[UPLC-Q-TOF-MS-based metabolomics reveals mechanism of Morinda officinalis iridoid glycosides in treating rheumatoid arthritis and bone loss].

This study aimed to investigate the therapeutic effects of Morinda officinalis iridoid glycosides(MOIG) on paw edema and bone loss of rheumatoid arthritis(RA) rats, and analyze its potential mechanism based on ultra-high performance liguid chromatography-guadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS) serum metabolomics. RA rats were established by injecting bovin type Ⅱ collagen. The collagen-induced arthritis(CIA) rats were administered drug by gavage for 8 weeks, the arthritic score were used to evaluate the severity of paw edem, serum bone metabolism biochemical parameters were measured by ELISA kits, Masson staining was used to observe the bone microstructure of the femur in CIA rats. UPLC-Q-TOF-MS was used to analyze the alteration of serum metabolite of CIA rats, principal component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA) were used to screen the potential biomarkers, KEGG database analysis were used to construct related metabolic pathways. The results demonstrated that the arthritic score, serum levels of IL-6 and parameters related with bone metabolism including OCN, CTX-Ⅰ, DPD and TRAP were significantly increased, and the ratio of OPG and RANKL was significantly decreased, the microstructure of bone tissue and cartilage were destructed in CIA rats, while MOIG treatments could significantly reduce arthritis score, mitigate the paw edema, reverse the changes of serum biochemical indicators related with bone metabolism, and improve the microstructure of bone tissue and cartilage of CIA rats. The non-targeted metabolomics results showed that 24 altered metabolites were identified in serum of CIA rats; compared with normal group, 13 significantly altered metabolites related to RA were identified in serum of CIA rats, mainly involving alanine, aspartate and glutamate metabolism; compared with CIA model group, MOIG treatment reversed the alteration of 15 differential metabolites, mainly involving into alanine, aspartate and glutamate metabolism, D-glutamine and D-glutamate metabolism, taurine and hypotaurine metabolism, valine, leucine and isoleucine biosynthesis. Therefore, MOIG significantly alleviated paw edema, improved the destruction of microstructure of bone and cartilage in CIA rats maybe through involving into the regulation of amino acid metabolism.

The role of gut microbiota in intestinal disease: from an oxidative stress perspective.

Recent studies have indicated that gut microbiota-mediated oxidative stress is significantly associated with intestinal diseases such as colorectal cancer, ulcerative colitis, and Crohn's disease. The level of reactive oxygen species (ROS) has been reported to increase when the gut microbiota is dysregulated, especially when several gut bacterial metabolites are present. Although healthy gut microbiota plays a vital role in defending against excessive oxidative stress, intestinal disease is significantly influenced by excessive ROS, and this process is controlled by gut microbiota-mediated immunological responses, DNA damage, and intestinal inflammation. In this review, we discuss the relationship between gut microbiota and intestinal disease from an oxidative stress perspective. In addition, we also provide a summary of the most recent therapeutic approaches for preventing or treating intestinal diseases by modifying gut microbiota.

Effects of grafting on chemical constituents, toxicological properties, antithrombotic activity, and myocardial infarction protection of styrax secreted from the trunk of Liquidambar orientalis Mill.

Styrax, the balsam refined from the trunk of Liquidambar orientalis Mill. has a variety of applications in the perfumery and medical industry, especially for use in traditional Chinese medicine. However, the resources of styrax are in shortage due to being endangered of this plant. Grafting can improve the adaptability of plants to unfavorable environmental conditions. We tried to graft the L. orientalis Mill. on L. formosana Hance which was widely distributed in Jiangsu and Zhejiang provinces of China in an attempt to obtain styrax from grafted L. orientalis Mill. (grafted styrax, SG). Whether SG can become an alternative application of commercially available styrax (SC) need be further investigated. The components of SG were analyzed by GC-MS, and the results showed that the chromatograms of SG, SC, and styrax standard (SS) were consistent. The ration of 12 major chemical components based peak area in SG, SC, and SS were 93.95%, 94.24%, and 95.86% respectively. The assessment of toxicity, antithrombotic activity, and myocardial infarction protection of SG and SC was evaluated by using the zebrafish model, the results showed that SG and SC have the similar toxicological properties as evidenced by acute toxicity test, developmental toxicity and teratogenicity, and long-term toxicity test. Both SG and SC significantly decreased the thrombosis and increased blood flow velocity of zebrafish induced by adrenaline hydrochloride, inhibited myocardial apoptosis, myocardial infarction and myocardial inflammation in zebrafish induced by isoproterenol hydrochloride. Moreover, SG had an obvious improvement effect on cardiac output, while SC has no effect. Collectively, SG is similar to SC in chemical composition, toxicological properties, antithrombotic activity, and myocardial infarction protection effects, and may be used as a substitute for styrax to reduce the collection for wild L. orientalis Mill. and increase the available styrax resources.

Application of tissue engineering techniques in tracheal repair: a bibliometric study.

Transplantation of tissue-engineered trachea is an effective treatment for long-segment tracheal injury. This technology avoids problems associated with a lack of donor resources and immune rejection, generating an artificial trachea with good biocompatibility. To our knowledge, a systematic summary of basic and clinical research on tissue-engineered trachea in the last 20 years has not been conducted. Here, we analyzed the development trends of tissue-engineered trachea research by bibliometric means and outlined the future perspectives in this field. The Web of Science portal was selected as the data source. CiteSpace, VOSviewer, and the Bibliometric Online Analysis Platform were used to analyze the number of publications, journals, countries, institutions, authors, and keywords from 475 screened studies. Between 2000 and 2023, the number of published studies on tissue-engineered trachea has been increasing. Biomaterials published the largest number of papers. The United States and China have made the largest contributions to this field. University College London published the highest number of studies, and the most productive researcher was an Italian scholar, Paolo Macchiarini. However, close collaborations between various researchers and institutions from different countries were generally lacking. Despite this, keyword analysis showed that manufacturing methods for tracheal stents, hydrogel materials, and 3D bioprinting technology are current popular research topics. Our bibliometric study will help scientists in this field gain an in-depth understanding of the current research progress and development trends to guide their future work, and researchers in related fields will benefit from the introduction to transplantation methods of tissue-engineered trachea.

We conducted a comprehensive bibliometric analysis of tissue-engineered trachea.We systematically outlined the preparation methods and current development forms of tissue-engineered trachea.We predicted future tissue-engineered trachea research trends from the perspectives of countries, institutions, researchers, and popular research topics.

Phylogeography of cultivated and wild ophiopogon japonicus based on chloroplast DNA: exploration of the origin and sustainable cultivation.

BACKGROUND: Ophiopogon japonicus, mainly planted in Sichuan (CMD) and Zhejiang (ZMD) province in China, has a lengthy cultivation history. During the long period of domestication, the genetic diversity of cultivated O. japonicus has substantially declined, which will affect the population continuity and evolutionary potential of this species. Therefore, it is necessary to clarify the phylogeography of cultivated O. japonicus to establish a theoretical basis for the utilization and conservation of the genetic resources of O. japonicus. RESULT: The genetic diversity and population structure of 266 O. japonicus individual plants from 23 sampling sites were analyzed based on 4 chloroplast DNA sequences (atpB-rbcL, rpl16, psbA-trnH and rpl20-5'rps12) to identify the effects of domestication on genetic diversity of cultivars and determine their geographic origins. The results showed that cultivated O. japonicus and wild O. japonicus had 4 and 15 haplotypes respectively. The genetic diversity of two cultivars (Hd = 0.35700, π = 0.06667) was much lower than that of the wild populations (Hd = 0.76200, π = 0.20378), and the level of genetic diversity in CMD (Hd = 0.01900, π = 0.00125) was lower than that in ZMD (Hd = 0.06900, π = 0.01096). There was significant difference in genetic differentiation between the cultivated and the wild (FST = 0.82044), especially between the two cultivars (FST = 0.98254). This species showed a pronounced phylogeographical structure (NST > GST, P < 0.05). The phylogenetic tree showed that the genetic difference between CMD and ZMD was not enough to distinguish the cultivars between the two producing areas by using O. amblyphyllus Wang et Dai as an outgroup. In addition, both CMD and ZMD have a closer relationship with wild populations in Sichuan than that in Zhejiang. The results of the TCS network and species distribution model suggested that the wild population TQ located in Sichuan province could serve as the ancestor of cultivated O. japonicus, which was supported by RASP analysis. CONCLUSION: These results suggest that cultivated O. japonicus has experienced dramatic loss of genetic diversity under anthropogenic influence. The genetic differentiation between CMD and ZMD is likely to be influenced by founder effect and strong artificial selection for plant traits. It appears that wild populations in Sichuan area are involved in the origin of not only CMD but also ZMD. In addition, we also raise some suggestions for planning scientific strategies for resource conservation of O. japonicus based on its genetic diversity and population structure.

Highly Effective Removal of Ofloxacin from Water with Copper-Doped ZIF-8.

Residual antibiotics in wastewater have gained widespread attention because of their toxicity to humans and the environment. In this work, Cu-doped ZIF-8s (Cu-ZIF-8s) were successfully synthesized by the impregnation of Cu2+ in ZIF-8 and applied in the removal of ofloxacin (OFX) from water. Remarkably, excellent adsorption performance was obtained in Cu-ZIF-8s, especially for Cu-ZIF-8-1, in which the adsorption capacity (599.96 mg·g-1) was 4.2 times higher than that of ZIF-8 and superior to various adsorbents reported previously. The adsorption kinetics and adsorption isotherm follow the pseudo-second-order model and the Langmuir model, respectively. Furthermore, the removal efficiencies of OFX in Cu-ZIF-8-1 reached over 90% at low concentrations. It was revealed that electrostatic interaction and complexation play important roles in the adsorption process. In addition, the material can be regenerated by simple methods. Therefore, the obtained Cu-doped MOFs may have a promising application in the treatment of antibiotic-containing wastewater.

Development of a multivariable clinical prediction model for liposomal doxorubicin-induced cardiotoxicity in adult breast cancer patients: a retrospective multicenter study.

Background: The clinical use of anthracyclines is limited by the risk of cardiotoxicity. So, we aim to develop a clinical prediction model for liposomal doxorubicin-induced cardiotoxicity in adult breast cancer patients. Methods: We designed a multicenter retrospective cohort study. A total of 257 hospitalized breast cancer patients treated with doxorubicin liposomes were finally enrolled in the study, including 58 patients from Beijing Friendship Hospital and 199 from Beijing Cancer Hospital. In all, 32 cases developed cardiotoxicity, including 4 at the Beijing Friendship Hospital and 28 at the Beijing Cancer Hospital. The study involved breast cancer patients with no pre-existing heart disease, whose clinical data were collected from their medical records. All patients underwent electrocardiogram (ECG) and/or left ventricular ejection fraction (LVEF) measurements prior to treatment with doxorubicin liposomes. Patients were clinically assessed after each cycle of treatment, and ECG and/or LVEF measurements were performed at least once after treatment. Liposomal doxorubicin-induced cardiotoxicity was defined when one of the following three conditions was met: (I) a reduction in LVEF of at least 5% from the baseline and the absolute value was less than 55%, accompanied by congestive heart failure (CHF) symptoms or signs; (II) a reduction in LVEF of at least 10% to an absolute value of less than 55%, without CHF symptoms or signs; (III) the definite diagnosis of CHF. Variables associated with cardiotoxicity were identified by univariate and multivariate logistic regression, and the consistency and differentiation of the final model were evaluated. Results: In our final model, age [odds ratio (OR): 5.626, 95% confidence interval (CI): 2.321 to 13.639], cancer metastasis (OR: 3.873, 95% CI: 1.220 to 12.299), paclitaxel (OR: 3.601, 95% CI: 1.010 to 12.843), and hypertension (OR: 2.435, 95% CI: 1.046 to 5.671) were significantly associated with cardiotoxicity. The final model was tested for Hosmer-Lemeshow goodness-of-fit, the χ2 was 2.696 and the P value was 0.747, and the resultant predictive model had an area under the receiver operating characteristic (ROC; AUC) curve of 0.781. Conclusions: This study established a risk prediction model for liposomal doxorubicin-induced cardiotoxicity in breast cancer patients and performed a stratified risk scores.

Population pharmacokinetics of methotrexate in paediatric patients with acute lymphoblastic leukaemia and malignant lymphoma.

This study aimed to identify physiological and pharmacogenomic covariates and develop a population pharmacokinetic model of high-dose methotrexate (HD-MTX) in Chinese paediatric patients with acute lymphoblastic leukaemia (ALL) and malignant lymphoma.A total of 731 MTX courses and 1658 MTX plasm concentrations from 205 paediatric patients with ALL and malignant lymphoma were analysing using a non-linear mixed-effects model technique. 47 SNPs in 16 MTX-related genes were genotyped and screened as covariates. A PPK model was established to determine the influence of covariates, such as body surface area (BSA), age, laboratory test value, and SNPs on the pharmacokinetic process of HD-MTX.Two-compartmental model with allometric scaling using BSA could nicely characterise the in vivo behaviour of HD-MTX. After accounting for body size, rs17004785 and rs4148416 were the covariates that influence MTX clearance (CL). The PPK model obtained was: CL = 9.33 * (BSA/1.73)0.75 * e0.13*rs17004785 * e0.39*rs4148416 * eηCL, Vc = 24.98 * (BSA/1.73) * eηvc, Q = 0.18 * (BSA/1.73)0.75 * eηQ and Vp = 4.70 * (BSA/1.73) * eηvp.The established model combined with the Bayesian approach could estimate individual pharmacokinetic parameters and optimise personalised HD-MTX therapy for paediatric patients with ALL and malignant lymphoma.

Sec-Dependent Secretion of Subtilase SptE in Haloarchaea Facilitates Its Proper Folding and Heterocatalytic Processing by Halolysin SptA Extracellularly.

In response to high-salt conditions, haloarchaea export most secretory proteins through the Tat pathway in folded states; however, it is unclear why some haloarchaeal proteins are still routed to the Sec pathway. SptE is an extracellular subtilase of Natrinema sp. strain J7-2. Here, we found that SptE precursor comprises a Sec signal peptide, an N-terminal propeptide, a catalytic domain, and a long C-terminal extension (CTE) containing seven domains (C1 to C7). SptE is produced extracellularly as a mature form (M180) in strain J7-2 and a proform (ΔS) in the ΔsptA mutant strain, indicating that halolysin SptA mediates the conversion of the secreted proform into M180. The proper folding of ΔS is more efficient in the presence of NaCl than KCl. ΔS requires SptA for cleavage of the N-terminal propeptide and C-terminal C6 and C7 domains to generate M180, accompanied by the appearance of autoprocessing product M120 lacking C5. At lower salinities or elevated temperatures, M180 and M120 could be autoprocessed into M90, which comprises the catalytic and C1 domains and has a higher activity than M180. When produced in Haloferax volcanii, SptE could be secreted as a properly folded proform, but its variant (TSptE) with a Tat signal peptide does not fold properly and suffers from severe proteolysis extracellularly; meanwhile, TSptE is more inclined to aggregate intracellularly than SptE. Systematic domain deletion analysis reveals that the long CTE is an important determinant for secretion of SptE via the Sec rather than Tat pathway to prevent enzyme aggregation before secretion. IMPORTANCE While Tat-dependent haloarchaeal subtilases (halolysins) have been extensively studied, the information about Sec-dependent subtilases of haloarchaea is limited. Our results demonstrate that proper maturation of Sec-dependent subtilase SptE of Natrinema sp. strain J7-2 depends on the action of halolysin SptA from the same strain, yielding multiple hetero- and autocatalytic mature forms. Moreover, we found that the different extra- and intracellular salt types (NaCl versus KCl) of haloarchaea and the long CTE are extrinsic and intrinsic factors crucial for routing SptE to the Sec rather than Tat pathway. This study provides new clues about the secretion and adaptation mechanisms of Sec substrates in haloarchaea.

Valproic Acid After Neurosurgery Induces Elevated Risk of Liver Injury: A Prospective Nested Case-Control Study.

BACKGROUND: Valproic acid (VPA) has been widely used to prevent epileptic seizures after neurosurgery in China. We have found that the incidence of liver injury (LI) in patients using VPA after neurosurgery is higher than that in other patients. OBJECTIVE: The objective of this study was to investigate the risk factors of LI in patients using VPA after neurosurgery. METHODS: A nested case-control study was conducted in patients using VPA after neurosurgery between September 2019 and March 2021. Cases of LI were matched to controls by age and body mass index (BMI). Conditional logistic regression was used to estimate matched odds ratios representing the odds of LI. A receiver operating characteristic curve was used to analyze the optimal cutoff condition. RESULTS: A total of 248 people (62 LI and 186 control) were enrolled. Among patients with vs without LI, the matched odds ratio for trough concentration of VPA was significant (matched odds ratio [OR], 1.09; 95% confidence interval [CI]: 1.01-1.19). The course of treatment (OR: 1.17, 95% CI: 1.02-1.33), Glasgow score (OR: 0.26, 95% CI: 0.10-0.67), gene polymorphisms of CYP2C19 (OR: 2.09, 95% CI: 1.03-146.93), and UGT1A6 (OR: 34.61, 95% CI: 1.19-1003.23) were all related to the outcome. The optimal cutoff of the course of treatment was 10 days, while the trough concentration of VPA was determined to be 66.16 mg/L. CONCLUSION: Length of treatment, VPA trough concentration, and Glasgow score were associated with LI in patients after neurosurgery. A gene test may be necessary for people who are prescribed VPA for a long time.

[Genetic diversity and genetic structures of original plants of Viticis Fructus:an SSR markers-based analysis].

The present study aimed to provide the protection strategies for wild germplasm resources of original plants of Viticis Fructus and a theoretical basis for the sustainable use of Viticis Fructus. The genetic diversity and genetic structures of the 232 indivi-duals in 19 populations of Vitex rotundifolia and V. trifolia were analyzed by eight SSR markers with tools such as Popgene32, GenAlex 6.502, and STRUCTURE. Bottleneck effect was detected for the population with more than 10 individuals. The results indicated that 42 and 26 alleles were detected from the populations of V. rotundifolia and V. trifolia, respectively, with average expected heterozygo-sities of 0.448 6 and 0.583 9, which are indicative of low genetic diversity. AMOVA revealed the obvious genetic variation of V. rotundifolia and V. trifolia within population(84.43%, P<0.01; 60.37%, P<0.01). Furthermore, in eight SSR loci, six from V. rotundifolia populations and two from V. trifolia populations failed to meet Hardy-Weinberg equilibrium expectations(P<0.05), which confirmed that the populations experienced bottleneck effect. As assessed by Mantel test, geographical distance posed slight impacts on the genetic variation between the populations of V. rotundifolia and V. trifolia. Principal component analysis(PCA) and STRUCTURE analysis demonstrated evident introgression of genes among various populations. The original plants of Viticis Fructus were confirmed low in genetic diversity and genetic differentiation level. Therefore, the protection of wild resources of original plants of Viticis Fructus should be strengthened to ensure its sustainable use.

Association of MTHFR and ABCB1 polymorphisms with MTX-induced mucositis in Chinese paediatric patients with acute lymphoblastic leukaemia, lymphoma or osteosarcoma-A retrospective cohort study.

WHAT IS KNOWN AND OBJECTIVE: MTX pharmacology and toxicity involve several metabolizing enzymes and transporters whose functions have been suggested to be altered by genetic polymorphisms. The current study is to investigate the relationship between the genetic variation and MTX-induced adverse drug effects. METHODS: A total of 80 paediatric patients (aged 1-14 years) were enrolled in this study. Toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 scoring system. Genotyping was performed by MassARRAY Assay method. Data were analysed using Spss statistical package version 17.0 and Plink v1.07 software. The HWE was tested by a chi-square test. The Fisher's exact test (chi-squaretest) was used to compare the distributions of genotypes between cases and controls. OR and 95%CI were applied to evaluate the association of genetic variants with the presence of mucositis using unconditional logistic regression. RESULTS AND DISCUSSION: Mucosal inflammatory injuries were found in 28 children. SNPs of rs1128503 (p = 0.0022, OR = 3.04, 95%CI = 1.39-6.64) and rs1045642 (p = 0.0052, OR = 2.38, 95%CI = 1.15-5.00) located in the gene of ABCB1 and SNPs of rs1801133 (p = 0.040, OR = 2.50, 95%CI = 1.06-5.88) located in the gene of MTHFR show marked impacts on the risk of developing mucositis. WHAT IS NEW AND CONCLUSION: SNPs of ABCB1 rs1128503, rs1045642 and MTHFR rs1801133 can be risk predictor for MTX-induced mucositis in Chinese paediatric patients diagnosed with acute lymphoblastic leukaemia, lymphoma or osteosarcoma.

Isolation, structural properties, bioactivities of polysaccharides from Dendrobium officinale Kimura et. Migo: A review.

Dendrobium officinale Kimura et Migo (D. officinale) is used as herbal medicine and new food resource in China, which is nontoxic and harmless, and can be used as common food. Polysaccharide as one of the main bioactive components in D. officinale, mainly composed of glucose and mannose (Manp: Glcp = 2.01:1.00-8.82:1.00), along with galactose, xylose, arabinose, and rhamnose in different molar ratios and types of glycosidic bonds. Polysaccharides of D. officinale exhibit a variety of biological effects, including immunomodulatory, anti-tumor, gastro-protective, hypoglycemic, anti-inflammatory, hepatoprotective, and vasodilating effects. This paper presents the extraction, purification, structural characteristics, bioactivities, structure-activity relationships and analyzes gaps in the current research on D. officinale polysaccharides. In addition, based on in vitro and in vivo experiments, the possible mechanisms of bioactivities of D. officinale polysaccharides were summarized. We hope that this work may provide helpful references and promising directions for further study and development of D. officinale polysaccharides.

Clinical Impact of the Adaptation of Initial Tacrolimus Dosing to the CYP3A5 Genotype After Kidney Transplantation: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: The aim of this systematic review and meta-analysis was to compare the clinical outcomes between genotype-guided and conventional tacrolimus doses in kidney transplantation patients. MATERIALS AND METHODS: We performed a comprehensive literature search of the PubMed, EMBASE, and Cochrane databases from the date of inception to 26 February 2020. References of the retrieved articles were also reviewed and any further relevant studies were included. The search terms included 'tacrolimus', 'cytochrome P-450 CYP3A', 'polymorphism, genetic', 'genomics', 'genome', 'genotype', 'genes', 'alleles', and 'pharmacogenetics'. RESULTS: Our study showed that the genotype-guided group included an increased proportion of patients with tacrolimus concentrations in the therapeutic range at steady state (risk ratio [RR] 1.40, 95% confidence interval [CI] 1.14-1.72, p = 0.001; high quality), with a trend for achieving therapeutic concentrations earlier compared with those in the conventional group. However, there was no statistical difference in the incidence of delayed graft function (RR 1.98, 95% CI 0.92-1.76, p = 0.12; moderate quality), incidence of acute rejection (RR 1.00, 95% CI 0.64-1.55, p = 1.00; moderate quality), incidence of graft survival censored for death (RR 1.02, 95% CI 0.98-1.06, p = 0.37; moderate quality), and incidence of adverse effects (AEs). CONCLUSIONS: Although the genotype-guided group had a higher proportion of patients within the targeted concentration and less median time to achieve the therapeutic range, the clinical endpoints, including delayed graft function, acute rejection, graft survival censored for death, and AEs were similar in both groups. All in all, evidence suggested there was no utility in pharmacogenetics for tacrolimus based on the cytochrome P450 (CYP) 3A5 genotype. Studies with Chinese and African American populations are needed due to the frequency of genetic polymorphisms of CYP3A5. Furthermore, a dosing algorithm that includes demographic and clinical factors plus multiple genetic variants should be added for consideration, and may optimize early tacrolimus exposure.

Population pharmacokinetics of sirolimus in Chinese adult liver transplant recipients: a retrospective study.

Considering the significant interindividual variability and a narrow therapeutic index, we aimed to determine the population pharmacokinetics (PPK) of sirolimus and identify the factors in Chinese adult liver transplant recipients.Data were retrospectively extracted from adult liver transplant recipients receiving sirolimus in our hospital. The trough blood concentration data, obtained from traditional therapeutic drug monitoring-based dose adjustments, were used to develop a population pharmacokinetic model by non-linear mixed-effects modelling (NONMEM). The effect of demographic features, biological characteristics and concomitant medications was measured. The final model was verified by visual prediction check (VPC), bootstrap, and simulation.One hundred and sixteen blood concentrations from 63 patients were analysed. The PPK of sirolimus could be described by a one-compartment model with first-order absorption. Covariate analysis indicated that voriconazole co-therapy significantly decreased the oral clearance (CL) of sirolimus. The results of VPC and Bootstrap demonstrated that the final pharmacokinetic model adequately predicted observed concentrations. The simulation results showed that the dosage regimen of sirolimus should be reduced to 0.25 ∼ 0.45 mg/day for adult liver transplant recipients co-administered with voriconazole. The present study developed and validated a sirolimus PPK model for Chinese adult liver transplant recipients, and voriconazole co-therapy was found to be a significant covariate in the model. These results provide important information for clinicians to optimise the treatment regimens of sirolimus in Chinese adult liver transplant recipients.

Effect of organic matters on anammox coupled denitrification system: when nitrite was sufficient.

Anaerobic ammonia oxidation (anammox) and denitrification can work together to weaken the influence of organic matter on anaerobic ammonia oxidation bacteria (AAOB) and improve nitrogen removal performance. As the common substrate of anammox and denitrification, nitrite will also affect nitrogen removal performance when it is insufficient, which is not conducive to reflect the endurance of anammox reactor to organic matter. The UASB continuous flow experiment was carried out to investigate the effect of the concentration of glucose and sodium acetate on nitrogen removal performance of anammox reactor under the condition of sufficient nitrite. With glucose as the organic matter, when the chemical oxygen demand (COD) concentration increased to 200 mg l-1, nitrogen removal performance of the system began to deteriorate significantly, and the anammox activity was significantly inhibited. With sodium acetate as the organic substance, the anammox activity was affected when the COD was 20 mg l-1. Adequate nitrite could relieve the inhibition of the coupling system by a low concentration (COD < 200 mg l-1) of glucose organic matter. However, it could not relieve the inhibitory effect of sodium acetate. With the increase of organic concentration, the biological density of AAOB in granular sludge gradually decreased, while the biological density of denitrifying bacteria increased gradually.

[Partial Nitrification Fast Start-up and Stable Performance of 15℃ SBBR].

In this study, controlled C/N effects on fast start-up and stable performance of partial nitrification process at 15℃ in a Sequenced Batch Biofilm Reactor (SBBR) were investigated. The results showed that partial nitrification successfully fast initiated when C/N was 1.5 but failed when C/N was 0/3 during 60 cycles. Fluorescence in situ hybridization and confocal laser scanning microscope (FISH-CLSM) results showed that ammonia oxidizing bacteria (AOB) was found as the dominant bacteria population when C/N was 1.5. When C/N were 0/3, there were almost no existence of AOB and nitrite oxidative bacteria (NOB). Partial nitrification could be stably achieved without carbon source. However, the addition of an appropriate amount of carbon can effectively improve the nitrification performance, and it is better for the stable operation of partial nitrification. In this experiment, partial nitrification was successfully initiated at high dissolved oxygen (DO) (about 9 mg·L-1) conditions. The average DO was maintained at about 6.5 mg·L-1 during the stable operation, which successfully decoupled partial nitrification from low DO concentration. Excessive residual ammonium concentration in the reactors effectively repressed the growth of NOB and guaranteed the stable operation of partial nitrification. At 15℃, full nitritation was more suitable for sidestream wastewater, while mainstream wastewater was more suitable for partial nitritation.

Genetic diversity and its conservation implications of Vitex rotundifolia (Lamiaceae) populations in East Asia.

Vitex rotundifolia is an important coastal and medicinal plant, and is recorded in the List of the Important Wild Plants for Conservation in China and Japan. However, an effective conservation strategy is lacking. In the present study, the genetic diversity and population structure were analyzed using phylogeographical methods based on the trnH-psbA and trnG-trnS intergenic spacers of the chloroplast DNA (cpDNA) sequences from 157 individuals from 25 sampling sites for V. rotundifolia and V. trifolia plus the internal transcribed spacer (ITS) of the nuclear ribosomal DNA (nrDNA) sequences of 177 individuals from 27 sampling sites. The results showed that V. rotundifolia and V. trifolia had eight cpDNA and two nrDNA haplotypes, respectively, and the V. rotundifolia has a low level of genetic diversity (haplotype diversity h d,cp = 0.360, h d,nr = 0.440), a more pronounced genetic differentiation among populations (population differentiation at the species level (G ST) = 0.201, population differentiation at the allele level (N ST) = 0.462), and an insignificantly different phylogeographical structure (N ST > G ST, P > 0.05). In addition, haplotype network analyses indicated that V. rotundifolia and V. trifolia have distinct haplotypes. Divergence dating based on BEAST software analyses showed that most cpDNA clades diverged in the late Pleistocene era. Demographic analysis indicated that V. rotundifolia underwent a rapid demographic expansion. Some scientific strategies are suggested for resource conservation of V. rotundifolia based on its genetic diversity and population structure.

Determination of the phytoremediation efficiency of Ricinus communis L. and methane uptake from cadmium and nickel-contaminated soil using spent mushroom substrate.

Spent mushroom substrate (SMS) as an organic amendment to plant production has received increasing attention on soil phytoremediation. However, organic amendments are known to contribute to greenhouse gas (GHG) emission from soils. Castor oil plant has a high biomass production and phytoremediation potential for heavy metal-contaminated soils. In the present study, the roles of SMS on phytoremediation efficiency of castor oil plant (Ricinus communis L.) from cadmium (Cd) and nickel (Ni)-contaminated soils were investigated, and the impact of SMS application on methane emission from the contaminated soil were evaluated. Pot experiments with SMS-amended and unamended contaminated soils were conducted to investigate Cd and Ni accumulation in R. communis and CH4 emission. After growing for 3 months in soils with the addition of Cd (10 mg/kg) and Ni (at rates of 200 and 600 mg/kg), the dry biomass and the concentrations of Cd and Ni in the R. communis were measured, and the mobility factors for Cd and Ni were calculated. To assess methane emission, CH4 fluxes and potential rates of CH4 production and oxidation were measured pre- and post-incubation. SMS addition significantly improved the growth of R. communis and gave 19.15~82.46% more dry weight as compared to the single plant cultivation in the contaminated soils. SMS also increased plant Cd uptake and the total amount of Cd accumulation in R. communis increased by 28.1-152.1%, respectively, in signal Cd treatment and Cd-Ni complexation treatment, as compared to the single plant cultivation. The high values of mobility factor for Cd in single plant cultivation and co-application of SMS and R. communis pointed to the potential of R. communis to the Cd mobilization from the contaminated soils. Moreover, the addition of SMS tended to stimulate CH4 uptake that the average increases in CH4 uptake rate were 3.84-fold (in controls) and 2.91-fold (in single Cd treated soils) by the co-application of SMS and R. communis as compared to the single plant cultivation. The results suggested that the application of SMS could improve the growth of R. communis in Cd and Ni-contaminated soil, enhance heavy metal bioaccumulation, and stimulate soil CH4 uptake. Therefore, SMS might be useful for enhancing phytoremediation of heavy metals and mitigate CH4 emission from the contaminated soil. In addition, results in the study implied that implementing carefully designed management strategies (e.g., application of organic residues) during contaminated soil remediation is a promising solution for agricultural waste management and soil phytoremediation.

[Achieving Partial Nitritation in a Continuous-flow Aerobic Granular Sludge Reactor at Different Temperatures Through Ratio Control].

Mature aerobic granular sludge (AGS) was inoculated in a continuous-flow reactor to treat low ammonia sewage, and the feasibility of achieving partial nitritation in a continuous-flow aerobic sludge system and the demand for R value (the ratio of dissolved oxygen and ammonia nitrogen) when partial nitritation is achieved at different temperatures (30, 20, and 10℃) were investigated. The control strategy was designed to maintain a constant ratio between dissolved oxygen (DO) and ammonia nitrogen (NH4+-N). The results revealed that stable nitritation in a continuous-flow aerobic sludge reactor could be achieved via ratio control, and the value of R were 0.50 (±0.05), 0.35 (±0.03), and 0.20 (±0.02) at the temperatures 30, 20, and 10℃, respectively, from which it can be concluded that stronger oxygen-limiting conditions were required when the temperature was lower. The experiment of fluorescence in situ hybridization (FISH) revealed that ammonia oxidizing bacteria (AOB) have a certain concentration, and the relative number of nitrite oxidizing bacteria (NOB) gradually reduced through the ratio control strategy. Based on the ratio control strategy and the characteristics of wastewater quality, full nitritation of high ammonia wastewater may be allowed; however, for low ammonia wastewater, only partial nitritation is recommended.