RESUMO
Innate immunity plays the most important system responsible for protecting crustaceans against invading pathogens. White spot syndrome virus (WSSV) is considered a serious pathogen in crustaceans with high cumulative mortality and morbidity in infected animals. Understanding the mechanism of the response of hosts to WSSV infection is necessary, which is useful for effective prevention in controlling infection. In this review, we summarize the participation of signaling pathways (toll, immune deficiency, JAK/STAT, endocytosis, mitogen-activated protein kinase, PI3K/Akt/mTOR, cGAS-STING, Wingless/Integrated signal transduction, and prophenoloxidase (proPO) cascade) and the activity of cells (apoptosis, autophagy, as well as, reactive oxygen species and antioxidant enzymes) in the cellular-mediated immune response of crustaceans during WSSV infection. The information presented in this current review is important for a better understanding of the mechanism of the response of hosts to pathogens. Additionally, this provides a piece of basic knowledge for discovering approaches to strengthen the immune system and resistance of cultured animals against viral infections.
Assuntos
Penaeidae , Vírus da Síndrome da Mancha Branca 1 , Animais , Vírus da Síndrome da Mancha Branca 1/fisiologia , Fosfatidilinositol 3-Quinases , Crustáceos , Transdução de Sinais , Imunidade InataRESUMO
Transition-metal phosphates have been widely applied as promising candidates for electrochemical energy storage and conversion. In this study, we report a simple method to prepare a N, F co-doped mesoporous cobalt phosphate with rich-oxygen vacancies by in-situ pyrolysis of a Co-phosphate precursor with NH4 + cations and F- anions. Due to this heteroatom doping, it could achieve a current density of 10â mA/cm2 at lower overpotential of 276â mV and smaller Tafel slope of 57.11â mV dec-1 on glassy carbon. Moreover, it could keep 92 % of initial current density for 35â h, indicating it has an excellent stability and durability. Furthermore, the optimal material applied in supercapacitor displays specific capacitance of 206.3â F g-1 at 1â A â g-1 and maintains cycling stability with 80 % after 3000 cycles. The excellent electrochemical properties should be attributed to N, F co-doping into this Co-based phosphate, which effectively modulates its electronic structure. In addition, its amorphous structure provides more active sites; moreover, its mesoporous structure should be beneficial to mass transfer and electrolyte diffusion.
RESUMO
Despite the low case fatality, Zika virus (ZIKV) infection has been associated with microcephaly in infants and Guillain-Barré syndrome. Antiviral and vaccine developments against ZIKV are still ongoing; therefore, in the meantime, preventing the disease transmission is critical. Primarily transmitted by Aedes species mosquitoes, ZIKV also can be sexually transmitted. We used AG129 mice lacking interferon-α/ß and -γ receptors to study the testicular pathogenesis and sexual transmission of ZIKV. Infection of ZIKV progressively damaged mouse testes, increased testicular oxidative stress as indicated by the levels of reactive oxygen species, nitric oxide, glutathione peroxidase 4, spermatogenesis-associated-18 homolog in sperm and pro-inflammatory cytokines including IL-1ß, IL-6, and G-CSF. We then evaluated the potential role of the antioxidant ebselen (EBS) in alleviating the testicular pathology with ZIKV infection. EBS treatment significantly reduced ZIKV-induced testicular oxidative stress, leucocyte infiltration and production of pro-inflammatory response. Furthermore, it improved testicular pathology and prevented the sexual transmission of ZIKV in a male-to-female mouse sperm transfer model. EBS is currently in clinical trials for various diseases. ZIKV infection could be on the list for potential use of EBS, for alleviating the testicular pathogenesis with ZIKV infection and preventing its sexual transmission.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Azóis/uso terapêutico , Compostos Organosselênicos/uso terapêutico , Doenças Virais Sexualmente Transmissíveis/tratamento farmacológico , Testículo/efeitos dos fármacos , Infecção por Zika virus/tratamento farmacológico , Zika virus/efeitos dos fármacos , Animais , Antioxidantes/uso terapêutico , Forma do Núcleo Celular/efeitos dos fármacos , Tamanho do Núcleo Celular/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Tamanho Celular/efeitos dos fármacos , Citocinas/metabolismo , Isoindóis , Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , Leucócitos/metabolismo , Leucócitos/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Estresse Oxidativo/efeitos dos fármacos , Receptores de Interferon/genética , Receptores de Interferon/metabolismo , Doenças Virais Sexualmente Transmissíveis/patologia , Doenças Virais Sexualmente Transmissíveis/transmissão , Doenças Virais Sexualmente Transmissíveis/virologia , Espermatogênese/efeitos dos fármacos , Espermatozoides/imunologia , Espermatozoides/metabolismo , Espermatozoides/patologia , Espermatozoides/virologia , Testículo/imunologia , Testículo/patologia , Testículo/virologia , Zika virus/imunologia , Zika virus/patogenicidade , Infecção por Zika virus/patologia , Infecção por Zika virus/transmissão , Infecção por Zika virus/virologiaRESUMO
Skin lightening among Eurasians is thought to have been a convergence occurring independently in Europe and East Asia as an adaptation to high latitude environments. Among Europeans, several genes responsible for such lightening have been found, but the information available for East Asians is much more limited. Here, a genome-wide comparison between dark-skinned Africans and Austro-Asiatic speaking aborigines and light-skinned northern Han Chinese identified the pigmentation gene OCA2, showing unusually deep allelic divergence between these groups. An amino acid substitution (His615Arg) of OCA2 prevalent in most East Asian populations-but absent in Africans and Europeans-was significantly associated with skin lightening among northern Han Chinese. Further transgenic and targeted gene modification analyses of zebrafish and mouse both exhibited the phenotypic effect of the OCA2 variant manifesting decreased melanin production. These results indicate that OCA2 plays an important role in the convergent skin lightening of East Asians during recent human evolution.
Assuntos
Povo Asiático/genética , Proteínas de Membrana Transportadoras/genética , Pigmentação da Pele/genética , Adolescente , Alelos , Substituição de Aminoácidos , Evolução Biológica , População Negra/genética , Criança , Etnicidade/genética , Evolução Molecular , Feminino , Frequência do Gene , Estudos de Associação Genética/métodos , Variação Genética , Genética Populacional/métodos , Haplótipos , Humanos , Masculino , Proteínas de Membrana Transportadoras/sangue , Proteínas de Membrana Transportadoras/metabolismo , Polimorfismo de Nucleotídeo Único , Seleção Genética , Pigmentação da Pele/fisiologia , População Branca/genética , Adulto JovemRESUMO
Mitochondria are highly dynamic subcellular organelles participating in many signaling pathways such as antiviral innate immunity and cell death cascades. Here we found that mitochondrial fusion was impaired in dengue virus (DENV) infected cells. Two mitofusins (MFN1 and MFN2), which mediate mitochondrial fusion and participate in the proper function of mitochondria, were cleaved by DENV protease NS2B3. By knockdown and overexpression approaches, these two MFNs showed diverse functions in DENV infection. MFN1 was required for efficient antiviral retinoic acid-inducible gene I-like receptor signaling to suppress DENV replication, while MFN2 participated in maintaining mitochondrial membrane potential (MMP) to attenuate DENV-induced cell death. Cleaving MFN1 and MFN2 by DENV protease suppressed mitochondrial fusion and deteriorated DENV-induced cytopathic effects through subverting interferon production and facilitating MMP disruption. Thus, MFNs participate in host defense against DENV infection by promoting the antiviral response and cell survival, and DENV regulates mitochondrial morphology by cleaving MFNs to manipulate the outcome of infection.
Assuntos
Vírus da Dengue/metabolismo , Dengue/metabolismo , GTP Fosfo-Hidrolases/metabolismo , Interações Hospedeiro-Parasita/imunologia , Dinâmica Mitocondrial/fisiologia , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Proteínas Mitocondriais/metabolismo , Animais , Western Blotting , Citometria de Fluxo , Humanos , Imunoprecipitação , Camundongos , Camundongos Knockout , Microscopia de Fluorescência , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Replicação Viral/imunologiaRESUMO
In the artistic sports program, the referee' scores directly determine the final results of the athletes. Wushu is a artistic sport that has a Chinese characteristic and has the potential to become an official competition at the Summer Olympic. In this study we tested whether a red uniform color affects Wushu Routine practitioners' ratings of athletes' position or movement of Wushu Routine. We also tested whether the effect varied depending on the gender of the athlete and the practitioner, and depending on whether female practitioners were in the ovulation phase of their menstrual cycle. Male (Experiment 1: N = 72) and female (Experiment 1: N = 72; Experiment 2: N = 52) participants who major in Wushu Routine were recruited to take a referee's perspective and rate the movement quality of male and female athletes wearing red or blue uniforms. The results of Experiment 1 showed that both male and female athletes wearing red uniform (compared to blue uniform) received higher ratings (p = .002, η2 = .066; p = .014, η2 = .043), and the red effect was especially strong when male practitioners rated female athletes (p = .002, η2 = .069). The results of Experiment 2, in an all-female sample, showed that in most cases there was no difference in ratings made by women in the ovulation and non-ovulation phases of their menstrual cycle, with the exception of their ratings of male athletes wearing red; in this condition, women gave higher ratings when they were in the ovulation phase of their cycle (p = .026). The results suggest that there is a red effect in an artistic sport like Wushu Routine, in which gender and the female menstrual cycle play an important role.
Assuntos
Julgamento , Artes Marciais , Humanos , Masculino , Feminino , Atletas , Ciclo Menstrual , OvulaçãoRESUMO
TiOxNy is a solid solution of cubic TiN and cubic TiO, with the ability to adjust its physical and chemical properties by modifying the O/N ratio, thus making it suitable for various applications. However, the synthesis of TiOxNy remains a significant challenge for inorganic chemists. In this work, we have successfully synthesized TiOxNy nanoparticles using the layered oxide Cs0.68Ti1.83O4 as the precursor and urea as the nitrogen source. The synthesis process was conducted within a temperature range of 800 to 1200 °C, leading to the transformation of the nitrided products from a two-dimensional layered precursor structure to a three-dimensional structure as the temperature increased. By varying the reaction temperature, the O/N ratio can be controlled. The experimental findings demonstrate that the nitrogen content in TiOxNy nanoparticles increases with rising temperature, ranging from TiO0.8N0.2 at 800 °C to TiO0.25N0.75 at 1200 °C. This work highlights the potential of the solid-state method in tailoring the properties of TiOxNy nanoparticles and presents a novel approach for synthesizing oxynitrides.
RESUMO
Color is not just about aesthetics but also communicates specific information and has important implications for psychological functioning. It has been shown that the color red enhances perceived attractiveness when evaluating the opposite sex, which we call the red-attractiveness effect. However, few studies have attached importance to the social context in which attractiveness ratings are made, which means that the red-attractiveness effect is rarely explained by analyzing the role of social context. We conducted two experiments to test the red-attractiveness effect in Chinese culture and the influence of context (affiliation or competitive) on the red-attractiveness effect. Experiment 1 (160 Chinese college students, 80 males) showed that the opposite-sex target in red, compared to white, was rated more attractive, and the red-attractiveness effect was applicable to Chinese culture. Experiment 2 (480 Chinese college students, 240 males) found that perceived attractiveness was strengthened in the affiliation context and weakened in the competitive context, that is, the main effect of context was significant. We did not find any significant effect of the color red in either context, that is, the color main effect was not significant. However, the results indicate that red can enhance perceived attractiveness when evaluating the opposite sex. This study demonstrates that the red attractiveness effect may exist in different cultural backgrounds and contexts.
Assuntos
Estética , Comportamento Sexual , Humanos , Masculino , Comportamento Sexual/psicologia , Estudantes/psicologia , População do Leste Asiático , Feminino , CorRESUMO
Layered oxynitrides are promising materials for visible light photocatalysis. However, the conventional method for the synthesis of oxynitrides using ammonia as a nitrogen source is dangerous. In this work, we successfully synthesized two layered tantalum oxynitrides, K1.35LaTa2O6.65N0.35 and K1.4Ca2Ta3O9.6N0.4, via a topochemical nitridation process using urea as a solid nitrogen source. Employing different characterization methods, we determined the structure and composition of layered oxynitrides. Furthermore, using Pt as a co-catalyst, these two layered oxynitrides showed excellent photocatalytic performances under visible light irradiation. In contrast to ammonia, urea process provides easy access for the synthesis of layered oxynitrides and sheds new light on the design of effective visible light-driven photocatalysts.
RESUMO
Root exudates are determined by plant species configuration and affect microbial community, which in turn affect purification efficiency of constructed wetlands (CWs). However, it is not well understood how plant configuration affects CW purification efficiency through specific root exudates. Herein, four mixed culture CWs were constructed; CW-G3 with Iris pseudacorus, Iris sibirica, Juncus effusus, and Hydrocotyle vulgaris showed the optimal diversity nutrients removal efficiency (TN: 94.2%, TP: 82.9%, COD: 74.7%). Highly increased antioxidant enzymes (peroxidase and catalase) reduced photosynthesis-negative enzyme (malondialdehyde) activity of plants in CW-G3, which ensured oxygen (O2) and organic carbon (OC) production and successfully released to rhizosphere by well-developed root aeration tissues. Further, CW-G3 enriched higher abundance of genus Saccharimonadales and Flavobacterium, which benefited nitrogen removal. Moreover, as OC, higher contents of maltose in CW-G3 (6.6 ~ 11.1-fold of that in other three CWs), as well as lauramide, choline, triethylamine and urocanic acid contributed to microbial denitrifying. Differently, higher contents of unsaturated fatty acids (linoleic acid and oleic acid) in other three CWs inhibited microbial nitrifying as inhibitors, which also proved by co-occurrent network. Thereby, plant configuration in CW-G3 provided higher O2 and OC contents for bacteria and reduced nitrifying inhibitors, which contributed to higher purifying efficiency. The study promoted the understanding about root exudates' effects on bacteria through plant configurations and improved the purification efficiency of CWs.
Assuntos
Gênero Iris , Eliminação de Resíduos Líquidos , Áreas Alagadas , Plantas , Bactérias , Nitrogênio , Exsudatos e TransudatosRESUMO
OBJECTIVE: Ankle fractures are often combined with syndesmotic instability, requiring reduction and stabilization. However, the optimal level for syndesmotic screw positioning remains unclear. This study aims to evaluate the effect of different syndesmotic screw insertion levels on postoperative clinical outcomes and determine whether an optimal level exists. METHODS: This retrospective study included data from 43 adult patients with acute closed ankle fractures combined with intraoperative evidence of unstable syndesmotic injuries who underwent open reduction internal fixation from January 1, 2017 to March 1, 2018 according to the inclusion and exclusion criteria. All 43 patients were divided into three groups based on the syndesmotic screw placement level: trans-syndesmotic group: screw level of 2-3 cm; inferior-syndesmotic group: screw level <2 cm; and supra-syndesmotic group: screw level >3 cm. Clinical outcomes were measured at the final follow-up, including the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, Olerud-Molander Ankle Score (OMAS), short-form 36-item questionnaire (SF-36), visual analogue scale (VAS) score and restrictions in ankle range of motion (ROM). The relationships between screw placement level and clinical outcomes were analyzed with the Kruskal-Wallis H-test and Spearman correlation analysis. RESULTS: The median follow-up duration was 15 months (range, 10-22 months). No patients developed fracture nonunion or malunion or experienced hardware failure. The outcome scoring systems showed an overall score for the entire group of 94.91 points for the AOFAS ankle-hindfoot score, 83.14 for the OMAS, 96.65 for the SF-36, 1.77 for the VAS, 9.14° for the restrictions in dorsiflexion, and 1.30° for the restrictions in plantarflexion. There were no significant differences among three groups in clinical outcomes (P > 0.05). Neither the AOFAS score nor OMAS had significant correlations with screw insertion level (P = 0.825 and P = 0.585, respectively). No postoperative arthritis or widening of the tibiofibular space was observed at the final follow-up. CONCLUSION: Different syndesmotic screw placement levels appear not to affect the clinical outcomes of ankle fractures with syndesmotic instability. No optimal level was observed in this study. Our findings suggest other clinically acceptable options apart from syndesmotic screw placement 2-3 cm above the ankle.
Assuntos
Fraturas do Tornozelo , Tornozelo , Adulto , Humanos , Fraturas do Tornozelo/cirurgia , Estudos Retrospectivos , Parafusos Ósseos , Fixação Interna de Fraturas , Resultado do Tratamento , Articulação do Tornozelo/cirurgiaRESUMO
Aquaculture plays an important role in contributing to global food security and nutrition; thus, the intensification and diversification of aquaculture are increasingly considered. However, paralleling the development of the industrial scale in aquaculture, the occurrence of diseases is always an important issue that causes great losses in economics. The finding of approaches that not only improve culture production but also reduce the impact of diseases in cultured animals is crucially essential. Previously, several studies have addressed the potential application of feed additives, such as prebiotics, probiotics, synbiotics, and microbial-derived metabolites (including short-chain fatty acids-SCFAs), in aquaculture. In this review, we provide an update focusing on the health benefits of dietary supplementation with a type of SCFAs, butyrate, and its producer, Clostridium butyricum, including their effects on growth, feed utilization, body composition, intestinal structure and function, antioxidant activity, immune response, and tolerance against stress and infection in aquatic animals. The outcomes of this study may indicate more benefits of the use of C. butyricum than that of butyrate (and its forms). This review provides general knowledge of the efficacy of butyrate and C. butyricum in aquaculture.
RESUMO
The butyrate-producing bacterium Clostridium butyricum has been proven to be important in improving the growth and health benefits of aquatic animals. In this study, C. butyricum G13 was isolated for the first time from the gut of the mud crab (Scylla paramamosain). The results of this study showed that C. butyricum G13 could produce a high concentration of butyric acid and grow well in a wide range of pHs (4 to 9) and NaCl (1 to 2.5%) and bile salt (0.2 to 1.0%) concentrations. In vitro characterization revealed that C. butyricum G13 is a Gram-positive and gamma-hemolytic bacterium sensitive to most antibiotics and shows hydrophobicity and the capacity to degrade starch. In vitro fermentation using mud crab gut contents showed that C. butyricum G13 alone or in combination with galactooligosaccharides (GOS) and/or resistant starch (RS) significantly increased butyric acid production and beneficially affected the abundance and diversity of intestinal microbiota. In addition, C. butyricum G13 can improve the survival rate of mud crabs and effectively maintain the normal structure of gut morphology after infection with Vibrio parahaemolyticus. In conclusion, C. butyricum G13 can be considered a potential probiotic that improves the immune capacity and confers health benefits on mud crabs. IMPORTANCE With the development of society, more and more aquatic animals are demanded. Intensification in the aquaculture scale is facing problems, such as disease outbreaks, eutrophication of water bodies, and misuse of antibiotics. Among these challenges, disease outbreak is the most important factor directly affecting aquaculture production. It is crucial to explore new approaches effective for the prevention and control of diseases. Probiotics have been widely used in aquaculture and have shown beneficial effects on the host. In this study, the butyrate-producing bacterium Clostridium butyricum G13 was isolated for the first time from the intestine of the mud crab through in vitro fermentation. The bacterium has probiotic properties and changes the gut microbiota to be beneficial to hosts in vitro as well as protecting hosts from Vibrio parahaemolyticus infection in vivo. The outcomes of this study indicate that C. butyricum G13 can be used as a potential probiotic in mud crab aquaculture.
Assuntos
Braquiúros , Clostridium butyricum , Probióticos , Animais , Braquiúros/metabolismo , Braquiúros/microbiologia , Ácido Butírico , Bactérias , Antibacterianos/farmacologia , Antibacterianos/metabolismo , IntestinosRESUMO
Patients with rhegmatogenous retinal detachment (RRD) require face-down positioning (FDP) for 3-6 months or longer after pars plana vitrectomy (PPV) combined with silicone oil (SO) tamponade. This paper aimed to identify the factors that influenced FDP compliance. This study adopted semi-structured interviews with patients who require FDP after SO tamponade. Constructivist grounded theory was utilized in this study. The qualitative data was analyzed and coded via NVivo 11.0 through open coding, axial coding and selective coding. Twenty-four RRD patients were involved. The interviews yielded five main themes that defined home FDP compliance were identified: posture discomfort, doctor-patient communication, psychological factors, occupational character, and family factors. A theoretical model of the influencing factors of postural compliance of FDP was constructed based on the interview analysis. A variety of factors can affect FDP conformity. We can increase compliance of RRD patients by enhancing comfort, encouraging doctor-patient communication, providing comprehensive care, promoting community-based intervention, and strengthening family education.
Assuntos
Descolamento Retiniano , Humanos , Descolamento Retiniano/cirurgia , Teoria Fundamentada , Acuidade Visual , Vitrectomia , Cooperação do PacienteRESUMO
Understanding the molecular mechanism of clear cell renal cell carcinoma (ccRCC) is essential for predicting the prognosis and developing new targeted therapies. Our study is to identify hub genes related to ccRCC and to further analyze its prognostic significance. The ccRCC gene expression profiles of GSE46699 from the Gene Expression Omnibus (GEO) database and datasets from the Cancer Genome Atlas Database The Cancer Genome Atlas were used for the Weighted Gene Co-expression Network Analysis (WGCNA) and differential gene expression analysis. We screened out 397 overlapping genes from the four sets of results, and then performed Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genome (KEGG) pathways. In addition, the protein-protein interaction (PPI) network of 397 overlapping genes was mapped using the STRING database. We identified ten hub genes (KNG1, TIMP1, ALB, C3, GPC3, VCAN, P4HB, CHGB, LGALS1, EGF) using the CytoHubba plugin of Cytoscape based on the Maximal Clique Centrality (MCC) score. According to Kaplan-Meier survival analysis, higher expression of LGALS1 and TIMP1 was related to poorer overall survival (OS) in patients with ccRCC. Univariate and multivariate Cox proportional hazard analysis showed that the expression of LGALS1 was an independent risk factor for poor prognosis. Moreover, the higher the clinical grade and stage of ccRCC, the higher the expression of LGALS1. LGALS1 may play an important role in developing ccRCC and may be potential a biomarker for prognosis and treatment targets.
RESUMO
PURPOSE: Bladder cancer is one of the most common malignancies of the urinary system, and its screening relies heavily on invasive cystoscopy, which increases the risk of urethral injury and infection. This study aims to use non-targeted metabolomics methods to screen for metabolites that are significantly different between the urine of bladder cancer patients and cancer-free controls. METHODS: In this study, liquid chromatography-mass spectrometry was used to analyze the urine of bladder cancer patients (n = 57) and the cancer-free controls (n = 38) by non-targeted metabolomic analysis and metabolite identification. RESULTS: The results showed that there were significant differences in the expression of 27 metabolites between bladder cancer patients and the cancer-free controls. CONCLUSION: In the multivariate statistical analysis of this study, the urinary metabolic profile data of bladder cancer patients were analyzed, and the receiver operating characteristic curve analysis showed that it is possible to perform non-invasive clinical diagnoses of bladder cancer through these candidate biomarkers.
Assuntos
Biomarcadores Tumorais/urina , Metaboloma , Neoplasias da Bexiga Urinária/urina , Biomarcadores Tumorais/metabolismo , Detecção Precoce de Câncer , Humanos , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/metabolismoRESUMO
The development of high-efficient and cost-effective electrocatalysts is crucial to remove nitrate pollutant in wastewater. Herein, we design and prepare mesoporous Co-doped Cu2(OH)2CO3 malachite nanosheets as an electrocatalyst toward highly efficient nitrate reduction using a facile CO2 bubble-assisted coprecipitation synthesis. The electrocatalytic performance is subject to the Co/Cu ratio of this malachite. Remarkably, compared with the pristine monometal Cu or Co-based electrocatalyst, the optimal electrocatalyst, 0.3Co@Cu2(OH)2CO3, displays fast and highly efficient removal capacity of nitrate with an impressive high total nitrogen (TN) removal of 8628.99 mg N g-1CoCu (398.79 mg N gcat-1 h-1), N2 selectivity of 97.11% as well as negligible nitrite product at 100 mg L-1 NO3--N and 2000 mg L-1 Cl- neutral electrolyte. Above all, high total nitrogen removal efficiency (81.92%) and chemical oxygen demand (73.74%) in actual wastewater. Its excellent electrocatalytic performance is achieved by regulating the electronic structure and the adsorption/desorption of the intermediate. This study discovers a new type of electrode materials for nitrate removal in wastewater.
RESUMO
Background: Traditional clinicopathological features (TNM, pathology grade) are often insufficient in predictive prognosis accuracy of clear cell renal cell carcinoma (ccRCC). The IL6-JAK-STAT3 pathway is aberrantly hyperactivated in many cancer types, and such hyperactivation is generally associated with a poor clinical prognosis implying that it can be used as a promising prognosis indicator. The relation between the IL6-JAK-STAT3 pathway and ccRCC remains unknown. Methods: We evaluated the levels of various cancer hallmarks and filtered out the promising risk hallmarks in ccRCC. Subsequently, a prognosis model based on these hallmark-related genes was established via weighted correlation network analysis and Cox regression analysis. Besides, we constructed a nomogram based on the previous model with traditional clinicopathological features to improve the predictive power and accuracy. Results: The IL6-JAK-STAT3 pathway was identified as the promising risk hallmarks in ccRCC, and the pathway-related prognosis model based on five genes was built. Also, the nomogram we developed demonstrated the strongest and most stable survival predictive ability. Conclusion: Our study would provide new insights for guiding individualized treatment of ccRCC patients.
RESUMO
The genus Flavivirus contains many important pathogens, including dengue virus (DENV), Zika virus (ZIKV), and Japanese encephalitis virus (JEV). AR-12 is a celecoxib-derived anticancer agent that possesses antiviral activity against a broad range of viruses. We pharmacologically exploited this unique activity to develop additional antiviral agents, resulting in the production of the AR-12 derivatives P12-23 and P12-34. At nanomolar concentrations, these compounds were effective in suppressing DENV, ZIKV and JEV replication, exhibiting 10-fold improvements in the efficacy and selectivity indices as compared to AR-12. Regarding the mode of antiviral action, P12-23 and P12-34 inhibited viral RNA replication but had no effect on viral binding, entry or translation. Moreover, these AR-12 derivatives co-localized with mitochondrial markers, and their antiviral activity was lost in mitochondria-depleted cells. Interestingly, exogenous uridine or orotate, the latter being a metabolite of the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH), abolished the antiviral activity of AR-12 and its derivatives. As DHODH is a key enzyme in the de novo pyrimidine biosynthesis pathway, these AR-12 derivatives may act by targeting pyrimidine biosynthesis in host cells to inhibit viral replication. Importantly, treatment with P12-34 significantly improved the survival of mice that were subcutaneously challenged with DENV. Thus, P12-34 may warrant further evaluation as a therapeutic to control flaviviral outbreaks.