Virulence of banana wilt-causing fungal pathogen Fusarium oxysporum tropical race 4 is mediated by nitric oxide biosynthesis and accessory genes.

Fusarium wilt of banana, caused by Fusarium oxysporum f. sp. cubense (Foc), is one of the most damaging plant diseases known. Foc race 1 (R1) decimated the Gros Michel-based banana (Musa acuminata) trade, and now Foc tropical race 4 (TR4) threatens global production of its replacement, the Cavendish banana. Here population genomics revealed that all Cavendish banana-infecting Foc race 4 strains share an evolutionary origin distinct from that of R1 strains. Although TR4 lacks accessory chromosomes, it contains accessory genes at the ends of some core chromosomes that are enriched for virulence and mitochondria-related functions. Meta-transcriptomics revealed the unique induction of the entire mitochondrion-localized nitric oxide (NO) biosynthesis pathway upon TR4 infection. Empirically, we confirmed the unique induction of a NO burst in TR4, suggesting that nitrosative pressure may contribute to virulence. Targeted mutagenesis demonstrated the functional importance of fungal NO production and the accessory gene SIX4 as virulence factors.

Genotype-phenotype correlation of SQSTM1 variants in patients with amyotrophic lateral sclerosis.

BACKGROUND: Several variants of sequestosome 1 (SQSTM1) were screened in patients with amyotrophic lateral sclerosis (ALS), while the pathogenicity and genotype-phenotype correlation remains unclear. METHODS: We screened variants of SQSTM1 gene in 2011 Chinese patients with ALS and performed a burden analysis focusing on the rare variants. Furthermore, we conducted a comprehensive analysis of patients with variants of SQSTM1 gene in patients with ALS from our cohort and published studies. RESULTS: In our cohort, we identified 32 patients with 25 different SQSTM1 variants with a mutant frequency of 1.6%. Notably, 26% (5/19) of the patients with ALS with SQSTM1 variant in our cohort had comorbid cognitive impairment and 43% (3/7) of them had behavioural variant frontotemporal dementia (FTD). Our meta-analysis found a total frequency of SQSTM1 variants in 7183 patients with ALS was 2.4%; burden analysis indicated that patients with ALS had enrichment of ultra-rare (minor allele frequency<0.01%) probably pathogenic variants in SQSTM1. Most variants were missense variants and distributed in various domains of p62 protein, some of which might be related to comorbidities of Paget's disease of bone and FTD. CONCLUSION: Our study established the largest cohort of patients with ALS with SQSTM1 variants, expanded the mutation spectrum and investigated the genotype-phenotype correlations of SQSTM1 variants.

Assessing green production efficiency and spatial characteristics of China's real estate industry based on the undesirable super-SBM model.

As China strives to balance rapid urbanization with environmental conservation, increasing attention is being paid to the pursuit of green production efficiency (GPE) in the real estate industry. The undesirable super-SBM model was used to calculate the GPE of China's real estate industry from 2001 to 2020. Additionally, GPE spatial distribution characteristics in China's real estate industry were analyzed using the standard deviation ellipse (SDE), Moran's index, Theil index, random kernel density estimation (RKDA), and spatial Markov chain (SMC) methods. The GPE exhibited a U-shaped trend, with 2008 as the inflection point, first decreasing and then increasing. It reached a maximum value of 0.747 in 2020. The Theil index increased from 0.043 to 0.121 nationwide, indicating the overall characteristics of low-level slow growth, and imbalance. Discrepancies in input-output scales, the southward shift of economic centers, and population movements contribute significantly to the disparities between the east and west, north and south, and regions divided by the Hu Huanyong Line (Hu Line). The GPE exhibited club convergence characteristics; however, polarization phenomena exist in local areas. Spatial spillover effects were also observed in GPE. Finally, we provide recommendations for promoting green development in the real estate industry, including green building technology, fiscal subsidy investment, and population migration management.

Associations of sugar intake, high-sugar dietary pattern, and the risk of dementia: a prospective cohort study of 210,832 participants.

BACKGROUND: Limited evidence demonstrated the potential relationship between dietary sugar intake and dementia. This association demands further clarification in a large-scale population. METHODS: A total of 210,832 participants from the UK Biobank cohort were included in this prospective cohort study. Absolute and relative sugar intake and high-sugar dietary scores were utilized to reflect dietary sugar intake. Absolute sugar intake was identified by the Oxford WebQ in the UK Biobank. Relative sugar intake was calculated by dividing the absolute sugar intake by total diet energy. High-sugar dietary pattern was identified using the method of reduced rank regression. Cox proportional hazards regression analyses and restricted cubic splines were performed to examine the longitudinal associations between dietary sugar intake and all-cause dementia and its main subtype, Alzheimer's disease. Explorative mediation analyses were conducted to explore underlying mechanisms. RESULTS: Increased absolute sugar intake (g/day) was significantly associated with a higher risk of all-cause dementia (HR = 1.003, [95%CI: 1.002-1.004], p < 0.001) and Alzheimer's disease (1.002, [1.001-1.004], 0.005). Relative sugar intake (%g/kJ/day) also demonstrated significant associations with all-cause dementia (1.317, [1.173-1.480], p < 0.001) and Alzheimer's disease (1.249, [1.041-1.500], 0.017), while the high-sugar dietary score was only significantly associated with a higher risk of all-cause dementia (1.090, [1.045-1.136], p < 0.001). In addition, both sugar intake and high-sugar dietary score demonstrated significant non-linear relationships with all-cause dementia and Alzheimer's disease (all p values for non-linearity < 0.05). CONCLUSIONS: Our study provided evidence that excessive sugar intake was associated with dementia. Controlling the excess consumption of dietary sugar may be of great public health implications for preventing dementia.

Relationship between Vitamin D Concentration and Lipid Concentration in Patients with NAFLD in the Hulunbuir Region of China.

BACKGROUND: We aimed to characterize the relationship between the serum 25-hydroxyvitamin D concentration and the circulating lipid concentrations of patients with NAFLD in the Hulunbuir region of China. METHODS: One hundred fifty-six patients, who were diagnosed with NAFLD in the Physical Examination Department of the Second Clinical College of Inner Mongolia University for the Nationalities between January 2021 and March 2023, were recruited as NAFLD group, and 160 healthy people were recruited as a control group during the same period. The serum 25(OH)VitD, TBIL, TG, TC, LDL-C, HDL-C, AST, ALT, GGT, and FPG activities of the participants were measured, and hepatic ultrasonography was performed. RESULTS: The BMI of the NAFLD group was higher than of the control group (p < 0.05). The serum 25(OH)VitD3 (p < 0.05) and the HDL-C concentrations of the NAFLD group were lower than those of the normal control group. However, the AST (p < 0.05), ALT (p < 0.05), and GGT (p < 0.05) activities, and the serum TG (p < 0.05), TC (p < 0.05), LDL-C (p < 0.05), and the fasting glucose (p < 0.05) concentrations of the NAFLD group were higher than those of the normal control group. The serum 25(OH)VitD3 concentrations of the NAFLD group significantly cor-related negatively with BMI (r = -0.302, p < 0.01), TG (r = -0.221, p < 0.05), and fasting glucose (r = -0.236, p < 0.05). The BMI, TG, and fasting glucose of vitamin D-deficient participants were higher than of the participants with adequate or insufficient levels of vitamin D (p < 0.05). Finally, the BMI of vitamin D-deficient participants was higher than of those with an adequate vitamin D status (p < 0.05). CONCLUSIONS: A deficiency of 25(OH)VitD is more common in people from the Hulunbuir region of China than elsewhere. In addition, the vitamin D status is significantly associated with NAFLD; as the serum vitamin D concentration decreases, patients with NAFLD show greater dyslipidemia and hyperglycemia and a higher BMI.

Au nanoparticles decorated ß-Bi2O3 as highly-sensitive SERS substrate for detection of methylene blue and methyl orange.

In this work, Au/Bi2O3 was synthesized by loading Au nanoparticles (NPs) onto ß-Bi2O3 by a simple solution reduction method. ß-Bi2O3 was synthesized by a precipitation-thermal decomposition procedure, which results in significantly improved SERS detection limits down to 10-9 M for methylene blue (MB) and 10-7 M for methyl orange (MO) as probe molecules, comparable to those reported for the best semiconductor SERS substrates. In particular, further deposition of Au NPs (5.20% wt%) onto ß-Bi2O3 results in a two-order-of-magnitude enhancement in detection sensitivity, achieving a detection limit of 10-11 M for MB and 10-9 M for MO. Under ultraviolet/visible irradiation, the Au/Bi2O3 hybrids substrate exhibits superior self-cleaning ability due to its photocatalytic degradation ability which can be applied repeatedly to the detection of pollutants. The advanced composite substrate simultaneously achieved ultra-low mass loading of Au NPs, outstanding detection performance, good reproducibility, high stability and self-cleaning ability. The development strategy of low load noble metal coupled high performance semiconductor ß-Bi2O3 to obtain nano-hybrid materials provides a method to balance SERS sensitivity, cost effectiveness and operational stability, and can be synthesized in large quantities, which is a key step towards commercialization and has good reliability prospects.

Upgrade of crystallography beamline BL19U1 at the Shanghai Synchrotron Radiation Facility.

BL19U1, an energy-tunable protein complex crystallography beamline at the Shanghai Synchrotron Radiation Facility, has emerged as one of the most productive MX beamlines since opening to the public in July 2015. As of October 2023, it has contributed to over 2000 protein structures deposited in the Protein Data Bank (PDB), resulting in the publication of more than 1000 scientific papers. In response to increasing interest in structure-based drug design utilizing X-ray crystallography for fragment library screening, enhancements have been implemented in both hardware and data collection systems on the beamline to optimize efficiency. Hardware upgrades include the transition from MD2 to MD2S for the diffractometer, alongside the installation of a humidity controller featuring a rapid nozzle exchanger. This allows users to opt for either low-temperature or room-temperature data collection modes. The control system has been upgraded from Blu-Ice to MXCuBE3, which supports website-mode data collection, providing enhanced compatibility and easy expansion with new features. An automated data processing pipeline has also been developed to offer users real-time feedback on data quality.

Albumin and multiple sclerosis: a prospective study from UK Biobank.

Background: Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system. While previous studies have indicated that albumin, the primary protein in human plasma, may exert influence on the inflammatory process and confer beneficial effects in neurodegenerative disorders, its role in the context of MS has been underexplored. Here, we aimed to explore the link between albumin and the risk of MS. Methods: Employing data from the UK Biobank, we investigated the association between baseline levels of serum and urine albumin and the risk of MS using Cox proportional hazards regression analysis. Results: A higher baseline level of serum albumin was associated with a lower risk of incident MS (HR=0.94, 95% CI: 0.91-0.98, P=7.66E-04). Subgroup analysis revealed a more pronounced effect in females, as well as participants with younger ages, less smoking and deficient levels of vitamin D. Conversely, no association was identified between baseline microalbuminuria level and risk of incident MS. Conclusion: Higher serum albumin level at baseline is linked to a reduced risk of MS. These results contribute to an enhanced understanding of albumin's role in MS, propose the potential use of albumin as a biomarker for MS, and have implications for the design of therapeutic interventions targeting albumin in clinical trials.

GIWAXS experimental methods at the NFPS-BL17B beamline at Shanghai Synchrotron Radiation Facility.

The BL17B beamline at the Shanghai Synchrotron Radiation Facility was first designed as a versatile high-throughput protein crystallography beamline and one of five beamlines affiliated to the National Facility for Protein Science in Shanghai. It was officially opened to users in July 2015. As a bending magnet beamline, BL17B has the advantages of high photon flux, brightness, energy resolution and continuous adjustable energy between 5 and 23 keV. The experimental station excels in crystal screening and structure determination, providing cost-effective routine experimental services to numerous users. Given the interdisciplinary and green energy research demands, BL17B beamline has undergone optimization, expanded its range of experimental methods and enhanced sample environments for a more user-friendly testing mode. These methods include single-crystal X-ray diffraction, powder crystal X-ray diffraction, wide-angle X-ray scattering, grazing-incidence wide-angle X-ray scattering (GIWAXS), and fully scattered atom pair distribution function analysis, covering structure detection from crystalline to amorphous states. This paper primarily presents the performance of the BL17B beamline and the application of the GIWAXS methodology at the beamline in the field of perovskite materials.

Ultra-high-performance liquid chromatography-mass spectrometry combined with molecular docking and molecular dynamics simulation reveals the source of bitterness in the traditional Chinese medicine formula Runchang-Tongbian.

The Runchang-Tongbian (RCTB) formula is a traditional Chinese medicine (TCM) formula consisting of four herbs, namely Cannabis Fructus (Huomaren), Rehmanniae Radix (Dihuang), Atractylodis Macrocephalae Rhizoma (Baizhu), and Aurantii Fructus (Zhiqiao). It is widely used clinically because of its beneficial effect on constipation. However, its strong bitter taste leads to poor patient compliance. The bitter components of TCM compounds are complex and numerous, and inhibiting the bitter taste of TCM has become a major clinical challenge. Here, we use ultra-high-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) and high-resolution mass spectrometry to identify 59 chemical components in the TCM compound RCTB formula. Next, four bitter taste receptors, TAS2R39, TAS2R14, TAS2R7, and TAS2R5, which are tightly bound to the compounds in RCTB, were screened as molecular docking receptors using the BitterX database. The top-three-scoring receptor-small-molecule complexes for each of the four receptors were selected for molecular dynamics simulation. Finally, seven bitter components were identified, namely six flavonoids (rhoifolin, naringin, poncirin, diosmin, didymin, and narirutin) and one phenylpropanoid (purpureaside C). Thus, we proposed a new method for identifying the bitter components in TCM compounds, which provides a theoretical reference for bitter taste inhibition in TCM compounds.

Peripheral immunity involvement in the cognitive impairment of sporadic amyotrophic lateral sclerosis.

Background: Recent research has indicated the significance of immune activation in amyotrophic lateral sclerosis (ALS). However, the impact of peripheral immunity on cognitive impairment in sporadic ALS remains poorly characterized. Therefore, we aim to assess the relationship between peripheral immune parameters and cognitive impairment in patients with sporadic ALS. Methods: A case-control study involving 289 patients with sporadic ALS was conducted. All participants underwent cognitive assessment and measurements of blood immune parameters. The main outcomes included adjusted odds ratios (ORs) in multivariate logistic regression analysis and adjusted coefficients in a multivariate linear regression model. Sensitivity analysis was performed with stratification by the King's clinical stage. Results: Cognitive impairment was observed in 98 (33.9%) patients. Higher counts of leukocyte (OR, 0.53; 95% CI, 0.29 to 0.95; p = 0.03), neutrophil (OR, 0.48; 95% CI, 0.26 to 0.88; p = 0.02), and monocyte (OR, 0.33; 95% CI, 0.18 to 0.60; p < 0.001) were significantly associated with better cognitive preformence in sporadic ALS, particularly among patients in King's clinical stages 1 and 2. Conversely, a higher percentage of CD4+ T cells was linked to an increased risk of cognitive impairment (OR, 2.79; 95% CI, 1.52 to 5.09; p = 0.001), particularly evident in patients in King's clinical stage 3. Conclusion: These results highlight the involvement of peripheral immunity in the cognitive impairment of sporadic ALS and suggest dynamic and intricate roles that vary across disease stages. Elucidating the links between immunity and ALS sheds light on the pathophysiological mechanisms underlying this fatal neurodegenerative disorder and informs potential immunotherapeutic strategies.

Amyotrophic lateral sclerosis patients with various gene mutations show diverse motor phenotypes and survival in China.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterised by progressive degeneration of motor neurons. Genetic factors have a substantial impact on ALS. Therefore, this study aimed to explore the correlation between genotype (SOD1, TARDBP, FUS, C9orf72) and phenotype in ALS. METHODS: Genetic analysis was performed on 2038 patients with ALS, among which 1696 patients with sporadic ALS (SALS) as controls for genotype-phenotype analysis, and 1602 SALS as controls for survival analysis. Logistic regression and Cox proportional hazards models were used for statistical analysis. RESULTS: A total of 172 patients with ALS with the gene mutations were included in the statistical analysis (SOD1, n=65; FUS, n=43; TARDBP, n=27; C9orf72, n=37). SOD1 mutations were more frequent in flail leg phenotype (OR 7.317, p=0.001) and less in bulbar phenotype (OR 0.222, p=0.038). C9orf72 expansions exhibited higher frequency in bulbar phenotype (OR 2.770, p=0.008). SOD1 and FUS mutations were significantly associated with earlier age of onset (HR 2.039, p<0.001; HR 1.762, p=0.001). The patients with SOD1 mutations, C9orf72 expansions and those carrying pathogenic FUS mutations had significantly increased death risk (HR 2.217, p<0.001; HR 1.694, p=0.008; HR 1.652, p=0.036). The increased risk of death in ALS with C9orf72 expansions was significant in females (HR 2.419, p=0.014) but not in males (HR 1.442, p=0.128). CONCLUSION: Our study revealed distinct motor phenotypic tendencies in patients with ALS with different genotypes, indicating variations in the vulnerability of motor neurons during the disease's progression. Furthermore, we made novel discoveries regarding survival of different gene mutations, warranting further investigation.

Clinical and genetic characteristics of ALS patients with variants in genes regulating DNA methylation.

BACKGROUND: Aberrant DNA methylation alterations are implicated in amyotrophic lateral sclerosis (ALS). Nevertheless, the influence of genetic variants in genes regulating DNA methylation on ALS patients is not well understood. Therefore, we aim to provide a comprehensive variant profile of genes related to DNA methylation (DNMT1, DNMT3A, DNMT3B, DNMT3L) and demethylation (TET1, TET2, TET3, TDG) and to investigate the association of these variants with ALS. METHODS: Variants were screened in a cohort of 2240 ALS patients from Southwest China, using controls from the Genome Aggregation Database (n = 9976) and the China Metabolic Analytics Project (n = 10,588). The over-representation of rare variants and their association with ALS risk were evaluated using Fisher's exact test with Bonferroni correction at both allele and gene levels. Kaplan-Meier analysis and Cox regression analysis were employed to explore the relationship between variants and survival. RESULTS: A total of 210 variants meeting the criteria were identified. Gene-based burden analysis identified a significant increase in ALS risk associated with rare variants in the TET2 gene (OR = 1.95, 95% CI = 1.29-2.88, P = 0.001). Survival analysis demonstrated that patients carrying variants in demethylation-related genes had a higher risk of death compared to those with methylation-related gene variants (HR = 1.29, 95% CI = 1.03-1.86, P = 0.039). CONCLUSIONS: This study provides a genetic variant profile of genes involved in DNA methylation and demethylation regulation, along with the clinical characteristics of ALS patients carrying these variants. The findings offer genetic evidence implicating disrupted DNA methylation dynamics in ALS.

Enhancing the health benefits of air quality improvement: a comparative study across diverse scenarios.

In many studies, linear methods were used to calculate health benefits of air quality improvement, but the relationship between air pollutants and diseases may be complex and nonlinear. In addition, previous studies using reference number as average number of diseases may overestimate the health benefits. Therefore, the nonlinear model estimation and resetting of the reference number were very important. Hospital admission data for coronary heart disease (CHD), meteorological data, and air pollutant data of Zibo City from 2015 to 2019 were collected. The generalized additive model (GAM) was used to explore the association between air pollutants and hospital admission for CHD, and to evaluate the effects on health benefits under different reference number settings. A total of 21,105 hospitalized cases for CHD were reported in Zibo during the study period. The results of the GAM showed there was a log-linear exposure-response relationship between O3 and hospital admissions for CHD, with RR (relative risk) of 1.0143 (95% CI: 1.0047 ~ 1.0239). There were log-nonlinear exposure-response relationships between PM10, PM2.5, SO2, and hospital admissions for CHD. With the increase of pollutants concentrations, the risk for hospital admission showed a trend of increasing first and then decreasing. Compared with the average hospital admissions as the reference number, health benefits calculated by hospital admissions predicted by the GAM model yielded lower. Using the World Health Organization air quality guidelines as reference, attributable fractions of O3, PM10, and PM2.5 were 1.97% (95% CI: 0.63 ~ 3.40%), 11.82% (95% CI: 8.60 ~ 15.24%), and 11.82% (95% CI: 8.79 ~ 15.04%), respectively. When quantifying health benefits brought by improving air quality, corresponding calculation methods should first be determined according to the exposure-response relationships between air pollutants and outcomes. Then, applying the average hospital admissions as reference number may overestimate health benefits resulting from improved air quality.

GWAS Identifies DPP6 as Risk Gene of Cognitive Decline in Parkinson's Disease.

BACKGROUND: Cognitive decline is among the most common non-motor symptoms in Parkinson's disease (PD), while its physiological mechanisms remain poorly understood. Genetic factors constituted a fundamental determinant in the heterogeneity of cognitive decline among PD patients. However, the underlying genetic background was still less studied. METHODS: To explore the genetic determinants contributing to cognitive decline in PD, we performed genome-wide survival analysis using a Cox proportional hazards model in a longitudinal cohort of 450 Chinese patients with PD, and further explored the functional effect of the target variant. Additionally, we built a clinical-genetic model by incorporating clinical characteristics and polygenic risk score (PRS) to predict cognitive decline in PD. RESULTS: The cohort was followed up for an average of 5.25 (SE = 2.46) years, with 95 incidents of cognitive impairment. We identified significant association between locus rs75819919 (DPP6) and accelerated cognitive decline (p = 8.63E-09, beta = 1.74, SE = 0.30). Dual-luciferase reporter assay suggested this locus might be involved in the regulation of DPP6 expression. Using data set from the UK Biobank, we identified rs75819919 was associated with cognitive performance in the general population. Incorporation of PRS increased the model's predictability, achieving an average AUC of 75.6% through fivefold cross-validation in 1 000 iterations. CONCLUSIONS: These findings improve the current understanding of the genetic etiology of cognitive impairment in PD, and provide a novel target DPP6 to explore therapeutic options. Our results also demonstrate the potential to develop clinical-genetic model to identify patients susceptible to cognitive impairment and thus provide personalized clinical guidance.

Herb induced liver injury by Xianling Gubao Tablets: A case assessed for causality using updated RUCAM and integrated evidence chain.

Objective: A typical case of Xianling Gubao (XLGB) Tablets-induced liver injury was systematically studied in the clinic and the laboratory. Methods: A patient with herb-induced liver injury (HILI) and a history of taking XLGB Tablets before disease onset was engaged as the study subject, and the case was diagnosed according to the updated Roussel Uclaf Causality Assessment Method (RUCAM) and the integrated evidence chain (iEC) method recommended by the Guidelines for Diagnosis and Treatment of Herb-induced Liver Injury (HILI Guidelines). Results: Clinical history, biochemical indexes and imaging tests were used to exclude the influence of fundamental diseases and confusing liver diseases such as viral, alcoholic and autoimmune liver diseases on the diagnosis. Based on an investigation of the patient's medication history, she was suspected to have HILI caused by XLGB Tablets, as the patient was only taking an oral preparation of XLGB Tablets, and the influence of other drugs on the diagnosis was excluded. This patient with alanine aminotransferase (ALT) ≥ 3 × upper limit of normal (ULN) and a calculated R of 6 was diagnosed with possible acute drug-induced hepatocellular injury. The relationship was considered "highly probable" (score of 9) using the updated RUCAM of 2016. Moreover, the fingerprint similarity between the preparation taken by the patient and a commercially available preparation was 0.99, suggesting that the patient was consuming XLGB Tablets rather than another drug. LC-MS technology and the Agilent Fake TCM-Drugs database were used to investigate the drug, and no chemical additions were found. Examination of the drug for pesticide residues, heavy metals, aflatoxins and other exogenous substances indicated compliance with the content limits of the Chinese Pharmacopoeia. Conclusion: In summary, the final diagnosis of XLGB-induced liver injury reached the clinical diagnosis of HILI and was acute severe hepatocellular injury type by the updated RUCAM and iEC. Therefore, this study provides scientific evidence regarding the causality evaluation of compound preparations of traditional Chinese medicines-induced liver injury.

Calcium channel blockers and Parkinson's disease: a systematic review and meta-analysis.

Background: The calcium channel has been considered to have great potential as a drug target for neuroprotective therapy in Parkinson's disease (PD), but previous studies yielded inconsistent results. Objectives: This study aimed to conduct a systematic review and meta-analysis to assess the relationship between using calcium channel blockers (CCBs) and the risk and progression of PD. Data sources and methods: The terms such as 'Parkinson's disease', 'PD', 'calcium channel blockers', and 'CCB' were used to search the literature published before 1 May 2023 in English databases, including PubMed, Embase, and Cochrane Library, for studies on CCB and PD. Data analysis was performed using Review Manager 5.3 software. Results: A total of 190 works of literature were preliminarily retrieved, and 177 works of literature were excluded by eliminating duplicates, reading abstracts, and reading full texts. A total of nine studies were finally included in the meta-analysis of the CCB and the risk of PD, and five studies were included in the systematic review of the CCB and the progression of PD. A total of 2,961,695 participants were included in the meta-analysis. The random-effects model was used for analysis due to significant heterogeneity. The main results of the meta-analysis showed that the use of CCB could reduce the risk of PD (relative risk 0.78, 95% confidence interval 0.62-0.99). Conclusion: CCB use was associated with a significantly reduced risk of PD. Whether CCB use has a disease-modifying effect on PD needs further study. Registration: PROSPERO: CRD42024508242.

The impact of maternal smoking during pregnancy and the age of smoking initiation on incident dementia: A prospective cohort study.

INTRODUCTION: The impact of early-life tobacco exposure on dementia has remained unknown. METHODS: Using the UK Biobank, the associations of maternal smoking during pregnancy (MSDP) and age of smoking initiation (ASI) with the onset time of all-cause dementia were estimated with accelerated failure time models. The effects of MSDP and ASI on brain structure and their genetic correlation to Alzheimer's disease (AD) were analyzed. A Mendelian randomization (MR) analysis was conducted. RESULTS: The time ratios for smokers starting in childhood, adolescence, and adulthood (vs never smokers) were 0.87 (0.76 to 0.99), 0.92 (0.88 to 0.96), and 0.95 (0.89 to 1.01). MSDP and smoking in adolescence altered many brain regions, including the hippocampus. In genetic analysis, MSDP was genetically and causally linked to AD, and a younger ASI was genetically correlated to a higher AD risk. DISCUSSION: Early-life smoking accelerated dementia onset and was genetically correlated to AD. MSDP demonstrated genetic and causal linkage to AD risks. HIGHLIGHTS: Unlike the commonly used Cox proportional hazards model, this article uses a parametric survival analysis method - the accelerated failure model - to explore the relationship between exposure to onset time. It can be used as an alternative method when the proportional hazards assumption is not met. Genetic analyses including genetic correlation study and MR analysis and brain structure analyses were conducted to support our findings and explore the potential mechanisms. The study reveals the relationship between different smoking initiation periods and the onset time of dementia and shows that earlier smoking exposure has a more significant impact on dementia. It emphasizes the importance of preventing early smoking. In the future, more research focusing on the relationship between early exposure and dementia is called for to provide more detailed prevention measures for dementia that cover all age groups.

Research on regenerative braking control of electric vehicles based on game theory optimization.

The energy-efficient, clean, and quiet attributes of electric vehicles offer solutions to conventional challenges related to resource scarcity and environmental pollution. Consequently, thorough research into harmonizing energy recuperation during braking, enhancing vehicle stability, and ensuring occupant comfort in electric vehicles is imperative for their effective advancement. The study introduces a regenerative braking control strategy for electric vehicles founded on game theory optimization to enhance braking performance and optimize braking energy utilization. Develop a regenerative braking control approach based on the dynamic model of an electric vehicle equipped with hub motors. Employing game theory, we establish participants, control variables, strategy sets, benefit functions, and constraints to optimize the coefficient K for regenerative braking. The efficacy and superiority of the control strategy model are validated through joint simulations using Matlab/Simulink and AVL Cruise. Research findings indicate: (1) Speed tracking error remains below 3% in both NEDC and CLTC-P simulations, underscoring the effectiveness of the dynamic model and control strategy devised in this study. (2) The energy recovery rate achieved by the game theory-based optimization strategy surpasses that of the Cruise self-contained strategy and fuzzy control strategy by 18.06% and 4.5% in the NEDC simulation, and by 13.48% and 3.85% in the CLTC-P simulation, respectively. The adhesion coefficient curves implemented on the front and rear axles, derived from the game theory optimization control strategy, closely approximate the ideal adhesion coefficient curve, leading to a substantial enhancement in the car's braking stability. The degree of jerk magnitude regulated by the game theory optimization strategy consistently falls within the ±3 m/s³ threshold, resulting in a considerable enhancement in the comfort of vehicle occupants. These outcomes underscore the efficacy of the game theory-based optimized control strategy in enhancing energy recovery, braking stability, and comfort throughout the braking process of the vehicle.

Follicular fluid exosome-derived miR-339-5p enhances in vitro maturation of porcine oocytes via targeting SFPQ, a regulator of the ERK1/2 pathway.

In this study, we aimed to investigate cytoplasmic maturation and miRNA expression of mature oocytes cultured in porcine follicular fluid exosomes. We also examined the effect of miR-339-5p on oocyte maturation. Twenty eight differentially expressed miRNAs were detected using miRNA-seq. We then transfected cumulus oocyte complexes with miR-339-5p mimics and inhibitor during culture. The results showed that exosomes increased endoplasmic reticulum levels and the amount of lipid droplets, and decreased ROS levels, lipid droplet size, and percentage of oocytes with abnormal cortical granule distribution. Overexpressing miR-339-5p significantly decreased cumulus expansion genes, oocyte maturation-related genes, target gene proline/glutamine-rich splicing factor (SFPQ), ERK1/2 phosphorylation levels, oocyte maturation rate, blastocyst rate, and lipid droplet number, but increased lipid droplet size and the ratio of oocytes with abnormal cortical granule distribution. Inhibiting miR-339-5p reversed the decrease observed during overexpression. Mitochondrial membrane potential and ROS levels did not differ significantly between groups. In summary, exosomes promote oocyte cytoplasmic maturation and miR-339-5p regulating ERK1/2 activity through SFPQ expression, thereby elevating oocyte maturation and blastocyst formation rate in vitro.