Structure and catalytic mechanism of exogenous fatty acid recycling by AasS, a versatile acyl-ACP synthetase.

Fatty acids (FAs) are essential building blocks for all the domains of life, of which bacterial de novo synthesis, called type II FA synthesis (FAS II), is energetically expensive. The recycling of exogenous FAs (eFAs) partially relieves the FAS II demand and, therefore, compromises the efficacy of FAS II-directed antimicrobials. The versatile acyl-acyl carrier protein (ACP) synthetase, AasS, enables bacterial channeling of diverse eFA nutrients through holo-ACP, an activated form of ACP.

Monitoring of single-nucleus chromatin landscape of ischemic stroke in mouse cerebral cortex across time.

Ischemic stroke constitutes a multifaceted neurological affliction that spans various cellular types. Lack of dynamic chromatin accessibility data after stroke is one of the obstacles to understanding this process. To gain insights into the variations in transcriptional regulation among various cell types subsequent to a stroke, we employed single-nucleus ATAC-seq to curate a chromatin accessibility compendium from the cerebral cortex of mice subjected to middle cerebral artery occlusion/reperfusion (MCAO/R).

LTX-315 is a novel broad-spectrum antimicrobial peptide against clinical multidrug-resistant bacteria.

Introduction: Infections stemming from multidrug-resistant bacteria present a substantial threat to public health today. Discovering or synthesizing novel compounds is crucial to alleviate this pressing situation.

Objective: The main purpose of this study is to verify the antibacterial activity of LTX-315 and explore its primary action mode.

Metallothionein rescues doxorubicin cardiomyopathy via mitigation of cuproptosis.

Doxorubicin (DOX), a chemotherapeutic agent utilized in the management of cancer, provokes cardiotoxicity although effective remedy is lacking. Given that DOX provokes oxidative stress and cell death in cardiomyocytes, this study evaluated the possible involvement of cuproptosis, a newly identified form of cell death, in DOX-instigated cardiac remodeling and contractile dysfunction, alongside the impact of the heavy metal scavenger metallothionein (MT) on DOX cardiomyopathy. Cardiac-specific MT transgenic and wild-type (WT) mice were treated with DOX (5 mg/kg/wk.

Qwen-2.5 Outperforms Other Large Language Models in the Chinese National Nursing Licensing Examination: Retrospective Cross-Sectional Comparative Study.

Background: Large language models (LLMs) have been proposed as valuable tools in medical education and practice. The Chinese National Nursing Licensing Examination (CNNLE) presents unique challenges for LLMs due to its requirement for both deep domain-specific nursing knowledge and the ability to make complex clinical decisions, which differentiates it from more general medical examinations. However, their potential application in the CNNLE remains unexplored.

Flap endonuclease 1 repairs DNA-protein cross-links via ADP-ribosylation-dependent mechanisms.

DNA-protein cross-links (DPCs) are among the most detrimental genomic lesions. They are ubiquitously produced by formaldehyde (FA), and failure to repair FA-induced DPCs blocks chromatin-based processes, leading to neurodegeneration and cancer. The type, structure, and repair of FA-induced DPCs remain largely unknown.

Flexible Site-Specific Labeling-Mediated Self-Assembly Sensor Based on Quantum Dots and LUMinescent AntiBody Sensor for Duplexed Detection of Antibodies.

Over recent years, the LUMinescent AntiBody Sensor (LUMABS) system, utilizing bioluminescence resonance energy transfer (BRET), has emerged as a highly effective method for antibody detection. This system incorporates NanoLuc (Nluc) as the donor and fluorescent protein (FP) as the acceptor. However, the limited Stokes shift of FP poses a challenge, as it leads to significant spectral cross-talk between the excitation and emission spectra.

Best Evidence Summary for the Improvement and Management of Disorders of Consciousness in Patients With Severe Brain Injury.

Background And Purpose: The treatment effect of consciousness after brain injury is currently uncertain. Thus, this study aimed to retrieve the evidence from neurologists around the world on the management of consciousness disorders in patients with severe brain injury and evaluate and summarize the evidence, providing the guidance on the related management for clinicians.

Methods: Following the evidence summary report standard of Fudan University Center for Evidence-Based Nursing, clinical guidelines, expert consensuses, systematic reviews, and evidence summaries were systematically retrieved from UpToDate; BMJ Best Practice; Guidelines International Network; the Cochrane Library; Embase; PubMed; Sinomed; Web of Science; CNKI; WanFang database; American Academy of Neurology (AAN); American Congress of Rehabilitation Medicine (ACRM); European Academy of Neurology; and National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR).

Integrated bioinformatics analysis and experimental validation of exosome-related gene signature in steroid-induced osteonecrosis of the femoral head.

Background: Steroid-induced osteonecrosis of the femoral head (SIONFH) is a universal hip articular disease and is very hard to perceive at an early stage. The understanding of the pathogenesis of SIONFH is still limited, and the identification of efficient diagnostic biomarkers is insufficient. This research aims to recognize and validate the latent exosome-related molecular signature in SIONFH diagnosis by employing bioinformatics to investigate exosome-related mechanisms in SIONFH.

Impact of RSVpreF vaccination on reducing the burden of respiratory syncytial virus in infants and older adults.

Respiratory syncytial virus (RSV) causes a substantial health burden among infants and older adults. Prefusion F protein-based vaccines have shown high efficacy against RSV disease in clinical trials, offering promise for mitigating this burden through maternal and older adult immunization. Employing an individual-based model, we evaluated the impact of RSV vaccination on hospitalizations and deaths in 13 high-income countries, assuming that the vaccine does not prevent infection or transmission.

Chemically engineered antibodies for autophagy-based receptor degradation.

Cell surface receptor-targeted protein degraders hold promise for drug discovery. However, their application is restricted because of the complexity of creating bifunctional degraders and the reliance on specific lysosome-shuttling receptors or E3 ubiquitin ligases. To address these limitations, we developed an autophagy-based plasma membrane protein degradation platform, which we term AUTABs (autophagy-inducing antibodies).

Sugemule-7 alleviates oxidative stress, neuroinflammation, and cell death, promoting synaptic plasticity recovery in mice with postpartum depression.

Postpartum depression (PPD) profoundly impacts the mental and physical health of women globally and is an incurable psychological disorder. Traditional pharmacological treatments often have strong side effects and may adversely affect infant health through breastfeeding, underscoring the critical need for natural and gentle treatment strategies. Sugemule-7, a traditional Chinese medicine comprising multiple natural plant ingredients, represents a potentially safer and more effective alternative.

Gaps in knowledge and management of iron deficiency in heart failure: a nationwide survey of cardiologists in China.

Background: Heart failure (HF) guidelines recommend routine testing for iron deficiency (ID) and, for those with ID, intravenous iron if the left ventricular ejection fraction is <50%. Guideline adherence to these recommendations by cardiologists in China is unknown.

Methods And Results: An independent academic web-based survey was designed and distributed via social networks to cardiologists across China.

Site-Specific Molecular Engineering of Nanobody-Glucoside Conjugates for Enhanced Brain Tumor Targeting.

Nanobodies play an increasingly prominent role in cancer imaging and therapy. However, their efficacy is often constrained by inadequate tumor penetration and rapid clearance from the bloodstream, particularly in brain tumors due to the intractable blood-brain barrier (BBB). Glycosylation is a favorable strategy for modulating the biological functions of nanobodies, including permeability and pharmacokinetics, but it also leads to heterogeneous glycan structures, which affect the targeting ability, stability, and quality of nanobodies.

CAGI6 ID panel challenge: assessment of phenotype and variant predictions in 415 children with neurodevelopmental disorders (NDDs).

The Genetics of Neurodevelopmental Disorders Lab in Padua provided a new intellectual disability (ID) Panel challenge for computational methods to predict patient phenotypes and their causal variants in the context of the Critical Assessment of the Genome Interpretation, 6th edition (CAGI6). Eight research teams submitted a total of 30 models to predict phenotypes based on the sequences of 74 genes (VCF format) in 415 pediatric patients affected by Neurodevelopmental Disorders (NDDs). NDDs are clinically and genetically heterogeneous conditions, with onset in infant age.

Metal-Catalyzed Abiotic Cleavage of C═C Bonds for Effective Fluorescence Imaging of Cu(II) and Fe(III) in Living Systems.

Imaging abnormal copper/iron with effective fluorescent tools is essential to comprehensively put insight into many pathological events. However, conventional coordination-based detection is mired in the fluorescence quenching induced by paramagnetic Cu(II)/Fe(III). Moreover, the strong chelating property of the probe will consume dissociative metal ions and inevitably interfere with the physiological microenvironment.

Identification of key risk areas and failure modes using the FMEA method for the prevention and control of major infectious diseases in a stomatology department.

Purpose: To perform risk assessment and analysis of potential infection during stomatology workflow in a hospital in the context of a major infectious disease outbreak, and to determine the key failure modes and measures to prevent and control infection.

Method: Following the Failure Modes and Effects Analysis (FMEA) method based on the stomatology workflow, the opinions of 30 domain-experts in related fields were collected through questionnaires to determine all potential failure modes in the severity (S), occurrence (O), and detectability (D) dimensions. The group score was then integrated through the median method and the risk priority number (RPN) was obtained.

A generalist medical language model for disease diagnosis assistance.

The delivery of accurate diagnoses is crucial in healthcare and represents the gateway to appropriate and timely treatment. Although recent large language models (LLMs) have demonstrated impressive capabilities in few-shot or zero-shot learning, their effectiveness in clinical diagnosis remains unproven. Here we present MedFound, a generalist medical language model with 176 billion parameters, pre-trained on a large-scale corpus derived from diverse medical text and real-world clinical records.

The gut-brain axis underlying hepatic encephalopathy in liver cirrhosis.

Up to 50-70% of patients with liver cirrhosis develop hepatic encephalopathy (HE), which is closely related to gut microbiota dysbiosis, with an unclear mechanism. Here, by constructing gut-brain modules to assess bacterial neurotoxins from metagenomic datasets, we found that phenylalanine decarboxylase (PDC) genes, mainly from Ruminococcus gnavus, increased approximately tenfold in patients with cirrhosis and higher in patients with HE. Cirrhotic, not healthy, mice colonized with R.

EBP1 potentiates amyloid β pathology by regulating γ-secretase.

The abnormal deposition of amyloid β (Aβ), produced by proteolytic cleavage events of amyloid precursor protein involving the protease γ-secretase and subsequent polymerization into amyloid plaques, plays a key role in the neuropathology of Alzheimer's disease (AD). Here we show that ErbB3 binding protein 1 (EBP1)/proliferation-associated 2G4 (PA2G4) interacts with presenilin, a catalytic subunit of γ-secretase, inhibiting Aβ production. Mice lacking forebrain Ebp1/Pa2g4 recapitulate the representative phenotypes of late-onset sporadic AD, displaying an age-dependent increase in Aβ deposition, amyloid plaques and cognitive dysfunction.

Exploring the potential association between serum selenium and hypertension in obese adult males in the United States.

Previous studies on the correlation between serum selenium and hypertension have yielded inconsistent results. Our previous analysis of participants from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 indicated that elevated serum selenium concentrations were associated with an increased risk of metabolic abnormalities in obese individuals, with the primary effect being on blood pressure in males. The aim of this study was to further elucidate the relationship between serum selenium and the risk of hypertension in obese males.

Differences in utilization and metabolism of Ulva lactuca polysaccharide by human gut Bacteroides species in the in vitro fermentation.

Ulva lactuca polysaccharide (ULP), a sulfated polysaccharide, has been widely used in Asia. However, its digestion process and utilization by gut microbiota remain poorly understood. In this study, the in vitro simulated digestion and fermentation were used to analyze the digestibility of ULP.

Antioxidant taurine inhibits chondrocyte ferroptosis through upregulation of OGT/Gpx4 signaling in osteoarthritis induced by anterior cruciate ligament transection.

Objective: The aim of this study was to investigate the potential molecular mechanisms by which taurine protects against cartilage degeneration.

Methods: The anterior cruciate ligament transection (ACLT) surgery was used to construct an animal model of osteoarthritis (OA). Metabolomics was used to identify characteristic metabolites in osteoarthritic chondrocytes.

Chromosome-level echidna genome illuminates evolution of multiple sex chromosome system in monotremes.

Background: A thorough analysis of genome evolution is fundamental for biodiversity understanding. The iconic monotremes (platypus and echidna) feature extraordinary biology. However, they also exhibit rearrangements in several chromosomes, especially in the sex chromosome chain.

Artificially tagging tumors with nano-aluminum adjuvant-tethered antigen mRNA recruits and activates antigen-specific cytotoxic T cells for enhanced cancer immunotherapy.

T cell therapy for solid tumors faces significant challenges due to the immune off-target attack caused by the loss of tumor surface antigens and inactivation in acidic tumor microenvironment (TME). Herein, we developed a bifunctional immunomodulator (MO@NAL) by loading ovalbumin (OVA; model antigen) mRNA (mOVA) onto lysozyme-coated layered double hydroxide nano-aluminum adjuvant (NA). The NA's inherent alkalinity effectively neutralizes the excess acid within the TME and suppresses regulatory T cells, creating a favorable microenvironment to enhance cytotoxic T cell infiltration and activation in tumors.