Lerociclib plus fulvestrant in patients with HR+/HER2- locally advanced or metastatic breast cancer who have progressed on prior endocrine therapy: LEONARDA-1 a phase III randomized trial.

Lerociclib (GB491), a highly selective oral CDK4/6 inhibitor, has displayed anti-tumor activity and differentiated safety and tolerability profile in previous ph1/2 clinical trials. The LEONARDA-1, a randomized, double-blind, phase III study, was conducted to evaluate the efficacy and safety of lerociclib in HR+/HER2- locally advanced or metastatic breast cancer patients, who had relapsed or progressed on prior endocrine therapy. A total of 275 patients were randomized at 1:1 ratio to receive lerociclib (137 patients, 150 mg twice daily) or placebo (138 patients) plus fulvestrant.

Resolving tissue complexity by multimodal spatial omics modeling with MISO.

Spatial molecular profiling has provided biomedical researchers valuable opportunities to better understand the relationship between cellular localization and tissue function. Effectively modeling multimodal spatial omics data is crucial for understanding tissue complexity and underlying biology. Furthermore, improvements in spatial resolution have led to the advent of technologies that can generate spatial molecular data with subcellular resolution, requiring the development of computationally efficient methods that can handle the resulting large-scale datasets.

A Global Collaborative Comparison of SARS-CoV-2 Antigenicity Across 15 Laboratories.

Setting up a global SARS-CoV-2 surveillance system requires an understanding of how virus isolation and propagation practices, use of animal or human sera, and different neutralisation assay platforms influence assessment of SARS-CoV-2 antigenicity. In this study, with the contribution of 15 independent laboratories across all WHO regions, we carried out a controlled analysis of neutralisation assay platforms using the first WHO International Standard for antibodies to SARS-CoV-2 variants of concern (source: NIBSC). Live virus isolates (source: WHO BioHub or individual labs) or spike plasmids (individual labs) for pseudovirus production were used to perform neutralisation assays using the same serum panels.

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.

CD36-mediated uptake of oxidized LDL induces double-negative regulatory T cell ferroptosis in metabolic dysfunction-associated steatotic liver disease.

Background: Metabolic alterations have been shown to instigate liver inflammation in metabolic dysfunction-associated steatotic liver disease (MASLD), but the underlying mechanism is not fully elucidated. During MASLD progression, intrahepatic CD3TCRαβCD4CD8 double negative T regulatory cells (DNT) decrease cell survival and immunosuppressive function, leading to aggravated liver inflammation. In this study, we aim to reveal the underlying mechanisms that cause changes in DNT during MASLD progression.

Sustained effects of repeated levodopa (L-DOPA) administration on reward circuitry, effort-based motivation, and anhedonia in depressed patients with higher inflammation.

Inflammatory biomarkers like C-reactive protein (CRP) are elevated in a subset of patients with depression and have been associated with lower functional connectivity (FC) in a ventral striatum (VS) to ventromedial prefrontal cortex (vmPFC) reward circuit and symptoms of anhedonia. Evidence linking these relationships to the effects of inflammation on dopamine is consistent with our recent findings that acute levodopa (L-DOPA) increased VS-vmPFC FC in association with deceased anhedonia in depressed patients with higher but not lower CRP (>2 versus ≤ 2 mg/L). To determine whether repeated L-DOPA administration caused sustained effects on FC and behavior in these patients, medically stable depressed outpatients with CRP > 2 mg/L and anhedonia (n = 18) received one week of three doses of L-DOPA (150-450 mg/day/week with carbidopa) or placebo in a randomized order.

Genome-wide single-cell and single-molecule footprinting of transcription factors with deaminase.

Decades of research have established that mammalian transcription factors (TFs) bind to each gene's regulatory regions and cooperatively control tissue specificity, timing, and intensity of gene transcription. Mapping the combination of TF binding sites genome wide is critically important for understanding functional genomics. Here, we report a technique to measure TFs' binding sites on the human genome with a near single-base resolution by footprinting with deaminase (FOODIE) on a single-molecule and single-cell basis.

Influence of Noncovalent Interaction on the Nucleophilicity and Electrophilicity of Metal Centers in [M(SCNEt)] (M = Ni, Pd, Pt).

A systematic theoretical study was performed on the electrophilic and nucleophilic properties of Group 10 square-planar metal compounds [M(SCNEt)] (M = Ni , Pd , and Pt ) and their complexes. The nucleophilic metal center and coordinated sulfur atom in [M(SCNEt)] facilitate the formation of metal-involving and conventional noncovalent bonds. The presence a heavier metal center results in a more negative electrostatic potential and a larger nucleophilicity, which in turn leads to the formation of stronger metal-involving noncovalent bonds than those formed by a lighter metal center.

GSK3β Deficiency Expands Obese Adipose Vasculature to Mitigate Metabolic Disorders.

Background: Maintaining a well-developed vascular system alongside adipose tissue (AT) expansion significantly reduces the risk of metabolic complications. Although GSK3β (glycogen synthase kinase-3 beta) is known for its role in various cellular processes, its specific functions in AT and regulation of body homeostasis have not been reported.

Methods: GSK3β-floxed and GSK3α-floxed mice were crossed with adiponectin-Cre mice to generate GSK3β or GSK3α adipocyte-specific knockout mice (GSK3β and GSK3α).

Accelerated spine MRI with deep learning based image reconstruction: a prospective comparison with standard MRI.

Rationale And Objectives: To evaluate the performance of deep learning (DL) reconstructed MRI in terms of image acquisition time, overall image quality and diagnostic interchangeability compared to standard-of-care (SOC) MRI.

Materials And Methods: This prospective study recruited participants between July 2023 and August 2023 who had spinal discomfort. All participants underwent two separate MRI examinations (Standard and accelerated scanning).

Sodium oligomannate disrupts the adherence of Rib bacteria to gut epithelia to block SAA-triggered Th1 inflammation in 5XFAD transgenic mice.

Sodium oligomannate (GV-971), an oligosaccharide drug approved in China for treating mild-to-moderate Alzheimer's disease (AD), was previously found to recondition the gut microbiota and limit altered peripheral Th1 immunity in AD transgenic mice. As a follow-up study, we here made advances by pinpointing a Lactobacillus murinus (L.m.

Modulating the local electron density at built-in interface iron single sites in Fe-CN/MoO heterostructure for enhanced CO reduction to CH and photo-Fenton reaction.

The catalytic efficiency of heterogeneous photocatalytic CO reduction and photo-Fenton HO activationisclosely related to the local electron density of reaction center atoms. However, electron-hole recombination from random charge transfer significantly restricts the targeted electron delivery to the active center. Herein, Fe-CN/MoO heterojunction with interfacial coordination of atomically dispersed Fe-N sites with the O interface of MoO was synthesized by simple hydrothermal method.

Optimal preservation condition for the extraction of cell-free DNA from bile of patients with biliary tract cancer.

Background: Patients with biliary tract cancer (BTC) often have dismal outcomes due to the poor performance of traditional methods for early diagnosis. Recently, bile cell-free DNA (cfDNA) has been reported as a potential liquid biopsy material for BTC diagnosis. However, bile is a complex alkaline aqueous medium, and the proper storage conditions for bile remain to be explored.

Root Endophytic Microorganisms Contribute to the Attribute of Full-Year Shooting in Woody Bamboo .

(Hsueh & Y.M. Yang ex Yi et al.

Efficacy and safety of GLP-1 analog ecnoglutide in adults with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 2 trial.

Glucagon-like peptide-1 (GLP-1) analogs are important therapeutics for type 2 diabetes and obesity. Ecnoglutide (XW003) is a novel, long-acting GLP-1 analog. We conducted a Phase 2, randomized, double-blind, placebo-controlled study enrolling 145 adults with T2DM.

Ziresovir in Hospitalized Infants with Respiratory Syncytial Virus Infection.

Background: Respiratory syncytial virus (RSV) is a leading cause of severe illness in infants, with no effective treatment. Results of a phase 2 trial suggested that ziresovir may have efficacy in the treatment of infants hospitalized with RSV infection.

Methods: In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial conducted in China, we enrolled participants 1 to 24 months of age who were hospitalized with RSV infection.