Microplastics impair wound healing via NAT10-mediated epigenetic dysregulation of FASN-PI3K/AKT signaling.

Microplastics (MPs) are environmental pollutants with potential health risks. This study examined the effect of MPs on wound healing in both diabetic and non-diabetic mice. MPs exposure significantly delayed wound healing, particularly in diabetic mice, with reduced epidermal thickness and impaired collagen deposition.

Spectrum and epidemiology of rare diseases in a Chinese natural population of 14.31 million residents, 2012-2023.

Background: Rare diseases, though individually uncommon, collectively affect a significant portion of the population. However, their epidemiology in China remains underexplored. A population-based rare disease registry comprising 14.

Discovery of novel cathepsin K inhibitors for osteoporosis treatment using a deep learning-based strategy.

Background: Cathepsin K (CTSK), a cysteine protease of the papain family, exhibits high expression in activated osteoclasts, making it a key therapeutic target for osteoporosis. However, there are currently no CTSK inhibitors available for clinical use.

Research Design And Methods: The authors employed a combination of deep learning approaches and experimental methods to identify novel CTSK inhibitors.

KCNH6 Potassium Channel Regulates Assembling of Mitochondrial Complex I and Promotes Insulin Secretion in Islet Beta Cells.

Mitochondrial glucose metabolism is critical for glucose-stimulated insulin secretion and glucose homeostasis in pancreatic β cells. We previously showed that KCNH6, a voltage-dependent potassium (Kv) channel, participated regulation of insulin secretion in pancreatic β cells, however, its role in mitochondrial metabolism remains unclear. Since we recently found that KCNH6 distributed in mitochondria, in this study, we investigated the role of KCNH6 in regulating mitochondrial function in pancreatic β cells by using a β cell-specific knockout (KCNH6-βKO) mouse model.

Resinacein S, a novel triterpenoid from functional mushroom Ganoderma resinaceum, curbs obesity by regulating thermogenesis and energy metabolism.

Ganoderma mushrooms are popularly used as dietary supplements to promote health around the world. However, their potential applications for the prevention and treatment of obesity needs to be further investigated. In this study, we isolated a novel triterpenoid from Ganoderma resinaceum, Resinacein S (Res S), and determined its absolute configuration.

Uncoupling protein 1 deficiency leads to transcriptomic differences in livers of pregnancy female mice and aggravates hepatic steatosis.

Pregnancy requires the coordination of metabolically active organs to support maternal nutrition and fetal growth. However, the metabolic cross-talk between adipose tissue and liver in females during pregnancy is still less clear. In this study, we evaluated the metabolic adaptations and phenotypes of liver in response to pregnancy-associated metabolic stress, particularly in the context of genetic ablation of Uncoupling protein 1 (Ucp1)-mediated catabolic circuit.

PAD4 Inhibitor-Loaded Magnetic FeO Nanoparticles for Magnetic Targeted Chemotherapy and Magnetic Resonance Imaging of Lung Cancer.

Introduction: Lung cancer is a major health concern worldwide owing to its high incidence and mortality rates. Therefore, identification of new therapeutic targets and strategies for lung cancer is critical for improving patient outcomes. Peptidyl arginine deiminase 4 (PAD4) promotes tumor growth and metastasis by catalyzing the citrullination of histones, making it a potential therapeutic target.

Low-dose quinine targets KCNH6 to potentiate glucose-induced insulin secretion.

Insulin secretion is mainly regulated by two electrophysiological events, depolarization initiated by the closure of adenosine triphosphate (ATP)-sensitive K+ (KATP) channels and repolarization mediated by K+ efflux. Quinine, a natural component commonly used for the treatment of malaria, has been reported to directly stimulate insulin release and lead to hypoglycemia in patients during treatment through inhibiting KATP channels. In this study, we verified the insulinotropic effect of quinine on the isolated mouse pancreatic islets.

Association between hydroxychloroquine use and risk of diabetes mellitus in systemic lupus erythematosus and rheumatoid arthritis: a UK Biobank-based study.

Context/objectives: Hydroxychoroquine has hypoglycemic effects and may reduce the risk of diabetes mellitus (DM). We determined the association between hydroxychoroquine use and the incidence of DM in a population-based cohort of pations with Rheumatic disease.

Methods: A prospective cohort study among 502392 Potentially eligible participants in the context of UK Biobank, recruitment to the database began between 2006 and 2010.

Rising incidence of obesity-related cancers among younger adults in China: A population-based analysis (2007-2021).

Background: Developing countries face an "obesity epidemic," particularly affecting children and younger adults. While obesity is a known risk factor for 12 types of cancer, primarily affecting older populations, its impact on younger generations is understudied.

Methods: This study analyzed data from a population-based cancer registry covering 14.

Potassium voltage-gated channel subfamily H member 2 (KCNH2) is a promising target for incretin secretagogue therapies.

Derived from enteroendocrine cells (EECs), glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are pivotal incretin hormones crucial for blood glucose regulation. Medications of GLP-1 analogs and GLP-1 receptor activators are extensively used in the treatment of type 2 diabetes (T2D) and obesity. However, there are currently no agents to stimulate endogenous incretin secretion.

Discovering novel Cathepsin L inhibitors from natural products using artificial intelligence.

Cathepsin L (CTSL) is a promising therapeutic target for metabolic disorders. Current pharmacological interventions targeting CTSL have demonstrated potential in reducing body weight gain, serum insulin levels, and improving glucose tolerance. However, the clinical application of CTSL inhibitors remains limited.

KCNH6 is essential for insulin secretion by regulating intracellular ER Ca store.

Appropriate Ca concentration in the endoplasmic reticulum (ER), modulating cytosolic Ca signal, serves significant roles in physiological function of pancreatic β cells. To maintaining ER homeostasis, Ca movement across the ER membrane is always accompanied by a simultaneous K flux in the opposite direction. KCNH6 was proven to modulate insulin secretion by controlling plasma membrane action potential duration and intracellular Ca influx.

KCNH6 channel promotes insulin exocytosis via interaction with Munc18-1 independent of electrophysiological processes.

Glucose-stimulated insulin secretion (GSIS) in pancreatic islet β-cells primarily relies on electrophysiological processes. Previous research highlighted the regulatory role of KCNH6, a member of the Kv channel family, in governing GSIS through its influence on β-cell electrophysiology. In this study, we unveil a novel facet of KCNH6's function concerning insulin granule exocytosis, independent of its conventional electrical role.

All-potassium channel CRISPR screening reveals a lysine-specific pathway of insulin secretion.

Objective: Genome-scale CRISPR-Cas9 knockout coupled with single-cell RNA sequencing (scRNA-seq) has been used to identify function-related genes. However, this method may knock out too many genes, leading to low efficiency in finding genes of interest. Insulin secretion is controlled by several electrophysiological events, including fluxes of K depolarization and K repolarization.

TC-Net: A joint learning framework based on CNN and vision transformer for multi-lesion medical images segmentation.

Background: With the rapid advancement of medical imaging technology, the demand for accurate segmentation of medical images is increasing. However, most existing methods are unable to capture locality and long-range dependency information in integrated ways for medical images.

Method: In this paper, we propose an elegant segmentation framework for medical images named TC-Net, which can utilize both the locality-aware and long-range dependencies in the medical images.

Association between Covid-19 vaccination and incidence of type 1 diabetes in China: Evidence from 14.14 million registered residents between 2007 and 2021.

Aims: Reports have suggested that COVID-19 vaccination may cause Type 1 diabetes (T1D), particularly fulminant T1D (FT1D). This study aimed to investigate the incidence of T1D in a general population of China, where>90% of the people have received three injections of inactivated SARS-Cov-2 vaccines in 2021.

Methods: A population-based registry of T1D was performed using data from the Beijing Municipal Health Commission Information Center.

An approach combining deep learning and molecule docking for drug discovery of cathepsin L.

Objectives: Cathepsin L (CTSL) is a promising therapeutic target for metabolic disorders and COVID-19. However, there are still no clinically available CTSL inhibitors. Our objective is to develop an approach for the discovery of potential reversible covalent CTSL inhibitors.

The signaling protein GIV/Girdin mediates the Nephrin-dependent insulin secretion of pancreatic islet β cells in response to high glucose.

Glucose-stimulated insulin secretion of pancreatic β cells is essential in maintaining glucose homeostasis. Recent evidence suggests that the Nephrin-mediated intercellular junction between β cells is implicated in the regulation of insulin secretion. However, the underlying mechanisms are only partially characterized.

Integrated Proteomics and Metabolomics Analyses of Serum in Chinese Patients with Severe and Active Graves' Orbitopathy: A Cross-sectional Study.

Objective: The present study aims to investigate the alterations of serum proteomic and metabolomic profiles in Chinese patients with severe and active Graves' Orbitopathy (GO).

Materials And Methods: Thirty patients with GO and 30 healthy volunteers were enrolled. The serum concentrations of FT3, FT4, T3, T4, and thyroid-stimulating hormone (TSH) were analyzed, after which TMT labeling-based proteomics and untargeted metabolomics were performed.

Tear-derived exosomal biomarkers of Graves' ophthalmopathy.

Graves' ophthalmopathy (GO), the most frequent extrathyroidal manifestation of Graves' disease (GD), can lead to a significant decline in the quality of life in patients. Exosomes, which contain proteins, lipids and DNA, play important roles in the pathological processes of various diseases. However, their roles in Graves' ophthalmopathy are still unclear.