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Droplet impact behavior is ubiquitous in various fields. However, the dynamics and spreading mechanisms of micro- and nanoscale droplet impact on curved surfaces, particularly in the case of multiple droplets, have yet to be fully elucidated. In this study, molecular dynamics (MD) methods are employed to investigate the dynamic evolution of double nanodroplet impact on a nano cylindrical wall. The effects of droplet spacing, initial impact velocity, and wall wettability on droplet impact characteristics are analyzed. The results demonstrate that there are five impact modes of nanoscale double-droplet impacts with nanocylinders: spreading-partial wrapping-splitting-complete detachment (SPSC), spreading-complete wrapping-complete attachment (SCC), spreading-partial wrapping-complete attachment (SPC), spreading-partial wrapping-partial attachment (SPP), and spreading-partial wrapping-fragmentation-partial attachment (SPFP). The droplet spacing has an insignificant effect on the impact modes but affects the droplets' spreading shape in both the axial and radial directions. The initial velocity and wall wettability have significant impacts on the droplet impact modes and liquid film spreading characteristics. As the initial velocity increases, the liquid film's radial and axial spreading distances gradually increase. Under hydrophobic conditions, the spreading of the droplet is dominant in the radial direction, while under hydrophilic conditions, the spreading is dominant in the axial direction. Properly reducing the droplet spacing, increasing the impact velocity, and enhancing the wall hydrophobicity can promote detaching the droplet from the cylindrical wall.
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Nowadays, flexible multifunctional composites are attracting much attention and are practically being used in various emerging electronic devices. However, most composites suffer from the disadvantages of high loadings of conductive fillers, complicated preparation processes, and low energy conversion efficiency. In this article, Caffeic acid-modified multiwalled carbon nanotubes (C-MWCNTs)/poly(3,4-ethylene dioxythiophene):polystyrene sulfonic acid (PEDOT:PSS)/polyimide (PI) composite films (CPFs) were prepared using a simple layer-by-layer deposition method. The "reinforced concrete" structure of the C-MWCNTs/PEDOT:PSS layer ensures high electrical conductivity of the film, while the PI layer provides excellent mechanical properties (72.69 MPa). The composite film exhibits excellent electrothermal response and thermal stability up to approximately 125 °C at 5 V. In addition, the good conductivity of the film provides its electromagnetic shielding effectiveness (32.69 dB). With these advantages, we expect that flexible CPFs will be widely utilized in wearable devices, electromagnetic interference (EMI) shielding applications, and thermal management of personal or electronic devices.
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With the popularization of 5G technology and the development of science and technology, flexible and transparent conductive films (TCF) are increasingly used in the preparation of optoelectronic devices such as electromagnetic shielding devices, transparent flexible heaters, and solar cells. Silver nanowires (AgNW) are considered the best material for replacing indium tin oxide to prepare TCFs due to their excellent comprehensive properties. However, the loose overlap between AgNWs is a significant reason for the high resistance. This article investigates a sandwich structured conductive network composed of AgNW and Ti3C2Tx MXene for high-performance EMI shielding and transparent electrical heaters. Polyethylene pyrrolidone (PVP) solution was used to hydrophilic modify PET substrate, and then MXene, AgNW, and MXene were assembled layer by layer using spin coating method to form a TCF with a sandwich structure. One-dimensional AgNW is used to provide electron transfer channels and improve light penetration, while two-dimensional MXene nanosheets are used for welding AgNWs and adding additional conductive channels. The flexible TCF has excellent transmittance (85.1 % at 550 nm) and EMI shielding efficiency (27.1 dB). At the voltage of 5 V, the TCF used as a heater can reach 85.6 °C. This work offers an innovative approach to creating TCFs for the future generation.
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BACKGROUND: Cutaneous melanoma (CM) has long been recognized as a lethal form of cancer. Despite persistent research endeavors, the precise underlying pathological mechanisms remain largely unclear, and the optimal treatment for this patient population remains undetermined. OBJECTIVES: This study aims to examine the causal associations between CM and 486 metabolites. METHODS: A two-sample Mendelian randomization (MR) analysis was conducted to ascertain the causal relationship between blood metabolites and CM. The causality analysis involved the inverse variance weighted (IVW) method, followed by the MR-Egger and weighted median (WM) methods. To increase the robustness of our findings, several sensitivity analyses, including the MR-Egger intercept, Cochran's Q test, and MR-pleiotropy residual sum and outlier (MR-PRESSO), were performed. The robustness of our results was further validated in independent outcome samples followed by a meta-analysis. Additionally, a metabolic pathway analysis was carried out. RESULTS: The two-sample MR analysis yielded a total of 27 metabolites as potential causal metabolites. After incorporating the outcomes of the sensitivity analyses, seven causal metabolites remained. Palmitoylcarnitine (OR 0.9903 95% CI 0.9848-0.9958, p = 0.0005) emerged as the sole metabolite with a significant causality after Bonferroni correction. Furthermore, the reverse MR analysis provided no evidence of reverse causality from CM to the identified metabolites. CONCLUSIONS: This study suggested a causal relationship between seven human blood metabolites and the development of CM, thereby offering novel insights into the underlying mechanisms involved. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. 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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Melanoma , Análise da Randomização Mendeliana , Neoplasias Cutâneas , Humanos , Melanoma/genética , Melanoma/sangue , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/sangue , Melanoma Maligno Cutâneo , Feminino , Medição de RiscoRESUMO
BACKGROUND: Observational studies have linked coffee, alcohol, tea, and sugar-sweetened beverage (SSB) consumption to facial skin aging. However, confounding factors may influence these studies. The present two-sample Mendelian randomization (MR) investigated the potential causal association between beverage consumption and facial skin aging. METHODS: The single-nucleotide polymorphisms (SNPs) associated with coffee, alcohol, and tea intake were derived from the IEU project. The SSB-associated SNPs were selected from a genome-wide association study (GWAS). Data on facial skin aging were derived from the largest GWAS involving 16 677 European individuals. The inverse variance-weighted (IVW) was the main MR analysis method, supplemented by other methods (MR-Egger, weighted median, simple mode, and weighted mode). The MR-Egger intercept analysis was used for sensitivity analysis. Moreover, we conducted a replication analysis using data from another GWAS dataset on coffee consumption to validate our findings. RESULTS: Four instrumental variables (IVs) sets were used to examine the causal association between beverage consumption (coffee, alcohol, tea, SSB) and facial skin aging. Our results revealed that genetically predicted higher coffee consumption reduced the risk of facial skin aging (OR: 0.852; 95% CI: 0.753-0.964; p = 0.011, IVW method). The sensitivity analysis confirmed the robustness of the findings, with no evidence of pleiotropy or heterogeneity. The results of replicated MR analysis on coffee consumption were consistent with the initial analysis (OR = 0.997; 95% CI = 0.996-0.999; p = 0.003, IVW method). CONCLUSIONS: This study manifests that higher coffee consumption is significantly associated with a reduced risk of facial skin aging. These findings can offer novel strategies for identifying the underlying etiology of facial skin aging.
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Café , Face , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Envelhecimento da Pele , Chá , Humanos , Envelhecimento da Pele/genética , Café/efeitos adversos , Chá/efeitos adversos , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/genética , Bebidas Adoçadas com Açúcar/efeitos adversos , Bebidas/efeitos adversosRESUMO
BACKGROUND: Hyaluronic acid (HA) injection is an effective method to correct tear trough deformity. Nevertheless, the quantitative data of cosmetic results and complications of HA injection in tear troughs remained unemployed. The purpose of this meta-analysis was to synthesize the current quantitative data on the aesthetic outcomes and adverse effects of tear trough deformity correction with HA injection. METHODS: This meta-analysis consulted PubMed, Embase, Web of Science, Scopus and Cochrane databases based on the search terms published before September 2022. Data extracted was analyzed to evaluate the satisfaction rates and complications of HA injection. Meta-analysis was performed using the random-effect model for overall and subgroup analysis. RESULTS: This meta-analysis comprised 31 reports involving 2556 participants. The pooled overall satisfaction rate was 91.0% (95% CI 84.9-95.7%). The pooled rates of swelling/edema and bruising/ecchymosis were 19.2% (95% CI 10.4-29.9%) and 18.4% (95% CI 10.1-28.4%), respectively. The pooled rates of redness/erythema, contour irregularity/lump and blue discoloration/Tyndall effect were 7.1% (95% CI 1.5-15.6%), 5.3% (95% CI 1.8-10.2%) and 0.9% (95% CI 0.0-2.5%), respectively. CONCLUSIONS: The present meta-analysis manifested a low risk of complication rate and a high satisfaction rate in tear trough rejuvenation with HA injection. LEVEL OF EVIDENCE I: 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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Blefaroplastia , Preenchedores Dérmicos , Ácido Hialurônico , Humanos , Blefaroplastia/métodos , Preenchedores Dérmicos/uso terapêutico , Ácido Hialurônico/uso terapêutico , Injeções , Resultado do TratamentoRESUMO
It is a common phenomenon that droplets collide with wires in industrial production, and their flow and heat-transfer behavior significantly impact the production efficiency. This article presents an experimental and numerical study on the impact of pure water droplets on hydrophilic stainless-steel wires. The dynamic behavior and solid-liquid heat-transfer law of droplet impacting the wire are emphatically analyzed. The impact position of the droplets has a significant effect on their morphology. Under the condition of low Weber number (We), eccentric impacts tend to cause droplets to separate from the wire. Additionally, both We and wire/droplet size ratio have noticeable effects on the droplet morphology. The smaller the We, the larger the wire/droplet size ratio, and the easier it is for droplets to be captured by wires. Conversely, as We increases and the wire-to-droplet size ratio decreases, some droplets become detached from the wire, primarily exhibiting a single-film falling mode. Furthermore, the impact morphology of droplets is influenced by the Ohnesorge number (Oh). The higher the Oh, the more inclined the droplet to develop a double-film falling mode. There is obvious field synergy in the process of droplet impacting on wire. The maximum heat flux is located at the three-phase contact line, while the minimum heat flux is observed at the bubble interface. The impact position of droplets influences the temperature distribution, although its impact on the magnitude of temperature variation is minimal.
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BACKGROUND: Single eyelids are common among Asians. It is not uncommon to see people with single eyelids raise their eyebrows to wide open their eyes. This results in frequent compensatory contraction of the frontalis muscle and thus leads to deep forehead wrinkles. Double-eyelid blepharoplasty creates a larger visual field. In theory, patients who receive the surgery will stop overusing the frontalis muscle. Therefore, the forehead wrinkles can be improved. METHODS: 35 patients who underwent double-eyelid blepharoplasty were enrolled. FACE-Q forehead wrinkle assessment scale was adopted to evaluate the forehead wrinkles preoperatively and postoperatively. In addition, anthropometric measurements were taken to indirectly evaluate frontalis muscle contraction in maximum eye-opening position. RESULTS: According to the FACE-Q scale, forehead wrinkles were improved after double-eyelid blepharoplasty, and the improvement was long-lasting in the 3-month follow-up. This was because the frontalis muscle contraction reduced after the surgery, as shown by the anthropometric measurements. CONCLUSION: This study used subjective and objective methods to prove that double-eyelid surgery improves forehead wrinkles. LEVEL OF EVIDENCE IV: 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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Blefaroplastia , Humanos , Blefaroplastia/métodos , Estudos Prospectivos , Testa/cirurgia , Pálpebras/cirurgia , Povo Asiático , Estudos RetrospectivosRESUMO
Micro-expression is a fleeting facial expression of emotion that usually occurs in high-stake situations and reveals the true emotion that a person tries to conceal. Due to its unique nature, recognizing micro-expression has great applications for fields like law enforcement, medical treatment, and national security. However, the psychological mechanism of micro-expression recognition is still poorly understood. In the present research, we sought to expand upon previous research to investigate whether the group membership of the expresser influences the recognition process of micro-expressions. By conducting two behavioral studies, we found that contrary to the widespread ingroup advantage found in macro-expression recognition, there was a robust ingroup disadvantage in micro-expression recognition instead. Specifically, in Study 1A and 1B, we found that participants were more accurate at recognizing the intense and subtle micro-expressions of their racial outgroups than those micro-expressions of their racial ingroups, and neither the training experience nor the duration of micro-expressions moderated this ingroup disadvantage. In Study 2A and 2B, we further found that mere social categorization alone was sufficient to elicit the ingroup disadvantage for the recognition of intense and subtle micro-expressions, and such an effect was also unaffected by the duration of micro-expressions. These results suggest that individuals spontaneously employ the social category information of others to recognize micro-expressions, and the ingroup disadvantage in micro-expression stems partly from motivated differential processing of ingroup micro-expressions.
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The incidence of liver diseases has been increasing steadily. However, it has some shortcomings, such as high cost and organ donor scarcity. The application of stem cell research has brought new ideas for the treatment of liver diseases. Therefore, it is particularly important to clarify the molecular and regulatory mechanisms of differentiation of bone marrow-derived stem cells (BMSCs) into liver cells. Herein, we screened differentially expressed genes between hepatocytes and untreated BMSCs to identify the genes responsible for the differentiation of BMSCs into hepatocytes. GSE30419 gene microarray data of BMSCs and GSE72088 gene microarray data of primary hepatocytes were obtained from the Gene Expression Omnibus database. Transcriptome Analysis Console software showed that 1896 genes were upregulated and 2506 were downregulated in hepatocytes as compared with BMSCs. Hub genes were analyzed using the STRING and Cytoscape v 3.8.2, revealing that twenty-four hub genes, play a pivotal role in the differentiation of BMSCs into hepatocytes. The expression of the hub genes in the BMSCs and hepatocytes was verified by reverse transcription-quantitative PCR (RT-qPCR). Next, the target miRNAs of hub genes were predicted, and then the lncRNAs regulating miRNAs was discovered, thus forming the lncRNA-miRNA-mRNA interaction chain. The results indicate that the lncRNA-miRNA-mRNA interaction chain may play an important role in the differentiation of BMSCs into hepatocytes, which provides a new therapeutic target for liver disease treatment.
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MicroRNAs , RNA Longo não Codificante , RNA Longo não Codificante/genética , Medula Óssea/metabolismo , RNA Mensageiro/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Hepatócitos/metabolismo , Biomarcadores , Células-Tronco/metabolismo , Redes Reguladoras de GenesRESUMO
As fleeting facial expressions which reveal the emotion that a person tries to conceal, micro-expressions have great application potentials for fields like security, national defense and medical treatment. However, the physiological basis for the recognition of these facial expressions is poorly understood. In the present research, we utilized a double-blind, placebo-controlled, mixed-model experimental design to investigate the effects of oxytocin on the recognition of micro-expressions in three behavioral studies. Specifically, in Studies 1 and 2, participants were asked to perform a laboratory-based standardized micro-expression recognition task after self-administration of a single dose of intranasal oxytocin (40 IU) or placebo (containing all ingredients except for the neuropeptide). In Study 3, we further examined the effects of oxytocin on the recognition of natural micro-expressions. The results showed that intranasal oxytocin decreased the recognition speed for standardized intense micro-expressions of surprise (Study 1) and decreased the recognition accuracy for standardized subtle micro-expressions of disgust (Study 2). The results of Study 3 further revealed that intranasal oxytocin administration significantly reduced the recognition accuracy for natural micro-expressions of surprise and disgust. The present research is the first to investigate the effects of oxytocin on micro-expression recognition. It suggests that the oxytocin mainly plays an inhibiting role in the recognition of micro-expressions and there are fundamental differences in the neurophysiological basis for the recognition of micro-expressions and macro-expressions.
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Non-fullerene acceptors (NFAs) carrying a 1,1-dicyanomethylene-3-indanone (IC) end-group are the most powerful ones to boost the power conversion efficiency of organic solar cells (OSCs). However, the well-known Knoevenagel condensation of the mono-halogenated IC end-group will result in an NFA isomeric effect, a chemical issue that needs to be addressed. Herein, facile preparations and separations of three well-defined mono-brominated isomers BTzIC-2Br-δ, BTzIC-2Br-γ, and BTzIC-2Br-δγ via column chromatography with a well-chosen mixing solvent were demonstrated for Knoevenagel condensation, and their structures were verified by NMR spectra and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) mass spectra. It is the first time that an asymmetric isomer BTzIC-2Br-δγ is reported, and the regioisomeric effect on optoelectronic properties can be investigated based on all three isomers. Moreover, the single-crystal structure was successfully achieved for the symmetric molecule BTzIC-2Br-γ. With benzodithiophene (BDT)-free PFBT4T-T20 as an easily accessible and low-cost polymer donor, the three isomers could show differentiated device performances, with a power conversion efficiency order of BTzIC-2Br-γ (16.00%) > BTzIC-2Br-δγ (15.81%) > BTzIC-2Br-δ (15.29%). The best efficiency of 16.00% achieved with BTzIC-2Br-γ is among the highest ones for binary OSCs based on the low-cost BDT-free donors. The facile and complete synthesis of isomeric NFAs with mono-halogenated IC end-groups would promote the elucidation of the structure-property relationship.
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Although optical engineering strategy has been utilized to optimize average visible transmittance (AVT) of semi-transparent organic solar cells (ST-OSCs), judicious selection of active layer materials should be more direct and basic. Herein, an efficient ternary active layer is constructed with a wide bandgap (3.0 eV) fluorescent polymer FC-S1 as host donor, a middle bandgap polymer PM6 as guest donor, and a narrow bandgap non-fullerene Y6-BO as acceptor. Using FC-S1 as the host donor can allow more visible photons to penetrate the device. In the absence of optical engineering, the ternary ST-OSC with FC-S1:PM6:Y6-BO = 1:0.3:1.5 active layer of 30 nm thickness displays a much higher AVT of 49.28% than that of 32.34% for a PM6:Y6-BO = 1.3:1.5 based binary ST-OSC. The ternary ST-OSC provides a good power conversion efficiency of 6.01%, only slightly lower than 7.15% for the binary ST-OSC. The ternary ST-OSC also demonstrates a color rendering index (CRI) of 87 and a correlated color temperature (CCT) of 6916 K, all better than CRI of 80 and CCT of 9022 K for the binary ST-OSC. Moreover, the backbone of FC-S1 is mainly composed by fluorene and carbazole, two easily-accessible aromatic rings, which would meet low-cost concern of ST-OSCs.
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Corantes , Polímeros , Temperatura , EngenhariaRESUMO
BACKGROUND: Diabetes mellitus (DM) is considered to be an important factor for bone degeneration disorders such as bone defect nonunion, which is characterized by physical disability and tremendous economy cost to families and society. Exosomal miRNAs of BMSCs have been reported to participate in osteoblastogenesis and modulating bone formation. However, their impacts on the development of bone degeneration in DM are not yet known. The role of miRNAs in BMSCs exosomes on regulating hyperglycemia bone degeneration was investigated in the present study. RESULTS: The osteogenic potential in bone defect repair of exosomes derived from diabetes mellitus BMSCs derived exosomes (DM-Exos) were revealed to be lower than that in normal BMSCs derived exosomes (N-Exos) in vitro and in vivo. Here, we demonstrate that miR-140-3p level was significantly altered in exosomes derived from BMSCs, ADSCs and serum from DM rats. In in vitro experiments, upregulated miR-140-3p exosomes promoted DM BMSCs differentiation into osteoblasts. The effects were exerted by miR-140-3p targeting plxnb1, plexin B1 is the receptor of semaphoring 4D(Sema4D) that inhibited osteocytes differentiation, thereby promoting bone formation. In DM rats with bone defect, miR-140-3p upregulated exosomes were transplanted into injured bone and accelerated bone regeneration. Besides, miR-140-3p in the exosomes was transferred into BMSCs and osteoblasts and promoted bone regeneration by targeting the plexin B1/RohA/ROCK signaling pathway. CONCLUSIONS: Normal-Exos and miR-140-3p overexpressed-Exos accelerated diabetic wound healing by promoting the osteoblastogenesis function of BMSCs through inhibition plexin B1 expression which is the receptor of Sema4D and the plexin B1/RhoA/ROCK pathway compared with diabetes mellitus-Exos. This offers a new insight and a new therapy for treating diabetic bone unhealing.
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Diabetes Mellitus Experimental , Exossomos , MicroRNAs , Animais , Proliferação de Células , Exossomos/metabolismo , Proteínas Ativadoras de GTPase , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Ratos , Receptores de Superfície CelularRESUMO
Obesity is a chronic epidemic disease worldwide which has become one of the important public health issues. It is a process that excessive accumulation of adipose tissue caused by long-term energy intake exceeding energy expenditure. So far, the prevention and treatment strategies of obesity on individuals and population have not been successful in the long term. Acetylation is one of the most common ways of protein post-translational modification (PTM). It exists on thousands of non-histone proteins in almost every cell chamber. It has many influences on protein levels and metabolome levels, which is involved in a variety of metabolic reactions, including sugar metabolism, tricarboxylic acid cycle, and fatty acid metabolism, which are closely related to biological activities. Studies have shown that protein acetylation levels are dynamically regulated by lysine acetyltransferases (KATs) and lysine deacetylases (KDACs). Protein acetylation modifies protein-protein and protein-DNA interactions and regulates the activity of enzymes or cytokines which is related to obesity in order to participate in the occurrence and treatment of obesity-related metabolic diseases. Therefore, we speculated that acetylation was likely to become effective means of controlling obesity in the future. In consequence, this review focuses on the mechanisms of protein acetylation controlled obesity, to provide theoretical basis for controlling obesity and curing obesity-related diseases, which is a significance for regulating obesity in the future. This review will focus on the role of protein acetylation in controlling obesity.
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Tecido Adiposo/metabolismo , Metabolismo Energético , Histonas/metabolismo , Obesidade/metabolismo , Processamento de Proteína Pós-Traducional , Acetilação , Tecido Adiposo/fisiopatologia , Adiposidade , Animais , Histona Desacetilases , Humanos , Lisina Acetiltransferases/metabolismo , Obesidade/fisiopatologia , Transdução de Sinais , Aumento de PesoRESUMO
BACKGROUND: Aberrant microRNA (miRNA) expression affects biologic processes and downstream genes that are crucial to CKD initiation or progression. The miRNA miR-204-5p is highly expressed in the kidney but whether miR-204-5p plays any role in the development of chronic renal injury is unknown. METHODS: We used real-time PCR to determine levels of miR-204 in human kidney biopsies and animal models. We generated Mir204 knockout mice and used locked nucleic acid-modified anti-miR to knock down miR-204-5p in mice and rats. We used a number of physiologic, histologic, and molecular techniques to analyze the potential role of miR-204-5p in three models of renal injury. RESULTS: Kidneys of patients with hypertension, hypertensive nephrosclerosis, or diabetic nephropathy exhibited a significant decrease in miR-204-5p compared with controls. Dahl salt-sensitive rats displayed lower levels of renal miR-204-5p compared with partially protected congenic SS.13BN26 rats. Administering anti-miR-204-5p to SS.13BN26 rats exacerbated interlobular artery thickening and renal interstitial fibrosis. In a mouse model of hypertensive renal injury induced by uninephrectomy, angiotensin II, and a high-salt diet, Mir204 gene knockout significantly exacerbated albuminuria, renal interstitial fibrosis, and interlobular artery thickening, despite attenuation of hypertension. In diabetic db/db mice, administering anti-miR-204-5p exacerbated albuminuria and cortical fibrosis without influencing blood glucose levels. In all three models, inhibiting miR-204-5p or deleting Mir204 led to upregulation of protein tyrosine phosphatase SHP2, a target gene of miR-204-5p, and increased phosphorylation of signal transducer and activator of transcription 3, or STAT3, which is an injury-promoting effector of SHP2. CONCLUSIONS: These findings indicate that the highly expressed miR-204-5p plays a prominent role in safeguarding the kidneys against common causes of chronic renal injury.
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Nefropatias Diabéticas/metabolismo , Hipertensão/metabolismo , Rim/metabolismo , Rim/patologia , MicroRNAs/metabolismo , Nefroesclerose/metabolismo , Adulto , Albuminúria/genética , Animais , Artérias/patologia , Pressão Sanguínea/efeitos dos fármacos , Nefropatias Diabéticas/patologia , Feminino , Fibrose , Técnicas de Silenciamento de Genes , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Masculino , Camundongos , Camundongos Knockout , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Nefroesclerose/etiologia , Nefroesclerose/patologia , Fosforilação , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Ratos , Reação em Cadeia da Polimerase em Tempo Real , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Cloreto de Sódio na Dieta/administração & dosagem , Regulação para CimaRESUMO
Nowadays, the use of MSCs has attracted considerable attention in the global science and technology field, with the self-renewal and multidirectional differentiation potential for diabetes, obesity treatment, bone repair, nerve repair, myocardial repair, and so on. Epigenetics plays an important role in the regulation of mesenchymal stem cell differentiation, which has become a research hotspot in the medical field. This review focuses on the role of lysine acetylation modification on the determination of MSC differentiation direction. During this progress, the recruitment of lysine acetyltransferases (KATs) and lysine deacetylases (KDACs) is the crux of transcriptional mechanisms in the dynamic regulation of key genes controlling MSC multidirectional differentiation.
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Cytokines are necessary to trigger the inflammatory response in kidney ischemia/reperfusion injury. Interleukin-17C (IL-17C), a unique member of the IL-17 family, is a cytokine produced by epithelial cells implicated in host defense and autoimmune diseases. However, little is known about the role of IL-17C in acute kidney injury. We investigated this and found that IL-17C was significantly increased in kidney biopsies of patients and mice with acute kidney injury. Exposure to hypoxia induced upregulation of IL-17C in kidney tubular epithelial cells. To further investigate the role of IL-17C, kidney ischemia/reperfusion injury was induced in mice. Inhibition of IL-17C action with a neutralizing antibody or IL-17 receptor E (IL-17RE) knockout attenuated tubular injury, kidney oxidative stress, and kidney inflammation. Mechanistically, both IL-17C neutralization and IL-17RE knockout attenuated TH17 activation and IL-17A expression in kidneys of mice with acute kidney injury. TNF-α and IL-1ß, downstream cytokines of IL-17C, were also reduced in IL-17C antibody pretreated and IL-17RE knockout mice. Additionally, IL-17C knockdown with siRNA decreased hypoxia-induced inflammation in kidney tubular cells and silencing IL-17RE abrogated the effects of IL-17C in kidney tubular cells. Thus, IL-17C may participate in the inflammatory response of acute kidney injury and inhibition of IL-17C or blockade of IL-17 RE may be a novel therapeutic strategy for the treatment of acute kidney injury.
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Interleucina-17 , Traumatismo por Reperfusão , Animais , Humanos , Isquemia , Rim , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Interleucina-17RESUMO
Renalase, a recently discovered secreted flavoprotein, exerts anti-apoptotic and anti-inflammatory effects against renal injury in acute and chronic animal models. However, whether Renalase elicits similar effects in the development of diabetic nephropathy (DN) remains unclear. The studies presented here tested the hypothesis that Renalase may play a key role in the development of DN and may have therapeutic potential for DN. Renalase expression was measured in human kidney biopsies with DN and in kidneys of db/db mice. The role of Renalase in the development of DN was examined using a genetically engineered mouse model: Renalase knockout mice with db/db background. The renoprotective effects of Renalase in DN was evaluated in db/db mice with Renalase overexpression. In addition, the effects of Renalase on high glucose-induced mesangial cells were investigated. Renalase was down-regulated in human diabetic kidneys and in kidneys of db/db mice compared with healthy controls or db/m mice. Renalase homozygous knockout increased arterial blood pressure significantly in db/db mice while heterozygous knockout did not. Renalase heterozygous knockout resulted in elevated albuminuria and increased renal mesangial expansion in db/db mice. Mesangial hypertrophy, renal inflammation, and pathological injury in diabetic Renalase heterozygous knockout mice were significantly exacerbated compared with wild-type littermates. Moreover, Renalase overexpression significantly ameliorated renal injury in db/db mice. Mechanistically, Renalase attenuated high glucose-induced profibrotic gene expression and p21 expression through inhibiting extracellular regulated protein kinases (ERK1/2). The present study suggested that Renalase protected against the progression of DN and might be a novel therapeutic target for the treatment of DN.
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Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/metabolismo , Rim/metabolismo , Monoaminoxidase/metabolismo , Albuminúria/metabolismo , Animais , Modelos Animais de Doenças , Humanos , Células Mesangiais/metabolismo , Células Mesangiais/patologia , Camundongos KnockoutRESUMO
Autografts are still regarded as the gold standard treatment for bone defects but they require additional surgery that causes pain for the patient. Thus, alternatives that can substitute for grafts are required. In the present study, a novel poly-GLP-1 molecule was developed using a polymeric pro-drug strategy which was found to accelerate bone healing in a mouse femoral defect model. Furthermore, the poly-GLP-1 molecule induced osteogenesis and inhibited adipogenesis in bone marrow-derived mesenchymal stem cells (BMSCs). The results demonstrate that poly-GLP-1 promoted M2 polarization of bone marrow-derived macrophages (BMDMs) and increased the levels of TGF-ß1 in the bone marrow, resulting in the migration of an increased number of CD29 + Sca-1 + BMSCs to the bone surface. Finally, we found that poly-GLP-1 facilitated the migration of BMSCs due to transduction of the Smad2 signaling pathway, causing increased numbers of CD31 + Endomucin + endothelial cells in bone marrow that promoted bone formation. These results support poly-GLP-1 as a potential bone-healing agent and suggest that it may play a promising role in the clinical treatment of fracture repair.