Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 173
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Adv Sci (Weinh) ; : e2309538, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491732

RESUMO

Memristors offer a promising solution to address the performance and energy challenges faced by conventional von Neumann computer systems. Yet, stochastic ion migration in conductive filament often leads to an undesired performance tradeoff between memory window, retention, and endurance. Herein, a robust memristor based on oxygen-rich SnO2 nanoflowers switching medium, enabled by seed-mediated wet chemistry, to overcome the ion migration issue for enhanced analog in-memory computing is reported. Notably, the interplay between the oxygen vacancy (Vo) and Ag ions (Ag+ ) in the Ag/SnO2 /p++ -Si memristor can efficiently modulate the formation and abruption of conductive filaments, thereby resulting in a high on/off ratio (>106), long memory retention (10-year extrapolation), and low switching variability (SV = 6.85%). Multiple synaptic functions, such as paired-pulse facilitation, long-term potentiation/depression, and spike-time dependent plasticity, are demonstrated. Finally, facilitated by the symmetric analog weight updating and multiple conductance states, a high image recognition accuracy of ≥ 91.39% is achieved, substantiating its feasibility for analog in-memory computing. This study highlights the significance of synergistically modulating conductive filaments in optimizing performance trade-offs, balancing memory window, retention, and endurance, which demonstrates techniques for regulating ion migration, rendering them a promising approach for enabling cutting-edge neuromorphic applications.

2.
Genome Res ; 34(2): 310-325, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38479837

RESUMO

In diploid mammals, allele-specific three-dimensional (3D) genome architecture may lead to imbalanced gene expression. Through ultradeep in situ Hi-C sequencing of three representative somatic tissues (liver, skeletal muscle, and brain) from hybrid pigs generated by reciprocal crosses of phenotypically and physiologically divergent Berkshire and Tibetan pigs, we uncover extensive chromatin reorganization between homologous chromosomes across multiple scales. Haplotype-based interrogation of multi-omic data revealed the tissue dependence of 3D chromatin conformation, suggesting that parent-of-origin-specific conformation may drive gene imprinting. We quantify the effects of genetic variations and histone modifications on allelic differences of long-range promoter-enhancer contacts, which likely contribute to the phenotypic differences between the parental pig breeds. We also observe the fine structure of somatically paired homologous chromosomes in the pig genome, which has a functional implication genome-wide. This work illustrates how allele-specific chromatin architecture facilitates concomitant shifts in allele-biased gene expression, as well as the possible consequential phenotypic changes in mammals.


Assuntos
Cromatina , Cromossomos , Animais , Suínos/genética , Cromatina/genética , Haplótipos , Cromossomos/genética , Genoma , Mamíferos/genética
3.
Artigo em Inglês | MEDLINE | ID: mdl-38484834

RESUMO

OBJECTIVE: To investigate the therapeutic effects of dry needling on lateral epicondylitis and identify a relatively more effective needling technique. DATA SOURCES: English databases (Pubmed, Web of Science, Scopus, EBSCO, ScienceDirect, Taylor & Francis, ProQuest, Cochrane, Ovid, and Embase) and Chinese databases (China National Knowledge Infrastructure, Wanfang, and VIP) were searched. STUDY SELECTION: This study included randomized controlled trials for comparing the effectiveness of dry needling with other treatment methods for lateral epicondylitis. The primary outcome measures were pain intensity and elbow disability, while the secondary outcome measures included grip strength and upper limb function. DATA EXTRACTION: Data extraction was performed by two researchers who used the Cochrane risk of bias analysis tool and the Physiotherapy Evidence Database checklist to assess the risk of bias and methodological quality of the included studies. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to assess the quality of evidence. DATA SYNTHESIS: A total of 17 studies that involved 979 subjects were included in this research. Dry needling exhibited a significant advantage in improving pain intensity among patients with lateral epicondylitis within 1 week after treatment (mean difference [MD]=-0.95, 95% confidence interval [CI], -1.88 to -0.02). Within 1 week and in the follow-ups that exceeded 1 week, dry needling also demonstrated better improvement in elbow disability (<1 week: standardized mean difference [SMD]=-1.37, 95% CI, -1.88 to -0.86; ≥1 week: SMD=-1.32, 95% CI, -2.23 to -0.4) and grip strength (<1 week: SMD=0.27, 95% CI, 0.01 to 0.53; ≥1 week: SMD=0.45, 95% CI, 0.02 to 0.88). Trigger point dry needling with local twitch response exhibited more significant improvement in pain intensity within 1 week (MD=-1.09, 95% CI, -1.75 to -0.44). CONCLUSIONS: Dry needling demonstrates good therapeutic effects on pain intensity (within 1 week), function, and grip strength among patients with lateral epicondylitis. Local twitch response is necessary in treatment that targets trigger points.

4.
Small ; : e2308213, 2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-38183335

RESUMO

Single-atom catalysts (SACs) hold immense promise in facilitating the rational use of metal resources and achieving atomic economy due to their exceptional atom-utilization efficiency and distinct characteristics. Despite the growing interest in SACs, only limited reviews have holistically summarized their advancements centering on performance metrics. In this review, first, a thorough overview on the research progress in SACs is presented from a performance perspective and the strategies, advancements, and intriguing approaches employed to enhance the critical attributes in SACs are discussed. Subsequently, a comprehensive summary and critical analysis of the electrochemical applications of SACs are provided, with a particular focus on their efficacy in the oxygen reduction reaction , oxygen evolution reaction, hydrogen evolution reaction , CO2 reduction reaction, and N2 reduction reaction . Finally, the outline future research directions on SACs by concentrating on performance-driven investigation, where potential areas for improvement are identified and promising avenues for further study are highlighted, addressing challenges to unlock the full potential of SACs as high-performance catalysts.

5.
Adv Mater ; 36(9): e2307393, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37739413

RESUMO

Optoelectronic memristors (OMs) have emerged as a promising optoelectronic Neuromorphic computing paradigm, opening up new opportunities for neurosynaptic devices and optoelectronic systems. These OMs possess a range of desirable features including minimal crosstalk, high bandwidth, low power consumption, zero latency, and the ability to replicate crucial neurological functions such as vision and optical memory. By incorporating large-scale parallel synaptic structures, OMs are anticipated to greatly enhance high-performance and low-power in-memory computing, effectively overcoming the limitations of the von Neumann bottleneck. However, progress in this field necessitates a comprehensive understanding of suitable structures and techniques for integrating low-dimensional materials into optoelectronic integrated circuit platforms. This review aims to offer a comprehensive overview of the fundamental performance, mechanisms, design of structures, applications, and integration roadmap of optoelectronic synaptic memristors. By establishing connections between materials, multilayer optoelectronic memristor units, and monolithic optoelectronic integrated circuits, this review seeks to provide insights into emerging technologies and future prospects that are expected to drive innovation and widespread adoption in the near future.

6.
Nat Immunol ; 25(1): 54-65, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38062135

RESUMO

The nature of activation signals is essential in determining T cell subset differentiation; however, the features that determine T cell subset preference acquired during intrathymic development remain elusive. Here we show that naive CD4+ T cells generated in the mouse thymic microenvironment lacking Scd1, encoding the enzyme catalyzing oleic acid (OA) production, exhibit enhanced regulatory T (Treg) cell differentiation and attenuated development of experimental autoimmune encephalomyelitis. Scd1 deletion in K14+ thymic epithelia recapitulated the enhanced Treg cell differentiation phenotype of Scd1-deficient mice. The dearth of OA permitted DOT1L to increase H3K79me2 levels at the Atp2a2 locus of thymocytes at the DN2-DN3 transition stage. Such epigenetic modification persisted in naive CD4+ T cells and facilitated Atp2a2 expression. Upon T cell receptor activation, ATP2A2 enhanced the activity of the calcium-NFAT1-Foxp3 axis to promote naive CD4+ T cells to differentiate into Treg cells. Therefore, OA availability is critical for preprogramming thymocytes with Treg cell differentiation propensities in the periphery.


Assuntos
Ácido Oleico , Timócitos , Animais , Camundongos , Ácido Oleico/metabolismo , Timo , Linfócitos T Reguladores , Diferenciação Celular , Fatores de Transcrição Forkhead/genética
7.
J Hazard Mater ; 465: 133074, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38029591

RESUMO

Public health depends on indoor air quality (IAQ), hence soft measurement techniques must be implemented in the subway environment for more precise and reliable monitoring of indoor particulate matter concentration levels. Adaptive boosting (AdaBoost), an ensemble learning technique, is simple to code and less prone to overfitting. Compared to a single model, it is better able to take into consideration the intricate elements included in air quality data. It is suggested to use an adaptive boosting of long short-term memory (AdaBoost-LSTM) model and kernel principal component analysis (KPCA) for ensemble learning. The kernel function and PCA are first coupled to create KPCA, which is a nonlinear dimensionality reduction method for IAQ. This removes the negative impacts of noise interference. The learning performance of LSTM is then enhanced using AdaBoost as an ensemble learning technique. The KPCA-AdaBoost-LSTM model can deliver higher modeling performance, according to the results. The R2 reached 0.9007 and 0.8995 when predicting PM2.5 in the hall and platform. SHapley Additive exPlanations (SHAP) analysis was used to interpret the input contributions of the model, enhancing the interpretability and transparency of the proposed soft sensor.

8.
Angew Chem Int Ed Engl ; 63(5): e202315003, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-37932862

RESUMO

Single-atom catalysts manifest nearly 100 % atom utilization efficiency, well-defined active sites, and high selectivity. However, their practical applications are hindered by a low atom loading density, uncontrollable location, and ambiguous interaction with the support, thereby posing challenges to maximizing their electrocatalytic performance. To address these limitations, the ability to arrange randomly dispersed single atoms into locally ordered single-atom catalysts (LO-SACs) substantially influences the electronic effect between reactive sites and the support, the synergistic interaction among neighboring single atoms, the bonding energy of intermediates with reactive sites and the complexity of the mechanism. As such, it dramatically promotes reaction kinetics, reduces the energy barrier of the reaction, improves the performance of the catalyst and simplifies the reaction mechanism. In this review, firstly, we introduce a variety of compelling characteristics of LO-SACs as electrocatalysts. Subsequently, the synthetic strategies, characterization methods and applications of LO-SACs in electrocatalysis are discussed. Finally, the future opportunities and challenges are elaborated to encourage further exploration in this rapidly evolving field.

9.
Nat Commun ; 14(1): 8042, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38052844

RESUMO

The respiratory system, especially the lung, is the key site of pathological injury induced by SARS-CoV-2 infection. Given the low feasibility of targeted delivery of antibodies into the lungs by intravenous administration and the short half-life period of antibodies in the lungs by intranasal or aerosolized immunization, mRNA encoding broadly neutralizing antibodies with lung-targeting capability can perfectly provide high-titer antibodies in lungs to prevent the SARS-CoV-2 infection. Here, we firstly identify a human monoclonal antibody, 8-9D, with broad neutralizing potency against SARS-CoV-2 variants. The neutralization mechanism of this antibody is explained by the structural characteristics of 8-9D Fabs in complex with the Omicron BA.5 spike. In addition, we evaluate the efficacy of 8-9D using a safe and robust mRNA delivery platform and compare the performance of 8-9D when its mRNA is and is not selectively delivered to the lungs. The lung-selective delivery of the 8-9D mRNA enables the expression of neutralizing antibodies in the lungs which blocks the invasion of the virus, thus effectively protecting female K18-hACE2 transgenic mice from challenge with the Beta or Omicron BA.1 variant. Our work underscores the potential application of lung-selective mRNA antibodies in the prevention and treatment of infections caused by circulating SARS-CoV-2 variants.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Animais , Camundongos , Feminino , Anticorpos Amplamente Neutralizantes , SARS-CoV-2/genética , COVID-19/prevenção & controle , Anticorpos Neutralizantes , Camundongos Transgênicos , RNA Mensageiro/genética , Pulmão , Anticorpos Antivirais , Glicoproteína da Espícula de Coronavírus/genética
10.
Cell Prolif ; : e13588, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38124457

RESUMO

'Requirements for Human Natural Killer Cells' is the latest set of guidelines on human NK cells in China, jointly drafted and agreed upon by experts from the Standards Committee of Chinese Society for Cell Biology. This standard specifies requirements for the human natural killer (NK) cells, including the technical requirements, test methods, test regulations, instructions for use, labeling requirements, packaging requirements, storage and transportation requirements, and waste disposal requirements of NK cells. This standard is applicable for the quality control of NK cells, derived from human tissues, or differentiated/transdifferentiated from stem cells. It was originally released by the Chinese Society for Cell Biology on 30 August, 2022. We hope that the publication of these guidelines will promote institutional establishment, acceptance, and execution of proper protocols and accelerate the international standardization of human NK cells for applications.

11.
Vet Med (Praha) ; 68(10): 392-402, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38028206

RESUMO

Rongchang piglets were easily induced to cold stress and diarrhoea in the winter when raised in an open hog house. However, they also gradually recovered under mid-cold stress. Other studies have suggested gut microbiome might be involved in the host energy metabolism to relieve stress. To study how to adapt Rongchang piglets to cold stress by gut microbiome, thirty Rongchang piglets were randomly divided into a mild cold stress group and a control group for 30 consecutive days. The findings revealed that the piglets had low growth performance and a high diarrhoea rate and mortality rate during the first half of the cold treatment, but subsequently stabilised. The level of cortisol (COR) also displayed a similar trend. In the mild cold stress group, the relative abundance of Muribaculaceae significantly increased on day 15, and the predominant bacterial on day 30 was Lactobacillus sp. Our results indicated that the Rongchang piglet's production performance and health were impaired at the start of the mild cold stress. However, as time passed, the body could progressively adapt to the low temperature, and Lactobacillus sp. participated in this process. This study provides new insight into how to alleviate health damage caused by cold stress.

12.
Cell Biosci ; 13(1): 202, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37932814

RESUMO

BACKGROUND: Ovarian cancer (OC) typically develops an immunosuppressive microenvironment by funtional changes of host immune cells. Dysregulated m6A level is associated with cancer progression via the intrinsic oncogenic pathways. However, the role of m6A in regulating host immune cell function during anti-tumor immunity needs comprehensive analysis. This study aimed to investigate the role of METTL3, a catalytic subunit of the methyltransferase complex, in regulating host immune cell response against OC. METHODS: In this study, myeloid-specific Mettl3 gene knockout (Mettl3-cKO) mice were bred using the Cre-LoxP system. Intraperitoneally injection of ID8 cells was used as a syngeneic OC model. Furthermore, the compositions of immune cell populations were analyzed by flow cytometry and single-cell sequencing. Moreover, chemokines and cytokines secretion were assessed using ELISA. Lastly, the role of METTL3 in regulating IL-1ß secretion and inflammasome activation in bone marrow-derived macrophages cocultured with ID8 cells was specified by ELISA and immunoblotting. RESULTS: It was revealed that OC cell growth was enhanced in Mettl3-cKO mice. Furthermore, a shift of decreased M1 to increased M2 macrophage polarization was observed during OC progression. Moreover, Mettl3 depletion in myeloid lineage cells increased secretion of CCL2 and CXCL2 in peritoneal lavage fluild. Interestingly, Mettl3 deficiency enhanced IL-1ß secretion induced by viable ID8 cells independent of inflammasome activation and cell death. Therefore, OC cells in tumor-bearing mice trigger a slight inflammatory response with a low-to-moderate secretion of pro-inflammatory cytokines and chemokines. CONCLUSION: This study provides new insights into METTL3-mediated m6A methylation, which regulates host immune response against OC.

13.
Yi Chuan ; 45(10): 922-932, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37872114

RESUMO

This study aimed to assess and compare the performance of different machine learning models in predicting selected pig growth traits and genomic estimated breeding values (GEBV) using automated machine learning, with the goal of optimizing whole-genome evaluation methods in pig breeding. The research employed genomic information, pedigree matrices, fixed effects, and phenotype data from 9968 pigs across multiple companies to derive four optimal machine learning models: deep learning (DL), random forest (RF), gradient boosting machine (GBM), and extreme gradient boosting (XGB). Through 10-fold cross-validation, predictions were made for GEBV and phenotypes of pigs reaching weight milestones (100 kg and 115 kg) with adjustments for backfat and days to weight. The findings indicated that machine learning models exhibited higher accuracy in predicting GEBV compared to phenotypic traits. Notably, GBM demonstrated superior GEBV prediction accuracy, with values of 0.683, 0.710, 0.866, and 0.871 for B100, B115, D100, and D115, respectively, slightly outperforming other methods. In phenotype prediction, GBM emerged as the best-performing model for pigs with B100, B115, D100, and D115 traits, achieving prediction accuracies of 0.547, followed by DL at 0.547, and then XGB with accuracies of 0.672 and 0.670. In terms of model training time, RF required the most time, while GBM and DL fell in between, and XGB demonstrated the shortest training time. In summary, machine learning models obtained through automated techniques exhibited higher GEBV prediction accuracy compared to phenotypic traits. GBM emerged as the overall top performer in terms of prediction accuracy and training time efficiency, while XGB demonstrated the ability to train accurate prediction models within a short timeframe. RF, on the other hand, had longer training times and insufficient accuracy, rendering it unsuitable for predicting pig growth traits and GEBV.


Assuntos
Genoma , Modelos Genéticos , Suínos/genética , Animais , Fenótipo , Genômica/métodos , Genótipo , Polimorfismo de Nucleotídeo Único
15.
Int Immunopharmacol ; 124(Pt A): 110942, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37716160

RESUMO

Peritoneal macrophages (PMs), which resided in peritoneal cavity, are crucial to maintain tissue homeostasis and immunity. Macrophage self-renewal and polarization states are critical for PM population homeostasis and function. However, the underlying molecular mechanism that regulates self-renewal and polarization of PMs is still unclear and needs to be explored. Here, we demonstrated that PMs self-renewal was stimulated by granulocyte macrophage colony-stimulating factor (GM-CSF), but not by macrophage colony-stimulating factor (M-CSF). Pharmacological inhibition of Bromodomain & Extraterminal (BET) Proteins by either JQ1 or ARV-825 significantly reduced GM-CSF-dependent peritoneal macrophage self-renewal by abrogating cell proliferation and decreasing self-renewal-related gene expression, such as MYC and Klf4, at transcriptional and protein levels. In addition, transcriptomic analysis showed that JQ1 blocked alternative PMs polarization by downregulating key transcriptional factor IRF4 expression, but not the activation of AKT or STAT6 in PMs. These findings illustrated that the significance of BET family proteins in GM-CSF-induced PMs self-renewal and IL-4-induced alternative polarization.

16.
Int J Biol Macromol ; 253(Pt 5): 127042, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37742894

RESUMO

Excessive expansion of adipocytes can have unhealthy consequences as excess free fatty acids enter other tissues and cause ectopic fat deposition by resynthesizing triglycerides. This lipid accumulation in various tissues is harmful and can increase the risk of related metabolic diseases such as type II diabetes, cardiovascular disease, and insulin resistance. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily that play a key role in energy metabolism as fatty acid metabolism sensors, and peroxisome proliferator-activated receptor γ (PPARγ) is the main subtype responsible for fat cell differentiation and adipogenesis. In this paper, we introduce the main structure and function of PPARγ and its regulatory role in the process of lipogenesis in the liver, kidney, skeletal muscle, and pancreas. This information can serve as a reference for further understanding the regulatory mechanisms and measures of the PPAR family in the process of ectopic fat deposition.


Assuntos
Diabetes Mellitus Tipo 2 , PPAR gama , Humanos , PPAR gama/genética , PPAR gama/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Metabolismo dos Lipídeos , Adipócitos/metabolismo , Adipogenia
17.
Theriogenology ; 211: 105-114, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37603936

RESUMO

Mummified piglets are among the leading causes of fertility loss and severely hamper reproductive performance in pigs. However, the contributions of genomic variation to the emergence of mummified piglets (MUM) have rarely been studied. This study aims to (1) elucidate the genetic architecture of MUM in sows of parity 1 - 3 using a single-step genome-wide association study (ssGWAS). The ssGWAS involved genotyping-by-sequencing of Large White and Landrace pig breeds. (2) Explore the biological role of the candidate genes at the cellular level. A total of 185 and 48 genome-wide significant SNPs are associated with MUM in Large White and Landrace pigs, explaining 0.01-36.52% genetic variance for different significant loci, respectively. All the significant SNPs are parity-specific, and the numerous, consecutive significant loci likely generated the nine significant peaks in different parities. Multiple candidate genes (including CYP24A1, FBXO30, and ARHGEF28) are associated with fetal congenital and maternal diseases. Collectively, CYP24A1 regulation contributes to steady-state levels of embryo development genes. CYP24A1 is involved in reproduction and, immune and gestational disorders. Thus, it is associated with known newborn death traits and MUM in Large White sows. Altogether, these results improve the current understanding of the genetic architecture of MUM and expand the knowledge on genetic variations for selecting against mummified piglets in pig breeding.


Assuntos
Morte Fetal , Vitamina D3 24-Hidroxilase , Animais , Feminino , Gravidez , Desenvolvimento Embrionário , Fertilidade , Estudo de Associação Genômica Ampla/veterinária , Suínos/genética , Doenças dos Suínos , Vitamina D3 24-Hidroxilase/genética , Sus scrofa
18.
Anal Chem ; 95(35): 13101-13112, 2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37526338

RESUMO

A new lateral flow immunoassay strip (LFIA) combining sensitive detection and identification of multiple bacteria remains a huge challenge. In this study, we first developed multifunctional urchin-shaped Au-Ag@Pt nanoparticles (UAA@P NPs) with a unique combination of colorimetric-SERS-photothermal-catalytic (CM/SERS/PT/CL) properties and integrated them with LFIA for multiplexed detection and specific discrimination of pathogenic bacteria in blood samples. Unlike the conventional LFIA that relied on antibody (Ab), this novel LFIA introduced 4-mercaptophenylboronic acid (4-MPBA) as an ideal Ab replacer that was functionalized on UAA@P NPs (UAA@P/M NPs) with outstanding binding and enrichment capacities toward bacteria. Taking Staphylococcus aureus (S. aureus) as model bacteria, the limit of detection (LOD) was 3 CFU/mL for SERS-LFIA, 27 CFU/mL for PT-LFIA, and 18 CFU/mL for CL-LFIA, three of which were over 330-fold, 37-fold, and 55-fold more sensitive than ordinary visual CM-LFIA, respectively. Besides, this SERS-LFIA is capable of identifying three types of bacterial spiked blood samples (E. coli, S. aureus, and P. aeruginosa) effectively according to specific bacterial Raman "fingerprints" by partial least-squares-discriminant analysis (PLS-DA). More importantly, this LFIA was successfully applied to blood samples with satisfactory recoveries from 90.3% to 108.8% and capable of identifying the infected patients (N = 4) from healthy subjects (N = 2) with great accuracy. Overall, the multimodal LFIA incorporates bacteria discrimination and quantitative detection, offering an avenue for early warning and diagnosis of bacterial infection.


Assuntos
Infecções Bacterianas , Nanopartículas Metálicas , Humanos , Escherichia coli , Staphylococcus aureus , Imunoensaio , Bactérias , Anticorpos , Infecções Bacterianas/diagnóstico , Limite de Detecção , Nanopartículas Metálicas/química , Ouro/química
19.
Acta Pharmacol Sin ; 44(9): 1867-1878, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37142684

RESUMO

Inhibition of NLRP3 inflammasome activation produces potent therapeutic effects in a wide array of inflammatory diseases. Bergapten (BeG), a furocoumarin phytohormone present in many herbal medicines and fruits, exibits anti-inflammatory activity. In this study we characterized the therapeutic potential of BeG against bacterial infection and inflammation-related disorders, and elucidated the underlying mechanisms. We showed that pre-treatment with BeG (20 µM) effectively inhibited NLRP3 inflammasome activation in both lipopolysaccharides (LPS)-primed J774A.1 cells and bone marrow-derived macrophages (BMDMs), evidenced by attenuated cleaved caspase-1 and mature IL-1ß release, as well as reduced ASC speck formation and subsequent gasdermin D (GSDMD)-mediated pyroptosis. Transcriptome analysis revealed that BeG regulated the expression of genes involved in mitochondrial and reactive oxygen species (ROS) metabolism in BMDMs. Moreover, BeG treatment reversed the diminished mitochondrial activity and ROS production after NLRP3 activation, and elevated the expression of LC3-II and enhanced the co-localization of LC3 with mitochondria. Treatment with 3-methyladenine (3-MA, 5 mM) reversed the inhibitory effects of BeG on IL-1ß, cleaved caspase-1 and LDH release, GSDMD-N formation as well as ROS production. In mouse model of Escherichia coli-induced sepsis and mouse model of Citrobacter rodentium-induced intestinal inflammation, pre-treatment with BeG (50 mg/kg) significantly ameliorated tissue inflammation and injury. In conclusion, BeG inhibits NLRP3 inflammasome activation and pyroptosis by promoting mitophagy and maintaining mitochondrial homeostasis. These results suggest BeG as a promising drug candidate for the treatment of bacterial infection and inflammation-related disorders.


Assuntos
Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Camundongos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose , Espécies Reativas de Oxigênio/metabolismo , 5-Metoxipsoraleno/farmacologia , Mitofagia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Caspase 1/metabolismo , Interleucina-1beta/metabolismo
20.
Genes (Basel) ; 14(4)2023 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-37107540

RESUMO

Noncoding RNAs (ncRNAs) called tsRNAs (tRNA-derived short RNAs) have the ability to regulate gene expression. The information on tsRNAs in fat tissue is, however, limited. By sequencing, identifying, and analyzing tsRNAs using pigs as animal models, this research reports for the first time the characteristics of tsRNAs in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). A total of 474 tsRNAs, 20 and 21 of which were particularly expressed in VAT and SAT, respectively, were found in WAT. According to the analysis of the tsRNA/miRNA/mRNA co-expression network, the tsRNAs with differential expression were primarily engaged in the endocrine and immune systems, which fall under the classification of organic systems, as well as the global and overview maps and lipid metropolis, which fall under the category of metabolism. This research also discovered a connection between the activity of the host tRNA engaged in translation and the production of tsRNAs. This research also discovered that tRF-Gly-GCC-037/tRF-Gly-GCC-042/tRF-Gly-CCC-016 and miR-218a/miR281b may be involved in the regulation of fatty acid metabolism in adipose tissue through SCD based on the tsRNA/miRNA/mRNA/fatty acid network. In conclusion, our findings enrich the understanding of ncRNAs in WAT metabolism and health regulation, as well as reveal the differences between SAT and VAT at the level of tsRNAs.


Assuntos
Gordura Intra-Abdominal , MicroRNAs , Animais , Suínos/genética , Gordura Intra-Abdominal/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Ácidos Graxos/metabolismo , RNA de Transferência/genética , RNA de Transferência/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...