ApoE3 R136S binds to Tau and blocks its propagation, suppressing neurodegeneration in mice with Alzheimer's disease.

PSEN1 E280A carrier for the APOE3 Christchurch variant (R136S) is protected against Alzheimer's disease (AD) symptoms with a distinct anatomical pattern of Tau pathology. However, the molecular mechanism accounting for this protective effect remains incompletely understood. Here, we show that the ApoE3 R136S mutant strongly binds to Tau and reduces its uptake into neurons and microglia compared with ApoE3 wild type (WT), diminishing Tau fragmentation by asparagine endopeptidase (AEP), proinflammatory cytokines by Tau pre-formed fibrils (PFFs) or β-amyloid (Aβ), and neurotoxicity.

Modular Construction of Multivariate Metal-Organic Frameworks for Luminescent Sensing.

Metal-organic frameworks (MOFs) have played a pivotal role as rapid and effective luminescent sensing materials. Numerous MOFs with diverse characteristics have been meticulously designed for target analytes. Previous studies have highlighted the factors of spectral characteristics, energy levels, interaction forces, and sensor stabilities for the luminescent sensing performance in response to a specific analyte.

Urinary metabolic alterations associated with occupational exposure to metals and polycyclic aromatic hydrocarbons based on non-target metabolomics.

Long-term occupational exposure to metals and organics have been reported to be under great health risks. However, limited data are available on the molecular mechanism between combined exposure to metals and polycyclic aromatic hydrocarbons (PAHs) and harmful health effects. In present work, non-target metabolomics study was conducted based on urine samples from nonferrous metal smelting workers (n = 207), surrounding residents (n = 180), and the control residents (n = 187) by using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS).

Polymorphisms, Homocysteine Elevation, and Ischemic Stroke Susceptibility in East Asian and European Populations.

Background And Objectives: Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme that regulates folate and homocysteine metabolism. Genetic variation in has been implicated in cerebrovascular disease risk, although research in diverse populations is lacking. We thus aimed to investigate the effect of genetically predicted MTHFR activity on risk of ischemic stroke (IS) and its main subtypes using a multiancestry Mendelian randomization (MR) approach.

Effect of an α-calcium sulfate hemihydrate/treated dentin matrix composite to regenerate bone in critically sized SD rat calvarial defects.

Introduction: α-Calcium sulfate hemihydrate (α-CSH) is a widely used artificial bone graft material, but it suffers from rapid deterioration and limited osteoinductivity. This study aims to develop composite cements by combining treated dentin matrix (TDM) with α-CSH to enhance osteogenic properties for the healing of bone deformities.

Methods: The composite cements were prepared by mixing treated dentin matrix (TDM) with α-calcium sulfate hemihydrate (α-CSH) and characterized for their mechanical, morphological, and chemical properties using a universal mechanical testing machine, scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier-transform infrared (FTIR) spectroscopy.

Investigating the Process of Autoimmune Inner Ear Disease: Unveiling the Intricacies of Pathogenesis and Therapeutic Strategies.

Autoimmune inner ear disease (AIED) is a rare condition characterized by immune-mediated damage to the inner ear, leading to progressive sensorineural hearing loss (SNHL) and vestibular symptoms such as vertigo and tinnitus. This study investigates the pathogenesis and therapeutic strategies for AIED through the analysis of three cases with different underlying autoimmune disorders: rheumatoid arthritis, relapsing polychondritis, and IgG4-related disease. The etiology of AIED involves complex immunopathological mechanisms, including molecular mimicry and the "bystander effect," with specific autoantibodies, such as those against heat shock protein 70 (HSP70), playing a potential role in cochlear damage.

Exploring the impact of fulvic acid and humic acid on heavy metal availability to alfalfa in molybdenum contaminated soil.

Humic substances, such as Fulvic acid (FA) and humic acid (HA), are widely used for the remediation of heavy metal-contaminated soils due to their ability to enhance metal mobility and facilitate plant uptake. In this study, we conducted a pot experiment with alfalfa to investigate the effects of FA and HA amendments on the mobility of molybdenum (Mo) in the soil, its uptake by alfalfa plants, and subsequent changes in the microbial community. The results demonstrated that both FA and HA influence Mo accumulation in the soil and plants.

The association of sexual frequency with cardiovascular diseases incidence and all-cause mortality.

Sexual activity exists in a complex relationship with human health. This study aims to elucidate the correlation between the sexual frequency and the incidence of cardiovascular diseases (CVD) and all-cause mortality among young and middle-aged adults of the United States. We analyzed 17,243 participants from the National Health and Nutrition Examination Survey(NHANES)(2005-2016), comparing CVD incidence and all-cause mortality risks across sexual frequencies using multivariable Logistic and Cox regression models.

A prodrug nanodevice co-delivering docetaxel and ROR1 siRNA for enhanced triple negative breast cancer therapy.

Triple-negative breast cancer (TNBC) has been a clinical challenge due to its high recurrence and metastasis rates. Chemotherapy remains the primary treatment for TNBC after surgery ablation, but it lacks targeted specificity and causes side effects in normal tissues. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is significantly expressed in TNBC cells, and small interference RNA (siRNA) targeting ROR1 can effectively suppress ROR1 gene expression, thereby inhibiting proliferation and metastasis.

Deciphering the mechanism of rhizosphere microecosystem in modulating rice cadmium accumulation via integrating metabolomics and metagenomics.

Cadmium (Cd) accumulation in rice poses significant risks to human health. The Cd accumulation levels vary widely among cultivars and are strongly associated with the rhizosphere microecosystem. However, the underlying mechanisms remain poorly understood.

CBL/Cbl-b mediates Fas degradation to reduce neuronal damage in experimental autoimmune encephalomyelitis.

Fas has been shown to positively regulate the differentiation of T helper 17 (Th17) cells in mouse models of experimental autoimmune encephalomyelitis (EAE). Fas protein expression is regulated by ubiquitination but has not been further studied. In this study, we investigated the role of the Fas ubiquitin ligase in Th17 cell differentiation and highlighted its potential as a therapeutic target for EAE.

G3BP1/2-Targeting PROTAC Disrupts Stress Granules Dependent ATF4 Migracytosis as Cancer Therapy.

Stress granules (SGs) are membraneless cytoplasmic compartments that form in response to stress stimuli. In these compartments, most translation factors stall, except for activating transcription factor 4 (ATF4), which is preferentially translated to ensure cell survival under stressful conditions. Cancer cells encounter various stress conditions in the tumor microenvironment during tumorigenesis; however, how they exploit the pro-survival effects of ATF4 in SGs remains unclear.

Revealing an unprecedented diversity of episymbiotic Saccharibacteria in a high-quality genome collection.

The episymbiotic Candidatus Saccharibacteria is the most studied lineage of candidate phyla radiation. Living an epiparasitic lifestyle, Saccharibacteria might be associated with human mucosal diseases by modulating the structure of the oral microbiome through interactions with host bacteria. However, the knowledge of Saccharibacterial genomic diversity and the potential underlying their adaptation to a wide range of habitats remains limited.

An artesunate-modified half-sandwich iridium(iii) complex inhibits colon cancer cell proliferation and metastasis through the STAT3 pathway.

Colon cancer is one of the most commonly diagnosed cancers and is recognized as the most aggressive tumor of the digestive system. Aberrant activation of signal transducer and activator of transcription 3 (STAT3) is associated with proliferation, metastasis and immunosuppression of the tumor cells. Here, to inhibit the STAT3 pathway and suppress metastasis in colon cancer cells, the half-sandwich iridium complex Ir-ART containing an artesunate-derived ligand was synthesized.

Machine learning-based prognostic model of lactylation-related genes for predicting prognosis and immune infiltration in patients with lung adenocarcinoma.

Background: Histone lactylation is a novel epigenetic modification that is involved in a variety of critical biological regulations. However, the role of lactylation-related genes in lung adenocarcinoma has yet to be investigated.

Methods: RNA-seq data and clinical information of LUAD were downloaded from TCGA and GEO datasets.

Deciphering the Role of Shank3 in Dendritic Morphology and Synaptic Function Across Postnatal Developmental Stages in the Shank3B KO Mouse.

Autism Spectrum Disorder (ASD) is marked by early-onset neurodevelopmental anomalies, yet the temporal dynamics of genetic contributions to these processes remain insufficiently understood. This study aimed to elucidate the role of the Shank3 gene, known to be associated with monogenic causes of autism, in early developmental processes to inform the timing and mechanisms for potential interventions for ASD. Utilizing the Shank3B knockout (KO) mouse model, we examined Shank3 expression and its impact on neuronal maturation through Golgi staining for dendritic morphology and electrophysiological recordings to measure synaptic function in the anterior cingulate cortex (ACC) across different postnatal stages.

The safety and efficacy of applying a high-current temporal interference electrical stimulation in humans.

Background: Temporal interference electrical stimulation (TI) is promise in targeting deep brain regions focally. However, limited electric field intensity challenges its efficacy.

Objective: This study aimed to introduce a high-current TI electrical stimulation protocol to enhance its intensity and evaluate its safety and efficacy when applied to the primary motor cortex (M1) in the human brain.

Exosomes secreted from M2-polarized macrophages inhibit osteoclast differentiation via CYLD.

Objective: Bone resorption mediated by osteoclast differentiation induces the occurrence of bone-related diseases. Macrophages, an origin of osteoclasts, whose M2 type can reduce inflammation-induced bone damage. We aimed to investigate the effect of M2 macrophage-derived exosomes on osteoclast formation and elucidate its underlying mechanism.

Efficacy and Safety of Bevacizumab Biosimilar (Encoda) Compared With Reference Bevacizumab (Avastin) in Patients With Metastatic Colorectal Cancer: A Multicenter, Real-World Study.

Background: The bevacizumab biosimilar (Encoda), which was approved by the National Medical Products Administration (NMPA) in China in 2019, is a biosimilar of bevacizumab. Approval of bevacizumab biosimilar (Encoda) for metastatic colorectal cancer (mCRC) was based on the extrapolation principle of biosimilar. However, there is currently no available data regarding the efficacy and safety of both bevacizumab biosimilar (Encoda) and bevacizumab in patients with mCRC.

Regnase-1 regulates inflammation in T cells of ankylosing spondylitis through the TRAF6.

The study aimed to investigate the regulatory role of Regnase-1 in ankylosing spondylitis (AS) inflammation. We collected 10 ml peripheral venous blood and epidemiological data from 45 AS patients and 45 healthy controls and performed enzyme-linked immunosorbent assay (ELISA) experiments to measure the levels of inflammatory cytokines. Then CD3 + T lymphocytes were isolated by magnetic bead sorting method, and the transcriptional levels of Regnase-1 and TNF receptor-associated factor 6 (TRAF6) were detected by real-time quantitative PCR (qRT-PCR).

The segmented flavivirus Alongshan virus reduces mitochondrial mass by degrading STAT2 to suppress the innate immune response.

Alongshan virus (ALSV) is a newly discovered pathogen in the family, characterized by a unique multi-segmented genome that is distantly related to the canonical flaviviruses. Understanding the pathogenic mechanism of this emerging segmented flavivirus is crucial for the development of effective intervention strategies. In this study, we demonstrate that ALSV can infect various mammalian cells and induce the expression of antiviral genes.

Effect of 0.05% cyclosporine A eye drops on the healing process of corneal epithelial defects in rats.

0.05% cyclosporine A eye drops is a kind of new medication for dry eye after corneal refractive surgeries. However, it is still unclear how this eye drops affect the healing process of corneal epithelial defects caused by operative procedures.

Liang-Ge-San Decoction Ameliorates Acute Respiratory Distress Syndrome via Suppressing p38MAPK-NF-κ B Signaling Pathway.

Objective: To explore the potential effects and mechanisms of Liang-Ge-San (LGS) for the treatment of acute respiratory distress syndrome (ARDS) through network pharmacology analysis and to verify LGS activity through biological experiments.

Methods: The key ingredients of LGS and related targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. ARDS-related targets were selected from GeneCards and DisGeNET databases.