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1.
Front Microbiol ; 15: 1428233, 2024.
Article de Anglais | MEDLINE | ID: mdl-38957619

RÉSUMÉ

African swine fever virus (ASFV) is notoriously known for evolving strategies to modulate IFN signaling. Despite lots of efforts, the underlying mechanisms have remained incompletely understood. This study concerns the regulatory role of viral inner membrane protein p17. We found that the ASFV p17 shows a preferential interaction with cGAS-STING-IRF3 pathway, but not the RIG-I-MAVS-NF-κB signaling, and can inhibit both poly(I:C)- and poly(A:T)-induced activation of IRF3, leading to attenuation of IFN-ß induction. Mechanistically, p17 interacts with STING and IRF3 and recruits host scaffold protein PR65A, a subunit of cellular phosphatase PP2A, to down-regulate the level of p-IRF3. Also, p17 targets STING for partial degradation via induction of cellular apoptosis that consequently inhibits activation of both p-TBK1 and p-IRF3. Thus, our findings reveal novel regulatory mechanisms for p17 modulation of IFN signaling and shed light on the intricate interplay between ASFV proteins and host immunity.

2.
Front Plant Sci ; 15: 1346182, 2024.
Article de Anglais | MEDLINE | ID: mdl-38952848

RÉSUMÉ

Accurate and real-time field wheat ear counting is of great significance for wheat yield prediction, genetic breeding and optimized planting management. In order to realize wheat ear detection and counting under the large-resolution Unmanned Aerial Vehicle (UAV) video, Space to depth (SPD) module was added to the deep learning model YOLOv7x. The Normalized Gaussian Wasserstein Distance (NWD) Loss function is designed to create a new detection model YOLOv7xSPD. The precision, recall, F1 score and AP of the model on the test set are 95.85%, 94.71%, 95.28%, and 94.99%, respectively. The AP value is 1.67% higher than that of YOLOv7x, and 10.41%, 39.32%, 2.96%, and 0.22% higher than that of Faster RCNN, SSD, YOLOv5s, and YOLOv7. YOLOv7xSPD is combined with the Kalman filter tracking and the Hungarian matching algorithm to establish a wheat ear counting model with the video flow, called YOLOv7xSPD Counter, which can realize real-time counting of wheat ears in the field. In the video with a resolution of 3840×2160, the detection frame rate of YOLOv7xSPD Counter is about 5.5FPS. The counting results are highly correlated with the ground truth number (R2 = 0.99), and can provide model basis for wheat yield prediction, genetic breeding and optimized planting management.

3.
Cell Death Dis ; 15(6): 392, 2024 Jun 04.
Article de Anglais | MEDLINE | ID: mdl-38834617

RÉSUMÉ

Keratinocyte proliferation and differentiation in epidermis are well-controlled and essential for reacting to stimuli such as ultraviolet light. Imbalance between proliferation and differentiation is a characteristic feature of major human skin diseases such as psoriasis and squamous cell carcinoma. However, the effect of keratinocyte metabolism on proliferation and differentiation remains largely elusive. We show here that the gluconeogenic enzyme fructose-1,6-bisphosphatase 1 (FBP1) promotes differentiation while inhibits proliferation of keratinocyte and suppresses psoriasis development. FBP1 is identified among the most upregulated genes induced by UVB using transcriptome sequencing and is elevated especially in upper epidermis. Fbp1 heterozygous mice exhibit aberrant epidermis phenotypes with local hyperplasia and dedifferentiation. Loss of FBP1 promotes proliferation and inhibits differentiation of keratinocytes in vitro. Mechanistically, FBP1 loss facilitates glycolysis-mediated acetyl-CoA production, which increases histone H3 acetylation at lysine 9, resulting in enhanced transcription of proliferation genes. We further find that the expression of FBP1 is dramatically reduced in human psoriatic lesions and in skin of mouse imiquimod psoriasis model. Fbp1 deficiency in mice facilitates psoriasis-like skin lesions development through glycolysis and acetyl-CoA production. Collectively, our findings reveal a previously unrecognized role of FBP1 in epidermal homeostasis and provide evidence for FBP1 as a metabolic psoriasis suppressor.


Sujet(s)
Différenciation cellulaire , Prolifération cellulaire , Fructose-1,6-diphosphatase , Histone , Kératinocytes , Psoriasis , Animaux , Humains , Souris , Acétyl coenzyme A/métabolisme , Acétylation , Modèles animaux de maladie humaine , Fructose-1,6-diphosphatase/métabolisme , Fructose-1,6-diphosphatase/génétique , Glycolyse , Histone/métabolisme , Kératinocytes/métabolisme , Kératinocytes/anatomopathologie , Souris de lignée C57BL , Psoriasis/anatomopathologie , Psoriasis/métabolisme , Psoriasis/génétique
4.
Sci Rep ; 14(1): 13435, 2024 06 11.
Article de Anglais | MEDLINE | ID: mdl-38862650

RÉSUMÉ

Diabetic corneal neuropathy (DCN) is a common diabetic ocular complication with limited treatment options. In this study, we investigated the effects of topical and oral fenofibrate, a peroxisome proliferator-activated receptor-α agonist, on the amelioration of DCN using diabetic mice (n = 120). Ocular surface assessments, corneal nerve and cell imaging analysis, tear proteomics and its associated biological pathways, immuno-histochemistry and western blot on PPARα expression, were studied before and 12 weeks after treatment. At 12 weeks, PPARα expression markedly restored after topical and oral fenofibrate. Topical fenofibrate significantly improved corneal nerve fibre density (CNFD) and tortuosity coefficient. Likewise, oral fenofibrate significantly improved CNFD. Both topical and oral forms significantly improved corneal sensitivity. Additionally, topical and oral fenofibrate significantly alleviated diabetic keratopathy, with fenofibrate eye drops demonstrating earlier therapeutic effects. Both topical and oral fenofibrate significantly increased corneal ß-III tubulin expression. Topical fenofibrate reduced neuroinflammation by significantly increasing the levels of nerve growth factor and substance P. It also significantly increased ß-III-tubulin and reduced CDC42 mRNA expression in trigeminal ganglions. Proteomic analysis showed that neurotrophin signalling and anti-inflammation reactions were significantly up-regulated after fenofibrate treatment, whether applied topically or orally. This study concluded that both topical and oral fenofibrate ameliorate DCN, while topical fenofibrate significantly reduces neuroinflammation.


Sujet(s)
Cornée , Diabète expérimental , Neuropathies diabétiques , Fénofibrate , Récepteur PPAR alpha , Animaux , Récepteur PPAR alpha/agonistes , Récepteur PPAR alpha/métabolisme , Souris , Fénofibrate/pharmacologie , Fénofibrate/administration et posologie , Diabète expérimental/traitement médicamenteux , Diabète expérimental/complications , Diabète expérimental/métabolisme , Neuropathies diabétiques/traitement médicamenteux , Neuropathies diabétiques/métabolisme , Cornée/métabolisme , Cornée/effets des médicaments et des substances chimiques , Cornée/innervation , Cornée/anatomopathologie , Mâle , Administration par voie orale , Administration par voie topique , Maladies de la cornée/traitement médicamenteux , Maladies de la cornée/étiologie , Maladies de la cornée/métabolisme , Maladies de la cornée/anatomopathologie , Souris de lignée C57BL , Protéomique/méthodes
5.
Anal Chem ; 96(25): 10356-10364, 2024 Jun 25.
Article de Anglais | MEDLINE | ID: mdl-38863415

RÉSUMÉ

Capillary electrophoresis with capacitively coupled contactless conductivity detection (CE-C4D) has proven to be an efficient technique for the separation and detection of charged inorganic, organic, and biochemical analytes. It offers several advantages, including cost-effectiveness, nanoliter injection volume, short analysis time, good separation efficiency, suitability for miniaturization, and portability. However, the routine determination of common inorganic cations (NH4+, K+, Na+, Ca2+, Mg2+, and Li+) and inorganic anions (F-, Cl-, Br-, NO2-, NO3-, PO43-, and SO42-) in water quality monitoring typically exhibits limits of detection of about 0.3-1 µM without preconcentration. This sensitivity often proves insufficient for the applications of CE-C4D in trace analysis situations. Here, we explore methods to push the detection limits of CE-C4D through a comprehensive consideration of signal and noise sources. In particular, we (i) studied the model of C4D and its guiding roles in C4D and CE-C4D, (ii) optimized the bandwidth and noise performance of the current-to-voltage (I-V) converter, and (iii) reduced the noise level due to the strong background signal of the background electrolyte by adaptive differential detection. We characterized the system with Li+; the 3-fold signal-to-noise (S/N) detection limit for Li+ was determined at 20 nM, with a linear range spanning from 60 nM to 1.6 mM. Moreover, the optimized CE-C4D method was applied to the analysis of common mixed inorganic cations (K+, Na+, Ca2+, Mg2+, and Li+), anions (F-, Cl-, Br-, NO2-, NO3-, PO43-, and SO42-), toxic halides (BrO3-) and heavy metal ions (Pb2+, Cd2+, Cr3+, Co2+, Ni2+, Zn2+, and Cu2+) at trace concentrations of 200 nM. All electropherograms showed good S/N ratios, thus proving its applicability and accuracy. Our results have shown that the developed CE-C4D method is feasible for trace ion analysis in water quality control.

6.
Cancer Res ; 2024 Jun 20.
Article de Anglais | MEDLINE | ID: mdl-38900939

RÉSUMÉ

Analysis of extracellular vesicles (EVs) is a promising noninvasive liquid biopsy approach for breast cancer (BC) detection, prognosis, and therapeutic monitoring. A comprehensive understanding of the characteristics and proteomic composition of BC-specific EVs from human samples is required to realize the potential of this strategy. In this study, we applied a mass spectrometry-based, data-independent acquisition (DIA) proteomic approach to characterize human serum EVs derived from patients with BC (n = 126) and healthy donors (HDs, n = 70) in a discovery cohort and validated the findings in five independent cohorts. Examination of the EV proteomes enabled construction of specific EV protein classifiers for diagnosing BC and distinguishing patients with metastatic disease. Of note, TALDO1 was found to be an EV biomarker of distant metastasis of BC. In vitro and in vivo analysis confirmed the role of TALDO1 in stimulating BC invasion and metastasis. Finally, high-throughput molecular docking and virtual screening of a library consisting of 271,380 small molecules identified a potent TALDO1 allosteric inhibitor, AO-022, which could inhibit BC migration in vitro and tumor progression in vivo. Together, this work elucidates the proteomic alterations in the serum EVs of BC patients to guide development of improved diagnosis, monitoring, and treatment strategies.

7.
Front Endocrinol (Lausanne) ; 15: 1409267, 2024.
Article de Anglais | MEDLINE | ID: mdl-38904038

RÉSUMÉ

Introduction: To explore whether blood flow-restrictive resistance exercise (BFRE) can be used as an alternative strategy to moderate-intensity resistance training (RT) to improve metabolic disorder and body composition in older adults with type 2 diabetes (T2DM). Methods: This is a single-blind, randomized, controlled trial. Ninety-eight older adults with T2DM were randomly divided into three groups: BFRE group (n = 34), RT group (n = 31) and control group (n = 33). Two exercise groups received supervised collective training for a period of six months, each lasting 50 min, three times a week. The primary outcomes included fasting plasma glucose (FPG), Glycosylated hemoglobin (HbA1c), blood lipids, blood pressure, and body composition. The secondary outcome was muscle performance. Results: After six months of intervention, the FPG, HbA1c, blood lipids, diastolic blood pressure, body composition, and muscle performance of the two exercise groups were significantly improved relative to the control group and baseline measurements (P < 0.05). There was no significant increase in lean mass between the two exercise groups compared to the control group and baseline (p > 0.05). There was no significant decrease in systolic blood pressure between the two exercise groups compared to the control group (p > 0.05), but it was significantly lower than their baseline (P < 0.05). There was no significant difference in all indicators between the two exercise groups at the baseline, third and sixth months of intervention (p > 0.05). Discussion: BFRE can safely and effectively improve the metabolic disorder and body composition of older adults with T2DM. For elderly exercise beginners, BFRE can be used as an alternative strategy to moderate-intensity resistance training. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=178886, identifier ChiCTR2300074357.


Sujet(s)
Composition corporelle , Diabète de type 2 , Entraînement en résistance , Humains , Diabète de type 2/thérapie , Diabète de type 2/physiopathologie , Diabète de type 2/sang , Entraînement en résistance/méthodes , Mâle , Femelle , Sujet âgé , Méthode en simple aveugle , Adulte d'âge moyen , Hémoglobine glyquée/analyse , Hémoglobine glyquée/métabolisme , Glycémie/métabolisme , Pression sanguine/physiologie , Débit sanguin régional/physiologie , Lipides/sang
8.
Org Lett ; 26(24): 5220-5225, 2024 Jun 21.
Article de Anglais | MEDLINE | ID: mdl-38856637

RÉSUMÉ

A visible-light-promoted radical gem-difunctionalization of trifluorodiazoethane with RSO2X (X = SeR', I) for the synthesis of α-seleno or α-iodo trifluoroethyl sulfones is described. This atom-economical reaction is external-photocatalyst- and additive-free and uses nontoxic ethyl acetate as the solvent. The resultant products, which incorporate sulfonyl, trifluoromethyl, and iodo or selenyl functional groups onto one carbon atom, can serve as versatile building blocks. A major synthetic application was demonstrated by ATRA reactions with various terminal alkynes.

9.
Cancer Discov ; 2024 Jun 25.
Article de Anglais | MEDLINE | ID: mdl-38922581

RÉSUMÉ

Comprehensive m6A epitranscriptome profiling of primary tumors remains largely uncharted. Here, we profiled the m6A epitranscriptome of 10 non-neoplastic lung (NL) tissues and 51 lung adenocarcinoma (LUAD) tumors, integrating the corresponding transcriptome, proteome and extensive clinical annotations. We identified distinct clusters and genes that were exclusively linked to disease progression through m6A modifications. In comparison with NL tissues, we identified 430 transcripts to be hypo-methylated and 222 to be hyper-methylated in tumors. Among these genes, EML4 emerged as a novel metastatic driver, displaying significant hyper-methylation in tumors. m6A modification promoted the translation of EML4, leading to its widespread overexpression in primary tumors. Functionally, EML4 modulated cytoskeleton dynamics through interacting with ARPC1A, enhancing lamellipodia formation, cellular motility, local invasion, and metastasis. Clinically, high EML4 protein abundance correlated with features of metastasis. METTL3 small molecule inhibitor markedly diminished both EML4 m6A and protein abundance, and efficiently suppressed lung metastases in vivo.

10.
Front Neurosci ; 18: 1402039, 2024.
Article de Anglais | MEDLINE | ID: mdl-38933814

RÉSUMÉ

Purpose: Sensorineural hearing loss (SNHL) is the most common form of sensory deprivation and is often unrecognized by patients, inducing not only auditory but also nonauditory symptoms. Data-driven classifier modeling with the combination of neural static and dynamic imaging features could be effectively used to classify SNHL individuals and healthy controls (HCs). Methods: We conducted hearing evaluation, neurological scale tests and resting-state MRI on 110 SNHL patients and 106 HCs. A total of 1,267 static and dynamic imaging characteristics were extracted from MRI data, and three methods of feature selection were computed, including the Spearman rank correlation test, least absolute shrinkage and selection operator (LASSO) and t test as well as LASSO. Linear, polynomial, radial basis functional kernel (RBF) and sigmoid support vector machine (SVM) models were chosen as the classifiers with fivefold cross-validation. The receiver operating characteristic curve, area under the curve (AUC), sensitivity, specificity and accuracy were calculated for each model. Results: SNHL subjects had higher hearing thresholds in each frequency, as well as worse performance in cognitive and emotional evaluations, than HCs. After comparison, the selected brain regions using LASSO based on static and dynamic features were consistent with the between-group analysis, including auditory and nonauditory areas. The subsequent AUCs of the four SVM models (linear, polynomial, RBF and sigmoid) were as follows: 0.8075, 0.7340, 0.8462 and 0.8562. The RBF and sigmoid SVM had relatively higher accuracy, sensitivity and specificity. Conclusion: Our research raised attention to static and dynamic alterations underlying hearing deprivation. Machine learning-based models may provide several useful biomarkers for the classification and diagnosis of SNHL.

11.
ACS Appl Mater Interfaces ; 16(25): 31922-31935, 2024 Jun 26.
Article de Anglais | MEDLINE | ID: mdl-38874539

RÉSUMÉ

Poly-l-lysine (PLL) and Matrigel, both classical coating materials for culture substrates in neural stem cell (NSC) research, present distinct interfaces whose effect on NSC behavior at cellular and molecular levels remains ambiguous. Our investigation reveals intriguing disparities: although both PLL and Matrigel interfaces are hydrophilic and feature amine functional groups, Matrigel stands out with lower stiffness and higher roughness. Based on this diversity, Matrigel surpasses PLL, driving NSC adhesion, migration, and proliferation. Intriguingly, PLL promotes NSC differentiation into astrocytes, whereas Matrigel favors neural differentiation and the physiological maturation of neurons. At the molecular level, Matrigel showcases a wider upregulation of genes linked to NSC behavior. Specifically, it enhances ECM-receptor interaction, activates the YAP transcription factor, and heightens glycerophospholipid metabolism, steering NSC proliferation and neural differentiation. Conversely, PLL upregulates genes associated with glial cell differentiation and amino acid metabolism and elevates various amino acid levels, potentially linked to its support for astrocyte differentiation. These distinct transcriptional and metabolic activities jointly shape the divergent NSC behavior on these substrates. This study significantly advances our understanding of substrate regulation on NSC behavior, offering novel insights into optimizing and targeting the application of these surface coating materials in NSC research.


Sujet(s)
Différenciation cellulaire , Prolifération cellulaire , Collagène , Association médicamenteuse , Laminine , Cellules souches neurales , Polylysine , Protéoglycanes , Polylysine/composition chimique , Cellules souches neurales/cytologie , Cellules souches neurales/métabolisme , Cellules souches neurales/effets des médicaments et des substances chimiques , Laminine/composition chimique , Laminine/pharmacologie , Collagène/composition chimique , Différenciation cellulaire/effets des médicaments et des substances chimiques , Prolifération cellulaire/effets des médicaments et des substances chimiques , Protéoglycanes/composition chimique , Protéoglycanes/pharmacologie , Animaux , Adhérence cellulaire/effets des médicaments et des substances chimiques , Mouvement cellulaire/effets des médicaments et des substances chimiques , Souris
12.
Am Heart J ; 2024 Jun 26.
Article de Anglais | MEDLINE | ID: mdl-38942221

RÉSUMÉ

BACKGROUND: It is currently uncertain whether the combination of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and high-intensity statin treatment can effectively reduce cardiovascular events in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) for culprit lesions. METHODS: This study protocol describes a double-blind, randomized, placebo-controlled, multicenter study aiming to investigate the efficacy and safety of combining a PCSK9 inhibitor with high-intensity statin therapy in patients with ACS following PCI. A total of 1212 patients with ACS and multiple lesions will be enrolled and randomly assigned to receive either PCSK9 inhibitor plus high-intensity statin therapy or high-intensity statin monotherapy. The randomization process will be stratified by sites, diabetes, initial presentation and use of stable (≥4 weeks) statin treatment at presentation. PCSK 9 inhibitor or its placebo is injected within 4 hours after PCI for the culprit lesion. The primary endpoint is the composite of cardiovascular death, myocardial infarction, stroke, re-hospitalization due to ACS or heart failure, or any ischemia-driven coronary revascularization at one-year follow-up between two groups. Safety endpoints mean PCSK 9 inhibitor and statin intolerance. CONCLUSION: The SHAWN study has been specifically designed to evaluate the effectiveness and safety of adding a PCSK9 inhibitor to high-intensity statin therapy in patients who have experienced ACS following PCI. The primary objective of this study is to generate new evidence regarding the potential benefits of combining a PCSK9 inhibitor with high-intensity statin treatment in reducing cardiovascular events among these patients.

13.
Front Pharmacol ; 15: 1393874, 2024.
Article de Anglais | MEDLINE | ID: mdl-38855745

RÉSUMÉ

Introduction: The prevalence of major depressive disorder (MDD) has gradually increased and has attracted widespread attention. The aim of this study was to investigate the effect of a probiotic compound consisting of Bacillus coagulans and Clostridium butyricum, on a mouse depression model. Methods: Mice were subjected to chronic unpredictable mild stress (CUMS) and then treated with the probiotics at different concentrations. And mice received behavior test such as forced swimming test and tail suspension test. After that, all mice were sacrificed and the samples were collected for analysis. Moreover, prefrontal cortex (PFC) gene expression and the gut microbiota among different groups were also analyzed. Results: Probiotics improved depressive-like behavior in CUMS mice, as indicated by decreased immobility time (p < 0.05) in the forced swimming test and tail suspension test. probiotics intervention also increased the level of 5-hydroxytryptamine (5-HT) in the prefrontal cortex and decreased the adrenocorticotropic hormone (ACTH) level in serum. In addition, by comparing the PFC gene expression among different groups, we found that the genes upregulated by probiotics were enriched in the PI3K-Akt signaling pathway in the prefrontal cortex. Moreover, we found that downregulated genes in prefrontal cortex of CUMS group such as Sfrp5 and Angpt2, which were correlated with depression, were reversed by the probiotics. Furthermore, the probiotics altered the structure of the gut microbiota, and reversed the reduction of cob(II)yrinate a,c-diamide biosynthesis I pathway in CUMS group. Several species like Bacteroides caecimuris and Parabacteroides distasoni, whose abundance was significantly decreased in the CUMS group but reversed after the probiotics intervention, showed significantly positive correlation with depression associated genes such as Tbxas1 and Cldn2. Discussion: These findings suggested that CUMS-induced depression-like behavior can be alleviated by the probiotics, possibly through alterations in the PFC gene expression and gut microbiota.

14.
Adv Mater ; : e2406164, 2024 Jun 25.
Article de Anglais | MEDLINE | ID: mdl-38924614

RÉSUMÉ

The quest for artificial light sources that mimic sunlight's spectral characteristics has been a long-standing endeavor, particularly for applications in anticounterfeiting, agriculture, and color hue detection. Conventional sunlight simulators, such as xenon lamps, are often cost-prohibitive and bulky, limiting their adoption. In this regard, the development of a series of single-phase phosphors Ca9LiMg1-xAl2x/3(PO4)7:0.1Eu2+ (x = 0-0.75) with sunlight-like emission described in this work holds immense promise as a compact and economical light source alternative. The phosphors have been obtained by an original heterovalent substitution method and emit a broad spectrum that encompasses the entire visible region, spanning from violet to deep red. Notably, the phosphor with x = 0.5 exhibits an impressive full width at half maximum of 330 nm. A synergistic interplay of experimental investigations and density-functional theory calculations unveils the underlying mechanism behind sunlight-like emission. It is attributed to the local structural perturbations introduced by the heterovalent substitution of Al3+ for Mg2+, leading to a varied distribution of Eu2+ within the lattice. Subsequent characterization of a series of organic dyes combining absorption spectroscopy with convolutional neural network analysis convincingly demonstrates the potential of this phosphor in portable photodetection devices. Broad-spectrum light source testing empowers our model to precisely differentiate dye patterns. This points to the phosphor being ideal for mimicking sunlight. And beyond this demonstrated application, we envision the phosphor's utility in other relevant domains, including visible light communication and smart agriculture. These findings not only enrich our understanding of luminescent materials design but also pave the way for advancements in various application areas. This article is protected by copyright. All rights reserved.

15.
Exp Dermatol ; 33(6): e15120, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38886965

RÉSUMÉ

Ageing is an inevitable biological process characterized by progressive decline in physiological functions. It is a complex natural phenomenon that will cause structural and functional decline. Despite substantial progress in understanding the mechanism of ageing, both predictive biomarkers and preventive therapies remain limited. Using Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning techniques, we identified Carboxypeptidase E (CPE) as a pivotal marker of skin ageing, based on ageing-related bulk transcriptome and single-cell transcriptome data. Next, our investigation reveals downregulation of CPE in replicative, UVA-induced, and H2O2-induced senescent human dermal fibroblast cells (HDFs). Furthermore, shRNA-mediated CPE knockdown induced HDFs senescence, and overexpression of CPE delayed HDFs senescence. Moreover, downregulated CPE inhibits collagen synthesis and induces inflammation, highlighting its potential as a therapeutic target for skin ageing. In conclusion, our study demonstrated that CPE functions as a predictor and optional target for therapeutic intervention of skin ageing.


Sujet(s)
Marqueurs biologiques , Vieillissement de la cellule , Biologie informatique , Fibroblastes , Vieillissement de la peau , Humains , Vieillissement de la peau/génétique , Fibroblastes/métabolisme , Marqueurs biologiques/métabolisme , Apprentissage machine , Transcriptome , Collagène/métabolisme , Régulation négative , Peau/métabolisme , Rayons ultraviolets , Peroxyde d'hydrogène/métabolisme
16.
Environ Res ; 257: 119298, 2024 May 31.
Article de Anglais | MEDLINE | ID: mdl-38823616

RÉSUMÉ

Antibiotic resistance poses a considerable global public health concern, leading to heightened rates of illness and mortality. However, the impact of seasonal variations and environmental factors on the health risks associated with antibiotic resistance genes (ARGs) and their assembly mechanisms is not fully understood. Based on metagenomic sequencing, this study investigated the antibiotic resistome, mobile genetic elements (MGEs), and microbiomes in a subtropical coastal ecosystem of the Beibu Gulf, China, over autumn and winter, and explored the factors influencing seasonal changes in ARG and MGE abundance and diversity. Results indicated that ARG abundance and diversity were higher in winter than in autumn, with beta-lactam and multidrug resistance genes being the most diverse and abundant, respectively. Similarly, MGE abundance and diversity increased in winter and were strongly correlated with ARGs. In contrast, more pronounced associations between microbial communities, especially archaea, and the antibiotic resistome were observed in autumn than in winter. The co-occurrence network identified multiple interactions between MGEs and various multidrug efflux pumps in winter, suggesting a potential for ARG dissemination. Multivariate correlation analyses and path modeling indicated that environmental factors driving microbial community changes predominantly influenced antibiotic resistome assembly in autumn, while the relative importance of MGEs increased significantly in winter. These findings suggest an elevated health risk associated with antimicrobial resistance in the Beibu Gulf during winter, attributed to the dissemination of ARGs by horizontal gene transfer. The observed seasonal variations highlight the dynamic nature of antibiotic resistance dissemination in coastal ecosystems, emphasizing the need for comprehensive surveillance and management measures to address the growing threat of antimicrobial resistance in vulnerable environments.

17.
Neurotherapeutics ; : e00380, 2024 Jun 04.
Article de Anglais | MEDLINE | ID: mdl-38839450

RÉSUMÉ

Calcium influx and subsequent elevation of the intracellular calcium concentration ([Ca2+]i) induce contractions of brain pericytes and capillary spasms following subarachnoid hemorrhage. This calcium influx is exerted through cation channels. However, the specific calcium influx pathways in brain pericytes after subarachnoid hemorrhage remain unknown. Transient receptor potential canonical 3 (TRPC3) is the most abundant cation channel potentially involved in calcium influx into brain pericytes and is involved in calcium influx into other cell types either via store-operated calcium entry (SOCE) or receptor-operated calcium entry (ROCE). Therefore, we hypothesized that TRPC3 is associated with [Ca2+]i elevation in brain pericytes, potentially mediating brain pericyte contraction and capillary spasms after subarachnoid hemorrhage. In this study, we isolated rat brain pericytes and demonstrated increased TRPC3 expression and its currents in brain pericytes after subarachnoid hemorrhage. Calcium imaging of brain pericytes revealed that changes in TRPC3 expression mediated a switch from SOCE-dominant to ROCE-dominant calcium influx after subarachnoid hemorrhage, resulting in significantly higher [Ca2+]i levels after SAH. TRPC3 activity in brain pericytes also contributed to capillary spasms and reduction in cerebral blood flow in an in vivo rat model of subarachnoid hemorrhage. Therefore, we suggest that the switch in TRPC3-mediated calcium influx pathways plays a crucial role in the [Ca2+]i elevation in brain pericytes after subarachnoid hemorrhage, ultimately leading to capillary spasms and a reduction in cerebral blood flow.

18.
Front Endocrinol (Lausanne) ; 15: 1400448, 2024.
Article de Anglais | MEDLINE | ID: mdl-38846493

RÉSUMÉ

Background and aims: According to previous studies, triglyceride-glucose (TyG) is related to chronic kidney disease (CKD), but no studies have explored the correlation between TyG and CKD among adults with metabolic dysfunction-associated fatty liver disease (MAFLD). We aimed to explore the associations of the TyG index with CKD among adults with MAFLD. Methods: In this retrospective observational cohort study, data from 11,860 participants who underwent a minimum of three health assessments between 2008 and 2015 were retrospectively collected. Participants were followed up until the final medical visit or health examination. CKD refers to an eGFR < 60 mL/min per 1·73 m2 or the occurrence of two or more incidents of proteinuria. Results: Within a median 10·02-year follow-up period, 2005 (16·9%) participants reported developing CKD. Multivariate Cox regression models indicated a noticeable correlation between the TyG index and CKD incidence (HR per unit increase, 1.19; 95% CI: 1.09-1.29) and between the TyG index and CKD incidence (HR per SD increase, 1.12; 95% CI: 1.06-1.18). The CKD incidence increased by 1.8 times in participants in the highest TyG index quartile relative to patients in the lowest quartile of the TyG index quartile (HR 1·18, 95% CI: 1.01-1.38, P = 0.007). According to subgroup analysis, an elevated TyG index is likely to become more harmful to participants younger than 60 years (P for interaction = 0.035). Conclusion: An elevated TyG index may increase CKD incidence among MAFLD adults, particularly among younger people. Early intervention may help reduce the incidence of CKD.


Sujet(s)
Glycémie , Insuffisance rénale chronique , Triglycéride , Humains , Insuffisance rénale chronique/sang , Insuffisance rénale chronique/épidémiologie , Mâle , Femelle , Adulte d'âge moyen , Triglycéride/sang , Études rétrospectives , Études de suivi , Adulte , Glycémie/analyse , Glycémie/métabolisme , Incidence , Stéatose hépatique non alcoolique/sang , Stéatose hépatique non alcoolique/épidémiologie , Stéatose hépatique non alcoolique/complications , Stéatose hépatique non alcoolique/métabolisme , Sujet âgé , Facteurs de risque
19.
J Infect Chemother ; 2024 May 31.
Article de Anglais | MEDLINE | ID: mdl-38823678

RÉSUMÉ

INTRUDUCTON: The most accurate method for detecting the pathogen of orthopedic implant-associated infections (OIAIs) is sonication fluid (SF). However, the frequency and duration of ultrasound significantly influence the number and activity of microorganisms. Currently, there is no consensus on the selection of these two parameters. Through this study, the choice of these two parameters is clarified. METHODS: We established five ultrasonic groups (40kHz/10min, 40kHz/5min, 40 kHz/1min, 20kHz/5min, and 10kHz/5min) based on previous literature. OIAIs models were then developed and applied to ultrasound group treatment. Subsequently, we evaluated the efficiency of bacteria removal by conducting SEM and crystal violet staining. The number of live bacteria in the SF was determined using plate colony count and live/dead bacteria staining. RESULTS: The results of crystal violet staining revealed that both the 40kHz/5min group and the 40kHz/10min group exhibited a significantly higher bacterial clearance rate compared to the other groups. However, there was no significant difference between the two groups. Additionally, the results of plate colony count and fluorescence staining of live and dead bacteria indicated that the number of live bacteria in the 40kHz/5min SF group was significantly higher than in the other groups. CONCLUSION: 40kHz/5min ultrasound is the most beneficial for the detection of pathogenic bacteria on the surface of orthopedic implants.

20.
Food Res Int ; 188: 114531, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38823850

RÉSUMÉ

Different emulsion gel systems are widely applied to deliver functional ingredients. The effects and mechanisms of ultrasound-assisted emulsification (UAE) treatment and carboxymethyl cellulose (CMC) modifying the curcumin delivery properties and in vitro digestibility of the myofibrillar protein (MP)-soybean oil emulsion gels were investigated. The rheological properties, droplet size, protein and CMC distribution, ultrastructure, surface hydrophobicity, sulfhydryl groups, and zeta potential of emulsion gels were also measured. Results indicate that UAE treatment and CMC addition both improved curcumin encapsulation and protection efficiency in MP emulsion gel, especially for the UAE combined with CMC (UAE-CMC) treatment which encapsulation efficiency, protection efficiency, the release rate, and bioaccessibility of curcumin increased from 86.75 % to 97.67 %, 44.85 % to 68.85 %, 18.44 % to 41.78 %, and 28.68 % to 44.93 % respectively. The protein digestibility during the gastric stage was decreased after the CMC addition and UAE treatment, and the protein digestibility during the intestinal stage was reduced after the CMC addition. The fatty acid release rate was increased after CMC addition and UAE treatment. Apparent viscosity, storage modulus, and loss modulus were decreased after CMC addition while increased after UAE and UAE-CMC treatment especially the storage modulus increased from 0.26 Pa to 41 Pa after UAE-CMC treatment. The oil size was decreased, the protein and CMC concentration around the oil was increased, and a denser and uniform emulsion gel network structure was formed after UAE treatment. The surface hydrophobicity, free SH groups, and absolute zeta potential were increased after UAE treatment. The UAE-CMC treatment could strengthen the MP emulsion gel structure and decrease the oil size to increase the curcumin delivery properties, and hydrophobic and electrostatic interaction might be essential forces to maintain the emulsion gel.


Sujet(s)
Carboxyméthylcellulose de sodium , Curcumine , Digestion , Émulsions , Gels , Interactions hydrophobes et hydrophiles , Rhéologie , Curcumine/composition chimique , Émulsions/composition chimique , Carboxyméthylcellulose de sodium/composition chimique , Gels/composition chimique , Protéines du muscle , Huile de soja/composition chimique , Viscosité , Taille de particule , Myofibrilles/composition chimique , Myofibrilles/métabolisme , Ondes ultrasonores
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