Boosting Reactive Oxygen Species Formation Over Pd and VOδ Co-Modified TiO2 for Methane Oxidation into Valuable Oxygenates.

Direct photocatalytic methane oxidation into value-added products provides a promising strategy for methane utilization. However, the inefficient generation of reactive oxygen species (ROS) partly limits the activation of CH4 . Herein, it is reported that Pd and VOδ co-modified TiO2 enables direct and selective methane oxidation into liquid oxygenates in the presence of O2 and H2 . Due to the extra ROS production from the in situ formed H2 O2 , a highly improved yield rate of 5014 µmol g-1  h-1 for liquid oxygenates with a selectivity of 89.3% is achieved over the optimized Pd0.5 V0.2 -TiO2 catalyst at ambient temperature, which is much better than those (2682 µmol g-1  h-1 , 77.8%) without H2 . Detailed investigations also demonstrate the synergistic effect between Pd and VOδ species for enhancing the charge carrier separation and transfer, as well as improving the catalytic activity for O2 reduction and H2 O2 production.

Natural small-molecules reverse Xeroderma Pigmentosum Complementation Group C (XPC) deficient-mediated drug-resistance in renal cell carcinoma.

BACKGROUND: Renal cancer is insensitive to radiotherapy or most chemotherapies. While the loss of the XPC gene was correlated with drug resistance in colon cancer, the expression of XPC and its role in the drug resistance of renal cancer have not yet been elucidated. With the fact that natural small-molecules have been adopted in combinational therapy with classical chemotherapeutic agents to increase the drug sensitivity and reduce adverse effects, the use of herbal compounds to tackle drug-resistance in renal cancer is advocated. PURPOSE: To correlate the role of XPC gene deficiency to drug-resistance in renal cancer, and to identify natural small-molecules that can reverse drug-resistance in renal cancer via up-regulation of XPC. METHODS: IHC was adopted to analyze the XPC expression in human tumor and adjacent tissues. Clinical data extracted from The Cancer Genome Atlas (TCGA) database were further analysed to determine the relationship between XPC gene expression and tumor staging of renal cancer. Two types of XPC-KD renal cancer cell models were established to investigate the drug-resistant phenotype and screen XPC gene enhancers from 134 natural small-molecules derived from herbal plants. Furthermore, the identified XPC enhancers were verified in single or in combination with FDA-approved chemotherapy drugs for reversing drug-resistance in renal cancer using MTT cytotoxicity assay. Drug resistance gene profiling, ROS detection assay, immunocytochemistry and cell live-dead imaging assay were adopted to characterize the XPC-related drug resistant mechanism. RESULTS: XPC gene expression was significantly reduced in renal cancer tissue compared with its adjacent tissue. Clinical analysis of TCGA database also identified the downregulated level of XPC gene in renal tumor tissue of stage IV patients with cancer metastasis, which was also correlated with their lower survival rate. 6 natural small-molecules derived from herbal plants including tectorigenin, pinostilbene, d-pinitol, polygalasaponin F, atractylenolide III and astragaloside II significantly enhanced XPC expression in two renal cancer cell types. Combinational treatment of the identified natural compound with the treatment of FDA-approved drug, further confirmed the up-regulation of XPC gene expression can sensitize the two types of XPC-KD drug-resistant renal cancer cells towards the FDA-approved drugs. Mechanistic study confirmed that GSTP1/ROS axis was activated in drug resistant XPC-KD renal cancer cells. CONCLUSION: XPC gene deficiency was identified in patient renal tumor samples, and knockdown of the XPC gene was correlated with a drug-resistant phenotype in renal cancer cells via activation of the GSTP1/ROS axis. The 6 identified natural small molecules were confirmed to have drug sensitizing effects via upregulation of the XPC gene. Therefore, the identified active natural small molecules may work as an adjuvant therapy for circumventing the drug-resistant phenotype in renal cancer via enhancement of XPC expression.

Gut microbial products valerate and caproate predict renal outcome among the patients with biopsy-confirmed diabetic nephropathy.

AIMS: Valerate and caproate are two subtypes of short-chain fatty acids produced by gut microbiota. We aimed to measure the serum valerate and caproate levels and analyze the associations between them and renal prognosis of diabetic nephropathy (DN). METHODS: The serum samples of patients with biopsy-confirmed diagnosis of DN were collected in the First Affiliated Hospital of Zhejiang University, from April 1, 2013, to March 31, 2018. One hundred patients were included and divided into an early DN group (eGFR ≥ 60 ml/min, n = 42) and an advanced DN group (eGFR < 60 ml/min, n = 58). The valerate and caproate were measured using gas chromatography-mass spectrometry. Participants were followed up until the cutoff date of August 31, 2018, or if they met the primary endpoint of end-stage renal disease (ESRD). RESULTS: There were 71 males and 29 females in this study, and 29 patients developed ESRD. We observed a significant lower concentration of valerate and caproate in the advanced DN group. There were negative correlations between valerate and glomerular classification (r = - 0.20, P = 0.03) and between caproate and interstitial fibrosis and tubular atrophy (IFTA) (r = - 0.24, P = 0.01). And there were positive correlations between valerate or caproate and eGFR (r = 0.22, P = 0.02; r = 0.38, P < 0.01). Multivariate Cox analysis revealed higher levels of valerate and caproate were negatively related to progression to ESRD (HR = 0.024, P = 0.016; HR = 0.543, P = 0.030). The area under the curve values of valerate and caproate levels were 0.66 and 0.63, respectively, in predicting progression to ESRD. CONCLUSION: This study showed alterations in serum valerate and caproate in DN and demonstrates lower valerate and caproate levels with progression of DN to ESRD.

Changes of gut microbiota in diabetic nephropathy and its effect on the progression of kidney injury.

PURPOSE: We aimed to illustrate gut microbiota and short chain fatty acid (SCFA) levels in diabetic nephropathy (DN) patients, and investigate the mechanism of sodium butyrate in diabetic mellitus (DM) rats. METHODS: Gut microbiota and serum SCFA levels were measured by 16S rDNA and GC-MS. After being built by streptozotocin (DM rats), the DM rats were administered 300 mg/kg sodium butyrate for 12 weeks (DM + BU rats). Gut microbiota, serum and fecal butyrate level were measured. RT-PCR, WB and transmission electron microscopy were performed to explore LC3mRNA or LC3B protein expression, and autophagosomes in kidney tissues. AMPK/mTOR protein expression in renal tissue were also measured. RESULTS: The gut microbial dysbiosis was found in DM and DN groups, and some SCFAs-producing bacteria were decreased in DN group. The serum butyrate concentrations were lower in SCFA-DN group compared with SCFA-HC group and SCFA-DM group in the other cohort. Serum butyrate level was positively correlated with eGFR. Sodium butyrate increased serum and fecal butyrate levels, and improved the enlargement of glomerular area and fibronectin and collagen IV expressions in renal tissues in DM + BU rats. The LC3 mRNA, LC3BII/I ratio and number of autophagosomes were increased in renal tissue of DM + BU rats. Higher p-AMPK/AMPK ratio and lower p-mTOR/ mTOR ratio were shown in renal tissue of DM + BU rats compared with DM rats. CONCLUSIONS: We found the decrease in SCFAs-producing bacteria and low SCFAs concentrations in DN patients. Oral butyrate supplementation may improve kidney injury in DM rats, possibly by increasing autophagy via activating AMPK/mTOR pathway.

The change of gut microbiota-derived short-chain fatty acids in diabetic kidney disease.

BACKGROUND: Previous studies found the dysbiosis of intestinal microbiota in diabetic kidney disease (DKD), especially the decreased SCFA-producing bacteria. We aimed to investigate the concentration of the stool and serum short-chain fatty acids (SCFAs), gut microbiota-derived metabolites, in individuals with DKD and reveal the correlations between SCFAs and renal function. METHODS: A total of 30 participants with DKD, 30 participants with type 2 diabetes mellitus (DM), and 30 normal controls (NC) in HwaMei Hospital were recruited from 1/1/2018 to 12/31/2019. Participants with DKD were divided into low estimated glomerular filtration rate (eGFR)(eGFR<60ml/min, n=14) and high eGFR (eGFR≥60ml/min, n=16) subgroups. Stool and serum were measured for SCFAs with gas chromatograph-mass spectrometry. RESULTS: The DKD group showed markedly lower levels of fecal acetate, propionate, and butyrate versus NC (p<0.001, p<0.001, p=0.018, respectively) [1027.32(784.21-1357.90)]vs[2064.59(1561.82-2637.44)]µg/g,[929.53(493.65-1344.26)]vs[1684.57(1110.54-2324.69)]µg/g,[851.39(409.57-1611.65)] vs[1440.74(1004.15-2594.73)]µg/g, respectively, and the lowest fecal total SCFAs concentration among the groups. DKD group also had a lower serum caproate concentration than that with diabetes (p=0.020)[0.57(0.47-0.61)]vs[0.65(0.53-0.79)]µmol/L. In the univariate regression analysis, fecal and serum acetate correlated with eGFR (OR=1.013, p=0.072; OR=1.017, p=0.032). The correlation between serum total SCFAs and eGFR showed statistical significance (OR=1.019, p=0.024) unadjusted and a borderline significance (OR=1.024, p=0.063) when adjusted for Hb and LDL. The decrease in serum acetate and total SCFAs were found of borderline significant difference in both subgroups (p=0.055, p=0.050). CONCLUSION: This study provides evidence that in individuals with DKD, serum and fecal SCFAs levels (fecal level in particular) were lowered, and there was a negative correlation between SCFAs and renal function.

[Influence of nitrate on the simultaneous methanogenesis and denitrification reaction of anaerobic biofilm and granular sludge].

The aims of this study are to further investigate the impact mechanism of nitrate on the simultaneous methanogenesis and denitrification (SMD) process of anaerobic biofilm, and to extend the application of the biofilm process in the treatment of high nitrogen and COD concentration organic wastewater. The SMD reactions were successfully carried out in a hybrid anaerobic biofilm and sludge reactor (HABSR) and an up-flow anaerobic sludge blanket (UASB), and the influence of nitrate on the performance of simultaneous carbon and nitrogen removal in biofilm and granular sludge were investigated using batch tests. The results showed that the nitrate concentration could obviously affect the carbon and nitrogen removal in both biofilm and granular sludge, and the increase of nitrate concentration had more serious impact on the granular sludge, and the biofilm presented higher COD and nitrogen removal efficiency and stronger resistance to toxic materials than the granular sludge. As the nitrate concentration was increased from 75 to 600 mg x L(-1), the COD removal rates were reduced from 273.26 to 0.1 mg x (h x g)(-1) in granular sludge and reduced from 95 to 1.7 mg x (h x g)(-1) in biofilm. At the same time, the denitrification rate of biofilm and granular sludge were increased form 21.43 and 22.31 mg x (h x g)(-1) to 83.72 and 61.06 mg x (h x g)(-1), respectively. The biofilm recovered the COD degradation rate more quickly and easily than the granular sludge, and the maximum COD removal rate reached 712.44 mg x (h x g)(-1). The nitrite accumulation was observed to be the major cause that affected the simultaneous carbon and nitrogen removal of biofilm and granular sludge. It's found that the maximum nitrite accumulation in biofilm was only one tenth of that of the granular sludge at the same nitrate concentration. The HABSR was proved to be an important alternative for SMD reaction employed in the treatment of high nitrogen and COD concentration organic wastewater.