Antiviral and anti-inflammatory activities of chemical constituents from twigs of Mosla chinensis Maxim.

Seven undescribed compounds, including three flavones (1-3), one phenylpropanoid (19), three monoaromatic hydrocarbons (27-29), were isolated from the twigs of Mosla chinensis Maxim together with twenty-eight known compounds. The structures were characterized by HRESIMS, 1D and 2D NMR, and ECD spectroscopic techniques. Compound 20 displayed the most significant activity against A/WSN/33/2009 (H1N1) virus (IC50 = 20.47 µM) compared to the positive control oseltamivir (IC50 = 6.85 µM). Further research on the anti-influenza mechanism showed that compound 20 could bind to H1N1 virus surface antigen HA1 and inhibit the early attachment stage of the virus. Furthermore, compounds 9, 22, 23, and 25 displayed moderate inhibitory effects on the NO expression in LPS inducing Raw 264.7 cells with IC50 values of 22.78, 20.47, 27.66, and 30.14 µM, respectively.

Improvement of performance for flexible film dosimeter by incorporating additive agents.

Objective.To evaluate the reduction in energy dependence and aging effect of the lithium salt of pentacosa-10,-12-diynoic acid (LiPCDA) films with additives including aluminum oxide (Al2O3), propyl gallate (PG), and disodium ethylenediaminetetracetate (EDTA).Approach. LiPCDA films exhibited energy dependence on kilovoltage (kV) and megavoltage (MV) photon energies and experienced deterioration over time. Evaluations were conducted with added Al2O3and antioxidants to mitigate these issues, and films were produced with and without Al2O3to assess energy dependence. The films were irradiated at doses of 0, 3, 6, and 12 cGy at photon energies of 75 kV, 105 kV, 6 MV, 10 MV, and 15 MV. For the energy range of 75 kV to 15 MV, the mean and standard deviation (std) were calculated and compared for the values normalized to the net optical density (netOD) at 6 MV, corresponding to identical dose levels. To evaluate the aging effect, PG and disodium EDTA were incorporated into the films: sample C with 1% PG, sample D with 2% PG, sample E with 0.62% disodium EDTA added to sample D, and sample F with 1.23% disodium EDTA added to sample D.Main results. Films containing Al2O3demonstrated a maximum 15.8% increase in mean normalized values and a 15.1% reduction in std, reflecting a greater netOD reduction at kV than MV energies, which indicates less energy dependence in these films. When the OD of sample 1-4 depending on the addition of PG and disodium EDTA, was observed for 20 weeks, the transmission mode decreased by 8.7%, 8.3%, 29.3%, and 27.3%, respectively, while the reflection mode was 5.4%, 3.0%, 37.0%, and 34.5%, respectively.Significance. Al2O3effectively reduced the voltage and MV energy dependence. PG was more effective than disodium EDTA in preventing the deterioration of film performance owing to the aging effect.

Alkaline sphingomyelinase deficiency impairs intestinal mucosal barrier integrity and reduces antioxidant capacity in dextran sulfate sodium-induced colitis.

BACKGROUND: Ulcerative colitis is a chronic inflammatory disease of the colon with an unknown etiology. Alkaline sphingomyelinase (alk-SMase) is specifically expressed by intestinal epithelial cells, and has been reported to play an anti-inflammatory role. However, the underlying mechanism is still unclear. AIM: To explore the mechanism of alk-SMase anti-inflammatory effects on intestinal barrier function and oxidative stress in dextran sulfate sodium (DSS)-induced colitis. METHODS: Mice were administered 3% DSS drinking water, and disease activity index was determined to evaluate the status of colitis. Intestinal permeability was evaluated by gavage administration of fluorescein isothiocyanate dextran, and bacterial translocation was evaluated by measuring serum lipopolysaccharide. Intestinal epithelial cell ultrastructure was observed by electron microscopy. Western blotting and quantitative real-time reverse transcription-polymerase chain reaction were used to detect the expression of intestinal barrier proteins and mRNA, respectively. Serum oxidant and antioxidant marker levels were analyzed using commercial kits to assess oxidative stress levels. RESULTS: Compared to wild-type (WT) mice, inflammation and intestinal permeability in alk-SMase knockout (KO) mice were more severe beginning 4 d after DSS induction. The mRNA and protein levels of intestinal barrier proteins, including zonula occludens-1, occludin, claudin-3, claudin-5, claudin-8, mucin 2, and secretory immunoglobulin A, were significantly reduced on 4 d after DSS treatment. Ultrastructural observations revealed progressive damage to the tight junctions of intestinal epithelial cells. Furthermore, by day 4, mitochondria appeared swollen and degenerated. Additionally, compared to WT mice, serum malondialdehyde levels in KO mice were higher, and the antioxidant capacity was significantly lower. The expression of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) in the colonic mucosal tissue of KO mice was significantly decreased after DSS treatment. mRNA levels of Nrf2-regulated downstream antioxidant enzymes were also decreased. Finally, colitis in KO mice could be effectively relieved by the injection of tertiary butylhydroquinone, which is an Nrf2 activator. CONCLUSION: Alk-SMase regulates the stability of the intestinal mucosal barrier and enhances antioxidant activity through the Nrf2 signaling pathway.

Tumor-associated macrophage-derived exosomal miR21-5p promotes tumor angiogenesis by regulating YAP1/HIF-1α axis in head and neck squamous cell carcinoma.

Extracellular vesicles (EVs) have recently received increasing attention as essential mediators of communication between tumor cells and their microenvironments. Tumor-associated macrophages (TAMs) play a proangiogenic role in various tumors, especially head and neck squamous cell carcinoma (HNSCC), and angiogenesis is closely related to tumor growth and metastasis. This research focused on exploring the mechanisms by which EVs derived from TAMs modulate tumor angiogenesis in HNSCC. Our results indicated that TAMs infiltration correlated positively with microvascular density in HNSCC. Then we collected and identified EVs from TAMs. In the microfluidic chip, TAMs derived EVs significantly enhanced the angiogenic potential of pHUVECs and successfully induced the formation of perfusable blood vessels. qPCR and immunofluorescence analyses revealed that EVs from TAMs transferred miR-21-5p to endothelial cells (ECs). And targeting miR-21-5p of TAMs could effectively inhibit TAM-EVs induced angiogenesis. Western blot and tube formation assays showed that miR-21-5p from TAM-EVs downregulated LATS1 and VHL levels but upregulated YAP1 and HIF-1α levels, and the inhibitors of YAP1 and HIF-1α could both reduce the miR-21-5p enhanced angiogenesis in HUVECs. The in vivo experiments further proved that miR-21-5p carried by TAM-EVs promoted the process of tumor angiogenesis via YAP1/HIF-1α axis in HNSCC. Conclusively, TAM-derived EVs transferred miR-21-5p to ECs to target the mRNA of LATS1 and VHL, which inhibited YAP1 phosphorylation and subsequently enhanced YAP1-mediated HIF-1α transcription and reduced VHL-mediated HIF-1α ubiquitination, contributing to angiogenesis in HNSCC. These findings present a novel regulatory mechanism of tumor angiogenesis, and miR-21-5p/YAP1/HIF-1α might be a potential therapeutic target for HNSCC.

Species-level Microbiota of Biting Midges and Ticks from Poyang Lake.

Objective: The purpose of this study was to investigate the bacterial communities of biting midges and ticks collected from three sites in the Poyang Lake area, namely, Qunlu Practice Base, Peach Blossom Garden, and Huangtong Animal Husbandry, and whether vectors carry any bacterial pathogens that may cause diseases to humans, to provide scientific basis for prospective pathogen discovery and disease prevention and control. Methods: Using a metataxonomics approach in concert with full-length 16S rRNA gene sequencing and operational phylogenetic unit (OPU) analysis, we characterized the species-level microbial community structure of two important vector species, biting midges and ticks, including 33 arthropod samples comprising 3,885 individuals, collected around Poyang Lake. Results: A total of 662 OPUs were classified in biting midges, including 195 known species and 373 potentially new species, and 618 OPUs were classified in ticks, including 217 known species and 326 potentially new species. Surprisingly, OPUs with potentially pathogenicity were detected in both arthropod vectors, with 66 known species of biting midges reported to carry potential pathogens, including Asaia lannensis and Rickettsia bellii, compared to 50 in ticks, such as Acinetobacter lwoffii and Staphylococcus sciuri. We found that Proteobacteria was the most dominant group in both midges and ticks. Furthermore, the outcomes demonstrated that the microbiota of midges and ticks tend to be governed by a few highly abundant bacteria. Pantoea sp7 was predominant in biting midges, while Coxiella sp1 was enriched in ticks. Meanwhile, Coxiella spp., which may be essential for the survival of Haemaphysalis longicornis Neumann, were detected in all tick samples. The identification of dominant species and pathogens of biting midges and ticks in this study serves to broaden our knowledge associated to microbes of arthropod vectors. Conclusion: Biting midges and ticks carry large numbers of known and potentially novel bacteria, and carry a wide range of potentially pathogenic bacteria, which may pose a risk of infection to humans and animals. The microbial communities of midges and ticks tend to be dominated by a few highly abundant bacteria.

Hydroxylamine-Mediated C(sp2)-H Trifluoromethylation of Terminal Alkenes.

Introduction of the trifluoromethyl (CF3) group into organic compounds has garnered substantial interest because of its significant role in pharmaceuticals and agrochemicals. Here, we report a hydroxylamine-mediated radical process for C(sp2)-H trifluoromethylation of terminal alkenes. The reaction shows good reactivity, impressive E/Z selectivity (up to >20 : 1), and broad functional group compatibility. Expansion of this approach to perfluoroalkylation and late-stage trifluoromethylation of bioactive molecules demonstrates its promising application potential. Mechanistic studies suggest that the reaction follows a radical addition and subsequent elimination pathway.

Inactivation of VRK1 sensitizes ovarian cancer to PARP inhibition through regulating DNA-PK stability.

Ovarian cancer is the leading cause of gynecologic cancer death. Among the most innovative anti-cancer approaches, the genetic concept of synthetic lethality is that mutations in multiple genes work synergistically to effect cell death. Previous studies found that although vaccinia-related kinase-1 (VRK1) associates with DNA damage repair proteins, its underlying mechanisms remain unclear. Here, we found high VRK1 expression in ovarian tumors, and that VRK1 depletion can significantly promote apoptosis and cell cycle arrest. The effect of VRK1 knockdown on apoptosis was manifested by increased DNA damage, genomic instability, and apoptosis, and also blocked non-homologous end joining (NHEJ) by destabilizing DNA-PK. Further, we verified that VRK1 depletion enhanced sensitivity to a PARP inhibitor (PARPi), olaparib, promoting apoptosis through DNA damage, especially in ovarian cancer cell lines with high VRK1 expression. Proteins implicated in DNA damage responses are suitable targets for the development of new anti-cancer therapeutic strategies, and their combination could represent an alternative form of synthetic lethality. Therefore, normal protective DNA damage responses are impaired by combining olaparib with elimination of VRK1 and could be used to reduce drug dose and its associated toxicity. In summary, VRK1 represents both a potential biomarker for PARPi sensitivity, and a new DDR-associated therapeutic target, in ovarian cancer.

DDX21 mediates co-transcriptional RNA m6A modification to promote transcription termination and genome stability.

N6-methyladenosine (m6A) is a crucial RNA modification that regulates diverse biological processes in human cells, but its co-transcriptional deposition and functions remain poorly understood. Here, we identified the RNA helicase DDX21 with a previously unrecognized role in directing m6A modification on nascent RNA for co-transcriptional regulation. DDX21 interacts with METTL3 for co-recruitment to chromatin through its recognition of R-loops, which can be formed co-transcriptionally as nascent transcripts hybridize onto the template DNA strand. Moreover, DDX21's helicase activity is needed for METTL3-mediated m6A deposition onto nascent RNA following recruitment. At transcription termination regions, this nexus of actions promotes XRN2-mediated termination of RNAPII transcription. Disruption of any of these steps, including the loss of DDX21, METTL3, or their enzymatic activities, leads to defective termination that can induce DNA damage. Therefore, we propose that the R-loop-DDX21-METTL3 nexus forges the missing link for co-transcriptional modification of m6A, coordinating transcription termination and genome stability.

The histologic features, molecular features, detection and management of serrated polyps: a review.

The serrated pathway to colorectal cancers (CRCs) is a significant pathway encompassing five distinct types of lesions, namely hyperplastic polyps (HPs), sessile serrated lesions (SSLs), sessile serrated lesions with dysplasia (SSL-Ds), traditional serrated adenomas (TSAs), and serrated adenoma unclassified. In contrast to the conventional adenoma-carcinoma pathway, the serrated pathway primarily involves two mechanisms: BRAF/KRAS mutations and CpG island methylator phenotype (CIMP). HPs are the most prevalent non-malignant lesions, while SSLs play a crucial role as precursors to CRCs, On the other hand, traditional serrated adenomas (TSAs) are the least frequently encountered subtype, also serving as precursors to CRCs. It is crucial to differentiate these lesions based on their unique morphological characteristics observed in histology and colonoscopy, as the identification and management of these serrated lesions significantly impact colorectal cancer screening programs. The management of these lesions necessitates the crucial steps of removing premalignant lesions and implementing regular surveillance. This article provides a comprehensive summary of the epidemiology, histologic features, molecular features, and detection methods for various serrated polyps, along with recommendations for their management and surveillance.

Meta-analysis of the human gut microbiome uncovers shared and distinct microbial signatures between diseases.

Microbiome studies have revealed gut microbiota's potential impact on complex diseases. However, many studies often focus on one disease per cohort. We developed a meta-analysis workflow for gut microbiome profiles and analyzed shotgun metagenomic data covering 11 diseases. Using interpretable machine learning and differential abundance analysis, our findings reinforce the generalization of binary classifiers for Crohn's disease (CD) and colorectal cancer (CRC) to hold-out cohorts and highlight the key microbes driving these classifications. We identified high microbial similarity in disease pairs like CD vs ulcerative colitis (UC), CD vs CRC, Parkinson's disease vs type 2 diabetes (T2D), and schizophrenia vs T2D. We also found strong inverse correlations in Alzheimer's disease vs CD and UC. These findings detected by our pipeline provide valuable insights into these diseases.

Phosphonium-Catalyzed Monoreduction of Bisphosphine Dioxides: Origin of Selectivity and Synthetic Applications.

Controlling product selectivity in successive reactions of the same type is challenging owing to the comparable thermodynamic and kinetic properties of the reactions involved. Here, the synergistic interaction of the two phosphoryl groups in bisphosphine dioxides (BPDOs) with a bromo-phosphonium cation was studied experimentally to provide a practical tool for substrate-catalyst recognition. As the eventual result, we have developed a phosphonium-catalyzed monoreduction of chiral BPDOs to access an array of synthetically useful bisphosphine monoxides (BPMOs) with axial, spiro, and planar chirality, which are otherwise challenging to synthesize before. The reaction features excellent selectivity and impressive reactivity. It proceeds under mild conditions, avoiding the use of superstoichiometric amounts of additives and metal catalysts to simplify the synthetic procedure. The accessibility and scalability of the reaction allowed for the rapid construction of a ligand library for optimization of asymmetric Heck-type cyclization, laying the foundation for a broad range of applications of chiral BPMOs in catalysis.

PMI-controlled mannose metabolism and glycosylation determines tissue tolerance and virus fitness.

Host survival depends on the elimination of virus and mitigation of tissue damage. Herein, we report the modulation of D-mannose flux rewires the virus-triggered immunometabolic response cascade and reduces tissue damage. Safe and inexpensive D-mannose can compete with glucose for the same transporter and hexokinase. Such competitions suppress glycolysis, reduce mitochondrial reactive-oxygen-species and succinate-mediated hypoxia-inducible factor-1α, and thus reduce virus-induced proinflammatory cytokine production. The combinatorial treatment by D-mannose and antiviral monotherapy exhibits in vivo synergy despite delayed antiviral treatment in mouse model of virus infections. Phosphomannose isomerase (PMI) knockout cells are viable, whereas addition of D-mannose to the PMI knockout cells blocks cell proliferation, indicating that PMI activity determines the beneficial effect of D-mannose. PMI inhibition suppress a panel of virus replication via affecting host and viral surface protein glycosylation. However, D-mannose does not suppress PMI activity or virus fitness. Taken together, PMI-centered therapeutic strategy clears virus infection while D-mannose treatment reprograms glycolysis for control of collateral damage.

Study on the Effect of Polyamine Water Treatment Agent on Metal Corrosion Inhibition in Boiler Steam-Water System.

A polyamine water treatment agent was prepared with the film-forming amine (N-oleyl-1,3-propylenediamine) and the neutralizing amine (cyclohexanamine) under optimal conditions. The copper sulfate liquid drop experiment showed that a protective film was formed by the polyamine water treatment agent on carbon steel. The analyses of the polarization curve and electrochemical impedance spectroscopy of carbon steel indicated that the polyamine water treatment agent exhibited geometric effects, which could inhibit both anode and cathode reactions of carbon steel, and the corrosion inhibition effect of the polyamine water treatment agent showed an extreme-concentration phenomenon. A metal corrosion experiment in a simulated boiler steam-water system indicated that the polyamine water treatment agent mitigated the corrosion of carbon steel at different temperatures, and the corrosion inhibition rates of the polyamine water treatment agent in liquid and gas environments at 150 °C were 53.84% and 67.43%, respectively, better than that at 350 °C. SEM-EDS characterization indicated that the formation of the corrosion product, iron oxide, on the carbon steel was reduced with the addition of the polyamine water treatment agent in the simulated boiler steam-water system.

Charge-Localized Retention and Long-Term Memory Enabled by Cooperating Sterically Confined Molecular Crystallization with Spiro[fluorene-9,9'-xanthene]-Based Csp3-Hindrance.

Charge localization of memory materials plays a crucial role in the endurance and retention ability of organic nonvolatile memory, which is completely opposite from the charge delocalization of high-mobility materials. However, charge transfer of both though-space and through-bond based on molecular design principles still faces challenges. Herein, a nonplanar wide-bandgap semiconductor with Csp3-hindrance (DOCH3-DDPA-SFX) has been designed and synthesized. An effective crystallization effect of self-assembled two-dimensional nanosheets on charge trapping dynamics and kinetics is visualized by Kelvin probe force microscopy (KPFM). The trapped charges are localized completely on a single nanosheet, which has better charge trapping and retention properties than an amorphous film. Meanwhile, crystallization also greatly improves structure stability. Combining DFT theoretical calculations, the mechanisms of localization and long-term retention are discussed. The steric crystallization effects on the charge localization will guide the effective design of single-component semiconducting charge-memory materials by molecular assembly and aggregate control for high-performance organic memory.

Nsp1 facilitates SARS-CoV-2 replication through calcineurin-NFAT signaling.

SARS-CoV-2, the causative agent of COVID-19, has been intensely studied in search of effective antiviral treatments. The immunosuppressant cyclosporine A (CsA) has been suggested to be a pan-coronavirus inhibitor, yet its underlying mechanism remained largely unknown. Here, we found that non-structural protein 1 (Nsp1) of SARS-CoV-2 usurped CsA-suppressed nuclear factor of activated T cells (NFAT) signaling to drive the expression of cellular DEAD-box helicase 5 (DDX5), which facilitates viral replication. Nsp1 interacted with calcineurin A (CnA) to displace the regulatory protein regulator of calcineurin 3 (RCAN3) of CnA for NFAT activation. The influence of NFAT activation on SARS-CoV-2 replication was also validated by using the Nsp1-deficient mutant virus. Calcineurin inhibitors, such as CsA and VIVIT, inhibited SARS-CoV-2 replication and exhibited synergistic antiviral effects when used in combination with nirmatrelvir. Our study delineated the molecular mechanism of CsA-mediated inhibition of SARS-CoV-2 replication and the anti-SARS-CoV-2 action of calcineurin inhibitors. IMPORTANCE: Cyclosporine A (CsA), commonly used to inhibit immune responses, is also known to have anti-SARS-CoV-2 activity, but its mode of action remains elusive. Here, we provide a model to explain how CsA antagonizes SARS-CoV-2 through three critical proteins: DDX5, NFAT1, and Nsp1. DDX5 is a cellular facilitator of SARS-CoV-2 replication, and NFAT1 controls the production of DDX5. Nsp1 is a viral protein absent from the mature viral particle and capable of activating the function of NFAT1 and DDX5. CsA and similar agents suppress Nsp1, NFAT1, and DDX5 to exert their anti-SARS-CoV-2 activity either alone or in combination with Paxlovid.

Development of a nomogram to predict 30-day mortality of sepsis patients with gastrointestinal bleeding: An analysis of the MIMIC-IV database.

Background: We aimed to establish and validate a prognostic nomogram model for improving the prediction of 30-day mortality of gastrointestinal bleeding (GIB) in critically ill patients with severe sepsis. Methods: In this retrospective study, the current retrospective cohort study extracted data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, then partitioned the cohort randomly into training and validation subsets. The cohort was partitioned into training and validation subsets randomly. Our primary endpoint was 30-day all-cause mortality. To reduce data dimensionality and identify predictive variables, the least absolute shrinkage and selection operator (LASSO) regression was employed. A prediction model was constructed by multivariate logistic regression. Model performance was evaluated using the concordance index (C-index), receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). Results: The analysis included 1435 total patients, comprising 1005 in the training cohort and 430 in the validation cohort. We found that age, smoking status, glucose, (BUN), lactate, Sequential Organ Failure Assessment (SOFA) score, mechanical ventilation≥48h (MV), parenteral nutrition (PN), and chronic obstructive pulmonary disease (COPD) independently influenced mortality in sepsis patients with concomitant GIB. The C-indices were 0.746 (0.700-0.792) and 0.716 (0.663-0.769) in the training and validation sets, respectively. Based on the area under the curve (AUC) and DCA, the nomogram exhibited good discrimination for 30-day all-cause mortality in sepsis with GIB. Conclusions: For sepsis patients complicated with GIB, we created a unique nomogram model to predict the 30-day all-cause mortality. This model could be a significant therapeutic tool for clinicians in terms of personalized treatment and prognosis prediction.

Development of a duplex droplet digital PCR assay for the detection of Burkholderia cepacia complex and Stenotrophomonas maltophilia in bloodstream infections.

Burkholderia cepacia complex (BCC) and Stenotrophomonas maltophilia are nosocomial pathogens that cause various infections and exhibit high resistance to multiple antimicrobial agents. In this study, we aimed to develop a duplex droplet digital PCR (ddPCR) assay for detecting BCC and S. maltophilia in bloodstream infections. We optimized the experimental conditions by setting the annealing temperature to 51°C and determining the optimal concentrations of primers and probes, as well as the thermal cycle numbers. The feasibility of the duplex ddPCR reaction system with the optimal conditions was established and verified through parallel reactions with reference strains of BCC and S. maltophilia. The specificity of the assay, tested with 33 reference strains, was found to be 100%. The duplex ddPCR assay demonstrated good repeatability and could detect as low as 5.35 copies/reaction of BCC and 7.67 copies/reaction of S. maltophilia. This level of sensitivity was consistent in the simulated blood and blood bottle samples. We compared nucleic acid extraction methods and found that the Chelex-100 boiling method and kit extraction method exhibited similar detection sensitivity, suggesting the potential application of the Chelex-100 boiling method in the ddPCR assay. In the clinical samples, the duplex ddPCR assay accurately detected BCC and S. maltophilia in 58 cases. In conclusion, our study successfully developed a duplex ddPCR assay that provides accurate and convenient detection of BCC and S. maltophilia in bloodstream infections.IMPORTANCEBurkholderia cepacia complex (BCC) and Stenotrophomonas maltophilia are implicated in a wide range of infections, including bloodstream infections (BSIs), pneumonia, and meningitis, and often exhibit high intrinsic resistance to multiple antimicrobial agents, limiting therapeutic options. The gold standard for diagnosing bloodstream infections remains blood culture. However, current blood culture detection and positivity rates do not meet the "rapid diagnosis" required for the diagnosis and treatment of critically ill patients with BSIs. The digital droplet PCR (ddPCR) method is a potentially more powerful tool in the diagnosis of BSIs compared to other molecular methods due to its greater sensitivity, specificity, accuracy, and reproducibility. In this study, a duplex ddPCR assay for the detection of BCC and S. maltophilia in BSIs was developed.

Healthy eating index-2015 and its association with the prevalence of stroke among US adults.

This study aims to investigate the relationship between the healthy eating index (HEI) and the prevalence of stroke within a diverse United States population. Employing a cross-sectional design, we utilized data sourced from the National Health and Nutrition Examination Survey (NHANES). Dietary information was collected from participants and HEI scores were computed. NHANES employed stratified multistage probability sampling, with subsequent weighted analysis following NHANES analytical guidelines. Thorough comparisons were made regarding the baseline characteristics of individuals with and without stroke. Weighted multivariable logistic regression analysis and restricted cubic spline (RCS) methods were employed to ascertain the association between stroke risk and HEI, with LASSO regression utilized to identify dietary factors most closely linked to stroke risk. Additionally, we constructed a nomogram model incorporating key dietary factors and assessed its discriminatory capability using the receiver operating characteristic (ROC) curve. Our study encompassed 43,978 participants, representing an estimated 201 million U.S. residents. Participants with a history of stroke exhibited lower HEI scores than their non-stroke counterparts. Logistic regression analysis demonstrated a robust association between lower HEI scores and stroke, even after adjusting for confounding variables. RCS analysis indicated a nonlinear negative correlation between HEI and stroke risk. Furthermore, detailed subgroup analysis revealed a significant gender-based disparity in the impact of dietary quality on stroke risk, with females potentially benefiting more from dietary quality improvements. Sensitivity analysis using unweighted logistic regression yielded results consistent with our primary analysis. The nomogram model, based on key dietary factors identified through LASSO regression, demonstrated favorable discriminatory power, with an area under the curve (AUC) of 79.3% (95% CI 78.4-81.2%). Our findings suggest that higher HEI scores are inversely related to the risk of stroke, with potential greater benefits for women through dietary quality enhancement. These results underscore the importance of improving dietary quality for enhanced stroke prevention and treatment.