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.

AoRan1 Is Involved in Regulating Conidiation, Stress Resistance, Secondary Metabolism, and Pathogenicity in .

is a representative nematode-trapping (NT) fungus that is able to capture, kill, and digest nematodes by producing specialized three-dimensional networks (traps) under nutrient-deprived conditions. Ran1 is a serine/threonine protein kinase that can act as a negative regulator of sexual conjugation and meiosis. However, the specific role of Ran1 remains largely unknown in NT fungi.

The Cryptochrome CryA Regulates Lipid Droplet Accumulation, Conidiation, and Trap Formation via Responses to Light in .

Light is a key environmental factor affecting conidiation in filamentous fungi. The cryptochrome/photolyase CryA, a blue-light receptor, is involved in fungal development. In the present study, a homologous CryA (AoCryA) was identified from the widely occurring nematode-trapping (NT) fungus , and its roles in the mycelial growth and development of were characterized using gene knockout, phenotypic comparison, staining technique, and metabolome analysis.

Functional Characterization of Ao4g24: An Uncharacterized Gene Involved in Conidiation, Trap Formation, Stress Response, and Secondary Metabolism in .

is a typical nematode-trapping (NT) fungus, which can secrete food cues to lure, capture, and digest nematodes by triggering the production of adhesive networks (traps). Based on genomic and proteomic analyses, multiple pathogenic genes and proteins involved in trap formation have been characterized; however, there are numerous uncharacterized genes that play important roles in trap formation. The functional studies of these unknown genes are helpful in systematically elucidating the complex interactions between and nematode hosts.

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.

Exploring Cancer Incidence Trends by Age and Sex Among 14.14 Million Individuals in China From 2007 to 2021: Population-Based Study.

Background: Sex is a crucial factor in the development, progression, and treatment of cancer, making it vital to examine cancer incidence trends by sex for effective prevention strategies.

Objective: This study aimed to assess the incidence of cancer in China between 2007 and 2021, with a focus on sex-based trends.

Methods: A population-based cancer registry comprising 14.

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.

The Arf-GAPs, AoAge1 and AoAge2, regulate diverse cellular processes, conidiation, trap formation, and secondary metabolism in Arthrobotrys oligospora.

Guanine nucleotide-binding proteins of the ADP ribosylation factor (Arf) family and their activating proteins (Arf-GAPs) are essential for diverse biological processes. Here, two homologous Arf-GAPs, Age1 (AoAge1) and Age2 (AoAge2), were identified in the widespread nematode-trapping fungus Arthrobotrys oligospora. Our results demonstrated that AoAge1, especially AoAge2, played crucial roles in mycelial growth, sporulation, trap production, stress response, mitochondrial activity, DNA damage, endocytosis, reactive oxygen species production, and autophagy.

Characterizing the Role of and in Mycelial and Conidial Development in and Their Role in Secondary Metabolism.

, a widespread nematode-trapping fungus which can produce conidia for asexual reproduction and form trapping devices (traps) to catch nematodes. However, little is known about the sporulation mechanism of . This research characterized the functions and regulatory roles of the upstream spore-producing regulatory genes, and , in .

Untargeted metabolomics uncovers metabolic dysregulation and tissue sensitivity in ACE2 knockout mice.

Angiotensin-converting enzyme 2 (ACE2) polymorphisms are associated with increased risk of type 2 diabetes mellitus (T2DM), obesity and dyslipidemia, which have been determined in various populations. Consistently, ACE2 knockout (ACE2 KO) mice display damaged energy metabolism in multiple tissues, especially the key metabolic tissues such as liver, skeletal muscle and epididymal white adipose tissue (eWAT) and show even more severe phenotype under high-fat diet (HFD) induced metabolic stress. However, the effects of ACE2 on global metabolomics profiling and the tissue sensitivity remain unclear.

AoPrdx2 Regulates Oxidative Stress, Reactive Oxygen Species, Trap Formation, and Secondary Metabolism in .

Prdx2 is a peroxiredoxin (Prx) family protein that protects cells from attack via reactive oxygen species (ROS), and it has an important role in improving the resistance and scavenging capacity of ROS in fungi. is a widespread nematode-trapping fungus that can produce three-dimensional nets to capture and kill nematodes. In this study, AoPrdx2, a homologous protein of Prx5, was investigated in via gene disruption, phenotypic analysis, and metabolomics.

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.

Identification of a transcription factor AoMsn2 of the Hog1 signaling pathway contributes to fungal growth, development and pathogenicity in Arthrobotrys oligospora.

Introduction: Arthrobotrys oligospora has been utilized as a model strain to study the interaction between fungi and nematodes owing to its ability to capture nematodes by developing specialized traps. A previous study showed that high-osmolarity glycerol (Hog1) signaling regulates the osmoregulation and nematocidal activity of A. oligospora.

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.

AoRab7A interacts with AoVps35 and AoVps41 to regulate vacuole assembly, trap formation, conidiation, and functions of proteasomes and ribosomes in Arthrobotrys oligospora.

Rab GTPases regulate vesicle trafficking in organisms and play crucial roles in growth and development. Arthrobotrys oligospora is a ubiquitous nematode-trapping (NT) fungus, it can form elaborate traps to capture nematodes. Our previous study found that deletion of Aorab7A abolished the trap formation and sporulation.

Cellular communication and fusion regulate cell fusion, trap morphogenesis, conidiation, and secondary metabolism in Arthrobotrys oligospora.

Signal-mediated cell fusion is vital for colony development in filamentous fungi. Arthrobotrys oligospora is a representative nematode-trapping (NT) fungus that produces adhesive networks (traps) to capture nematodes. Here, we characterized Aoadv-1, Aoso, Aoham-6, and Aoham-5 of A.

p21-activated kinase is involved in the sporulation, pathogenicity, and stress response of under the indirect regulation of Rho GTPase-activating protein.

The p21-GTPase-activated protein kinases (PAKs) participate in signal transduction downstream of Rho GTPases, which are regulated by Rho GTPase-activating proteins (Rho-GAP). Herein, we characterized two orthologous Rho-GAPs (AoRga1 and AoRga2) and two PAKs (AoPak1 and AoPak2) through bioinformatics analysis and reverse genetics in , a typical nematode-trapping (NT) fungus. The transcription analyses performed at different development stages suggested that and play a crucial role during sporulation and trap formation, respectively.

AoMedA has a complex regulatory relationship with AoBrlA, AoAbaA, and AoWetA in conidiation, trap formation, and secondary metabolism in the nematode-trapping fungus .

The asexual sporulation of filamentous fungi is an important mechanism for their reproduction, survival, and pathogenicity. In and several filamentous fungi, BrlA, AbaA, and WetA are the key elements of a central regulatory pathway controlling conidiation, and MedA is a developmental modifier that regulates temporal expression of central regulatory genes; however, their roles are largely unknown in nematode-trapping (NT) fungi. is a representative NT fungus, which can capture nematodes by producing adhesive networks (traps).

Fus3 regulates asexual development and trap morphogenesis in the nematode-trapping fungus .

Mitogen-activated protein kinase (MAPK) Fus3 is an essential regulator of cell differentiation and virulence in fungal pathogens of plants and animals. However, the function and regulatory mechanism of MAPK signaling in nematode-trapping (NT) fungi remain largely unknown. NT fungi can specialize in the formation of "traps", an important indicator of transition from a saprophytic to a predatory lifestyle.