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Heart regeneration was mainly achieved by intrinsic capacity. Exosomes are crucial in cardiovascular disease, yet their involvement in myocardial regeneration remains underexplored. To understand the role of cardiomyocyte-derived exosomes (CM-Exos) in heart regeneration. We established mouse models of myocardial infarction and apical resection in neonates to investigate the potential benefits of exosomes in response to injury. Rab27a knockout (KO) mice were constructed as an exosome decrease model. Distinct fibrosis appears in the infarcted and resection area in the KO mice 21 days after heart injury. The proliferation marker pH 3, Ki67, and Aurora B were detected 3 days after surgery, which decreased in KO mice compared to WT mice. Intravenous injection of CM-Exos increased cardiomyocyte proliferation and partially restored heart function in KO mice. Rab27a knockdown in vitro reduced the expression of pH 3, Ki67, and Aurora B positive cardiomyocytes. However, the supplementation of CM-Exos increased the proliferation of cardiomyocytes. Exosomal miRNA sequencing was subsequently applied, and miR-21-5p was a promising candidate that promoted cardiomyocyte proliferation through its target genes Spry-1 and PDCD4. Intravenous injection of miR-21-5p exhibited similar proliferative effects as CM-Exos. Our results indicate that CM-Exos promotes cardiomyocyte cycle reentry by delivering miR-21-5p, highlighting the endogenous factors of myocardial regeneration., (© 2024 Federation of American Societies for Experimental Biology.)

Objective: Previous studies have reported that vitamin D deficiency increased the risk of Alzheimer's disease (AD) dementia in older adults. However, little is known about how vitamin D is involved in the pathophysiology of AD. Thus, this study aimed to examine the association and interaction of serum vitamin D levels with in vivo AD pathologies including cerebral beta-amyloid (Aβ) deposition and neurodegeneration in nondemented older adults., Methods: 428 Nondemented older adults were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease, a prospective cohort that began in 2014. All participants underwent comprehensive clinical assessments, measurement of serum 25-hydroxyvitamin D (25[OH]D), and multimodal brain imaging including Pittsburgh compound B (PiB) positron emission tomography and magnetic resonance imaging. Global PiB deposition was measured for the Aβ biomarker. Intracranial volume-adjusted hippocampal volume (HVa) was used as a neurodegeneration biomarker., Results: Overall, serum 25(OH)D level was not associated with either Aβ deposition or HVa after controlling for age, sex, apolipoprotein E ε4 positivity, and vascular risk factors. However, serum 25(OH)D level had a significant moderating effect on the association between Aβ and neurodegeneration, with lower serum 25(OH)D level significantly exacerbating cerebral Aβ-associated hippocampal volume loss (B = 34.612, p = 0.008)., Conclusion: Our findings indicate that lower serum vitamin D levels may contribute to AD by exacerbating Aβ-associated neurodegeneration in nondemented older adults. Further studies to explore the potential therapeutic effect of vitamin D supplementation on the progression of AD pathology will be necessary.

Objective: Bipolar disorder (BD) is marked by significant change in mood and energy levels with sleep disturbance a common feature, resulting in diminished quality of life and impaired daily functioning. This study assessed the association between BD-polygenic risk scores (PRS) and hypnotics in bipolar I disorder (BD-I) patients., Methods: Large-sample data were collected from the genome-wide association study of a multicenter Bipolar Genomic Study, and 1,394 BD-I patients with available medication information were divided into two groups depending on whether they used hypnotics or not. The Diagnostic Interview for Genetic Studies (DIGS) score was used to assess the clinical manifestations and function of the participants and the association between the use of hypnotics and genetic risk was analyzed., Results: Of the 1,394 total participants, 556 (40%) patients received hypnotics, mostly benzodiazepines, administered singly or in combination with other sleeping agents such as, Z-drugs, melatonin-related drugs, and trazodone. The DIGS score was significantly higher for negative categories in the group prescribed hypnotics as was the BD-PRS score, according to the four p value thresholds ( p = 0.3, 0.2, 0.1, and 0.05). Logistic regression analysis confirmed a statistically significant association between the BD-PRS and hypnotic use., Conclusion: Our results suggest an association between hypnotic use and genetic susceptibility to BD. Sleep disturbances in participants were based on the prescription status of hypnotics supporting the hypothesis that sleep disturbances may be associated with genetic aspects of BD-I. Further genetic studies on genetic overlaps between BD and specific phenotypes or medication responses are required.

Objective: Ultradian rhythms are biological rhythms with periods of a few seconds to a few hours. Along with circadian rhythms, ultradian rhythms influence human physiology. However, such rhythms have not been studied as intensively as circadian rhythms. This study aimed to identify ultradian rest-activity rhythms induced by the dopamine D2/D3 agonist quinpirole in mice., Methods: We used 10 mice from the Institute of Cancer Research. Quinpirole was administered at a dose of 0.5 mg/kg. We assessed free rest-activity using infrared detectors and conducted wavelet analysis to measure the period and its variation. We also used the paired t test to compare ultradian rhythm patterns., Results: Quinpirole did not significantly change total 24-hour locomotor activity ( p = 0.065). However, it significantly increased locomotor activity during the dark phase ( p = 0.001) and decreased it during the light phase ( p = 0.016). In the continuous wavelet transform analysis, the mean period was 5.618 hours before quinpirole injection and 4.523 hours after injection. The period showed a significant decrease ( p = 0.040), while the variation remained relatively consistent before and after quinpirole injection., Conclusion: This study demonstrated ultradian rest-activity rhythms induced by quinpirole using wavelet analysis. Quinpirole-induced ultradian rhythms exhibited rapid oscillations with shortened periods and increased activity during the dark phase. To better understand these changes in ultradian rhythms caused by quinpirole, it is essential to compare them with the effects of other psychopharmacological agents. Furthermore, investigating the pharmacological impact on ultradian rest-activity rhythms may have valuable applications in clinical studies.

Objective: We intended to investigate the relationships between visual sensory impairment (VSI) or auditory sensory impairment (ASI) and brain pathological changes associated with cognitive decline in older adults., Methods: We primarily tried to examine whether each sensory impairment is related to Alzheimer's disease (AD) pathology, specifically beta-amyloid (Aβ) deposition, through both cross-sectional and longitudinal approaches in cognitively unimpaired older adults. Self-report questionnaires on vision and hearing status were administered at the baseline. Neuroimaging scans including brain [ 11 C] Pittsburgh Compound B PET and MRI, as well as clinical assessments, were performed at baseline and 2-year follow-up., Results: Cross-sectional analyses showed that the VSI-positive group had significantly higher Aβ deposition than the VSI-negative group, whereas there was no significant association between ASI positivity and Aβ deposition. Longitudinal analyses revealed that VSI positivity at baseline was significantly associated with increased Aβ deposition over 2 years (β = 0.153, p = 0.025), although ASI positivity was not (β = 0.045, p = 0.518). VSI positivity at baseline was also significantly associated with greater atrophic changes in AD-related brain regions over the 2-year follow-up period (β = -0.207, p = 0.005), whereas ASI positivity was not (β = 0.024, p = 0.753). Neither VSI nor ASI positivity was related to cerebrovascular injury, as measured based on the white matter hyperintensity volume., Conclusion: The findings suggest that VSI is probably related to AD-specific pathological changes, which possibly mediate the reported relationship between VSI and cognitive decline. In contrast, ASI appears not associated with AD pathologies but may contribute to cognitive decline via other mechanisms.

Biliary tract carcinoma (BTC) is a group of malignant tumors that originate in the digestive system and occurs with a high incidence in China. Few consistent and comparable assessments of BTC disease burden have been conducted at national or subnational levels, and little is known about the demographic, temporal, and geographic patterns of epidemiological characteristics and disease burden of BTC in China. The incidence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs) due to premature death and years lived with disability (YLDs) of BTC were comprehensively examined by age, sex, and calendar year in the Chinese population, using the methodological framework and analytical strategies used for the 2021 Global Burden of Disease study. All-age incidence increased from 17,077 to 51,720 between 1990 and 2021, and the age-standardized incidence rate rose by 13.62%; all-age deaths increased from 17,251 to 37,833, but the age-standardized mortality rate fell by nearly one-fifth. The DALYs rose by 89.57% while the age-standardized DALY rate fell by 23.24%. Variations of the tendencies in BTC burden were found between sexes and age groups. Data for each provincial region indicate that coastal eastern provincial regions have higher incidence and YLD levels, whereas northern provincial regions have higher mortality, DALY, and YLL levels. The proportions of DALYs attributable to high body mass index (BMI) illustrate the growing attribution obesity has made, and high BMI usually puts more burden on northern provincial regions. These results provide evidence to support precise, targeted, and customed public health strategies aimed at enhancing biliary tract health among the Chinese population., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Selenium (Se)-enriched yeast is a good nutritional source for human being. Kazachstania unispora (K. unispora) has shown the positive physiological functionality for human health, whose potential for Se enrichment, however, remains elusive. This study demonstrated the ability of K. unispora to convert inorganic Se to organic Se, and then comprehensively investigated the accumulation and metabolism of Se in K. unispora. The results indicated that K. unispora can effectively accumulate organic Se, of which 95% of absorbed Se was converted to organic forms. Among these organic Se, 46.17% of them was bound to protein and 16.78% was combined with polysaccharides. In addition, some of the organic Se was metabolized to selenomethionine (30.26%) and selenocystine (3.02%), during which four low-molecular weight selenometabolites were identified in K. unispora. These findings expand the scope of Se-enriched yeast species, and provide useful knowledge for further investigation of Se enrichment mechanism in K. unispora., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could appear to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: The expression profiles of placental genes are crucial for understanding the pathogenesis of fetal development and placental-origin pregnancy syndromes. However, owing to ethical limitations and the risks of puncture sampling, it is difficult to obtain placental tissue samples repeatedly, continuously, multiple times, or in real time. Establishing a non-invasive method for predicting placental gene expression profiles through maternal plasma cell-free DNA (cfDNA) sequencing, which carries information about the source tissue and gene expression, can potentially solve this problem., Methods: Peripheral blood and placental samples were collected simultaneously from pregnant women who underwent cesarean section. Deep sequencing was performed on the separated plasma cfDNA and single-cell sequencing was performed on peripheral blood mononuclear cells (PBMC), chorioamniotic membranes (CAM), placental villi (PV), and decidua basalis (DB). The aggregation of corresponding information for each gene was combined with the transcriptome of PBMCs and a differential resolution transcriptome of the placenta. This combined information was then utilized for the construction of gene expression prediction models. After training, all models evaluated the correlation between the predicted and actual gene expression levels using external test set data., Results: From five women, more than 20 million reads were obtained using deep sequencing for plasma cfDNA; PBMCs obtained 32,401 single-cell expression profiles; and placental tissue obtained 156,546 single-cell expression profiles (59,069, 44,921, and 52,556 for CAM, PV, and DB, respectively). The cells in the PBMC and placenta were clustered and annotated into five and eight cell types, respectively. A "DEPICT" gene expression prediction model was successfully constructed using deep neural networks. The predicted correlation coefficients were 0.75 in PBMCs, 0.84 in the placenta, and 0.78, 0.80, and 0.77 in CAM, BP, and PV respectively, and greater than 0.68 in different cell lines in the placenta., Conclusion: The DEPICT model, which can noninvasively predict placental gene expression profiles based on maternal plasma cfDNA fragmentation characteristics, was constructed to overcome the limitation of the inability to obtain real-time placental gene expression profiles and to improve research on noninvasive prediction of placental origin pregnancy syndrome., 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 B.V.)

With the rising epidemic of obesity, metabolic syndrome, and type 2 diabetes mellitus in China, metabolic dysfunction-associated non-alcoholic fatty liver disease has become the most prevalent chronic liver disease. This condition frequently occurs in Chinese patients with alcoholic liver disease and chronic hepatitis B. To address the impending public health crisis of non-alcoholic fatty liver disease and its underlying metabolic issues, the Chinese Society of Hepatology and the Chinese Medical Association convened a panel of clinical experts to revise and update the "Guideline of prevention and treatment of non-alcoholic fatty liver disease (2018, China)". The new edition, titled "Guideline for the prevention and treatment of metabolic dysfunction-associated fatty liver disease (Version 2024)", offers comprehensive recommendations on key clinical issues, including screening and monitoring, diagnosis and evaluation, treatment, and follow-up for metabolic dysfunction-associated fatty liver disease and metabolic dysfunction-associated steatotic liver disease. Metabolic dysfunction-associated fatty liver disease is now the preferred English term and is used interchangeably with metabolic dysfunction-associated steatotic liver disease. Additionally, the guideline emphasizes the importance of multidisciplinary collaboration among hepatologists and other specialists to manage cardiometabolic disorders and liver disease effectively., Competing Interests: JGF has been an Associate Editor of Journal of Clinical and Translational Hepatology since 2013. YMN has been an Editorial Board Member of Journal of Clinical and Translational Hepatology since 2022. JDJ and LW have been Executive Associate Editors of Journal of Clinical and Translational Hepatology since 2013. CS has been an Editorial Board Member of Journal of Clinical and Translational Hepatology since 2020. JL has been an Editorial Board Member of Journal of Clinical and Translational Hepatology since 2024. The other authors have no conflict of interests related to this publication., (© 2024 Authors.)

Competing Interests: Competing interests statement:The authors declare no competing interest.

Controlling the microenvironment surrounding the pluripotent stem cells (PSCs) is a pivotal strategy for regulating cellular differentiation. Surface nanotopography is one of the key factors influencing the lineage-specific differentiation of PSCs. However, much of the underlying mechanism remains unknown. In this study, we focused on the effects of gradient nanotopography on the differentiation of embryoid bodies (EBs). EBs were cultured on three differently sized nanopillar surfaces (Large, 280-360; Medium, 200-280; Small, 120-200 nm) for spontaneous cardiomyocyte differentiation without chemical stimuli. The large nanotopography significantly promoted cardiogenesis, with increased expression of cardiac markers such as α-MHC, cTnT, and cTnI, and redistributed vinculin expression to the contact area. In addition, the small and medium nanotopographies also influenced EB differentiation, affecting both cardiogenesis and hematopoiesis to varying degrees. The phosphorylation of focal adhesion kinase (FAK) decreased in the EBs on the large nanotopography compared to that in the EBs cultured on the flat surface. The gradient nanotopography with 280-360 nm nanopillars is beneficial for the cardiogenesis of EBs in a FAK-dependent manner. This study provides valuable insights into controlling stem cell differentiation through nanotopographical cues, thereby advancing our understanding of the microenvironmental regulation in stem cell-based cardiac tissue engineering., 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 Inc.)

The 4-coumarate coenzyme A ligase (4CL) plays a critical role in the phenylpropane metabolic pathway and is a key enzyme in plant growth metabolism and stress responses. Using bioinformatics methods, 50 Me4CL gene were identified within the cassava genome u, and a comprehensive analysis of the cassava 4CL gene family was conducted. The results showed that these 50 4CL proteins are divided into four subfamilies, with members within the same subfamily sharing similar or identical gene structures. Co-linearity analysis revealed that cassava and rubber trees have the highest number of homologous genes, indicating a close homologous relationship between them. Analysis of 20 cis-acting elements in the promoter region of Me4CL32 revealed the presence of hormone-responsive elements such as gibberellin, auxin, abscisic acid, and as well as elements related to meristematic tissue regulation. results Quantitative real-time PCR (qRT-PCR) results showed that Me4CL32 gene expression changes in response to abiotic stressors (drought, salt, cold, heat) and hormonal stimuli(GA3 and ABA), indicating that Me4CL32 can respond to both environmental pressures and hormone signals. RNA-seq transcriptome and single-cell transcriptome analyses were used to examine the expression patterns of Me4CLs. Additionally, subcellular localization studies demonstrated that the Me4CL32 protein is confined to the chloroplasts of cassava leaves.Investigating the functionality of this gene family aids in comprehending plant growth, development, and stress resistance mechanisms. Furthermore, it furnishes a theoretical basis for future research on developing resilient cassava germplasm and the enhancing cassava's environmental tolerance., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Osteoporosis (OP) predominantly affects elderly individuals. Stem cells show potential for treating OP. However, animal models with normal immune function can eliminate implanted human cells. This study utilized naturally aging NOD/SCID mice, which exhibit immunodeficiency, to create a human osteoporosis model. This approach helps to minimize the premature immune clearance of transplanted allogeneic or xenogeneic cells in preclinical studies, allowing for a more accurate replication of the clinical pharmacological and pharmacokinetic processes involved in stem cell interventions for osteoporosis. NOD/SCID mice were fed until 12, 32, and 43 weeks of age, respectively, and then euthanized. We harvested lumbar vertebra for Micro-Computed Tomography (Micro-CT) scanning and pathological examination. Additionally, we performed biomechanical testing of lumbar vertebra to assess the severity of osteoporosis. We utilized real-time RT-PCR to assess gene expression changes associated with bone metabolism, aging, inflammation, oxidative stress, and the Tgf-β1/Smad3 signaling pathway. In addition, the protein expression levels of P16, Tgf-β1 and Smad3 were detected using Western Blotting (WB). In comparison to 12-week-old mice, the 32-week-old and 43-week-old mice displayed significantly sparser and fractured trabeculae in their lumbar vertebra, lower bone mineral density (BMD), and changes in bone microstructural parameters (∗∗P < 0.01, ∗∗∗P < 0.001). Additionally, compared to 12-week-old mice, the 32-week-old and 43-week-old mice exhibited decreased expression of osteogenic genes (Alp, Opg, Sp7, Col1a1), increased expression of osteoclastic gene (Rankl), the number of TRAP-positive osteoclasts significantly increased in 32-week-old and 43-week-old mice compared to 12-week-old mice. The expression of genes related to aging and inflammatory (P16, Il-1β, Tnf-α) increases with advancing age (∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001). The expression of oxidative stress-related genes (Sod1, Sod2, Foxo3, Nrf2), as well as Tgf-β1 and Smad3 decreased with age (∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001). As age increases, the levels of P16 protein increase, Tgf-β1 and Smad3 proteins decrease. Our study successfully replicated osteoporosis models in NOD/SCID mice at both 32 and 43 weeks, with the latter exhibiting more severe osteoporosis. This condition seems to be driven by factors such as aging, inflammation, oxidative stress, and the Tgf-β1/Smad3 signaling pathway., Competing Interests: Declaration of competing interest Zhaoxia Ma, Lihua Qiu, Jinyan Li, Zhen Wu, Shu Liang, Yunhui Zhao, Jinmei Yang, Min Hu and Yanjiao Li 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: As a pivotal pathway of programmed cell death, necroptosis significantly contributes to the pathogenesis of respiratory disorders. However, its role in asthma is not yet fully elucidated. Therefore, this study aimed to identify markers associated with necroptosis, evaluate their functions in asthma, and explore potential therapeutic agents targeting necroptosis for the management of asthma., Methods: Firstly, machine learning algorithms, including Least Absolute Shrinkage and Selection Operator (LASSO), Random Forest, and Support Vector Machine-Recursive Feature Elimination (SVM-RFE), were utilized to identify necroptosis-related differentially expressed genes (NRDEGs) in asthma patients compared to healthy controls. Concurrently, the expression of NRDEGs was validated using external datasets, Western blot, and quantitative real-time polymerase chain reaction (qPCR). Secondly, the clinical relevance of NRDEGs was assessed through Receiver Operating Characteristic (ROC) curve analysis and correlation with clinical indicators. Thirdly, the relationship between NRDEGs and pulmonary immune cell infiltration, as well as the signaling interactions between different cells types, were analyzed through immune infiltration and single-cell analysis. Fourthly, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), were conducted to elucidate the functional roles of NRDEGs. Finally, compounds targeting NRDEGs were screened, and their binding affinities were evaluated using molecular docking studies., Results: In asthma, necroptosis is activated, leading to the identification of four NRDEGs: NLRP3, PYCARD, ALOX15, and VDAC3. Among these, NLRP3, PYCARD, and ALOX15 are upregulated, whereas VDAC3 is downregulated in asthma. Comprehensive clinical evaluations indicated that NRDEGs hold diagnostic value for asthma. Specifically, NLRP3 was inversely correlated with forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), while VDAC3 showed an inverse correlation with sputum neutrophils. Conversely, ALOX15 expression was positively correlated with fractional exhaled nitric oxide (FeNO) levels, as well as sputum eosinophils, blood eosinophils, and blood IgE levels. Subsequent immune infiltration analysis revealed associations between NRDEGs and activated dendritic cells, mast cells, and eosinophils. Single-cell RNA sequencing (scRNA-seq) further confirmed the communication signals between myeloid dendritic cells, fibroblasts, neutrophils, and helper T cells, predominantly related to fibrosis and immune-inflammatory responses. Pathway enrichment analysis demonstrated that NRDEGs are involved in ribosomal function, oxidative phosphorylation, and fatty acid metabolism. Finally, resveratrol and triptonide were identified as potential therapeutic agents targeting the proteins encoded by NRDEGs for asthma treatment., Conclusions: The necroptosis pathway is activated in asthma, with NRDEGs-namely PYCARD, NLRP3, ALOX15, and VDAC3-correlated with declines in lung function and airway inflammation. These genes serve as reliable predictors of asthma risk and are involved in the regulation of the immune-inflammatory microenvironment. Resveratrol and triptolide have been identified as promising therapeutic candidates due to their potential to target the proteins encoded by these genes., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Sodium-dependent glucose cotransporter-2 (SGLT2) inhibitors, antidiabetic drugs that reduce blood sugar levels by inhibiting glucose reabsorption in the renal proximal tubules, also ameliorate nonalcoholic fatty liver disease (NAFLD). This study aimed to examine the effects of SGLT2 inhibition on hepatic steatosis and nonalcoholic steatohepatitis (NASH) using an in vitro model of NAFLD progression. HepG2 cells and a coculture of Hepa1c1c7 and Raw 264.7 cells were treated with 400 μM palmitic acid (PA), followed by treatment with or without 10 μM empagliflozin and dapagliflozin. In HepG2 cells, PA increased hepatic lipid accumulation, the expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), exocytosis mediators (VAMP3 and SNAP23), and ER stress markers (GRP78, PERK, IRE1α, ATF6, ATF4, and CHOP), and the gene and protein expression of CD36. SGLT2 inhibitors reversed the effects of PA. SGLT2 inhibition via siRNA reduced proinflammatory-cytokine gene expression in thapsigargin-treated HepG2 cells. Transfection with CD36 siRNA reversed the elevated ATF4 and CHOP expression in PA-treated HepG2 cells. SGLT2 inhibition via an SGTL2 inhibitor and SGLT2 siRNA reduced CD36, Tnf-α, Il-6, Il-1β, Vamp2, Snap23, Atf4, and Chop expression in the PA-treated Hepa1c1c7-Raw 264.7 cell coculture and suppressed Tnf-α release in the Hepa1c1c7-Raw 264.7 cell coculture treated with lipopolysaccharide and PA. These findings indicate that SGLT2 inhibitors inhibited NAFLD progression by reducing hepatic lipid accumulation and inflammation., 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 Inc.)

Competing Interests: Funding Support and Author Disclosures Dr Neuen has received fees for travel support, advisory boards, and scientific presentations from AstraZeneca, Bayer, Boehringer Ingelheim, Cambridge Healthcare Research, Cornerstone Medical Education, the Limbic, Janssen, Medscape, Novo Nordisk, and Travere Therapeutics; and has served on clinical trial committees for studies sponsored by AstraZeneca, Bayer, and CSL Behring, with all honoraria paid to The George Institute for Global Health. Dr Ostrominski has received research funding from the National Institutes of Health (grant 5T32HL007604-39). Dr Claggett as received consulting fees from Alnylam, Cardurion, Corvia, Cytokinetics, Intellia, and Rocket. Dr McCausland has received research funding from National Institutes of Health, Satellite Healthcare, Fifth Eye, Novartis, and Lexicon paid directly to his institution; and has received consulting fees from GlaxoSmithKline and Zydus Therapeutics. Dr Badve has received consulting fees from Bayer, AstraZeneca, GlaxoSmithKline, and Vifor Pharma; has received speaker fees from Bayer, AstraZeneca, Pfizer, and Vifor Pharma (all honoraria paid to his institution); and has received nonfinancial research support from Bayer. Dr Arnott has received honoraria from AstraZeneca, Novo Nordisk, and Amgen. Dr Heerspink has received grants or contracts from AstraZeneca, Boehringer Ingelheim, Janssen, and Novo Nordisk; has received consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim, CSL Behring, Dimerix, Eli Lilly, Gilead, Janssen, Novo Nordisk, Novartis, and Travere Therapeutics; and has received payment or honoraria for speaking from AstraZeneca and Novo Nordisk. Dr Jun has been responsible for research projects that have received unrestricted research funding from Boehringer Ingelheim and Eli Lilly Alliance. Dr Pollock serves as an Advisory Board member for AstraZeneca, Boehringer Ingelheim, Eli Lilly, and Vifor Pharma; and has received speaker fees for AstraZeneca, Janssen-Cilag, Novartis, Otsuka, and Vifor Pharma. Dr Jardine is supported by an National Health and Medical Research Council investigator grant; has been responsible for research projects that have received funding from Amgen, Baxter, CSL, Dimerix, Eli Lilly, Gambro, and Merck Sharp & Dohme; and has received fees for advisory, steering committee, scientific presentations, or a combination of these from Akebia, Amgen, AstraZeneca, Baxter, Bayer, Boehringer Ingelheim, Cesas Linx, Chinook, CSL, Janssen, Medscape, Merck Sharp & Dohme, Occuryx, Roche, and Vifor with any consultancy, honoraria, or travel support paid to her institution. Dr Mahaffey has received research support from Afferent, Amgen, Apple, AstraZeneca, Cardiva Medical, Daiichi, Ferring, Google (Verily), Johnson & Johnson, Luitpold, Medtronic, Merck, National Institutes of Health, Novartis, Sanofi, St Jude, and Tenax; and has served as a consultant (speaker fees for CME events only) for Abbott, Ablynx, AstraZeneca, Baim Institute, Boehringer Ingelheim, Bristol Myers Squibb, Elsevier, GlaxoSmithKline, Johnson & Johnson, MedErgy, Medscape, Mitsubishi Tanabe, Myokardia, the National Institutes for Health, Novartis, Novo Nordisk, Portola, Radiometer, Regeneron, Springer Publishing, and the University of California-San Francisco. Dr Perkovic serves as a board director for St Vincent’s Health Australia, Victor Chang Cardiac Research Institute, and Mindgardens; and has received honoraria for steering committee roles, scientific presentations, advisory board attendance, or a combination of these from Abbvie, Amgen, AstraZeneca, Bayer, Baxter, Boehringer Ingelheim, Chinook, Durect, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Merck, Mitsubishi Tanabe, Mundipharma, Novartis, Novo Nordisk, Otsuka, Pharmalink, Pfizer, Reata, Travere, Relypsa, Roche, Sanofi, Servier, and Tricida. Dr Solomon has received research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lilly, Mesoblast, MyoKardia, National Institutes of Health/NHLBI, Neurotronik, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI; and has consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellPro-Thera, Moderna, American Regent, and Sarepta. Dr Vaduganathan has received research grant support, served on advisory boards, or had speaker engagements with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Bristol Myers Squibb, Boehringer Ingelheim, Chiesi, Cytokinetics, Fresenius Medical Care, Idorsia Pharmaceuticals, Lexicon Pharmaceuticals, Merck, Milestone Pharmaceuticals, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health; and participates on clinical trial committees for studies sponsored by AstraZeneca, Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Cerebral small vascular disease (CSVD) has a high incidence worldwide, but its pathological mechanisms remain poorly understood due to the lack of proper animal models. The current animal models of CSVD have several limitations such as high mortality rates and large-sized lesions, and thus it is urgent to develop new animal models of CSVD. Ultrasound can activate protoporphyrin to produce reactive oxygen species in a liquid environment. Here we delivered protoporphyrin into cerebral small vessels of rat brain through polystyrene microspheres with a diameter of 15 μm, and then performed transcranial ultrasound stimulation (TUS) on the model rats. We found that TUS did not affect the large vessels or cause large infarctions in the brain of model rats. The mortality rates were also comparable between the sham and model rats. Strikingly, TUS induced several CSVD-like phenotypes such as cerebral microinfarction, white matter injuries and impaired integrity of endothelial cells in the model rats. Additionally, these effects could be alleviated by antioxidant treatment with N-acetylcysteine (NAC). As control experiments, TUS did not lead to cerebral microinfarction in the rat brain when injected with the polystyrene microspheres not conjugated with protoporphyrin. In sum, we generated a rat model of CSVD that may be useful for the mechanistic study and drug development for CSVD., Competing Interests: Declaration of competing interest The authors declare that there is no competing interest., (Copyright © 2024. Published by Elsevier Inc.)

Piperlongumine (PLM), a natural compound isolated from long peppers, has been reported to possess multiple pharmacological roles, including anti-tumor and anti-diabetic. However, the pharmacological role of PLM on adipogenesis is still unknown. In this study, we found that PLM strongly inhibited 3T3-L1 adipocyte differentiation. This inhibition was determined by the accumulation of lipid droplets and intracellular triglycerides. In addition, PLM downregulated both the mRNA and protein expression of adipogenic transcription factors, including CCAAT-enhancer binding proteins β (C/EBPβ), C/EBPα, and peroxisome proliferator-activated receptor γ (PPARγ). Based on the time-course experiment, we found that the inhibitory effect of PLM on adipogenesis was mainly involved in the early stage of adipogenesis. Studying these differential effects could uncover new mechanisms for regulating adipogenesis and new chemicals for treating obesity., 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.)

Objectives: To observe the effect of electroacupuncture (EA) of "Jiaji" (EX-B2) on expression of high mobility group box 1 (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) related proteins and inflammation-related factors in spinal cord injury (SCI) rats, so as to explore the dynamic process of inhibiting inflammatory response in rats with SCI, and to provide a new idea and theoretical basis of molecular biology for the treatment of SCI., Methods: Fifty-four SD rats were randomly divided into sham operation, model, and EA groups ( n =18 in each group), which were further divided into 3 d, 7 d and 14 d subgroups, with 6 rats at each time point. The SCI model was established according to the Allen's method. Rats in EA group received EA (1 mA, 100 Hz) intervention at EX-B2 of T9 and T11 24 hours after modeling for 30 min, once a day for 3 d, 7 d, or 14 d, respectively. The motor function of rats' hind limbs was evaluated using BBB scale, the morphological structure of rats' spinal cord tissue was observed by H.E. staining. The contents of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in spinal cord tissue were detected by ELISA. Western blot and immunofluorescence staining were used to detect the relative protein expression and fluorescence positive expression of HMGB1, TLR4 and NF-κB p65 in spinal cord tissue, respectively., Results: Compared with the sham operation group, the BBB scores after modeling and on day 3, 7 and 14 were all decreased ( P <0.05), while the contents of iNOS and COX-2 in spinal cord tissue, the protein expression and fluorescence positive expression of HMGB1, TLR4, and NF-κB p65 were increased ( P <0.05) in the model group. In comparison with the model group, the BBB scores on day 3, 7 and 14 were obviously increased ( P <0.05), while the contents of iNOS and COX-2, the protein expression and fluorescence positive expression of HMGB1, TLR4, and NF-κB p65 were significantly down-regulated in the EA group ( P <0.05)., Conclusions: EA of "Jiaji" can promote the recovery of SCI neurological function, which may be related to its function in regulating the HMGB1/TLR4/NF-κB signaling pathway, down-regulating the expression of iNOS and COX-2, and inhibiting the neuroinflammatory response after SCI.

Dissolved organic carbon (DOC) and dissolved inorganic carbon (DIC) significantly affect the aquatic carbon budget and ecosystem functions. Small ponds are abundant globally and widely distributed especially in agricultural watersheds, however, the variability of DOC and DIC, along with their driving factors, remains poorly understood, which likely hampers the understanding of carbon cycle of inland waters. The presented study was designed to fill the knowledge gap based on a detailed year-long field investigation via examining DOC and DIC concentrations across ponds with differing functionalities (e.g. sewage ponds, irrigation ponds, and natural ponds) of a typical agricultural watershed in eastern China. Our results found a pronounced impact of human activities on pond DOC and DIC, with higher DOC occurring in sewage ponds (10.84 ± 2.83 mg L -1 ) and irrigation ponds (9.09 ± 2.57 mg L -1 ) and peak DIC in irrigation ponds (20.36 ± 2.49 mg L -1 ) compared to that at natural ponds (DOC: 7.54 ± 2.55 mg L -1 ; DIC: 11.16 ± 3.85 mg L -1 ) with less human activity. The positive correlations between DOC/DIC and key environmental variables (e.g. nutrients and chlorophyll-a) further demonstrated that human activity can either directly increase the carbon concentrations via pollutant discharge, or indirectly increase DOC concentration via stimulating primary production. Meanwhile, field measurements found precipitation and temperature play roles in determining the carbon variability. Specifically, precipitation increased the DOC of these ponds via enhancing land-based carbon inputs, and decrease the DIC of irrigation ponds via diluting. Temperature can influence the carbon dynamics through increasing primary productivity and metabolism. Our study underscores the roles of human and natural influences in determining the large variations of DOC and DIC in small ponds, which should be considered to better understand the carbon dynamic variability of human-impacted small aquatic systems., 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.)

Iron (Fe) plaque, which forms on the surface of rice roots, plays a crucial role in immobilizing heavy metal(loids), thus reducing their accumulation in rice plants. However, the principal factors influencing Fe plaque formation and its adsorption capacity for heavy metal(loid)s throughout the rice plant's lifecycle remain poorly understood. Thus, this study investigated the dynamics of Fe plaque formation and its ability to adsorb cadmium (Cd) and arsenic (As) across different growth stages, aiming to identify the key drivers behind these processes. The findings reveal that the rate of radial oxygen loss (ROL) and the abundance of plaque-associated microbes are the primary drivers of Fe plaque formation, with their relative importance ranging from 1.4% to 81%. Similarly, the adsorption of As by Fe plaque is principally determined by the rate of ROL and the quantity of Fe plaque, with subsequent effects from the total Fe in rhizospheric soil, arsenate-reducing bacteria, and organic matter-degrading bacteria. The relative importance of these factors ranges from 6.0% to 11.7%. By contrast, the adsorption of Cd onto Fe plaque is primarily affected by competition for adsorption sites with ammonium in soils and the presence of organic matter-degrading bacteria, contributing 25.5% and 23.5% to the adsorption process, respectively. These findings provide significant insights into the development of Fe plaque and its absorption of heavy metal(loid)s throughout the lifecycle of rice plants., 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.)

Plastics aging reduces resistance to microbial degradation. Plastivore Tenebrio molitor rapidly biodegrades polystyrene (PS, size: < 80 μm), but the effects of aging on PS biodegradation by T. molitor remain uncharacterized. This study examined PS biodegradation over 24 days following three pre-treatments: freezing with UV exposure (PS1), UV exposure (PS2), and freezing (PS3), compared to pristine PS (PSv) microplastic. The pretreatments deteriorated PS polymers, resulting in slightly higher specific PS consumption (602.8, 586.1, 566.7, and 563.9 mg PS·100 larvae -1 ·d -1 , respectively) and mass reduction rates (49.6 %, 49.5 %, 49.2 %, and 48.7 %, respectively) in PS1, PS2, and PS3 compared to PSv. Improved biodegradation correlated with reduced molecular weights and the formation of oxidized functional groups. Larvae fed more aged PS exhibited greater gut microbial diversity, with microbial community and metabolic pathways shaped by PS aging, as supported by co-occurrence network analysis. These findings indicated that the aging treatments enhanced PS biodegradation by only limited extent but impacted greater on gut microbiome and bacterial metabolic genes, indicating that the T. molitor host have highly predominant capability to digest PS plastics and alters gut microbiome to adapt the PS polymers fed to them., 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 B.V.)

As a novel pollutant, microplastic pollution has become a global environmental concern. Melatonin (MT) has a protective effect on the damage caused by pollutants. However, there is still a lack of research on the transgenerational toxicity of microplastics and the alleviation of microplastics toxicity by MT. In this study, the adult zebrafish was exposed to (0, 0.1 and 1 mg/L) polystyrene nanoplastics (PSNP) with or without (1 μM) MT for 14 days, and embryos (F1) were used for experiments. Our study found that long-term exposure of parents to 1 mg/L PSNP reduced fertilization rate and survival rate of offspring, increased the deformity rate and induced embryos to hatch in advance. The growth inhibition of offspring was related to the gene transcription of the growth hormone/insulin-like growth factor axis. Moreover, PSNP caused oxidative stress in offspring, damaged immune system, reduced antioxidant capacity and induced apoptosis. MT supplementation could effectively alleviate the developmental toxicity and oxidative damage of offspring, but the negative effects brought by PSNP could not be completely eliminated. Our research provided a new reference for the protective effect of MT on transgenerational toxicity induced by PSNP., 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.)

Root resource acquisition strategies play a crucial role in understanding plant water uptake and drought adaptation. However, the interrelationships among mycorrhizal associations, root hair development, and fine root strategies, as well as the disparities between C 3 and C 4 grasses, remain largely unknown. A pot experiment was conducted to determine leaf gas exchange, root morphology, root hair, mycorrhizal fungi, and biomass allocation of three C 4 grasses and four C 3 grasses, common species of grasslands in Northeast China, under the control and drought conditions. Compared to the C 3 grasses, the C 4 grasses increased specific surface area by decreasing tissue density, yet exhibited root hair factor at only 21 % of the C 3 grasses. Under the drought conditions, the C 4 grasses exhibited more intense and extensive adjustments in root traits, characterized by shifts toward a more conservative morphology with increased root diameter and tissue density, as well as reduced mycorrhizal colonization rates. These adaptations led to a decrease in root absorptive function, which was compensated in the C 4 grasses by greater root biomass partitioning and root hair factor. Variances in root strategies between plants functional groups were closely related to leaf photosynthetic rate, water and nitrogen use efficiency. We observed that the C 4 grasses prefer direct acquisition of soil resources through the fine root pathway over the root hair or mycorrhizal pathway, suggesting a 'do-it-yourself' approach. These findings provide valuable insights into how plant communities of different photosynthetic types might respond to future climate change., Competing Interests: Declaration of competing interest We have no conflict of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Assessing the bioaccessibility and bioavailability of cadmium (Cd) is crucial for effective evaluation of the exposure risk associated with intake of Cd-contaminated rice. However, limited studies have investigated the influence of gut microbiota on these two significant factors. In this study, we utilized in vitro gastrointestinal simulators, specifically the RIVM-M (with human gut microbial communities) and the RIVM model (without gut microbial communities), to determine the bioaccessibility of Cd in rice. Additionally, we employed the Caco-2 cell model to assess bioavailability. Our findings provide compelling evidence that gut microbiota significantly reduces Cd bioaccessibility and bioavailability (p<0.05). Notably, strong in vivo-in vitro correlations (IVIVC) were observed between the in vitro bioaccessibilities and bioavailabilities, as compared to the results obtained from an in vivo mouse bioassay (R 2  = 0.63-0.65 and 0.45-0.70, respectively). Minerals such as copper (Cu) and iron (Fe) in the food matrix were found to be negatively correlated with Cd bioaccessibility in rice. Furthermore, the results obtained from the toxicokinetic (TK) model revealed that the predicted urinary Cd levels in the Chinese population, based on dietary Cd intake adjusted by in vitro bioaccessibility from the RIVM-M model, were consistent with the actual measured levels (p > 0.05). These results indicated that the RIVM-M model represents a potent approach for measuring Cd bioaccessibility and underscore the crucial role of gut microbiota in the digestion and absorption process of Cd. The implementation of these in vitro methods holds promise for reducing uncertainties in dietary exposure assessment., 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.)

P-type organic cathode materials typically exhibit high redox potentials and fast redox kinetics, presenting broad application prospects in aqueous zinc batteries (AZBs). However, most of the reported p-type organic cathode materials exhibit limited capacity (<100 mAh g -1 ), which is attributable to the low mass content ratio of oxidation-reduction active functional groups in these materials. Herein, we report a high-capacity p-type organic material, 5,12-dihydro-5,6,11,12-tetraazatetracene (DHTAT), for aqueous zinc batteries. Both experiments and calculation indicate the charge storage of DHTAT mainly involves the adsorption/desorption of ClO 4 - on the -NH- group. Benefitting from the high mass content ratio of the -NH- group in DHATA molecule, the DHATA electrode demonstrates a remarkable capacity of 224 mAh g -1 at a current density of 50 mA g -1 with a stable voltage of 1.12 V. Notably, after 5000 cycles at a high current density of 5 A g -1 , DHTAT retains 73 % of its initial capacity, showing a promising cycling stability. In addition, DHTAT also has good low-temperature performance and can stably cycle at -40 °C for 4000 cycles at 1 A g -1 , making it a competitive candidates cathode material for low-temperature batteries., (© 2024 Wiley-VCH GmbH.)

Psychrophilic bacteria, the dominant spoilage organisms in raw milk, secrete heat-stable extracellular proteases and lipases that lead to the decomposition of milk and dairy products. In this study, we investigated psychrophilic bacteria in 165 raw milk samples collected across four seasons and six regions in China using shotgun metagenomic sequencing and traditional culture methods. The isolated psychrophilic bacteria were classified into 40 genera and 185 species. Pseudomonas was the most prevalent, accounting for 51.13 % of the genera, while Lactococcus and Chryseobacterium were also notably abundant (> 6.0 %). Metagenomic sequencing revealed that Pseudomonas (47.9 %), Stenotrophomonas (9.75 %), Sphingomonas (6.73 %), Latilactobacillus (6.38 %) and Lactococcus (5.16 %) were the dominant genera in the raw milk samples. The diversity of psychrophilic bacteria in raw milk was strongly influenced by seasonal variations, with the sampling region being a less significant factor. KEGG annotation indicated that carbohydrate and amino acid metabolism were the primary metabolic pathways in these bacteria. Metagenomic sequencing not only accurately identifies species but also provides functional insights into psychrophilic bacteria in raw milk, aiding in understanding their activities, promoting their control on farms, and ultimately improving raw milk quality., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Considering the characteristics and operating environment of remotely controlled miniature soft robots, achieving delicate adhesion control over various target surfaces is a substantial challenge. In particular, the ability to delicately grasp wrinkled and soft biological and nonbiological surfaces with low preload without causing damage is essential. The proposed adhesive robotic system, inspired by the secretions from a velvet worm, uses a structured magnetorheological material that exhibits precise adhesion control with stability and repeatability by the rapid stiffness change controlled by an external magnetic field. The proposed adhesion protocol involves controlling soft-state adhesion, maintaining a large contact area, and enhancing the elastic modulus, and the mechanical structure enhances the effectiveness of this protocol. Demonstrations of the remote adhesive robot include stable transportation in soft and wet organs, unscrewing a nut from a bolt, and supporting mouse tumor removal surgery. These results indicate the potential applicability of the soft adhesive robot in biomedical engineering, especially for targeting small-scale biological tissues and organisms.

Background: In the process of food production, ciprofloxacin (CIP), a highly prescribed fluoroquinolone antibiotic, is often excessively used to reduce the risk of bacterial infection. However, this overuse can cause severe harm to human health, including allergic responses, gastrointestinal complications, and potential renal dysfunction. The development of a robust and precise detection method for CIP is crucial, given the interconnection between food security and human health. Compared to the single-mode detection methods currently in use, dual-mode detection provides enhanced accuracy in detecting results due to its inherent self-validation and self-correction capabilities., Results: Herein, a photoelectrochemical and photoelectrochromic self-validated dual-mode sensing platform was developed to detect CIP in milk by laser etching method, signal generation (SG) region, signal output (SO) region and conductive channel was integrated on the same fluoide-doped tin oxide electrode and Ti 3 C 2 /ZnO composite was modified in the electron SG region, and Prussian blue (PB) was electrodeposited in the SO region. By irradiating the SG region, photogenerated electrons are generated and injected into the SO region through the conductive pathway, resulting in the reduction of the PB to Prussian white (PW). Because the binding of CIP to its specifically recognized aptamers hinders electron transfer, a "Signal-Off" response mechanism can be used for simultaneous quantitative detection of CIP using photocurrent or color changes, which presents a great advantage in the detection process., Significance: By integrating different detection mechanisms within a single linear range, the constructed dual-mode sensor has a wide detection range and low detection limit in milk samples. Additionally, it shows good selectivity in anti-interference experiments, providing a new idea for the development of visual analysis and detection platforms for food safety., 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.)

Rapid and accurate characterization and quantitation of blood barbiturates and their combination drugs are very important for the clinical treatment of acute barbiturate poisoning. A comparison of dried blood spot (DBS) and traditional liquid-liquid extraction (LLE) in the pre-treatment stage, as well as a comparison of gas chromatography-mass spectrometry (GC-MS), gas chromatography-tandem mass spectrometry (GC-MS/MS), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) as instrumental analysis methods, revealed differences in the analysis results of barbiturates and their combination drugs under different conditions. Based on these findings, we introduce a DBS-GC-MS/MS method. The developed and validated method showed good selectivity, sensitivity (LOD: 0.1 μg mL -1 , LOQ: 0.2 μg mL -1 ), linearity (R 2 >0.9992), trueness (<15 %, except for carbamazepine, at 29.4 %), and precision (<15 %). Recovery was also good for most target compounds, but significant matrix effects were evident. Compared with the LLE method, the DBS method has the benefits of easy sample collection, storage, and transport, as well as simple pre-treatment and reduced reagent and energy consumption. Compared to LC-MS/MS, GC-MS/MS requires no switching between positive and negative ion modes and uses the MRM detection mode, meaning that more information about the sample compounds can be obtained in less analysis time. Using actual sample analysis, we have demonstrated the advantages of the DBS-GC-MS/MS method for the qualitative and quantitative analysis of barbiturates and poisoning events due to combinations of these drugs. Comparison of the three instruments and the two treatment methods revealed their analysis characteristics. From the perspective of practical application, the broad practical value and advantages of DBS should be embraced in more applications, and future analytical laboratory development should continue to recognize GC-MS/MS as a useful supplement to LC-MS/MS., 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.)

Microinfarcts are widespread in the elderly, accompanied by varying degrees of cognitive decline. Continuous theta burst stimulation (cTBS) has been demonstrated to be neuroprotective on cognitive dysfunction, but the underlying cellular mechanism has been still not clear. In the present study, we evaluated the effects of cTBS on cognitive function and brain pathological changes in mice model of microinfarcts. The spatial learning and memory was assessed by Morris water maze (MWM), Glymphatic clearance efficiency was evaluated using in vivo two-photon imaging. The loss of neurons, activation of astrocytes and microglia, the expression and polarity distribution of the astrocytic aquaporin-4 (AQP4) were assessed by immunofluorescence staining. Our results showed that cTBS treatment significantly improved the spatial learning and memory, accelerated the efficiency of glymphatic clearance, up-regulated the AQP4 expression and improved the polarity distribution of AQP4 in microinfarcts mice. Besides, cTBS treatment increased the number of surviving neurons, whereas decreased the activated astrocytes and microglia. Our study suggested that cTBS accelerated glymphatic clearance and inhibited the excessive gliogenesis, which ultimately exerted neuroprotective effects on microinfarcts mice., (Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)

To examine whether cognitive frailty serves as a predictor of hospitalisation in older adults. PubMed, Web of Science, Embase, Scopus and Cochrane Library databases were systematically searched from inception to February 6, 2024. The reviewers independently selected studies, extracted data and evaluated the quality of studies. Stata 15.1 Software was used to perform the meta-analysis. A total of 13 articles were included in this study, including 34 230 participants. The results suggested that cognitive frailty was associated with hospitalisation in older adults (odds ratio (OR) = 1.79, 95% CI: 1.33-2.42, P < 0.001). The risk of hospitalisation for patients with cognitive frailty was 1.76 times higher than that for patients without cognitive frailty (relative risk = 1.76, 95% CI: 1.48-2.08, P < 0.001). According to different models of cognitive frailty, the results of subgroup analysis showed that the frail + cognitive impairment group had the highest risk of hospitalisation (OR = 2.22, 95% CI: 1.51-3.26, P < 0.001). Subgroup analysis based on study design showed that the incidence of hospitalisation was lowest in the cohort study group (OR = 1.51, 95% CI: 1.14-2.00, P = 0.004). This study suggested that cognitive frailty was an important predictor of hospitalisation in older adults. Future studies are needed to investigate the impact of cognitive frailty on hospitalisation in older adults, as this may help reduce hospitalisation rates and improve patients' quality of life., (© 2024 Japanese Psychogeriatric Society.)

Metal-free photosensitizers for the construction of low-cost and eco-friendly dye-sensitized photoelectrochemical cells (DSPECs) have recently been greatly improved, but the optimization of water oxidation catalysts (WOCs) used in DSPECs based on metal-free dyes has received little attention. Herein, a series of polymer networks (RuTPA, RuCz, RuPr and RuTz) assembled by ruthenium WOCs (RuCHO) with various organic donors are constructed and combined with calixarene dyes to prepare DSPEC devices. The FTO|TiO2|C4BTP+RuTPA photoanode shows the best performance with 85% Faraday efficiency for oxygen production and 477 μA cm-2 photocurrent density after 200 s chopping irradiation at 0 V vs. Ag/AgCl, one of the highest records among other reported dye-sensitized photoanodes. Compared to monomeric RuCHO, Ru-based polymers with lower Ru content have higher activity and stability due to their rapid electron transfer and anti-aggregation ability. Meanwhile, RuTPA loaded electrodes show better performance due to the lower overpotential of the water oxidation reaction caused by the higher electron donating ability of its donor. This pioneering work incorporates Ru polymer networks as WOCs into the calixarene-sensitized DSPEC system, which has significant potential as a highly efficient and stable photoelectrochemical water splitting device., (© 2024 Wiley‐VCH GmbH.)

Purpose: This study aims to investigate the clinical and genetic features and change of clinical spectrum of primary hyperparathyroidism (PHPT) in children and adolescents., Methods: The clinical and follow-up data of 74 pediatric patients (onset age ≤ 18 years) with PHPT during 1975-2022 were retrospectively analyzed. For comparison, patients were divided into four subgroups according to their time of diagnosis. Genetic analysis was conducted in 40 patients., Results: Pediatric PHPT cases increased largely over time [34 cases (45.9%) in 2015-2022]. The rate of asymptomatic PHPT increased by time (14.7% in 2015-2022 vs. 0% before 2015), in accordance with routine screening of serum calcium becoming a more frequent reason for clinic visit (17.6% in 2015-2022 vs. 0% before 2015). Skeletal manifestation significantly decreased in recent years (64.7% in 2015-2022 vs. 100.0% in 1975-1994, P < 0.05). Sixty-seven patients (90.5%) of the whole cohort underwent parathyroidectomy. Atypical parathyroid adenoma and parathyroid carcinoma occurred in 13.4% and 4.5% of the surgical cases, respectively. Recurrence and persistence of PHPT were observed in 17.9% of postsurgical patients. Germline rare variations (RVs) of PHPT-related genes were found in 42.5% (17/40) of all cases with genetic testing. Compared with no-variation group, the variation group had higher incidence of multiple parathyroid lesions (42.8% vs. 4.3%, P = 0.014), and lower rate of benign lesions and higher rate of recurrence and persistence., Conclusion: Milder cases of Pediatric PHPT are coming to clinical attention probably due to routine lab testing. Genetic testing is recommended for pediatric PHPT patients., Competing Interests: Declarations. Conflict of interest: All the authors have no conflicts of interest to declare that are relevant to the content of this article., (© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Background: The genus Amorphophallus (Araceae) contains approximately 250 species, most of which have high ecological and economic significance. The chloroplast genome data and the comprehensive analysis of the chloroplast genome structure of Amorphophallus is limited. In this study, four chloroplast genomes of Amorphophallus were sequenced and assembled. For the first time, comparative analyses of chloroplast genomes were conducted on the 13 Amorphophallus species in conjunction with nine published sequences., Results: The Amorphophallus chloroplast genomes exhibited typical quadripartite structures with lengths ranging from 164,417 to 177,076 bp. These structures consisted of a large single copy (LSC, 90,705 - 98,561 bp), a small single copy (SSC, 14,172 - 21,575 bp), and a pair of inverted repeats (IRs, 26,225 - 35,204 bp). The genomes contain 108 - 113 unique genes, including 76 - 79 protein-coding genes, 28 - 29 tRNA genes, and 4 rRNA genes. The molecular structure, gene order, content, codon usage, long repeats, and simple sequence repeats (SSRs) within Amorphophallus were generally conserved. However, several variations in intron loss and gene expansion on the IR-SSC boundary regions were found among these 13 genomes. Four mutational hotspot regions, including trnM-atpE, atpB, atpB-rbcL and ycf1 were identified. They could identify and phylogeny future species in the genus Amorphophallus. Positive selection was found for rpl36, ccsA, rpl16, rps4, rps8, rps11, rps12, rps14, clpP, rps3, ycf1, rpl20, rps2, rps18, rps19, atpA, atpF, rpl14, rpoA, rpoC1, rpoC2 and rps15 based on the analyses of Ka/Ks ratios. Phylogenetic inferences based on the complete chloroplast genomes revealed a sister relationship between Amorphophallus and Caladieae. All Amorphophallus species formed a monophyletic evolutionary clade and were divided into three groups, including CA-II, SEA, and CA-I. Amorphophallus albus, A. krausei, A. kachinensis and A. konjac were clustered into the CA-II clade, A. paeoniifolius and A. titanum were clustered into the SEA clade, A. muelleri 'zhuyajin1', Amorphophallus sp, A. coaetaneus, A. tonkinensis and A. yunnanensis were clustered into CA- I clade., Conclusions: The genome structure and gene content of Amorphophallus chloroplast genomes are consistent across various species. In this study, the structural variation and comparative genome of chloroplast genomes of Amorphophallus were comprehensively analyzed for the first time. The results provide important genetic information for species classification, identification, molecular breeding, and evolutionary exploration of the genus Amorphophallus., Competing Interests: Declarations. Ethics approval and consent to participate: The materials involved in the article does not an endangered or protected species; therefore, permission is not required to collect this species. Research on these species, including the collection of plant materials has been carried out in accordance with guidelines provided by Kunming University. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Aims/introduction: Diabetic kidney disease (DKD) is a major cause of kidney failure. FOS-like antigen 2 (FOSL2) has been revealed to be increased in kidney biopsies of patients with lupus nephritis, while its association with DKD remains unsolved. This study aimed to characterize the role of FOSL2 in DKD and its mechanism., Method: The kidney tissues of DKD mice induced by STZ and a high-fat diet were subjected to PAS and Masson's staining. Glomerular mesangial cells (MCs) were treated with high glucose (HG) or normal glucose (NG). CCK-8 and EdU assays were performed to detect cell proliferation, and immunoblotting was conducted to analyze ECM deposition. ChIP-qPCR was performed on MCs to detect the binding of FOSL2 on the TGF-β1 promoter and a dual-luciferase assay to detect the impact of FOSL2 on the transcription of the TGF-β1 promoter., Results: FOSL2 was elevated in the kidney tissues of DKD mice. Knockdown of FOSL2 reduced the mRNA expression of TGF-β1 to decrease the protein expression of GLUT1 and mTOR in the kidney tissues of DKD mice, and TGF-β1 reversed the effects caused by knockdown of FOSL2. The mTOR inhibitor Rapamycin alleviated kidney injury in the presence of FOSL2. Knockdown of FOSL2 inhibited the proliferation and improved ECM deposition of MCs, which were reversed by TGF-β1. Rapamycin and GLUT1 inhibitor BAY-876 reversed the promotion effect of FOSL2 on the proliferation of NG-MCs/HG-MCs and improved ECM deposition of MCs., Conclusions: Our data demonstrated that FOSL2 accentuates DKD in mice by increasing TGF-β1-induced GLUT1/mTOR signaling., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Pseudoalteromonas are widely distributed in marine extreme habitats and exhibit diverse extracellular protease activity, which is essential for marine biogeochemical cycles. However, our understanding of viruses that infect Pseudoalteromonas remains limited. This study isolated a virus infecting Pseudoalteromonas nigrifaciens from Xiaogang in Qingdao, China. vB&#95;PunP&#95;Y3 comprises a linear, double-strand DNA genome with a length of 48,854 bp, encoding 52 putative open reading frames. Transmission electron microscopy demonstrates the short-tailed morphology of vB&#95;PunP&#95;Y3. Phylogenetic and genome-content-based analysis indicate that vB&#95;PunP&#95;Y3 represents a novel virus family named as Poorviridae , along with three high-quality uncultivated viral genomes. Biogeographical analyses show that Poorviridae is distributed across five viral ecological zones, and is predominantly detected in the Antarctic, Arctic, and bathypelagic zones. Comparative genomics analyses identified three of the seven hallmark proteins of N4-like viruses (DNA polymerase, major capsid protein, and virion-encapsulated RNA polymerase) from vB&#95;PunP&#95;Y3, combing with the protein tertiary structures of the major capsid protein, suggesting that vB&#95;PunP&#95;Y3 might evolve from the N4-like viruses., Importance: vB&#95;PunP&#95;Y3 is a unique strain containing three of the seven hallmark proteins of N4-like viruses, but is grouped into a novel family-level viral cluster with three uncultured viruses from metagenomics, named Poorviridae . This study enhanced the understanding about the genetic diversity, evolution, and distribution of Pseudoalteromonas viruses and provided insights into the novel evolution mechanism of marine viruses.

In this study, we introduced Matini-Net, which is a versatile framework for feature engineering and automated architecture design for materials informatics research using deep neural networks. Matini-Net provides the flexibility to design feature-based, graph-based, and combinations of these models, accommodating both single- and multimodal model architectures. For validation, we performed a performance evaluation on the MatBench benchmarking dataset of five properties, targeting five types of regression architectures that can be designed using Matini-Net. When applied to each of the five material property datasets, the best model performance for the various architectures exhibited R 2 > 0.84. This highlights the usefulness and flexibility of Matini-Net for accelerating materials discovery. Specifically, this framework was developed for researchers with limited experience in deep learning to easily apply it to research through automated feature engineering, hyperparameter tuning, and network construction. Moreover, Matini-Net improves the model interpretability by performing an importance analysis of the selected features. We believe that by employing Matini-Net, machine and deep learning can be applied more easily and effectively in various types of materials research.

Research on magnetically resonant wireless power transfer (MRWPT) is actively pursued for diverse applications. Dependent on magnetic fields for wireless power transfer (WPT), MRWPT encounters a challenge due to the absence of monopole magnetic properties, impacting power transfer efficiency (PTE) sensitivity to receiver arrangement. Despite extensive research, achieving the desired receiver freedom remains a persistent challenge-a core limitation rooted in magnetic field-based WPT. To address this, electrically resonant wireless power transfer (ERWPT) is proposed, utilizing an open bifilar coil at a resonant frequency. Experimental results demonstrate nonradiative power transfer of up to 50 watts and 46% PTE over a distance of 2 meters, maintaining consistent PTE performance. This phenomenon arises from the electric charge's monopole capability, distinguishing it from the limitations associated with magnetic fields. The practical viability of this system is delved and suggest directions for further investigation. ERWPT overcomes MRWPT challenges, ensuring lateral plane consistent efficiency and offering a breakthrough for practical wireless power applications., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

ABATRACTTwo new compounds, namely, isorhamnenin-3- O -neohesperidin-6''-linoleic acid ester ( 1 ) and isorhamnenin-3- O -neohesperidin-6''-palmitate ( 2 ), along with 17 known compounds, were isolated from Pollen Typhae Carbonisatus (PTC). Their structures were elucidated on the basis of one-dimensional (1D)-, two-dimensional (2D)-nuclear magnetic resonance (NMR), and high-resolution electrospray ionization mass spectrometry (HRESIMS) spectroscopic data analyses. The two new compounds ( 1 and 2 ) exhibited a protective effect in a dose-dependent manner and promoted tube generation in the oxygen-glucose deprivation/reoxygenation (OGD/R)-induced human brain microvascular endothelial cells (HBMECs).

Aim: To map the existing evidence and identify research gaps regarding the self-management of prediabetes or type 2 diabetes among first-generation immigrants ≥ 18 years., Design: A scoping review followed the JBI guidelines and was in accordance with the PRISMA extension for Scoping Reviews., Methods: A systematic search of CINAHL, Cochrane, EMBASE, MEDLINE, PsycINFO, ProQuest, SCOPUS and the Web of Science was conducted. Grey literature and reference lists of included studies were searched for additional citations. Articles published in English from the database inception to February 2023 were included., Results: We included 96 studies, of which 28.1% were published within the last 5 years. Most studies (71.9%) were conducted in the United States. Study participants were recruited mainly from community settings and English was their second language. The most common study methodologies used were cross-sectional surveys and phenomenological interviews. Only two studies specifically focussed on individuals with prediabetes. Multiple factors, such as age, gender, country of origin and other societal, linguistic, cultural and resource barriers or facilitators, as well as patient's cultural unique experiences, were of particular significance for self-management behaviours. Although several studies reported that culturally tailored interventions were feasible and acceptable among first-generation immigrants living with type 2 diabetes but not prediabetes, the duration and intensity of these interventions varied., Conclusion: Health professionals should consider various demographic, societal, linguistic and cultural factors, such as participants' low English language proficiency, and provide appropriate support for this group to ensure better self-management behaviours. Tailoring interventions to individual and cultural preferences in collaboration with key stakeholders is crucial for adult immigrants with prediabetes and type 2 diabetes across diverse cultural and ethnic groups., Impact: Developing and applying culturally tailored self-management interventions for the targeted population, particularly those with prediabetes, should be an important direction for future research. No Patient or Public Contribution., (© 2024 John Wiley & Sons Ltd.)

Background: The pathogenesis of psoriasis, an inflammatory skin disease, is incompletely understood. Growing evidence substantiates the involvement of stromal cells in the inflammatory process., Objectives: To investigate the roles of stromal cells, including fibroblasts, vascular endothelial cells (VECs) and smooth muscle cells (VSMCs), in the psoriatic inflammatory microenvironment and the possible underlying mechanisms involved., Methods: This study employed combination of single-cell, spatial transcriptome and bulk RNA sequencing using lesional and nonlesional skin samples from patients with psoriasis vulgaris (PV) and healthy skin samples from unaffected individuals., Results: Through the analysis of transcriptome from 364,098 single cells, we uncovered WNT5A+ fibroblasts, ITIH5+ VECs and VCAN+ VSMCs with the significantly increased cell proportions in the papillary dermis of lesional skin. We defined eight unique subclusters of fibroblasts in the skin and observed a shift of WIF1+ fibroblasts towards WNT5A+ fibroblasts, with abnormal activation of the non-canonical Wnt signaling pathway and increased capabilities of angiogenesis and pro-inflammatory. For the microvascular cells, VSMCs could undergo phenotypic transformation from a contractile phenotype to a synthetic phenotype in the development of psoriatic inflammation. ITIH5+ VECs and VCAN+ VSMCs were identified with an essential role in regulating angiogenesis and vascular remodeling involved in the mechanism of psoriatic pathological changes. Ligand receptor analyses demonstrated WNT5A+ fibroblasts were extensively implicated in interactions with various cell types in skin, especially with ITIH5+ VECs and VCAN+ VSMCs within the papillary dermis., Conclusions: Interactions of stromal cells in the papillary dermis were identified as possible pathogenic elements in psoriasis vulgaris. Improving the inflammatory microenvironment by targeting stromal cells might be a potential treatment strategy for psoriasis., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Diabetic peripheral neuropathy (DPN) is the most common complication of type 2 diabetes mellitus (T2DM) and is often accompanied by a variety of cognitive and emotional deficits, but the neurologic mechanisms underlying these deficits have not been fully elucidated. Therefore, this study aimed to use independent component analysis to explore the changes in the characteristics within the intrinsic network and to reveal patterns of interactions between networks in patients with DPN. Forty-one patients with T2DM who showed DPN, 37 patients with T2DM who did not show DPN (NDPN group), and 43 healthy controls (HC) underwent a neuropsychological assessment and resting-state functional magnetic resonance imaging examinations to examine the patterns of intra- and inter-network variations in the patients with T2DM at different clinical stages (with and without DPN). The relationships of intra- and inter-network functional connectivity (FC) with clinical/cognitive variables were also examined. In comparison with the NDPN group and HC, patients with DPN showed decreased FC within the visual network and sensorimotor network (SMN). Moreover, in comparison with the HC group, patients with DPN showed decreased FC within the anterior default mode network and increased FC within the basal ganglia network. Inter-network analysis showed decreased FC between the SMN and salience network in patients with DPN relative to the NDPN and HC groups. The decreased FC within the bilateral paracentral lobule (BA 6) of SMN was associated with Color Trails Test part 1 scores (r = -0.302, P = 0.007) and disease duration (r = -0.328, P = 0.003) in all patients with T2DM. In conclusion, the results revealed that patients with DPN have abnormal FC in multiple resting-state intrinsic networks in addition to the SMN, and that decreased FC between the SMN and salience network may be involved in the neural basis of abnormal sensorimotor function in patients with DPN., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Ningnanmycin has been proven to effectively inhibit infection by potato virus Y (PVY), although its underlying mechanisms remain unclear. In this study, we report a novel finding that ningnanmycin affects PVY replication. Two approaches were employed: studies using PVY movement-deficient mutants suggest that ningnanmycin, at a concentration of 500 μg/mL, inhibits PVY replication. Ningnanmycin interacts with the PVY-encoded coat protein (CP) with a binding constant of 1.34 μmol/L, and key amino acids Glu 168 and Thr 206 are involved in this interaction. Additionally, ningnanmycin induces the expression of antiviral response genes in Nicotiana benthamiana , including PRXIIB , PRXIIE , PUB4 , and PER42 . Furthermore, studies revealed that the overexpression of PUB4 in N. benthamiana confers resistance to PVY infection. These findings highlight the mechanisms by which ningnanmycin activates the PUB4 gene and suppresses CP assembly, thereby inhibiting PVY in N. benthamiana . This study represents an important step toward elucidating the molecular mechanism underlying the antiviral activity of ningnanmycin.

Copper (Cu), an indispensable micronutrient for the sustenance of living organisms, contributes significantly to a vast array of fundamental metabolic processes. The human body maintains a relatively low concentration of copper, which is mostly found in the bones, liver, and brain. Despite its low concentration, Cu plays a crucial role as an indispensable element in the progression and pathogenesis of central nervous system (CNS) diseases. Extensive studies have been conducted in recent years on copper homeostasis and copper-induced cell death in CNS disorders, including glioma, Alzheimer's disease, Amyotrophic lateral sclerosis, Huntington's disease, and stroke. Cuproptosis, a novel copper-induced cell death pathway distinct from apoptosis, necrosis, pyroptosis, and ferroptosis, has been identified as potentially intricately linked to the pathogenic mechanisms underlying various CNS diseases. Therefore, a systematic review of copper homeostasis and cuproptosis and their relationship with CNS disorders could deepen our understanding of the pathogenesis of these diseases. In addition, it may provide new insights and strategies for the treatment of CNS disorders., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objectives: This study aimed to investigate the outcomes and effectiveness of different antithrombotic regimens at discharge in nonvalvular atrial fibrillation (NVAF) patients with acute ischemic stroke (AIS) and competing large artery atherosclerosis (LAA) mechanisms., Methods: In an observational study, we retrospectively analyzed the clinical and follow-up data of NVAF patients with AIS from January 2018 to December 2021 (NCT04080830). The subjects were grouped into 2 groups based on the presence or absence of competing LAA mechanisms. Stroke severity, short-term prognosis, and ischemic recurrence (a composite of ischemic stroke/TIA, myocardial infarction, or systemic embolism after index stroke), were compared between the 2 groups. Antithrombotic regimens at discharge were further categorized into antiplatelet and anticoagulant subgroups to analyze their effectiveness., Results: Five hundred-one NVAF patients with AIS (129 with and 372 without competing LAA mechanisms) were included. Compared with the other group, the group with competing LAA mechanisms had a higher proportion of patients with a nondisabling mRS score (P<0.001), lower mortality rates at the 90-day follow-up (P=0.048), and higher 180-day ischemic outcomes (P=0.023). Subgroup analysis showed that the ischemic outcomes were not significantly different (P=0.166) between the anticoagulant and antiplatelet subgroups in patients with competing LAA mechanisms. In contrast, it was numerically higher in the anticoagulant subgroup., Conclusion: NVAF patients with AIS due to competing LAA mechanisms had mild severity and a comfortable short-term prognosis; however, these patients had a higher risk of ischemic events. The optimal antithrombotic regimens in these patients remain unclear, and stroke mechanisms should be considered., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)