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Chemical pollution is a global threat to human health, yet the toxicity mechanisms of most contaminants remains unknown. Here, we applied an ultrahigh-throughput affinity selection-mass spectrometry (AS-MS) platform to systematically identify protein targets of prioritized chemical contaminants. After benchmarking the platform, we screened 50 human proteins against 481 prioritized chemicals, including 446 ToxCast chemicals and 35 per- and polyfluoroalkyl substances (PFAS). Among 24,050...

Microplastics are complex contaminants, potentially posing both a physical and chemical risk to aquatic organisms. To better understand the physical and chemical impacts of microplastics, we conducted a large in situ pelagic mesocosm experiment in a freshwater boreal lake at the International Institute for Sustainable Development-Experimental Lakes Area. An equal mixture of polyethylene, polystyrene, and polyethylene terephthalate fragments with and without chemical additives were added to...

Alcoholic hepatitis (AH) is an acute form of alcohol-associated liver disease with very few treatment options. Recent studies highlighted liver metabolic reprogramming in AH as an indicator of severity. We aim at identifying new intervention points to reverse liver metabolic dysregulation across varying degrees of AH. We develop 89 personalized genome-scale metabolic models by integrating a generic human cellular metabolic model with liver transcriptomics data from AH patients with varying...

BACKGROUND: Antibiotic misuse is a key driver of antimicrobial resistance globally, with high rates of inappropriate use observed in rural China. We evaluated the effectiveness of a comprehensive package based on quantified point-of-care testing (POCT) for C-reactive protein and serum amyloid A (CRP&SAA) in reducing inappropriate antibiotic use for acute respiratory infections (ARIs) in village clinics in rural China.

Diagnosing lymphoma traditionally relies on invasive tissue biopsies, which can yield insufficient material for histopathological evaluation and carry a risk of complications. Minimally invasive assessment of cell-free DNA (cfDNA) in plasma offers a promising alternative for lymphoma detection that could aid the rapid evaluation of malignant vs. benign lymphadenopathy. Here, we examine the methylome of plasma samples from 165 lymphoma patients and 47 controls using cell-free methylated DNA...

Fungal pathogens pose an increasing threat to human health. The limited diversity of antifungal drug classes and the rapid emergence of resistance highlight the urgent need for the identification and development of agents with novel mechanisms of action. Here, we identified NPD2560, a coumarin-derived compound, as an antifungal agent that exhibits fungicidal activity against Candida krusei, a clinically challenging non-albicans Candida species often associated with treatment failure....

CONCLUSIONS: These findings enhance our understanding of how early life factors, particularly LTRAU, and genetic factors synergistically affect AR risk, offering valuable insights for prevention and treatment strategies.

CONCLUSION: This study provides the first longitudinal mapping of clinical and neural trajectories in an RCT of EEG-NFB for PTSD, demonstrating early stabilization of response and identifying neural mechanisms associated with symptom improvement. These findings may inform the optimization of EEG-NFB protocols and support its role as an adjunctive, symptom-stabilizing scaffold for psychotherapy.

CONCLUSION: This is the largest multinational study to date evaluating the incidence and risk factors for the development of a femoral nerve palsy in these children. The incidence of femoral nerve palsy was 3.1%. The severity of DDH was identified as a significant risk factor for its development. The use of a Pavlik harness was significantly associated with the development of a femoral nerve palsy. Understanding the factors which influence its development will be important to optimize outcomes...

We present Orobas, a computational approach for transforming raw read count data from CRISPR-Cas9 chemical-genetic screens into quantitative interaction scores. We describe steps for computing differential interaction scores with statistical tests that account for multiple CRISPR guides per gene. We then outline approaches for post-processing differential log(2)-fold-change scores across multiple screens, incorporating normalization to reduce technical artifacts and correct batch effects.

STUDY QUESTION: Is the hydrolase ABHD2 required for progesterone-induced Ca2+ influx via CatSper and the resulting motility responses in human sperm?

Chlorinated ethanes, such as 1,1,1-trichloroethane (1,1,1-TCA) and 1,1-dichloroethane (1,1-DCA), are common groundwater contaminants that undergo abiotic and biotic transformation, although the specific mechanisms remain unresolved. Compound-specific isotope analysis (CSIA) can provide insight into transformation mechanisms, but its application to chlorinated ethanes has been limited compared to the extensive literature on chlorinated ethenes. This study presents the first dual-element stable...

Natural genetic variation shapes how microbial populations adapt to environmental and chemical challenges, but scalable approaches to map genotype-phenotype relationships across diverse genetic backgrounds remain limited. Here, we developed a systematically barcoded collection of 520 Saccharomyces cerevisiae natural isolates that captures the ecological, geographical and genetic diversity of the species. Using pooled barcode sequencing, we profiled fitness responses to over 600 bioactive and...

Inflammation activates blood cells, contributing to ageing and malignancy^(1-3). Haematopoietic stem cells (HSCs) survive a lifetime of infection to sustain life-long haematopoiesis^(1-9), but how human HSCs respond and adapt to inflammatory stress is largely unknown. Here, to empirically understand this adaptation, we developed xenograft inflammation-recovery models and performed single-cell multiomics on xenografted human HSCs. Two transcriptionally and epigenetically distinct HSC subsets were...

Pediatric brain tumors are highly prevalent and remain one of the leading causes of cancer-related deaths in children. There are numerous different brain tumor types that are now well characterized by magnetic resonance imaging (MRI), patient clinical course, and neuropathological and molecular genetic alterations. One of the challenges with treating pediatric brain tumors with systemic chemotherapy is the inability of several chemotherapeutic agents to cross the blood-brain barrier (BBB), which...

Ex vivo expansion of mobilized peripheral blood (mPB) hematopoietic stem cells (HSCs) represents a promising approach to advance cell and gene therapy strategies yet is hampered by loss of stem cell function when applying commonly used culture protocols. We performed in-depth characterization of mPB expansion cultures by single cell RNA sequencing, which highlighted differentiation trajectories with preservation of lineage fidelity in committed progenitors. Defining a putative HSC cluster...

Antioxidants added to tires to prevent degradation have recently been recognized as emerging environmental contaminants. While their acute aquatic toxicity has raised concern, these compounds are also emitted to the atmosphere and can be associated with particulate matter (PM). On PM they can react heterogeneously with oxidants, producing a range of transformation products (TPs) with unknown impacts to human health via inhalation. Here, we show through laboratory experiments that many previously...

The important role of paternal health in reproductive success, particularly time to pregnancy (TTP) and miscarriage, is gaining recognition. This scoping review aims to identify, consolidate and analyze the literature on paternal preconception health related to TTP and miscarriage. This review was conducted using the Joanna Briggs Institute methodology. The Medline, PsycINFO, Embase, Scopus and CINAHL databases were searched from January 1, 2013-July 26, 2025. Two independent reviewers screened...

Early recognition of patients at risk for deterioration in the emergency department (ED) is critical for patient safety. Traditional early warning scores rely on structured triage data and often perform poorly in the dynamic ED environment. We developed and evaluated two machine learning models integrating structured triage data with transformer-based embeddings of free-text nursing triage notes to predict early clinical deterioration prior to initial physician assessment, designed as a...

CONCLUSIONS: In this single-institution cohort of patients with recurrent ependymoma and long-term follow-up, gross total resection of recurrence was associated with better survival, and locally recurrent patients treated with CSI-RT2 had longer OS. Further work is required to determine the independent effects of CSI-RT2 together with the extent of re-resection.