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An applicable and highly efficient methodology for the preparation of medium- and long-chain triglycerides (MLCTs) via the enzymatic transesterification of coconut oil with long-chain fatty acid triglycerides, named camellia oil, olive oil, linseed oil, algal oil, and rapeseed oil, respectively, has been proposed. The novel system achieved equilibrium in 5 min, and the MLCT yield ranged from 78.7 to 83.8 %. This is the fastest record reported to date. The catalytic efficiency of the novel biocatalyst, CSL@HMS-C 8 , was 140 g/g•h, 1.43 times higher compared to the control (free lipase), and it retained 62.5 % of its relative activity after 15 cycles. A UPLC-MS provided an accurate structural analysis of the MLCTs, and molecular docking analysis was performed to understand the binding interactions between the protein and molecules. The method of preparing MLCT enriched with functional fatty acids in this paper is efficient, broadly applicable, economical, and promising for industrial applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.) more...

Aims: Mitochondrial oxidative stress (MOS) is a key contributor to poor cardiac function and a major driver of myocardial ischemia-reperfusion injury (MIRI). Our previous research demonstrated that stem cell-derived nanovesicles (NVs) enhanced cardiac function following ischemia-reperfusion (I/R) injury, although the underlying mechanisms remain unclear. We constructed and characterized miR-222-3p-loaded NVs., Materials and Methods: An in vitro hypoxia-reoxygenation (H/R) model was established using H9C2 cardiomyocytes. Mitochondrial oxidative respiratory function was assessed using Seahorse XF technology, while mitochondrial reactive oxygen species (mtROS) levels were quantified via flow cytometry. Additional assessments included mitochondrial permeability transition pore (mPTP) status, mitochondrial membrane potential, and mitochondrial DNA (mtDNA) integrity. An in vivo H/R model was developed using C57BL/6 mice. The therapeutic effects of NVs on MOS reduction and cardiac function improvement were evaluated through Masson's staining, immunofluorescence, echocardiography, transmission electron microscopy (TEM), and positron emission tomography/computed tomography (PET/CT)., Key Findings: RNA immunoprecipitation (RIP) confirmed that miR-222-3p directly targets cyp1a1. Overexpression of miR-222-3p or knockdown of cyp1a1 significantly improved mitochondrial activity in cardiomyocytes and conferred protection against I/R injury. Conversely, overexpression of cyp1a1 abrogated the protective effects of miR-222-3p. In vivo, NV treatment enhanced cardiac function, reduced MOS, and improved mitochondrial respiratory capacity in MIRI model mice. NV treatment, via miR-222-3p-mediated suppression of cyp1a1, mitigates MOS, enhances mitochondrial respiratory function, and improves cardiac outcomes in MIRI models., Significance: These findings provide a foundational basis for the clinical translation of NV-based therapies., Competing Interests: Declaration of competing interest None., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.) more...

Background: Spine grapes are widely cultivated in southern China because of their strong adaptability to hot and humid climates. As a wild species native to China, spine grape (Vitis davidii Foëx) was studied as a resource of proanthocyanidins (PAs). PA composition, biosynthesis, and histochemistry in different tissues (skins, seeds, and stems) during berry development were analyzed in this study., Results: The findings revealed that PA accumulation occurred in concurrence with flowering and was completed by veraison. High-performance liquid chromatographic results showed that the epicatechin type was the most dominant. The skins were more likely to accumulate PA polymers. Reverse transcription-quantitative polymerase chain reaction analysis revealed that the expression levels of structural genes (flavonoid-3'-hydroxylase, flavonoid-3'5'-hydroxylase, dihydroflavonol 4-reductase, leucoanthocyanidin reductase, and leucoanthocyanidin dioxygenase) were positively associated with PA dynamic changes. Histochemical results revealed that PAs in skins were mainly found in the hypodermis of the exocarp, PAs in seeds were mainly found in the middle layer of the outer integument of the testa, and PAs in stems were mainly found in the phloem., Conclusion: This study provides a clear understanding of the spatial and temporal accumulation of PAs in spine grape, and forms a basis for the analysis of structural profiles and synthesis of PAs and their biological effects. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.) more...

Heavy metals like Cu(II) and oxytetracycline (OTC) frequently coexist in livestock manure and wastewater due to their widespread use as feed additives, forming Cu(II)-OTC complexes that influence OTC transport and transformation in groundwater. This study investigates Cu(II)-mediated OTC transformation on Fe-bearing smectite under dark, anoxic conditions. Results show that OTC adsorption on Fe-bearing smectite undergoes further transformation. Cu(II)-OTC complexes significantly enhance OTC adsorption, accounting for 23.6%, 99.4%, and 92.9% of total OTC at pH 3, 5, and 8.5, respectively, but inhibit OTC transformation. FTIR, XPS, and UPLC-QTOF analyses reveal redox reactions between Cu(II)-OTC complexes and Fe-bearing smectite, reducing Fe(III) to Fe(II). Transformation primarily involves the tricarbonylamide group at pH 3 and 5, extending to the dimethylamino group at pH 8.5. A kinetic model of OTC transformation identifies two key parameters: the transformation rate (k') and the reactive site quantity (S rxn ). The k' varies with pH as follows: pH 3 < pH 8.5 < pH 5, while Fe concentration exhibits an inverse relationship with k', suggesting that mineral dissolution reduces the redox activity of Fe-bearing smectite. Furthermore, a linear correlation between the fraction of redox-active Cu(II)-OTC complexes and S rxn indicates that Cu(II) complexation occupies reactive sites on Fe-bearing smectite, inhibiting transformation. These findings highlight the importance of considering heavy metal-antibiotic interactions when assessing groundwater risks., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Ltd.) more...

Atherosclerosis (AS) is increasingly recognized as a chronic inflammatory disease that significantly compromises vascular health and serves as a major contributor to cardiovascular diseases. KCTD10, a protein implicated in a variety of biological processes, has garnered significant attention for its role in cardiovascular diseases and metabolic regulation. As a member of the KCTD protein family, KCTD10 is characterized by the presence of a T1 domain that interacts with voltage-gated potassium channels, a critical interaction for modulating channel activity and intracellular signal transduction. In our study, KCTD10 was identified as a focal point through an integrative analysis of differentially expressed genes (DEGs) across multiple datasets (GSE43292 and GSE9820) from the GEO database, aligned with immune-related gene sets from the ImmPort database. Advanced analytical tools, including Lasso regression and Support Vector Machine-Recursive Feature Elimination (SVM-RFE), were employed to refine our gene selection. We further applied Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) to these gene sets, revealing significant enrichment in immune-related pathways. The relationship between KCTD10 expression and immune processes was examined using CIBERSORT and ESTIMATE algorithms to assess tumor microenvironment characteristics, suggesting increased immune cell infiltration associated with higher KCTD10 expression. Validation of these findings was conducted using data from the GSE9820 dataset. Among 10 DEGs linked with KCTD10, 13 were identified as hub genes through LASSO and SVM-RFE analyses. Functional assays highlighted KCTD10's role in enhancing viral defense mechanisms, cytokine production, and immune cascades. Notably, KCTD10 expression correlated positively with several immune cells, including naive CD4 + T cells, eosinophils, resting NK cells, neutrophils, M0 macrophages, and particularly M1 macrophages, indicating a significant association. This research elucidates the complex relationship between KCTD10 and AS, underscoring its potential as a novel biomarker for diagnosing and monitoring the disease. Our findings provide a solid foundation for further investigations, suggesting that targeting KCTD10-related pathways could markedly advance our understanding and management of AS, offering new avenues for therapeutic intervention., Competing Interests: Declarations. Competing interests: The authors declare that they have no conflict of interest. Ethics approval: This manuscript is not a clinical trial, hence the ethics approval and consent to participation are not applicable. Consent for publication: All authors have read and approved this manuscript to be considered for publication., (© 2025. The Author(s).) more...

The immunosuppressive tumor microenvironment (TME) plays a crucial role in the progression and treatment resistance of melanoma. Modulating the TME is thus a key strategy for enhancing therapeutic outcomes. Previousstudies have identified clonidine (CLD), an α2-adrenergic receptor agonist, as a promising agent that enhances T lymphocyte infiltration and reduces myeloid-derived suppressor cells within the TME, thereby promoting antitumor immune responses. In this study, we discovered that CLD reshaped the melanoma immune microenvironment, facilitating T-cell activation and exerting antitumor effects. However, the high doses of CLD required for effective TME modulation pose significant toxicity concerns, limiting its clinical applicability. To address this, we employed the controllable cavitation-on-a-chip (CCC) platform to formulate CLD-loaded liposomes and optimize their size. This approach aimed to enhance the precision and efficacy of drug delivery while reducing systemic side effects. Our results demonstrated that size-specific CLD liposomes, particularly those at 50 nm, significantly improved tumor growth inhibition and immune cell infiltration within the TME. Moreover, these optimized liposomes mitigate adverse effects associated with high-dose CLD treatment. This study indicates the potential of CCC-optimized CLD liposomes as a safer and more effective melanoma therapy, highlighting the critical interplay between liposome size control and therapeutic outcomes in cancer treatment., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2025. Published by Elsevier B.V.) more...

Dramatic changes in climate and soil environments have made growing conditions for crops more challenging. These crops are subject to a range of abiotic stresses in different environments, which can lead to significant yield losses, resulting in economic and environmental damages. Herein, we report a straightforward one-pot hydrothermal method for creating carbon dots codoped with copper and nitrogen (Cu,N-CDs). Under salt stress conditions, Cu,N-CDs demonstrate the ability to alleviate oxidative damage in cucumber seedlings by modulating antioxidant defense mechanisms and scavenging reactive oxygen species (ROS). Cucumber seedling biomass accumulation is greatly enhanced by Cu,N-CDs treatment in the presence of a ROS burst, leading to a notable rise in the dry weight, plant height, and fresh weight. Cu,N-CDs mitigate oxidative damage in cucumber seedlings by activating antioxidant defense systems, specifically enhancing the activities of superoxide dismutase (+34.08%), catalase (+28.11%), peroxidase (+17.54%), and ascorbate peroxidase (+31.54%) to scavenge ROS. Furthermore, Cu,N-CDs can enhance the levels of nonenzymatic elements within the antioxidant system, such as polyphenols (+23.60%), flavonoids (+15.43%), and carotenoid content (+51.73%), which strengthen the scavenging ability of cucumber seedlings against ROS. Meanwhile, Cu,N-CDs can induce a significant increase of soluble sugar and soluble protein content by 27.27 and 32.58%, respectively, which improves the osmotic pressure as well as stress tolerance of plants. Additionally, the accumulation of biomass was aided by the increase in the photosynthetic pigment content that Cu,N-CDs treatment can produce. more...

Objective: To investigate the endocardial myocardial biopsy and ultrastructural features of heart failure patients with reduced ejection fraction, to determine their histopathologic phenotype, and to explore the diagnostic utility of endomyocardial biopsy in such patients. Methods: A total of 35 patients with heart failure with reduced ejection fraction diagnosed at Beijing Anzhen Hospital and underwent endomyocardial biopsy were collected between January 2022 and December 2023. The clinical features, histopathological, and ultrastructural characteristics were analyzed and compared with 11 patients with heart failure with preserved ejection fraction. Results: The age ranged from 35-58 years, with median age of 51 years; there were 26 males and 9 females. Myocardial fibrosis and myocardial fiber disorders were the most common histopathologic changes [97.1% (34/35) and 74.3% (26/35), respectively]. Myocardial fibrosis was not statistically different between the heart failure with reduced ejection fraction group and the heart failure with preserved ejection fraction group [13.3% (5.7%-21.4%) vs. 13.2% (9.3%-34.2%), P= 0.279]. Significant ultrastructural changes were dense mitochondrial proliferation, vacuolar degeneration, and disorganized arrangement of myocardial fibers with localized lysis and fracture. After endomyocardial biopsy, the etiology was identified in 11 patients (31.4%,11/35), with a prevalence of cardiac amyloidosis of 17.1% (6/35). Conclusions: Endomyocardial biopsy is useful for early diagnosis and precise treatment in patients presenting with heart failure with reduced ejection fraction. Histopathological and ultrastructural analyses can uncover potential treatments, and predict and improve prognosis by providing relevant information for understanding the pathogenesis and clinical evolution. more...

The impact of induced emotional states on duration perception remains unclear. This study investigated duration distortion in emotional states through two meta-analyses based on 17 English articles (28 studies) retrieved from the PubMed and Web of Science databases, published up to March 19, 2024. Meta-Analysis 1 examined both the distortion direction (i.e., underestimation or overestimation compared to neutral states) and the distortion degree (i.e., the extent to which perceived duration deviated from that in neutral states). Meta-Analysis 2 focused solely on the degree of distortion. The results indicated that when both the direction and degree were considered, the findings on duration distortion in emotional states were inconsistent. However, when the direction of distortion was not considered, there was a significant effect on the degree of duration distortion in emotional states. Moderator analysis revealed that the emotional valence moderated the effect size of emotion states on the degree of duration distortion, regardless of whether the direction of distortion was considered. While duration measurement paradigm only moderates the degree of duration distortion without direction. Specifically, the duration overestimation effect was observed in negative states when the distortion direction was considered. A greater distortion degree was observed in negative emotional states or duration judgment tasks. However, neither emotional arousal nor the duration itself moderated the distortion degree, irrespective of whether the direction of distortion was considered. These findings underscore the importance of considering the influence of induced emotional states on the degree of duration distortion, in addition to the direction., Competing Interests: Declarations. Conflict of interest: The authors declare no conflict of interest., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.) more...

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality globally, predominantly associated with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. These infections drive persistent liver inflammation, culminating in cellular dysregulation, fibrosis, and cancer. Despite advancements in targeted therapies, drug resistance and the lack of reliable biomarkers for patient stratification still terribly hinder the treatment of viral HCC. To this end, the review delves into the intricate mechanisms underlying the malignant transformation of viral hepatitis to HCC, including viral integration, genomic instability, epigenetic modifications, oxidative stress, gut microbiota dysbiosis, chronic inflammation, immune escape, and abnormal signaling pathways, highlighting their complex interactions and synergies. Cutting-edge preclinical and clinical advancements in HCC management, including lifestyle modifications, drug therapies, immunotherapies, gene-based approaches, and innovative treatments, are further investigated, with particular priority given to their therapeutic potential and future applications in overcoming current limitations. By synthesizing recent scientific and clinical insights, this review aims to deepen the understanding of HCC pathogenesis in the context of chronic viral hepatitis, paving the way for novel therapeutic targets and personalized treatment strategies, ultimately improving patient outcomes., Competing Interests: The authors declare no conflicts of interest., (© 2025 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.) more...

Background: Limited evidence was available on the association of the integrated effect of multidimensional lifestyle factors with AF incidence among Chinese old adults. This cohort study was to examine the effect of combined lifestyle factors on AF risk among Chinese older adults., Methods: A total of 3,253 adults aged 60 years or more from the Guangzhou Heart Study were successfully followed up. The healthy lifestyle score (HLS) was established using a weighted approach from seven dimensions of lifestyles, including diet quality, leisure-time physical activity, sleep quality, alcohol drinking, smoking, mental status, and waist-to-hip ratio. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using the Cox proportional hazard regression model., Results: During a median of 31.13 months of follow-up, 76 (2.34%) new-onset of AF were observed. After adjustment for confounders, HLS was associated with a 46% (HR: 0.54, 95% CI: 0.32-0.93) reduced AF risk when comparing the high with low tertiles of weight HLS, with an exposure-response trend. Every 0.1-unit increment of HLS was associated with 49% reduced AF risk. The protective effect of HLS on AF incidence was remarkable in the young-old (HR: 0.47, 95% CI: 0.29-0.79) but not in the old-old (HR: 0.85, 95% CI: 0.29-2.48), when comparing the high with low tertiles., Conclusion: The results suggest that higher HLS was associated with lower AF incidence among Chinese old adults, and the findings highlight the need to consider multi-dimensional lifestyles when developing health promotion strategies to lower the risk of new-onset AF the risk of new-onset AF., Competing Interests: Declarations. Ethical approval: This study was approved by the Medical Research Ethics Committee of Guangdong Provincial People’s Hospital and by the Ethical Review Committee for Biomedical Research, School of Public Health, Sun Yat-sen University. The study was performed in line with the Declaration of Helsinki and all participants provided informed consent. Consent to participants: The participants were required to sign a written informed consent form before joining the study. Patients and/or the public were not involved in the design, conduct, reporting, or dissemination plans of this research. Consent for publication: All co-authors provided comments and approved the final version. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).) more...

Rechargeable aluminum-ion batteries with graphite as cathode material are highly attractive for energy storage due to their low cost, high abundance, and high capacity. Although some techniques have been employed to investigate intercalation/deintercalation behavior of AlCl4- in graphite materials, the microscopic mechanism remains ambiguous and controversial, leading to a question that needs to be answered. Therefore, direct and in-situ characterization of nanoscale variations in the z direction is a reliable avenue to finding the answer to the intercalation stage mechanism. In this work, in-situ AFM was used to directly monitor the intercalation/deintercalation process of AlCl4- in highly oriented pyrolytic graphite, pyrolytic graphite and natural graphite electrode materials. We demonstrate that during the initial stage of intercalation, AlCl4- ions tend to intercalate intensively into the same graphite layer, and that as potential increases the intercalation of AlCl4- ions displays a mixed-staged process. Moreover, during the intercalation of AlCl4- into the pyrolytic graphite electrode, noticeable exfoliation of the graphite layers was observed. This phenomenon accounts for the energy loss that occurs in the initial cycles of the graphite/Al battery system. Finally, we propose an optimization strategy to prevent exfoliation., (© 2025 Wiley‐VCH GmbH.) more...

Magnesium hydroxide (Mg(OH)₂) dosing is widely applied for sewer odour control. However, its impact on the fate of biomarkers used for wastewater-based epidemiology (WBE) has been overlooked. This study investigated the long-term and short-term impact of Mg(OH)₂ dosing on in-sewer transformation of 20 biomarkers. The dosing duration and amount of Mg(OH)₂ were specifically controlled in laboratory-scale sewer reactors, which led to long-term biofilm adaptation and instant change of wastewater pH. Mg(OH)₂ dosing rapidly inhibited H₂S at high pH levels and changed microbial community structure after long-term exposure. The transformation of biomarkers was a combined result of pH-driven abiotic process and biodegradation in the dosing-impacted sewers. The high stability of biomarkers like acesulfame and carbamazepine was unaffected by Mg(OH)₂ dosing. Most unstable biomarkers like caffeine, codeine and nicotine presented less degradation and extended half-lives in sewers received either long-term or short-term dosing, compared to their rapid losses under normal sewer conditions. This study provides a comprehensive understanding of both instant and lasting impacts of Mg(OH)₂ dosing on microbial community, biological activity, and biomarker stability in sewers. The longer half-lives of biomarkers in Mg(OH) 2 -dosed sewers benefited WBE application due to the improved detection reliability and less uncertainty related to biomarker loss, suggesting that chemical dosing information is required for accurate WBE estimation within a catchment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.) more...

Hyaluronic acid (HA) is a natural polymer that can be degraded by hyaluronate lyase into oligomers with diverse biological activities. In this study, a novel hyaluronate lyase (named HCLase6) of polysaccharide lyase family 6 from Microbulbifer sp. ALW1 was cloned and characterized. Optimal temperature and pH for HCLase6 was determined to be 40 ℃ and 5.0, respectively. It displayed good stability at temperature up to 45 ℃ and in the pH range of 4.0-9.0. In addition, HCLase6 demonstrated good tolerance to detergents of Tween 20, Tween 80 and SDS, and was halophilic and halotolerant to Na + . Molecular dynamics simulations indicated that the presence of Na + increased the flexibility of the loop region adjacent to the active pocket of HCLase6, altered the surface hydrophobicity and electrostatic potential, and strengthened the motion correlation between amino acid residues. Notably, the enzymatic products of HA oligosaccharides (O-HA) produced by HCLase6 showed significantly enhanced free radical scavenging activities and iron reducing power. They also exhibited the antioxidant activity in human keratinocytes cells after exposure to PM SRM 1648a. This study provides the knowledge of the enzymatic properties of HCLase6 and a reference for its industrial application., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Conflict of interest: The authors declare no conflict of interest., (© 2025. The Author(s), under exclusive licence to Springer Nature B.V.) more...

Vacancy defects can enhance the surface activity of photocatalyst by providing additional reactive sites, facilitating the adsorption and transformation of reactants. Therefore, by tuning the type and concentration of vacancy defects, the performance of photocatalyst can be optimized, thereby increasing their application potential in environmental remediation and energy conversion. In this work, tunable nitrogen vacancies g-C 3 N 4 photocatalysts were prepared and treated by sodium hypophosphite (NHPO) with reducibility. Systematic characterization confirmed that the N defect sites are primarily located at the 2-coordinated N on the aromatic rings, and all the NHPO-treated g-C 3 N 4 possess greater abundance of N defects compared to the reference g-C 3 N 4 . This improvement endowed it with superior photogenerated carrier separation and migration efficiency, resulting in significantly enhanced photocatalytic reduction performance. Specifically, under simulating solar light irradiation for 4 h, the g-C 3 N 4 treated with the optimal concentration of NHPO achieved CO 2 reduction efficiencies of 36.55 μmol g -1 and 3.36 μmol g -1 for CO and CH 4 , respectively, which are more than quadrupling that of the reference g-C 3 N 4 . Additionally, it demonstrated remarkable catalytic efficiency in photocatalytic hydrogen evolution (5852 μmol g -1 ), achieving 3.3 folds than that of the reference g-C 3 N 4 , further supporting the universality of the enhanced photocatalytic performance of NHPO-treated g-C 3 N 4 . The possible photocatalytic mechanism is elucidated to clarify the photogenerated carrier transfer path in rich N vacancies g-C 3 N 4 . This finding provides valuable guidance for introducing tunable N vacancies on g-C 3 N 4 through environmentally friendly chemical redox methods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.) more...

We report the complete biosynthesis of antifungal papulacandins through heterologous expression and enzymatic assays. The papulacandin biosynthesis follows a convergent five-component strategy, involving a linear polyketide chain that is synthesized and installed to the aryl-glucoside by a polyketide synthase fused with a C-terminal acyltransferase domain. The formation of the challenging tricyclic benzannulated spiroketal core is initiated by the C -glycosylation of 5-(hydroxymethyl)resorcinol, followed by spirocyclization catalyzed by a Fe(II)/α-ketoglutarate-dependent oxygenase PpcE. more...

Objectives: Global countries often apply containment policies (CPs) to combat infectious disease surges. Whether countries with longer cumulative duration of CPs are associated with slower long-term epidemic progression necessitates a thorough evaluation., Methods: We collected CP and COVID-19 data of 185 territories during 2020-2022, with a total of 23 CPs. By using the target-trial-emulation and cloning-censoring-weighting approaches, we assessed the effectiveness of CPs with different cumulative durations in delaying countries from reaching the 1% and 10% cumulative infection incidence endpoints (i.e., 10,000 and 100,000 COVID-19 cases per million population respectively) over a three-year observation period., Results: For reaching the 1% cumulative infection incidence, recommending closing workplaces, and limiting gatherings to 10 people, each presented that longer cumulative duration of those CPs is associated with a lower proportion of countries achieving this endpoint throughout 2020-2022. For reaching the 10% cumulative infection incidence, mandatory bans on public events and domestic movements, closing public transports, screening and quarantining inbound tourists, each showed similar associations. Notably, long-lasting border bans upon high-risk regions are associated with a higher proportion of countries reaching the 10% cumulative infection incidence., Conclusion: From the long-term perspective, we highlight CPs that warrant extending the duration to achieve slower epidemic progression. By contrast, our findings demonstrate the limited effectiveness of ban on regions in slowing the long-term epidemic progression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Ltd.) more...

Skeletal muscle atrophy is a common complication in patients with type 2 diabetes (T2D) and is associated with dysfunction of muscle satellite cells. The activation and proliferation of muscle satellite cells involve a switch in glucose metabolism, which is regulated by driving the acetylation of histones to control the expression of related genes. Studies have confirmed that resistance exercise can improve insulin resistance and activate muscle satellite cells, but the specific molecular mechanisms are not yet clear. This study aims to investigate whether resistance exercise can promote the proliferation of muscle satellite cells and improve muscle atrophy in type 2 diabetic rats by enhancing glucose metabolism in skeletal muscles. A T2D rat model was induced by combining a high-fat diet with streptozotocin injection. After 8 weeks of resistance exercise, the activity of key enzymes (Pyruvate Kinase, Phosphofructokinase, Pyruvate Dehydrogenase) in glucose metabolism in the skeletal muscles of T2D rats significantly increased, the expression of Sirtuin 1 (Sirt1) and Nicotin -amide Phosphoribosyltransferase (Nampt) in the skeletal muscles of the rats decreased, and the expression of acetylation of lysine 16 on histone H4 (H4K16ac) significantly increased, indicating an elevated level of the H4K16ac. The expression of paired box 7 (Pax7) and myogenic differentiation (MyoD) was significantly upregulated, indicating that exercise promoted the proliferation of muscle satellite cells. These results suggest that resistance exercise may promote glucose metabolism in skeletal muscles of T2D rats by regulating the activity of key enzymes in sugar metabolism, further regulating Sirt1-mediated histone H4K16ac, thereby promoting the proliferation of muscle satellite cells and improving muscle atrophy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.) more...

Alzheimer's disease (AD) is a leading neurodegenerative disorder, characterized by progressive cognitive decline and memory impairment, with a complex etiology involving genetic, environmental, and lifestyle factors. Traditionally, AD has been studied in isolation, but emerging evidence highlights its interconnectedness with various comorbidities across multiple organ systems. This study introduces a Disease-Wide Association Study (DWAS) approach to explore the disease continuum centered around AD. Using the FinnGen cohort, which includes over 392,000 participants, this study systematically analyzed the comorbidities associated with AD, spanning cardiovascular, metabolic, musculoskeletal, digestive, and oncological conditions. These findings reveal that AD is part of a much broader, systemic disease continuum, with shared pathophysiological mechanisms, including chronic inflammation, metabolic dysregulation, and vascular health, which may influence AD onset and progression. Temporal analysis of pre- and post-AD comorbidities identifies modifiable risk factors such as hypertension, atherosclerosis, and type 2 diabetes that may not only precede AD but also exacerbate its progression. The study emphasizes the importance of an integrated care approach for AD patients, addressing both neurological and systemic health to improve outcomes. Furthermore, by identifying modifiable risk factors, this research opens new avenues for early interventions aimed at delaying or preventing AD. These findings challenge the traditional view of AD as an isolated disease and provide insights into the shared etiology of AD and its comorbidities, offering potential targets for personalized therapeutic strategies and public health policies., Competing Interests: Declaration of competing interest The funders had no role in the study design, data analysis, data interpretation, and writing of this manuscript. This study was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Elsevier Inc. All rights reserved.) more...

Liquid crystal monomers (LCMs) are potentially persistent, bioaccumulative, and toxic emerging pollutants. However, their occurrence in outdoor PM 2.5 and related human exposure risks remain unknown. In this study, 32 composite samples were analyzed, which were prepared from daily PM 2.5 samples collected throughout the year 2021 -2022 in Beijing, China. In total, fifty-six of 78 LCMs were presented at a median concentration of 66.0 pg/m 3 (range: 13.3-375.6 pg/m 3 ), with fluorinated LCMs (FBAs) predominating and accounting for 90.7 % of the total LCMs. This concentration surpasses that of halogenated persistent organic pollutants (e.g., polychlorinated dibenzo-p-dioxins/furans) in ambient PM 2.5 . Higher concentrations of LCMs were found in spring and summer compared to autumn and winter, which could be explained by correlations of concentrations with temperature (p < 0.05). Trans,trans-3,4-Difluoro-4'-(4'-pentylbicyclohexyl-4-yl)biphenyl, trans,trans-3,4-Difluoro-4'-(4'-propylbicyclohexyl-4-yl)biphenyl, and trans,trans-3,4,5-Trifluoro-4'-(4'-propylbicyclohexyl-4-yl)biphenyl were identified for the first time as dominant compounds in ambient samples. Based on predicted biological toxicities, 48 LCMs were categorized as high priority due to their high potential for human absorption, including several compounds previously overlooked. The non-carcinogenic risks of LCMs through inhalation and dermal were negligible for children and adults. This study firstly established a priority list of LCMs in PM 2.5 , highlighting the need for heightened awareness of their health risks., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.) more...

The importance of the tumor microenvironment in dynamically modulating neoplastic process, fostering proliferation, survival and migration is now widely appreciated. Therapeutics directed to various components of tumor microenvironment, especially tumor-associated macrophages and myeloid-derived suppressor cells (MDSCs), have become an attractive avenue for cancer immunotherapy. Virus-like particles (VLPs) derived from cowpea chlorotic mottle viruses (CCMV) have been used extensively in biotechnology and are ideal platforms for the targeted delivery of therapeutic drugs for cancer immunotherapy. Here, oxidative dsDNAs, which have excellent immunostimulatory effects, are encapsulated into CCMV (CPD VLPs). CPD VLPs could be effectively taken up by macrophages and subsequently trigger Cyclic GMP-AMP synthase-stimulator of interferon genes pathway and NLRP3/Caspase-1/Gasdermin D -dependent pyroptosis pathway. To increase tumor-targeting specificity and reduce toxicity in bystander healthy tissues, peptides targeting MDSCs are conjugated to the exterior surfaces of the CPD VLPs named CPD-TP VLPs. CPD-TP VLPs can home to tumor side and induce a robust antitumor response by reprogramming tumor microenvironment. Notably, CPD-TP VLPs administration is also efficacious against lung metastasis from breast cancer. Moreover, the combination of CPD-TP VLPs with programmed cell death protein 1 (PD-1) blockade could improve therapeutic response of PD-1 antibody treatment in "immune-cold" mouse tumor models. Therefore, this study presents a novel design for VLP-based cancer vaccine., Competing Interests: Declaration of competing interest All authors declare no financial/commercial conflicts of interest., (Copyright © 2025 Elsevier B.V. All rights reserved.) more...

The performance of water electrolysis is profoundly influenced by the behavior of the gas bubbles generated at the electrode surface. In order to improve the efficiency of bubble transportation, various nanostructures for the catalyst layer (CL), such as nanorods (NRs) or nanoparticles (NPs), have been proposed. However, there is still a lack of complete understanding about the relationship between the catalyst layer morphology and bubble evolution, which has a considerable impact on bubble transport. This study examines the effect of the catalyst layer morphology on the growth and detachment of bubbles in water electrolysis by employing the Lattice Boltzmann (LB) model. The performance of three different catalyst layer morphologies, namely, nanorods, nanoparticles, and hierarchical nanostructures, on bubble dynamics is estimated. The results suggest that the catalyst layer morphology is characterized by two factors: the bubble contact area and the electrochemically active surface area, which varies the bubble diameter, detachment time, and, subsequently, the bubble coverage. As a result, the energy efficiency of water electrolysis is influenced, aligned with experimental data that show a voltage differential of 148 mV at a current density of 0.65 A/cm 2 . This study highlights the significance of improving the structure of the catalyst layer to boost the efficiency of water electrolysis systems. more...

Engineering aqueous electrolytes with an ionic liquid (IL) for the zinc (Zn) metal anode has been reported to enhance the electrochemical performances of the Zn metal batteries (ZMBs). Despite these advancements, the effects of IL and the mechanisms involving their anions and cations have been scarcely investigated. Here, we introduce a novel electrolyte design strategy that synergizes anion-cation chemistry using a halogen-based IL and elucidates the underlying mechanism. The strongly and preferentially adsorbed halogen anions guide the formation of a water-poor electrical double layer (EDL) by imidazole-based cations, resulting in the formation of a halide-rich inorganic interphase. This synergistic interaction significantly mitigates Zn anode corrosion at the anode-electrolyte interface, while the halide-rich interphase promotes dense Zn deposition. Consequently, the battery exhibits superior performance, including high reversibility (99.74%) and an ultralong cycle life (20,000 cycles). This synergistic anion-cation chemistry strategy combines the traditional single solid electrolyte interphase and the classic EDL mechanism, substantially enhancing the electrochemical performance of ZMBs. more...

Macrocycles are abundantly used by nature to enable cell-permeable bioactive molecules. Synthetic non-peptidic macrocycles are also increasingly considered as modalities for difficult-to-bind proteins but guidelines for macrocyclization are only beginning to emerge. Macrocycles are thought to constrain the available conformations but also to allow for residual flexibility, the latter being poorly understood. Here we show that even medium-sized macrocycles display an unexpected high conformational plasticity, even when bound to their protein target. Minor modification of the linker region of macrocycles can shift the conformational ensemble to distinct conformational subclasses, each constituting distinct three-dimensional scaffolds for further optimization. This led to several new ligands with improved affinity and beneficial physicochemical parameters for the FK506-binding protein 51, a promising target for depression, obesity and chronic pain. Importantly, none of the beneficial modifications could have been identified by classical medicinal chemistry as they only work in the macrocyclic context. Our results show that macrocyclization can do more than keeping loose ends together but rather provide a platform for multiple series of macrocycles with distinct binding modes., (© 2025 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.) more...

This study aimed to develop and evaluate the protective immunity of a ROP27 DNA vaccine against Eimeria tenella (E. tenella) in chickens. E. tenella is a parasitic protozoan that poses a significant threat to the poultry industry. The rhoptry protein 27 (ROP27) of E. tenella has been shown to have immunoprotective properties. However, traditional protein expression methods are time-consuming and labor-intensive, limiting large-scale production. In this study, we developed a pVAX-ROP27 DNA vaccine and confirmed its expression in chickens using RT-PCR and Western blot analysis. The protective immunity of the DNA vaccine was evaluated through an animal experiment with different immunization doses. The results confirmed the successful construction of the pVAX-ROP27 DNA vaccine and its in vivo expression. Chickens immunized with the vaccine at different doses showed significant improvements in average weight gain, relative weight gain rate (RWG), cecal lesion score reduction (RLS), and oocyst reduction rate, as well as a decrease in oocysts per gram (OPG). The group immunized with 100 μg/feather of pVAX-ROP27 exhibited the most significant effect, achieving an anticoccidial index (ACI) of 179.80. Additionally, levels of IL-2, IFN-γ, IL-6, IgG, and IgY significantly increased with the number of immunizations, whereas IL-4 and IL-10 showed no significant differences. Histopathological analysis of the ceca revealed that lesions were least severe in the 100 μg/feather pVAX-ROP27 immunized group. These findings suggest that the pVAX-ROP27 DNA vaccine offers immune protection against E. tenella infection and could serve as a promising candidate for preventing and controlling chicken coccidiosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.) more...

Purpose: A noninvasive method for evaluating the infiltration of CD8 + T cells in tumors is urgently needed to monitor the response to immunotherapy. This study investigated the performance of a [ 68 Ga]Ga-NODAGA-SNA006 in positron emission tomography (PET) imaging of CD8 + T cells in patients with solid malignancies., Methods: This human dose-escalation PET imaging study involved eleven patients (lung cancer, 8; gastric carcinoma, 1; esophageal carcinoma, 2). Approximately 150 MBq of [ 68 Ga]Ga-NODAGA-SNA006 with varying nanobody masses (100 µg, 300 µg, 500 µg, 800 µg) was administered, and PET/computed tomography (CT) scans were performed at 15-30, 60-90 and 120 min postinjection (p.i.). Data regarding biodistribution, pharmacokinetics and radiation dosimetry were evaluated. CD8 + T-cell infiltration in biopsy samples was also measured via immunohistochemistry (IHC) for correlation analysis with the tumor uptake of [ 68 Ga]Ga-NODAGA-SNA006 PET., Results: [ 68 Ga]Ga-NODAGA-SNA006 was well tolerated by all eleven subjects. The highest radioactive uptake was observed in the spleen, followed by the kidneys and bladder. Liver uptake decreased with increasing nanobody mass. Rapid clearance (t 1/2 <30 min) of [ 68 Ga]Ga-NODAGA-SNA006 from whole blood and serum was observed. Furthermore, 68 Ga uptake in tumors (SUVmean) exhibited a linear relationship with CD8 + T-cell infiltration in biopsy samples (R 2  = 0.757, p = 0.011), suggesting that the tumor uptake of [ 68 Ga]Ga-NODAGA-SNA006 may represent the degree of CD8 + T-cell infiltration in the tumor., Conclusion: The use of [ 68 Ga]Ga-NODAGA-SNA006 is safe, feasible, and well tolerated. [ 68 Ga]Ga-NONAGA-SNA006 PET imaging can accurately detect CD8 expression inside tumors with favorable pharmacokinetics, thus providing a feasible method for noninvasive quantitative assessment of CD8 + T-cell tumor infiltration and monitoring the response to immunotherapy., Trial Registration: NCT05126927 (19 November 2021, retrospectively registered)., Competing Interests: Declarations. Compliance with ethical standards: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the Helsinki Declaration. This study was approved by the Research Ethics Board of the First Affiliated Hospital of Soochow University (Date: October 12, 2021/No:288) and all patients signed a written informed consent form before study participation (ClinicalTrials.gov identifier NCT05126927). Consent to participate: All participants involved in the study provided written informed consent. Competing interests: The authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.) more...

This study examines the impact of estrogenic compounds like bisphenol A (BPA), estradiol (E2), and zearalenone (ZEA) on human ovarian cancer, focusing on constructing a risk model, conducting gene set variation analysis (GSVA), and evaluating immune infiltration. Differential gene expression analysis identified 980 shared differentially expressed genes (DEGs) in human ovarian cells exposed to BPA, E2, and ZEA, indicating disruptions in ribosome biogenesis and RNA processing. Using the cancer genome atlas ovarian cancer (TCGA-OV) dataset, a least absolute shrinkage and selection operator (LASSO)-based risk model was developed incorporating prognostic genes 4-hydroxyphenylpyruvate dioxygenase like (HPDL), Thy-1 cell surface antigen (THY1), and peptidase inhibitor 3 (PI3). This model effectively stratified ovarian cancer patients into high-risk and low-risk categories, showing significant differences in overall survival, disease-specific survival, and progression-free survival. GSVA analysis linked HPDL expression to pathways related to the cell cycle, DNA damage, and repair, while THY1 and PI3 were associated with apoptosis, hypoxia, and proliferation pathways. Immune infiltration analysis revealed distinct immune cell profiles for high and low-expression groups of HPDL, THY1, and PI3, indicating their influence on the tumor microenvironment. The findings demonstrate that estrogenic compounds significantly alter gene expression and oncogenic pathways in ovarian cancer. The risk model integrating HPDL, THY1, and PI3 offers a strong prognostic tool, with GSVA and immune infiltration analyses providing insights into the interplay between these genes and the tumor microenvironment, suggesting potential targets for personalized therapies. more...

Henoch-Schönlein purpura (HSP) is an autoimmune vasculitis affecting multiple organs, and the understanding of circulating immune cell types and their states associated with disease subtypes of HSP remains incomplete. Here, we performed a comprehensive assessment of peripheral blood mononuclear cells of healthy donors and HSP patients, using both single-cell RNA sequencing and multiparameter flow cytometry. We revealed that HSP patients exhibited broad immune activation, evidenced by increased proportions of Effector memory CD8+ T, CD14+ monocytes, Tfh, Th2, Th17, Plasma, and B cells and decreased proportions of Naïve CD4+ T, Treg, Th1, and NK cells. Notably, we identified that cytotoxic effector T cell subsets were enriched in skin and renal type of HSP, whereas Plasma, B, and Tfh cells were expanded in joint and abdominal type of HSP. In conclusion, our findings highlight the dynamic nature of immune responses throughout the progression of HSP with different clinical manifestations., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.) more...

Fungal infections affect over 13 million people worldwide and are responsible for 1.5 million deaths annually. Some deep cutaneous fungal infections may extend the dermal barriers to cause systemic infection, resulting in substantial morbidity and mortality. However, the management of deep cutaneous fungal infection is challenging and yet overlooked by traditional treatments, which only offer limited drug availability within deep tissue. In this study, we have developed an electrically stimulated microneedle patch to deliver miconazole into the subcutaneous layer. We tested its antifungal efficacy using in vitro and ex vivo models that mimic fungal infection. Moreover, we confirmed its anti-fungal and wound-healing effects in a murine subcutaneous fungal infection model. Furthermore, our findings also showed that the combination of miconazole and applied current synergistically stimulated the nociceptive sensory nerves, thereby activating protective cutaneous immunity mediated by dermal dendritic and γδ-T cells. Collectively, this study provides a new strategy for minimally invasive delivery of therapeutic agents and the modulation of the neuro-immune axis in deep tissue., (Copyright © 2024. Published by Elsevier Ltd.) more...

Background: Perioperative strokes may promote postoperative neurocognitive dysfunction. This study thus evaluated the incidence of postoperative strokes and the association between strokes and postoperative neurocognitive outcomes in older patients recovering from noncardiac surgery., Methods: The Postoperative Covert Stroke and Cognitive Dysfunction among Elderly Patients Undergoing Noncardiac Surgery study (PRECISION) was a two-center prospective cohort study evaluating patients aged 60 yr or older who had elective, noncardiac inpatient surgery at two Chinese academic centers. Postoperative strokes were evaluated by scheduled magnetic resonance brain imaging within 7 days. The primary outcome was the cumulative incidence of postoperative stroke. Secondary outcomes included postoperative delirium within the first 5 days after surgery, neurocognitive decline at 12 months, and the association between stroke and neurocognitive dysfunction., Results: Among 934 patients (mean age, 67 yr; 45% male) included in the analyses, two thirds had neurosurgical craniotomies. There were 111 (11.9%; 95% CI, 9.8 to 14.0%) covert strokes within 7 days after surgery and no overt strokes. Postoperative delirium was observed in 117 patients (12.5%; 95% CI, 10.4 to 14.7%) within 5 days, and neurocognitive decline was observed in 147 patients (18.8%; 95% CI, 16.0 to 21.5%) at 1 yr after surgery. Postoperative covert strokes were significantly associated with delirium (adjusted odds ratio, 2.18; 95% CI, 1.31 to 3.62; P = 0.003) and 1-yr neurocognitive decline (adjusted odds ratio, 2.33; 95% CI, 1.31 to 4.13; P = 0.004) in overall participants., Conclusions: Among patients aged 60 yr and older who had major noncardiac surgery, mainly intracranial, one in nine patients experienced a perioperative covert stroke. Covert strokes more than doubled the risk of postoperative delirium and long-term neurocognitive decline. Covert perioperative strokes are common and clinically meaningful., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.) more...

As socioeconomic development progresses, nuclear energy and technology advance rapidly. Concurrently, nuclear accidents may result in the release of additional radioactive isotopes into the environment. Groundwater and oceans are key pathways for radioactive nuclides in the environmental cycle, with aquatic organisms being particularly vulnerable to radiation exposure. Aquatic model organisms are essential for studying radiation effects on non-human species in aquatic environments and for extrapolating dose-response relationships to humans. However, current models for calculating radiation doses in the aquatic model organism zebrafish remain underdeveloped. To better elucidate the mechanisms of radiation damage effects, integrating Micro-CT and 3D modeling techniques, a series of zebrafish mesh-type models (including adults and larvae, named zebrafish-mesh family: ZF-mesh family) with multiple internal organs are established in this study. The Monte Carlo software PHITS is used to simulate and calculate the Absorbed Fractions (AFs) and S-values for single-energy electrons ranging from 0.001 to 10 MeV, single-energy photons from 0.001 to 5 MeV, and eight radioactive nuclides commonly found in nuclear power plant liquid effluents: 3 H, 14 C, 90 Sr, 106 Ru, 134 Cs, 137 Cs, 60 Co, 131 I, across various source-target organ configurations. The results indicate that the mesh-type models of zebrafish at multiple developmental stages can be used for radiation dosimetry calculations. Analysis of the dosimetry parameter database, established through Monte Carlo calculations with this series of mesh-type models, shows that the maximum difference in self-AFs between the geometric and curved models reaches 52.8%. Comparisons between models at different developmental stages show that the impact of radioactive nuclides on internal organs depends on both the decay properties of the nuclides and the organ volumes. For adult fish, the dose contribution from 90 Sr is most significant, reaching up to 1.81 ×10 -5 mGy·MBq -1 ·s -1 in the heart of male fish. In larvae fish, 14 C has the most notable impact, with a dose rate of 4.38 ×10 -3 mGy·MBq -1 ·s -1 in the heart at 48 h post-fertilization (hpf). Comparisons of yolk mass changes at various developmental stages in larvae fish reveal that organ location is a key factor influencing self-AFs. This influence is often more significant than the variations caused by changes in organ volume. Due to the small size of zebrafish organs, the increase in energy deposition caused by secondary electrons is not evident in adult fish. In the smallest larvae hearts, no increase in energy deposition is observed. In summary, detailed surface modeling of model organisms across multiple developmental stages and the establishment of a comprehensive dosimetric parameter database are crucial. This approach significantly improves the reliability of radiation impact assessments for non-human species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.) more...

The herbal formula Sinisan (SNS) is a commonly used treatment for depression; however, its mechanism of action remains unclear. This article uses a combination of the GEO database, network pharmacology and molecular docking technologies to investigate the mechanism of action of SNS. The aim is to provide new insights and methods for future depression treatments. The study aims to extract effective compounds and targets for the treatment of depression from the T CMSP database. Relevant targets were searched using the GEO, Disgenet, Drugbank, PharmGKB and T T D databases, followed by screening of core targets. In addition, GO and KEGG pathway enrichment analyses were performed to explore potential pathways for the treatment of depression. Molecular docking was used to evaluate the potential targets and compounds and to identify the optimal core protein-compound complex. Molecular dynamics was used to further investigate the dynamic variability and stability of the complex. The study identified 118 active SNS components and 208 corresponding targets. Topological analysis of P P I networks identified 11 core targets. GO and KEGG pathway enrichment analyses revealed that the mechanism of action for depression involves genes associated with inflammation, apoptosis, oxidative stress, and the MAP K3 and P I3K-Akt signalling pathways. Molecular docking and dynamics simulations showed a strong binding affinity between these compounds and the screened targets, indicating promising biological activity. The present study investigated the active components, targets and pathways of SNS in the treatment of depression. Through a preliminary investigation, key signalling pathways and compounds were identified. These findings provide new directions and ideas for future research on the therapeutic mechanism of SNS and its clinical application in the treatment of depression. more...

Among individuals who wear removable dentures, there is a significant likelihood, reaching up to 70 %, of experiencing a condition known as denture-induced stomatitis. To address this issue, a commonly used method involves soaking dentures in denture cleansers to eliminate microorganisms. However, the prolonged use of this cleaning method has resulted in the emergence of drug resistance. Composite antibacterial nanomaterials possess excellent chemical, physical, and antibacterial properties, not only allowing the individual components to function but sometimes also leading to synergistic effects that enhance antibacterial performance. In this study, we have successfully synthesized a new benzpyrole derivant/iodocuprate bio-nanomaterial, (TMBI) 2 (Cu 2 I 4 ) (TMBI = 1,1,2,3-Tetramethyl-1H-benzo[e]indolium cation), that demonstrates remarkable resistance to Candida albicans, Streptococcus mutans, and dental plaque biofilm.It can effectively clean the surfaces of denture bases by removing Candida albicans, Streptococcus mutans, and dental plaque biofilm. Prolonged immersion in this material does not significantly affect the common mechanical properties of polymethyl methacrylate (PMMA) denture bases. At effective antibacterial concentrations, this nanomaterial (TMBI) 2 (Cu 2 I 4 ) demonstrates no residual cytotoxicity on PMMA denture bases after immersion and maintains excellent hemocompatibility. These findings indicate that (TMBI) 2 (Cu 2 I 4 ) has the potential to be a promising denture cleanser., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dali Zheng reports financial support was provided by Fujian Provincial Department of Science and Technology. Ming Zheng reports financial support was provided by Fujian Provincial Health Commission. Dali Zheng, Ming Zheng, Chenglu Ruan, Haohong Li has patent #“A novel denture cleanser: Benzpyrole Derivant/Iodocuprate Hybrid” (Chinese Patent Application# 202411111241.3) issued to Chinese National Intellectual Property Office. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.) more...

Cholestatic liver diseases are characterized by excessive bile acid accumulation in the liver. Endothelial cells (ECs) shape the local microenvironment in both normal conditions and liver injury, yet their role in cholestasis is unclear. Through a comparative analysis of single-cell RNA sequencing data from various murine models of liver injury, we identify distinctive Myc activation within ECs during obstructive cholestasis resulting from bile duct ligation (BDL). Myc overexpression in ECs significantly upregulates P-selectin, increasing neutrophil infiltration and worsening cholestatic liver injury. This process occurs through the FXR, activated by chenodeoxycholic acid (CDCA) and its conjugate TCDCA. Inhibiting P-selectin with PSI-697 reduces neutrophil recruitment and alleviates injury. Cholestatic patient liver samples also show elevated Myc and P-selectin in ECs, along with increased neutrophils. The findings identify ECs as key drivers of cholestatic liver injury through a Myc-driven program and suggest that targeting the CDCA/FXR/Myc/P-selectin axis may offer a therapeutic approach., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).) more...

The prevalence of hyperlipidemia is gradually increasing globally, posing a serious threat to public health. Previous studies have shown that paeoniflorin (PF) effectively improved abnormal lipid metabolism in atherosclerotic mice. However, the anti-hyperlipidemia effect and potential mechanism of paeoniflorin remain unclear. The gut microbiota (GM) is closely related to hyperlipidemia. This study was aimed to investigate effects of PF on improving the health of high-fat diet (HFD)-induced hyperlipidemic mice by modulating GM. A hyperlipidemic mouse model was established using an HFD, and the hypolipidemic effect of PF was detected in vivo. Besides16S ribosomal RNA sequencing and SCFAs metabolic analysis were performed to explore the lipid-lowering mechanism of PF. Importantly, fecal microbiota transplantation (FMT) experiments were conducted to verify the lipid-lowering mechanism of PF. The results showed that PF significantly inhibited the development of hyperlipidemia, reduced serum lipid and inflammatory cytokine levels, and improved liver steatosis. In addition, 16S rRNA sequencing revealed that PF treatment significantly increased the relative abundance of Lactobacillus, Coprococcus, Blautia, Roseburia, and Bacteroides while reducing the relative abundance of Prevotella. Meanwhile, the results of targeted metabolomics indicate that PF therapy can effectively restore butyric acid and propionic acid levels in the intestine. The FMT experiments further demonstrated that PF improved hyperlipidemia by regulating GM and its metabolites. The above results provide a valuable theoretical basis for the development and application of PF as a functional food for hyperlipidemia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.) more...

Rheumatoid arthritis (RA) is an autoimmune disease characterized by destructive effects. Although current therapies utilizing antibodies against inflammatory cytokines have shown some success, the inhibition of a single inflammatory molecule may not suffice to impede the progression of RA due to the intricate pathogenesis involving multiple molecules. In this study, we have developed an intelligent transformable peptide, namely BP-FFVLK-DSGLDSM (BFD). BFD has the ability to self-assemble into spherical nanoparticles in water or in the blood circulation to facilitate their delivery and distribution. When endocytosed into immune cells, BFD can identify and attach to phosphorylation sites on IκBα and in situ transform into a nanofibrous network coating NF-κB/IκBα complexes, blocking the phosphorylation and degradation of IκBα. As a result, BFD enables decreasing expression of proinflammatory mediators. In the present study, we demonstrate that BFD exhibits notable efficacy in alleviating arthritis-related manifestations, such as joints and tissues swelling, as well as bone and cartilage destruction on the collagen-induced arthritis (CIA) rat model. The investigation of intracellular biodistribution, phosphorylation of IκBα, and cytokine detection in culture medium supernatant, joint tissue, and serum exhibits strong associations with therapeutic outcomes. The utilization of transformable peptide presents a novel approach for the management of inflammatory diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.) more...

Objective: To investigate the function of mitophagy in instructing T-cell differentiation of patients with rheumatoid arthritis (RA)., Method: The mRNA and protein levels of optic atrophy protein-1 were detected in T cells from 94 RA patients and 37 age- and sex-matched healthy individuals by quantitative polymerase chain reaction and Western blotting. The impact of mitophagy on the differentiation of T cells was determined by flow cytometry. The therapeutic effect of targeting mitophagy was explored in humanized RA chimeras., Results: Our study showed that T cells exerted high levels of mitophagy in RA patients. Since multiple T-cell subtypes play crucial roles in RA, we determined that mitophagy had a significant impact on the differentiation of tissue-resident memory T (Trm) cells, but not Th1 or Th17 cells. Importantly, we demonstrated that inhibiting mitophagy significantly reduced the number of Trm cells and downregulated inflammatory responses, as evidenced by diminished levels of T cell receptor β, interferon-γ, and interleukin-17A, in the humanized RA chimeras., Conclusions: Mitophagy is elevated in RA T cells, leading to maldifferentiation of Trm cells in RA patients. Since these findings were obtained from clinical patients, mitophagy may be a potential therapeutic target for RA treatment. more...

Potassium-sulfur (K-S) batteries are severely limited by the sluggish reaction kinetics of the cyclooctasulfur (cyclo-S 8 ) electrode with low conductivity, which urgently requires a novel cathode to facilitate activity to improve sulfur utilization. In this study, using the wet chemistry method, the molecular clip of Li + is created to replace cyclo-S 8 molecular with the highly active chain-like S 6 2- molecular. The molecular clip strategy effectively lowers the reaction barrier in potassium-sulfur systems, and the stretching of S─S bonds weakens the binding between sulfur atoms, facilitating the transformation of potassium polysulfides (KPSs). The as-prepared cathode exhibits a reversible capacity of 894.8 mAh g -1 at a current rate of 0.5 C. It maintains a long cycle life of 1000 cycles with a stable coulombic efficiency in the potassium-sulfur cells without cathode catalysts. Operando XRD and Raman spectra combined with density functional theory (DFT) calculations, revealing the high efficiency of enhanced conversion of potassium polysulfide for high-performance K-S batteries., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.) more...

Purpose: The monoacylglycerol lipase (MAGL) plays a pivotal role in modulating the endocannabinoid system and is considered an attractive therapeutic target for diseases in both the central nervous system and periphery. The current study aimed to develop and evaluate a suitable carbon-11 labeled tracer for imaging MAGL in preclinical studies., Methods: (R)-YH168 was synthesized via a multi-step pathway and its half-maximal inhibitory concentration (IC 50 ) values were measured using an enzymatic assay. Radiosynthesis of (R)-[ 11 C]YH168 was accomplished by 11 C-methylation via Suzuki cross-coupling of a pinacol boron precursor. In vitro autoradiography was performed using brain tissues from MAGL knockout and the corresponding wild-type mice. The metabolic stability of (R)-[ 11 C]YH168 in mouse brain and plasma was assessed 5 min after injection. Dynamic PET scans were conducted on anesthetized mice and rhesus monkey. For studies in non-human primates, arterial blood samples were analyzed to obtain the input function for kinetic modeling. Blocking studies with the irreversible MAGL inhibitor PF-06795071 were performed to assess the binding specificity of (R)-[ 11 C]YH168., Results: (R)-[ 11 C]YH168 was synthesized via Suzuki coupling of the phenyl boronic ester with [ 11 C]CH 3 I in the presence of palladium catalyst. In vitro autoradiography revealed a heterogeneous distribution pattern of (R)-[ 11 C]YH168 with higher binding to MAGL-rich brain regions in wild-type mouse brain slices compared to that of MAGL knockout mice. Dynamic PET imaging in wild-type and MAGL knockout mice confirmed its high specificity and selectivity in mouse brains. In the rhesus monkey, (R)-[ 11 C]YH168 displayed good brain permeability. High levels of radioactivity uptake were seen in the cingulate cortex, frontal cortex, cerebellum, occipital cortex, and hippocampus, consistent with MAGL expression. The one-tissue compartment model was appropriate for fitting the regional time-activity curves and provided reliable volume of distribution values across all brain regions. Pretreatment with PF-06795071 (0.1 mg/kg) resulted in almost complete blockade (> 95%) of radioactivity uptake, demonstrating binding specificity of (R)-[ 11 C]YH168 to MAGL in the non-human primate brain. The regional non-displaceable binding potential follows the rank order of cingulate cortex ~ frontal cortex ~ insula > putamen > temporal cortex > caudate ~ occipital cortex ~ thalamus > nucleus accumbens ~ hippocampus ~ cerebellum ~ globus pallidus > substantia nigra > amygdala., Conclusion: (R)-[ 11 C]YH168 is a promising PET probe for imaging and quantifying MAGL in the brains of mice and non-human primates. This 11 C-labeled tracer holds great potential for translation into human subjects and offers the possibility of performing multiple PET scans on the same subject within a single day., Competing Interests: Declarations. Ethical approval: This study was performed in agreement with the international and national law and institutional guidelines of radiation safety protection. In vivo experiments were approved by the local veterinarian department and ethics committee and conducted in accordance with the internal and national law of animal protections. Institutional review board statement: All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. In particular, all animal experiments were carried out according to the guidelines of the Swiss Regulations for Animal Welfare. The preclinical studies have been ethically approved by the Veterinary Office of Canton Zurich (License N° (ZH28/ 2018). The protocol of PET study in rhesus monkey (Macaca mulatta) was approved by the Yale University Institutional Animal Care and Use Committee. Conflict of interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024. The Author(s).) more...

Unipolar depression is typically regarded as a psychiatric disorder, yet it frequently coexists with various major diseases. This study employs a Disease-Wide Association Study (DWAS) approach to map the disease continuum surrounding unipolar depression, analyzing data from a registry cohort of 392,423 individuals, including 43,280 diagnosed cases of unipolar depression. Significant associations were identified between depression and comorbidities across multiple organ systems, including both mental and physical disorders. Next, temporal analysis categorized these comorbidities based on their onset relative to depression into short-term (1-year), mid-term (5-year), and long-term (15-year) periods, discovering temporal consistent associations with comorbidities such as schizophrenia, anxiety disorders, post-traumatic stress disorder (PTSD), asthma, hypothyroidism, type 2 diabetes, cardiac arrhythmias, and cancer. These findings highlight the interconnected nature of depression within a broader disease continuum network. Recognizing depression within this systemic framework supports the adoption of personalized medicine strategies tailored to individual comorbidity profiles, enabling therapeutic targeting of shared pathogenic mechanisms that concurrently address both depression and its associated comorbidities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. and ECNP. All rights reserved.) more...

The current study isolated a homogeneous polysaccharide (AP) with a molecular weight of 7.9 kDa from the pomace of Fuji apples. AP was found to consists of rhamnose, galactose, arabinose, glucose, and galacturonic acid in a ratio of 4.3:5.2:2.6:1.0:11.9. Ten sugar residues in AP, including T-Araf, 1,5-Araf, 1,2-Rhap, 1,3-Rhap, T-Galp, 1,3,5-Araf, 1,4-Galp, 1,4-GalpA, 1,6-Glcp, and 1,3,6-Glcp were identified using methylation and GC-MS. Combined with 1D and 2D NMR, it was further revealed that AP possesses a backbone of α-Galp-(1 → [3)-α-Rhap-(1 → 2)-α-Rhap-(1] 2  → [4)-α-GalpA-(1] 10  → 3,6)-β-Glcp-(1 → 6)-β-Glcp-(1 → 4)-β-Galp-(1 → 4)-β-Galp-(1→, with two branches: α-Araf-(1 → 5)-α-Araf-(1 → 5)-α-Araf-(1 → 3,5)-α-Araf-(1 → 6)-β-Glcp-(1→ and →3)-α-Rhap-(1 → 5)-α-Araf-(1 → 3,6)-β-Glcp-(1→ bonded to the C-3 of β-1,3,6-Glcp. AP significantly inhibited the release of cytokines and inflammatory mediators, such as TNF-α, IL-1β, IL-6, reactive oxygen species (ROS) and nitric oxide (NO). Western blotting results indicated that AP treatment markedly downregulated iNOS and NF-κB protein expression in LPS-induced RAW264.7 cells, leading to decreased levels of phosphorylated proteins (p-NF-κB and p-ΙκΒα) and preventing the degradation of ΙκΒα. Furthermore, in LPS-induced RAW264.7 macrophages, AP inhibited the expression of TLR4 protein, which in turn inhibited the activity of the NF-κB pathway. The findings demonstrated that AP exhibits anti-inflammatory properties in vitro by targeting the TLR4/NF-κB signaling pathway, thus impeding the nuclear translocation of NF-κBp65, suppressing the expression of related pro-inflammatory factors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.) more...

Polyethylene terephthalate (PET) waste significantly contributes to the global plastic crisis, but enzymatic conversion has become an efficient and environmentally friendly strategy to combat it. Therefore, this study explored the Re-face selective depolymerization mechanisms of a novel PET-degradation peptidase, hydrolase 202. Theoretical calculations revealed that the first step, a catalytic triad-assisted nucleophilic attack, is the rate-determining step. The corresponding Boltzmann-weighted average barrier was 21.6 kcal/mol. Furthermore, hydrolase 202 degraded Re-face PET more effectively than FAST-PETase, whereas other reported PET hydrolases (e.g., FAST-PETase) degraded Si-face PET more effectively. The hydrogen bond network significantly influenced the depolymerization efficiency. We also identified correlations between 24 important structural and charge features and energy barriers. Key charge, distance, and angle features were responsible for the superiority of the Re-face depolymerization. Finally, we identified residues that may affect the depolymerization efficiency of hydrolase 202, such as Glu215. These findings offer new insights into the potential engineering of PETases and may enhance enzymatic PET waste recycling., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.) more...

Gastric cancer (GC) has a poor prognosis and high mortality because it is often diagnosed at an advanced stage. Targeted therapeutics are considered an important class for advanced GC treatment. However, the fewer effective therapeutic targets and the poor coverage of the GC population limit the use of GC targeted therapies. Recent research suggests that the AXL receptor tyrosine kinase (AXL) plays an vital role in the survival and proliferation of GC cells, and blocking AXL pathway may be an effective strategy for targeted therapies. On the other hand, the affibody molecule, with its small size and faster penetration of tissue, has great potential in tumor imaging and targeted therapy. In this study, we report the novel AXL-binding affibody molecules (Z AXL :239) screened by a phage-displayed peptide library. The Z AXL :239 could specifically bind and interact with AXL proteins in vitro and in vivo, as demonstrated by surface plasmon resonance, co-immunoprecipitation, immuno-fluorescence co-localization, and near infrared fluorescent imaging. In addition, Z AXL :239 affibody molecules could significantly inhibit the proliferative activity and induce apoptosis of AXL-positive GC cells by decreasing the phosphorylation levels of the PI3K/AKT1 and MEK/ERK pathway, leading to the suppression of the downstream nuclear protein c-myc. Moreover, Z AXL :239 was found to have significant anti-tumor effects in AXL-positive GC transplantation tumor nude mouse models. In brief, we provide strong evidence that the novel Z AXL :239 affibody molecules have great potential as a potent tumor-specific molecular imaging and targeted therapeutic agents for GC., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interest., (© 2024. The Author(s).) more...

Descurainia sophia L. is one of the most problematic broad-leaf weed infesting winter wheat in China, and have evolved resistance to acetolactate synthase (ALS)-inhibiting herbicide of tribenuron-methyl. At least four ALS isozymes (ALS1 ∼ ALS4) exist in D. sophia, but these four ALS isozymes are not present in all D. sophia. In addition, amino acid mutations in ALS are mainly responsible for D. sophia resistance to tribenuron-methyl. In this study, D. sophia populations carrying homozygous mutation of Pro197Ser/Thr/Leu/Ala/His in ALS1 or in ALS2 were purified, respectively. Resistant D. sophia populations carrying mutant ALS exhibited 17 ∼ 694 folds resistance to tribenuorn-methyl. In addition, tribenuron-methyl resistance in D. sophia carrying ALS1 mutation was about 2.3 ∼ 11.4 folds higher than D. sophia with the same mutation in ALS2. The reduced binding affinity of ALS to tribenuron-methyl was mainly responsible for D. sophia resistance to tribenuron-methyl. However, the increase in resistance of D. sophia was not linear with the decrease of binding affinity of ALS to tribenuron-methyl. These results indicate that the effects of resistance mutations on ALS1 and ALS2 isozymes are not the same, and the ALS1 and ALS2 function differently in resistance evolution of D. sophia to tribenuron-methyl., (Copyright © 2024 Elsevier Inc. All rights reserved.) more...

Commercialization of lithium-sulfur (Li-S) batteries is largely limited by polysulfide shuttling and sluggish kinetics. Herein, 2D nanochannel interlayer composed of alternatively-stacked porous silica nanosheets (PSN) and Ti 3 C 2 T x -MXene are developed. The 2D nanochannels with selective cation transport characteristics facilitate lithium ion rapid transport, while reject the translocation of polysulfide anions across the separator. The hydroxylated MXene shifts the p-band center of the surface O on PSN closer to the Fermi level, leading to strong absorptive/catalytic effect for polysulfides and thus fast polysulfide transformation kinetics. Together with the ion/electron bi-conduction function of PSN/MXene, the Li-S batteries deliver high initial capacity of 1443 mAh g -1 at 0.1 C, low-capacity decay rate of 0.049% per cycle over 800 cycles at 2 C, and excellent rate capability. At a high sulfur loading of 5.2 mg cm -2 , the cells present higher areal specific capacity than commercial lithium ion batteries. The pouch cells with lean electrolyte (E/S = 3.9 µL mg -1 ) yield a capacity of 2-Ah at 100 mA, high energy density and excellent cycling stability. This contribution opens up new avenues for expanding application of 2D nanofluidics in electrochemical energy storage and conversion., (© 2025 Wiley‐VCH GmbH.) more...

Sustained-release ocular drug delivery systems with minimal invasiveness are critical for managing eye diseases that cause blindness. An innovative platform is presented for painless and long-term sustained ocular drug delivery utilizing controllably biodegradable silicon nanoneedles (Si NNs) conjugated with bevacizumab (Bev) integrated into a tear-soluble subconjunctival patch. The biocompatible patch facilitates easy application in the subconjunctival area of the eye and rapid dissolution in less than one minute upon contact with the tear film in the sclera, eliminating the need for removal procedures. The Si NNs, fabricated with precise control over their degradation kinetics, enable sustained and controlled release of Bev into the ocular tissues. This platform offers enhanced patient comfort, reduced risk of complications, and prolonged therapeutic efficacy. In vivo studies using a rabbit model of retinal neovascularization (RNV), a clinically relevant proliferative diabetic retinopathy (PDR), demonstrate the platform's ability to reduce RNV by 85% over a year, with no observable side effects. These results highlight the potential of this drug delivery method to penetrate the sclera and releaseBev gradually, providing a promising alternative for long-term, controllable ocular therapy. This technology represents a significant advancement in painless, convenient, and effective treatment for eye diseases requiring sustained drug delivery., (© 2025 Wiley‐VCH GmbH.) more...

Background and Aim: Difference in metabolic status may cause inconsistent association between body mass index (BMI) and chronic kidney disease (CKD) in men and women. This study aimed to quantify sex-specific association between cumulative BMI (cumBMI) and incident CKD by different metabolic status., Methods and Results: Participants free of CKD from the Kailuan Study were followed biennially from baseline (June 2006 to October 2007) to December 2019. cumBMI was calculated by use of follow-up BMI and follow-up time and was divided into low weight (<18.5 kg/m 2 ), normal weight (18.5-23.9 kg/m 2 ), overweight (24-27.9 kg/m 2 ), and obesity (≥28 kg/m 2 ) according to Chinese criteria. Metabolic health was defined as the absence of hypertension, dyslipidemia, and diabetes at baseline. CKD was defined as having estimated glomerular filtration rate <60 mL/min/1.73 m 2 . This study included 76984 participants, with a mean age of 50.0 ± 11.6 years and 80.0 % of men. Overweight (HR = 1.24, 95 % CI: 1.16-1.31) and obesity (HR = 1.94, 95 % CI: 1.77-2.12) were associated with higher risk of incident CKD in men regardless of metabolic status. Corresponding population attributable risk percentages for overweight and obesity were 10.3 % (95%CI: 7.1-12.9) and 12.7 % (95%CI: 10.6-14.7), respectively. However, low weight (HR = 1.56, 95 % CI: 1.05-2.30) and obesity (HR = 1.32, 95 % CI: 1.01-1.73) were associated with higher risk of incident CKD in metabolically healthy women but not in metabolically unhealthy women., Conclusions: This study demonstrated sex- and metabolic-specific associations between BMI and CKD occurrence and advocates an individualized weight management strategy., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.) more...

Background: High-density lipoprotein-cholesterol (HDL-C) has been considered a cardioprotective factor for several decades. However, its association with outcomes in patients with heart failure with reduced ejection fraction (HFrEF) remains controversial. We aimed to investigate the association of HDL-C, apolipoprotein A-I (apoA-I), and the HDL-C/apoA-I ratio with multiple outcomes of HFrEF patients and establish prognostic models using machine learning methods., Methods and Results: This was a retrospective, single-center study. The associations between lipid levels and multiple outcomes were examined using logistic regression analysis. Prognostic models for multiple outcomes were further established using four machine learning methods. A total of 352 HFrEF patients were visited successfully. In the multivariable-adjusted logistic regression analysis, HDL-C did not show a significant association with any of the studied outcomes; apoA-I was marginally unassociated with all-cause rehospitalization (adjusted odds ratio [aOR] = 0.62, p = 0.063) but was significantly negatively associated with all-cause death (aOR = 0.53, p = 0.038), rehospitalization for cardiovascular or cerebrovascular disease (aOR = 0.43, p < 0.001), and rehospitalization for heart failure (aOR = 0.55, p = 0.024); apoA-I was also significantly positively associated with left ventricular ejection fraction (LVEF) improvement (aOR = 2.00, p = 0.039). Although several p-values were not statistically significant, both the first and third HDL-C/apoA-I groups showed an increased incidence rate for all adverse outcomes compared with the middle group and a decreased incidence rate for LVEF improvement. In the machine learning analysis, the support vector machine and extreme gradient boosting models demonstrated better predictive performance. For each outcome prognosis, apoA-I and logarithmic N-terminal pro-B-type natriuretic peptide were automatically selected., Conclusion: Among HFrEF patients, apoA-I may be a better marker for predicting outcomes than HDL-C. Both low and high levels of HDL-C/apoA-I may indicate a poor prognosis of HFrEF patients., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024. Published by Elsevier B.V.) more...