Lactate dehydrogenase B deficiency-dependent hyperlactatemia coordinates with necroptosis to worsen septic liver and kidney injuries.

Hyperlactatemia is intimately correlated with severity and poor prognosis of patients with sepsis. However, little experimental evidence on this process is known. We report here that lactate dehydrogenase B (LDHB), the glycolytic enzyme that catalyzes conversion of lactate to pyruvate, is transcriptionally downregulated in blood samples of hyperlactatemic patients, while mice receiving lactate injection have reduced LDHB activity in liver and kidney.

Construction of Large-Scale Bioengineered Hair Germs and In Vivo Transplantation.

Hair follicle (HF) regeneration technology holds promise for treating hair loss, but creating a biomimetic structure that mimics the natural follicle microenvironment remains challenging. Here a novel bioengineered hair germ (BHG) is developed using thermodynamically incompatible mucopolysaccharides to enhance HF regeneration efficiency. Mucopolysaccharide-based hydrogels are synthesized by grafting amino and diethylamino groups (dihydroxyphenylalanine-grafted hyaluronic acid (HME) hydrogels) for rapid gelation and strong wetting adhesion.

Self-Supervised Anomaly Detection With Neural Transformations.

Data augmentation plays a critical role in self-supervised learning, including anomaly detection. While hand-crafted transformations such as image rotations can achieve impressive performance on image data, effective transformations of non-image data are lacking. In this work, we study learning such transformations for end-to-end anomaly detection on arbitrary data.

Diagnosis and treatment of a rare bilateral primary thyroid cancer: a case report.

Preoperative ultrasound examination of thyroid nodules is the most economical and effective screening method for diagnosing thyroid nodules. Fine-needle aspiration biopsy (FNAB) cytology guided by ultrasound has high sensitivity and specificity in distinguishing benign and malignant thyroid nodules. However, approximately 25% of thyroid nodules cannot be determined by FNAB, and accurate differentiation of benign and malignant thyroid nodules is critical for patient prognosis.

Neutrophil Depletion Reduced the Relative Abundance of Unsaturated Long-Chain Fatty Acid Synthesis Microbiota and Intestinal Lipid Absorption.

As immune cells, neutrophils serve as the first line of defense against infections; however, the mechanism by which neutrophils regulate lipid metabolism is unknown. The neutrophil depletion group was treated with 100 μg InVivoMAb anti-mouse Ly6G 6 times, whereas the control group mice were intraperitoneally injected with the same quantity of InVivoMAb rat IgG2a. Body fat content, triglycerides (TGs), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) in the jejunum and ileum, as well as 9 long-chain fatty acids (LCFAs) in the intestinal contents were significantly decreased.

A Chinese patient with cardiogenic stroke and warfarin resistance: a case report.

Background: Warfarin is the most commonly used oral anticoagulant drug in clinical practice due to its effective anticoagulant effect and low cost. Warfarin plays a crucial role in the anticoagulant treatment of patients with thrombotic diseases such as atrial fibrillation, heart valve replacement, and deep vein thrombosis. In general, low-dose warfarin can effectively achieve the optimal international normalized ratio (INR) for patients requiring anticoagulation therapy.

Impaired inflammatory resolution with severe SARS-CoV-2 infection in leptin knock out obese hamster.

Comorbidities, such as obesity, increase the risk of severe COVID-19. However, the mechanisms underlying severe illnesses in individuals with obesity are poorly understood. Here, we used gene-edited leptin knock out ( ) obese hamsters to establish a severe infection model.

Structural insights into prolactin-releasing peptide receptor signaling and G-protein coupling selectivity.

Prolactin-releasing peptide receptor (PrRPR), a notable member of the class A peptide-GPCR (G-protein-coupled receptor) family, regulates diverse physiology functions upon activation by PrRP. Herein, we reveal that PrRPR could engage with not only the G pathway but also the G pathway. We further resolve the structures of the PrRPR-G and PrRPR-G complexes using cryoelectron microscopy (cryo-EM), with PrRP31 as the endogenous ligand.

Hesperetin mitigates adipose tissue inflammation to improve obesity-associated metabolic health.

Metabolically unhealthy obesity (MUO) poses significant health risks, including increased susceptibility to type 2 diabetes and cardiovascular diseases. Hesperetin is a key bioactive compound found in citrus fruits. Previous studies have shown that hesperetin can correct metabolic abnormalities and mitigate the progression of various metabolic disorders, but the underlying mechanisms remain unclear.

Analysis of clinical characteristics and risk factors for patients with heat stroke in western China in 2022: a multicenter retrospective study.

Objectives: To analyzed the clinical characteristics and treatment modalities of heat stroke (HS) and to identify risk factors for a poor prognosis of HS and provide reference suggestions for its treatment and prevention.

Measurements And Main Results: We enrolled a total of 247 patients, with hypertension, diabetes, and psychosis being the top three comorbidities associated with HS. The incidence of HS was higher among males and older individuals.

Recent advances in PKC inhibitor development: Structural design strategies and therapeutic applications.

Protein kinase C (PKC) isozymes play critical roles in diverse cellular processes and are implicated in numerous diseases, including cancer, diabetes, and autoimmune disorders. Despite extensive research efforts spanning four decades, only one PKC inhibitor has received clinical approval, highlighting the challenges in developing selective and efficacious PKC-targeting therapeutics. Here we review recent advances in the development of small-molecule PKC inhibitors, focusing on structural design strategies, pharmacological activities, and structure-activity relationships.

Incidence and risk of endocrine and metabolic abnormalities linked to PARP inhibitors in solid tumors: a meta-analysis.

Background: Poly (ADP-ribose) polymerase inhibitors (PARPi) serve as crucial therapeutic agents in solid tumor treatment. Preclinical investigations suggest a potential protective function of PARPi against endocrine and metabolic impairments. Nevertheless, the existing body of evidence remains inconclusive on this aspect.

The neutrophil-lymphocyte ratio as a risk factor for all-cause mortality among individuals with resolved HBV infection: evidence from the NHANES 1999-2018.

Background: Inflammation is a critical component in the process of resolved hepatitis B virus (HBV) infection. The neutrophil-to-lymphocyte ratio (NLR) serves as a sensitive indicator of systemic inflammation and immune activation. Our study aimed to investigate the correlation between elevated NLR levels and the risk of all-cause mortality in patients with resolved HBV infection.

Comprehensive Identification of Gene Family in Oliv. and Functional Analysis of in Drought Tolerance.

The transcription factors in the ABA Response Element Binding (AREB) protein family were differentially regulated under multiple stress conditions; however, functional analyses of AREB in Oliv. had not been conducted previously. In the present study, the comprehensive identification of the gene family and the function of in response to drought stress in were elucidated.

Effects of silymarin on insulin resistance and sensitivity: A systematic review and meta-analysis of randomized controlled trials.

Objective: This study aims to evaluate the effect of silymarin on insulin resistance and insulin sensitivity through a systematic review and meta-analysis of randomized controlled trials (RCTs).

Methods: We searched PubMed, Embase, Web of Science, and Cochrane Library up to September 2024 for relevant RCTs. The intervention required silymarin supplementation for at least 4 weeks.

The Identification and Characterization of the Gene Family in Oliv. Heteromorphic Leaves Provide a Theoretical Basis for the Functional Study of .

Oliv. typically has four kinds of heteromorphic leaves: linear (Li), lanceolate (La), ovate (Ov) and broad ovate (Bo). Heteromorphic leaves help adapt to extreme desert environments and further contribute to protection against land desertification in Northwest China.

Multi Characteristic Analysis of Vascular Cambium Cells in Reveals Its Anti-Aging Strategy.

All multicellular organisms undergo senescence, but the continuous division of the vascular cambium in plants enables certain tree species to survive for hundreds or even thousands of years. Previous studies have focused on the development of the vascular cambium, but the mechanisms regulating age-related changes remain poorly understood. This study investigated age-related changes in the vascular cambium of trees aged 50 to 350 years.

A higher order PUF complex is central to regulation of C. elegans germline stem cells.

PUF RNA-binding proteins are broadly conserved stem cell regulators. Nematode PUF proteins maintain germline stem cells (GSCs) and, with key partner proteins, repress differentiation mRNAs, including gld-1. Here we report that PUF protein FBF-2 and its partner LST-1 form a ternary complex that represses gld-1 via a pair of adjacent FBF binding elements (FBEs) in its 3'UTR.

A two-sample Mendelian randomization study reveals the causal effects of statin medication on gut microbiota abundance in the European population.

Background: Observational studies have reported changes in gut microbiota abundance caused by long-term statin medication therapy. However, the causal relation between statin medication and gut microbiota subsets based on genetic variants remains unclear.

Methods: We used genome-wide association study (GWAS) data on statin medication from the FinnGen database and gut microbiota abundance GWAS data from the IEU OpenGWAS project.

The Impact of Immune Cells, Metabolites, Inflammatory Factors, and Circulating Proteins on Atopic Dermatitis: Insights from a Mendelian Randomization Study.

Background: The onset of atopic dermatitis (AD) is complex, and its specific pathological mechanisms have not yet been fully elucidated.

Methods: Using circulating multi-omics as the exposure factors and AD as the outcome, we conducted univariable MR analysis. The circulating multi-omics data included immunomics (731 immune cell types), proteomics (4907 plasma proteins), metabolomics (1400 metabolites and 486 additional metabolites), and 91 inflammatory factors.

Resveratrol: A Narrative Review Regarding Its Mechanisms in Mitigating Obesity-Associated Metabolic Disorders.

Resveratrol (RSV) is a naturally occurring astragalus-like polyphenolic compound with remarkable weight loss properties. However, the mechanism of RSV in treating obesity is unclear. In this narrative review, we explored electronic databases (PubMed) for research articles from 2021 to the present using the keywords "resveratrol" and "obesity".

A Nucleotide-Binding Domain Leucine-Rich Repeat Gene Regulates Plant Growth and Defense Against Chewing Herbivores.

Plant nucleotide-binding leucine-rich repeat immune receptor genes (NLRs) play an important role in plant defenses against pathogens, pathogenic nematodes, and piercing-sucking herbivores. However, little is known about their functions in plant defenses against chewing herbivores. Here, we identified a plasma membrane-localized coiled-coil-type NLR protein, OsPik-2-like, whose transcript levels were induced by the infestation of rice leaf folder (LF, ) larvae, and by treatment with mechanical wounding.

An improved sample selection framework for learning with noisy labels.

Deep neural networks have powerful memory capabilities, yet they frequently suffer from overfitting to noisy labels, leading to a decline in classification and generalization performance. To address this issue, sample selection methods that filter out potentially clean labels have been proposed. However, there is a significant gap in size between the filtered, possibly clean subset and the unlabeled subset, which becomes particularly pronounced at high-noise rates.

Blocking Adipocyte YY1 Decouples Thermogenesis From Beneficial Metabolism by Promoting Spermidine Production.

Unlabelled: The accumulation of mitochondria in thermogenic adipose tissue (i.e., brown and beige fat) increases energy expenditure, which can aid in alleviating obesity and metabolic disorders.