Greater adherence to the Mediterranean Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet is associated with lower risk of inflammatory bowel disease: a prospective cohort study.

Background: The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet is emerging as a promising candidate for preventive measures against inflammatory bowel disease (IBD), though there is currently no direct evidence from population-based studies. This study aims to bridge the gap in understanding of the association of the MIND diet with IBD risk. Methods: We utilized data from 187 490 participants in the UK Biobank who provided dietary information and were free of IBD at baseline. Dietary information was obtained using a validated web-based 24-hour dietary recall questionnaire. A MIND diet score was evaluated based on the intake of ten beneficial and five unhealthy food groups and the scores were further grouped into tertiles. The outcome of interest was incident IBD, Crohn's disease (CD), and ulcerative colitis (UC). Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models adjusted for demographic characteristics, lifestyle factors, cancer history, and other dietary factors. Mediation analyses were performed to evaluate the role of systemic inflammation and metabolic disorders represented by the integrated biomarkers in the MIND diet-IBD association. Results: After a mean follow-up of 10.7 years, we documented 825 incident IBD cases (250 CD and 575 UC). The average age of the participants was 56.2 years, of which 55.0% were females. We found that greater adherence to the MIND diet, represented by a higher diet score, was associated with a lower risk of IBD (HRcomparing extreme tertiles 0.74, 95% CI 0.62-0.90, p = 0.002; p for trend = 0.005), CD (HR 0.66, 95% CI 0.47-0.94, p = 0.022; p for trend = 0.023), and UC (HR 0.78, 95% CI 0.62-0.98, p = 0.031; p for trend = 0.022). The associations were partially mediated by metabolic and inflammation status (mediation proportion: 5.5-15.9%). Conclusion: We found higher adherence to the MIND diet was associated with a lower risk of IBD, and that inflammatory and metabolic conditions may play an important role in the underlying mechanistic pathways.

Characteristics of tandem repeat inheritance and sympathetic nerve involvement in GAA-FGF14 ataxia.

BACKGROUND: Intronic GAA repeat expansion ([GAA] ≥250) in FGF14 is associated with the late-onset neurodegenerative disorder, spinocerebellar ataxia 27B (SCA27B, GAA-FGF14 ataxia). We aim to determine the prevalence of the GAA repeat expansion in FGF14 in Chinese populations presenting late-onset cerebellar ataxia (LOCA) and evaluate the characteristics of tandem repeat inheritance, radiological features and sympathetic nerve involvement. METHODS: GAA-FGF14 repeat expansion was screened in an undiagnosed LOCA cohort (n = 664) and variations in repeat-length were analyzed in families of confirmed GAA-FGF14 ataxia patients. Brain magnetic resonance imaging (MRI) was used to evaluate the radiological feature in GAA-FGF14 ataxia patients. Clinical examinations and sympathetic skin response (SSR) recordings in GAA-FGF14 patients (n = 16) were used to quantify sympathetic nerve involvement. RESULTS: Two unrelated probands (2/664) were identified. Genetic screening for GAA-FGF14 repeat expansion was performed in 39 family members, 16 of whom were genetically diagnosed with GAA-FGF14 ataxia. Familial screening revealed expansion of GAA repeats in maternal transmissions, but contraction upon paternal transmission. Brain MRI showed slight to moderate cerebellar atrophy. SSR amplitude was lower in GAA-FGF14 patients in pre-symptomatic stage compared to healthy controls, and further decreased in the symptomatic stage. CONCLUSIONS: GAA-FGF14 ataxia was rare among Chinese LOCA cases. Parental gender appears to affect variability in GAA repeat number between generations. Reduced SSR amplitude is a prominent feature in GAA-FGF14 patients, even in the pre-symptomatic stage.

Influence of protective clothing and masks on facial trustworthiness in an investment game: insights from a Chinese population study.

Facial features are important sources of information about perceived trustworthiness. Masks and protective clothing diminish the visibility of facial cues by either partially concealing the mouth and nose or covering the entire face. During the pandemic, the use of personal protective equipment affected and redefined who trusts whom in society. This study used the classical investment game of interpersonal trust with Chinese participants to explore the impact of occlusion on interpersonal trust. Faces with moderate initial trustworthiness were occluded by a mask or protective clothing in Experiment 1 and were digitally occluded by a square in Experiment 2, and faces with three levels of initial trustworthiness were occluded by a mask in Experiment 3. Results showed that both undergraduates (Experiment 1a) and non-student adults (Experiment 1b) perceived the faces with protective clothing as more trustworthy than faces wearing standard masks and faces not wearing masks. Faces with the top halves showing were perceived as trustworthy as full faces, while faces with the bottom halves showing were perceived as less trustworthy. The effect of masks is weak and complex. Masks reduced participants' trust in faces with high initial trustworthiness, had no effect on faces with low and moderate initial trustworthiness, and only slightly increased the trust of undergraduates in faces with moderate initial trustworthiness. Our findings indicate that the lack of information caused by occlusion and the social significance associated with occlusion collectively affect people's trust behavior in Chinese society. We believe the findings of this study will be useful in elucidating the effects of personal protective equipment usage on perceptions of trustworthiness.

Stress response of Salmonella Newport with various sequence types toward plasma-activated water: Viable but nonculturable state formation and outer membrane vesicle production.

This study aims to investigate the response of Salmonella Newport to plasma-activated water (PAW), a novel disinfectant that attracts attention due to its broad-spectrum antimicrobial efficacy and eco-friendliness. In this work, we demonstrated that S. Newport of different sequence types (STs) could be induced into the viable but nonculturable (VBNC) state by PAW treatment. Notably, a remarkable 99.96% of S. Newport ST45 strain entered the VBNC state after a 12-min PAW treatment, which was the fastest observed among the five S. Newport STs (ST31, ST45, ST46, ST166, ST2364). Secretion of outer membrane vesicles was observed in ST45, suggesting a potential strategy against PAW treatment. Genes related to oxidative stress (sodA, katE, trxA), outer membrane proteins (ompA, ompC, ompD, ompF) and virulence (pagC, sipC, sopE2) were upregulated in the PAW-treated S. Newport, especially in ST45. A reduction of 38-65% in intracellular ATP level after PAW treatment was observed, indicating a contributor to the formation of the VBNC state. In addition, a rapid method for detecting the proportion of VBNC cells in food products based on pagC was established. This study contributes to understanding the formation mechanism of the VBNC state in S. Newport under PAW stress and offers insights for controlling microbial risks in the food industry.

Integrated Janus nanofibers enabled by a co-shell solvent for enhancing icariin delivery efficiency.

During the past several decades, nanostructures have played their increasing influences on the developments of novel nano drug delivery systems, among which, double-chamber Janus nanostructure is a popular one. In this study, a new tri-channel spinneret was developed, in which two parallel metal capillaries were nested into another metal capillary in a core-shell manner. A tri-fluid electrospinning was conducted with a solvent mixture as the shell working fluid for ensuring the formation of an integrated Janus nanostructure. The scanning electronic microscopic results demonstrated that the resultant nanofibers had a linear morphology and two distinct compartments within them, as indicated by the image of a cross-section. Fourier Transformation Infra-Red spectra and X-Ray Diffraction patterns verified that the loaded poorly water-soluble drug, i.e. icariin, presented in the Janus medicated nanofibers in an amorphous state, which should be attributed to the favorable secondary interactions between icariin and the two soluble polymeric matrices, i.e. hydroxypropyl methyl cellulose (HPMC) and polyvinylpyrrolidone (PVP). The in vitro dissolution tests revealed that icariin, when encapsulated within the Janus nanofibers, exhibited complete release within a duration of 5 min, which was over 11 times faster compared to the raw drug particles. Furthermore, the ex vivo permeation tests demonstrated that the permeation rate of icariin was 16.2 times higher than that of the drug powders. This improvement was attributed to both the rapid dissolution of the drug and the pre-release of the trans-membrane enhancer sodium lauryl sulfate from the PVP side of the nanofibers. Mechanisms for microformation, drug release, and permeation were proposed. Based on the methodologies outlined in this study, numerous novel Janus nanostructure-based nano drug delivery systems can be developed for poorly water-soluble drugs in the future.

Higher Dietary Quercetin Intake Is Associated with Lower Risk of Adverse Outcomes among Individuals with Inflammatory Bowel Disease in a Prospective Cohort Study.

BACKGROUND: Cumulative preclinical evidence reported quercetin, a major flavonoid, can attenuate the disease activity of inflammatory bowel diseases (IBD). However, there is limited evidence that supports the benefits of quercetin for patients with IBD. OBJECTIVES: To investigate whether dietary quercetin intake is associated with adverse outcomes among individuals with IBD in a prospective cohort study. METHODS: We included 2293 participants with IBD (764 Crohn's disease [CD] and 1529 ulcerative colitis [UC]) from the UK Biobank. Dietary information was collected using validated 24-h dietary assessments, and quercetin intake was estimated based on national nutrient databases. Two outcomes, enterotomy and all-cause mortality, were obtained based on the national data. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: After a mean (standard deviation) follow-up of 9.6 (1.8) y, we documented 193 enterotomy events and 176 deaths. Compared with participants with the lowest quartile intake of quercetin, those in the highest quartiles were associated with lower risk of enterotomy (HR: 0.46; 95% CI: 0.28, 0.76) and all-cause mortality (HR: 0.53; 95% CI: 0.33, 0.83) in IBD. The inverse associations between quercetin and enterotomy were consistent in CD (HR: 0.30; 95% CI: 0.12, 0.78) but not UC (HR: 0.58; 95% CI: 0.32, 1.07), while the inverse associations between quercetin and mortality were consistent both in CD (HR: 0.37; 95% CI: 0.15, 0.92) and UC (HR: 0.55; 95% CI: 0.31, 0.95). CONCLUSIONS: Higher dietary intake of quercetin was associated with lower risk of enterotomy and all-cause mortality in IBD. Our study provides novel evidence that further suggests the benefits of quercetin for patients with IBD, while also calling for further validation in other cohorts and clinical trials.

Electrosprayed Eudragit RL100 nanoparticles with Janus polyvinylpyrrolidone patches for multiphase release of paracetamol.

Advanced nanotechniques and the corresponding complex nanostructures they produce represent some of the most powerful tools for developing novel drug delivery systems (DDSs). In this study, a side-by-side electrospraying process was developed for creating double-chamber nanoparticles in which Janus soluble polyvinylpyrrolidone (PVP) patches were added to the sides of Eudragit RL100 (RL100) particles. Both sides were loaded with the poorly water-soluble drug paracetamol (PAR). Scanning electron microscope results demonstrated that the electrosprayed nanoparticles had an integrated Janus nanostructure. Combined with observations of the working processes, the microformation mechanism for creating the Janus PVP patches was proposed. XRD, DSC, and ATR-FTIR experiments verified that the PAR drug was present in the Janus particles in an amorphous state due to its fine compatibility with the polymeric matrices. In vitro dissolution tests verified that the Janus nanoparticles were able to provide a typical biphasic drug release profile, with the PVP patches providing 43.8 ± 5.4% drug release in the first phase in a pulsatile manner. In vivo animal experiments indicated that the Janus particles, on one hand, could provide a faster therapeutic effect than the electrosprayed sustained-release RL100 nanoparticles. On the other hand, they could maintain a therapeutic blood drug concentration for a longer period. The controlled release mechanism of the drug was proposed. The protocols reported here pioneer a new process-structure-performance relationship for developing Janus-structure-based advanced nano-DDSs.

Analysis of brain structural covariance network in Cushing disease.

Background: Cushing disease (CD) is a rare clinical neuroendocrine disease. CD is characterized by abnormal hypercortisolism induced by a pituitary adenoma with the secretion of adrenocorticotropic hormone. Individuals with CD usually exhibit atrophy of gray matter volume. However, little is known about the alterations in topographical organization of individuals with CD. This study aimed to investigate the structural covariance networks of individuals with CD based on the gray matter volume using graph theory analysis. Methods: High-resolution T1-weighted images of 61 individuals with CD and 53 healthy controls were obtained. Gray matter volume was estimated and the structural covariance network was analyzed using graph theory. Network properties such as hubs of all participants were calculated based on degree centrality. Results: No significant differences were observed between individuals with CD and healthy controls in terms of age, gender, and education level. The small-world features were conserved in individuals with CD but were higher than those in healthy controls. The individuals with CD showed higher global efficiency and modularity, suggesting higher integration and segregation as compared to healthy controls. The hub nodes of the individuals with CD were Short insular gyri (G_insular_short_L), Anterior part of the cingulate gyrus and sulcus (G_and_S_cingul-Ant_R), and Superior frontal gyrus (G_front_sup_R). Conclusions: Significant differences in the structural covariance network of patients with CD were found based on graph theory. These findings might help understanding the pathogenesis of individuals with CD and provide insight into the pathogenesis of this CD.

Association between alcohol consumption and peripheral artery disease: Two de novo prospective cohorts and a systematic review with meta-analysis.

AIMS: The association between alcohol consumption and risk of peripheral artery disease (PAD) is inconclusive. We conducted this study to examine the association between alcohol consumption and PAD risk in two de novo cohort studies and a meta-analysis of observational studies. METHODS AND RESULTS: A systematic review was conducted to identify studies on alcohol consumption in relation to PAD risk. We further used data from two cohorts of 70,116 Swedish and 405,406 British adults and performed a meta-analysis of results from previously published studies and current cohort studies. There was a U-shaped association between alcohol consumption and incident PAD risk in the Swedish and British cohorts. The meta-analysis of results of these two cohorts and previously published studies found that compared with non- or never-drinkers, the relative risk of PAD was 0.83 (95% confidence interval [CI] 0.77-0.89), 0.81 (95% CI 0.74-0.90), and 0.94 (95% CI 0.83-1.07) for light, moderate, and high-to-heavy alcohol drinkers, respectively. The nonlinear meta-analysis revealed a possibly U-shaped association between alcohol consumption and PAD risk (P-nonlinearity <0.001). The risk of PAD was observed to be the lowest for 2 drinks/week and to be pronounced for ≥10 drinks/week. All these associations persisted in a sensitivity meta-analysis including cohort and other type of observational studies. CONCLUSION: Alcohol intake ≤ 2 drinks/week was associated with a reduced risk of PAD and the risk of PAD became pronounced with intake ≥10 drinkers/week.

The association between alcohol consumption and the risk of peripheral artery disease is conflicting between studies and thus remains undetermined. In the two de novo cohort analyses, we found a U-shaped association between alcohol consumption and peripheral artery disease risk in the Swedish and British populations. In the meta-analysis, light-to-moderate consumption of alcohol was associated with a reduced risk of peripheral artery disease. The dose-response meta-analysis showed that the risk of peripheral artery disease became pronounced for alcohol consumption ≥10 drinkers/week. This is an observational study that cannot infer causality between alcohol consumption and peripheral artery disease risk. We are not able to assess the specific associations to different types of alcoholic beverages.

Identifying gray matter alterations in Cushing's disease using machine learning: An interpretable approach.

BACKGROUND: Cushing's Disease (CD) is a rare clinical syndrome characterized by excessive secretion of adrenocorticotrophic hormone, leading to significant functional and structural brain alterations as observed in Magnetic Resonance Imaging (MRI). While traditional statistical analysis has been widely employed to investigate these MRI changes in CD, it has lacked the ability to predict individual-level outcomes. PURPOSE: To address this problem, this paper has proposed an interpretable machine learning (ML) framework, including model-level assessment, feature-level assessment, and biology-level assessment to ensure a comprehensive analysis based on structural MRI of CD. METHODS: The ML framework has effectively identified the changes in brain regions in the stage of model-level assessment, verified the effectiveness of these altered brain regions to predict CD from normal controls in the stage of feature-level assessment, and carried out a correlation analysis between altered brain regions and clinical symptoms in the stage of biology-level assessment. RESULTS: The experimental results of this study have demonstrated that the Insula, Fusiform gyrus, Superior frontal gyrus, Precuneus, and the opercular portion of the Inferior frontal gyrus of CD showed significant alterations in brain regions. Furthermore, our study has revealed significant correlations between clinical symptoms and the frontotemporal lobes, insulin, and olfactory cortex, which also have been confirmed by previous studies. CONCLUSIONS: The ML framework proposed in this study exhibits exceptional potential in uncovering the intricate pathophysiological mechanisms underlying CD, with potential applicability in diagnosing other diseases.

Risk of subsequent gastrointestinal disease assessed by skeletal muscle strength and mass in a prospective cohort study.

Skeletal muscle may mutually interact with gastrointestinal disease through metabolic homeostasis and nutritional status and therefore may be a marker for early risk detection. We conducted a prospective cohort analysis including 393,606 participants (mean age 56.0 years, 53.9% female) from the UK Biobank. The exposures were grip strength and skeletal muscle mass (SMM). The primary outcomes were 24 incident gastrointestinal diseases. During a mean follow-up of 12.1 years, we found that one sex-specific SD increase in grip strength and SMM were associated with reduced risk of 16 and 19 gastrointestinal diseases, respectively. For grip strength, the HRs ranged from 0.94 (for ulcerative colitis) to 0.80 (for liver cancers). For SMM, the HRs ranged from 0.92 (for colorectal cancer) to 0.51 (for non-alcoholic fatty liver disease). Our finding suggested that grip strength and SMM might be significant indicators for gastrointestinal diseases risk screen.

A new In Situ Oxidized 2D Layered MnBi2Te4 Cathode for High-Performance Aqueous Zinc-Ion Battery.

Recently, aqueous zinc ion batteries (AZIBs) with the superior theoretical capacity, high safety, low prices, and environmental protection, have emerged as a contender for advanced energy storage. However, challenges related to cathode materials, such as dissolution, instability, and structural collapse, have hindered the progress of AZIBs. Here, a novel AZIB is constructed using an oxidized 2D layered MnBi2Te4 cathode for the first time. The oxidized MnBi2Te4 cathode with large interlayer spacing and low energy barrier for zinc ion diffusion at 240 °C, exhibited impressive characteristics, including a high reversibility capacity of 393.1 mAh g-1 (0.4 A g-1), outstanding rate performance, and long cycle stability. Moreover, the corresponding aqueous button cell also exhibits excellent electrochemical performance. To demonstrate the application in practice in the realm of flexible wearable electronics, a quasi-solid-state micro ZIB (MZIB) is constructed and shows excellent flexibility and high-temperature stability (the capacity does not significantly degrade when the temperature reaches 100 °C and the bending angle exceeds 150°). This research offers effective tactics for creating high-performance cathode materials for AZIBs.

Remediation potential of an immobilized microbial consortium with corn straw as a carrier in polycyclic aromatic hydrocarbons contaminated soil.

Polycyclic aromatic hydrocarbons (PAHs) are widespread in soils and threaten human health seriously. The immobilized microorganisms (IM) technique is an effective and environmentally sound approach for remediating PAH-contaminated soil. However, the knowledge of the remedial efficiency and the way IM operates using natural organic materials as carriers in complex soil environments is limited. In this study, we loaded a functional microbial consortium on corn straw to analyze the effect of IM on PAH concentration and explore the potential remediation mechanisms of IM in PAH-contaminated soil. The findings revealed that the removal rate of total PAHs in the soil was 88.25% with the application of IM after 20 days, which was 39.25% higher than the control treatment, suggesting that IM could more easily degrade PAHs in soil. The findings from high-throughput sequencing and quantitative PCR revealed that the addition of IM altered the bacterial community structure and key components of the bacterial network, enhanced cooperative relationships among bacteria, and increased the abundance of bacteria and functional gene copies such as nidA and nahAc in the soil, ultimately facilitating the degradation of PAHs in the soil. This study enhances our understanding of the potential applications of IM for the treatment of PAH-contaminated soil.

Circulating 25-hydroxyvitamin D concentration can predict bowel resection risk among individuals with inflammatory bowel disease in a longitudinal cohort with 13 years of follow-up.

BACKGROUND: Although the beneficial properties of vitamin D in anti-inflammation and immunity-modulation are promising in the management of inflammatory bowel disease (IBD), data were limited for the critical IBD prognosis. The association between serum vitamin D levels and the risk of bowel resection in individuals with IBD remains largely unknown. MATERIALS AND METHODS: We performed a longitudinal cohort study among 5474 individuals with IBD in the UK Biobank. Serum 25-hydroxyvitamin D [25(OH)D] was measured using direct competitive chemiluminescent immunoassay. Bowel resection events were ascertained via national inpatient data. Multivariable-adjusted Cox proportional hazard regression was used to examine the association between serum 25(OH)D and bowel resection risk, presented with hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted cubic spline (RCS) was used to evaluate dose-response associations. RESULTS: During a mean follow-up of 13.1 years, we documented 513 incident bowel resection cases. Compared to participants with vitamin D deficiency, non-deficient participants showed a significantly reduced bowel resection risk in IBD (HR 0.72, 95% CI 0.59-0.87, P=0.001), Crohn's disease (CD, HR 0.74, 95% CI 0.56-0.98, P=0.038), and ulcerative colitis (UC, HR 0.73, 95% CI 0.57-0.95, P=0.020). When comparing extreme quintiles of 25(OH)D level, participants with IBD showed a 34% reduced risk of bowel resection (95% CI 11%-51%, P=0.007) and participants with UC showed a 46% reduced risk (95% CI 19%-64%, P=0.003), while this association was not significant in CD (HR 0.93, 95% CI 0.59-1.45, P=0.740). Linear dose-response associations were observed using the RCS curve (all P-nonlinearity>0.05). CONCLUSION: Increased serum level of 25(OH)D is independently associated with reduced bowel resection risk in IBD. This association was significant in UC but may not be stable in CD. Vitamin D deficiency is a risk factor for bowel resection in individuals with IBD, and may be an effective metric in predicting and risk-screening surgical events.

O-arm guided minimally invasive resection of intrathoracic epidural schwannoma: how I do it.

BACKGROUND: Schwannomas are the most common intrathoracic neurogenic tumors. In the past, they were often treated by traditional open surgery. Video-assisted thoracic surgery (VATS) has also been used for some large tumors. Recently, minimally invasive posterior neurosurgical technique provides a new option for some of these tumors. METHOD: Here, we describe the specific steps involved in the O-arm guided minimally invasive removal of intrathoracic epidural schwannoma, as well as its advantages and limitations. CONCLUSION: O-arm guided minimally invasive resection of intrathoracic epidural schwannoma is safe and effective and causes little damage.

Risk Assessment for Gastrointestinal Diseases via Clinical Dimension and Genome-Wide Polygenic Risk Scores of Type 2 Diabetes: A Population-Based Cohort Study.

OBJECTIVE: We aimed to evaluate whether individuals with type 2 diabetes (T2D) were at higher risk of developing a wide range of gastrointestinal diseases based on a population-based cohort study. RESEARCH DESIGN AND METHODS: This study included 374,125 participants free of gastrointestinal disorders at baseline; of them, 19,719 (5.27%) with T2D were followed-up by linking to multiple medical records to record gastrointestinal disease diagnoses. Multivariable Cox models were used to estimate the hazard ratios (HRs) and CIs. Logistic models were used to examine the associations between polygenic risk scores (PRS) and clinical gastrointestinal phenotypes. RESULTS: During a median follow-up of 12.0 years, we observed the new onset of 15 gastrointestinal diseases. Compared with nondiabetes, participants with T2D had an increased risk of gastritis and duodenitis (HR 1.58, 95% CI 1.51-1.65), peptic ulcer (HR 1.56, 95% CI 1.43-1.71), diverticular disease (HR 1.19, 95% CI 1.14-1.24), pancreatitis (HR 1.45, 95% CI 1.24-1.71), nonalcoholic fatty liver disease (HR 2.46, 95% CI 2.25-2.69), liver cirrhosis (HR 2.92, 95% CI 2.58-3.30), biliary disease (HR 1.18, 95% CI 1.10-1.26), gastrointestinal tract cancers (HR 1.28, 95% CI 1.17-1.40), and hepatobiliary and pancreatic cancer (HR 2.32, 95% CI 2.01-2.67). Positive associations of PRS of T2D with gastritis, duodenitis, and nonalcoholic fatty liver disease were also observed. CONCLUSIONS: In this large cohort study, we found that T2D was associated with increased risks of a wide range of gastrointestinal outcomes. We suggest the importance of early detection and prevention of gastrointestinal disorders among patients with T2D.

Long-term risk of venous thromboembolism among patients with gastrointestinal non-neoplastic and neoplastic diseases: A prospective cohort study of 484 211 individuals.

We conducted a prospective cohort study to examine the associations of 21 gastrointestinal diseases with the risk of incident venous thromboembolism (VTE). The study included 485 936 UK Biobank participants free of baseline VTE. The gastrointestinal diseases were defined by the International Classification of Disease (ICD)-9 and 10 codes with data from the nationwide inpatient data set, the primary care data set, and the cancer registries. Incident VTE cases were defined by ICD-9 and 10 codes with data from the nationwide inpatient data set. Cox proportional hazards regression was used to estimate the associations of baseline gastrointestinal diseases with incident VTE risk. During a median follow-up of 12.0 years, 13 646 incident VTE cases were diagnosed. Eleven gastrointestinal diseases (nine non-neoplastic and two neoplastic) were associated with an increased risk of incident VTE after Bonferroni corrections. The risk of VTE was >50% higher among patients with gallbladder and biliary tract cancer (hazard ratio [HR] 3.15, 95% confidence interval [CI] 95% CI 1.74-5.70), pancreatic cancer (HR 2.84, 95% CI 1.65-4.91), cirrhosis (HR 2.34, 95% CI 1.96-2.79), Crohn's disease (HR 1.61, 95% CI 1.33-1.95), or pancreatitis (HR 1.57, 95% CI 1.31-1.88) compared with individuals without each of these diseases. We observed multiplicative interactions of age, sex, and body mass index with some gastrointestinal diseases (p < .05). A more pronounced, increased risk of VTE was found among younger, female, or obese patients. The study suggests a 50% higher risk of developing VTE among patients with gallbladder and biliary tract cancer, pancreatic cancer, cirrhosis, Crohn's disease, or pancreatitis.

An enzyme-pHBH method for specific quantification of porphyran.

Porphyran, the major polysaccharide extracted from Porphyra, exhibits tremendous potential for development as functional food or pharmaceutical due to its multiple biological activities. The quantitative analysis of porphyran is important for the quality control in product development. However, the specific quantitative method of porphyran has not been established, and the lack of reference substance makes the quantification more challenging. Here, a common component of porphyran, with high purity, similar molecular weight distribution, sourced from different Porphyra producing areas in China was first prepared by a series of isolation and purification steps, and utilized as the reference substance for porphyran quantification. Subsequently, the porphyran was fully degraded into oligosaccharides by using a ß-porphyranase, followed by employing para-hydroxybenzoic acid hydrazide (pHBH) method to detect the content of the generated reducing sugar. The enzyme-pHBH method for porphyran specific quantification was established. Results showed that this method was validated with good linearity, high accuracy and precision, and reliability. Addtionally, NaCl with a concentration below 0.5 %, alcohol under 8 % and other polysaccharide including chitosan, agarose, chondrotin sulfate, alginate, hyaluronic acid and κ-carrageenan did not interfere with this method. This approach is promising for quality control of the porphyran products and offers a feasible strategy for the specific quantification of other polysaccharides.

Multi-omic insight into the molecular networks of mitochondrial dysfunction in the pathogenesis of inflammatory bowel disease.

BACKGROUND: Mitochondrial dysfunction has been linked to the development of inflammatory bowel disease (IBD), but the genetic pathophysiology was not fully elucidated. We employed Mendelian randomization and colocalization analyses to investigate the associations between mitochondrial-related genes and IBD via integrating multi-omics. METHODS: Summary-level data of mitochondrial gene methylation, expression and protein abundance levels were obtained from corresponding methylation, expression and protein quantitative trait loci studies, respectively. We obtained genetic associations with IBD and its two subtypes from the Inflammatory Bowel Disease Genetics Consortium (discovery), the UK Biobank (replication), and the FinnGen study (replication). We performed summary-data-based Mendelian randomization analysis to assess the associations of mitochondrial gene-related molecular features with IBD. Colocalization analysis was further conducted to assess whether the identified signal pairs shared a causal genetic variant. FINDINGS: After integrating the multi-omics data between mQTL-eQTL and eQTL-pQTL, we identified two mitochondrial genes, i.e., PARK7 and ACADM, with tier 1 evidence for their associations with IBD and ulcerative colitis (UC). PDK1 and FISI genes were associated with UC risk with tier 2 and tier 3 evidence, respectively. The methylation of cg05467918 in ACADM was associated with lower expression of ACADM, which fits with the positive effect of cg05467918 methylation on UC risk. Consistently, the inverse associations between gene methylation and gene expression were also observed in PARK7 (cg10385390) and PDK1 (cg17679246), which were corroborated with the protective role in UC. At circulating protein level, genetically predicted higher levels of PARK7 (OR 0.36, 95% CI 0.25-0.52) and HINT1 (OR 0.47, 95% CI 0.30-0.74) were inversely associated with IBD risk; genetically predicted higher level of HINT1 was associated with a decreased risk of Crohn's disease (CD) (OR 0.26, 95% CI 0.14-0.49) and a higher level of ACADM (OR 0.67, 95% CI 0.55-0.83), PDK1 (OR 0.63, 95% CI 0.49-0.81), FIS1 (OR 0.63, 95% CI 0.47-0.83) was associated with a decreased risk of UC. INTERPRETATION: We found that the mitochondrial PARK7 gene was putatively associated with IBD risk, and mitochondrial FIS1, PDK1, and ACADM genes were associated with UC risk with evidence from multi-omics levels. This study identified mitochondrial genes in relation to IBD, which may enhance the understanding of the pathogenic mechanisms of IBD development. FUNDING: XL is supported by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001) and Healthy Zhejiang One Million People Cohort (K-20230085).