD-L1 is the key question, which largely determines the outcome of the immune checkpoint inhibitors (ICIs) based therapy. However, besides the transcription level, the protein stability of PD-L1 is closely correlated with its function and has drawn increasing attention. In this study, EZH2 inhibition enhances PD-L1 expression and protein stability, and the deubiquitinase ubiquitin-specific peptidase 22 (USP22) is identified as a key mediator in this process.

Utilizing the scale-invariant feature transform algorithm to align distance matrices facilitates systematic protein structure comparison.

Motivation: Protein structure comparison is pivotal for deriving homological relationships, elucidating protein functions, and understanding evolutionary developments. The burgeoning field of in-silico protein structure prediction now yields billions of models with near-experimental accuracy, necessitating sophisticated tools for discerning structural similarities among proteins, particularly when sequence similarity is limited.

Results: In this article, we have developed the align distance matrix with scale (ADAMS) pipeline, which synergizes the distance matrix alignment method with the scale-invariant feature transform algorithm, streamlining protein structure comparison on a proteomic scale.

Targeting LTA4H facilitates the reshaping of the immune microenvironment mediated by CCL5 and sensitizes ovarian cancer to Cisplatin.

Ovarian cancer is the most lethal and aggressive gynecological cancer with a high recurrence rate and is often diagnosed late. In ovarian cancer, multiple metabolic enzymes of lipid metabolism are abnormally expressed, resulting in metabolism disorder. As a characteristic pathway in polyunsaturated fatty acid (PUFA) metabolism, arachidonic acid (AA) metabolism is disturbed in ovarian cancer.

A plant flavonol and genetic suppressors rescue a pathogenic mutation associated with kinesin in neurons.

KIF1A, a microtubule-based motor protein responsible for axonal transport, is linked to a group of neurological disorders known as KIF1A-associated neurological disorder (KAND). Current therapeutic options for KAND are limited. Here, we introduced the clinically relevant KIF1A(R11Q) variant into the homolog UNC-104, resulting in uncoordinated animal behaviors.

Inhibition of the chromatin remodeling factor NURF rescued sterility by a clinic variant of NuRD.

The nucleosome remodeling and deacetylase (NuRD) complex is essential for gene expression and cell fate determination, and missense mutations of NuRD caused neurodevelopmental diseases. However, the molecular pathogenesis of clinic NuRD variants is unknown. Here, we introduced a clinic CHD3 (L915F) variant into homologue LET-418, impairing germline and vulva development and ultimately causing animal sterility.

Advances in regulation and function of stearoyl-CoA desaturase 1 in cancer, from bench to bed.

Stearoyl-CoA desaturase 1 (SCD1) converts saturated fatty acids to monounsaturated fatty acids. The expression of SCD1 is increased in many cancers, and the altered expression contributes to the proliferation, invasion, sternness and chemoresistance of cancer cells. Recently, more evidence has been reported to further support the important role of SCD1 in cancer, and the regulation mechanism of SCD1 has also been focused.

Oridonin inhibits inflammation of epithelial cells dual-targeting of CD31 Keap1 to ameliorate acute lung injury.

Introdcution: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are major causes of COVID-19 mortality. However, drug delivery to lung tissues is impeded by endothelial cell barriers, limiting the efficacy of existing treatments. A prompt and aggressive treatment strategy is therefore necessary.

EZH2 Inhibitors Suppress Colorectal Cancer by Regulating Macrophage Polarization in the Tumor Microenvironment.

EZH2 inhibitors (EZH2i), a class of small-molecule inhibitors that target EZH2 to exert anti-tumor functions, have just been approved by the US Food and Drug Administration (FDA) in treatment of adults and adolescents with locally advanced or metastatic epithelioid sarcoma. The application of EZH2i in several solid tumors is still in different stages of clinical trials and needs to be further validated. As a key epigenetic regulator, besides its role in controlling the proliferation of tumor cells, EZH2 has been implicated in the regulation of various immune cells including macrophages.

IKK mediates homeostatic function in inflammation competitively phosphorylating AMPK and IB.

Inhibitor of nuclear factor kappa-B kinase subunit beta (IKK) is one of important kinases in inflammation to phosphorylate inhibitor of nuclear factor kappa-B (IB) and then activate nuclear factor kappa-B (NF-B). Inhibition of IKK has been a therapeutic strategy for inflammatory and autoimmune diseases. Here we report that IKK is constitutively activated in healthy donors and healthy (cysteine 46 mutated to alanine) knock-in mice although they possess intensive IKK-IB-NF-B signaling activation.

Synthesis and identification of lithocholic acid 3-sulfate as RORγt ligand to inhibit Th17 cell differentiation.

Primary bile acids (BAs), products of cholesterol metabolism and clearance, are synthesized in the liver and released into the intestine to facilitate the digestion and absorption of lipids. BAs are further converted by gut commensal bacteria into secondary colonic BAs and the metabolism disorder is closely linked to cholestatic liver diseases via regulating immune response. However, the effect and underlying mechanism of these host-microorganism biliary metabolites on T lymphocyte remain unclear.

Dysregulated lipid metabolism blunts the sensitivity of cancer cells to EZH2 inhibitor.

Background: Sensitivity has been a key issue for Enhancer of zeste homolog 2 (EZH2) inhibitors in cancer therapy. The EZH2 inhibitor EPZ-6438 was first approved by the US Food and Drug Administration (FDA) in 2020. However, its inadequate anti-cancer activity in solid tumors limits its clinical application.

Easy or Not-The Advances of EZH2 in Regulating T Cell Development, Differentiation, and Activation in Antitumor Immunity.

Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of polycomb repressive complex 2 (PRC2), which regulates downstream gene expression by trimethylation of lysine 27 in histone H3 (H3K27me3). EZH2 mutations or overexpressions are associated with many types of cancer. As inhibition of EZH2 activity could upregulate the expression of tumor suppressor genes, EZH2 has recently become an interesting therapeutic target for cancer therapy.

Cytotoxicity Evaluation of Chloroquine and Hydroxychloroquine in Multiple Cell Lines and Tissues by Dynamic Imaging System and Physiologically Based Pharmacokinetic Model.

Chloroquine (CQ) and hydroxychloroquine (HCQ) have been challenged in treating COVID-19 patients and still under debate due to the uncertainty regarding the effectiveness and safety, and there is still lack of the systematic study on the toxicity of these two drugs. To further uncover the toxicity profile of CQ and HCQ in different tissues, we evaluated the cytotoxicity of them in eight cell lines and further adopted the physiologically based pharmacokinetic models to predict the tissue risk, respectively. Retina, myocardium, lung, liver, kidney, vascular endothelium, and intestinal epithelium originated cells were included in the toxicity evaluation of CQ and HCQ, respectively.

The key points in the pre-analytical procedures of blood and urine samples in metabolomics studies.

Background: Metabolomics provides measurement of numerous metabolites in human samples, which can be a useful tool in clinical research. Blood and urine are regarded as preferred subjects of study because of their minimally invasive collection and simple preprocessing methods. Adhering to standard operating procedures is an essential factor in ensuring excellent sample quality and reliable results.

Sex-determining region Y box 4 (SOX4) suppresses Hepatitis B virus replication by inhibiting hepatocyte nuclear factor 4α expression.

Hepatitis B virus (HBV) infection is still a health care crisis in the world, and a considerable number of chronic hepatitis B patients die of end-stage liver diseases, including liver cirrhosis and hepatocellular carcinoma. A previous study has reported that sex-determining region Y box 4 (SOX4) promotes HBV replication by binding to the AACAAAG motif in the viral genome. However, such SOX4 binding site was not found in the genome of the majority of HBV genotype strains.