Immunological dynamics in orthotopic versus subcutaneous murine models of HPV-positive oropharyngeal cancer.

The necessity of reliable preclinical models for evaluating the efficacy of novel therapeutic strategies is imperative. Nevertheless, the degree to which tumor-bearing murine models represent the immunological characteristics of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) has largely been unexplored. Utilizing single-cell RNA sequencing technology, our research elucidated that subcutaneous (SC) murine models more accurately reflect the early immunogenic phase of human HPV-positive OPSCC, marked by a stage-dependent increase in effector T cell infiltration.

TLR4group 2 innate lymphoid cells contribute to persistent type 2 immunity in airway diseases.

Group 2 innate lymphoid cells (ILC2s) directly contribute to local inflammation in type 2 inflammatory airway diseases. Here, we identify ILC2 subsets by single cell RNA sequencing in chronic rhinosinusitis with nasal polyps (CRSwNP) and in a memory inflammatory mouse model. We find that toll-like receptor 4 (TLR4)ILC2s, with similar markers to their human counterparts, expresse memory cell markers, persist over time, and respond more vigorously to a secondary unrelated antigen challenge in the mouse model.

NEXN deficiency leads to dilated cardiomyopathy in human pluripotent stem cell-derived cardiomyocytes.

Background: Dilated cardiomyopathy (DCM) constitutes a major cause of heart failure, characterized by high mortality rates and a limited availability of effective therapeutic options. A substantial body of evidence indicates that mutations in the Nexilin (NEXN) gene are significant pathogenic contributors to DCM, but the pathogenic mechanism for dilated cardiomyopathy is unclear.

Methods: A human NEXN homozygous knockout cardiomyocyte model was established by combining CRISPR/Cas9 gene editing technology and human induced pluripotent stem cells (hiPSCs)-directed differentiation technology.

Metabolism-related gene PDK1 regulates myocardial cell remodeling and its mechanism.

Background: The progression of ischemic heart disease results from various forms of cardiomyopathies, which begin with cardiac remodelling. Pyruvate Dehydrogenase Kinase 1 (PDK1) is one of the basic kinase family components responsible for oxidative phosphorylation. However, due to the lack of a suitable research model, there is no evidence that remodelling pathogenesis in humans causes death by PDK1 knockout (KO).

Long Non-Coding RNA IGFRIL Couples with PTBP1 to Destabilize IGFBP3 mRNA to Promote the IGF1R-AKT-mTOR Axis and Hepatocellular Carcinoma.

The incomplete understanding of the IGFR pathway activation mechanism limits its clinical application in hepatocellular carcinoma (HCC). Here, a transcriptome-wide screening is performed and a novel HCC-associated lncRNA, named IGFR-inducing lncRNA (IGFRIL) is identified. IGFRIL is frequently upregulated in HCC tissues and predicts poor clinical outcomes.

Degradation of thiamphenicol by electroactive biofilm coupled with N-MnO modified layer double hydroxides as cathode in microbial fuel cell.

N-doped MnO composite NiAl-Layer double hydroxides (N-MnO@NiAl-LDH) with a ping-pong chrysanthemum like structure was prepared by hydrothermal method as a cathode catalyst in microbial fuel cells (MFCs) in previous study, which demonstrating excellent catalytic performance. This study investigated the power generation performance and the degradation of thiamphenicol (TAP) in N-MnO@NiAl-LDH-cathode MFC. After the addition of TAP, the maximum power density generated by N-MnO@NiAl-LDH-cathode MFC was 537.

Nonlinear dynamics and mechanisms of digital inclusive finance on county-level public services in China: Threshold and mediation analyses.

Counties, as fundamental administrative units in China, play a pivotal role in advancing digital inclusive finance and improving public services. Despite their significance in bridging regional disparities and promoting grassroots development, research focusing specifically on counties remains insufficient. This article aims to explore the relationship between digital inclusive finance and county-level public service quality by constructing a comprehensive evaluation system.

The impact and moderating mechanisms of digital inclusive finance on public services in Chinese counties.

This article selects data from 1445 counties across three regions of China (Eastern, Central, and Western) between 2008 and 2022. It constructs evaluation index systems for the quality of livelihood and infrastructure public services and uses the entropy weight method to measure and analyze the spatiotemporal evolution characteristics of these two types of public services. The article employs a Spatial Durbin Model with two-way fixed effects to explore the spatial spillover effects and moderating mechanisms of the digital inclusive finance on the quality of livelihood and infrastructure public services in Chinese counties, while also analyzing the regional heterogeneity of the digital inclusive finance's impact across the Eastern, Central, and Western regions.

Development and validation of a new predictive model for in-hospital postoperative major adverse cardiovascular and cerebrovascular events after general anesthesia in nonagenarians undergoing non-cardiac surgery.

Background: Major adverse cardiac and cerebrovascular events (MACCE) following noncardiac surgery are the main cause of perioperative mortality. However, there are few evidence-based prediction models available for predicting the risk of MACCE. We aimed to analyze the risk factors of MACCE in patients aged 90 and older and to construct a prediction model, ultimately leading to the development of a nomogram.

Simultaneous determination of pyroxasulfone and its metabolites in wheat: Implications for safe application.

Understanding pyroxasulfone residue dynamics in wheat under China's climatic and soil conditions is critical for establishing rational usage guidelines, setting maximum residue limits, and safeguarding human health. Field trials were conducted across 10 major wheat-producing regions to evaluate the residues of 40 % pyroxasulfone suspensions in winter wheat. A UPLC-MS/MS method was developed to simultaneously quantify pyroxasulfone and four metabolites in grains and straw.

Optimal array design of deficient coding metasurfaces for terahertz beam steering via phase-gradient approaching.

Confronted with the low reconfigurability of switches and materials with continuously tunable refractive indices, terahertz active coding metasurfaces suffer from narrow phase shift ranges and low quantization precision. To address the consequent terahertz beam-steering deterioration, an array-level optimization framework from the principle of phase-coding modulation and genetic algorithm (GA) has evolved, enabling enhanced beam steering on deficient 2-bit coding metasurfaces. Unlike traditional exhaustive iterative optimization methods, a near-optimal initial population from a phase-gradient approaching algorithm combined with objective directivity functions significantly improves the beam steering performance in fewer iterations.

Rare damaging variants in the sex differences of congenital heart disease: an exome sequencing study.

Background: Congenital heart disease (CHD) exhibits a marked male predominance in birth prevalence, yet the genetic mechanisms underlying this sex disparity remain poorly understood. This study investigates the contribution of rare damaging variants on autosomes and the X chromosome to sex differences in foetal CHD.

Methods: Parents of foetuses with CHD were recruited for the study.

Functional analysis of JPH2-knockout cardiomyocytes identifies ECCD as a novel indicator in a human cardiac modelJPH2.

Background: Junctophilin-2 (JPH2) is a vital protein in cardiomyocytes, anchoring T-tubule and sarcoplasmic reticulum membranes to facilitate excitation-contraction coupling, a process essential for cardiac contractile function. Dysfunction of JPH2 is associated with cardiac disorders such as heart failure; however, prior studies using mouse models or primary human cardiomyocytes are limited by interspecies differences or poor cell viability, respectively. This study aimed to investigate JPH2's role in human cardiac function and disease using a novel stem cell-derived model, while introducing a new indicator to evaluate related cardiac impairments.

Generation of a human embryonic stem cell line (WAe009-A-3B) carrying homozygous TNNT2 gene knockout by CRISPR/Cas9 editing.

The TNNT2 gene encodes cardiac troponin T (cTnT), a critical protein in cardiac muscle contraction. Mutations in TNNT2 are associated with various cardiomyopathies, including hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), which contribute to significant morbidity and mortality. In this study, we established a novel TNNT2 knockout human embryonic stem cell (hESC) line, WAe009-A-3B, utilizing the CRISPR/Cas9 genome editing system.

Amphiregulin Mediates Epithelial Cell-Eosinophil Interactions and Amplifies Inflammation in Chronic Rhinosinusitis With Nasal Polyps.

Background: Eosinophils easily accumulate in the intra-epithelial layer and subepithelial regions in eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP). While several factors influence the migration of eosinophils from peripheral blood to extravascular tissues, the triggers and role of eosinophils near the epithelial layer in CRSwNP remain unclear.

Methods: We examined interactions between eosinophils and epithelial cells using co-culture systems.

Role of CD44CCR2CD64monocyte-derived macrophage in chronic rhinosinusitis with nasal polyps.

Heterogeneity of monocyte-derived macrophages (MDMs) is gradually recognized in polyp tissue of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the contributions of MDM subsets for sustaining inflammation remain unclear. This study therefore aimed to characterize MDM subsets in polyp tissues and estimate their functions.

The impact of anesthesia methods on postoperative outcomes of lower limb surgeries in elderly patients over 90 years old: A multicenter propensity-matched study.

Purpose: This study aimed to assess the impact of different anesthesia methods on postoperative outcomes of lower limb surgeries in elderly patients over 90 years old.

Patients And Methods: We retrospectively reviewed the medical records of elderly patients over 90 years old who underwent lower limb surgeries at Chongqing University Center Hospital, the Affiliated Hospital of Southwest Medical University, and Chongqing General Hospital from January 2012 to December 2022. The patients were categorized into two groups based on the anesthesia method employed: the general anesthesia (GA) group and the regional anesthesia (RA) group.

Adsorption characteristics of sulfate reducing bacteria Clostridium sp. on lignite surface.

Biogenic coal bed methane has attracted great attention in recent years. During the process of biogas production, the interaction between microorganisms and coal is a crucial step. Sulfate-reducing bacteria (SRB) play an important role in biogas production.

Circular CRISPR Edits Human Pluripotent Stem Cells for Disease Modeling.

The CRISPR system has been widely used for human pluripotent stem cell (hPSC) disease modeling. Circular RNA can effectively reduce RNA immunogenicity and improve RNA stability, thus contributing to in vivo DNA editing. In this study, we briefly describe the process of circularizing guide RNA and CRISPR base editing elements and using them to establish stem cell disease models.

The impact of digital village construction on poverty vulnerability among rural households.

Against the backdrop of consolidating the achievements of poverty alleviation and promoting rural revitalization, whether digital village construction can alleviate the risk of rural families returning to poverty and then help long-term poverty prevention needs systematic and scientific empirical investigation. Using data from the 2020 China Rural Revitalization Survey (CRRS), this paper analyzes the impact of digital village construction on rural household poverty vulnerability and explores its potential channels. The results show that (1) digital village construction can significantly alleviate the poverty vulnerability of rural households.

New insights into the endotypes of chronic rhinosinusitis in the biologic era.

Chronic rhinosinusitis (CRS) exhibits significant heterogeneity and has been generally classified as type 1 (T1), T2, and T3 endotypes according to the histopathologic and inflammatory features of the nasal mucosa. T2 inflammation has been regarded as the predominant endotype of CRS linked to disease severity and refractory conditions. The development of biological agents that specifically target key molecules involved in T2 inflammation offers a highly effective and promising therapeutic approach for CRS.

Risk Assessment of Global Animal Melioidosis Under Current and Future Climate Scenarios.

Melioidosis is a zoonotic disease that is caused by , which is a serious public health and safety risk. In order to explore the global animal melioidosis risk distribution and its dynamic response to future climate scenarios, we collected global data about reported animal incidence sites. Data regarding the density of in the environment were created by collecting and sorting information about the occurrence sites in contaminated air, soil, and water.

Efficacy and safety of GR1802 in uncontrolled chronic rhinosinusitis with nasal polyps: Placebo-controlled phase 2 trial.

Background: Anti-IL-4 receptor subunit alpha (IL-4Rα) treatments can effectively treat eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP). However, their impact on the overall population of patients with uncontrolled CRSwNP remains unclear.

Objectives: We evaluated the safety and efficacy of GR1802, a novel anti-IL-4Rα monoclonal antibody, in patients with uncontrolled CRSwNP.