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1.
PLoS One ; 19(4): e0298963, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38568932

RESUMO

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common functional bowel disorders and dysmetabolism plays an important role in the pathogenesis of disease. Nevertheless, there remains a lack of information regarding the causal relationship between circulating metabolites and IBS. A two-sample Mendelian randomization (MR) analysis was conducted in order to evaluate the causal relationship between genetically proxied 486 blood metabolites and IBS. METHODS: A two-sample MR analysis was implemented to assess the causality of blood metabolites on IBS. The study utilized a genome-wide association study (GWAS) to examine 486 metabolites as the exposure variable while employing a GWAS study with 486,601 individuals of European descent as the outcome variable. The inverse-variance weighted (IVW) method was used to estimate the causal relationship of metabolites on IBS, while several methods were performed to eliminate the pleiotropy and heterogeneity. Another GWAS data was used for replication and meta-analysis. In addition, reverse MR and linkage disequilibrium score regression (LDSC) were employed for additional assessment. Multivariable MR analysis was conducted in order to evaluate the direct impact of metabolites on IBS. RESULTS: Three known and two unknown metabolites were identified as being associated with the development of IBS. Higher levels of butyryl carnitine (OR(95%CI):1.10(1.02-1.18),p = 0.009) and tetradecanedioate (OR(95%CI):1.13(1.04-1.23),p = 0.003)increased susceptibility of IBS and higher levels of stearate(18:0)(OR(95%CI):0.72(0.58-0.89),p = 0.003) decreased susceptibility of IBS. CONCLUSION: The metabolites implicated in the pathogenesis of IBS possess potential as biomarkers and hold promise for elucidating the underlying biological mechanisms of this condition.


Assuntos
Síndrome do Intestino Irritável , Humanos , Síndrome do Intestino Irritável/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Carnitina , Causalidade
2.
Int J Biol Macromol ; 261(Pt 1): 129619, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38272407

RESUMO

Chronic pain constitutes an abnormal pain state that detrimentally affects the quality of life, daily activities, occupational performance, and stability of mood. Despite the prevalence of chronic pain, effective drugs with potent abirritation and minimal side effects remain elusive. Substantial studies have revealed aberrant activation of the matrix metalloproteinases (MMPs) in multiple chronic pain models. Additionally, emerging evidence has demonstrated that the downregulation of MMPs can alleviate chronic pain in diverse animal models, underscoring the unique and crucial role of MMPs in different stages and types of chronic pain. This review delves into the mechanistic insights and roles of MMPs in modulating chronic pain. The aberrant activation of MMPs has been linked to neuropathic pain through mechanisms involving myelin abnormalities in peripheral nerve and spinal dorsal horn (SDH), hyperexcitability of dorsal root ganglion (DRG) neurons, activation of N-methyl-d-aspartate receptors (NMDAR) and Ca2+-dependent signals, glial cell activation, and proinflammatory cytokines release. Different MMPs also contribute significantly to inflammatory pain and cancer pain. Furthermore, we summarized the substantial therapeutic potential of MMP pharmacological inhibitors across different types of chronic pain. Overall, our findings underscore the promising therapeutic prospects of MMPs targeting for managing chronic pain.


Assuntos
Dor Crônica , Neuralgia , Animais , Dor Crônica/tratamento farmacológico , Qualidade de Vida , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Neurônios/metabolismo , Metaloproteinases da Matriz/metabolismo , Hiperalgesia
3.
Acta Psychol (Amst) ; 243: 104146, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38237473

RESUMO

METHODOLOGY: A total of 379 college students from 22 classes in 3 universities in Nanjing, who received online teaching, were selected as the participants in this study. The purpose of this thesis is to explore the influence mechanism of mindful agency on their identification by using the Mindful Agency Scale for College Students, the Scale for Identification of College Students with Online Teaching, the Online Learning Self-Efficacy Scale for Adult Learners, and the Questionnaire on Online Self-Disciplined Learning for College Students, which were proven effective in previous studies. In all these studies, the coefficients of Cronbach's α are all above 85. RESULTS: The study's findings demonstrated that, in addition to directly and favorably predicting identification with online teaching, mindful agency also had an impact on identification through the mediating effects of self-efficacy in online learning and self-disciplined learning online. CONCLUSIONS: By identifying the two intermediary pathways and the orderly chain structure pathways in which mindful agency influences college students' identification with online teaching, this study contributes to the theoretical research on mindfulness in online teaching contexts, the expansion of empirical research on the impact of mindful agency on identification with online teaching, and the development of practical reference materials for improving identification with online teaching.


Assuntos
Instrução por Computador , Atenção Plena , Autocontrole , Adulto , Humanos , Autoeficácia , Estudantes
4.
Inorg Chem ; 63(4): 2138-2147, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38237037

RESUMO

Expediting the torpid kinetics of the oxygen reduction reaction (ORR) at the cathode with minimal amounts of Pt under acidic conditions plays a significant role in the development of proton exchange membrane fuel cells (PEMFCs). Herein, a novel Pt-N-C system consisting of Pt single atoms and nanoparticles anchored onto the defective carbon nanofibers is proposed as a highly active ORR catalyst (denoted as Pt-N-C). Detailed characterizations together with theoretical simulations illustrate that the strong coupling effect between different Pt sites can enrich the electron density of Pt sites, modify the d-band electronic environments, and optimize the oxygen intermediate adsorption energies, ultimately leading to significantly enhanced ORR performance. Specifically, the as-designed Pt-N-C demonstrates exceptional ORR properties with a high half-wave potential of 0.84 V. Moreover, the mass activity of Pt-N-C reaches 193.8 mA gPt-1 at 0.9 V versus RHE, which is 8-fold greater than that of Pt/C, highlighting the enormously improved electrochemical properties. More impressively, when integrated into a membrane electrode assembly as cathode in an air-fed PEMFC, Pt-N-C achieved a higher maximum power density (655.1 mW cm-2) as compared to Pt/C-based batteries (376.25 mW cm-2), hinting at the practical application of Pt-N-C in PEMFCs.

5.
Aging Dis ; 15(1): 186-200, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37307838

RESUMO

Chronic pain is a notable health concern because of its prevalence, persistence, and associated mental stress. Drugs targeting chronic pain with potent abirritation, and minimal side effects remain unidentified. Substantial evidence indicates that the Janus Kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway plays a distinct and critical role in different stages of chronic pain. Aberrant activation of the JAK2/STAT3 signaling pathway is evident in multiple chronic pain models. Moreover, an increasing number of studies have demonstrated that the downregulation of JAK2/STAT3 can attenuate chronic pain in different animal models. In this review, we investigated the mechanism and role of the JAK2/STAT3 signaling pathway in modulating chronic pain. The aberrant activation of JAK2/STAT3 can trigger chronic pain by interacting with microglia and astrocytes, releasing proinflammatory cytokines, inhibiting anti-inflammatory cytokines, and regulating synaptic plasticity. We also retrospectively reviewed current reports on JAK2/STAT3 pharmacological inhibitors that demonstrated their significant therapeutic potential in different types of chronic pain. In summary, our results provide strong evidence that the JAK2/STAT3 signaling pathway is a promising therapeutic target for chronic pain.


Assuntos
Dor Crônica , Janus Quinase 2 , Animais , Dor Crônica/tratamento farmacológico , Fator de Transcrição STAT3/genética , Estudos Retrospectivos , Transdução de Sinais , Citocinas/metabolismo
6.
Commun Biol ; 6(1): 1243, 2023 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-38066175

RESUMO

Protein post-translational modifications (PTMs) with various acyl groups play central roles in Streptomyces. But whether these acyl groups can be further modified, and the influences of these potential modifications on bacterial physiology have not been addressed. Here in Streptomyces roseosporus with rich crotonylation, a luciferase monooxygenase LimB is identified to elaborately regulate the crotonylation level, morphological development and antibiotic production by oxidation on the crotonyl groups of an acetyl-CoA synthetase Acs. This chemical modification on crotonylation leads to Acs degradation via the protease ClpP1/2 pathway and lowered intracellular crotonyl-CoA pool. Thus, we show that acyl groups after PTMs can be further modified, herein named post-PTM modification (PPM), and LimB is a PTM modifier to control the substrate protein turnover for cell development of Streptomyces. These findings expand our understanding of the complexity of chemical modifications on proteins for physiological regulation, and also suggest that PPM would be widespread.


Assuntos
Ligases , Streptomyces , Acetilcoenzima A , Oxigenases de Função Mista , Proteínas
7.
Front Psychol ; 14: 1185896, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37691806

RESUMO

Introduction: Sleep quality has a significant impact on the health-related quality of life, particularly among college students. This study proposes a framework for identifying factors that influence college students' sleep quality, including stress, self-control, bedtime habits, and neighborhood environment. Methods: The study employed a cross-sectional analytical approach on a convenience sample of 255 medical students from a private university in China during the 2021/2022 academic year, of which 80.39% (205) were women. Two complementary methodologies, partial least squares-structural equation modeling (PLS-SEM), and fuzzy sets qualitative comparative analysis (fsQCA), were utilized in the study. Results: The results of the PLS-SEM analysis suggest that Stress and Self-control act as mediating variables in the model, with Bedtime habits and Neighborhood environment influencing sleep quality through these variables. Additionally, the fsQCA analysis reveals that Bedtime habits and Neighborhood environment can combine with Stress and Self-control, respectively, to influence sleep quality. Discussion: These findings provide insight into how multiple factors, such as Stress, Self-control, Bedtime habits, and Neighborhood environment, can impact college students' sleep quality, and can be used to develop intervention programs aimed at improving it. Moreover, the use of both methodologies enables the expansion of new methodological approaches that can be applied to different contexts.

8.
Cancer Res ; 83(18): 3115-3130, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37522838

RESUMO

Several emerging therapies kill cancer cells primarily by inducing necrosis. As necrosis activates immune cells, potentially, uncovering the molecular drivers of anticancer therapy-induced necrosis could reveal approaches for enhancing immunotherapy efficacy. To identify necrosis-associated genes, we performed a genome-wide CRISPR-Cas9 screen with negative selection against necrosis-inducing preclinical agents BHPI and conducted follow-on experiments with ErSO. The screen identified transient receptor potential melastatin member 4 (TRPM4), a calcium-activated, ATP-inhibited, sodium-selective plasma membrane channel. Cancer cells selected for resistance to BHPI and ErSO exhibited robust TRPM4 downregulation, and TRPM4 reexpression restored sensitivity to ErSO. Notably, TRPM4 knockout (TKO) abolished ErSO-induced regression of breast tumors in mice. Supporting a broad role for TRPM4 in necrosis, knockout of TRPM4 reversed cell death induced by four additional diverse necrosis-inducing cancer therapies. ErSO induced anticipatory unfolded protein response (a-UPR) hyperactivation, long-term necrotic cell death, and release of damage-associated molecular patterns that activated macrophages and increased monocyte migration, all of which was abolished by TKO. Furthermore, loss of TRPM4 suppressed the ErSO-induced increase in cell volume and depletion of ATP. These data suggest that ErSO triggers initial activation of the a-UPR but that it is TRPM4-mediated sodium influx and cell swelling, resulting in osmotic stress, which sustains and propagates lethal a-UPR hyperactivation. Thus, TRPM4 plays a pivotal role in sustaining lethal a-UPR hyperactivation that mediates the anticancer activity of diverse necrosis-inducing therapies. SIGNIFICANCE: A genome-wide CRISPR screen reveals a pivotal role for TRPM4 in cell death and immune activation following treatment with diverse necrosis-inducing anticancer therapies, which could facilitate development of necrosis-based cancer immunotherapies.


Assuntos
Trifosfato de Adenosina , Canais de Cátion TRPM , Camundongos , Animais , Necrose/metabolismo , Morte Celular , Membrana Celular/metabolismo , Trifosfato de Adenosina/metabolismo , Sódio/metabolismo , Canais de Cátion TRPM/genética , Canais de Cátion TRPM/metabolismo
9.
Sci Rep ; 13(1): 12320, 2023 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-37516775

RESUMO

Oral health is crucial for health-related quality of life. However, the research on the factors affecting oral health status is not comprehensive enough. This investigation aimed to evaluate the multifaceted determinants of college students' oral health status and explore the impact of social support, oral health literacy, attitudes, behaviors, and self-efficacy on OHRQoL. By surveying 822 students from a university. Baseline data included sociodemographics (gender, age), social support (MSPSS scale), oral health self-efficacy (SESS scale), oral health knowledge, attitudes, and practices (KAP questionnaire), and OHRQoL (OHIP-14 scale). Based on social cognitive theory, partial least squares structural equation modeling (PLS-SEM) and fuzzy set qualitative comparative analysis (fsQCA) were used to examine the relationship between the study variables. PLS-SEM results showed that knowledge, attitude, and practice predicted OHRQoL through self-efficacy. FsQCA results showed that the combination of different variables was sufficient to explain OHRQoL. The conclusion was that self-efficacy plays an important role and the combination of high-level knowledge, positive attitudes, and strong self-efficacy was important in improving OHRQoL. The results of this study provided a reference for the oral health strategy planning of college students in China.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Qualidade de Vida , Humanos , Autoeficácia , Estudantes , Apoio Social
10.
Psychol Res Behav Manag ; 16: 1957-1973, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37275276

RESUMO

Background: Research on the restorative environment has long focused on the natural environment, while the research on the humanistic social environment is still in its infancy. In particular, there has been no special research on the restoration of festival environments. Methods: Based on attention restoration theory (ART), Rites of Passage, and social time, a theoretical model of the restorativeness of folk festival environments was established. Through an empirical study of the Qinhuai Lantern Festival Event, the model was tested by structural equation modeling. Results: Overall, there were two paths, direct and indirect, for the positive prediction of restoration by being away and compatibility; fascination direct positive predict restoration, and extent could indirectly positive predict restoration through liminal experience; time of visiting played a moderating role in the positive prediction of liminal experience by being away; the direct positive prediction of restoration by extent was significant and moderating during the Lantern Festival and the lantern fair period. Conclusion: The folk festival environment is restorative. Folk festival environment restoration has the internal mechanism of "environment restoration feature perception → liminal experience → restoration". The restoration of the folk festival environment is moderated by social time. Significance: This is the first time that attention restoration theory (ART) has been applied to the study of a "hard fascination" humanistic social environment, thus yielding empirical evidence for the development of this theory. The results suggest management requirements for the improvement of the indication system of festival tourism destinations and the promotion of rest and leisure facilities, and management tips for the timing decision of festival activities against the background of the COVID-19 epidemic.

11.
Plants (Basel) ; 12(11)2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37299158

RESUMO

Tomato yellow leaf curl disease (TYLCD) has become the key limiting factor for the production of tomato in many areas because of the continuous infection and recombination of several tomato yellow leaf curl virus (TYLCV)-like species (TYLCLV) which produce novel and destructive viruses. Artificial microRNA (AMIR) is a recent and effective technology used to create viral resistance in major crops. This study applies AMIR technology in two ways, i.e., amiRNA in introns (AMINs) and amiRNA in exons (AMIEs), to express 14 amiRNAs targeting conserved regions in seven TYLCLV genes and their satellite DNA. The resulting pAMIN14 and pAMIE14 vectors can encode large AMIR clusters and their function in silencing reporter genes was validated with transient assays and stable transgenic N. tabacum plants. To assess the efficacy of conferring resistance against TYLCLV, pAMIE14 and pAMIN14 were transformed into tomato cultivar A57 and the resulting transgenic tomato plants were evaluated for their level of resistance to mixed TYLCLV infection. The results suggest that pAMIN14 transgenic lines have a more effective resistance than pAMIE14 transgenic lines, reaching a resistance level comparable to plants carrying the TY1 resistance gene.

12.
Plast Reconstr Surg ; 152(5): 1047-1056, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37014962

RESUMO

BACKGROUND: The aim of this study was to determine the clinical outcomes of vascularized hemi-metatarsal composite tissue transfer for the reconstruction of type IIIB hypoplastic thumbs. METHODS: Twenty-eight patients with type IIIB hypoplastic thumbs treated with vascularized hemi-metatarsal composite tissue transfer were included in this retrospective study with a mean follow-up of 2.4 years. Preoperative digital subtraction angiography was performed to examine the vessel variance. Clinical measures included grip and pinch strength, scar status, and Kapandji thumb opposition score. Subjective Pediatric Outcomes Data Collection Instrument scores and parent satisfaction were also evaluated. RESULTS: Radial arteries were hypoplastic in 82.1% of the cases, and the common palmar digital artery was chosen as the recipient vessel for the tissue transfer. There was no neurovascular complication. The only donor-site complication was a metatarsal fracture that healed with casting. Key pinch and tripod pinch were 29.5% and 45.8% of the normal side, respectively. The mean grip strength was 51.7% of the unaffected side. The mean Kapandji score was 6. The Pediatric Outcomes Data Collection Instrument scores were high for global function; upper extremity function; transfer; and basic mobility, happiness, and comfort. The Vancouver Scar Scale showed an average score of 2.1. All parents were satisfied with the clinical outcomes. CONCLUSION: Vascularized hemi-metatarsal composite tissue transfer for type IIIB thumb hypoplasia can provide improved subjective outcomes and is a feasible method for the attainment of a five-digit hand. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.


Assuntos
Ossos do Metatarso , Polegar , Criança , Humanos , Polegar/anormalidades , Estudos Retrospectivos , Cicatriz
13.
Transl Pediatr ; 12(3): 462-469, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37035396

RESUMO

Background: Many human mobility restrictions have been adopted during the novel 2019 coronavirus disease (COVID-19) pandemic. Here we explored the effects of psychological interventions on the mental health status of medical students under the regular prevention and control of the pandemic. Methods: By voluntarily participating in interest groups, 121 third-year medical undergraduate students in a university in Jiangsu Province underwent psychological interventions for 1 year. Their mental status was assessed by using Zung's Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), and Somatic Self-rating Scale (SSS) before and after the interventions. Psychological coping styles were compared by using the trait coping style questionnaire (TCSQ). Each assessment scale is evaluated every 3 months, with the first survey results as the baseline data and compared with the last results. The resulting data was passed by SPSS 23 0 for normal testing and Analysis of Variance (ANOVA). Results: During the regular response to the COVID-19 pandemic, the prevalence of anxiety, depression, and somatization symptoms was 25.62% vs. 7.44%, 28.93% vs. 18.18%, and 21.49% vs. 9.92%, respectively, before and after psychological interventions (all P<0.05). The positive (31.73±4.26 vs. 38.26±3.72) and negative (27.69±3.19 vs. 20.73±2.8) coping styles significantly differed before and after intervention (both P<0.05). Conclusions: Varying degrees of anxiety, depression, and somatization symptoms can occur in medical students during the regular response to COVID-19 pandemic, highlighting the impact of public health emergencies on college students. Interest group-based psychological intervention, along with individual mental health counseling, can positively promote the mental health of college students and effectively improve their anxiety.

14.
Melanoma Res ; 33(6): 492-505, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36988403

RESUMO

Human cutaneous melanoma (CM) is a highly invasive malignancy arising from melanocytes, and accompanied by ever-increasing incidence and mortality rates worldwide. Interestingly, microRNAs (miRNAs) possess the ability to regulate CM cell biological functions, resulting in the aggressive progression of CM. Nevertheless, a comprehensive understanding of the underlying mechanism remains elusive. Accordingly, the current study sought to elicit the functional role of miR-141-3p in human CM cells in association with fibroblast growth factor 13 (FGF13) and the MAPK pathway. First, miR-141-3p expression patterns were detected in human CM tissues and cell lines, in addition to the validation of the targeting relationship between miR-141-3p and FGF13. Subsequently, loss- and gain-of-function studies of miR-141-3p were performed to elucidate the functional role of miR-141-3p in the malignant features of CM cells. Intriguingly, our findings revealed that FGF13 was highly expressed, whereas miR-141-3p was poorly expressed in the CM tissues and cells. Further analysis highlighted FGF13 as a target gene of miR-141-3p. Meanwhile, overexpression of miR-141-3p inhibited the proliferative, invasive, and migratory abilities of CM cells, while enhancing their apoptosis accompanied by downregulation of FGF13 and the MAPK pathway-related genes. Collectively, our findings highlighted the inhibitory effects of miR-141-3p on CM cell malignant properties via disruption of the FGF13-dependent MAPK pathway, suggesting a potential target for treating human CM.


Assuntos
Melanoma , MicroRNAs , Neoplasias Cutâneas , Humanos , Melanoma/genética , Melanoma/patologia , Proteínas Quinases Ativadas por Mitógeno , Neoplasias Cutâneas/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Linhagem Celular Tumoral , Proliferação de Células
15.
ACS Appl Mater Interfaces ; 15(14): 18450-18462, 2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-36989350

RESUMO

Li-rich Mn-based layered oxides (LLOs) are one of the most promising cathode materials, which have exceptional anionic redox activity and a capacity that surpasses 250 mA h/g. However, the change from a layered structure to a spinel structure and unstable anionic redox are accompanied by voltage attenuation, poor rate performance, and problematic capacity. The technique of stabilizing the crystal structure and reducing the surface oxygen activity is proposed in this paper. A coating layer and highly concentrated oxygen vacancies are developed on the material's surface, according to scanning electron microscopy, transmission electron microscopy, and X-ray photoelectron spectroscopy. In situ EIS shows that structural transformation and oxygen release are inhibited during the first charge and discharge. Optimized 3@LRMA has an average attenuation voltage of 0.55 mV per cycle (vs 1.7 mV) and a capacity retention rate of 93.4% after 200 cycles (vs 52.8%). Postmortem analysis indicates that the successful doping of Al ions into the crystal structure effectively inhibits the structural alteration of the cycling process. The addition of oxygen vacancies reduces the surface lattice's redox activity. Additionally, surface structure deterioration is successfully halted by N- and Cl-doped carbon coating. This finding highlights the significance of lowering the surface lattice oxygen activity and preventing structural alteration, and it offers a workable solution to increase the LLO stability.

16.
Molecules ; 28(5)2023 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-36903419

RESUMO

The acidic extracellular microenvironment has become an effective target for diagnosing and treating tumors. A pH (low) insertion peptide (pHLIP) is a kind of peptide that can spontaneously fold into a transmembrane helix in an acidic microenvironment, and then insert into and cross the cell membrane for material transfer. The characteristics of the acidic tumor microenvironment provide a new method for pH-targeted molecular imaging and tumor-targeted therapy. As research has increased, the role of pHLIP as an imaging agent carrier in the field of tumor theranostics has become increasingly prominent. In this paper, we describe the current applications of pHLIP-anchored imaging agents for tumor diagnosis and treatment in terms of different molecular imaging methods, including magnetic resonance T1 imaging, magnetic resonance T2 imaging, SPECT/PET, fluorescence imaging, and photoacoustic imaging. Additionally, we discuss relevant challenges and future development prospects.


Assuntos
Neoplasias , Medicina de Precisão , Humanos , Peptídeos/química , Imageamento por Ressonância Magnética , Concentração de Íons de Hidrogênio , Microambiente Tumoral
17.
Biochim Biophys Acta Mol Basis Dis ; 1869(4): 166656, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36706797

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder worldwide. Immune response gene 1 (IRG1) catalyzes the production of bio-active itaconate, which is actively involved in the regulation of signal transduction. A recent study has found that the expression of IRG1 was significantly down-regulated in obesity-associated fatty liver, but the potential roles of IRG1 in the development NAFLD remain unclear. The present study found that genetic deletion of IRG1 aggravated high fat diet (HFD)-induced metabolic disturbance, including obesity, dyslipidemia and insulin resistance. In addition, HFD induced more severe liver steatosis and higher serum ALT and AST level in IRG1 KO mice, which were accompanied with altered expression of genes involved in lipid uptake, synthesis and catabolism. RNA-seq and immunoblot analysis indicated that deficiency of IRG1 is associated with suppressed activation of AKT, a master metabolic regulator. Mechanistically, IRG1/itaconate enhanced the antioxidative NRF2 pathway and prevented redox-sensitive suppression of AKT. Interestingly, supplementation with 4-octyl itaconate (4-OI), a cell-permeable derivate of itaconate, alleviated HFD-induced oxidative stress, AKT suppression and liver steatosis. Therefore, IRG1 probably functions as a protective regulator in the development of NAFLD and the cell-permeable 4-OI might have potential value for the pharmacological intervention of NAFLD.


Assuntos
Dieta Hiperlipídica , Hidroliases , Hepatopatia Gordurosa não Alcoólica , Proteínas Proto-Oncogênicas c-akt , Animais , Camundongos , Dieta Hiperlipídica/efeitos adversos , Hidroliases/genética , Hidroliases/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/complicações , Obesidade/complicações , Obesidade/metabolismo , Oxirredução , Proteínas Proto-Oncogênicas c-akt/metabolismo
18.
PLoS One ; 17(12): e0279274, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36574367

RESUMO

BACKGROUND: Some studies found that red blood cell count (RBC) was an unrecognized risk factor for non-alcoholic fatty liver disease (NAFLD). While the epidemiological data underpinning the evidence is very limited. As there are some differences between the latest criteria of metabolic dysfunction-associated fatty liver disease (MAFLD) and NAFLD, itis necessary to evaluate the relationship between RBC and MAFLD. METHODS: We performed a cross-sectional analysis of the National Health and Nutritional Examination Survey (NHANES)2017-2018 cohort, including 4477 participants. Hepatic steatosis was determined when the value of controlled attenuation parameter (CAP) obtained by Fibroscan was ≥274 dB/m. Multivariate logistic regression analysis was used to estimate the association between RBC and MAFLD. We estimated the adjusted odds ratio (OR) of RBC for MAFLD, and the nonlinear relationship between RBC and MAFLD was further described using smooth curve fittings and threshold-effect analysis. RESULTS: We found that MAFLD risk was significantly higher according to RBC quartiles. The adjusted odds ratio (OR) and 95% confidence intervals (CIs)for the highest RBC quartile were 1.5(1.0, 2.3) for male and 1.1 (0.8, 1.6) for female, respectively. As for male, a non-linear relationship was discovered between RBCs and MAFLD, with a RBC threshold of 4.2. The effect sizes and confidence intervals on the right side of the inflection point were 1.5 (1.0, 2.0) (P for nonlinearity = 0.027). The sensitivity analysis showed a similar result. CONCLUSION: We demonstrated that that elevated RBC level is associated with the higher risk of MAFLD in male. The positive relationship was not significant in females after full adjustment. Our finding provided novel evidence indicating that RBCs might be a potential biomarker for MAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Feminino , Humanos , Masculino , Estudos Transversais , Inquéritos Nutricionais , Contagem de Eritrócitos , Eritrócitos
19.
Appl Opt ; 61(22): 6414-6419, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-36255865

RESUMO

Laser-generated ultrasonic wave characteristics in the rail foot weld were simulated and reported for qualitative analysis and evaluation of sub-millimeter-level crack growth. Numerical analyses using the finite element method (FEM), the propagation characteristics, and displacement field distribution of a laser-generated ultrasonic wave after the interaction with cracks were fully demonstrated. By calculating displacement amplitude distribution, the optimal sensing position and area were the laser incident point and the upper surface, respectively. Crack growth degree toward the rail bottom and axial direction can be confirmed by analyzing time and amplitude of the echoes originating from the rail bottom and crack surface reflection. By combining time with peak intensity of the echo reflection from the rail bottom, the sub-millimeter-level crack growth process inside the rail foot weld is capable of acquiring and evaluating. The results justify that the laser ultrasonic technique, characterized by laser excitation and laser detection, is a competitive nondestructive testing technique for sub-millimeter-level crack growth evaluation and detection inside the rail foot weld.


Assuntos
Lasers , Ultrassom
20.
ACS Omega ; 7(35): 31597-31606, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36092563

RESUMO

The structure and surface-interface instability of LiCoO2 thin-film electrodes during charge-discharge cycles are one of the main factors leading to the deterioration of electrochemical performance. Element doping and surface coating are effective strategies to tackle this issue. In this work, Al-doped and in situ Al2O3-coated LiCoO2 composite thin-film electrodes are prepared by magnetron sputtering. The results show that the resultant composite thin-film electrodes exhibited excellent cycling stability, with a discharge specific capacity of 40.2 µAh um-1 cm-2 after 240 cycles at 2.5 µA cm-2, with a capacity retention rate of 94.14%, compared to a discharge capacity of the unmodified sample of only 37.7 µAh um-1 cm-2 after 110 cycles, with a capacity retention rate of 80.04%. In addition, the rate performance of the prepared LiCoO2 film is significantly improved, and the discharge specific capacity of the Al-doped sample reaches 43.5 µAh um-1 cm-2 at 100 µA cm-2, which is 38.97% higher than that of the unmodified sample (31.3 µAh um-1 cm-2). The enhancement of electrochemical performance is mainly attributed to the synergistic effect of Al doping and in situ Al2O3 coating. The metal Al forms a conductive network in the film, while part of the Al will enter the LiCoO2 lattice to form a LiAl y Co1-y O2 solid solution, promoting the transport of lithium ions and improving the stability of the electrode structure. The in situ continuous deposition of the coating optimizes the active material coating-electrolyte interface.

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