OSR1 suppresses oral squamous cell carcinoma proliferation and migration via the AXIN2/ß-catenin pathway.

OBJECTIVES: The odd-skipped related transcription factor 1 (OSR1) gene exerts distinct regulatory effects on tumorigenesis and development in various cancer types. However, the precise role of OSR1 in oral squamous cell carcinoma (OSCC) remains to be elucidated. METHODS: GEPIA 2 and TCGA databases were utilized to analyze the OSR1 expression in head and neck squamous cell carcinoma (HNSC) patients and its impact on prognosis. Hematoxylin-eosin staining, immunohistochemistry, immunofluorescence, western blotting, and RT-qPCR were employed to detect the OSR1 expression in OSCC tissues and cells. Lentivirus transfection was utilized for overexpression and downexpression of OSR1 in OSCC. CCK8 cell proliferation assay, colony formation and cell scratch assay were conducted to investigate the effects of OSR1 on biological behavior of OSCC cells. Western blotting and RT-qPCR were applied to investigate the regulatory mechanism of OSR1 on AXIN2/ß-catenin signaling pathway. RESULTS: OSR1 expression was significantly decreased in HNSC patients, OSCC tissues and cells, leading to a decrease in 5-year survival rate. OSR1 overexpression inhibited the proliferation and migration of OSCC cells, and the AXIN2/ß-catenin signaling pathway was inhibited. Silencing OSR1 had the opposite effect. CONCLUSIONS: OSR1 functioned as a tumor suppressor gene in OSCC proliferation and migration by regulating the AXIN2/ß-catenin signaling pathway.

Characterization and discrimination of donkey milk lipids and volatiles across lactation stages.

The lipid and flavor in milk are key factors that affect its quality, which profiles during donkey lactation are not yet clear. In this study, the lipids and volatile compounds (VOCs) in donkey milk from stages of lactation were analyzed by using LC-MS and GC-IMS. A total of 1774 lipids were identified in donkey milk, spanning over 6 major categories and attributed to 30 subclasses. The 233 differentially expressed lipids were identified between donkey colostrum and mature milk, which participate in 20 metabolic pathways, including glycerophospholipid, linoleic acid, and sphingolipid. Additionally, 35 VOCs in donkey milk were identified, including 28.57% aldehydes, 28.57% ketones, 25.71% esters, and 8.57% alcohols. Of these VOCs, 15 were determined to be characteristic flavors in donkey milk, mainly including methyl 2-methylbutanoate, 2-pentanone, and butyl acetate. 11 significantly different VOCs were found between the groups. Acetone, 2-heptanone, and ethyl acetate-m were considered potential discriminatory markers.

Toxicological effects of di(2-ethylhexyl)phthalate on dandelions: Insights into physiological, metabolic, and molecular docking perspectives.

Di(2-ethylhexyl)phthalate (DEHP) is one of the most widely used plasticizers in plastic manufacturing. However, the toxicological effects of DEHP on dandelions remain poorly understood. This study comprehensively analyzed and explored the response mechanisms of dandelions to 1, 10, 50, and 100 mg L-1 DEHP influencing the morphophysiological growth, metabolomics, and molecular docking. DEHP reduced chlorophyll synthesis, inhibited plant growth, and induced oxidative-state-associated stress, which was manifested by the excessive production of reactive oxygen species, an increase in antioxidant enzyme activities, and enhanced synthesis of some osmoregulatory compounds, including proline and soluble protein. An analysis of the integrated biological response index showed that the toxicity was dose-dependent. Molecular docking demonstrated that DEHP could bind stably to three enzymes, and the binding energy was peroxidase (POD) > catalase (CAT) > superoxide dismutase (SOD). Metabolomics revealed that metabolite abundance and metabolic pathways were altered by DEHP, with 88 and 72 primary metabolites identified in shoots and roots, respectively. Amino acid, sugar, and organic acid metabolism were severely disturbed, with the most significant effects being on carbohydrate metabolism, valine, leucine, and isoleucine biosynthesis. Our study elucidated the influence of DEHP exposure on dandelions, providing new insights into the toxicity mechanisms and toxicological risk assessment.

XBB.1.16-RBD-based trimeric protein vaccine can effectively inhibit XBB.1.16-included XBB subvariant infection.

The newly identified XBB.1.16-containing sublineages, including XBB.1.5, have become the prevailing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant in circulation. Unlike previous Omicron XBB variants (e.g., XBB.1.5 and XBB.1.9) harboring the F486P substitution, XBB.1.16 also carries a T478R substitution in the receptor-binding domain (RBD). Numerous researchers have delved into the high transmissibility and immune evasion of XBB.1.16 subvariant. Therefore, developing a new vaccine targeting XBB.1.16, including variants of concern (VOCs), is paramount. In our study, we engineered a recombinant protein by directly linking the S-RBD sequence of the XBB.1.16 strain of SARS-CoV-2 to the sequences of two heptad repeat sequences (HR1 and HR2) from the SARS-CoV-2 S2 subunit. Named the recombinant RBDXBB.1.16-HR/trimeric protein, this fusion protein autonomously assembles into a trimer. Combined with an MF59-like adjuvant, the RBDXBB.1.16-HR vaccine induces a robust humoral immune response characterized by high titers of neutralizing antibodies against variant pseudovirus and authentic VOCs and cellular immune responses. Additionally, a fourth heterologous RBDXBB.1.16-HR vaccine enhances both humoral and cellular immune response elicited by three-dose mRNA vaccines. These findings demonstrate that the recombinant RBDXBB.1.16-HR protein, featuring the new T478R mutation, effectively induces solid neutralizing antibodies to combat newly emerged XBB variants.

Intestinal Parasitic Infections May Be Overlooked Drivers of the Tuberculosis Pandemic.

The burden of tuberculosis (TB) is disproportionate in tropical and subtropical regions, where parasitic coinfections are common. Given the significant geographical overlap between TB and intestinal parasitic infections, it is important to consider the implications of intestinal parasitic infections for the TB pandemic. Intestinal parasitic infections have been theorized to increase vulnerability to TB by altering the inflammatory milieu, inducing undernutrition that blunts the immune response, and affecting drug pharmacokinetics. In this perspective piece, we provide a background of the epidemiological and immunological evidence that links parasitic infections to increased risk of TB progression and worse treatment outcomes. We also identify gaps in our knowledge and call for increased research on TB-parasitic coinfections to ensure action on a potentially widespread TB comorbidity.

Deep cervical lymph nodes in Parkinson's disease and atypical Parkinson's disease: A potential ultrasound biomarker for differential diagnosis.

Background: Parkinson's disease (PD) is a common degenerative disease caused by abnormal accumulation of α-synuclein. The glymphatic pathway is essential for removing macromolecular proteins including α-synuclein from the brain, which flows into deep cervical lymph nodes (DCLNs) through meningeal lymphatics. As a terminal station for the cerebral lymphatic system drainage, DCLNs can be easily assessed clinically. Objectives: Although the drainage function of the cerebral lymphatic system is impaired in PD, the correlation between DCLNs and PD remains unknown. Design: Single-center retrospective cross-sectional study. Methods: The size of the DCLNs were measured using ultrasound. The Movement Disorder Society Sponsored Revision Unified Parkinson's Disease Rating Scale and other scales were used to assess PD motor and non-motor symptoms. Results: Compared with the healthy control (HC) and the atypical Parkinson's disease (AP) groups, the size of the second and third DCLNs in the Parkinson's disease (PD) group was significantly smaller (P < .05). The width diameter of the third DCLN (DCLN3(y)) was significantly smaller in the PD group than in the AP group (P = .014). DCLN3(y) combined with a variety of clinical features improved the sensitivity of AP identification (sensitivity = .813). Conclusion: DCLNs were able to distinguish HC, PD and AP and were mainly located in Robbins ΙΙA level. PD and AP were associated with different factors that influenced the size of the DCLNs. DCLN3(y) plays an important role in differentiating PD from AP, which, combined with other clinical features, has the ability to distinguish PD from AP; in particular, the sensitivity of AP diagnosis was improved.

Deep cervical lymph nodes, a potential marker for the diagnosis of PD and AP. Deep cervical lymph nodes (DCLNs) were able to distinguish HC, PD and AP and were mainly located in Robbins ΙΙA level. PD and AP were associated with different factors that influenced the size of the DCLNs. DCLN3(y) plays an important role in differentiating PD from AP, which, combined with other clinical features, has the ability to distinguish PD from AP; in particular, the sensitivity of AP diagnosis was improved. DCLN has potential diagnostic value in differentiating PD from AP.

Transcriptome mechanisms of dandelion under stress of polystyrene and dibutyl phthalate and quantitative tracing of nanoplastics.

Polystyrene nanoplastics (PS NPs) and dibutyl phthalate (DBP) pollution pose significant risks to ecosystems and contribute to bioaccumulation in plants, yet uptake mechanisms and combined toxicity are poorly understood. We used fluorescent labeling and europium-doped PS NPs to reveal the absorption and translocation of NPs by dandelions and conducted a transcriptomic analysis under PS NPs and DBP exposure. The results indicated that NPs are transported horizontally through the intercellular gaps at the root tips and primary root-lateral root junctions via the apoplastic pathway, followed by longitudinal transport through the xylem vessels under the transpiration stream. Co-exposure significantly reduced the bioconcentration factors of dandelion seedlings by 113 % but increased the NP transfer factors by 33.8 %. Transcriptomic analysis confirmed that exposure to PS NPs and DBP activated gene expression in dandelion shoots and roots. The differentially expressed genes were primarily involved in the photosynthesis, plant hormone signal transduction, and phenylpropanoid biosynthesis pathways. Weighted gene co-expression network analysis identified key genes and hub transcription factors playing crucial roles in regulating dandelion's response to combined stress. Our study provides new insights into the plant toxicity mechanism underlying the interaction between PS NPs and DBP, highlighting the adverse effects of the combined pollution on plant health.

Vagus Nerve and Gut-Brain Communication.

The vagus nerve, as an important component of the gut-brain axis, plays a crucial role in the communication between the gut and brain. It influences food intake, fat metabolism, and emotion by regulating the gut-brain axis, which is closely associated with the development of gastrointestinal, psychiatric, and metabolism-related disorders. In recent years, significant progress has been made in understanding the vagus-mediated regulatory pathway, highlighting its profound implications in the development of many diseases. Here, we summarize the latest advancements in vagus-mediated gut-brain pathways and the novel interventions targeting the vagus nerve. This will provide valuable insights for future research on treatment of obesity and gastrointestinal and depressive disorders based on vagus nerve stimulation.

Bencaosome [16:0 Lyso PA+XLGB28-sRNA] improves osteoporosis by simultaneously promoting osteogenesis and inhibiting osteoclastogenesis in mice.

Osteoporosis (OP) is a systemic metabolic bone disease resulting in reduced bone strength and increased susceptibility to fractures, making it a significant public health and economic problem worldwide. The clinical use of anti-osteoporosis agents is limited because of their serious side effects or the high cost of long-term use. The Xianlinggubao (XLGB) formula is an effective traditional Chinese herbal medicine commonly used in orthopedics to treat osteoporosis; however, its mechanism of action remains unclear. In this study, we screened 40 small RNAs derived from XLGB capsules and found that XLGB28-sRNA targeting TNFSF11 exerted a significant anti-osteoporosis effect in vitro and in vivo by simultaneously promoting osteogenesis and inhibiting osteoclastogenesis. Oral administration of bencaosome [16:0 Lyso PA+XLGB28-sRNA] effectively improved bone mineral density and reduced the damage to the bone microstructure in mice. These results suggest that XLGB28-sRNA may be a novel oligonucleotide drug that promotes osteogenesis and inhibits osteoclastogenesis in mice.

Oral administration of herbal oligonucleotide drug JGL-sRNA-h7 ameliorates hyperglycemia in db/db mice and beagle dogs.

Type 2 diabetes mellitus is a prevalent metabolic disease, posing a considerable threat to public health. Oligonucleotide drugs have proven to be a promising field of therapy for the diseases. In this study, we reported that a herbal small RNA (sRNA), JGL-sRNA-h7 (B34735529, F1439.L002444.A11), could exhibit potent hypoglycemic effects by targeting glucose-6-phosphatase. Oral administration of sphingosine (d18:1)-JGL-sRNA-h7 bencaosomes ameliorated hyperglycemia and diabetic kidney injury better than metformin in db/db mice. Furthermore, glucose tolerance was also improved in sphingosine (d18:1)-JGL-sRNA-h7 bencaosomes-treated beagle dogs. Our study indicates that JGL-sRNA-h7 could be a promising hypoglycemic oligonucleotide drug.

Effect of cadmium and polystyrene nanoplastics on the growth, antioxidant content, ionome, and metabolism of dandelion seedlings.

Cadmium is the most prevalent heavy metal pollutant in the environment and can be readily combined with micro/nanoplastics (M/NPs) to change their bioavailability. In the present study, we comprehensively investigated the effect of polystyrene (PS) NPs on dandelion plants grown under Cd stress. Cd exposure significantly inhibited the growth of dandelion seedlings, resulting in a decrease in seedling elongation from 26.47% to 28.83%, a reduction in biomass from 29.76% to 54.14%, and an exacerbation of lipid peroxidation and oxidative stress. The interaction between PS NPs and Cd resulted in the formation of larger aggregates, with the Cd bioavailability reduced by 12.56%. PS NPs affect ion absorption by regulating reactive oxygen production and increasing superoxide dismutase activity, thereby mitigating the adverse effects of Cd. PSCd aggregates induced significant changes in the metabolic profiles of dandelions, affecting various carbohydrates related to alcohols, organic acids, sugar metabolism, and bioactive components related to flavonoids and phenolic acids. Furthermore, based on a structural equation model, exposure to PSCd activated oxidative stress and nutrient absorption, thereby affecting plant growth and Cd accumulation. Overall, our study provides valuable insights into the effects of PS NPs on Cd bioavailability, accumulation, and plant growth, which are crucial for understanding the food safety of medicinal plants in a coexistence environment.

Targeting c-Myc transactivation by LMNA inhibits tRNA processing essential for malate-aspartate shuttle and tumour progression.

BACKGROUND: A series of studies have demonstrated the emerging involvement of transfer RNA (tRNA) processing during the progression of tumours. Nevertheless, the roles and regulating mechanisms of tRNA processing genes in neuroblastoma (NB), the prevalent malignant tumour outside the brain in children, are yet unknown. METHODS: Analysis of multi-omics results was conducted to identify crucial regulators of downstream tRNA processing genes. Co-immunoprecipitation and mass spectrometry methods were utilised to measure interaction between proteins. The impact of transcriptional regulators on expression of downstream genes was measured by dual-luciferase reporter, chromatin immunoprecipitation, western blotting and real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) methods. Studies have been conducted to reveal impact and mechanisms of transcriptional regulators on biological processes of NB. Survival differences were analysed using the log-rank test. RESULTS: c-Myc was identified as a transcription factor driving tRNA processing gene expression and subsequent malate-aspartate shuttle (MAS) in NB cells. Mechanistically, c-Myc directly promoted the expression of glutamyl-prolyl-tRNA synthetase (EPRS) and leucyl-tRNA synthetase (LARS), resulting in translational up-regulation of glutamic-oxaloacetic transaminase 1 (GOT1) as well as malate dehydrogenase 1 (MDH1) via inhibiting general control nonrepressed 2 or activating mechanistic target of rapamycin signalling. Meanwhile, lamin A (LMNA) inhibited c-Myc transactivation via physical interaction, leading to suppression of MAS, aerobic glycolysis, tumourigenesis and aggressiveness. Pre-clinically, lobeline was discovered as a LMNA-binding compound to facilitate its interaction with c-Myc, which inhibited aminoacyl-tRNA synthetase expression, MAS and tumour progression of NB, as well as growth of organoid derived from c-Myc knock-in mice. Low levels of LMNA or elevated expression of c-Myc, EPRS, LARS, GOT1 or MDH1 were linked to a worse outcome and a shorter survival time of clinical NB patients. CONCLUSIONS: These results suggest that targeting c-Myc transactivation by LMNA inhibits tRNA processing essential for MAS and tumour progression.

Effects of polyethylene and biodegradable microplastics on the physiology and metabolic profiles of dandelion.

Biodegradable plastics, such as poly(butylene adipate terephthalate) (PBAT) and polylactic acid (PLA), are potential alternatives to conventional polyethylene (PE), both of which are associated with the production of microplastics (MPs). However, the toxicity of these compounds on medicinal plants and their differential effects on plant morphophysiology remain unclear. This study supplemented soils with MPs sized at 200 µm at a rate of 1% w/w and incubated them for 50 days to investigate the impact of MPs on the growth and metabolites of dandelion (Taraxacum mongolicum Hand.-Mazz.). The results demonstrated that the investigated MPs decreased the growth of dandelion seedlings, induced oxidative stress, and altered the activity of antioxidant enzymes (superoxide dismutase, peroxidase, and catalase). Based on the comprehensive toxicity assessment results, the ecological toxicity was in the following order: PE MPs > PBAT MPs > PLA MPs. Metabolomics analyses revealed metabolic reprogramming in dandelion plants, leading to the enrichment of numerous differentially accumulated metabolites (DAMs) in the leaves. These pathways include carbohydrate metabolism, energy metabolism, and biosynthesis of secondary metabolites, suggesting that dandelions respond to MP stress by enhancing the activity of sugar, organic acid, and amino acid metabolic pathways. In addition, phenolic acids and flavonoids are critical for maintaining the balance in the antioxidant defense system. Our results provide substantial insights into the toxicity of biodegradable MPs to plants and shed light on plant defense and adaptation strategies. Further assessment of the safety of biodegradable MPs in terrestrial ecosystems is essential to provide guidance for environmentally friendly management.

Undernourished Household Contacts Are at Increased Risk of Tuberculosis (TB) Disease, but not TB Infection-a Multicenter Prospective Cohort Analysis.

Undernutrition is the leading risk factor for tuberculosis (TB) globally and in India. This multicenter prospective cohort analysis from India suggests that undernutrition is associated with increased risk of TB disease but not TB infection among household contacts of persons with TB.

Characterization of lipids and volatile compounds in boiled donkey meat by lipidomics and volatilomics.

Lipids are crucial substances for the formation and retention of volatile compounds (VOCs). The lipid and VOC profiles of boiled donkey meat were investigated by lipidomics and volatilomics. In total, 4277 lipids belonging to 39 subclasses were identified, comprising 26.93% triglycerides (TGs), 15.74% phosphatidylcholins (PCs), and 9.40% phosphatidylethanolamines. The relative percentage of TG in the meat significantly decreases (p < 0.001) from 0 to 40 min, after which there is no significant change, whereas PCs, sphingomyelins, and methyl phosphatidylcholines (MePCs) show the opposite trend. TG(16:1_18:1_18:2) and TG(16:0_16:1_18:2) appear to be key lipids for retaining VOCs in boiled donkey meat. Furthermore, PC(18:3e_16:0) and MePC(31:0e) were found to be potential markers for discriminating donkey meat. A total of 83 VOCs were detected, including 25.30% aldehydes, 18.07% hydrocarbons, 14.46% ketones, and 13.25% alcohols. Eleven characteristic VOCs with relative odor activity values >1 were identified as the predominant flavor compounds in boiled donkey meat, mainly hexanal and 1-octen-3-ol. Of the 258 differential lipids, 72 of them, especially polyunsaturated-fatty acid-rich lipids, are the main contributors to the formation of VOCs. Together, the key lipids for retention and formation of VOCs in donkey meat were revealed, providing a theoretical basis for VOC regulation.

The cGAS-Ku80 complex regulates the balance between two end joining subpathways.

As the major DNA sensor that activates the STING-TBK1 signaling cascade, cGAS is mainly present in the cytosol. A number of recent reports have indicated that cGAS also plays critical roles in the nucleus. Our previous work demonstrated for the first time that cGAS is translocated to the nucleus upon the occurrence of DNA damage and inhibits homologous recombination (HR), one of the two major pathways of DNA double strand break (DSB) repair. However, whether nuclear cGAS regulates the other DSB repair pathway, nonhomologous end joining (NHEJ), which can be further divided into the less error-prone canonical NHEJ (c-NHEJ) and more mutagenic alternative NHEJ (alt-NHEJ) subpathways, has not been characterized. Here, we demonstrated that cGAS tipped the balance of the two NHEJ subpathways toward c-NHEJ. Mechanistically, the cGAS-Ku80 complex enhanced the interaction between DNA-PKcs and the deubiquitinase USP7 to improve DNA-PKcs protein stability, thereby promoting c-NHEJ. In contrast, the cGAS-Ku80 complex suppressed alt-NHEJ by directly binding to the promoter of Polθ to suppress its transcription. Together, these findings reveal a novel function of nuclear cGAS in regulating DSB repair, suggesting that the presence of cGAS in the nucleus is also important in the maintenance of genome integrity.

Lysophosphatidic acid responsive photosensitive supramolecular organic frameworks for tumor imaging, drug loading, and photodynamic therapy.

Supramolecular organic frameworks have been widely applied for biological detection and drug delivery. In this study, a supramolecular organic framework (SOF) is constructed through the self-assembly of a highly photosensitive triarylphosphine oxide guest molecule, OTPP-6-Methyl, with cucurbit [8] uril (CB [8]). The formation of the SOF gradually enhances the weak fluorescence of OTPP-6-Methyl owing to the restriction of the molecular folding motion. Although the high positive charge of OTPP-6-Methyl facilitates binding to various negatively charged substances, the SOF system only demonstrated an obvious fluorescence response to LPA, a biomarker of ovarian cancer, via the disassembly of SOF and subsequent binding of OTPP-6-Methyl with LPA. The fluorescence changes during the entire process are insufficient to allow the sensitive detection of LPA; thus, we further designed a FRET system by introducing Cy5, which can act as an energy receptor to achieve a ratiometric readout for LPA. The tumor-targeting cRGD group was introduced into the SOF system as part of another guest molecule, OTPP-5-M-1-cRGD, to improve the tumor-targeting ability of the SOF system. The SOF system further improves the photosensitivity of guest molecules, and is therefore used in the in vivo imaging of ovarian cancer subcutaneous tumors and as a DDS for loading DOX for the combined in vivo chemotherapy and photodynamic treatment of tumors.

Isotope engineering for spin defects in van der Waals materials.

Spin defects in van der Waals materials offer a promising platform for advancing quantum technologies. Here, we propose and demonstrate a powerful technique based on isotope engineering of host materials to significantly enhance the coherence properties of embedded spin defects. Focusing on the recently-discovered negatively charged boron vacancy center ([Formula: see text]) in hexagonal boron nitride (hBN), we grow isotopically purified h10B15N crystals. Compared to [Formula: see text] in hBN with the natural distribution of isotopes, we observe substantially narrower and less crowded [Formula: see text] spin transitions as well as extended coherence time T2 and relaxation time T1. For quantum sensing, [Formula: see text] centers in our h10B15N samples exhibit a factor of 4 (2) enhancement in DC (AC) magnetic field sensitivity. For additional quantum resources, the individual addressability of the [Formula: see text] hyperfine levels enables the dynamical polarization and coherent control of the three nearest-neighbor 15N nuclear spins. Our results demonstrate the power of isotope engineering for enhancing the properties of quantum spin defects in hBN, and can be readily extended to improving spin qubits in a broad family of van der Waals materials.

Environmental governance-public supervision and participation nexus under state supervision system and carbon neutrality targets in China.

China is now experiencing severe environmental issues due to its rapid socio-economic advancement. Environmental governance is crucial to preserving China's rapidly degrading natural ecology. Public supervision and participation are important factors that effectively promote environmental quality. Therefore, this analysis primarily examines the relationship between China's public participation and environmental governance. Hence, the primary focus of the analysis is to investigate the asymmetric impact of public participation on environmental governance from 1996 to 2020. We have employed the nonlinear QARDL model that estimates the short- and long-run impact across different quantiles. The study's results support that long-run estimates for positive change in environmental NGOs (ENGOs) are significantly positive for almost all quantiles, while those for negative change in ENGOs are negative and have a significant impact at higher quantiles. In the short run, the estimates of positive change in ENGOs are positive and significant; however, the negative change in ENGOs does not significantly impact environmental governance at lower quantiles. The Wald test also confirms the asymmetric impact of ENGOs on environmental governance across various quantiles in short and long run. The findings of this analysis underscore the critical role of public supervision and participation in influencing environmental governance in China.

Assessment of bidirectional relationships between multiple sclerosis and epilepsy: A two-sample Mendelian randomization study.

BACKGROUND AND OBJECTIVE: Epidemiological studies indicate that multiple sclerosis (MS) is associated with epilepsy. However, the causality and directionality of this association remain under-elucidated. This study aimed to reveal the causality between MS and epilepsy. METHODS: A two-sample Mendelian randomization (MR) analysis was performed by using summarized statistics derived from large genome-wide association studies of MS and epilepsy. We used the inverse variance weighted method as the primary approach, and then four other MR methods to bidirectionally evaluate the causality of the association between MS and epilepsy. Additional sensitivity analyses were performed to measure the robustness of the findings. RESULTS: Genetically predicted MS was positively correlated with developing all epilepsy [odds ratio (OR) = 1.027 (1.003-1.051), P  =  0.028] and generalized epilepsy [OR = 1.050 (1.008-1.094), P = 0.019]. In the reverse MR analysis, all epilepsy [OR = 1.310 (1.112-1.543), P = 0.001], generalized epilepsy [OR = 1.173 (1.010-1.363), P = 0.037], and focal epilepsy [OR = 1.264 (1.069-1.494), P  =  0.006] elevated the risk of developing MS. The result remained robust and congruous across all sensitivity analyses conducted. CONCLUSIONS: MS is potentially associated with a higher risk of developing epilepsy. Furthermore, epilepsy may be a causal determinant of MS risk. These findings may further the understanding of the interaction of the two conditions.