Stroke is the second leading cause of death globally. Oxidative stress plays a critical role in the development of stroke. The Oxidative Balance Score (OBS) is a tool used to assess the combined impact of diet and lifestyle on the body's antioxidant capacity.
View Article and Find Full Text PDFThe SARS-CoV-2 virus mutates rapidly, reducing the effectiveness of antibodies. The novel Class IV antibody IY2A partially unfolds the receptor-binding domain (RBD), allowing tolerance of antigenic variations and effectively neutralizing Omicron variants. In this study, we used molecular dynamics simulations and alanine scanning combined with interaction entropy method to elucidate how IY2A maintains its binding affinity across Omicron variants.
View Article and Find Full Text PDFSpectrochim Acta A Mol Biomol Spectrosc
June 2025
Methyltransferase VP39 is an important target for the treatment of monkeypox, and inhibition of VP39 can effectively suppresses the transcription and translation of early viral RNA. However, very few inhibitors have been designed against VP39 and other viral MTases. In this work, four inhibitors (SFG, TO507, TO427 and TO1119) were used to investigate the binding mechanism with VP39.
View Article and Find Full Text PDFAims: We aimed to develop Ferroptosis-Related Gene (FRG) signatures to predict overall survival (OS) along with disease-free survival (DFS) in individuals with colorectal cancer (CRC).
Background: Prediction of CRC prognosis is challenging. Ferroptosis constitutes a newly reported kind of cell death, and its association with CRC prognosis remains unexplored.
With the ability to reveal allosteric sites, Ponatinib and Ponatinib Hybrid Inhibitor 1 (PHI1) are novel inhibitors of BRAF, a potent oncogene that activates the MAPK pathway. PHI1 also exhibits unique positive cooperativity, with enhanced inhibition on the other monomer when one monomer of the BRAF dimer bound to an inhibitor. The abovementioned properties lack rigorous theoretical verification, so this study compared the interaction mechanisms of four inhibitor types and explored the source of the cooperativity of PHI1 via various computational methods.
View Article and Find Full Text PDFDNA N6-methyladenine (6mA) is a potential epigenetic mark involved in gene transcription in eukaryotes, yet the regulatory mechanism governing its methyltransferase (MTase) activity remains obscure. Here, we exploited the 6mA MTase AMT1 to elucidate its auto-regulation in the unicellular eukaryote Tetrahymena thermophila. The detailed endogenous localization of AMT1 in vegetative and sexual stages revealed a correlation between the 6mA reestablishment in the new MAC and the occurrence of zygotically expressed AMT1.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Stable inheritance of DNA N-methyladenine (6mA) is crucial for its biological functions in eukaryotes. Here, we identify two distinct methyltransferase (MTase) complexes, both sharing the catalytic subunit AMT1, but featuring AMT6 and AMT7 as their unique components, respectively. While the two complexes are jointly responsible for 6mA maintenance methylation, they exhibit distinct enzymology, DNA/chromatin affinity, genomic distribution, and knockout phenotypes.
View Article and Find Full Text PDFAddressing the frequent emergence of SARS-CoV-2 mutant strains requires therapeutic approaches with innovative neutralization mechanisms. The targeting of multivalent nanobodies can enhance potency and reduce the risk of viral escape, positioning them as promising drug candidates. Here, the synergistic mechanisms of the two types of nanobodies are investigated deeply.
View Article and Find Full Text PDFA panel of ferrocenyl-substituted curcumin derivatives has been designed and synthesized as protein tyrosine phosphatase proto-oncogene SHP-2 inhibitors. Antiproliferative activities of the synthesized compounds were tested against colorectal cancer cell lines (including RKO, SW480, and CT26). Compound showed excellent activities against the tested cell lines with IC values of 5.
View Article and Find Full Text PDFJ Chem Theory Comput
December 2024
Accurate calculation of solvation energies has long fascinated researchers, but complex interactions within bulk water molecules pose significant challenges. Currently, molecular solvation energy calculations are mostly based on implicit solvent approximations in which the solvent molecules are treated as continuum dielectric media. However, the implicit solvent approach is not ideal because it lacks certain real solvation effects, such as that of the first solvation shell, etc.
View Article and Find Full Text PDFThe ciliate Tetrahymena thermophila is a well-established unicellular model eukaryote, contributing significantly to foundational biological discoveries. Despite its acknowledged importance, current studies on Tetrahymena biology face challenges due to gene annotation inaccuracy, particularly the notable absence of untranslated regions (UTRs). To comprehensively annotate the Tetrahymena macronuclear genome, we collected extensive transcriptomic data spanning various cell stages.
View Article and Find Full Text PDFPhys Chem Chem Phys
December 2024
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic and a serious impact on human life and health. The spread of this virus, coupled with the emergence of many mutants, has posed increasingly formidable challenges to the design and development of antiviral drugs. Recently, it has been discovered that dalbavancin can bind to angiotensin-converting enzyme 2 (ACE2) of host cells with high affinity, blocking the interaction between the spike protein and ACE2, thereby making it a potentially promising anti-SARS-CoV-2 drug.
View Article and Find Full Text PDFThe photothermal sensitivity of tobacco refers to the degree to which tobacco responds to changes in light and temperature conditions in its growth environment, which is crucial for determining the planting area of cultivars and improving tobacco yield and quality. In order to accurately and effectively evaluate the photothermal sensitivity of tobacco cultivars, this study selected five cultivars and their hybrid combinations with significant differences planted under different ecological conditions from 2021 to 2022 as materials. The experiment was conducted in two locations with significant differences in temperature and light.
View Article and Find Full Text PDFBackground: Recent evidence indicates that general anesthesia and sleep-wake behavior share some overlapping neural substrates. γ-Aminobutyric acid-mediated (GABAergic) neurons in the central amygdala have a high firing rate during wakefulness and play a role in regulating arousal-related behaviors. The objective of this study was to investigate whether central amygdala GABAergic neurons participate in the regulation of isoflurane general anesthesia and uncover the underlying neural circuitry.
View Article and Find Full Text PDFThis study aims to uncover the heterogeneity of endothelial cells (ECs) in colorectal cancer (CRC) and their crucial role in angiogenesis, with a special focus on tip cells. Using single-cell RNA sequencing to profile ECs, our data suggests that CRC ECs predominantly exhibit enhanced angiogenesis and decreased antigen presentation, a shift in phenotype largely steered by tip cells. We also observed that an increase in the density and proportion of tip cells correlates with CRC occurrence, progression, and poorer patient prognosis.
View Article and Find Full Text PDFAims: Cancer-related thrombosis (CAT) is a common complication in cancer patients, significantly impacting their quality of life and survival prospects. Nattokinase (NK) has potent thrombolytic properties, however, its efficacy is limited by low oral bioavailability and the risk of severe allergic reactions with intravenous use. Heparin (HP) is a widely used anticoagulant in clinical settings.
View Article and Find Full Text PDFBackground: The emergence of robotic surgical systems compensated for the technological shortcomings of laparoscopic approaches. However, whether robotic gastrectomy (RG) has better perioperative outcomes and survival than laparoscopic gastrectomy (LG) for gastric cancer (GC) is still unclear but increasingly drawing attention.
Materials And Methods: In this systematic review and meta-analysis, we searched PubMed, EMBASE, Web of Science, and Cochrane Library as of 20 January 2024, and referenced a list of eligible articles for all published studies comparing RG and LG for patients with GC.
Akkermansia muciniphila (A. muciniphila), a probiotic, has been linked to macrophage phenotypic polarization in different diseases. However, the role and mechanisms of A.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Basis Dis
June 2024
Background: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a global health crisis, with genetic mutations and evolution further creating uncertainty about epidemic risk. It is imperative to rapidly determine the nucleic acid sequence of SARS-CoV-2 and its variants to combat the coronavirus pandemic. Our goal was to develop a rapid, room-temperature, point-of-care (POC) detection system to determine the nucleic acid sequences of SARS-CoV-2 isolates, especially omicron variants.
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