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.

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.

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.

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.

The recombinant Newcastle disease virus Anhinga strain expressing human TRAIL exhibit antitumor effects on a glioma nude mice model.

Oncolytic virus therapy is perhaps the next major breakthrough in cancer treatment following the success in immunotherapy using immune checkpoint inhibitors. However, the potential oncolytic ability of the recombinant newcastle disease virus (NDV) Anhinga strain carried with tumor necrosis factor-related apoptosis inducing ligand (TRAIL) has not been fully explored at present. In the present study, the recombinant NDV/Anh-TRAIL that secretes soluble TRAIL was constructed and the experiment results suggested NDV/Anh-TRAIL as a promising candidate for glioma therapy. Growth kinetic and TRAIL secreted quantity of recombinant NDV/Anh-TRAIL virus were measured. Cytotoxic and cell apoptosis were analyzed for its anti-glioma therapy in vitro. Nude mice were used for the in vivo evaluation. Both tumor volume and mice behavior after injection were observed. The recombinant virus replicated with the same kinetics as the parental virus and the highest expression of TRAIL (77.8 ng/L) was found at 48 hours. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a tetrazole and flow cytometry data revealed that the recombinant NDV/Anh-TRAIL (56.1 ± 8.2%) virus could induce a more severe apoptosis rate, when compared with the NDV wild type (37.2 ± 7.0%) and mock (7.0 ± 1.8%) groups (P < .01), in U251 cells. Furthermore, in the present animal study, the average tumor volume was smaller in the NDV/Anh-TRAIL group (97.21 mm3 ), when compared with the NDV wild type (205.03 mm3 , P < .05) and PBS (310.30 mm3 , P < .01) groups.

Effects of tillage management on soil carbon decomposition and its relationship with soil chemistry properties in rice paddy fields.

Decreasing the soil organic carbon (SOC) decomposition is critical to improve the quality of the soil and mitigate atmospheric CO2 emissions. To improve the ability to protect the SOC by optimizing tillage management, this study investigated the laboratory-based SOC mineralization (decomposition) and soil chemical properties under different tillage practices, including no tillage with straw mulch (NTS), rotary tillage with straw incorporated (RTS), moldboard plow tillage with straw incorporated (CTS) and moldboard plow tillage with straw removal (CT). Soil samples of six sampling dates from April 2017 to October 2018 were incubated at 25 °C and 70% water holding capacity for 60 d. Repeated Variance Analyses were conducted to compare the means of different treatments. The results showed that the average cumulative SOC mineralization (Cm) at the 0-5 cm soil depth was 7.09 g CO2 kg-1 soil under NTS, which was higher (P < 0.05) than that of the other treatments. However, the C mineralizability at both the 0-5 and 5-10 cm soil depths were lower (P < 0.05) under the NTS (0.16 and 0.15 g CO2 g-1 SOC) compared with the CTS and CT. Non-microbial CO2 emissions (CO2 emissions in sterilized soil) contributed to the lower C mineralizability under NTS, due to the lower mineralizability (0.041-0.089 g CO2 g-1 SOC) of sterilized soil under this treatment. Furthermore, some of the abiotic factors (e.g., C/N ratio and SOC content) significantly correlated with the Cm and C mineralizability. These factors might be critical for the ability to protect SOC under NTS. In summary, conservation tillage is an optimal management due to its protection on SOC, and part of this protection appeared to have been contributed by the soil abiotic factors, which were formed by long-term tillage management.

Dynamics in soil organic carbon of wheat-maize dominant cropping system in the North China Plain under tillage and residue management.

A site experiment was conducted to assess temporal dynamics of soil organic carbon (SOC) and the drivers under no-tillage (NT) and residue retention (RR) in the North China Plain (NCP). The results indicated that NT and RR can significantly increase SOC up to a depth of 30 cm. On average, NT increased SOC by 8.1-34.5% compared with PT, and RR increased SOC by 3.5-14.4% compared with R0 at 0-10 cm. Increases in SOC under NT or RR could be increased by 4-10 percentage points through the significantly positive interactions of NT and RR. Among the sources of SOC variations, tillage-induced variations accounted for 74.4 and 44.3% of the total variations in SOC at 0-5 cm for wheat and maize season, respectively. Experimental duration was also a significant source of variation. Stepwise regression indicated dynamics in SOC at 0-5 cm mainly due to the positive effects of precipitation, the negative effects of soil bulk density for the wheat season, the negative effects of radiation for the maize season, and antagonistic effects of temperature between wheat and maize season. Generally, positive effects of NT and RR on SOC were both confirmed, but fluctuations and variations induced by interactions of practices and seasonal climatic conditions were also significant in the NCP.

Improving the specific antitumor efficacy of ONC by fusion with N-terminal domain of transferrin.

Onconase (ONC) as a novel anti-tumor drug has a significant killing effect on a variety of tumor cells. Drug delivery system mediated by transferrin (TF) and TF receptor (TfR), which can significantly increase the amount of drug uptake in the tumor cells, enhance the initiative target efficiency of drugs and reduce its toxic side effects. It has been widely used in drug delivery and clinical trials. In this study, the rONC-TFn was expressed in Escherichia coli by linking ONC with the N-terminal domain of TF (TFn). ELISA and competitive binding analysis demonstrated that rONC-TFn can bind to TfR. The rONC-TFn protein showed much higher cytotoxicity to the cultured HepG2 and Hela cells than rONC. These results suggested that the N-terminal domain protein of TF promoted the tumor targeting of ONC, and thus the rONC-TFn fusion protein may be further developed as a potential targeted anti-tumor drug.

FGF21 ameliorates nonalcoholic fatty liver disease by inducing autophagy.

The aim of this study is to evaluate the role of fibroblast growth factor 21 (FGF21) in nonalcoholic fatty liver disease (NAFLD) and seek to determine if its therapeutic effect is through induction of autophagy. In this research, Monosodium L-glutamate (MSG)-induced obese mice or normal lean mice were treated with vehicle, Fenofibrate, and recombinant murine FGF21, respectively. After 5 weeks of treatment, metabolic parameters including body weight, blood glucose and lipid levels, hepatic and fat gene expression levels were monitored and analyzed. Also, fat-loaded HepG2 cells were treated with vehicle or recombinant murine FGF21. The expression levels of proteins associated with autophagy were detected by western blot, real-time PCR, and transmission electron microscopy (TEM). Autophagic flux was monitored by laser confocal microscopy and western blot. Results showed that FGF21 significantly reduced body weight (P < 0.01) and serum triglyceride, improved insulin sensitivity, and reversed hepatic steatosis in the MSG model mice. In addition, FGF21 significantly increased the expression of several proteins related to autophagy both in MSG mice and fat-loaded HepG2 cells, such as microtubule associated protein 1 light chain 3, Bcl-2-interacting myosin-like coiled-coil protein-1 (Beclin-1), and autophagy-related gene 5. Furthermore, the evidence of TEM revealed an increased number of autophagosomes and lysosomes in the model cells treated with FGF21. In vitro experimental results also showed that FGF21 remarkably increased autophagic flux. Taken together, FGF21 corrects multiple metabolic parameters on NAFLD in vitro and in vivo by inducing autophagy.

Recombinant Newcastle disease virus (NDV/Anh-IL-2) expressing human IL-2 as a potential candidate for suppresses growth of hepatoma therapy.

Newcastle disease virus (NDV) have shown oncolytic therapeutic efficacy in preclinical study and are currently approved for clinical trials. NDV Anhinga strain which is a mesogenic strain should be classified as lytic strain and has a therapeutic efficacy in hepatocellular cancer. In this study, we evaluated the capacity of NDV Anhinga strain to elicit immune reaction in vivo and the possibility for using as a vaccine vector for expressing tumor therapeutic factors. Interleukin-2 (IL-2) could boost the immune response against the tumor cells. Therefore, we use NDV Anhinga strain as backbone to construct a recombinant virus (NDV/Anh-IL-2) expressing IL-2. The virus growth curve showed that the production of recombinant NDV/Anh-IL-2 was slightly delayed compared to the wild type. The NDV/Anh-IL-2 strain could express soluble IL-2 and effectively inhibit the growth of hepatocellular carcinoma in vivo. 60 days post-treatment, mice which were completely cured by previous treatment were well protected when rechallenged with the same tumor cell. From the H&E-stained sections, intense infiltration of lymphocyte was observed in the NDV Anhinga strain treated group, especially in NDV/Anh-IL-2 group. The NDV Anhinga strain could not only kill the tumor directly, but could also elicit immune reaction and a potent immunological memory when killing tumor in vivo. In conclusion, the Anhinga strain could be an effective vector for tumor therapy; the recombinant NDV/Anh-IL-2 strain expressing soluble IL-2 is a promising candidate for hepatoma therapy.

Concentrations, spatial distribution, and risk assessment of soil heavy metals in a Zn-Pb mine district in southern China.

China is one of the largest producers and consumers of lead and zinc in the world. Lead and zinc mining and smelting can release hazardous heavy metals such as Cd, Pb, Zn, and As into soils, exerting health risks to human by chronic exposure. The concentrations of Cd, Zn, Pb, and As in soil samples collected from a Pb-Zn mining area with exploitation history of 60 years were investigated. Health risks of the heavy metals in soil were evaluated using US Environmental Protection Agency (US EPA) recommended method. A geo-statistical technique (Kriging) was used for the interpolation of heavy metals pollution and Hazard Index (HI). The results indicated that the long-term Pb/Zn mining activities caused the serious pollution in the local soil. The concentrations of Cd, As, Pb, and Zn in topsoil were 40.3 ± 6.3, 103.7 ± 37.3, 3518.4 ± 896.1, and 10,413 ± 2973.2 mg/kg dry weight, respectively. The spatial distribution of the four metals possessed similar patterns, with higher concentrations around Aayiken (AYK), Maseka (MSK), and Kuangshan (KS) area and more rapidly dropped concentrations at upwind direction than those at downwind direction. The main pollutions of Cd and Zn were found in the upper 60 cm, the Pb was found in the upper 40 cm, and the As was in the upper 20 cm. The mobility of metals in soil profile of study area was classed as Cd > Zn â‰« Pb > As. Results indicated that there was a higher health risk (child higher than adult) in the study area. Pb contributed to the highest Hazard Quotient (57.0 ~ 73.9 %) for the Hazard Index.

[Therapeutic efficacy of three bispecific antibodies on rheumatoid arthritis mice models].

In order to obtain the lead compound for treatment of rheumatoid arthritis (RA), in this study, therapeutic efficacy of three bispecific antibodies (BsAB-1, BsAB-2 and BsAB-3) against both hIL-1beta and hIL-17 were compared on CIA model mice. First, by ELISA method we compared the binding capacity of the three bispecific antibodies to the two antigens. The results showed that all three antibodies could simultaneously bind both antigens, among these antibodies, BsAB-1 was superior over BsAB-2 and BsAB-3. CIA model was established with chicken type II collagen (CII) and developed RA-like symptoms such as ankle swelling, skin tight, hind foot skin hyperemia. The CIA mice were treated with three antibodies once every two days for total of 29 days. Compared with the CIA model mice, the RA-like symptoms of the antibody treated-mice significantly relieved, while the BsAB-1 treated-mice were almost recovered. CII antibody level in the serum and cytokines (IL-2, IL-1beta, IL-17A and TNF-alpha) expression in the spleen were examined. Compared with the CIA model mice, all three antibodies could significantly reduce CII antibody and cytokine expression levels. BsAB-1 antibody was more potent than BsAB-2 and BsAB-3. In summary, BsAB-1 is superior over BsAB-2 and BsAB-3 in amelioration of RA symptoms and regulation of CII antibody production and pro-inflammatory cytokine expression, therefore, BsAB-1 can be chosen as a lead compound for further development of drug candidate for treatment of RA.

Effects of 3-year organic farming management on soil antibiotic resistant genes and virulence factors in a double rice cropping system.

Investigating the antibiotic resistance genes (ARGs) and virulence factors (VFs) within soil microbial communities is crucial for understanding microbial ecology and the evolution of antibiotic resistance. However, the study of ARGs, VFs, and their predominant microbial hosts in soils under varying rice production management practices remains largely underexplored. To this end, a three-year field experiment was conducted under organic management within a double rice cropping system in South China. The study revealed that, in contrast to conventional management (CK), organic farming practices did not significantly alter the total reads of ARGs and VFs. However, there was a notable alteration in the ARGs abundance at the antibiotic class level, such as an increase (P < 0.05) in the abundance of Multidrug ARGs (by 1.7 %) and a decrease (P < 0.05) in Rifamycin (by 17.5 %) and Fosfomycin ARGs (by 15.3 %). Furthermore, a significant shift in VFs was observed under organic farming compared to CK, characterized by an increase (P < 0.05) in offensive VFs and a decrease (P < 0.05) in nonspecific VFs and the regulation of virulence-associated genes. Key microbial taxa identified as influencing ARGs and VFs in the tested soil samples, e.g., Proteobacteria. The findings highlight the need for more detailed attention to soil ecology within organic rice production systems in South China, particularly concerning the significant alterations observed in ARGs and VFs.

Fibroblast growth factor 21 alleviates idiopathic pulmonary fibrosis by inhibiting PI3K-AKT-mTOR signaling and stimulating autophagy.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive pulmonary disease with an unclear pathogenesis and no available specific drug treatment. The principal etiological factors are lung inflammation caused by environmental factors, damage to alveolar epithelial cells, leading to epithelial-mesenchymal transition (EMT), and the abnormal proliferation of fibroblasts. Here, we have demonstrated that fibroblast growth factor 21 (FGF21) ameliorates IPF via the autophagy pathway. We administered FGF21 to bleomycin (BLM)-treated mice, which ameliorated their defects in lung function, reduced the accumulation of collagen, restored tissue structure, reduced the deposition of hydroxyproline, reduced the expression of collagen I and α-SMA and increased the expression of E-cadherin. The expression of LC3BII and the number of autophagosomes were significantly higher in the lungs. The expression of AKT and mTOR was significantly reduced by FGF21 treatment. We also determined the effects of FGF21 in A549 cells treated with TGF-ß, and found that FGF21 significantly inhibits activation of the AKT signaling pathway, thereby reducing TGF-ß-induced EMT and preventing the uncontrolled proliferation of fibroblasts. We conclude that FGF21 ameliorates IPF by inhibiting the PI3K-AKT-mTOR signaling pathway and activating autophagy, which provides a theoretical basis for FGF21 to be used for the treatment of IPF.

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.

Atmosphere-dependent combustion of Ganoderma lucidum biomass toward its enhanced transformability into green energy.

Globally, the circular efficiency of biomass resources has become a priority due to the depletion and negative environmental impacts of fossil fuels. This study aimed to quantify the atmosphere-dependent combustion of Ganoderma lucidum (GL) biomass and its thermodynamic and kinetic parameters toward enhancing its circularity and transformability characteristics. The GL combustion occurred in the three stages of moisture removal, volatile release, and coke combustion. Combustion performance characteristics were more favorable in the N2/O2 atmosphere than in the CO2/O2 atmosphere under the same heating rates. The rising heating rate facilitated the release of volatiles. According to the model-free methods of Ozawa-Flynn-Wall and Kissinger-Akahira-Sunose, the activation energies essential for the primary reaction were 283.09 kJ/mol and 288.28 kJ/mol in the N2/O2 atmosphere and 233.09 kJ/mol and 235.64 kJ/mol in the CO2/O2 atmosphere. The gaseous products of the GL combustion included CH4, H2O, C = O, CO, CO2, NH3, C = C, and C-O(H). Ash prepared in both atmospheres exhibited a tendency for slag formation, with oxy-fuel combustion lowering its risk. This study thus provides a theoretical and practical basis for transforming GL residues into a sustainable energy source.

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.

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.