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1.
Chemosphere ; : 143443, 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39368498

RESUMO

Landfills are struggling to accommodate the increasing amounts of carbon soot ash waste from oil refineries. Due to extensive industrial productions, large quantities of lead ions are released into the environment, which not only pollutes the environment but also affects flora and fauna. In this work, these urgent environmental issues will be tackled by studying the use of modified carbon soot ash for specific heavy metal adsorption. Carbon soot ash modified with chemical leaching and physical ball-milling was loaded onto the surface of graphene oxide. This adsorbent was found to selectively adsorb and remove toxic lead ions (>99%) from a mixed heavy metal solution. The adsorption efficiency was found to increase with temperature (20-60 °C) and pH (2-8). Langmuir isotherm and pseudo-second order kinetics were found to fit the adsorption process through curve fitting, where the adsorbent reached a maximum capacity of 194.55 mg/g. Potential mechanisms for lead adsorption and metal specificity are also discussed here. This work aligns with the waste-to-resource pathway, where waste carbon soot ash is diverted from landfilling and is formulated as a specific heavy metal adsorbent, that shows promise for environmental remediation.

2.
Neurol Sci ; 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39271636

RESUMO

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder marked by the degeneration of motor neurons and progressive muscle weakness. Heredity plays an important part in the pathogenesis of ALS. Recently, with the emergence of the oligogenic pathogenic mechanism in ALS and the ongoing discovery of new mutated genes and genomic variants, there is an emerging need for larger-scale and more comprehensive genetic screenings in higher resolution. In this study, we performed whole-genome sequencing (WGS) on 34 familial ALS probands lacking the most common disease-causing mutations to explore the genetic landscape of Chinese ALS patients further. Among them, we identified a novel ARPP21 c.1231G > A (p.Glu411Lys) variant and two copy number variations (CNVs) affecting the PFN1 and RBCK1 genes in a patient with ALS-frontotemporal dementia (FTD). This marks the first report of an ARPP21 variant in Chinese ALS-FTD patients, providing fresh evidence for the association between ARPP21 and ALS. Our findings also underscore the potential role of CNVs in ALS-FTD, suggesting that the cumulative effect of multiple rare variants may contribute to disease onset. Furthermore, compared to the averages in our cohort and the reported Chinese ALS population, this patient displayed a shorter survival time and more rapid disease progression, suggesting the possibility of an oligogenic mechanism in disease pathogenesis. Further research will contribute to a deeper understanding of the rare mutations and their interactions, thus advancing our understanding of the genetic mechanisms underlying ALS and ALS-FTD.

3.
BMC Public Health ; 24(1): 2539, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39294669

RESUMO

BACKGROUND: Body roundness index (BRI) is an anthropometric measure related to obesity, combining waist circumference (WC) and height to more accurately reflect body fat. This study aims to investigate the relationship between BRI and the risk of hypertension using data from a prospective cohort study in Southwest China. METHODS: Data for the study were derived from Guizhou Population Health Cohort Study (GPHCS), established in 2010. A total of 9,280 participants (aged 18 to 95 years, mean 41.53 ± 14.15 years) from 48 townships across 12 districts/counties were surveyed at baseline through multistage stratified random cluster sampling. Cox proportional risk models were employed to analyze the association between BRI and the risk of hypertension, estimating hazard ratios (HRs) and 95% confidence intervals (CIs) after adjusting for confounding factors. The relationship between BRI and the onset time of hypertension was analyzed using the time failure acceleration model. RESULTS: Over a median follow-up period of 6.64 years, 1,157 participants were diagnosed with hypertension. After adjusting for confounding variables, each unit increase in BRI was associated with a 17% increase in hypertension risk (HR = 1.17, 95% CI: 1.11, 1.24, P for trend < 0.001). Compared to participants in the first quartile (Q1) of BRI, the risk of hypertension for those in the third quartile (Q3) and fourth quartile (Q4) was 1.31 (95% CI: 1.10, 1.56) and 1.53 (95% CI: 1.28, 1.84), respectively. Each unit increase in BRI advanced the onset of hypertension by 0.26 years (95% CI: 0.16, 0.35). CONCLUSION: This study indicates that BRI has a positive association with hypertension and can accelerate the onset of hypertension in the Chinese population. It is suggested that reducing BRI by controlling abdominal fat may be one of the effective measure to prevent hypertension.


Assuntos
Hipertensão , Humanos , Hipertensão/epidemiologia , Pessoa de Meia-Idade , China/epidemiologia , Masculino , Feminino , Adulto , Estudos Prospectivos , Idoso , Adolescente , Adulto Jovem , Idoso de 80 Anos ou mais , Fatores de Risco , Circunferência da Cintura , Medição de Risco , Estatura , Modelos de Riscos Proporcionais , Obesidade/epidemiologia
4.
Environ Res ; 261: 119695, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39102936

RESUMO

Available evidence suggests that air pollutants can cause stroke, but little research has investigated the confounding effects of urban-rural differences. Here, we investigated the urban-rural difference in the correlation between particulate matter (PM2.5 and PM10) exposure and stroke. This cohort study was based on a prospective multi-city community-based cohort (Guizhou Population Health Cohort Study (GPHCS)) in Guizhou Province, China. A total of 7988 eligible individuals (≥18 years) were enrolled with baseline assessments from November 2010 to December 2012, and follow-up was completed by June 2020. Two major particulate matters (PMs, including PM2.5 and PM10) were assessed monthly from 2000 by using satellite-based spatiotemporal models. The risk of stroke was estimated using a Cox proportional hazard regression model. The association between particulate matters' exposure and stroke in different areas (total, urban, and rural) and the potential modification effect of comorbidities (hypertension, diabetes, and dyslipidemia) and age (≤65/>65 years) were examined using stratified analyses. The risk of stroke increased for every 10 µg/m3 increase in mean PMs' concentrations during the previous 1 year at the residential address (HR: 1.26, 95%CI: 1.24, 1.29 (PM2.5); HR: 1.13, 95%CI: 1.11, 1.15 (PM10)). The presence of diabetes and dyslipidemia increased the risk of PM10-induced stroke in whole, urban, and rural areas. Specifically, people living in rural areas were more likely to experience the effects of PMs in causing a stroke. The risk of stroke due to PMs was statistically increased in the young and older populations living in rural areas. In conclusion, long-term exposure to PMs increased the risk of stroke and such association was more pronounced in people living in rural areas with lower income levels. Diabetes and dyslipidemia seemed to strengthen the association between PMs and stroke.


Assuntos
Poluentes Atmosféricos , Material Particulado , População Rural , Acidente Vascular Cerebral , Humanos , Material Particulado/análise , Pessoa de Meia-Idade , Masculino , Feminino , Acidente Vascular Cerebral/epidemiologia , China/epidemiologia , Idoso , Poluentes Atmosféricos/análise , Incidência , População Rural/estatística & dados numéricos , Adulto , Exposição Ambiental , Estudos Prospectivos , População Urbana/estatística & dados numéricos , Cidades/epidemiologia , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Estudos de Coortes
5.
Artigo em Inglês | MEDLINE | ID: mdl-39017714

RESUMO

Benign prostatic hyperplasia (BPH) is a prevalent urological condition that predominantly affects the geriatric male population, resulting in lower urinary tract symptoms. Saw palmetto is a traditional Chinese medicine for treating BPH. This study aimed to investigate the potential therapeutic mechanisms of saw palmetto in BPH treatment. The active ingredients and potential targets of saw palmetto were obtained through the TCMSP database. BPH-related targets were retrieved from the GeneCards database. PPI, GO, and KEEG analyses were performed to predict the potential therapeutic mechanism. The active ingredient-common target and common target-pathway networks were constructed by Cytoscape software. Molecular docking and cellular experiments were carried out to further validate the potential mechanism. We obtained 13 active components in saw palmetto and 56 common targets in BPH treatment. KEEG analysis showed that the estrogen signaling pathway was the most enriched and exhibited a close association with BPH. PPI analysis, along with ingredient-target and target-pathway network analyses, indicated that stigmasterol was the core ingredient and PGR, NCOA1, and NCOA2 were identified as the hub genes mediating the effects of saw palmetto against BPH. In addition, molecular docking showed that stigmasterol had strong binding to PGR, NCOA1, and NCOA2. Cellular experiments revealed that stigmasterol significantly increased the percentage of BPH-1 cells in the G0/G1 phase and inhibited cell viability and division. Furthermore, it notably reduced the expression of PGR, NCOA1, and NCOA2. Saw palmetto might inhibit cell viability and division by suppressing the expression of PGR, NCOA1, and NCOA2, thereby playing a therapeutic role in treating BPH.

6.
Int J Mol Sci ; 25(13)2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-39000042

RESUMO

Recent studies have hinted at a potential link between Alzheimer's Disease (AD) and cancer. Thus, our study focused on finding genes common to AD and Liver Hepatocellular Carcinoma (LIHC), assessing their promise as diagnostic indicators and guiding future treatment approaches for both conditions. Our research utilized a broad methodology, including differential gene expression analysis, Weighted Gene Co-expression Network Analysis (WGCNA), gene enrichment analysis, Receiver Operating Characteristic (ROC) curves, and Kaplan-Meier plots, supplemented with immunohistochemistry data from the Human Protein Atlas (HPA) and machine learning techniques, to identify critical genes and significant pathways shared between AD and LIHC. Through differential gene expression analysis, WGCNA, and machine learning methods, we identified nine key genes associated with AD, which served as entry points for LIHC analysis. Subsequent analyses revealed IKBKE and HSPA1A as shared pivotal genes in patients with AD and LIHC, suggesting these genes as potential targets for intervention in both conditions. Our study indicates that IKBKE and HSPA1A could influence the onset and progression of AD and LIHC by modulating the infiltration levels of immune cells. This lays a foundation for future research into targeted therapies based on their shared mechanisms.


Assuntos
Doença de Alzheimer , Carcinoma Hepatocelular , Biologia Computacional , Proteínas de Choque Térmico HSP70 , Neoplasias Hepáticas , Humanos , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Aprendizado de Máquina
7.
Front Endocrinol (Lausanne) ; 15: 1399859, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39036053

RESUMO

Background: Metabolic syndrome(MetS) and depression are independently associated with type 2 diabetes (T2DM) risk. However, little is known about the combined effect of MetS and depression on the risk of T2DM. The present study aims to prospectively explore the impact of MetS and depression on T2DM susceptibility among the Chinese general population. Methods: 6489 general population without T2DM adults in Southwest China were recruited from 2010 to 2012. Depression and MetS were prospectively assessed using a 9-item Patient Health Questionnaire(PHQ-9) and Guideline for the prevention and treatment of type 2 diabetes mellitus in China (2020 edition) (CDS2020) during 2016-2020, respectively. Modified Poisson regression models were conducted to estimate relative risk(RR) and 95% confidence intervals (95%CI) for independent and combined associations of MetS and depression with an incidence of T2DM. Results: During a median follow-up of 6.6 years, 678 cases of T2DM were documented. Individuals with MetS were 1.33 times more likely to develop T2DM than those without MetS. The corresponding RR(95%CI) for depression with no depression was 1.45(1.22-1.72). Notably, compared with no MetS or depression, the multivariate-adjusted RR for a combined effect of MetS and depression on the risk of T2DM was 2.11(1.39-3.22). Moreover, an increased risk of T2DM was more apparent in those ≥ 60 years, males, and overweight. Conclusions: Individuals with multimorbidity of MetS and depression are at a higher risk of T2DM compared with those with no MetS or depression.


Assuntos
Depressão , Diabetes Mellitus Tipo 2 , Síndrome Metabólica , Multimorbidade , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/complicações , Masculino , Feminino , China/epidemiologia , Pessoa de Meia-Idade , Depressão/epidemiologia , Adulto , Estudos de Coortes , Idoso , Estudos Prospectivos , Fatores de Risco , Incidência , Seguimentos
8.
Am J Clin Exp Immunol ; 13(3): 68-87, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39022791

RESUMO

BACKGROUND: Whole-body vibration (WBV) is a commonly used physical exercise for disease prevention and rehabilitation. Recent studies indicated the beneficial mechanism of WBV may be associated with its anti-inflammatory potential, however, its regulatory roles on different inflammatory mediators remained controversial. The aim of this study was to perform a meta-analysis to re-confirm the effects of WBV exercise on various inflammatory factors. METHODS: The PubMed, EMBASE and Cochrane Library databases were searched up to September 2023 to collect all articles comparing WBV with control (or post-pre trials). The effect size was expressed as the standardized mean difference (SMD) and 95% confidence intervals (CI). RESULTS: A total of 31 eligible studies were included, including 14 pre-clinical and 17 clinical studies. The meta-analysis of pre-clinical studies showed that compared with the control group, WBV exercise could significantly reduce the level of IL-6 (SMD: -1.03, 95% CI: -1.93, -0.13), TNF-α (SMD: -1.36, 95% CI: -2.54, -0.17) (for disease subgroup), IL-1ß (SMD: -2.20, 95% CI: -3.24, -1.15), IFN-γ (SMD: -1.91, 95% CI: -2.71, -1.12), IL-4 (SMD: -0.71, 95% CI: -1.39, -0.03) and IL-17 (SMD: -1.32, 95% CI: -2.05, -0.59) overall. Pooling of clinical studies revealed WBV exercise significantly reduced the level of TNF-α (WBV vs control: SMD: -1.11, 95% CI: -2.16, -0.06; post vs pre: SMD: -1.29, 95% CI: -1.91, -0.67), CRP (SMD: -3.59, 95% CI: -6.36, -0.82, P = 0.011) and enhanced the level of IL-10 (WBV vs control: SMD: 2.90, 95% CI: 1.10, 4.71; post vs pre: SMD: 1.75, 95% CI: 0.64, 2.87) and IL-6 (SMD: 0.91, 95% CI: 0.31, 1.52) (healthy subgroup). CONCLUSION: WBV may be an effective prevention and rehabilitation tool for inflammatory diseases.

9.
Small ; : e2404984, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39031101

RESUMO

The instability to moisture, heat, and ultraviolet (UV) light is the main problem in the application of quantum dot solar cells (QDSCs). Thin film encapsulation can effectively improve their operational stability. However, it is difficult to achieve multiple barrier effects with single layer of encapsulated film. Here, a hybrid thin-film encapsulation strategy is reported to encapsulate lead sulfide QDSCs, which can isolate moisture and partial thermal, and prevent the penetration of UV light, thus retarding the surface oxidation process of the quantum dots. After 60 h, the encapsulated device retains a normalized power conversion efficiency of 83.8% and 80.6% at 85% humidity and 75 °C, respectively, which is three and six times of the value obtained in unencapsulated devices. At continuous UV illumination, encapsulated device exhibits five times higher stability than the reference. This strategy provides the way for the overall improvement of the operating stability of lead sulfide QDSCs in harsh environments of high humidity, high temperature, and UV light.

10.
Artigo em Inglês | MEDLINE | ID: mdl-39054009

RESUMO

The human in vitro organotypic air-liquid-interface (ALI) airway tissue model is structurally and functionally similar to the human large airway epithelium and, as a result, is being used increasingly for studying the toxicity of inhaled substances. Our previous research demonstrated that DNA damage and mutagenesis can be detected in human airway tissue models under conditions used to assess general and respiratory toxicity endpoints. Expanding upon our previous proof-of-principle study, human airway epithelial tissue models were treated with 6.25-100 µg/mL ethyl methanesulfonate (EMS) for 28 days, followed by a 28-day recovery period. Mutagenesis was evaluated by Duplex Sequencing (DS), and clonal expansion of bronchial-cancer-specific cancer-driver mutations (CDMs) was investigated by CarcSeq to determine if both mutation-based endpoints can be assessed in the same system. Additionally, DNA damage and tissue-specific responses were analyzed during the treatment and following the recovery period. EMS exposure led to time-dependent increases in mutagenesis over the 28-day treatment period, without expansion of clones containing CDMs; the mutation frequencies remained elevated following the recovery. EMS also produced an increase in DNA damage measured by the CometChip and MultiFlow assays and the elevated levels of DNA damage were reduced (but not eliminated) following the recovery period. Cytotoxicity and most tissue-function changes induced by EMS treatment recovered to control levels, the exception being reduced proliferating cell frequency. Our results indicate that general, respiratory-tissue-specific and genotoxicity endpoints increased with repeat EMS dosing; expansion of CDM clones, however, was not detected using this repeat treatment protocol. DISCLAIMER: This article reflects the views of its authors and does not necessarily reflect those of the U.S. Food and Drug Administration. Any mention of commercial products is for clarification only and is not intended as approval, endorsement, or recommendation.


Assuntos
Dano ao DNA , Metanossulfonato de Etila , Mutação , Humanos , Metanossulfonato de Etila/farmacologia , Metanossulfonato de Etila/toxicidade , Mutação/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Mutagênese/efeitos dos fármacos , Mutagênicos/toxicidade , Brônquios/efeitos dos fármacos , Brônquios/citologia
11.
Chem Soc Rev ; 53(15): 7784-7827, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-38953906

RESUMO

High-quality transparent electrodes are indispensable components of flexible optoelectronic devices as they guarantee sufficient light transparency and electrical conductivity. Compared to commercial indium tin oxide, metal nanowires are considered ideal candidates as flexible transparent electrodes (FTEs) owing to their superior optoelectronic properties, excellent mechanical flexibility, solution treatability, and higher compatibility with semiconductors. However, certain key challenges associated with material preparation and device fabrication remain for the practical application of metal nanowire-based electrodes. In this review, we discuss state-of-the-art solution-processed metal nanowire-based FTEs and their applications in flexible and stretchable optoelectronic devices. Specifically, the important properties of FTEs and a cost-benefit analysis of existing technologies are introduced, followed by a summary of the synthesis strategy, key properties, and fabrication technologies of the nanowires. Subsequently, we explore the applications of metal-nanowire-based FTEs in different optoelectronic devices including solar cells, photodetectors, and light-emitting diodes. Finally, the current status, future challenges, and emerging strategies in this field are presented.

12.
Mayo Clin Proc ; 99(10): 1589-1605, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39001774

RESUMO

OBJECTIVE: To investigate the causal effect of protein intake on hypertension and the related mediating pathways. PATIENTS AND METHODS: Using genome-wide association study summary statistics of European ancestry, we applied univariable and multivariable Mendelian randomization to estimate the bidirectional associations of relative protein intake and related metabolomic signatures with hypertension (FinnGen: Ncase=42,857/Ncontrol=162,837; UK Biobank: Ncase=77,723/Ncontrol=330,366) and blood pressure (International Consortium of Blood Pressure: N=757,601) and two-step Mendelian randomization to assess the mediating roles of 40 cardiometabolic factors therein. Mendelian randomization estimates of hypertension from FinnGen and UK Biobank were meta-analyzed without heterogeneity. We performed the study from May 15, 2023, to September 15, 2023. RESULTS: Each 1-SD higher relative protein intake was causally associated with 69% (odds ratio, 0.31; 95% CI, 0.11 to 0.89) lower hypertension risk independent of the effects of other macronutrients, and was the only macronutrient associated with 2.21 (95% CI, 0.52 to 3.91) mm Hg lower pulse pressure, in a unidirectional manner. Higher plant protein-related metabolomic signature (glycine) was associated with lower hypertension risk and pulse pressure, whereas higher animal protein-related metabolomic signatures (leucine, isoleucine, valine, and isovalerylcarnitine [only systolic blood pressure]) were associated with higher hypertension risk, pulse pressure, and systolic blood pressure. The effect of relative protein intake on hypertension was causally mediated by frailty index (mediation proportion, 40.28%), monounsaturated fatty acids (13.81%), saturated fatty acids (11.39%), grip strength (5.34%), standing height (3.99%), and sitting height (3.61%). CONCLUSION: Higher relative protein intake causally reduces the risk of hypertension, partly mediated by physical fitness and circulating fatty acids.


Assuntos
Proteínas Alimentares , Ácidos Graxos , Estudo de Associação Genômica Ampla , Hipertensão , Análise da Randomização Mendeliana , Aptidão Física , Humanos , Hipertensão/epidemiologia , Hipertensão/sangue , Hipertensão/genética , Proteínas Alimentares/administração & dosagem , Ácidos Graxos/sangue , Aptidão Física/fisiologia , Masculino , Feminino , Pressão Sanguínea/fisiologia , Pessoa de Meia-Idade
13.
Nat Hum Behav ; 8(9): 1798-1809, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38886532

RESUMO

Mental well-being relates to multitudinous lifestyle behaviours and morbidities and underpins healthy aging. Thus far, causal evidence on whether and in what pattern mental well-being impacts healthy aging and the underlying mediating pathways is unknown. Applying genetic instruments of the well-being spectrum and its four dimensions including life satisfaction, positive affect, neuroticism and depressive symptoms (n = 80,852 to 2,370,390), we performed two-sample Mendelian randomization analyses to estimate the causal effect of mental well-being on the genetically independent phenotype of aging (aging-GIP), a robust and representative aging phenotype, and its components including resilience, self-rated health, healthspan, parental lifespan and longevity (n = 36,745 to 1,012,240). Analyses were adjusted for income, education and occupation. All the data were from the largest available genome-wide association studies in populations of European descent. Better mental well-being spectrum (each one Z-score higher) was causally associated with a higher aging-GIP (ß [95% confidence interval (CI)] in different models ranging from 1.00 [0.82-1.18] to 1.07 [0.91-1.24] standard deviations (s.d.)) independent of socioeconomic indicators. Similar association patterns were seen for resilience (ß [95% CI] ranging from 0.97 [0.82-1.12] to 1.04 [0.91-1.17] s.d.), self-rated health (0.61 [0.43-0.79] to 0.76 [0.59-0.93] points), healthspan (odds ratio [95% CI] ranging from 1.23 [1.02-1.48] to 1.35 [1.11-1.65]) and parental lifespan (1.77 [0.010-3.54] to 2.95 [1.13-4.76] years). Two-step Mendelian randomization mediation analyses identified 33 out of 106 candidates as mediators between the well-being spectrum and the aging-GIP: mainly lifestyles (for example, TV watching and smoking), behaviours (for example, medication use) and diseases (for example, heart failure, attention-deficit hyperactivity disorder, stroke, coronary atherosclerosis and ischaemic heart disease), each exhibiting a mediation proportion of >5%. These findings underscore the importance of mental well-being in promoting healthy aging and inform preventive targets for bridging aging disparities attributable to suboptimal mental health.


Assuntos
Estudo de Associação Genômica Ampla , Envelhecimento Saudável , Análise da Randomização Mendeliana , Saúde Mental , Humanos , Envelhecimento Saudável/genética , Envelhecimento Saudável/psicologia , Satisfação Pessoal , Feminino , Masculino , Longevidade/genética , Depressão/genética , Depressão/epidemiologia , Idoso , Fenótipo , Nível de Saúde , Resiliência Psicológica , Pessoa de Meia-Idade , Neuroticismo , Envelhecimento/genética , Envelhecimento/psicologia
14.
J Leukoc Biol ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38833584

RESUMO

As one molecule related to cytotoxicity, surface expression of C-X3-C motif receptor 1 (CX3CR1) was highly correlated with intracellular granzyme B (GZMB) in NK and cytolytic T cells. However, the expression of CX3CR1 and GZMB in B cells has not been clarified, and their clinical significance in systemic lupus erythematosus (SLE) remains unclear. This study aimed to clarify the changes and clinical significance of peripheral blood B cells expressing GZMB and/or CX3CR1 in SLE. Peripheral blood was collected from 39 SLE patients and 48 healthy controls. We found that GZMB and CX3CR1 expression varied in different B-cell subsets, with plasmablasts possessing the highest positive percentages, consistent with bioinformatics prediction. GZMB+ and CX3CR1+ percentages in circulating B cells and plasmablasts were increased in SLE patients. CX3CR1 was upregulated on B cells after in vitro stimulation. Notch intracellular domain (NICD) expression was significantly decreased in plasmablasts of SLE patients and CX3CR1 in plasmablasts was downregulated with the addition of JAG1. In conclusion, GZMB and CX3CR1 were increased in B cells and in plasmablasts of SLE patients and CX3CR1 was negatively regulated by Notch signal in plasmablasts, which may be involved in SLE pathogenesis.

15.
Genes (Basel) ; 15(6)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38927616

RESUMO

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by progressive damage to both upper and lower motor neurons. Genetic factors are known to play a crucial role in ALS, as genetic studies not only advance our comprehension of disease mechanisms but also help unravel the complex phenotypes exhibited by patients. To gain further insights into the genetic landscape of ALS in the Chinese population and explore genotype-phenotype correlations among individuals, we conducted whole-genome sequencing to screen genes in 34 Chinese familial ALS (FALS) probands lacking the most common ALS-associated genes. Within this cohort, we identified a rare heterozygous missense mutation in the N-terminal domain of KIF5A (c.86A>G) in one of the probands. This finding is significant as mutations in the KIF5A gene have been implicated in ALS in European cohorts since 2018, predominantly characterized by C-terminal mutations. Analysis of the clinical phenotype within this familial lineage revealed a delayed onset of symptoms, an extended survival duration, and initial manifestations in both upper limbs. These observations underscore the clinical heterogeneity observed in ALS patients harboring KIF5A mutations. In conclusion, our study contributes to the growing body of evidence linking KIF5A to ALS and enhances our understanding of the intricate genetic landscape of this disease.


Assuntos
Esclerose Lateral Amiotrófica , Cinesinas , Mutação de Sentido Incorreto , Sequenciamento Completo do Genoma , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/patologia , China , População do Leste Asiático/genética , Cinesinas/genética , Mutação , Linhagem , Fenótipo
16.
Ann Clin Transl Neurol ; 11(7): 1852-1867, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38775214

RESUMO

OBJECTIVE: The present study aimed to investigate the specific alterations of brain networks in patients with post-stroke depression (PSD), and further assist in elucidating the brain mechanisms underlying the PSD which would provide supporting evidence for early diagnosis and interventions for the disease. METHODS: Resting-state functional magnetic resonace imaging data were acquired from 82 nondepressed stroke patients (Stroke), 39 PSD patients, and 74 healthy controls (HC). Voxel-wise degree centrality (DC) conjoined with seed-based functional connectivity (FC) analyses were performed to investigate the PSD-related connectivity alterations. The relationship between these alterations and depression severity was further examined in PSD patients. RESULTS: Relative to both Stroke and HC groups, (1) PSD showed increased centrality in regions within the default mode network (DMN), including contralesional angular gyrus (ANG), posterior cingulate cortex (PCC), and hippocampus (HIP). DC values in contralesional ANG positively correlated with the Patient Health Questionnaire-9 (PHQ-9) scores in PSD group. (2) PSD exhibited increased connectivity between these three seeds showing altered DC and regions within the DMN: bilateral medial prefrontal cortex and middle temporal gyrus and ipsilesional superior parietal gyrus, and regions outside the DMN: bilateral calcarine, ipsilesional inferior occipital gyrus and contralesional lingual gyrus, while decreased connectivity between contralesional ANG and contralesional supramarginal gyrus. Moreover, these FC alterations could predict PHQ-9 scores in PSD group. INTERPRETATION: These findings highlight that PSD was related with increased functional connectivity strength in some areas within the DMN, which might be attribute to the specific alterations of connectivity between within DMN and outside DMN regions in PSD.


Assuntos
Depressão , Imageamento por Ressonância Magnética , Rede Nervosa , Acidente Vascular Cerebral , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/diagnóstico por imagem , Idoso , Depressão/fisiopatologia , Depressão/etiologia , Depressão/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Conectoma , Rede de Modo Padrão/fisiopatologia , Rede de Modo Padrão/diagnóstico por imagem , Adulto
17.
BMC Public Health ; 24(1): 1211, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38693482

RESUMO

PURPOSE: To investigate the correlation between socioeconomic status (SES) and the incidence of hypertension among adults aged 18 or above in southwest China. METHODS: A multistage proportional stratified cluster sampling method was employed to recruited 9280 adult residents from 12 counties in southwest China, with all participants in the cohort tracked from 2016 to 2020. The questionnaire survey gathered information on demographics, lifestyle habits, and household income. The physical exam recorded height, weight, and blood pressure. Biochemical tests measured cholesterol levels. The chi-square test was employed to assess the statistical differences among categorical variables, while the Cox proportional hazards regression model was applied to evaluate the association between socioeconomic status (SES) and the incidence of hypertension. RESULTS: The finally effective sample size for the cohort study was 3546 participants, after excluding 5734 people who met the exclusion criteria. Adults in the highest household income group had a significantly lower risk of hypertension compared to those in the lowest income group (HR = 0.636, 95% CI: 0.478-0.845). Besides, when compared to individuals in the illiterate population, the risk of hypertension among adults with elementary school, junior high school, senior high school and associate degree educational level decreased respectively by 34.4% (HR = 0.656, 95%CI: 0.533-0.807), 44.9% (HR = 0.551, 95%CI: 0.436-0.697), 44.9% (HR = 0.551, 95%CI: 0.405-0.750), 46.1% (HR = 0.539, 95%CI: 0. 340-0.854). After conducting a thorough analysis of socioeconomic status, compared with individuals with a score of 6 or less, the risk of hypertension in participants with scores of 8, 10, 11, 12, and greater than 12 decreased respectively by 23.9% (HR = 0.761, 95%CI: 0.598-0.969), 29.7% (HR = 0.703, 95%CI: 0.538-0.919), 34.0% (HR = 0.660, 95%CI: 0.492-0.885), 34.3% (HR = 0.657, 95%CI: 0.447-0.967), 43.9% (HR = 0.561, 95%CI: 0.409-0.769). CONCLUSION: The findings indicate a negative correlation between socioeconomic status and hypertension incidence among adults in southwest China, suggesting that individuals with higher socioeconomic status are less likely to develop hypertension.


Assuntos
Hipertensão , Classe Social , Humanos , China/epidemiologia , Hipertensão/epidemiologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Incidência , Estudos de Coortes , Adulto Jovem , Adolescente , Idoso , Fatores de Risco , Inquéritos e Questionários
18.
Front Endocrinol (Lausanne) ; 15: 1302387, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38562413

RESUMO

Objective: Visceral adipose tissue assessment holds significant importance in hypertension prevention. This study aimed to explore the association between the Metabolic Score for Visceral Fat (METS-VF), a new indicator based on laboratory and anthropometry measures, and hypertension risk and to further investigate the association between the METS-VF and the risk of hypertension in different ethnic groups. Methods: In this study, a total of 9,280 people from 48 townships in 12 districts (counties) of Guizhou Province were selected for the survey using a multistage cluster random sampling method, and 5,127 cases were finally included in the analysis after excluding those with missing relevant data, losing visits, dying at follow-up, those who suffered from hypertension at baseline, and those whose information on the outcome of hypertension was not clear. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) between METS-VF and incident hypertension, and an accelerated failure time (AFT) model was applied to analyze the association between METS-VF and the onset time of hypertension. Results: The total person-years (PYs) of the 5,127 subjects were 36,188.52 years, and the median follow-up time was 6.64 years. During follow-up, 1,127 patients were newly diagnosed with hypertension, and the incidence density was 31.14/1,000 PYs. After adjusting for multivariables, compared with the METS-VF first (Q1), the third (Q3) and fourth (Q4) groups of the METS-VF increased by 29.9% and 61.5%, respectively (HR = 1.299 [1.061, 1.590] and 1.615 [1.280, 2.036]). The risk of hypertension increased with higher METS-VF values (HR = 1.323 [1.167, 1.500], ptrend < 0.001). In the Han Chinese population, Q2 and Q3 increased the risk of hypertension (HR = 1.459 [1.111, 1.917], 1.999 [1.417, 2.718]), and the onset of hypertension was advanced by 0.653 (ß = -0.653 (-0.930, -0.375]) years for per 1 unit increase in METS-VF. However, these associations were not found in ethnic minorities. Conclusion: METS-VF was significantly positively associated with the risk of hypertension, and the association was different among ethnic groups.


Assuntos
Hipertensão , Síndrome Metabólica , Humanos , Gordura Intra-Abdominal , Síndrome Metabólica/epidemiologia , Etnicidade , Estudos Prospectivos , Hipertensão/complicações
19.
World J Gastroenterol ; 30(8): 901-918, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38516242

RESUMO

BACKGROUND: Metadherin (MTDH) is a key oncogene in most cancer types, including hepatocellular carcinoma (HCC). Notably, MTDH does not affect the stemness pheno-type or immune infiltration of HCC. AIM: To explore the role of MTDH on stemness and immune infiltration in HCC. METHODS: MTDH expression in HCC tissues was detected using TCGA and GEO databases. Immunohistochemistry was used to analyze the tissue samples. MTDH was stably knocked down or overexpressed by lentiviral transfection in the two HCC cell lines. The invasion and migration abilities of HCC cells were evaluated using Matrigel invasion and wound healing assays. Next, we obtained liver cancer stem cells from the spheroids by culturing them in a serum-free medium. Gene expression was determined by western blotting and quantitative reverse transcri-ption PCR. Flow cytometry, immunofluorescence, and tumor sphere formation assays were used to characterize stem-like cells. The effects of MTDH inhibition on tumor growth were evaluated in vivo. The correlation of MTDH with immune cells, immunomodulators, and chemokines was analyzed using ssGSEA and TISIDB databases. RESULTS: HCC tissues expressed higher levels of MTDH than normal liver tissues. High MTDH expression was associated with a poor prognosis. HCC cells overexpressing MTDH exhibited stronger invasion and migration abilities, exhibited a stem cell-like phenotype, and formed spheres; however, MTDH inhibition attenuated these effects. MTDH inhibition suppressed HCC progression and CD133 expression in vivo. MTDH was positively correlated with immature dendritic, T helper 2 cells, central memory CD8+ T, memory B, activated dendritic, natural killer (NK) T, NK, activated CD4+ T, and central memory CD4+ T cells. MTDH was negatively correlated with activated CD8+ T cells, eosinophils, activated B cells, monocytes, macrophages, and mast cells. A positive correlation was observed between the MTDH level and CXCL2 expression, whereas a negative correlation was observed between the MTDH level and CX3CL1 and CXCL12 expression. CONCLUSION: High levels of MTDH expression in patients with HCC are associated with poor prognosis, promoting tumor stemness, immune infiltration, and HCC progression.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Linfócitos T CD8-Positivos , Fatores de Transcrição/genética , Células-Tronco/patologia , Fenótipo , Linhagem Celular Tumoral , Proteínas de Membrana/genética , Proteínas de Ligação a RNA/genética
20.
Environ Sci Technol ; 58(13): 5832-5843, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38511412

RESUMO

Photosensitizer-mediated abiotic oxidation of Mn(II) can yield soluble reactive Mn(III) and solid Mn oxides. In eutrophic water systems, the ubiquitous algal extracellular organic matter (EOM) is a potential photosensitizer and may have a substantial impact on the oxidation of Mn(II). Herein, we focused on investigating the photochemical oxidation process from Mn(II) to solid Mn oxide driven by EOM. The results of irradiation experiments demonstrated that the generation of Mn(III) intermediate was crucial for the successful photo oxidization of Mn(II) to solid Mn oxide mediated by EOM. EOM can serve as both a photosensitizer and a ligand, facilitating the formation of the Mn(III)-EOM complex. The complex exhibited excellent efficiency in removing 17α-ethinylestradiol. Furthermore, the complex underwent decomposition as a result of reactions with reactive intermediates, forming a solid Mn oxide. The presence of nitrate can enhance the photochemical oxidation process, facilitating the conversion of Mn(II) to Mn(III) and then to solid Mn oxide. This study deepens our grasp of Mn(II) geochemical processes in eutrophic water and its impact on organic micropollutant fate.


Assuntos
Etinilestradiol , Óxidos , Óxidos/química , Fármacos Fotossensibilizantes , Compostos de Manganês/química , Oxirredução , Água/química
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