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1.
Brain Behav ; 14(7): e3605, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38956819

RESUMO

BACKGROUND: High-frequency repeated transcranial magnetic stimulation (rTMS) stimulating the primary motor cortex (M1) is an alternative, adjunctive therapy for improving the motor symptoms of Parkinson's disease (PD). However, whether the high frequency of rTMS positively correlates to the improvement of motor symptoms of PD is still undecided. By controlling for other parameters, a disease animal model may be useful to compare the neuroprotective effects of different high frequencies of rTMS. OBJECTIVE: The current exploratory study was designed to compare the protective effects of four common high frequencies of rTMS (5, 10, 15, and 20 Hz) and iTBS (a special form of high-frequency rTMS) and explore the optimal high-frequency rTMS on an animal PD model. METHODS: Following high frequencies of rTMS application (twice a week for 5 weeks) in a MPTP/probenecid-induced chronic PD model, the effects of the five protocols on motor behavior as well as dopaminergic neuron degeneration levels were identified. The underlying molecular mechanisms were further explored. RESULTS: We found that all the high frequencies of rTMS had protective effects on the motor functions of PD models to varying degrees. Among them, the 10, 15, and 20 Hz rTMS interventions induced comparable preservation of motor function through the protection of nigrostriatal dopamine neurons. The enhancement of brain-derived neurotrophic factor (BDNF), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT-2) and the suppression of TNF-α and IL-1ß in the nigrostriatum were involved in the process. The efficacy of iTBS was inferior to that of the above three protocols. The effect of 5 Hz rTMS protocol was weakest. CONCLUSIONS: Combined with the results of the present study and the possible side effects induced by rTMS, we concluded that 10 Hz might be the optimal stimulation frequency for preserving the motor functions of PD models using rTMS treatment.


Assuntos
Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Transtornos Parkinsonianos , Probenecid , Estimulação Magnética Transcraniana , Animais , Estimulação Magnética Transcraniana/métodos , Camundongos , Masculino , Probenecid/farmacologia , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/terapia , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/fisiopatologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Córtex Motor/metabolismo , Córtex Motor/fisiopatologia , Neurônios Dopaminérgicos/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Interleucina-1beta/metabolismo , Substância Negra/metabolismo , Corpo Estriado/metabolismo , Proteínas Vesiculares de Transporte de Monoamina/metabolismo , Intoxicação por MPTP/terapia , Intoxicação por MPTP/prevenção & controle , Intoxicação por MPTP/metabolismo , Intoxicação por MPTP/fisiopatologia , Atividade Motora/fisiologia , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia
2.
Nat Cell Biol ; 26(7): 1110-1123, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38997457

RESUMO

Migrasomes are organelles that are generated by migrating cells. Here we report the key role of neutrophil-derived migrasomes in haemostasis. We found that a large number of neutrophil-derived migrasomes exist in the blood of mice and humans. Compared with neutrophil cell bodies and platelets, these migrasomes adsorb and enrich coagulation factors on the surface. Moreover, they are highly enriched with adhesion molecules, which enable them to preferentially accumulate at sites of injury, where they trigger platelet activation and clot formation. Depletion of neutrophils, or genetic reduction of the number of these migrasomes, significantly decreases platelet plug formation and impairs coagulation. These defects can be rescued by intravenous injection of purified neutrophil-derived migrasomes. Our study reveals neutrophil-derived migrasomes as a previously unrecognized essential component of the haemostasis system, which may shed light on the cause of various coagulation disorders and open therapeutic possibilities.


Assuntos
Coagulação Sanguínea , Plaquetas , Camundongos Endogâmicos C57BL , Neutrófilos , Neutrófilos/metabolismo , Animais , Humanos , Plaquetas/metabolismo , Camundongos , Hemostasia , Movimento Celular , Ativação Plaquetária , Masculino , Fatores de Coagulação Sanguínea/metabolismo , Fatores de Coagulação Sanguínea/genética
3.
Environ Sci Pollut Res Int ; 31(33): 45747-45760, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38977552

RESUMO

High alkalinity content of bauxite residue is a major factor that hinders resource reutilization and pollutes the environment. Although acid neutralization is a direct and effective method, the amount of acid and secondary waste of sodium salt are still difficult problems to solve. Herein, we innovatively integrated an electric field into the acid neutralization dealkalization of bauxite residue and analyzed the dealkalization behavior by thermodynamics, kinetics, and mineral transformation. The results show that the pH of the anode chamber was maintained at the acidic levels of 3-6 after 30 min of galvanostatic electrolysis, and bauxite residue can realize dealkalization by acid neutralization. In the anode chamber, Na+ was released into the leachate via the reactions of Na3Al3Si3O12 and the removal of encapsulated soluble alkali. The stainless steel wire mesh anode exhibited its superiority and decreased the Na2O content in bauxite residue from 9.48 to 3.13% through convective mass transfer driven by the electric field and steady-state diffusion under stirring. This research provides a promising method for the electricity-driven dealkalization of bauxite residue, thus facilitating the development of multifield coupling theory and the application of electric fields in the alumina industry.


Assuntos
Óxido de Alumínio , Eletricidade , Minerais , Termodinâmica , Óxido de Alumínio/química , Cinética , Minerais/química , Concentração de Íons de Hidrogênio
4.
Acta Pharm Sin B ; 14(7): 2901-2926, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39027258

RESUMO

Despite the considerable advancements in chemotherapy as a cornerstone modality in cancer treatment, the prevalence of complications and pre-existing diseases is on the rise among cancer patients along with prolonged survival and aging population. The relationships between these disorders and cancer are intricate, bearing significant influence on the survival and quality of life of individuals with cancer and presenting challenges for the prognosis and outcomes of malignancies. Herein, we review the prevailing complications and comorbidities that often accompany chemotherapy and summarize the lessons to learn from inadequate research and management of this scenario, with an emphasis on possible strategies for reducing potential complications and alleviating comorbidities, as well as an overview of current preclinical cancer models and practical advice for establishing bio-faithful preclinical models in such complex context.

5.
Eur J Prev Cardiol ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39024416

RESUMO

BACKGROUND: Despite numerous risk factors being associated with hypertension, the breadth of research remains constrained, with a notable absence of systematic, data-driven exploration into established and novel factors across a broad spectrum of exposures. This study aims to construct an atlas on known and emerging factors for hypertension through comprehensive epidemiological and genetic analyses. METHODS: We conducted exposome-wide association studies (ExWAS) via Cox regression models on two equally sized datasets for discovery and replication in UK Biobank, a large prospective cohort study. A maximum of 10,806 exposome variables were included in ExWAS and were grouped into 13 categories: genomics, sociodemographic, lifestyle, physical measure, biomarkers, medical history, imaging markers, sex-specific factors, psychosocial factors, cognitive function indicators, local environment, family history, and early life factors. The credibility of epidemiological associations was assessed through meta-analyses. The genetic underpinnings were explored through linkage-disequilibrium score regression (LDSC), quantifying global genetic correlation. Two-sample Mendelian randomization (MR) studies were conducted to investigate the causal effects of each exposure on hypertension, with co-analyses undertaken to identify associations supported by both epidemiological and genetic evidence. RESULTS: This study included 214,957 UK Biobank participants, hypertension-free at baseline. In our ExWAS analyses, 964 significant exposome variables were replicated. In meta-analyses, 462 were backed by convincing and highly suggestive evidence. Among 10,765 exposures in LDSC, 1923 had global genetic correlations with hypertension. The MR analyses yielded robust evidence for a causal relationship with 125 phenotypes, probable evidence for 270 phenotypes, and suggestive evidence for 718 phenotypes. Co-analyses identified 146 associations supported by strong epidemiological and genetic evidence. These primarily encompassed traits like anthropometry, lung function, lipids, and factors such as urate and walking pace. This coverage further extended from well-studied factors (like BMI and physical activity) to less explored exposures (including high light scatter reticulocyte count and age at first live). All study results are compiled in a webserver for user-friendly exploration of exposure-hypertension associations. CONCLUSION: This study provides an atlas on established and novel risk factors for hypertension, underpinned by epidemiological and causal evidence. Our findings present a multiple perspective to prioritize hypertension prevention strategies, encompassing modifiable risk factors like television watching time and walking pace. The study also emphasized the roles of urate in hypertension pathogenesis. Consequently, our study may serve as a critical guide for hypertension prevention and bear significant clinical implications.


Researchers have created a comprehensive map that identifies and analyses a wide array of risk factors linked to the development of high blood pressure, using extensive data from the UK Biobank. The study revealed 964 significant factors related to lifestyle, environment, and genetics that could influence the risk of developing hypertension, with 462 of these factors showing strong evidence of a link.Key lifestyle-related findings include the impact of behaviors such as television watching and walking pace on hypertension risk, suggesting that modifiable habits can be targeted for prevention strategies.

6.
Circ Res ; 135(3): e76-e93, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-38841840

RESUMO

BACKGROUND: Despite advances in understanding hypertension's genetic structure, how noncoding genetic variants influence it remains unclear. Studying their interaction with DNA methylation is crucial to deciphering this complex disease's genetic mechanisms. METHODS: We investigated the genetic and epigenetic interplay in hypertension using whole-genome bisulfite sequencing. Methylation profiling in 918 males revealed allele-specific methylation and methylation quantitative trait loci. We engineered rs1275988T/C mutant mice using CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9), bred them for homozygosity, and subjected them to a high-salt diet. Telemetry captured their cardiovascular metrics. Protein-DNA interactions were elucidated using DNA pull-downs, mass spectrometry, and Western blots. A wire myograph assessed vascular function, and analysis of the Kcnk3 gene methylation highlighted the mutation's role in hypertension. RESULTS: We discovered that DNA methylation-associated genetic effects, especially in non-cytosine-phosphate-guanine (non-CpG) island and noncoding distal regulatory regions, significantly contribute to hypertension predisposition. We identified distinct methylation quantitative trait locus patterns in the hypertensive population and observed that the onset of hypertension is influenced by the transmission of genetic effects through the demethylation process. By evidence-driven prioritization and in vivo experiments, we unearthed rs1275988 in a cell type-specific enhancer as a notable hypertension causal variant, intensifying hypertension through the modulation of local DNA methylation and consequential alterations in Kcnk3 gene expression and vascular remodeling. When exposed to a high-salt diet, mice with the rs1275988C/C genotype exhibited exacerbated hypertension and significant vascular remodeling, underscored by increased aortic wall thickness. The C allele of rs1275988 was associated with elevated DNA methylation levels, driving down the expression of the Kcnk3 gene by attenuating Nr2f2 (nuclear receptor subfamily 2 group F member 2) binding at the enhancer locus. CONCLUSIONS: Our research reveals new insights into the complex interplay between genetic variations and DNA methylation in hypertension. We underscore hypomethylation's potential in hypertension onset and identify rs1275988 as a causal variant in vascular remodeling. This work advances our understanding of hypertension's molecular mechanisms and encourages personalized health care strategies.


Assuntos
Metilação de DNA , Hipertensão , Locos de Características Quantitativas , Animais , Hipertensão/genética , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Camundongos , Estudo de Associação Genômica Ampla , Canais de Potássio de Domínios Poros em Tandem/genética , Canais de Potássio de Domínios Poros em Tandem/metabolismo , Camundongos Endogâmicos C57BL , Humanos , Epigênese Genética , Predisposição Genética para Doença , Cloreto de Sódio na Dieta/efeitos adversos , Pressão Sanguínea/genética
7.
Spectrochim Acta A Mol Biomol Spectrosc ; 321: 124730, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38943757

RESUMO

Most known chemiluminescence (CL) systems are flash-type that generate weak luminescence and decline quickly after dozens of seconds, while the glow-type CL systems have stable emission for an extended period to achieve accurate quantitation. In this work, a long-term CL system based on hydrazine-hydrate (N2H4·H2O) modified carbon quantum dots (N-CQDs) as a luminescent probe, with K2S2O8 and H2O2 as co-reactants, was proposed. The CL emission enhanced by H2O2 increased 18-fold more than that of N-CQDs and K2S2O8 direct reaction, and decayed by 5% of the maximum intensity over 700 s. In the reaction system, K2S2O8 and H2O2 co-reactants can promote each other to continuously generate corresponding radicals (•OH, O2•-, 1O2), which in turn trigger the CL emission of N-CQDs. This phenomenon was identified as the primary cause for the production of persistent CL. In addition, a stable and selective CL sensor based on the N-CQDs-K2S2O8-H2O2 CL enhancing system was developed for ascorbic acid quantitation in the linear range from 0.1 to 10.0 mM with a detection limit of 0.036 mM. The method has been applied to the analysis of tablet samples and holds potential in pharmaceutical analysis field.

8.
Nat Commun ; 15(1): 4376, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38782890

RESUMO

Topologically associating domains (TADs), megabase-scale features of chromatin spatial architecture, are organized in a domain-within-domain TAD hierarchy. Within TADs, the inner and smaller subTADs not only manifest cell-to-cell variability, but also precisely regulate transcription and differentiation. Although over 20 TAD callers are able to detect TAD, their usability in biomedicine is confined by a disagreement of outputs and a limit in understanding TAD hierarchy. We compare 13 computational tools across various conditions and develop a metric to evaluate the similarity of TAD hierarchy. Although outputs of TAD hierarchy at each level vary among callers, data resolutions, sequencing depths, and matrices normalization, they are more consistent when they have a higher similarity of larger TADs. We present comprehensive benchmarking of TAD hierarchy callers and operational guidance to researchers of life science researchers. Moreover, by simulating the mixing of different types of cells, we confirm that TAD hierarchy is generated not simply from stacking Hi-C heatmaps of heterogeneous cells. Finally, we propose an air conditioner model to decipher the role of TAD hierarchy in transcription.


Assuntos
Benchmarking , Cromatina , Cromatina/química , Humanos , Biologia Computacional/métodos , Software , Montagem e Desmontagem da Cromatina
9.
Histol Histopathol ; : 18759, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38804139

RESUMO

Serrated lesions are precursors of some colon cancers. The expression of galectin-3 has been reported to be involved in BRAF and KRAS mutations (the key pathogenic drivers of serrated lesions). This study aimed to investigate the expression intensity and subcellular localization of galectin-3 in serrated colon lesions by immunohistochemistry. The results demonstrated that, regarding expression intensity, galectin-3 expression in serrated colon lesions was significantly upregulated; regarding subcellular localization, the membrane expression of hyperplastic polyps/ sessile serrated lesions (HP/SSL) was weakened, the structure was disorganized and that of traditional serrated adenoma (TSA) was significantly weakened or disappeared, and the nuclear expression of both was positive; in the dysplasia of SSL (SSL-D) and TSA (TSA-HD), galectin-3 expression intensity remained high, and was weakened or disappeared in some nuclei, the expression disorder of the SSL-D cell membrane was reduced, the polarity of the cell was restored, weak expression appeared in the local cell membrane of TSA-HD, and the "serrated" structure of both was reduced or disappeared and seemed to revert more to that seen in common adenomas. In summary, abnormal galectin-3 expression occurs in the early stages of serrated lesions, its expression is characteristic, the dynamic changes in galectin-3 expression are closely related to the histopathological changes and progression of serrated lesions, and further accumulated molecular alterations contribute to this process.

10.
Front Public Health ; 12: 1345244, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694976

RESUMO

Background: The global population is experiencing a rapid rise in the quantity and percentage of older people. In an effort to enhance physical activity among older adults, active video games (AVGs) are being suggested as a compelling alternative and are currently under scrutiny to evaluate their efficacy in promoting the health of older people. Objective: This review aims to synthesize current studies and formulate conclusions regarding the impact of AVGs on the health-related physical fitness of older adults. Methods: Seven databases (PubMed, Web of Science, SCOPUS, SPORTDiscus, EMBASE, MEDLINE, and CINAHL) were searched from inception to January 21, 2024. Eligible studies included randomized controlled trials examining the effect of AVGs compared to control conditions on health-related physical fitness outcomes in older adults. The methodological quality of the included trials was assessed using the PEDro scale, and the certainty of evidence was evaluated using the GRADE approach. A random-effects model was used to calculate effect sizes (ES; Hedge's g) between experimental and control groups. Results: The analysis included 24 trials with a total of 1428 older adults (all ≥ 60 years old). Compared to controls, AVGs produced significant increases in muscular strength (moderate ES = 0.64-0.68, p < 0.05) and cardiorespiratory fitness (moderate ES = 0.79, p < 0.001). However, no significant effects were found for body composition (trivial ES = 0.12-0.14; p > 0.05) and flexibility (trivial ES = 0.08; p = 0.677). The beneficial effects of AVGs were greater after a duration of ≥ 12 vs. < 12 weeks (cardiorespiratory fitness; ES = 1.04 vs. 0.29, p = 0.028) and following ≥ 60 minutes vs. < 60 minutes of session duration (muscular strength; ES = 1.20-1.24 vs. 0.27-0.42, p < 0.05). Conclusion: AVGs appear to be an effective tool for enhancing muscular strength and cardiorespiratory fitness in older adults, although their impact on improving body composition and flexibility seems limited. Optimal improvement in cardiorespiratory fitness is associated with a longer duration of AVGs (≥ 12 weeks). Moreover, a session duration of ≥ 60 minutes may provide greater benefits for the muscular strength of older adults. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=482568, identifier CRD42023482568.


Assuntos
Aptidão Física , Jogos de Vídeo , Humanos , Aptidão Física/fisiologia , Idoso , Força Muscular/fisiologia , Pessoa de Meia-Idade , Exercício Físico , Masculino , Feminino , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Sci Rep ; 14(1): 11272, 2024 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760392

RESUMO

Plyometric training (PT) is an effective training method for improving physical fitness among trained individuals; however, its impact on health-related physical fitness in untrained participants remains ambiguous. Therefore, this meta-analysis aimed to evaluate the effects of PT on health-related physical fitness among untrained participants. Six electronic databases (PubMed, CINAHL Plus, MEDLINE Complete, Web of Science Core Collection, SCOPUS, and SPORTDiscus) were systematically searched until March 2024. We included controlled trials that examined the effects of PT on health-related physical fitness indices in untrained participants. Twenty-one studies were eligible, including a total of 1263 participants. Our analyses revealed small to moderate effects of PT on body mass index, muscular strength, cardiorespiratory fitness, and flexibility (ES = 0.27-0.61; all p > 0.05). However, no significant effects were detected for body fat percentage and lean mass (ES = 0.21-0.41; all p > 0.05). In conclusion, the findings suggest that PT may be potentially effective in improving health-related physical fitness indices (i.e., body mass index, muscular strength, cardiorespiratory fitness, and flexibility) in untrained participants. However, the results should be interpreted cautiously due to data limitations in some fitness variables.


Assuntos
Índice de Massa Corporal , Aptidão Cardiorrespiratória , Força Muscular , Aptidão Física , Exercício Pliométrico , Humanos , Aptidão Física/fisiologia , Força Muscular/fisiologia , Exercício Pliométrico/métodos , Aptidão Cardiorrespiratória/fisiologia , Masculino , Feminino , Adulto
12.
Heliyon ; 10(9): e30721, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38742075

RESUMO

Purpose: To evaluate abnormalities in serum and aqueous humor uric acid (UA) levels in primary angle closure glaucoma (PACG). Methods: Patients with PACG and age-similar and gender-similar controls (patients scheduled for cataract extraction) were enrolled prospectively. Serum UA levels were determined by enzymatic colorimetry; aqueous humor UA levels by Enzyme-Linked ImmunoSorbent Assay. A t-test was used to compare UA levels between PACG patients and controls, with one-way ANOVA used to compare levels across PACG subgroups with differing disease severity. Comparisons between PACG patients and controls were adjusted for systemic and ocular confounding factors using binary logistic regression. Results: In all, 131 PACG patients and 112 controls were included. The serum UA level was 266 ± 69 µmol/L in the PACG group and 269 ± 73 µmol/L in the control group (p = 0.71). The aqueous humor UA level was 35.4 ± 8.2 µmol/L in the PACG group and 53.9 ± 18.6 µmol/L in the control group (p < 0.001). This difference remained significant after adjusting for age, gender, systolic blood pressure, diastolic blood pressure, body mass index, axial length, central corneal thickness, anterior chamber depth, lens thickness, white-to-white distance, corneal endothelial cell density, and serum UA level (odds ratio: 0.88, 95 % confidence interval: 0.83-0.93, p < 0.001). Conclusion: Aqueous humor UA levels differ between PACG patients and controls, but serum UA levels do not. This indicates that local UA plays a role in the pathogenesis of PACG, but systemic UA does not.

13.
Am J Physiol Renal Physiol ; 326(6): F988-F1003, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38634138

RESUMO

Acid sphingomyelinase (ASM) has been reported to increase tissue ceramide and thereby mediate hyperhomocysteinemia (hHcy)-induced glomerular nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome activation, inflammation, and sclerosis. In the present study, we tested whether somatic podocyte-specific silencing of Smpd1 gene (mouse ASM gene code) attenuates hHcy-induced NLRP3 inflammasome activation and associated extracellular vesicle (EV) release in podocytes and thereby suppresses glomerular inflammatory response and injury. In vivo, somatic podocyte-specific Smpd1 gene silencing almost blocked hHcy-induced glomerular NLRP3 inflammasome activation in Podocre (podocyte-specific expression of cre recombinase) mice compared with control littermates. By nanoparticle tracking analysis (NTA), floxed Smpd1 shRNA transfection was found to abrogate hHcy-induced elevation of urinary EV excretion in Podocre mice. In addition, Smpd1 gene silencing in podocytes prevented hHcy-induced immune cell infiltration into glomeruli, proteinuria, and glomerular sclerosis in Podocre mice. Such protective effects of podocyte-specific Smpd1 gene silencing were mimicked by global knockout of Smpd1 gene in Smpd1-/- mice. On the contrary, podocyte-specific Smpd1 gene overexpression exaggerated hHcy-induced glomerular pathological changes in Smpd1trg/Podocre (podocyte-specific Smpd1 gene overexpression) mice, which were significantly attenuated by transfection of floxed Smpd1 shRNA. In cell studies, we also confirmed that Smpd1 gene knockout or silencing prevented homocysteine (Hcy)-induced elevation of EV release in the primary cultures of podocyte isolated from Smpd1-/- mice or podocytes of Podocre mice transfected with floxed Smpd1 shRNA compared with WT/WT podocytes. Smpd1 gene overexpression amplified Hcy-induced EV secretion from podocytes of Smpd1trg/Podocre mice, which was remarkably attenuated by transfection of floxed Smpd1 shRNA. Mechanistically, Hcy-induced elevation of EV release from podocytes was blocked by ASM inhibitor (amitriptyline, AMI), but not by NLRP3 inflammasome inhibitors (MCC950 and glycyrrhizin, GLY). Super-resolution microscopy also showed that ASM inhibitor, but not NLRP3 inflammasome inhibitors, prevented the inhibition of lysosome-multivesicular body interaction by Hcy in podocytes. Moreover, we found that podocyte-derived inflammatory EVs (released from podocytes treated with Hcy) induced podocyte injury, which was exaggerated by T cell coculture. Interstitial infusion of inflammatory EVs into renal cortex induced glomerular injury and immune cell infiltration. In conclusion, our findings suggest that ASM in podocytes plays a crucial role in the control of NLRP3 inflammasome activation and inflammatory EV release during hHcy and that the development of podocyte-specific ASM inhibition or Smpd1 gene silencing may be a novel therapeutic strategy for treatment of hHcy-induced glomerular disease with minimized side effect.NEW & NOTEWORTHY In the present study, we tested whether podocyte-specific silencing of Smpd1 gene attenuates hyperhomocysteinemia (hHcy)-induced nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome activation and associated inflammatory extracellular vesicle (EV) release in podocytes and thereby suppresses glomerular inflammatory response and injury. Our findings suggest that acid sphingomyelinase (ASM) in podocytes plays a crucial role in the control of NLRP3 inflammasome activation and inflammatory EV release during hHcy. Based on our findings, it is anticipated that the development of podocyte-specific ASM inhibition or Smpd1 gene silencing may be a novel therapeutic strategy for treatment of hHcy-induced glomerular disease with minimized side effects.


Assuntos
Hiper-Homocisteinemia , Inflamassomos , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR , Podócitos , Esfingomielina Fosfodiesterase , Animais , Esfingomielina Fosfodiesterase/genética , Esfingomielina Fosfodiesterase/metabolismo , Podócitos/metabolismo , Podócitos/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Hiper-Homocisteinemia/metabolismo , Hiper-Homocisteinemia/complicações , Hiper-Homocisteinemia/genética , Inflamassomos/metabolismo , Inflamassomos/genética , Glomérulos Renais/patologia , Glomérulos Renais/metabolismo , Glomerulonefrite/patologia , Glomerulonefrite/metabolismo , Glomerulonefrite/genética , Inativação Gênica , Camundongos , Camundongos Endogâmicos C57BL , Vesículas Extracelulares/metabolismo , Masculino , Modelos Animais de Doenças
14.
Microbiol Res ; 284: 127725, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38663233

RESUMO

Increasing studies have focused on the relationship between Desulfovibrio bacteria (DSV) and host health in recent years. However, little is known about the mechanisms by which DSV affects host health and the strategies to accurately regulate DSV numbers. This review mainly presents the relationship between DSV and host health, potential modulatory strategies, and the potential mechanisms affecting host health. Evidence suggests that DSV can both promote host health and induce the occurrence and development of disease, and these effects are closely related to its metabolites (e.g., H2S and short-chain fatty acids) and biofilm. DSV abundance in the intestine is influenced by probiotics, prebiotics, diet, lifestyle, and drugs.


Assuntos
Biofilmes , Desulfovibrio , Microbioma Gastrointestinal , Probióticos , Desulfovibrio/metabolismo , Desulfovibrio/fisiologia , Humanos , Microbioma Gastrointestinal/fisiologia , Biofilmes/crescimento & desenvolvimento , Intestinos/microbiologia , Prebióticos , Animais , Ácidos Graxos Voláteis/metabolismo , Sulfeto de Hidrogênio/metabolismo , Dieta
15.
Opt Lett ; 49(8): 2165-2168, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38621102

RESUMO

We experimentally generate nondiffracting speckles that carry non-Markovian properties by encoding the wavefront of a monochromatic laser beam with ring-shaped non-Markovian phases. The resulting non-Markovian nondiffracting fields present a ring-shaped pattern and central dark notches, which are analyzed with an expression of the orbital angular momentum spectra of the wavefront possessing ring-shaped non-Markovian phases. Furthermore, we demonstrate that the intensity profiles of these non-Markovian nondiffracting fields exhibit stability over multiple Rayleigh ranges, and their statistical properties could be controlled with the non-Markovianity of the input phase masks. This work presents an approach for simultaneously tailoring the diffracting property and non-Markovianity of optical fields and provides a deeper understanding of non-Markovian processes.

16.
Chemosphere ; 355: 141779, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38537709

RESUMO

To ensure good air quality during the China International Import Expo (CIIE) event, stringent emission-reduction measures were implemented in Shanghai. To assess the efficacy of these measures, this study measured typical categories of intermediate/semi volatile organic compounds (I/SVOCs), including alkanes (C10-C26 n-alkanes and pristane), EPA-priority polycyclic aromatic hydrocarbons (PAHs), alkylnaphthalenes, benzothiazole (BTH) and chlorobenzenes (CBs), at an urban site of Shanghai before and during two CIIE events (2019 and 2020; non-CIIE versus CIIE). The average concentrations of alkanes and PAHs during both 2019 and 2020 CIIE events decreased by approximately 41% and 17%, respectively, compared to non-CIIE periods. However, the decline in BTH and CBs was only observed during CIIE-2019. Secondary organic aerosol (SOA) formation from alkanes, PAHs and BTH was evaluated under atmospheric conditions, revealing considerable SOA contributions from dimethylnaphthalenes and BTH. Positive matrix factorization (PMF) analysis further revealed that life-related sources, such as cooking and residential emissions, make a noticeable contribution (21.6%) in addition to the commonly concerned gasoline-vehicle sources (31.5%), diesel-related emissions (20.8%), industrial emissions (18.6%) and ship emissions (7.5%). These findings provide valuable insights into the efficacy of the implemented measures in reducing atmospheric I/SVOCs levels. Moreover, our results highlight the significance of exploring additional individual species of I/SVOCs and life-related sources for further research and policy development.


Assuntos
Poluentes Atmosféricos , Hidrocarbonetos Policíclicos Aromáticos , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , China , Compostos Orgânicos Voláteis/análise , Monitoramento Ambiental/métodos , Alcanos/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Aerossóis/análise , Emissões de Veículos/análise , Material Particulado/análise
17.
Materials (Basel) ; 17(5)2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38473646

RESUMO

In the field of highway construction, the application of styrene-butadiene rubber (SBR)-modified asphalt has gained popularity across different levels of road surfaces. A crucial aspect in ensuring the efficacy of this modification lies in the compatibility between SBR and the matrix asphalt. To address this, the current study utilizes molecular dynamics simulation as a technique. By establishing a model for the SBR-modified asphalt mixture, the research quantifies the compatibility level between the SBR modifier and the asphalt. The aim is to uncover the underlying mechanisms of compatibility between the SBR modifier and the base asphalt, ultimately contributing to the improvement of the storage stability of SBR-modified asphalt, which holds significant importance. The investigation began with the creation of models for both the base asphalt and the SBR modifier. A model for the SBR-modified asphalt blending system was then formulated based on these initial models. After undergoing geometry optimization and annealing procedures, the model attained its lowest energy state, providing a reliable basis for examining the performance of SBR-modified asphalt. The study proceeded to calculate solubility parameters and interaction energies of the system to evaluate the compatibility between the SBR modifier and the base asphalt at various temperatures. The analysis of these parameters shed light on the compatibility mechanism between the two components. Notably, it was found that at a temperature of 160 ℃, the compatibility was significantly enhanced. The findings were further corroborated through scanning electron microscope and rheological tests. The outcomes of this research offer theoretical guidance for the application of SBR-modified asphalt.

18.
Heliyon ; 10(6): e28051, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38533062

RESUMO

Skill-related physical fitness significantly correlates with sports performance. Plyometric training (PT) is an effective method for improving physical fitness in athletes. However, its impact on skill-related physical fitness in badminton players remains uncertain. Therefore, this systematic review and meta-analysis aimed to evaluate the effectiveness of PT on skill-related physical fitness in badminton players. Five electronic databases (Web of Science, PubMed, SCOPUS, MEDLINE, and SPORTSDiscus) were searched until February 2024. A PICOS approach was used to identify inclusion criteria, (1) healthy badminton players, (2) a PT program, (3) an active control group, (4) a measure of skill-related physical fitness before and after PT, and (5) randomized controlled studies. The PEDro scale was used to assess the methodological quality of PT studies, while the level of evidence certainty was determined through the GRADE framework. The calculation of effect sizes (ESs) was based on mean values and standard deviations, and heterogeneity was measured with the I2 statistic. The extended Egger's test was employed to check for publication bias. Eleven studies comprising 445 badminton players were eligible for inclusion. The analysis revealed significant small-to-moderate effects of PT on power (ES = 0.60, p < 0.001), agility (ES = 0.96, p < 0.001), speed (ES = 0.63, p = 0.001), and balance (ES = 0.89; p = 0.013). However, no significant effect was observed for reaction time (ES = 0.56; p = 0.189). The certainty of evidence for outcomes was graded as either low or very low. In conclusion, our findings demonstrate that PT improved power, agility, speed, and balance, but not reaction time in badminton players. However, the small number of studies and the very low to low certainty evidence mean that these results need to be interpreted with caution.

19.
Behav Sci (Basel) ; 14(3)2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38540510

RESUMO

Motor imagery training is a common mental strategy used by tennis players and coaches to improve learning and performance; however, the effect of motor imagery training on service performance in tennis players is questionable. This review aims to consolidate existing research regarding the effects of motor imagery training on the service performance of tennis players. A systematic search was conducted following the PRISMA guidelines, using PubMed, Web of Science, SCOPUS, and SPORTDiscus to identify articles published until December 2023. Eligible studies comprised controlled trials that investigated the impact of motor imagery on service performance outcomes in tennis players. The methodological quality of individual studies was assessed using the Cochrane RoB-2 and ROBINS-I tools. GRADE was applied to assess the certainty of the evidence. Nine trials including 548 participants met the inclusion criteria. The results indicated that motor imagery training improved service accuracy and technique but did not affect service speed or return accuracy in tennis players. In conclusion, the certainty of the evidence that motor imagery training may be effective in improving service accuracy and technique in tennis players is low to very low. However, more experimental work is needed to obtain stronger conclusions.

20.
Int J Mol Sci ; 25(6)2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38542120

RESUMO

China leads the world in freshwater pearl production, an industry in which the triangle sail mussel (Sinohyriopsis cumingii) plays a pivotal role. In this paper, we report a high-quality chromosome-level genome assembly of S. cumingii with a size of 2.90 Gb-the largest yet reported among bivalves-and 89.92% anchorage onto 19 linkage groups. The assembled genome has 37,696 protein-coding genes and 50.86% repeat elements. A comparative genomic analysis revealed expansions of 752 gene families, mostly associated with biomineralization, and 237 genes under strong positive selection. Notably, the fibrillin gene family exhibited gene family expansion and positive selection simultaneously, and it also exhibited multiple high expressions after mantle implantation by transcriptome analysis. Furthermore, RNA silencing and an in vitro calcium carbonate crystallization assay highlighted the pivotal role played by one fibrillin gene in calcium carbonate deposition and aragonite transformation. This study provides a valuable genomic resource and offers new insights into the mechanism of pearl biomineralization.


Assuntos
Bivalves , Unionidae , Animais , Biomineralização/genética , Bivalves/genética , Bivalves/química , Unionidae/genética , Unionidae/metabolismo , Carbonato de Cálcio , Água Doce , Fibrilinas/metabolismo
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