Gene editing of a carcinogenic liver fluke tetraspanin impairs parasite surface biogenesis and extracellular vesicle uptake by human host cells.

Opisthorchiasis remains a significant public health concern throughout Southeast Asia. The liver fluke Opisthorchis viverrini resides within the biliary tract and chronic infection leads to bile duct cancer, or cholangiocarcinoma. Here, we examined the functions of liver fluke tetraspanins, four-transmembrane domain proteins expressed on the surface of the fluke tegument and extracellular vesicles (EVs) derived from this syncytial surface.

Highly stable Cas9 promotes HBV genome destruction by antagonizing HSC70-mediated degradation.

As a naturally-existing adaptive immune system of prokaryotes against phages and foreign genetic materials, CRISPR/Cas9 system has been widely used to combat with various viral infections. However, its ability to destroy the constantly replicating viral genome and subsequently clear viral infections still needs further improvement. This study found that Cas9 protein was mainly degraded through the chaperone mediated autophagy (CMA)-lysosome pathway in human cells, which was mediated by the binding between heat shock cognate protein 70 (HSC70) and Cas9 protein.

Reproductive Outcomes Following Open Maternal-Fetal Surgery for Myelomeningocele Closure: Analysis of MOMS Trial Participants.

Background: In utero closure of myelomeningocele has become an accepted alternative in the management of prenatally diagnosed spina bifida. Maternal reproductive risk has been previously described based on registry data and institutional outcomes. Here we aim to provide maternal reproductive outcomes from participants in the Management of Myelomeningocele Study.

Host Immune Response in Chronic Hepatitis Delta: Implications for Pathogenesis and Therapy.

Chronic hepatitis delta (CHD) represents the most severe form of viral hepatitis due to rapid disease progression towards liver cancer, leading to high morbidity and mortality. Hepatitis delta virus (HDV) can only infect individuals who are infected with hepatitis B. So far, there is no cure or vaccine for HDV.

A Genome-Wide Association Study of Circulating Serum Choline, Betaine, Dimethylglycine, and Their Ratios.

Genetic variation has been thought to alter the human dietary requirement for choline and subsequent circulating levels of its metabolites betaine and dimethylglycine (DMG). The aim of this genome-wide association study (GWAS) was to identify single nucleotide polymorphisms (SNPs) associated with serum choline, betaine, and dimethylglycine (DMG) as well as choline-to-betaine and betaine-to-DMG ratios. Data from the Collaborative Study of Genes, Nutrients and Metabolites (CSGNM; = 2402) were used to model individual associations of choline, betaine, and DMG circulating metabolites and their ratios with 680,975 SNPs, using linear regression.

Free vs. Local Tissue Transfer and Reconstruction in Pediatric Head and Neck Cancer Patients: A Comparable Complication Outcome Review.

: Reconstructive outcomes following head and neck (H&N) cancer resection in pediatric patients remain understudied, particularly regarding the comparative efficacy of free versus local tissue transfer. : A retrospective review was conducted on pediatric patients undergoing malignant H&N tumor resection at a tertiary center from 2007 to 2024. Patients were stratified by reconstruction type (free vs.

Sensory Circumventricular Organ Insulin Signaling in Cardiovascular and Metabolic Regulation.

Central nervous system (CNS) insulin signaling is involved in a broad array of cardiometabolic physiology, including glucose and lipid metabolism, feeding, energy expenditure, and blood pressure regulation. A key role for hypothalamic neuroendocrine and autonomic centers in regulating insulin-associated cardiovascular and metabolic physiology has been highlighted. However, it is still unclear which CNS site(s) initiate insulin-dependent neural cascades.

Gut-brain nexus: Mapping multimodal links to neurodegeneration at biobank scale.

Alzheimer's disease (AD) and Parkinson's disease (PD) are influenced by genetic and environmental factors. We conducted a biobank-scale study to (i) identify endocrine, nutritional, metabolic, and digestive disorders with potential causal or temporal associations with AD/PD risk before diagnosis; (ii) assess plasma biomarkers' specificity for AD/PD in the context of co-occurring gut related traits and disorders; and (iii) integrate multimodal datasets to enhance AD/PD prediction. Our findings show that several disorders were associated with increased AD/PD risk before diagnosis, with variation in the strength and timing of associations across conditions.

Synchronized dynamics of dengue across the Americas.

Dengue is endemic throughout the tropical areas of the Americas, but little is known about its regional dynamics. We examined seasonal and multiannual dengue trends across the Americas and possible underlying mechanisms using monthly dengue surveillance data from 14 countries. We collected monthly dengue case data from 241 subnational locations in 14 countries, ranging from 1985 to 2018 (6 to 22 years), and used wavelet analysis to isolate seasonal (8 to 16 months) and multiannual (17+ months) patterns.

Restoring a Healthy Relationship with Food by Decoupling Stress and Eating: A Translational Review of Nutrition and Mental Health.

Psychological stress and dietary behavior are interdependent forces that greatly influence mental and physical health. Thus, both what and how we eat impact our well-being. Maladaptive eating patterns, such as eating in response to emotional cues rather than physiological hunger, have become increasingly common amid modern stressors and an ultra-processed food environment.

Exploring Neutrophil Extracellular Traps in Cardiovascular Pathologies: The Impact of Lipid Profiles, PAD4, and Radiation.

Neutrophil extracellular traps (NET) have emerged as critical players in the pathogenesis of atherosclerosis and other cardiovascular diseases (CVD). These web-like structures, composed of DNA, histones, and granule proteins released by neutrophils, contribute significantly to both inflammation and thrombosis. This manuscript offers a comprehensive review of the recent literature on the involvement of NET in atherosclerosis, highlighting their interactions with various pathophysiological processes and their potential as biomarkers for CVD.

Eosinophils in Rheumatoid Arthritis: A Multifaceted Role in the Pathogenesis of the Disease.

Eosinophils are multifunctional granulocytes that contribute to the initiation and modulation of inflammation. Accumulating evidence suggests that eosinophils are adaptable leukocytes that orchestrate the resolution of inflammatory responses. The most prevalent chronic inflammatory illness, rheumatoid arthritis (RA), is typified by persistent synovitis that makes it hard for the disease to go away on its own.

What is the clinical evidence to support off-label rapamycin therapy in healthy adults?

Low dose rapamycin therapy has been proposed as a longevity candidate in healthy aging adults. We present a review of the evidence for low dose rapamycin and rapalog therapies in healthy human adults and model the findings of one cohort study using the PhenoAge model. Despite the preclinical evidence supporting the use of sirolimus to enhance mean and maximal lifespan, the data in humans have yet to establish that rapamycin, or its analogues, is a proven seno-therapeutic that can delay aging in healthy older adults.

Oxytocin Receptor Expression and Activation in Parasympathetic Brainstem Cardiac Vagal Neurons.

Autonomic imbalance-particularly reduced activity from brainstem parasympathetic cardiac vagal neurons (CVNs)-is a major characteristic of many cardiorespiratory diseases. Therapeutic approaches to selectively enhance CVN activity have been limited by the lack of defined, translationally relevant targets. Previous studies have identified an important excitatory synaptic pathway from oxytocin (OXT) neurons in the paraventricular nucleus of the hypothalamus to brainstem CVNs, suggesting that OXT could provide a key selective excitation of CVNs.

Comparative single-cell lineage tracing identifies distinct adipocyte precursor dynamics in skin and inguinal fat.

White adipose tissue supports essential physiological functions through adipocyte precursor cells (APCs), comprising progenitors and preadipocytes, which generate mature adipocytes during depot expansion. Using single-cell RNA sequencing-based lineage tracing, we characterize APCs in skin adipose tissue-a depot uniquely capable of rapid adipogenesis compared with other sites, such as inguinal adipose. We identify a previously uncharacterized population of immature preadipocytes and reveal distinct differentiation potentials among APCs.

Metabolism-Driven Colorimetric "Read-to-Answer" Sensor Array for Bacterial Discrimination and Antimicrobial Susceptibility Testing.

Due to the complexity of clinical samples, rapid and reliable bacterial identification and antimicrobial susceptibility testing (AST) remain challenging. To address these challenges, we developed a colorimetric sensing platform for bacterial identification and AST in clinical samples based on bacterial metabolism-driven synthesis of gold nanoparticles (AuNPs) via hydrogen peroxide (HO) mediation. In this strategy, bacteria metabolic differences among bacterial species were converted into distinct colorimetric signals.

Platelet and Fibrinogen Contribution to Clot Strength in Premature Neonates with Sepsis.

: Platelet transfusions are administered to preterm neonates with thrombocytopenia prophylactically to decrease their bleeding risk. The amplitude difference between the extrinsic rotational thromboelastometry (EXTEM) and the fibrinogen rotational thromboelastometry (FIBTEM) assays is considered an index of platelet contribution to clot strength, guiding transfusion management. The difference in maximum clot elasticity (MCE) (namely the platelet contribution to clot elasticity-MCEplatelet) is considered highly accurate.

From science to impact: Conserving ecological connectivity in large conservation landscapes.

Implementing ecological connectivity conservation in large landscapes requires cutting-edge science combined with consideration of ecological, socioeconomic, and cultural factors that collectively shape the outcomes of conservation efforts. We outline a theory of change (ToC) for connectivity conservation to improve the ecological condition of landscapes and biodiversity and the ecosystem services upon which humans depend. We review connectivity conservation efforts on four continents in large landscapes that span gradients of latitude, fragmentation, biodiversity value, socioeconomic characteristics, and the richness of data used to assess connectivity and target action.

Differential BACH1 Expression in Basal-like Breast Tumors of Black Women Identified via Immunohistochemistry.

BACH1 has been identified as a functional regulator of cancer metastasis and metabolic signaling in breast cancer cells. However, the clinical relevance of BACH1 expression in breast tumors remains poorly understood. Using a tissue microarray from a cohort of 130 patients, we assessed the expression of BACH1 and its known target gene, MCT1 (encoded by ), through immunohistochemistry (IHC).

Ecoregional distributions of the world's freshwater vertebrate species.

Large-scale conservation of biodiversity requires understanding how species are distributed around the world. The first global delineation of freshwater ecoregions (Abell et al. 2008) integrated hydrological boundaries and fish biogeographic patterns to recognize 426 distinctive zones.

Patent foramen ovale closure vs medical therapy in secondary prevention of stroke and TIA: A systemic review and meta-analysis.

Importance: Percutaneous Patent Foramen Ovale (PFO) closure reduces recurrent ischemic stroke and transient ischemic attack (TIA) in cryptogenic stroke patients. The publication of additional studies and the inclusion of a larger patient population necessitate an updated analysis to evaluate its efficacy and safety compared to medical therapies and across different age groups.

Objective: To compare the efficacy and safety of PFO closure versus medical therapy for the secondary prevention of stroke and TIA.

Reimagining Integrative Medicine Fellowship Core Competencies with a Health Equity Lens.

Integrative medicine (IM) fellowships have grown significantly over the past decade. This review examines gaps in the original IM competencies and key revisions aligned with the Accreditation Council for Graduate Medical Education (ACGME) domains, informed by a multi-phase stakeholder engagement process. A task force from the Academic Consortium for Integrative Medicine and Health conducted a systematic review of existing IM competencies, ACGME core competencies, and relevant Diversity, Equity, and Inclusion (DEI) frameworks.