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Carbazole, as one of the most important organic frameworks, has been used in optoelectronic materials and biochemistry. However, the synthesis of C4-substituted carbazole has always been an unsolved problem. This report describes the one-step synthesis of C4-aminated carbazoles and their derivatives through the series reaction of C-H amination and arylation. The substrate scope is wide. C4-Amino carbazoles substituted by C2, C6, C7, and C8 methyl groups, especially carbazole derivatives of fused rings, pyridine, and dibenzofuran, can be synthesized.
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BACKGROUND: Polycystic ovary syndrome is a metabolic and hormonal disorder that is closely linked to oxidative stress. Within individuals diagnosed with PCOS, changes occur in the ovaries, resulting in an excessive buildup of iron and peroxidation of lipids, both of which may be associated with the occurrence of ferroptosis. Baicalein, a flavonoid found in the roots of Scutellaria baicalensis and widely known as Chinese skullcap, is known for its anti-inflammatory and anti-ferroptotic properties, which protect against various diseases. Nevertheless, there has been no investigation into the impact of baicalein on polycystic ovary syndrome. PURPOSE: This study aimed to correlate ferroptosis with polycystic ovary syndrome and to assess the effects of baicalein on ovarian dysfunction and placental development in pregnant patients. STUDY DESIGN AND METHODS: Polycystic ovary syndrome was induced in a rat model through the administration of dehydroepiandrosterone, and these rats were treated with baicalein. Oxidative stress and inflammation levels were assessed in serum and ovaries, and tissue samples were collected for histological and protein analyses. Furthermore, different groups of female rats were mated with male rats to observe pregnancy outcomes and tissue samples were obtained for histological, protein, and RNA sequencing. Then, RNA sequencing of the placenta was performed to determine the key genes involved in ferroptosis negative regulation (FNR) signatures. RESULTS: Baicalein was shown to reduce ovarian oxidative stress and pathology. Baicalein also ameliorated polycystic ovary syndrome by decreasing lipid peroxidation and chronic inflammation and modulating mitochondrial functions and ferroptosis in the ovaries. Specifically, glutathione peroxidase and ferritin heavy chain 1 were considerably downregulated in polycystic ovary syndrome gravid rats compared to their expression in the control group, and most of these differences were reversed after baicalein intervention. CONCLUSIONS: Our findings, initially, indicated that baicalein could potentially enhance the prognosis of individuals suffering from polycystic ovary syndrome by reducing oxidative stress and ferroptosis, thus potentially influencing the formulation of a therapeutic approach to address this condition.
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Ferroptose , Flavanonas , Ovário , Estresse Oxidativo , Placenta , Síndrome do Ovário Policístico , Síndrome do Ovário Policístico/tratamento farmacológico , Feminino , Flavanonas/farmacologia , Ferroptose/efeitos dos fármacos , Animais , Estresse Oxidativo/efeitos dos fármacos , Gravidez , Placenta/efeitos dos fármacos , Placenta/metabolismo , Ovário/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Scutellaria baicalensis/química , Modelos Animais de Doenças , Peroxidação de Lipídeos/efeitos dos fármacos , MasculinoRESUMO
Seeking an excellent electrocatalyst is the trickiest issue for the application of urea electro-oxidation and electro-detection. Phosphorus-doped nickel plating on carbon fibers (Ni-P/CF) is synthesized by simple electroless plating. SEM results exhibit that the Ni-P densely and uniformly grows onto the surface of carbon fibers (CF), forming carbon fibers-like nanoarchitectures. Benefiting from the carbon fibers-like nano architectures with abundant exposed active sites on the surface of CF, electron transfer can be synchronously facilitated, and Ni-P/CF displays superior urea electrooxidation (UOR) performance with potentials of 1.40 V to reach 100 mA cm-2. Impressively, it can maintain at 20 mA cm-2 for 48 h without evident activity attenuation, demonstrating robust durability. Cycle stability shows that the voltage has only increased by 10 mV at 300 mA cm-2 from the 10th to 20000th cycles. Most importantly, Ni-P/CF at a length of 100 cm with good reproducibility was successfully synthesized, denoting great potential for large-scale industrial production. Therefore, this work not only affords cost-effective tactics for urea-rich wastewater degradation but also can achieve practical medical applications.
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PURPOSE: Children and adolescents (<18 years old) who sustain a spinal cord injury (SCI) should ideally be managed in specialized rehabilitation services. This project aims to describe the organization of pediatric SCI in ten rehabilitation units in seven countries and to qualitatively explore psychosocial aspects of adolescents living with SCI. METHODS: A multicenter cross-sectional project is planned, using quantitative (web survey) and qualitative (interview) methods in ten rehabilitation units from Norway, Sweden, United States, Israel, PR China, Russia and Palestine. Individual interviews will be conducted with ≥20 adolescents aged 13-17 years at least 6 months' post rehabilitation. RESULTS: Units involved will be described and compared, according to funding, attachment to an acute SCI unit, catchment area, number of beds, admittance and discharge procedures, availability of services, staff/patient ratio, content and intensity of rehabilitation programs, length of stay, measurement methods, follow-up services, health promotion services, and pediatric SCI prevention acts. The semi-structured interview guide will include experiences from acute care and primary rehabilitation, daily life, school, contact with friends, leisure time activities, peers, physical and psychological health, and the adolescents' plans for the future. CONCLUSION: Based on the present protocol, this project is likely to provide new insight and knowledge on pediatric SCI rehabilitation and increase the understanding of pediatric SCI in adolescents and their families internationally.
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Reabilitação Neurológica , Traumatismos da Medula Espinal , Adolescente , Criança , Estudos Transversais , Promoção da Saúde , Humanos , Estudos Multicêntricos como Assunto , Alta do Paciente , Traumatismos da Medula Espinal/reabilitação , Estados UnidosRESUMO
OBJECTIVE: To study the activation of mannose-binding lectin (MBL) complement in STZ-induced diabetic nephropathy (DN) rats and its relationship with NF-kappaB. METHODS: Sprague-Dawley (SD) rats were randomly divided into two groups: normal control and diabetic nephropathy. Diabetes was induced by intraperitoneal injection of STZ. Five rats were sacrificed at the end of week 1, 2, 4, 8 respectively. Blood glucose, 24 h urine, 24 h urinary albumin, serum creatinine (Scr), body mass and kidney mass were examined at the same time points respectively. Creatinine clearance and renal hypertrophy index were calculated. The renal expression of MBL, membrane attack complex (MAC) and NF-kappaB were determined by immunohistochemistry. RESULT: MBL, MAC and NF-kappaB expression were significantly increased in glomerulus of diabetic nephropathy rats compared to the controls. The expression of MBL was positively correlated with NF-kappaB expression. CONCLUSION: The activation of mannose-binding lectin complement participates in the onset and development of DN.
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Lectina de Ligação a Manose da Via do Complemento/fisiologia , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/metabolismo , Lectina de Ligação a Manose/metabolismo , NF-kappa B/metabolismo , Animais , Nefropatias Diabéticas/etiologia , Rim/metabolismo , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
Osteosarcoma (OS) is the most common histological form of primary bone cancer. It is most prevalent in teenagers and young adults. The present study aims at exploring the regulatory effect of microRNA-340 (miR-340) on OS cell proliferation, invasion, migration, and apoptosis via regulating the Notch signaling pathway by targeting ß-catenin (cadherin-associated protein) 1 (CTNNB1). OS tissues belonging to 45 patients and normal femoral head tissues of 45 amputees were selected. Cells were allocated to different groups. In situ hybridization was performed to determine the positive rate of miR-340 expression while immunohistochemistry was used to determine that of CTNNB1 and B-cell lymphoma 2 (Bcl-2). We used a series of experiments to measure the expressions of related factors and assess rates of cell proliferation, migration, invasion, cycle, and apoptosis respectively. Our results show that miR-340 was expressed a higher level in normal tissue than OS tissue. Expression of Notch, CTNNB1, hairy and enhancer of split 1 (Hes1), Bcl-2, Runt-related transcription factor 2 (Runx2), and osteocalcin increased and that of miR-340, Bcl-2 interacting mediator of cell death (BIM), and Bcl-2 associated protein X (Bax) decreased in OS tissues. U-2OS cell line had the highest miR-340 expression. We also found that the up-regulation of miR-340 had increased expression of miR-340, BIM, and Bax but decreased expression of Notch, CTNNB1, Hes1, Bcl-2, Runx2, and osteocalcin. Up-regulation of miR-340p lead to increased cell apoptosis, suppressed cell proliferation, migration, and invasion. Our study demonstrates that overexpression of miR-340 could suppress OS cell proliferation, migration, and invasion as well as promoting OS cell apoptosis by inactivating the Notch signaling pathway via down-regulating CTNNB1. Functional miR-340 overexpression might be a future therapeutic strategy for OS.
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Neoplasias Ósseas/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Osteossarcoma/genética , Receptores Notch/metabolismo , beta Catenina/genética , Adolescente , Apoptose , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Criança , Feminino , Humanos , Masculino , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Transdução de Sinais , Regulação para Cima , beta Catenina/metabolismoRESUMO
Osteoporosis (OP) is a serious health problem that contributes to osteoporotic structural damage and bone fragility. MicroRNAs (miRNAs) can exert important functions over bone endocrinology. Therefore, it is of substantial significance to clarify the expression and function of miRNAs in bone endocrine physiology and pathology to improve the potential therapeutic value for metabolism-related bone diseases. We explored the effect of microRNA-182-5p (miR-182-5p) on osteoblast proliferation and differentiation in OP rats after alendronate (ALN) treatment by targeting adenylyl cyclase isoform 6 (ADCY6) through the Rap1/mitogen-activated protein kinase (MAPK) signaling pathway. Rat models of OP were established to observe the effect of ALN on OP, and the expression of miR-182-5p, ADCY6 and the Rap1/MAPK signaling pathway-related genes was determined. To determine the roles of miR-182-5p and ADCY6 in OP after ALN treatment, the relationship between miR-182 and ADCY6 was initially verified. Osteoblasts were subsequently extracted and transfected with a miR-182-5p inhibitor, miR-182-5p mimic, si-ADCY6 and the MAPK signaling pathway inhibitor U0126. Cell proliferation, apoptosis and differentiation were also determined. ALN treatment was able to ease the symptoms of OP. miR-182-5p negatively targeted ADCY6 to inhibit the Rap1/MAPK signaling pathway. Cells transfected with miR-182 inhibitor decreased the expression of ALP, BGP and COL I, which indicated that the down-regulation of miR-182-5p promoted cell differentiation and cell proliferation and inhibited cell apoptosis. In conclusion, the present study shows that down-regulated miR-182-5p promotes the proliferation and differentiation of osteoblasts in OP rats through Rap1/MAPK signaling pathway activation by up-regulating ADCY6, which may represent a novel target for OP treatment.
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Adenilil Ciclases/genética , MicroRNAs/genética , Osteoporose/genética , Proteínas de Ligação a Telômeros/genética , Adenilil Ciclases/efeitos dos fármacos , Alendronato/administração & dosagem , Animais , Butadienos/administração & dosagem , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , MAP Quinase Quinase 1/antagonistas & inibidores , MAP Quinase Quinase 1/genética , Nitrilas/administração & dosagem , Osteoblastos/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Osteoporose/patologia , Ratos , Complexo Shelterina , Transdução de Sinais/efeitos dos fármacosRESUMO
The applicability of bentonite-supported nanoscale zero-valent iron (B-nZVI) as a catalyst to activate persulfate (PS) for the simultaneous removal of Cr(VI) and phenol was systematically investigated in this study. Experimental results demonstrated that phenol degradation was significantly enhanced under acidic condition and with oxygen supply, whereas the Cr(VI) reduction was not obviously declined. The removal efficiencies of Cr(VI) and phenol in B-nZVI/PS combined system were 99.8 and 72.3%, respectively. Cr(VI) reduction and phenol oxidation was simultaneously achieved in B-nZVI/PS combined system, which provided a promising environmental treatment for industrial wastewater containing metal ions and organic compounds. An acidic condition was more favorable to the decomposition of persulfate for the production of sulfate radicals. Radical scavenging tests revealed that the predominant reactive oxygen species for phenol degradation was SO4(-), neither HO nor O2(-). A reaction mechanism, which involves the Cr(VI) removal mainly by the reduction of nZVI and the degradation of phenol mainly by the SO4(-) from the decomposition of persulfate, was proposed. These findings revealed that B-nZVI/PS combined system has a potential in the environmental remediation polluted jointly by organic compounds and/or heavy metals.
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A five-year field trial was conducted at the surrounding area of Dabao Mountain Mine to explore the feasibility and availability of using kenaf (Hibiscus cannabinus) , a fiber crop with strong heavy metals tolerance and potential economic value, to reclaim the multi-metal contaminated acidic farmland soil. Different amendments were applied prior to the kenaf planting to evaluate their effects on the soil properties and kenaf growth. After the amendments application, the kenaf could grow well on the heavy metals contaminated soil with the Pb, Zn, Cu, Cd, and As concentrations being 1600, 440, 640, 7. 6, and 850 mg . kg-1, respectively. Among the amendments, dolomite and fly ash had better effects than limestone and organic fertilizer. With the application of dolomite and fly ash, the aboveground dry mass production of kenaf reached 14-15 t . hm-2, which was similar to that on normal soils, and the heavy metal concentrations in the bast fiber and stem of kenaf decreased significantly, as compared with the control. The mass of the bast fiber accounted for 32% -38% of the shoot production, and the extractable heavy metal concentrations in the bast fiber could meet the standard of 'technical specifications of ecological textiles' in China, suggesting that the bast fiber had potential economic value. It was suggested that planting kenaf combining with dolomite/fly ash application could be an effective measure to reclaim the multi-metal contaminated acidic farmland soil.
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Recuperação e Remediação Ambiental/métodos , Hibiscus/metabolismo , Metais Pesados/isolamento & purificação , Poluentes do Solo/isolamento & purificação , Ácidos , Biodegradação Ambiental , Produtos Agrícolas/crescimento & desenvolvimento , Hibiscus/crescimento & desenvolvimento , Metais , Metais Pesados/metabolismo , Mineração , Poluentes do Solo/metabolismoRESUMO
Although the role of muscle LIM protein (MLP, also known as CRP3), a LIM-only protein of LIM domain-containing protein family, is well-characterized, the mechanism by which the MLP gene expresses remains unclear. Herein, we demonstrate that myogenin and myocyte enhancer factor 2C (MEF2C) cooperate in activating the MLP gene in myogenesis. RT-PCR, real-time PCR and Western blotting showed that overexpression of myogenin or myogenin plus MEF2C led to induction of the MLP gene in differentiating C2C12 and NIH3T3 fibroblasts. By contrary, knocking-down of myogenin by RNA interference (RNAi) suppressed MLP expression in differentiating C2C12. Deletion and reporter enzyme assay revealed that the promoter activity was determined largely by the region extending from -260 to -173, which containing three E-box (CANNTG motif) candidates. Site-directed mutagenesis demonstrated that the E-box at position -186 to -180 was crucial for activating the promoter by myogenin. Furthermore, MEF2C could enhance myogenin-mediated activation of the promoter. In addition, chromatin immunoprecipitation (ChIP) and re-ChIP showed that myogenin and MEF2C were associated with the activated MLP promoter. Together, these results suggest that myogenin and MEF2C cooperate in the MLP gene activation. The linking of the MLP gene activation with myogenin and MEF2C may facilitate myogenin-mediated differentiation of striated muscle.