The vasodilator hydralazine (HYZ) has been used clinically for ~ 70 years and remains on the World Health Organization's List of Essential Medicines as a therapy for preeclampsia. Despite its longstanding use and the concomitant progress toward a general understanding of vasodilation, the target and mechanism of HYZ have remained unknown. We show that HYZ selectively targets 2-aminoethanethiol dioxygenase (ADO) by chelating its metal cofactor and alkylating one of its ligands.
View Article and Find Full Text PDFPatients with metastatic pancreatic ductal adenocarcinoma survive longer if disease spreads to the lung but not the liver. Here we generated overlapping, multi-omic datasets to identify molecular and cellular features that distinguish patients whose disease develops liver metastasis (liver cohort) from those whose disease develops lung metastasis without liver metastases (lung cohort). Lung cohort patients survived longer than liver cohort patients, despite sharing the same tumor subtype.
View Article and Find Full Text PDFWater purification has always been a critical yet challenging issue. In this study, an organic-inorganic composite membrane was developed using 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-oxidized bacterial cellulose (BC) nanofibers and hydroxyapatite nanowires (HAPNW) with tunable wettability for advanced membrane separation applications. The resulting free-standing TEMPO-BC/HAPNW filter membrane exhibited strong mechanical strength, high flexibility, exceptional deformability, and a high pure water flux of up to 800 L·m·h due to its porous architecture and inherent hydrophilicity.
View Article and Find Full Text PDFIntroduction: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease discovered in China in 2009. SFTS monitoring has been carried out since 2010 in mainland China. In recent years, human infection with SFTS virus (SFTSV) has frequently been detected in Jiujiang of Jiangxi Province, Central China.
View Article and Find Full Text PDFBackground: The effect of embolization of the middle meningeal artery in patients with subacute or chronic subdural hematoma is uncertain.
Methods: We performed a multicenter, open-label, randomized trial in China, involving patients with symptomatic nonacute subdural hematoma with mass effect. Patients were assigned to undergo burr-hole drainage or receive nonsurgical treatment at the surgeon's discretion, and patients in each group were then randomly assigned, in a 1:1 ratio, to undergo middle meningeal artery embolization with liquid embolic material or to receive usual care.
Purpose To evaluate the performance of the winning machine learning models from the 2023 RSNA Abdominal Trauma Detection AI Challenge. Materials and Methods The competition was hosted on Kaggle and took place between July 26 and October 15, 2023. The multicenter competition dataset consisted of 4274 abdominal trauma CT scans, in which solid organs (liver, spleen, and kidneys) were annotated as healthy, low-grade, or high-grade injury.
View Article and Find Full Text PDFPurpose To evaluate the performance of the top models from the RSNA 2022 Cervical Spine Fracture Detection challenge on a clinical test dataset of both noncontrast and contrast-enhanced CT scans acquired at a level I trauma center. Materials and Methods Seven top-performing models in the RSNA 2022 Cervical Spine Fracture Detection challenge were retrospectively evaluated on a clinical test set of 1828 CT scans (from 1829 series: 130 positive for fracture, 1699 negative for fracture; 1308 noncontrast, 521 contrast enhanced) from 1779 patients (mean age, 55.8 years ± 22.
View Article and Find Full Text PDFThe emergence of biobank-level datasets offers new opportunities to discover novel biomarkers and develop predictive algorithms for human disease. Here, we present an ensemble machine-learning framework (machine learning with phenotype associations, MILTON) utilizing a range of biomarkers to predict 3,213 diseases in the UK Biobank. Leveraging the UK Biobank's longitudinal health record data, MILTON predicts incident disease cases undiagnosed at time of recruitment, largely outperforming available polygenic risk scores.
View Article and Find Full Text PDFGenetic variation in the human leukocyte antigen (HLA) loci is associated with risk of immune-mediated diseases, but the molecular effects of HLA polymorphism are unclear. Here we examined the effects of HLA genetic variation on the expression of 2940 plasma proteins across 45,330 Europeans in the UK Biobank, with replication analyses across multiple ancestry groups. We detected 504 proteins affected by HLA variants (HLA-pQTL), including widespread trans effects by autoimmune disease risk alleles.
View Article and Find Full Text PDFKidneys are intricate three-dimensional structures in the body, yet the spatial and molecular principles of kidney health and disease remain inadequately understood. We generated high-quality datasets for 81 samples, including single-cell, single-nuclear, spot-level (Visium) and single-cell resolution (CosMx) spatial-RNA expression and single-nuclear open chromatin, capturing cells from healthy, diabetic and hypertensive diseased human kidneys. Combining these data, we identify cell types and map them to their locations within the tissue.
View Article and Find Full Text PDFWith the increase of oily wastewater discharge and the growing demand for clean water supply, high throughput green materials for oil-water separation with anti-pollution and self-cleaning ability are urgently needed. Herein, the polysaccharide-based composite aerogels of CMC/SA@TiO-MWCNTs (CSTM) with fast photo-driven self-cleaning ability have been prepared by a simple freeze-drying and ionic cross-linking strategy. The introduction of TiO /MWCNTs nanocomposites effectively improves the underwater oleophobic and mechanical properties of polysaccharide aerogels and enables their photo-driven self-cleaning ability for efficient oil-water separation and purification of complex oily wastewater.
View Article and Find Full Text PDFHuntington's disease (HD) is an autosomal dominant disease caused by the expansion of cytosine-adenine-guanine (CAG) repeats in one copy of the gene (mutant HTT, mHTT). The unaffected gene encodes wild-type HTT (wtHTT) protein, which supports processes important for the health and function of the central nervous system. Selective lowering of mHTT for the treatment of HD may provide a benefit over nonselective HTT-lowering approaches, as it aims to preserve the beneficial activities of wtHTT.
View Article and Find Full Text PDFPenpulimab is an anti-programmed cell death-1 (PD-1) IgG1 antibody with no Fc gamma receptor (FcγR) binding activity, and thus theoretically reduced immune-related adverse events (irAEs) while maintaining efficacy. This single-arm, phase II trial conducted across 20 tertiary care centers in China enrolled adult patients with metastatic nasopharyngeal carcinoma (NPC) who had failed two or more lines of previous systemic chemotherapy. Patients received 200-mg penpulimab intravenously every 2 weeks (4 weeks per cycle) until disease progression or intolerable toxicities.
View Article and Find Full Text PDFEukaryotic cells are compartmentalized by membrane-bounded organelles to ensure that specific biochemical reactions and cellular functions occur in a spatially restricted manner. The subcellular localization of proteins is largely determined by their intrinsic targeting signals, which are mainly constituted by short peptides. A complete organelle targeting signal may contain a core signal (CoreS) as well as auxiliary signals (AuxiS).
View Article and Find Full Text PDFIn cancer treatment, therapeutic strategies that integrate tumor-specific characteristics (i.e., precision oncology) are widely implemented to provide clinical benefits for cancer patients.
View Article and Find Full Text PDFBackground And Purpose: The Brain Tumor Reporting and Data System (BT-RADS) is a structured radiology reporting algorithm that was introduced to provide uniformity in posttreatment primary brain tumor follow-up and reporting, but its interrater reliability (IRR) assessment has not been widely studied. Our goal is to evaluate the IRR among neuroradiologists and radiology residents in the use of BT-RADS.
Materials And Methods: This retrospective study reviewed 103 consecutive MR studies in 98 adult patients previously diagnosed with and treated for primary brain tumor (January 2019 to February 2019).
Ticks are a major parasite on the Qīnghăi-Tibet Plateau, western China, and represent an economic burden to agriculture and animal husbandry. Despite research on tick-borne pathogens that threaten humans and animals, the viromes of dominant tick species in this area remain unknown. In this study, we collected Dermacentor nuttalli ticks near Qīnghăi Lake and identified 13 viruses belonging to at least six families through metagenomic sequencing.
View Article and Find Full Text PDFLead halide perovskite quantum dots (QDs) are promising semiconductors for next-generation photoelectric devices. However, the development of perovskite QDs-based multifunctional materials still needs to be addressed in order to further advance the application of perovskite QDs. Herein, a successful synthesis of Janus microfibers array Janus membrane (JMAJM) with up-down structure and multifunction of luminescence, magnetism and electroconductivity is firstly achieved based on CsPbBr QDs through a parallel electrospinning.
View Article and Find Full Text PDFPlastic pollution, particularly microplastic (MP) and nanoplastic (NP) pollution, has become a significant concern. This study explores the use of porous wood for filtration to remove MPs and NPs and investigates their removal mechanisms. Undecorated fir wood with a thickness of 4 mm achieves a 91% removal rate for model polystyrene (PS) MPs (2.
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