Improvement in XIa Selectivity of Snake Venom Peptide Analogue BF9-N17K Using P2' Amino Acid Replacements.

Coagulation factor XIa is a new serine-protease family drug target for next-generation anticoagulants. With the snake venom Kunitz-type peptide BF9 as the scaffold, we obtained a highly active XIa inhibitor BF9-N17K in our previous work, but it also inhibited the hemostatic target plasmin. Here, in order to enhance the selectivity of BF9-N17K toward XIa, four mutants, BF9-N17K-L19A, BF9-N17K-L19S, BF9-N17K-L19D, and BF9-N17K-L19K, were further designed using the P2' amino acid classification scanning strategy.

METTL3 alters AK3 RNA expression in an m6A-dependent manner to affect the proliferation and metastasis of hepatocellular carcinoma.

In recent years, the significance of N6-methyladenosine (m6A) modification in the process of tumorigenesis has garnered substantial attention from researchers in the field. Among the myriad of factors involved, METTL3, which functions as an m6A methyltransferase, has emerged as a critical player in this context. This enzyme has been shown to participate actively in the regulation of RNA stability and expression across a diverse array of tumors.

Differences in HDL-related coronary heart disease risk between individuals with and without diabetes.

Background And Aims: High-density lipoprotein (HDL) might lose atheroprotective functions in the presence of diabetes. We sought to examine associations of HDL cholesterol (HDL-C) and HDL particle (HDL-P) subclasses with risk of coronary heart disease (CHD) stratified by diabetes.

Methods: We included 393,516 participants (20,691 diabetics and 372,825 nondiabetics) from the UK Biobank.

Serum 25-hydroxyvitamin D concentrations, vitamin D receptor polymorphisms, and risk of infections among individuals with type 2 diabetes: a prospective cohort study.

Background: Evidence on the association between serum 25-hydroxyvitamin D [25(OH)D] and infections among patients with type 2 diabetes (T2D), a group susceptible to vitamin D deficiency and infections, is limited.

Objectives: We aimed to examine this association in individuals with T2D, and to evaluate whether genetic variants in vitamin D receptor (VDR) would modify this association.

Methods: This study included 19,851 participants with T2D from United Kingdom Biobank.

Associations Between Beverage Consumption and Risk of Microvascular Complications Among Individuals With Type 2 Diabetes.

Context: The relationship between the consumption of different beverages and the risk of microvascular complications in individuals with type 2 diabetes (T2D) is unclear.

Objective: To investigate the association of individual beverage consumption, including artificially sweetened beverages (ASBs), sugar-sweetened beverages (SSBs), tea, coffee, natural juice, and yogurt, with the risk of microvascular complications in adults with T2D.

Methods: This cohort study included 6676 participants with T2D who were free of macrovascular and microvascular complications at baseline in the UK Biobank.

Association of Ultraprocessed Food Consumption with Risk of Cardiovascular Disease Among Individuals with Type 2 Diabetes: Findings from the UK Biobank.

Scope: Among patients with diabetes, who have modified nutritional behavior and a higher risk of cardiovascular disease (CVD), the influence of ultraprocessed foods (UPFs) on CVD remains unknown. The study aims to evaluate the association between UPF intake and the risk of CVD among individuals with type 2 diabetes (T2D) and further examine the potential biological pathways linking the association.

Methods And Results: This study includes 5405 participants with T2D who provided at least one 24-h dietary recall from the UK Biobank study.

Cationicity Enhancement on the Hydrophilic Face of Ctriporin Significantly Reduces Its Hemolytic Activity and Improves the Antimicrobial Activity against Antibiotic-Resistant ESKAPE Pathogens.

The ESKAPE pathogen-associated antimicrobial resistance is a global public health issue, and novel therapeutic strategies are urgently needed. The short cationic antimicrobial peptide (AMP) family represents an important subfamily of scorpion-derived AMPs, but high hemolysis and poor antimicrobial activity hinder their therapeutic application. Here, we recomposed the hydrophilic face of Ctriporin through lysine substitution.

Function and Mechanism of Antiviral Wasp Venom Peptide Protopolybia-MP III and Its Derivatives against HSV-1.

Viruses are one of the leading causes of human disease, and many highly pathogenic viruses still have no specific treatment drugs. Therefore, producing new antiviral drugs is an urgent matter. In our study, we first found that the natural wasp venom peptide Protopolybia-MP III had a significant inhibitory effect on herpes simplex virus type 1 (HSV-1) replication by using quantitative real-time PCR (qPCR), Western blotting, and plaque-forming assays.

Correction: Immunoassay-aptasensor for the determination of tumor-derived exosomes based on the combination of magnetic nanoparticles and hybridization chain reaction.

[This corrects the article DOI: 10.1039/D0RA10159A.].

Loss of KLF15 impairs endometrial receptivity by inhibiting EMT in endometriosis.

The impaired endometrial receptivity is a major factor contributing to infertility in patients with endometriosis (EM), but the underlying mechanism remains unclear. Our study aimed to investigate the role of Kruppel-like factor 15 (KLF15) in endometrial receptivity and its regulation in EM. We observed a significant decrease in KLF15 expression in the mid-secretory epithelial endometrial cells of EM patients compared to normal females without EM.

Circulating concentrations of bile acids and prevalent chronic kidney disease among newly diagnosed type 2 diabetes: a cross-sectional study.

Background: The relationship between circulating bile acids (BAs) and kidney function among patients with type 2 diabetes is unclear. We aimed to investigate the associations of circulating concentrations of BAs, particularly individual BA subtypes, with chronic kidney disease (CKD) in patients of newly diagnosed type 2 diabetes.

Methods: In this cross-sectional study, we included 1234 newly diagnosed type 2 diabetes who participated in an ongoing prospective study, the Dongfeng-Tongji cohort.

Gut microbiota-derived secondary bile acids, bile acids receptor polymorphisms, and risk of cardiovascular disease in individuals with newly diagnosed type 2 diabetes: a cohort study.

Background: Secondary bile acids (SBAs), the products of bacterial metabolism, are ligands of the nuclear farnesoid X receptor (FXR) and have been implicated in cardiovascular health. Diet can modulate gut microbiota composition and bile acid metabolism.

Objectives: We aimed to examine the associations of circulating SBAs and their receptor polymorphisms with the risk of incident cardiovascular disease (CVD) among people with type 2 diabetes (T2D).

Modifiable Lifestyle Factors, Genetic Risk, and Incident Peripheral Artery Disease Among Individuals With Type 2 Diabetes: A Prospective Study.

Objective: To prospectively evaluate the association between modifiable lifestyle factors and peripheral artery disease (PAD) among individuals with type 2 diabetes (T2D).

Research Design And Methods: We included 14,543 individuals with T2D from the UK Biobank. We defined a weighted healthy lifestyle score using nonsmoking, regular physical activity, high-quality diet, moderate alcohol consumption, optimal waist-to-hip ratio, and adequate sleep duration, and categorized into unfavorable, intermediate, and favorable lifestyles.

Associations of Nut Consumption with All-Cause Mortality among Individuals with Type 2 Diabetes.

Background: Nuts are energy-dense, high-fat foods, and whether nut consumption influences mortality risk among individuals with type 2 diabetes (T2D) remains unclear.

Objectives: This study aimed to investigate the associations of nut consumption with all-cause mortality among adults with T2D and to further explore the potential mediation effects of cardiometabolic biomarkers.

Methods: The current analysis included 5090 US participants with T2D from the National Health and Nutrition Examination Survey (1999-2014).

Associations of Glucose Metabolism Status with Brain Macrostructure and Microstructure: Findings from the UK Biobank.

Context: Evidence linking glucose metabolism status with brain macro- and microstructure is limited and inconsistent.

Objective: We aim to investigate the associations of glucose metabolism status with brain macrostructure and microstructure, including brain volumes, subcortical gray matter volumes, and white matter microstructural metrics.

Methods: This study enrolled 29 251 participants from the UK Biobank.

Association of healthy sleep pattern with risk of recurrent cardiovascular events among patients with coronary heart disease.

Aims: To examine the association of a healthy sleep pattern with the risk of recurrent cardiovascular events among patients with coronary heart disease (CHD).

Methods And Results: This prospective cohort study included 21 193 individuals with CHD from the UK Biobank. A healthy sleep score was generated based on a combination of chronotype, sleep duration, insomnia, and excessive daytime sleepiness.

Associations of Clinical Risk Factors and Novel Biomarkers With Age at Onset of Type 2 Diabetes.

Context: Younger onset of type 2 diabetes (T2D) was associated with higher risks of vascular complications and mortality.

Objective: To prospectively assess risk profiles for incident T2D stratified by age at onset.

Methods: A total of 471 269 participants free of T2D at baseline were included from the UK Biobank.

Diets, Gut Microbiota and Metabolites.

The gut microbiota refers to the gross collection of microorganisms, estimated trillions of them, which reside within the gut and play crucial roles in the absorption and digestion of dietary nutrients. In the past decades, the new generation 'omics' (metagenomics, transcriptomics, proteomics, and metabolomics) technologies made it possible to precisely identify microbiota and metabolites and describe their variability between individuals, populations and even different time points within the same subjects. With massive efforts made, it is now generally accepted that the gut microbiota is a dynamically changing population, whose composition is influenced by the hosts' health conditions and lifestyles.

Associations of Serum 25(OH)D With Risk of Recurrent Cardiovascular Events in Individuals With Coronary Heart Disease.

Context: Few studies have examined the relationship between vitamin D and the risk of recurrent cardiovascular (CV) events in people with coronary heart disease (CHD).

Objective: This study aimed to investigate the associations of serum 25-hydroxyvitamin D (25(OH)D) concentration and the vitamin D receptor (VDR) polymorphisms with the risk of recurrent CV events in individuals with established CHD.

Methods: A total of 22 571 participants with CHD were included from the UK Biobank.