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Vacancy-ordered perovskites and derivatives represent an important subclass of hybrid metal halides with promise in applications including light emitting devices and photovoltaics. Understanding the vacancy-property relationship is crucial for designing related task-specific materials, yet research in this field remains sporadic. For the first time, we use the Connolly surface to quantitatively calculate the volume of vacancy (Vâ¡, â¡ = vacancy) in vacancy-ordered double perovskite derivatives (VDPDs). A relationship between void fraction and the structure, photoluminescent properties and humidity stability was established based on zero-dimensional (0-D) [N(alkyl)4]2Sbâ¡Cl5â¡'-type VDPDs. Compared with the more commonly studied A2M(IV)X6â¡-type double perovskite (A = cation, M = metal ion, X = halide), [N(alkyl)4]2Sbâ¡Cl5â¡' features double vacancy sites. Our results demonstrate an inverse relationship between the photoluminescent quantum yield and Vâ¡ in 0-D VDPDs. Additionally, structural transformation from A2SbCl5 to A3Sb2Cl9 was first reported, during which the novel 'gate-opening' gas adsorption phenomenon was observed in VDPDs for the first time, as evidenced by 'S'-shaped sorption isotherms for water vapor, indicating a cation-controlled water-vapor response behavior. A mixed-cation strategy was developed to modulate the humidity stability of VDPDs. Characterized by controllable water-responsive behavior and unique 'on-off-on' luminescent switching, A2M(III)â¡X5â¡'-type materials show great promise for multi-level information anti-counterfeiting applications.
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Low-salt pickled vegetables are in line with a healthier diet, yet ensuring consistent quality of such products is challenging. In this study, low-salt tuber mustard pickles fermented with Lactiplantibacillus plantarum LPP95 in the presence of chitosan and inulin were analyzed over a 30-day period, and quality changes were evaluated. Total acid productions along with high bacterial counts (106â¯CFU/mL) were observed in the initial 20â¯days during indoor storage temperature, in which the reduced fiber aperture was found significantly lead to an increase in crispness (16.94⯱â¯1.87â¯N) and the maintenance of a low nitrate content (1.23⯱â¯0.01â¯mg/kg). Moreover, the combined pickling treatment resulted in higher malic acid content, lower tartaric acid content, and a decrease in the content of bitter amino acids (e.g., isoleucine and leucine), thus leading to an increase in the proportion of sweet amino acids. Additionally, combined pickling led to the production of unique volatile flavor compounds, especially the distinct spicy flavor compounds isothiocyanates. Moreover, the combined pickling treatment resulted in an increase in the abundance of Lactiplantibacillus and promoted microbial diversity within the fermentation system. Thus, the synergistic effect among chitosan, inulin, and L. plantarum LPP95 significantly enhanced the quality of pickles. The study offers a promising strategy to standardize the quality of low-salt fermented vegetables.
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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.
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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.
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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.
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Oxyde d'aluminium , Électricité , Minéraux , Thermodynamique , Oxyde d'aluminium/composition chimique , Cinétique , Minéraux/composition chimique , Concentration en ions d'hydrogèneRÉSUMÉ
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.
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Modèles animaux de maladie humaine , Souris de lignée C57BL , Syndromes parkinsoniens , Probénécide , Stimulation magnétique transcrânienne , Animaux , Stimulation magnétique transcrânienne/méthodes , Souris , Mâle , Probénécide/pharmacologie , Syndromes parkinsoniens/induit chimiquement , Syndromes parkinsoniens/thérapie , Syndromes parkinsoniens/métabolisme , Syndromes parkinsoniens/physiopathologie , Facteur neurotrophique dérivé du cerveau/métabolisme , Cortex moteur/métabolisme , Cortex moteur/physiopathologie , Neurones dopaminergiques/métabolisme , Transporteurs de la dopamine/métabolisme , Interleukine-1 bêta/métabolisme , Substantia nigra/métabolisme , Corps strié/métabolisme , Transporteurs vésiculaires des monoamines/métabolisme , Intoxication au MPTP/thérapie , Intoxication au MPTP/prévention et contrôle , Intoxication au MPTP/métabolisme , Intoxication au MPTP/physiopathologie , Activité motrice/physiologie , 1-Méthyl-4-phényl-1,2,3,6-tétrahydropyridine/pharmacologieRÉSUMÉ
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.
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Coagulation sanguine , Plaquettes , Souris de lignée C57BL , Granulocytes neutrophiles , Granulocytes neutrophiles/métabolisme , Animaux , Humains , Plaquettes/métabolisme , Souris , Hémostase , Mouvement cellulaire , Activation plaquettaire , Mâle , Facteurs de la coagulation sanguine/métabolisme , Facteurs de la coagulation sanguine/génétiqueRÉSUMÉ
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.
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Méthylation de l'ADN , Hypertension artérielle , Locus de caractère quantitatif , Animaux , Hypertension artérielle/génétique , Hypertension artérielle/métabolisme , Hypertension artérielle/physiopathologie , Mâle , Souris , Étude d'association pangénomique , Canaux potassiques à pores à domaines en tandem/génétique , Canaux potassiques à pores à domaines en tandem/métabolisme , Souris de lignée C57BL , Humains , Épigenèse génétique , Prédisposition génétique à une maladie , Chlorure de sodium alimentaire/effets indésirables , Pression sanguine/génétiqueRÉSUMÉ
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 (â¢OH, O2â¢-, 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.
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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.
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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.
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Référenciation , Chromatine , Chromatine/composition chimique , Humains , Biologie informatique/méthodes , Logiciel , Assemblage et désassemblage de la chromatineRÉSUMÉ
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.
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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.
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Indice de masse corporelle , Capacité cardiorespiratoire , Force musculaire , Aptitude physique , Exercice de pliométrie , Humains , Aptitude physique/physiologie , Force musculaire/physiologie , Exercice de pliométrie/méthodes , Capacité cardiorespiratoire/physiologie , Mâle , Femelle , AdulteRÉSUMÉ
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.
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Aptitude physique , Jeux vidéo , Humains , Aptitude physique/physiologie , Sujet âgé , Force musculaire/physiologie , Adulte d'âge moyen , Exercice physique , Mâle , Femelle , Essais contrôlés randomisés comme sujetRÉSUMÉ
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.
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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.
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Biofilms , Desulfovibrio , Microbiome gastro-intestinal , Probiotiques , Desulfovibrio/métabolisme , Desulfovibrio/physiologie , Humains , Microbiome gastro-intestinal/physiologie , Biofilms/croissance et développement , Intestins/microbiologie , Prébiotiques , Animaux , Acides gras volatils/métabolisme , Sulfure d'hydrogène/métabolisme , Régime alimentaireRÉSUMÉ
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.
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Hyperhomocystéinémie , Inflammasomes , Souris knockout , Protéine-3 de la famille des NLR contenant un domaine pyrine , Podocytes , Sphingomyeline phosphodiesterase , Animaux , Sphingomyeline phosphodiesterase/génétique , Sphingomyeline phosphodiesterase/métabolisme , Podocytes/métabolisme , Podocytes/anatomopathologie , Protéine-3 de la famille des NLR contenant un domaine pyrine/métabolisme , Protéine-3 de la famille des NLR contenant un domaine pyrine/génétique , Hyperhomocystéinémie/métabolisme , Hyperhomocystéinémie/complications , Hyperhomocystéinémie/génétique , Inflammasomes/métabolisme , Inflammasomes/génétique , Glomérule rénal/anatomopathologie , Glomérule rénal/métabolisme , Glomérulonéphrite/anatomopathologie , Glomérulonéphrite/métabolisme , Glomérulonéphrite/génétique , Extinction de l'expression des gènes , Souris , Souris de lignée C57BL , Vésicules extracellulaires/métabolisme , Mâle , Modèles animaux de maladie humaineRÉSUMÉ
Background: To explore the genetic defects of a Chinese family with complete Schubert-Bornschein type congenital stationary night blindness (CSNB). Methods: A Chinese family with complete Schubert-Bornschein type CSNB was enrolled in this study. The detailed ocular presentations of the patient were recorded. Targeted gene sequencing including 156 genes related to retinal diseases was used to detect the gene mutation. Sanger sequencing was performed to validate the potential pathogenic variants, and segregation analysis was performed on all available family members. Bioinformatics analysis was performed to predict the impact of the mutations. Results: By targeted gene sequencing and Sanger sequencing, we identified compound heterozygous mutations in GRM6: c.152G>T (p.Gly51Val) and c.727delG (p.Val243SerfsX21). Segregation analysis demonstrated that the mother of the proband carried the missense mutation (c.152G>T) while her father carried the frameshift mutation (c.727delG), indicating CSNB was autosomal recessively inherited in this family. Several bioinformatics prediction programs revealed the mutations were "Damaging" or "Disease Causing" and conservation analysis showed both the codons Gly51 and Val243 were highly conserved among species, suggesting the changes were pathogenic. Conclusion: By targeted gene sequencing and Sanger sequencing, we detected compound heterozygous mutations (c.152G>T, p.Gly51Val and c.727delG, p.Val243SerfsX21) in GRM6. The mutations co-segregated with the phenotype of the family members and are considered to be responsible for complete Schubert-Bornschein type CSNB. However, functional experiments in the future are needed to confirm the pathogenicity of the variants and to elucidate their exact molecular mechanisms causing CSNB.
RÉSUMÉ
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.
RÉSUMÉ
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.