The transcriptional repressor HEY2 regulates mitochondrial oxidative respiration to maintain cardiac homeostasis.

Energy deprivation and metabolic rewiring of cardiomyocytes are widely recognized hallmarks of heart failure. Here, we report that HEY2 (a Hairy/Enhancer-of-split-related transcriptional repressor) is upregulated in hearts of patients with dilated cardiomyopathy. Induced Hey2 expression in zebrafish hearts or mammalian cardiomyocytes impairs mitochondrial respiration, accompanied by elevated ROS, resulting in cardiomyocyte apoptosis and heart failure.

L3MBTL3 and STAT3 collaboratively upregulate SNAIL expression to promote metastasis in female breast cancer.

The STAT3 pathway promotes epithelial-mesenchymal transition, migration, invasion and metastasis in cancer. STAT3 upregulates the transcription of the key epithelial-mesenchymal transition transcription factor SNAIL in a DNA binding-independent manner. However, the mechanism by which STAT3 is recruited to the SNAIL promoter to upregulate its expression is still elusive.

E3 ligase FBXW7 suppresses brown fat expansion and browning of white fat.

Thermogenic fat, including brown and beige fat, dissipates heat via thermogenesis and enhances energy expenditure. Thus, its activation represents a therapeutic strategy to combat obesity. Here, we demonstrate that levels of F-box and WD repeat domain-containing 7 (FBXW7), an E3 ubiquitin protein ligase, negatively correlate with thermogenic fat functionality.

Quorum sensing signals of the grapevine crown gall bacterium, sp. Rr2-17: use of inducible expression and polymeric resin to sequester acyl-homoserine lactones.

Background: A grapevine crown gall tumor strain, sp. strain Rr2-17 was previously reported to accumulate copious amounts of diverse quorum sensing signals during growth. Genome sequencing identified a single luxI homolog in strain Rr2-17, suggesting that it may encode for a AHL synthase with broad substrate range, pending functional validation.

Chromatin Topological Domains Associate With the Rapid Formation of Tandem Duplicates in Plants.

In eukaryotes, chromatin is compacted within nuclei under the principle of compartmentalization. On top of that, condensin II establishes eukaryotic chromosome territories, while cohesin organizes the vertebrate genome by extruding chromatin loops and forming topologically associating domains (TADs). Thus far, the formation and roles of these chromatin structures in plants remain poorly understood.

In vivo adenine base editing ameliorates Rho-associated autosomal dominant retinitis pigmentosa.

Mutations in the Rhodopsin (RHO) gene are the main cause of autosomal dominant retinitis pigmentosa (adRP), 84% of which are pathogenic gain-of-function point mutations. Treatment strategies for adRP typically involve silencing or ablating the pathogenic allele, while normal RHO protein replacement has no meaningful therapeutic benefit. Here, we present an adenine base editor (ABE)-mediated therapeutic approach for adRP caused by RHO point mutations in vivo.

The rat osteoarthritis bone score for histological pathology relevant to human bone marrow lesions and pain.

Objectives: Histological osteochondral characteristics of inflammation, fibrosis, vascularity, cartilage islands, vessels entering cartilage, thickened trabeculae and cysts are associated with bone marrow lesions (BMLs) in human knee osteoarthritis (OA). We identified and developed a method for scoring comparable pathology in two rat OA knee pain models.

Methods: Rats (n ​= ​8-10 per group) were injected with monoiodoacetate (MIA) or saline, or underwent meniscal transection (MNX) or sham surgery.

NPR1 promotes blue light-induced plant photomorphogenesis by ubiquitinating and degrading PIF4.

Light is a major determinant of plant growth and survival. NONEXPRESSER OF PATHOGENESIS-RELATED GENES 1 (NPR1) acts as a receptor for salicylic acid (SA) and serves as the key regulator of SA-mediated immune responses. However, the mechanisms by which plants integrate light and SA signals in response to environmental changes, as well as the role of NPR1 in regulating plant photomorphogenesis, remain poorly understood.

Supervised Screening of EGFR Inhibitors Validated through Computational Structural Biology Approaches.

One of the prominent challenges in breast cancer (BC) treatment is human epidermal growth factor receptor (EGFR) overexpression, which facilitates tumor proliferation and presents a viable target for anticancer therapies. This study integrates multiomics data to pinpoint promising therapeutic compounds and employs a machine learning (ML)-based similarity search to identify effective alternatives. We used BC cell line data from the Cancer Cell Line Encyclopedia (CCLE) and Genomics of Drug Sensitivity in Cancer (GDSC) databases and single-cell RNA sequencing (scRNA-seq) information that established afatinib as an efficacious candidate demonstrating superior IC values.

Age-associated accumulation of RAB9 disrupts oocyte meiosis.

The critical role of some RAB family members in oocyte meiosis has been extensively studied, but their role in oocyte aging remains poorly understood. Here, we report that the vesicle trafficking regulator, RAB9 GTPase, is essential for oocyte meiosis and aging in humans and mice. RAB9 was mainly located at the meiotic spindle periphery and cortex during oocyte meiosis.

β2-tubulin and its promoter in the brown planthopper: A versatile tool for genetic control strategies.

At present, the application of CRISPR/Cas9 technology for genetic manipulation in insects is predominantly concentrated on Diptera model species, including Drosophila and mosquitoes. In contrast, non-model insects such as the brown planthoppers (BPH, Nilaparvata lugens), a major insect pest of rice, have received less attention in genetic manipulation due to insufficient tools. Here, the analysis of spatiotemporal expression patterns revealed that β2-tubulin in BPH (NlB2t) was predominantly concentrated in male adults and male testis, exhibiting high expression levels.

Lipoprotein (a) in the Full Spectrum of MASLD; Evidence from Histologically and Genetically Characterized Cohorts.

Background And Aims: Lipoprotein(a) (Lp(a)) is an emerging biomarker for cardiometabolic factors. We studied the role of Lp(a) in the full spectrum of metabolic dysfunction-associated steatotic liver disease (MASLD).

Methods: Three independent analyses were implemented using a multi-center, cross-sectional, liver biopsy-based study (n=332) (Study 1) and the UK Biobank prospective study (n=270,004) (Study 2, median follow-up=12.

How to build the virtual cell with artificial intelligence: Priorities and opportunities.

Cells are essential to understanding health and disease, yet traditional models fall short of modeling and simulating their function and behavior. Advances in AI and omics offer groundbreaking opportunities to create an AI virtual cell (AIVC), a multi-scale, multi-modal large-neural-network-based model that can represent and simulate the behavior of molecules, cells, and tissues across diverse states. This Perspective provides a vision on their design and how collaborative efforts to build AIVCs will transform biological research by allowing high-fidelity simulations, accelerating discoveries, and guiding experimental studies, offering new opportunities for understanding cellular functions and fostering interdisciplinary collaborations in open science.

Design, synthesis, and biological evaluations of 5-aryl-pyrazole-3-carboxamide derivatives as selective CB2 receptor agonists for the treatment of colitis.

Synthetic CB2 receptor agonists exhibit great potential in the treatment of neurodegenerative diseases, chronic and neuropathic pain, cancer, and inflammation-associated pathologies while avoiding adverse psychoactive effects caused by interactions with CB1 receptors. Herein, a class of 5-aryl-pyrazole-3-carboxamide derivatives was thus designed, synthesized, and biologically evaluated. Among the compounds tested, compound 33, one of the most potent leads, showed a remarkably high potency and selectivity at the CB2 receptor (EC = 16.

TAM-Derived Exosomes Promote EMT by Upregulating lncRNA MIR4435-2HG in Head and Neck Cancer.

Objective: This study aimed to investigate the impact of tumor-associated macrophage (TAM)-derived exosomes on epithelial-mesenchymal transition (EMT) in head and neck squamous cell carcinoma (HNSCC) and the underlying mechanisms involved.

Subjects And Methods: Exosomes were isolated and characterized using transmission electron microscopy, nanoparticle size analysis, and western blotting. The effect on EMT in HNSCC cells was assessed using wound healing, transwell invasion, and EMT marker assays.

Diet-gut microbiome interaction and its impact on host blood glucose homeostasis: a series of nutritional n-of-1 trials.

Background: The interplay between diet and gut microbiome substantially influences host metabolism, but uncertainties remain regarding their relationships tailored for each subject given the huge inter-individual variability. Here we aim to investigate diet-gut microbiome interaction at single-subject resolution and explore its effects on blood glucose homeostasis.

Methods: We conducted a series of nutritional n-of-1 trials (NCT04125602), in which 30 participants were assigned high-carbohydrate (HC) and low-carbohydrate (LC) diets in a randomized sequence across 3 pair of cross-over periods lasting 72 days.

A visually-induced optogenetically-engineered system enables autonomous glucose homeostasis in mice.

With the global population increasing and the demographic shifting toward an aging society, the number of patients diagnosed with conditions such as peripheral neuropathies resulting from diabetes is expected to rise significantly. This growing health burden has emphasized the need for innovative solutions, such as brain-computer interfaces. brain-computer interfaces, a multidisciplinary field that integrates neuroscience, engineering, and computer science, enable direct communication between the human brain and external devices.

Intelligent identification of foodborne pathogenic bacteria by self-transfer deep learning and ensemble prediction based on single-cell Raman spectrum.

Foodborne pathogenic infections pose a significant threat to human health. Accurate detection of foodborne diseases is essential in preventing disease transmission. This study proposed an AI model for precisely identifying foodborne pathogenic bacteria based on single-cell Raman spectrum.

Screening and verification of differentially expressed serum proteins in children with severe adenovirus pneumonia.

Background: Human adenoviruses are prevalent pathogens that cause severe acute respiratory infections. The clinical presentation of the adenoviral pneumonia is varied; in severe cases, they may cause systemic multi-system damages. Currently, early clinical differential diagnosis is difficult under the existing testing methods, the study identified potential biomarkers by screening and validating differentially expressed proteins (DEPs), and aimed at distinguishing between severe and non-severe adenovirus pneumonia in children aged <14 years.