Upregulation of PECTATE LYASE5 by a NAC transcription factor promotes fruit softening in apple.

Flesh firmness is a critical breeding trait that determines consumer selection, shelf life, and transportation. The genetic basis controlling firmness in apple (Malus×domestica Borkh.) remains to be fully elucidated. We aimed to decipher genetic variance for firmness at harvest and develop potential molecular markers for marker-assisted breeding. Maturity firmness for 439 F1 hybrids from a cross of 'Cripps Pink' and 'Fuji' was determined in 2016 and 2017. The phenotype segregated extensively, with a Gaussian distribution. In a combined bulked segregant analysis (BSA) and RNA-sequencing analysis, eighty-four differentially expressed genes were screened from the 10 QTL regions. Interestingly, next-generation re-sequencing analysis revealed a Harbinger-like transposon element insertion upstream of the candidate gene PECTATE LYASE5 (MdPL5); the genotype was associated with flesh firmness at harvest. The presence of this transposon repressed MdPL5 expression and was closely linked to the extra-hard phenotype. MdPL5 was demonstrated to promote softening in apples and tomatoes. Subsequently, using the MdPL5 promoter as bait, MdNAC1-L was identified as a transcription activator that positively regulates ripening and softening in the developing fruit. We also demonstrated that MdNAC1-L could induce the up-regulation of MdPL5, MdPG1, and the ethylene-related genes MdACS1 and MdACO1. Our findings provide insight into TE-related genetic variation and the PL-mediated regulatory network for the firmness of apple fruit.

Plasma IL-6 levels and their association with brain health and dementia risk: A population-based cohort study.

BACKGROUND: Recent studies have associated immune abnormalities with dementia. IL-6 is a crucial cytokine in inflammatory responses, and recent evidence has linked elevated IL-6 levels to changes in brain structure and cognitive decline. However, the connection between IL-6 levels, cognition, brain volumes, and dementia risk requires exploration in large prospective cohorts. METHODS: This study utilized a longitudinal cohort from the UK Biobank to analyze the correlation between IL-6 expression levels, cognitive performance, and cortical and subcortical brain volumes through linear regression. Additionally, we assessed the association between IL-6 levels and long-term dementia risk using Cox regression analysis. We also used one-sample Mendelian randomization to analyze the impact of genetic predisposition of dementia on elevated IL-6 levels. RESULTS: A total of 50,864 participants were included in this study, with 1,391 new cases of all-cause dementia identified. Higher plasma IL-6 levels are associated with cortical and subcortical atrophy in regions such as the fusiform, thalamus proper, hippocampus, and larger ventricle volumes. IL-6 levels are negatively associated with cognitive performance in pair matching, numeric memory, prospective memory, and reaction time tests. Furthermore, elevated IL-6 levels are linked to a 23-35 % increased risk of all-cause dementia over an average follow-up period of 13.2 years. The one-sample Mendelian randomization analysis did not show associations between the genetic predisposition of dementia and elevated IL-6 levels. CONCLUSIONS: Increased IL-6 levels are associated with worse cognition, brain atrophy, and a heightened risk of all-cause dementia. Our study highlights the need to focus on the role of peripheral IL-6 levels in managing brain health and dementia risk.

Exogenous Methyl Jasmonate (MeJA) Improves 'Ruixue' Apple Fruit Quality by Regulating Cell Wall Metabolism.

'Ruixue' apples were used as the test material to study the effect of 10 µM methyl jasmonate (MeJA) on the quality and cell wall metabolism of apples after 18 d of storage. The results showed that MeJA significantly decreased the respiratory rate, reduced the titratable acid content and maintained a high soluble solids content. MeJA has been shown to suppress the activities and gene expressions of WSP, CSP, ISP, and cellulose in contrast to the control group, thereby maintaining a lower cell permeability and higher exocarp firmness. MeJA significantly decreased the expression of MdACS, MdACO, MdPL, Mdgal, and MdPG genes in the apple exocarp when compared to the control group. In addition, the overexpression of MdPL18 increased the content of cell wall polysaccharides such as WSP and CSP, enhanced cell wall-degrading enzyme activities, and accelerated fruit ripening and softening, whereas silencing MdPL18 did the opposite. Together, these results demonstrate that exogenous MeJA maintains the Ruixue apple fruit quality by regulating the metabolism of cell wall substances.

Comparison of Fruit Texture and Storage Quality of Four Apple Varieties.

Fruit texture and storage properties of various apple varieties exhibit significant variation. The rate of fruit softening post-harvest plays a crucial role in determining fruit quality and shelf life. This research utilized four apple varieties as test subjects to investigate the internal factors influencing fruit texture changes among different varieties. By monitoring changes in relevant physiological indicators during the post-harvest texture softening process, the study examined fruit quality, cell wall material content, hydrolase activity, and gene transcription levels during storage of 'Orin', 'RX', 'RXH', and 'Envy' apples. Initial fruit softening was primarily linked to heightened post-harvest fruit respiration intensity, ethylene production, and rapid amylase activity. Subsequent softening was associated with increased activity of water-soluble pectin (WSP), cellulose (CEL), and other hydrolases. With the extension of the storage period, the fruit cells of the four varieties became more loosely arranged, resulting in larger intercellular gaps. Variations in WSP and cellulose content, CEL activity, and relative expression of Mdß-gal were observed among the different apple varieties, potentially accounting for the disparities in fruit texture.

Effects of Different Pre-Harvest Bagging Times on Fruit Quality of Apple.

Pre-harvest bagging can improve fruit color and protects against diseases. However, it was discovered that improper bagging times could lead to peel browning in production. Using the Ruixue apple variety as the research model, a study was conducted to compare the external and internal quality of fruits bagged at seven different timings between 50 and 115 days after full bloom (DAFB). Our findings indicate that delaying the bagging time can reduce the occurrence of peel browning in Ruixue apples. Compared to the control, the special bag reduced the browning index by 22.95%. However, the fruit point index of Ruixue fruits increased by 65.05% at 115 DAFB compared to 50 DAFB when bagging was delayed. The chlorophyll content of Ruixue fruits in special bags generally increased and then decreased, with the highest chlorophyll content of Ruixue fruits in special bags at 90 DAFB, which was 26.02 mg·kg-1. When the bagging process was delayed, the soluble solids, total phenols, and flavonoids content in the fruits increased, while the number of control volatiles decreased by 10. After two years of testing, results show that using special fruit bags at 90 DAFB bagging can significantly improve the fruit quality of Ruixue apple.

Single-cell landscape of immune cells during the progression from HBV infection to HBV cirrhosis and HBV-associated hepatocellular carcinoma.

Introduction: Immune cells play crucial roles in the development of chronic hepatitis B virus (HBV) infection, leading to cirrhosis and hepatocellular carcinoma (HCC). However, their functions at different disease stages are not fully understood. Methods: In this study, we used single-cell RNA sequencing (scRNA-seq) to characterize the human liver immune microenvironment at different disease stages. We analyzed scRNA-seq data from 118,455 immune cells obtained from livers of six healthy individuals, four patients with HBV infection, five patients with HBV cirrhosis, and three patients with HBV-associated HCC. Results: Our results showed an accumulation of scar-associated macrophages during disease progression, and we identified two relevant immune subsets, Macrophage-CD9/IL18 and macrophage-CD9/IFI6. Macrophage-CD9/IL18 expanded from HBV infection to cirrhosis, while macrophage-CD9/IFI6 expanded from cirrhosis to HCC. We verified the existence of Macrophage-CD9/IFI6 using multiplex immunofluorescence staining. We also found an increase in cytotoxic NK Cell-GNLY during progression from cirrhosis to HCC. Additionally, the proportion of CD4 T cell-TNFAIP3, CD8 T cell-TNF (effector CD8 T cells), and CD8 T cell-CD53 increased, while the proportion of Treg cells decreased from HBV infection to cirrhosis. The proportion of Treg and CD8 T cell-LAG3 (Exhausted CD8 T cell) enhanced, while the proportion of CD8 T cell-TNF (effector CD8 T cells) decreased from cirrhosis to HCC. Furthermore, GSEA enrichment analyses revealed that MAPK, ERBB, and P53 signaling pathways in myeloid cells were gradually inhibited from HBV infection to cirrhosis and HCC. Discussion: Our study provides important insights into changes in the hepatic immune environment during the progression of HBV-related liver disease, which may help improve the management of HBV-infected liver diseases.

ERGPNet: lesion segmentation network for COVID-19 chest X-ray images based on embedded residual convolution and global perception.

The Segmentation of infected areas from COVID-19 chest X-ray (CXR) images is of great significance for the diagnosis and treatment of patients. However, accurately and effectively segmenting infected areas of CXR images is still challenging due to the inherent ambiguity of CXR images and the cross-scale variations in infected regions. To address these issues, this article proposes a ERGPNet based on embedded residuals and global perception, to segment lesion regions in COVID-19 CXR images. First, aiming at the inherent fuzziness of CXR images, an embedded residual convolution structure is proposed to enhance the ability of internal feature extraction. Second, a global information perception module is constructed to guide the network in generating long-distance information flow, alleviating the interferences of cross-scale variations on the algorithm's discrimination ability. Finally, the network's sensitivity to target regions is improved, and the interference of noise information is suppressed through the utilization of parallel spatial and serial channel attention modules. The interactions between each module fully establish the mapping relationship between feature representation and information decision-making and improve the accuracy of lesion segmentation. Extensive experiments on three datasets of COVID-19 CXR images, and the results demonstrate that the proposed method outperforms other state-of-the-art segmentation methods of CXR images.

Transcription Factor MdbHLH093 Enhances Powdery Mildew Resistance by Promoting Salicylic Acid Signaling and Hydrogen Peroxide Accumulation.

Powdery mildew is an apple disease caused by the obligate trophic fungus Podosphaera leucotricha. Basic helix-loop-helix (bHLH) transcription factors play important roles in plant development and stress responses, and they have been widely studied in model plants such as Arabidopsis thaliana. However, their role in the stress response of perennial fruit trees remains unclear. Here, we investigated the role of MdbHLH093 in the powdery mildew of apples. The expression of MdbHLH093 was significantly induced during the infection of apples with powdery mildew, and the allogenic overexpression of MdbHLH093 in A. thaliana enhanced the resistance to powdery mildew by increasing the accumulation of hydrogen peroxide (H2O2) and activating the salicylic acid (SA) signaling pathway. The transient overexpression of MdbHLH093 in apple leaves increased the resistance to powdery mildew. Conversely, when MdbHLH093 expression was silenced, the sensitivity of apple leaves to powdery mildew was increased. The physical interaction between MdbHLH093 and MdMYB116 was demonstrated by yeast two-hybrid, bi-molecular fluorescence complementation, and split luciferase experiments. Collectively, these results indicate that MdbHLH093 interacts with MdMYB116 to improve apple resistance to powdery mildew by increasing the accumulation of H2O2 and activating the SA signaling pathway, as well as by providing a new candidate gene for resistance molecular breeding.

Ultra-Short-Term Wind Power Forecasting Based on CGAN-CNN-LSTM Model Supported by Lidar.

Accurate prediction of wind power is of great significance to the stable operation of the power system and the vigorous development of the wind power industry. In order to further improve the accuracy of ultra-short-term wind power forecasting, an ultra-short-term wind power forecasting method based on the CGAN-CNN-LSTM algorithm is proposed. Firstly, the conditional generative adversarial network (CGAN) is used to fill in the missing segments of the data set. Then, the convolutional neural network (CNN) is used to extract the eigenvalues of the data, combined with the long short-term memory network (LSTM) to jointly construct a feature extraction module, and add an attention mechanism after the LSTM to assign weights to features, accelerate model convergence, and construct an ultra-short-term wind power forecasting model combined with the CGAN-CNN-LSTM. Finally, the position and function of each sensor in the Sole du Moulin Vieux wind farm in France is introduced. Then, using the sensor observation data of the wind farm as a test set, the CGAN-CNN-LSTM model was compared with the CNN-LSTM, LSTM, and SVM to verify the feasibility. At the same time, in order to prove the universality of this model and the ability of the CGAN, the model of the CNN-LSTM combined with the linear interpolation method is used for a controlled experiment with a data set of a wind farm in China. The final test results prove that the CGAN-CNN-LSTM model is not only more accurate in prediction results, but also applicable to a wide range of regions and has good value for the development of wind power.

Changes in the VOC of Fruits at Different Refrigeration Stages of 'Ruixue' and the Participation of Carboxylesterase MdCXE20 in the Catabolism of Volatile Esters.

Aroma is a crucial quality attribute of apple fruit, which significantly impacts its commercial value and consumer choice. Despite its importance the volatile aroma substances produced by the new variety 'Ruixue' after harvest remain unclear. In this study, we utilized headspace solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) to investigate the changes in volatile substances, fruit hardness, crispness, and related aroma synthase activity of commercially mature 'Ruixue' apples during cold storage. Our findings revealed a gradual decline in fruit firmness and brittleness of 'Ruixue' apples during cold storage, with hexyl acetate, hexyl caproate, and hexyl thiocyanate being the main hexyl esters detected. To gain a better understanding of the metabolic pathway of esters, we identified 42 MdCXE gene members that are associated with ester degradation. Through RT-qPCR analysis, we discovered that carboxylesterase MdCXE20 exhibited higher expression levels compared to other MdCXE genes during cold storage. To confirm the role of MdCXE20, we conducted a transient injection of apple fruits and observed that overexpression of MdCXE20 led to the degradation of esters such as hexyl hexanoate, butyl hexanoate, butyl 2-methylbutyrate, hexyl butyrate, and hexyl 2-methylbutyrate. The results of the study showed that the virus-induced gene silencing of MdCXE20 found the opposite results. Additionally, the esters of OE-MdCXE20 callus showed a lower content of ester VOC than the control callus, according to the homologous stable transformation of 'Wanglin' callus. Overall, these findings suggest that the MdCXE20 gene plays a crucial role in the decrease of esters in 'Ruixue' apples, which ultimately affects their flavor.

Genetic analysis and QTL mapping of aroma volatile compounds in the apple progeny 'Fuji' × 'Cripps Pink'.

Aroma is an essential trait for apple fruit quality, but the understanding of biochemical mechanisms underlying aroma formation is still limited. To better characterize and assess the genetic potential for improving aroma quality for breeding, many efforts have been paid to map quantitative trait loci (QTLs) using a saturated molecular linkage map. In the present study, aroma profiles in ripe fruit of F1 population between 'Fuji' and 'Cripps Pink' were evaluated by gas chromatography-mass spectrometry (GC-MS) over 2019 and 2020 years, and the genetics of volatile compounds were dissected. In total, 38 volatile compounds were identified in 'Fuji' × 'Cripps Pink' population, including 23 esters, 3 alcohols, 7 aldehydes and 5 others. With the combination of aroma phenotypic data and constructed genetic linkage map, 87 QTLs were detected for 15 volatile compounds on 14 linkage groups (LGs). Among them, a set of QTLs associated with ester production identified and confirmed on LG 6. A candidate gene MdAAT6 in the QTL mapping interval was detected. Over-expression of MdAAT6 in tomato and apple fruits showed significantly higher esters accumulation compared to the control, indicating it was critical for the ester production. Our results give light on the mode of inheritance of the apple volatilome and provide new insights for apple flavor improvement in the future.

Spatio-temporal variation of soil microplastics as emerging pollutant after long-term application of plastic mulching and organic compost in apple orchards.

Microplastics (MPs) pollution in agroecosystems have aroused great alarm and widespread concern. However, the spatial distribution and temporal variation characteristics of MPs in apple orchards with long-term plastic mulching and organic compost input are still poorly understood. This study investigated MPs accumulation characteristics and vertical distribution after applying plastic mulch and organic compost in apple orchards for 3 (AO-3), 9 (AO-9), 17 (AO-17), and 26 (AO-26) years on the Loess Plateau. The clear tillage (no plastic mulching and organic composts) area was used as a control (CK). At a soil depth of 0-40 cm, AO-3, AO-9, AO-17, and AO-26 treatments increased the abundances of MPs, and the black fibers and fragments of rayon and polypropylene were dominant. In the 0-20 cm soil layer, the abundances of MPs increased with the treatment time; the abundance was 4333 pieces kg-1 after 26 years of treatment, gradually decreasing with soil depth. In different treatments and soil layers, the percentages of MPs <1000 µm were dominant (>50%). The AO-17 and AO-26 treatments significantly increased the MPs with the size of 0-500 µm at 0-40 cm and the abundances of pellets in 0-60 cm soil. In conclusion, the long-term (≥17 years) application of plastic mulching and organic composts increased the abundances of small particles at 0-40 cm, and plastic mulching contributed the most to MPs, while organic composts increased the complexity and diversity of MPs.

Association between childhood trauma and white matter deficits in first-episode schizophrenia.

OBJECTIVE: This study aimed to investigate the relationship between childhood trauma (ChT) and white matter (WM) deficits in first-episode schizophrenia (FES). METHODS: A total of 103 individuals with FES and 206 healthy control individuals (HCs) were enrolled and assessed based on ChT Questionnaire (CTQ) and Positive and Negative Symptoms Scale (PANSS). Diffusion tensor imaging was acquired on a Signa 3.0 T scanner. Map of fractional anisotropy (FA) was analyzed using Tract-Based Spatial Statistics. Hierarchical logistic regression analyses were used to examine associations of sociodemographic characteristics, total CTQ scores, and WM deficits. RESULTS: Compared with the HCs group, the FES group showed significantly lower FA in several WM bundles (left anterior thalamic radiation, left inferior frontal-occipital fasciculus, left cingulum, forceps major, and forceps minor), and the mean FA value in these WM bundles was inversely related to the total CTQ score. In addition, a higher CTQ score may increase the risk of schizophrenia, while higher FA values may decrease the risk of schizophrenia. CONCLUSION: This study demonstrates that individuals with FES evince widespread cerebral WM abnormalities and that these abnormalities were associated with ChT. These results provide clues about the neural basis and potential biomarkers of schizophrenia.

Transcriptomic and metabolomic analysis reveals a protein module involved in preharvest apple peel browning.

Peel browning is a natural phenomenon that adversely affects the appearance of fruits. Research on the regulation of browning in apples (Malus × domestica Borkh.) has mainly focused on postharvest storage, while studies at the preharvest stage are relatively rare. Apple is an economically important horticultural crop prone to peel browning during growth, especially when the fruits are bagged (dark conditions). The present study's integrated transcriptomics and metabolomics analysis revealed that preharvest apple peel browning was primarily due to changes in phenolics and flavonoids. The detailed analysis identified MdLAC7's (laccase 7) role in the preharvest apple peel browning process. Transient injection, overexpression, and CRISPR/Cas9 knockout of the MdLAC7 gene in apple fruit and calli identified vallinic acid, anthocyanidin, tannic acid, sinapic acid, and catechinic acid as its catalytic substrates. In addition, yeast one-hybrid assay, electrophoretic mobility shift assay, luciferase reporter assay, and ChIP-PCR analysis revealed that MdWRKY31 binds to the promoter of MdLAC7 and positively regulates its activity to promote peel browning of bagged fruits (dark conditions). Interestingly, upon light exposure, the light-responsive transcription factor MdHY5 (ELONGATED HYPOCOTYL 5) bound to the promoter of MdWRKY31 and inhibited the gene's expression, thereby indirectly inhibiting the function of MdLAC7. Subsequent analysis showed that MdHY5 binds to the MdLAC7 promoter at the G-box1/2 site and directly inhibits its expression in vivo. Thus, the study revealed the MdLAC7-mediated mechanism regulating preharvest apple peel browning and demonstrated the role of light in inhibiting MdLAC7 activity and subsequently reducing peel browning. These results provide theoretical guidance for producing high-quality apple fruits.

Methylorubrum rhodesianum M520 as a biocontrol agent against Meloidogyne incognita (Tylenchida: Heteroderidae) J2s infecting cucumber roots.

AIMS: Root-knot nematodes (RKNs) are plant pathogens that cause huge economic losses worldwide. The biological management of RKNs may be a sustainable alternative to chemical control methods. Here, the biocontrol potential of Methylorubrum rhodesianum M520 against the RKN Meloidogyne incognita was investigated to theoretically support its application as a biocontrol agent in field production. METHODS AND RESULTS: In-vitro assays showed 91.9% mortality of M. incognita second-stage juveniles in the presence of strain M520 and that the hatching rate of M. incognita eggs was 21.7% lower than that of eggs treated with sterile water. In pot experiments, the M520 treatment caused 70.8% reduction in root-knots and increased plant shoot length and stem and root fresh weights, compared to control plant values. In split-root experiments, cucumber roots treated with M520 showed 25.6% decrease in root gall number, compared to that in control roots. CONCLUSION: M520 has multiple mechanisms against RKNs and might be used as a biocontrol agent against M. incognita in cucumber, laying a foundation for further studying M520 biocontrol against RKNs.

Plasma Membrane-Localized Transporter MdSWEET12 Is Involved in Sucrose Unloading in Apple Fruit.

Sugar content is an important factor determining the flavor in apple fruit. Sugar unloading is a prerequisite step for sugar accumulation. However, little is known about sugar unloading mechanisms in apple. Transcriptomic sequencing of two apple varieties, "Envy" and "Pacific Rose," with significantly different sugar content was performed. MdSWEET12a from the SWEET transporter family was differentially expressed. Further study of the MdSWEET12a showed that this plasma membrane-localized transporter protein-encoding gene was mainly expressed in sieve element-companion cells (SE-CC) in the fruit, which was positively correlated with the sucrose accumulation during the development of "Envy" apple. Consistently manipulating the gene expression through either transient overexpression or silencing significantly increased or decreased the sugar content in apple fruit, respectively. Complementary growth experiments in mutant yeast cells indicated that MdSWEET12a transported sucrose. Heterologous expression of MdSWEET12a in tomato increased the expression of genes related to sugar metabolism and transport, leading to increased sugar content. These findings underpin the involvement of MdSWEET12a in sugar unloading in apple fruit.

Variation in Cell Wall Metabolism and Flesh Firmness of Four Apple Cultivars during Fruit Development.

Fruit ripening and softening are highly complex processes, and there is an interplay and coordination between the metabolic pathways that are involved in the biological processes. In this study, we aimed to elucidate the variation in the characters and possible causes of cell wall materials and morphological structure during apple fruits development. We studied the cell wall material (CWM), structure, cellular morphology, hydrolase activity, and the transcriptional levels of the related genes in four apple varieties 'Ruixue' and 'Ruixianghong' and their parents ('Pink Lady' and 'Fuji') during fruit development. The decrease in the contents of CWMs, sodium carbonate soluble pectin, hemicellulose, and cellulose were positively correlated with the decline in the hardness during the fruit development. In general, the activities of polygalacturonase, ß-galactosidase, and cellulase enzymes increased during the late developmental period. As the fruit grew, the fruit cells of all of the cultivars gradually became larger, and the cell arrangement became more relaxed, the fruit cell walls became thinner, and the intercellular space became larger. In conclusion, the correlation analysis indicated that the up-regulation of the relative expression levels of ethylene synthesis and cell wall hydrolase genes enhanced the activity of the cell wall hydrolase, resulting in the degradation of the CWMs and the depolymerization of the cell wall structure, which affected the final firmness of the apple cultivars in the mature period.

Associations between urban birth or childhood trauma and first-episode schizophrenia mediated by low IQ.

Exposure to urban birth, childhood trauma, and lower Intelligence Quotient (IQ) were the most well-established risk factors for schizophrenia in developed countries. In developing countries, whether urban birth is a risk factor for schizophrenia and how these factors are related to one another remain unclear. This study aimed to investigate whether IQ mediates the relationship between urban birth or childhood trauma and first-episode schizophrenia (FES) in China. Birthplace, childhood trauma questionnaire (CTQ), and IQ were collected from 144 patients with FES and 256 healthy controls (HCs). Hierarchical logistic regression analysis was conducted to investigate the associations between birthplace, childhood trauma, IQ, and FES. Furthermore, mediation analysis was used to explore the mediation of IQ in the relationship between birthplace or childhood trauma and FES. After adjusting for age, sex and educational attainment, the final model identified urban birth (odds ratio (OR) = 3.15, 95% CI = 1.54, 6.44) and childhood trauma (OR = 2.79, 95% CI = 1.92, 4.06) were associated an elevated risk for FES. The 52.94% total effect of birthplace on the risk of FES could be offset by IQ (indirect effect/direct effect). The association between childhood trauma and FES could be partly explained by IQ (22.5%). In total, the mediation model explained 70.5% of the total variance in FES. Our study provides evidence that urban birth and childhood trauma are associated with an increased risk of FES. Furthermore, IQ mediates the relationship between urban birth or childhood trauma and FES.

The causal relationship between neuromyelitis optica spectrum disorder and other autoimmune diseases.

Objectives: The coexistence of neuromyelitis optica spectrum disorder (NMOSD) with other autoimmune diseases has been well recognized. However, the causal association between these two conditions has not been fully studied. The etiology and therapies of NMOSD coexisting with autoimmune diseases also need to be elucidated. Methods: We performed two-sample Mendelian randomization (MR) analysis to examine the causality. Genome-wide association (GWAS) summary data from NMOSD, autoimmune thyroid disease (AITD), systemic lupus erythematosus (SLE), and Sjogren's syndrome (SS) were used to identify genetic instruments. Causal single-nucleotide polymorphisms (SNPs) were annotated and searched for cis-expression quantitative trait loci (cis-eQTL) data. Pathway enrichment analysis was performed to identify the mechanism of NMOSD coexisting with AITD, SLE, and SS. Potential therapeutic chemicals were searched using the Comparative Toxicogenomics Database. Results: The MR analysis found that AITD, SLE, and SS were causally associated with NMOSD susceptibility, but not vice versa. Gene Ontology (GO) enrichment analysis revealed that MHC class I-related biological processes and the interferon-gamma-mediated signaling pathway may be involved in the pathogenesis of NMOSD coexisting with AITD, SLE, and SS. A total of 30 chemicals were found which could inhibit the biological function of cis-eQTL genes. Conclusions: Our findings could help better understand the etiology of NMOSD and provide potential therapeutic targets for patients with coexisting conditions.