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ABSTRACT: The role of microRNAs in regulating tubulointerstitial fibrosis, a key feature of progressive chronic kidney disease, is of significant importance. LIN28A has been reported to attenuate renal fibrosis in obstructive nephropathy. Here, our objective was to investigate the precise biological function of the miR-92a-3p/LIN28A axis in tubulointerstitial fibrosis. The human renal proximal tubular epithelial (HK-2) cell line was exposed to transforming growth factor (TGF)-ß1, establishing an in vitro model mimicking tubulointerstitial fibrosis. Luciferase reporter assay was utilized to investigate the relationship between miR-92a-3p and LIN28A. Cell transfection techniques were employed to modify the expression of miR-92a-3p and LIN28A. An in vivo model of tubulointerstitial fibrosis was created by inducing unilateral ureteral obstruction (UUO) in C57BL/6N mice. Our initial observations showed that TGF-ß1 treatment of HK-2 cells and the UUO mice model led to an increase in miR-92a-3p expression and a decrease in LIN28A expression. We confirmed that miR-92a-3p directly targeted LIN28A in HK-2 cells. In TGF-ß1-stimulated HK-2 cells, knocking down miR-92a-3p notably reduced the levels of alpha smooth muscle actin and vimentin and concurrently enhanced the expression of E-cadherin. These changes were counteracted upon transfection with si-LIN28A. Thus, directing interventions toward miR-92a-3p holds the potential to emerge as a viable therapeutic approach for addressing tubulointerstitial fibrosis.
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Replacement of liquid electrolytes with polymer gel electrolytes is recognized as a general and effective way of solving safety problems and achieving high flexibility in wearable batteries1-6. However, the poor interface between polymer gel electrolyte and electrode, caused by insufficient wetting, produces much poorer electrochemical properties, especially during the deformation of the battery7-9. Here we report a strategy for designing channel structures in electrodes to incorporate polymer gel electrolytes and to form intimate and stable interfaces for high-performance wearable batteries. As a demonstration, multiple electrode fibres were rotated together to form aligned channels, while the surface of each electrode fibre was designed with networked channels. The monomer solution was effectively infiltrated first along the aligned channels and then into the networked channels. The monomers were then polymerized to produce a gel electrolyte and form intimate and stable interfaces with the electrodes. The resulting fibre lithium-ion battery (FLB) showed high electrochemical performances (for example, an energy density of about 128 Wh kg-1). This strategy also enabled the production of FLBs with a high rate of 3,600 m h-1 per winding unit. The continuous FLBs were woven into a 50 cm × 30 cm textile to provide an output capacity of 2,975 mAh. The FLB textiles worked safely under extreme conditions, such as temperatures of -40 °C and 80 °C and a vacuum of -0.08 MPa. The FLBs show promise for applications in firefighting and space exploration.
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Background: Cuproptosis is a recently discovered form of nonapoptotic programmed cell death. However, no research on cuproptosis in the context of adrenocortical carcinoma has been conducted, and the prognostic value of assessing cuproptosis remains unclear. Methods: In this study, we established comprehensive models to assess gene expression changes, mutation status, and prognosis prediction and developed a prognostic nomogram for cuproptosis-related genes. Using data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Genotype-Tissue Expression (GTEx) databases, an analysis of 11 cuproptosis-related genes was performed. Additionally, a risk scoring method and nomogram were used to assess the relationships among cuproptosis-associated genes, transcript expression, clinical characteristics, and prognosis. The connections among tumors, immune checkpoints, and immune infiltration were also analyzed. Results: The patterns observed in patients with adrenocortical carcinoma who were assessed using cuproptosis-associated risk scores provide useful information for understanding gene mutations, clinical outcomes, immune cell infiltration, and immune checkpoint analysis results. FDX1, LIPT1, MTF1, COX11, CYP2D6, DLAT, ATP7Band CDKN2A were differentially expressed in patients with adrenocortical carcinoma and normal controls. In addition, higher risk scores were significantly associated with poor overall survival and progression-free interval. The nomogram model subsequently developed to facilitate the clinical application of the analysis showed good predictive and calibration capabilities. GSE10927 and GSE33371 were used for independent cohort validation. Moreover, CDKN2A, FDX1, and other cuproptosis-related genes were significantly associated with immune infiltration and checkpoints. Conclusion: We confirmed that our model had excellent predictive ability in patients with adrenocortical carcinoma. Therefore, an in-depth evaluation of patients using cuproptosis-related risk scores is clinically essential and can assist in therapy in the future.
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BACKGROUND: Somatosensory deficits are common symptoms post stroke. Repetitive transcranial magnetic stimulation (rTMS) over the motor cortex is able to promote motor rehabilitation, whereby its impact on somatosensory functioning remains unknown. This study was designed to evaluate the association between somatosensory deficits and corticospinal excitability following stroke, with the purpose to provide insights on rTMS interventions for the management of somatosensory deficits. METHODS: Somatosensory functioning and corticospinal excitability (motor-evoked potential, MEP; cortical silence period, CSP) were evaluated from a group of sixteen patients with unilateral ischemic stroke in the acute or subacute phase. RESULTS: Results indicated that the uncommon presentation of larger MEPs in ipsilesional vs. contralesional motor cortex was associated with worse somatosensory function compared to those with a smaller MEP in ipsilesional motor cortex. Moreover, increased MEP ratio (ipsilesional vs. contralesional motor cortex) was associated with better somatosensory function in patients with well-preserved somatosensory function. CONCLUSIONS: In well-recovered patients, an increased MEP ratio between the ipsilesional and contralesional motor cortex could be an indicator of improved somatosensory functioning following stroke.
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Accidente Cerebrovascular Isquémico , Corteza Motora , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/complicaciones , Estimulación Magnética Transcraneal/métodos , Rehabilitación de Accidente Cerebrovascular/métodos , Accidente Cerebrovascular Isquémico/complicacionesRESUMEN
OBJECTIVE: Ribosomal protein S15A (RPS15A) has been identified as a new oncogene in several tumors, but its functional role in secondary hyperparathyroidism (SHPT) characterized by increased serum parathyroid hormone (PTH) level and parathyroid cell proliferation remains unclear. METHODS: A rat model of SHPT was successfully established with a high-phosphorus diet plus 5/6 nephrectomy. ELISA assay was used to determine PTH, calcium and phosphorus and ALP activity. Cell proliferation was analyzed by Cell counting Kit-8 (CCK-8) assay. Flow cytometry assay was utilized to determine cell cycle distribution and apoptosis in parathyroid cells. LY294002, an inhibitor of PI3K/AKT signaling, was used to elucidate the relationship between RPS15A and PI3K/AKT signaling. Immunohistochemical (IHC) staining, quantitative real time PCR and western blot analysis were applied to determine related molecular levels. RESULTS: Our data showed an upregulation of RPS15A and activated PI3K/AKT signaling pathway in the parathyroid gland tissues of SHPT rats, accompanied with increased PTH, calcium and phosphorus levels. Knockdown of RPS15A decreased parathyroid cell proliferation, induced cell cycle arrest and apoptosis. Treatment with LY294002 reversed the effects of pcDNA3.1-RPSH15A in parathyroid cells. CONCLUSIONS: Our study demonstrated RPS15A-mediated PI3K/AKT pathway as a novel molecular mechanism in the pathogenesis of SHPT, which may provide a new drug target in the future.
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Hiperparatiroidismo Secundario , Proteínas Proto-Oncogénicas c-akt , Ratas , Animales , Fosfatidilinositol 3-Quinasas , Calcio , Hiperparatiroidismo Secundario/patología , Transducción de Señal , Hiperplasia , Hormona Paratiroidea , Proliferación Celular , Fósforo/farmacología , ApoptosisRESUMEN
Vascular calcification (VC) is prevalent in uremia patients, lacking effective molecular biomarkers. This study was conducted to explore the role of serum cell division cycle 42 (CDC42) in the diagnosis of uremic VC incidence and progression. We enrolled 104 uremia patients and selected arcus aortae calcification (AAC) as the outcome phenotype. Levels of CDC42, 1,25-dihydroxy vitamin D (1,25(OH) 2-D), fibroblast growth factor-23 (FGF-23), and other laboratory parameters in the blood were measured. The receiver operator characteristic curve, the Pearson test, and the multivariate Logistic regression were used for the analysis of CDC42 diagnostic values, correlation analysis, and screening of VC risk factors, respectively. CDC42 was higher in the serum of uremia patients with VC and elevated with the increase in AAC level. Serum CDC42 level>1.025 was predictive of VC incidence with 83.58% sensitivity and 56.76% specificity, and CDC42 level>1.280 was predictive of VC progression with 73.33% sensitivity and 68.18% specificity. Serum CDC42 was positively correlated with 1,25(OH) 2-D and FGF-23. Uremia patients with higher serum CDC42 had a higher probability of VC incidence and progression. Generally, serum CDC42 helped the diagnosis of uremic VC incidence and progression and was an independent risk factor for uremic VC progression.
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Uremia , Calcificación Vascular , Humanos , Relevancia Clínica , Incidencia , Calcificación Vascular/epidemiología , Uremia/complicaciones , Uremia/epidemiología , BiomarcadoresRESUMEN
PURPOSE: Patients with chronic kidney disease (CKD) have an associated burden of coronary artery disease, including chronic total occlusions (CTO). It is unclear how the presence of CKD affects the outcomes of CTO revascularization. Previous reviews have not taken into account all relevant published studies that examined the association of CKD with outcomes of CTO revascularization. METHODS: A systematic search was conducted using PubMed, Scopus, and Google Scholar databases for studies investigating patients with or without CKD who also had coronary chronic total occlusion undergoing revascularization procedures Statistical analysis was performed using STATA software. Effect sizes were reported as pooled relative risk (RR). RESULTS: A total of 13 studies were included. CKD patients showed elevated risk of in-hospital mortality (RR 4.25, 95% CI 2.64, 6.82) and mortality at latest follow-up (RR 3.24, 95% CI 2.56, 4.11), elevated risk of major cardio or cerebrovascular events (RR 1.65, 95% CI 1.38, 1.98), major bleeding (RR 2.85, 95% CI 1.96, 4.13), and contrast-induced acute kidney injury (RR 3.06, 95% CI 1.70, 5.52). CKD patients also showed lower chances of technical success (RR 0.95, 95% CI 0.91, 1.00). CONCLUSIONS: The presence of CKD increases the risk of mortality, complications and adversely affects the success of CTO revascularization. Patients with CKD undergoing revascularization should have their kidney function comprehensively evaluated and these patients should be carefully monitored.
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Enfermedad de la Arteria Coronaria , Oclusión Coronaria , Intervención Coronaria Percutánea , Insuficiencia Renal Crónica , Humanos , Enfermedad Crónica , Enfermedad de la Arteria Coronaria/complicaciones , Oclusión Coronaria/complicaciones , Oclusión Coronaria/cirugía , Riñón/fisiología , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/métodos , Insuficiencia Renal Crónica/complicaciones , Factores de Riesgo , Resultado del TratamientoRESUMEN
Fibre lithium-ion batteries are attractive as flexible power solutions because they can be woven into textiles, offering a convenient way to power future wearable electronics1-4. However, they are difficult to produce in lengths of more than a few centimetres, and longer fibres were thought to have higher internal resistances3,5 that compromised electrochemical performance6,7. Here we show that the internal resistance of such fibres has a hyperbolic cotangent function relationship with fibre length, where it first decreases before levelling off as length increases. Systematic studies confirm that this unexpected result is true for different fibre batteries. We are able to produce metres of high-performing fibre lithium-ion batteries through an optimized scalable industrial process. Our mass-produced fibre batteries have an energy density of 85.69 watt hour per kilogram (typical values8 are less than 1 watt hour per kilogram), based on the total weight of a lithium cobalt oxide/graphite full battery, including packaging. Its capacity retention reaches 90.5% after 500 charge-discharge cycles and 93% at 1C rate (compared with 0.1C rate capacity), which is comparable to commercial batteries such as pouch cells. Over 80 per cent capacity can be maintained after bending the fibre for 100,000 cycles. We show that fibre lithium-ion batteries woven into safe and washable textiles by industrial rapier loom can wirelessly charge a cell phone or power a health management jacket integrated with fibre sensors and a textile display.
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Cobalto/química , Suministros de Energía Eléctrica , Electrónica , Litio/química , Óxidos/química , Textiles , Dispositivos Electrónicos Vestibles , Grafito/química , Humanos , Iones , Masculino , Tecnología InalámbricaRESUMEN
BACKGROUND: Secondary hyperparathyroidism, a condition of excess parathyroid hormone (PTH, Pth) production, is often seen in chronic kidney disease (CKD) patients with elevated fibroblast growth factor 23 (FGF23, Fgf23). Elevated FGF23 levels stimulate secondary hyperparathyroidism-associated parathyroid αKlotho signaling. As overexpression of rationally selected microRNAs can suppress target gene activation, we hypothesized that microRNA-based suppression of parathyroid FGF23/αKlotho axis activity may be a potential strategy to combat secondary hyperparathyroidism. METHODS: In vitro luciferase assays and human parathyroid adenoma cell experiments were used to determine miR-129-1-3p's effects on αKlotho expression in vitro. We also studied the effects of parathyroid-specific miR-129-1 overexpression (miR-129Ox) in CKD and non-CKD mice and parathyroid tissue cultures derived therefrom. RESULTS: miR-129-1-3p directly targets the αKlotho mRNA strand in human parathyroid cells. miR-129Ox CKD mice and control CKD mice displayed comparable serum levels of calcium, phosphate, Fgf23, and 1,25-dihydroxyvitamin D (1,25(OH)2D). However, miR-129Ox CKD mice displayed reduced parathyroid αKlotho expression and lower circulating Pth levels. In vitro culture of miR-129Ox CKD murine parathyroid tissue showed suppressed responses to Fgf23, with decreased Pth secretion and diminished cell proliferation after four days. CONCLUSIONS: miR-129 negatively regulates pro-proliferative, Pth-inducing Fgf23/αâKlotho signaling in the parathyroid glands of CKD mice.
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Factores de Crecimiento de Fibroblastos/metabolismo , Glucuronidasa/metabolismo , Hiperparatiroidismo Secundario/prevención & control , MicroARNs/metabolismo , Insuficiencia Renal Crónica/metabolismo , Transducción de Señal , Animales , Ensayo de Inmunoadsorción Enzimática , Factor-23 de Crecimiento de Fibroblastos , Células HEK293 , Humanos , Hiperparatiroidismo Secundario/etiología , Proteínas Klotho , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Glándulas Paratiroides/metabolismo , Insuficiencia Renal Crónica/complicaciones , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
OBJECTIVE: Coronary artery calcification (CAC) is a common complication in end-stage renal disease (ESRD) patients undergoing maintenance hemodialysis (MHD), and the extent of CAC is a predominant predictor of cardiovascular outcomes in MHD patients. In this study, we sought to uncover the relationship between circulating miRNA-29b, sclerostin levels, CAC, and cardiovascular events (CVEs) in MHD patients. METHODS: This study recruited patients receiving MHD for at least three months in the Hainan General Hospital between January 2016 and June 2019, and all patients were followed up 24 months for CVEs. The serum level of sclerostin was determined by enzyme-linked immunosorbent assay (ELISA) and miRNA-29b expression by real-time qPCR (RT-qPCR). All patients received cardiac CT scans to evaluate CAC, and CAC scores were expressed in Agatston units. The MHD patients with CACs <100 were arranged into the CAC (<100) group, those with 100-400 CACs into the CAC (100-400) group, and those with CACs >400 into the CAC (>400) group. Net reclassification index (NRI) and integrated discrimination index (IDI) were calculated to assess the predictive performance of serum sclerostin level for the occurrence of CVEs. RESULTS: Compared with the CAC (<100) group, the CAC (>400) group had higher proportions of older patients, hypertension and diabetes mellitus patients, longer dialysis duration, higher mean arterial pressure (MAP), higher levels of high-sensitivity C-reactive protein (hs-CRP), alkaline phosphatase (ALP), and phosphate (P < 0.05). It was found that the CAC (100-400) and CAC (>400) groups exhibited higher serum levels of sclerostin but lower levels of miRNA-29b than the CAC (<100) group (P < 0.05) and the CAC (>400) group had a higher level of sclerostin and a lower level of miRNA-29b than the CAC (100-400) group (P < 0.05). The circulating level of miRNA-29b was negatively correlated with the serum level of sclerostin in MHD patients (r = -0.329, P < 0.01). The multivariate logistic regression analysis showed that hs-CRP, phosphate, sclerostin, and miRNA-29b were independent risk factors for CAC in MHD patients (P < 0.05, Table 2). ROC for prediction of CAC by sclerostin yielded 0.773 AUC with 95% CI 0.683-0.864 (P < 0.01). As depicted by Kaplan-Meier curves of CVE incidence in MHD patients according to median sclerostin (491.88 pg/mL) and median miRNA-29b (Ct = 25.15), we found that serum levels of sclerostin and miRNA-29b were correlated with the incidence of CVEs in MHD patients. When a new model was used to predict the incidence of CVEs, NRI 95% CI was 0.60 (0.16-1.03) (P < 0.05) and IDI 95% CI was 0.002 (-0.014 to 0.025) (P < 0.05), suggesting that sclerostin added into the old model could improve the prediction of the incidence of CVEs. CONCLUSIONS: These data suggest that circulating miRNA-29b and sclerostin levels are correlated with CAC and incidence of CVEs in MHD patients. Higher sclerostin and lower miRNA-29b may serve as independent risk factors for the incidence of CVEs in MHD patients.
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Modern electronic devices are moving toward miniaturization and integration with an emerging focus on wearable electronics. Due to their close contact with the human body, wearable electronics have new requirements including low weight, small size, and flexibility. Conventional 3D and 2D electronic devices fail to efficiently meet these requirements due to their rigidity and bulkiness. Hence, a new family of 1D fiber-shaped electronic devices including energy-harvesting devices, energy-storage devices, light-emitting devices, and sensing devices has risen to the challenge due to their small diameter, lightweight, flexibility, and weavability into soft textile electronics. The application challenges faced by fiber and textile electronics from single fiber-shaped devices to continuously scalable fabrication, to encapsulation and testing, and to application mode exploration, are discussed. The evolutionary trends of fiber and textile electronics are then summarized. Finally, future directions required to boost their commercialization are highlighted.
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BACKGROUND: Stroke is accompanied by a distinguished inflammatory reaction that is initiated by the infiltration of immunocytes, expression of cytokines, and other inflammatory mediators. As natural killer cells (NK cells) are a type of cytotoxic lymphocyte critical to the innate immune system, we investigated the mechanism of NK cells-induced brain injuries after cerebral ischemia and the chemotactic effect of IP-10 simultaneously. METHODS: NK cells infiltration, interferon-gamma (IFN-γ) and IP-10 expression were detected by immunohistochemistry, immunofluorescence, PCR and flow cytometry in human and C57/BL6 wild type mouse ischemic brain tissues. The ischemia area was detected via 2,3,5-triphenyltetrazolium chloride staining. CXCR3 mean fluorescence intensity of isolated NK cells was measured by flow cytometry. The neuronal injury made by NK cells was examined via apoptosis experiment. The chemotactic of IP-10 was detected by migration and permeability assays. RESULTS: In human ischemic brain tissue, infiltrations of NK cells were observed and reached a peak at 2 to 5 days. In a permanent middle cerebral artery occlusion (pMCAO) model, infiltration of NK cells into the ischemic infarct region reached their highest levels 12 hours after ischemia. IFN-γ-positive NK cells and levels of the chemokine IP-10 were also detected within the ischemic region, from 6 hours up to 4 days after pMCAO was performed, and IFN-γ levels decreased after NK cells depletion in vivo. Co-culture experiments of neural cells with NK cells also showed that neural necrosis was induced via IFN-γ. In parallel experiments with IP-10, the presence of CXCR3 indicates that NK cells were affected by IP-10 via CXCR3, and the effect was dose-dependent. After IP-10 depletion in vivo, NK cells decreased. In migration assays and permeability experiments, disintegration of the blood-brain barrier (BBB) was observed following the addition of NK cells. Moreover, in the presence of IP-10 this injury was aggravated. CONCLUSIONS: All findings support the hypothesis that NK cells participate in cerebral ischemia and promote neural cells necrosis via IFN-γ. Moreover, IP-10 intensifies injury to the BBB by NK cells via CXCR3.