Intramolecular DNA Wheel Construction for Highly Sensitive Electrochemical Detection of miRNA.

Accurate and reliable quantification of disease-related biomolecules is essential for clinical diagnosis. In this study, a novel electrochemical approach is developed based on a target triggered DNA nanostructural switch from a hairpin dimer to a double-stranded wheel. During the process, electrochemical species get closer to the electrode interface, and the multiple intramolecular strand displacements are beneficial to low abundant target analysis.

Early and Late Outcomes With the Absorb Bioresorbable Vascular Scaffold: Final Report From the ABSORB Clinical Trial Program.

Background: The risk-benefit ratio of the Absorb bioresorbable vascular scaffold (BVS) may vary before and after 3 years, the time point of complete bioresorption of the poly-L-lactic acid scaffold.

Objectives: The aim of this study was to determine the time-varying outcomes of the Absorb BVS compared with cobalt-chromium everolimus-eluting stents (EES) from a large individual-patient-data pooled analysis of randomized trials.

Methods: The individual patient data from 5 trials that randomized 5,988 patients undergoing percutaneous coronary intervention to the Absorb BVS vs EES with 5-year follow-up were pooled.

Clinical characteristics and influencing factors of hyperkyphosis in a Chinese Cohort with axial spondyloarthritis: a multicentre retrospective study.

Objective: This study aimed to investigate the clinical characteristics and influencing factors of axial spondyloarthritis (axSpA) hyperkyphosis in a Chinese cohort.

Methods: A cross-sectional study was conducted on 607 patients with axSpA attending 12 hospitals across 11 centers from March 2022 to March 2024.Univariate and multivariate logistic regression analyses were used to explore the relevant influencing factors of hyperkyphosis.

The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial.

Objective: To evaluate whether the immunomodulatory drug thymosin α1 reduces mortality in adults with sepsis.

Design: Multicentre, double blinded, placebo controlled phase 3 trial.

Setting: 22 centres in China, September 2016 to December 2020.

Mechanistic insights into ferroptosis and apoptosis pathways: Synergistic effects of multi-organ toxicity and transgenerational effects induced by co-exposure of epoxiconazole and aflatoxin B1 in zebrafish.

Introduction: In the environment, mycotoxins and fungicides frequently coexist, potentially causing synergistic risks to organisms. Epoxiconazole (EPO) and aflatoxin B1 (AFB1) are a common fungicide and mycotoxins, respectively, which are widely present in the environment and have toxic effects on multiple organs once entering the organism, but it is still unclear whether the co-exposure has a synergistic toxic effect.

Objectives: This study delves into the molecular mechanisms underlying the co-exposure to EPO and AFB1, emphasizing multi-organ toxicity in female zebrafish (F0 generation) and potential transgenerational impacts on the offspring embryos (F1 generation) through multi-omics approaches.

Extending breast cancer screening beyond age 45-64 years in China: a cost-effectiveness analysis.

The optimal breast cancer (BC) screening age in China remains uncertain. In this study, we evaluated the benefits, harms, and cost-effectiveness of lowering the screening starting age from 45 to 35 years and extending the stopping age from 64 to 79 years in Chinese women at an average risk of progressing BC. Biennial screening showed a lower incremental cost-effectiveness ratio (ICER) compared to annual screening.

U2AF1 mutation causes an oxidative stress and DNA repair defect in hematopoietic and leukemic cells.

U2AF1 is a core component of spliceosome and controls cell-fate specific alternative splicing. U2AF1 mutations have been frequently identified in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients, and mutations in U2AF1 are associated with poor prognosis in hematopoietic malignant diseases. Here, by forced expression of mutant U2AF1 (U2AF1 S34F) in hematopoietic and leukemic cell lines, we find that U2AF1 S34F causes increased reactive oxygen species (ROS) production.

Quality of life and functional outcomes in patients with locally advanced rectal cancer receiving total neoadjuvant therapy versus concurrent chemoradiotherapy: An analysis of the XXX trial.

Objective: To explore differences in the effects of total neoadjuvant therapy (TNT) and preoperative concurrent chemoradiotherapy (CRT) on quality of life and functional outcomes in patients with locally advanced rectal cancer.

Methods: In the study, 591 patients with distal or middle-third, clinical primary tumor stage cT3-4 and/or regional lymph node-positive rectal cancer were randomly assigned (1:1) to receive short-term radiotherapy (25 Gy in five fractions) followed by 4 cycles of CAPOX (TNT group, n=297) or standard concurrent chemoradiotherapy (50 Gy in 25 fractions concurrently with oral capecitabine) (CRT group, n=294) before surgery. After a 6-year follow-up, the surviving patients were sent surveys, including the EORTC QLQ-C30, EORTC QLQ-CR29, and Wexner incontinence score questionnaires.

Nuclear adenine activates hnRNPA2B1 to enhance antibacterial innate immunity.

Bacterial infection reprograms cellular metabolism and epigenetic status, but how the metabolic-epigenetic crosstalk empowers host antibacterial defense remains unclear. Here, we report that heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) is a sensor for metabolite adenine to launch an antimicrobial innate response through increasing Il1b transcription. Myeloid cell-specific Hnrnpa2b1-cKO mice are more susceptible to bacterial infection, while interleukin 1 beta (IL-1β) supplementation rescues the phenotype.

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.

The ER protein CANX (calnexin)-mediated autophagy protects against alzheimer disease.

Although the relationship between macroautophagy/autophagy and Alzheimer disease (AD) is widely studied, the underlying mechanisms are poorly understood, especially the regulatory role of the initiation signaling of autophagy on AD. Here, we find that the ER transmembrane protein CANX (calnexin) is a novel interaction partner of the autophagy-inducing kinase ULK1 and is required for ULK1 recruitment to the ER under basal or starved conditions. Loss of CANX results in the inactivity of ULK1 kinase and inhibits autophagy flux.

Epidemiology and clinical outcomes in skin and soft tissue nontuberculous mycobacteria infections: A retrospective study.

Background: Nontuberculous mycobacteria (NTM) are emerging pathogens responsible for increasing skin and soft tissue infections (SSTIs) globally. However, the diagnosis and treatment of NTM SSTIs face significant challenges due to the lack of standardized guidelines. This study reviewed the clinical characteristics, diagnostic challenges, and treatment outcomes of NTM SSTIs in a large cohort from a tertiary referral center in Beijing, China.

DIFLF: A domain-invariant features learning framework for single-source domain generalization in mammogram classification.

Background And Objective: Single-source domain generalization (SSDG) aims to generalize a deep learning (DL) model trained on one source dataset to multiple unseen datasets. This is important for the clinical applications of DL-based models to breast cancer screening, wherein a DL-based model is commonly developed in an institute and then tested in other institutes. One challenge of SSDG is to alleviate the domain shifts using only one domain dataset.

Transcriptome analysis reveals the DNA replication genes response to Vibrio anguillarum and NNV infection in Jinhu grouper (Epinephelus fuscoguttatus♀ × Epinephelus tukulal♂).

Vibrio anguillarum acts as an infectious agent in the aquaculture industry that causes a fatal hemolytic septicaemic disease in fish and shellfish. Viral nervous necrosis (VNN) disease seriously impacts the healthy development of the aquaculture industry. While the detrimental effects of V.

Validation of the 9th edition of the TNM staging system for limited-stage small cell lung cancer after Resection: A multicenter study.

Objectives: The 9th edition of the tumor-node-metastasis (TNM) staging system for lung cancer was proposed at the 2023 World Conference on Lung Cancer in Singapore. This study aimed to externally validate and compare the latest staging of small-cell lung cancer (SCLC).

Methods: Four hundred and eight patients with limited-stage SCLC were collected after lung resection from four centers.

Maternal derived antibodies and avian β-defensins expression patterns and their correlation in the yolk sac tissue of different chicken breeds (Gallus gallus).

The expression of maternal derived antibodies (MDAs) and avian β-defensins (AvBDs) in yolk sac tissue may be age-specific and influenced by breed, thereby immunological window difference in hatchlings. This study investigated the mRNA expression of MDAs and AvBDs in the yolk sac tissues of Beijing You and Hy-Line Gray chickens from the embryonic day (ED)7 to 3 days after hatch (DAH). Hy-Line showed a higher embryo bodyweight and a lower residual yolk weight at ED17 (P < 0.

Molecular insights into developmental toxicity induced by PCB77 exposure on zebrafish via integrating transcriptomics with adverse outcome pathway.

Polychlorinated biphenyls (PCBs), a typical type of persistent organic pollutants (POPs), were previously widely employed as insulating and heat exchange fluids in transformers and capacitors. Despite knowledge of its adverse effects, the precise mechanism underlying PCB77 toxicity remains enigmatic. In this study, we utilized zebrafish as a model organism to explore the toxic effects of various concentrations of PCB77 (10, 200, and 1000 μg/L) and its molecular toxicity mechanisms.

Widely targeted metabolomics analysis reveals dynamic changes in metabolites of 'Hass' avocado during postharvest ripening period.

Avocado (Persea americana Mill) is a climacteric fruit harvested at the green stage that ripens postharvest to become edible. The 'Hass' cultivar, known for its rich, buttery flavor and pear-shaped appearance, was studied for metabolite changes during postharvest ripening using UPLC-MS/MS approach. The 16-day ripening period could be divided into three stages: evolution (days 1-9), edible ripe (days 10-15) and overripe (day 16).

Robust and Regular Micronano Binary Texture on the Complex Curved Surface for Enhanced Reendothelialization and Antithrombotic Performance.

Blood-contacting medical devices can easily trigger immune responses, leading to thrombosis and hyperblastosis. Constructing microtexture that provides efficient antithrombotic and rapid reendothelialization performance on complex curved surfaces remains a pressing challenge. In this work, we present a robust and regular micronano binary texture on the titanium surface, characterized by exceptional mechanical strength and precisely controlled wettability to achieve excellent hemocompatibility.

A phase 1 trial of prizloncabtagene autoleucel, a CD19/CD20 CAR T-cell therapy for relapsed/refractory B-cell non-Hodgkin lymphoma.

Prizloncabtagene autoleucel (prizlon-cel), a novel bispecific chimeric antigen receptor (CAR) T-cell, targets and eliminates CD19/CD20 positive tumor cells. This phase 1, open-label study investigated the safety and efficacy of prizlon-cel in patients with relapsed/refractory B-cell non-Hodgkin Lymphoma (r/r B-NHL). Patients with CD19 and/or CD20-positive r/r B-NHL received a 3-day lymphodepletion (cyclophosphamide: 300 mg/m2/d; fludarabine: 30 mg/m2/d) followed by an intravenous dose of prizlon-cel.

Comparison the Cosmetic Outcome of the Triangular Flap Insertion Versus Direct Linear Resection in Correction of Dog Ear Deformities on the Face-A Prospective and Randomized Controlled Trial.

Background: Compared with direct linear resection, the triangular flap insertion method is a correction method that purportedly reduces the incision tension of dog ears deformity. Randomized clinical trials comparing these 2 methods seem to be limited or absent.

Objective: A randomized study was planned to compare the cosmetic effect and scar in the defect area between the triangular flap insertion method and direct linear resection in the repair of dog ear deformities after the suture of the facial circular defect.

Separation of Three Polar Compounds with Similar Polarities from Swertia mussotii by a Combination of Two Counter-Current Chromatography Modes.

Separation of polar compounds especially with similar polarities is challenging. In the present study, three polar compounds with similar polarities, including gentiopicroside, sweroside and mangiferin, have been successfully separated from Swertia mussotii by a combination of two counter-current chromatography modes. With the selected solvent system of ethyl acetate/n-butanol/water (8/2/10, v/v), a continuous injection mode was firstly employed.

Macrophage-specific in vivo RNA editing promotes phagocytosis and antitumor immunity in mice.

Macrophages play a central role in antitumor immunity, making them an attractive target for gene therapy strategies. However, macrophages are difficult to transfect because of nucleic acid sensors that can trigger the degradation of foreign plasmid DNA. Here, we developed a macrophage-specific editing (MAGE) system by which compact plasmid DNA encoding a CasRx editor can be delivered to macrophages by a poly(β-amino ester) (PBAE) carrier to bypass the DNA sensor and enable RNA editing in vitro and in vivo.