Associations of the EAT-Lancet reference diet with metabolic dysfunction-associated steatotic liver disease and its severity: A multicohort study.

BACKGROUND AND AIMS: The EAT-Lancet Commission devised a globally sustainable dietary pattern to jointly promote human health and sustainability. However, the extent to which this diet supports metabolic dysfunction-associated steatotic liver disease (MASLD) has not yet been assessed. This study aimed to investigate the association between the EAT-Lancet diet and the risk of MASLD and its severity. APPROACH AND RESULTS: This prospective multicohort study included 15,263 adults from the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) cohort, 1137 adults from the Guangzhou Nutrition and Health Study (GNHS) cohort, and 175,078 adults from the UK Biobank. In addition, 228 Chinese adults from the Prospective Epidemic Research Specifically of Non-alcoholic Steatohepatitis (PERSONS) with biopsy-proven MASLD were included. An EAT-Lancet diet index was created to reflect adherence to the EAT-Lancet reference diet. The TCLSIH cohort recorded 3010 MASLD cases during 53,575 person-years of follow-up, the GNHS cohort documented 624 MASLD cases during 6454 person-years of follow-up, and the UK Biobank developed 1350 MASLD cases during 1,745,432 person-years of follow-up. In multivariable models, participants in the highest tertiles of the EAT-Lancet diet index had a lower risk of MASLD compared with those in the lowest tertiles (TCLSIH: HR = 0.87, 95% CI: 0.78, 0.96; GNHS: HR = 0.79, 95% CI: 0.64, 0.98; UK Biobank: HR = 0.73, 95% CI: 0.63, 0.85). Moreover, liver-controlled attenuation parameter decreased with increasing the diet index in individuals with biopsy-proven MASLD (ß = -5.895; 95% CI: -10.014, -1.775). CONCLUSIONS: Adherence to the EAT-Lancet reference diet was inversely associated with the risk of MASLD as well as its severity.

Erythrocyte Very Long-Chain Saturated Fatty Acids, Gut Microbiota-Bile Acid Axis, and Incident Coronary Artery Disease in Adults: A Prospective Cohort Study.

BACKGROUND: Prior research has highlighted inverse associations between concentrations of circulating very long-chain saturated fatty acids (VLCSFAs) and coronary artery disease (CAD). However, the intricate links involving VLCSFAs, gut microbiota, and bile acids remain underexplored. OBJECTIVES: This study examined the association of erythrocyte VLCSFAs with CHD incidence, focusing on the mediating role of gut microbiota and fecal bile acids. METHODS: This 10-y prospective study included 2383 participants without CHD at baseline. Erythrocyte VLCSFAs [arachidic acid (C20:0), behenic acid (C22:0), and lignoceric acid (C24:0)] were measured using gas chromatography at baseline, and 274 CHD incidents were documented in triennial follow-ups. Gut microbiota in 1744 participants and fecal bile acid metabolites in 945 participants were analyzed using 16S ribosomal ribonucleic acid sequencing and ultra-performance liquid chromatography-tandem mass spectrometry at middle-term. RESULTS: The multivariable-adjusted hazard ratios (95% confidence interval) for CHD incidence in highest compared with lowest quartiles were 0.87 (0.61, 1.25) for C20:0, 0.63 (0.42, 0.96) for C22:0, 0.59 (0.41, 0.85) for C24:0, and 0.57 (0.39, 0.83) for total VLCSFAs. Participants with higher total VLCSFA concentrations exhibited increased abundances of Holdemanella, Coriobacteriales Incertae Sedis spp., Ruminococcaceae UCG-005 and UCG-010, and Lachnospiraceae ND3007 group. These 5 genera generated overlapping differential microbial scores (ODMSs) that accounted for 11.52% of the total VLCSFAs-CHD association (Pmediation = 0.018). Bile acids tauro_α_ and tauro_ß_muricholic acid were inversely associated with ODMS and positively associated with incident CHD. Opposite associations were found for glycolithocholic acid and glycodeoxycholic acid. Mediation analyses indicated that glycolithocholic acid, glycodeoxycholic acid, and tauro_α_ and tauro_ß_muricholic acid explained 56.40%, 35.19%, and 26.17% of the ODMS-CHD association, respectively (Pmediation = 0.002, 0.008, and 0.020). CONCLUSIONS: Elevated erythrocyte VLCSFAs are inversely associated with CHD risk in the Chinese population, with gut microbiota and fecal bile acid profiles potentially mediating this association. The identified microbiota and bile acid metabolites may serve as potential intervention targets in future studies. This trial was registered at registry name as NCT03179657.

Effect of Wei Qi Booster on immune and anti-oxidative function in aged mice.

This research was conducted to examine the impact of Wei Qi Booster (WQB) on immune parameters and anti-oxidative function in aged mice. Fifty aged mice were randomly assigned to five different groups. Group A was designated as the control group. Mice in Group B were receiving Levamisole at 10 mg/kg body weight. Each mouse in groups C, D and E received 0.1, 1, and 2% WQB, respectively. Another ten young mice, designated as group F, were fed regularly. The mice were fed according to the above methods for 28 days. Results showed that relative to the control group, the body weight and immune organs indexes experienced a substantial rise in the group with 1% WQB. In addition, 1% WQB could improve the activity of SOD and reduce the MDA levels. Expressions of CD4 and sIgA increased while CD8 decreased in the jejunum of aged mice treated with WQB. IL2 and IFN-γ levels increased in the 1% WQB group, showing no notable difference compared to the young mice group. The results demonstrated that WQB can elevate immune levels and enhance anti-oxidative functions in aged mice.

Impact of dairy supplementation on bone acquisition in children's limbs: a 12-month cluster-randomized controlled trial and meta-analysis.

The impact of milk on bone health in rural preschoolers is under-researched. This study, through a clinical trial and a meta-analysis, finds that milk supplementation enhances forearm and calcaneus bone acquisition in children, supporting the benefits of daily milk consumption. PURPOSE: This study evaluated the impact of dairy supplementation on bone acquisition in children's limbs through a cluster-randomized controlled trial and a meta-analysis. METHODS: The trial involved 315 children (4-6 year) from Northwest China, randomized to receive either 390 ml of milk daily (n = 215) or 20-30 g of bread (n = 100) over 12 months. We primarily assessed bone mineral density (BMD) and content (BMC) changes at the limbs, alongside bone-related biomarkers, measured at baseline, the 6th and 12th months. The meta-analysis aggregated BMD or BMC changes in the forearm/legs/calcaneus from published randomized trials involving children aged 3-18 years supplemented with dairy foods (vs. control group). RESULTS: Of 278 completed the trial, intention-to-treat analysis revealed significant increases in BMD (4.05% and 7.31%) and BMC (4.69% and 7.34%) in the left forearm at the 6th and 12th months in the milk group compared to controls (P < 0.001). The calcaneus showed notable improvements in BMD (2.01%) and BMC (1.87%) at 6 months but not at 12 months. Additionally, milk supplementation was associated with beneficial changes in bone resorption markers, parathyroid hormone (- 12.70%), insulin-like growth factor 1 (6.69%), and the calcium-to-phosphorus ratio (2.22%) (all P < 0.05). The meta-analysis, encompassing 894 children, indicated that dairy supplementation significantly increased BMD (SMD, 0.629; 95%CI: 0.275, 0.983) and BMC (SMD, 0.616; 95%CI: 0.380, 0.851) (P < 0.05) in the arms, but not in the legs (P > 0.05). CONCLUSION: Milk supplementation significantly improves bone health in children's forearms, underscoring its potential as a strategic dietary intervention for bone development. Trial registration NCT05074836.

Correlation between serum trimethylamine-N-oxide and body fat distribution in middle-aged and older adults: a prospective cohort study.

BACKGROUND: Trimethylamine-N-oxide (TMAO) is linked with obesity, while limited evidence on its relationship with body fat distribution. Herein, we investigated the associations between serum TMAO and longitudinal change of fat distribution in this prospective cohort study. METHODS: Data of 1964 participants (40-75y old) from Guangzhou Nutrition and Health Study (GNHS) during 2008-2014 was analyzed. Serum TMAO concentration was quantified by HPLC-MS/MS at baseline. The body composition was assessed by dual-energy X-ray absorptiometry at each 3-y follow-up. Fat distribution parameters were fat-to-lean mass ratio (FLR) and trunk-to-leg fat ratio (TLR). Fat distribution changes were derived from the coefficient of linear regression between their parameters and follow-up duration. RESULTS: After an average of 6.2-y follow-up, analysis of covariance (ANCOVA) and linear regression displayed women with higher serum TMAO level had greater increments in trunk FLR (mean ± SD: 1.47 ± 4.39, P-trend = 0.006) and TLR (mean ± SD: 0.06 ± 0.24, P-trend = 0.011). Meanwhile, for women in the highest TMAO tertile, linear mixed-effects model (LMEM) analysis demonstrated the annual estimated increments (95% CI) were 0.03 (95% CI: 0.003 - 0.06, P = 0.032) in trunk FLR and 1.28 (95% CI: -0.17 - 2.73, P = 0.083) in TLR, respectively. In men, there were no similar significant observations. Sensitivity analysis yielded consistent results. CONCLUSION: Serum TMAO displayed a more profound correlation with increment of FLR and TLR in middle-aged and older community-dwelling women in current study. More and further studies are still warranted in the future. TRIAL REGISTRATION: NCT03179657.

Effects of transcranial direct current stimulation on different cognitive domains in Alzheimer's disease: a meta-study.

BACKGROUND: Numerous studies have investigated the potential effects of transcranial direct current stimulation (tDCS) on improving symptoms related to Alzheimer's disease (AD). However, these studies have produced inconsistent results, leading to a need for further investigation. METHODS: A comprehensive search was conducted, including articles published from the initial availability date to 5 April 2024. The extracted study data were analyzed using STATA 12.0 software. The standard mean difference (SMD) and a 95% confidence interval (CI) were calculated to assess the effects of tDCS. RESULTS: A total of 18 studies assessing the effects of tDCS on AD were included in the study. The study revealed that tDCS has an immediate positive impact on general cognitive, executive, language, and visuospatial function. However, the study did not observe any other significant effect of tDCS treatment on improvements in brain function, including long-term effects on general cognitive, attention, language, and memory function, as well as immediate effects on attention and memory function. CONCLUSIONS: In conclusion, the study suggests that tDCS may be a promising intervention for improving the cognitive function of patients with AD. However, given the complex and multifactorial nature of AD, further well-designed studies with larger sample sizes are necessary to clarify the effectiveness of tDCS and determine the optimal combination of tDCS parameters.

Clinical characteristics and prognosis of early diagnosed Wilson's disease: A large cohort study.

BACKGROUND AND AIMS: Few studies have focused on the outcomes of Wilson's disease (WD) diagnosed before age of 5 years. This study aimed to summarize the clinical features of early diagnosed WD and analyse treatment outcomes and the risk factors associated with treatment failure. METHODS: A total of 139 children confirmed with WD before 5 years were enrolled in this study. Only patients with follow-up over 1 year were analysed with Kaplan-Meier survival analysis. The composite outcomes included death, progression to liver failure or acute hepatitis, development of renal or neurological symptoms and persistent elevation of alanine aminotransferase (ALT). The treatment failure was defined as occurrence of at least one of above outcomes. RESULTS: Among 139 WD patients at diagnosis, two (1.4%) WD patients presented with symptomatic liver disease, whereas 137 (98.6%) were phenotypically asymptomatic, including 135 with elevated ALT and 2 with normal liver function. Median serum ceruloplasmin (Cp) was 3.1 mg/dL, and urinary copper excretion was 87.4 µg/24-h. There were 71 variants identified in the the copper-transporting ATPase beta gene, and 29 were loss of function (LOF). 51 patients with LOF variant were younger at diagnosis and had lower Cp than 88 patients without LOF. Among 93 patients with over 1 year of follow-up, 19 (20.4%) received zinc monotherapy, and 74 (79.6%) received a zinc/D-penicillamine combination therapy. 14 (15.1%) patients underwent treatment failure, and its occurrence was associated with poor compliance (p < .01). CONCLUSIONS: Cp is a reliable biomarker for early diagnosis, and zinc monotherapy is an effective treatment for WD during early childhood. Good treatment compliance is critical to achieve a favourable outcome.

Mapping the gut microecological multi-omics signatures to serum metabolome and their impact on cardiometabolic health in elderly adults.

BACKGROUND: Mapping gut microecological features to serum metabolites (SMs) will help identify functional links between gut microbiome and cardiometabolic health. METHODS: This study encompassed 836-1021 adults over 9.7 year in a cohort, assessing metabolic syndrome (MS), carotid atherosclerotic plaque (CAP), and other metadata triennially. We analyzed mid-term microbial metagenomics, targeted fecal and serum metabolomics, host genetics, and serum proteomics. FINDINGS: Gut microbiota and metabolites (GMM) accounted for 15.1% overall variance in 168 SMs, with individual GMM factors explaining 5.65%-10.1%, host genetics 3.23%, and sociodemographic factors 5.95%. Specifically, GMM elucidated 5.5%-49.6% variance in the top 32 GMM-explained SMs. Each 20% increase in the 32 metabolite score (derived from the 32 SMs) correlated with 73% (95% confidence interval [CI]: 53%-95%) and 19% (95% CI: 11%-27%) increases in MS and CAP incidences, respectively. Among the 32 GMM-explained SMs, sebacic acid, indoleacetic acid, and eicosapentaenoic acid were linked to MS or CAP incidence. Serum proteomics revealed certain proteins, particularly the apolipoprotein family, mediated the relationship between GMM-SMs and cardiometabolic risks. INTERPRETATION: This study reveals the significant influence of GMM on SM profiles and illustrates the intricate connections between GMM-explained SMs, serum proteins, and the incidence of MS and CAP, providing insights into the roles of gut dysbiosis in cardiometabolic health via regulating blood metabolites. FUNDING: This study was jointly supported by the National Natural Science Foundation of China, Key Research and Development Program of Guangzhou, 5010 Program for Clinical Research of Sun Yat-sen University, and the 'Pioneer' and 'Leading goose' R&D Program of Zhejiang.

Zone Evaluation: Revealing Spatial Bias in Object Detection.

A fundamental limitation of object detectors is that they suffer from "spatial bias", and in particular perform less satisfactorily when detecting objects near image borders. For a long time, there has been a lack of effective ways to measure and identify spatial bias, and little is known about where it comes from and what degree it is. To this end, we present a new zone evaluation protocol, extending from the traditional evaluation to a more generalized one, which measures the detection performance over zones, yielding a series of Zone Precisions (ZPs). For the first time, we provide numerical results, showing that the object detectors perform quite unevenly across the zones. Surprisingly, the detector's performance in the 96% border zone of the image does not reach the AP value (Average Precision, commonly regarded as the average detection performance in the entire image zone). To better understand spatial bias, a series of heuristic experiments are conducted. Our investigation excludes two intuitive conjectures about spatial bias that the object scale and the absolute positions of objects barely influence the spatial bias. We find that the key lies in the human-imperceptible divergence in data patterns between objects in different zones, thus eventually forming a visible performance gap between the zones. With these findings, we finally discuss a future direction for object detection, namely, spatial disequilibrium problem, aiming at pursuing a balanced detection ability over the entire image zone. By broadly evaluating 10 popular object detectors and 5 detection datasets, we shed light on the spatial bias of object detectors. We hope this work could raise a focus on detection robustness. The source codes, evaluation protocols, and tutorials are publicly available at https://github.com/Zzh-tju/ZoneEval.

Moderating effects of PER3 gene DNA methylation on the association between problematic mobile phone use and chronotype among Chinese young adults: Focus on gender differences.

Objective: To investigate the rates of problematic mobile phone use (PMPU) and chronotypes in young adults, and examine the associations of PMPU with chronotypes, as well as its gender differences. Furthermore, we explored the moderating role of PER3 gene DNA methylation on the associations. Methods: From April to May 2019, a total of 1,179 young adults were selected from 2 universities in Anhui and Jiangxi provinces. The Self-rating Questionnaire for Adolescent Problematic Mobile Phone Use (SQAPMPU) and reduced Morningness-Eveningness Questionnaire (rMEQ) were adopted to investigate PMPU and chronotypes in young adults, respectively. Moreover, 744 blood samples were collected to measure PER3 gene DNA methylation. Multivariate logistic regression models were established to analyze the associations between PMPU and chronotypes. Moderating analysis was used to determine whether PER3 gene DNA methylation moderated the relationships between PMPU and chronotypes. Results: The prevalence of PMPU, morning chronotypes (M-types), neutral chronotypes (N-types), and evening chronotypes (E-types) of young adults were 24.6%, 18.4%, 71.1%, and 10.5%, respectively. Multivariate logistic regression results indicated that PMPU was positively correlated with E-types (OR = 3.53, 95%CI: 2.08-6.00), and the association was observed only in females after stratified by gender (OR = 5.36, 95%CI: 2.70-10.67). Furthermore, PER3 gene DNA methylation has a negative moderating role between PMPU and chronotypes and has a sex-based difference. Conclusions: This study can provide valuable information for the prevention and control of circadian rhythm disturbance among young adults from the perspective of epidemiology and biological etiology.

Effects of Silybum marianum, Pueraria lobate, combined with Salvia miltiorrhiza tablets on non-alcoholic fatty liver disease in adults: A triple-blind, randomized, placebo-controlled clinical trial.

BACKGROUND & AIMS: Several medicinal plant extracts have demonstrated hepatoprotective effects. However, data are scarce regarding their combined effects on non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the effects of tablets containing Silybum marianum, Pueraria lobata, and Salvia miltiorrhiza (SPS) on NAFLD progression in Chinese adults. METHODS: In this randomized, triple-blind, placebo-controlled clinical trial, 121 NAFLD patients (60 female and 61 male), diagnosed via magnetic resonance imaging (MRI) and aged 18-65 years, were enrolled. Participants were randomly allocated to receive SPS tablets (n = 60; three tablets per dose, twice daily) or placebo (n = 61) for 24 weeks. Each SPS tablet contained approximately 23.0 mg of silybin, 11.4 mg of puerarin, and 10.9 mg of salvianolic acid. There were no differences in appearance, taste and odour between the SPS tablets and placebo manufactured by BYHEALTH Co., LTD (Guangzhou, China). The primary endpoints were changes in the liver fat content (LFC) and steatosis grade from baseline to 24 weeks. Secondary outcomes included changes in biomarkers/scores of liver fibrosis and steatosis, oxidative stress, inflammatory cytokines, alcohol metabolism, and glucose metabolism. RESULTS: A total of 112 participants completed the research. The intention-to-treat results showed a trend toward reduction in both absolute LFC (-0.52%) and percentage of LFC (-4.57%) in the SPS group compared to the placebo group after 24 weeks, but these changes didn't reach statistical significance (p > 0.05). The SPS intervention (vs. placebo) significantly decreased hypersensitive C-reactive protein level (-6.76%) and increased aldehyde dehydrogenase activity (+18.1%) at 24 weeks post-intervention (all p < 0.05). Per-protocol analysis further supported these effects. This trial is registered at Clinical Trials.gov (NCT05076058). CONCLUSION: SPS supplementation may have potential benefits in improving NAFLD, but further larger-scale trials are necessary to confirm these findings.

Relationship between Circulating 25-Hydroxyvitamin D and Metabolic Syndrome in Chinese Adults: A Large Nationwide Longitudinal Study.

OBJECTIVE: This study investigated the association of circulating levels of 25-hydroxyvitamin D (25[OH]D) with the risk of metabolic syndrome (MetS) and its components in adults. METHODS: This nationwide cohort involved 23,810 Chinese adults attending annual health evaluations. Serum 25(OH)D levels, MetS status, and covariates were determined at each examination. Among them, 8146, 3310, and 1971 completed two, three, and more than three evaluations, respectively. A hybrid mixed-effects and Cox regression model was employed to determine the cross-sectional and longitudinal relationships. RESULTS: The odds ratios (ORs) and 95% confidence intervals (CIs) of MetS were significantly lower in individuals within quartile 4 (vs. 1) of serum 25(OH)D for both between-individual (0.43 [0.35, 0.52]) and within-individual comparisons (0.60 [0.50, 0.73]), respectively (all p-trends < 0.001). Among the MetS components, the corresponding ORs (95% CI) in between- and within-individual comparisons were 0.40 (0.29, 0.54) and 0.26 (0.19, 0.36) for abdominal obesity, 0.49 (0.41, 0.58) and 0.78 (0.66, 0.93) for high triglycerides, 0.70 (0.59, 0.82) and 0.75 (0.64, 0.87) for hypertriglyceridemia, 0.48 (0.39, 0.59) and 0.87 (0.71, 1.07) for low HDL cholesterol, and 0.92 (0.76, 1.12) and 0.49 (0.41, 0.59) for hypertension, respectively. Decreased hazard ratios (95% CIs) in quartile 4 (vs. 1) of 25(OH)D were found for MetS (0.80 [0.65, 1.00]), high triglycerides (0.76 [0.62, 0.92]), abdominal obesity (0.77 [0.63, 0.96]), and low HDL cholesterol (0.64 [0.50, 0.81]). CONCLUSIONS: Decreased concentrations of serum 25(OH)D correlate significantly to a heightened MetS risk and specific components. Our findings underscore the potential preventive function of circulating vitamin D concerning metabolic disorders.

A mathematical model for HIV dynamics with multiple infections: implications for immune escape.

Multiple infections enable the recombination of different strains, which may contribute to viral diversity. How multiple infections affect the competition dynamics between the two types of strains, the wild and the immune escape mutant, remains poorly understood. This study develops a novel mathematical model that includes the two strains, two modes of viral infection, and multiple infections. For the representative double-infection case, the reproductive numbers are derived and global stabilities of equilibria are obtained via the Lyapunov direct method and theory of limiting systems. Numerical simulations indicate similar viral dynamics regardless of multiplicities of infections though the competition between the two strains would be the fiercest in the case of quadruple infections. Through sensitivity analysis, we evaluate the effect of parameters on the set-point viral loads in the presence and absence of multiple infections. The model with multiple infections predict that there exists a threshold for cytotoxic T lymphocytes (CTLs) to minimize the overall viral load. Weak or strong CTLs immune response can result in high overall viral load. If the strength of CTLs maintains at an intermediate level, the fitness cost of the mutant is likely to have a significant impact on the evolutionary dynamics of mutant viruses. We further investigate how multiple infections alter the viral dynamics during the combination antiretroviral therapy (cART). The results show that viral loads may be underestimated during cART if multiple-infection is not taken into account.

Homologous Design and Three-Dimensional Quantitative Structure-Activity Relationship Study of Acaricidal 2,4-Diphenyloxazolines Containing Different Heteroatoms and Alkyl Chains.

In order to speculate the three-dimensional structure of the potential binding pocket of the chitin synthase inhibitor, a series of 2,4-diphenyloxazoline derivatives with different lengths of alkyl chains and heteroatoms were designed and synthesized by a homologous strategy. The bioassay results indicate that both the length of the alkyl chains and the type of substituents can affect the acaricidal activity against mite eggs. Compounds containing chloropropyl, alkoxyalkyl, and para-substituted phenoxyalkyl or phenylthioalkyl groups exhibit good activity, while those containing steric hindrance substituents or carbonyl substituents on the benzene ring exhibit reduced activity. Three-dimensional quantitative structure-activity relationship (3D-QSAR) study showed that there may be a narrow hydrophobic region deep in the pocket, and the steric effect plays a more important role than the electrostatic effect. The current work will provide assistance for future molecular design and target binding research.

Mechanisms of surface groups regulating developmental toxicity of graphene-based nanomaterials via glycerophospholipid metabolic pathway.

Surface modification of graphene-based nanomaterials (GBNs) may occur in aquatic environment and during intentional preparation. However, the influence of the surface groups on the developmental toxicity of GBNs has not been determined. In this study, we evaluated the developmental toxicity of three GBNs including GO (graphene oxide), RGO (reduced GO) and RGO-N (aminated RGO) by employing zebrafish embryos at environmentally relevant concentrations (1-100 µg/L), and the underlying metabolic mechanisms were explored. The results showed that both GO and RGO-N disturbed the development of zebrafish embryos, and the adverse effect of GO was greater than that of RGO-N. Furthermore, the oxygen-containing groups of GBNs play a more important role in inducing developmental toxicity compared to size, defects and nitrogen-containing groups. Specifically, the epoxide and hydroxyl groups of GBNs increased their intrinsic oxidative potential, promoted the generation of ROS, and caused lipid peroxidation. Moreover, a significant decrease in guanosine and abnormal metabolism of multiple glycerophospholipids were observed in all three GBN-treated groups. Nevertheless, GO exposure triggered more metabolic activities related to lipid peroxidation than RGO or RGO-N exposure, and the disturbance intensity of the same metabolite was greater than that of the other two agents. These findings reveal underlying metabolic mechanisms of GBN-induced developmental toxicity.

Analysis of a diffusive two-strain malaria model with the carrying capacity of the environment for mosquitoes.

We propose a malaria model involving the sensitive and resistant strains, which is described by reaction-diffusion equations. The model reflects the scenario that the vector and host populations disperse with distinct diffusion rates, susceptible individuals or vectors cannot be infected by both strains simultaneously, and the vector population satisfies the logistic growth. Our main purpose is to get a threshold type result on the model, especially the interaction effect of the two strains in the presence of spatial structure. To solve this issue, the basic reproduction number (BRN) R0i and invasion reproduction number (IRN) Rˆ0i of each strain (i = 1 and 2 are for the sensitive and resistant strains, respectively) are defined. Furthermore, we investigate the influence of the diffusion rates of populations and vectors on BRNs and IRNs.

Gut microbiota-bile acid axis mediated the beneficial associations between dietary lignans and hyperuricemia: a prospective study.

Background: The escalating prevalence of hyperuricemia is emerging as a significant public health concern. The association between dietary lignans and hyperuricemia is yet to be fully elucidated. Our study aims to evaluate the relationships between dietary lignan intake and hyperuricemia among middle-aged and elderly Chinese individuals, with an additional focus on investigating the underlying mechanisms. Methods: Dietary lignan intake was measured using a validated Food Frequency Questionnaire in 3801 participants at the baseline. Among them, 2552 participants were included in the longitudinal study with a median follow-up of 10.5 years. The gut microbiota was analyzed by shotgun metagenome sequencing in 1789 participants, and the targeted fecal metabolome was determined in 987 participants using UPLC-MS/MS at the midpoint of follow-up. Results: The multivariable-adjusted HRs (95% CIs) for hyperuricemia incidence in the highest quartile (vs. the lowest quartile) of dietary intake of total lignans, matairesinol, pinoresinol, and secoisolariciresinol were 0.93 (0.78-1.10), 0.77 (0.66-0.90), 0.83 (0.70-0.97), and 0.85 (0.73-1.00), respectively. The gut microbial and fecal metabolic compositions were significantly different across the dietary lignan groups and the hyperuricemia groups. The beneficial associations between dietary lignans and hyperuricemia might be mediated by several gut microbes (e.g., Fusobacterium mortiferum and Blautia sp. CAG-257) and the downstream bile acid products (e.g., NorCA, glycochenodeoxycholic acid, and glycoursodeoxycholic acid). Conclusion: We found that dietary lignans were inversely associated with hyperuricemia incidence, and the gut microbiota-bile acid axis might mediate this association. Our findings provide new perspectives on precise therapeutic targets and underlying mechanisms for conditions associated with elevated uric acid.

Peak Performance: Characteristics and Key Factors in the Development of the World Top-8 Swimmers Based on Longitudinal Data.

PURPOSE: This study aimed to investigate the peak performance characteristics of the world top-8 swimmers and the key factors involved in the journey toward achieving better peak performance. METHODS: The results of the world top-8 swimmers from 2001 to 2022 were collected from the World Aquatics performance database. Progression to peak performance was tracked with individual quadratic trajectories (1191 cases). Utilizing k-means clustering to group competitive feature variables, this study investigated key developmental factors through a binary logistic regression model, using the odds ratio (OR) to represent whether a factor was favorable (OR > 1) or unfavorable (OR < 1). RESULTS: Significant differences (P < .001) in the peak age between men (23.54/3.80) and women (22.31/4.60) were noticed, while no significant differences (P > .05) in the peak-performance window for both sexes appeared. Peak performance occurred at later ages for the sprint for both sexes, and women had a longer duration in peak-performance window for sprint (P < .05). Peak-performance occurred at later ages for the breaststroke and butterfly for both sexes (P < .05). Binary logistic regression revealed that high first-participation performance (OR = 1.502), high major-competition performance (OR = 4.165), early first-major-competition age (OR = 1.441), participation frequency above 4 times/year in both phase 2 (4.3-8.0 times/y, OR = 3.940; 8.1-20.0 times/y, OR = 5.122) and phase 3 (4.1-7.5 times/y: OR = 5.548; 7.7-15.0 times/y: OR = 7.526), and a career length of 10 years or more (10-15 y, OR = 2.102; 16-31 y, OR = 3.480) were favorable factors for achieving better peak performance. CONCLUSIONS: Peak performance characteristics varied across sex, swimming stroke, and race distance in the world top-8 swimmers. Meanwhile, the research indicated that certain specific developmental factors were key conditions for the world top-8 swimmers to achieve better peak performance in the future.

Gut microbiome features and metabolites in non-alcoholic fatty liver disease among community-dwelling middle-aged and older adults.

BACKGROUND: The specific microbiota and associated metabolites linked to non-alcoholic fatty liver disease (NAFLD) are still controversial. Thus, we aimed to understand how the core gut microbiota and metabolites impact NAFLD. METHODS: The data for the discovery cohort were collected from the Guangzhou Nutrition and Health Study (GNHS) follow-up conducted between 2014 and 2018. We collected 272 metadata points from 1546 individuals. The metadata were input into four interpretable machine learning models to identify important gut microbiota associated with NAFLD. These models were subsequently applied to two validation cohorts [the internal validation cohort (n = 377), and the prospective validation cohort (n = 749)] to assess generalizability. We constructed an individual microbiome risk score (MRS) based on the identified gut microbiota and conducted animal faecal microbiome transplantation experiment using faecal samples from individuals with different levels of MRS to determine the relationship between MRS and NAFLD. Additionally, we conducted targeted metabolomic sequencing of faecal samples to analyse potential metabolites. RESULTS: Among the four machine learning models used, the lightGBM algorithm achieved the best performance. A total of 12 taxa-related features of the microbiota were selected by the lightGBM algorithm and further used to calculate the MRS. Increased MRS was positively associated with the presence of NAFLD, with odds ratio (OR) of 1.86 (1.72, 2.02) per 1-unit increase in MRS. An elevated abundance of the faecal microbiota (f__veillonellaceae) was associated with increased NAFLD risk, whereas f__rikenellaceae, f__barnesiellaceae, and s__adolescentis were associated with a decreased presence of NAFLD. Higher levels of specific gut microbiota-derived metabolites of bile acids (taurocholic acid) might be positively associated with both a higher MRS and NAFLD risk. FMT in mice further confirmed a causal association between a higher MRS and the development of NAFLD. CONCLUSIONS: We confirmed that an alteration in the composition of the core gut microbiota might be biologically relevant to NAFLD development. Our work demonstrated the role of the microbiota in the development of NAFLD.

Cognitive trajectories in older adults and the role of depressive symptoms: A 7-year follow-up study.

OBJECTIVES: To examine different trajectories of cognitive changes in elderly adults and explore the mediating role of depressive symptoms. DESIGN: A 7-year, community-based, prospective cohort study. SETTING: The downtown neighborhood of Shanghai, China. PARTICIPANTS: A cohort of 394 older adults, with an average age of 71.8 years, was recruited in 2015 and has been reassessed every two years until 2021. METHODS: Latent Class Growth Analysis was used to model aging trajectories and Linear Mixed-Effect Models for Repeated Measures were used to estimate the least squares mean changes of cognition between subjects with depression (DEP+) and without (DEP-) across all visits. RESULTS: Three cognitive trajectories were identified: the "successful aging" (SA) trajectory had the best and most consistent performance (n=229, 55.9%); the "normal aging" (NA) trajectory showed lower but stable cognition (n=141, 37.3%); while the "cognitive decline" (CD) trajectory displayed poor and declining cognition (n=24, 6.8%). Depressive symptoms were found to be influential across all trajectories. In the CD trajectory, the MoCA scores of the DEP+ group increased in within-group comparisons and were significantly higher than those of the DEP- group at visits 1 and 3 in between-group comparisons. A similar trend was observed in the NA trajectory, though it did not reach statistical significance. CONCLUSIONS: Our research suggests that mild and decreasing depressive symptoms can be a reversible factor that might slow down the irreversible cognitive decline in the elderly. Therefore, we suggest that even mild depressive symptoms in the elderly should be monitored and detected.