Sex-differential responses to immune checkpoint inhibitors across the disease continuum unified by tumor mutational burden.

While the efficacy of immune checkpoint inhibitors (ICIs) in advanced non-small-cell lung cancer (NSCLC) is well-established, sex-based differences in treatment responses remain insufficiently explored. This study examines how sex disparities impact ICI treatment outcomes in advanced-stage NSCLC, focusing on the role of tumor mutational burden (TMB) in these differences. This study analyzed data from 174 advanced-stage, chemotherapy-naïve, NSCLC patients treated with ICIs, including PD-1/PD-L1 and CTLA-4 inhibitors, to assess sex differences in treatment response and survival outcomes.

Serum STARD4-AS1 As a Novel Marker for Gastric Cancer Diagnosis and Promotes Gastric Cancer Progression.

Background: Gastric cancer (GC) is a lethal malignant tumor necessitating high-sensitivity detection to improve diagnostic accuracy and the prognosis of patients. Alterations in long noncoding RNAs can influence cancer progression through various mechanisms. Our study tried to explore the potential of STARD4-AS1 as a GC biomarker and its mechanism of action in GC development.

Geographical analysis of malignant tumor incidence and treatment in China.

Malignant tumors have a severe impact on both patients and their families, and the treatment of malignant tumors is a fundamental component of public health security. Therefore, the issue of malignant tumors is a significant focus in the construction of "Healthy China." There are notable spatial disparities in both the incidence and treatment of malignant tumors in China.

Genome-Wide Association Study and Meta-Analysis Uncovers Key Candidate Genes for Body Weight Traits in Chickens.

Background: Genome-wide association studies (GWAS) have been extensively employed to elucidate the genetic architecture of body weight (BW) traits in chickens, which represent key economic indicators in broiler production. With the growing availability of genomic data from diverse commercial and resource chicken populations, a critical challenge lies in how to effectively integrate these datasets to enhance sample size and thereby improve the statistical power for detecting genetic variants associated with complex traits.

Methods: In this study, we performed a multi-population GWAS meta-analysis on BW traits across three genetically distinct chicken populations, focusing on BW at 56, 70, and 84 days of age: P1 (N301 Yellow Plumage Dwarf Chicken Line; = 426), P2 (F2 reciprocal cross: High Quality Line A × Huiyang Bearded chicken; = 494), and P3 (F2 cross: Black-bone chicken × White Plymouth Rock; = 223).

Breaking antibiotic resistance: Sunlight-powered calcium peroxide for dual bactericidal and genetic elimination.

Antibiotic-resistant bacteria (ARB) and associated antibiotic resistance genes (ARGs) have emerged as critical waterborne contaminants, posing serious public health risks. This study proposes a disinfection strategy through sunlight powered calcium peroxide (CaO) treatment that simultaneously inactivates ARB and degrades ARGs in aquatic environments. Solar irradiation combined with CaO (3.

Ruxolitinib, a novel JAK/STAT-targeted therapy through restoring mucosal homeostasis for chronic rhinosinusitis with nasal polyps.

Background: The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway plays a crucial role in regulating immune function and inflammatory responses. Dysregulation of this pathway has been implicated in numerous disorders, including chronic rhinosinusitis with nasal polyps (CRSwNP). However, the potential therapeutic efficacy of targeted JAK inhibition in CRSwNP remains underexplored and requires further investigation.

BnaGSK3-BnaIDD16 module negatively regulates branch angle in Brassica napus.

Brassinosteroids (BRs) play a key role in regulating plant height and leaf angle in plants. However, the mechanism underlying the BR signaling pathway involved in branch angle regulation is poorly understood. Here, we isolated a rapeseed (Brassica napus L.

Rapid and actionable nasal-swab screening supports antimicrobial stewardship in patients with pneumonia: a prospective study.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) nasal screening by polymerase chain reaction (PCR) is a rapid diagnostic tool with a high negative predictive value for pneumonia caused by MRSA. MRSA remains an important emerging pathogen in China and at present, there is little published data on the effect of rapid MRSA test results on antibiotic utilization for pneumonia.

Methods: A total of 300 inpatients who met the criteria of pneumonia in a tertiary general hospital were randomly assigned to a notification group (NG, n = 150) or a control group (CG, n = 150).

A salt-driven mechanism for precise chirality sorting of carbon nanotubes.

Sorting single-wall carbon nanotubes (SWCNTs) by chirality/handedness is of substantial scientific and technological importance. Existing sorting methods often lack simplicity, reproducibility and scalability. Here, we demonstrate a salt-driven SWCNT sorting mechanism that addresses these challenges.

External strain on the plasma membrane is relayed to the endoplasmic reticulum by membrane contact sites and alters cellular energetics.

Mechanotransduction is essential for living cells to adapt to their extracellular environment. However, it is unclear how the biophysical adaptation of intracellular organelles responds to mechanical stress or how these adaptive changes affect cellular homeostasis. Here, using the tendon cell as a mechanosensitive cell type within a bioreactor, we show that the tension of the plasma membrane (PM) and the endoplasmic reticulum (ER) adaptively increases in response to repetitive external stimuli.

Rictor Ameliorates Acute Antibody-Mediated Rejection Following Kidney Transplantation by Suppressing Macrophage M1 Polarization Through p65-NLRP3 Axis.

Antibody-mediated rejection (ABMR) represents the leading cause of kidney allograft failure over a long term after transplantation. Early infiltration of macrophages predicts the adverse outcome of grafts, yet the underlying mechanisms remain to be elucidated. Significant infiltration of M1 macrophages and upregulation of Rictor in macrophages are observed in ABMR allografts.

ENPP1 governs the metabolic regulation of effector T cells in autoimmunity by detecting cytosolic mitochondrial DNA.

T cells play a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE), yet the underlying molecular mechanisms governing their fate remain elusive. Here, we identify cytosolic mitochondrial DNA (mtDNA) as an intrinsic trigger for driving effector T cell differentiation in patients with SLE. Specifically, accumulated cytosolic mtDNA is sensed by ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), which enhances the transcription of GLUT1 and glycolysis in SLE T cells.

RNA Dynamics Regulate Transcriptional Condensate Vivacity to Drive Gene Coordination.

Unlabelled: Transcriptional condensates (TCs), enriched with Mediator, orchestrate super-enhancer (SE)-driven gene expression critical for cell identity. However, how their dynamic physical properties shape transcriptional activities remains unclear. Here, we reveal a previously unknown regulatory axis wherein dynamic features of enhancer RNA (eRNA), transcribed but rapidly degraded by the RNA exosome, maintain optimal TC fluidity and stability.

An optimal subsampling design for large-scale Cox model with censored data.

Subsampling designs are useful for reducing computational load and storage cost for large-scale data analysis. For massive survival data with right censoring, we propose a class of optimal subsampling designs under the widely-used Cox model. The proposed designs utilize information from both the outcome and the covariates.

Thinking bipolar disorder as a symptom rather than a disease.

Bipolar affective disorder (BAD), a major global health challenge, has traditionally been classified as a distinct psychiatric condition characterized by episodes of mania and depression. Recent findings suggest that BAD may not represent a singular disease but rather a manifestation of broader, interconnected pathophysiological processes underlying mood dysregulation. This study proposes a paradigm shift, conceptualizing BAD as a shared symptom reflecting common pathophysiological mechanisms rather than a discrete disorder.

Super-high tumor mutational burden predicts complete remission following immunotherapy: from Peto's paradox to druggable cancer hallmark.

Background: The somatic mutation theory predicts that cancer risk should scale proportionally with lifetime cell divisions; yet large-bodied and long-lived species exhibit lower-than-expected cancer incidence-a long-standing contradiction termed Peto's paradox. Resolving this paradox and clarifying how tumor mutational burden (TMB) shapes treatment response to immune-checkpoint inhibitor (ICI) therapy remain unmet needs in precision oncology.

Methods: This study analyzed three data streams: (1) human cancer incidence data from North American registries; (2) cancer mortality records for 110,148 mammals (191 species) linked to body mass, life expectancy, and cancer risk, and (3) >30,000 tumors profiled in three independent pan-cancer cohorts and clinical outcomes in >2,700 ICI-treated patients.

C-reactive protein-to-albumin ratio predicts outcome of neoadjuvant chemotherapy for colorectal liver metastases: A multicenter prediction model.

Background: Neoadjuvant chemotherapy for patients with colorectal liver metastasis often results in varying outcomes. This study aimed to develop a clinical prediction model incorporating the C-reactive protein-to-albumin ratio to determine neoadjuvant chemotherapy efficacy in patients with colorectal liver metastasis METHODS: This retrospective study included 1,335 patients with colorectal liver metastasis who received neoadjuvant chemotherapy. Patients were classified into high and low C-reactive protein-to-albumin ratio groups on the basis of an optimal cutoff value.

Effect of three cannulated compression screws combined with an obstructing screw on the biomechanical performance of pauwels type III femoral neck fractures: a finite element analysis.

Background: Obstructing screws (OS) are an effective surgical method for treating Pauwels type III femoral neck fractures. This study compared the mechanical properties of various surgical techniques for treating such fractures using finite element analysis.

Methods: An ideal finite element model of the femur was established based on computed tomography scans of healthy individuals.

PAD2 disturbs cardiomyocyte calcium homeostasis by citrullinating SERCA2a protein in hemorrhagic shock induced arrhythmia.

Background: Malignant arrhythmia induced by traumatic hemorrhage is a leading cause of early mortality in hemorrhagic shock. Understanding the mechanisms driving these arrhythmias and identifying therapeutic targets are critical for improving early survival in patients with traumatic hemorrhagic shock.

Methods: Peripheral blood samples from patients with hemorrhagic shock were collected and analyzed for peptidylarginine deiminase 2 (PAD2) protein levels using ELISA.

Deconvoluting TCR-dependent and -independent activation is vital for reliable Ag-specific CD4 T cell characterization by AIM assay.

Activation-induced marker (AIM) assays identify antigen (Ag)-specific T cells, but recent studies revealed AIM T helper cell 17 (T17)-like (CCR6) and circulating T follicular helper cells (cTfh) were not associated with peptide/HLA tetramer staining. We show that CD39 regulatory T cell (T)-like and CD26 T22-like cells undergo T cell receptor (TCR)-independent activation by cytokines during Ag stimulation, leading to nonspecific up-regulation of AIM readouts. Transcriptional analysis enabled discrimination of bona fide Ag-specific T cells from cytokine-activated T and T22 cells.

COVID-19 Predisposition Inherently Increases Cardiovascular Risk Before SARS-CoV-2 Infection.

As COVID-19 transitions to an endemic stage, its long-term impacts on health, particularly cardiovascular disease (CVD), remain significant. While prior studies have focused on cardiovascular complications following SARS-CoV-2 infection, the question of inherent cardiovascular risk associated with genetic predisposition to COVID-19 has been less explored. This study investigates whether individuals genetically predisposed to COVID-19 may also be at higher risk for CVD, independent of actual infection.

Exploring the association between plasma lipids changes and embolization recurrence following intravenous thrombolysis with alteplase in acute ischemic stroke based on lipidomics.

Background: Alteplase is a widely used thrombolytic therapy for acute ischemic stroke (AIS). However, the efficacy of intravenous thrombolysis (IVT) with alteplase varies due to individual factors, and some patients are prone to embolization recurrence (ER) after IVT. The mechanisms underlying these variations are not fully understood.

Mitophagy-mediated S1P facilitates muscle adaptive responses to endurance exercise through SPHK1-S1PR1/S1PR2 in slow-twitch myofibers.

Endurance exercise triggers adaptive responses especially in slow-twitch myofibers of skeletal muscles, leading to the remodeling of myofiber structure and the mitochondrial network. However, molecular mechanisms underlying these adaptive responses, with a focus on the fiber type-specific perspective, remains largely unknown. In this study we analyzed the alterations of transcriptomics and metabolomics in distinct skeletal myofibers in response to endurance exercise.