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Abstract We investigated fasting hypertriglyceridemia as predictors of all‐cause, cardiovascular, and non‐cardiovascular mortality in an elderly male Chinese population, while accounting for various conventional cardiovascular risk factors. Our participants were elderly men recruited from residents living in a suburban town of Shanghai (≥60 years of age, n = 1583). Hypertriglyceridemia was defined as a fasting serum triglycerides concentration ≥1.70 mmol/L. Subgroup analyses were performed according to current smoking (yes vs. no), alcohol intake (yes vs. no), and the presence and absence of hypertension and hyperglycemia. During a median of 7.9 years follow‐up, all‐cause, cardiovascular, and non‐cardiovascular deaths occurred in 279, 112, and 167 participants, respectively. After adjustment for confounding factors, fasting hypertriglyceridemia was not significantly (p ≥ .33) associated with the risk of all‐cause, cardiovascular, and non‐cardiovascular mortality. However, there was significant (p = .03) interaction between hypertriglyceridemia and the presence and absence of hypertension in relation to all‐cause mortality. In normotensive, but not hypertensive individuals, hypertriglyceridemia was significantly associated with a higher risk of all‐cause mortality (hazard ratio 1.57, 95% confidence interval 1.06–2.31). In further non‐parametric analyses in normotensive individuals, the age‐standardized rate for all‐cause mortality increased from 18.9 in quartile 1 to 20.0, to 24.7, and to 39.9 per 1000 person‐years in quartiles 2, 3, and 4 of serum triglycerides concentration, respectively (ptrend = .0004). Similar results were observed for cardiovascular mortality. Our study in elderly male Chinese showed that fasting hypertriglyceridemia was associated with a higher risk of all‐cause and cardiovascular mortality in patients with normotension but not those with hypertension.

Abstract Background Venoms have repeatedly evolved over 100 occasions throughout the animal tree of life, making them excellent systems for exploring convergent evolutionary novelty. Growing evidence supports that venom evolution is predominantly driven by prey or host-related selection pressures, and the expression patterns of venom glands reflect adaptive evolution. However, it remains elusive whether the evolution of expression patterns in venom glands is likewise a convergent evolution driven by their prey/host species. Results We utilized parasitoid wasps that had independently adapted to Drosophila hosts as models to investigate the convergent evolution of venom gland transcriptomes in 19 hymenopteran species spanning ~ 200 million years of evolution. Comparative transcriptome analysis reveals that the global expression patterns among the venom glands of Drosophila parasitoid wasps do not achieve higher similarity compared to non-Drosophila parasitoid wasps. Further evolutionary analyses of expression patterns at the single gene, orthogroup, and Gene Ontology (GO) term levels indicate that some orthogroups/GO terms show correlation with the Drosophila parasitoid wasps. However, these groups rarely include genes highly expressed in venom glands or putative venom genes in the Drosophila parasitoid wasps. Conclusions Our study suggests that convergent evolution may not play a predominant force shaping gene expression levels in the venom gland of the Drosophila parasitoid wasps, offering novel insights into the co-evolution between venom and prey/host.

Abstract Objective This study aims to investigate the role of the triglyceride glucose (TyG) index in differentiating cardiogenic stroke (CE) from large atherosclerotic stroke (LAA). Method In this retrospective study, patients with acute ischemic stroke were recruited from the First Affiliated Hospital of Soochow University, Lianyungang Second People’s Hospital and Lianyungang First People’s Hospital. Their general data, medical history and laboratory indicators were collected and TyG index was calculated. Groups were classified by the TyG index quartile to compare the differences between groups. Logistic regression was utilized to assess the relationship between the TyG index and LAA. The receiver operating characteristic curve (ROC) curve was used to evaluate the diagnostic efficiency of the TyG index in differentiating LAA from CE. Result The study recruited 1149 patients. After adjusting for several identified risk factors, groups TyG-Q2, TyG-Q3, and TyG-Q4 had a higher risk of developing LAA compared to group TyG-Q1(odds ratio (OR) = 1.63,95% confidence interval (CI) = 1.11–2.39, OR = 1.72,95%CI = 1.16–2.55, OR = 2.06,95%CI = 1.36–3.09). TyG has certain diagnostic value in distinguishing LAA from CE(AUC = 0.595, 95%CI0.566–0.623;P

Objective With the steady advancement of technology and China's dual carbon process, the application of hydrogen energy in urban transportation is increasing. To reduce the overall energy consumption of fuel cell/supercapacitor hybrid power system for virtual-rail trams, an energy management method based on optimal power consumption is proposed. Method Based on the power distribution of virtual-rail trams in different operating states, an instantaneous power consumption function for the hybrid power system is jointly constructed by fitting approximation and combining the power consumption models of fuel cell systems and supercapacitor systems. By optimizing and solving the power consumption function, the optimal output power of the fuel cell system is obtained. The online control capability of the proposed method is verified using a semi-physical simulation platform and actual operational data of the virtual-rail tram. Result & Conclusion Experimental results show that under the control of the proposed method, the fuel cell system maintains a stable output power under complex conditions, with an average electricity-to-hydrogen conversion efficiency of 54.84%. This can effectively reduce the operation and maintenance costs of virtual-rail trams.

Objective Equivalent hydrogen consumption, as a method for optimizing fuel economy, performs poorly in following the state of charge of energy storage systems. Therefore, it is necessary to improve it to achieve dynamic balance of interval state of charge. Method Based on the conventional equivalent hydrogen consumption algorithm, the hydrogen consumption function of the system is optimized. By adding a voltage balance coefficient, it ensures that the supercapacitor will not be overcharged or over-discharged during vehicle operation. Then, through minimization solution, real-time allocation of power to the system is achieved. Result & Conclusion Based on the operational data of virtual-rail trams, the proposed method is validated on a semi-physical simulation platform. Experimental results show that the improved equivalent hydrogen consumption algorithm can achieve energy distribution of hybrid power systems under complex working conditions. The added voltage balance coefficient ensures that the voltage of the supercapacitor at the end of the vehicle interval remains within a reasonable range.

AIM: To assess the repeatability, interocular correlation, and agreement of quantitative swept-source optical coherence tomography angiography (OCTA) optic nerve head (ONH) parameters in healthy subjects. METHODS: Thirty-three healthy subjects were enrolled. The ONH of both eyes were imaged four times by a swept-source-OCTA using a 3 mm ×3 mm scanning protocol. Images of the radial peripapillary capillary were analyzed by a customized Matlab program, and the vessel density, fractal dimension, and vessel diameter index were measured. The repeatability of the four scans was determined by the intraclass correlation coefficient (ICC). The most well-centered optic disc from the four repeated scans was then selected for the interocular correlation and agreement analysis using the Pearson correlation coefficient, ICC and Bland-Altman plots. RESULTS: All swept-source-OCTA ONH parameters exhibited certain repeatability, with ICC>0.760 and coefficient of variation (CoV)≤7.301%. The obvious interocular correlation was observed for papillary vessel density (ICC=0.857), vessel diameter index (ICC=0.857) and fractal dimension (ICC=0.906), while circumpapillary vessel density exhibited moderate interocular correlation (ICC=0.687). Bland-Altman plots revealed an agreement range of -5.26% to 6.21% for circumpapillary vessel density. CONCLUSION: OCTA ONH parameters demonstrate good repeatability in healthy subjects. The interocular correlations of papillary vessel density, fractal dimension and vessel diameter index are high, but the correlation for circumpapillary vessel density is moderate.

BackgroundPolycystic Ovary Syndrome (PCOS) represents a complex endocrine disorder characterized by a significant interplay with metabolic dysfunction and obesity. This research endeavors to elucidate the causal dynamics among plasma metabolites, proteins, and PCOS, alongside Body Mass Index (BMI), to pinpoint prospective therapeutic interventions.MethodsThis investigation employed Mendelian randomization (MR) analyses combined with data derived from the National Health and Nutrition Examination Survey (NHANES) to explore the relationships between 1,400 plasma metabolites and PCOS, factoring in BMI adjustments. Additionally, the study examined the influence of plasma proteins and performed a retrospective cross-sectional analysis focusing on retinol consumption and testosterone levels.ResultsMR analyses showed metabolite Glycosyl-N-(2-hydroxynervonoyl)-sphingosine (GNS) and protein Keratin 19 (KRT19) were identified as significant markers in the context of PCOS and BMI adjustments. A Phenome-Wide Association Study (PheWAS) underscored the linkage between KRT19 and BMI, while gene-drug interaction findings demonstrated a connection between KRT19 and retinol. Analysis for NHANES data disclosed a negative correlation between retinol intake and testosterone levels, particularly within normal weight and obese cohorts, suggesting the feasibility of dietary interventions for PCOS management.ConclusionThe study sheds light on the intricate interactions between plasma metabolites, proteins, and PCOS, considering BMI variations, and highlights KRT19 protein as a promising therapeutic target. The outcomes support the integration of retinol consumption into dietary strategies to regulate testosterone levels and potentially alleviate PCOS symptoms, underscoring the necessity for personalized nutritional and therapeutic approaches in the effective management of PCOS.

Quantitative micro-elastography (QME) is a compression-based optical coherence elastography technique enabling the estimation of tissue mechanical properties on the micro-scale. QME utilizes a compliant layer as an optical stress sensor, placed between an imaging window and tissue, providing quantitative estimation of elasticity. However, the implementation of the layer is challenging and introduces unpredictable friction conditions at the contact boundaries, deteriorating the accuracy and reliability of elasticity estimation. This has largely limited the use of QME to ex vivo studies and is a barrier to clinical translation. In this work, we present a novel implementation by affixing the stress sensing layer to the imaging window and optimizing the layer thickness, enhancing the practical use of QME for in vivo applications by eliminating the requirement for manual placement of the layer, and significantly reducing variations in the friction conditions, leading to substantial improvement in the accuracy and repeatability of elasticity estimation. We performed a systematic validation of the integrated layer, demonstrating >30% improvement in sensitivity and the ability to provide mechanical contrast in a mechanically heterogeneous phantom. In addition, we demonstrate the ability to obtain accurate estimation of elasticity (

IntroductionRecent studies increasingly suggest that moderate-to-vigorous physical activity (MVPA) impacts cognitive risk. However, the bidirectional nature of this relationship warrants further exploration. To address this, we employed a Mendelian randomization (MR) approach, analyzing two distinct samples.MethodsThese analyses utilized published genome-wide association study (GWAS) summary statistics for MVPA (n = 377,234) and cognitive performance (n = 257,841). Our primary method was the inverse variance weighted (IVW) model with random effects, aiming to deduce potential causal links. Additionally, we employed supplementary methods, including MR Egger regression, Weighted median, Weighted mode, and Simple mode. For sensitivity analysis, tools like the MR Egger test, Cochran’s Q, MR PRESSO, and leave-one-out (LOO) were utilized.ResultsOur findings indicate a decrease in cognitive risk with increased MVPA (Odds Ratio [OR] = 0.577, 95% Confidence Interval [CI]: 0.460–0.723, p = 1.930 × 10–6). Furthermore, enhanced cognitive levels corresponded to a reduced risk of inadequate MVPA (OR = 0.866, 95% CI: 0.839–0.895, p = 1.200 × 10–18).DiscussionIn summary, our study demonstrates that MVPA lowers cognitive risk, while poor cognitive health may impede participation in MVPA. Overall, these findings provide valuable insights for developing personalized prevention and intervention strategies in health and sports sciences.

Advanced manufacturing research for sustainable battery life cycles is of utmost importance to reach net zero carbon emissions (European Commission, 2023a) as well as several of the United Nations Sustainable Development Goals (UNSDGs), for example: 30% reduction of CO2 emission, 10 million job opportunities and access to electricity for 600 million people (World Economic Forum, 2019). This editorial paper highlights international motivations for pursuing more sustainable manufacturing practices and discusses key research topics in battery manufacturing. Batteries will be central to our sustainable future as generation and storage become key components to on-demand energy supply. Four underlying themes are identified to address industrial needs in this field: 1. Digitalizing and automating production capabilities: data-driven solutions for production quality, smart maintenance, automation, and human factors, 2. Human-centric production: extended reality for operator support and skills development, 3. Circular battery life cycles: circular battery systems supported by service-based and other novel business models, 4. Future topics for battery value chains: increased industrial resilience and transparency with digital product passports, and next-generation battery chemistries. Challenges and opportunities along these themes are highlighted for transforming battery value chains through circularity and more sustainable production, with a particular emphasis on lithium-ion batteries (LIB). The paper concludes with directions for further research to advance a circular and sustainable battery value chain through utilizing the full potential of digitalization realising a cleaner, more energy-efficient society.

Glycogen Storage Disease Type VII (GSD VII) is a rare glycogen metabolism disorder resulting from mutations in the PFKM gene, inherited in an autosomal recessive manner. It is characterized by exercise intolerance, muscle cramps, myoglobinuria, compensatory hemolysis, and later onset de novo myasthenia and mild myopathy, contributing to its clinical heterogeneity and diagnostic challenges. Here, we report a rare case of a 17-year-old Chinese woman exhibiting substantial muscle weakness and compensated hemolysis. Muscle biopsies showed glycogen deposition, and blood tests showed hyperuricemia and significantly elevated creatine kinase. Whole genome sequencing (WGS) and whole exome sequencing (WES) identified two compound heterozygous mutations in the PFKM (NM_000289.6) gene: c.626G>A and c.1376G>A in exons 7 and 15, respectively. According to the clinical presentation, diagnostic examination, and WES results, the patient was finally diagnosed with GSDVII. The discovery of these two new PFKM mutations expands the genetic spectrum, and understanding the clinical manifestations of these mutations is critical to preventing diagnostic delays and timely intervention and treatment.

Abstract The clinical effects of Schisandra chinensis against human disease are well-documented; however, studies on its application in controlling plant pathogens are limited. Here, we investigated its inhibitory effect on the growth of Alternaria alternata, a fungus which causes significant post-harvest losses on apples, known as black spot disease. S. chinensis fruit extract exhibited strong inhibitory effects on the growth of A. alternata with an EC50 of 1882.00 mg/L. There were 157 compounds identified in the extract by high performance liquid chromatography-mass spectrometry, where benzocaine constituted 14.19% of the extract. Antifungal experiments showed that the inhibitory activity of benzocaine on A. alternata was 43.77-fold higher than the crude extract. The application of benzocaine before and after A. alternata inoculation on apples prevented the pathogen infection and led to mycelial distortion according to scanning electron microscopy. Transcriptome analysis revealed that there were 4226 genes differentially expressed between treated and untreated A. alternata-infected apples with benzocaine. Metabolomics analysis led to the identification of 155 metabolites. Correlation analysis between the transcriptome and metabolome revealed that benzocaine may inhibit A. alternata growth via the beta-alanine metabolic pathway. Overall, S. chinensis extract and benzocaine are environmentally friendly plant-based fungicides with potential to control A. alternata.

Abstract Neoadjuvant chemoimmunotherapy has emerged as a potential treatment option for resectable head and neck squamous cell carcinoma (HNSCC). In this single-arm phase II trial (NCT04826679), patients with resectable locally advanced HNSCC (T2‒T4, N0‒N3b, M0) received neoadjuvant chemoimmunotherapy with camrelizumab (200 mg), nab-paclitaxel (260 mg/m2), and cisplatin (60 mg/m2) intravenously on day one of each three-week cycle for three cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included pathologic complete response (pCR), major pathologic response (MPR), two-year progression-free survival rate, two-year overall survival rate, and toxicities. Here, we report the perioperative outcomes; survival outcomes were not mature at the time of data analysis. Between April 19, 2021 and March 17, 2022, 48 patients were enrolled and received neoadjuvant therapy, 27 of whom proceeded to surgical resection and remaining 21 received non-surgical therapy. The ORR was 89.6% (95% CI: 80.9, 98.2) among 48 patients who completed neoadjuvant therapy. Of the 27 patients who underwent surgery, 17 (63.0%, 95% CI: 44.7, 81.2) achieved a MPR or pCR, with a pCR rate of 55.6% (95% CI: 36.8, 74.3). Treatment-related adverse events of grade 3 or 4 occurred in two patients. This study meets the primary endpoint showing potential efficacy of neoadjuvant camrelizumab plus nab-paclitaxel and cisplatin, with an acceptable safety profile, in patients with resectable locally advanced HNSCC.

Abstract Purpose Gasless robot-assisted transaxillary hemithyroidectomy (RATH) is regarded as an alternative surgical option for thyroid operations. However, the associated steep learning curve is a clinical concern. This study evaluated the learning curve of RATH for surgeons without experience of endoscopic surgery and the early surgical outcomes of RATH. Methods We conducted a retrospective study of patients who underwent gasless RATH and conventional hemithyroidectomy (CH) at Sun Yat-sen University Cancer Center, Guangzhou, China, from June 2021 to August 2022. The learning curve and early surgical outcomes of gasless RATH were evaluated. And the early surgical outcomes of gasless RATH were compared to CH. Results In total, 105 patients who underwent gasless RATH and 104 patients who underwent CH were matched and assessed. The cumulative sum techniques (CUSUM) analysis showed that the peak point of gasless RATH operative time occurred at the 31st case. No clear single peak was identified in the CUSUM plot for drainage amount and blood loss. No significant difference in perioperative complications was observed between these two groups. Moreover, the number of postoperative patients who got sense of thyroid area traction were fewer in the gasless RATH group (n = 11, 10.5%) than in the CH group (n = 32, 30.8%). Conclusion Gasless RATH can be considered as an alternative approach to the conventional open procedure, as it is an easy remote access technique, with shorter learning curves and certain advantage such as less sense of thyroid area traction.

Abstract Nicotinamide phosphoribosyltransferase (NAMPT) plays an important role in the biosynthesis of nicotinamide adenine dinucleotide (NAD+) via the nicotinamide (NAM) salvage pathway. While the structural biochemistry of eukaryote NAMPT has been well studied, the catalysis mechanism of prokaryote NAMPT at the molecular level remains largely unclear. Here, we demonstrated the NAMPT-mediated salvage pathway is functional in the Gram-negative phytopathogenic bacterium Xanthomonas campestris pv. campestris (Xcc) for the synthesis of NAD+, and the enzyme activity of NAMPT in this bacterium is significantly higher than that of human NAMPT in vitro. Our structural analyses of Xcc NAMPT, both in isolation and in complex with either the substrate NAM or the product nicotinamide mononucleotide (NMN), uncovered significant details of substrate recognition. Specifically, we revealed the presence of a NAM binding tunnel that connects the active site, and this tunnel is essential for both catalysis and inhibitor binding. We further demonstrated that NAM binding in the tunnel has a positive cooperative effect with NAM binding in the catalytic site. Additionally, we discovered that phosphorylation of the His residue at position 229 enhances the substrate binding affinity of Xcc NAMPT and is important for its catalytic activity. This work reveals the importance of NAMPT in bacterial NAD+ synthesis and provides insights into the substrate recognition and the catalytic mechanism of bacterial type II phosphoribosyltransferases.

Proliferative vitreoretinopathy(PVR) is a type of fibrotic eye disease with a poor clinical prognosis. Increasing evidence has shown that the primary pathological mechanism of PVR is the epithelial-mesenchymal transition(EMT) of retinal pigment epithelium(RPE) cells. Histone deacetylase 3(HDAC3) is a crucial enzyme involved in regulating the acetylation level of proteins. Several studies have reported associations between HDAC3 levels and EMT in various tumors; however, the specific effect of HDAC3 on PVR remains largely unknown. The current study found that HDAC3 was highly expressed in both human PVR membranes and experimental PVR. In vivo, silencing HDAC3 in RPE cells reduced their ability to develop experimental PVR through suppression of EMT. In vitro, inhibition of HDAC3 in RPE cells suppressed EGF-mediated cell proliferation, migration, and EMT. Additionally, overexpression of HDAC3 in RPE cells promoted cell proliferation, migration, and EMT. Mechanistically, the results of chromatin immunoprecipitation(ChIP) and luciferase assays revealed a direct binding of the transcription factor MAZ to the promoter region of HDAC3, thereby promoting its transcription. Furthermore, It was demonstrated that HDAC3 facilitated EMT by interacting with AKT and contributing to its deacetylation. In summary, our findings indicated the involvement of HDAC3 in the EMT of RPE cells, as well as its role in PVR through the regulation of the AKT pathway. These results suggested that targeting HDAC3 could be a potential strategy for preventing and treating PVR.

In this study, it is the first that the Viticis Fructus (VF) was used as the raw material for extracting total flavonoids using the ultrasound-assisted enzyme extraction (UAE) method. Response surface methodology was employed to determine the optimal extraction parameters. The optimal conditions were as follows: 60 % ethanol solution as the extract solvent, material–liquid ratio of 1:25, pH value of 4, enzyme addition amount of 1.5 %, enzymatic hydrolysis time of 30 min, enzymatic hydrolysis temperature of 40 ℃, and ultrasonic time of 50 min. Comparing the total flavonoid yield of VF and processed VF (PVF) extracted using different methods, it was observed that UAE resulted in a higher total flavonoid yield compared to traditional ultrasound extraction and enzyme extraction. Additionally, the total flavonoid yield of PVF extracted by all three methods was generally higher than that of VF. The PVF solution extracted by UAE also demonstrated better in vitro antioxidant activity compared to VF. These results suggest that UAE is an effective method to enhance the activity of natural total flavonoids. The study of the physicochemical properties and in vitro antioxidant activity of VF and PVF showed that the total flavonoid yield and antioxidant activity significantly increased after VF stir-frying, indicating that their efficacy can also be enhanced.

Introduction: Primary Sjögren's syndrome (PSS) is a systemic autoimmune disease that mainly affects exocrine glands. Little is known about PSS associated cervical and intracranial cerebral large-vessel vasculitis outside of individual case reports. Methods: We present 5 cases of ischemic stroke or transient ischemic stroke (TIA) caused by PSS associated cervical and intracranial large-vessel vasculitis. Literature review was performed to summarize and identify the demographic, clinical features, treatment, and prognosis of this condition. Results: The review resulted in 8 included articles with 8 patients, plus our 5 new patients, leading to a total of 13 subjects included in the analysis. The median age was 43 (range, 17–69) years old, among which 69.2 % (9/13) were female, and 92.3 % (12/13) came from Asia. Among them, 84.6 % (11/13) presented with cerebral infarction and 70.0 % (7/10) with watershed infarction. Middle cerebral artery (MCA) (6/13, 46.2 %) and internal carotid artery (ICA) (6/13, 46.2 %) were the most frequently involved arteries. Remarkable vessel wall concentric thickening and enhancement was observed in 57.1 % (4/7) patients and intravascular thrombi was identified in 28.6 % (2/7) patients. Glucocorticoid combined with non-glucocorticoid immunosuppressants (8/12, 66.7 %) were the most often chosen medication therapy and 4 patients received surgical intervention. Conclusion: Asian females are the most vulnerable population to ischemic stroke or TIA due to PSS associated cervical and intracranial large-vessel vasculitis. Cerebral infarctions were characterized by recurrence and watershed pattern. Magnetic resonance vessel wall imaging (MR-VWI) helps to identify the inflammatory pathology of large vessel lesion in PSS.

BackgroundThe association between dietary zinc intake and epilepsy remains unclear. This study aimed to investigate the relationship between zinc intake from the diet and epilepsy, employing Mendelian randomization (MR) to explore potential causal links between zinc and epilepsy.MethodsThe cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2013 and 2018. Among the 4,434 participants included, 1.5% (67/4,434) reported having epilepsy. Restricted cubic spline models and logistic regression models were employed to examine the relationships between dietary zinc intakes and epilepsy. Subsequently, a 2-sample Mendelian randomization (MR) analysis was conducted using the inverse variance weighted (IVW) approach as the primary analysis.ResultsIn the restricted cubic spline (RCS) analysis, the relationship between dietary zinc consumption and epilepsy displayed an L-shaped curve (nonlinear, p = 0.049). After multivariate adjustments, the adjusted odds ratios for epilepsy in T2 (5.0–11.0 mg/day) and T3 (≥11.0 mg/day) were 0.49 (95% confidence interval [CI]: 0.26–0.92, p = 0.026) and 0.60 (95% CI: 0.31–1.17, p = 0.132), respectively, compared to the lowest dietary zinc consumption tertile (T1, ≤5.0 mg/day). The IVW method indicated that genetically predicted zinc intake per standard-deviation increase was inversely associated with three types of epilepsy, including all types of epilepsy (OR = 1.06, 95% CI: 1.02–1.11, p = 0.008), generalized epilepsy (OR = 1.13, 95% CI: 1.01–1.25, p = 0.030), and focal epilepsy (documented hippocampal sclerosis) (OR = 1.01, 95% CI: 1.00–1.02, p = 0.025).ConclusionOur findings suggest that a daily zinc intake ranging from 5.0 to 11.0 mg is associated with the lowest risk of epilepsy. Furthermore, Mendelian randomization (MR) studies provide additional support for the existence of a causal relationship between zinc and epilepsy.

BackgroundPrevious studies suggest a link between diet-derived circulating antioxidants and epilepsy, but the causal relationship is unclear. This study aims to investigate the causal effect of these antioxidants on epilepsy.MethodsTo assess the causal link between dietary antioxidants and epilepsy risk, we conducted a two-sample Mendelian randomization (MR) analysis. This involved examining antioxidants such as zinc, selenium, α- and γ-tocopherol, vitamin A (retinol), vitamin C (ascorbate), and vitamin E (α-tocopherol). We utilized instrumental variables (IVs) which were genetic variations highly associated with these commonly used antioxidants. Exposure data were sourced from a comprehensive genome-wide association study (GWAS). We aggregated data from the International League Against Epilepsy (ILAE) Consortium sample, which included various types of epilepsy, as an outcome variable. Finally, we applied the inverse variance weighting method and conducted sensitivity analyses for further validation.ResultsBased on the primary MR estimates and subsequent sensitivity analyses, the inverse variance weighting (IVW) method revealed that a genetically predicted increase in zinc per standard deviation was positively associated with three types of epilepsy. This includes all types of epilepsy (OR = 1.06, 95% CI: 1.02–1.11, p = 0.008), generalized epilepsy (OR = 1.13, 95% CI: 1.01–1.25, p = 0.030), and focal epilepsy (documented hippocampal sclerosis) (OR = 1.01, 95% CI: 1.00–1.02, p = 0.025). However, there is no evidence indicating that other antioxidants obtained from the diet affect the increase of epilepsy either positively or negatively.ConclusionOur research indicates that the risk of developing epilepsy may be directly linked to the genetic prediction of zinc, whereas no such association was found for other antioxidants.