Causal association between major depressive disorder and venous thromboembolism: a bidirectional mendelian randomization study.

Purpose: Major depressive disorder (MDD) and venous thromboembolism (VTE) may be linked in observational studies. However, the causal association remains ambiguous. Therefore, this study investigates the causal associations between them. Methods: We performed a two-sample univariable and multivariable bidirectional Mendelian randomization (MR) analysis to evaluate the associations between MDD and VTE. The summary genetic associations of MDD statistics were obtained from the Psychiatric Genomics Consortium and UK Biobank. Information on VTE, deep vein thrombosis (DVT), and pulmonary embolism (PE) were obtained from the FinnGen Biobank. Inverse-variance weighting was used as the main analysis method. Other methods include weighted median, MR-Egger, Simple mode, and Weighted mode. Results: Univariable MR analysis revealed no significant associations between MDD and VTE risk (odds ratio (OR): 0.936, 95% confidence interval (CI): 0.736-1.190, p = 0.590); however, after adjusting the potential relevant polymorphisms of body mass index and education, the multivariable MR analysis showed suggestive evidence of association between them (OR: 1.163, 95% CI: 1.004-1.346, p = 0.044). Univariable MR analysis also revealed significant associations between MDD and PE risk (OR: 1.310, 95% CI: 1.073-1.598, p = 0.008), but the association between them was no longer significant in MVMR analysis (p = 0.072). We found no significant causal effects between MDD and DVT risk in univariable or multivariable MR analyses. There was also no clear evidence showing the causal effects between VTE, PE, or DVT and MDD risk. Conclusion: We provide suggestive genetic evidence to support the causal association between MDD and VTE risk. No causal associations were observed between VTE, PE, or DVT and MDD risk. Further validation of these associations and investigations of potential mechanisms are required.

Pathogenesis of depression and the potential for traditional Chinese medicine treatment.

Depression is a prevalent mental disorder that significantly diminishes quality of life and longevity, ranking as one of the primary causes of disability globally. Contemporary research has explored the potential pathogenesis of depression from various angles, encompassing genetics, neurotransmitter systems, neurotrophic factors, the hypothalamic-pituitary-adrenal axis, inflammation, and intestinal flora, among other contributing factors. In addition, conventional chemical medications are plagued by delayed onset of action, persistent adverse effects, and restricted therapeutic efficacy. In light of these limitations, the therapeutic approach of traditional Chinese medicine (TCM) has gained increasing recognition for its superior effectiveness. Numerous pharmacological and clinical studies have substantiated TCM's capacity to mitigate depressive symptoms through diverse mechanisms. This article attempts to summarize the mechanisms involved in the pathogenesis of depression and to describe the characteristics of herbal medicines (including compounded formulas and active ingredients) for the treatment of depression. It further evaluates their effectiveness by correlating with the multifaceted pathogenesis of depression, thereby furnishing a reference for future research endeavors.

Structural characterization of the glucan from Gastrodia elata Blume and its ameliorative effect on DSS-induced colitis in mice.

The polysaccharide glucan was extracted from Gastrodia elata Blume, and its structural characterizations and beneficial effects against acute dextran sulfate sodium (DSS)-induced ulcerative colitis were investigated. The results showed that a polysaccharide GP with a molecular weight of 811.0 kDa was isolated from G. elata Blume. It had a backbone of α-D-1,4-linked glucan with branches of α-d-glucose linked to the C-6 position. GP exhibited protective effects against DSS-induced ulcerative colitis, and reflected in ameliorating weight loss and pathological damages in mice, increasing colon length, inhibiting the expression of inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß), decreasing the levels of inflammatory related proteins NLRP3 and ASC, and elevating the anti-inflammatory cytokine interleukin-10 (IL-10) level in mouse colon tissues. GP supplementation also reinforced the intestinal barrier by promoting the expression of ZO-1, Occludin, and MUC2 of colon tissues, and positively regulated intestinal microbiota. Thus, GP treatment possessed a significant improvement in ulcerative colitis in mice, and it was expected to be developed as a functional food.

Metal-detection based techniques and their applications in metallobiology.

Metals are essential for human health and play a crucial role in numerous biological processes and pathways. Gaining a deeper insight into these biological events will facilitate novel strategies for disease prevention, early detection, and personalized treatment. In recent years, there has been significant progress in the development of metal-detection based techniques from single cell metallome and proteome profiling to multiplex imaging, which greatly enhance our comprehension of the intricate roles played by metals in complex biological systems. This perspective summarizes the recent progress in advanced metal-detection based techniques and highlights successful applications in elucidating the roles of metals in biology and medicine. Technologies including machine learning that couple with single-cell analysis such as mass cytometry and their application in metallobiology, cancer biology and immunology are also emphasized. Finally, we provide insights into future prospects and challenges involved in metal-detection based techniques, with the aim of inspiring further methodological advancements and applications that are accessible to chemists, biologists, and clinicians.

Mechanistic insights into bismuth(iii) inhibition of SARS-CoV-2 helicase.

The COVID-19 pandemic caused by SARS-CoV-2 resulted in a global public health crisis. In addition to vaccines, the development of effective therapy is highly desirable. Targeting a protein that plays a critical role in virus replication may allow pan-spectrum antiviral drugs to be developed. Among SARS-CoV-2 proteins, helicase (i.e., non-structural protein 13) is considered as a promising antiviral drug target due to its highly conserved sequence, unique structure and function. Herein, we demonstrate SARS-CoV-2 helicase as a target of bismuth-based antivirals in virus-infected mammalian cells by a metal-tagged antibody approach. To search for more potent bismuth-based antivirals, we further screened a panel of bismuth compounds towards inhibition of ATPase and DNA unwinding activity of nsp13 and identified a highly potent bismuth compound Bi(5-aminotropolonate)3, namely Bi(Tro-NH2)3 with an IC50 of 30 nM for ATPase. We show that bismuth-based compounds inhibited nsp13 unwinding activity via disrupting the binding of ATP and the DNA substrate to viral helicase. Binding of Bi(iii) to nsp13 also abolished the interaction between nsp12 and nsp13 as evidenced by immunofluorescence and co-immunoprecipitation assays. Finally, we validate our in vitro data in SARS-CoV-2 infected mammalian cells. Notably, Bi(6-TG)3 exhibited an EC50 of 1.18 ± 0.09 µM with a selective index of 847 in VeroE6-TMPRSS2 infected cells. This study highlights the important role of helicase for the development of more effective antiviral drugs to combat SARS-CoV-2 infection.

Research progress on the mechanism of action and clinical application of remote ischemic post-conditioning for acute ischemic stroke.

Remote ischemic post-conditioning (RIPostC) can reduce cerebral ischemia reperfusion injury (IRI) by inducing endogenous protective effects, the distal limb ischemia post-treatment and in situ ischemia post-treatment were classified according to the site of intervention. And in the process of clinical application distal limb ischemia post-treatment is more widely used and more conducive to clinical translation. Therefore, in this paper, we review the mechanism of action and clinical application of RIPostC in cerebral ischemia, hoping to provide reference help for future experimental directions and clinical translation.

Effects of two fillers and process conditions on the water treatment efficiency of a continuous packed bed biofilm reactor.

This study evaluated the treatment efficiency of two selected fillers and their combination for improving the water quality of aquaculture wastewater using a packed bed biofilm reactor (PBBR) under various process conditions. The fillers used were nanosheet (NS), activated carbon (AC), and a combination of both. The results indicated that the use of combined fillers and the hydraulic retention time (HRT) of 4 h significantly enhanced water quality in the PBBR. The removal rates of chemical oxygen demand, NO2-─N, total suspended solids（TSS）, and chlorophyll a were 63.55%, 74.25%, 62.75%, and 92.85%, respectively. The microbiota analysis revealed that the presence of NS increased the abundance of microbial phyla associated with nitrogen removal, such as Nitrospirae and Proteobacteria. The difference between the M1 and M2 communities was minimal. Additionally, the microbiota in different PBBR samples displayed similar preferences for carbon sources, and carbohydrates and amino acids were the most commonly utilized carbon sources by microbiota. These results indicated that the combination of NS and AC fillers in a PBBR effectively enhanced the treatment efficiency of aquaculture wastewater when operated at an HRT of 4 h. The findings provide valuable insights into optimizing the design of aquaculture wastewater treatment systems.

A skin-specific α-Synuclein seeding amplification assay for diagnosing Parkinson's disease.

The seeding amplification assay (SAA) has recently emerged as a valuable tool for detecting α-synuclein (αSyn) aggregates in various clinically accessible biospecimens. Despite its efficiency and specificity, optimal tissue-specific conditions for distinguishing Parkinson's disease (PD) from non-PD outside the brain remain underexplored. This study systematically evaluated 150 reaction conditions to identify the one with the highest discriminatory potential between PD and non-synucleinopathy controls using skin samples, resulting in a modified SAA. The streamlined SAA achieved an overall sensitivity of 92.46% and specificity of 93.33% on biopsy skin samples from 332 PD patients and 285 controls within 24 h. Inter-laboratory reproducibility demonstrated a Cohen's kappa value of 0.87 (95% CI 0.69-1.00), indicating nearly perfect agreement. Additionally, αSyn seeds in the skin were stable at -80 °C but were vulnerable to short-term exposure to non-ultra-low temperatures and grinding. This study thoroughly investigated procedures for sample preprocessing, seed amplification, and storage, introducing a well-structured experimental framework for PD diagnosis using skin samples.

The Novel-B-Cell-Related Gene Signature Predicts the Prognosis and Immune Status of Patients with Esophageal Carcinoma.

BACKGROUND: The current understanding of the prognostic significance of B cells and their role in the tumor microenvironment (TME) in esophageal carcinoma (ESCA) is limited. METHODS: We conducted a screening for B-cell-related genes through the analysis of single-cell transcriptome data. Subsequently, we developed a B-cell-related gene signature (BRGrisk) using LASSO regression analysis. Patients from The Cancer Genome Atlas cohort were divided into a training cohort and a test cohort. Patients were categorized into high- and low-risk groups based on their median BRGrisk scores. The overall survival was assessed using the Kaplan-Meier method, and a nomogram based on BRGrisk was constructed. Immune infiltration profiles between the risk groups were also compared. RESULTS: The BRGrisk prognostic model indicated significantly worse outcomes for patients with high BRGrisk scores (p < 0.001). The BRGrisk-based nomogram exhibited good prognostic performance. Analysis of immune infiltration revealed that patients in the high-BRGrisk group had notably higher levels of immune cell infiltration and were more likely to be in an immunoresponsive state. Enrichment analysis showed a strong correlation between the prognostic gene signature and cancer-related pathways. IC50 results indicated that patients in the low-BRGrisk group were more responsive to common drugs compared to those in the high-BRGrisk group. CONCLUSIONS: This study presents a novel BRGrisk that can be used to stratify the prognosis of ESCA patients and may offer guidance for personalized treatment strategies aimed at improving prognosis.

PGM5-AS1 Promotes Progression of Diffuse Large B-Cell Lymphoma and Immune Escape by Regulating miR-503-5p.

Purpose: Diffuse large B-cell lymphoma (DLBCL) is a prevalent malignant condition with a dismal prognosis. LncRNA PGM5 antisense RNA 1 (PGM5-AS1) appears to be intricately involved in the progression of DLBCL, yet the modulatory mechanism remains unclear. The purpose of this study was to explore the expression of lncRNA PGM5-AS1 in DLBCL and its effect on the disease progression of DLBCL, as well as to explore its mechanisms. Patients and Methods: A total of 35 patients were included in the study. The expression levels of PGM5-AS1 and miR-503-5p in DLBCL tumor tissues and cell lines were detected by RT-qPCR. Cell proliferation was assessed using CCK8. Apoptosis rate was determined by flow cytometry. Cell invasion was examined by transwell assays. The specific interaction between PGM5-AS1 and miR-503-5p was verified through dual luciferase reporter gene assays. The immune related factors were detected by ELASA kits. The CD8+ T cells cytotoxicity was evaluated by LDH cytotoxicity kit. Results: In DLBCL tumor tissues and cells, upregulated PGM5-AS1 expression, downregulated miR-503-5p expression, and elevated PD-L1 expression were observed. PGM5-AS1 functioned as a regulator in controlling DLBCL cell proliferation, apoptosis, and invasion by downregulating miR-503-5p expression. When CD8+ T cells were co-cultured with cells transfected with si-PGM5-AS1, the secretion of immunoregulatory factors increased, and the cytotoxicity of CD8+ T cells increased. These effects were mitigated by miR-503-5p inhibitors. Conclusion: PGM5-AS1 accelerated DLBCL development and facilitated tumor immune escape through the miR-503-5p. Our discoveries offered an insight into lncRNA PGM5-AS1 serving as a prospective therapeutic target for DLBCL.

Neurosyphilis Presenting as Psychiatric Symptoms at Younger Age: A Case Report.

Neurosyphilis is a central nervous system infection caused by Treponema pallidum that imitates various neurological and mental disorders. Therefore, patients with this disease are prone to misdiagnoses. Here, we report a case of neurosyphilis with a psychotic disorder as the main manifestation. A young girl exhibited mental and behavioural abnormalities after a heartbreak, which manifested as alternating low mood, emotional irritability, and a lack of interest in social relations, followed by memory loss. The cerebrospinal fluid protein - Treponema pallidum particle agglutination test was positive, the toluidine red unheated serum test titre was 1:4, the white blood cell count was 5 × 10^6/L, the cerebrospinal fluid protein level was 0.97 g/L, and the brain CT was abnormal. After admission, the possibility of neurosyphilis was considered and the patient received intravenous penicillin G treatment. The patient's clinical symptom ms improved. This case emphasises that doctors should maintain clinical suspicion of Treponema pallidum infection in adolescent patients with mental abnormalities.

Analysis on the pathogenesis and treatment progress of NRG1 fusion-positive non-small cell lung cancer.

Lung cancer persistently leads as the primary cause of morbidity and mortality among malignancies. A notable increase in the prevalence of lung adenocarcinoma has become evident in recent years. Although targeted therapies have shown in treating certain subsets of non-small cell lung cancers (NSCLC), a significant proportion of patients still face suboptimal therapeutic outcomes. Neuregulin-1 (NRG1), a critical member of the NRG gene family, initially drew interest due to its distribution within the nascent ventricular endocardium, showcasing an exclusive presence in the endocardium and myocardial microvessels. Recent research has highlighted NRG1's pivotal role in the genesis and progression across a spectrum of tumors, influencing molecular perturbations across various tumor-associated signaling pathways. This review provides a concise overview of NRG1, including its expression patterns, configuration, and fusion partners. Additionally, we explore the unique features and potential therapeutic strategies for NRG1 fusion-positive occurrences within the context of NSCLC.

KLSD: a kinase database focused on ligand similarity and diversity.

Due to the similarity and diversity among kinases, small molecule kinase inhibitors (SMKIs) often display multi-target effects or selectivity, which have a strong correlation with the efficacy and safety of these inhibitors. However, due to the limited number of well-known popular databases and their restricted data mining capabilities, along with the significant scarcity of databases focusing on the pharmacological similarity and diversity of SMIKIs, researchers find it challenging to quickly access relevant information. The KLIFS database is representative of specialized application databases in the field, focusing on kinase structure and co-crystallised kinase-ligand interactions, whereas the KLSD database in this paper emphasizes the analysis of SMKIs among all reported kinase targets. To solve the current problem of the lack of professional application databases in kinase research and to provide centralized, standardized, reliable and efficient data resources for kinase researchers, this paper proposes a research program based on the ChEMBL database. It focuses on kinase ligands activities comparisons. This scheme extracts kinase data and standardizes and normalizes them, then performs kinase target difference analysis to achieve kinase activity threshold judgement. It then constructs a specialized and personalized kinase database platform, adopts the front-end and back-end separation technology of SpringBoot architecture, constructs an extensible WEB application, handles the storage, retrieval and analysis of the data, ultimately realizing data visualization and interaction. This study aims to develop a kinase database platform to collect, organize, and provide standardized data related to kinases. By offering essential resources and tools, it supports kinase research and drug development, thereby advancing scientific research and innovation in kinase-related fields. It is freely accessible at: http://ai.njucm.edu.cn:8080.

SP1 undergoes phase separation and activates RGS20 expression through super-enhancers to promote lung adenocarcinoma progression.

Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death worldwide, but the underlying molecular mechanisms remain largely unclear. The transcription factor (TF) specificity protein 1 (SP1) plays a crucial role in the development of various cancers, including LUAD. Recent studies have indicated that master TFs may form phase-separated macromolecular condensates to promote super-enhancer (SE) assembly and oncogene expression. In this study, we demonstrated that SP1 undergoes phase separation and that its zinc finger 3 in the DNA-binding domain is essential for this process. Through Cleavage Under Targets & Release Using Nuclease (CUT&RUN) using antibodies against SP1 and H3K27ac, we found a significant correlation between SP1 enrichment and SE elements, identified the regulator of the G protein signaling 20 (RGS20) gene as the most likely target regulated by SP1 through SE mechanisms, and verified this finding using different approaches. The oncogenic activity of SP1 relies on its phase separation ability and RGS20 gene activation, which can be abolished by glycogen synthase kinase J4 (GSK-J4), a demethylase inhibitor. Together, our findings provide evidence that SP1 regulates its target oncogene expression through phase separation and SE mechanisms, thereby promoting LUAD cell progression. This study also revealed an innovative target for LUAD therapies through intervening in SP1-mediated SE formation.

Characterization of the covalent binding of cyanidin-3-glucoside to bovine serum albumin and its inhibition mechanism for advanced nonenzymatic glycosylation reactions.

Nonenzymatic glycosylation of proteins can generate advanced glycosylation end products, which are closely associated with the pathogenesis of certain chronic physiological diseases and aging. In this study, we characterized the covalent binding of cyanidin-3-glucoside (C3G) to bovine serum albumin (BSA) and investigated the mechanism by which this covalent binding inhibits the nonenzymatic glycosylation of BSA. The results indicated that the covalent interaction between C3G and BSA stabilized the protein's secondary structure. Through liquid chromatography-electrospray ionization tandem mass spectrometry analysis, we identified the covalent binding sites of C3G on BSA as lysine, arginine, asparagine, glutamine, and cysteine residues. This covalent interaction significantly suppressed the nonenzymatic glycosylation of BSA, consequently reducing the formation of nonenzymatic glycosylation products. C3G competitively binds to nonenzymatic glycosylation sites (e.g., lysine and arginine) on BSA, thereby impeding the glycosylation process and preventing the misfolding and structural alterations of BSA induced by fructose. Furthermore, the covalent attachment of C3G to BSA preserves the secondary structure of BSA and hinders subsequent nonenzymatic glycosylation events.

Exploring new frontiers: a rare case of catheter ablation for persistent atrial fibrillation in a patient with cor triatriatum sinister guided by intracardiac echocardiography.

BACKGROUND: Cor triatriatum sinister (CTS) is an uncommon congenital cardiac anomaly. Atrial fibrillation (AF) is commonly the initial symptom in patients with CTS, occurring in approximately 32% of the cases. The complexity of performing AF catheter ablation, particularly in cases with persistent AF, increases in patients with CTS due to its unique structural challenges. CASE PRESENTATION: We report the treatment course of a 60-year-old male patient diagnosed with CTS, who underwent catheter ablation of drug-refractory, persistent AF. The complex anatomical structure of the condition made catheter ablation of AF challenging. To navigate these challenges, we performed comprehensive assessments using transthoracic echocardiography and transesophageal echocardiography, along with cardiac computed tomography angiography, prior to treatment initiation. The intricate anatomy of CTS was further clarified during the procedure via intracardiac echocardiography (ICE). Additionally, the complexity of catheter manipulation was further reduced with the aid of the VIZIGO sheath and the vein of Marshall ethanol infusion to achieve effective mitral isthmus blockage, thereby circumventing the impact of the CTS membrane. CONCLUSIONS: This case underscores the complexity and potential of advanced ablation techniques in managing cardiac arrhythmias associated with unusual cardiac anatomies. During the procedure, ICE facilitated detailed modeling of the left atrium, including the membranous structure and its openings, thus providing a clearer understanding of CTS. It is noteworthy that the membrane within the CTS may serve as a potential substrate for arrhythmias, which warrants further validation through larger sample studies.

Construction of Bi/Bi2O3 particles embedded in carbon sheets for boosting the storage capacity of potassium-ion batteries.

Bismuth-based materials have attracted interest in potassium-ion batteries (PIBs). However, the large volume expansion prevents further use of bismuth-based materials for potassium storage. This work employs a two-step synthesis method to innovatively synthesize of Bi/Bi2O3 nanoparticles assembled on N-doped porous carbon sheets (Bi/Bi2O3@CN). The layered structures with uniformly shaped and N-doped porous carbon skeleton buffer the expansion of Bi and the Bi/Bi2O3 particles increase the capacity of potassium storage. In brief, the Bi/Bi2O3@CN served as anode in half-cell of PIBs have a good rate capacity of more than 234.7 mAh/g at 20 A/g. The specific capacity retention was 73 % compared with 322.16 mAh/g at 1 A/g, demonstrating good holding capacity for diverse current densities. The cycle also displays 163 mAh/g after 1500 cycles at 2 A/g in the KPF6 metal salt solution, showing its potential as one of the anode materials in PIBs.

In vivo quantitative characterization of nano adjuvant transport in the tracheal layer by photoacoustic imaging.

Adjuvants are indispensable ingredients in vaccine formulations. Evaluating the in vivo transport processes of adjuvants, particularly for inhalation formulations, presents substantial challenges. In this study, a nanosized adjuvant aluminum hydroxide (AlOOH) was synthesized and labeled with indocyanine green (ICG) and bovine serum albumin (BSA) to achieve strong optical absorption ability and high biocompatibility. The adjuvant nanomaterials (BSA@ICG@AlOOH, BIA) were delivered as an aerosol into the airways of mice, its distribution was monitored using photoacoustic imaging (PAI) in vivo. PAI results illustrated the gradual cross-layer transmission process of BIA in the tracheal layer, traversing approximately 250 µm from the inner layer of the trachea to the outer layer. The results were consistent with pathology. While the intensity of the BIA reduced by approximately 46.8% throughout the transport process. The ability of PAI for quantitatively characterized the dynamic transport process of adjuvant within the tracheal layer may be widely used in new vaccine development.

Myasthenia gravis due to anti-PD-1 treatment for an advanced colon cancer patient: a case report and literature review.

With the advancement of cancer treatment technologies, immunotherapy has begun to be widely utilized. Colon cancer is one of the most common types of cancer, with metastasis being a frequent occurrence in late-stage patients. Hence, immunotherapy, as an emerging and potentially effective treatment modality, merits exploration to enhance patient survival rates and clinical benefits. However, various immune-related adverse events cannot be entirely avoided. Myasthenia gravis induced by immunotherapy serves as a rare but potentially lethal adverse event, and it has been increasingly reported. Understanding the mechanisms of irAEs can aid in controlling the side effects induced by treatment. Here, we reported a case of myasthenia gravis occurring after anti-PD-1 therapy for late-stage colon cancer.

Correlation between dietary factors and Parkinson's disease revealed by the analysis of Mendelian randomization.

Background: The intricate interplay between dietary habits and the development of Parkinson's Disease (PD) has long been a subject of scientific inquiry. Mendelian Randomization (MR) emerges as a potent tool, harnessing genetic variants to infer causality in observational data. While evidence links diet to Parkinson's Disease (PD) etiology, a thorough MR exploration of dietary impacts on PD, particularly involving gut microbiota, is still emerging. Methods: This research leverages the IEU Open GWAS project's vast GWAS database to address the knowledge gap in understanding diet's influence on PD, employing a diverse range of dietary variables. Our holistic dataset includes various foods like processed fava beans, bap, red wine, to cheese, reflecting a commitment to untangling dietary complexities in PD etiology. Advancing from initial dietary-PD associations, we innovatively explore the gut microbiota, focusing on Parabacteroides goldsteinii, in relation to bap intake and PD, employing MR. Utilizing weighted median, MR-Egger, and inverse variance weighting methods, we ensure rigorous causality assessments, meticulously mitigating pleiotropy and heterogeneity biases to uphold finding validity. Results: Our findings indicate red wine (OR: 1.031; 95% CI 1.001-1.062; p = 0.044) and dried fruit consumption (OR: 2.019; 95% CI 1.052-3.875; p = 0.035) correlate with increased PD risk, whereas broad beans (OR: 0.967; 95% CI 0.939-0.996; p = 0.024) and bap intake (OR: 0.922; 95% CI 0.860-0.989; p = 0.023) show protective effects against PD. Employing MR, specifically the IVW method, revealed a significant inverse association between bap intake and gut microbiota, marked by an 8.010-fold decrease in Parabacteroides goldsteinii per standard deviation increase in bap intake (95% CI 1.005-63.818, p = 0.049). Furthermore, a connection between PD and Parabacteroides goldsteinii was observed (OR: 0.810; 95% CI 0.768-0.999; p = 0.049), suggesting a potential microbiota-mediated pathway in PD etiology. Conclusion: Our study links dietary habits to PD risk, showing higher PD risk with red wine and dried fruit consumption, and a protective effect from broad beans and bap. Using MR, we found bap intake inversely correlates with Parabacteroides goldsteinii in the gut, suggesting bap influences microbiota. Further, higher Parabacteroides goldsteinii levels correlate with lower PD risk, highlighting a complex interplay of diet, gut microbiome, and neurological health. These insights shed light on potential dietary interventions for PD.