Multicyclic Ligation-Driven Self-Assembly of Magnetic Nanobundles for Sensitive Profiling of Multiple Repair Glycosylases in Cancer Cells.

Base excision repair (BER) enzymes are essential for maintaining genomic stability and contribute significantly to disease pathogenesis, but simultaneous monitoring of multiple BER enzymes remains a challenge due to their mechanistic diversity and lack of versatile detection platforms. Herein, we demonstrate for the first time multicyclic ligation-driven self-assembly of magnetic nanobundles for sensitive profiling of multiple repair glycosylases in cancer cells. In this assay, we design two programmable dsDNA substrates with the incorporation of 8-oxo-7,8-dihydroguanine (8-oxoG) and uracil (U) base lesions, which can be cleaved by Fpg and UDG to generate nicking sites, respectively.

External validation of N2H3 nomogram to predict outcomes in patients with acute ischemic stroke treated by intravenous thrombolysis.

Background: The N2H3 model was evaluated for forecasting the 3-month outcomes for patients experiencing acute ischemic stroke who received intravenous thrombolysis (IVT), in our previous study. The present study aimed to validate the predictive ability of the N2H3 model and to compare its accuracy to the THRIVE-c and START models (both of which are widely employed for prognostic predictions following IVT).

Methods: Our study prospectively enrolled consecutive stroke patients who received IVT from 16 hospitals.

Engineering of a multi-modular CRISPR biomachine for ultrasensitive monitoring of β-glucosyltransferase activity.

β: [note: ":" is changed to "-"] Glucosyltransferase (β-GT) is a pivotal enzymatic tool for 5-hydroxymethylcytosine (5-hmC) detection, and it can specifically catalyze the glycosylation of 5-hmC. This enzymatic reaction plays a crucial role in modulating bacteriophage-specific gene expression and facilitating the survival of bacteriophages and parasites within host cells. Herein, we engineer a multi-modular and structurally ordered CRISPR/Cas-based biomachine by integrating 5-hmC glycosylation-triggered palindrome-primed hyperbranched rolling circle amplification (PP-HRCA) for ultrasensitive analysis of exogenous β-GT activity.

Substantia Nigra Hyperechogenicity Predicts Parkinson's Disease Risk in Patients With Essential Tremor and Undetermined Tremor: Dual-Cohort Longitudinal Evidence With 8-Year Follow-Up and Bayesian Validation.

Background And Objectives: Transcranial sonography (TCS)-detected substantia nigra hyperechogenicity (SN+) is a potential biomarker for Parkinson's disease (PD). While SN+ may indicate PD risk in essential tremor (ET), longitudinal undetermined tremor (UT) data are lacking; insufficient cross-cohort validation hinders clinical translation. This study aimed to evaluate the predictive efficacy of SN+ for 8-year PD risk and its subtype-specific differences in ET/UT populations.

Distinct nucleus accumbens neural pathways underlie separate behavioral features of chronic pain and comorbid depression.

The comorbidity of depressive symptoms in chronic pain has been recognized as a key health issue. However, whether discrete circuits underlie behavioral subsets of chronic pain and comorbid depression has not been addressed. Here, we report that dopamine 2 (D2) receptor-expressing medium spiny neurons in the nucleus accumbens medial shell (mNAcSh) mediate pain hypersensitivity and depression-like behaviors in mice after nerve injury.

Association between the PSCA rs2976392 polymorphism and susceptibility to gastric cancer: a meta-analysis.

Background: Genetic polymorphisms, such as PSCA rs2976392, have been implicated in gastric carcinogenesis, but it is unclear whether there is a direct association. Thus, we conducted a comprehensive meta-analysis to evaluate the association between the PSCA rs2976392 polymorphism and susceptibility to gastric cancer (GC).

Methods: A systematic search of the PubMed, Web of Science, Embase, and Cochrane Library databases was performed up to 13 March 2025.

Bioactive Isobenzofuranone and Isochromenones From a Marine-Derived Fungus Penicillium sp.: Isolation, Characterization, and Inhibitory Activity Against α-Glucosidase.

The chemical investigation of the marine-derived fungus Penicillium sp. led to the isolation of three new secondary metabolites, including one isobenzofuranone (1) and two isochromenones (2 and 3), along with five known compounds (4-8). The structures of the new compounds, including their absolute configurations, were elucidated through comprehensive nuclear magnetic resonance, optical rotatory dispersion, and electronic circular dichroism spectral analyses.

[Effects of Bortezomib Combined with Polyphyllin Ⅶ on Proliferation, Apoptosis and Oxidative Stress of Myeloma Cells].

Objective: To investigate the effects of bortezomib (BTZ) combined with polyphyllin Ⅶ (PP7) on proliferation, apoptosis and oxidative stress of myeloma cell line ARH-77.

Methods: MTT assay was used to detect the inhibitory effects of different concentrations of BTZ, PP7 monotherapy, and their combination on the proliferation of ARH-77 cells. In subsequent experiments, the cells were divided into 4 groups: control group (no drug added), BTZ (15 nmol/L) group, PP7 (1.

Tumor microenvironment-responsive dynamic self-assembly of DNAzyme nanowires for high-contrast imaging of multiple messenger RNAs and chemotherapy.

Messenger RNAs (mRNAs) are a category of protein-coding RNA, and their dysregulation is closely implicated in diverse cancers. Static DNA nanodevices have been engineered for the imaging and therapy, but they rely on the pre-assembly of DNA components and are limited by the low imaging contrast. Herein, we demonstrate the tumor microenvironment-responsive dynamic self-assembly of DNAzyme nanowires for high-contrast imaging of multiple mRNAs and chemotherapy.

Associations of first-trimester TMAO and its precursors with gestational diabetes mellitus: a pilot prospective cohort study.

Aims: We aimed to provide a comprehensive understanding of the associations between Trimethylamine-N-oxide (TMAO), its precursor and gestational diabetes mellitus (GDM).

Methods: In this prospective study, 940 women were included in a Chinese single -center pregnant cohort. First trimester plasma concentrations of TMAO and its precursors (betaine, choline, L-carnitine, and trimethylamine) were measured using UPLC-ESI-MS/MS.

Prediction of outcomes following intravenous thrombolysis in patients with acute ischemic stroke using serum UCH-L1, S100β, and NSE: a multicenter prospective cohort study employing machine learning methods.

Background: Acute ischemic stroke (AIS) is a leading cause of mortality and disability worldwide. Intravenous thrombolysis (IVT) improves recovery, but predicting outcomes remains challenging. Machine learning (ML) and biomarkers like ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), S100 calcium-binding protein β (S100β), and neuron-specific enolase (NSE) may enhance prognostic accuracy.

Geraniin Promotes Osteoblast Proliferation, Bone Formation, and Autophagy by Regulating the PI3K/Akt/mTOR Cascade to Improve Glucocorticoid-Induced Osteoporosis.

Geraniin is a plant natural product that has been testified to perfect osteoporosis (OP). However, Geraniin's impacts on osteoblast autophagy and its latent molecular mechanisms remain uncertain. In this study, Geraniin's impacts on autophagy in osteoblasts were figured out and its molecular mechanism was uncovered.

Safety of Surgery within 24 h following Colonoscopy for Colorectal Cancer: A Retrospective Propensity Scores Matched Analysis.

Introduction: In clinical practice, clinicians often perform repeat colonoscopy before colorectal cancer (CRC) surgery to accurately assess tumor location, size, and the presence of other underlying lesions. No previous study has reported the safety of the interval from colonoscopy to laparoscopic CRC surgery on surgical outcomes. The purpose of this study was to evaluate the safety of the interval from colonoscopy to laparoscopic CRC surgery on surgical outcomes using propensity score matching (PSM).

CAFs activated by YAP1 upregulate cancer matrix stiffness to mediate hepatocellular carcinoma progression.

Background: The stiffness of the matrix is closely related to the progression of hepatocellular carcinoma (HCC). Although direct targeting of stromal rigidity in HCC remains a clinical challenge, cancer-associated fibroblasts (CAFs) are considered key contributors to this process. Given the heterogeneity of CAFs, this study explored the relationship between specific CAF subsets and liver cancer matrix stiffness, aiming to identify novel therapeutic targets for HCC patients.

Lentivirus-mediated overexpression of netrin-1/DCC co-expression promotes axonal regeneration and functional recovery in spinal cord injury via the inhibition of the NgR1-RhoA-ROCK signaling pathway.

Spinal cord injury (SCI) seriously affects the health of humans and quality of life, causing disabilities. Due to the ever-increasing traffic and cases of natural disasters, such as earthquakes, the incidence of SCI increases every year, thus causing a huge economic burden to society and patients. The lack of neurotrophic factors in the area affected by SCI and the presence of inhibitory factors for axonal regeneration are important reasons that make spinal cord regeneration and repair extremely difficult.

Impact of 222-nm ultraviolet disinfection combined with psychological care on the emotional and hospital infection of critical patients.

Background: Empathetic psychological care improves mood and enhances the quality of life in critically ill patients.

Aim: To study the impact of combining 222-nm ultraviolet (UV) disinfection with empathetic psychological care on emotional states, nosocomial infection rates, and quality of life in critically ill patients.

Methods: A total of 202 critically ill patients admitted to Beijing Ditan Hospital (December 2023 to May 2024) were randomly assigned to control (Ctrl, = 101) or observation groups (Obs, = 101).

Effects of Prolonged Pomace Contact on Color and Mouthfeel Characteristics in Merlot Wine During the Ageing Process Under Microwave Irradiation.

Wine color and mouthfeel are essential organoleptic characteristics considered by consumers. In this paper, the potential impacts on color and mouthfeel characteristics in wine, without pomace or prolonged pomace contact after different microwave treatment times, were investigated during storage. The results indicated that the trend changes in color and mouthfeel related parameters (including visible spectrum, brightness, red hue, yellow hue, color difference, saturation, hue angle, total polyphenol content, total monomer anthocyanins, total tannins, total flavan-3-ols, epigallocatechin, catechin, epicatechin, epicatechin gallate, and fluorescence spectrum) after microwave-treated and natural aged wines without pomace and prolong pomace contact were very similar.

Construction of a hierarchical DNA circuit for single-molecule profiling of locus-specific N-methyladenosine-MALAT1 in clinical tissues.

N-methyladenosine (mA) is the most important internal methylation in eukaryotic RNAs, and it is critically implicated in diverse RNA metabolisms for cancer development. Because epigenetic modifications do not interfere with Watson-Crick base pairing and mA modification is not susceptible to chemical decorations, standard hybridization-based techniques cannot be applied for sensing mA in RNAs. Consequently, the development of new methods for accurate and sensitive profiling of locus-specific mA in RNAs remains a great challenge.

Safety and Efficacy of Remote Ischemic Conditioning in Patients With Intravenous Thrombolysis: The SERIC-IVT Trial.

Background: Approximately half of the patients with acute ischemic stroke who receive intravenous thrombolysis (IVT) do not achieve an excellent outcome. Remote ischemic conditioning (RIC) as a promising neuroprotective treatment may improve clinical outcomes in this population. This study aimed to assess the efficacy and safety of RIC in patients with IVT.

Advancing the understanding and management of blastic plasmacytoid dendritic cell neoplasm: Insights from recent case studies.

We specifically discuss the mechanisms of the pathogenesis, diagnosis, and management of blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare but aggressive haematologic malignancy characterized by frequent skin manifestations and systemic dissemination. The article enriches our understanding of BPDCN through detailed case reports showing the clinical, immunophenotypic, and histopathological features that are critical for diagnosing this disease. These cases highlight the essential role of pathologists in employing advanced immunophenotyping techniques to accurately identify the disease early in its course and guide treatment decisions.

Construction of an end-repairing-engineered quadratic in vitro transcription machine for single-molecule monitoring of alkaline phosphatase in human cancers.

Alkaline phosphatase (ALP) is an essential hydrolase widely present in humans, and it extensively acts as a biomarker for multiple human diseases. Conventional ALP assays suffer from complicated synthesis, tedious operation, low sensitivity, and large sample consumption. Herein, we construct an end-repairing-engineered quadratic in vitro transcription machine for single-molecule monitoring of ALP in diverse cancers with 3'-phosphoryl (PO) nucleic acid as a macromolecular substrate.

Analysis of the characteristics of intestinal microbiota in patients with different severity of obstructive sleep apnea.

Intestinal microbiota imbalance plays an important role in the progression of obstructive sleep apnea (OSA), and is considered to be the main mediator that triggers metabolic comorbidities. Here, we analyzed the changes in intestinal microbiota in patients with different severities of OSA based on apnea hypopnea index (AHI) classification, and explored the role of intestinal microbiota in the severity of OSA. This study included 19 healthy volunteers and 45 patients with OSA [5 ≤ AHI < 15 (n = 14), 15 ≤ AHI < 30 (n = 13), AHI ≥ 30 (n = 18)].

SEC16A Variants Predispose to Chronic Pancreatitis by Impairing ER-to-Golgi Transport and Inducing ER Stress.

Chronic pancreatitis (CP) is a complex disease with genetic and environmental factors at play. Through trio exome sequencing, a de novo SEC16A frameshift variant in a Chinese teenage CP patient is identified. Subsequent targeted next-generation sequencing of the SEC16A gene in 1,061 Chinese CP patients and 1,196 controls reveals a higher allele frequency of rare nonsynonymous SEC16A variants in patients (4.