Identification of a novel nonsense mutation in α-galactosidase A that causes Fabry disease in a Chinese family.

Fabry disease, a lysosomal storage disease, is an uncommon X-linked recessive genetic disorder stemming from abnormalities in the alpha-galactosidase gene (GLA) that codes human alpha-Galactosidase A (α-Gal A). To date, over 800 GLA mutations have been found to cause Fabry disease (FD). Continued enhancement of the GLA mutation spectrum will contribute to a deeper recognition and underlying mechanisms of FD. In this study, a 27-year-old male proband exhibited a typical phenotype of Fabry disease. Subsequently, family screening for Fabry disease was conducted, and high-throughput sequencing was employed to identify the mutated gene. The three-level structure of the mutated protein was analyzed, and its subcellular localization and enzymatic activity were determined. Apoptosis was assessed in GLA mutant cell lines to confirm the functional effects. As a result, a new mutation, c.777_778del (p. Gly261Leufs*3), in the GLA gene was identified. The mutation caused a frameshift during translation and the premature appearance of a termination codon, which led to a partial deletion of the domain in C-terminal region and altered the protein's tertiary structure. In vitro experiments revealed a significant reduction of the enzymatic activity in mutant cells. The expression was noticeably decreased at the mRNA and protein levels in mutant cell lines. Additionally, the subcellular localization of α-Gal A changed from a homogeneous distribution to punctate aggregation in the cytoplasm. GLA mutant cells exhibited significantly higher levels of apoptosis compared to wild-type cells.

Comparative study on fecal flora and blood biochemical indexes in normal and diarrhea British Shorthair cats.

In recent years, 16S ribosomal DNA (16S rDNA) sequencing has been widely developed. In the present study, we investigated the changes of fecal flora analyzed by sequencing of 16S rDNA and the alteration of blood biochemical indexes in cats during diarrhea. Seven normal fecal samples and seven fecal samples of British Shorthair cats with bacterial diarrhea about 6 months old were collected. The 16S rDNA V3 region of the bacteria was amplified for high-throughput sequencing. Finally, species analysis at various levels was performed. At the same time, samples of blood were taken to examine the changes of biochemical indexes in cats with diarrhea. The abundance and diversity of microflora in the healthy group were greater than those in the diarrhea group. The normal floras in the feces of healthy cats were Firmicutes, Actinobacteria, Bacteroidetes and Proteobacteria. The content of Proteobacteria and Firmicutes varied greatly in diarrheal cats. In addition, the number of white blood cells, lymphocytes, neutrophils, and globulin were increased in cats with diarrhea, whereas albumin level was decreased in diarrheal cats. In conclusion, the present study suggests 16SrDNA technology showed that the intestinal Proteus was abundant, and the content of Firmicutes was scarce in cats with diarrhea. Escherichia-Shigella was the main pathogens in this sample. Rapid blood biochemical tests may help clinicians to assess the severity and prognosis of cats with diarrhea.

Radical-Mediated Cascade Spirocyclization of N-Benzylacrylamides with Polyhaloalkanes: Access to Polyhalo-Substituted Azaspirocyclohexadienones.

A novel and mild metal-free catalyzed radical-mediated cascade spirocyclization of N-benzylacrylamides with polyhaloalkanes is proposed for the preparation of polyhalo-substituted azaspirocyclohexadienones. Notably, polyhaloalkanes are employed as efficient alkyl radical sources via the cleavage of C(sp3)-H bonds. This protocol undergoes a cascade radical addition and intramolecular cyclization/dearomatization process, and enables the easy construction of multiple chemical bonds and a spiro ring in a single reaction.

Dual roles of ANGPTL4 in multiple inflammatory responses in stomatitis mice.

BACKGROUND: Stomatitis is inflammation of the oral mucosa. Angiopoietin-like protein 4 (ANGPTL4) has pleiotropic functions both anti-inflammatory and pro-inflammatory properties. In the present study, we tested whether there is a correlation between increased ANGPTL4 expression and inflammation in stomatitis mice and the mechanisms involved. METHODS AND RESULTS: In this study, the oral mucosa of mice was burned with 90% phenol and intraperitoneal injection of 5-fluorouracil to establish the model of stomatitis mice. The pathological changes of stomatitis mice were observed by H&E staining of paraffin section. The expressions of cytokines and ANGPTL4 were detected by fluorescence quantitative PCR, and the protein levels of ANGPTL4 were detected by western blot. Compared with control group, the oral mucosal structure of model mice was damaged. The expression of ANGPTL4 were significantly increased concomitantly with elevated production of anti-inflammatory cytokine (peroxisome proliferator-activated receptor alpha) and pro-inflammatory cytokines [nuclear transcription factor-kappa B, interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α] in mice with stomatitis. CONCLUSIONS: This study suggests that ANGPTL4 may be a double-edged sword in multiple inflammatory responses in stomatitis mice.

Whole exome sequencing identifies monogenic forms of nephritis in a previously unsolved cohort of children with steroid-resistant nephrotic syndrome and hematuria.

BACKGROUND: Alport syndrome (AS), atypical hemolytic-uremic syndrome (aHUS), and fibronectin-glomerulopathy (FG) are rare forms of glomerular diseases that manifest in a combination of proteinuria, hematuria, and hypertension, referred to as nephritic syndrome. Due to phenotypic overlays, steroid-resistant nephrotic syndrome (SRNS) and nephritic syndrome have been difficult to discern diagnostically. SRNS is more common than nephritic syndrome and is the second leading cause of childhood-onset CKD. Fourteen monogenic causes of AS, aHUS, and FG and 60 monogenic causes of SRNS have been identified. As whole exome sequencing (WES) allows for unequivocal molecular genetic diagnostics, we hypothesize to be able to identify causative mutations in genes known to cause nephritic syndrome in patient cohorts with a clinical diagnosis of SRNS. METHODS: We identified patients with hematuria and steroid-resistant proteinuria in an international patient cohort that we had submitted to WES and who were unsolved for known monogenic causes of SRNS. These 70 patients from 65 individual families were subsequently analyzed for causative mutations in 14 AS, aHUS, or FG causing genes. WES data were compared to a control cohort of 76 patients from 75 families that were diagnosed with nephronophthisis-related ciliopathies (NPHP-RC) and to a control cohort of 83 individuals from 75 families with SRNS, but without hematuria. RESULTS: We detected likely pathogenic genetic variants in 3 of 65 families (4.6%) in 2 of the 14 genes analyzed. CONCLUSIONS: We confirmed that in cohorts of childhood-onset SRNS, patients with nephritic syndrome can be discerned by WES. The findings highlight the importance of clinical genetic testing for therapeutic and preventative measures in patients with proteinuria. A higher resolution version of the Graphical abstract is available as Supplementary information.

Down-regulation of serum miR-151a-3p is associated with renal tissue activity in class IV lupus nephritis.

OBJECTIVES: The aim of this study was to explore the value of serum miRNA for evaluating renal tissue activity in patients with class IV lupus nephritis (LN). METHODS: First, we used a microRNA array to identify miRNAs differentially expressed between class IV LN patients and healthy volunteers (n=4/group). Then, we analysed the association between these identified miRNAs and renal tissue activity in class IV LN patients. Finally, to validate the results, 20 class IV LN patients (confirmed by renal biopsy) and 20 healthy control volunteers were further studied. RESULTS: We found 23 miRNAs to be significantly differentially expressed between the 2 groups. We selected 5 of these miRNAs (miR-3165, miR-4762-5p, miR-146a-5p, miR-151a-3p, and miR-21-5p) for further experiments. In validation experiments, expression of miRNA-151a-3p was significantly down-regulated in the class IV LN group compared to that in the control group (p<0.01) and was negatively correlated with the activity index (AI) in the class IV LN group(r=-0.526, p=0.017); the internal correlation was described with a linear fitting equation (p<0.01). CONCLUSIONS: Serum miR-151a-3p expression was decreased in class IV LN patients compared with healthy control volunteers and was negatively correlated with renal tissue activity. Thus, miR-151a-3p may play a employed for diagnosing class IV LN and evaluating renal tissue activity.

ANGPTL3 is part of the machinery causing dyslipidemia majorily via LPL inhibition in mastitis mice.

Previous investigations have shown that inflammation induces changes in lipid and lipoprotein metabolism, and increased expression of angiopoietin-like protein 3 (ANGPTL3) contributes to the development of dyslipidemia. Here we investigated whether there is a correlation between increased ANGPTL3 expression and dyslipidemia in mastitis mice. Thirty mice were divided into two groups: control group and Staphylococcus aureus (S. aureus)-induced mastitis mice group. Changes in the levels of blood lipids [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C)]; activity of myeloperoxidase (MPO); concentrations of plasma inflammation biomarkers [interferon-γ (IFNγ), tumor necrosis factor α (TNFα), and interleukin-1α (IL-1α)]; concentration of plasma ANGPTL3 protein; lipoprotein lipase (LPL) activities in postheparin plasma; expressions of hepatic N-acetylgalactosaminyltransferase 2 (GALNT2), hepatic ANGPTL3 and adipose LPL were determined. The major results indicated specific pathological mammary tissue changes, elevated MPO activity, reduced GALNT2 mRNA expression, elevated ANGPTL3 mRNA and protein expression and reduced LPL mRNA and protein expression. In plasma samples the S.aureus infused mice displayed elevated ANGPTL3 protein concentration, TG, TC and LDL-C levels, and reduced postheparin LPL activities and HDL-C level. The data suggests that ANGPTL3 is part of the machinery causing dyslipidemia majorily via LPL inhibition in mastitis mice.

Icariin improves eNOS/NO pathway to prohibit the atherogenesis of apolipoprotein E-null mice.

Impaired endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) pathway induces atherogenesis. The present study examined whether icariin improves the eNOS/NO pathway to prohibit the atherogenesis of apolipoprotein E-null (ApoE-/-) mice. In vitro, primary human umbilical vein endothelial cells (HUVECs) were randomly divided into 7 groups: control; vehicle; icariin 10; lyphosphatidylcholine (LPC) group; LPC + icariin 1; LPC + icariin 3; and LPC + icariin 10. In vivo, 80 mice were separated randomly into 4 groups (n = 20): control, ApoE-/-, ApoE-/- + icariin 10, and ApoE-/- + icariin 30. ApoE-/- mice had significantly more atherosclerosis in the aortic root together with increased aortic ROS production, body mass, plasma triglyceride (TG) and total cholesterol (TC) concentration, decreased aortic eNOS expression, and plasma NO concentration. LPC (10 µg/mL) treatment induced a big decline in NO level in the conditioned medium and eNOS expression, and an increase in intracellular reactive oxygen species (ROS) production in HUVECs. Icariin treatment decreased atherogenesis, ROS production, body mass, plasma TG concentration, and plasma TC concentration, and increased NO concentration and eNOS expression. These findings suggested icariin could improve eNOS/NO-pathway to prohibit the atherogenesis of apolipoprotein E-null mice by restraining oxidative stress.

Angiopoietin-like protein 2 may mediate the inflammation in murine mastitis through the activation of interleukin-6 and tumour necrosis factor-α.

Mastitis is the inflammation of the mammary gland. Recent research has shown that Angiopoietin-like protein 2 (ANGPTL2) is a key inflammatory mediator. In the present study, we tested whether there is a correlation between increased ANGPTL2 expression and inflammation in response to Staphylococcus aureus in murine mastitis and the mechanisms involved. Thirty mice were divided into two groups: blank control group, challenged group. The entire infused mammary glands were removed to observe the changes of histopathology, myeloperoxidase (MPO) activity, production of tumour necrosis factor-α (TNF-α) and interleukin (IL)-6, and genes expression of ANGPTL2, TNF-α and IL-6. In challenged group, the structure of mammary glands was damaged and the large areas of cell fragments were observed. The MPO activity, IL-6 and TNF-α concentrations, ANGPTL2, IL-6, and TNF-α mRNA levels were significantly elevated in challenged group compared with blank control group. The present findings indicate ANGPTL2 may mediate the inflammation in murine mastitis through the activation of IL-6 and TNF-α.

Anti-inflammatory properties of kaempferol via its inhibition of aldosterone signaling and aldosterone-induced gene expression.

Osteopontin (OPN), also called cytokine Eta-1, is a pro-inflammatory cytokine. Recent studies have shown that aldosterone increases OPN gene expression in endothelial cells. As a flavonoid compound, kaempferol has potent anti-inflammatory properties, but whether kaempferol regulates aldosterone signaling and aldosterone-induced gene expression is still unknown. Human umbilical vein endothelial cells (HUVECs) were pretreated with kaempferol (0, 1, 3, or 10 µmol/L) for 1 h prior to exposure to aldosterone (10(-6) mol/L) for 24 h. Aldosterone induced generation of reactive oxygen species; OPN and cluster of differentiation 44 gene expression; phospho-p38 MAPK and NF-κB binding activity. The effect of aldosterone was abrogated by kaempferol and spironolactone (10(-6) mol/L). The present results suggest that kaempferol exerts its anti-inflammatory properties via its inhibition of aldosterone signaling and aldosterone-induced gene expression in HUVECs.

Four novel mutations identified in the COL4A3, COL4A4 and COL4A5 genes in 10 families with Alport syndrome.

BACKGROUND: Alport syndrome (AS) is an inherited nephropathy caused by mutations in the type IV collagen genes. It is clinically characterized by damage to the eyes, ears and kidneys. Diagnosis of AS is hampered by its atypical clinical picture, particularly when the typical features, include persistent hematuria and microscopic changes in the glomerular basement membrane (GBM), are the only clinical manifestations in the patient. METHODS: We screened 10 families with suspected AS using whole exome sequencing (WES) and analyzed the harmfulness, conservation, and protein structure changes of mutated genes. In further, we performed in vitro functional analysis of two missense mutations in the COL4A5 gene (c.2359G > C, p.G787R and c.2605G > A, p.G869R). RESULTS: We identified 11 pathogenic variants in the type IV collagen genes (COL4A3, COL4A4 and COL4A5). These pathogenic variants include eight missense mutations, two nonsense mutations and one frameshift mutation. Notably, Family 2 had digenic mutations in the COL4A3 (p.G1170A) and UMOD genes (p.M229K). Family 3 had a digenic missense mutation (p.G997E) in COL4A3 and a frameshift mutation (p.P502L fs*151) in COL4A4. To our knowledge, four of the 11 mutations are novel mutations. In addition, we found that COL4A5 mutation relation mRNA levels were significantly decreased in HEK 293 T cell compared to control, while the cellular localization remained the same. CONCLUSIONS: Our research expands the spectrum of COL4A3-5 pathogenic variants, which is helpful for clinical and scientific research.

TG-interacting factor 1 improves risk stratification in patients with NPM1-mutated acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous disease characterized by diverse genetic abnormalities. The NPM1 is the most commonly mutated gene in newly diagnosed patients. Optimizing risk stratification in this population could facilitate more rational clinical decision-making. OBJECTIVES: To identify biomarkers that optimize risk stratification in AML patients with NPM1 mutations. MATERIAL AND METHODS: Acute myeloid leukemia patients from multiple centers were included in this study. Univariate, multivariate and Kaplan-Meier survival analyses were used to assess risk factors and clinical outcomes. The gene set enrichment analysis (GSEA) was conducted to identify the related enrichment of biological function. RESULTS: TG-interacting factor 1 (TGIF1) is a good prognostic indicator of disease progression in AML patients. It is closely related to NPM1 mutation, in which age and TGIF1 expression are independent prognostic factors. Multicenter data sources have shown that high expression of TGIF1 is beneficial for AML, regardless of whether patients received bone marrow transplantation. In the NPM1-mutated AML group, age, FLT3-ITD and TGIF1 were independent prognostic factors. Moreover, the NPM1-mutated subgroup could be well dichotomized into 2 groups with distinct prognoses through TGIF1 combined with European LeukemiaNet (ELN) 2017 risk stratification. CONCLUSIONS: The TGIF1 has an important value in the prognosis of AML. The NPM1-mutated patients were further subdivided into risk stratification groups based on TGIF1 expression, which could optimize the ELN 2017 to achieve individualized treatment.

Incidence Trends of Inherited Anemias at the Global, Regional, and National Levels Over Three Decades.

Inherited anemia continues to pose a significant public health concern on a global scale, owing to its extensive geographical prevalence, substantial patient population, and profound ramifications. Here, we investigated detailed information on inherited anemias (including thalassemias, thalassemias trait, sickle cell disease, sickle cell trait, G6PD deficiency, and G6PD trait) for the period 1990-2019 from the Global Burden of Disease study. Over the course of three decades, there has been a persistent rise in the incidence of inherited anemias worldwide, culminating in a total of 44,896,026 incident cases in 2019. However, the prevalence of inherited anemias has exhibited a consistent downward trend over successive years. Significantly, these inherited anemias primarily impact females, exhibiting a male-to-female ratio of 1:1.88. Among males, the most prevalent inherited anemia is G6PD deficiency, whereas G6PD trait prevails among females. The incidence rates of inherited anemias and their temporal trend exhibited significant variations across different regions, with Central Sub-Saharan Africa displaying the highest incidence rates and Central Latin America experiencing the most substantial decline. The findings of this study suggest a significant correlation between the Socio-Demographic index (SDI) and incidence rates of inherited anemias, particularly in regions with lower SDI levels such as Africa and South Asia. These results contribute valuable insights for the analysis of global trends in the burden of inherited anemias.

Selective transformation and removal of As(III) by constructed Fe-N bonds: The generation of singlet oxygen from the photoexcitation of MnPc leads to abundant ZnFe-LDH interface OH radical.

In this study, MnPc intercalated Zn/Fe layered double hydroxides (MnPc/ZF-LDH) were synthesized by pillared intercalation modification with different MnPc intercalation amounts and used for the selective transformation and removal of As(III) from the arsenate-phosphate mixed solution. Fe-N bonds were constructed by the complexation of MnPc and iron ions on the Zn/Fe layered double hydroxides (ZF-LDH) interface. The DFT calculation results show that the binding energy of Fe-N bonded to arsenite (-3.75 eV) was higher than that of phosphate (-3.16 eV), resulting in MnPc/ZnFe-LDH exhibiting high As(III) selective adsorption performance and anchoring it rapidly in the arsenite -phosphate mixed solution. The maximum adsorption capacity of 1MnPc/ZF-LDH for As(III) could reach 180.7 mg·g-1 under dark conditions. MnPc also acts as a photosensitizer to provide more active species for the photocatalytic reaction. A series of experiments demonstrated that MnPc/ZF-LDH exhibits high As(III) selective photocatalytic performance. A total of 10 mg·L-1 of As(III) was completely removed in the reaction system within 50 min in a single As(III) environment. In an environment with As(III) and PO43-, it achieved 80.0 % removal efficiency of As(III) and showed a good reuse effect. The introduction of MnPc could improve the utilization of visible light by the MnPc/ZnFe-LDH. The singlet oxygen generated from photoexciting MnPc leads to abundant ZnFe-LDH interface OH. In addition, MnPc/ZnFe-LDH shows good recyclability, making it a promising multifunctional material for the purification of arsenic-polluted sewage.

A randomized trial of Trendelenburg position for acute moderate ischemic stroke.

We aim to explore the effect of head-down position (HDP), initiated within 24 hours of onset, in moderate anterior circulation stroke patients with probable large artery atherosclerosis (LAA) etiology. This investigator-initiated, multi-center trial prospective, randomized, open-label, blinded-endpoint, multi-center and phase-2 trial was conducted in China and completed in 2021. Eligible patients were randomly assigned (1:1) into the HDP group receiving -20° Trendelenburg, or control group receiving standard care according to national guideline. The primary endpoint was proportion of modified Rankin Scale (mRS) of 0 to 2 at 90 days, which is a scale for measuring the degree of disability after stroke. 90-day mRS was assessed by a certified staff member who was blinded to group assignment. A total of 96 patients were randomized (47 in HDP group and 49 in control group) and 94 (97.9%) patients were included in the final analysis: 46 in HDP group and 48 in control group. The proportion of favorable outcome was 65.2% (30/46) in the HDP group versus 50.0% (24/48) in the control group (unadjusted: OR 2.05 [95%CI 0.87-4.82], P = 0.099). No severe adverse event was attributed to HDP procedures. This work suggests that the head-down position seems safe and feasible, but does not improve favorable functional outcome in acute moderate stroke patients with LAA. This trial was registered with ClinicalTrials.gov, NCT03744533.

HSP47 regulates ECM accumulation in renal proximal tubular cells induced by TGF-ß1 through ERK1/2 and JNK MAPK pathways.

Heat shock protein (HSP)47 is a collagen-specific molecular chaperone that is essential for the biosynthesis of collagen molecules. It is likely that increased levels of HSP47 contribute to the assembly of procollagen and thereby cause an excessive accumulation of collagens in disease processes associated with fibrosis. Although HSP47 promotes renal fibrosis, the underlying mechanism and associated signaling events have not been clearly delineated. We examined the role of HSP47 in renal fibrosis using a rat unilateral ureteral obstruction model and transforming growth factor (TGF)-ß(1)-treated human proximal tubular epithelial (HK-2) cells. An upregulation of HSP47 in both in vivo and in vitro models was observed, which correlated with the increased synthesis of extracellular matrix (ECM) proteins and expression of tissue-type plasminogen activator inhibitor (PAI)-1. Blockade of HSP47 by short interfering RNA suppressed the expression of ECM proteins and PAI-1. In addition, TGF-ß(1)-induced HSP47 expression in HK-2 cells was attenuated by ERK1/2 and JNK MAPK inhibitors. These data suggest that ERK1/2 and JNK signaling events are involved in modulating the expression of HSP47, the chaperoning effect of which on TGF-ß(1) would ultimately contribute to renal fibrosis by enhancing the synthesis and deposition of ECM proteins.

Universal and Sensitive Drug Assessment Biosensing Platform Using Optimal Mechanical Beating Detection of Single Cardiomyocyte.

The preclinical assessment of efficacy and safety is essential for cardiovascular drug development in order to guarantee effective prevention and treatment of cardiovascular disease and avoid human health endangerment and a huge waste of resources. Rhythmic mechanical beating as one of the crucial cardiomyocyte properties has been exploited to establish a drug assessment biosensing platform. However, the conventional label-free biosensing platforms are difficult to perform high-throughput and high-resolution mechanical beating detection for a single cardiomyocyte, while label-based strategies are limited by pharmacologically adverse effects and phototoxicity. Herein, we propose a biosensing platform involving the multichannel electrode array device and the universal mechanical beating detection system. The platform can determine the optimal characteristic working frequency of different devices and dynamically interrogate the viability of multisite single cardiomyocytes to establish the optimized cell-based model for sensitive drug assessment. The subtle changes of mechanical beating signals induced by cardiovascular drugs can be detected by the platform, thereby demonstrating its high performance in pharmacological assessment. The universal and sensitive drug assessment biosensing platform is believed to be widely applied in cardiology investigating and preclinical drug screening.

Anodic Stripping Voltammetric Analysis of Trace Arsenic(III) on a Au-Stained Au Nanoparticles/Pyridine/Carboxylated Multiwalled Carbon Nanotubes/Glassy Carbon Electrode.

A Au-stained Au nanoparticle (Aus)/pyridine (Py)/carboxylated multiwalled carbon nanotubes (C-MWCNTs)/glassy carbon electrode (GCE) was prepared for the sensitive analysis of As(III) by cast-coating of C-MWCNTs on a GCE, electroreduction of 4-cyanopyridine (cPy) to Py, adsorption of gold nanoparticles (AuNPs), and gold staining. The Py/C-MWCNTs/GCE can provide abundant active surface sites for the stable loading of AuNPs and then the AuNPs-initiated Au staining in HAuCl4 + NH2OH solution, giving a large surface area of Au on the Aus/Py/C-MWCNTs/GCE for the linear sweep anodic stripping voltammetry (LSASV) analysis of As(III). At a high potential-sweep rate of 5 V s-1, sharp two-step oxidation peaks of As(0) to As(III) and As(III) to As(V) were obtained to realize the sensitive dual-signal detection of As(III). Under optimal conditions, the ASLSV peak currents for oxidation of As(0) to As(III) and of As(III) to As(V) are linear with a concentration of As(III) from 0.01 to 8 µM with a sensitivity of 0.741 mA µM-1 and a limit of detection (LOD) of 3.3 nM (0.25 ppb) (S/N = 3), and from 0.01 to 8.0 µM with a sensitivity of 0.175 mA µM-1 and an LOD of 16.7 nM (1.20 ppb) (S/N = 3), respectively. Determination of As(III) in real water samples yielded satisfactory results.

Simultaneous oxidation of As(III) and reduction of Cr(VI) by NiS-CdS@biochar through efficient oxalate activation: The key role of enhanced generation of reactive oxygen species.

The reutilization of exhausted biochar is attracting extensive interest among researchers. In this study, the biochar generated from Chinese fir with natural regular porous structure that adsorbed Cd2+/Ni2+ at different concentration levels was used as the precursor, and then combined with simple hydrothermal vulcanization and ion deposition to generate the p-n heterojunction between NiS and CdS compounds (NiS-CdS@C) in situ. The hybrids with 3 cycles of NiS deposition reduced the interfacial transmission resistance from 80 Ω to 40 Ω, and increased photocurrent density by 5 times, thus effectively promoting the separation of photogenerated electrons and holes. The simultaneous removal of As(III) and Cr(VI) was selected to evaluate the oxidation and reduction capacity of the visible light/NiS-CdS@C/oxalate system. The results indicated that 10 mg/L As(III) and Cr(VI) were completely and simultaneously removed with 0.75 mM oxalate addition within 40 min in the system, and the NiS-CdS@C presented good durability and stability for oxalate activation. Electron paramagnetic resonance (EPR) and quenching experiments demonstrated that oxalate was activated by holes under light to produce •CO2- and enhanced the generation of additional •OH and •O2-, further contributing to the oxidation of As(III) and reduction of Cr(VI).

Kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis of apolipoprotein E deficient mice.

Recent studies show that osteopontin (OPN) and its receptor cluster of differentiation 44 (CD44) are two pro-inflammatory cytokines contributing to the development of atherosclerosis. The objective of this study was to explore the inhibitory effect of kaempferol, a naturally occurring flavonoid compound, on atherogenesis and the mechanisms involved. The experiments were performed in aorta and plasma from C57BL/6J control and apolipoprotein E-deficient (ApoE(-/-)) mice treated or not with kaempferol (50 or 100mg/kg, intragastrically) for 4 weeks. Kaempferol treatment decreased atherosclerotic lesion area, improved endothelium-dependent vasorelaxation, and increased the maximal relaxation value concomitantly with decrease in the half-maximum effective concentration, plasma OPN level, aortic OPN expression, and aortic CD44 expression in ApoE(-/-) mice. In addition, treatment with kaempferol also significantly decreased reactive oxygen species production in mice aorta. The present results suggest that kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis of ApoE(-/-) mice.