Structural Insights into an Antiparallel Chair-Type G-Quadruplex From the Intron of NOP56 Oncogene.

G-quadruplex (G4) structures play important roles in various biological processes, especially the gene regulation. Nucleolar protein 56 (NOP56) is an essential component in ribosome biogenesis while its overexpression associates with various types of cancers, rendering it a significant therapeutic target. Here for the first time, an antiparallel chair-type G4 structure formed by a 21-nt DNA sequence from the intron 1 of NOP56 is reported, and its high-resolution structure is determined using solution nuclear magnetic resonance spectroscopy.

Fragmentation pattern-based nontargeted screening strategy uncovered novel halogenated nucleotides in drinking water.

Halogenated nucleotides have been reported as emerging disinfection byproducts in drinking water and the identification of halogenated nucleotides is a challenging but worthwhile endeavor due to their high risk, diverse chemical structures and scarcity of chemical standards. To improve the recognition efficiency of halogenated nucleotides in complex environmental matrices with multiple halogen ions, a fragmentation pattern-based nontargeted screening strategy was developed, which combines halogen isotope features and characteristic product ions to identify halogenated nucleotides within extensive datasets from high-resolution mass spectrometry. The data were preliminary screened based on the halogen isotope features of chemicals with varying halogen atom counts, followed by further identification using shared fragments with m/z values of 78.

sp. nov., isolated from the China Space Station.

Understanding the characteristics of microbes during long-term space missions is essential for safeguarding the health of astronauts and maintaining the functionality of spacecraft. In this study, a Gram-positive, aerobic, spore-forming, rod-shaped strain JL1B1071 was isolated from the surface of hardware on the China Space Station. This strain belongs to the genus , with its closest relative being ATCC 4513.

Safety profiles of sevoflurane in pediatric patients: a real-world pharmacovigilance assessment based on the FAERS database.

Objective: This study aimed to evaluate the safety profile of sevoflurane in pediatric populations using real-world data.

Methods: Data were extracted from the Food and Drug Administration Adverse Event Reporting System (FAERS) from the first quarter of 2004 to the third quarter of 2024. We analyzed reports where sevoflurane was the primary suspect in individuals aged 0-18, employing disproportionality analysis to detect adverse events associated with sevoflurane.

NK cell-based immunotherapy for hepatocellular carcinoma: Challenges and opportunities.

Hepatocellular carcinoma (HCC) remains one of the most challenging malignancies globally, characterized by significant heterogeneity, late-stage diagnosis, and resistance to treatment. In recent years, the advent of immune-checkpoint blockades (ICBs) and targeted immune cell therapies has marked a substantial advancement in HCC treatment. However, the clinical efficacy of these existing therapies is still limited, highlighting the urgent need for new breakthroughs.

Development and Evaluation of a Hypertension Prediction Model for Community-Based Screening of Sleep-Disordered Breathing.

Purpose: Approximately 30% of patients with sleep-disordered breathing (SDB) present with masked hypertension, primarily characterized by elevated nighttime blood pressure. This study aimed to develop a hypertension prediction model tailored for primary care physicians, utilizing simple, readily available predictors derived from type IV sleep monitoring devices.

Patients And Methods: Participants were recruited from communities in Guangdong Province, China, between April and May 2021.

Small CAG Repeat RNA Forms a Duplex Structure with Sticky Ends That Promote RNA Condensation.

Biomolecular condensation lays the foundation of forming biologically important membraneless organelles, but abnormal condensation processes are often associated with human diseases. Ribonucleic acid (RNA) plays a critical role in the formation of biomolecular condensates by mediating the phase transition through its interactions with proteins and other RNAs. However, the physicochemical principles governing RNA phase transitions, especially for short RNAs, remain inadequately understood.

DNA Self-Assembly Generated by Aptamer-Triggered Rolling Circle Amplification Cascades for Profiling Colorectal Cancer-Derived Small Extracellular Vesicles.

The analysis of small extracellular vesicles (sEVs) has shown clinical significance in early cancer diagnostics and considerable potential in prognostic assessment and therapeutic monitoring, offering possibilities for precise clinical intervention. Despite recent diagnostic progress based on blood-derived sEVs, the inability to specifically profile multiple parameters of sEVs proteins has hampered advancement in clinical applications. Herein, we report an approach to profile colorectal cancer (CRC)-derived sEVs by using multiaptamer-triggered rolling circle amplification (RCA) cascades.

Artificial dynamic structure ensemble-guided rational design of a universal RNA aptamer-based sensing tag.

Artificially functional RNAs, such as fluorogenic RNA aptamer (FRApt)-based biosensing tag, represent significant advancements in various biological applications but are limited by the lack of insight into dynamic structure ensembles and universal design concepts. Through the development of an artificial RNA structure ensemble, we rationally established an RNA reconstitution model, "SSPepper-Apt," to generate a universal fluorogenic RNA biosensing tag. By utilizing various target-recognizing RNA motifs, SSPepper-Apt enables the modular generation of sensing tags for low-background, highly selective imaging of metabolites, peptides, and proteins in living cells.

Elucidating the molecular mechanisms of CCR5-containing extracellular vesicles in vitro and in a rat model of experimental Rheumatoid arthritis.

Extracellular vesicles from Rheumatoid arthritis (RA) derived synovial fibroblasts (EVs) have been implicated in the pathogenesis of RA, acting as mediators of cell-to-cell communication. This study aimed to elucidate the role of the chemokine receptor CCR5 and EVs positive for CCR5 (EVs) in RA, focusing on their impact on cartilage destruction and bone erosion in a rat model of Adjuvant-induced arthritis (AIA). In vivo experiments were conducted using AIA rats, treated with either EVs, EVs without CCR5 (EVs), or EVs which encapsulated the CCR5 antagonist Maraviroc.

Structure-based investigation of a DNA aptamer targeting PTK7 reveals an intricate 3D fold guiding functional optimization.

DNA aptamers have emerged as novel molecular tools in disease theranostics owing to their high binding affinity and specificity for protein targets, which rely on their ability to fold into distinctive three-dimensional (3D) structures. However, delicate atomic interactions that shape the 3D structures are often ignored when designing and modeling aptamers, leading to inefficient functional optimization. Challenges persist in determining high-resolution aptamer-protein complex structures.

Elevated serum levels of soluble B-cell maturation antigen as a prognostic biomarker for multiple myeloma.

Serum B-cell maturation antigen (sBCMA) levels can serve as a sensitive biomarker in multiple myeloma (MM). In the research setting, sBCMA levels can be accurately detected by enzyme-linked immunosorbent assay (ELISA), but the approach has not been approved for clinical use. Here, we used a novel chemiluminescence method to assess sBCMA levels in 759 serum samples from 17 healthy donors and 443 patients with plasma cell (PC) diseases including AL amyloidosis, POEMS syndrome, and MM.

An "All-In-One" Immunomodulator-Engineered Clinical Translatable Immunotherapy of Advanced Hepatocellular Carcinoma.

Clinical treatment of advanced hepatocellular carcinoma (HCC) remains a significant challenge. Utilizing 1-bromoacetyl-3,3-dinitroazetidine (RRx-001) to downregulate the expression of innate immune checkpoint molecule, cluster of differentiation 47 (CD47), provides a powerful means for treating advanced HCC containing abundant immunosuppressive macrophages. Herein engineering of a previously optimized Doxorubicin (DOX)-delivery nanoplatform based on sodium alginate is reported to further co-deliver RRx-001 (biotinylated aldehyde alginate-doxorubicin micelle prodrug nanoplatform, BEA-D@R) for efficient immunotherapy of advanced HCC.

Prognostic significance and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer: A clinicopathological study.

Background: The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis. SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.

Aim: To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer.

Structural investigation of pathogenic RFC1 AAGGG pentanucleotide repeats reveals a role of G-quadruplex in dysregulated gene expression in CANVAS.

An expansion of AAGGG pentanucleotide repeats in the replication factor C subunit 1 (RFC1) gene is the genetic cause of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS), and it also links to several other neurodegenerative diseases including the Parkinson's disease. However, the pathogenic mechanism of RFC1 AAGGG repeat expansion remains enigmatic. Here, we report that the pathogenic RFC1 AAGGG repeats form DNA and RNA parallel G-quadruplex (G4) structures that play a role in impairing biological processes.