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.

Trivalent recombinant protein vaccine induces cross-neutralization against XBB lineage and JN.1 subvariants: preclinical and phase 1 clinical trials.

The immune escape capacities of XBB variants necessitate the authorization of vaccines with these antigens. In this study, we produce three recombinant trimeric proteins from the RBD sequences of Delta, BA.5, and XBB.

Comparison of L L Polyethylene Glycol Plus Ascorbic Acid and Oral Sodium Sulfate Tablets for Colonoscopy Bowel Preparation.

A low-volume (1 L) polyethylene glycol plus ascorbic acid (PEG-A) solution and an oral sodium sulfate tablet (OST) formulation are recently introduced agents for colonoscopy bowel preparation. This study investigated the efficacy, safety, and tolerability of 1 L PEG-A vs. OST.

BCL11A +58/+55 enhancer-editing facilitates HSPC engraftment and HbF induction in rhesus macaques conditioned with a CD45 antibody-drug conjugate.

Editing the +58 region of the BCL11A erythroid enhancer has shown promise in treating β-globin disorders. To address variations in fetal hemoglobin (HbF) response, we investigated editing both +58 and +55 enhancers. Rhesus macaques transplanted with edited hematopoietic stem/progenitor cells (HSPCs) following busulfan conditioning exhibited durable, high-level (∼90%) editing frequencies post transplantation with sustained HbF reactivation over 4 years, without hematological perturbations.

The Effects of Thunb. on the Alleviation of Joint Pain: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Arthritis is mainly a geriatric disease that causes joint pain and lowers the quality of life. This clinical trial was performed to evaluate the efficacy of Thunb. (HY-LL) in alleviating joint pain.

Integrative Multiomics in the Lung Reveals a Protective Role of Asporin in Pulmonary Arterial Hypertension.

Background: Integrative multiomics can elucidate pulmonary arterial hypertension (PAH) pathobiology, but procuring human PAH lung samples is rare.

Methods: We leveraged transcriptomic profiling and deep phenotyping of the largest multicenter PAH lung biobank to date (96 disease and 52 control) by integration with clinicopathologic data, genome-wide association studies, Bayesian regulatory networks, single-cell transcriptomics, and pharmacotranscriptomics.

Results: We identified 2 potentially protective gene network modules associated with vascular cells, and we validated , coding for asporin, as a key hub gene that is upregulated as a compensatory response to counteract PAH.

Visualization of the Extracranial Branches of the Trigeminal Nerve Using Improved Motion-Sensitized Driven Equilibrium-Prepared 3D Inversion Recovery TSE Sequence.

Background And Purpose: Visualization of the extracranial trigeminal nerve is crucial to detect nerve pathologic alterations. This study aimed to evaluate visualization of the extracranial trigeminal nerve using 3D inversion recovery TSE with an improved motion-sensitized driven equilibrium (iMSDE) pulse.

Materials And Methods: In this prospective study, 35 subjects underwent imaging of the trigeminal nerve using conventional 3D inversion recovery TSE, 3D inversion recovery TSE with an iMSDE pulse, and contrast-enhanced 3D inversion recovery TSE.

Rare-Earth Metalloligands for LowValent Cobalt Complexes: Fine Electronic Tuning Co→RE Dative Interactions.

Rare-earth metalloligand supported low-valent cobalt complexes were synthesized by utilizing a small-sized heptadentate phosphinomethylamine H and a large-sized arene-anchored hexadentate phosphinomethylamine H ligand precursors. The RE(III)-Co(-I)-N (RE = Sc, Lu, Y, Gd, La) complexes containing rare-earth metals including the smallest Sc and largest La were characterized by multinuclear NMR spectroscopy, X-ray diffraction analysis, electrochemistry, and computational studies. The Co(-I)→RE(III) dative interactions were all polarized with major contributions from the 3d orbital of the cobalt center, which was slightly affected by the identity of rare-earth metalloligands.

A heterogeneous pharmaco-transcriptomic landscape induced by targeting a single oncogenic kinase.

Over-activation of the epidermal growth factor receptor (EGFR) is a hallmark of glioblastoma. However, EGFR-targeted therapies have led to minimal clinical response. While delivery of EGFR inhibitors (EGFRis) to the brain constitutes a major challenge, how additional drug-specific features alter efficacy remains poorly understood.

Real-world and clinical trial outcomes in large B-cell lymphoma with axicabtagene ciloleucel across race and ethnicity.

Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Despite extensive data supporting its use, outcomes stratified by race and ethnicity groups are limited. Here, we report clinical outcomes with axi-cel in patients with R/R LBCL by race and ethnicity in both real-world and clinical trial settings.

Joint representation and visualization of derailed cell states with Decipher.

Biological insights often depend on comparing conditions such as disease and health, yet we lack effective computational tools for integrating single-cell genomics data across conditions or characterizing transitions from normal to deviant cell states. Here, we present Decipher, a deep generative model that characterizes derailed cell-state trajectories. Decipher jointly models and visualizes gene expression and cell state from normal and perturbed single-cell RNA-seq data, revealing shared and disrupted dynamics.

Quartet DNA reference materials and datasets for comprehensively evaluating germline variant calling performance.

Background: Genomic DNA reference materials are widely recognized as essential for ensuring data quality in omics research. However, relying solely on reference datasets to evaluate the accuracy of variant calling results is incomplete, as they are limited to benchmark regions. Therefore, it is important to develop DNA reference materials that enable the assessment of variant detection performance across the entire genome.

Fertility-preserving myeloablative conditioning using single-dose CD117 antibody-drug conjugate in a rhesus gene therapy model.

Hematopoietic stem cell (HSC) gene therapy has curative potential; however, its use is limited by the morbidity and mortality associated with current chemotherapy-based conditioning. Targeted conditioning using antibody-drug conjugates (ADC) holds promise for reduced toxicity in HSC gene therapy. Here we test the ability of an antibody-drug conjugate targeting CD117 (CD117-ADC) to enable engraftment in a non-human primate lentiviral gene therapy model of hemoglobinopathies.

STING signaling promotes NK cell antitumor immunity and maintains a reservoir of TCF-1 NK cells.

Natural killer (NK) cells are cytotoxic innate lymphocytes that eradicate tumor cells. Inducing durable antitumor immune responses by NK cells represents a major priority of cancer immunotherapy. While cytosolic DNA sensing plays an essential role in initiating antitumor immunity, the role of NK cell-intrinsic STING signaling remains unclear.

sp. nov. and sp. nov., two novel halophilic actinobacteria isolated from halophytes.

A polyphasic approach was used to describe two halophilic actinobacterial strains, designated LSu2-4 and RSe5-2, which were isolated from halophytes [ (L.) Dum. and (L.

Interaction mechanism and spatial effect of cross-regional haze pollution based on a multisectoral economy-energy-environment (3E) model and the evidence from China.

The transboundary characteristics and multisectoral factor interaction mechanism of haze pollution have aroused widespread attention but remain understudied. This article proposes a comprehensive conceptual model that clarifies regional haze pollution, further establishes a theoretical framework on a cross-regional, multisectoral economy-energy-environment (3E) system, and attempts to empirically investigate the spatial effect and interaction mechanism employing a spatial-econometrics model based on China's province-level regions. The results demonstrate that (1) regional haze pollution is a transboundary atmospheric state formed by the accumulation and agglomeration of various emission pollutants; moreover, there is a "snowball" effect and a spatial spillover effect.

Umbilical cord DNA methylation is associated with body mass index trajectories from birth to adolescence.

Background: DNA methylation (DNAm) in cord blood has been associated with various prenatal factors and birth outcomes. This study sought to fill an important knowledge gap: the link of cord DNAm with child postnatal growth trajectories from birth to age 18 years (y).

Methods: Using data from a US predominantly urban, low-income, multi-ethnic birth cohort (N = 831), we first applied non-parametric methods to identify body-mass-index percentile (BMIPCT) trajectories from birth to age 18 y (the outcome); then, conducted epigenome-wide association study (EWAS) of the outcome, interrogating over 700,000 CpG sites profiled by the Illumina Infinium MethylationEPIC BeadChip.

The Unexpected Role of Cations in the Self-Assembly of Positively Charged Amphiphiles at Liquid/Liquid Interfaces.

Conventional wisdom suggests that cations play a minimal role in the assembly of cationic amphiphiles. Here, we show that at liquid/liquid (L/L) interfaces, specific cation effects can modulate the assemblies of hydrophobic tails in an oil phase despite being attached to cationic headgroups in the aqueous phase. We used oligo-dimethylsiloxane (ODMS) methyl imidazolium amphiphiles to identify these specific interactions at hexadecane/aqueous interfaces.

Network pharmacology and experiment-based strategy to investigate mechanisms of JingFangFuZiLiZhong formula for ulcerative colitis.

Background: Ulcerative colitis (UC), a chronic inflammatory disease, often cause carcinogenesis, disability, and intestinal perforation. The JingFangFuZiLiZhong formula (JFFZLZ) shows a good effect against UC in the clinic. Hence, we aim to investigate the mechanisms between JFFZLZ and UC network pharmacology data mining and experiments.

Association Between DNA Methylation and Blood Pressure: A 5-Year Longitudinal Twin Study.

Background: Previous EWASs (Epigenome-Wide Association Studies) have reported hundreds of blood pressure (BP) associated 5'-cytosine-phosphate-guanine-3' (CpG) sites. However, their results were inconsistent. Longitudinal observations on the temporal relationship between DNA methylation and BP are lacking.