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Spinal cord injury creates an inflammatory microenvironment that regulates the capacity of transplanted human Neural Stem Cells (hNSC) to migrate, differentiate, and repair injury. Despite similarities in gene expression and markers detected by immunostaining, hNSC populations exhibit heterogeneous therapeutic potential. This heterogeneity derives in part from the epigenetic landscape in the hNSC genome, specifically methylation (5mC) and hydroxymethylation (5hmC) state, which may affect the response of transplanted hNSC in the injury microenvironment and thereby modulate repair capacity. We demonstrate a significant up-regulation of methylcytosine dioxygenase 2 gene (TET2) expression in undifferentiated hNSC derived from human embryonic stem cells (hES-NSC), and report that this is associated with hES-NSC competence for differentiation marker expression. TET2 protein catalyzes active demethylation and TET2 upregulation could be a signature of pluripotent exit, while shaping the epigenetic landscape in hES-NSC. We determine that the inflammatory environment overrides epigenetic programming in vitro and in vivo by directly modulating TET2 expression levels in hES-NSC to change cell fate. We also report the effect of cell fate and microenvironment on differential methylation 5mC/5hmC balance. Understanding how the activity of epigenetic modifiers changes within the transplantation niche in vivo is crucial for assessment of hES-NSC behavior for potential clinical applications., (© 2024. The Author(s).)

Background Early-life exposure to famine may influence the occurrence of chronic diseases and aging in midlife among those exposed. This study aims to explore the relationship between exposure to the Chinese Great Famine and aging in middle-aged individuals. Methods Participants born in 1963-1965 (unexposed), 1959-1961 (in utero exposure), and 1955-1957 (childhood exposure) from the Kailuan Study were included. Their biological age at 2010, 2014, and 2018 was investigated, and age acceleration (biological age minus actual age) was calculated to assess aging. Logistic regression analysis was employed to describe the relationship between famine exposure and the aging risk. Subgroup and sensitivity analysis were conducted to explore differences and stability in this relationship among different groups. Results A total of 17,543 participants were included in this study. Among them, 12,762 (72.7%) were male, and 4,781 (27.3%) were female, with 2,543 participants experiencing aging events. Compared to unexposed participants, those exposed during childhood and in utero exhibited a 1.69-fold (OR = 1.69, 95%CI: 1.53-1.87) and 1.22-fold (OR = 1.22, 95%CI: 1.08-1.37) increased risk of aging. Subgroup analysis revealed an interaction with income (P for interaction = 0.008), and additional interaction analysis suggested that increasing income could partially mitigate the detrimental effects of early-life famine exposure. Furthermore, experiencing famine in severely affected regions exacerbated the risk of aging (OR = 1.41, 95%CI: 1.21-1.63). Conclusion Exposure to famine in utero or during childhood may elevate the risk of midlife aging among exposed individuals, and these relationships are influenced by the severity of famine exposure. Increasing income may also help mitigate these effects.Trial registration: Kailuan study, ChiCTRTNRC11001489. Registered July 19, 2015 Retrospectively registered, https//www.chictr.org.cn/showprojEN.html?proj=8050&u_atoken=af46a0dee8d73f320bb5459ab7bbcfa9&u_asig=1a0c381017255295896468605e00cf ., (© 2024. The Author(s).)

Insufficient activation of stimulator of interferon genes (STING) signaling pathway in tumor-associated dendritic cells limits the efficiency of tumor immunotherapy. Herein, the "three-in-one" IAHA-LaP/siPTPN6 NPs containing lanthanum ions (La 3+ ), cGAMP, and PTPN6 siRNA are developed for triple amplification of the STING pathway. In vitro results demonstrate that La 3+ significantly promotes cGAMP-mediated activation of the STING pathway by enhancing the phosphorylation of STING, TBK1, IRF3, and NF-κB p65. Moreover, the IAHA-LaP/siPTPN6 NPs further significantly enhance the phosphorylation of STING and NF-κB p65 and augment K63-linked ubiquitination of STING protein via siPTPN6-mediated downregulation of SHP-1 protein. Furthermore, NPs improve the secretion of IFNβ (2.4-fold), IL-6 (1.5-fold), and TNF-α (1.4-fold), thereby promoting DCs maturation compared to the mixture of La 3+ and cGAMP. In vivo results show that the IAHA-LaP/siPTPN6 NPs remarkably inhibit primary tumor growth by increasing the percentage of mature DCs in tumor-draining lymph nodes, polarizing M2/M1 phenotype in TME, and promoting the infiltration of CD8 + T cells into tumors. Moreover, these NPs dramatically prevent the growth of distal tumor by inducing systemic anti-tumor immunity and generating a long-term anti-tumor memory for protection against tumor recurrence in mice bearing bilateral B16F10. These IAHA-LaP/siPTPN6 NPs may offer a promising platform for robust anti-tumor immune responses., (© 2024 Wiley‐VCH GmbH.)

In this paper, we propose a dynamic authorizable ciphertext image retrieval scheme based on secure neural network inference that effectively enhances the security of image retrieval while preserving privacy. To ensure the privacy of the original image and enable feature extraction without decryption operations, we employ a secure neural network for feature extraction during the index construction stage of encrypted images. Additionally, we introduce a dynamic authenticatable ciphertext retrieval algorithm to enhance system flexibility and security by enabling users to quickly and flexibly retrieve authorized images. Experimental results demonstrate that our scheme guarantees data image privacy throughout the entire process from upload to retrieval compared to similar literature schemes. Furthermore, our scheme ensures data availability while maintaining security, allowing users to conveniently perform image retrieval operations. Although overall efficiency may not be optimal according to experimental results, our solution satisfies practical application needs in cloud computing environments by providing an efficient and secure image retrieval solution., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhang, Hong. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To evaluate the feasibility of using a multigene signature to tailor individualised adjuvant therapy for patients with operable triple negative breast cancer., Design: Randomised, multicentre, open label, phase 3 trial., Setting: 7 cancer centres in China between 3 January 2016 and 17 July 2023., Participants: Female patients aged 18-70 years with early triple negative breast cancer after definitive surgery., Interventions: After risk stratification using the integrated signature, patients at high risk were randomised (1:1) to receive an intensive adjuvant treatment comprising four cycles of docetaxel, epirubicin, and cyclophosphamide followed by four cycles of gemcitabine and cisplatin (arm A; n=166) or a standard treatment of four cycles of epirubicin and cyclophosphamide followed by four cycles of docetaxel (arm B; n=170). Patients at low risk received the same adjuvant chemotherapy as arm B (arm C; n=168)., Main Outcome Measures: The primary endpoint was disease-free survival in the intention-to-treat analysis for arm A versus arm B. Secondary endpoints included disease-free survival for arm C versus arm B, recurrence-free survival, overall survival, and safety., Results: Among the 504 enrolled patients, 498 received study treatment. At a median follow-up of 45.1 months, the three year disease-free survival rate was 90.9% for patients in arm A and 80.6% for patients in arm B (hazard ratio 0.51, 95% confidence interval (CI) 0.28 to 0.95; P=0.03). The three year recurrence-free survival rate was 92.6% in arm A and 83.2% in arm B (hazard ratio 0.50, 95% CI 0.25 to 0.98; P=0.04). The three year overall survival rate was 98.2% in arm A and 91.3% in arm B (hazard ratio 0.58, 95% CI 0.22 to 1.54; P=0.27). The rates of disease-free survival (three year disease-free survival 90.1% v 80.6%; hazard ratio 0.57, 95% CI 0.33 to 0.98; P=0.04), recurrence-free survival (three year recurrence-free survival 94.5% v 83.2%; 0.42, 0.22 to 0.81; P=0.007), and overall survival (three year overall survival 100% v 91.3%; 0.14, 0.03 to 0.61; P=0.002) were significantly higher in patients in arm C than in those in arm B with the same chemotherapy regimen. The incidence of grade 3-4 treatment related adverse events were 64% (105/163), 51% (86/169), and 54% (90/166) for arms A, B, and C, respectively. No treatment related deaths occurred., Conclusions: The multigene signature showed potential for tailoring adjuvant chemotherapy for patients with operable triple negative breast cancer. Intensive regimens incorporating gemcitabine and cisplatin into anthracycline/taxane based therapy significantly improved disease-free survival with manageable toxicity., Trial Registration: ClinicalTrials.gov NCT02641847., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from the National Key Research and Development Project of China, National Natural Science Foundation of China, Science and Technology Commission of Shanghai Municipality, Shanghai Key Laboratory of Breast Cancer, SHDC Municipal Project for Developing Emerging and Frontier Technology in Shanghai Hospitals, and CSPC Pharmaceutical Co Ltd, Shijiazhuang, China, for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Atrazine (ATZ), a widely used herbicide, disrupts mitochondrial function and lipid metabolism in the liver. Melatonin (MLT), a naturally synthesized hormone, combats mitochondrial dysfunction and alleviates lipid toxicity. However, the mechanisms behind ATZ-induced lipid metabolism toxicity and the protective effects of MLT remain unexplored. Mice were randomly assigned to four groups: control (Con), 5 mg/kg MLT, 170 mg/kg ATZ, and a cotreatment group receiving 170 mg/kg ATZ with 5 mg/kg MLT (ATZ+MLT). Additionally, we analyzed the effects of MLT and Rab8a on mRNA and proteins related to mitochondrial function and lipid metabolism disrupted by ATZ in AML12 cells. In conclusion, ATZ induced mitochondrial stress and disrupted fatty acid metabolism in mouse hepatocytes and AML12 cells. Exogenous MLT restores Rab8a levels, regulating fatty acid utilization in mitochondria and mitochondrial function. Notably, targeting Rab8a does not significantly affect mitochondrial function but prevents ATZ-induced lipid metabolism disorders in hepatocytes.

Salinity gradient energy is a chemical potential energy between two solutions with different ionic concentrations, which is also an ocean energy at the junction of rivers and seas. In our original work, the device "activated carbon//(0.083 M Na 2 SO 4 , 0.5 M Na 2 SO 4 )//vanadium pentoxide" for the conversion of salinity gradient energy was designed, and the conversion value of 6.29 J g -1 was obtained. However, the low specific surface area of the original V 2 O 5 inevitably resulted in limited active sites and slow ionic transport rates, and the inherent lower conductivity and narrower layer spacing of the original V 2 O 5 also resulted in poor electrode kinetic performance and cycle stability, hindering its practical application. To solve the above problems, the present work provides a strategy of using polyaniline (PANI) molecule chain intercalation to regulate the layer spacing of the original V 2 O 5 , and through the expansion and traction of the layer spacing, the composite PANI/V 2 O 5 (PVO) with high specific surface area is prepared and used as an anode material for electrochemical conversion of salinity gradient energy application. The significantly increased layer spacing of the crystal plane (001) corresponding to the original V 2 O 5 was confirmed with the PANI by the hydrogen bonding and the van der Waals force. The high specific surface area of the composite provides more electrochemical active sites to realize a fast Na + migration rate and high specific capacitance. Meanwhile, the inserted PANI molecule chain, which acts not only as a pillar enlarging the Na + diffusion channel but also as an anchor locking the gap between V 2 O 5 bilayers, improves the structural stability of the V 2 O 5 electrode during the electrochemical conversion process. The proposed insertion strategy for the conductive polymer PANI has created a new way to improve the cycle stability performance of the salinity gradient energy conversion device.

Background: Increasing evidence suggests that environmental factors play a crucial role in the pathogenesis of Parkinson's disease (PD). Humans are simultaneously exposed to multiple brominated flame retardants (BFRs) in the environment. However, the relationship between BFRs and PD remains unclear. This study was designed to investigate the overall association between BFRs and PD in a nationally representative US population and to further identify significant chemicals., Methods: This study used data from 7,161 NHANES participants from 2009 through 2016. The serum BFRs registry included PBDE-28, PBDE-47, PBDE-85, PBDE-99, PBDE-100, PBDE-153, PBDE-154, PBDE-183, PBDE-209, and PBB-153. A survey-weighted generalized logistic regression model with restricted cubic splines (RCS) was used to evaluate the association between single BFRs exposure and periodontitis. Meanwhile, weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were used to evaluate the overall association of mixed frankincense powder with periodontitis and to identify significant chemicals. Sensitivity analysis was performed to evaluate the robustness of the results., Results: Among the 7,161 participants, 65 had PD. PD patients were older (mean age 57.79 vs. 46.57 years) and had a higher proportion of females (70.86%) compared to non-PD participants. Serum levels of PBB-153 were significantly higher in those with PD. Logistic regression analyses revealed a non-linear, inverted U-shaped relationship between serum PBB-153 and PD risk. The risk of PD increased with higher PBB-153 levels up to the 3rd quartile (Q3), beyond which the risk declined (Q3 vs. Q1: OR = 4.98, 95% CI = 1.79-13.86; Q4 vs. Q1: OR = 3.23, 95% CI = 1.03-10.08). PBB-153 (43.40%), PBDE-153 (24.75%), and PBDE-85 (19.51%) contributed most to the weighted quantile sum index associated with PD risk. Bayesian kernel machine regression confirmed the inverted U-shaped dose-response pattern for PBB-153 and the overall BFR mixture. Restricted cubic spline analyses corroborated the non-linear relationship between PBB-153 and PD, which was more pronounced among women and those aged 37-58 years. Sensitivity analyses substantiated these findings., Conclusion: This nationally representative cross-sectional study revealed a novel non-linear, inverted U-shaped relationship between serum levels of the brominated flame retardant PBB-153 and Parkinson's disease risk in U.S. adults. The risk increased with higher PBB-153 exposure up to a point, beyond which it declined. This complex dose-response pattern highlights the importance of considering potential hormetic mechanisms and effect modifiers when evaluating environmental exposures and neurodegenerative diseases. Further research is warranted to elucidate the underlying biological pathways and inform risk mitigation strategies., Competing Interests: 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 Lv, Zhang, Li, Zhang, Yixi, Yang and Wang.)

Background: cfDNA fragmentomics-based liquid biopsy is a potential option for noninvasive bladder cancer (BLCA) detection that remains an unmet clinical need., Methods: We assessed the diagnostic performance of cfDNA hotspot-driven machine-learning models in a cohort of 55 BLCA patients, 51 subjects with benign conditions, and 11 healthy volunteers. We further performed functional bioinformatics analysis for biological understanding and interpretation of the tool's diagnostic capability., Results: Urinary cfDNA hotspots-based machine-learning model enabled effective BLCA detection, achieving high performance (area under curve 0.96) and an 87% sensitivity at 100% specificity. It outperformed models using other cfDNA-derived features. In stage-stratified analysis, the sensitivity at 100% specificity of the urine hotspots-based model was 71% and 92% for early (low-grade Ta and T1) and advanced (high-grade T1 and muscle-invasive) disease, respectively. Biologically, cfDNA hotspots effectively retrieved regulatory elements and were correlated with the cell of origin. Urine cfDNA hotspots specifically captured BLCA-related molecular features, including key functional pathways, chromosome loci associated with BLCA risk as identified in genome-wide association studies, or presenting frequent somatic alterations in BLCA tumors, and the transcription factor regulatory landscape., Conclusions: Our findings support the applicability of urine cfDNA fragmentation hotspots for noninvasive BLCA diagnosis, as well as for future translational study regarding its molecular pathology and heterogeneity., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Electrochemical reduction of CO 2 into high-value-added products is a potential approach to solving environmental problems but is limited by poor product selectivity and low efficiency. Metal-organic framework (MOF) materials have been considered one of the most promising catalysts, but their application is limited by complicated preparation processes, especially during the synthesis of organic ligands. In this work, a new three-dimensional Cu-MOF ( JXUST-301 ) with high porosity was constructed based on the naphthalene diimide (NDI) ligand. Furthermore, JXUST-301 with ligand defects ( JXUST-301D ) originating from the missing NDI unit was synthesized via an in situ reaction. The presence of ligand defects endows JXUST-301D with a better CO 2 RR performance with a FE C2 of 56.7% and a j C2 of -162.4 mA cm -2 . Mechanistic studies revealed that the hierarchical pore structure and amino sites are created from the absence of the NDI unit, which promotes the exposure of catalytically active sites and CO 2 enrichment. Furthermore, the electronic structure of the Cu sites is modulated to upshift the d-band center, facilitating chemical adsorption and activation of key reaction intermediates. This work provides new insight into the in situ preparation of efficient Cu-MOF catalysts by introducing defects for the CO 2 RR.

Alkali-activated concrete (AAC), produced from industrial by-products like fly ash and slag, offers a promising alternative to traditional Portland cement concrete by significantly reducing carbon emissions. Yet, the inherent variability in AAC formulations presents a challenge for accurately predicting its compressive strength using conventional approaches. To address this, we leverage machine learning (ML) techniques, which enable more precise strength predictions based on a combination of material properties and cement mix design parameters. In this study, we curated an extensive dataset comprising 1756 unique AAC mixtures to support robust ML-based modeling. Four distinct input variable schemes were devised to identify the optimal predictor set, and a comparative analysis was performed to evaluate their effectiveness. After this, we investigated the performance of several popular ML algorithms, including random forest (RF), adaptive boosting (AdaBoost), gradient boosting regression trees (GBRTs), and extreme gradient boosting (XGBoost). Among these, the XGBoost model consistently outperformed its counterparts. To further enhance the predictive accuracy of the XGBoost model, we applied four state-of-the-art optimization techniques: the Gray Wolf Optimizer (GWO), Whale Optimization Algorithm (WOA), beetle antennae search (BAS), and Bayesian optimization (BO). The optimized XGBoost model delivered superior performance, achieving a remarkable coefficient of determination (R 2 ) of 0.99 on the training set and 0.94 across the entire dataset. Finally, we employed SHapely Additive exPlanations (SHAP) to imbue the optimized model with interpretability, enabling deeper insights into the complex relationships governing AAC formulations. Through the lens of ML, we highlight the benefits of the multi-faceted synergistic approach for AAC strength prediction, which combines careful input parameter selection, optimal hyperparameter tuning, and enhanced model interpretability. This integrated strategy improves both the robustness and scalability of the model, offering a clear and reliable prediction of AAC performance.

Growing evidence suggests that heart failure (HF) is associated with an increased risk of depressive disorders and anxiety. However, the existing studies were observational and may have confounded and not reflected true causal relationships. This study collected genetic instruments about HF, depression, and anxiety from publicly available genetic summary data. Two-sample Mendelian randomization (MR) analysis was performed, with inverse-variance weighted designated as the primary approach for determining causal effects. Secondary analyses included MR-Egger regression and the weighted media method. Additionally, we conducted MR pleiotropy residual sum and outlier to address horizontal pleiotropy. Cochran Q test, MR-Egger intercept test, and leave-one-out analysis were used to assess the robustness of the findings. The significance is determined by a P-value below .05. Gene prediction result revealed that HF did not exhibit a significant association with elevated incidence of depression by inverse-variance weighted method no matter HF from the Heart Failure Molecular Epidemiology for Therapeutic Targets Consortium (odds ratio [OR] = 1.05, 95% confidence interval [CI] = 0.93-1.18, P = .424 for major depressive disorder, MDD; OR = 1.01, 95% CI = 0.94-1.09, P = .782 for major depression) or the FinnGen Consortium (OR = 1.03, 95% CI = 0.92-1.15, P = .644 for MDD; OR = 1.00, 95% CI = 0.94-1.07, P = .962 for major depression). In contrast, the results of HF on anxiety exhibited inconsistency (OR = 1.60, 95% CI = 1.10-2.31, P = .013 for Heart Failure Molecular Epidemiology for Therapeutic Targets Consortium; OR = 1.42, 95% CI = 0.91-2.21, P = .123 for FinnGen Consortium); however, a combined effect analysis indicated support causal relationship between HF and the risk of anxiety (OR = 1.52, 95% CI = 1.07-2.00, P < .001). Our findings did not reveal evidence to confirm a causal association between HF and depression. However, our results provide support for a causal effect of HF on the risk of anxiety., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: To investigate the molecular mechanisms underlying the influence of hypoxia and alpha-ketoglutaric acid (α-KG) on scleral collagen expression., Methods: Meta-analysis and clinical statistics were used to prove the changes in choroidal thickness (ChT) during myopia. The establishment of a hypoxic myopia model (HYP) for rabbit scleral fibroblasts through hypoxic culture and the effects of hypoxia and α-KG on collagen expression were demonstrated by Sirius red staining. Transcriptome analysis was used to verify the genes and pathways that hypoxia and α-KG affect collagen expression. Finally, real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used for reverse verification., Results: Meta-analysis results aligned with clinical statistics, revealing a thinning of ChT, leading to scleral hypoxia. Sirius red staining indicated lower collagen expression in the HYP group and higher collagen expression in the HYP+α-KG group, showed that hypoxia reduced collagen expression in scleral fibroblasts, while α-KG can elevated collagen expression under HYP conditions. Transcriptome analysis unveiled the related genes and signaling pathways of hypoxia and α-KG affect scleral collagen expression and the results were verified by RT-qPCR., Conclusion: The potential molecular mechanisms through which hypoxia and α-KG influencing myopia is unraveled and three novel genes TLCD4 , TBC1D4 , and EPHX3 are identified. These findings provide a new perspective on the prevention and treatment of myopia via regulating collagen expression., Competing Interests: Conflicts of Interest: Sun Y, None; Li ZZ, None; Yang J, None; Sha YR, None; Hou XY, None; Fu H, None; Li JY, None; Bai SC, None; Xie YF, None; Wang GH, None., (International Journal of Ophthalmology Press.)

Background: The superiority between TAF and ETV remains unclear. Which is the best choice for patients with CHB? Thus, this meta-analysis aimed to evaluate the efficacy and safety of TAF and ETV for patients with CHB., Methods: MEDLINE/PubMed, Cochrane Library, EMBASE, Web of Science and CNKI were searched for eligible studies from inception to January 2024 and a meta-analysis was done., Results: 24 trials with a total of 6753 subjects were screened. TAF significantly improved 12- and 24-week complete virological response (CVR), 12-week biochemical response (BR) and 24-week HBeAg loss, but could not improve 48- and 96-week CVR, 24-, 48- and 96-week BR, 96-week HBeAg loss, adverse events, 48-week HBsAg decline and loss, 12-, 24- and 48-week HBeAg seroconversion, 96-week HCC incidence compared to ETV. Subgroup analysis was conducted according to race, research type and switching. Different results were obtained from different subgroups., Conclusions: TAF was superior to ETV at 12- and 24-week CVR, 12-week BR and 24-week HBeAg loss. Race and switching might affect the efficacy of TAF and ETV., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is a common neurosurgical disorder with high morbidity and poor prognosis, and the associated delayed cerebral ischemia (DCI) is a key factor contributing to poor prognosis. Despite extensive research on the risk factors associated with DCI development, the evidence remains conflicting. Therefore, this meta-analysis of case-control studies aimed to investigate the risk factors for DCI occurrence during hospitalization in patients with aSAH., Methods: We systematically searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials for eligible studies published before November 20, 2023. Two independent reviewers extracted relevant data from the included studies using a pre-established data extraction form. The primary outcome was DCI occurrence during hospitalization in patients with aSAH., Results: A total of 42 studies involving 21,726 patients with aSAH were included. The pooled meta-analysis showed that female sex; Hunt-Hess, modified Fisher, and World Federation of Neurosurgical Societies scale scores of 4-5, 3-4, and 4-5, respectively; vasospasm; combined intraventricular hemorrhage; pre-existing hypertension; hydrocephalus; intracranial infections; and high white blood cell count on admission were independent risk factors for the development of postoperative DCIs in patients with aSAH., Conclusions: Patients with aSAH who have a Hunt-Hess scale score ≥4, a modified Fisher scale score ≥3, a WFNS scale score ≥4, intraventricular hemorrhage, pre-existing hypertension, cerebral vasospasm, a high white blood cell count on admission, intracranial infection, and female sex are at high risk of DCI and hence should be carefully monitored in the intensive care unit., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Prior research show that relative deprivation can decrease individuals' psychological well-being. However, the underlying mechanism between relative deprivation and psychological well-being remains unclear. To explore the mediating effects of self-efficacy and self-control on the relationship between relative deprivation and psychological well-being. 426 undergraduate students submitted the online survey that assessed their psychological well-being, relative deprivation, self-efficacy and self-control. Students experienced high levels of psychological well-being, moderate to high levels of relative deprivation and moderate levels of self-efficacy and self-control. Parallel mediators of self-efficacy and self-control on the relationship between relative deprivation and psychological well-being were significant (each p < 0.01). This study explores the underlying mechanism between relative deprivation and psychological well-being by identifying the parallel mediators of self-efficacy and self-control. Effective interventions should be taken to alleviate students' relative deprivation and promote their self-efficacy, self-control and psychological well-being during future pandemics., (© 2024. The Author(s).)

The prevalence of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) and carbapenem-resistant Enterobacterales (CRE) has become a global public health problem. ESBL-E/CRE colonization can increase the risk of infection in patients and lead to poor disease prognosis. We conducted a systematic review and meta-analysis to evaluate current decolonization strategies regarding ESBL-E/CRE and their efficacy. A literature search was conducted until August 2023 on the five databases to review decolonization strategies associated with ESBL-E/CRE. A meta-analysis was conducted using RevMan 5.4 to compare differences in the decolonization strategy with placebo controls. The primary outcome was decolonization rates, with secondary outcomes of attributable death and adverse events. Quality of identified studies was determined using the Newcastle-Ottawa scale and cochrane risk assessment tool. Random and fixed effects meta-analyses were performed to calculate pooled value. A total of 25 studies were included. In five randomized controlled trial (RCT) studies, the decolonization effect of selective digestive decontamination(SDD) on ESBL-E/CRE at the end of treatment was significantly better in the experimental group than the controls [risk radio (RR): 3.30; 95% CI 1.78-6.14]. In three n-RCT studies, the decolonization effect in the experimental group was still better than the controls one month after SDD therapy [odds ratio (OR): 4.01; 95% CI 1.88-8.56]. The combined decolonization rates reported by six single-arm trial studies of SDD therapy ranged from 53.8 to 68.0%. Additionally, TSA analysis confirmed the effectiveness of SDD therapy. In studies on Faecal microbiota transplantation (FMT) therapy, the decolonization effect of the experimental group was significantly better than the controls 1 month after treatment (OR: 2.57; 95% CI 1.07-6.16). In studies without a control group and with varying follow-up times, the decolonization rates varied widely but indicated the effectiveness trend of FMT therapy (61.3-81.2%). Currently, research on the decolonization effect of probiotic therapy on ESBL-E/CRE is insufficient, and only a systematic review was conducted. SDD and FMT strategies have short-term benefits for ESBL-E/CRE decolonization, but long-term effects are unclear. The effect of probiotic therapy on ESBL-E/CRE decolonization is an interesting topic that still requires further investigation., (© 2024. The Author(s).)

Pyroptosis, driven by the N-terminal domain of gasdermin proteins (GSDM), promotes antitumor immunity by attracting lymphocytes to the tumor microenvironment (TME). However, current pyroptosis-inducing therapies like drug injections and phototherapy are limited to localized treatments, making them unsuitable for widespread or microscopic metastatic lesions. This study engineered oncolytic M1 viruses (rM1-mGSDME&#95;FL and rM1-mGSDME&#95;NT) to selectively deliver GSDME to tumor cells. These modified viruses enhanced tumor cell death in breast cancer models, suppressed tumor growth, extended survival in mice, and boosted immune cell infiltration, demonstrating significant anticancer potential through pyroptosis induction., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Background and Aims: The phenomenon of myosteatosis, characterized by the accumulation of ectopic fat within and surrounding skeletal muscle, has been identified as a potential adverse factor in the prognosis of individuals with cancer. This systematic review and meta-analysis sought to examine the association between myosteatosis and survival rates as well as postoperative complications in patients diagnosed with pancreatic cancer (PC)., Methods: A systematic search was conducted on Web of Science, Embase, and Pubmed until March 25, 2024, to identify pertinent articles assessing the prognostic significance of myosteatosis in patients with PC, utilizing the search terms: myosteatosis, PC, and prognosis. The selected studies were utilized to investigate the prognostic impact of myosteatosis on the survival of PC patients. Forest plots and pooled effects models were employed to present the findings of this meta-analysis. The quality of the included studies was evaluated using the Newcastle-Ottawa Scale (NOS). A total of 565 studies were initially identified from the three databases, with 14 retrospective cohort studies ultimately included in the final quantitative analysis., Results: The meta-analysis revealed a significant association between myosteatosis and both overall survival (OS) [Hazard Ratio (HR): 1.55, 95 % Confidence Interval (CI): 1.40-1.72, P < 0.001, I 2  = 0.0 %] and recurrence-free survival (RFS) (HR 1.48, 95 % CI: 1.17-1.86, P = 0.001, I 2  = 0.0 %) in patients diagnosed with PC. Subgroup analyses revealed that myosteatosis continued to be a negative prognostic factor in PC across various treatment modalities, patient populations, and myosteatosis assessment methods. Additionally, myosteatosis was identified as a risk factor for postoperative complications, with a pooled odds ratio of 2.20 (95 % CI: 1.45-3.35, P < 0.001, I 2  = 37.5 %). All included studies achieved NOS scores of 6 or higher, indicating a relatively high level of methodological quality., Conclusion: These results suggest that myosteatosis is significantly associated with both survival outcomes and postoperative complications in patients with PC., Competing Interests: Conflict of interest There is no conflict of interest., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Cardiac troponin I (cTnI) has been widely used in clinical diagnosis of acute myocardial infarction (AMI). Herein, a sensitive electrochemical biosensor for cTnI analysis was designed, in which the simple synthesized Pd@PdPtCo mesoporous nanopolyhedras (MNPs) were utilized as signal amplifiers. The mesoporous polyhedral structure of Pd@PdPtCo MNPs endows them with more specific surface area and more active sites, as well as the synergistic effect between multiple metal elements, all of which increase the electrocatalytic performance of Pd@PdPtCo MNPs in efficiently oxidizing hydroquinone (HQ) to benzoquinone (BQ). Experimental results showed that Pd@PdPtCo MNPs had better performance in oxidation of HQ to BQ compared with their corresponding monometallic and bimetallic nanomaterials. With the aid of the interaction between antigens and antibodies, the peak current of HQ to BQ showed an upward trend with increasing concentration of cTnI, thus the quantitative detection of cTnI could be achieved. Under optimal conditions, the biosensor prepared in this work has a wider linear range (1.0 × 10 -4 -200 ng mL -1 ) and a lower detection limit (0.031 pg mL -1 ) than other sensors reported in literatures, coupled by good stability and high sensitivity. More importantly, it also performed well in complex serum environment, proving that the electrochemical sensor has a practical application potential in this field., 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.)

Background: The metastasis of hepatocellular carcinoma (HCC) leads to a poor prognosis, wherein the activation of Notch1 is an essential contributor. Cepharanthine (Cep) has been identified for its effective antiviral function and versatile intracellular targets. Our previous study has only reported the anti-cancer efficacy of Cep in lung cancer, without an in-depth exploration. Herein, the present study aims to investigate the anti-metastasis effect in HCC, the target involved, and the molecular mechanism of Cep., Methods: Stable over-expression of Notch1-N1ICD yielded C5WN1 cells compared with C5WBF344 cells. The C5WN1 cells and C5WN1 cell-bearing mice were applied as the HCC model. The bioinformatics analysis, RNA sequencing, molecular docking, cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS), microscale thermophoresis (MST), and transient knockdown techniques were carried out to identify the underlying target. The apoptosis assay, immunofluorescent staining, qRT-PCR, Western blots, Elisa, flow cytometry, migration and scratching experiments, Transmission electron microscopy (TEM), laser scanning confocal microscopy (LSCM), micro-computed tomography (micro-CT), and histopathological experiments were conducted to assay the anti-HCC efficacy, functions, and mechanism., Results: Notch1 had an increased expression in HCC and contributed to metastasis thereupon. Surprisingly, Cep (2 μg/ml in vitro, 5 mg kg -1 in vivo) presented potent Notch1 signaling pathway inhibitory effect and anti-metastasis efficacy in C5WN1 cells and in situ mice models as evidenced by reduced Notch1/MMP-2/MMP-9 expression, TGF-β release, decreased cell migration, diminished pulmonary metastases, and prolonged survival. RNA sequencing showed that the differential gene of Cep-treated HCC cells was positioned in the endoplasmic reticulum (ER). Molecular docking, CETSA, DARTS, and MST further identified that the possible target of Cep was GRP78, which was distributed in the ER. As expected, Cep (2 μg/ml) up-regulated the critical molecules of ER stress such as GRP78, induced β-amyloid accumulation, and promoted calcium burst in HCC. In contrast, suppression of GRP78 attenuated Cep-induced ER stress. Furthermore, inhibition of ER stress abated Cep-induced Notch1 inactivation and HCC cells' migration., Conclusions: Taken together, the present study finds that Cep possesses excellent anti-metastasis of HCC, wherein the GRP78 could be directly bound and activated by Cep, leading to ER stress and Notch1 blockage. This study reveals for the first time the effect, critical target, and mechanism of the Cep-mediated anti-cancer effect, providing novel insights into the molecular target therapy by phytomedicine., 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 GmbH. All rights reserved.)

Objective: To explore the relationship between anion gap (AG) and length of stay (LOS) in patients undergoing hip fracture surgery., Methods: Clinical data of patients diagnosed with hip fracture and undergoing surgery were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Logistic regression analysis by adjusting different covariables and threshold effect analysis were used to analyze the relationship between AG and LOS. Subgroup analysis and interaction test were also performed to detect their relationship. Receiver Operating Characteristic (ROC) analysis was performed to identify the prediction performance and cutoff value of AG.Kaplan-Meier (KM) survival analysis was used to explore the influence of AG on overall survival., Results: A total of 1508 patients were enrolled and the median LOS was 4.9 days. The correlation between AG and LOS > 7 days was observed among 3 regression models when regarding AG as continuous variables (all OR > 1, all P < 0.05). After stratifying samples with AG quartiles, their relationship was only presented in the Q4 group both in model 1 and model 2 (all P < 0.001). The risk of LOS > 7 days gradually increased with increasing AG quartiles (all P for trend < 0.05). Further, threshold effect analysis found that their association was mainly observed when AG ≥ 14 mEq/L (OR = 1.122, P < 0.001). Subgroup analysis showed that their correlation was not influenced by sex, age, BMI, ethnicity, classification of fracture, therapeutic method, CHD, hypertension, osteoporosis, diabetes and admitted to the ICU (all P for interaction > 0.05). ROC analysis identified 14.5 as the cutoff value of AG for predicted LOS > 7 days. Survival analysis found that patients in the AG < 14.5 group had better overall survival., Conclusion: In patients undergoing hip fracture surgery, the AG was positively correlated with LOS, and 14.5 mEq/L AG was the cutoff value for predicting LOS > 7 days. The cutoff value can favorably distinguish the survival difference of patients., (© 2024. The Author(s).)

Background: Several recent studies have confirmed that intratumoural microorganisms can affect the occurrence and development of hepatocellular carcinoma (HCC); however, their role in tumor progression remains unclear. Hence, there is a need for further research on the role of intratumoural microorganisms in HCC., Aim: To investigate the changes in intratumoural microorganisms in HCC and the effect of Propionibacterium on HCC progression., Methods: HCC and normal liver tissue specimens were subjected to fluorescence in situ hybridization (FISH). After performing 16S rRNA sequencing on HCC and peritumoral tissues to analyze the differences between the two groups. Propionibacterium was cocultured with HCC cells in vitro . Changes in cell proliferation and migration capacity were evaluated. The expression of NF-κB pathway related proteins in tumor cells was compared. The orthotopic liver implantation model and the subcutaneous xenograft model were constructed. liver tissues and subcutaneous tumors were collected 2 weeks later., Results: FISH demonstrated the presence of microorganisms in HCC and normal liver tissues. 16S rRNA sequencing revealed an abundance of Lysobacter , Lachnospiraceae , Pseudomonas , and Lactobacillus in HCC tissues. The distribution and abundance of Propionibacterium showed differences between HCC and peritumoral tissues ( P < 0.05). In vitro studies demonstrated that Propionibacterium and its metabolite propionic acid (PA) inhibited the proliferation and migration of HCC cells ( P < 0.05). The expression of the proteins in NF-κB signaling pathway also decreased in HCC cells ( P < 0.05)., Conclusion: Microorganisms in HCC and normal liver tissues displayed significant disparities. The PA-producing bacterium Propionibacterium in HCC exerts an effect on the NF-κB pathway, thereby affecting the biological behavior of HCC., Competing Interests: Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Regulated cell death (RCD) is a genetically controlled form of cell death that plays an important role in organogenesis, tissue remodeling, and pathogenesis of cancers. Transforming growth factor-beta-activation kinase 1 (TAK1) is a member of the serine/threonine protein kinase family, which can respond to internal and external stimuli and participate in inflammatory responses through multiple signaling pathways and cellular processes. In the last two decades, the regulatory roles of TAK1 at the crossroads of multiple RCD pathways, including apoptosis, necroptosis, pyroptosis, and PANoptosis were revealed by 801 articles retrieved from the Web of Science Core Collection database. To analyze global research trends and hotspots concerning the role of TAK1 in RCD, the bibliometric and visualized analysis were applied in the current study., Methods: The data for this bibliometrics study were retrieved from the Web of Science Core Collection database. The search formula was (TS=(Apoptosis) OR TS=(pyroptosis) OR TS=(Necroptosis) OR TS=(PANoptosis) OR TS=(Autophagy) OR TS=(Ferroptosis) OR TS=(cuproptosis)) AND ((TS=(TAK1)) OR TS=(MAP3K7)). The co-occurrence and co-cited analysis on basic bibliometric parameters were conducted by VOSviewer. The dual-map overlay of journals, citation bursts, keyword timelines, and keyword bursts were analyzed by CiteSpace., Results: A total of 801 articles from 46 countries have been included in the analysis. The number of publications demonstrates a consistent increase from 1999 to 2024. The primary research institutions driving this field are Osaka University Notably, the Journal of Biological Chemistry stands out as the most popular journal in this domain. These publications collectively involve contributions from 4663 authors, with Jun Tsuji emerging as a prolific author. Jun Tsuji also gains the highest co-citation frequency. Emerging research hotspots are encapsulated by keywords, including apoptosis, NF-κB, inflammation, autophagy, and TNFα., Conclusion: This is the first bibliometric and visualized study to analyze the global trends and hotspots of TAK1 in RCD. Based on the analysis of 801 articles, the results provide a retrospective and comprehensive visualized view of the research hotspots and frontiers of TAK1 at the crossroads of multiple RCD signaling pathways and propose ideas for guiding their future investigations in molecular mechanisms and therapeutic strategies in this field., Competing Interests: 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. The reviewer GY declared a shared affiliation, with no collaboration, with one of the authors, RL, to the handling editor at the time of the review., (Copyright © 2024 Huang, He, Wan, Ban, Chen, Hu, Wan, Lu, Zhang and Xiong.)

Metabolic reprogramming precedes most alterations during pathological cardiac hypertrophy and heart failure (HF). Recent studies have revealed that Phosphofructokinase, platelet (PFKP) has a wealth of metabolic and non-metabolic functions. In this study, we explored the role of PFKP in cardiac hypertrophic growth and HF. The expression level of PFKP was elevated both in pathological cardiac remodeling mouse model challenged by transverse aortic constriction (TAC) surgery and in the neonatal rat cardiomyocytes (NRCMs) stimulated by phenylephrine (PE). In global PFKP knockout (PFKP-KO) mice, cardiac hypertrophy was ameliorated under TAC surgery, while overexpression of PFKP by intravenous injection of adeno-associated virus 9 (AAV9) under the cardiac troponin T (cTnT) promoter worsened myocardial hypertrophy and fibrosis. In NRCMs, small interfering RNA (SiRNA) knockdown or adenovirus (Adv) overexpression of PFKP was employed and the intervention of PFKP showed a similar phenotype. Mechanistically, immunoprecipitation combined with liquid chromatography-tandem mass spectrometry (IP-MS/MS) analysis was used to identify the interacting proteins of PFKP. Eukaryotic translation initiation factor 2 subunit beta (EIF2S2) was identified as the downstream target of PFKP. In the PE-stimulated NRCM hypertrophy model and mouse TAC model, knocking down EIF2S2 after PFKP overexpression reduced the synthesis of new proteins and alleviated the hypertrophy phenotype. Our findings illuminate that PFKP participates in pathological cardiac hypertrophy partly by regulating protein synthesis through EIF2S2, which provides a new clue for the involvement of metabolic intermediates in signal transduction., 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 Author(s). Published by Elsevier B.V. All rights reserved.)

This review explores calixarenes, a prominent family of third-generation supramolecules celebrated for their distinct hollow, cavity-shaped structures. These macrocycles are intricately assembled by linking multiple phenolic units orthogonally through methylene (-CH 2 -), sulfur (-S-), or sulfonyl (-SO 2 -) bridges. This structural framework plays a pivotal role in the intricate assembly of nanoclusters, significantly advancing the field of cluster chemistry. A key focus of current research is the remarkable ability of calixarenes to stabilize titanium-oxo clusters. Our review details the application of calixarenes in constructing titanium-oxo cluster structures, emphasizing how these clusters, when encapsulated within calixarenes, exploit flexible coordination sites for structural modifications and serve as foundational units for more complex assemblies. Additionally, we investigate how these calixarene-stabilized metal-oxo clusters function as versatile scaffolds for catalytically active metal ions, facilitating the creation of bimetallic nanoclusters. These clusters not only exhibit unique structural diversity but also demonstrate exceptional catalytic efficiency. This review aims to inspire ongoing exploration and innovation in the use of calixarenes for the synthesis and application of advanced cluster materials.

The progression of gastric cancer involves a complex multi-stage process, with gastroscopy and biopsy being the standard procedures for diagnosing gastric diseases. This study introduces an innovative non-invasive approach to differentiate gastric disease stage using gastric fluid samples through machine-learning-assisted surface-enhanced Raman spectroscopy (SERS). This method effectively identifies different stages of gastric lesions. The XGBoost algorithm demonstrates the highest accuracy of 96.88% and 91.67%, respectively, in distinguishing chronic non-atrophic gastritis from intestinal metaplasia and different subtypes of gastritis (mild, moderate, and severe). Through blinded testing validation, the model can achieve more than 80% accuracy. These findings offer new possibilities for rapid, cost-effective, and minimally invasive diagnosis of gastric diseases., Competing Interests: Declaration of competing interest The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Electrocatalytic nitrate removal offers a sustainable approach to alleviate nitrate pollution and to boost the anthropogenic nitrogen cycle, but it still suffers from limited removal efficiency at high rates, especially at low levels of nitrate. Herein, we report the near-complete removal of low-level nitrate (10-200 ppm) within 2 h using ultrathin cobalt-based nanosheets (CoNS) containing surface oxygen, which was fabricated from in-situ electrochemical reconstruction of conventional nanosheets. The average nitrate removal of 99.7 % with ammonia selectivity of 98.2 % in 9 cyclic runs ranked in the best of reported catalysts. Powered by a solar cell under the winter sun, the full-cell nitrate electrolysis system, equipped with ultrathin CoNS, achieved 100 % nitrogen gas selectivity and 99.6 % total nitrogen removal. The in-situ Fourier Transform Infrared included experiments and theoretical computations revealed that in-situ electrochemical reconstruction not only increased electrochemical active surface area but also constructed surface oxygen in active sites, leading to enhanced stabilization of nitrate adsorption in a symmetry breaking configuration and charge transfer, contributing to near-complete nitrate removal on ultrathin CoNS. This work provides a strategy to design ultrathin nanocatalysts for nitrate removal., 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.)

Background: Sympathetic hyperactivity contributes to the pathogenesis of hypertension. However, it is unclear whether the excessive sympathetic activity is an independent and crucial factor for vascular remodeling in hypertension. This study focused on the effect of local sympathetic denervation with superior cervical ganglionectomy (SCGx) on vascular remodeling., Methods: Surgical bilateral SCGx was performed in 9-week-old male Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Control rats received sham-operation without SCGx. All measurements were made 4 weeks after the surgery., Results: The effectiveness of SCGx was confirmed by the eye features of Horner syndrome, greatly reduced tyrosine hydroxylase (TH) contents in the superior cervical ganglion (SCG)-innervated arteries in the head. Although SCGx had no significant effects on blood pressure and heart rate in WKY and SHR, it attenuated vascular remodeling of facial artery and superficial temporal artery in SHR, two representative SCG-innervated extracranial arteries, without significant effects on non-SCG-innervated thoracic aorta and mesenteric artery. SCGx-treated SHR had more auricular blood flow and retina microvasculature than sham-operated SHR. However, SCGx had only a mild effect in attenuating the vascular remodeling of basilar artery and middle cerebral artery, two representative SCG-innervated intracranial arteries, in SHR. SCGx-treated SHR exhibited upregulation of α-smooth muscle actin, downregulation of proliferating cell nuclear antigen, and attenuation of oxidative stress and inflammation in facial artery and superficial temporal artery., Conclusions: Sympathetic denervation by SCGx in SHR attenuated local vascular remodeling, suggesting that sympathetic overactivity is a crucial pathogenic factor of vascular remodeling in SHR., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Agroforestry system with high biodiversity augments ecosystem stability and minimizes its vulnerability to environmental disturbances and disease. Deciphering the underlying mechanisms of interspecies allelopathic interactions in disease suppression in agroforestry offer a sustainable strategy for plant disease management. Here, we utilized Panax ginseng cultivated under Pinus koraiensis forests, where the occurrences of Alternaria leaf spot are low, as a research model to investigate the role of allelochemicals in disease suppression. Our findings demonstrate that foliar application of leachates from the needles of P. koraiensis effectively enhanced the resistance of P. ginseng against Alternaria leaf spot. Through GC-MS analysis, we identified and quantified endo-borneol as a key compound in the leachates of P. koraiensis, and validated its capacity to prime resistance in its neighbor P. ginseng. We discovered that endo-borneol not only directly activates defense-related pathways of P. ginseng to induce resistance, but also indirectly recruits its rhizospheric beneficial microbiota by enhancing the secretion of ginsenosides, thereby triggering induced systemic resistance (ISR). Importantly, the higher concentrations of endo-borneol from 10 to 100 mg/L demonstrated a stronger capacity to induce plant resistance and enhance root secretion to recruit more microbiota compared with the lower concentrations from 0.01 to 1 mg/L. Moreover, endo-borneol exhibited antifungal activity against the growth of the pathogen Alternaria panax when its concentrations exceeding 10 mg/L. These results reveal the multifaceted functions of allelochemical endo-borneol in disease suppression in agroforestry system and highlight its potential as an environmental-friendly compound for sustainable agriculture., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Though the survival of breast cancer (BC) patients with malignant pleural effusion (MPE) has been studied, this has not been specifically studied in the luminal B subtype. Therefore, this study investigated the characteristics and survival of luminal B-BC patients presenting with MPE., Methods: We retrospectively analyzed 141 patients diagnosed with postoperative advanced Luminal B breast cancer, including 54 cases with MPE and 87 cases without MPE at the Tianjin Cancer Hospital from January 2012 to January 2015. We assessed the clinical characteristics between the groups., Results: The mean age of all patients was 47 years, with no significant difference between the two groups. Altogether, 29 (33%), 24 (28%), 28 (32%), 45 (52%), and 10 (11%) patients had lung, liver, bone, lymph node, and chest wall metastases, respectively. In addition. The difference in overall survival between the two groups was not significant (P>0.05). However, cox regression analysis showed that only the tumor clinical stage at initial diagnosis was related to short overall survival. Further, we conducted a subgroup analysis and found that the higher the clinical stage at initial diagnosis in age < 50 years patients, the shorter the overall survival, while age > 50 years patients was not. (P < 0.05)., Conclusions: There was no difference in the overall survival between luminal B-BC patients with MPE and those without. Clinical stages at initial diagnosis were an independent prognostic factor for age < 50 years luminal B BC with MPE overall survival. Our results may help clinicians make positive decisions regarding personalized treatment of luminal B-BC with MPE., (© 2024. The Author(s).)

In this work, a superhydrophobic polypropylene (PP) replica with nanowires is fabricated using an injection compression molding (ICM) process. The morphology, superhydrophobicity and fog water harvesting efficiency of the as-prepared PP replica surface are investigated. Morphological characterization indicates that the PP replica surface exhibits nanowires with intertwined tips. Compared to the untreated PP surface (referred to as the PP counterpart), the PP replica surface shows a higher contact angle (CA) and lower rolling angle (RA). Furthermore, the complete transfer of a water droplet with no volume loss from the PP replica surface to the filter paper shows that nanowires on the PP replica surface are responsible for the superhydrophobic and low-adhesive properties of the surface. The Cassie-Baxter state with a CA of ∼153°, low ice adhesion strength (13.3 kPa at -20 °C) and good fog water harvesting efficiency (∼7.26 g m -2 s -1 ) demonstrate that the prepared PP replica has economic potential for fog water harvesting applications., Competing Interests: 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., (This journal is © The Royal Society of Chemistry.)

Catalytic enantioselective preparation of alkene atropisomers with multiple stereogenic elements and discovery of their applications have become significant but challenging issues in the scientific community due to the unique structures of this class of atropisomers. We herein report the first catalytic atroposelective preparation of cyclopentenyl[b]indoles, a new kind of alkene atropisomers, with stereogenic point and axial chirality via an unusual rearrangement reaction of 3-indolylmethanols under asymmetric organocatalysis. Notably, this novel type of alkene atropisomers have promising applications in developing chiral ligands or organocatalysts, discovering antitumor drug candidates and fluorescence imaging materials. Moreover, the theoretical calculations have elucidated the possible reaction mechanism and the non-covalent interactions to control the enantioselectivity. This approach offers a new synthetic strategy for alkene atropisomers with multiple stereogenic elements, and represents the first catalytic enantioselective rearrangement reaction of 3-indolylmethanols, which will advance the chemistry of atropisomers and chiral indole chemistry., (© 2024 Wiley-VCH GmbH.)

Purpose: Transformational leadership among core hospital leaders boosts medical organizations' competitiveness, adaptability, and sustainability, which is jointly affected by individual, organizational and environmental factors. This study aims to unpack its configurational framework and propose strategies to strengthen core hospital leaders' transformational leadership., Patients and Methods: Data were collected from an online questionnaire among 31 core hospital leaders. The fuzzy-set qualitative comparative analysis (fsQCA) was used to explore the causal mechanism of high-level transformational leadership. We enrich this mechanism by professional background, critical thinking, initiative spirit, family-work conflict, job satisfaction, subordinates' followership, and work pressure., Results: Result shows initiative spirit is the only necessary condition (consistency=0.911) for the formation of high-level transformational leadership among core hospital leaders. Three configurations are the sufficient conditions that lead to high-level transformational leadership among core hospital leaders with two different professional backgrounds (overall solution consistency= 0.952)., Conclusion: Core hospital leaders' initiative spirit is an indispensable condition for improving high-level transformational leadership, emphasizing the necessity for core leaders to be proactive in order to develop such leadership. Besides, the study also uncovered three configurations are the sufficient conditions for core hospital leaders with diverse professional backgrounds to achieve high-level transformational leadership. This finding offers significant insights into hospital management practices, suggesting that core hospital leaders' work should be managed in a personalized manner based on their professional backgrounds, thereby fostering favorable conditions conducive to the development of their high-level transformational leadership capabilities. Furthermore, the central insight of this study is that the formation of high-level transformational leadership contingent upon the collaboration of professional background, critical thinking, initiative spirit, family-work conflict, job satisfaction, subordinates' followership, and work pressure, contributing to a holistic and more rigorous view for the development of transformational leadership., Competing Interests: The authors declare no conflict of interest., (© 2024 Zhang et al.)

Background: The CCDC22 gene plays vital roles in regulating the NF-κB pathway, an essential pathway for neuroinflammation, neurodevelopment, and epileptogenesis. Previously, variants in CCDC22 were reported to be associated with intellectual disability. This study aimed to explore the association between CCDC22 and epilepsy., Methods: Trios-based whole-exome sequencing (WES) was performed in a cohort of patients with epilepsy of unknown cause recruited from the China Epilepsy Gene 1.0 Project. Damaging effects of variants were analysed using protein modelling., Results: Hemizygous missense CCDC22 variants were identified in three unrelated cases. These variants had no hemizygous frequencies in controls. All missense variants identified in this study were predicted to be "damaging" by multiple in silico tools and to alter the hydrogen bonds with surrounding residues and/or protein stability. The three patients presented with focal epilepsy of varying severity, including one with refractory seizures and focal cortical dysplasia (FCD) and two with seizures responding to antiseizure medicine. Notably, the variant associated with the severe phenotype was located in the coiled-coil domain and predicted to alter hydrogen bonding and protein stability, whereas the two variants associated with mild epilepsy were located outside functional domains and had moderate molecular alterations. Analysis of spatiotemporal expression indicated that CCDC22 was expressed in brain subregions with three peaks in the fetal stage, infancy, and early adulthood, especially in the fetal stage, explaining the occurrence of developmental abnormities., Significance: CCDC22 variants are potentially associated with X-linked focal epilepsy and FCD. The molecular subregional effects supported the occurrence of FCD., Competing Interests: Declaration of competing interest All the authors declare that there are no conflicts of interest., (Copyright © 2024 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: Conflicts of interest None disclosed.

Early vascular healing after drug-eluting stent (DES) implantation is associated with better outcomes and lower incidence of in-stent thrombosis. To examine vascular healing response in patients with non-ST elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI) guided by optical coherence tomography (OCT) versus angiography alone. Sixty patients were randomized 1:1:1 to OCT-guided PCI with 3-month OCT follow-up (O3 group, n = 20), angiography-guided PCI with 3-month OCT follow-up (A3 group, n = 20), or angiography-guided PCI with 6-month OCT follow-up (A6 group, n = 20). The primary endpoint was the proportion of covered struts at 3- or 6-month follow-up. The proportion of covered struts in the O3 group was significantly higher than in the A3 group (95.2% vs. 92.3%, p < 0.001), but lower than in the A6 group (95.2% vs. 97.4%, p < 0.001). The O3 group had a lower proportion of incomplete strut apposition (ISA) than the A3 group (0.46% vs. 0.76%, p = 0.006), and higher than the A6 group (0.46% vs. 0.27%, p = 0.018) at follow-up. The optimal cut-off value of ISA after implantation of DES for predicting stent coverage at 3 and 6-month follow-up was 200 μm and 308 μm, respectively. Only one patient experienced target lesion revascularization in the A3 group during a 3-year clinical follow-up. In patients with NSTE-ACS undergoing PCI with DES, OCT guidance achieved higher strut coverage compared with angiography guidance at 3-month follow-up. However, the difference in the strut coverage between the OCT-guided group and the angiography-guided group at 6 months indicates that the degree of endothelialization may be more time-dependent instead of invasive device guidance., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The transition of stem cells from a quiescent state to an active state is a finely tuned process that requires the dismantling of the quiescence program and the establishment of a cell cycle-promoting transcriptional landscape. Whether epigenetic processes control stem cell states to promote the regeneration of adult tissues remains elusive. In this study, we show that a repressive histone modification, H2AK119ub, is dynamic between quiescent and active hair follicle stem cells (HFSCs) in the adult murine skin. Ablation of H2AK119ub in HFSCs leads to impaired quiescence leading to premature activation and an eventual exhaustion of HFSC pool. Transcriptional and chromatin studies revealed that H2AK119ub directly represses a proliferation promoting transcriptional program in the HFSCs to preserve quiescence. Lastly, we identify that the inhibitory FGF signaling produced by the hair follicle niche keratinocytes maintains H2AK119ub in quiescent HFSCs. Together, these findings reveal that a repressive histone mark, H2AK119ub, is under the dynamic regulation of inhibitory niche signaling to prevent the untimely establishment of an activated state to preserve SC function and longevity.

Vascular calcification (VC) arises from the accumulation of calcium salts in the intimal or tunica media layer of the aorta, contributing to higher risk of cardiovascular events and mortality. Despite this, the mechanisms driving VC remain incompletely understood. We previously described that nesfatin-1 functioned as a switch for vascular smooth muscle cells (VSMCs) plasticity in hypertension and neointimal hyperplasia. In this study, we sought to investigate the role and mechanism of nesfatin-1 in VC. The expression of nesfatin-1 was measured in calcified VSMCs and aortas, as well as in patients. Loss- and gain-of-function experiments were evaluated the roles of nesfatin-1 in VC pathogenesis. The transcription activation of nesfatin-1 was detected using a mass spectrometry. We found higher levels of nesfatin-1 in both calcified VSMCs and aortas, as well as in patients with coronary calcification. Loss-of-function and gain-of-function experiments revealed that nesfatin-1 was a key regulator of VC by facilitating the osteogenic transformation of VSMCs. Mechanistically, nesfatin-1 promoted the de-ubiquitination and stability of BMP-2 via inhibiting the E3 ligase SYTL4, and the interaction of nesfatin-1 with BMP-2 potentiated BMP-2 signaling and induced phosphorylation of Smad, followed by HDAC4 phosphorylation and nuclear exclusion. The dissociation of HDAC4 from RUNX2 elicited RUNX2 acetylation and subsequent nuclear translocation, leading to the transcription upregulation of OPN, a critical player in VC. From a small library of natural compounds, we identified that Curculigoside and Chebulagic acid reduced VC development via binding to and inhibiting nesfatin-1. Eventually, we designed a mass spectrometry-based DNA-protein interaction screening to identify that STAT3 mediated the transcription activation of nesfatin-1 in the context of VC. Overall, our study demonstrates that nesfatin-1 enhances BMP-2 signaling by inhibiting the E3 ligase SYTL4, thereby stabilizing BMP-2 and facilitating the downstream phosphorylation of SMAD1/5/9 and HDAC4. This signaling cascade leads to RUNX2 activation and the transcriptional upregulation of MSX2, driving VC. These insights position nesfatin-1 as a potential therapeutic target for preventing or treating VC, advancing our understanding of the molecular mechanisms underlying this critical cardiovascular condition., (© 2024. The Author(s).)

Background: To assess the association between periodontal disease (PD) and the prognosis of chronic kidney disease (CKD)., Methods: A systematic literature search was conducted using PubMed, Embase, and Cochrane Library to identify eligible cohort studies until April 2023. Relative risk (RR) with a 95% confidence interval (CI) was used to evaluate the strength of the relationship between PD and CKD prognosis using the random-effects model., Results: 10 cohort studies involving 10,144 patients with CKD were selected for the meta-analysis. The summary results indicated that PD was associated with an increased risk of all-cause mortality in patients with CKD (RR:1.32; 95%CI:1.10-1.59; 𝑝 = 0.003). Although no association was observed between PD and the risk of cardiac death in patients with CKD (𝑝 = 0.180), while sensitivity analysis revealed PD may be associated with the risk of cardiac death (RR:1.31; 95%CI:1.05-1.64; 𝑝 = 0.017). In addition, subgroup analyses revealed that the strength of the association of PD with the risks of all-cause mortality and cardiac death varies when stratified by region, male proportion, comparison, CKD stage, and adjusted level., Conclusion: Herein, PD might exert a harmful effect on the subsequent risks of all-cause mortality and cardiac death in patients with CKD., Competing Interests: Conflict of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Rational design of robust photocatalytic systems to direct capture and in-situ convert diluted CO 2 from flue gas is a promising but challenging way to achieve carbon neutrality. Here, we report a new type of host-guest photocatalysts by integrating CO 2 -enriching ionic liquids and photoactive metal-organic frameworks PCN-250-Fe 2 M (M = Fe, Co, Ni, Zn, Mn) for artificial photosynthetic diluted CO 2 reduction in gas-solid phase. As a result, [Emim]BF 4 (39.3 wt%)@PCN-250-Fe 2 Co exhibits a record high CO 2 -to-CO reduction rate of 313.34 μmol g -1 h -1 under pure CO 2 atmosphere and 153.42 μmol g -1 h -1 under diluted CO 2 (15%) with about 100% selectivity. In scaled-up experiments with 1.0 g catalyst and natural sunlight irradiation, the concentration of pure and diluted CO 2 (15%) could be significantly decreased to below 85% and 10%, respectively, indicating its industrial application potential. Further experiments and theoretical calculations reveal that ionic liquids not only benefit CO 2 enrichment, but also form synergistic effect with Co 2+ sites in PCN-250-Fe 2 Co, resulting in a significant reduction in Gibbs energy barrier during the rate-determining step of CO 2 -to-CO conversion., (© 2024. The Author(s).)

Context/objective: The 13-item Patient Activation Measure (PAM-13) is the most widely used generic patient activation measure, but spinal cord injury (SCI) related psychometric evaluation of PAM-13 has not been explored globally. This study aimed to assess the validity of the Chinese version of the PAM-13 (PAM-13-C) for individuals with chronic spinal cord injury (CSCI)., Design: Cross-sectional study., Setting: Shanghai Sunshine Rehabilitation Center, and some participants were recruited in a WeChat group (the most commonly used social media platform in China)., Participants: 284 individuals with spinal cord injury who had lived with the injury for ≥0.5 year., Interventions: NA., Outcome Measures: The PAM-13-C, global QoL, seven-item generalized anxiety disorder scale (GAD-7) and nine-item patient health questionnaire (PHQ-9), and General Self-Efficacy Scale (GSES) were used., Results: The mean (SD) PAM-13-C score was 57.4 (16.5). The highest percentage of NA could be observed in item 9 (12.0%). Floor and ceiling effects of the total scores of PAM-13-C were small (0.7% and 6.7%), but a ceiling effect could be observed among all items. Exploratory Factor Analysis supported a one-factor model of the PAM-13-C (CFI = 0.97; RMSEA = 0.07). Construct validity was established through correlation analysis among the PAM-13-C, GAD-7/PHQ-9, global QoL, and GSES. The PAM-13-C demonstrated excellent internal consistency (Cronbach's α  = 0.95) and acceptable test-retest reliability., Conclusion: The PAM-13-C is a reliable and valid measure of patient activation for individuals with CSCI in China.

Telangiectasia macularis multiplex acquisita is an acquired cutaneous telangiectasis of unknown aetiology, and it lacks both effective and cost-efficient treatment. This study aims to identify a novel potential associated factor of the disease and explore feasible therapeutic interventions. In this retrospective case series study, 46 Chinese patients diagnosed with telangiectasia macularis multiplex acquisita between 1 January 2007 and 18 May 2023 were included. The median age of onset was 43 years (23 to 60 years), and the male to female ratio was 10.5:1. Besides previously reported associations including chronic liver disorders, alcohol consumption, and smoking, a potential association was found between use of calcium channel blockers and development of telangiectasia macularis multiplex acquisita. Twenty-two of 27 hypertensive patients took calcium channel blockers, with 17 followed up. Ten out of 17 displayed a range of improvements following the cessation of calcium channel blockers; 1 patient reported no lesion change post-discontinuation of calcium channel blockers; 1 patient continued their medication but showed partial improvement after 2 pulsed dye laser treatments; 1 patient observed lesion colour lightening without altering hypertensive medication or other specific treatments; and another 4 kept their previous hypertensive regimen due to blood pressure stability concerns, with no change in their lesions. The study proposes that cessation of calcium channel blockers can be a novel therapeutic approach for affected individuals.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by a progressive loss of nigrostriatal dopaminergic neurons. Inhibitors of monoamine oxidase B (MAO-B) have shown promise in alleviating motor symptoms and reducing oxidative stress associated with PD. In this study, we report the novel use of an azastilbene-based compound library for screening human (h)MAO-B, followed by optimization of initial hits to obtain compounds with low nanomolar inhibitory potencies (compound 9, IC 50  = 42 nM) against hMAO-B. To ensure specificity and minimize false positives due to non-specific hydrophobic interactions, we performed comprehensive selectivity profiling against hMAO-A, butyrylcholinesterase (hBChE) and acetylcholinesterase (hAChE) - enzymes with hydrophobic active sites that are structurally distinct from hMAO-B. Docking analysis with Glide provided valuable insights into the binding interactions between the inhibitors and hMAO-B and also explained the selectivity against hMAO-A. In the cell-based model of Parkinson's disease, one of the compounds significantly reduced rotenone-induced accumulation of reactive oxygen species. In addition, these compounds showed a protective effect against acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor dysfunction in PD model mice and reduced MPTP-induced loss of striatal tyrosine hydroxylase-positive neurons in the substantia nigra. These results make azastilbene-based compounds a promising new class of hMAO-B inhibitors with potential therapeutic applications in Parkinson's disease and related neurodegenerative disorders., 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 Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: This systematic review aims to (1) summarize the demographic and clinical characteristics of patients with nontuberculous mycobacterial (NTM) infections following cosmetic procedures; (2) summarize the frequency of pathogenic NTM species; and (3) review and analyze the antibiotics choice as well as treatment outcomes., Methods: We conducted a systematic search of three electronic databases (Scopus, Embase, and PubMed) from inception to March 31, 2024. We presented demographic and clinical features and the main antibiotic strategy, along with etiological information., Results: A total of 200 patients were included in the analysis, with a median onset age of 38.0 years. The median latency period before the illness was 28 days. Nodules were the most frequently reported type of lesion, occurring in 31.0% (n = 62/200) of cases. Mycobacterium abscessus was the most commonly found NTM (45%). Clarithromycin was the most commonly applied (64.0%, n = 128/200), followed by amikacin (31.0%, n = 62/200). The median treatment duration was 6 months (0.25, 24). The overall treatment effectiveness rate was 97.4% (n = 148/152)., Conclusion: NTM infections caused by cosmetic procedures are rapidly increasing worldwide and present diagnostic and treatment challenges. Dermatologists and aesthetic practitioners should be aware of this relatively uncommon disease. Further research is needed to standardize management algorithms., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024. Published by Elsevier Ltd.)

TNFα and related inflammatory factor antibody drugs have been orchestrated for the treatment of inflammatory bowel disease (IBD). However, antibody drugs elicited inevitable disadvantages and small molecule drugs are in an urgent need. Herein, we described the discovery, design, synthesis, and SAR studies from furanone glycoside compound Phoenicein (hit) isolated from Chimonanthus salicifolius to D228 (lead). Remarkably, D228 exhibited good inhibitory activity on B and T lymphocyte and excellent anti-IBD efficacy in vivo . Mechanistically, D228 alleviated the inflammation response by downregulating the MyD88/TRAF6/p38 signaling. Importantly, the relationship of D228 , Phoenicein , and their aglycone 7a was deduced: D228 could be considered as a prodrug and metabolized to intermediate Phoenicein . In turn, Phoenicein released their shared active aglycone 7a . Additionally, D228 demonstrated good and balanced profiles of safety and efficacy both in vitro and in vivo . These results suggested that D228 could be used as an ideal lead and potentially utilized for IBD chemotherapy.

Nervous system diseases are a global health problem, and with the increase in the elderly population around the world, their incidence will also increase. Harmful substances in the environment are closely related to the occurrence of nervous system diseases. China is a large agricultural country, and thus the insecticide cyfluthrin has been widely used. Cyfluthrin is neurotoxic, but the mechanism of this injury is not clear. Inflammation is an important mechanism for the occurrence of nervous system diseases. Mitochondria are the main regulators of the inflammatory response, and various cellular responses, including autophagy, directly affect the regulation of inflammatory processes. Mitochondrial damage is related to mitochondrial quality control (MQC) and PTEN-induced kinase 1 (PINK1). As an anti-inflammatory factor, stimulator of interferon genes (STING) participates in the regulation of inflammation. However, the relationship between STING and mitochondria in the process of cyfluthrin-induced nerve injury is unclear. This study established in vivo and in vitro models of cyfluthrin exposure to explore the role of MQC and to clarify the mechanism of action of STING and PINK1. Our results showed that cyfluthrin can increase the reactive oxygen species (ROS) level, resulting in mitochondrial damage and inflammation. In this process, an imbalance in MQC leads to the aggravation of mitochondrial damage, and high STING expression drives the occurrence of inflammation. We established a differential expression model of STING and PINK1 to further determine the underlying mechanism and found that the interaction between STING and PINK1 regulates MQC to affect the levels of mitochondrial damage and inflammation. When STING and PINK1 expression are downregulated, mitochondrial damage and STING-induced inflammation are significantly alleviated. In summary, a synergistic effect between STING and PINK1 on cyfluthrin-induced neuroinflammation may exist, which leads to an imbalance in MQC by inhibiting mitochondrial biogenesis and division/fusion, and PINK1 can reduce STING-driven inflammation., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: This study aimed to assess the causal relationships between vitamin D levels and ocular disorders., Methods: Independent genetic variables were obtained from genome-wide association studies (GWAS) and publicly available databases. The summary statistics for 25-hydroxyvitamin D (25(OH)D) were obtained from two large-scale GWAS studies, with sample sizes of 324,105 and 417,580 European individuals. The genetic variants of myopia, primary open angle glaucoma (POAG), anterior iridocyclitis, senile cataract, diabetic retinopathy (DR), retinal vein occlusion (RVO), wet age-related macular degeneration (WAMD) and optic neuritis were extracted from the latest release of FinnGen consortium, which contains genome data from Finnish participants. Subsequently, Mendelian randomization (MR) analyses were conducted to obtain effect estimates. Additionally, we performed multivariable MR analysis and mediation analysis to validate the results., Results: In the discovery dataset, genetically predicted vitamin D concentration was found to be causally associated with an increased risk of WAMD, (odd ratio (OR) = 1.35, 95% confidence interval (CI) = 1.09-1.67, P IVW = 0.005). However, no causal effects of genetically predisposed vitamin D levels on the risk of most types of ocular disorders were observed. Reverse MR revealed no causal relationships between the ocular diseases and vitamin D concentrations. The MR analyses of the validation dataset yielded consistent results. Additionally, the causal effect of vitamin D levels on the risk of WAMD remained significant after adjusting for potential confounders in the multivariable MR analysis (OR = 1.86, 95% CI = 1.26-2.73, P IVW = 0.002)., Conclusion: Our MR analysis results provide robust evidence of a causal relationship between genetically predicted 25(OH)D levels and an increased risk of WAMD in European population. These findings offer important insights into the management and control of ocular disorders., Competing Interests: 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 Fan, Shi, Li, Li and Yu.)

Background: Due to it containing cellulose, hemicellulose, and lignin with abundant specific functional groups which could interact with organic dyes, garlic peel (GP) might be used as an efficient biosorbent. The aim of this study is to evaluate the adsorption performances of GP-based bio-adsorbents and obtain optimum preparation conditions., Methods: GP-based bio-adsorbents were prepared by thermal pyrolysis under different temperatures (150-400 °C). The morphologies, chemical states, and surface functional groups of the adsorbents were analyzed by X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). Batch experiments were conducted to investigate the adsorption of methylene blue (MB) under various conditions, including contact time, contact temperature, initial dye concentration, and initial pH value. The equilibrium adsorption data were fitted to different kinetic and isothermal models, and the adsorption thermodynamics were also calculated. Significant Findings: The physicochemical properties of the GP-based bio-adsorbents were primarily dominated by the pyrolysis temperature, because their morphologies and surface functional groups of GP-based bio-adsorbents significantly varied with the changes in pyrolysis temperature. The adsorption capacity of GP materials for MB decreased as the pyrolysis temperature increased. At an initial concentration of 50.00 mg L -1 , GP150 possessed a higher adsorption capacity of 167.74 mg g -1 toward MB. The possible adsorbate-adsorbent interactions, including electrostatic attraction, hydrogen bonding, and π-π stacking, were recognized. After 10 consecutive adsorption-desorption cycles, GP150 maintained a high removal rate (88%) for MB, demonstrating its excellent adsorption performance, good reusability, and potential application in the treatment of MB-contaminated water.