PRMT5 Inhibition Reduces Hyperinflammation in a Murine Model of Secondary Hemophagocytic Lymphohistiocytosis (HLH).

Hemophagocytic lymphohistiocytosis (HLH) is a rare but aggressive and potentially lethal hyperinflammatory syndrome characterized by pathologic immune activation and excessive production of proinflammatory cytokines leading to tissue damage and multisystem organ failure. There is an urgent need for the discovery of novel targets and development of therapeutic strategies to treat this rare but deadly syndrome. Protein Arginine Methyltransferase 5 (PRMT5) mediates T cell-based inflammatory responses, making it a potential actionable target for the treatment of HLH.

One-Step Ethylene Purification from Ternary Mixture through Adaptive Recognition Sites.

One-step adsorptive purification of ethylene (C2H4) from ternary mixture comprising of acetylene (C2H2), ethylene (C2H4) and carbon dioxide (CO2) is a great challenge in the chemical industry. Herein, a microporous metal-organic framework (FJI-H38) has been reported, which possesses a high density of electronegative O/N binding sites and appropriate pore size. Notably, at 0.

Effectiveness of a 2-dose varicella vaccination program in Changzhou, China, during the transitional period (2017-2022): a registry-based case-cohort study.

Background: The benefits of improving coverage and timeliness of varicella vaccination need to be quantified in countries where varicella vaccine (VarV) has not yet been included in national immunization programs. This longitudinal study analyzed the vaccine effectiveness (VE) of the varicella vaccination program implemented in Changzhou City during the transitional period (2017-2022).

Methods: Using the Immunization Information System and National Notifiable Infectious Disease Surveillance System registry data, this retrospective case-cohort study assessed the VEs of varicella vaccination for Changzhou children born from 2016 to 2021.

Fear of progression and quality of life in patients with heart failure: a cross-sectional study on the multiple mediation of psychological distress and resilience.

Background: Existing research indicates that fear of progression influences the quality of life of patients with various diseases. However, the influence of fear of progression on the quality of life of patients with heart failure and its underlying mechanisms remain unclear. This study aimed to identify the link between fear of progression and quality of life in patients with heart failure and explore the multiple mediating roles of psychological distress and resilience in this association.

Inhalation of multiple pen caps causing bronchial foreign bodies: a rare case in an older child.

Background: Foreign body inhalation is rare in older children, often leading to underdiagnosis and delayed treatment. Most cases involve a single foreign body, but instances of multiple foreign bodies are exceedingly uncommon. This report presents a case of an elder child who inhaled two pen caps, emphasizing the need for clinical vigilance and thorough medical history collection.

Safety, efficacy, and immunogenicity of a novel IgG degrading enzyme (KJ103): results from two randomised, blinded, phase 1 clinical trials.

The approved intravenous adeno-associated virus (AAV) therapies are limited by the widespread prevalence of pre-existing anti-AAV antibodies in the general population, which are known to restrict patients' ability to receive gene therapy and limit transfection efficacy in vivo. To address this challenge, we have developed a novel recombinant human immunoglobulin G degrading enzyme KJ103, characterized by low immunogenicity and clinical value for the elimination of anti-AAV antibodies in gene transfer. Herein, we conducted two randomized, blinded, placebo-controlled, single ascending dose Phase I studies in China and New Zealand, to evaluate the pharmacokinetics, pharmacodynamics, safety and immunogenicity of KJ103 in healthy volunteers.

Equity analysis of bus network balance from the perspective of spatial morphology and service capability.

A balanced and equitable bus network layout plays a crucial role in the efficient operation of cities. The layout of urban bus networks is influenced by various factors, including urban planning, population size, industrial distribution, and road network layout. Forming a comprehensive indicator system and analyzing the balance and fairness of bus network layouts are key research areas.

Topographic Axes of Wiring Space Converge to Genetic Topography in Shaping Human Cortical Layout.

Genetic information is involved in the gradual emergence of cortical areas since the neural tube begins to form, shaping the heterogeneous functions of neural circuits in the human brain. Informed by invasive tract-tracing measurements, the cortex exhibits marked interareal variation in connectivity profiles, revealing the heterogeneity across cortical areas. However, it remains unclear about the organizing principles possibly shared by genetics and cortical wiring to manifest the spatial heterogeneity across cortex.

A nanobody-enzyme fusion protein targeting PD-L1 and sialic acid exerts anti-tumor effects by C-type lectin pathway-mediated tumor associated macrophages repolarizing.

Aberrant sialylated glycosylation in the tumor microenvironment is a novel immune suppression pathway, which has garnered significant attention as a targetable glycoimmune checkpoint for cancer immunotherapy to address the dilemma of existing therapies. However, rational drug design and in-depth mechanistic studies are urgently required for tumor sialic acid to become valuable glycoimmune targets. In this study, we explored the positive correlation of PD-L1 and sialyltransferase expression in clinical colorectal cancer tissues and identified their mutual regulation effects in macrophages.

Ghrelin Promotes Chronic Diabetic Wound Healing by Regulating Keratinocyte Proliferation and Migration Through the ERK1/2 Pathway.

Delayed wound healing is a complication of diabetes mellitus and can lead to infection, sepsis, and amputation. Despite the currently available treatments, the global burden of diabetes-related wounds is growing; thus, more effective therapy for diabetic wounds is urgently needed. Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, is a 28-amino acid peptide hormone.

A paper-based SERS/colorimetry substrate for reliable detection.

For on-site analysis, the combination of surface enhanced Raman scattering (SERS) and colorimetry, as a dual-mode detection, can effectively improve the accuracy of detection, and reduce the influence of instrument fluctuation, which greatly improves the accuracy and reliability of the results. However, the preparation of SERS/colorimetry substrates are usually time-consuming and costly, which limits their practical applications. In this paper, a hydrophobic paper-based SERS/colorimetry substrate can be prepared by a simple spraying method.

Ticks jump in a warmer world: Global distribution shifts of main pathogenic ticks are associated with future climate change.

In recent decades, the threats of ticks and tick-borne diseases (TBDs) increased extensively with environmental change, urbanization, and rapidly changing interactions between human and animals. However, large-scale distribution of tick and TBD risks as well as their relationship with environmental change remain inadequately unclear. Here, we first proposed a "tick-pathogen-habitat-human" model to project the global potential distribution of main pathogenic ticks using a total of 70,714 occurrence records.

Heat-inactivated Lactobacillus casei strain GKC1 Mitigates osteoporosis development in vivo via enhanced osteogenesis.

Osteoporosis, a significant bone disease predominantly affecting elderly and postmenopausal women, leads to increased bone fragility and fracture risk, presenting a major public health concern with substantial socioeconomic implications. This study investigated the therapeutic potential of Lactobacillus strains, known for their immunomodulatory properties, in an ovariectomy-induced osteoporosis mouse model. Among three tested strains Lactobacillus casei GKC1, Lactobacillus rhamnosus GKLC1, and Lactobacillus johnsonii GKJ2, GKC1 demonstrated superior efficacy in promoting osteogenesis-related gene expression, including alkaline phosphatase (ALP), bone morphogenetic protein 2 (BMP2) and runt-related transcription factor 2 (RUNX2).

Insights into tumor-derived exosome inhibition in cancer therapy.

Exosomes are critical mediators of cell-to-cell communication in physiological and pathological processes, due to their ability to deliver a variety of bioactive molecules. Tumor-derived exosomes (TDEs), in particular, carry carcinogenic molecules that contribute to tumor progression, metastasis, immune escape, and drug resistance. Thus, TDE inhibition has emerged as a promising strategy to combat cancer.

ACC treatment induced alterations in flavonoid accumulation in Toxicodendron vernicifluum.

Lacquer tree (Toxicodendron vernicifluum) is an important economic crop and is rich in flavonoids. ACC (1-aminocyclopropane-1-carboxylic acid) is the precursor to ethylene. ACC treatment can induce physiological and biochemical responses in plants.

Detection of epileptogenic zones in people with epilepsy using optimized EEG-fMRI.

Purpose: Concurrent electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) have been used to assist in the presurgical localization of seizure foci in people with epilepsy. Our study aimed to examine the clinical feasibility of an optimized concurrent EEG-fMRI protocol.

Methods: The optimized protocol employed a fast-fMRI sequence (sampling rate = 10 Hz) with a spare arrangement, which allowed a time window of 1.

Permeability Benchmarking: Guidelines for Comparing , , and Measurements.

Permeability is a measure of the degree to which cells can transport molecules across biological barriers. Units of permeability are distance per unit time (typically cm/s), where accurate measurements are needed to define drug delivery in homeostasis and to model dysfunction occurring during disease. This perspective offers a set of community-led guidelines to benchmark permeability data across multidisciplinary approaches and different biological contexts.

Activation of locus coeruleus noradrenergic neurons rapidly drives homeostatic sleep pressure.

Homeostatic sleep regulation is essential for optimizing the amount and timing of sleep for its revitalizing function, but the mechanism underlying sleep homeostasis remains poorly understood. Here, we show that optogenetic activation of locus coeruleus (LC) noradrenergic neurons immediately increased sleep propensity following a transient wakefulness, contrasting with many other arousal-promoting neurons whose activation induces sustained wakefulness. Fiber photometry showed that repeated optogenetic or sensory stimulation caused a rapid reduction of calcium activity in LC neurons and steep declines in noradrenaline/norepinephrine (NE) release in both the LC and medial prefrontal cortex (mPFC).

Development of PROTACs targeting estrogen receptor: an emerging technique for combating endocrine resistance.

Despite the success of endocrine therapies in treating ER-positive breast cancer, the development of resistance remains a significant challenge. Estrogen receptor targeting proteolysis-targeting chimeras (ER PROTACs) offer a unique approach by harnessing the ubiquitin-proteasome system to degrade ER, potentially bypassing resistance mechanisms. In this review, we present the drug design, efficacy and early clinical trials of these ER PROTACs.

Prospective Multi-Site Validation of AI to Detect Tuberculosis and Chest X-Ray Abnormalities.

Background: Using artificial intelligence (AI) to interpret chest X-rays (CXRs) could support accessible triage tests for active pulmonary tuberculosis (TB) in resource-constrained settings.

Methods: The performance of two cloud-based CXR AI systems - one to detect TB and the other to detect CXR abnormalities - in a population with a high TB and human immunodeficiency virus (HIV) burden was evaluated. We recruited 1978 adults who had TB symptoms, were close contacts of known TB patients, or were newly diagnosed with HIV at three clinical sites.

Ultrasound combined with contrast‑enhanced ultrasound in the diagnosis of primary squamous cell carcinoma of the thyroid: A case report and literature review.

Primary squamous cell carcinoma of the thyroid (PSCCT) is a rare malignancy with a poor prognosis. Therefore, early diagnosis and treatment are critical to the survival of patients and to improve their quality of life. However, diagnosing this illness is challenging.

ABCA1-Super Enhancer RNA Promotes Cholesterol Efflux, Reduces Macrophage-Mediated Inflammation and Atherosclerosis.

We describe a previously uncharacterized ATP-binding cassette A1 super enhancer RNA (ABCA1-seRNA)-mediated cholesterol efflux. In addition, it promoted macrophage inflammatory cytokine release, and was causally correlated with coronary artery disease severity. Mechanistically, ABCA1-seRNA upregulated cholesterol efflux by interacting with mediator complex subunit 23 and recruiting retinoid X receptor-alpha and liver X receptor-alpha to promote ABCA1 transcription in a manner.

The relationship between smoking and recurrent aphthous stomatitis: A Mendelian randomization study.

Introduction: Existing research suggests an association between smoking and the incidence of recurrent aphthous stomatitis (RAS); however, the causal relationship remains ambiguous. We employed Mendelian randomization (MR) to clarify the potential causal association between smoking and the risk of developing RAS.

Methods: We utilized genome-wide association study (GWAS) sequencing data related to smoking from the Finnish database as instrumental variables (IVs) and GWAS data for RAS from the UK Biobank (UKB) as the outcome to perform a two-sample MR analysis.