Highly efficient visible-light photocatalytic ethane oxidation into ethyl hydroperoxide as a radical reservoir

Photocatalytic ethane conversion into value-added chemicals is a great challenge especially under visible light irradiation. The production of ethyl hydroperoxide (CH CH OOH), which is a promising radical reservoir for regulating the oxidative stress in cells, is even more challenging due to its facile decomposition. Here, we demonstrated a design of a highly efficient visible-light-responsive photocatalyst, Au/WO , for ethane oxidation into CH CH OOH, achieving an impressive yield of 1887 μmol g in two hours under visible light irradiation at room temperature for the first time. Furthermore, thermal energy was introduced into the photocatalytic system to increase the driving force for ethane oxidation, enhancing CH CH OOH production by six times to 11 233 μmol g at 100 °C and achieving a significant apparent quantum efficiency of 17.9% at 450 nm. In addition, trapping active species and isotope-labeling reactants revealed the reaction pathway. These findings pave the way for scalable ethane conversion into CH CH OOH as a potential anticancer drug

Effect of metabotropic glutamate receptor 3 genotype on N-acetylaspartate levels and neurocognition in non-smoking, active alcoholics

BACKGROUND: We studied the effects of single nucleotide polymorphisms (SNPs) in the metabotropic glutamate receptor 3 (GRM3) gene on brain N-acetylaspartate (NAA) concentrations and executive function (EF) skills in non-smoking, active alcoholics, and evaluated associations between these variables. METHODS: SNPs (rs6465084, rs1468412, and rs2299225) in GRM3 were genotyped in 49 male, non-smoking, alcohol-dependent patients and 45 healthy control subjects using ligase detection reactions. NAA/creatine (Cr) ratios in left prefrontal gray matter (GM) and white matter (WM), left parietal GM, left parietal WM, and cerebellar vermis regions were measured by Proton (1) H Magnetic resonance spectroscopy (MRS). EF was measured by the Wisconsin Card Sorting Test (WCST). RESULTS: Compared to controls, alcoholics had lower NAA/Cr ratios in prefrontal GM and WM regions and performed more poorly on all EF tests (P < 0.001). Alcoholics with the A/A genotype for SNP rs6465084 had lower NAA/Cr ratios in prefrontal GM and WM regions and had poorer EF skills than alcoholics who were G-carriers for this SNP (P < 0.01). Non-alcoholics with the A/A genotype for rs6465084 also had lower NAA/Cr levels in prefrontal GM and made more random errors in the WCST than G-carriers (P < 0.01). The A/A genotype group for SNP rs6465084 was significantly different from the G carriers for the variables of NAA/Cr ratios and WCST scores in both alcoholics and controls (P < 0.05). Alcoholics who were T-carriers for rs1468412 had lower NAA/Cr ratios in prefrontal GM and showed poorer EF skills (P < 0.05). No effects of rs2299225 genotype on NAA/Cr or executive skills were observed. NAA/Cr in left prefrontal regions correlated with certain parameters of EF testing in both alcoholics and controls (P < 0.05), but the significance of this correlation among alcoholics disappeared after adjustment for the effects of genotype. CONCLUSIONS: Our results provide evidence that glutamate system dysfunction may play a role in the prefrontal functional abnormalities seen in alcohol dependence. It is possible that certain GRM3 SNP genotypes (the A/A genotype of rs6465084 and the T allele of rs1468412) may further lower NAA/Cr levels and EF skills in addition to the effect of alcohol

The impact on the soil microbial community and enzyme activity of two earthworm species during the bioremediation of pentachlorophenol-contaminated soils

The ecological effect of earthworms on the fate of soil pentachlorophenol (PCP) differs with species. This study addressed the roles and mechanisms by which two earthworm species (epigeic Eisenia fetida and endogeic Amynthas robustus E. Perrier) affect the soil microbial community and enzyme activity during the bioremediation of PCP-contaminated soils. A. robustus removed more soil PCP than did E. foetida. A. robustus improved nitrogen utilisation efficiency and soil oxidation more than did E. foetida, whereas the latter promoted the organic matter cycle in the soil. Both earthworm species significantly increased the amount of cultivable bacteria and actinomyces in soils, enhancing the utilisation rate of the carbon source (i.e. carbohydrates, carboxyl acids, and amino acids) and improving the richness and evenness of the soil microbial community. Additionally, earthworm treatment optimized the soil microbial community and increased the amount of the PCP-4-monooxygenase gene. Phylogenic classification revealed stimulation of indigenous PCP bacterial degraders, as assigned to the families Flavobacteriaceae, Pseudomonadaceae and Sphingobacteriacea, by both earthworms. A. robustus and E. foetida specifically promoted Comamonadaceae and Moraxellaceae PCP degraders, respectively

Long Noncoding RNA HOTTIP Promotes Mouse Hepatic Stellate Cell Activation via Downregulating miR-148a

Background/Aims: HOTTIP is a critical modulator in human diseases including liver cancer, but its role and molecular biological mechanisms in liver fibrosis are still unclear. Methods: The expression profile of HOTTIP during the progression of liver fibrosis was detected in human liver samples and in CCl4-treated mice using qRT-PCR. The expressing sh-HOTTIP adenoviral vector was used to reduce HOTTIP levels in vivo. Dual-Luciferase Reporter Assay was performed to validate the interaction between miR-148a and HOTTIP, TGFBR1, or TGFBR2. Results: HOTTIP expressions in fibrotic liver samples and cirrhotic liver samples were significantly upregulated compared with healthy liver controls, and cirrhotic samples exhibited the highest levels of HOTTIP. Moreover, HOTTIP expressions were substantially induced in the liver tissues and hepatic stellate cells (HSC) of CCl4-treated mice. Ad-shHOTTIP delivery could alleviate CCl4- induced liver fibrosis in mice. Down-regulation of HOTTIP inhibited the viability and activation of HSCs in vitro, and HOTTIP negatively regulated miR-148a expression in HSCs. miR-148a had a negative effect on HSC activation by targeting TGFBR1 and TGFBR2. Conclusion: HOTTIP is involved in the progression of liver fibrosis by promoting HSC activation. The high level of HOTTIP downregulates miR-148a, thus to increase the level of TGFBR1 and TGFBR2 and contribute to liver fibrosis

Effects of two ecological earthworm species on atrazine degradation performance and bacterial community structure in red soil

Vermicomposting is an effective and environmentally friendly approach for eliminating soil organic contamination. Atrazine is one of the most commonly applied triazinic herbicides and frequently detected in agricultural soils. This study investigated the roles and mechanisms of two earthworm species (epigeic Eisenia foetida and endogeic Amynthas robustus) in microbial degradation of atrazine. Both earthworms accelerated atrazine degradation performance from 39.0% in sterile soils to 94.9%–95.7%, via neutralizing soil pH, consuming soil humus, altering bacterial community structure, enriching indigenous atrazine degraders and excreting the intestinal atrazine-degrading bacteria. Rhodoplanes and Kaistobacter were identified as soil indigenous degraders for atrazine mineralization and stimulated by both earthworm species. A. robustus excreted the intestinal Cupriavidus and Pseudomonas, whereas Flavobacterium was released by E. foetida. This study provides a comprehensive understanding of the distinct effects of two earthworm species on soil microbial community and atrazine degradation, offering technical supports to apply vermicomposting in effective soil bioremediation

The Transcription Factor GLI1 Mediates TGFb1 Driven EMT in Hepatocellular Carcinoma via a SNAI1-Dependent Mechanism

The role of the epithelial-to-mesenchymal transition (EMT) during hepatocellular carcinoma (HCC) progression is well established, however the regulatory mechanisms modulating this phenomenon remain unclear. Here, we demonstrate that transcription factor glioma-associated oncogene 1 (GLI1) modulates EMT through direct up-regulation of SNAI1 and serves as a downstream effector of the transforming growth factor-b1 (TGFb1) pathway, a well-known regulator of EMT in cancer cells. Overexpression of GLI1 increased proliferation, viability, migration, invasion, and colony formation by HCC cells. Conversely, GLI1 knockdown led to a decrease in all the above-mentioned cancer-associated phenotypes in HCC cells. Further analysis of GLI1 regulated cellular functions showed that this transcription factor is able to induce EMT and identified SNAI1 as a transcriptional target of GLI1 mediating this cellular effect in HCC cells. Moreover, we demonstrated that an intact GLI1-SNAI1 axis is required by TGFb1 to induce EMT in these cells. Together, these findings define a novel cellular mechanism regulated by GLI1, which controls the growth and EMT phenotype in HCC.National Institutes of Health Grants CA100882 and CA128633 (to LRR) and CA165076; the Mayo Clinic Center for Cell Signaling in Gastroenterology (NIDDK P30DK084567) (to MEFZ); the Mayo Clinic Cancer Center (CA15083), the Mayo Clinic Center for Translational Science Activities (NIH/NCRR CTSA Grant Number KL2 RR024151), and an American Gastroenterological Association Foundation for Digestive Health and Nutrition Bridging Grant (to LRR)

Effects of simulated heat waves on cardiovascular functions in senile mice

The mechanism of the effects of simulated heat waves on cardiovascular disease in senile mice was investigated. Heat waves were simulated in a TEM1880 meteorological environment simulation chamber, according to a heat wave that occurred in July 2001 in Nanjing, China. Eighteen senile mice were divided into control, heat wave, and heat wave BH4 groups, respectively. Mice in the heat wave and heat wave BH4 groups were exposed to simulated heat waves in the simulation chamber. The levels of ET-1, NO, HSP60, SOD, TNF, sICAM-1, and HIF-1a in each group of mice were measured after heat wave simulation. Results show that heat waves decreased SOD activity in the myocardial tissue of senile mice, increased NO, HSP60, TNF, sICAM-1, and HIF-1a levels, and slightly decreased ET-1 levels, BH4 can relieve the effects of heat waves on various biological indicators. After a comprehensive analysis of the experiments above, we draw the followings conclusions regarding the influence of heat waves on senile mice: excess HSP60 activated immune cells, and induced endothelial cells and macrophages to secrete large amounts of ICAM-1, TNF-a, and other inflammatory cytokines, it also activated the inflammation response in the body and damaged the coronary endothelial cell structure, which increased the permeability of blood vessel intima and decreased SOD activity in cardiac tissues. The oxidation of lipoproteins in the blood increased, and large amounts of cholesterol were generated. Cholesterol penetrated the intima and deposited on the blood vessel wall, forming atherosclerosis and leading to the occurrence of cardiovascular disease in senile mice. These results maybe are useful for studying the effects of heat waves on elderly humans, which we discussed in the discussion chapter.Peer reviewedComputer Scienc

Triple-Negative Breast Cancer Risk Genes Identified by Multigene Hereditary Cancer Panel Testing

Background: Germline genetic testing with hereditary cancer gene panels can identify women at increased risk of breast cancer. However, those at increased risk of triple-negative (estrogen receptor-negative, progesterone receptor-negative, human epidermal growth factor receptor-negative) breast cancer (TNBC) cannot be identified because predisposition genes for TNBC, other than BRCA1, have not been established. The aim of this study was to define the cancer panel genes associated with increased risk of TNBC. Methods: Multigene panel testing for 21 genes in 8753 TNBC patients was performed by a clinical testing laboratory, and testing for 17 genes in 2148 patients was conducted by a Triple Negative Breast Cancer Consortium(TNBCC) of research studies. Associations between deleterious mutations in cancer predisposition genes and TNBC were evaluated using results from TNBC patients and reference controls. Results: Germline pathogenic variants in BARD1, BRCA1, BRCA2, PALB2, and RAD51D were associated with high risk (odds ratio > 5.0) of TNBC and greater than 20% lifetime risk for overall breast cancer among Caucasians. Pathogenic variants in BRIP1, RAD51C, and TP53 were associated with moderate risk (odds ratio > 2) of TNBC. Similar trends were observed for the African American population. Pathogenic variants in these TNBC genes were detected in 12.0% (3.7% non-BRCA1/2) of all participants. Conclusions: Multigene hereditary cancer panel testing can identify women with elevated risk of TNBC due to mutations in BARD1, BRCA1, BRCA2, PALB2, and RAD51D. These women can potentially benefit from improved screening, risk management, and cancer prevention strategies. Patients with mutations may also benefit from specific targeted therapeutic strategies.Peer reviewe

The Antimicrobial Peptide Mastoparan X Protects Against Enterohemorrhagic Escherichia coli O157:H7 Infection, Inhibits Inflammation, and Enhances the Intestinal Epithelial Barrier

Escherichia coli can cause intestinal diseases in humans and livestock, destroy the intestinal barrier, exacerbate systemic inflammation, and seriously threaten human health and animal husbandry development. The aim of this study was to investigate whether the antimicrobial peptide mastoparan X (MPX) was effective against E. coli infection. BALB/c mice infected with E. coli by intraperitoneal injection, which represents a sepsis model. In this study, MPX exhibited no toxicity in IPEC-J2 cells and notably suppressed the levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), myeloperoxidase (MPO), and lactate dehydrogenase (LDH) released by E. coli. In addition, MPX improved the expression of ZO-1, occludin, and claudin and enhanced the wound healing of IPEC-J2 cells. The therapeutic effect of MPX was evaluated in a murine model, revealing that it protected mice from lethal E. coli infection. Furthermore, MPX increased the length of villi and reduced the infiltration of inflammatory cells into the jejunum. SEM and TEM analyses showed that MPX effectively ameliorated the jejunum damage caused by E. coli and increased the number and length of microvilli. In addition, MPX decreased the expression of IL-2, IL-6, TNF-α, p-p38, and p-p65 in the jejunum and colon. Moreover, MPX increased the expression of ZO-1, occludin, and MUC2 in the jejunum and colon, improved the function of the intestinal barrier, and promoted the absorption of nutrients. This study suggests that MPX is an effective therapeutic agent for E. coli infection and other intestinal diseases, laying the foundation for the development of new drugs for bacterial infections