Tenecteplase Thrombolysis for Stroke up to 24 Hours After Onset With Perfusion Imaging Selection: The CHABLIS-T II Randomized Clinical Trial.

Background: Whether it is effective and safe to extend the time window of intravenous thrombolysis up to 24 hours after the last known well is unknown. We aimed to determine the efficacy and safety of tenecteplase in Chinese patients with acute ischemic stroke due to large/medium vessel occlusion within an extended time window.

Methods: Patients with ischemic stroke presenting 4.

Advances in biopharmaceutical products for hemophilia.

Hemophilia is caused by the deficiency of clotting factors due to a single genetic abnormality. Replacement therapies have evolved from plasma-derived to recombinant coagulation factor concentrates but continue to have certain limitations. Monoclonal antibodies are clinical prophylactic treatment options unaffected by inhibitors and have better compliance than coagulation factor concentrates for patients with hemophilia.

DCBLD1 Modulates Angiogenesis by Regulation of the VEGFR-2 Endocytosis in Endothelial Cells.

Background: Unwanted angiogenesis is involved in the progression of various malignant tumors and cardiovascular diseases, and the factors that regulate angiogenesis are potential therapeutic targets. We tested the hypothesis that DCBLD1 (discoidin, CUB, and LCCL domain-containing protein 1) is a coreceptor of VEGFR-2 (vascular endothelial growth factor receptor-2) and modulates angiogenesis in endothelial cells.

Methods: A carotid artery ligation model and retinal angiogenesis assay were used to study angiogenesis using globe knockout or endothelial cell-specific conditional knockout mice in vivo.

Associations of Metabolically Healthy Obesity and Retinal Age Gap.

Purpose: We investigated the association between metabolically healthy obesity (MHO) and retinal age gap and explored potential sex differences in this association.

Methods: This study included 30,335 participants from the UK Biobank. Body mass index (BMI) was classified into normal weight, overweight, and obesity.

A pan-orthoebolavirus neutralizing antibody encoded by mRNA effectively prevents virus infection.

is a genus of hazardous pathogens that has caused over 30 outbreaks. However, currently approved therapies are limited in scope, as they are only effective against the Ebola virus and lack cross-protection against other orthoebolaviruses. Here, we demonstrate that a previously isolated human-derived antibody, 2G1, can recognize the glycoprotein (GP) of every orthoebolavirus species.

Groundwater-derived carbon stimulates headwater stream CO emission potential on the Qinghai-Tibet Plateau.

CO emissions from headwater streams are a crucial component of greenhouse gas flux in inland waters. However, the influence of groundwater, a major contributor to streams in the Asian Water Tower (Qinghai-Tibet Plateau, QTP), on CO levels remains unclear. This study employed stable isotope analysis and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) to demonstrate that groundwater-derived dissolved inorganic carbon (DIC) significantly enhanced CO supersaturation in the Shuiluo stream on the QTP.

DNA Methylation Age Mediates Effect of Metabolic Profile on Cardiovascular and General Aging.

Background: Alterations in lipid metabolism and DNA methylation are 2 hallmarks of aging. Connecting metabolomic, epigenomic, and aging outcomes help unravel the complex mechanisms underlying aging. We aimed to assess whether DNA methylation clocks mediate the association of circulating metabolites with incident atherosclerotic cardiovascular disease (ASCVD) and frailty.

Reaction-induced unsaturated Mo oxycarbides afford highly active CO conversion catalysts.

Sustainable CO conversion is crucial in curbing excess emissions. Molybdenum carbide catalysts have demonstrated excellent performances for catalytic CO conversion, but harsh carburization syntheses and poor stabilities make studies challenging. Here an unsaturated Mo oxide (MoO) shows a high activity for the reverse water-gas shift reaction, without carburization pretreatments, and remains stable for 2,000 h at 600 °C.

Omega-3 Polyunsaturated Fatty Acids as a Protective Factor for Myopia.

Purpose: Animal models suggest omega-3 polyunsaturated fatty acids (PUFAs) may protect against myopia by modulating choroidal blood perfusion, but clinical evidence is scarce and mixed. We aimed to determine the causality between omega-3 PUFAs and myopia using Mendelian randomization (MR) analysis.

Design: Two-sample MR analysis.

Bronchoscopy-Guided High-Power Microwave Ablation in an in vivo Porcine Lung Model.

Introduction: Percutaneous microwave ablation (MWA) is clinically accepted for the treatment of lung tumors and oligometastatic disease. Bronchoscopic MWA is under development and evaluation in the clinical setting. We previously reported on the development of a bronchoscopy-guided MWA system integrated with clinical virtual bronchoscopy and navigation and demonstrated the feasibility of transbronchial MWA, using a maximum power of 60 W at the catheter input.

Outcomes of inadequate empiric therapy and timing of newer antibacterial therapy in hospitalized adults with culture-positive Enterobacterales and Pseudomonas aeruginosa: a multicenter analysis.

Background: Infections caused by multi-drug resistant Gram-negative pathogens are associated with worse clinical outcomes in critically ill patients. We evaluated hospital outcomes based on adequacy of overall and newer antibacterial therapy for Enterobacterales (ENT) and Pseudomonas aeruginosa (PsA) in US patients.

Methods: Hospitalized adults ≥ 18 years old with facility-reported antibiotic susceptibility from 2018-2022 across 161 facilities in the BD Insights Research Database were identified as ENT- or PsA-positive.

A cis-acting ligase ribozyme generates circular RNA in vitro for ectopic protein functioning.

Delivering synthetic protein-coding RNA bypassing the DNA stage for ectopic protein functioning is a novel therapeutic strategy. Joining the linear RNA head-to-tail covalently could be a state-of-the-art strategy for functioning longer. Here we enroll a cis-acting ligase ribozyme (RzL) to generate circular RNA (circRNA) in vitro for ectopic protein expression.

Targeting Catechol-O-Methyltransferase Induces Mitochondrial Dysfunction and Enhances the Efficacy of Radiotherapy in Glioma.

Radiotherapy (RT) is commonly used to try to eliminate any remaining tumor cells following surgical resection of glioma. However, tumor recurrence is prevalent, highlighting the unmet medical need to develop therapeutic strategies to enhance the efficacy of RT in glioma. Focusing on the radiosensitizing potential of the currently approved drugs known to cross the blood-brain barrier can facilitate rapid clinical translation.

Do low skeletal muscle bulk and disturbed body fat mass impact tumor recurrence in stage I/II hepatocellular carcinoma undergoing surgery? An observational cohort study.

Introduction: The influence of deranged body composition on stage I/II hepatocellular carcinoma (HCC) after surgery remains undetermined. The current study aimed to investigate the impact of low skeletal muscle bulk and disturbed body fat mass on the recurrence outcome of stage I/II HCC patients undergoing liver resection. The associated metabolomic alterations were also assessed.

A novel bispecific antibody targeting two overlapping epitopes in RBD improves neutralizing potency and breadth against SARS-CoV-2.

SARS-CoV-2 has been evolving into a large number of variants, including the highly pathogenic Delta variant, and the currently prevalent Omicron subvariants with extensive evasion capability, which raises an urgent need to develop new broad-spectrum neutralizing antibodies. Herein, we engineer two IgG-(scFv) form bispecific antibodies with overlapping epitopes (bsAb1) or non-overlapping epitopes (bsAb2). Both bsAbs are significantly superior to the parental monoclonal antibodies in terms of their antigen-binding and virus-neutralizing activities against all tested circulating SARS-CoV-2 variants including currently dominant JN.

T1-Weighted Imaging-Based Hippocampal Radiomics in the Diagnosis of Alzheimer's Disease.

Rationale And Objectives: To investigate the potential of T1-weighted imaging (T1WI)-based hippocampal radiomics as imaging markers for the diagnosis of Alzheimer's disease (AD) and their efficacy in discriminating between mild cognitive impairment (MCI) and dementia in AD.

Methods: A total of 126 AD patients underwent T1WI-based magnetic resonance imaging (MRI) examinations, along with 108 age-sex-matched healthy controls (HC). This was a retrospective, single-center study conducted from November 2021 to February 2023.

Enhancing Machine-Learning Prediction of Enzyme Catalytic Temperature Optima through Amino Acid Conservation Analysis.

Enzymes play a crucial role in various industrial production and pharmaceutical developments, serving as catalysts for numerous biochemical reactions. Determining the optimal catalytic temperature () of enzymes is crucial for optimizing reaction conditions, enhancing catalytic efficiency, and accelerating the industrial processes. However, due to the limited availability of experimentally determined data and the insufficient accuracy of existing computational methods in predicting , there is an urgent need for a computational approach to predict the values of enzymes accurately.

Pembrolizumab for advanced urothelial carcinoma: exploratory ctDNA biomarker analyses of the KEYNOTE-361 phase 3 trial.

Circulating tumor DNA (ctDNA) is emerging as a potential biomarker in early-stage urothelial cancer, but its utility in metastatic disease remains unknown. In the phase 3 KEYNOTE-361 study, pembrolizumab with and without chemotherapy was compared with chemotherapy alone in patients with metastatic urothelial cancer. The study did not meet prespecified efficacy thresholds for statistical significance.

A potent Henipavirus cross-neutralizing antibody reveals a dynamic fusion-triggering pattern of the G-tetramer.

The Hendra and Nipah viruses (HNVs) are highly pathogenic pathogens without approved interventions for human use. In addition, the interaction pattern between the attachment (G) and fusion (F) glycoproteins required for virus entry remains unclear. Here, we isolate a panel of Macaca-derived G-specific antibodies that cross-neutralize HNVs via multiple mechanisms.