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1.
Article En | MEDLINE | ID: mdl-38887029

BACKGROUND: This study aimed to assess the association between outdoor activity and myopia among children and adolescents and investigate whether sleep time could mediate this relationship. METHODS: This cross-sectional study was performed on students aged 4-16 years in China, from August 2021 to January 2022. Outdoor activity was assessed by the Assessment Questionnaire of Exposure to Sunlight Activities for Students (AQESAS). Binary logistic regression combined with the mediation analysis was used to analyze the association of AQESAS with myopia and the mediating effect of sleep time on this relationship. RESULTS: The prevalence of myopia was 53.51% (N = 1609). Multivariate logistic regression analysis showed that more sleep time (OR = 0.794, 95%CI: 0.707-0.893) and a higher score of AQESAS (OR = 0.989, 95%CI: 0.981-0.996) were significantly associated with a decreased risk of myopia. Mediation analysis revealed that sleep time plays a mediating role in the association between outdoor activity and myopia (ACME = -0.0006, P < 0.001), and the mediation proportion was 19.7%. CONCLUSION: Outdoor activity affects myopia directly and indirectly through sleep time. The result suggested that children may be able to reduce the risk of myopia by promoting sleep through increased awareness of outdoor activity and exposure to sunlight.

2.
Hum Resour Health ; 22(1): 42, 2024 Jun 19.
Article En | MEDLINE | ID: mdl-38898452

BACKGROUND: Job burnout is a prevalent and emerging challenge in the primary medical system, causing mass turnover, especially of primary medical staff. Little attention has been paid to the different dimensions of job burnout (emotional exhaustion, personality disintegration, and reduced sense of achievement), which may hinder efforts to tackle high turnover intention among primary medical staff. From the perspective of conservation of resources theory, social support and psychological capital are basic resources with potential to diminish job burnout and thus lower turnover intention. However, there is insufficient research evidence on the relationships between social support, psychological capital, and the three dimensions of job burnout within the primary medical system. OBJECTIVES: Focusing on primary medical staff, this study conducts a path analysis to examine the correlations between two types of resources (social support and psychological capital) and the three dimensions of job burnout, and to test the impact of the latter on turnover intention. Based on the results, effective management strategies to improve the work stability of primary medical staff are proposed. METHODS: Multi-stage cluster random sampling was used to select participants in Anhui Province, China. Data were collected using a self-administered questionnaire containing measures of the main variables and demographic questions. In total, 1132 valid questionnaires were returned by primary medical staff. Structural equation modeling was used for path analysis of the data. RESULTS: Social support was negatively associated with emotional exhaustion (ß = - 0.088, P = 0.020), personality disintegration (ß = - 0.235, P < 0.001), and reduced sense of achievement (ß = - 0.075, P = 0.040). Moreover, psychological capital was negatively associated with emotional exhaustion (ß = - 0.079, P = 0.030), personality disintegration (ß = - 0.156, P < 0.001), and reduced sense of achievement (ß = - 0.432, P < 0.001). All three dimensions of job burnout positively affected turnover intention (emotional exhaustion: ß = 0.246, P < 0.001; personality disintegration: ß = 0.076, P = 0.040; reduced sense of achievement: ß = 0.119, P = 0.001). CONCLUSIONS: The results highlight the importance of social support and psychological capital for diminishing the three dimensions of job burnout for primary medical staff and, in turn, lowering their turnover intention. Accordingly, to alleviate job burnout and improve staff retention, material and psychological supports from leaders, colleagues, family, relatives, and friends are essential, as are measures to improve the psychological energy of primary medical staff.


Burnout, Professional , Medical Staff , Personnel Turnover , Social Support , Burnout, Professional/psychology , Personnel Turnover/statistics & numerical data , Social Support/psychology , Medical Staff/psychology , Medical Staff/statistics & numerical data , China , Surveys and Questionnaires , Humans , Male , Female , Young Adult , Adult , Middle Aged
3.
bioRxiv ; 2024 May 21.
Article En | MEDLINE | ID: mdl-38826308

Intra-articular delivery of disease-modifying osteoarthritis drugs (DMOADs) is likely to be most effective in early post-traumatic osteoarthritis (PTOA) when symptoms are minimal and patients are physically active. DMOAD delivery systems therefore must withstand repeated mechanical loading without affecting the drug release kinetics. Although soft materials are preferred for DMOAD delivery, mechanical loading can compromise their structural integrity and disrupt drug release. Here, we report a mechanically resilient soft hydrogel that rapidly self-heals under conditions resembling human running while maintaining sustained release of the cathepsin-K inhibitor L-006235 used as a proof-of-concept DMOAD. Notably, this hydrogel outperformed a previously reported hydrogel designed for intra-articular drug delivery, used as a control in our study, which neither recovered nor maintained drug release under mechanical loading. Upon injection into mouse knee joints, the hydrogel showed consistent release kinetics of the encapsulated agent in both treadmill-running and non-running mice. In a mouse model of aggressive PTOA exacerbated by treadmill running, L-006235 hydrogel markedly reduced cartilage degeneration. To our knowledge, this is the first hydrogel proven to withstand human running conditions and enable sustained DMOAD delivery in physically active joints, and the first study demonstrating reduced disease progression in a severe PTOA model under rigorous physical activity, highlighting the hydrogel's potential for PTOA treatment in active patients.

4.
Transl Vis Sci Technol ; 13(6): 4, 2024 Jun 03.
Article En | MEDLINE | ID: mdl-38864819

Purpose: This study aimed to investigate the prevalence of myopia and determine the association between physical activity and risk of myopia among primary school students in Tianjin, China. Methods: A cross-sectional study was conducted among subjects from nine primary schools. All of the subjects underwent visual acuity and spherical equivalent (SE) with noncycloplegic autorefraction measurement. Myopia was defined as an SE refraction ≤-0.50D and an uncorrected visual acuity <5.0 in either eye. Physical activity was measured via the Physical Activity Questionnaire for Children. Data were analyzed using the Pearson χ2 test and binary logistic regression. Stratification analysis by sex was also performed. Results: A total of 2976 participants (1408 boys and 1568 girls) aged six to 12 years (mean age 8.82 years) were included in this study. The overall prevalence of myopia was 52.92%. When stratified according to physical activity, myopia prevalence significantly decreased with increasing physical activity levels (χ2 trend test = 127.63, P < 0.001). In the binary logistic regression analysis, after adjusting for age, sex, and school region, the odds ratio for the association between physical activity and myopia was 0.762 (95% confidence interval, 0.675-0.862, P < 0.001). When stratified by sex, the significant statistical association between physical activity and myopia both can be found in two groups (P < 0.05). Conclusions: Higher levels of physical activity were independently associated with decreased risk of myopia. The significant reverse statistical association between physical activity and myopia can be found in male or female groups. Translational Relevance: Taking part in physical activities may be an effective way to reduce the prevalence of myopia.


Exercise , Myopia , Humans , Cross-Sectional Studies , Male , Female , Myopia/epidemiology , Prevalence , China/epidemiology , Child , Students/statistics & numerical data , Schools , Refraction, Ocular/physiology , Risk Factors , Visual Acuity/physiology , Surveys and Questionnaires
5.
Blood Purif ; 2024 Jun 12.
Article En | MEDLINE | ID: mdl-38865971

BACKGROUND: Continuous renal replacement therapy (CRRT) is a primary form of renal support for patients with acute kidney injury in an intensive care unit. Making an accurate decision of discontinuation is crucial for the prognosis of patients. Previous research has mostly focused on the univariate and multivariate analysis of factors in CRRT, without the capacity to capture the complexity of the decision-making process. The present study thus developed a dynamic, interpretable decision model for CRRT discontinuation. METHODS: The study adopted a cohort of 1234 adult patients admitted to an intensive care unit in the MIMIC-IV database. We used the extreme gradient boosting (XGBoost) machine learning algorithm to construct dynamic discontinuation decision models across four time points. Shapley additive explanation (SHAP) analysis was conducted to show the contribution of an individual feature to the model output. RESULTS: Of the 1234 included patients with CRRT, 596 (48.3%) successfully discontinued CRRT. The dynamic prediction by the XGBoost model produced an area under the curve of 0.848 and accuracy, sensitivity, and specificity of 0.782, 0.786, and 0.776, respectively. The XGBoost model was thus far superior to other test models. SHAP demonstrated that the features that contributed most to the model results were the sequential organ failure assessment score, serum lactate level, and 24-hour urine output. CONCLUSIONS: Dynamic decision models supported by machine learning are capable of dealing with complex factors in CRRT and effectively predicting the outcome of discontinuation.

6.
ACS Omega ; 9(22): 23971-23983, 2024 Jun 04.
Article En | MEDLINE | ID: mdl-38854519

Accurately determining the adsorption capacity of Longmaxi shale in complex structural areas is crucial for evaluating the shale gas resources in northeastern Chongqing. However, studies on the pore characteristics and methane adsorption capacity of these Longmaxi shales are currently limited. In this paper, we collected core samples from the YDB-1 well in northeastern Chongqing and determined the pore structure and adsorption capacity of the Longmaxi shale using low-pressure gas adsorption and high-temperature, high-pressure methane adsorption experiments, respectively. The results indicate that the adsorption capacity of shale in complex structural areas is significantly positively correlated with the organic matter (OM) content, weakly positively correlated with the quartz content, and weakly negatively correlated with clay minerals. Meanwhile, gas-in-place content is simultaneously controlled by the pressure and temperature of the reservoir, and with increasing depth, the adsorbed gas rapidly increases to a maximum value (at 0.8 km) and then slowly decreases, whereas the free gas continuously increases. Compared with the shale in the stable structural areas, the Longmaxi shale in complex structural areas usually develops OM-hosted pores and intergranular pores of OM and minerals and contains more micropores due to tectonic compression, resulting in a relatively larger specific surface area and adsorption capacity. This is the reason shale in complex structural areas has high development potential. The final result can provide an important basis for the evaluation of the gas content and the optimization of dessert areas in the Lower Paleozoic shale gas in southern China.

7.
Clin Transl Oncol ; 2024 Jun 19.
Article En | MEDLINE | ID: mdl-38898352

OBJECTIVE: This study aimed to explore the effect of narrative nursing on improving the negative emotions, sleep quality, and quality of life of patients with moderate to severe cancer pain. METHODS: A total of 80 patients with moderate to severe cancer pain who had been hospitalized in the lymphoma oncology department in our hospital from March 2019 to September 2021 were selected as the study subjects and randomly divided into the conventional nursing and narrative nursing groups, with 40 cases in each group. A conventional nursing intervention was conducted for one group, and narrative nursing was provided for the second group in addition to the conventional nursing. The anxiety and depression, sleep quality, quality of life, and satisfaction with pain management of the patients in the two groups were compared before and after the intervention. RESULTS: In the narrative nursing group, the self-rating anxiety scale and self-rating depression scale scores were significantly lower than those in the conventional nursing group after the intervention (P < 0.05). The scores for sleep quality, sleep duration, sleep efficiency, and daytime dysfunction and the total Pittsburgh Sleep Quality Index scores were significantly lower in the narrative nursing group compared with the conventional care group (P < 0.05). The scores for the physical function, living ability, social adaptation, and psychological status items in the Quality of Life Questionnaire Core 30 were significantly higher in the narrative nursing group than in the conventional care group (P < 0.05). The patients' satisfaction with pain management was higher in the narrative nursing group than in the conventional care group (P < 0.05). CONCLUSION: Narrative nursing can alleviate the negative emotions of anxiety and depression in patients with moderate to severe cancer pain and improve their sleep quality, quality of life, and pain management satisfaction.

8.
Int J Mol Sci ; 25(11)2024 May 30.
Article En | MEDLINE | ID: mdl-38892188

Pygopus (Pygo) has been identified as a specific nuclear co-activator of the canonical Wingless (Wg)/Wnt signaling pathway in Drosophila melanogaster. Pygo proteins consist of two conserved domains: an N-terminal homologous domain (NHD) and a C-terminal plant homologous domain (PHD). The PHD's ability to bind to di- and trimethylated lysine 4 of histone H3 (H3K4me2/3) appears to be independent of Wnt signaling. There is ongoing debate regarding the significance of Pygo's histone-binding capacity. Drosophila Pygo orthologs have a tryptophan (W) > phenylalanine (F) substitution in their histone pocket-divider compared to vertebrates, leading to reduced histone affinity. In this research, we utilized CRISPR/Cas9 technology to introduce the Pygo-F773W point mutation in Drosophila, successfully establishing a viable homozygous Pygo mutant line for the first time. Adult mutant flies displayed noticeable abnormalities in reproduction, locomotion, heart function, and lifespan. RNA-seq and cluster analysis indicated that the mutation primarily affected pathways related to immunity, metabolism, and posttranslational modification in adult flies rather than the Wnt signaling pathway. Additionally, a reduction in H3K9 acetylation levels during the embryonic stage was observed in the mutant strains. These findings support the notion that Pygo plays a wider role in chromatin remodeling, with its involvement in Wnt signaling representing only a specific aspect of its chromatin-related functions.


Drosophila Proteins , Drosophila melanogaster , Wnt Signaling Pathway , Animals , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Wnt Signaling Pathway/genetics , Drosophila melanogaster/genetics , Drosophila melanogaster/metabolism , Histones/metabolism , Histones/genetics , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Mutation , CRISPR-Cas Systems
9.
Article En | MEDLINE | ID: mdl-38837922

Flocking control of autonomous underwater vehicles (AUVs) has been regarded as the basis of many sophisticated marine coordination missions. However, there is still a research gap on the flocking of AUVs in weak communication and complex marine environment. This article attempts to fill up the above research gap from graph theory and intelligent learning perspectives. We first employ the bearing rigidity graph to describe the topology relationships of AUVs, through which an iterative gradient decent-based localization estimator is provided to obtain the position information. In order to improve the localization accuracy and energy efficiency, a min-weighted bearing rigidity graph generation strategy is developed. Along with this, we adopt the semi-supervised broad learning system (BLS) to design the model-free flocking controllers for AUVs in obstacle environment. The innovations of this article are summarized as follows: 1) the min-weighted bearing rigidity-based localization strategy can balance the localization accuracy and communication consumption as compared to the neighboring rule-based solutions and 2) the semi-supervised broad learning-based flocking controller can decrease the training time and solve the label limit over the supervised learning-based controllers. Finally, simulation and experimental studies are provided to verify the effectiveness.

10.
J Glob Health ; 14: 04140, 2024 Jun 21.
Article En | MEDLINE | ID: mdl-38898796

Background: There is increasing evidence on the link between environmental factors and myopia in children and adolescents, yet with inconsistent conclusions. We investigated the associations between socioeconomic inequalities and green space with myopia in school-aged students participating in the Tianjin Child and Adolescent Research of Eye (TCARE) study. Methods: We obtained data from a population-based dynamic cohort study conducted in Tianjin, China, in 2021 and followed up in 2022. We included 1 245 271 participants from 16 districts with an average age of 11.6 years (standard deviation = 3.3) in our analysis. We synthesized their area-level SES through a prediction model that combined economic, educational, and health care variables and assessed the greenness levels surrounding the school using the Normalized Difference Vegetation Index (NDVI) based on data obtained through satellite remote sensing. We performed generalised linear mixed effects analyses for each myopia outcome separately, with adjustments for students' sex, years of education completed, and the school's geographical location. Results: We observed that students living in low SES areas had the highest prevalence of myopia (60.7%) in the last screening in 2022, as well as a higher incidence of one-year myopia (26.4%) compared to those residing in middle SES areas (22.7%). With a 0.1 increase in the 250, 500, and 1000 m buffer NDVI, the prevalence of myopia dropped by 6.3% (odds ratio (OR) = 0.937; 95% confidence interval (CI) = 0.915, 0.960), 7.7% (OR = 0.923; 95% CI = 0.900, 0.946), and 8.7% (OR = 0.913; 95% CI = 0.889, 0.937), respectively. The interaction analysis showed that low SES and low greenness exacerbate the prevalence of myopia. Findings from longitudinal analyses consistently demonstrated a correlation between higher values of NDVI and a slower progression of myopia. These findings remained robust across sensitivity analyses, including for variables on parental myopia and students' behaviors. Conclusions: Exposure to green spaces could play a crucial role in slowing the progression of myopia among school-aged students. Myopia control policies should prioritise young populations residing in low SES areas with limited access to green spaces, as they face the highest potential risks.


Myopia , Socioeconomic Factors , Students , Humans , Myopia/epidemiology , Female , Male , China/epidemiology , Child , Adolescent , Cohort Studies , Students/statistics & numerical data , Prevalence , Parks, Recreational/statistics & numerical data , Socioeconomic Disparities in Health , East Asian People
11.
Front Chem ; 12: 1417763, 2024.
Article En | MEDLINE | ID: mdl-38887698

Introduction: Facial nerve injury significantly impacts both the physical and psychological] wellbeing of patients. Despite advancements, there are still limitations associated with autografts transplantation. Consequently, there is an urgent need for effective artificial grafts to address these limitations and repair injuries. Recent years have witnessed the recognition of the beneficial effects of chitosan (CS) and graphene in the realm of nerve repair. Dental pulp stem cells (DPSCs) hold great promise due to their high proliferative and multi-directional differentiation capabilities. Methods: In this study, Graphene/CS (G/CST) composite tubes were synthesized and their physical, chemical and biological properties were evaluated, then DPSCs were employed as seed cells and G/CST as a scaffold to investigate their combined effect on promoting facial nerve injury repair. Results and Disscussion: The experimental results indicate that G/CST possesses favorable physical and chemical properties, along with good cyto-compatibility. making it suitable for repairing facial nerve transection injuries. Furthermore, the synergistic application of G/CST and DPSCs significantly enhanced the repair process for a 10 mm facial nerve defect in rabbits, highlighting the efficacy of graphene as a reinforcement material and DPSCs as a functional material in facial nerve injury repair. This approach offers an effective treatment strategy and introduces a novel concept for clinically managing facial nerve injuries.

12.
Front Nutr ; 11: 1378884, 2024.
Article En | MEDLINE | ID: mdl-38725578

Myofibrillar proteins are an important component of proteins. Flavor characteristics are the key attributes of food quality. The ability of proteins to bind flavor is one of their most fundamental functional properties. The dynamic balance of release and retention of volatile flavor compounds in protein-containing systems largely affects the sensory quality and consumer acceptability of foods. At present, research on flavor mainly focuses on the formation mechanism of flavor components, while there are few reports on the release and perception of flavor components. This review introduces the composition and structure of myofibrillar proteins, the classification of flavor substances, the physical binding and chemical adsorption of myofibrillar proteins and volatile flavor substances, as well as clarifies the regulation law of flavor substances from the viewpoint of endogenous flavor characteristics and exogenous environment factors, to provide a theoretical reference for the flavor regulation of meat products.

13.
World J Clin Cases ; 12(14): 2404-2411, 2024 May 16.
Article En | MEDLINE | ID: mdl-38765738

BACKGROUND: Human cystic echinococcosis (CE) is a life-threatening zoonosis caused by the Echinococcus granulosus (sensu lato). Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality in the world. The coexistence of CE and HCC is exceedingly rare, and only several well-documented cases have been reported. In addition to this coexistence, there is no report of the coexistence of CE, HCC, and liver abscess to date. Herein, we aimed to report a case of coexistence of liver abscess, hepatic CE, and HCC. CASE SUMMARY: A 65-year-old herdsman presented to the department of interventional therapy with jaundice, right upper abdominal distension and pain for 10 d. Laboratory test showed that he had positive results for HBsAg, HBeAb, HBcAb, and echinococcosis IgG antibody. The test also showed an increased level of alpha fetoprotein of 3400 ng/mL. An abdominal computed tomography (CT) scan revealed an uneven enhanced lesion of the liver at the arterial phase with enhancement and was located S4/8 segment of the liver. In addition, CT scan also revealed a mass in the S6 segment of the liver with a thick calcified wall and according to current guideline and medical images, the diagnoses of hepatic CE (CE4 subtype) and HCC were established. Initially, transarterial chemoembolization was performed for HCC. In the follow-up, liver abscess occurred in addition to CE and HCC; thus, percutaneous liver puncture drainage was performed. In the next follow-up, CE and HCC were stable. The liver abscess was completely resolved, and the patient was discharged with no evidence of recurrence. CONCLUSION: This is the first reported case on the coexistence of liver abscess, hepatic CE, and HCC. Individualized treatment and multidisciplinary discussions should be performed in this setting. Therefore, treatment and diagnosis should be based on the characteristics of liver abscess, hepatic CE, and HCC, and in future clinical work, it is necessary to be aware of the possibility of this complex composition of liver diseases.

14.
Nat Commun ; 15(1): 3902, 2024 May 09.
Article En | MEDLINE | ID: mdl-38724527

Radiation-induced in situ tumor vaccination alone is very weak and insufficient to elicit robust antitumor immune responses. In this work, we address this issue by developing chiral vidarabine monophosphate-gadolinium nanowires (aAGd-NWs) through coordination-driven self-assembly. We elucidate the mechanism of aAGd-NW assembly and characterize their distinct features, which include a negative surface charge, ultrafine topography, and right-handed chirality. Additionally, aAGd-NWs not only enhance X-ray deposition but also inhibit DNA repair, thereby enhancing radiation-induced in situ vaccination. Consequently, the in situ vaccination induced by aAGd-NWs sensitizes radiation enhances CD8+ T-cell-dependent antitumor immunity and synergistically potentiates the efficacy immune checkpoint blockade therapies against both primary and metastatic tumors. The well-established aAGd-NWs exhibit exceptional therapeutic capacity and biocompatibility, offering a promising avenue for the development of radioimmunotherapy approaches.


Nanowires , Polymers , Nanowires/chemistry , Animals , Mice , Polymers/chemistry , Cell Line, Tumor , Gadolinium/chemistry , Gadolinium/pharmacology , Mice, Inbred C57BL , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/drug effects , Cancer Vaccines/immunology , Female , Humans , Vaccination/methods , Neoplasms/immunology
15.
Heliyon ; 10(9): e29849, 2024 May 15.
Article En | MEDLINE | ID: mdl-38699021

Background: Rheumatoid arthritis is a systemic inflammatory autoimmune disease that severely impacts physical and mental health. Autophagy is a cellular process involving the degradation of cellular components in lysosomes. However, from a bioinformatics perspective, autophagy-related genes have not been comprehensively elucidated in rheumatoid arthritis. Methods: In this study, we performed differential analysis of autophagy-related genes in rheumatoid arthritis patients using the GSE93272 dataset from the Gene Expression Omnibus database. Marker genes were screened by least absolute shrinkage and selection operator. Based on marker genes, we used unsupervised cluster analysis to elaborate different autophagy clusters, and further identified modules strongly associated with rheumatoid arthritis by weighted gene co-expression network analysis. In addition, we constructed four machine learning models, random forest model, support vector machine model, generalized linear model and extreme gradient boosting based on marker genes, and based on the optimal machine learning model, a nomogram model was constructed for distinguishing between normal individuals and rheumatoid arthritis patients. Finally, five external independent rheumatoid arthritis datasets were used for the validation of our results. Results: The results showed that autophagy-related genes had significant expression differences between normal individuals and osteoarthritis patients. Through least absolute shrinkage and selection operator screening, we identified 31 marker genes and found that they exhibited significant synergistic or antagonistic effects in rheumatoid arthritis, and immune cell infiltration analysis revealed significant changes in immune cell abundance. Subsequently, we elaborated different autophagy clusters (cluster 1 and cluster 2) using unsupervised cluster analysis. Next, further by weighted gene co-expression network analysis, we identified a brown module strongly associated with rheumatoid arthritis. In addition, we constructed a nomogram model for five marker genes (CDKN2A, TP53, ATG16L2, FKBP1A, and GABARAPL1) based on a generalized linear model (area under the curve = 1.000), and the predictive efficiency and accuracy of this nomogram model were demonstrated in the calibration curves, the decision curves and the five external independent datasets were validated. Conclusion: This study identified marker autophagy-related genes in rheumatoid arthritis and analyzed their impact on the disease, providing new perspectives for understanding the role of autophagy-related genes in rheumatoid arthritis and providing new directions for its individualized treatment.

16.
Gut Microbes ; 16(1): 2351532, 2024.
Article En | MEDLINE | ID: mdl-38727248

Emerging evidence indicates that alteration of gut microbiota plays an important role in chronic kidney disease (CKD)-related vascular calcification (VC). We aimed to investigate the specific gut microbiota and the underlying mechanism involved in CKD-VC. We identified an increased abundance of Prevotella copri (P. copri) in the feces of CKD rats (induced by using 5/6 nephrectomy followed by a high calcium and phosphate diet) with aortic calcification via amplicon sequencing of 16S rRNA genes. In patients with CKD, we further confirmed a positive correlation between abundance of P. copri and aortic calcification scores. Moreover, oral administration of live P. copri aggravated CKD-related VC and osteogenic differentiation of vascular smooth muscle cells in vivo, accompanied by intestinal destruction, enhanced expression of Toll-like receptor-4 (TLR4), and elevated lipopolysaccharide (LPS) levels. In vitro and ex vivo experiments consistently demonstrated that P. copri-derived LPS (Pc-LPS) accelerated high phosphate-induced VC and VSMC osteogenic differentiation. Mechanistically, Pc-LPS bound to TLR4, then activated the nuclear factor κB (NF-κB) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome signals during VC. Inhibition of NF-κB reduced NLRP3 inflammasome and attenuated Pc-LPS-induced VSMC calcification. Our study clarifies a novel role of P. copri in CKD-related VC, by the mechanisms involving increased inflammation-regulating metabolites including Pc-LPS, and activation of the NF-κB/NLRP3 signaling pathway. These findings highlight P. copri and its-derived LPS as potential therapeutic targets for VC in CKD.


Gastrointestinal Microbiome , Lipopolysaccharides , NF-kappa B , Prevotella , Renal Insufficiency, Chronic , Signal Transduction , Toll-Like Receptor 4 , Vascular Calcification , Animals , Vascular Calcification/metabolism , Vascular Calcification/pathology , NF-kappa B/metabolism , Lipopolysaccharides/metabolism , Rats , Renal Insufficiency, Chronic/metabolism , Renal Insufficiency, Chronic/microbiology , Renal Insufficiency, Chronic/chemically induced , Renal Insufficiency, Chronic/pathology , Humans , Male , Toll-Like Receptor 4/metabolism , Toll-Like Receptor 4/genetics , Prevotella/metabolism , Rats, Sprague-Dawley , Myocytes, Smooth Muscle/metabolism , Osteogenesis/drug effects , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/pathology , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Feces/microbiology , Inflammasomes/metabolism
17.
Angew Chem Int Ed Engl ; : e202403241, 2024 May 06.
Article En | MEDLINE | ID: mdl-38710651

Exocytosis involving the fusion of intracellular vesicles with cell membrane, is thought to be modulated by the mechanical cues in the microenvironment. Single-cell electrochemistry can offer unique information about the quantification and kinetics of exocytotic events; however, the effects of mechanical force on vesicular release have been poorly explored. Herein, we developed a stretchable microelectrode with excellent electrochemical stability under mechanical deformation by microfabrication of functionalized poly(3,4-ethylenedioxythiophene) conductive ink, which achieved real-time quantitation of strain-induced vesicular exocytosis from a single cell for the first time. We found that mechanical strain could cause calcium influx via the activation of Piezo1 channels in chromaffin cell, initiating the vesicular exocytosis process. Interestingly, mechanical strain increases the amount of catecholamines released by accelerating the opening and prolonging the closing of fusion pore during exocytosis. This work is expected to provide revealing insights into the regulatory effects of mechanical stimuli on vesicular exocytosis.

18.
Sci Total Environ ; 936: 173261, 2024 Aug 01.
Article En | MEDLINE | ID: mdl-38761934

Dams worldwide commonly accelerate the eutrophication of reservoirs. While the seasonal hypoxia in deep reservoirs is widely acknowledged, there is limited research on its impact on benthic phosphorus (P) cycling and P fraction release from the reservoir sediments. Here we show that seasonal hypoxia enhances sediment P release and P fluxes at the sediment-water interface (SWI) which might alter P dynamics in deep reservoirs. We conducted a detailed measurement of sediment P fractions through the SEDEX approach, combined with a labile P gradient analysis using the diffusive gradients in thin films (DGT) technique to understand P cycling patterns in sediments during the transition period from spring (oxic) to late summer (hypoxic) conditions. The sediment P pool was predominantly composed of iron-bound phosphorus (Fe-P, 76-80 %), primarily due to the widespread occurrence of lateritic red soil (rich in Fe2O3/MnO2) in subtropical areas. More organic-P was observed in summer compared to spring. A significant increase in labile P occurred at the depth of 0-4 cm and 0-1 cm in spring and summer, respectively, where sediment P release was primarily governed by the reduction of Fe-P and the generation of S2-. A higher apparent fluxes of phosphate across the SWI were observed in summer characterized by higher temperature and lower oxygen levels. The current results suggest that seasonal hypoxia was a crucial factor affecting P cycling and diffusion in deep reservoirs. These findings present important implications for the ecology and management of the watershed-coast ecosystem.

19.
Bioorg Chem ; 148: 107491, 2024 Jul.
Article En | MEDLINE | ID: mdl-38788365

As a consequence of somatosensory nervous system injury or disease, neuropathic pain is commonly associated with chemotherapies, known as chemotherapy-induced peripheral neuropathy (CIPN). However, the mechanisms underlying CIPN-induced proteome aggregation in neuronal cells remain elusive due to limited detection tools. Herein, we present series sensors for fluorescence imaging (AggStain) and proteomics analysis (AggLink) to visualize and capture aggregated proteome in CIPN neuronal cell model. The environment-sensitive AggStain imaging sensor selectively binds and detects protein aggregation with 12.3 fold fluorescence enhancement. Further, the covalent AggLink proteomic sensor captures cellular aggregated proteins and profiles their composition via LC-MS/MS analysis. This integrative sensor platform reveals the presence of proteome aggregation in CIPN cell model and highlights its potential for broader applications in assessing proteome stability under various cellular stress conditions.


Antineoplastic Agents , Peripheral Nervous System Diseases , Proteome , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/metabolism , Humans , Proteome/analysis , Proteome/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Molecular Structure , Protein Aggregates/drug effects , Optical Imaging , Dose-Response Relationship, Drug , Proteomics , Fluorescent Dyes/chemistry , Fluorescent Dyes/pharmacology
20.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2734-2744, 2024 May.
Article Zh | MEDLINE | ID: mdl-38812174

Prunella vulgaris, aptly named for its withering at the summer solstice, displays significant variation in quality arising from differing harvest time. However, research on the chemical composition changes of its spikes at various stages is limited, and the specific metabolites remain unclear. In order to elucidate the metabolites and metabolic pathways of the spikes of P. vulgaris, the current study deployed ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) and targeted metabolomics to characterize the compound variability in the spikes of P. vulgaris across different periods. Multivariate statistical techniques such as principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to identify the differences in metabolites, and relevant metabolic pathways were analyzed. A total of 602 metabolites were identified by metabolomics, of which organic acids and their derivatives were the most abundant, followed by flavonoids. Multiple differential metabolites, including p-hydroxybenzoic acids and gallic acids were identified based on variable importance in projection(VIP)>1 and P<0.05. The results of enrichment analysis suggested that isoflavonoids biosynthesis, aminobenzoate degradation, benzoate degradation, anthocyanins biosynthesis, metabolic pathways, microbial metabolism in different environments, secondary plant metabolite biosynthesis, tryptophan metabolism, and phenylpropanoid synthesis were the main metabolic pathways. These results intend to elucidate the dynamic changes of differential metabolites of P. vulgaris and provide a theoretical basis for further study of the harvesting mechanism of spikes of P. vulgaris.


Metabolomics , Prunella , Tandem Mass Spectrometry , Prunella/chemistry , Prunella/metabolism , Tandem Mass Spectrometry/methods , Chromatography, High Pressure Liquid , Metabolomics/methods , Liquid Chromatography-Mass Spectrometry
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