Hepatitis E virus causes apoptosis of ovarian cells in hens and resulting in a decrease in egg production.

Previous studies have shown that avian hepatitis E virus (HEV) decreases egg production by 10-40% in laying hens, but have not fully elucidated the mechanism of there. In this study, we evaluated the replication of avian HEV in the ovaries of laying hens and the mechanism underlying the decrease in egg production. Forty 150-days-old commercial laying hens were randomly divided into 2 groups of 20 hens each. A total of 1 mL (104GE) of avian HEV stock was inoculated intravenously into each chicken in the experimental group, with 20 chickens in the other group serving as negative controls. Five chickens from each group were necropsied weekly for histopathological examination. The pathogenicity of avian HEV has been characterized by seroconversion, viremia, fecal virus shedding, ovarian lesions, and decreased egg production. Both positive and negative-strand avian HEV RNA, and ORF2 antigens can be detected in the ovaries, suggesting that avian HEV can replicate in the ovaries and serve as an important extrahepatic replication site. The ovaries of laying hens underwent apoptosis after avian HEV infection. These results indicate that avian HEV infection and replication in ovarian tissues cause structural damage to the cells, leading to decreased egg production.

Impact of nanodroplets on cone-textured surfaces.

Molecular dynamics simulations have been performed to study the dynamics of nanodroplets impacting on a flat superhydrophobic surface and surfaces covered with nanocone structures. We present a panorama of nanodroplet behaviors for a wide range of impact velocities and different cone geometrics, and develop a model to predict whether a nanodroplet impacting onto cone-textured surfaces will touch the underlying substrate during impact. The advantages and disadvantages of applying nanocone structures to the solid surface are revealed by the investigations into restitution coefficient and contact time. The effects of nanocone structures on droplet bouncing dynamics are probed using momentum analysis rather than conventional energy analysis. We further demonstrate that a single Weber number is inadequate for unifying the dynamics of macroscale and nanoscale droplets on cone-textured surfaces, and propose a combined dimensionless number to address it. The extensive findings of this study carry noteworthy implications for engineering applications, such as nanoprinting and nanomedicine on functional patterned surfaces, providing fundamental support for these technologies.

Observation of the effect of angiojet to treat acute lower extremity arterial embolization.

BACKGROUND: Through significant advances in the treatment of peripheral arterial occlusive disease, acute ischemia of the lower extremity is still associated with significant morbidity, limb threat and mortality. The two main causes of acute ischemia in lower extremities are arterial embolism and atherosclerotic arteries. Timely recognition and treatment of acute limb ischemia in emergency situations is essential in order to minimize the duration of ischemia. AIM: To investigate the application effect of angiojet thrombolysis in the treatment of acute lower extremity arterial embolization. METHODS: Sixty-two patients with acute lower extremity arterial embolization admitted to our hospital from May 2018 to May 2020 were selected. Among them, the observation group (twenty-eight cases) had received angiojet thrombolysis, and the control group (thirty-four cases) had received femoral artery incision and thrombectomy. After thrombus clearance, significant residual stenosis of the lumen was combined with balloon dilation and/or stent implantation. When the thrombus removal was not satisfactory, catheter-directed thrombolysis was performed. The incidence of postoperative complications, recurrence rate and recovery of the two groups were compared. RESULTS: There were no significant differences in postoperative recurrence (target vessel reconstruction rate), anklebrachial index and the incidence of postoperative complications between the two groups (P > 0.05); there were statistically significant differences in postoperative pain score and postoperative rehabilitation between the two groups (P < 0.05). CONCLUSION: The application of angiojet in the treatment of acute lower limb artery thromboembolism disease is safe and effective, minimally invasive, quicker recovery after operation, less postoperative complications, which is more suitable for the treatment of femoral popliteal arterial thromboembolism lesions. If the thrombus removal is not satisfactory, the combination of coronary artery aspiration catheter and catheterized directed thrombolysis can be used. Balloon dilation and stent implantation can be considered for obvious lumen stenosis.

[Characteristics of Typical Soil Acidification and Effects of Heavy Metal Speciation and Availability in Southwest China].

Using a spatial instead of temporal approach, soil samples were collected from the main types and different stages of acidification in Southwest China, and the characteristics of soil physicochemical properties, acid-buffering properties, and heavy metal fugacity patterns were analyzed, combined with biological experiments in small cabbage pots, to explore the coupling relationship between soil acidification and changes in heavy metal morphological activity. The results showed that the exchangeable salt-based ions of the soil decreased with increasing acidification in purple and yellow soils, caused by the loss of exchangeable Ca2+. The acid-buffering capacity of purple and yellow soils was higher at pH>7.50 and pH<4.50. The acid-buffering capacity of yellow soils was strongly correlated with the content of soil exchangeable salt-based ions, and the increase in acid-buffering capacity was related to the rate of depletion of soil salt-based ions with the increase in acid addition. The distribution of Cd and Pb in the soil was closely related to the soil type and degree of acidification: in the purple and yellow soils, Cd and Pb were mainly in the exchangeable and residue states, and the proportions of the exchangeable state and residue state increased and decreased, respectively, with increasing acidification; in the red soils, the residue state and Fe-Mn bound state were predominant; the Fe-Mn bound state of Cd was 2.15 and 1.73 times higher than that of the purple and yellow soils, respectively, and the Fe-Mn bound state of Pb was 4.30 and 3.91 times higher than that of purple and yellow soils, which was related to the higher iron content in red soils. Pot experiments showed that soil acidification inhibited the growth of Chinese cabbage to a certain extent, and the biomass of Chinese cabbage in the heavily acidified yellow soil (pH<5.70) was significantly lower than that in the non-acidified yellow soil.

Accurate Determination of Trace Cadmium in Soil Samples with Graphite Furnace Atomic Absorption Spectrometry Using Metal-Organic Frameworks as Matrix Modifiers.

Cadmium (Cd) is a highly toxic heavy metal that is widely distributed in soils at low concentrations. Its volatilization loss occurs at an ashing temperature higher than 350 °C. Accordingly, the accurate determination of its concentration in soils often requires the addition of chemical modifiers by graphite furnace atomic absorption spectrometry (GFAAS) to improve the thermal stability of Cd. In this work, a metal-organic framework (MOF, UIO-66-NH2) was utilized as a matrix modifier to improve accuracy in determining Cd in soils using GFAAS. The Cd signal, as influenced by drying and pyrolysis temperature and special gas, was also investigated, and the measuring conditions were optimized (2 µg L-1 Cd concentrations, matrix modifier: UIO-66-NH2, pyrolysis temperature: 550 °C, atomization temperature: 1650 °C, and special gas: air). The limit of detection (LOD) and the characteristic mass for Cd in soil were 3.84 ng g-1 and 0.80 pg, respectively. Five soil standard reference materials (SRMs) were analyzed for Cd to verify the effectiveness of the optimized measuring conditions. The soil Cd concentrations obtained were in remarkable agreement with the reference values. Moreover, the mechanism of UIO-66-NH2 on the graphite platform was investigated in the drying and pyrolysis steps by scanning electron microscopy (SEM), Fourier transform infrared (FT-IR), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). During the drying steps, many functional groups of the matrix were activated, and Cd2+ could be captured on its surface. After the pyrolysis step, the structure matrix collapsed and was partially decomposed into ZrO2, and subsequently, an intermediate state of ZrO2-(CdO) appeared at high temperatures, which came from the active binding sites on the zirconium oxide octahedron nodes.

[Effects of Interaction of Zinc and Cadmium on Growth and Cadmium Accumulation of Brassica campestris L.]

The interaction between different elements is an efficient means to control the heavy metal accumulation in crops. Phosphorus (P) and zinc (Zn), as essential nutrient elements of plants, have been shown to have important impacts on cadmium (Cd) accumulation in crops through interactions with each other. However, the function of the simultaneous interaction of P, Zn, and Cd on vegetable growth and Cd accumulation remains unclear. Herein, using a single-factor level design with two alternating fixed factors, pot experiments were conducted to study the impact and mechanism of this simultaneous interaction at different levels of P, Zn, and Cd on Brassica campestris L. growth, antioxidant enzyme activity, and Zn and Cd accumulation with neutral purple soil as the substrate. The results showed that the addition of an appropriate amount of P and Zn could promote the growth of Brassica campestris L. and inhibit its Cd accumulation, through different mechanisms. P mainly reduced the Cd availability in soil and improved the crop resistance, whereas Zn mainly promoted the dilution effect by the crop growth and its physiological antagonism. The antioxidant capacity of Brassica campestris L. was significantly inhibited when 1 mg·kg-1 exogenous Cd was added to the soil, along with decreased activities of CAT and POD and high accumulation of MDA. Notably, both P and Zn could improve the antioxidant capacity and relieve Cd toxicity by increasing CAT activity, without obviously influencing POD activity. The highest yield of Brassica campestris L. (55.72 g·pot-1) was attained when the ratio of stress concentration for exogenous P, Zn, and Cd[ω(Cd):ω(Zn):ω(P)] was 1:10:200. Furthermore, the Cd content in the edible part was also lower than the national standard requirement of 50 µg·kg-1for Cd in green leafy vegetables (GB 2762-2017). In addition, the accumulation of Cd was further decreased when the proportion of P and Zn was increased, along with a decreased yield of the vegetable. Therefore, a proper application of P and Zn fertilizers could simultaneously reduce Cd accumulation and increase crop yield and thus contribute to achieving safe vegetable production.

[Effects of Water Management on the Transformation of Iron Oxide Forms in Paddy Soils and Its Coupling with Changes in Cadmium Activity].

The transformation of iron oxide forms in the process of soil water management in paddy fields has an important impact on soil cadmium (Cd) activity and accumulation in rice. The test soil for this experiment was purple paddy soil in southwest China contaminated with exogenously added Cd. Through indoor cultivation experiments, the effects of water management (continuous flooding, CW; alternating wet and dry, DW) combined with iron oxide application (goethite, G-Fe; iron powder, Fe) on the pH, redox state (Eh, pe+pH), iron oxide form conversion, and Cd bioavailability changes in Cd-contaminated soil were studied. Meanwhile, the coupling relationship between the transformation of iron oxide form and the evolution of soil Cd activity driven by water management were also analyzed. The results showed that DTPA-Cd content was decreased by 17.7%-39.2% after 93 days of flooding, indicating that CW could significantly reduce soil Cd bioavailability. CW combined with Fe or G-Fe application significantly enhanced the passivating effect on soil Cd. Among them, the DTPA-Cd content of G-Fe application was reduced by 24.3% compared with that of the CK after 14 d of flooding; thus, G-Fe was effective in short-term passivation. The reduction in DTPA-Cd content of Fe application was 39.2% after 93 d of flooding, so Fe was able to passivate soil Cd continuously. It was also found that the application of iron oxides under alternating wet and dry conditions had no passivating effect on soil Cd. Furthermore, based on correlation analysis, the formation of amorphous iron (Feo) (P<0.01) was verified as the main reason for the change in Cd bioavailability of Cd in the soil:firstly, the soil pH gradually declined to 7.4, and the soil was kept at reduction conditions under CW, which promoted the morphology transformation from the crystalline state (Fec) to Feo. This transformation subsequently pushed the Cd transformation from the exchangeable state to the iron-manganese combined state and thus resulted in the significant decrease in Cd bioavailability. Meanwhile, the content and proportion of Feo were also significantly increased by the application of CW combined with Fe or G-Fe, thus further enhancing its Cd passivating effect on the soil. This research provides a scientific basis for the optimal water management and the application of iron-containing passivation agent in the safe use of Cd-contaminated paddy soils.

The determination of regulating thresholds of soil pH under different cadmium stresses using a predictive model for rice safe production.

Regulating soil pH becomes a crucial practice to alleviate cadmium (Cd) contamination. However, little is known about the threshold of soil pH for the safe production of rice at various soil Cd levels. In this paper, the relationships between soil pH values and the contents of available Cd extracted by calcium chloride (CaCl2-Cd) in neutral and acidic soils were studied by mandatory acidification with H+ addition or neutralization with lime at various soil Cd levels. The results showed that the soil CaCl2-Cd contents dramatically decreased with increasing soil pH, and a logarithmic function could well describe the relations of soil CaCl2-Cd contents and soil pH at constant total Cd (CaCl2-Cd model). The Cd contents in rice grain (grain-Cd) in relation to soil CaCl2-Cd was further established through modified rice pot experiments. A model for the prediction of Cd content in rice grains (grain-Cd model) was set up, though which the grain-Cd content could be predicted based on soil pH and total Cd content. 122 data pairs of rice grain-Cd contents obtained at various soil total Cd contents and pH were employed from the literature to verify the reliability of the established model, approximately 95.08% of those data favorably located within the 1:1 line ± 0.5 unit area of the grain-Cd model. Notably, this model can be applied to determine the thresholds of soil pH at a specific Cd pollution level. For instance, to achieve a rice grain-Cd contents matching the Chinese national food safety limit of 0.2 mg kg-1, the soil pH thresholds were estimated to be 5.05, 5.70, and 6.02 at soil Cd contents of 0.3, 0.6, and 0.8 mg kg-1, respectively. In addition, the established model can also be used to estimate the health risk from rice in broad regions with various soil pH values and Cd contents.

Antibiotic pretreatment attenuates liver ischemia-reperfusion injury by Farnesoid X receptor activation.

Prophylactic antibiotics (Abx) are used before liver surgery, and the influence of antibiotic pretreatment on hepatic ischemia-reperfusion injury (IRI) remains unclear. Hence, we explored the impact of Abx pretreatment on hepatic IRI in the present work. The gut microbiota has an essential role in hepatic bile acid (BA) metabolism, and we assumed that depletion of the gut microbiota could affect the composition of hepatic BAs and affect liver IRI. The IRI model demonstrated that Abx pretreatment attenuated liver IRI by alleviating cell apoptosis, reducing the inflammatory response, and decreasing the recruitment of CCR2+ monocytes. Mechanistically, Abx pretreatment reshaped the gut microbiota, especially decreasing the relative abundance of Firmicutes and increasing the relative abundance of Clostridium, which were related to the transformation of BAs and were consistent with the altered bile acid species (unconjugated BAs, especially UDCA). These altered BAs are known FXR agonists and lead to the activation of the farnesoid X receptor (FXR), which can directly bind to the FXR response element (FXRE) harbored in the TLR4 promoter and further suppress downstream mitogen-activated protein kinase (MAPK) and nuclear kappa B (NF-κB) pathways. Meanwhile, the CCL2-CCR2 axis was also involved in the process of FXR activation, as we confirmed both in vivo and in vitro. Importantly, we proved the importance of FXR in mice and clinical occlusion samples, which were inversely correlated with liver injury. Taken together, our study identified that Abx pretreatment before liver resection was a beneficial event by activating FXR, which might become a potential therapeutic target in treating liver injury.

An E2F5-TFDP1-BRG1 Complex Mediates Transcriptional Activation of MYCN in Hepatocytes.

Liver regeneration is characterized by cell cycle reentrance of hepatocytes. N-Myc, encoded by MYCN, is a member of the Myc family of transcription factors. Elevation of MYCN expression has been noted in the course of liver regeneration whereas the underlying mechanism remains unclear. Here we describe that up-regulation of MYCN expression, as measured by quantitative PCR, Western blotting, and immunohistochemical staining, paralleled liver regeneration in animal and cell models. MYCN expression was up-regulated as a result of transcriptional activation. Ingenuity pathway analysis (IPA) revealed several up-stream transcriptional regulators for MYCN and RNA interference validated E2F5 and TFDP1 as essential for hepatocyte growth factor (HGF)-induced MYCN trans-activation. Further examination showed that deficiency of BRG1, a chromatin remodeling protein, attenuated MYCN induction during liver regeneration. BRG1 interacted with and was recruited by E2F5/TFDP1 to the MYCN promoter. Mechanistically, BRG1 might play a role regulating histone H3 acetylation and H3K4 trimethylation and facilitating/stabilizing the binding of RNA polymerase II surrounding the MYCN promoter. Over-expression of ectopic MYCN in BRG1-null hepatocytes overcame deficiency of proliferation. Importantly, a positive correlation between MYCN expression and BRG1/E2F5/TFDP1 expression was observed in human liver specimens. In conclusion, our data identify a novel epigenetic pathway where an E2F5-TFDP1-BRG1 complex regulates MYCN transcription to promote liver regeneration.

[Screening and Evaluation of Methods for Determining Available Lead (Pb) and Cadmium (Cd) in Farmland Soil].

The accumulation of heavy metals in crops is largely dependent on the availability of heavy metals in soils. Due to the differences of soil types and pollution characteristics, there is no widely recognized method for the determination of the bio-available heavy metals in soils such as Pb and Cd. In order to screen and establish suitable methods, the extractable abilities of five extractants (CaCl2, NH4OAc, HCl, EDTA, and DTPA) and Gradient Diffusion Film Technology (DGT) on four typical farmland soils with very different properties in Chongqing (acid purple soil, neutral purple soil, calcareous yellow soil and calcareous purple soil) were systematically compared. Simultaneously, pot experiments were carried out with Lolium perenne L. as an indicator plant to explore the relationship between the extractable soil Pb and Cd and their accumulation in plants. The feasibility of the tested methods were evaluated based on the extractability and co-relationships. The results showed that the extractability of the tested extractants for soil Pb and Cd varied a lot. HCl showed highest extractability on Pb in acid purple soil and calcareous yellow soil, while EDTA did the best in neutral purple soil and calcareous purple soil; HCl showed best extractability in all soils except calcareous purple soil, where EDTA was the best. Considering the correlation between the extraction amount and uptake by plant, all the extraction methods could be applied for the evaluation of the bioavailability of soils Pb and Cd except CaCl2 for Pb due to its weak extractability for Pb for a specific soil type. For the comparison of heavy bioavailability in different soil types, EDTA-extractable Pb and DGT-extractable Cd were recommended due to their well co-relationships between extractable amount in soil and uptake by plant (Lolium perenne L.) as indicated by the correlation coefficients of 0.941 and 0.919, respectively. HCl was relatively suitable as Cd extractant compared to others if DGT method could not be used.

Rhizosphere dissolved organic matter and iron plaque modified by organic amendments and its relations to cadmium bioavailability and accumulation in rice.

Organic amendments can modify rhizosphere dissolved organic matter (DOM) properties and Fe-plaque quantity, thereby affecting cadmium (Cd) bioavailability and uptake by rice. Pot experiments were conducted to investigate effects of biochar (BC) and vermicompost (VC) at different rates (0, 1%, and 5%) on rhizosphere DOM characteristics and Fe-plaque quantity, and their impacts on Cd bioavailability and accumulation in high and low Cd-accumulation rice cultivars (HAC and LAC). Soil DOM was characterized by ultraviolet-visible (UV-Vis) and fluorescence excitation-emission matrix (EEM) spectrum analyses. Hydroponic experiments were conducted to investigate effects of BC- or VC-derived DOM combined Fe-plaque on Cd uptake by rice. Results showed that increasing rates of organic amendments increased DOM concentration while decreased Cd availability in rhizosphere and bulk soils and Cd contents in rice tissues. The Cd reduction in LAC grains (31.9%-72.7%) was better than that in HAC grains (6.3%-25.4%) after organic amendment addition. Soil DOM properties were modified by organic amendments towards higher aromaticity, molecular weight, and stability. VC resulted in a greater increase of humic-like fractions but reduced protein-like proportions in rhizosphere DOM over BC. Negative correlations were observed between humic-like fractions and available Cd in the rhizosphere. Likewise, VC (especially 5%VC) promoted the formation of Fe-plaque and limited Cd soil-to-root transport, while BC groups showed a reverse trend. The results of hydroponic experiments confirmed BC- and VC-derived DOM and Fe-plaque further inhibited Cd uptake by rice via the complexation with Cd and the sequestration of Cd, respectively. Hence, VC application combined with low Cd-accumulation rice could be an effective strategy for the safe utilization of Cd-contamination soils.

SS-31 Protects Liver from Ischemia-Reperfusion Injury via Modulating Macrophage Polarization.

Ischemia-reperfusion injury (IRI) is a common complication in liver surgeries. It is a focus to discover effective treatments to reduce ischemia-reperfusion injury. Previous studies show that oxidative stress and inflammation response contribute to the liver damage during IRI. SS-31 is an innovated mitochondrial-targeted antioxidant peptide shown to scavenge reactive oxygen species and decrease oxidative stress, but the protective effects of SS-31 against hepatic IRI are not well understood. The aim of our study is to investigate whether SS-31 could protect the liver from damages induced by IRI and understand the protective mechanism. The results showed that SS-31 treatment can significantly attenuate liver injury during IRI, proved by HE staining, serum ALT/AST, and TUNEL staining which can assess the degree of liver damage. Meanwhile, we find that oxidative stress and inflammation were significantly suppressed after SS-31 administration. Furthermore, the mechanism revealed that SS-31 can directly decrease ROS production and regulate STAT1/STAT3 signaling in macrophages, thus inhibiting macrophage M1 polarization. The proinflammation cytokines are then significantly reduced, which suppress inflammation response in the liver. Taken together, our study discovered that SS-31 can regulate macrophage polarization through ROS scavenging and STAT1/STAT3 signaling to ameliorate liver injury; the protective effects against hepatic IRI suggest that SS-31 may be an appropriate treatment for liver IRI in the clinic.

Inhibition of HMGB1 Suppresses Hepatocellular Carcinoma Progression via HIPK2-Mediated Autophagic Degradation of ZEB1.

Autophagy is a conserved catabolic process maintaining cellular homeostasis and reportedly plays a critical role in tumor progression. Accumulating data show that autophagic activity is inhibited in hepatocellular carcinoma. However, the underlying molecular basis of impaired autophagy in HCC remains unclear. In this study, we revealed that autophagic activity was suppressed by HMGB1 in a HIPK2-dependent way. Targeting HMGB1 could inhibit the degradation of HIPK2, as a result of which, autophagic degradation of ZEB1 was enhanced by reprogramming glucose metabolism/AMPK/mTOR axis. Moreover, we demonstrated that selectively degradation of ZEB1 was responsible for HCC growth inhibition in HMGB1 deficient cells. Lastly, we found the combination therapy of HMGB1 inhibitor and rapamycin achieved a better anti-HCC effect. These results demonstrate that impaired autophagy is controlled by HMGB1 and targeting HMGB1 could suppress HCC progression via HIPK2-mediated autophagic degradation of ZEB1.

Elevated HMGB1 expression induced by hepatitis B virus X protein promotes epithelial-mesenchymal transition and angiogenesis through STAT3/miR-34a/NF-κB in primary liver cancer.

HBV infection plays a crucial role in primary liver cancer development. Also, HBV related liver cancer has higher invasiveness and earlier discovered distant metastasis. HBV-encoded X protein (HBx) exerts various biological functions on liver cancer progression, including proliferation, invasion, and venous metastasis. There is evidence that High-mobility group box 1 (HMGB1) promotes epithelial-mesenchymal transition (EMT) and angiogenesis of tumors, including liver cancer. Therefore, this study investigates whether HMGB1 mediates HBx-induced EMT and angiogenesis in HBV related liver cancer. We collected 76 tumor samples of primary liver cancer patients to analyze the relationship between HMGB1 and portal vein tumor thrombus (PVTT) in HBV related liver cancer. To test the influence of HMGB1 on EMT and angiogenesis, we constructed HBx lentivirus transfected HepG2/Huh7 cell lines and performed invasion assays, tube formation and in vivo metastatic experiments. We evaluated HMGB1 and STAT3/miR-34a/NF-κB pathway in vivo and in vitro by immunoblot, quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence and immunohistochemistry analysis. Subsequent RNA interference (RNAi) and luciferase reporter assay were conducted to detect the functional correlation between HMGB1 and STAT3/miR-34a/NF-κB pathway. Our results showed enhanced expression of HMGB1 in HBV related liver cancer, especially with PVTT, while HMGB1 expression was associated with tumor invasion and metastasis. Further experiments indicated that the activation of STAT3 mediated HBx-induced HMGB1, which is involved in EMT and tumor angiogenesis. Besides, HMGB1 expression stimulated by HBx was dependent on the activation of the NF-κB signaling pathway, which was inhibited by miR-34a, while STAT3 suppressed the expression of miR-34a. Moreover, extracellular HMGB1 induced the IL-6/STAT3/miR-34a axis activation, which indicated a reciprocal relationship between HMGB1 and miR-34a. Collectively, our study provided evidence to reveal that HBx-mediated high expression of HMGB1 accounted for EMT and tumor angiogenesis in HBV related liver cancer, and HMGB1 may be a potential target for predicting venous metastasis.

Protective Properties of FOXO1 Inhibition in a Murine Model of Non-alcoholic Fatty Liver Disease Are Associated With Attenuation of ER Stress and Necroptosis.

AIM: The pathogenesis of non-alcoholic fatty liver disease is currently unclear, however, lipid accumulation leading to endoplasmic reticulum stress appears to be pivotal in the process. At present, FOXO1 is known to be involved in NAFLD progression. The relationship between necroptosis and non-alcoholic steatohepatitis has been of great research interest more recently. However, whether FOXO1 regulates ER stress and necroptosis in mice fed with a high fat diet is not clear. Therefore, in this study we analyzed the relationship between non-alcoholic steatohepatitis, ER stress, and necroptosis. MAIN METHODS: Male C57BL/6J mice were fed with an HFD for 14 weeks to induce non-alcoholic steatohepatitis. ER stress and activation of necroptosis in AML12 cells were evaluated after inhibition of FOXO1 in AML12 cells. In addition, mice were fed with AS1842856 for 14 weeks. Liver function and lipid accumulation were measured, and further, ER stress and necroptosis were evaluated by Western Blot and Transmission Electron Microscopy. KEY FINDINGS: Mice fed with a high fat diet showed high levels of FOXO1, accompanying activation of endoplasmic reticulum stress and necroptosis. Further, sustained PA stimulation caused ER stress and necroptosis in AML12 cells. At the same time, protein levels of FOXO1 increased significantly. Inhibition of FOXO1 with AS1842856 alleviated ER stress and necroptosis. Additionally, treatment of mice with a FOXO1 inhibitor ameliorated liver function after they were fed with a high fat diet, displaying better liver condition and lighter necroptosis. SIGNIFICANCE: Inhibition of FOXO1 attenuates ER stress and necroptosis in a mouse model of non-alcoholic steatohepatitis.

Mitigation of rice cadmium (Cd) accumulation by joint application of organic amendments and selenium (Se) in high-Cd-contaminated soils.

A pot experiment was conducted to investigate the possible mediatory effect of organic amendments (vermicompost and biochar) and selenium (Se) on Cd bioaccumulation in both rice cultivars (high-Cd accumulation rice: Yuzhenxiang (YZX) and low-Cd accumulation rice: Changliangyou772 (CLY)) in high-Cd-contaminated soils. The results showed that Cd sensitivity and tolerance were cultivar-dependent, and grain Cd contents for CLY accorded with the Chinese national food safety standards (0.2 mg kg-1), whereas grain Cd levels for YZX were 1.4-5.8 times higher than those for CLY. Soil applications of amendments decreased grain Cd levels by 3.5%-36.9% for YZX and 36.1%-74.4% for CLY. Moreover, vermicompost (VC) was more effective in reducing Cd bioaccumulation than biochar (BC). A combination of Se and organic amendments could significantly increase grain Se contents and help further reduce grain Cd levels by 5.8%-20.8%, compared to the single organic amendments. This mitigation progress could be attributed to the changes of Cd translocation and distribution among rice tissues and the inhibition of Cd bioavailability in soil through the alteration in soil properties. Organic amendments, especially high dose (5%), increased soil pH and organic matter contents, and correspondingly decreased soil Cd bioavailability. A sequential extraction analysis suggested that organic amendments and Se facilitated the transformation of soil Cd from the bioavailable form to the immobilized Cd form, and thus decreased grain Cd levels. Hence, co-applications of organic amendments and Se in combination with low-Cd accumulation cultivar could be an effective strategy for both Se needs of humans and safe utilization of Cd polluted soil.