Cullin 3 RING E3 ligase inactivation causes NRF2-dependent NADH reductive stress, hepatic lipodystrophy, and systemic insulin resistance.

Cullin RING E3 ligases (CRL) have emerged as key regulators of disease-modifying pathways and therapeutic targets. Cullin3 (Cul3)-containing CRL (CRL3) has been implicated in regulating hepatic insulin and oxidative stress signaling. However, CRL3 function in liver pathophysiology is poorly defined. Here, we report that hepatocyte Cul3 knockout results in rapid resolution of steatosis in obese mice. However, the remarkable resistance of hepatocyte Cul3 knockout mice to developing steatosis does not lead to overall metabolic improvement but causes systemic metabolic disturbances. Liver transcriptomics analysis identifies that CRL3 inactivation causes persistent activation of the nuclear factor erythroid 2-related factor 2 (NRF2) antioxidant defense pathway, which also reprograms the lipid transcriptional network to prevent TG storage. Furthermore, global metabolomics reveals that NRF2 activation induces numerous NAD+-consuming aldehyde dehydrogenases to increase the cellular NADH/NAD+ ratio, a redox imbalance termed NADH reductive stress that inhibits the glycolysis-citrate-lipogenesis axis in Cul3 knockout livers. As a result, this NRF2-induced cellular lipid storage defect promotes hepatic ceramide accumulation, elevates circulating fatty acids, and worsens systemic insulin resistance in a vicious cycle. Hepatic lipid accumulation is restored, and liver injury and hyperglycemia are attenuated when NRF2 activation and NADH reductive stress are abolished in hepatocyte Cul3/Nrf2 double-knockout mice. The resistance to hepatic steatosis, hyperglycemia, and NADH reductive stress are observed in hepatocyte Keap1 knockout mice with NRF2 activation. In summary, our study defines a critical role of CRL3 in hepatic metabolic regulation and demonstrates that the CRL3 downstream NRF2 overactivation causes hepatic metabolic maladaptation to obesity and insulin resistance.

Comparing letrozole and mifepristone pre-treatment in medical management of first trimester missed miscarriage: a prospective open-label non-inferiority randomised controlled trial.

OBJECTIVE: To investigate whether letrozole pre-treatment is non-inferior to mifepristone pre-treatment, followed by misoprostol, for complete evacuation in the medical treatment of first-trimester missed miscarriage. DESIGN: Prospective open-label non-inferiority randomised controlled trial. SETTING: A university-affiliated hospital. POPULATION: We recruited 294 women diagnosed with first-trimester missed miscarriage who opted for medical treatment. METHODS: Participants were randomly assigned to: (i) the mifepristone group, who received 200 mg mifepristone orally followed 24-48 h later by 800 µg misoprostol vaginally; or (ii) the letrozole group, who received 10 mg letrozole orally once-a-day for 3 days, followed by 800 µg misoprostol vaginally on the third (i.e. last) day of letrozole administration. MAIN OUTCOME MEASURES: The primary outcome was the rate of complete evacuation without surgical intervention at 42 days post-treatment. Secondary outcomes included induction-to-expulsion interval, adverse effects, women's satisfaction, number of doses of misoprostol required, duration of vaginal bleeding, pain score on the day of misoprostol administration and other adverse events. RESULTS: The complete evacuation rates were 97.8% (95% CI 95.1%-100%) and 97.2% (95% CI 94.4%-99.9%) in the letrozole and mifepristone groups, respectively (p ≤ 0.001 for non-inferiority). The mean induction-to-tissue expulsion interval in the letrozole group was longer compared with the mifepristone group (15.4 vs 9.0 h) (p = 0.03). The letrozole group had less heavy post-treatment bleeding and an earlier return of menses. There were no statistically significant differences in the number of doses of misoprostol required, the duration of vaginal bleeding, the pain score on the day of misoprostol administration and the rate of other adverse events between the two groups. The majority of the women (91.2% and 93.9% in the letrozole and mifepristone groups, respectively) were satisfied with their treatment option. CONCLUSIONS: Letrozole is non-inferior to mifepristone as a pre-treatment, followed by misoprostol, for the medical treatment of first-trimester missed miscarriage.

Combining ASBT inhibitor and FGF15 treatments enhances therapeutic efficacy against cholangiopathy in female but not male Cyp2c70 KO mice.

Therapeutic reduction of hydrophobic bile acids exposure is considered beneficial in cholestasis. The Cyp2c70 KO mice lack hydrophilic muricholic acids and have a human-like hydrophobic bile acid pool resulting in hepatobiliary injury. This study investigates if combining an apical sodium-dependent bile acid transporter inhibitor GSK2330672 (GSK) and fibroblast growth factor-15 (FGF15) overexpression, via simultaneous inhibition of bile acid synthesis and gut bile acid uptake, achieves enhanced therapeutic efficacy in alleviating hepatobiliary injury in Cyp2c70 KO mice. The effects of GSK, adeno-associated virus (AAV)-FGF15, and the combined treatment on bile acid metabolism and cholangiopathy were compared in Cyp2c70 KO mice. In female Cyp2c70 KO mice with more severe cholangiopathy than male Cyp2c70 KO mice, the combined treatment was more effective in reversing portal inflammation, ductular reaction, and fibrosis than AAV-FGF15, while GSK was largely ineffective. The combined treatment reduced bile acid pool by ∼80% compared to ∼50% reduction by GSK or AAV-FGF15, and enriched tauro-conjugated ursodeoxycholic acid in the bile. Interestingly, the male Cyp2c70 KO mice treated with AAV-FGF15 or GSK showed attenuated cholangiopathy and portal fibrosis but the combined treatment was ineffective despite reducing bile acid pool. Both male and female Cyp2c70 KO mice showed impaired gut barrier integrity. AAV-FGF15 and the combined treatment, but not GSK, reduced gut exposure to lithocholic acid and improved gut barrier function. In conclusion, the combined treatment improved therapeutic efficacy against cholangiopathy than either single treatment in the female but not male Cyp2c70 KO mice by reducing bile acid pool size and hydrophobicity.

Chromium transformation driven by iron redox cycling in basalt-derived paddy soil with high geological background values.

The flooding and drainage of paddy fields has great effects on the transformation of heavy metals, however, the transformation of Cr in basalt-derived paddy soil with high geological background values was less recognized. The typical basalt-derived paddy soil was incubated under alternating redox conditions. The Cr fractions and the dynamics of Fe/N/S/C were examined. The HCl-extractable Cr increased under anaerobic condition and then decreased during aerobic stage. The UV-vis spectra of the supernatant showed that amounts of colloids were released under anaerobic condition, and then re-aggregated during aerobic phase. The scanning transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) revealed that Fe oxides were reduced and became dispersed during anaerobic stage, whereas Fe(II) was oxidized and recrystallized under aerobic condition. Based on these results, a kinetic model was established to further distinguish the relationship between the transformation of Cr and Fe. During anaerobic phase, the reduction of Fe(III) oxides not only directly released the structurally bound Cr, but also enhanced the breakdown of soil aggregation and dissolution of organic matter causing indirect mobilization of Cr. During aerobic phase, the oxidation of Fe(II) and further recrystallization of newly formed Fe(III) oxides might induce the re-aggregation of soil colloids and further incorporation of Cr. In addition, the kinetic model of Cr and Fe transformation was further verified in the pot experiment. The model-based findings demonstrated that the Cr transformation in the basalt-derived paddy soil with high geological background values was highly driven by redox sensitive iron cycling.

ADAM17 mediates ectodomain shedding of the soluble VLDL receptor fragment in the retinal epithelium.

Very low-density lipoprotein receptor (VLDLR) is a multifunctional transmembrane protein. Beyond the function of the full-length VLDLR in lipid transport, the soluble ectodomain of VLDLR (sVLDLR) confers anti-inflammatory and antiangiogenic roles in ocular tissues through inhibition of canonical Wnt signaling. However, it remains unknown how sVLDLR is shed into the extracellular space. In this study, we present the first evidence that a disintegrin and metalloprotease 17 (ADAM17) is responsible for sVLDLR shedding in human retinal pigment epithelium cells using pharmacological and genetic approaches. Among selected proteinase inhibitors, an ADAM17 inhibitor demonstrated the most potent inhibitory effect on sVLDLR shedding. siRNA-mediated knockdown or CRISPR/Cas9-mediated KO of ADAM17 diminished, whereas plasmid-mediated overexpression of ADAM17 promoted sVLDLR shedding. The amount of shed sVLDLR correlated with an inhibitory effect on the Wnt signaling pathway. Consistent with these in vitro findings, intravitreal injection of an ADAM17 inhibitor reduced sVLDLR levels in the extracellular matrix in the mouse retina. In addition, our results demonstrated that ADAM17 cleaved VLDLR only in cells coexpressing these proteins, suggesting that shedding occurs in a cis manner. Moreover, our study demonstrated that aberrant activation of Wnt signaling was associated with decreased sVLDLR levels, along with downregulation of ADAM17 in ocular tissues of an age-related macular degeneration model. Taken together, our observations reveal the mechanism underlying VLDLR cleavage and identify a potential therapeutic target for the treatment of disorders associated with dysregulation of Wnt signaling.

Multiple effects of nitrate amendment on the transport, transformation and bioavailability of antimony in a paddy soil-rice plant system.

Nitrate (NO3-) is known to be actively involved in the processes of mineralization and heavy metal transformation; however, it is unclear whether and how it affects the bioavailability of antimony (Sb) in paddy soils and subsequent Sb accumulation in rice. Here, the effects of NO3- on Sb transformation in soil-rice system were investigated with pot experiments over the entire growth period. Results demonstrated that NO3- reduced Sb accumulation in brown rice by 15.6% compared to that in the control. After amendment with NO3-, the Sb content in rice plants increased initially and then gradually decreased (in roots by 46.1%). During the first 15 days, the soil pH increased, the oxidation of Sb(III) and sulfides was promoted, but the reduction of iron oxide minerals was inhibited, resulting in the release of adsorbed and organic-bound Sb from soil. The microbial arsenite-oxidizing marker gene aoxB played an important role in Sb(III) oxidation. From days 15 to 45, after NO3- was partially consumed, the soil pH decreased, and the reductive dissolution of Fe(III)-bearing minerals was enhanced; consequently, iron oxide-bound Sb was transformed into adsorbed and dissolved Sb species. After day 45, NO3- was completely reduced, Sb(V) was evidently reduced to Sb(III), and green rust was generated gradually. Thus, the available Sb decreased due to its enhanced affinity for iron oxides. Moreover, NO3- inhibited the reductive dissolution of iron minerals, which ultimately caused low Sb availability. Therefore, NO3- can chemically and biologically reduce the Sb availability in paddy soils and alleviate Sb accumulation in rice. This study provides a potential strategy for decreasing Sb accumulation in rice in the Sb-contaminated sites.

Canonical Wnt Signaling Promotes Neovascularization Through Determination of Endothelial Progenitor Cell Fate via Metabolic Profile Regulation.

Endothelial progenitor cells (EPCs) contribute to blood vessel formation. Canonical Wnt signaling plays an important role in physiological and pathological angiogenesis and EPC fate regulation. However, the mechanism for Wnt signaling to regulate EPC fate in neovascularization (NV) has not been clearly defined. Here, we showed that very low-density lipoprotein receptor knockout (Vldlr -/- ) mice, a model of ocular NV induced by Wnt signaling overactivation, have increased EPC numbers in the bone marrow, blood, and retina, as well as an elevated mitochondrial membrane potential indicating higher mitochondrial function of EPCs in the circulation. Isolated EPCs from Vldlr -/- mice showed overactivated Wnt signaling, correlating with increased mitochondrial function, mass, and DNA copy numbers, compared with WT EPCs. Our results also demonstrated that Wnt signaling upregulated mitochondrial biogenesis and function, while inhibiting glycolysis in EPCs, which further decreased EPC stemness and promoted EPCs to a more active state toward differentiation, which may contribute to pathologic vascular formation. Fenofibric acid, an active metabolite of fenofibrate, inhibited Wnt signaling and mitochondrial function in EPCs and decreased EPC numbers in Vldlr -/- mice. It also decreased mitochondrial biogenesis and reactive oxygen species production in Vldlr -/- EPCs, which may be responsible for its therapeutic effect on diabetic retinopathy. These findings demonstrated that Wnt signaling regulates EPC fate through metabolism, suggesting potential application of the EPC metabolic profile as predictor and therapeutic target for neovascular diseases. Stem Cells 2019;37:1331-1343.

Fenofibrate-Loaded Biodegradable Nanoparticles for the Treatment of Experimental Diabetic Retinopathy and Neovascular Age-Related Macular Degeneration.

Fenofibrate is a peroxisome proliferator-activated receptor α (PPARα) agonist and has been shown to have therapeutic effects on diabetic retinopathy (DR). However, the effects of fenofibrate through systemic administration are not as potent as desired due to inefficient drug delivery to the retina. The present study aimed to explore the sustained therapeutic effects of fenofibrate-loaded biodegradable nanoparticles (NP) on both DR and neovascular age-related macular degeneration (AMD). Fenofibrate was successfully encapsulated into poly(lactic- co-glycolic acid) (PLGA) NP (Feno-NP), and Feno-NP were optimized by varying polymer composition to achieve high drug loading and prolonged drug release. The Feno-NP made of PLGA 34 kDa demonstrated a drug content of 6% w/w and a sustained drug release up to 60 days in vitro. Feno-NP (PLGA 34 kDa) was selected for following in vivo studies, and one single intravitreal (IVT) injection of Feno-NP into rat eyes with a 30G fine needle maintained sustained fenofibric acid drug level in the eye for more than 60 days. The efficacy of Feno-NP in DR and neovascular AMD was investigated using streptozotocin (STZ)-induced diabetic rats, laser-induced choroidal neovascularization (CNV) rats, and very low-density lipoprotein receptor knockout ( Vldlr -/-) mice. Therapeutic effects of Feno-NP were evaluated by measuring electroretinogram (ERG), retinal vascular leakage, leukostasis, CNV size, and retinal levels of vascular endothelial growth factor (VEGF) and intracellular adhesion molecule-1 (ICAM-1). In diabetic rats, Feno-NP ameliorated retinal dysfunctions, reduced retinal vascular leakage, inhibited retinal leukostasis, and downregulated the overexpression of VEGF and ICAM-1 at 8 weeks after one IVT injection. In addition, Feno-NP reduced retinal vascular leakage and CNV formation in both CNV rats and Vldlr -/- mice. Moreover, no toxicity of Feno-NP or Blank-NP to retinal structure and function was detected. Feno-NP exhibited good physiochemical characteristics and controlled drug release profile, conferring prolonged beneficial effects on DR and neovascular AMD.

Morphological Redescription and Molecular Identification of Trichodina reticulata Hirschmann & Partsch, 1955 (Ciliophora, Mobilida, Trichodinidae) with the Supplemental New Data of SSU rDNA and ITS-5.8S rDNA.

During a survey of trichodinids in Chongqing, China, two populations of Trichodina reticulata Hirschmann & Partsch, 1955 were isolated from gills of the freshwater fishes, Carassius auratus and Ctenopharyngodon idellus, and 11 molecular samples containing small subunit (SSU) rDNA and internal transcribed spacer (ITS)-5.8S rDNA were newly sequenced. Both populations fell within the range of morphometry and corresponded well with the diagnostic morphological features of Trichodina reticulata Hirschmann & Partsch, 1955. It should be noted that one population possessed obvious central granules in the adhesive disc, while the other one did not. The detailed morphological redescription for these two populations is given in this work. Although some intraspecific differences were found, both populations were confirmed as Trichodina reticulata based on the morphological study and molecular data, including the sequence analysis of the primary and secondary structures of SSU rDNA, genetic distances and phylogenetic tree. Our study supports the assertion that central granules in the adhesive disc might be an auxiliary feature rather than a heritable character for determining taxonomic affiliations among trichodinids.

A New Molecular Approach Based on the Secondary Structure of Ribosomal RNA for Phylogenetic Analysis of Mobilid Ciliates.

We analyzed the secondary structure of the small subunit (SSU) rRNA genes of Mobilida (Ciliophora, Peritrichia) and found that the secondary structures of some regions within the SSU-rRNA gene are distinct between the families Trichodinidae and Urceolariidae. Therefore, some of these important regions including H10, H11, H17, H47, H29, H30, H37, E10-1, H45-H46, and V4 (E23-4, E23-7) could be used as the barcodes for classification of these two families. In contrast, V4 (E23-1, E23-2) belongs to a hypervariable region and is not a good barcode at the genus level because of its great inter-specific variation. Our results indicated that the comprehensive analysis of the secondary structure of SSU-rRNA genes is a reliable auxiliary approach for phylogenic study of mobilid ciliates. It was further found that the coevolution between hosts or habitats and the Mobilida ciliates was existent, because the host types and their habitats were critical ecological factors that influenced the evolution of Mobilida ciliates.

[Progress in Application of Two-Dimensional Correlation Spectroscopy for Detection of Food Quality].

In recent years, the food safety and quality has always been a serious issue. Therefore, it is urgent to develop a rapid and widely available method to determine the quality of food. Due to high spectral resolution, good spectral selectivity and good ability of spectrogram analysis, the technology of two-dimensional (2D) correlation spectroscopy is an effective method for solving three major problems encountered by the conventional one-dimensional (1D) spectrum: low selectivity of the spectra, difficulty in extracting the information of the spectral feature and difficulty in spectrogram analysis. Therefore, 2D correlation spectroscopy, which is suited to distinguish similar samples hardly distinguished by the conventional 1D spectroscopy, has been successfully applied in many complex biological systems. The developmental process, the experimental way to obtain spectrum, the fundamental mathematical principle and the properties of 2D correlation spectroscopy were introduced in this paper. At the same time, it is pointed out that the origin of weak characteristic bands of substance can be verified in terms of the positive or negative corss peaks in synchronous 2D correlation spectrum combined with the existence or inexistence of corss peaks in asynchronous 2D correlation spectrum. The application of 2D near-infrared, mid-infrared, fluorescence, and raman correlation spectroscopy in the detection of food quality and adulteration, concentrated specifically on diary product, wine, oil, meat, honey, and rice were reviewed. Finally, the limitations and future development prospects were pointed out.

[Discrimination of adulterated milk based on Euclidian distances between two-dimensional infrared correlation spectra].

Based on Euclidian distances between synchronous two-dimensional infrared correlation spectra, in terms of the average Euclidian distances between unknown samples and "extreme samples", and average intra- and inter-Euclidian distances of samples in the calibration set, a new method for the discrimination of adulterated milk was proposed. Sixteen pure milk samples were collected and 16 adulterated milk samples with urea (0.01-0.3 g x L(-1)), and 16 adulterated milk samples with melamine (0.01-0.3 g x L(-1)) samples were prepared, respectively. The IR absorption spectra of all samples were measured at room temperature. The synchronous two-dimensional correlation spectra were generated from concentration-dependent spectral variation of adulterant in milk. The Euclidian distances were calculated between synchronous two-dimensional infrared correlation spectra of all samples. Then, the classification models were built respectively for adulterated milk with urea, and adiulterated milk with melamine. The "extreme samples", average intra- and inter-Euclidian distances were determined. Finally, the unknown samples in prediction set were predicted using constructed models in terms of classification rules of adulterated milk. The classification accuracy rates for pure milk and adulterated milk were 100%. The effectiveness of the proposed method was verified. The results obtained in this study revealed that synchronous two-dimensional infrared correlation spectra in combination with Euclidian distance has a feasible potential to discriminate adulterated milk and pure milk.

Pulmonary endometriosis presenting as multiple nodules and pseudocavities.

Pulmonary endometriosis is a rare disease of uncertain pathogenesis which generally presents with the cyclic clinical symptoms and catamenial changes noticed on computer tomography during menstruation. We report a case of a 33-year-old woman with recurrent hemoptysis for 1 year. The patient did not exhibit a temporal relationship between her periods and the onset of hemoptysis. A chest computed tomography scan showed multiple pseudocavities in the lower lobe of the right lung and multiple nodules in both lower lobes of the lungs. The right lower lobe wedge resection was performed. Postoperative pathological examination showed pulmonary endometriosis which is a rare cause of hemoptysis.

Integration with carbon capture technology enables a positive carbon balance for sustainable rice paddy remediation with calcium­silicon composites.

In situ stabilization technologies based on lime-derived materials are extensively used for remediating Cd-contaminated paddy soils. However, the environmental impacts and carbon budget associated with these technologies throughout the paddy soil remediation life cycle are gaining increasing attention. Herein, through paddy field trials, two representative lime-derived materials, quicklime and calcium-silicon composite (Ca/Si), are evaluated for their remediation effectiveness and environmental sustainability in the remediation of Cd-contaminated soils. The results demonstrate that both quicklime and Ca/Si can reduce Cd bioavailability and enable the safe use of rice grain. Nevertheless, the life cycle assessment score of the quicklime case is 4.4 times that of the Ca/Si case, indicating that the quicklime case has a greater negative impact on the environment. Furthermore, the net ecosystem carbon budget analysis reveals that both lime-derived materials exhibit outward carbon emissions throughout their life cycle, in which the carbon emission of the quicklime case (-20.2 t CO2-eq/ha) is 20 times that of the Ca/Si case (-1 t CO2-eq/ha). Moreover, the implementation of carbon capture technology results in the Ca/Si case achieving a positive carbon budget and contributing to a carbon neutrality plan. Conversely, the quicklime case falls short, affording only a 24.8 % reduction in carbon emissions. Overall, this study provides valuable insights into the environmental sustainability of different lime-derived materials for paddy soil remediation and carbon mitigation.

Deletion of hepatocyte cysteine dioxygenase type 1, a bile acid repressed gene, enhances glutathione synthesis and ameliorates acetaminophen hepatotoxicity.

Liver is a major organ that metabolizes sulfur amino acids cysteine, which is the substrate for the synthesis of many essential cellular molecules including GSH, taurine, and coenzyme A. Bile acid-activated farnesoid x receptor (FXR) inhibits cysteine dioxygenase type 1 (CDO1), which mediates hepatic cysteine catabolism and taurine synthesis. To define the impact of bile acid inhibition of CDO1 on hepatic sulfur amino acid metabolism and antioxidant capacity, we developed hepatocyte-specific CDO1 knockout mice (Hep-CDO1 KO) and hepatocyte specific CDO1 transgenic mice (Hep-CDO1 Tg). Liver metabolomics revealed that genetic deletion of hepatic CDO1 reduced de novo taurine synthesis but had no impact on hepatic taurine abundance or bile acid conjugation. Consistent with reduced cysteine catabolism, Hep-CDO1 KO mice showed increased hepatic cysteine abundance but unaltered methionine cycle intermediates and coenzyme A synthesis. Upon acetaminophen overdose, Hep-CDO1 KO mice showed increased GSH synthesis capacity and alleviated liver injury. In contrast, hepatic CDO1 overexpression in Hep-CDO1 Tg mice stimulated hepatic cysteine to taurine conversion, resulting in reduced hepatic cysteine abundance. However, Hep-CDO1 Tg mice and WT showed similar susceptibility to acetaminophen-induced liver injury. Hep-CDO1 Tg mice showed similar hepatic taurine and coenzyme A compared to WT mice. In summary, these findings suggest that bile acid and FXR signaling inhibition of CDO1-mediated hepatic cysteine catabolism preferentially modulates hepatic GSH synthesis capacity and antioxidant defense, but has minimal effect on hepatic taurine and coenzyme A abundance. Repression of hepatic CDO1 may contribute to the hepatoprotective effects of FXR activation under certain pathologic conditions.

Glycine-ß-Muricholic Acid Improves Liver Fibrosis and Gut Barrier Function by Reducing Bile Acid Pool Size and Hydrophobicity in Male Cyp2c70 Knockout Mice.

Cyp2c70 knockout mice lack the enzyme that produces muricholic acids and show a "human-like" hydrophobic bile acid pool-induced hepatobiliary injury. In this study, we investigated the potential anti-cholestasis effect of glycine-conjugated ß muricholic acid (G-ß-MCA) in male Cyp2c70 KO mice based on its hydrophilic physiochemical property and signaling property as an farnesoid X receptor (FXR) antagonist. Our results showed that G-ß-MCA treatment for 5 weeks alleviated ductular reaction and liver fibrosis and improved gut barrier function. Analysis of bile acid metabolism suggested that exogenously administered G-ß-MCA was poorly absorbed in the small intestine and mostly deconjugated in the large intestine and converted to taurine-conjugated MCA (T-MCA) in the liver, leading to T-MCA enrichment in the bile and small intestine. These changes decreased the biliary and intestine bile acid hydrophobicity index. Furthermore, G-ß-MCA treatment decreased intestine bile acid absorption via unknown mechanisms, resulting in increased fecal bile acid excretion and a reduction in total bile acid pool size. In conclusion, G-ß-MCA treatment reduces the bile acid pool size and hydrophobicity and improves liver fibrosis and gut barrier function in Cyp2c70 KO mice.

Insight into universality and characteristics of nitrate reduction coupled with arsenic oxidation in different paddy soils.

Nitrate reduction coupled with arsenic (As) oxidation strongly influences the bioavailability and toxicity of As in anaerobic environments. In the present study, five representative paddy soils developed from different parent materials were used to investigate the universality and characteristics of nitrate reduction coupled with As oxidation in paddy soils. Experimental results indicated that 99.8 % of highly toxic aqueous As(III) was transformed to dissolved As(V) and Fe-bound As(V) in the presence of nitrate within 2-8 d, suggesting that As was apt to be reserved in its low-toxic and nonlabile form after nitrate treatment. Furthermore, nitrate additions also significantly induced the higher abundance of 16S rRNA and As(III) oxidase (aioA) genes in the five paddy soils, especially in the soils developed from purple sand-earth rock and quaternary red clay, which increased by 10 and 3-5 times, respectively, after nitrate was added. Moreover, a variety of putative novel nitrate-dependent As(III)-oxidizing bacteria were identified based on metagenomic analysis, mainly including Aromatoleum, Paenibacillus, Microvirga, Herbaspirillum, Bradyrhizobium, Azospirillum. Overall, all these findings indicate that nitrate reduction coupled with As(III) oxidation is an important nitrogen-As coupling process prevalent in paddy environments and emphasize the significance of developing and popularizing nitrate-based biotechnology to control As pollution in paddy soils and reduce the risk of As compromising food security.

Distinct arsenic uptake feature in rice reveals the importance of N fertilization strategies.

The environmental behavior of arsenic (As) is commonly affected by the biogeochemical processes of iron (Fe) and nitrogen (N). In this study, field experiments were conducted to explore As uptake in rice and As translation and distribution in As-contaminated iron-rich paddy soils after applying different forms of N fertilizers, including urea (CO(NH2)2), ammonium bicarbonate (NH4HCO3), nitrate of potash (KNO3), and ammonium bicarbonate + nitrate of potash (NH4HCO3 + KNO3). The results indicated that applying nitrate N fertilizer inhibited the reduction and dissolution of As-bearing iron minerals and promoted microbial-mediated As(III) oxidation in flooded soil, thus reducing the soil As bioavailability. The concentrations of total As and inorganic As ratio (iAs/TAs) in rice grain decreased by 32.4 % and 15.4 %, respectively. However, the application of ammonium nitrogen promoted the reductive dissolution of As-bearing iron minerals and stimulated microbial As(V) reduction in flooded soil, leading to the release of As from soil to porewater. The total As concentration and inorganic As uptake ratio in rice grain increased by 20.1 % and 6.2 %, respectively, when urea was applied, and by 29.6 % and 10.5 %, respectively, when ammonium bicarbonate was applied. However, the simultaneous application of NH4+ and NO3- had no significant effect on As concentration in rice grain and its transformation in paddy soils. Ammonium nitrogen enhanced the organic As concentration in rice grain because the increased As(III) promoted As methylation in soil. In contrast, nitrate decreased the organic As uptake by rice grain because the decreased As(III) diminished As methylation in soil. The results provide reasonable N fertilization strategies for regulating the As biogeochemical process and reducing the risk of As contamination in rice.

Transformation kinetics of exogenous nickel in a paddy soil during anoxic-oxic alteration: Roles of organic matter and iron oxides.

Nickel is generally released from flooded soils; however, the key Ni transformation processes in soils that are freshly contaminated by Ni2+ during anoxic-oxic alteration remain unclear. We developed a kinetic model to investigate the Ni transformation in paddy soils under anoxic and oxic conditions based on the results of the seven-step sequential extraction, determination of dissolved and soil organic matter, and surface site quantification, which provide the kinetic data of different Ni fractions, organic matter, and reactive sites for modeling. The dissolved, exchangeable, and specifically adsorbed Ni was gradually transferred to fulvic complex, humic complex, Fe-Mn oxide bound, and sulfide bound Ni after 40 d of anoxic incubation due to the increase in pH and soil surface sites, which were mainly induced by Fe(III) oxide reduction and soil organic matter release. The introduction of oxygen triggered a rapid release of Ni, which was ascribed to the decrease in pH and soil surface sites caused by Fe(II) oxidation and carbon re-immobilization. Kinetic modeling demonstrated that complexation with soil organic matter dominated Ni immobilization under anoxic conditions, while organic matter and Fe-Mn oxides contributed similarly to Ni release under oxic conditions, although the majority of Ni remained complexed with soil organic matter. These findings are important for the evaluation and prediction of Ni behavior in paddy soils with exogenous Ni during flooding-drainage practices.

Dark Side of Ammonium Nitrogen in Paddy Soil with Low Organic Matter: Stimulation of Microbial As(V) Reduction and As(III) Transfer from Soil to Rice Grains.

The bioavailability of arsenic (As) is influenced by ammonium (NH4+-N) fertilization, but the underlying mechanisms controlling As transformation in soil-rice systems are still not fully understood. The effects of two NH4+-N fertilizers, urea and NH4HCO3, on the transformation of As in a paddy soil with low organic matter content and transfer in rice plants were investigated. Treatments with urea and NH4HCO3 significantly increased arsenite (As(III)) concentration in porewater, bioavailable As in rhizosphere soil, and the relative abundance of the As(V) respiratory reductase gene (arrA) and As(III) methyltransferase gene (arsM). Furthermore, the relative expression of As transporter genes in rice roots, such as OsLsi1, OsLsi2, and OsLsi3, was upregulated, and the translocation efficiency of As(III) from rice roots to brown rice was promoted. Subsequently, As(III) accumulation in brown rice significantly increased. Therefore, attention should be paid to As-contaminated paddy fields with NH4+-N fertilization.