Wheel-shaped polyoxometalates as nanozymes for autophagy-augmented and phototherapy-involved cancer nanotherapy.

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A self-assembled nanoparticle vaccine elicits effective neutralizing antibody response against EBV infection.

Background: Epstein-Barr virus (EBV) is a significant global public health concern because of its association with various malignancies and autoimmune diseases. Over 90% of the global population is chronically infected with EBV, impacting numerous cancer-related cases annually. However, none of the effective prophylactic vaccines against EBV is approved at present.

A tactfully designed photothermal agent collaborating with ascorbic acid for boosting maxillofacial wound healing.

Maxillofacial injuries that may cause severe functional and aesthetic damage require effective and immediate management due to continuous exposure to diverse microbial populations. Moreover, drug resistance, biofilm formation, and oxidative stress significantly impede timely bacterial removal and immune function, making the exploration of advanced materials for maxillofacial wound healing an appealing yet highly challenging task. Herein, a near-infrared photothermal sterilization agent was designed, encapsulated with liposomes and coated with ascorbic acid known for its antioxidant and immune-regulatory functions.

Ceftriaxone-associated dysbiosis decreases voriconazole bioavailability by upregulating intestinal P-glycoprotein expression through activation of the Nrf2-mediated signalling pathway.

Objectives: The purpose of this study was to investigate the effect of intestinal dysbiosis on the bioavailability of voriconazole and to explore any underlying mechanisms.

Method: Sprague-Dawley rats were randomly divided into two groups: a normal control group and a ceftriaxone-associated dysbiotic group. The composition of the intestinal flora was examined using 16S rRNA sequencing analysis.

Prevalence of Site-Specific Infection and Macrolide and Fluoroquinolone-Associated Mutations in Men Who Have Sex with Men in Shenzhen, China.

Background: (MG) poses a growing public health concern due to the escalating antimicrobial resistance. We aimed to assess site-specific MG infection and its correlates and macrolide and fluoroquinolones mutations among men who have sex with men (MSM) in Shenzhen, China.

Methods: Samples were obtained from different anatomic sites of MSM based on their sexual behavior.

Targeting ROR2 homooligomerization disrupts ROR2-dependent signaling and suppresses stem-like cell properties of human breast adenocarcinoma.

Breast cancer stem-like cells (CSCs) are enriched following treatment with chemotherapy, and posited as having a high level of plasticity and enhanced tumor-initiation capacity, which can enable cancer relapse. Here, we show that such features are shared by breast cancer (BCA) cells that express receptor tyrosine kinase-like orphan receptor (ROR2), which is expressed primarily during embryogenesis and by various cancers. We find that Wnt5a can induce ROR2 homooligomerization to activate noncanonical Wnt signaling and enhance tumor-initiation capacity of BCA cells.

Identification of a binding site for small molecule inhibitors targeting human TRPM4.

Transient receptor potential (TRP) melastatin 4 (TRPM4) protein is a calcium-activated monovalent cation channel associated with various genetic and cardiovascular disorders. The anthranilic acid derivative NBA is a potent and specific TRPM4 inhibitor, but its binding site in TRPM4 has been unknown, although this information is crucial for drug development targeting TRPM4. We determine three cryo-EM structures of full-length human TRPM4 embedded in native lipid nanodiscs without inhibitor, bound to NBA, and an anthranilic acid derivative, IBA.

Computational frameworks transform antagonism to synergy in optimizing combination therapies.

While drug combinations are increasingly important in disease treatment, predicting their therapeutic interactions remains challenging. This review systematically analyzes computational methods for predicting drug combination effects through multi-omics data integration. We comprehensively assess key algorithms including DrugComboRanker and AuDNNsynergy, and evaluate integration approaches encompassing kernel regression and graph networks.

Correlation of dyslipidemia characterized by abnormal cholesterol in first trimester with early pregnancy loss: a retrospective study.

Purpose: Dyslipidemia has been linked to adverse pregnancy outcomes in observational studies. This study aimed to explore how variations in lipid levels during the first trimester might influence early pregnancy loss (EPL).

Methods: Blood samples from pregnant women were analyzed to examine the relationship between EPL and lipid metabolism using logistic regression and restricted cubic splines (RCS).

Co-exposure to polycyclic aromatic hydrocarbons and nicotine and their associations with cognitive impairment risk in older adults from southern China.

Exposure to polycyclic aromatic hydrocarbons (PAHs) and tobacco smoke is widespread and linked to various adverse health outcomes. Their potential to disturb the neurological system has raised much concern, particularly among older adults. Thus, we conducted a case-control study to assess the associations between co-exposure to PAHs and nicotine, and the risk of cognitive impairment and oxidative stress in older adults.

IgA class switching enhances neutralizing potency against SARS-CoV-2 by increased antibody hinge flexibility.

IgA antibodies are critical components of the mucosal immune barrier, providing essential first-line defense against viral infections. In this study, we investigated the impact of antibody class switching on neutralization efficacy by engineering recombinant antibodies of different isotypes (IgA1, IgG1) with identical variable regions from SARS-CoV-2 convalescent patients. A potent, broad-spectrum neutralizing monoclonal antibody CAV-C65 exhibited a ten-fold increase in neutralization potency upon switching from IgG1 to IgA1 monomer.

IBI310 plus sintilimab vs. placebo plus sintilimab in recurrent/metastatic cervical cancer: A double-blind, randomized controlled trial.

Background: It remains unclear whether adding CTLA-4 blockade to PD-1/PD-L1 blockade improves clinical outcomes in cervical cancer (CC).

Methods: In this randomized, double-blind, placebo-controlled, phase 2 study (ClinicalTrials.gov: NCT04590599), patients with recurrent/metastatic CC (R/M CC) who experienced disease progression after or during platinum-based chemotherapy were enrolled from 37 centers across China and randomly assigned (1:1), stratified by PD-L1 expression and prior treatment lines, to receive either IBI310 plus sintilimab or placebo plus sintilimab intravenously every 3 weeks for 12 weeks, followed by sintilimab alone.

CDK14 regulates the development and repair of lung.

Cyclin-dependent kinases (CDK) 14 regulates cell cycle, tumor expansion by influencing the downstream targets of the canonical Wnt signaling pathway. However, the function of CDK14 during organ development and regeneration has not been investigated in genetically-modified animals. Here, we found that genetic ablation of Cdk14 influenced pulmonary vascular endothelial cells and alveolar epithelial cells during mice embryonic development as well as repair of lung after bleomycin or lipopolysaccharide induced injury.

CK2α-mediated phosphorylation of DUB3 promotes YAP1 stability and oncogenic functions.

The aberrant upregulation of Yes-associated protein 1 (YAP1) in a variety of solid cancers contributes to tumor progression and poor clinical outcomes, rendering it an appealing therapeutic target. However, effective therapies to directly target YAP1 remain challenging. In this study, we perform a high-throughput screening and identify Casein kinase II (CK2) as an uncharacterized upstream regulator of YAP1 turnover in cancer cells of ovarian cancer and several other cancer types.

Transcriptional regulation of Rankl by Txnip-Ecd in aging and diabetic related osteoporosis.

Introduction: Bone homeostasis between osteoclast bone resorption and osteoblastic bone formation is tightly regulated by a series of factors such as the receptor activator of nuclear factor-κB ligand (RANKL). Denosumab that neutralizes RANKL is effective and widely applied in the treatment of postmenopausal osteoporosis. However, factors that participated in the RANKL-related bone remodeling process in primary and secondary osteoporosis are less known.

Efficacy of immune checkpoint inhibitors in the treatment of soft tissue sarcoma: A systematic review and meta-analysis of clinical trials.

Background: Soft tissue sarcomas (STS) are a heterogeneous group of tumors with diverse clinical and molecular characteristics, characterized by limited treatment options and poor prognosis. Immune checkpoint inhibitors (ICIs) have emerged as promising therapies for STS, yet comprehensive evaluations of their efficacy, especially in combination with other treatments, are scarce.

Methods: We conducted a systematic review and meta-analysis of clinical trials on ICIs in STS treatment, sourced from PubMed, Embase, and the Cochrane Central Register of Controlled Trials up to May 31, 2024.

Protocol for genetic analysis of population-scale ultra-low-depth sequencing data.

Non-invasive prenatal testing (NIPT) not only enables the detection of chromosomal anomalies in fetuses but also generates vast amounts of ultra-low-depth sequencing data, which can be leveraged for population genomic studies. Here, we present a protocol designed for massive ultra-low-depth sequencing datasets. We detail the steps for data processing, quality control, and genotype imputation, followed by genome-wide association study (GWAS) and post-GWAS analyses.

Development and validation of the Information Literacy Measurement Scale (ILMS-34) in Chinese public health practitioners.

Background: Public health professionals (PHPs) have increasing information needs to inform evidence-based public health decisions and practice, which requires good information literacy. A comprehensive and reliable assessment tool is necessary to assess PHPs' literacy and guide future promotion programs. However, there is a lack of measurement tools specifically for the information literacy of PHPs.

SRT3025-loaded cell membrane hybrid liposomes (3025@ML) enhanced anti-tumor activity of Oxaliplatin via inhibiting pyruvate kinase M2 and fatty acid synthase.

Background: Bladder cancer is one of the most common malignancies of the urinary system. Despite significant advances in diagnosis and treatment, the compromised therapeutic effect of chemotherapeutic agents, such as Oxaliplatin (OXA), remains a major clinical challenge. Thus, a combination therapy is required to enhance the OXA's therapeutic effectiveness and improve patient outcomes.

Cross-sectional and longitudinal associations between serum vitamin D and continuous metabolic syndrome score among children and adolescents: roles of levels of inflammation in peripheral blood.

Background: Serum vitamin D deficiency is intricately linked to metabolic disorders, however, evidence on its association with continuous metabolic risk in children and adolescents remains insufficient. This study aims to elucidate the relationship between serum vitamin D levels and continuous metabolic risk.

Methods: The cross-sectional analysis involved 4490 participants aged 6 ~ 18, and the longitudinal investigation included 1398 individuals aged 6 ~ 12 years.

hsa_circ_0001599 promotes odontogenic differentiation of human dental pulp stem cells by increasing ITGA2 expression and stability.

Dental pulp regeneration is significantly aided by human dental pulp stem cells (hDPSCs). An increasing number of studies have demonstrated that circular RNAs (circRNAs) are crucial in the multidirectional differentiation of many mesenchymal stem cells, but their specific functions and mechanisms remain unknown. This work aimed at elucidating the molecular mechanism by which hsa_circ_0001599 works in hDPSCs during odontogenic differentiation.

Molecular architecture of human LYCHOS involved in lysosomal cholesterol signaling.

Lysosomal membrane protein LYCHOS (lysosomal cholesterol signaling) translates cholesterol abundance to mammalian target of rapamycin activation. Here we report the 2.11-Å structure of human LYCHOS, revealing a unique fusion architecture comprising a G-protein-coupled receptor (GPCR)-like domain and a transporter domain that mediates homodimer assembly.

Enhancing biosensing of trace tau protein in clinical samples via emergence macroscopic directed aggregation.

Alzheimer's disease (AD) is an irreversible neurodegenerative disorder that poses a significant risk to human health and well-being. The high cost and invasiveness of neuroimaging and cerebrospinal fluid (CSF) analysis underscores the necessity for accessible early screening via blood samples. In this study, we developed an ultrasound-based strategy for emergent macroscopic that enhances the acoustic response enrichment of specific proteins by introducing functionalized microspheres.

Metabolomic profiles in allergic rhinitis: a systematic review and meta-analysis.

Background: Allergic rhinitis (AR) is a prevalent chronic inflammatory condition that significantly impacts patient quality of life and poses a substantial public health burden. Recent advancements in metabolomics have facilitated a deeper understanding of the metabolic pathways involved in AR, offering potential for new biomarkers and therapeutic targets.

Objective: This article aims to conduct a systematic review and meta-analysis of clinical studies summarizing the metabolomic profiles of allergic rhinitis (AR) to gain deeper insights into the metabolic changes and pathological processes underlying AR.

Consensus and guidelines on diagnosis and management of polypoidal choroidal vasculopathy (PCV) from the Asia-Pacific Vitreo-retina Society (APVRS).

A panel of 21 international experts are formed by the Asia-Pacific Vitreo-retina Society to work out the consensus and guidelines on polypoidal choroidal vasculopathy (PCV). PCV is a common subtype of neovascular age-related macular degeneration and is more prevalent in Asian populations. Recent advancement in imaging technology allows greater understanding of the disease process of PCV.