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Background: Capsule of alkaloids from leaf of Alstonia scholaris (CALAS) is a new investigational botanical drug (No. 2011L01436) for respiratory disease. Clinical population pharmacokinetics (PK), metabolomics and therapeutic data are essential to guide dosing in patients. Previous research has demonstrated the potential therapeutic effect of CALAS on acute bronchitis. Further clinical trial data are needed to verify its clinical efficacy, pharmacokinetics behavior, and influence of dosage and other factors.Purpose: To verify the clinical efficacy and explore the potential biomarkers related to CALAS treatment for acute bronchitis.Materials and Methods: Oral CALAS was assessed in a randomized, double-blind, placebo-controlled trial. Fifty-five eligible patients were randomly assigned to four cohorts to receive 20, 40 or 80 mg, of CALAS three times daily for seven days, or placebo. Each CALAS cohort included 15 subjects, and the placebo group included 10 subjects. A population PK model of CALAS was developed using plasma with four major alkaloid components. Metabolomics analysis was performed to identify biomarkers correlated with the therapeutic effect of CALAS, and efficacy and safety were assessed based on clinical symptoms and adverse events.Results: The symptoms of acute bronchitis were alleviated by CALAS treatment without serious adverse events or clinically significant changes in vital signs, electrocardiography or upper abdominal Doppler ultrasonography. Moreover, one compartment model with first-order absorption showed that an increase in aspartate transaminase will reduce the clearance (CL) of scholaricine, and picrinine CL was inversely proportional to body mass index, while 19-epischolaricine and vallesamine CL increased with aging. The serum samples from acute bronchitis patients at different time points were analyzed using UPLC-QTOF in combination with the orthogonal projection to latent structures-discriminant analysis, which indicated higher levels of lysophosphatidylcholines, lysophosphatidylethanolamines and amino acids with CALAS treatment than with placebo.Conclusion: This is the first study to evaluate the clinical efficacy and explored the potential biomarkers related to CALAS therapeutic mechanism of acute bronchitis by means of clinical trial combined the metabolomics study. This exploratory study provides a basis for further research on clinical efficacy and optimal dosing regimens based on pharmacokinetics behavior. Additional acute bronchitis patients and CALAS PK samples collected in future studies may be used to improve model performance and maximize its clinical value. [ABSTRACT FROM AUTHOR]

Highlights • Metagenomic approach revealed the effects of antibiotics on anaerobic digestion. • Antibiotics impacted archaeal community and genes encoding fatty acid degradation. • All methanogenesis pathways were influenced by antibiotics pressure. • Antibiotics increased the antimicrobial resistant risks of digested sludge. • Positive association among antibiotics, ARG and specific microbe were found. Abstract Continuous stirred-tank digesters with tetracyclines and sulfonamides were operated to investigate the impacts of antibiotic pressure on sludge anaerobic digestion. The versatile methanogen Methanosarcinales and strictly hydrogenotrophic methanogen Methanobacteriales increased and decreased by 21.1% and 10.9% under antibiotic pressure, respectively. KEGG analysis revealed that hydrogenotrophic and acetoclastic methanogenesis pathways were all affected. The decrease in abundance of function genes involved in lipid metabolism, carbohydrate metabolism, and fatty acid degradation, would lead to a reduction in methane production by 25%. Network analysis indicated positive associations among tetracycline residuals, abundance of resistance genes (ARGs), and specific member of potential hosts. Over 1000 ARG subtypes were widely detected in sludge, including macrolide (28%), tetracycline (24%), fluoroquinolone (20%), and peptide (20%) resistance genes. AD process exposed to long-term antibiotic would increase the diversity and abundance of ARG, enhance the association of ARG with specific microbes, and select bacteria able to perform chemotaxis mechanism. [ABSTRACT FROM AUTHOR]

Understanding of how anaerobic digestion (AD)-related microbiomes are constructed by operational parameters or their interactions within the biochemical process is limited. Using high-throughput sequencing and molecular ecological network analysis, this study shows the succession of AD-related microbiome hosting diverse members of the phylum Actinobacteria , Bacteroidetes , Euryarchaeota , and Firmicutes , which were affected by organic loading rate (OLR) and hydraulic retention time (HRT). OLR formed finer microbial network modules than HRT (12 vs . 6), suggesting the further subdivision of functional components. Biomarkers were also identified in OLR or HRT groups (e.g. the family Actinomycetaceae , Methanosaetaceae and Aminiphilaceae ). The most pair-wise link between Firmicutes and biogas production indicates the keystone members based on network features can be considered as markers in the regulation of AD. A set of 40% species (“core microbiome”) were similar across different digesters. Such noteworthy overlap of microbiomes indicates they are generalists in maintaining the ecological stability of digesters. [ABSTRACT FROM AUTHOR]

Spread of antibiotic resistance genes (ARGs) originating from sewage sludge is highlighted as an eminent health threat. This study established a thermophilic anaerobic digester using one-step startup strategy to quickly remove tetracycline and sulfonamides resistance genes from sewage sludge. At least 20 days were saved in the startup period from mesophilic to thermophilic condition. Based on the results of 16S rDNA amplicons sequencing and predicted metagenomic method, the successful startup largely relied on the fast colonization of core thermophilic microbial population (e.g. Firmicutes , Proteobacteria , Actinobacteria ). Microbial metabolic gene pathways for substrate degradation and methane production was also increased by one-step mode. In addition, real-time quantitative PCR approach revealed that most targeted tetracycline and sulfonamides resistance genes ARGs ( sul I, tet A, tet O, tet X) were substantially removed during thermophilic digestion (removal efficiency > 80%). Network analysis showed that the elimination of ARGs was attributed to the decline of their horizontal ( int I1 item) and vertical (potential hosts) transfer-related elements under high-temperature. This research demonstrated that rapid startup thermophilic anaerobic digestion of wastewater solids would be a suitable technology for reducing quantities of various ARGs. [ABSTRACT FROM AUTHOR]

Abstract: Actinomycetes degrade cellulose and solubilize lignin during composting. Changes in the diversity of the actinomycetal communities and the 16S rDNA copy numbers of actinomycetes were monitored by denaturing gradient gel electrophoresis (DGGE) and quantitative PCR (qPCR), respectively, during continuous thermophilic composting (CTC) and traditional composting (TC). qPCR indicated that the copy numbers from the CTC samples were 25–80% higher than those from the TC samples during similar phases of active composting and they were lower than 3×109 gene copies/g (dry weight) in the mature compost from both runs. DGGE showed a more diverse actinomycetal community in the CTC than in TC, averaging 16 bands as compared to 12 bands, at the post peak temperature phase. The study suggested that temperatures higher than 50°C in CTC benefited the growth of actinomycetes. [ABSTRACT FROM AUTHOR]

Abstract: Fewer and fewer municipal solid wastes are treated by composting in China because of the disadvantages of enormous investment, long processing cycle and unstable products in a conventional composting treatment. In this study, a continuous thermophilic composting (CTC) method, only a thermophilic phase within the process, has been applied to four bench-scale composting runs, and further compared with a conventional composting run by assessing the indexes of pH, total organic carbon (TOC), total Kjeldahl nitrogen (TKN), C/N ratio, germination index (GI), specific oxygen uptake rate (SOUR), dissolved organic carbon (DOC) and dehydrogenase activity. After composting for 14days, 16days, 18days and 19days in the four CTC runs, respectively, mature compost products were obtained, with quality similar to or better than which had been stabilized for 28days in run A. The products from the CTC runs also showed favorable stability in room temperature environment after the short-term composting at high temperature. The study suggested CTC as a novel method for rapid degradation and maturation of organic municipal solid wastes. [Copyright &y& Elsevier]