Dynamic cortical inhibition imbalance as a biomarker of clinical progression in early Parkinson's disease.

Objective: The role of bilateral cortical inhibition in motor compensation during the progression of early Parkinson's disease (PD) remains unclear. This study aims to investigate the dynamic balance of between-hemispheric inhibition and the clinical relevance of its neurophysiological indicators.

Methods: Paired-pulse TMS was used to investigate the activity of different intracortical inhibitory circuits in 90 PD patients and 43 healthy controls during the "on medication" state.

CAFs promote immune evasion in gastric cancer through histone lactylation-mediated suppression of NCAPG ubiquitination.

Background: Cancer-associated fibroblasts (CAFs) can facilitate tumor progression through multiple approaches. Research indicates that CAFs in various tumors exhibit robust lactate metabolism, ultimately becoming the primary source of lactate in the tumor microenvironment. Emerging evidence has established that CAFs could orchestrate gastric cancer (GC) immune evasion.

A Novel Anti-BoNT/A Neutralizing Antibody Possessed Overlapped Epitope with SV2 and Had Prolonged Half-Life In Vivo.

The C-terminus of the BoNT/A heavy chain (BoNT/AHC) mediates binding to its receptor, SV2, a critical step for toxicity. Antibody inhibition of this interaction enhances neuronal survival. We previously identified a functional anti-BoNT/AHC nanobody, HM.

Zanthoxylum armatum DC. Extract induced liver injury via DNA double-strand breaks-mediated cellular senescence pathway.

Aim Of The Study: To comprehensively explore the impact of Zanthoxylum armatum DC. (ZADC) on liver injury and disclose its mechanistic underpinnings, thereby laying a scientific foundation for the secure application of ZADC.

Materials And Methods: The ethyl acetate extract of ZADC (ZADC-EA) was subjected to analysis via Q-Orbitrap LC-MS/MS.

Hydrophilic Iridium Bis-N-Heterocyclic Carbene Complexes Catalyze Linear-Selective, Additive-Free Hydroaminomethylation of Long-Chain Olefins in Water.

Aqueous hydroaminomethylation (HAM) of olefins generally requires the use of organic solvents, additives, and high-pressure hydrogen to synthesize amines in satisfactory yields and selectivity. Herein, we accomplish the HAM reactions of long-chain olefins in water without organic solvent or additives by using a hydrophilic bis-NHC-Ir complex as the catalyst. A broad scope of long-chain olefins and amines is well compatible, affording corresponding higher amines in up to 99% yields with excellent linear/branched (l/b) selectivity (up to 94/6).

NaCl-thermal synergy mediates structural transitions in hsian-tsao polysaccharide-myosin complexes to influence flavor-binding selectivity.

Hsian-tsao polysaccharide (HTP) with preferable gel-enhancing and bioactive properties improved surimi quality. This study elucidated how NaCl concentration (0.2-1.

Study on the Competitive Binding of Food Ingredients and Gambogic Acid to Plasma Proteins: Insights From Spectroscopy, Docking, and Cell Assay.

Human serum albumin (HSA) is the most abundant protein in plasma and an important transporter of exogenous small molecules. In this paper, the binary interaction of HSA with gambogic acid (GA), theophylline (TP), and quercetin (QC) and the ternary interaction of the HSA-QC system in the presence of food components were studied. Fluorescence emission and UV-Vis absorption spectra analysis showed that all three compounds bind HSA via a static quenching model.

PagMIR166c targets PagECH2 to regulate cambial differentiation into secondary xylem, cell expansion, and lignin deposition via different auxin signaling pathways in poplar stems.

Secondary xylem, a key trait of trees, is the main source of tree biomass. MicroRNAs (miRNAs) play important regulatory roles in the secondary xylem formation; however, the underlying regulatory mechanisms are far from being completely elucidated. In this study, we provide the first evidence that PagMIR166c is involved in the secondary xylem formation in poplar stems.

Dietary sugar intervention: A promising approach for cancer therapy.

Cancer constitutes a significant global health challenge, with altered metabolism being a hallmark feature of cancer cells. Diet can directly modulate systemic metabolite levels, thereby exerting both direct and indirect influences on tumor progression. The primary mechanisms include: (1) directly altering signaling pathways related to tumor cell proliferation or apoptosis, (2) indirectly affecting tumor progression by modulating nutrient availability or immune cell function in the tumor microenvironment, and (3) influencing tumor development through changes in gut microbiota composition or metabolic activity.

A Cyclized Bivalent Aptamer-Based Protein Degrader Targeting Receptor Tyrosine Kinases Overcomes Resistance to Inhibitors in Lung Cancer.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the standard first-line treatment for nonsmall cell lung cancer (NSCLC) with EGFR mutations. However, their clinical success is limited by the eventual development of acquired resistance in patients mainly induced by EGFR mutations and the activation of alternative signaling pathways (e.g.

Precise Editing of chNHE1 Gene via CRISPR/Cas9 Generates ALV-J-Resistant Chicken Primordial Germ Cell.

Avian leukosis virus subgroup J (ALV-J), an α-retrovirus, mediates infection by binding to the host-specific receptor chNHE1 (chicken sodium-hydrogen exchanger type 1), leading to immunosuppression and tumorigenesis, which severely threatens the sustainable development of the poultry industry. Studies have shown that the tryptophan residue at position 38 (W38) of the chNHE1 protein is the critical site for ALV-J infection. In this study, we employed the CRISPR/Cas9 system to construct a lentiviral vector targeting the W38 site of chNHE1, transfected it into chicken primordial germ cells (PGCs), and validated its antiviral efficacy through ALV-J infection assays, successfully establishing an in vitro gene-editing system for chicken PGCs.

PRMT1 oligomerization regulates RNA-binding protein cascade to promote pancreatic cancer.

PRMT1 is the predominant type I protein arginine methyltransferase responsible for generating monomethylarginine and asymmetric dimethylarginine (MMA and ADMA) in various protein substrates. It regulates numerous biological processes, including RNA metabolism, mRNA splicing, DNA damage repair, and chromatin dynamics. The crystal structure of rat PRMT1 has been previously reported as a homodimer; however, higher-order oligomeric species of human PRMT1 have been observed in vivo, and their structural basis remains elusive.

Breaking barriers in ICD classification with a robust graph neural network for hierarchical coding.

The accurate classification of International Classification of Diseases (ICD) codes is a complex and critical multi-label task in clinical documentation, involving the assignment of diagnostic codes to medical discharge summaries. Existing automated methods face challenges due to the sparsity and nuanced nature of medical text, while traditional backpropagation-based models often lack flexibility and robustness. To address these issues, we propose Labeled Graph Generation with Node Representation Grasp (LGG-NRGrasp), an advanced adversarial learning framework that models ICD coding as a labeled graph generation problem.

DivPro: diverse protein sequence design with direct structure recovery guidance.

Motivation: Structure-based protein design is crucial for designing proteins with novel structures and functions, which aims to generate sequences that fold into desired structures. Current deep learning-based methods primarily focus on training and evaluating models using sequence recovery-based metrics. However, this approach overlooks the inherent ambiguity in the relationship between protein sequences and structures.

Deep Mining of Novel Acylated Polyamines by Integrated Prior-Knowledge-Guided Prediction and Chemical Isotope Labeling-Based Metabolomics.

Acylated polyamines (acyl-PAs) are gaining significant attention due to their involvement in various diseases. However, their annotation and quantification remain challenging, as robust analytical methods are lacking, with only a few acyl-PAs characterized to date. In this study, we integrated prior-knowledge-guided prediction with chemical isotope labeling-based metabolomics to identify novel acyl-PAs.

Heavy metal release from two typical tire microplastics under different simulated environments and bioavailability assessment in China.

Little information is available on the release and associated bioavailability of heavy metals (HMs) in tire repair-polished debris (TRD) and recycled tire crumb (RTC). Thus, simulated TRD from 4 tire brands, TRD in auto repair shops and RTC in artificial turf from the northern and southern region of China were prepared to investigate HMs release under different simulated environments of acid rain and seawater and assess the associated bioavailability. The average contents of zinc (Zn), arsenic (As), and cadmium (Cd) were 11.

Strain-Induced Robust Skyrmion Lattice at Room Temperature in van der Waals Ferromagnet.

Manipulating topological magnetic orders of 2D magnets by strain, once achieved, offers enormous potential for future low-power flexible spintronic applications. In this work, by placing FeGaTe (FGaT), a room-temperature 2D ferromagnet, on flexible substrate, a field-free and robust formation of skyrmion lattice induced by strain is demonstrated. By applying a minimal strain of ≈0.

Investigation of the relationship between chronic hepatitis B and tuberculosis using bioinformatics and systems biology approaches.

Background: Hepatitis B virus (HBV) is a globally prevalent pathogen that poses significant public health challenges. Active HBV replication can trigger immune responses that result in liver damage. Tuberculosis (TB), caused by (), remains one of the leading causes of death from a single infectious agent worldwide.

The differential role of spousal collaboration on pain reactivity to daily stressors in older couples with and without multiple chronic conditions.

Background: Spousal collaboration has been considered as important coping resource to deal with aging-related health problems, but little is known about the role of spousal collaboration on the everyday stress-reactivity process in couples facing multiple chronic conditions (MCCs).

Purpose: We examined the within-person association of daily stressors and pain, and whether spousal collaboration played a differential role in moderating this association in older couples living with and without MCCs.

Methods: Data were drawn from an ecological momentary assessment (EMA) research, wherein two sub-samples of older married couples (including 52 dyads facing couple-level MCCs and 55 dyads without couple-level MCCs) reported 7671 (89.

Roscovitine Improved the Cytoplasmic Maturation of Bovine Oocytes and Subsequent Embryo Quality.

This study examined the effects of different concentrations of roscovitine (ROSC) on cytoplasmic maturation in bovine oocytes and subsequent embryo development. Oocytes were prematured with ROSC at concentrations of 0, 25, 37.5, 50 and 75 µM for 6 h.

A multi-gene predictive model for the radiation sensitivity of nasopharyngeal carcinoma based on machine learning.

Radiotherapy resistance in nasopharyngeal carcinoma (NPC) is a major cause of recurrence and metastasis. Identifying radiotherapy-related biomarkers is crucial for improving patient survival outcomes. This study developed the nasopharyngeal carcinoma radiotherapy sensitivity score (NPC-RSS) to predict radiotherapy response.

Integrated Metabolomics and Network Pharmacology to Reveal the Mechanisms of Extract Against Respiratory Syncytial Virus.

To investigate the therapeutic impact of extract (FS) on RSV-infected mice and explore its antiviral pharmacodynamic foundations. Methods: An integrated analytical approach, combining UPLC-Q-TOF/MS with network pharmacology, was employed to analyze and identify the chemical constituents in FS, particularly those exhibiting antiviral properties against RSV. The study integrated network pharmacology and metabolomics for further analysis, and molecular docking and interaction experiments were conducted to validate the pharmacodynamic mechanisms.

Hyaluronan-based hydrogel achieves in situ administration of protocatechualdehyde to polarize macrophages to M2 phenotype for diabetic wound therapy.

Wound healing destruction brings disability and mortality to patients with diabetes mellitus. Macrophages maintain pro-inflammatory M1 phenotype to halt diabetic wound recovery. Strategies to polarize M1 macrophages into anti-inflammatory and pro-healing M2 phenotype can propel diabetic wound recovery.

Lowering the Selinexor Dose within the Pomalidomide and Dexamethasone Combination Regimen Elicits Fewer Side Effects While Comparable Efficacy Against Relapsed/Refractory Multiple Myeloma.

Background: As a novel oral Exportin 1 (XPO1) inhibitor, selinexor at 80 or 100 mg has demonstrated efficacy in treating relapsed/refractory multiple myeloma (RRMM), nonetheless, this dosage has shown poor tolerability.

Objective: To explore the optimal dosage of selinexor, we evaluated the efficacy and safety of 60 vs 40 mg selinexor, combine with regimen comprising pomalidomide and dexamethasone in RRMM.

Design: 21 patients with RRMM were enrolled to receive selinexor (60 or 40 mg once weekly), together with pomalidomide (4 mg/day on days 1-21) and dexamethasone (40 mg once weekly); the SPD-60 group (6 patients) vs SPD-40 group (15 patients).