RESUMO
The activable NIR-based phototheranostic nanoplatform (NP) is considered an efficient and reliable tumor treatment due to its strong targeting ability, flexible controllability, minimal side effects, and ideal therapeutic effect. This work describes the rational design of a second near-infrared (NIR-II) fluorescence imaging-guided organic phototheranostic NP (FTEP-TBFc NP). The molecular-engineered phototheranostic NP has a sensitive response to glutathione (GSH), generating hydrogen sulfide (H2S) gas, and delivering ferrocene molecules in the tumor microenvironment (TME). Under 808 nm irradiation, FTEP-TBFc could not only simultaneously generate fluorescence, heat, and singlet oxygen but also greatly enhance the generation of reactive oxygen species to improve chemodynamic therapy (CDT) and photodynamic therapy (PDT) at a biosafe laser power of 0.33 W/cm2. H2S inhibits the activity of catalase and cytochrome c oxidase (COX IV) to cause the enhancement of CDT and hypothermal photothermal therapy (HPTT). Moreover, the decreased intracellular GSH concentration further increases CDT's efficacy and downregulates glutathione peroxidase 4 (GPX4) for the accumulation of lipid hydroperoxides, thus causing the ferroptosis process. Collectively, FTEP-TBFc NPs show great potential as a versatile and efficient NP for specific tumor imaging-guided multimodal cancer therapy. This unique strategy provides new perspectives and methods for designing and applying activable biomedical phototheranostics.
Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Microambiente Tumoral , Fotoquimioterapia/métodos , Terapia Combinada , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Imagem Óptica , Linhagem Celular Tumoral , Nanomedicina Teranóstica/métodosRESUMO
MyD88 has been implicated in the tumourigenesis, metastasis and recurrence of breast cancer (BC). Here we utilized TJ-M2010-2 (TJ), an inhibitor of MyD88 homodimerimerization, and siMyD88 to suppress the function of MyD88 in MCF-7 and MDA-MB-231 cells. BC cells were treated in vitro and xenografted into nude mice to generate a model in vivo. TJ inhibited BC cell growth by impeding proliferation rather than by promoting apoptosis in vitro. Additionally, TJ and siMyD88 significantly attenuated cell migration and invasion, inhibited EMT-like progression and reduced cytokine (IL-6, IL-8, TGF-ß1 and TNF-α) secretion induced by LPS. In vivo, TJ significantly hindered tumour growth in mice. Notably, TJ also decreased the secretion of IL-6, IL-8, TGF-ß1, and TNF-α and M2 macrophage infiltration in the tumour microenvironment. The expression of MyD88, TRAF6, NF-κB p65, Snail, MMP-2, MMP-9, p-GSK-3ß and p-Akt was significantly downregulated by TJ in BC cells and tumour tissues. Collectively, these results suggest that a MyD88 inhibitor (TJ) may be a promising therapeutic modality for treating BC patients.
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Neoplasias da Mama/patologia , Movimento Celular/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/metabolismo , Fator 88 de Diferenciação Mieloide/antagonistas & inibidores , NF-kappa B/metabolismo , Transdução de Sinais , Tiazóis/farmacologia , Animais , Apoptose/efeitos dos fármacos , Neoplasias da Mama/irrigação sanguínea , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Regulação para Baixo/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Humanos , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Fator 88 de Diferenciação Mieloide/metabolismo , Invasividade Neoplásica , Proteínas de Neoplasias/metabolismo , Neovascularização Patológica/patologia , Piperazinas , Transdução de Sinais/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
With our improved understanding of the biological behavior of breast cancer, minimally invasive intervention is urgently needed for personalized treatment of early disease. Intraductal therapy is one such minimally invasive approach. With the help of appropriate tools, technologies using the intraductal means of entering the ducts may be used both to diagnose and treat lesions in the mammary duct system with less trauma and at the same time avoid systemic toxicity. Traditional agents such as those targeting pathways, endocrine therapy, immunotherapy, or gene therapy can be used alone or combined with other new technologies, such as nanomaterials, through the intraductal route. Additionally, relevant mammary tumor models in rodents which reflect changes in the tumor microenvironment will help deepen our understanding of their biological behavior and heterogeneity. This article reviews the current status and future prospects of intraductal therapy in breast cancer, with emphasis on ductal carcinoma in situ.
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Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Feminino , HumanosRESUMO
Postoperative cognitive dysfunction (POCD) is deemed to a severe surgical complication without effective treatment. Previous work has confirmed the important modulatory role of hydrogen sulfide (H2S) in cognitive function. This study was proposed to explore whether H2S relieves POCD and the possible mechanisms. We demonstrated that NaHS (a donor of H2S) reversed the inhibited endogenous H2S generation in the hippocampus of postoperative rats. NaHS attenuated the cognitive impairment of postoperative rats in the Y-maze, Novel object recognition, and Morris water maze tests. NaHS enhanced the expressions of synaptic plasticity-related proteins, synapsin-1 and PSD-95, increased the synaptic density, and decreased the destruction of synaptic structures in the hippocampus of postoperative rats. Moreover, NaHS promoted Warburg effect in the hippocampus of postoperative rats, as reflected by increases in the expressions of hexokinase 2, pyruvate kinase M2, lactate dehydrogenase A, and pyruvate dehydrogenase kinase 1, an enhancement in the content of lactate, and a reduction in the expression of pyruvate dehydrogenase. The inhibitor of Warburg effect, 2-Deoxy-D-glucose (2-DG), not only reversed NaHS-enhanced Warburg effect in the hippocampus of postoperative rats, but also significantly abolished NaHS-exerted protective effect on cognitive function. Furthermore, 2-DG reversed NaHS-exerted enhancement in the expressions of synapsin-1 and PSD-95, increase in the synaptic density, and decrease in the destruction of synaptic structures in the hippocampus of postoperative rats. Collectively, these results indicate that H2S alleviates POCD through enhancing hippocampal Warburg effect, which subsequently improves synaptic plasticity in the hippocampus.
Assuntos
Hipocampo/efeitos dos fármacos , Sulfeto de Hidrogênio/farmacologia , Plasticidade Neuronal/efeitos dos fármacos , Complicações Cognitivas Pós-Operatórias/tratamento farmacológico , Animais , Cognição/efeitos dos fármacos , Desoxiglucose/farmacologia , Masculino , Substâncias Protetoras/farmacologia , Ratos , Ratos Sprague-Dawley , Sulfetos/farmacologiaRESUMO
Although highly accurate molecular processes and various messenger RNA (mRNA) quality control and ribosome proofreading mechanisms are used by organisms to transcribe their genes and maintain the fidelity of genetic information, errors are inherent in all biological systems. Low-level translation errors caused by an imbalance of homologous and nonhomologous amino acids caused by stress conditions are particularly common. Paradoxically, advantageous phenotypic diversity can be generated by such errors in eukaryotes through unknown molecular processes. Here, we found that the significant cadmium-resistant phenotype was correlated with an increased mistranslation rate of the mRNA in Saccharomyces cerevisiae. This phenotypic change was also related to endogenous sulfur amino acid starvation. Compared with the control, the mistranslation rate caused by cadmium was significantly increased (p < .01). With the increase of cysteine contents in medium, the mistranslation rate of WT(BY4742a) decreased significantly (p < .01). This demonstrates that cadmium treatment and sulfur amino acid starvation both can induce translation errors. Although cadmium uptake is independent of the Sul1 transporter, cadmium-induced mRNA mistranslation is dependent on the sulfate uptake of the Sul1p transporter. Furthermore, cadmium-induced translation errors depend on methionine biosynthesis. Taken together, cadmium causes endogenous sulfur starvation, leading to an increase in the mRNA mistranslation, which contributes to the resistance of yeast cells to cadmium. We provide a new pathway mediating the toxicity of cadmium, and we propose that altering mRNA mistranslation may portray a different form of environmental adaptation.
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Cádmio/farmacologia , Biossíntese de Proteínas/efeitos dos fármacos , RNA Mensageiro/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Meios de Cultura/química , Metionina/biossíntese , Fenótipo , Saccharomyces cerevisiae/efeitos dos fármacos , Transportadores de Sulfato , Enxofre/químicaRESUMO
BACKGROUND: Adipocytes make up the major component of breast tissue, accounting for 90% of stromal tissue. Thus, the crosstalk between adipocytes and breast cancer cells may play a critical role in cancer progression. Adipocyte-breast cancer interactions have been considered important for the promotion of breast cancer metastasis. However, the specific mechanisms underlying these interactions are unclear. In this study, we investigated the mechanisms of adipocyte-mediated breast cancer metastasis. METHODS: Breast cancer cells were cocultured with mature adipocytes for migration and 3D matrix invasion assays. Next, lentivirus-mediated loss-of-function experiments were used to explore the function of lysyl hydroxylase (PLOD2) in breast cancer migration and adipocyte-dependent migration of breast cancer cells. The role of PLOD2 in breast cancer metastasis was further confirmed using orthotopic mammary fat pad xenografts in vivo. Clinical samples were used to confirm that PLOD2 expression is increased in tumor tissue and is associated with poor prognosis of breast cancer patients. Cells were treated with cytokines and pharmacological inhibitors in order to verify which adipokines were responsible for activation of PLOD2 expression and which signaling pathways were activated in vitro. RESULTS: Gene expression profiling and Western blotting analyses revealed that PLOD2 was upregulated in breast cancer cells following coculture with adipocytes; this process was accompanied by enhanced breast cancer cell migration and invasion. Loss-of-function studies indicated that PLOD2 knockdown suppressed cell migration and disrupted the formation of actin stress fibers in breast cancer cells and abrogated the migration induced by following coculture with adipocytes. Moreover, experiments performed in orthotopic mammary fat pad xenografts showed that PLOD2 knockdown could reduce metastasis to the lung and liver. Further, high PLOD2 expression correlated with poor prognosis of breast cancer patients. Mechanistically, adipocyte-derived interleukin-6 (IL-6) and leptin may facilitate PLOD2 upregulation in breast cancer cells and promote breast cancer metastasis in tail vein metastasis assays. Further investigation revealed that adipocyte-derived IL-6 and leptin promoted PLOD2 expression through activation of the JAK/STAT3 and PI3K/AKT signaling pathways. CONCLUSIONS: Our study reveals that adipocyte-derived IL-6 and leptin promote PLOD2 expression by activating the JAK/STAT3 and PI3K/AKT signaling pathways, thus promoting breast cancer metastasis.
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Adipócitos/metabolismo , Neoplasias da Mama/patologia , Interleucina-6/metabolismo , Leptina/metabolismo , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/metabolismo , Regulação para Cima , Células 3T3-L1 , Adipocinas/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular , Feminino , Técnicas de Silenciamento de Genes , Humanos , Janus Quinases/metabolismo , Camundongos , Metástase Neoplásica , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/deficiência , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/genética , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Microambiente TumoralRESUMO
BACKGROUND: Chylopericardium effusion is characterized by the accumulation of milky effusion in the pericardium. It is often idiopathic but it can be secondary to trauma, chest radiation, tuberculosis and malignancy. If cardiac tamponade ensues, it becomes life-threatening. Herein we describe chylopericardium tamponade in a child with IgA nephropathy. To the best of our knowledge, this is the first reported case of chylopericardium tamponade in IgA nephropathy. CASE PRESENTATION: A 6 years old boy with IgA nephropathy presented with dyspnea, orthopnea, pretibial pitting edema, ascites and fever. Muffled heart sounds and hepatomegaly were also noted. Echocardiography and thoracic CT revealed that there was a large volume of hydropericardium. Moreover, the pericardial milky fluid by pericardiocentesis was analyzed and chylopericardium effusion was eventually confirmed. Pericardial drainage was continued and his diet was modified to low fat, rich MCT and high protein. Complete remission was achieved after 3 weeks of this combined treatment. CONCLUSION: Chylopericardial tamponade could be a rare and life-threatening complication of IgA nephropathy. Etiological analysis is critical for determining the therapeutic approach in patients with pericardial effusion.
Assuntos
Tamponamento Cardíaco/etiologia , Glomerulonefrite por IGA/complicações , Derrame Pericárdico/etiologia , Tamponamento Cardíaco/diagnóstico por imagem , Tamponamento Cardíaco/terapia , Criança , Dieta com Restrição de Gorduras , Dieta Rica em Proteínas , Drenagem , Ecocardiografia , Humanos , Masculino , Derrame Pericárdico/diagnóstico por imagem , Derrame Pericárdico/terapia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Previous studies have shown that cyclooxygenase-2, a key enzyme that converts arachidonic acid to prostaglandins, is involved in anxiety and cognitive processes, but few studies have investigated the effects of chronic administration of cyclooxygenase-2 inhibitors on anxiety, learning and memory under normal physiological conditions. The aim of the study was to investigate the effects of chronic administration of parecoxib, a cyclooxygenase-2 inhibitor, on anxiety behavior and memory performance under normal physiological conditions and to explore the possible neural mechanism underlying parecoxib-mediated effects. METHODS: Adult male ICR mice were randomly divided into four groups: the control group and three parecoxib groups. Mice received normal saline or parecoxib (2.5, 5.0 or 10 mg/kg) intraperitoneal injection once a day for 21 days, respectively. Elevated plus-maze, novel object recognition and Y maze tests were conducted on day 23, 24 and 26, respectively. Four additional groups that received same drug treatment were used to measure synaptophysin protein levels by western blot and prostaglandin E2 (PGE2) levels by ELISA in the amygdala and hippocampus on day 26. RESULTS: Chronic parecoxib exerted an anxiolytic-like effect in the plus-maze test test, and enhanced memory performance in the novel object recognition and Y maze tests. Western blot analysis showed that chronic parecoxib down-regulated synaptophysin levels in the amygdala and up-regulated synaptophysin levels in the hippocampus. ELISA assay showed that chronic parecoxib inhibited PGE2 in the hippocampus but not amygdala. CONCLUSIONS: Chronic parecoxib exerts anxiolytic-like and memory enhancing effects, which might be mediated through differential modulation of synaptophysin and PGE2 in the amygdala and hippocampus.
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Ansiolíticos/administração & dosagem , Hipocampo/efeitos dos fármacos , Isoxazóis/administração & dosagem , Aprendizagem em Labirinto/efeitos dos fármacos , Nootrópicos/administração & dosagem , Sinaptofisina/biossíntese , Animais , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Relação Dose-Resposta a Droga , Esquema de Medicação , Expressão Gênica , Hipocampo/metabolismo , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos ICR , Distribuição Aleatória , Sinaptofisina/genéticaRESUMO
BACKGROUND: The aim of this study was to evaluate the influence of RGC-32 (response gene to complement 32) on cell cycle progression in renal tubular epithelial cell injury. METHODS: NRK-52E cells with overexpressed or silenced RGC-32 were constructed via transient transfection with RGC-32 expression plasmid and RGC-32 siRNA plasmid, and the cell cycle distribution was determined. The expression levels of fibrosis factors, including smooth muscle action (α-SMA), fibronectin (FN) and E-cadherin, were assessed in cells with silenced RGC-32. RESULTS: The cells were injured via TNF-α treatment, and the injury was detectable by the enhanced expression of neutrophil gelatinase-associated lipocalin (NGAL). RGC-32 expression also increased significantly. The number of cells at G2/M phase increased dramatically in RGC-32 silenced cells, indicating that RGC-32 silencing induced G2/M arrest. In addition, after treatment with TNF-α, the NRK-52E cells with silenced RGC-32 showed significantly increased expression of α-SMA and FN, but decreased expression of E-cadherin. CONCLUSIONS: The results of this study suggest that RGC-32 probably has an important impact on the repair process of renal tubular epithelial cells in vitro by regulating the G2/M phase checkpoint, cell fibrosis and cell adhesion. However, the exact mechanism needs to be further elucidated.
Assuntos
Proteínas de Ciclo Celular/fisiologia , Células Epiteliais/fisiologia , Túbulos Renais/fisiologia , Pontos de Checagem da Fase M do Ciclo Celular , Proteínas Musculares/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Regeneração , Actinas/genética , Animais , Caderinas/genética , Linhagem Celular , Células Epiteliais/metabolismo , Fibronectinas/genética , Regulação da Expressão Gênica , Túbulos Renais/metabolismo , RatosRESUMO
Unfolded protein response (UPR) is an important cellular phenomenon induced by over-accumulation of unfolded proteins in the endoplasmic reticulum (ER) lumen. ER stress and UPR are implicated in human diseases such as diabetes, atherosclerosis and neurodegenerative diseases. Current methods for measuring ER stress levels and UPR activation usually include cells lysis and other complicated procedures such as reverse transcription-PCR (RT-PCR). These methods typically have low sensitivity and are not suitable for live detection. In this study, we developed a dual-luciferase gene reporter system to monitor UPR activation in live cells of the yeast Saccharomyces cerevisiae by taking advantage of the HAC1 intron and its unconventional splicing-regulation mechanism. We showed that this reporter can be used to monitor UPR in live cells with high sensitivity.
Assuntos
Estresse do Retículo Endoplasmático , Genes Reporter , Saccharomyces cerevisiae/genética , Resposta a Proteínas não Dobradas , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Íntrons , Luciferases/genética , Luciferases/metabolismo , Splicing de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismoRESUMO
Chromium is a significant mutagen and carcinogen in environment. We compared the effects of tri- and hexavalent chromium on cytotoxicity and oxidative stress in yeast. Cell growth was inhibited by Cr(3+) or Cr(6+), and Cr(6+) significantly increased the lethal rate compared with Cr(3+). Both Cr(3+) and Cr(6+) can enter into the yeast cells. The percent of propidium iodide permeable cells treated with Cr(3+) is almost five times as that treated with the same concentration of Cr(6+). Levels of TBARS, O2 (-), and carbonyl protein were significantly increased in both Cr(6+)- and Cr(3+)-treated cells in a concentration- and time-dependent manner. Moreover, the accumulation of these stress markers in Cr(6+)-treated cells was over the Cr(3+)-treated ones. The decreased GSH level and increased activity of GPx were observed after 300 µM Cr(6+)-exposure compared with the untreated control, whereas there was no other change of GSH content in cells treated with Cr(3+) even at very high concentration. Exposure to both Cr(3+) and Cr(6+) resulted in the decrease of activities of SOD and catalase. Furthermore, the effect of Cr(6+) is stronger than that of Cr(3+). Null mutation sensitivity assay demonstrated that the gsh1 mutant was sensitive to Cr(6+) other than Cr(3+), the apn1 mutant is more sensitive to Cr(6+) than Cr(3+), and the rad1 mutant is sensitive to both Cr(6+) and Cr(3+). Therefore, Cr(3+) can be concluded to inhibit cell growth probably due to the damage of plasma membrane integrality in yeast. Although both tri- and hexavalent chromium can induce cytotoxicity and oxidative stress, the action mode of Cr(3+) is different from that of Cr(6+), and serious membrane damage caused by Cr(3+) is not the direct consequence of the increase of lipid peroxidation.
Assuntos
Cromo/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Saccharomyces cerevisiae/efeitos dos fármacos , Antioxidantes/metabolismo , Membrana Celular/efeitos dos fármacos , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Viabilidade Microbiana/efeitos dos fármacos , Saccharomyces cerevisiae/metabolismoRESUMO
Against the background of increasingly severe environmental problems, green development has gained widespread attention, and green innovation has thus become crucial for enterprises. This study used 2007-2019 data from listed A-share companies in China to evaluate the effect of senior executives' overseas experience on corporate green innovation. The results showed that senior executives' overseas experience could promote green innovation in companies. This positive effect was more significant for private enterprises and high-tech enterprises, especially in eastern China. The CEO pay regulation have a significant negative moderating effect on this positive effect. This study enriches upper echelons theory and provides theoretical support for government agencies to accelerate innovative green development strategies. The results can also provide a decision-making basis for governments to formulate policies to promote enterprises' green development.
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Pessoal Administrativo , China , Humanos , Setor PrivadoRESUMO
BACKGROUND: Recent advances in gene editing technology have opened up new avenues for in vivo gene therapy, which holds great promise as a potential treatment method for dilated cardiomyopathy (DCM). The CRISPR-Cas13 system has been shown to be an effective tool for knocking down RNA expression in mammalian cells. PspCas13b, a type VI-B effector that can be packed into adeno-associated viruses and improve RNA knockdown efficiency, is a potential treatment for diseases characterized by abnormal gene expression. RESULTS: Using PspCas13b, we were able to efficiently and specifically knockdown the mutant transcripts in the AC16 cell line carrying the heterozygous human TNNT2R141W (hTNNT2R141W) mutation. We used adeno-associated virus vector serotype 9 to deliver PspCas13b with specific single guide RNA into the hTNNT2R141W transgenic DCM mouse model, effectively knocking down hTNNT2R141W transcript expression. PspCas13b-mediated knockdown significantly increased myofilament sensitivity to Ca2+, improved cardiac function, and reduced myocardial fibrosis in hTNNT2R141W DCM mice. CONCLUSIONS: These findings suggest that targeting genes through Cas13b is a promising approach for in vivo gene therapy for genetic diseases caused by aberrant gene expression. Our study provides further evidence of Cas13b's application in genetic disease therapy and paves the way for future applicability of genetic therapies for cardiomyopathy.
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The basic tribological experiments have reported that nano-graphene lubricating oil has excellent anti-friction and anti-wear properties, which has been widely concerned. However, the real anti-friction effect of nano-graphene lubricating oil and its impact on engine power performance, economic performance and emission performance remain to be proved. This has seriously hindered the popularization and application of nano-graphene lubricating oil in the engine field. In this paper, nano-graphene powder was chemically grafted to prepare nano-graphene lubricating oil with high dispersion stability. The influence of nano-graphene on physicochemical properties of lubricating oil was studied, and the influence of nano-graphene on engine power performance, economic performance and emission performance was explored. The results show that after modification, the dispersion of nano-graphene in lubricating oil is improved. Compared with pure lubricating oil, the addition of nano-graphene makes the kinematic viscosity of lubricating oil slightly lower, and has little effect on the density, flash point, pour point and total acid value of lubricating oil. The reversed towing torque of nano-graphene lubricating oil is reduced by 1.82-5.53%, indicating that the friction loss decreases. The specific fuel consumption of the engine is reduced, which indicates that the fuel economic performance is improved. Engine HC+NOX, CH4, CO2 emissions do not change much, but particulate matter (PM) emissions increase by 8.85%. The quantity concentration of nuclear particles, accumulated particles and total particles of nano-graphene lubricating oil are significantly higher than that of pure lubricating oil. And the increase of the quantity concentration of accumulated particles is more obvious than that of nuclear particles, and the larger the load, the more obvious this phenomenon. In order to apply nano-graphene lubricating oil to the engine, it is also necessary to further study its impact on the post-processing system, adjust the control strategy of the post-processing system and then test and calibrate.
Assuntos
Grafite , Lubrificantes , Viscosidade , Grafite/química , Lubrificantes/química , Gasolina/análise , Nanoestruturas/química , Óleos/química , Lubrificação , Emissões de Veículos/análiseRESUMO
Nano-graphene lubricating oil with appropriate concentration shows excellent performance in reducing friction and wear under different working conditions of diesel engines, and has been widely concerned. Lubricating oil has a significant impact on particulate matter (PM) emissions. At present, there are few studies on the impact of nano-graphene lubricating oil on the physicochemical properties of PM. In order to comprehensively evaluate the impact of nano-graphene lubricating oil on diesel engines, this paper mainly focused on the effects of lubricating oil nano-graphene additives on the particle size distribution and physicochemical properties of PM. The results show that, compared with pure lubricating oil, the total number of nuclear PM and accumulated PM of nano-graphene lubricating oil is significantly increased. The fractal dimension of PM of nano-graphene lubricating oil increases and its structure becomes more compact. The average fringe separation distance of basic carbon particles decreases, the average fringe length increases. The degree of ordering and graphitization of basic carbon particles are higher. The fringe tortuosity of basic carbon particles decreases, and the fluctuation of carbon layer structure of basic carbon particles decreases. Aliphatic substances in PM are basically unchanged, aromatic components and oxygen functional groups increase. The initial PM oxidation temperature and burnout temperature increase, the maximum oxidation rate temperature and combustion characteristic index decrease, and the activation energy increases, making it more difficult to oxidize. This was mainly caused by the higher graphitization degree of PM of nano-graphene lubricating oil and the increased content of aromatic substances.
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The CYP2D6 gene has been suggested to play an important role in the pathogenesis of lung cancer. However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the association of CYP2D6 T188C variant with lung cancer. Published literature from PubMed, Embase, Chinese National Knowledge Infrastructure and Wanfang data were retrieved. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using fixed- or random-effects model. A total of nine studies (1,516 lung cancer cases and 1,950 controls) for CYP2D6 T188C variant were included in the meta-analysis. The meta-analysis indicated that compared with CYP2D6 TT genotype, non-TT genotype (CC or CT) was significantly associated with lung cancer in the Chinese (OR = 1.61, 95 % CI = 1.38-1.87, p < 0.001), with no evidence of between-study heterogeneity (I (2) = 0.0 %, p = 0.991). The sensitivity analysis indicated that the association was stable and no publication bias was detected. The present meta-analysis supported the positive association of CYP2D6 T188C variant with lung cancer in the Chinese. Further large-scale studies with the consideration for gene-gene/gene-environment interactions should be conducted to investigate the association.
Assuntos
Citocromo P-450 CYP2D6/genética , Neoplasias Pulmonares/genética , China , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , RiscoRESUMO
BACKGROUND: Mutations in canonical transient receptor potential channel 6 (TRPC6) have been identified as responsible for the development of focal segmental glomerulosclerosis, a proteinuric disease with steroid resistance and poor prognosis. This study explores the prevalence of TRPC6 variants in Chinese children with idiopathic nephrotic syndrome (INS), the genotype/phenotype correlation of TRPC6 variants, the therapeutic response, and the underlying molecular mechanism. METHODS: Fifty-one children with sporadic INS were enrolled: 23 steroid-sensitive cases and 28 steroid-resistant cases Polymerase chain reaction was used to amplify 13 exons and the promoter sequences of TRPC6 before sequencing. The expression of TRPC6 in renal tissues was illustrated by immunohistochemistry staining. The transcriptional activity of variants in TRPC6 promoter was measured by the luciferase assay. RESULTS: Three variants (-254C>G, rs3824934; +43C/T, rs3802829; and 240 G>A, rs17096918) were identified. The allele frequency of the -254C>G single-nucleotide polymorphism (SNP) in the steroid-resistant nephrotic syndrome (SRNS) patients (40.5%) was higher than that in the steroid-sensitive nephrotic syndrome subjects (27.1%; P = 0.046). The -254C>G SNP enhanced transcription from TRPC6 promoter in vitro and was associated with increased TRPC6 expression in renal tissues of SRNS patients. CONCLUSION: -254C>G, a SNP underlying enhanced TRPC6 transcription and expression, may be correlated with the development of steroid resistance in Chinese children with INS.
Assuntos
Povo Asiático/genética , Síndrome Nefrótica/congênito , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Canais de Cátion TRPC/genética , Transcrição Gênica/genética , Sequência de Bases , Criança , Éxons/genética , Frequência do Gene , Humanos , Imuno-Histoquímica , Rim/metabolismo , Luciferases , Dados de Sequência Molecular , Síndrome Nefrótica/genética , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Canal de Cátion TRPC6RESUMO
Purpose: As a rare collagen type IV hereditary kidney disease, X-linked Alport syndrome (XLAS) is the most common form of Alport syndrome, the prevalence of which is estimated at 1:10,000 of the population, four times higher than the prevalence rate of autosomal recessive Alport syndrome. To describe a series of eight XLAS children with persistent hematuria and proteinuria and the clinical outcomes after hydroxychloroquine (HCQ) treatment to assess its efficacy as early intervention. Patients and Methods: The study retrospectively analysed 8 patients with persistent hematuria and proteinuria at different onset ages who were diagnosed with XLAS and been treated with HCQ. The urinary erythrocyte count, urinary albuminn were measured. Descriptive statistics were used to estimate the patients' responses to HCQ treatment after one month, three months, and six months. Results: After the first month, the three months, and the six months of HCQ treatment, the urinary erythrocyte counts of four, seven, and eight children were significantly reduced; the decreasing proteinuria was found in two, four, and five children. Only one child with increasing proteinuria was found after 1-month HCQ treatment. This proteinuria was maintained after 3-month HCQ treatment but decreased to minor after 6-month HCQ treatment. Conclusion: We present the first potential efficacy of HCQ treatment in XLAS with hematuria and persistent proteinuria. It suggested that HCQ could be an effective treatment to ameliorate hematuria and proteinuria.
RESUMO
BACKGROUND: Hyperuricemia (HUA) is a crucial factor contributing to some chronic diseases among adults. In past observational literatures, scholars have debated the effectiveness of dietary pattern on HUA and inconsistencies exist. Given this condition, the study aimed to provide a comparative assessment of the relation between dietary pattern and HUA risk and offer implications to policy makers. METHODS: A systematic research was undertaken in PubMed, Web of Science, Cochrane, Embase, Medicine, ScienceDirect and Medline to identify observational studies examining the effect of dietary pattern on HUA, and search period was from past to January 2022. Meta analysis was applied by using the Stata version 11.0 software. RESULTS: A total of 34,583 adults from 8 observational studies, 45,525 adults from 6 observational studies were included to examine the effectiveness of "healthy" and "meat/western" dietary patterns on HUA risk respectively. The findings suggested that "healthy" dietary pattern significantly decreased the HUA risk (ORâ =â 0.73; 95% CI: 0.61-0.88) both in Eastern countries (ORâ =â 0.79; 95% CI: 0.64-0.98) and Western countries (ORâ =â 0.53; 95% CI: 0.30-0.92) while the "Meat/Western" pattern increased the HUA possibilities (ORâ =â 1.26; 95% CI: 1.17-1.37). Stratified analysis exhibited that "healthy" pattern reduced HUA risk in adults was more effective in cohort study (ORâ =â 0.79; 95% CI: 0.72-0.86). CONCLUSIONS: This study's findings highlighted the potential benefit of healthy dietary pattern in decreasing HUA risk. Accordingly, implementing policy makers of countries should enhance to appeal adults to keep a healthy diet, offer financial support to low-income staff, or provide guidelines for adult's dietary behavior changes. TRIAL REGISTRATION NUMBER: INPLASY: INPLASY202290034.
Assuntos
Hiperuricemia , Adulto , Humanos , Estudos de Coortes , Dieta Saudável , Dieta Ocidental , Hiperuricemia/epidemiologia , Hiperuricemia/etiologia , Estudos Observacionais como AssuntoRESUMO
A wide range of Cu(II)-catalyzed C-H activation reactions have been realized since 2006, however, whether a C-H metalation mechanism similar to Pd(II)-catalyzed C-H activation reaction is operating remains an open question. To address this question and ultimately develop ligand accelerated Cu(II)-catalyzed C-H activation reactions, realizing the enantioselective version and investigating the mechanism is critically important. With a modified chiral BINOL ligand, we report the first example of Cu-mediated enantioselective C-H activation reaction for the construction of planar chiral ferrocenes with high yields and stereoinduction. The key to the success of this reaction is the discovery of a ligand acceleration effect with the BINOL-based diol ligand in the directed Cu-catalyzed C-H alkynylation of ferrocene derivatives bearing an oxazoline-aniline directing group. This transformation is compatible with terminal aryl and alkyl alkynes, which are incompatible with Pd-catalyzed C-H activation reactions. This finding provides an invaluable mechanistic information in determining whether Cu(II) cleaves C-H bonds via CMD pathway in analogous manner to Pd(II) catalysts.