Identifying potential causal effects of Parkinson's disease: A polygenic risk score-based phenome-wide association and mendelian randomization study in UK Biobank.

There is considerable uncertainty regarding the associations between various risk factors and Parkinson's Disease (PD). This study systematically screened and validated a wide range of potential PD risk factors from 502,364 participants in the UK Biobank. Baseline data for 1851 factors across 11 categories were analyzed through a phenome-wide association study (PheWAS). Polygenic risk scores (PRS) for PD were used to diagnose Parkinson's Disease and identify factors associated with PD diagnosis through PheWAS. Two-sample Mendelian randomization (MR) analysis was employed to assess causal relationships. PheWAS results revealed 267 risk factors significantly associated with PD-PRS among the 1851 factors, and of these, 27 factors showed causal evidence from MR analysis. Compelling evidence suggests that fluid intelligence score, age at first sexual intercourse, cereal intake, dried fruit intake, and average total household income before tax have emerged as newly identified risk factors for PD. Conversely, maternal smoking around birth, playing computer games, salt added to food, and time spent watching television have been identified as novel protective factors against PD. The integration of phenotypic and genomic data may help to identify risk factors and prevention targets for PD.

Regional brain structural network topology mediates the associations between white matter damage and disease severity in first-episode, Treatment-naïve pubertal children with major depressive disorder.

Puberty is a vulnerable period for the onset of major depressive disorder (MDD) due to considerable neurodevelopmental changes. Prior diffusion tensor imaging (DTI) studies in depressed youth have had heterogeneous participants, making assessment of early pathology challenging due to illness chronicity and medication confounds. This study leveraged whole-brain DTI and graph theory approaches to probe white matter (WM) abnormalities and disturbances in structural network topology related to first-episode, treatment-naïve pediatric MDD. Participants included 36 first-episode, unmedicated adolescents with MDD (mean age 15.8 years) and 29 age- and sex-matched healthy controls (mean age 15.2 years). Compared to controls, the MDD group showed reduced fractional anisotropy in the internal and external capsules, unveiling novel regions of WM disruption in early-onset depression. The right thalamus and superior temporal gyrus were identified as network hubs where betweenness centrality changes mediated links between WM anomalies and depression severity. A diagnostic model incorporating demographics, DTI, and network metrics achieved an AUROC of 0.88 and a F1 score of 0.80 using a neural network algorithm. By examining first-episode, treatment-naïve patients, this work identified novel WM abnormalities and a potential causal pathway linking WM damage to symptom severity via regional structural network alterations in brain hubs.

The association between inflammatory cytokines and sarcopenia-related traits: a bi-directional Mendelian randomization study.

BACKGROUND: Sarcopenia is among the most common musculoskeletal illnesses, yet its underlying biochemical mechanisms remain incompletely understood. Identifying the relationship of inflammatory cytokines with sarcopenia components would help understand the etiology of sarcopenia. We performed a bi-directional Mendelian randomization study to explore the causal relationship between 41 inflammatory cytokines and sarcopenia-related traits. METHODS: The study was performed in two stages using bidirectional dual-sample Mendelian randomization. We obtained aggregated statistical data on inflammatory factors, low grip strength, and ALM from genome-wide association studies. To explore the causal association between exposure and outcomes, we primarily utilized the inverse variance weighted strategy. Furthermore, we conducted sensitivity analyses through the use of Mendelian randomization (MR) Egger, weighted median and simple mode methods. To evaluate robustness of the results and to identify and adjust for horizontal pleiotropy, we performed the MR Pleiotropy RESidual Sum and Outlier test, the MR Egger intercept test, and a leave-one-out analysis. RESULTS: The results displayed a potential association between interleukin-10 (OR: 1.046, 95% CI: 1.002-1.093, p = 0.042) and vascular endothelial growth factor (OR: 1.024, 95% CI: 1.001-1.047, p = 0.038) and the risk of low hand-grip strength. Moreover, interferon gamma-induced protein 10 (OR: 1.010, 95% CI: 1.000-1.019, p = 0.042) and macrophage colony-stimulating factor (OR: 1.010, 95% CI: 1.003-1.017, p = 0.003) were significantly linked to a higher risk of ALM. CONCLUSION: We identified a causal relationship between multiple inflammatory factors and sarcopenia-related traits. Our study offers valuable insights into innovative methods for the sarcopenia prevention and treatment by regulating inflammatory factors.

The mutual interplay between NTRK fusion genes and human papillomavirus infection in cervical cancer progression (Review).

Cervical cancer is a significant global health concern, with a substantial portion of cases attributed to human papillomavirus (HPV) infection. Recent advancements in molecular profiling have identified distinct subtypes of cervical cancer based on their genomic alterations. One such subgroup is neurotrophic tropomyosin receptor kinase (NTRK) fusion-positive cervical cancers, characterized by gene fusions involving the NTRK genes. Although both NTRK fusion genes and HPV infections are independently recognized as significant risk factors in cervical cancer, their interplay and mutual effects on cancer progression are not yet fully understood. The present review is the first of its kind to explore the potential interplay between NTRK fusion genes and HPV infections. It surveys in detail how their combined effect can influence the signaling pathways during cervical cancer development and progression. Moreover, the present study discussed the clinical features, histopathological examinations, treatment procedures and follow-up outcomes of NTRK-fusion gene-positive cervical cancer. The present review may help in the understanding of the management and treatment of such rare, lethal and resistant cervical cancers.

Mutation Breeding of Monascus to Produce a High Yield of Orange Pigment and Low Citrinin Content Using the ARTP Method.

Monascus is a filamentous fungus with a long history of application in China, which can produce a variety of secondary metabolites, including Monascus red pigments, Monascus orange pigments, Monascus yellow pigments, and citrinin. There is widespread attention being paid to natural pigments because of their safety. Among the many natural pigments, orange pigment has a wide range of applications because of its unique color, but current production levels in the orange pigment industry are limited to a certain extent due to the insufficiently wide range of sources and low production. In this study, the ARTP mutation was used to obtain a strain with high-yield orange pigment and low citrinin. The strain RS7 was obtained through two-step mutagenesis, and all three pigments were improved to different degrees. The color value of orange pigment was elevated from the original 108 U/mL to 180 U/mL, an increase of 66.7% compared to the original strain, and the citrinin content was reduced by 69%. The result of microscopic morphology showed that RS7 has more wrinkles and is more convex than the R1 strain, but there was little change between the two strains. Therefore, the ARTP mutation influenced the growth and the biosynthesis of pigments in Monascus. In addition, the conditions of ultrasonic extraction of Monascus pigments were optimized using the response surface, and the separation of pigments was achieved with the method of thin-layer chromatography. Pigment stability results showed that the temperature had no significant effect on orange pigment, while tea polyphenol could improve its stability. This study generated a strain with high-yielding orange pigment and could lay a foundation for the future application of Monascus orange pigment in the food industry.

Role of blood metabolites in mediating the effect of gut microbiome on the mutated-RAS/BRAF metastatic colorectal cancer-specific survival.

BACKGROUND: Recent studies have linked alterations in the gut microbiome and metabolic disruptions to the invasive behavior and metastasis of colorectal cancer (CRC), thus affecting patient prognosis. However, the specific relationship among gut microbiome, metabolite profiles, and mutated-RAS/BRAF metastatic colorectal cancer (M-mCRC) remains unclear. Furthermore, the potential mechanisms and prognostic implications of metabolic changes induced by gut microbiome alterations in patients with M-mCRC still need to be better understood. METHODS: We conducted Mendelian randomization (MR) to evaluate the causal relationship of genetically predicted 196 gut microbiome features and 1400 plasma metabolites/metabolite ratios on M-mCRC-specific survival. Additionally, we identified significant gut microbiome-metabolites/metabolite ratio associations based on M-mCRC. Metabolite information was annotated, and functional annotation and pathway enrichment analyses were performed on shared proteins corresponding to significant metabolite ratios, aiming to reveal potential mechanisms by which gut microbiome influences M-mCRC prognosis via modulation of human metabolism. RESULTS: We identified 11 gut microbiome features and 49 known metabolites/metabolite ratios correlated with M-mCRC-specific survival. Furthermore, we identified 17 gut microbiome-metabolite/metabolite ratio associations specific to M-mCRC, involving eight lipid metabolites and three bilirubin degradation products. The shared proteins corresponding to significant metabolite ratios were predominantly localized within the integral component of the membrane and exhibited enzymatic activities such as glucuronosyltransferase and UDP-glucuronosyltransferase, crucial in processes such as glucuronidation, bile secretion, and lipid metabolism. Moreover, these proteins were significantly enriched in pathways related to ascorbate and aldarate metabolism, pentose and glucuronate interconversions, steroid hormone biosynthesis, and bile secretion. CONCLUSION: Our study offers novel insights into the potential mechanisms underlying the impact of the gut microbiome on the prognosis of M-mCRC. These findings serve as a meaningful reference for exploring potential therapeutic targets and strategies in the future.

Organic Thermoelectric Materials for Wearable Electronic Devices.

Wearable electronic devices have emerged as a pivotal technology in healthcare and artificial intelligence robots. Among the materials that are employed in wearable electronic devices, organic thermoelectric materials possess great application potential due to their advantages such as flexibility, easy processing ability, no working noise, being self-powered, applicable in a wide range of scenarios, etc. However, compared with classic conductive materials and inorganic thermoelectric materials, the research on organic thermoelectric materials is still insufficient. In order to improve our understanding of the potential of organic thermoelectric materials in wearable electronic devices, this paper reviews the types of organic thermoelectric materials and composites, their assembly strategies, and their potential applications in wearable electronic devices. This review aims to guide new researchers and offer strategic insights into wearable electronic device development.

Identifying novel proteins for migraine by integrating proteomes from blood and CSF with genome-wide association data.

BACKGROUND: Proteome-wide Mendelian randomization studies have been increasingly utilized to identify potential drug targets for diseases. We aimed to identify potential therapeutic targets for migraine and its subtypes through the application of Mendelian randomization and co-localization analysis methods. METHODS: We utilized cis-protein quantitative trait loci data for 1378 plasma proteins available from two studies with 7213 individuals and 35,559 individuals, respectively. Summary data for migraine and its subtypes were obtained from a genetic study involving up to 1,339,303 individuals. Proteins that passed both the discovery and validation Mendelian randomization analysis, sensitivity analysis, heterogeneity test, and pleiotropy test, were associated with ≥2 outcomes, and received strong support from co-localization analysis (PP.H4.abf ≥0.80) and were classified as tier 1 proteins. RESULTS: We identified three tier 1 proteins (LRP11, ITIH1, and ADGRF5), whose genes have not been previously identified as causal genes for migraine in genetic studies. LRP11 was significantly associated with the risk of any migraine (OR [odds ratio] = 0.968, 95% CI [confidence interval] = 0.955-0.981, p = 1.27 × 10-6) and significantly/suggestively associated with three migraine subtypes. ITIH1 was significantly associated with the risk of any migraine (OR = 1.044, 95% CI = 1.024-1.065, p = 1.08 × 10-5) and migraine with visual disturbances. ADGRF5 was significantly associated with the risk of any migraine (OR = 0.964, 95% CI = 0.946-0.982, p = 8.74 × 10-5) and suggestively associated with migraine with aura. The effects of LRP11 and ADGRF5 were further replicated using cerebrospinal fluid protein data. Apart from ADGRF5, there was no evidence of potential adverse consequences when modulating the plasma levels. We also identified another four proteins (PLCG1, ARHGAP25, CHGA, and MANBA) with no potential adverse consequences when modulating the plasma levels, and their genes were not reported by previous genetic studies. CONCLUSIONS: We found compelling evidence for two proteins and suggestive evidence for four proteins that could be promising targets for migraine treatment without significant adverse consequences. The corresponding genes were not reported in previous genetic studies. Future studies are needed to confirm the causal role of these proteins and explore the underlying mechanisms.

Delivery of exogenous miR-19b by Wharton's Jelly Mesenchymal Stem Cells attenuates transplanted kidney ischemia/reperfusion injury by regulating cellular metabolism.

Renal ischemia-reperfusion injury (IRI) frequently occurs following kidney transplantation, and exosomes derived from umbilical cord mesenchymal stem cells (WJ-MSC-Exos) have shown promise in treating IRI in transplanted kidneys. Our study delved into the potential mechanism of WJ-MSC-Exos in ameliorating IRI in transplanted kidneys, revealing that miR-19b is abundantly present in WJ-MSC-Exos. Both in vivo and in vitro experiments demonstrated that the absence of miR-19b abolished the protective effects of WJ-MSC-Exos against renal IRI. Mechanistically, miR-19b suppressed glycogen synthase kinase-3ß (GSK3ß) expression, thereby stabilizing PDXK protein through direct binding. Treatment with WJ-MSC-Exos led to reduced PDXK levels and enhanced pyridoxine accumulation, ultimately mitigating IRI in transplanted kidneys and I/R-induced HK2 cell apoptosis. These findings elucidate the underlying mechanism of WJ-MSC-Exos in alleviating IRI in transplanted kidneys, unveiling novel therapeutic targets for post-kidney transplantation IRI and providing a solid theoretical foundation for the clinical application of WJ-MSC-Exos in IRI treatment post-transplantation.

The potential protective role of peripheral immunophenotypes in Alzheimer's disease: a Mendelian randomization study.

Introduction: Alzheimer's disease (AD) is the most widespread neurodegenerative disease in the world. Previous studies have shown that peripheral immune dysregulation plays a paramount role in AD, but whether there is a protective causal relationship between peripheral immunophenotypes and AD risk remains ambiguous. Methods: Two-sample Mendelian randomization (MR) was performed using large genome-wide association study (GWAS) genetic data to assess causal effects between peripheral immunophenotypes and AD risk. Utilizing the genetic associations of 731 immune cell traits as exposures. We adopted the inverse variance weighted method as the primary approach. The Weighted median and MR-Egger regression methods were employed as supplements. Various sensitivity analyses were performed to assess the robustness of the outcomes. Results: Based on the IVW method, we identified 14 immune cell traits that significantly reduced the risk of AD, of which six demonstrated statistical significance in both IVW and Weighted median methods. Among the seven immune traits, four were related to regulatory T (Treg) cells : (1) CD25++ CD45RA- CD4 not regulatory T cell % T cell (odds ratio (OR) [95% confidence interval (CI)] = 0.96 [0.95, 0.98], adjusted P = 1.17E-02), (2) CD25++ CD45RA- CD4 not regulatory T cell % CD4+ T cell (OR [95% CI] = 0.97 [0.96, 0.99], adjusted P = 3.77E-02), (3) Secreting CD4 regulatory T cell % CD4 regulatory T cell (OR [95% CI] = 0.98 [0.97, 0.99], adjusted P = 7.10E-03), (4) Activated & secreting CD4 regulatory T cell % CD4 regulatory T cell(OR [95% CI] = 0.98 [0.97, 0.99], adjusted P = 7.10E-03). In addition, HLA DR++ monocyte % monocyte (OR [95% CI] = 0.93 [0.89, 0.98], adjusted P = 4.87E-02) was associated with monocytes, and HLA DR on myeloid Dendritic Cell (OR [95% CI] = 0.93 [0.89, 0.97], adjusted P = 1.17E-02) was related to dendritic cells (DCs). Conclusion: These findings enhance the comprehension of the protective role of peripheral immunity in AD and provide further support for Treg and monocyte as potential targets for immunotherapy in AD.

MTF1 genetic variants are associated with lung cancer risk in the Chinese Han population.

BACKGROUND: Metal-regulatory transcription factor 1 (MTF1), a conserved metal-binding transcription factor in eukaryotes, regulates the proliferation of cancer cells by activating downstream target genes and then participates in the formation and progression of tumors, including lung cancer (LC). The expression level of MTF1 is down-regulated in LC, and high expression of MTF1 is associated with a good prognosis of LC. However, the association between MTF1 polymorphism and LC risk has not been explored. METHODS: The genotyping of MTF1 Single nucleotide polymorphisms (SNPs) including rs473279, rs28411034, rs28411352, and rs3748682 was identified by the Agena MassARRAY system among 670 healthy controls and 670 patients with LC. The odds ratio (OR) and 95% confidence intervals (CI) were calculated by logistics regression to assess the association of these SNPs with LC risk. RESULTS: MTF1 rs28411034 (OR 1.22, 95% CI 1.03-1.45, p = 0.024) and rs3748682 (OR 1.24, 95% CI 1.04-1.47, p = 0.014) were associated with higher LC susceptibility overall. Moreover, the effect of rs28411034 and rs3748682 on LC susceptibility was observed in males, subjects with body mass index (BMI) ≥ 24 kg/m2, smokers, drinkers, and patients with lung squamous carcinoma (OR and 95% CI > 1, p < 0.05). Besides, rs28411352 (OR 0.73, 95% CI 0.55-0.97, p = 0.028,) showed protective effect for reduced LC risk in drinkers. CONCLUSIONS: We were first who reported that rs28411034 and rs3748682 tended to be relevant to increased LC susceptibility among the Chinese Han population. These results of this study could help to recognize the pathogenic mechanisms of the MTF1 gene in LC progress.

Hexokinase 2 nonmetabolic function-mediated phosphorylation of IκBα enhances pancreatic ductal adenocarcinoma progression.

Aberrant signaling in tumor cells induces nonmetabolic functions of some metabolic enzymes in many cellular activities. As a key glycolytic enzyme, the nonmetabolic function of hexokinase 2 (HK2) plays a role in tumor immune evasion. However, whether HK2, dependent of its nonmetabolic activity, plays a role in human pancreatic ductal adenocarcinoma (PDAC) tumorigenesis remains unclear. Here, we demonstrated that HK2 acts as a protein kinase and phosphorylates IκBα at T291 in PDAC cells, activating NF-κB, which enters the nucleus and promotes the expression of downstream targets under hypoxia. HK2 nonmetabolic activity-promoted activation of NF-κB promotes the proliferation, migration, and invasion of PDAC cells. These findings provide new insights into the multifaceted roles of HK2 in tumor development and underscore the potential of targeting HK2 protein kinase activity for PDAC treatment.

Thalassotalea psychrophila sp. nov., Thalassotalea nanhaiensis sp. nov. and Thalassotalea fonticola sp. nov., three psychrophilic bacteria isolated from deep-sea sediment.

Three psychrophilic bacteria, designated as strains SQ149T, SQ345T, and S1-1T, were isolated from deep-sea sediment from the South China Sea. All three strains were the most closely related to Thalassotalea atypica RZG4-3-1T based on the 16S rRNA gene sequence analysis (similarity ranged from 96.45 to 96.67 %). Phylogenetic analysis based on the 16S rRNA gene and core-genome sequences showed that three strains formed a cluster within the genus Thalassotalea. The average amino acid identity, average nucleotide identity, and digital DNA-DNA hybridization values among the three strains and closest Thalassotalea species were far below the cut-off value recommended for delineating species, indicating they each represented a novel species. All three strains were Gram-stain-negative, rod-shaped, and contained summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c) as the predominant fatty acid, Q-8 as the major respiratory quinone, and phosphatidylethanolamine and phosphatidylglycerol as predominant polar lipids. Based on the genomic, phylogenetic, and phenotypic characterizations, each strain is considered to represent a novel species within the genus Thalassotalea, for which the names Thalassotalea psychrophila sp. nov. (type strain SQ149T=MCCC 1K04231T=JCM 33807T), Thalassotalea nanhaiensis sp. nov. (type strain SQ345T=MCCC 1K04232T=JCM 33808T), and Thalassotalea fonticola sp. nov. (type strain S1-1T=MCCC 1K06879T=JCM 34824T) are proposed.

Association between egg consumption and mortality risk in United States adults with established coronary heart disease or stroke: A cohort study using data from NHANES 1999-2018.

BACKGROUND: To investigate the relationship between egg consumption and mortality in individuals with pre-existing coronary heart disease or stroke. METHODS: This study utilized data from the National Health and Nutrition Examination Survey conducted between 1999 and 2018. Egg consumption was evaluated through 24 h dietary recalls at baseline. Mortality status was tracked until December 31, 2019. Survey-weighted Cox proportional hazards models were utilized. RESULTS: The study involved 3,975 participants aged 20 years or older with a median follow-up of 89.00 months. A total of 1,675 individuals died during follow-up. Compared to individuals who did not consume eggs, the consumption of 0-50 g/day (hazard ratio [HR] = 1.033, 95% confidence interval [CI] =0.878-1.214) was not found to have a significant association with all-cause mortality. However, consuming 50-100 g/day (HR = 1.281, 95% CI = 1.004-1.635) and >100 g/day (HR = 1.312, 95% CI =1.036-1.661) exhibited a significant association with an increased risk of all-cause mortality. We identified a non-liner relationship between egg consumption and cardiovascular mortality, where the risk was found to be lowest at an intake of about 50 g/day. For individuals consuming more than 50 g/day, each additional 50 g increment in egg consumption was significantly linked to an elevated risk of cardiovascular mortality (HR = 1.276, 95% CI = 1.009-1.614). CONCLUSION: In U.S. adults with pre-existing cardiovascular disease, a significant positive association was found between consuming over 50 g of eggs per day and the risk of mortality, highlighting the importance of moderate intake.

Celastrol mediates CAV1 to attenuate pro-tumorigenic effects of senescent cells.

BACKGROUND: Cellular senescence is an emerging hallmark of cancers, primarily fuels cancer progression by expressing senescence-associated secretory phenotype (SASP). Caveolin-1 (CAV1) is a key mediator of cell senescence. Previous studies from our group have evidenced that the expression of CAV1 is downregulated by Celastrol (CeT). PURPOSE: To investigate the impact of CeT on cellular senescence and its subsequent influence on post-senescence-driven invasion, migration, and stemness of clear cell renal cell carcinoma (ccRCC). STUDY DESIGN AND METHODS: The expression levels of CAV1, canonical senescence markers, and markers associated with epithelial-mesenchymal transition (EMT) and stemness in clinical samples were assessed through Pearson correlation analysis. Senescent cell models were induced using DOX, and their impact on migration, invasion, and stemness was evaluated. The effects of CeT treatment on senescent cells and their pro-tumorigenic effects were examined. Subsequently, the underlying mechanism of CeT were explored using lentivirus transfection and CRISPR/Cas9 technology to silence CAV1. RESULTS: In human ccRCC clinical samples, the expression of the canonical senescence markers p53, p21, and p16 are associated with ccRCC progression. Senescent cells facilitated migration, invasion, and enhanced stemness in both ccRCC cells and ccRCC tumor-bearing mice. As expected, CeT treatment reduced senescence markers (p16, p53, p21, SA-ß-gal) and SASP factors (IL6, IL8, CXCL12), alleviating cell cycle arrest. However, it did not restore the proliferation of senescent cells. Additionally, CeT suppressed senescence-driven migration, invasion, and stemness. Further investigations into the underlying mechanism demonstrated that CAV1 is a critical mediator of cell senescence and represents a potential target for CeT to attenuate cellular senescence. CONCLUSIONS: This study presents a pioneering investigation into the intricate interplay between cellular senescence and ccRCC progression. We unveil a novel mechanism of CeT to mitigate cellular senescence by downregulating CAV1, thereby inhibiting the migration, invasion and stemness of ccRCC driven by senescent cells. These findings provide valuable insights into the underlying mechanisms of CeT and its potential as a targeted therapeutic approach for alleviating the aggressive phenotypes associated with senescent cells in ccRCC.

Interventional effects of Pueraria oral liquid on T2DM rats and metabolomics analysis.

Pueraria lobata, commonly known as kudzu, is a medicinal and food plant widely used in the food, health food, and pharmaceutical industries. It has clinical pharmacological effects, including hypoglycemic, antiinflammatory, and antioxidant effects. However, its mechanism of hypoglycemic effect on type 2 diabetes mellitus (T2DM) has not yet been elucidated. In this study, we prepared a Pueraria lobata oral liquid (POL) and conducted a comparative study in a T2DM rat model to evaluate the hypoglycemic effect of different doses of Pueraria lobata oral liquid. Our objective was to investigate the hypoglycemic effect of Puerarin on T2DM rats and understand its mechanism from the perspective of metabolomics. In this study, we assessed the hypoglycemic effect of POL through measurements of FBG, fasting glucose tolerance test, plasma lipids, and liver injury levels. Furthermore, we examined the mechanism of action of POL using hepatic metabolomics. The study's findings demonstrated that POL intervention led to improvements in weight loss, blood glucose, insulin, and lipid levels in T2DM rats, while also providing a protective effect on the liver. Finally, POL significantly affected the types and amounts of hepatic metabolites enriched in metabolic pathways, providing an important basis for revealing the molecular mechanism of Pueraria lobata intervention in T2DM rats. These findings indicate that POL may regulate insulin levels, reduce liver damage, and improve metabolic uptake in the liver. This provides direction for new applications and research on Pueraria lobata to prevent or improve T2DM.

Occurrence, Risk Implications, Prevention and Control of CIT in Monascus Cheese: A Review.

Monascus is a filamentous fungus that has been used in the food and pharmaceutical industries. When used as an auxiliary fermenting agent in the manufacturing of cheese, Monascus cheese is obtained. Citrinin (CIT) is a well-known hepatorenal toxin produced by Monascus that can harm the kidneys structurally and functionally and is frequently found in foods. However, CIT contamination in Monascus cheese is exacerbated by the metabolic ability of Monascus to product CIT, which is not lost during fermentation, and by the threat of contamination by Penicillium spp. that may be introduced during production and processing. Considering the safety of consumption and subsequent industrial development, the CIT contamination of Monascus cheese products needs to be addressed. This review aimed to examine its occurrence in Monascus cheese, risk implications, traditional control strategies, and new research advances in prevention and control to guide the application of biotechnology in the control of CIT contamination, providing more possibilities for the application of Monascus in the cheese industry.

Association between irritable bowel syndrome and Parkinson's disease by Cohort study and Mendelian randomization analysis.

This study aimed to investigate the association between irritable bowel syndrome (IBS) and Parkinson's disease (PD) utilizing prospective cohort study and Mendelian randomization. The dataset contained a substantial cohort of 426,911 participants from the UK Biobank, discussing the association between IBS and PD with Cox proportional hazards models and case-control analysis while adjusting for covariates such as age, gender, ethnicity and education level. In univariate Cox regression model, the risk of PD was reduced in IBS patients (HR: 0.774, 95%CI: 0.625-0.956, P = 0.017), but the statistical significance diminished in the three models after adjusting for other variables. In a few subgroup analyses, IBS patients are less likely to develop into PD, and patients diagnosed with IBS after 2000 also had a lower risk (HR: 0.633, 95%CI: 0.403-0.994, P = 0.047) of subsequently developing PD. In addition, we matched five healthy control participants based on gender and age at the end of the study for each IBS patient diagnosed during the follow-up period, and logistic regression results (OR:1.239, 95%CI: 0.896-1.680, P = 0.181) showed that IBS was not associated with the risk of PD. Mendelian randomization did not find significant evidence of the causal relationship between IBS and Parkinson's disease (OR: 0.801, 95%CI: 0.570-1.278, P = 0.204). Overall, we suggest that IBS status is not associated with the risk of developing PD, and that these findings provide valuable insights into the clinical management and resource allocation of patients with IBS.