Population pharmacokinetics of cyclosporine A in pediatric patients with thalassemia undergoing allogeneic hematopoietic stem cell transplantation.

PURPOSE: To establish the population pharmacokinetics (PPK) model of cyclosporine A(CsA) in pediatric patients with thalassemia undergoing allogeneic hematopoietic stem cell transplantation (HSCT), aiming at providing a reference for clinical dose individualization of CsA. METHODS: Children with thalassemia who underwent allogeneic HSCT were enrolled retrospectively. The PPK structural model and the random variable model of CsA were established on NONMEN. And goodness of fit plots (GOFs), visual predictive check (VPC), and bootstrap and normalized prediction distribution errors (NPDE) were used to evaluate the final model. RESULTS: A one-compartment model with first-order absorption was employed to fit the base model. A total of 74 pediatric patients and 600 observations of whole blood concentration were included. The final model included weight (WT) in clearance (CL), alongside post-operative day (POD), fluconazole (FLUC), voriconazole (VORI), posaconazole (POSA), and red blood cell count (RBC) significantly. All the model evaluations were passed. CONCLUSION: In the PPK model based on the pediatric cohort on CsA with thalassemia undergoing allogeneic HSCT, WT, POD, FLUC, VORI, POSA, and RBC were found to be the significant factors influencing CL of CsA. The reliability and robustness of the final model were excellent. It is expected that the PPK model can assist in individualizing dosing strategy clinically.

Therapeutic effect of long-acting FGF21 with controlled site-specific modification on nonalcoholic steatohepatitis.

FGF21 plays an active role in the treatment of type 2 diabetes, obesity, nonalcoholic fatty liver disease (NAFLD), and nonalcoholic steatohepatitis (NASH). However, the short half-life and poor stability of wild-type FGF21 limit its clinical application. Previous studies found that PEGylation can significantly increase the stability of FGF21. However, the uneven distribution of PEGylation sites in FGF21 makes it difficult to purify PEG-FGF21, thereby affecting its yield, purity, and activity. To obtain long-acting FGF21 with controlled site-specific modification, we mutated lysine residues in FGF21, resulting in PEGylation only at the N-terminus of FGF21 (mFGF21). In addition, we modified mFGF21 molecules with different PEG molecules and selected the PEG-mFGF21 moiety with the highest activity. The yield of PEG-mFGF21 in this study reached 1 g/L (purity >99 %), and the purification process was simple and efficient with strong quality controllability. The half-life of PEG-mFGF21 in rats reached 40.5-67.4 h. Pharmacodynamic evaluation in mice with high-fat, high-cholesterol- and methionine and choline deficiency-induced NASH illustrated that PEG-mFGF21 exhibited long-term efficacy in improving liver steatosis and reducing liver cell damage, inflammation, and fibrosis. Taken together, PEG-mFGF21 could represent a potential therapeutic drug for the treatment of NASH.

Substation of vermicompost mitigates Cd toxicity, improves rice yields and restores bacterial community in a Cd-contaminated soil in Southern China.

Cadmium (Cd) contamination in agricultural soil is a global concern for soil health and food sustainability because it can cause Cd accumulation in cereal grains. An in-situ stabilizing technology (using organic amendments) has been widely used for Cd remediation in arable lands. Therefore, the current study examined the influence of vermicompost (VC) on soil biochemical traits, bacterial community diversity and composition, Cd uptake and accumulation in rice plants and grain yield in a Cd-contaminated soil during the late growing season in 2022. Different doses of VC (i.e., V1 = 0 t ha-1, V2 = 3 t ha-1 and V3 = 6 t ha-1) and two concentrations of Cd (i.e., Cd1 = 0 and Cd2 = 50 mg Cd Kg-1 were used. We performed high-throughput sequencing of 16S ribosomal RNA gene amplicons to characterize soil bacterial communities. The addition of VC considerably affected the diversity and composition of the soil bacterial community; and increased the relative abundance of phyla Chloroflexi, Proteobacteria, Acidobacteriota, Plantomycetota, Gemmatimonadota, Patescibacteria and Firmicute. In addition, VC application, particularly High VC treatment, exhibited the highest bacterial diversity and richness (i.e., Simpson, Shannon, ACE, and Chao 1 indexes) of all treatments. Similarly, the VC application increased the soil chemical traits, including soil pH, soil organic carbon (SOC), available nitrogen (AN), total nitrogen (TN), total potassium (TK), total phosphorous (TP) and enzyme activities (i.e., acid phosphatase, catalase, urease and invertase) compared to non-VC treated soil under Cd stress. The average increase in SOC, TN, AN, TK and TP were 5.75%, 41.15%, 18.51%, 12.31%, 25.45% and 29.67%, respectively, in the High VC treatment (Pos-Cd + VC3) compared with Cd stressed soil. Redundancy analysis revealed that the leading bacterial phyla were associated with SOC, AN, TN, TP and pH, although the relative abundance of Firmicutes, Proteobacteria, Bacteroidata, and Acidobacteria on a phylum basis and Actinobacteria, Gammaproteobacteria and Myxococcia on a class basis, were highly correlated with soil environmental factors. Moreover, the VC application counteracted the adverse effects of Cd on plants and significantly reduced the Cd uptake and accumulation in rice organs, such as roots, stem + leaves and grain under Cd stress conditions. Similarly, applying VC significantly increased the fragrant rice grain yield and yield traits under Cd toxicity. The correlation analysis showed that the increased soil quantities traits were crucial in obtaining high rice grain yield. Generally, the findings of this research demonstrate that the application of VC in paddy fields could be useful for growers in Southern China by sustainably enhancing soil functionality and crop production.

Environmentally persistent free radicals on photoaged microplastics from disposable plastic cups induce the oxidative stress-associated toxicity.

Microplastics (MPs) are ubiquitous environmental contaminants that exerting multiple toxicological effects. Most studies have focused primarily on the models of unaged MPs and lack environmental relevance. The generation and toxicity of environmentally persistent free radicals (EPFRs) on photoaging MPs from disposable plastic cups (DPC-MPs) have not been well studied. Here, the formation of EPFRs on photoaged DPC-MPs and their toxic effects in nematodes were investigated. UV irradiation generated EPFRs, which influenced the characterization of DPC-MPs. Exposure to photoaged DPC-MPs at environmentally relevant concentrations （100-1000 µg/L） reduced the locomotion behavior, body length, and brood size. The Reactive oxygen species (ROS) production, lipofuscin accumulation, malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were increased along with the downregulation of the expression levels of associated genes, such as clk-1, clt-1, and gst-4，in nematodes. Moreover, the toxicity and oxidative stress response of nematodes were significantly inhibited due to N-acetyl-l-cysteine (NAC). Pearson's correlation analysis revealed that the oxidative stress was significantly associated with adverse physiological effects. Therefore, EPFRs on photoaged DPC-MPs cause toxicity in nematodes, and oxidative stress is important for regulating toxicity. This study offers novel insights into the potential risks of DPC-MPs under UV irradiation, highlighting the need to consider the role of EPFRs in toxicity assessments of DPC-MPs.

Fetal Glucocorticoid Mediates the Association between Prenatal Per- and Polyfluoroalkyl Substance Exposure and Neonatal Growth Index: Evidence from a Birth Cohort Study.

Glucocorticoid plays a key role in the growth and organ maturation of fetus. However, the effect of glucocorticoid on the association between per- and polyfluoroalkyl substance (PFAS) exposure and fetal growth is still unknown. We detected cord cortisol (active glucocorticoid in human) and 34 PFAS concentrations in the maternal serum samples, which were collected from 202 mother-fetus pairs in the Maoming Birth Cohort from 2015 to 2018. The mediation effect of cord cortisol on the association between maternal PFAS and the neonatal growth index (NGI) was estimated. We found that higher PFAS concentrations were associated with lower NGI in terms of ponderal index, birth weight (BW), head circumference (HC), and its z-scores (BWZ and HCZ) (P < 0.05). Fetal cortisol could mediate 12.6-27.3% of the associations between PFAS and NGI. Specifically, cord cortisol mediated the association between branched perfluorooctane sulfonate (branched PFOS) and HCZ by 20.4% and between perfluorooctanoate (PFOA) and HCZ by 27.3%. Our findings provide the first epidemiological data evincing that fetal cortisol could mediate the association between prenatal PFAS exposure and fetal growth. Further investigations are recommended to elucidate the interactions among cord cortisol, PFAS, and fetal growth.

Exogenous TiO2 Nanoparticles Alleviate Cd Toxicity by Reducing Cd Uptake and Regulating Plant Physiological Activity and Antioxidant Defense Systems in Rice (Oryza sativa L.).

Cadmium (Cd) is a potentially hazardous element with significant biological toxicity, negatively affecting plant growth and physio-biochemical metabolism. Thus, it is necessary to examine practical and eco-friendly approaches to reduce Cd toxicity. Titanium dioxide nanoparticles (TiO2-NPs) are growth regulators that help in nutrient uptake and improve plant defense systems against abiotic and biological stress. A pot experiment was performed in the late rice-growing season (July-November) 2022 to explore the role of TiO2-NPs in relieving Cd toxicity on leaf physiological activity, biochemical attributes, and plant antioxidant defense systems of two different fragrant rice cultivars, i.e., Xiangyaxiangzhan (XGZ) and Meixiangzhan-2 (MXZ-2). Both cultivars were cultivated under normal and Cd-stress conditions. Different doses of TiO2-NPs with and without Cd-stress conditions were studied. The treatment combinations were: Cd-, 0 mg/kg CdCl2·2.5 H2O; Cd+, 50 mg/kg CdCl2·2.5 H2O; Cd + NP1, 50 mg/kg Cd + 50 TiO2-NPs mg/L; Cd + NP2, 50 mg/kg Cd + 100 TiO2-NPs mg/L; Cd + NP3, 50 mg/kg Cd + 200 TiO2-NPs mg/L; Cd + NP4, 50 mg/kg Cd + 400 TiO2-NPs mg/L. Our results showed that the Cd stress significantly (p < 0.05) decreased leaf photosynthetic efficiency, stomatal traits, antioxidant enzyme activities, and the expression of their encoding genes and protein content. Moreover, Cd toxicity destabilized plant metabolism owing to greater accretion of hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels at vegetative and reproductive stages. However, TiO2-NPs application improved leaf photosynthetic efficacy, stomatal traits, and protein and antioxidant enzyme activities under Cd toxicity. Application of TiO2-NPs decreased the uptake and accumulation of Cd in plants and levels of H2O2 and MDA, thereby helping to relieve Cd-induced peroxidation damage of leaf membrane lipids by enhancing the activities of different enzymes like ascorbate peroxidase (APX), catalase (CAT), peroxidase (POS), and superoxide dismutase (SOD). Average increases in SOD, APX, CAT, and POS activities of 120.5 and 110.4%, 116.2 and 123.4%, 41.4 and 43.8%, and 36.6 and 34.2% in MXZ-2 and XGZ, respectively, were noted in Cd + NP3 treatment across the growth stages as compared with Cd-stressed plants without NPs. Moreover, the correlation analysis revealed that the leaf net photosynthetic rate is strongly associated with leaf proline and soluble protein content, suggesting that a higher net photosynthetic rate results in higher leaf proline and soluble protein content. Of the treatments, the Cd + NP3 (50 mg/kg Cd + 200 mg/L TiO2-NPs) performed the best for both fragrant rice cultivars under Cd toxicity. Our results showed that TiO2-NPs strengthened rice metabolism through an enhanced antioxidant defense system across the growth stages, thereby improving plant physiological activity and biochemical characteristics under Cd toxicity.

Design and pharmaceutical evaluation of bifunctional fusion protein of FGF21 and GLP-1 in the treatment of nonalcoholic steatohepatitis.

Fibroblast growth factor 21 (FGF21) and glucagon-like peptide-1 (GLP-1) may be useful for the treatment of type 2 diabetes, obesity, and non-alcoholic fatty liver disease (NAFLD). Previous studies have shown that GLP-1 may synergize with FGF21 in the regulation of glucose and lipid metabolism. Currently, no approved drug therapy is available for non-alcoholic steatohepatitis (NASH). Here, we constructed and screened dual-targeting fusion proteins of GLP-1 and FGF21, connected by elastin-like polypeptides (ELPs), to investigate whether a combination of these two hormones would have therapeutic effects in models of NASH. The temperature phase transition and release of the hormones under physiological conditions were studied to identify a bifunctional fusion protein of FGF21 and GLP-1 (GEF) that was highly stable and showed sustained release. We further evaluated the quality and therapeutic efficacy of GEF in three mouse models of NASH. We successfully synthesized a novel recombinant bifunctional fusion protein with high stability and low immunogenicity. The GEF protein synthesized ameliorated hepatic lipid accumulation, hepatocyte damage, and inflammation; prevented the progression of NASH in the three models; reduced glycemia; and caused weight loss. This novel GEF molecule may be suitable for clinical use for the treatment of NAFLD/NASH and related metabolic diseases.

Effects of contrasting tillage managements on the vertical distribution of plant- and microbial-derived carbon in rice paddy.

Soil microbial necromass is considered a persistent component of soil organic carbon (SOC), constituting the final product of the microbial carbon pump (MCP). However, the mechanisms involved in the effects of tillage and rice residue managements on the vertical distribution of microbial necromass and plant residues in rice paddy soils remain unclear, limiting knowledge of SOC sequestration mechanisms. Therefore, we estimated microbial- and plant-derived C by biomarker amino sugars (AS) and lignin phenols (VSC) at the 0-30 cm soil depth, as well as their relationships with SOC contents and mineralization in a rice paddy soil under contrasting tillage practices, namely no-tillage (NT), reduced tillage (RT), and conventional tillage (CT). The results showed that the SOC contents in the rice paddy soil were positively correlated with soil AS and VSC contents. The NT resulted in significantly higher (P < 0.05) AS (expressed as per kilogram soil) at the 0-10 cm and 10-30 cm soil depths by 45-48 % than RT and CT. However, microbial-derived C contents and SOC mineralization were not significantly changed by NT. In contrast, the plant-derived C contents in the total SOC decreased significantly under the NT scenario, suggesting the consumption of plant-derived C even with more rice residue inputs (at the 0-10 cm soil depth). In summary, 5-year short-term NT management with more rice residue mulch on the soil surface in rice paddy maintained a low plant-derived C content (at a sampling date before rice transplanting), suggesting a different mode of C sequestration, except for the protection of plant-derived C under anaerobic conditions.

Photoaged microplastics induce neurotoxicity via oxidative stress and abnormal neurotransmission in zebrafish larvae (Danio rerio).

Microplastics (MPs) are ubiquitous environmental contaminants and cause neurotoxicity in various organisms. However, previous studies that analyzed the effects of MPs mainly focused on virgin polystyrene (V-PS) as representative models of MPs, and the mechanism underlying the neurotoxicity of photoaged polystyrene (P-PS) remains largely unknown. In this study, zebrafish (Danio rerio) were exposed to environmentally relevant concentrations (0.1-100 µg/L) of V-PS and P-PS(10 µm). The results indicated that UV radiation accelerated the aging process and changed physical and chemical properties of PS. Whereas exposure to both V-PS and P-PS at low concentrations (100 µg/L) significantly reduced the locomotor behavior of zebrafish larvae, P-PS caused more severe neurotoxicity compared to V-PS. The activity of antioxidant enzymes (SOD, CAT, and GST) and MDA content were significantly altered in zebrafish exposed to 10-100 µg/L of P-PS. Similarly, exposure to P-PS significantly increased neurotransmitter (5-HT, GABA, DA, and ACh) levels and activity of AChE, ChAT, and ChE. Star plots based on integrated biomarker response (IBR) values showed more incline toward neurotransmitter biomarkers in response to increasing P-PS concentration, and the behavioral parameters negatively correlated with the neurotransmitter biomarkers. Further investigations revealed that the expression of neurotransmission- (e.g., ache, drd3, 5th2c, and gat1) and oxidative stress- (e.g., cat1, sod1, gpx1a, and gstrl) related genes was significantly affected by PS in larval zebrafish. Thus, this study provides new insights on the potential risks of MPs into the environment.

Biosynthesis of 2-Acetyl-1-pyrroline in Fragrant Rice: Recent Insights into Agro-management, Environmental Factors, and Functional Genomics.

Rice is a staple food for more than half of the world's population, and rice fragrance is a key quality attribute which is highly desired by consumers and attracts premium prices in the international market. There are around 200 volatile compounds involved in rice fragrance, but 2-acetyl-1-pyrroline (2-AP) has been considered a master regulator of aroma in fragrant rice. Consequently, efforts were made to increase the 2-AP contents in the grain by managing agronomical practices or by using modern functional genomic tools, which successfully converted nonfragrant cultivars to fragrant rice. Furthermore, environmental factors were also reported to influence the 2-AP contents. However, a comprehensive analysis of 2-AP biosynthesis in response to agro-management practices, environmental factors, and the application of functional genomic tools for fragrant rice production was missing. In this Review, we summarize how micro/macronutrients, cultivation practices, amino acid precursors, growth regulators, and environmental factors, such as drought, salinity, light, and temperature, influence the 2-AP biosynthesis to modulate the aroma of fragrant rice. Furthermore, we also summarized the successful conversion of nonfragrant rice cultivars to fragrant rice using modern gene editing tools, such as RNAi, TALENS, and CRISPR-Cas9. Finally, we discussed and highlighted the future perspective and challenges related to the aroma of fragrant rice.

Straw incorporation interacting with earthworms mitigates N2O emissions from upland soil in a rice-wheat rotation system.

Intensive attentions have been paid to the positive effects on nitrous oxide (N2O) production under straw return or the presence of earthworms. Straw return as a sustainable practice can promote earthworm growth, how the interactions between straw and earthworms affect N2O production is still not well known. A split-plot field experiment (straw return as main plot and earthworm addition as subplot) was performed to quantify the interactive effects of straw and earthworm on N2O emissions from a wheat field and to determine the underlying mechanisms from nitrification and denitrification processes. The results showed that straw return significantly increased N2O emissions by 41.0 % under no earthworm addition but decreased it by 19.0 % under earthworm addition compared with straw removal (P < 0.05). The significant interaction between straw and earthworm benefits the mitigation of N2O emissions. Random forest model showed that denitrification and nitrification were dominant processes to affect N2O emissions at the jointing and booting growth stages of wheat, respectively. The interaction between straw and earthworm significantly decreased the abundances of N2O-producing bacterial genes such as nirS and nirK at the jointing stages, and AOB at the booting stages. The contrasting mechanisms in regulating N2O emissions at different growth stages should be considered in nitrogen recycling models to accurately predict available N and N2O dynamics. Our findings suggest that N2O emissions under straw return can be weakened with the increasing earthworm populations under the scenario of widely used conservation practices (e.g., straw return and no-till) due to significant interaction between straw and earthworms.

A 40 % paddy surface soil organic carbon increase after 5-year no-tillage is linked with shifts in soil bacterial composition and functions.

Soil organic carbon (SOC) is related to soil fertility, crop yield, and climate change mitigation. Paddy soil is a significant carbon (C) sink, but its C sequestration potential has not been realized as the various driving factors are still not fully understood. We performed a 5-year paddy field experiment in southern China to estimate tillage effects on SOC accumulation and its relation with soil bacteria. The C input from rice residue, SOC content, CO2 flux, soil bacterial community composition, and predicted functions were analyzed. No-tillage (NT) increased (p < 0.05) rice residue C inputs (by 12.6 %-15.9 %), SOC (by 40 % at the surface soil layer compared with conventional tillage, CT), and CO2 fluxes compared with reduced tillage (RT) and CT. Also, NT significantly altered the soil bacterial community. The random forest model showed that the predicted bacterial functions of "Degradation/Utilization/Assimilation Other", "C1 Compound Assimilation", and "Amin and Polyamine Degradation" were the most important functions associated with SOC accumulation. Analysis of metabolic pathway differences indicated that NT significantly decreased the BENZCOA-PWY (anaerobic aromatic compound degradation) and the AST-PWY (L-arginine degradation II). Therefore, the rapid paddy SOC increase is associated with both residue C input (from higher rice yields) and the degradation functions regulated by soil bacteria.

Dosage optimization of voriconazole in children with haematological malignancies based on population pharmacokinetics.

WHAT IS KNOWN AND OBJECTIVES: Voriconazole has a complex pharmacokinetic profile and exhibits different pharmacokinetic characteristics in adults and children. Nevertheless, few studies have been conducted on the population pharmacokinetics (PPK) of voriconazole in children with haematological malignancies. This study aims to build a PPK model and propose a suitable voriconazole treatment scheme for children with haematological malignancies. METHODS: We retrospectively collected 146 samples from 67 children aged from 1.08 to 17.92 years. The PPK model was established using nonlinear mixed effects modelling (NONMEM). Dosage simulations were conducted on the basis of the final model's covariates. RESULTS AND DISCUSSION: Data were fully characterized by a one-compartment model with first-order absorption and elimination. The weight (WT), CYP2C19 phenotype, and Albumin (ALB) were notable covariates for clearance (CL). The typical values of CL, the volume of distribution (V), and oral bioavailability (F) were 2.29 L/h, 76 L, and 0.902, respectively. The proposed doses for different CYP2C19 genotypes were presented in this ranking: EM (extensive metabolizer) > IM (intermediate metabolizer) > PM (poor metabolizer). Furthermore, higher dosages for light WT patients were recommended while lower ALB levels required lower doses. The probability of achieving the target (PTA) for the recommended doses ranged from 72.2% to 99%. WHAT IS NEW AND CONCLUSION: We successfully built a voriconazole PPK model for children with hematologic malignancies. Dosing regimens were developed for different patients based on the final model, which could enhance the rational use of voriconazole in children with haematological malignancies.

Population pharmacokinetics of mycophenolate mofetil in pediatric patients early after liver transplantation.

Objective: To investigate the factors influencing the pharmacokinetics of mycophenolate mofetil (MMF) in pediatric patients after liver transplantation, and to establish a population pharmacokinetics model, which can provide a reference for clinical dosage adjustment. Methods: A prospective study in a single center was performed on pediatric patients who were administrated with mycophenolate mofetil dispersible tablets (MMFdt) for at least 4 days after liver transplantation continuously. Blood samples were collected in ethylene diamine tetraacetic acid anticoagulant tubes before dosing and 0.5, 1, 2, 4, 8, and 12 h after the morning intake of MMFdt. The concentrations of mycophenolic acid (MPA) in plasma were assayed with a validated reverse-phase high-performance liquid chromatography method. UGT1A8 518C > G, UGT1A9 -275T > A, UGT1A9 -2152C > T, UGT2B7 211G > T, SLC O 1B1 521T > C polymorphism were determined by Sanger sequencing. Nonlinear mixed effects modeling was used to establish the population pharmacokinetics (PPK) model. The predictability and stability of the model were internally evaluated by the goodness of fit plots, visual prediction check, normalized prediction errors, and bootstraps. Results: A two-compartment model with first-order absorption and first-order elimination was established with 115 MPA concentrations from 20 pediatric patients. The final model were: CL/F (L/h) = 14.8×(WT/7.5)0.75×(DOSE/11.16)0.452×е0.06, Ka (h-1) = 2.02×(WT/7.5)-0.25, Vc/F (L) = 6.01×(WT/7.5), Vp/F (L) = 269 (fixed), Q/F (L/h) = 15.4×(WT/7.5)0.75×е1.39. Where CL/F was the apparent clearance rate, Ka was the absorption rate constant, Vc/F was the apparent distribution volume of the central compartment, Vp/F was the apparent distribution volume of the peripheral compartment, Q/F was the atrioventricular clearance rate, WT was the body weight of the subject, and DOSE was the MMFdt administered dose. The model indicated there was large inter-individual variability in CL/F and Q/F after multiple dosing of MMFdt. Internal evaluation results showed that the final model had good stability and prediction performance. Conclusion: A stable and predictive population pharmacokinetic model of MMFdt in pediatric patients after the early stage of liver transplantation was established. The pediatric patient's weight and the dose of MMFdt can be a reference to adjust the MMFdt dose.

Residues of neonicotinoid insecticides in surface sediments in lakes and rivers across Jiangsu Province: Impact of regional characteristics and land use types.

Neonicotinoid insecticides (NNIs) had been detected in soil and surface water frequently because of extensive use worldwide, however, data regarding regional characteristics and potential influential factors of sediment were scarce. In the present study, eight NNIs were analyzed in 86 surface sediment samples from different regions (central cities, rural areas and suburbs) and land use types (construction land and crop land) in Jiangsu Province. NNIs were widespread in the sediments, with a mean value of 1.73 ± 0.89 ng g-1 dry weight (dw) (ranged from 0.41 to 3.87 ng g-1 dw). Imidaclothiz (IMIZ), dinotefuran (DIN) and nitenpyram (NIT) were the dominant compounds in the surface sediment, accounted for half of combined total. The results of regional distribution analysis show that NNIs were at higher concentrations in rural areas and crop land, while the residues of NNIs in lakes were more severe compare with rivers in Jiangsu Province. Region characteristics and land use types have an influence on residues of NNIs in surface sediment. Principal component analysis showed that residues of NNIs in surface sediment in Jiangsu Province mainly originated from protect grain crops (maize), fruit (apples, pears) and vegetables in agricultural systems. The residues of NNIs were found to be mostly concentrated in the northwest and northeast in Jiangsu Province, where were the area of intensive agriculture. To investigate the residues of NNIs, while identify the contributing factors, could provide a scientific basis for basic of region environment management and pollution control.

[Expression, purification and bioactivity analysis of a recombinant fusion protein rHSA-hFGF21 in Pichia pastoris].

Human fibroblast growth factor 21 (hFGF21) has become a candidate drug for regulating blood glucose and lipid metabolism. The poor stability and short half-life of hFGF21 resulted in low target tissue availability, which hampers its clinical application. In this study, the hFGF21 was fused with a recombinant human serum albumin (HSA), and the resulted fusion protein rHSA-hFGF21 was expressed in Pichia pastoris. After codon optimization, the recombinant gene fragment rHSA-hFGF21 was inserted into two different vectors (pPIC9k and pPICZαA) and transformed into three different strains (X33, GS115 and SMD1168), respectively. We investigated the rHSA-hFGF21 expression levels in three different strains and screened an engineered strain X33-pPIC9K-rHSA-hFGF21 with the highest expression level. To improve the production efficiency of rHSA-hFGF21, we optimized the shake flask fermentation conditions, such as the OD value, methanol concentration and induction time. After purification by hollow fiber membrane separation, Blue affinity chromatography and Q ion exchange chromatography, the purity of the rHSA-hFGF21 protein obtained was 98.18%. Compared to hFGF21, the biostabilities of rHSA-hFGF21, including their resistance to temperature and trypsinization were significantly enhanced, and its plasma half-life was extended by about 27.6 times. Moreover, the fusion protein rHSA-hFGF21 at medium and high concentration showed a better ability to promote glucose uptake after 24 h of stimulation in vitro. In vivo animal studies showed that rHSA-hFGF21 exhibited a better long-term hypoglycemic effect than hFGF21 in type 2 diabetic mice. Our results demonstrated a small-scale production of rHSA-hFGF21, which is important for large-scale production and clinical application in the future.

Characteristics, source apportionment and health risk assessment of heavy metals in urban road dust of the Pearl River Delta, South China.

To investigate the characteristics of heavy metals (As, Cd, Cr, Cu, Pb, Hg, Ni and Zn) in urban road dust from different cities and functional areas in the Pearl River Delta (PRD), South China, a total of 294 dust samples were analyzed. The contamination characteristics and health risk of heavy metals in the dust were assessed, their chemical speciation were distinguished, and their sources were identified by the correlations, cluster and principal component analysis (PCA). The mean concentrations of As (15.89 mg/kg), Cd (1.59 mg/kg), Cr (143.75 mg/kg), Cu (184.42 mg/kg), Pb (114.82 mg/kg), Hg (0.11 mg/kg), Ni (41.53 mg/kg) and Zn (645.94 mg/kg) in urban road dust were in high or moderate levels compare with other previous researches. In this case, the contamination of Cr, Cu, Ni and Zn in the industrial area (IA) and the contamination of Cd and Hg in the commercial area (CA) were significantly higher relative to other functional areas (P < 0.05), and the contamination of heavy metals in Foshan City was significantly higher than other cities (P < 0.01). The order of mobility of the heavy metals with higher concentration in urban road dust of the Pearl River Delta declined in the following order: Zn, Ni, Cu, Pb and Cr. Statistical analysis result showed the contaminated heavy metals in urban road dust were mainly contributed by industrial activities, traffic activities and building pollution. There were no significant carcinogenic and noncarcinogenic risks for adults, children however showed significant noncarcinogenic effect caused by As and Cr in partial points, albeit with low contamination level of the two metals. The ingestion was a principal pathway for heavy metals via urban road dust to exposure population. More protection measures should be considered to reduce children's exposure to the dust, especially in the CA and IA.

Synergetic removal of thallium and antimony from wastewater with jacobsite-biochar-persulfate system.

Both of thallium (Tl) and antimony (Sb) are toxic elements in the natural environment. Emerging Tl and Sb pollution in water has gradually gained public concerns globally. However, limited technologies are available for co-removal of Tl and Sb from wastewater. Herein, an novel system was successfully fabricated to enhance the synergetic removal of both Tl and Sb in wastewater. In this study, MnFe2O4-biochar composite (MFBC) facilely synthesized by a one-pot hydrothermal method was used as adsorbent and persulfate (PS) activator for simultaneously removing Tl and Sb from wastewater. The optimal reaction conditions for best removal efficiency of Tl and Sb simultaneously were obtained by using the response surface design combined with Box-Behnken Design (BBD) model. Results unveiled that the average removal rates of Tl and Sb can achieve 98.33% and 89.14%, respectively under the optimal reaction conditions. Electron Spin Resonance (ESR), and radical quenching experiments showed that OH• and SO4•- play a critical role in the removal of Tl-Sb compound pollution. Via using different characterization, it is revealed that the mechanism of removing Tl-Sb containing wastewater by MFBC-1.4/PS system is oxidation, adsorption, complexation and ion exchange. All these results indicate that MFBC-1.4/PS technology is prospective in highly effective removal of Tl and Sb from wastewater simultaneously.

Thallium and potentially toxic elements distribution in pine needles, tree rings and soils around a pyrite mine and indication for environmental pollution.

In this study, the distributions of thallium (Tl), and other potential toxic elements, such as Cd, Co, Cu, Pb, Sr, As, Cr, Ni, Zn, and Mn in needles, tree rings and soils of pine trees in one of the largest pyrite mining areas in the world, i.e., Yunfu, China were investigated. The results showed that pseudo-total Tl concentration of the tree rings ranged from 0.41 to 2.03 mg/kg (average: 1.12 mg/kg) during the year of 1998 to 2011. This indicates an overall obvious enrichment of Tl. Further investigation of element level variations in the pine needles showed a negative correlation between Tl content and the distance from the mining area. The results of Principal Component Analysis additionally demonstrated that Tl in the tree rings was most likely derived from the pine needles. Notably, Tl contents in the tree rings exhibited generally similar distribution pattern to the annual production intensity of Yunfu pyrite mining activities. The findings suggest that metal(loid)s in particular of Tl in pine tree rings can be used as alternative proxies to approximatively reconstruct the chronological change of atmospheric environmental pollution induced by pyrite associated mining/smelting activities.

Thallium isotopic compositions as tracers in environmental studies: A review.

Thallium is a highly poisonous heavy metal. Since Tl pollution control has been neglected worldwide until the present, countless Tl pollutants have been discharged into the environment, endangering the safety of drinking water, farmland soil, and food chain, and eventually posing a great threat to human health. However, the source, occurrence, pathway and fate of Tl in the environment remains understudied. As Tl in non-contaminated systems and from anthropogenic origin exhibits generally different isotopic signatures, which can provide fingerprint information and a novel way for tracing the anthropogenic Tl sources and understanding the environmental processes. This review summarizes: (i) the state-of-the-art development in highly-precise determination analytical method of Tl isotopic compositions, (ii) Tl isotopic fractionation induced by the low-temperature surface biogeochemical process, (iii) Tl isotopic signature of pollutants derived from anthropogenic activities and isotopic fractionation mechanism of Tl related to the high-temperature industrial activities, and (iv) application of Tl isotopic composition as a new tracer emerging tracer for source apportionment of Tl pollution. Finally, the limitations and possible future research about Tl isotopic application in environmental contamination is also proposed: (1) Tl fractionation mechanism in different environmental geochemistry processes and industrial activities should be further probed comprehensively; (2) Tl isotopes for source apportionment should be further applied in other different high Tl-contaminated scenarios (e.g., agricultural systems, water/sediment, and atmosphere).