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Background: Developmental Dysplasia of the Hip (DDH) is a skeletal disorder where late-presenting forms often escape early diagnosis, leading to limb and pain in adults. The genetic basis of DDH is not fully understood despite known genetic predispositions. Methods: We employed Whole Genome Sequencing (WGS) to explore the genetic factors in late-presenting DDH in two unrelated families, supported by phenotypic analyses and in vitro validation. Results: In both cases, a novel de novo heterozygous missense mutation in RAF1 (c.193A>G [p.Lys65Glu]) was identified. This mutation impacted RAF1 protein structure and function, altering downstream signaling in the Ras/ERK pathway, as demonstrated by bioinformatics, molecular dynamics simulations, and in vitro validations. Conclusion: This study contributes to our understanding of the genetic factors involved in DDH by identifying a novel mutation in RAF1. The identification of the RAF1 mutation suggests a possible involvement of the Ras/ERK pathway in the pathogenesis of late-presenting DDH, indicating its potential role in skeletal development.
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Optical coherence tomography (OCT), owing to its non-invasive nature, has demonstrated tremendous potential in clinical practice and has become a prevalent diagnostic method. Nevertheless, the inherent speckle noise and low sampling rate in OCT imaging often limit the quality of OCT images. In this paper, we propose a lightweight Transformer to efficiently reconstruct high-quality images from noisy and low-resolution OCT images acquired by short scans. Our method, PSCAT, parallelly employs spatial window self-attention and channel attention in the Transformer block to aggregate features from both spatial and channel dimensions. It explores the potential of the Transformer in denoising and super-resolution for OCT, reducing computational costs and enhancing the speed of image processing. To effectively assist in restoring high-frequency details, we introduce a hybrid loss function in both spatial and frequency domains. Extensive experiments demonstrate that our PSCAT has fewer network parameters and lower computational costs compared to state-of-the-art methods while delivering a competitive performance both qualitatively and quantitatively.
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Segmentation of the temporomandibular joint (TMJ) disc and condyle from magnetic resonance imaging (MRI) is a crucial task in TMJ internal derangement research. The automatic segmentation of the disc structure presents challenges due to its intricate and variable shapes, low contrast, and unclear boundaries. Existing TMJ segmentation methods often overlook spatial and channel information in features and neglect overall topological considerations, with few studies exploring the interaction between segmentation and topology preservation. To address these challenges, we propose a Three-Branch Jointed Feature and Topology Decoder (TFTD) for the segmentation of TMJ disc and condyle in MRI. This structure effectively preserves the topological information of the disc structure and enhances features. We introduce a cross-dimensional spatial and channel attention mechanism (SCIA) to enhance features. This mechanism captures spatial, channel, and cross-dimensional information of the decoded features, leading to improved segmentation performance. Moreover, we explore the interaction between topology preservation and segmentation from the perspective of game theory. Based on this interaction, we design the Joint Loss Function (JLF) to fully leverage the features of segmentation, topology preservation, and joint interaction branches. Results on the TMJ MRI dataset demonstrate the superior performance of our TFTD compared to existing methods.
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Transtornos da Articulação Temporomandibular , Articulação Temporomandibular , Humanos , Articulação Temporomandibular/diagnóstico por imagem , Articulação Temporomandibular/patologia , Disco da Articulação Temporomandibular/patologia , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Transtornos da Articulação Temporomandibular/patologia , Imageamento por Ressonância Magnética/métodos , MovimentoRESUMO
BACKGROUND & AIMS: Endoplasmic reticulum (ER) membrane protein complex subunit 10 (EMC10) has been implicated in obesity. Here we investigated the roles of the two isoforms of EMC10, including a secreted isoform (scEMC10) and an ER membrane-bound isoform (mEMC10), in metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: Manifold steatotic mouse models and HepG2 cells were employed to investigate the role of EMC10 in the regulation of hepatic PERK-eIF2α-ATF4 signaling and hepatosteatosis. The therapeutic effect of scEMC10-neutralizing antibody on mouse hepatosteatosis was explored. Associations of MASLD with serum scEMC10 and hepatic mEMC10 were determined in two cohorts of participants with MASLD. RESULTS: scEMC10 promoted, while mEMC10 suppressed, the activation of hepatic PERK-eIF2α-ATF4 signaling. Emc10 gene knockout exacerbated, while hepatic overexpression of mEMC10 ameliorated, hepatic ER stress and steatosis in mice challenged with either a methionine- and choline-deficient diet or tunicamycin, highlighting a direct, suppressive role of mEMC10 in MASLD via modulation of hepatic ER stress. Overexpression of scEMC10 promoted, whereas neutralization of circulating scEMC10 prevented, hepatosteatosis in mice with fatty liver, suggesting a role of scEMC10 in MASLD development. Clinically, serum scEMC10 was increased, while hepatic mEMC10 was decreased, in participants with MASLD. Correlative analysis indicated that serum scEMC10 positively, whereas hepatic mEMC10 negatively, correlated with liver fat content and serum ALT, AST, and GGT. CONCLUSIONS: These findings demonstrate a novel isoform-specific role for EMC10 in the pathogenesis of MASLD and identify the secreted isoform as a tractable therapeutic target for MASLD via antibody-based neutralization. IMPACT AND IMPLICATIONS: We have shown the role of EMC10 in the regulation of energy homeostasis and obesity. In this study, we determine the distinct roles of the two isoforms of EMC10 in the regulation of hepatic endoplasmic reticulum stress and steatosis in mice, and report on the associations of the different EMC10 isoforms with metabolic dysfunction-associated steatotic liver disease in humans. Our findings delineate a novel regulatory axis for hepatosteatosis and identify EMC10 as a modulator of the PERK-eIF2α-ATF4 signaling cascade that may be of broad physiological significance. Moreover, our pre-clinical and clinical studies provide evidence of the therapeutic potential of targeting scEMC10 in MASLD.
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In the context of high-quality economic development in China, it is important to promote green innovation development by protecting intellectual property rights (IPR). Taking the pilot policy of the intellectual property courts in Beijing, Shanghai, and Guangzhou for example in a quasi-natural experiment, this article examines the effect of IPR protection on the development of corporate green innovation and its mechanisms by using a difference-in-differences model and a mediating effect model based on Chinese enterprise data from 2011 to 2019. The study found that first, IPR protection promotes enterprise green technological innovation; second, IPR protection affects green innovation through enterprise financing constraints and R&D investment; that is, increasing enterprise R&D investment and alleviating enterprise financing constraints are two important channels through which IPR protection promotes enterprise green technological innovation.
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BACKGROUND: In cases where the upper arm exhibits an irregular cylindrical appearance with subcutaneous fat concentrated primarily in the posterior lateral aspect, traditional localized fat suction techniques may lead to uneven or disharmonious results when addressing this concern. Many practitioners have turned to circumferential fat suction methods using multi-incision approaches to ensure effective results and fat removal. However, these methods often involve numerous incisions and complex procedures, necessitating the development of new, more efficient surgical techniques. METHODS: We collected and screened patients who underwent upper arm circumferential liposuction with a double incision technique at our hospital from October 2020 to February 2023. A total of 496 cases were included in our retrospective analysis, in which we examined factors such as the length of surgery, arm circumference before and after surgery, subcutaneous tissue thickness before and after surgery, fat suction volume, postoperative satisfaction, and postoperative complications of the patients. RESULTS: The average length of surgery was 71.7 min. 458 cases (92.3%) showed significant improvement, 23 cases (4.6%) reported satisfaction, and 10 cases (2.0%) were essentially satisfied. Additionally, 339 cases (68.3%) experienced an improvement in skin laxity. Four cases (0.8%) developed localized hard nodules with slight tenderness in the early postoperative period, which resolved without special treatment after observation and follow-up for 1-3 months. Three cases (0.6%) reported localized pain or numbness, and they were given oral medication. Their symptoms disappeared after 1-3 months of observation and follow-up. Three cases (0.6%) had localized pain or numbness, and their symptoms disappeared. All of these cases improved and resolved after one month of taking mecobalamin tablets. There were also three cases (0.6%) with mild pigmentation of the incision and two cases (0.4%) with mild limitation of unilateral upper arm abduction movement. However, upper arm activities were not affected after three months to one year of follow-up. No serious complications were reported, resulting in an overall satisfaction rate of 99.0%. CONCLUSION: The double incision upper arm liposuction is safe, effective, time-saving, with high satisfaction and fewer complications, and is worthy of clinical popularization and application. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of contents or the online Instructions to Authors www.springer.com/00266 .
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Initially, anode-free Li metal batteries present a promising power source that merges the high production feasibility of Li-ion batteries with the superb energy capabilities of Li-metal batteries. However, their application confronts formidable challenges of extremely short lifespan due to the inadequacy of zero-Li-excess cell configuration against irreversible Li loss. A Li compensation coupled interface engineering strategy is reported for realizing long-life quasi-solid-state anode-free batteries. The Li2 S is utilized as a sacrificial Li supplement to effectively counterbalance irreversible Li loss without damage to cell chemistry. Meanwhile, it demonstrates remarkable efficacy in establishing a robust yet slender inorganic-organic hybrid solid-state interphase for inhibiting cell degradation by dead and dendritic Li. This strategy enables quasi-solid-state anode-free batteries with a long lifespan of 500 cycles. The Ah-scale quasi-solid-state pouch cells, featuring a high-loading LiFePO4 cathode and lean gel polymer electrolyte, exhibit a high specific energy of 300 Wh kgcell -1 . This achievement translates into an improvement of 46% in gravimetric energy and 94% in volumetric energy compared to LiFePO4 ||graphite batteries while outperforming LiFePO4 ||Li-metal batteries by 22-47% in volumetric energy. Such quasi-solid-state anode-free cells also demonstrate good safety, showcasing remarkable resistance against nail penetration in ambient air without failure, smoke, or fire accidents.
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Objective: This study is aimed to determine the metabolomic effects of the hybrid medicine formula Yi-Qi-Bu-Shen (YQBS) on the neurotransmitter aspects of cognitive impairment in diabetic rats. Methods: In the current study, streptozotocin (STZ) was used to induce diabetic animal model in male Sprague Dawley (SD) rats. After successful establishment of diabetic SD rats' model, age-matched healthy SD rats and diabetic SD rats were treated with low and high doses of YQBS, and then tested for learning memory ability and analyzed for pathological changes. In addition, neurotransmitter metabolic changes in hippocampal subdivisions of rats from different treated groups were analyzed using liquid chromatography-mass spectrometry (LC-MS) technique. Results: YQBS could significantly improve memory-cognitive impairment in diabetic rats as evidenced by the shortening of latency to target and the reduction of latency first entrance to target. Moreover, YQBS also improved the pathological alterations in the hippocampal region in the brains of diabetic rats. Metabolomic analysis showed that the expression of noradrenaline hydrochloride was down-regulated and the expressions of levodopa and 5-hydroxytryptophan were up-regulated in the hippocampal tissues of diabetic rats treated with YQBS. Conclusion: These findings demonstrate that YQBS has protective effects against diabetic cognitive dysfunction, which might act through alteration in tyrosine and tryptophan metabolism.
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Gaucher disease (GD), one of the most common lysosomal storage diseases, is caused by GBA1 mutations resulting in defective glucocerebrosidase (GCase) and consequent accumulation of its substrates ß-glucosylceramide (ß-GlcCer). We reported progranulin (PGRN), a secretary growth factor-like molecule and an intracellular lysosomal protein was a crucial co-factor of GCase. PGRN binds to GCase and recruits Heat Shock Protein 70 (Hsp70) to GCase through its C-terminal Granulin (Grn) E domain, termed as ND7. In addition, both PGRN and ND7 are therapeutic against GD. Herein we found that both PGRN and its derived ND7 still displayed significant protective effects against GD in Hsp70 deficient cells. To delineate the molecular mechanisms underlying PGRN's Hsp70-independent regulation of GD, we performed a biochemical co-purification and mass spectrometry with His-tagged PGRN and His-tagged ND7 in Hsp70 deficient cells, which led to the identification of ERp57, also referred to as protein disulfide isomerase A3 (PDIA3), as a protein that binds to both PGRN and ND7. Within type 2 neuropathic GD patient fibroblasts L444P, bearing GBA1 L444P mutation, deletion of ERp57 largely abolished the therapeutic effects of PGRN and ND7, as manifested by loss of effects on lysosomal storage, GCase activity, and ß-GlcCer accumulation. Additionally, recombinant ERp57 effectively restored the therapeutic effects of PGRN and ND7 in ERp57 knockout L444P fibroblasts. Collectively, this study reports ERp57 as a previously unrecognized binding partner of PGRN that contributes to PGRN regulation of GD.
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Doença de Gaucher , Progranulinas , Humanos , Doença de Gaucher/tratamento farmacológico , Doença de Gaucher/genética , Doença de Gaucher/metabolismo , Glucosilceramidase/genética , Glucosilceramidase/metabolismo , Glucosilceramidase/uso terapêutico , Lisossomos/metabolismo , Mutação , Progranulinas/genética , Progranulinas/metabolismo , Progranulinas/uso terapêutico , Isomerases de Dissulfetos de Proteínas/genética , Isomerases de Dissulfetos de Proteínas/metabolismo , Isomerases de Dissulfetos de Proteínas/uso terapêuticoRESUMO
INTRODUCTION: The relationship between progesterone (P) and diabetic nephropathy (DKD) is unclear. Herein, we investigated the relationship between progesterone and DKD in men and postmenopausal women with type 2 diabetes mellitus. MATERIALS AND METHODS: We recruited 3,556 male and postmenopausal female patients and obtained the dominance ratio (OR) and corresponding 95% confidence intervals (CIs) associated with progesterone by logistic regression analysis after adjusting for potentially confounding variants. RESULTS: We found that progesterone levels were significantly lower in the massive proteinuria and microproteinuria groups compared with the non-DKD group for male patients. Also, microproteinuria and massive proteinuria prevalence were higher in the first (lowest) progesterone quartile than in the second to fourth quartiles. After adjusting for confounders, compared with the first (lowest) progesterone quartile group, the OR for the second to fourth quartiles in the male microproteinuria subgroup, were: Q2: 0.846 (95% CI: 0.581-1.233, P = 0.385); Q3: 0.667 (95% CI: 0.45-0988, P = 0.044); Q4: 0.597 (95% CI: 0.393-0.907, P = 0.016). In the male massive proteinuria subgroup, the OR for the third quartile group was 0.418 (95% CI: 0.201-0.867, P = 0.019). In contrast, no significant association was detected between progesterone and DKD prevalence in the female group. CONCLUSIONS: Progesterone levels were negatively associated with DKD incidence in hospitalized male patients with type 2 diabetes mellitus.
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Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Humanos , Masculino , Feminino , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Estudos Retrospectivos , Progesterona , Estudos Transversais , Nefropatias Diabéticas/etiologia , Proteinúria/complicaçõesRESUMO
Solid-state polymer electrolytes (SPEs) attract great interest in developing high-performance yet reliable solid-state batteries. However, understanding of the failure mechanism of the SPE and SPE-based solid-state batteries remains in its infancy, posing a great barrier to practical solid-state batteries. Herein, the high accumulation and clogging of "dead" lithium polysulfides (LiPS) on the interface between the cathode and SPE with intrinsic diffusion limitation is identified as a critical failure cause of SPE-based solid-state Li-S batteries. It induces a poorly reversible chemical environment with retarded kinetics on the cathode-SPE interface and in bulk SPEs, starving the Li-S redox in solid-state cells. This observation is different from the case in liquid electrolytes with free solvent and charge carriers, where LiPS dissolve but remain alive for electrochemical/chemical redox without interfacial clogging. Electrocatalysis demonstrates the feasibility of tailoring the chemical environment in diffusion-restricted reaction media for reducing Li-S redox failure in the SPE. It enables Ah-level solid-state Li-S pouch cells with a high specific energy of 343 Wh kg-1 on the cell level. This work may shed new light on the understanding of the failure mechanism of SPE for bottom-up improvement of solid-state Li-S batteries.
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Type 2 diabetes (T2D) is a complex chronic disease with substantial phenotypic heterogeneity affecting millions of individuals. Yet, its relevant metabolites and etiological pathways are not fully understood. The aim of this study is to assess a broad spectrum of metabolites related to T2D in a large population-based cohort. We conducted a metabolomic analysis of 4,281 male participants within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. The serum metabolomic analysis was performed using an LC-MS/GC-MS platform. Associations between 1,413 metabolites and T2D were examined using linear regression, controlling for important baseline risk factors. Standardized ß-coefficients and standard errors (SEs) were computed to estimate the difference in metabolite concentrations. We identified 74 metabolites that were significantly associated with T2D based on the Bonferroni-corrected threshold (P < 3.5 × 10-5). The strongest signals associated with T2D were of carbohydrates origin, including glucose, 1,5-anhydroglucitol (1,5-AG), and mannose (ß = 0.34, -0.91, and 0.41, respectively; all P < 10-75). We found several chemical class pathways that were significantly associated with T2D, including carbohydrates (P = 1.3 × 10-11), amino acids (P = 2.7 × 10-6), energy (P = 1.5 × 10-4), and xenobiotics (P = 1.2 × 10-3). The strongest subpathway associations were seen for fructose-mannose-galactose metabolism, glycolysis-gluconeogenesis-pyruvate metabolism, fatty acid metabolism (acyl choline), and leucine-isoleucine-valine metabolism (all P < 10-8). Our findings identified various metabolites and candidate chemical class pathways that can be characterized by glycolysis and gluconeogenesis metabolism, fructose-mannose-galactose metabolism, branched-chain amino acids, diacylglycerol, acyl cholines, fatty acid oxidation, and mitochondrial dysfunction.NEW & NOTEWORTHY These metabolomic patterns may provide new additional evidence and potential insights relevant to the molecular basis of insulin resistance and the etiology of T2D.
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Diabetes Mellitus Tipo 2 , Neoplasias , Humanos , Masculino , Diabetes Mellitus Tipo 2/metabolismo , beta Caroteno , alfa-Tocoferol , Estudos Transversais , Manose , Galactose , Metabolômica , Ácidos GraxosRESUMO
AIM: The aim of this study was to investigate the lived experience of people with diabetic retinopathy and to understand the impact of the disease on them including the practical problems faced in the day-to-day life. DESIGN: Descriptive qualitative research. METHODS: A convenience sample of 11 patients with diabetic retinopathy who were hospitalized in a tertiary hospitals in Shandong province of China were enrolled. Data were collected using semi-structured in-depth interviews. The six-stage thematic analysis of Braun and Clarke was used for data analysis. RESULTS: Three themes and 12 sub-themes were extracted, namely: countdown to darkness (lack of disease knowledge, bystander's perspective, distrust of grassroots hospitals); Endless abyss (action restrictions, social isolation, stigma, lost of meaning in life, catastrophizing explanations, a heavy burden); Light chaser (craving for light, turning points in behaviour, self-adjustment).
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Diabetes Mellitus , Retinopatia Diabética , Humanos , Estigma Social , Isolamento Social , Pesquisa Qualitativa , PercepçãoRESUMO
Circadian rhythm is an inherent endogenous biological rhythm in living organisms. However, with the improvement of modern living standards, many factors such as prolonged artificial lighting, sedentarism, short sleep duration, intestinal flora and high-calorie food intake have disturbed circadian rhythm regulation on various metabolic processes, including GLP-1 secretion, which plays an essential role in the development of various metabolic diseases. Herein, we focused on GLP-1 and its circadian rhythm to explore the factors affecting GLP-1 circadian rhythm and its potential mechanisms and propose some feasible suggestions to improve GLP-1 secretion.
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Peptídeo 1 Semelhante ao Glucagon , Transtornos do Sono-Vigília , Humanos , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Ritmo Circadiano/fisiologia , Sono/fisiologia , IluminaçãoRESUMO
Based on conservation of resource theory, this study adopts an experience sampling method to build a cross-hierarchical mode to investigate the internal mechanism between supervisor helping behavior and employee voice behavior. The empirical results from 76 employees' dynamic data show that the supervisor helping behavior has no significant direct effect on the employee voice behavior; thriving at work plays a mediating role between supervisor helping behavior and employee voice behavior. Psychological availability, as a moderator, not only positively moderates the effect of supervisor helping behavior on thriving at work but also positively moderates the mediation of thriving at work on the relationship between supervisor helping behavior and employee voice behavior. From the dynamic perspective, this study adds to the literature on supervisor helping behavior and employee voice behavior, and it has practical implications on managerial decision-making.
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Anode-free lithium batteries without lithium metal excess are a practical option to maximize the energy content beyond the conventional design of Li-ion and Li metal batteries. However, their performance and reliability are still limited by using low-capacity oxygen-releasing intercalation cathodes and flammable liquid electrolytes. Herein, we propose quasi-solid-state anode-free batteries containing lithium sulfide-based cathodes and non-flammable polymeric gel electrolytes. Such batteries exhibit an energy density of 1323 Wh L-1 at the pouch cell level. Moreover, the lithium sulfide-based anode-free cell chemistry endows intrinsic safety thanks to a lack of uncontrolled exothermic reactions of reactive oxygen and excess Li inventory. Furthermore, the non-flammable gel electrolyte, developed from MXene-doped fluorinated polymer, inhibits polysulfide shuttling, hinders Li dendrite formation and further secures cell safety. Finally, we demonstrate the improved cell safety against mechanical, electrical and thermal abuses.
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Recent years have witnessed thriving efforts in pursuing high-energy batteries at an unaffordable cost of safety. Herein, a high-energy and safe quasi-solid-state lithium battery is proposed by solid-state redox chemistry of polymer-based molecular Li2 S cathode in a fireproof gel electrolyte. This chemistry fully eliminates not only the negative effect of extremely reactive Li metal and oxygen species on cell safety but also the damage of electrode reversibility by soluble redox intermediates. The molecular Li2 S cathode exhibits an exceptional lifetime of 2000 cycles, 100% Coulombic efficiency, high capacity of 830 mA h g-1 with ultralow capacity loss of 0.005-0.01% per cycle and superior rate capability up to 10 C. Meanwhile, it shows high stability in the carbonate-involving electrolyte for maximizing the compatibility with carbonate-efficient Si anode. The optimized cell chemistry exerts high energy over 750 W h kg-1 for 500 cycles with fast rate response, high-temperature adaptability, and no self-discharge. A fire-retardant composite gel electrolyte is developed to further strengthen the intrinsic safe redox between the Li2 S cathode and the Si anode, which secures remarkable safety against extreme abuse of overheating, short circuits, and mechanical damage in air/water or even when on fire.
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Safety risks stem from applying extremely reactive alkali metal anodes and/or oxygen-releasing cathodes in flammable liquid electrolytes restrict the practical use of state-of-the-art high-energy batteries. Here, we propose a intrinsically safe solid-state cell chemistry to satisfy both high energy and cell reliability. An all-solid-state rechargeable battery is designed by energetic yet stable multielectron redox reaction between Li2S cathode and Si anode in robust solid-state polymer electrolyte with fast ionic transport. Such cells can deliver high specific energy of 500 to 800 Wh kg−1 for 500 cycles with fast rate response, negligible self-discharge, and good temperature adaptability. Integrating intrinsic safe cell chemistry to robust cell design further guarantees reversible energy storage against extreme abuse of overheating, overcharge, short circuit, and mechanical damage in the air and water. This work may shed fresh insight into bridging the huge gap between high energy and safety of rechargeable cells for feasible applications and recycle.
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BACKGROUND: MicroRNAs (miRNAs) have been shown to play a crucial role in inflammation regulation; however, their relationship with inflammation in acute gouty arthritis has not been fully elucidated. Herein, we conducted a study to explore the regulatory roles of miR-223-3p and miR-22-3p in gouty-associated inflammation. METHODS: In vitro and in vivo experiments were conducted to examine the molecular mechanisms of miRNA regulation in gouty inflammation. Dual-luciferase reporter assay was used to verify the direct target of miR-223-3p and miR-22-3p. RESULTS: We found that miR-223-3p and miR-22-3p interacted with the 3' untranslated region segment of NLRP3 (nucleotide-binding domain leucine-rich repeat [NLR] and pyrin domain containing receptor 3) and inhibited its expression. A decreased expression of miR-223-3p and miR-22-3p was observed in both mice air pouch synovium and phorbol myristrate acetate-treated THP-1 cells stimulated with monosodium urate (P < .05). Compared with the negative control group, NLRP3 expression at the transcript and protein level in miR-223-3p and miR-22-3p overexpression group significantly decreased after 6 hours of monosodium urate treatment in vivo and in vitro (P < .05). The results of the dual-luciferase reporter assay demonstrated that miR-223-3p and miR-22-3p directly targeted NLRP3. CONCLUSION: The findings of the present study show that miR-223-3p and miR-22-3p can reduce the inflammatory effects of gout by inhibiting the expression of NLRP3.
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Artrite Gotosa/metabolismo , Inflamassomos/metabolismo , Inflamação/metabolismo , MicroRNAs/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Regiões 3' não Traduzidas , Animais , Artrite Gotosa/induzido quimicamente , Artrite Gotosa/imunologia , Artrite Gotosa/prevenção & controle , Sítios de Ligação , Modelos Animais de Doenças , Regulação para Baixo , Humanos , Inflamassomos/genética , Inflamação/induzido quimicamente , Inflamação/imunologia , Inflamação/prevenção & controle , Masculino , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Transdução de Sinais , Células THP-1 , Ácido ÚricoRESUMO
The MXenes attract great interest in catalytic and energy applications but suffer from inferior redox activity. An efficient strategy is presented to boost the intrinsic electrochemical activity of MXenes for electrocatalysis in various chemical environments by utilizing their plasmonic response to electromagnetic waves. The resulting significant thermoplasmonic effect lowers the endothermic enthalpy and potential barrier to the hydrogen evolution reaction (HER) in the Vis/near-IR region. Simultaneous hot-electron injection in a prolonged sub-femtosecond to picosecond timescale also remarkably facilitates interfacial charge transfer and decreases the activation energy of the reaction. Both effects boost the HER activity of various types of MXenes over fivefold with improved kinetics and Faradaic efficiency over a broad pH range.