Gaucher disease protects against tuberculosis.

Biallelic mutations in the glucocerebrosidase (GBA1) gene cause Gaucher disease, characterized by lysosomal accumulation of glucosylceramide and glucosylsphingosine in macrophages. Gaucher and other lysosomal diseases occur with high frequency in Ashkenazi Jews. It has been proposed that the underlying mutations confer a selective advantage, in particular conferring protection against tuberculosis. Here, using a zebrafish Gaucher disease model, we find that the mutation GBA1 N370S, predominant among Ashkenazi Jews, increases resistance to tuberculosis through the microbicidal activity of glucosylsphingosine in macrophage lysosomes. Consistent with lysosomal accumulation occurring only in homozygotes, heterozygotes remain susceptible to tuberculosis. Thus, our findings reveal a mechanistic basis for protection against tuberculosis by GBA1 N370S and provide biological plausibility for its selection if the relatively mild deleterious effects in homozygotes were offset by significant protection against tuberculosis, a rampant killer of the young in Europe through the Middle Ages into the 19th century.

Tumor Receptor-Mediated Morphological Transformation and In Situ Polymerization of Diacetylene-Containing Lipidated Peptide Amphiphile on Cell Membranes for Tumor Suppression.

In situ polymerization on cell membranes can decrease cell mobility, which may inhibit tumor growth and invasion. However, the initiation of radical polymerization traditionally requires exogenous catalysts or free radical initiators, which might cause side effects in normal tissues. Herein, we synthesized a Y-type diacetylene-containing lipidated peptide amphiphile (TCDA-KFFFFK(GRGDS)-YIGSR, Y-DLPA) targeting integrins and laminin receptors on murine mammary carcinoma 4T1 cells, which underwent nanoparticle-to-nanofiber morphological transformation and in situ polymerization on cell membranes. Specifically, the polymerized Y-DLPA induced 4T1 cell apoptosis and disturbed the substance exchange and metabolism. In vitro assays demonstrated that the polymerized Y-DLPA nanofibers decreased the migration capacity of 4T1 cells, potentially suppressing tumor invasion and metastasis. When administered locally to 4T1 tumor-bearing mice, the Y-DLPA nanoparticles formed a biomimetic extracellular matrix that effectively suppressed tumor growth. This study provides an in situ polymerization strategy that can serve as an effective drug-free biomaterial with low side effects for antitumor therapy.

Lithium Bromide-Promoted Formal C(sp3)-H Bond Insertion Reactions of ß-Carbonyl Esters with Sulfoxonium Ylides to Synthesize 1,4-Dicarbonyl Compounds.

A LiBr-promoted formal C(sp3)-H bond insertion reaction between ß-carbonyl esters and sulfoxonium ylides is established. This practical reaction has a wide range of substrate scope for both ß-carbonyl esters and sulfoxonium ylides to give a variety of 1,4-dicarbonyl compounds with 43-94% yields. The reaction features transition-metal-free reaction conditions and exclusive C-alkylation chemselectivity. The use of bench-stable sulfoxonium ylides overcomes previous methods that require transition metal as catalysts and unstable diazo compounds or toxic haloketones as alkylation reagents.

Causal effects of sleep traits on metabolic syndrome and its components: a Mendelian randomization study.

PURPOSE: Previous observational studies have suggested an association between sleep disturbance and metabolic syndrome (MetS). However, it remains unclear whether this association is causal. This study aims to investigate the causal effects of sleep-related traits on MetS using Mendelian randomization (MR). METHODS: Single-nucleotide polymorphisms strongly associated with daytime napping, insomnia, chronotype, short sleep, and long sleep were selected as genetic instruments from the corresponding genome-wide association studies (GWAS). Summary-level data for MetS were obtained from two independent GWAS datasets. Univariable and multivariable MR analyses were conducted to investigate and verify the causal effects of sleep traits on MetS. RESULTS: The univariable MR analysis demonstrated that genetically predicted daytime napping and insomnia were associated with increased risk of MetS in both discovery dataset (OR daytime napping = 1.630, 95% CI 1.273, 2.086; OR insomnia = 1.155, 95% CI 1.108, 1.204) and replication dataset (OR daytime napping = 1.325, 95% CI 1.131, 1.551; OR insomnia = 1.072, 95% CI 1.046, 1.099). For components, daytime napping was positively associated with triglycerides (beta = 0.383, 95% CI 0.160, 0.607) and waist circumference (beta = 0.383, 95% CI 0.184, 0.583). Insomnia was positively associated with hypertension (OR = 1.101, 95% CI 1.042, 1.162) and waist circumference (beta = 0.067, 95% CI 0.031, 0.104). The multivariable MR analysis indicated that the adverse effect of daytime napping and insomnia on MetS persisted after adjusting for BMI, smoking, drinking, and another sleep trait. CONCLUSION: Our study supported daytime napping and insomnia were potential causal factors for MetS characterized by central obesity, hypertension, or elevated triglycerides.

Investigating the shared genetic architecture between breast and ovarian cancers.

High heritability and strong correlation have been observed in breast and ovarian cancers. However, their shared genetic architecture remained unclear. Linkage disequilibrium score regression (LDSC) and heritability estimation from summary statistics (ρ-HESS) were applied to estimate heritability and genetic correlations. Bivariate causal mixture model (MiXeR) was used to qualify the polygenic overlap. Then, stratified-LDSC (S-LDSC) was used to identify tissue and cell type specificity. Meanwhile, the adaptive association test called MTaSPUsSet was performed to identify potential pleiotropic genes. The Single Nucleotide Polymorphisms (SNP) heritability was 13% for breast cancer and 5% for ovarian cancer. There was a significant genetic correlation between breast and ovarian cancers (rg=0.21). Breast and ovarian cancers exhibited polygenic overlap, sharing 0.4 K out 2.8 K of causal variants. Tissue and cell type specificity displayed significant enrichment in female breast mammary, uterus, kidney tissues, and adipose cell. Moreover, the 74 potential pleiotropic genes were identified between breast and ovarian cancers, which were related to the regulation of cell cycle and cell death. We quantified the shared genetic architecture between breast and ovarian cancers and shed light on the biological basis of the co-morbidity. Ultimately, these findings facilitated the understanding of disease etiology.

Transcriptional level of inflammation markers associates with short-term brain structural changes in first-episode schizophrenia.

BACKGROUND: Inflammation has been implicated in the pathology of schizophrenia and may cause neuronal cell death and dendrite loss. Neuroimaging studies have highlighted longitudinal brain structural changes in patients with schizophrenia, yet it is unclear whether this is related to inflammation. We aim to address this question, by relating brain structural changes with the transcriptional profile of inflammation markers in the early stage of schizophrenia. METHODS: Thirty-eight patients with first-episode schizophrenia and 51 healthy controls were included. High-resolution T1-weighted magnetic resonance imaging (MRI) and clinical assessments were performed at baseline and 2 ~ 6 months follow-up for all subjects. Changes in the brain structure were analyzed using surface-based morphological analysis and correlated with the expression of immune cells-related gene sets of interest reported by previous reviews. Transcriptional data were retrieved from the Allen Human Brain Atlas. Furthermore, we examined the brain structural changes and peripheral inflammation markers in association with behavioral symptoms and cognitive functioning in patients. RESULTS: Patients exhibited accelerated cortical thickness decrease in the left frontal cortices, less decrease or an increase in the superior parietal lobule and right lateral occipital lobe, and increased volume in the bilateral pallidum, compared with controls. Changes in cortical thickness correlated with the transcriptional level of monocyte across cortical regions in patients (r = 0.54, p < 0.01), but not in controls (r = - 0.05, p = 0.76). In addition, cortical thickness change in the left superior parietal lobule positively correlated with changes in digital span-backward test scores in patients. CONCLUSIONS: Patients with schizophrenia exhibit regional-specific cortical thickness changes in the prefrontal and parietooccipital cortices, which is related to their cognitive impairment. Inflammation may be an important factor contributing to cortical thinning in first-episode schizophrenia. Our findings suggest that the immunity-brain-behavior association may play a crucial role in the pathogenesis of schizophrenia.

Differential expression of diacylglycerol kinase ζ is involved in inferior parietal lobule-related dysfunction in schizophrenia with cognitive impairments.

BACKGROUND: Cognitive impairment is the main factor in the poor prognosis of schizophrenia, but its mechanism remains unclear. The inferior parietal lobule (IPL) is related to various clinical symptoms and cognitive impairment in schizophrenia. We aimed to explore the relationship between IPL-related functions and cognitive impairment in schizophrenia. METHODS: 136 schizophrenia patients and 146 demographically matched healthy controls were enrolled for a cross-sectional study. High-spatial-resolution structural and resting-state functional images were acquired to demonstrate the alternations of brain structure and function. At the same time, the digit span and digit symbol coding tasks of the Chinese Wechsler Adult Intelligence Test Revised (WAIS-RC) were utilized in assessing the subjects' cognitive function. Patients were divided into cognitive impairment and normal cognitive groups according to their cognitive score and then compared whether there were differences between the three groups in fractional amplitude of low-frequency fluctuation (fALFF). In addition, we did a correlation analysis between cognitive function and the fALFF for the left IPL of patients and healthy controls. Based on the Allen Human Brain Atlas, we obtained genes expressed in the left IPL, which were then intersected with the transcriptome-wide association study results and differentially expressed genes in schizophrenia. RESULTS: Grouping of patients by the backward digit span task and the digit symbol coding task showed differences in fALFF values between healthy controls and cognitive impairment patients (P < 0.05). We found a negative correlation between the backward digit span task score and fALFF of the left IPL in healthy controls (r = - 0.388, P = 0.003), which was not seen in patients (r = 0.203, P = 0.020). In addition, none of the other analyses were statistically significant (P > 0.017). In addition, we found that diacylglycerol kinase ζ (DGKζ) is differentially expressed in the left IPL and associated with schizophrenia. CONCLUSION: Our study demonstrates that the left IPL plays a vital role in cognitive impairment in schizophrenia. DGKζ may act as an essential regulator in the left IPL of schizophrenia patients with cognitive impairment.

Assessment of the impact of shift work on thyroid disorders: a systematic review and meta-analysis.

PURPOSE: Shift work including night work is a common work pattern worldwide and researchers have no consensus on the impact of shift work on thyroid disorders. We aimed to conduct a meta-analysis to summarize the evidence from published studies to ascertain the impact of shift work on thyroid disorders. METHODS: Studies on the link between shift work and thyroid disorders published in Pubmed, Embase, Medline, and Cochrane databases by September 2021 were searched. Newcastle-Ottawa scale was used to assess the quality of included studies. The Mantel-Haenszel statistical method and the inverse-variance statistical method were used to evaluate the pooled results of dichotomous and continuous variables, respectively. Study heterogeneity analysis was performed using I2 statistics. Sensitivity analysis was conducted by omitting one study each time and re-calculating the pooled results of the remaining studies. RESULTS: Seven eligible studies were included in the systematic review and meta-analysis. The results showed that shift work would lead to an increase in TSH (SMD: 0.30; 95%CI: 0.05-0.55; P = 0.02; I2 = 64%) and FT4 (SMD: 0.21; 95%CI: 0.02-0.40; P = 0.03; I2 = 0%). However, shift work had no clear effect on the risk of positive thyroid autoantibodies (OR: 1.26; 95%CI: 0.62-2.55; P = 0.52; I2 = 63%). CONCLUSION: Shift work may be associated with abnormal TSH and FT4 levels. Thyroid health is affected in shift workers and it is advisable to remind patients to get good sleep the night before testing thyroid function.

Spatial distribution and driving factors of the associations between temperature and influenza-like illness in the United States: a time-stratified case-crossover study.

BACKGROUND: Several previous studies investigated the associations between temperature and influenza in a single city or region without a national picture. The attributable risk of influenza due to temperature and the corresponding driving factors were unclear. This study aimed to evaluate the spatial distribution characteristics of attributable risk of Influenza-like illness (ILI) caused by adverse temperatures and explore the related driving factors in the United States. METHODS: ILI, meteorological factors, and PM2.5 of 48 states in the United States were collected during 2011-2019. The time-stratified case-crossover design with a distributed lag non-linear model was carried out to evaluate the association between temperature and ILI at the state level. The multivariate meta-analysis was performed to obtain the combined effects at the national level. The attributable fraction (AF) was calculated to assess the ILI burden ascribed to adverse temperatures. The ordinary least square model (OLS), spatial lag model (SLM), and spatial error model (SEM) were utilized to identify driving factors. RESULTS: A total of 7,716,115 ILI cases were included in this study. Overall, the temperature was negatively associated with ILI risk, and lower temperature gave rise to a higher risk of ILI. AF ascribed to adverse temperatures differed across states, from 49.44% (95% eCI: 36.47% ~ 58.68%) in Montana to 6.51% (95% eCI: -6.49% ~ 16.46%) in Wisconsin. At the national level, 29.08% (95% eCI: 27.60% ~ 30.24%) of ILI was attributable to cold. Per 10,000 dollars increase in per-capita income was associated with the increment in AF (OLS: ß = -6.110, P = 0.021; SLM: ß = -5.496, P = 0.022; SEM: ß = -6.150, P = 0.022). CONCLUSION: The cold could enhance the risk of ILI and result in a considerable proportion of ILI disease burden. The ILI burden attributed to cold varied across states and was higher in those states with lower economic status. Targeted prevention programs should be considered to lower the burden of influenza.

Effects of diabetes mellitus complicated by admission hyperglycemia on clot histological composition and ultrastructure in patients with acute ischemic stroke.

BACKGROUND: Type 2 diabetes mellitus (T2DM) affects the occurrence and prognosis of acute ischemic stroke (AIS). However, the impact of diabetes on thrombus characteristics is unclear. The relationship between the composition and ultrastructure of clots and DM with admission hyperglycemia was investigated. METHODS: Consecutive patients with AIS who underwent endovascular thrombus retrieval between June 2017 and May 2021 were recruited. The thrombus composition and ultrastructure were evaluated using Martius scarlet blue stain and scanning electron microscopy. Clot perviousness was evaluated via thrombus attenuation increase on computed tomography angiography (CTA) versus non-contrast CT. Patients with admission hyperglycemia DM (ahDM) and those without DM (nonDM) were compared in terms of thrombus composition, ultrastructure, and perviousness. RESULTS: On admission, higher NIHSS scores (17 vs. 12, respectively, p = 0.015) was evident in ahDM patients. After the 90-day follow-up, the rates of excellent outcomes (mRS 0-1) were lower in patients with ahDM (16.6%, p = 0.038), but functional independence (mRS 0-2) and handicapped (mRS 3-5) were comparable between patients with ahDM and nonDM. The outcome of mortality was higher in patients with ahDM (33.3%, p = 0.046) than in nonDM patients. Clots in patients with ahDM had more fibrin (39.4% vs. 25.0%, respectively, p = 0.007), fewer erythrocyte components (21.2% vs. 41.5%, respectively, p = 0.043), equivalent platelet fraction (27.7% vs. 24.6%, respectively, p = 0.587), and higher WBC counts (4.6% vs. 3.3%, respectively, p = 0.004) than in nonDM patients. The percentage of polyhedral erythrocytes in thrombi was significantly higher in ahDM patients than in nonDM patients (68.9% vs. 45.6%, respectively, p = 0.007). The proportion of pervious clots was higher in patients nonDM than in patients with ahDM (82.61% vs. 40%, respectively, p = 0.026). CONCLUSION: Patients with ahDM presented with greater stroke severity on admission and poorer functional outcomes after 3 months. Clots in patients with ahDM had more fibrin, leucocytes, and fewer erythrocyte components than in patients nonDM. The content of polyhedral erythrocytes and impervious clots proportion were significantly higher in thrombi of patients with AIS and ahDM. Further research is required to validate these findings.

Trends and influence factors in the prevalence, intervention, and control of metabolic syndrome among US adults, 1999-2018.

AIM: We aimed to describe the trends in the prevalence, intervention, and control of metabolic syndrome (MetS) among US adults through 1999-2018. Additionally, the influence factors of MetS and its control were further explored. METHODS: We included participants older than 20 using the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 (n = 22,114). The rate of prevalence, intervention, and control of MetS were caculated by survey weights. Joinpoint regression and survey-weighted generalized linear models were used to analyze trends and influence factors, respectively. RESULTS: The prevalence of MetS increased from 28.23 to 37.09% during 1999-2018 (P for trend < 0.05). The former smoker (OR = 1.20, 95%CI: 1.07, 1.36) and current smoker (OR = 1.27, 95%CI: 1.11, 1.45) increased the prevalence of MetS. While vigorous activity (OR = 0.53, 95%CI: 0.47, 0.61) decreased it. Among MetS components, the prevalence of elevated blood-glucose (from 21.18 to 34.68%) and obesity (from 44.81 to 59.06%) raised (P for trend < 0.05), with an uptrend in the use of antidiabetic (from 9.87 to 28.63%) and a downtrend of vigorous activity (from 23.79 to 16.53%) (P for trend < 0.05). Decreased trends were observed in the control of Hb1Ac (< 7%) (from 87.13 to 84.06%) and BMI (<25 kg/m2) (from 11.36 to 7.49%). Among MetS underwent antidiabetic, 45-64 years old and male decreased the control of Hb1Ac (< 7%). The control of BMI (<25 kg/m2) among individuals with physical activity was reduced mainly in the population of younger (aged 20-44 years old), male, non-Hispanic black, middle income and smoker (former and current). CONCLUSIONS: The prevalence of MetS increased significantly through 1999-2018. Elevated blood glucose and obesity were the main causes of MetS burden. Quitting smoking and increasing physical activity may decrease the prevalence of MetS. In the control of blood-glucose and obesity, we should screen out the focus population to modify treatment and improve lifestyle.

Magnetic Resonance Imaging throughout the Clinical Course of Schizophrenia: Neurobiological Underpinnings and Clinical Implications.

As a non-invasive detection method and an advanced imaging method, magnetic resonance imaging (MRI) has been widely used in the research of schizophrenia. Although a large number of neuroimaging studies have confirmed that MRI can display abnormal brain phenotypes in patients with schizophrenia, no valid uniform standard has been established for its clinical application. On the basis of previous evidence, we argue that MRI is an important tool throughout the whole clinical course of schizophrenia. The purpose of this commentary is to systematically describe the role of MRI in schizophrenia and to provide references for its clinical application.

Statistical Inference of Inverted Exponentiated Rayleigh Distribution under Joint Progressively Type-II Censoring.

Inverted exponentiated Rayleigh distribution is a widely used and important continuous lifetime distribution, which plays a key role in lifetime research. The joint progressively type-II censoring scheme is an effective method used in the quality evaluation of products from different assembly lines. In this paper, we study the statistical inference of inverted exponentiated Rayleigh distribution based on joint progressively type-II censored data. The likelihood function and maximum likelihood estimates are obtained firstly by adopting Expectation-Maximization algorithm. Then, we calculate the observed information matrix based on the missing value principle. Bootstrap-p and Bootstrap-t methods are applied to get confidence intervals. Bayesian approaches under square loss function and linex loss function are provided respectively to derive the estimates, during which the importance sampling method is introduced. Finally, the Monte Carlo simulation and real data analysis are performed for further study.

Application of new international classification of adult-onset diabetes in Chinese inpatients with diabetes mellitus.

BACKGROUND: To determine whether the new international cluster-based classification method can be applied to Chinese inpatients with diabetes mellitus (DM). METHODS: Adult patients with DM hospitalized in our tertiary care centre from January 2017 to December 2018 were included in the study. K-means cluster analysis was done in clusters based on glutamic acid decarboxylase antibodies, body mass index, glycosylated haemoglobin, homeostasis model-assessed beta cell function, insulin resistance index, and age at diagnosis of DM. Chi-square test was used to analyse inter-subgroup differences in DM-related complications and family history of DM. p < 0.05 was considered significant. RESULTS: A total of 1152 inpatients with DM were included in the study. Five subgroups were obtained by cluster analysis with highest proportion of population in mild obesity-related DM subgroup (34.55%), followed by mild age-related DM (21.55%), severe insulin deficiency DM (20.51%), severe insulin resistance DM (19.02%), and severe autoimmune DM subgroup (4.36%). The prevalence of diabetic retinopathy, diabetic peripheral vascular disease, diabetic ketosis, coronary heart disease, hypertension, and family history of DM differed significantly among the subgroups (p < 0.05 for all). CONCLUSIONS: This cluster-based classification could be applied to hospitalized adult patients with DM in China. It might help in strategizing for DM patients, and hence, improve management of DM in these patients.

Fault diagnosis of landing gear retraction system with bond graph under uncertain conditions.

Given the lack of sufficient historical data for aircraft landing gear retractor systems, a model-based fault diagnosis approach is needed to overcome this data deficiency. Meanwhile, inherent uncertainties are inevitable in engineering practice, and it is a great challenge to construct a model that accurately reflects the complexity of the actual system under uncertain conditions. Due to the urgent need for reliable model-based diagnostic methods and the need to cope with inherent uncertainties, this paper proposes an improved fault diagnostic method aimed at increasing the diagnostic efficiency of the landing gear retractor system, a critical component in aircraft take-off and landing operations. Due to a lack of historical data, the model-based fault diagnosis method can solve the problem of lack of data. The proposed uncertainty method addresses the challenge of multiple sources of uncertainty by using subsystems to reduce complexity. Fault diagnosis is achieved by comparing residuals with thresholds derived from a diagnostic bond graph (DBG) model. To address the problem of limited fault data, we modeled and simulated the landing gear retractor system using AMESim®. In addition, the linear fractional transform (LFT) approach has been used to resolve parametric uncertainties, but is unable to resolve system structural uncertainties. Therefore, we also analyzed the comparative fault diagnosis results derived from the linear fractional transformation-DBG (LFT-DBG) and the subsystem-DBG approaches. The experimental results support the effectiveness of the subsystem approach in improving fault diagnosis accuracy and reliability, highlighting its potential as a viable diagnostic strategy in aerospace engineering applications.

Causal association of rheumatoid arthritis with frailty and the mediation role of inflammatory cytokines: A Mendelian randomization study.

BACKGROUND: Previous observational studies have suggested the association between rheumatoid arthritis (RA) and frailty. However, it remains obscure whether this association is causal. This study aims to investigate the causal association of RA with frailty and the mediation effect of inflammatory cytokines using Mendelian randomization (MR) design. METHODS: Summary-level data for RA (N = 58,284), frailty index (FI) (N = 175,226), Fried frailty score (FFS) (N = 386,565), and 41 inflammatory cytokines (N = 8,293) were obtained from recent genome-wide association studies. Univariable and multivariable MR analyses were conducted to investigate and verify the causal association of RA with frailty. The potential mediation effects of inflammatory cytokines were estimated using two-step MR. RESULTS: Univariable inverse variance weighted MR analysis suggested that genetically determined RA was associated with increased FI (beta=0.021; 95 % CI: 0.012, 0.03; p = 2.2 × 10-6) and FFS (beta=0.011; 95 %CI: 0.007, 0.015; p = 8.811 × 10-8). The consistent results were observed in multivariable MR analysis after adjustment for asthma, smoking, BMI, physical activity, telomere length, and depression. Mediation analysis showed evidence of an indirect effect of RA on FI through monokine induced by interferon-gamma (MIG) with a mediated proportion of 9.8 % (95 %CI: 4.76 %, 19.05 %), on FFS via MIG and stromal cell-derived factor-1 alpha with a mediated proportion of 9.6 % (95 %CI: 0 %, 18.18 %) and 8.44 % (95 %CI: 0 %, 18.18 %), respectively. CONCLUSION: This study provided credible evidence that genetically predicted RA was associated with a higher risk of frailty. Additionally, inflammatory cytokines were involved in the mechanism of RA-induced frailty.

Vitamin D deficiency increases the risk of diabetic peripheral neuropathy in elderly type 2 diabetes mellitus patients by predominantly increasing large-fiber lesions.

AIMS: This study explores the link between Vitamin D deficiency (VDD) and diabetic peripheral neuropathy (DPN) in elderly type 2 diabetes mellitus (T2DM) patients. METHODS: Involving 257 elderly T2DM patients, the study utilized propensity score matching to balance age, sex, and diabetes duration. VDD was defined as serum 25-hydroxyvitamin D [25(OH)D] levels below 20 ng/ml. Large nerve fiber lesions were evaluated by electromyogram, while small nerve fiber lesions were assessed by measuring skin conductance. RESULTS: DPN patients had notably lower serum 25(OH)D levels than non-DPN patients [15.05 vs. 18.4 ng/ml, P = 0.018]. VDD was identified as an independent risk factor for DPN (odds ratio = 2.488, P = 0.008) in multivariate logistic regression analysis. Spearman's correlation showed negative correlations between serum 25(OH)D levels and specific nerve latencies, and positive correlations with specific nerve velocities and amplitudes. The VDD group exhibited longer median sensory nerve latencies and motor evoked potential latencies compared to the vitamin D-sufficient group. Further, VDD is associated with the prolongation of the median motor nerve latency (odds ratio = 1.362, P = 0.038). CONCLUSIONS: VDD is independently associated with a higher risk of DPN. VDD may promote the development of DPN by affecting large nerve fibers.

Biochar immobilized hydrolase degrades PET microplastics and alleviates the disturbance of soil microbial function via modulating nitrogen and phosphorus cycles.

Microplastics (MPs) pose an emerging threat to soil ecological function, yet effective solutions remain limited. This study introduces a novel approach using magnetic biochar immobilized PET hydrolase (MB-LCC-FDS) to degrade soil polyethylene terephthalate microplastics (PET-MPs). MB-LCC-FDS exhibited a 1.68-fold increase in relative activity in aquatic solutions and maintained 58.5 % residual activity after five consecutive cycles. Soil microcosm experiment amended with MB-LCC-FDS observed a 29.6 % weight loss of PET-MPs, converting PET into mono(2-hydroxyethyl) terephthalate (MHET). The generated MHET can subsequently be metabolized by soil microbiota to release terephthalic acid. The introduction of MB-LCC-FDS shifted the functional composition of soil microbiota, increasing the relative abundances of Microbacteriaceae and Skermanella while reducing Arthobacter and Vicinamibacteraceae. Metagenomic analysis revealed that MB-LCC-FDS enhanced nitrogen fixation, P-uptake and transport, and organic-P mineralization in PET-MPs contaminated soil, while weakening the denitrification and nitrification. Structural equation model indicated that changes in soil total carbon and Simpson index, induced by MB-LCC-FDS, were the driving factors for soil carbon and nitrogen transformation. Overall, this study highlights the synergistic role of magnetic biochar-immobilized PET hydrolase and soil microbiota in degrading soil PET-MPs, and enhances our understanding of the microbiome and functional gene responses to PET-MPs and MB-LCC-FDS in soil systems.

Associations of Dietary Diversity Trajectories with Frailty among Chinese Older Adults: A Latent Class Trajectory Analysis Based on a CLHLS Cohort.

BACKGROUND: High dietary diversity has been found to be associated with frailty. However, the trajectory of dietary diversity intake in relation to frailty is unclear. METHODS: Using the latent class trajectory modeling approach, we identified distinctive dietary variety trajectory groups among 2017 participants based on the Chinese Longitudinal Healthy Longevity Survey acquired at four time points within a 10-year period. Frailty status was assessed using a frailty index comprising 37 health deficits. Dietary diversity was quantified using the dietary variety score (DVS), based on food category consumption frequency. Logistic regression analyses were employed to explore the association between DVS change trajectories and frailty. RESULTS: This study identified two distinct DVS trajectories: "Moderate-Slow decline-Slow growth", encompassing 810 (40.16%) individuals, and "Moderate-Slow growth-Accelerated decline", including 1207 (59.84%) individuals. After adjusting for covariates, the odds ratio for DVS in the "Moderate-Slow decline-Slow growth" group was 1.326 (95% confidence interval: 1.075-1.636) compared to the "Moderate-Slow growth-Accelerated decline" group. The "Moderate-Slow decline-Slow growth" trajectory continued to decrease and was maintained at a low level in the early stages of aging. CONCLUSION: Sustaining a high dietary diversity trajectory over time, particularly in the early stages of aging, could potentially decrease the risk of frailty among older Chinese adults.

Metabolic score and its components are associated with carotid plaque prevalence in young adults.

PURPOSE: No study has comprehensively assessed the relationship of metabolic factors including insulin resistance, hypertension, hyperuricemia, and hypercholesterolemia with the development of carotid plaque. Therefore, we constructed metabolic scores based on the above metabolic factors and examined its association with carotid plaque in young and older Chinese adults. METHODS: This study included 17,396 participants who underwent carotid ultrasound examinations, including 14,173 young adults (<65 years) and 3,223 older adults (≥65 years). Individual metabolic score was calculated using triglyceride-glucose (TyG) index, mean arterial pressure (MAP), uric acid, and total cholesterol (TC). Logistic regression models were conducted to examine the role of metabolic score and its components in the prevalence of carotid plaque. The nonlinear relationship was examined using restricted cubic spline regression. Meanwhile, subgroup, interaction, and sensitivity analyses were conducted. RESULTS: The multivariate logistic regression analysis showed that TyG (OR: 1.088; 95%CI: 1.046-1.132), MAP (OR: 1.121; 95%CI: 1.077-1.168), TC (OR: 1.137; 95%CI: 1.094-1.182) and metabolic score (OR: 1.064; 95%CI: 1.046-1.082) were associated with carotid plaque prevalence in young adults rather than older adults. The nonlinear association was not observed for metabolic scores and carotid plaque. Subgroup analyses showed significant associations between metabolic scores and carotid plaque prevalence in men, women, normal-weight, and overweight young adults. No interaction of metabolic score with sex and BMI were observed. CONCLUSIONS: The results support that control of TyG, MAP, TC, and metabolic scores is a key point in preventing the prevalence of carotid plaque in the young adults.