Bovis calculus sativus improves cognitive function after ischemic stroke by regulating PKA/CREB/Sirt1/eIF2α signaling pathway.

Ethnopharmacological Relevance: Bovis calculus sativus (BCS) is a traditional medicinal agent known for its pharmacological properties, which include heat-clearing, mental faculty revitalization, liver-cooling, and anticonvulsant effects. It is widely used application in the treatment of ischemic stroke accompanied by cognitive impairment; however, further research is necessary to clarify its effects and underlying mechanisms.

Aim Of The Study: This study examined the therapeutic potential of BCS in mitigating ischemic stroke-induced cognitive impairment induced by ischemic stroke, focusing on its mechanism of action in enhancing synaptic plasticity via the PKA/CREB/Sirt1/eIF2α signaling pathway.

α-Ketoglutarate dictates AMPK protein synthesis for energy sensing in human cancers.

The energy sensor AMP-activated protein kinase (AMPK) promotes tumor cell survival under stress but how to prevent AMPK activation to blunt tumor progression remains unclear. Here we show that the metabolite α-ketoglutarate (α-KG) dictates AMPK translation through a TET-YBX1 axis, which can be exploited to sensitize human cancer cells to energy stress. α-KG-deficient cells fail to activate AMPK under glucose starvation, which elicits cytosolic NADPH depletion and disulfidptosis.

Defined human tri-lineage brain microtissues.

Microglia are the immune cells of the central nervous system and are thought to be key players in both physiological and disease conditions. Several microglial features are poorly conserved between mice and human, such as the function of the neurodegeneration-associated immune receptor Trem2. Induced pluripotent stem cell (iPSC)-derived microglia offer a powerful opportunity to generate and study human microglia.

Protocol for elucidating metabolite binding and regulation of TET2 dioxygenase.

Epigenetic enzyme activity is coupled to cellular metabolism through their reliance on metabolic cofactors and substrates. Here, we describe steps for combining biochemical assays and saturation transfer difference (STD) NMR spectroscopy to experimentally validate metabolite binding and assess the effect on TET2 activity. This protocol enables the identification of both TET2 activators and inhibitors, providing a framework for studying the interplay between metabolism and epigenetic regulation.

Development and Validation of Survival Prediction Models for Patients With Pineoblastomas Using Deep Learning: A SEER-Based Study.

Purpose: Pineoblastomas (PBs) are rare central nervous system tumors primarily affecting children and adolescents, with limited data on clinical characteristics and survival outcomes. Prognosis prediction models for this disease are lacking. The purpose of this study was to develop deep learning (DL) models for predicting 3-year survival in patients with pineoblastoma.

Roles of JUN and MMP1 in lung cancer brain metastases.

Lung cancer brain metastases refer to intracranial space-occupying lesions formed by the metastasis of tumor cells from the lung to the brain parenchyma or dissemination in the meninges. The datasets GSE200563 and GSE126548 for lung cancer brain metastasis were obtained from gene expression omnibus database with the platform files GPL21697 and GPL16791. Differentially expressed genes analysis was conducted, followed by weighted gene co-expression network analysis, construction and analysis of protein-protein interaction networks, functional enrichment analysis, gene set enrichment analysis, comparative toxicogenomics database analysis.

Facile synthesis and biological evaluation of [a]-benzannulated BODIPY derivatives as novel heavy-atom-free photosensitizers for photodynamic anticancer therapy.

Boron dipyrromethenes (BODIPYs) have garnered significant attention for their broad applications in photodynamic anticancer therapy. However, the development of these materials remains a challenging task, partially due to their low singlet oxygen (O) quantum yield usually require incorporating heavy atoms and high laser power density to produce thermal energy and synergistically enhance photodynamic therapy (PDT). Concerns about potential dark toxicity of heavy atoms and the strong photothermal radiation causing acute pain significantly reduces patient compliance, hinders the broader clinical application of PDT.

Genetic landscape of hereditary cardiomyopathies and arrhythmias in China.

Hereditary cardiomyopathies and arrhythmias are major contributors to cardiovascular morbidity and mortality. The advent of next-generation sequencing (NGS) has made genetic testing more accessible, which is crucial for precise diagnosis and targeted therapeutic strategies. The aim of this study is to explore the landscape of genetic variants, the relationship between specific variants and clinical phenotypes, and the impact on clinical decision-making in China.

Comparative analysis of artificial intelligence tools for the dissemination of colorectal cancer screening guidelines: a novel perspective on early screening education.

This study systematically evaluated the effectiveness of three artificial intelligence (AI) tools-ChatGPT-4o, Claude3.5, and DeepSeek-in disseminating colorectal cancer screening guidelines to non-medical populations. Using uniform instructions aligned with the Chinese society of clinical oncology 2024 standards, the AI-generated content was analyzed for accuracy, clarity, and rigor, supplemented by a cross-evaluation mechanism to quantify performance.

Exploring the effects of food by-product HMF on pepsin structure, function, and physiological activity from a binding perspective.

5-Hydroxymethylfurfural (HMF) derived from the Maillard reaction poses significant health risks including neurotoxicity and carcinogenicity. Upon ingestion with food, HMF can interact with pepsin, a pivotal enzyme in the human digestive system. This study explores their interactions and examines the impact of these interactions on the conformation and function of pepsin.

Automated ejection fraction and risk stratification in cardiomyopathy patients with diverse LV geometry using 2D echocardiography.

Cardiomyopathy often alters left ventricular geometry (LVG), impairing cardiac function. We developed a deep learning (DL) model to estimate left ventricular ejection fraction (LVEF) from echocardiographic images while accounting for LVG variability and assessed prognostic factors across LVG subtypes. For all patients with cardiomyopathy, we computed LV volume on apical two- and four-chamber views processed with novel DeepLabV3+ algorithm and calculate EF using Simpson's method.

Research Waste in Temporomandibular Disorders Among Registered Randomised Controlled Trials: A Meta-Epidemiologic Study.

Background: Temporomandibular disorders (TMDs) are multifactorial conditions with diverse clinical presentations, making standardised treatment approaches difficult to establish. Despite an increasing number of randomised controlled trials (RCTs) globally, methodological inconsistencies and research waste remain significant obstacles to evidence integration.

Objective: This study systematically analysed 103 TMDs-related RCTs registered on ClinicalTrials.

Association of cross-life-cycle body size and genetic risk with cardio-renal-metabolic conditions in adulthood: evidence from a prospective cohort study.

Background: The aim of this study was to investigate the longitudinal associations between the body size trajectory and the cardio-renal-metabolic (CRM) conditions in adulthood, and evaluate the joint association between body size trajectory and polygenic risk scores (PRS) of CRM conditions.

Methods: This prospective cohort study included 441 470 UK Biobank participants aged 40 to 70 years, recruited between March 2006 and July 2010. CRM conditions were defined as the occurrence of any of cardiovascular disease (CVD), chronic kidney disease (CKD), and type 2 diabetes (T2D).

Nitrate supplementation affects taste by changing the oral metabolome and microbiome.

Nitrate, an inorganic anion found in various foods is also present in saliva and has emerged as a potential prebiotic for the oral microbiome. Salivary glands concentrate nitrate from the bloodstream and release it into the oral cavity via the anion transporter sialin SLC17A5. In previous studies dietary nitrate supplementation altered oral bacteria composition, favouring genera like Rothia and Neisseria while reducing Streptococcus, Veillonella, Prevotella, and Actinomyces.

Sevoflurane: A dual modulator of miR‑211‑5p and mitochondrial apoptosis in glioma therapy.

The present study aimed to investigate how sevoflurane (SEV) regulated the apoptosis of glioma cells through the mitochondrial apoptosis pathway. First, an evaluation was performed on the viability, apoptosis, mitochondrial reactive oxygen species levels, mitochondrial membrane potential and apoptosis and autophagy‑related protein expression of glioma cells according to experimental groups. Next, the expression of microRNA‑211‑5p (miR‑211‑5p), silent information regulator 1 (SIRT1) and phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (AKT) signaling pathway was detected by reverse transcription‑quantitative PCR or western blotting.

Structural and functional alterations of human serum albumin (HSA) induced by TBBPS-BME: A spectroscopic, computational, and molecular dynamics study.

Tetrabromobisphenol S Dimethyl Ether (TBBPS-BME) serves as a substitute for Tetrabromobisphenol A (TBBPA). It exhibits a greater potential for bioaccumulation, potentially posing substantial risks to environmental health and human safety. This research utilized a variety of spectroscopic and computational modeling methods to investigate structural and functional alterations of human serum albumin (HSA) induced by TBBPS-BME.

ANXA11 biomolecular condensates facilitate protein-lipid phase coupling on lysosomal membranes.

Phase transitions of cellular proteins and lipids play a key role in governing the organisation and coordination of intracellular biology. Recent work has raised the intriguing prospect that phase transitions in proteins and lipids can be co-regulated. Here we investigate this possibility in the ribonucleoprotein (RNP) granule-ANXA11-lysosome ensemble, where ANXA11 tethers RNP granules to lysosomal membranes to enable their co-trafficking.

Prognostic significance of alterations in peripheral cellular and humoral immune biomarkers during radiochemotherapy in head and neck cancer patients.

Background: The impacts of radiochemotherapy on peripheral blood cell and lymphocyte cell counts, immunoglobulin (Ig) and complement levels remain unclear. This study aims to investigate the above parameters regulated by radiotherapy (RT), induction chemotherapy (ICT) and concurrent chemotherapy (CCT) in head and neck cancer (HNC) patients.

Methods: Patients with non-metastatic HNC treated by conventional intensity-modulated radiation therapy (IMRT) were enrolled in this study.

CD19-targeted HSP90 inhibitor nanoparticle combined with TKIs reduces tumor burden and enhances T-cell immunity in murine B-cell malignancies.

Conventional chemotherapies for B-cell malignancies are often limited by drug resistance and significant side effects due to non-specific targeting. This research aimed to improve treatment efficacy by developing nano-delivery systems that specifically target tumor cells, thereby enhancing therapeutic precision and reducing off-target toxicity. The construction, biocompatibility, and targeting capability of CD19@NP/17-DMAG were evaluated using TEM, HPLC, FTIR spectroscopy, CCK-8 assay, flow cytometry (FC), and IVIS imaging.

Pathogen-derived glyoxylate inhibits Tet2 DNA dioxygenase to facilitate bacterial persister formation.

Pathogenic bacterial persistence enables survival during antibiotic treatment, leading to treatment failure and recurrent infections, yet its underlying mechanisms remain unclear. Here, we reveal that glyoxylate, a metabolite originally evolved for alternative carbon utilization, functions as a signaling molecule to reprogram the host transcriptome and promote persister formation. Glyoxylate inhibits the DNA dioxygenase TET2, suppressing pro-inflammatory gene expression and attenuating host immune defense.

Molecular insight on conformational alterations and functional changes of acetylcholinesterase induced by an emerging environmental pollutant 6PPD-quinone.

The emerging pollutant N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-quinone) has attracted broad attention because of its widespread presence and harmful impacts, including hepatotoxicity and neurotoxicity. Acetylcholinesterase (AChE) is commonly used as a classical biomarker for assessing toxicity in the nervous system. Here, the interaction mechanism between AChE and 6PPD-quinone was investigated using a combination of multispectral and computational approaches, including enzyme activity assay, fluorescence thermodynamic titration, circular dichroism (CD) spectroscopy, molecular dynamics (MD) simulation, computational alanine scanning (CAS), and free energy landscape (FEL) analysis, among others.

Molecular mechanism of interaction between SHORT VEGETATIVE PHASE and APETALA1 in Arabidopsis thaliana.

Point mutations were introduced into specific leucine (L) amino acids within the K domain of SHORT VEGETATIVE PHASE (SVP), and their effects on the SVP-AP1 interaction were assessed. Yeast two-hybrid experiments and β-galactosidase activity assays demonstrated that SVP maintained its capacity to interact with APETALA1 (AP1) despite point mutations at the 108th, 116th, 119th, and 127th leucine residues, where leucine was substituted with alanine (A). However, the mutation of the leucine residue at position 124 to alanine abolished the interaction between SVP and AP1 regardless of whether the mutation was singular or combined with others.

Associations between oral behaviors, temporomandibular disorder subtypes and psychological distress in adult women: a retrospective case-control study.

Oral behaviors and psychological distress are known to be related to temporomandibular disorders (TMDs). However, the relationship between various oral behaviors and specific TMD subgroups in adult women experiencing psychological distress is still unclear. To investigate the relationship between various oral behaviors and different TMD subgroups with different psychological distress states.

Simplified Jaw Functional Limitation Scale for Temporomandibular Disorders: Psychometric Evaluation.

Objective: This study aimed to simplify the Jaw Functional Limitation Scale (JFLS) and evaluate its reliability and validity in assessing jaw function in patients with temporomandibular disorders (TMD) in primary care.

Methods: TMD patients and non-TMD participants were assessed using Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). Demographic data and the 8-item JFLS questionnaire were collected to quantify jaw functional restriction.