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Glioblastoma (GBM) is the most malignant and challenging type of astrocytoma and also notoriously acknowledged as the most common primary brain tumor globally. Currently, chemotherapy is the most master therapy for tumor and is essential in clinical treatment for GBM. Nevertheless, the characterization of chemotherapy resistance seriously hinders clinical chemotherapy treatment. Accordingly, there are imperious demands for the exploitation of novel chemosensitizer to promote the efficacy of chemotherapy. Our current study was conducted to probe into the potential impacts of microRNA (miR)-640 on the chemosensitivity in GBM and the associated underlying mechanism. Initially, TargetScan software was utilized to predict the targeted genes of miR-640, and the target relationship between miR-640 and Bcl-2-modifying factor (BMF) was validated by double luciferase report assay. Additionally, to explore the role of miR-640/BMF in U251 cells, miR-640 inhibitor/BMF-siRNA was used. U251 cells were processed with 100 µM temozolomide (TMZ) and detected with CCK-8 kit. Eventually, RT-qPCR and Western blotting were used for evaluating Bcl-2, Bax mRNA, and protein expression level. Flow cytometry analysis was performed to measure cellular apoptosis. Initially, the results indicated that BMF was the target gene of miR-640. MiR-640 negatively regulated BMF expression in GBM cells. Besides, the findings revealed that miR-640 inhibition significantly inhibited U251 cell proliferation, promoted cell apoptosis, and increased the sensitivity of GBM cells to TMZ by targeting BMF. Moreover, BMF overexpression significantly suppressed U251 cell proliferation, induced cell apoptosis, and increased the sensitivity of GBM cells to TMZ. Inhibition of miR-640 expression enhances chemosensitivity of human GBM cells to TMZ by targeting BMF.
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Neoplasias Encefálicas , Glioblastoma , MicroRNAs , Humanos , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , MicroRNAs/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Resistencia a Medicamentos Antineoplásicos/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Apoptose/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Regulação Neoplásica da Expressão GênicaRESUMO
Given the high content of Ca2+ in waste paper recycling wastewater, the anaerobic granular sludge (AnGS) undergoes calcification during wastewater treatment and affects the treatment efficiency. To restore the activity of calcified AnGS and improve the performance of AnGS, four types of N-acyl-homoserine lactones (AHLs) were added to the AnGS system while papermaking wastewater treatment. The addition of N-butyryl-DL-homoserine lactone(C4-HSL) and N-octanoyl-DL-homoserine lactone (C8-HSL) had an inhibitory affect the COD removal efficiency and SMA of sludge at the inception. The addition of N-hexanoyl-L-homoserine lactone (C6-HSL) has no obvious effect on the COD removal efficiency, but can improve the SMA of sludge more obviously. The addition of N-(ß-ketocaproyl)-DL-homoserine lactone (3O-C6-HSL) can increased COD removal efficiency and promoted SMA together obviously. The addition of C6-HSL and 3O-C6-HSL can increase volatile suspended solid (VSS)/total suspended solid (TSS), and regulate extracellular polymeric substance (EPS) secretion in AnGS. Analysis of microbial sequencing revealed changes in the microbial community structure following AHL addition, which enhanced the methane metabolism pathway in sludge. The addition of C6-HSL, C8-HSL, and 3O-C6-HSL increased Methanosaeta population, thus increasing the aceticlastic pathway in sludge. Thus, exogenous AHLs can play an important role in regulating microbial community structure, and in improving the performance of AnGS.
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Lactonas/administração & dosagem , Microbiota/efeitos dos fármacos , Esgotos , Anaerobiose , Matriz Extracelular de Substâncias Poliméricas/metabolismo , Metano/metabolismo , Papel , Águas ResiduáriasRESUMO
BACKGROUND: Hypoxia induced injury of pulmonary microvascular endothelial barrier is closely related to the pathogenesis of acute lung injury after lung transplantation. VE-cadherin is an important structural molecule for pulmonary microvascular endothelial barrier. In this study, we aim to investigate the roles of VE-cadherin in hypoxia induced injury of pulmonary microvascular endothelial barrier. METHODS: Rat model of hypoxia and cultured pulmonary microvascular endothelial cells (PMVECs) were utilized. Determination of PMVECs apoptosis, skeleton combination was conducted to verify the effects of hypoxia on injury of pulmonary microvascular endothelial barrier. In addition, VE-cadherin expression was modulated by administration of siRNA in order to investigate the roles of VE-cadherin in hypoxia induced PMVECs apoptosis and skeleton recombination. RESULTS: Our data indicated that expression of VE-cadherin was down-regulated in hypoxia-exposed PMVECs. Whereas, in the cells treated using siRNA, down-regulation of VE-cadherin did not trigger PMVECs apoptosis, but it increased the sensitivity of PMVECs to the hypoxia induced apoptosis. In cases of hypoxia, the expression of VE-cadherin was significantly down-regulated, together with endothelial skeleton recombination and increase of permeability, which then triggered endothelial barrier dysfunction. CONCLUSIONS: These data verify that VE-cadherin expression played an important role in hypoxia induced PMVECs apoptosis and cellular skeletal recombination.
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Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/fisiopatologia , Antígenos CD/fisiologia , Caderinas/fisiologia , Endotélio Vascular/patologia , Endotélio Vascular/fisiopatologia , Microcirculação , Circulação Pulmonar , Animais , Apoptose , Permeabilidade da Membrana Celular , Células Cultivadas , Modelos Animais de Doenças , Regulação para Baixo , Células Endoteliais/patologia , Hipóxia , Masculino , Ratos Sprague-DawleyRESUMO
Isolation of specific rare cell subtypes from whole blood is critical in cellular analysis and important in basic and clinical research. Traditional immunomagnetic cell capture suffers from suboptimal sensitivity, specificity, and time- and cost-effectiveness. Mimicking the features of octopuses, a device termed a "NanoOctopus" was developed for cancer cell isolation in whole blood. The device consists of long multimerized aptamer DNA strands, or tentacle DNA, immobilized on magnetic microparticle surfaces. Their ultrahigh sensitivity and specificity are attributed to multivalent binding of the tentacle DNA to cell receptors without steric hindrance. The simple, quick, and noninvasive capture and release of the target cells allows for extensive downstream cellular and molecular analysis, and the time- and cost-effectiveness of fabrication and regeneration of the devices makes them attractive for industrial manufacture.
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Aptâmeros de Nucleotídeos/química , Proteínas Sanguíneas/isolamento & purificação , Proteínas Sanguíneas/metabolismo , Separação Celular/métodos , Nanotecnologia/métodos , Células Neoplásicas Circulantes/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Proteínas Sanguíneas/análise , Estudos de Casos e Controles , Humanos , Fenômenos Magnéticos , Microesferas , Células Neoplásicas Circulantes/química , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologiaRESUMO
Objective- Mitochondria are the important yet most underutilized target for cardio-cerebrovascular function integrity and disorders. The Tom (translocases of outer membrane) complex are the critical determinant of mitochondrial homeostasis for making organs acclimate physiological and pathological insults; however, their roles in the vascular system remain unknown. Approach and Results- A combination of studies in the vascular-specific transgenic zebrafish and genetically engineered mice was conducted. Vascular casting and imaging, endothelial angiogenesis, and mitochondrial protein import were performed to dissect potential mechanisms. A loss-of-function genetic screening in zebrafish identified that selective inactivation of the tomm7 (translocase of outer mitochondrial membrane 7) gene, which encodes a small subunit of the Tom complex, specially impaired cerebrovascular network formation. Ablation of the ortholog Tomm7 in mice recapitulated cerebrovascular abnormalities. Restoration of the cerebrovascular anomaly by an endothelial-specific transgenesis of tomm7 further indicated a defect in endothelial function. Mechanistically, Tomm7 deficit in endothelial cells induced an increased import of Rac1 (Ras-related C3 botulinum toxin substrate 1) protein into mitochondria and facilitated the mitochondrial Rac1-coupled redox signaling, which incurred angiogenic impairment that underlies cerebrovascular network malformation. Conclusions- Tomm7 drives brain angiogenesis and cerebrovascular network formation through modulating mitochondrial Rac1 signaling within the endothelium.
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Encéfalo/irrigação sanguínea , Proteínas de Transporte/metabolismo , Células Endoteliais/enzimologia , Endotélio Vascular/enzimologia , Proteínas de Membrana/metabolismo , Mitocôndrias/enzimologia , Proteínas Mitocondriais/metabolismo , Neovascularização Fisiológica , Neuropeptídeos/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo , Animais , Proteínas de Transporte/genética , Células Cultivadas , Transtornos Cerebrovasculares/enzimologia , Transtornos Cerebrovasculares/genética , Endotélio Vascular/embriologia , Regulação da Expressão Gênica no Desenvolvimento , Regulação Enzimológica da Expressão Gênica , Humanos , Proteínas de Membrana/genética , Camundongos Knockout , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , Proteínas Mitocondriais/genética , Neovascularização Fisiológica/genética , Neuropeptídeos/genética , Transdução de Sinais , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética , Proteínas rac1 de Ligação ao GTP/genéticaRESUMO
BACKGROUND Acute lung injury in children is a complicated disease linked to the inflammation response. MicroRNA (miRNA) plays a vital role in acute lung injury. However, the role of miR-30b-5p in the pathogenesis of acute lung injury is not clear. The purpose of our study was to investigate the alteration of miR-30b-5p, suppressor of cytokine signaling 3 (SOCS3), in children with acute lung injury, and also in a mouse model of acute lung injury induced by the endotoxin lipopolysaccharide (LPS). MATERIAL AND METHODS The levels of miR-30b-5p, SOCS3, FKN (fractalkine), tumor necrosis factor (TNF)-α, NF-κB (nuclear factor kappa-light-chain-enhancer of activated B), interleukin-6 (IL-6), and IL-8 were detected by ELISA (enzyme-linked immunosorbent assay), western blot, and qRT-PCR (quantitative reverse transcription polymerase chain reaction) assay. The alveolar permeability index and the ratio of wet weight/dry weight (W/D) were measured. Then, we examined the inflammation and apoptosis using hematoxylin and eosin (H&E) staining and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay. Additionally, SOCS3 was investigated as a direct target of miR-30a-5p in RAW264.7 cells by dual-luciferase reporter assays. RESULTS Our study indicated that the level of miR-30b-5p was decreased and the levels of SOCS3, FKN, TNF-α, NF-κB, IL-6, and IL-8 were increased in lung tissue, serum, and bronchoalveolar lavage fluid of mice with acute lung injury induced by LPS. In addition, LPS increased alveolar permeability index and the ratio of W/D and induced inflammatory responses, including the activation of the NF-kB pathway in a mouse model. Furthermore, SOCS3 was confirmed to be a target of miR-30a-5p in RAW264.7 cells. CONCLUSIONS Our data demonstrated an important role for miR-30b-5p in acute lung injury inflammation and suggested that miR-30b-5p might be an important therapy target in children with acute lung injury.
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Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/patologia , MicroRNAs/genética , Lesão Pulmonar Aguda/metabolismo , Animais , Apoptose/efeitos dos fármacos , Quimiocina CX3CL1/metabolismo , Criança , Pré-Escolar , Modelos Animais de Doenças , Feminino , Humanos , Lactente , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/metabolismo , NF-kappa B/metabolismo , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Proteína 3 Supressora da Sinalização de Citocinas/genética , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
We demonstrate an electric control metamaterials-high electron mobility transistors (HEMTs) integrated terahertz (THz) modulator whose switching ability is developed by utilizing the symmetric quadruple-split-ring resonators (SRRs) metamaterial configuration and operating voltage is reduced by incorporating the HEMT elements. Meanwhile, the high switching speed of the HEMT implies that the THz modulator has a high potential in modulation speed. Under a reverse gate voltage of -4 V, the THz modulator exhibits a modulation depth of 80% at 0.86 THz and a phase shift of 0.67 rad (38.4°) at 0.77 THz, respectively. In addition, a modulation speed over 2.7 MHz is achieved and an improvement in the modulation speed of hundreds of MHz with optimum RC time constant is expected to achieve for the THz modulator.
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A novel biosensing platform was developed by integrating an aptamer-based DNA biosensor with graphene oxide (GO) for rapid and facile detection of adenosine triphosphate (ATP, as a model target). The DNA biosensor, which is locked by GO, is designed to contain two sensing modules that include recognition site for ATP and self-replication track that yields the nicking domain for Nt.BbvCI. By taking advantage of the different binding affinity of single-stranded DNA, double-stranded DNA and aptamer-target complex toward GO, the DNA biosensor could be efficiently released from GO in the presence of target with the help of a complementary DNA strand (CPDNA) that partially hybridizes to the DNA biosensor. Then, the polymerization/nicking enzyme synergetic isothermal amplification could be triggered, leading to the synthesis of massive DNA amplicons, thus achieving an enhanced sensitivity with a wide linear dynamic response range of four orders of magnitude and good selectivity. This biosensing strategy expands the applications of GO-DNA nanobiointerfaces in biological sensing, showing great potential in fundamental research and biomedical diagnosis.
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Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , DNA/análise , Grafite/química , DNA/químicaRESUMO
OBJECTIVE: To develop a simple scoring system based on preprocedural clinical features that is capable of predicting contrast-induced acute kidney injury (CI-AKI) before percutaneous coronary intervention (PCI). BACKGROUND: CI-AKI is associated with increased in-hospital morbidity and mortality, prolonged hospitalization, and long-term renal impairment. Although several scoring methods have been developed to determine risk of CI-AKI, no simple scoring method based on PCI preprocedural clinical features yet exists for Chinese patients. METHODS: A total of 2,500 Chinese patients were randomly and retrospectively assigned in a 3:2 manner to create a training and validation dataset, respectively. CI-AKI was defined as an increase of ≥25% or ≥0.5 mg/dL serum creatinine within 5 days after PCI. Preprocedural clinical variables showing independent correlation to CI-AKI were used to derive the risk score from the training dataset and then subsequently tested in the validation dataset. The odds ratios from multivariate logistic regression were used to assign a weighted integer to age ≥70 years = 4, history of myocardial infarction = 5, diabetes mellitus = 4, hypotension = 6, left ventricular ejection fraction ≤45% = 4, anemia = 3, creatinine clearance rate <60 mL/min = 7, decreased high-density lipoprotein <1 mmol/L= 3, and urgent PCI = 3. Summation of the integers represented the total risk score. RESULTS: The overall incidence of CI-AKI in the training dataset was 16.4% [246/1500; 5.4% for low (≤7) and 61.3% for very high (≥17) risk scores]. The rates of CI-AKI, 1-year dialysis, and 1-year mortality increased significantly with each group (Cochran-Armitage test of trend, P < 0.001). The risk score facilitated appropriate classification of patients with low and high risk for CI-AKI after PCI in the validation dataset (c-statistic = 0.82). CONCLUSION: Risk classification based on the most significantly correlated parameters is useful for predicting CI-AKI before contrast exposure. The simple preprocedural score showed excellent predictive ability for identifying patients at high risk of nephropathy and those with deteriorative prognosis after PCI.
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Injúria Renal Aguda/induzido quimicamente , Meios de Contraste/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Injúria Renal Aguda/sangue , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/terapia , Idoso , Biomarcadores/sangue , China/epidemiologia , Creatinina/sangue , Técnicas de Apoio para a Decisão , Mortalidade Hospitalar , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Intervenção Coronária Percutânea/mortalidade , Valor Preditivo dos Testes , Prognóstico , Diálise Renal , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de TempoRESUMO
This study investigated the effect of different concentrations of Mn2+ on the removal of nitrate by anaerobic sludge and changes in the microbial communities through batch experiments. The results showed that the addition of Mn2+ promoted nitrate removal by anaerobic sludge; the nitrate was completely removed within 6 d in the treatment group with >5 mM Mn2+. With the increase in Mn2+, the concentration of nitrite and nitrous oxide increased in the first 4 d and then decreased to 0 µM after 8 d of incubation. The increasing tendency of ammonium increased firstly and then decreased with the addition of Mn2+ compared to A. Moreover, the Mn2+ removal efficiency gradually decreased with the increase of Mn2+ concentration. The changes of microflora structure in sludge before and after adding Mn2+ were analyzed, and the results revealed that the microbial communities in the sludge may have evolved towards an energy-efficient association of short-cut nitrification, denitrification, and anaerobic ammonia oxidation after adding Mn2+. Mn2+ stimulated the removal of nitrate by anaerobic sludge mainly by promoting the growth of PHOS-HE36.
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Aerospace magnetic material scraps are abundant in cobalt and nickel. Sulfuric acid leaching process is an efficient method for extracting them. But it is a non-selective process, a significant amount of iron dissolves in the solution. This study focuses on the selective removal of iron from this solution using the jarosite process. Eh-pH diagram of K-S-Fe-H2O system was established. Based on thermodynamic analysis, H2O2 is used to oxidize Fe2+ into Fe3+, achieving efficient and selective removal of iron from the solution containing cobalt and nickel. The optimal conditions are as follows: temperature 95°C, K2SO4 dosage coefficient 1.5, seed dosage 10 g/L, time 90 min, pH 1.76, and endpoint pH controlled at approximately 3. Under these conditions, the iron removal efficiency is above 99%, while the loss ratios of cobalt and nickel are below 2%. The product is characterized by XRD and SEM-EDS. Results indicate that the product is jarosite ((K,H3O)Fe3(SO4)2(OH)6), exhibiting an ellipsoid structure with the mean particle size in the range of 0.2-5.0 µm. Temperature, pH value and seed dosage significantly affect reaction rate, particle size and crystallinity, and K2SO4 dosage mainly affects reaction rate and the morphology of jarosite. The jarosite crystallization kinetics can be described by the Avrami equation, with an Avrami index (n) of approximately 2.5 and the apparent activation energy of 42.68 kJ/mol.
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Ferro , Ácidos Sulfúricos , Ácidos Sulfúricos/química , Ferro/química , Níquel/química , Cobalto/química , Concentração de Íons de Hidrogênio , Compostos Férricos/química , Sulfatos/química , Peróxido de Hidrogênio/química , Temperatura , TermodinâmicaRESUMO
Polylactic acid (PLA) has inherent drawbacks, such as its amorphous structure, which affect its mechanical and barrier properties. The use of nanofibrillated cellulose (NFC) mixed with PLA for the production of composites has been chosen as a solution to the above problems. A PLA/NFC composite was produced by solution casting. Before use, the cellulose was modified using a silane coupling agent. The composite films were investigated via X-ray diffraction, as well as by mechanical, physical, thermal analyses and by differential scanning calorimeter. The crystallinity was four times that of pure PLA and the water vapor transmission rate decreased by 76.9% with the incorporation of 10 wt% of NFC. The tensile strength of PLA/NFC blend films increased by 98.8% with the incorporation of 5 wt% of NFC. The study demonstrates that the addition of NFC improved the properties of PLA. This provides a solid foundation for the enhancement of the performance of PLA products.
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Background and Aims: As a biomarker of insulin resistance (IR) in patients with acute myocardial infarction (AMI), the triglyceride-glucose index (TyG index) has received significant attention. However, most research on AMI has focused on male patients, as it is traditionally believed to primarily affect males. Therefore, this study was conducted on a female population with AMI to investigate the potential correlation between the TyG index and their outcomes. Methods: A total of 320 women who were admitted to Fujian Provincial Hospital for AMI between January 2017 and December 2019 were included in this study. The TyG index was calculated using the following formula: ln [fasting triglycerides (TG) (mg/dL) × fasting plasma glucose (FPG) (mg/dL)/2]. The primary endpoint of the study was the occurrence of major adverse cardiovascular and cerebrovascular events (MACCEs), which included all-cause mortality, myocardial infarction, repeat revascularization, rehospitalization for heart failure and stroke. The association between the TyG index and unfavorable outcomes in female patients was investigated using the Cox proportional hazards regression model. Results: It was ultimately estimated that 111 patients developed MACCEs. Females with high TyG indices had a higher prevalence of diabetes, elevated heart rates, and hemoglobin A1c, as well as a higher likelihood of undergoing thrombus aspiration and stent placement. The TyG index was found to be positively correlated with the prevalence of hypertension, diabetes, low-density lipoprotein cholesterol, hemoglobin A1c, and damaged vessels. However, this correlation was modest, yet statistically significant. Furthermore, after adjusting for conventional risk factors, the TyG index (HR: 4.292, 95% CI: 2.784-6.616, p < 0.001) was independently associated with MACCEs. Conclusion: As an independent risk predictor, the TyG index has the potential to enhance clinical outcomes for women with AMI.
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Purpose: Temperature changes unfavorably impact on cardiovascular disease. However, the association between temperature changes and coronary artery disease (CAD) is not well documented. This study aimed to explore the association between daily mean temperature and daily CAD hospital admissions on the southeast coast of China (Fuzhou City). Methods: A total of 1883 CAD patients who underwent percutaneous coronary intervention between 2017 and 2019 were obtained. The severity of CAD was evaluated by the Gensini score. Distributed lag non-linear model (DLNM) combined with a quasi-Poisson regression model was used to examine the delayed effect between daily mean temperature and daily CAD hospital admissions. Stratified analyses were performed by Gensini score and severity of lesions. The relative risk (RR) with a 95% confidence interval (CI) was used to assess the relationship. Results: Extreme cold (8°C) (RR=0.49, 95% CI: 0.25-0.99) and moderate cold (10°C) (RR=0.56, 95% CI: 0.31-0.99) daily mean temperature with a lag of 0-20 days were correlated with lower risk of daily CAD hospital admissions. Moderate heat (30°C) (RR=1.80, 95% CI: 1.01-3.20) and extreme heat (32°C) (RR=2.02, 95% CI: 1.01-4.04) daily mean temperature with a lag of 0-20 days related to a higher risk of daily CAD hospital admissions. Similar results were observed for daily mean temperature with a lag of 0-25 days. Stratified analysis showed the lagged effect of daily mean temperature (lag 0, 0-5, 0-15, 0-20, and 0-25 days) on the daily CAD hospital admissions was observed only in patients with a Gensini score ≤39 (tertile 1). Conclusion: Cold temperatures may have a protective effect on daily CAD hospital admissions in the Fuzhou area, whereas hot temperatures can have an adverse effect.
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Dissolvable polymeric microneedles (DPMNs) have emerged as a powerful technology for the localized treatment of diseases, such as melanoma. Herein, we fabricated a DPMN patch containing a potent enzyme-nanozyme composite that transforms the upregulated glucose consumption of cancerous cells into lethal reactive oxygen species via a cascade reaction accelerated by endogenous chloride ions and external near-infrared (NIR) irradiation. This was accomplished by combining glucose oxidase (Gox) with a NIR-responsive chloroperoxidase-like copper sulfide (CuS) nanozyme. In contrast with subcutaneous injection, the microneedle system highly localizes the treatment, enhancing nanomedicine uptake by the tumor and reducing its systemic exposure to the kidneys and spleen. NIR irradiation further controls the potency and toxicity of the formulation by thermally disabling Gox. In a mouse melanoma model, this unique combination of photothermal, starvation, and chemodynamic therapies resulted in complete tumor eradication (99.2 ± 0.8 % reduction in tumor volume within 10 d) without producing signs of systemic toxicity. By comparison, other treatment combinations only resulted in a 42-76.5 % reduction in tumor growth. The microneedle patch design is therefore not only highly potent but also with regulated toxicity and improved safety.
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Melanoma , Neoplasias , Animais , Camundongos , Glucose Oxidase , Transporte Biológico , Cloretos , Cobre , Modelos Animais de Doenças , Peróxido de Hidrogênio , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
The cancer-associated alternative splicing (AS) events generate cancer-related transcripts which are involved in uncontrolled cell proliferation and drug resistance. However, the key AS variants implicated in tamoxifen (TAM) resistance in breast cancer remain elusive. In the current study, we investigated the landscape of AS events in nine pairs of primary and relapse breast tumors from patients receiving TAM-based therapy. We unrevealed a notable association between the inclusion of exon 7.2 in the 5'untranslated region (5'UTR) of ALDOA mRNA and TAM resistance. Mechanistically, the inclusion of ALDOA exon 7.2 enhances the translation efficiency of the transcript, resulting in increased ALDOA protein expression, mTOR pathway activity, and the promotion of TAM resistance in breast cancer cells. Moreover, the inclusion of exon 7.2 in ALDOA mRNA is mediated by MSI1 via direct interaction. In addition, elevated inclusion of ALDOA exon 7.2 or expression of MSI1 is associated with an unfavorable prognosis in patients undergoing endocrine therapy. Notably, treatment with Aldometanib, an ALDOA inhibitor, effectively restrains the growth of TAM-resistant breast cancer cells in vitro and in vivo. The present study unveils the pivotal role of an AS event in ALDOA, under the regulation of MSI1, in driving TAM resistance in breast cancer. Therefore, this study provides a promising therapeutic avenue targeting ALDOA to combat TAM resistance.
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Processamento Alternativo , Neoplasias da Mama , Resistencia a Medicamentos Antineoplásicos , Tamoxifeno , Humanos , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias da Mama/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico , Processamento Alternativo/genética , Feminino , Camundongos , Animais , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Antineoplásicos Hormonais/farmacologia , Antineoplásicos Hormonais/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Éxons/genética , Camundongos Nus , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
PURPOSE: To construct and validate a nomogram for predicting depression after acute coronary stent implantation for risk assessment. METHODS: This study included 150 patients with acute coronary syndrome (ACS) who underwent stent implantation. Univariate analysis was performed to identify the predictors of postoperative depression among the 24 factors. Subsequently, multivariate logistic regression was performed to incorporate the significant predictors into the prediction model. The model was developed using the "rms" software package in R software, and internal validation was performed using the bootstrap method. RESULTS: Of the 150 patients, 82 developed depressive symptoms after coronary stent implantation, resulting in an incidence of depression of 54.7%. Univariate analysis showed that sleep duration ≥7 h, baseline GAD-7 score, baseline PHQ-9 score, and postoperative GAD-7 score were associated with the occurrence of depression after stenting in ACS patients (all p < 0.05). Multivariate logistic regression analysis revealed that major life events in the past year (OR = 2.783,95%CI: 1.121-6.907, p = 0.027), GAD-7 score after operation (OR = 1.165, 95% CI: 1.275-2.097, p = 0.000), and baseline PHQ-9 score (OR = 3.221, 95%CI: 2.065-5.023, p = 0.000) were significant independent risk factors for ACS patients after stent implantation. Based on these results, a predictive nomogram was constructed. The model demonstrated good prediction ability, with an AUC of 0.857 (95% CI = 0.799-0.916). The correction curve showed a good correlation between the predicted results and the actual results (Brier score = 0.15). The decision curve analysis and prediction model curve had clinical practical value in the threshold probability range of 7 to 94%. CONCLUSIONS: This nomogram can help to predict the incidence of depression and has good clinical application value. This trial is registered with ChiCTR2300071408.
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AIM: This study aims to explore the possible effect of Astragaloside IV (AS-IV) on necrotizing enterocolitis (NEC) neonatal rat models and verify the possible implication of TNF-like ligand 1 A (TL1A) and NF-κB signal pathway. METHODS: NEC neonatal rat models were established through formula feeding, cold/asphyxia stress and Lipopolysaccharide (LPS) gavage method. The appearance, activity and skin as well as the pathological status of rats subjected to NEC modeling were assessed. The intestinal tissues were observed after H&E staining. The expression of oxidative stress biomarkers (SOD, MDA and GSH-Px) and inflammatory cytokines (TNF-α, IL-1ß and IL-6) were detected by ELISA and qRT-PCR. Western blotting and immunohistochemistry were applied to detect expressions of TL1A and NF-κB signal pathway-related proteins. Cell apoptosis was assessed by TUNEL. RESULTS: NEC neonatal rat models were established successfully, in which TL1A was highly expressed and NF-κB signal pathway was activated, while TL1A and NF-κB signal pathway can be suppressed by AS-IV treatment in NEC rats. Meanwhile, inflammatory response in intestinal tissues was increased in NEC rat models and AS-IV can attenuate inflammatory response in NEC rats through inhibiting TL1A and NF-κb signal pathway. CONCLUSION: AS-IV can inhibit TL1A expression and NF-κb signal pathway to attenuate the inflammatory response in NEC neonatal rat models.
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Enterocolite Necrosante , NF-kappa B , Ratos , Animais , NF-kappa B/metabolismo , Animais Recém-Nascidos , Enterocolite Necrosante/tratamento farmacológico , Enterocolite Necrosante/metabolismo , Enterocolite Necrosante/patologia , Ligantes , Ratos Sprague-Dawley , Transdução de Sinais , Inflamação/patologia , Modelos Animais de DoençasRESUMO
As an effective antioxidant enzyme, superoxide dismutase (SOD) has been widely used as a food supplement, cosmetic additive, and therapeutic agent. However, oral delivery of SOD is challenging due to its relative instability, limited bioavailability, and low absorption efficiency in the gastrointestinal (GI) tract. We addressed these issues using a highly stable superoxide dismutase (hsSOD) generated from a hot spring microbial sample. This SOD exhibited a specific activity of 5000 IU/mg while retaining its enzymatic activity under low pH environments of an artificial GI system and in the presence of surfactants and various proteolytic enzymes. The inhibitory effects of hsSOD against skin-aging was evaluated under both in vitro and in vivo experiments using fibroblast cell and D-galactose induced aging-mouse models, respectively. Effective oral delivery of hsSOD promises wide applicability in pharmaceutical and food industries.
Assuntos
Envelhecimento da Pele , Animais , Camundongos , Superóxido Dismutase/farmacologia , Antioxidantes/farmacologia , Preparações Farmacêuticas , EnvelhecimentoRESUMO
A multilayered structure incorporating a metal-dielectric subwavelength grating, with the characteristic of polarization separation for visible light and the capability of creating reflection resonance and distinctive polarization-dependent color effects, is proposed. Its reflection resonance and color for TE and TM polarizations are discussed, as well as the influence of its structural parameters on them. Moreover, a reflection filter with characteristics of red for TE-polarized light, green for TM-polarized light, and yellow for daylight is designed and fabricated by replacing its grating region with a sinusoidal grating, and its related characteristics also are verified. The structure and its properties can achieve practical applications in various fields, such as color security, image reproduction, color filtering, and polarization-based information hiding.