ZNFX1 functions as a master regulator of epigenetically induced pathogen mimicry and inflammasome signaling in cancer.

DNA methyltransferase and poly (ADP-ribose) polymerase inhibitors (DNMTis, PARPis) induce a stimulator of interferon genes (STING)-dependent pathogen mimicry response (PMR) in ovarian and other cancers. Here, we showed that combining DNMTis and PARPis upregulates expression of the nucleic-acid sensor NFX1-type zinc finger-containing 1 protein (ZNFX1). ZNFX1 mediated induction of PMR in mitochondria, serving as a gateway for STING-dependent interferon/inflammasome signaling.

The MR1/MAIT cell axis enhances dystrophic neurite development in Alzheimer's disease.

Introduction: Plaques are a hallmark feature of Alzheimer's disease (AD). We found that the loss of mucosal-associated invariant T (MAIT) cells and their antigen-presenting molecule MR1 caused a delay in plaque pathology development in AD mouse models. However, it remains unknown how this axis is impacting dystrophic neurites.

Epidemiology of pulmonary embolism in China, 2021: a nationwide hospital-based study.

Background: Pulmonary embolism (PE) as a preventable and potentially fatal noncommunicable disease was believed to have a lower incidence in Asian populations compared to Western populations. However, the incidence and mortality rates of PE in China and the impact of venous thromboembolism (VTE) prevention system constructions on PE still lack nationwide evidence.

Methods: For this nationwide hospital-based observational study, we used data from the National Hospital Quality Monitoring System (HQMS) and public database in China.

Seasonal shifts in respiratory pathogen co-infections and the associated differential induction of cytokines in children.

In the post-pandemic era, research on respiratory diseases should refocus on pathogens other than the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Respiratory pathogens, highly infectious to children, with to different modes of infection, such as single-pathogen infections and co-infections. Understanding the seasonal patterns of these pathogens, alongside identifying single infections and co-infections and their impact on the pediatric immune status, is crucial for clinical diagnosis, treatment, and prognosis in children.

Edaravone Protects Trophoblast Cells From Hypoxic Injury in Preeclampsia: Inhibition of the PI3K/AKT Pathway as a Promising Therapeutic Approach.

Objective: Preeclampsia (PE) is a multifaceted medical condition that manifests during pregnancy, characterized by hypertension and damage to multiple organs. In PE, the placenta's impaired functionality leads to continuous hypoxia in placental tissues, which is considered the primary cause of the condition. Inhibition of hypoxia-induced injury in trophoblast cells presents a potential therapeutic strategy for PE.

Association between various types of corticosteroids and mortality for severe community-acquired pneumonia in adults: a systematic review and network meta-analysis.

Objective: This study aims to conduct a systematic review and network meta-analysis to evaluate the efficacy and safety of specific corticosteroids, including but not limited to hydrocortisone, methylprednisolone, prednisolone, and dexamethasone, in the treatment of severe community-acquired pneumonia (SCAP). Efficacy will be assessed using specific outcomes, such as 30-day mortality and the requirement for mechanical ventilation. Safety evaluations will include adverse events like gastrointestinal bleeding and healthcare-associated infections.

Impact of SGLT2 Inhibitors on Left Ventricular Remodeling in Diabetic Patients with Acute Myocardial Infarction.

Objective: To assess the effect of sodium-glucose cotransporter 2 inhibitors (SGLT2-I) on cardiac remodeling and prognosis in type 2 diabetes mellitus (T2DM) patients presenting with acute myocardial infarction (AMI).

Methods: In this single-center retrospective active-comparator study, consecutive diabetic AMI patients undergoing percutaneous coronary intervention (PCI) between 2021 and 2023 were enrolled. Patients were divided into SGLT2-I users and non-SGLT2-I users based on discharge medications.

Serum proteome profiling reveals HGFA as a candidate biomarker for pulmonary arterial hypertension.

Background: Identification and validation of potential biomarkers could facilitate the identification of pulmonary arterial hypertension (PAH) and thus aid to study their roles in the disease process.

Methods: We used the isobaric tag for relative and absolute quantitation approaches to compare the protein profiles between the serum of PAH patients and the controls. Bioinformatics analyses and enzyme-linked immunosorbent assay (ELISA) identification of PAH patients and the controls were performed to identify the potential biomarkers.

Efficacy of restrictive versus liberal transfusion strategies in patients with traumatic brain injury: a systematic review and meta-analysis of randomized controlled trials.

Background: The effects of restrictive versus liberal transfusion strategies in critically ill patients with traumatic brain injury (TBI) and anemia, particularly in adult patients with moderate to severe TBI, remain inconclusive. Therefore, this systematic review and meta-analysis aim to evaluate the comparative impact of restrictive and liberal red blood cell transfusion strategies among critically ill adult patients with moderate to severe TBI.

Methods: We conducted a search of PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials from their inception through October 20, 2024, to identify randomized controlled trials that compared restrictive (transfusions at a hemoglobin level of ≤ 7 g/dL) and liberal (transfusions at a hemoglobin level of ≤ 9-10 g/dL) transfusion strategies in adult patients with TBI.

Effects of Saccharomyces boulardii on microbiota composition and metabolite levels in the small intestine of constipated mice.

Saccharomyces boulardii (S. boulardii) is a fungal probiotic used to treat digestive disorders. However, the mechanism(s) by which S.

Polycomb group protein Mel18 inhibits hematopoietic stem cell self-renewal through repressing the transcription of self-renewal and proliferation genes.

Polycomb group (PcG) proteins play important roles in hematopoietic stem cell (HSC) self-renewal. Mel18 and Bmi1 are homologs of the PCGF subunit within the Polycomb repressive complex 1 (PRC1). Bmi1 (PCGF4) enhances HSC self-renewal and promotes terminal differentiation.

Microglial Lyzl4 Facilitates β-Amyloid Clearance in Alzheimer's Disease.

Alzheimer's Disease (AD) is a neurodegenerative condition characterized by the accumulation and deposition of amyloid-β (Aβ) aggregates in the brain. Despite a wealth of research on the toxicity of Aβ and its role in synaptic damage, the mechanisms facilitating Aβ clearance are not yet fully understood. However, microglia, the primary immune cells of the central nervous system, are known to maintain homeostasis through the phagocytic clearance of protein aggregates and cellular debris.

High-throughput development and characterization of new functional nanobodies for gene regulation and epigenetic control in human cells.

Controlling gene expression and chromatin state via the recruitment of transcriptional effector proteins to specific genetic loci has advanced the potential of mammalian synthetic biology, but is still hindered by the challenge of delivering large chromatin regulators. Here, we develop a new method for generating small nanobodies against human chromatin regulators that can repress or activate gene expression. We start with a large and diverse nanobody library and perform enrichment against chromatin regulatory complexes using yeast display, followed by high-throughput pooled selection for transcriptional control when recruited to a reporter in human cells.

Resolvin D2/GPR 18 axis ameliorates pressure overload-induced heart failure by inhibiting pro-inflammatory macrophage polarization.

Accumulating evidence has revealed that chronic unresolved inflammation can cause significant tissue damage and can be a key mediator of advanced heart failure (HF). Resolvin (Rv) D2, a member of specialized pro-resolving lipid mediators (SPMs), plays a protective role in various diseases by facilitating resolution. However, whether RvD2 participates in the pathogenesis of HF is still unclear.

ZNFX1 is a Novel Master Regulator in Epigenetically-induced Pathogen Mimicry and Inflammasome Signaling in Cancer.

DNA methyltransferase and poly(ADP-ribose) polymerase inhibitors (DNMTis, PARPis) induce a stimulator of interferon (IFN) genes (STING)-dependent pathogen mimicry response (PMR) in ovarian (OC) and other cancers. We now show that combining DNMTis and PARPis upregulates expression of a little-studied nucleic-acid sensor, NFX1-type zinc finger-containing 1 protein (ZNFX1). We demonstrate that ZNFX1 is a novel master regulator for PMR induction in mitochondria, serving as a gateway for STING-dependent PMR.

Inhibition of Glutamate-to-Glutathione Flux Promotes Tumor Antigen Presentation in Colorectal Cancer Cells.

Colorectal cancer (CRC) cells display remarkable adaptability, orchestrating metabolic changes that confer growth advantages, pro-tumor microenvironment, and therapeutic resistance. One such metabolic change occurs in glutamine metabolism. Colorectal tumors with high glutaminase (GLS) expression exhibited reduced T cell infiltration and cytotoxicity, leading to poor clinical outcomes.

LGR6 protects against myocardial ischemia-reperfusion injury via suppressing necroptosis.

Regulated necrosis (necroptosis) and apoptosis are important biological features of ischemia-reperfusion (I/R) injury. However, the molecular mechanisms underlying myocardial necroptosis remain elusive. Leucine rich repeat containing G protein-coupled receptor 6 (LGR6) has been reported to play important roles in various cardiovascular disease.

Multimodal contrastive learning for spatial gene expression prediction using histology images.

In recent years, the advent of spatial transcriptomics (ST) technology has unlocked unprecedented opportunities for delving into the complexities of gene expression patterns within intricate biological systems. Despite its transformative potential, the prohibitive cost of ST technology remains a significant barrier to its widespread adoption in large-scale studies. An alternative, more cost-effective strategy involves employing artificial intelligence to predict gene expression levels using readily accessible whole-slide images stained with Hematoxylin and Eosin (H&E).

Prognostic value of pre-treatment neutrophil-to-lymphocyte ratio in patients with brain metastasis from cancer: a meta-analysis.

Evidence shows that inflammatory responses play an essential role in the development of brain metastases (BM). The goal of this meta-analysis was to critically evaluate the literature regarding the use of the neutrophil to lymphocyte ratio (NLR) to predict the prognosis of patients with BM to help clinicians institute early interventions and improve outcomes. We conducted systematic review and meta-analysis, utilizing data from prominent databases, including PubMed, Cochrane Library and China National Knowledge Infrastructure databases.

Can digital technology adoption promote environmental innovation in small and medium-sized enterprises (SMEs)? Evidence from China.

Despite the widespread acknowledgment in both industry and academia of the substantial potential of digital technology for fostering innovation and sustainable development, there remains uncertainty surrounding whether integrating these technologies can improve environmental innovation in small and medium-sized enterprises (SMEs) due to the liability of smallness. This paper utilizes a panel dataset comprising 1036 Chinese manufacturing SMEs listed between 2011 and 2020 to investigate the influence of different digital technology adoption strategies-specifically, digital technology adoption breadth (DTAB) and digital technology adoption depth (DTAD)-on SMEs' environmental innovation. Additionally, we examine the moderating effects of government subsidies and industrial agglomeration on these relationships.