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Lead nitrate (LN) is frequently employed as an activator in the flotation of cassiterite using hydroxamic acids as the collectors. This study investigated the effect of LN on the hydrophobic aggregation of cassiterite when benzohydroxamic acid (BHA), hexyl hydroxamate (HHA), and octyl hydroxamate (OHA) were used as the collectors through micro-flotation, focused beam reflectance measurement (FBRM) and a particle video microscope (PVM), zeta potential, and the extended DLVO theory. Micro-flotation tests confirmed that LN activated the flotation of cassiterite using the hydroxamic acids as collectors. Focused beam reflectance measurement (FBRM) and a particle video microscope (PVM) were used to capture in situ data on the changes in size distribution and morphology of cassiterite aggregates during stirring. The FBRM and PVM image results indicated that the addition of LN could promote the formation of hydrophobic aggregates of fine cassiterite, when BHA or HHA was used as the collector, and reduce the dosage of OHA needed to induce the formation of hydrophobic aggregates of cassiterite. The extended DLVO theory interaction energies indicated that the presence of LN could decrease the electrostatic interaction energies (Vedl) and increase the hydrophobic interaction energies (Vhy) between cassiterite particles, resulting in the disappearance of the high energy barriers that existed between the particles in the absence of LN. Thus, cassiterite particles could aggregate in the presence of LN when BHA, HHA, or a low concentration of OHA was used as the collector.

Abstract Background Shenkang injection has been used clinically to lower creatinine levels. This study explored the mechanism of Shenkang injection on protecting kidney function from hyperglycemia-mediated damage. Methods This study utilized a STreptoZotocin (STZ)-induced rat model of diabetes. In total, 60 rats were randomized into either the control group (n = 15) injected with vehicle or treatment group (n = 45) injected with STZ to induce hyperglycemia. Eight weeks after diabetes onset, diabetic rats were further randomized to receive different treatments for 4 consecutive weeks, including vehicle (diabetic nephropathy group, n = 15), Shenkang (n = 15), or Valsartan (n = 15). At 12 weeks, a series of urine and blood measures were examined and damage to the kidney tissue was examined using histology. Expression of nephrin and transforming growth factor-β1 (TGF-β1) were characterized using immunohistochemistry and Western blot. Results Compared to the control group, rats in the diabetic nephropathy group showed significant kidney damage demonstrated by high kidneyindex, high levels of urinary albumin, albumin/creatinine ratio (ACR), blood urea nitrogen as well as histological evidence. Shenkang injection significantly improved kidney function in the diabetic rats by decreasing kidney index, ACR, and serum creatinine. Shenkang treatment also mitigated kidney damage, improved nephrin expression, and decreased TGF-β1 expression in the kidneys. Conclusions Shenkang treatment protected renal function in diabetic rats by increasing nephrin expression, which protects diabetic rats from hyperglycemia-mediated kidney damage.

Abstract. Background:. The hepatitis B virus (HBV) vaccine has been efficiently used for decades. However, hepatocellular carcinoma caused by HBV is still prevalent globally. We previously reported that interferon (IFN)-induced tripartite motif-containing 25 (TRIM25) inhibited HBV replication by increasing the IFN expression, and this study aimed to further clarify the anti-HBV mechanism of TRIM25. Methods:. The TRIM25-mediated degradation of hepatitis B virus X (HBx) protein was determined by detecting the expression of HBx in TRIM25-overexpressed or knocked-out HepG2 or HepG2-NTCP cells via Western blotting. Co-immunoprecipitation was performed to confirm the interaction between TRIM25 and HBx, and colocalization of TRIM25 and HBx was identified via immunofluorescence; HBV e-antigen and HBV surface antigen were qualified by using an enzyme-linked immunosorbent assay (ELISA) kit from Kehua Biotech. TRIM25 mRNA, pregenomic RNA (pgRNA), and HBV DNA were detected by quantitative real-time polymerase chain reaction. The retinoic acid-inducible gene I (RIG-I) and pgRNA interaction was verified by RNA-binding protein immunoprecipitation assay. Results:. We found that TRIM25 promoted HBx degradation, and confirmed that TRIM25 could enhance the K90-site ubiquitination of HBx as well as promote HBx degradation by the proteasome pathway. Interestingly, apart from the Really Interesting New Gene (RING) domain, the SPRY domain of TRIM25 was also indispensable for HBx degradation. In addition, we found that the expression of TRIM25 increased the recognition of HBV pgRNA by interacting with RIG-I, which further increased the IFN production, and SPRY, but not the RING domain is critical in this process. Conclusions:. The study found that TRIM25 interacted with HBx and promoted HBx-K90-site ubiquitination, which led to HBx degradation. On the other hand, TRIM25 may function as an adaptor, which enhanced the recognition of pgRNA by RIG-I, thereby further promoting IFN production. Our study can contribute to a better understanding of host-virus interaction.

Oxidative stress, as an important pathogenic factor, plays a critical role in acetaminophen (APAP) overdose-induced acute liver failure (ALF). Thus, an antioxidative strategy may be a good way to alleviate APAP-induced liver damage. Previous research has reported that Orientin (Ori) possesses antioxidant, anti-inflammatory and anticancer effects. This study aimed to explore whether Ori can protect against APAP-induced oxidative stress and to elucidate its underlying mechanism. Our results indicated that Ori alleviated APAP-induced hepatic pathological changes by reducing mouse mortality, inhibiting the expression of cytochrome P450 2E1 (CYP2E1), maintaining a normal liver structure, and reducing the levels of serum alanine transaminase (ALT) and serum aspartate aminotransferase (AST). Moreover, Ori protected against APAP-induced oxidative damage by decreasing the formation of malondialdehyde (MDA) and myeloperoxidase (MPO) and increasing the levels of superoxide dismutase (SOD) and the GSH-to-GSSG ratio. Moreover, Ori regulated APAP-induced hepatocyte apoptosis and mitochondrial dysfunction by inhibiting cytochrome c mitochondrial translocation and c-jun N-terminal kinase phosphorylation, promoting Bcl-2 expression and reducing Bax and caspase-3 cleavage. Furthermore, Ori not only obviously promoted Nrf2 nuclear translocation but also activated the antioxidant-related proteins HO-1, GCLC, GCLM and NQO1. Therefore, Ori prevented APAP-induced hepatocyte oxidative damage and mitochondrial dysfunction via Nrf2-mediated and JNK/cytochrome c/caspase-3 signaling pathways.

Extracting iron while minimizing the health and environmental risks associated with arsenic contamination necessitates the removal of arsenic from arsenic-bearing iron ores to ensure a safe and sustainable supply of this metal for industries. The beneficiation of iron minerals and arsenic-bearing minerals from arsenic-bearing iron ores with a calcification-magnetizing roasting and low-intensity magnetic separation (CMR-LMS) process is investigated in this work. The results show that the process is successful in extracting iron minerals and eliminating arsenic-containing minerals. The roasting involves two key steps: calcification and magnetizing, which change hematite and goethite into magnetite and arsenic-bearing minerals into calcium arsenates. The process’s separation efficiency of the CMR-LMS is closely linked to the parameters such as roasting temperature, roasting time, coke, alkalinity, and the liberation of gangue minerals from iron minerals. Through grinding and secondary magnetic separation, the iron minerals and gangue components, as well as arsenic, in roasted sand can be further separated. The optimum procedure results in a high-grade iron concentrate with an iron assay of 65.65%, an Fe recovery rate of 80.07%, and an arsenic content of 0.085%, while achieving a 93.29% As removal rate from the original ore that has 45.32% Fe and 0.70% As.

ABSTRACT Hepatitis B virus (HBV)‐related diseases are among the major diseases that affect millions of people worldwide. These diseases are difficult to eradicate and thus pose a serious global health challenge. There is an urgent need to understand the cross talk mechanism between HBV and the host. Cholesterol‐25‐hydroxylase (CH25H) and its enzymatic product, 25‐hydroxycholesterol (25HC), were previously shown to exhibit effective broad‐spectrum antiviral activity. However, the role of CH25H in the regulation of HBV infection and replication remains unclear. The present study reported increased expression of CH25H in HBV-infected patients compared to healthy subjects. Importantly, higher expression of CH25H expression was found to be associated with low HBV replication. Additionally, the present study aimed to identify CH25H mutants, which would lack hydroxylase activity but retain antiviral activity toward HBV infection and replication. Interestingly, it was observed that both CH25H and its mutants interacted with HBx protein and inhibited nuclear translocation of HBx. In particular, CH25H interacted with the C-terminal region of HBx, while transmembrane region 3 of CH25H was found to be critical for CH25H–HBx interaction and inhibition of HBV replication. The study results suggested that 25HC promoted HBV infection but not HBV replication. Thus, the results of the present study suggested the involvement of a dual mechanism in CH25H-mediated regulation of HBV replication. The study clearly demonstrated cross talk between HBV and the host through CH25H–HBx axis. IMPORTANCE The enzymatic product of CH25H, 25-hydroxycholesterol (25HC), has been previously shown to play a critical role in the blockage of the cell-virus fusion in response to viral infection. However, our study indicates a dual role of CH25H in regulating HBV. We find the CH25H-mediated inhibition of HBV replication is independent on its enzyme activity and CH25H binds to HBx and inhibits HBx nucleus translocation. We are interested to find out 25HC promotes HBV infection.

Owing to its broad-spectrum antivirus activities, interferon (IFN) is an important alternative agent for use in the treatment of hepatitis B virus (HBV)-infected patients; however, the mechanism involved in the inhibition of HBV infection and replication by IFN remains unclear. We previously reported that the induction of TRIM5γ is important in the IFN treatment of HBV patients as it promotes the degradation of the HBx protein, while the manner in which TRIM5γ is induced by IFN and how TRIM5γ interacts with HBx remain unestablished until date. Our present findings confirmed the TRIM5γ-HBx-DDB1 interactions in the HBV-infected Primary human hepatocytes (PHH), and we further found that STAT3, and not STAT1, was responsible for the induction of TRIM5γ upon IFN stimulation and that the zinc binding site His123 on the BBOX domain was a decisive site in the interaction between TRIM5γ BBOX and HBx. In addition, based on the BBOX domain, we detected a 7-amino acid peptide with the potential of promoting HBx degradation and inhibiting HBV replication. On the other hand, we noted that the TRIM5γ expression was inhibited by HBV in chronically HBV infected patients. Thus, our study identified the crucial role of STAT3 in the induction of TRIM5γ, as well as proposed a 7-amino acid, small peptide as a potential candidate for the development of therapeutic agents targeting HBx.

Background: Lotensin has been shown to have a protective function in the early stage of chronic renal failure. However, its role in the intermediate and late stages of chronic renal failure remains largely unknown. The present study aimed to investigate the role and underlying mechanism of lotensin in advanced chronic kidney disease. Methods: Female Wistar rats were randomly divided into three groups (n = 10): sham group, 5/6 nephrectomy (5/6 Nx) group, and lotensin group (oral administration of lotensin for 9 weeks following 5/6 Nx). Rats were sacrificed and pathological parameters were measured. Western blot assay and immunohistochemical staining were performed to detect the expression of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) in kidney tissues. Results: Compared to the 5/6 Nx group, lotensin administration significantly decreased 5/6 Nx-induced elevation in blood urea nitrogen, serum creatinine and 24-h urinary protein excretion (UPE) rates, but markedly increased red blood cell count, plasma albumin and hemoglobin levels, along with improved renal morphology. Mechanistically, lotensin dramatically downregulated the renal expression of TGF-β1 and α-SMA induced by 5/6 Nx. Conclusions: Lotensin protects against advanced chronic kidney disease in rats with 5/6 Nx through the downregulation of TGF-β1 and α-SMA.

Therapeutic administration of type I IFN (IFN-I) is a common treatment option for individuals suffering from hepatitis B virus (HBV) infection. IFN-I therapy, however, has a relatively low response rate in HBV-infected patients and can induce serious side-effects, limiting its clinical efficacy. There is, thus, a clear need to understand the molecular mechanisms governing the influence of IFN-I therapy in HBV treatment in order to improve patient outcomes. In this study, we explored the interactions between HBV and IFITs (IFN-induced proteins with tetratricopeptide repeats), which are classical IFN-inducible genes. Specifically, we found that HBV patients undergoing IFN-I therapy exhibited elevated expression of IFITs in their peripheral blood mononuclear cells (PBMCs). We further observed upregulation in the expressions of IFIT1, IFIT2, and IFIT3 in cells transfected with the pHBV1.3 plasmid, which yields infectious virions in hepatic cells. We additionally found that HBx, which is the only regulatory protein encoded within the HBV genome, activates NF-κB, which in turn directly drives IFIT3 transcription. When IFIT3 was overexpressed in HepG2 cells, HBV replication was enhanced. Together, these results suggest that IFIT genes may unexpectedly enhance viral replication, thus making these genes potential therapeutic targets in patients with HBV.

Hepatitis B virus (HBV) remains a major cause of hepatic disease that threatens human health worldwide. Type I IFN (IFN-I) therapy is an important therapeutic option for HBV patients. The antiviral effect of IFN is mainly mediated via upregulation of the expressions of the downstream IFN-stimulated genes. However, the mechanisms by which IFN induces ISG production and inhibits HBV replication are yet to be clarified. TRIM14 was recently reported as a key molecule in the IFN-signaling pathway that regulates IFN production in response to viral infection. In this study, we sought to understand the mechanisms by which IFN restricts HBV replication. We confirmed that TRIM14 is an ISG in the hepatic cells, and that the pattern-recognition receptor ligands polyI:C and polydAdT induce TRIM14 dependent on IFN-I production. In addition, IFN-I-activated STAT1 (but not STAT3) directly bound to the TRIM14 promoter and mediated the induction of TRIM14. Interestingly, TRIM14 played an important role in IFN-I-mediated inhibition of HBV, and the TRIM14 SPRY domain interacted with the C-terminal of HBx, which might block the role of HBx in facilitating HBV replication by inhibiting the formation of the Smc-HBx–DDB1 complex. Thus, our study clearly demonstrates that TRIM14 is a STAT1-dependent ISG, and that the IFN-I–TRIM14–HBx axis shows an alternative way to understand the mechanism by which IFN-I inhibits virus replication.

Acetaminophen (APAP) overdose-induced fatal hepatotoxicity is majorly characterized by overwhelmingly increased oxidative stress while enhanced nuclear factor-erythroid 2-related factor 2 (Nrf2) is involved in prevention of hepatotoxicity. Although Licochalcone A (Lico A) upregulates Nrf2 signaling pathway against oxidative stress-triggered cell injury, whether it could protect from APAP-induced hepatotoxicity by directly inducing Nrf2 activation is still poorly elucidated. This study aims to explore the protective effect of Lico A against APAP-induced hepatotoxicity and its underlying molecular mechanisms. Our findings indicated that Lico A effectively decreased tert-butyl hydroperoxide (t-BHP)- and APAP-stimulated cell apoptosis, mitochondrial dysfunction and reactive oxygen species generation and increased various anti-oxidative enzymes expression, which is largely dependent on upregulating Nrf2 nuclear translocation, reducing the Keap1 protein expression, and strengthening the antioxidant response element promoter activity. Meanwhile, Lico A dramatically protected against APAP-induced acute liver failure by lessening the lethality; alleviating histopathological liver changes; decreasing the alanine transaminase and aspartate aminotransferase levels, malondialdehyde formation, myeloperoxidase level and superoxide dismutase depletion, and increasing the GSH-to-GSSG ratio. Furthermore, Lico A not only significantly modulated apoptosis-related protein by increasing Bcl-2 expression, and decreasing Bax and caspase-3 cleavage expression, but also efficiently alleviated mitochondrial dysfunction by reducing c-jun N-terminal kinase phosphorylation and translocation, inhibiting Bax mitochondrial translocation, apoptosis-inducing factor and cytochrome c release. However, Lico A-inhibited APAP-induced the lethality, histopathological changes, hepatic apoptosis, and mitochondrial dysfunction in WT mice were evidently abrogated in Nrf2-/- mice. These investigations firstly implicated that Lico A has protective potential against APAP-induced hepatotoxicity which may be strongly associated with the Nrf2-mediated defense mechanisms.