SEAD reference panel with 22,134 haplotypes boosts rare variant imputation and genome-wide association analysis in Asian populations.

Limited whole genome sequencing (WGS) studies in Asian populations result in a lack of representative reference panels, thus hindering the discovery of ancestry-specific variants. Here, we present the South and East Asian reference Database (SEAD) panel ( https://imputationserver.westlake.

Engineered extrachromosomal oncogene amplifications promote tumorigenesis.

Focal gene amplifications are among the most common cancer-associated mutations but have proven challenging to engineer in primary cells and model organisms. Here we describe a general strategy to engineer large (more than 1 Mbp) focal amplifications mediated by extrachromosomal DNAs (ecDNAs) in a spatiotemporally controlled manner in cells and in mice. By coupling ecDNA formation with expression of selectable markers, we track the dynamics of ecDNA-containing cells under physiological conditions and in the presence of specific selective pressures.

Feasibility of Sub-milliSievert Low-dose Computed Tomography with Deep Learning Image Reconstruction in Evaluating Pulmonary Subsolid Nodules: A Prospective Intra-individual Comparison Study.

Rationale And Objectives: To comprehensively assess the feasibility of low-dose computed tomography (LDCT) using deep learning image reconstruction (DLIR) for evaluating pulmonary subsolid nodules, which are challenging due to their susceptibility to noise.

Materials And Methods: Patients undergoing both standard-dose CT (SDCT) and LDCT between March and June 2023 were prospectively enrolled. LDCT images were reconstructed with high-strength DLIR (DLIR-H), medium-strength DLIR (DLIR-M), adaptive statistical iterative reconstruction-V level 50% (ASIR-V-50%), and filtered back projection (FBP); SDCT with FBP as the reference standard.

Integrative mapping of human CD8 T cells in inflammation and cancer.

CD8 T cells exhibit remarkable phenotypic diversity in inflammation and cancer. However, a comprehensive understanding of their clonal landscape and dynamics remains elusive. Here we introduce scAtlasVAE, a deep-learning-based model for the integration of large-scale single-cell RNA sequencing data and cross-atlas comparisons.

Relationship Between Physical Literacy and Cardiorespiratory Fitness in Children and Adolescents: A Systematic Review and Meta-analysis.

Background: Physical literacy (PL) can positively affect the health of children, adolescents, and adults, and is closely related to cardiorespiratory fitness (CRF).

Objective: To perform a systematic review and meta-analysis to examine the relationship between overall physical literacy (PL) and CRF in children and adolescents.

Methods: Cross-sectional, cohort and experimental studies on the relationship between PL and CRF in children and adolescents were collected by searching the Web of Science Core Collection, PubMed, EBSCOhost, ScienceDirect, Cochrane Library and China National Knowledge Infrastructure (CNKI) databases.

Design of customized coronavirus receptors.

Although coronaviruses use diverse receptors, the characterization of coronaviruses with unknown receptors has been impeded by a lack of infection models. Here we introduce a strategy to engineer functional customized viral receptors (CVRs). The modular design relies on building artificial receptor scaffolds comprising various modules and generating specific virus-binding domains.

Membrane-Free Water Electrolysis for Hydrogen Generation with Low Cost.

Conventional water electrolysis relies on expensive membrane-electrode assemblies and sluggish oxygen evolution reaction (OER) at the anode, which makes the cost of green hydrogen (H) generation much higher than that of grey H. Here, we develop an innovative and efficient membrane-free water electrolysis system to overcome these two obstacles simultaneously. This system utilizes the thermodynamically more favorable urea oxidation reaction (UOR) to generate clean N over a new class of Cu-based catalyst (CuO) for replacing OER, fundamentally eliminating the explosion risk of H and O mixing while removing the need for membranes.

Tailoring smart hydrogels through manipulation of heterogeneous subdomains.

The mechanical interactions among integrated cellular structures in soft tissues dictate the mechanical behaviors and morphogenetic deformations observed in living organisms. However, replicating these multifaceted attributes in synthetic soft materials remains a challenge. In this work, we develop a smart hydrogel system featuring engineered stiff cellular patterns that induce strain-driven heterogeneous subdomains within the hydrogel film.

A randomized phase 2 study of HLX22 plus trastuzumab biosimilar HLX02 and XELOX as first-line therapy for HER2-positive advanced gastric cancer.

Background: Gastric cancer is the fifth most common cancer and the fourth most common cause of cancer death worldwide, yet the prognosis of advanced disease remains poor.

Methods: This was a randomized, double-blinded, phase 2 trial (ClinicalTrials.gov: NCT04908813).

Assessing and engineering the IscB-ωRNA system for programmed genome editing.

OMEGA RNA (ωRNA)-guided endonuclease IscB, the evolutionary ancestor of Cas9, is an attractive system for in vivo genome editing because of its compact size and mechanistic resemblance to Cas9. However, wild-type IscB-ωRNA systems show limited activity in human cells. Here we report enhanced OgeuIscB, which, with eight amino acid substitutions, displayed a fourfold increase in in vitro DNA-binding affinity and a 30.

Sex-dependent associations of serum BDNF, glycolipid metabolism and cognitive impairments in Parkinson's disease with depression: a comprehensive analysis.

Brain-derived neurotrophic factor (BDNF) and glycolipid metabolism have been implicated in cognitive impairments and depression among Parkinson's disease (PD). However, the role of sex differences in this relationship remains elusive. This study aimed to investigate the potential sex differences in the link between serum BDNF levels, glycolipid metabolism and cognitive performance among depressive PD patients.

Preclinical study and phase II trial of adapting low-dose radiotherapy to immunotherapy in small cell lung cancer.

Background: Immune checkpoint inhibitors (ICIs) provide modest but unsatisfactory benefits for extensive-stage small cell lung cancer (ES-SCLC). Developing strategies for treating ES-SCLC is critical.

Methods: We preliminarily explored the outcomes of salvage low-dose radiotherapy (LDRT) plus ICI on refractory SCLC patients.

YAP represses the TEAD-NF-κB complex and inhibits the growth of clear cell renal cell carcinoma.

The Hippo pathway is generally understood to inhibit tumor growth by phosphorylating the transcriptional cofactor YAP to sequester it to the cytoplasm and reduce the formation of YAP-TEAD transcriptional complexes. Aberrant activation of YAP occurs in various cancers. However, we found a tumor-suppressive function of YAP in clear cell renal cell carcinoma (ccRCC).

Targeting SOX13 inhibits assembly of respiratory chain supercomplexes to overcome ferroptosis resistance in gastric cancer.

Therapeutic resistance represents a bottleneck to treatment in advanced gastric cancer (GC). Ferroptosis is an iron-dependent form of non-apoptotic cell death and is associated with anti-cancer therapeutic efficacy. Further investigations are required to clarify the underlying mechanisms.

Pharmacokinetic/Pharmacodynamic Assessment of the Structural Refinement of Clopidogrel Focusing on the Balance between Bioactivation and Deactivation.

The delicate balance between ischemic and bleeding risks is a critical factor in antiplatelet therapy administration. Clopidogrel and prasugrel, belonging to the thienopyridine class of antiplatelet drugs, are known for their variability in individual responsiveness and high incidence of bleeding events, respectively. The present study is centered on the development and assessment of a range of deuterated thienopyridine derivatives, leveraging insights from structure-pharmacokinetic relationships of clopidogrel and prasugrel.

On-Line pH Measurement Cation Exchange Kinetics of Y-Exchanged Alginic Acid for YO Nanoparticles Synthesis.

A new sol-gel method that employs cation exchange from an aqueous metal ion solution with H ions of granulated alginic acid was developed for synthesizing high-purity YO nanoparticles. In this study, the cation exchange kinetics of H~Y in aqueous solution were analyzed using on-line pH technology and off-line inductively coupled plasma-atomic emission spectrometry (ICP-AES) analysis. Pseudo 2nd-order models were utilized to evaluate the parameters of the kinetics, suggesting that the concentration of H~Y involved in the cation exchange reaction was 1:1.