Chronic effects of benzalkonium chlorides on short chain fatty acids and methane production in semi-continuous anaerobic digestion of waste activated sludge.

As an emerging pollutant, benzalkonium chlorides (BACs) potentially enriched in waste activated sludge (WAS). However, the microbial response mechanism under chronic effects of BACs on acidogenesis and methanogenesis in anaerobic digestion (AD) has not been clearly disclosed. This study investigated the AD (by-)products and microbial evolution under low to high BACs concentrations from bioreactor startup to steady running. It was found that BACs can lead to an increase of WAS hydrolysis and fermentation, but a disturbance to acidogenic bacteria also occurred at low BACs concentration. A noticeable inhibition to methanogenesis occurred when BAC concentration was up to 15 mg/g TSS. Metagenomic analysis revealed the key genes involved in acetic acid (HAc) biosynthesis (i.e. phosphate acetyltransferase, PTA), ß-oxidation pathway (acetyl-CoA C-acetyltransferase) and propionic acid (HPr) conversion was slightly promoted compared with control. Furthermore, BACs inhibited the acetotrophic methanogenesis (i.e. acetyl-CoA synthetase), especially BAC concentration was up to 15 mg/g TSS, thereby enhanced short chain fatty acids (SCFAs) accumulation. Overall, chronic stimulation of functional microorganisms with increasing concentrations of BACs impact WAS fermentation.

Efficient methane production from waste activated sludge and Fenton-like pretreated rice straw in an integrated bio-electrochemical system.

Integrated microbial electrolysis cell-anaerobic digestion (MEC-AD) systems have demonstrated potential advantages for methane production in the presence of small amounts of residual inhibitors. In this study, a series of tests were conducted to analyse the acidification and methanogenesis performance of pretreated rice straw (RS) in anaerobic digestion (AD) and MEC-AD systems after the addition of Fenton-like reagents. The results indicated that the short-chain acids (SCFAs) accumulations reached 2284.64 ± 21.57 mg COD/L with a dosage ratio of 1/4 (g RS/g VSS sludge) in the MEC-AD system and that methane production increased by 63.8% compared with that of an individual AD system. In the interim, the net energy output reached 1.09 × 103 J/g TCOD, which was 1.23 times higher than that of the AD system. The residual Fe3+/Fe2+ in the pretreatment reagent was capable of promoting acidification and methanogenesis in sludge and RS fermentation. The RS hydrolysis products could constrain methanogenesis, which can be mitigated by introducing an MEC. The microbiological analyses revealed that the MEC strongly increased the enrichment of hydrogenotrophic methanogens, especially Methanobacterium (61.16%). Meanwhile, the Syntrophomonas and Acetobacterium abundances increased to 2.81% and 2.65%, respectively, which suggested the reinforcement of acetogenesis and methanogenesis. Therefore, the enhanced hydrogenotrophic methanogens might have served as the key for enhancing the efficiency of methanogenesis due to the introduction of an MEC.

Whole-Brain Radiotherapy Can Improve the Survival of Patients with Multiple Brain Metastases from Non-Small Cell Lung Cancer Treated by Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors.

OBJECTIVE: To observe whether whole-brain radiotherapy (WBRT) can bring survival benefits to patients with multiple brain metastases (BM) from non-small cell lung cancer (NSCLC) treated by epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) and determine the best time for WBRT intervention. METHODS: A retrospective analysis was performed on 148 patients diagnosed with EGFR gene-mutated NSCLC. All patients had multiple BM and received EGFR-TKI targeted therapy, which was performed to observe whether WBRT can bring survival benefits, and whether the choice of WBRT timing affects the survival of patients. RESULTS: Among the 148 patients with NSCLC treated with EGFR-TKI, 76 received WBRT; 72 were without WBRT. WBRT can reduce the intracranial progression rate in the patients (19.7% vs 33.3%, P=0.040), thus improving the intracranial progression-free survival (iPFS) (median iPFS: 11.9 months versus 10.2 months, P=0.039) and overall survival (OS) (median OS: 21.0 months versus 16.7 months, P=0.043). Multivariate analysis showed that WBRT (HR=0.606; 95% CI: 0.403-0.912, P=0.016) and the low Eastern Cooperative Oncology Group performance status (HR=1.884; 95% CI: 1.120-3.170, P=0.017) are independent prognostic factors in all patients. Further subgroup analysis showed that the choice of WBRT time had no effect on patient survival. CONCLUSION: WBRT can improve the survival of patients with multiple BM from NSCLC receiving EGFR-TKI targeted therapy and is an independent prognostic factor. The choice of RT time has no effect on patient survival.

A tree shrew model for steroid-associated osteonecrosis.

Osteonecrosis is a common human disease in orthopedics. It is difficult to treat, and half of patients may need artificial joint replacement, resulting in a considerable economic burden and a reduction in quality of life. Hormones are one of the major causes of osteonecrosis and high doses of corticosteroids are considered the most dangerous factor. Because of the complexity of treatment, we still need a better animal model that can be widely used in drug development and testing. Tree shrews are more closely related to primates than rodents. As such, we constructed a successful tree shrew model to establish and evaluate steroid-associated osteonecrosis (SAON). We found that low-dose lipopolysaccharide (LPS) combined with high-dose methylprednisolone (MPS) over 12 weeks could be used to establish a tree shrew model with femoral head necrosis. Serum biochemical and histological analyses showed that an ideal model was obtained. Thus, this work provides a useful animal model for the study of SAON and for the optimization of treatment methods.

Alkaline aided thermophiles pretreatment of waste activated sludge to increase short chain fatty acids production: Microbial community evolution by alkaline on hydrolysis and fermentation.

Adding alkaline into an anaerobic waste activated sludge (WAS) fermentation with thermophilic bacteria pretreatment could efficiently improve short-chain fatty acids (SCFAs) accumulation to 3550 ± 120 mg COD/L. The acidification rate in combined test was 21.2%, while that was 15.6% and 10.7% in sole thermophilic bacteria pretreatment and control tests respectively. Four distinct groups of microbes could be identified with noticeable shifts using the combined pretreatments, and tremendous effects were analyzed on organic content especially of the soluble proteins and SCFAs concentrations. Particularly, alkaline addition would significantly change the functional microbial structures, including the decrease of Caloramator with the function of thermophilic proteolytic and the increase of Acidobacteria TM7 and Petrimonas sp. The results above suggested that alkaline addition could decrease the hydrolytic substances consume by thermotolerance bacteria and final improve SCFAs accumulation in fermentation process.

Identification of key pathways and genes in nasopharyngeal carcinoma using bioinformatics analysis.

Nasopharyngeal carcinoma (NPC) is one of the most common malignancies in the head and neck. The aim of the current study was to identify the key pathways and genes involved in NPC through bioinformatics analysis and to identify potential molecular mechanisms underlying NPC proliferation and progression. Three gene expression profiles (GSE12452, GSE34573 and GSE64634) were downloaded from the Gene Expression Omnibus database. A total of 76 samples were analyzed, of which 59 were NPC samples and 17 were normal samples. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were subsequently conducted. The protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed using Cytoscape software. Analysis of GSE12452, GSE34573 and GSE64634 datasets identified 1,301 (553 upregulated and 748 downregulated), 1,232 (348 upregulated and 884 downregulated) and 1,218 (555 upregulated and 663 downregulated) DEGs, respectively. Using Venn diagram analysis, 268 DEGs (59 upregulated and 209 downregulated) that intersected all three datasets, were selected for further analysis. The results of GO analysis revealed that upregulated DEGs were significantly enriched in biological processes, including 'cell adhesion', 'cell division', 'mitosis' and 'mitotic cell cycle'. The downregulated DEGs were mainly enriched in 'microtubule-based movement', 'cilium movement', 'cilium axoneme assembly' and 'epithelial cell differentiation'. The KEGG pathway analysis results revealed that the upregulated DEGs were highly associated with several pathways, including 'extracellular matrix-receptor interaction', 'human papillomavirus infection', 'arrhythmogenic right ventricular cardiomyopathy' and 'focal adhesion', whereas the downregulated DEGs were enriched in 'metabolic pathways', 'Huntington's disease', 'fluid shear stress and atherosclerosis' and 'chemical carcinogenesis'. On the basis of the PPI network of the DEGs, the following top 10 hub genes were identified: Dynein axonemal light intermediate chain 1, dynein axonemal intermediate chain 2, calmodulin 1, coiled-coil domain containing 114, dynein axonemal heavy chain 5, radial spoke head 9 homolog, radial spoke head component 4A, NDC80 kinetochore complex component, thymidylate synthetase and coiled-coil domain containing 39. In conclusion, by performing a comprehensive bioinformatics analysis of DEGs, putative targets that could be used to elucidate the molecular mechanisms underlying NPC were identified.

Splice Variants of the Castor WRI1 Gene Upregulate Fatty Acid and Oil Biosynthesis When Expressed in Tobacco Leaves.

The plant-specific WRINKLED1 (WRI1) is a member of the AP2/EREBP class of transcription factors that positively regulate oil biosynthesis in plant tissues. Limited information is available for the role of WRI1 in oil biosynthesis in castor bean (Ricinus connunis L.), an important industrial oil crop. Here, we report the identification of two alternatively spliced transcripts of RcWRI1, designated as RcWRI1-A and RcWRI1-B. The open reading frames of RcWRI1-A (1341 bp) and RcWRI1-B (1332 bp) differ by a stretch of 9 bp, such that the predicted RcWRI1-B lacks the three amino acid residues "VYL" that are present in RcWRI1-A. The RcWRI1-A transcript is present in flowers, leaves, pericarps and developing seeds, while the RcWRI1-B mRNA is only detectable in developing seeds. When the two isoforms were individually introduced into an Arabidopsiswri1-1 loss-of-function mutant, total fatty acid content was almost restored to the wild-type level, and the percentage of the wrinkled seeds was largely reduced in the transgenic lines relative to the wri1-1 mutant line. Transient expression of each RcWRI1 splice isoform in N. benthamiana leaves upregulated the expression of the WRI1 target genes, and consequently increased the oil content by 4.3-4.9 fold when compared with the controls, and RcWRI1-B appeared to be more active than RcWRI1-A. Both RcWRI1-A and RcWRI1-B can be used as a key transcriptional regulator to enhance fatty acid and oil biosynthesis in leafy biomass.

Downregulation of P-gp, Ras and p-ERK1/2 contributes to the arsenic trioxide-induced reduction in drug resistance towards doxorubicin in gastric cancer cell lines.

Multidrug resistance (MDR) to doxorubicin (DOX) limits its effectiveness against tumor cells. Arsenic trioxide (As2O3) has been reported to reduce MDR in various types of cancer, but the mechanisms involving Ras and p-glycoprotein (P-gp) remain to be fully elucidated. The objectives of the present study were to evaluate As2O3 in reversing MDR to DOX, and to identify the association in antitumor activities between the effectiveness of DOX and Ras/phosphorylated (p­) extracellular signal­regulated kinase (ERK)1/2 signaling in SGC7901/ADM and SGC7901/S human gastric cancer cell lines. Cytotoxicity and sensitivity towards As2O3 were assessed using non­toxic and mildly­toxic concentrations (0.1 and 0.5 µM, respectively). The reversing effect of As2O3 on MDR was investigated prior to and following treatment with a cytokine activation of the recombinant human granulocyte colony stimulating factor ERK pathway. The SGC7901/ADM and SGC7901/S cells had the same sensitivity to As2O3. The SGC7901/ADM cells were resistant to DOX and As2O3 treatment reduced the level of resistance to DOX (P<0.01). The expression of P­glycoprotein (P-gp) in the SGC7901/ADM cells was higher than in the SGC7901/S cells (P<0.001). As2O3 treatment decreased the levels of P­gp in a time­ and dose­dependent manner (P<0.01). The expression of Ras was higher in the SGC7901/ADM cells than in the SGC7901/S cells, while the expression of p­ERK1/2 remained the same. As2O3 decreased the levels of Ras and p­ERK1/2 (P<0.01). Following pretreatment with rhG­CSF, the levels of Ras and p­ERK1/2 were further decreased (P<0.01). Drug­resistant gastric cancer cells had higher expression levels of P­gp and Ras, but not of p­ERK1/2. Non­ and mildly­toxic doses of As2O3 reduced MDR to DOX through Ras/p-ERK1/2 signaling.

[Distribution of cytomegalovirus DNA in vascular tissues and the relationship between virus and atherosclersogenesis].

OBJECTIVE: To explore the distribution of cytomegalovirus (CMV) in vascular tissues and the relationship between virus and atherosclerogenesis after CMV infecting mice. METHODS: (1) C57 BL/6J Murine model of CMV infection was established by intraperitoneal injection of CMV lethiferous amount. (2) After 12 weeks of CMV infection, the sera, carotids, aorta, hearts and postcaval veins from the mice were collected under euthanasia. The tissues would be used to DNA extraction, PCR and pathological examination. (3) Interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1) in serum were measured with ILELISA. RESULTS: (1) The typical pathologic feature in 2 aorta samples of 6 mice infected by CMV was found and the mice uninfected by CMV did not show any pathologic change. (2) CMV DNA appeared in 6 aorta, 6 postcaval veins, 4 carotids and 4 heart tissues including endocardium, cardiac muscle and coronary artery from the CMV infected mice. CMV DNA was not found in the vascular and heart tissues from 6 mice uninfected by CMV. (3) The ELISA test showed the significant difference (Mann-Witney test of Nonparametric Test, P < 0.05) in serum IL-6 (Median among 25% and 75% percentile: 113.7 pg/ml vs. 49.77 pg/ml) and MCP-1 (Median among 25% and 75% percentile: 128.7 pg/ml vs. 45.36 pg/ml) between CMV infected mice and uninfected mice. CONCLUSION: Cardiovascular cells are CMV latent reservoir in host body and CMV infection and the cytokines induced by CMV infection probably relate to atherosclerogenesis.

[Study on the micro-identification of insect material medicine].

OBJECTIVE: To seek microstructure characters and method of insect material medicines. METHOD: Insect material medicines and Chinese patent medicines containing these medicines were observed and compared with OLYMPUS. RESULT: The texture of integumentary cells, the shape and size of hair socket and bristle were important characters for species identification. CONCLUSION: This method can effectively identify 8 insect medicines, which provides some data and foundation for Chinese patent medicines' identification containing insects medicines and making quality standard for new drugs.