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Aim: The aim of the present study was to identify and characterize the functions of key microbes mediating nitrification.Methodology: After sampling the biofilm from a submerged biofilter in a marine aquaculture system, selective media were used to isolate microbial strains involved in nitrification. Isolates were identified using physiological and biochemical assays and sequencing of 16S rRNA gene. Nitrogen removal under different conditions was characterized. Nitrogen removal pathway was characterized by a 15N tracer experiment. Representation of key microbes in the biolfim was characterized by metagenomics analysis. Results: Single-factor tests showed that Halomonas sp. strain Z8 exhibited good heterotrophic nitrification and aerobic denitrification abilities, with maximum NH4+-N, NO2--N and No3--N removal rates of 2.37, 1.28 and 1.7 mg N l-1 hr-1, respectively. The 15N isotope tracer experiment confirmed the aerobic nitrogen removal pathway of strain Z8. Average NO3-removal efficiencies were all above 80% in an aerated moving bed bioreactor inoculated with strain Z8 and employed to treat synthetic marine aquaculture wastewater. Metagenomic microbial community analysis revealed that Halomonas sp. Z8 was one of the dominant taxa at genus level, suggesting a vital role in removing nitrate from bioreactor
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Background: As an immune checkpoint, upregulation of B and T lymphocyte attenuator (BTLA) contributes to T-cell exhaustion in chronic infection. However, the characteristics of BTLA on T cells of patients with pulmonary tuberculosis (PTB) are still uncovered. Aims: The aim of the study was to elucidate the dynamics and clinical significance of BTLA expression on circulating CD4+ and CD8+ T cells of PTB patients. Materials and Methods: BTLA expression on T cells from PTB patients with smear positivity (n = 86) and healthy controls (HCs) (n = 40) were determined using flow cytometry. Results: The levels of BTLA expression on circulating CD4+ and CD8+ T cells of PTB patients with smear positivity were both upregulated, compared with HC. At the same time, the levels of BTLA expression on CD4+ and CD8+ T cells of patients with retreatment were both higher than that of those with initial treatment and gradually upregulated along with the increase of the bacillary load in sputum. In addition, the patients with lung cavity were discovered to present higher levels of BTLA expression on CD4+ and CD8+ T cells than those without lung cavity. Whereas we noted that there was no correlation between the levels of BTLA expression and the positivity or negativity of anti-Mycobacterium tuberculosis antibody. Conclusions: The levels of BTLA expression were upregulated on CD4+ and CD8+ T cells of PTB patients and associated with disease progression. Thereby, BTLA expression on T cells may be considered as a potential clinical indicator and utilized as a therapeutic target for PTB.
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Cardiac remodeling involves changes in heart shape, size, structure, and function after injury to the myocardium. The proinflammatory adaptor protein myeloid differentiation protein 88 (MyD88) contributes to cardiac remodeling. To investigate whether excessive MyD88 levels initiate spontaneous cardiac remodeling at the whole-organism level, we generated a transgenic MyD88 mouse model with a cardiac-specific promoter. MyD88 mice (male, 20-30 g, n=∼80) were born at the expected Mendelian ratio and demonstrated similar morphology of the heart and cardiomyocytes with that of wild-type controls. Although heart weight was unaffected, cardiac contractility of MyD88 hearts was mildly reduced, as shown by echocardiographic examination, compared with wild-type controls. Moreover, the cardiac dysfunction phenotype was associated with elevation of ANF and BNP expression. Collectively, our data provide novel evidence of the critical role of balanced MyD88 signaling in maintaining physiological function in the adult heart.
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Animales , Masculino , Conejos , Remodelación Ventricular/fisiología , Factor 88 de Diferenciación Mieloide/metabolismo , Cardiopatías/fisiopatología , Tamaño de los Órganos , Ratones Transgénicos , Ecocardiografía , Western Blotting , Factor Natriurético Atrial/metabolismo , Péptido Natriurético Encefálico/metabolismo , Factor 88 de Diferenciación Mieloide/genética , Puntuaciones en la Disfunción de Órganos , Cardiopatías/metabolismo , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/patología , Contracción Miocárdica/fisiología , Miocardio/patologíaRESUMEN
BACKGROUND: Oxaliplatin based chemotherapy regimen was one of the most used chemotherapy modality for metastatic colorectal cancer. The purpose of this meta‑analysis was to assess the clinical activity and toxicities of cetuximab plus oxaliplatin‑based chemotherapy regimen for metastatic colorectal Cancer. METHODS: We searched the clinical studies about the cetuximab plus oxaliplatin‑based chemotherapy regimen versus oxaliplatin‑based chemotherapy alone for metastatic colorectal cancer in the databases of PubMed, EMBASE, Cochran, and CNKI. The data of response and toxicities were extracted and pooled by random or fixed effects model. And publication bias was evaluated by begg’s funnel plot and egger’s regression test. RESULTS: Seven papers were included in this study. Adding cetuximab to oxaliplatin‑based chemotherapy regime can significant increase response rate in K‑RAS mutation metastatic colorectal patients (odds ratio [OR]: 1.45, 95% confidence interval [CI]: 1.17–1.80, Z = 3.38, P = 0.001) and metastatic colorectal patients without knowing the K‑RAS status (OR: 1.36, 95% CI: 1.11–1.65, Z = 1.89, P = 0.003). But for patients with mutated K‑RAS, the improvement for objective response rate was not statistical significant (OR: 0.70, 95% CI: 0.49–1.01, Z = 3.00, P = 0.058) when adding cetuximab to oxaliplatin‑based chemotherapy regime. The pooled results indicating the rash and diarrhea risk was significantly increased in the combined treatment group (P < 0.05). The toxicity of peripheral neuritis was decreased by adding the cetuximab (P < 0.05). And other toxicities were not statistical different between the two groups (P > 0.05). Significant publication bias was found in toxicities evaluation. CONCLUSION: Cetuximab plus oxaliplatin‑based chemotherapy regimen significant increase the response rate for metastatic colorectal cancer. But the some toxicities such rash and diarrhea risk was also increased.
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Siva-1 induces apoptosis in multiple pathological processes and plays an important role in the suppression of tumor metastasis, protein degradation, and other functions. Although many studies have demonstrated that Siva-1 functions in the cytoplasm, a few have found that Siva-1 can relocate to the nucleus. In this study, we found that the first 33 amino acid residues of Siva-1 are required for its nuclear localization. Further study demonstrated that the green fluorescent protein can be imported into the nucleus after fusion with these 33 amino acid residues. Other Siva-1 regions and domains showed less effect on Siva-1 nuclear localization. By site-mutagenesis of all of these 33 amino acid residues, we found that mutants of the first 1-18 amino acids affected Siva-1 nuclear compartmentalization but could not complete this localization independently. In summary, we demonstrated that the N-terminal 33 amino acid residues were sufficient for Siva-1 nuclear localization, but the mechanism of this translocation needs additional investigation.
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The surveillance of sensitivity of P. falciparum to pyronaridine/sulfadoxine/pyrimethamine has been carried out in Diaoluo area in Hainan Province where chloroquine-resistant falciparum malaria is endemic, covering an area of 406 square kilometers, with a population of 3745 in 1986. From 1986 all outpatients diagnosed as falciparum malaria were administered with PND/S/P as the only antimalarial. In vivo sensitivity of P. falciparum was measured in some patients who were treated in hospital. It was demonstrated that P. falciparum in the Diaoluo area has retained its sensitivity to a single oral dose of PND/S/P of 500/1,000/50 mg with 100% cure rate for at least 5 years.
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Adolescente , Adulto , Anciano , Animales , Antimaláricos/farmacología , Niño , China , Combinación de Medicamentos , Resistencia a Medicamentos , Quimioterapia Combinada , Humanos , Malaria/tratamiento farmacológico , Persona de Mediana Edad , Naftiridinas/farmacología , Plasmodium falciparum/efectos de los fármacos , Pirimetamina/farmacología , Sulfadoxina/farmacologíaRESUMEN
The triple combination of pyronaridine, sulfadoxine and pyrimethamine which has been proven to be efficient in delaying emergence of drug resistance of rodent malarial parasites was further studied for potential application to malaria control. The antimalarial effect of the triple combination on Plasmodium berghei ANKA-infected mice and the toxic effects in mice and rats were additive. A single dose of pyronaridine 500 mg in combination with sulfadoxine, 1000 or 1500 mg, and pyrimethamine, 50 or 75 mg, given to 72 acute falciparum malaria patients resulted in a 100% cure rate with nil or mild side effects, and no recrudescence of asexual parasite over 4-week follow-up. Preliminary experiments on the drug effect on sporogony showed that the drug combination at the dose used could not completely interrupt the sporozoite formation although many retarded oocysts were found.