Search Results (11,602)

Medical intervention for ischemic heart disease began approximately 150 years ago with nitrates, and for nearly a century thereafter, little fundamental progress was made. With the advent of the left internal thoracic artery to the left anterior descending artery (LITA-LAD) bypass in the 1960s, treatment entered a new stage; however, its essential significance remained insufficiently recognized for many years. Numerous studies were subsequently conducted to evaluate alternative or parallel treatment strategies, but these investigations also helped bring the durable capacity of LITA-LAD to perfuse ischemic myocardium into sharper focus. Over the past quarter century, the treatment of ischemic heart disease has remained in a state of uncertainty, and its central prognostic foundation has often been obscured, although in recent years this uncertainty has begun to resolve. In this review, we reexamine the historical process by which the significance of LITA-LAD remained incompletely appreciated in parts of the cardiology and cardiac surgical communities. We further outline how the principal basis of the long-term prognostic benefit conferred by LITA-LAD gradually became evident and define the contemporary roles of medical therapy and percutaneous coronary intervention in relation to LITA-LAD-based coronary artery bypass grafting (CABG). Full article

Saline–alkali stress is a widespread adversity that severely affects plant growth and productivity. Plant-specific NAC transcription factors (TFs) play a crucial role in various pathways associated with stress responses. However, the function of NAC proteins in conferring tolerance to abiotic stress, along with the underlying mechanisms in apple (Malus domestica), remains incompletely understood. In this study, we identified MdNAC17 from the transcriptome of apple leaves under saline–alkali stress. The overexpression of MdNAC17 in apple calli tissue and Malus hupehensis roots significantly improved resistance to saline–alkali stress by enhancing reactive oxygen species (ROS) scavenging. Transgenic apple plants exhibited higher photosynthetic capacity and antioxidant enzyme activity, as well as less membrane damage. In contrast, silencing MdNAC17 using virus-induced gene silencing (VIGS) technology resulted in the opposite phenotype. Furthermore, MdNAC17 is associated with changes in the transcriptional levels of genes involved in Na⁺/K⁺ homeostasis. Overall, our results demonstrate that MdNAC17 positively regulates saline–alkali tolerance in apple. Full article

H9N2 avian influenza viruses inherently carry cross-species transmission potential, making continuous surveillance critical for pandemic prevention. This study focused on monitoring the 2024 H9N2 epidemic in Jiangsu Province’s external environment, analyzing its molecular evolution and receptor binding properties, assessing cross-species transmission and pandemic risks, and investigating serological antibody levels across different human populations. Environmental samples were collected from live poultry markets, farms, slaughterhouses, and bird habitats across Jiangsu, screened via quantitative PCR (qPCR), with positive samples used for virus isolation and whole-genome sequencing. Receptor binding properties were tested by hemagglutination assay, and H9N2 antibody levels were measured in 370 occupationally exposed individuals and 240 non-exposed individuals using hemagglutination inhibition (HI) assays. Among the 5779 collected samples, 6.89% tested H9N2-positive, and 12 strains belonging to the Eurasian lineage Y280-like clade G57 genotype were successfully isolated. All strains carried the HA-Q226L mutation, with 11 showing preferential binding to human α-2,6 receptors and one strain possessing dual receptor binding capability. Internal genes harbored mammalian adaptation mutations, and M2 proteins contained mutations conferring complete resistance to amantadine-class antiviral drugs. Serological tests revealed antibody positive rates of 4.05% in exposed populations and 2.5% in non-exposed populations, with no statistically significant difference between groups. These findings confirm that Jiangsu’s circulating H9N2 viruses have acquired human receptor preference and mammalian adaptation, posing silent infection and pandemic risks. Enhanced surveillance and the development of candidate vaccine stockpiles are strongly recommended. Full article

Background: Varicella remains a common vaccine-preventable disease in China. Although Anhui Province recommended a two-dose varicella vaccine (VarV) schedule in 2021, real-world evidence on the incremental benefit of the second dose is limited. Methods: A prospective cohort study among children aged 1–12 years was conducted in Anhui Province from July 2022 to August 2025. Children aged 1–3 years who had received one dose of the human diploid cell line-based (SV-1) VarV and children aged 4–12 years whose second dose was the SV-1 VarV were enrolled in the exposed group and were compared with children who had no history of VarV and those who had received only one dose of the VarV, respectively. Varicella cases were collected through active follow-up and surveillance systems. Vaccine effectiveness (VE) and incremental VE were estimated as [1 − relative risk (RR)] × 100%, where the RRs were calculated based on the incidence densities of breakthrough varicella. Results: Overall, 50,054 participants were finally enrolled, contributing 125,351.5 person-years and 105 valid cases. The VE in children aged 1–3 years was 79.1% (95%CI: 42.8–92.4%). Among children aged 4–12 years, the incremental VE was 65.0% (95%CI: 41.9–78.9%), with incremental VEs of 60.1% (95%CI: 22.3–79.5%) for ages 4–6 years and 72.7% (95%CI: 37.8–88.0%) for ages 7–12 years. Conclusions: One-dose SV-1 VarV provided substantial protection in young children, and a second dose conferred significant additional protection in children aged 4–12 years, supporting strengthened implementation of the two-dose strategy and catch-up vaccination among school-aged children. Full article

Glycine betaine transport systems are widely exploited by bacteria to survive osmotic stress and represent potential entry routes for antimicrobial delivery. Here, we investigate the bactericidal glycine betaine analog Tox-GB and its uptake, intracellular fate, and antimicrobial activity in Escherichia coli K-12 under osmotic stress. We show that the xenobiotic enters cells via a hierarchical uptake route involving the osmotically regulated compatible solute transporters ProU and ProP, ABC- and MFS-type transporters, respectively. ProU functions as the primary high-affinity transporter at low concentrations, whereas ProP provides a secondary uptake route at somewhat higher substrate levels. Loss of either transporter confers partial resistance, while simultaneous inactivation of both systems causes full resistance, underscoring their functional redundancy and the robustness of Tox-GB import. Intracellularly, Tox-GB undergoes oxygen-dependent degradation, yielding 4-nitrobenzaldehyde and dimethylglycine. While 4-nitrobenzaldehyde contributes to toxicity under aerobic conditions, Tox-GB remains bactericidal under anaerobic conditions, indicating additional oxygen-independent mechanisms involving either the parent compound or unidentified metabolites. These findings suggest a complex intracellular fate and multifactorial mode of action. Despite initial promise as a Trojan horse antimicrobial strategy, the use of Tox-GB for practical applications faces key limitations. Resistance readily emerges via transporter inactivation, and intrinsic resistance occurs in species lacking appropriate compatible solute uptake systems. Structural constraints in glycine betaine transporters further restrict design flexibility. Osmotic regulation limits activity to specific niches, and potential host toxicity stemming from reactive metabolites raises safety concerns. Collectively, these findings highlight the mechanistic complexity and translational challenges faced by glycine betaine–derived xenobiotics as antimicrobial agents. Full article

Background/Objectives: Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer with a 40% recurrence rate. However, reliable biomarkers for early recurrence detection or treatment guidance are lacking, especially for virus-negative tumors. Circulating tumor DNA (ctDNA), a fragment of tumor-derived cell-free DNA in blood, has emerged across multiple cancers as a minimally invasive precision biomarker to detect minimal residual disease (MRD); predict recurrence; and monitor treatment response. This review’s objective was to summarize recent advances in ctDNA as a tool for therapeutic decision-making in MCC, contextualized by findings in other malignancies. Methods: A comprehensive literature review was performed, focusing on studies published between 2016 and 2026 that evaluate ctDNA in MCC and other cancers. Key prospective trials, observational studies, and case reports were identified through PubMed and relevant conference proceedings. Data on ctDNA assay methods (tumor-informed vs. tumor-agnostic), clinical sensitivity, lead time for recurrence detection, and predictive value for therapy response were extracted and synthesized. Results: Across cancers such as colorectal, lung, and melanoma, ctDNA positivity after curative treatment predicts relapse months in advance of imaging and can guide adjuvant therapy decisions. In MCC, recent studies demonstrate that ctDNA levels correlate with MCC tumor burden and exhibit high sensitivity and specificity for clinically evident disease. Stage I-III MCC patients who were ctDNA-positive within four months of treatment had a 7.4-fold higher recurrence risk within the subsequent 12–18 months of follow-up. Serial ctDNA monitoring may enable earlier intervention in otherwise asymptomatic ctDNA-positive MCC cases, helping distinguish responders from non-responders. Conclusions: ctDNA is an emerging precision biomarker that offers significant prognostic and surveillance utility in MCC. It enables earlier detection of recurrence, potentially allowing treatment to begin before clinical disease manifests. It also helps stratify patients by risk and treatment response, informing personalized surveillance intensity and therapeutic choices. Integrating ctDNA monitoring into MCC management could improve outcomes by guiding timely interventions, although prospective trials are needed to confirm that ctDNA-guided decisions translate to improved patient survival. Formal cost-effectiveness analyses have not yet been conducted and represent an important area for future investigation. Full article

Ubiquitin-specific protease 22 (USP22) regulates epigenetic gene expression by deubiquitinating histone H2B (H2Bub1) and upregulating oncogenic proteins and pathways, while antagonizing p53-mediated tumor suppression. USP22 is frequently overexpressed in cancers and associated with therapy resistance and poor prognosis yet remains largely untargeted pharmacologically. Here, using a fluorescence-based USP22 deubiquitinase assay to screen the LOPAC^®1280 library, we identified β-Lapachone, a natural ortho-naphthoquinone with strong anticancer activities, as a potent USP22 inhibitor. β-Lapachone potently inhibited USP22 enzymatic activity, with a half-maximal inhibitory concentration (IC₅₀) of ~0.75 μM, and molecular docking revealed its occupation of the catalytic pocket adjacent to the USP22 active-site triad, supporting a potential binding mode. Functionally, β-Lapachone suppressed proliferation and induced apoptosis in A549 and H1299 RAS-mutant lung adenocarcinoma (LUAD) cells, while USP22 knockout conferred marked resistance, indicating partial USP22 dependence. In patient-derived LUAD models, β-Lapachone inhibited sphere formation and reduced CD133⁺ cancer stem cell populations. Notably, it synergized with cisplatin to enhance DNA damage and apoptosis. In vivo, β-Lapachone significantly suppressed tumor growth in a syngeneic KRAS-mutant/p53-Null mouse lung cancer model and further potentiated cisplatin-induced antitumor effects. Collectively, these findings identify β-Lapachone as a potent inhibitor of USP22 and validate USP22 inhibition as a key mechanism underlying its anticancer activity in LUAD cells, both in vitro and in vivo. Full article

Glioblastoma (GB) is the most aggressive primary central nervous system tumor in adults and the most common malignant primary brain tumor, representing approximately 50.9% of all malignant CNS tumors, with a median overall survival of approximately 14.6 months despite standard multimodal treatment, consisting of surgical resection, concurrent radiotherapy, and temozolomide (TMZ), followed by adjuvant TMZ (Stupp protocol). Tumor recurrence is inevitable and attributed to diffuse infiltration of neoplastic cells into the brain parenchyma, marked intratumoral heterogeneity, the presence of glioma stem cells, and the protection conferred by the BBB. Flavonoids are plant-derived polyphenolic compounds with more than 8000 identified. They have attracted growing interest as potential therapeutic agents because of their capacity to modulate multiple oncogenic signaling pathways and their favorable toxicity profile. Here we synthesize the preclinical evidence on the main flavonoids with documented activity in GB models, with emphasis on quercetin, apigenin, luteolin, and EGCG, while distinguishing glioblastoma-specific evidence from indirect findings derived from other experimental systems. We analyze their underlying molecular mechanisms, including induction of apoptosis through the intrinsic and extrinsic pathways, inhibition of cell proliferation and angiogenesis, suppression of migration and invasion, epigenetic modulation, and, particularly, the capacity to target the glioma stem cell population. We also examine the limited oral bioavailability and restricted penetration across the BBB, as these factors remain major barriers to translational development. We conclude with an analysis of emerging nanotechnological strategies, targeted delivery systems, and synergistic combinations with conventional chemotherapeutic agents, together with a cautious assessment of the current clinical evidence, which remains insufficient to support the use of flavonoids outside controlled clinical trials. Full article

Osteoporosis (OP) is a complex disease in which several immune-related genes have been identified as contributing to susceptibility and disease progression. Despite efforts to achieve functional validation, many of these genes, such as interferon-gamma (IFNG), remain the subject of unresolved mechanisms. The present study aimed to examine whether the IFNG -1616 (G>A, rs2069705) polymorphism was associated with postmenopausal OP. A total of 251 OP patients and 115 healthy controls were genotyped to assess the association between the IFNG -1616 (G>A, rs2069705) polymorphism and osteoporosis. To further investigate the biological role of IFN-γ in bone metabolism, human SaOs-2 osteosarcoma cells were treated with recombinant IFN-γ (2 and 100 U/mL), and calcification and cell viability were evaluated using Alizarin Red staining and the MTT assay, respectively. We found that the IFNG rs2069705 G allele was associated with an increased risk of OP (OR = 1.45, 95% CI = 1.03–2.05, p = 0.03). Furthermore, serum IFN-γ levels did not differ significantly between genotype groups. In SaOs-2 cells, IFN-γ (2 U/mL) significantly increased viability (p = 0.017) and enhanced calcification in a dose-dependent manner. The IFNG rs2069705 G allele may confer susceptibility to postmenopausal OP. IFN-γ promotes osteoblast viability and mineralization at low concentrations, suggesting a potential anabolic role that warrants further investigation in human primary osteoblasts. Full article

Objectives: The optimal conduit strategy for coronary artery bypass grafting (CABG) in patients with moderate left ventricular dysfunction (LVEF 30–49%) remains debated. While total arterial grafting (TAG) has shown benefits in broader populations, its role in this higher-risk subgroup is unclear. This study aimed to compare short-term outcomes and long-term survival between single arterial grafting (SAG) and TAG in patients with moderate LV dysfunction undergoing CABG. Methods: A retrospective analysis of 1866 patients was performed, with 640 patients matched using propensity scores (320 SAG vs. 320 TAG). Preoperative, intraoperative, and postoperative variables were assessed. Survival was evaluated using Kaplan–Meier analysis and Cox regression. Results: Matched cohorts were well balanced across baseline characteristics. Long-term survival at 10 and 15 years was numerically higher in the TAG group (85.8% and 79.7%) compared to SAG (81.7% and 74.2%), though not statistically significant (log-rank p = 0.862). Multivariate Cox regression identified age (HR 1.045, p < 0.001), NYHA class (NYHA III HR 0.610, p = 0.003), previous cardiac surgery (HR 0.501, p = 0.006), and off-pump CABG (HR 1.521, p < 0.001) as independent predictors of mortality. Grafting strategy (TAG vs. SAG) was not independently associated with long-term mortality (HR 1.005, p = 0.966). Conclusion: TAG is safe and feasible in patients with moderate LV dysfunction undergoing isolated CABG, with comparable short-term outcomes. Although unadjusted analyses suggested improved long-term survival, this difference was not observed after propensity matching or multivariable adjustment, and grafting strategy was not independently associated with mortality. Full article

A time-saving approach to gelatin-based hydrogels with versatile properties is highly desirable. Herein, we report the rapid fabrication of new gelatin-containing hydrogels with favorable mechanical properties, biocompatibility and antibacterial capability. Frontal polymerization (FP) of acrylic acid (AA), acrylamide (AM), hydroxypropyl acrylate (HPA) with gelatin methacryloyl (GelMA) enables the rapid formation of multifunctional hydrogels within 7 min, providing a highly efficient route for gelatin-based hydrogel fabrication. The effect of GelMA content on FP features and hydrogel properties was systematically investigated. The resultant hydrogels show attractive collective properties with tensile strength up to 101.3 kPa, elongation at break up to 227.7%, cell viability of 96% after 24 h, and antibacterial activity against S. aureus (92.2%). In addition, the FP of the hydrogels with use of forsythia-derived carbon dots (F-CDs) as bioactive nanofillers is explored, conferring the hydrogels with enhanced mechanical performance and biocompatibility, demonstrating the applicability of this FP strategy upon incorporating functional additives. This work provides a simple and effective approach for the rapid preparation of gelatin-containing hydrogels with versatile functions promising for biomedical applications such as wound healing and tissue engineering. Full article

Objectives: Explore and compare the effects of 8-week time-restricted eating (TRE), walking exercise, and their combination on fat and lean muscle distribution in female college students with hidden obesity. Methods: A total of 68 participants were randomly assigned to four groups: Control (CON), TRE, Exercise (EXE), and TRE + EXE. An 8-week intervention was begun according to a predetermined experimental plan, comparing changes in body fat and lean tissue indices before and after the intervention. Results: Before and after the intervention, the TRE group showed a significant decrease in body mass, body mass index (BMI), and total lean mass (p < 0.05). The EXE group saw a significant reduction in visceral fat area, visceral fat mass, and visceral fat volume (p < 0.01). The TRE + EXE group experienced a significant decrease in android lean mass (p < 0.05); Comparing before and after the intervention, there were no statistically significant differences in the body fat percentage, total fat mass, fat and lean in the android and gynoid areas, and %fat in trunk/%fat in legs among the CON, TRE, EXE, and TRE + EXE groups (p > 0.05). After the intervention, there were no significant differences in the body fat percentage, total fat mass, total lean mass, fat and lean in the android and gynoid areas, %fat in trunk/%fat in legs, visceral fat area, visceral fat mass, visceral fat volume, subcutaneous fat area, subcutaneous fat mass, and subcutaneous fat volume among the four groups (p > 0.05). Conclusions: An 8-week TRE intervention in young women with hidden obesity reduced body mass and BMI but also decreased total lean mass, potentially compromising metabolic health, with no statistically significant changes in total body fat or regional fat distribution. Walking exercise showed significant reductions in visceral adiposity indicators (VFA, VFM, VFV), whereas the combined TRE + EXE group did not achieve comparable reductions. These findings suggest that while isolated TRE facilitates body mass loss, it carries a distinct risk of muscle tissue loss and may not confer comparable benefits on visceral fat reduction as walking exercise. However, the generalizability of these preliminary observations is constrained by methodological limitations including retrospective registration, participant attrition, and restricted statistical power. Consequently, these exploratory outcomes must be interpreted with caution, warranting future robust, large-scale trials with enhanced compliance monitoring to optimize prescriptive guidelines for this specific cohort. Full article

Drawing on sport tourism, sport ecology, and environmental policy scholarship, this narrative review argues that the event schedule architecture should be positioned as a strategic tool for managing sport-tourism externalities. Evaluation against standard instrument-choice criteria shows that the schedule architecture performs strongly in regards to cost-effectiveness, uncertainty handling, and institutional compatibility, but faces serious political feasibility constraints rooted in regulatory capture, the absence of mandatory environmental impact assessment, and misalignment between organization-level commitments and league-level scheduling authority. Five research gaps are identified and matched with a research agenda covering political economy, quantitative instrument comparison, procedural reform design, demographic and geographic extension, and causal evaluation. The contribution frames the event schedule architecture as a strategic-management instrument for sport-tourism sustainability and connects it to Sustainable Development Goals 11, 12, 13, and 17. Full article

The 9th National Congress of the Italian Society for Virology (SIV-ISV), entitled “One Virology—One Health”, took place in Turin at the Centro Congressi Lingotto from 22 to 24 June 2025. The meeting highlighted recent multidisciplinary and translational developments in virology, with a strong focus on the integration of the One Health perspective. Major themes included viral emergence and surveillance, genomic sequencing and bioinformatics, virus–host interactions, viral immunology and vaccines, structural and physical virology, environmental and food virology, zoonoses and animal infections, diagnostics and antiviral therapy, virus-based biotechnology and plant virology. The Congress aimed to: (i) bring together clinicians, basic researchers, veterinarians, environmental microbiologists, bioinformaticians, public-health professionals and industry to share methodologies and best practices; (ii) provide an interactive scientific environment promoting discussion and collaboration between senior investigators and trainees through plenaries, joint society sessions, invited talks, oral communications selected from abstracts, poster sessions, and mentoring panels; and (iii) identify priorities and inspire new research directions at the interface of human, animal and environmental health. More than 400 participants from national and international institutions attended the meeting, featuring distinguished plenary speakers, joint sessions with global networks, and numerous presentations of original unpublished data. This report summarizes the meeting’s scientific highlights, cross-disciplinary discussions, and proposed actions to strengthen One Health surveillance, computational infrastructures, and translational applications of viral biology. Full article

In this study, we propose a hybrid cryptanalytic technique targeting the RSA cryptosystem when instantiated with small private exponents. By integrating the continued fraction approach with Coppersmith’s lattice-based technique, we formulate a novel vulnerability framework. Utilizing an innovative relationship extracted from continued fraction convergents, we deduce an improved upper bound for the secret key: $d<N^{1-\alpha /3-\gamma /2}$. In this context, $\alpha :={log}_{N}e$ and $\gamma :={log}_N|p+q-S|$, where S serves as a known approximation of the prime sum $p+q$. As an extension of our preliminary conference proceedings, this paper supplies comprehensive proofs for all theoretical propositions, performs a comprehensive parameter sensitivity evaluation, and provides bounds for partial prime exposure scenarios. Empirical evaluations confirm the theoretical mechanics of our framework, demonstrating that it offers improved bounds in specific partial leakage scenarios compared to traditional lattice-only baselines. Full article