Integrative analysis of circadian clock with prognostic and immunological biomarker identification in ovarian cancer.

Objective: To identify circadian clock (CC)-related key genes with clinical significance, providing potential biomarkers and novel insights into the CC of ovarian cancer (OC). Methods: Based on the RNA-seq profiles of OC patients in The Cancer Genome Atlas (TCGA), we explored the dysregulation and prognostic power of 12 reported CC-related genes (CCGs), which were used to generate a circadian clock index (CCI). Weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network were used to identify potential hub genes. Downstream analyses including differential and survival validations were comprehensively investigated. Results: Most CCGs are abnormally expressed and significantly associated with the overall survival (OS) of OC. OC patients with a high CCI had lower OS rates. While CCI was positively related to core CCGs such as ARNTL, it also showed significant associations with immune biomarkers including CD8+ T cell infiltration, the expression of PDL1 and CTLA4, and the expression of interleukins (IL-16, NLRP3, IL-1ß, and IL-33) and steroid hormones-related genes. WGCNA screened the green gene module to be mostly correlated with CCI and CCI group, which was utilized to construct a PPI network to pick out 15 hub genes (RNF169, EDC4, CHCHD1, MRPL51, UQCC2, USP34, POM121, RPL37, SNRPC, LAMTOR5, MRPL52, LAMTOR4, NDUFB1, NDUFC1, POLR3K) related to CC. Most of them can exert prognostic values for OS of OC, and all of them were significantly associated with immune cell infiltration. Additionally, upstream regulators including transcription factors and miRNAs of key genes were predicted. Conclusion: Collectively, 15 crucial CC genes showing indicative values for prognosis and immune microenvironment of OC were comprehensively identified. These findings provided insight into the further exploration of the molecular mechanisms of OC.

Aerobic degradation of parent triisobutyl phosphate and its metabolite diisobutyl phosphate in activated sludge: Degradation pathways and degrading bacteria.

Although organophosphate esters (OPEs) degradation has been widely studied, the degradation of their metabolites is always ignored. Triisobutyl phosphate (TiBP), a typical alkyl-OPEs, is of emerging concern because of its potential ecotoxicity in the environment. This study provides comprehensive understanding about the degradation of TiBP and one of its metabolites, diisobutyl phosphate (DiBP) using activated sludge (AS). The results showed that TiBP and DiBP were degraded mainly through hydrolysis, dehydrogenation, and hydroxylation. The degradation kinetics indicated that DiBP had similar transformation rates to its parent TiBP in AS, highlighting the importance of metabolite DiBP study. Dehydrogenase, hydroxylase, phosphotriesterase, phosphodiesterase, and phosphomonoesterase played an important role in contributing to TiBP and its metabolites degradation via enzyme activity analysis. Besides, the expression of genes encoding these enzymes in bacteria and the relative abundance change of bacterial populations indicated that Sphingomonas and Pseudomonas may be the degrading bacteria of TiBP and Pseudomonas may be the main degrading bacteria of DiBP. This study provides new perspectives for metabolite DiBP and its parent TiBP degradation. It highlights that the formation and degradation of metabolites must be considered into the future researches.

Triisobutyl phosphate biodegradation by enriched activated sludge consortia: Degradation mechanism and bioaugmentation potential.

This study investigated the ability of activated sludge (AS) to biodegrade triisobutyl phosphate (TiBP) after acclimation in an AS bioreactor by adding 50 mg/L TiBP. The bioreactor significantly increased the biotransformation rate of TiBP (2.15-12.7 d-1) over two months of acclimation. Seven transformation products (TPs) of TiBP were identified by high-resolution mass spectrometry, and hydrolysis, hydroxylation and dehydrogenation were the major biodegradation pathways of TiBP. TiBP degradation solutions at 0, 3, 7, and 10 h showed significantly toxic effects on zebrafish embryos, while the toxicity of TiBP degradation solutions at 24 h significantly decreased. Pseudomonas was inferred to be a specific bacterial population in the TiBP metabolic microbial consortium (TMMC) that degrades TiBP (p < 0.001). When TMMC (0.5, 1, and 2 gss/L) was introduced into AS, the TiBP biotransformation rates (1.97, 2.05, and 2.26 d-1 at 1.0 mg/L TiBP, and 0.09, 0.11, and 0.83 d-1 at 30.0 mg/L TiBP) were significantly enhanced compared to the control (0.31 and 0.07 d-1) without TMMC inoculation. In general, this study provides new insights into the key species populations that accelerate TiBP degradation and promote the development of TiBP reduction biotechnology in WWTPs.

Simultaneous heterotrophic and FeS2-based ferrous autotrophic denitrification process for low-C/N ratio wastewater treatment: Nitrate removal performance and microbial community analysis.

Heterotrophic-autotrophic denitrification reduces the cost of wastewater treatment and the risk of excess chemical oxygen demanded (COD) in the effluent. A mixotrophic denitrification system involving mixed heterotrophic and ferrous autotrophic bacteria was investigated to treat low-C/N ratio (C/N, defined as chemical oxygen demand (COD)/total nitrogen (TN)) wastewater with pyrite and organic carbon as electron donors. The system yielded effluent total nitrogen (TN) of 0.38 mg/L in 48 h due to a synergistic effect when the C/N ratio was 0.5 and influent nitrate nitrogen (NO3--N) was 20 mg/L; this TN value was significantly lower than those of the heterotrophic system (14.08 mg/L) and ferrous autotrophic system (12.00 mg/L). The highest abundance of the narG gene was observed in the mixotrophic denitrification system, along with more abundant microbial species. The dominant denitrification bacteria in each system included Thaurea, Ferritrophicum, Pseudomonas, and Thiobacillus, which varied with the initial inoculum source and the environment. Nevertheless, the abundance of the heterotrophic bacteria Thaurea decreased with prolonged operation of the systems. Together, these results implied that the simultaneous heterotrophic and FeS2-based ferrous autotrophic denitrification process can be an alternative approach for the treatment of low-C/N ratio wastewater.

Effect of nutrient level on phytoplankton community structure in different water bodies.

Increasing levels of pollution within water bodies can cause eutrophication and an associated rapid growth in and reproduction of phytoplankton. Although most frequently occurring in bodies of water such as lakes and dams, in recent years an increasing number of river systems in China have suffered serious algal blooms. The community structure of phytoplankton may differ, however, dependent on the hydrodynamic conditions and nutrient levels within the water body. The field investigation results obtained from a stagnant river in Suzhou City and Taihu Lake, China, showed that in water with higher concentrations of nitrogen and phosphorus, Chlorophyta became the predominant species and in water with lower concentrations of nitrogen and phosphorus, Cyanobacteria became the predominant species. Growth experiments with competitive species, Microcystis aeruginosa Kütz and Scenedesmus quadricauda (Turp.), were conducted at three different nutrient levels. The biomass of algae in pure and mixed cultures was measured under conditions of different N/P ratios at oligotrophic, eutrophic and hypertrophic nutrient levels. The results indicated that the most suitable state for the growth and reproduction of M. aeruginosa and S. quadricauda were eutrophic conditions in both pure and mixed cultures. Under competition, however, the lower medium nutrient levels favoured M. aeruginosa, while the higher medium nutrient levels better suited S. quadricauda. Under similar hydrodynamic conditions, the community structure of phytoplankton in the water body was determined by the dominant species in competition for nutrients.

Clogging processes caused by biofilm growth and organic particle accumulation in lab-scale vertical flow constructed wetlands.

The accumulation of organic matter in substratum pores is regarded as an important factor causing clogging separately in the subsurface flow constructed wetlands. In this study, the developing process of clogging caused by biofilm growth or organic particle accumulation instead of total organic matter accumulation was investigated in two grdups of lab-scale vertical flow constructed wetlands (VFCWs), which were fed with glucose (dissolved organic matter) and starch (particulate organic matter) influent. Results showed that the growth of biofilms within the substratum pores certainly caused remarkable reduction of effective porosity, especially for the strong organic wastewater, whereas its influence on infiltration rate was negligible. It was implied that the most important contribution of biofilm growth to clogging was accelerating the occurrence of clogging. In comparison with biofilm growth, particles accumulation within pores could rapidly reduce infiltration rate besides effective porosity and the clogging occurred in the upper 0-15 cm layer. With approximately equal amount of accumulated organic matter, the effective porosity of the clogged layer in starch-fed systems was far less than that of glucose-fed systems, which indicated that composition and accumulation mode in addition to the amount of the accumulated organic matter played an important role in causing clogging.

Effects of glucose and starch on the toxicity of nitrobenzene to plants and microbes in constructed wetlands.

Photosynthetic pigment content, antioxidant enzyme activities of plants, microbial enzyme activities and community structure were analyzed to investigate the effects of glucose and starch on the toxicity of nitrobenzene (NB) to plants and microbes in constructed wetlands (CWs). As the influent NB concentration increased from 10 mg/L to 100 mg/L, the NB removal efficiency of the blank group decreased from 97.1% to 75.02%. However, the NB removal efficiencies of the external carbon source groups were maintained at nearly 100%. External carbon sources accelerated the transformation process of NB to aniline (AN), thus decreasing NB toxicity to the microbes and plants. When the influent NB concentration reached 100 mg/L, the NB removal rates and NB reductase activities of the external carbon source groups were 2.4 times and 4 times higher, respectively, than those of the blank group. Most of the dominant genera found in the three CWs could reduce nitroaromatics to the corresponding aromatic amines according to the results of high-throughput sequencing. The performance of NB removal in the CWs indicated the potential of CWs for NB treatment and the necessity of external carbon sources under high NB concentrations.

HILI destabilizes microtubules by suppressing phosphorylation and Gigaxonin-mediated degradation of TBCB.

Human PIWIL2, aka HILI, is a member of PIWI protein family and overexpresses in various tumors. However, the underlying mechanisms of HILI in tumorigenesis remain largely unknown. TBCB has a critical role in regulating microtubule dynamics and is overexpressed in many cancers. Here we report that HILI inhibits Gigaxonin-mediated TBCB ubiquitination and degradation by interacting with TBCB, promoting the binding between HSP90 and TBCB, and suppressing the interaction between Gigaxonin and TBCB. Meanwhile, HILI can also reduce phosphorylation level of TBCB induced by PAK1. Our results showed that HILI suppresses microtubule polymerization and promotes cell proliferation, migration and invasion via TBCB for the first time, revealing a novel mechanism for HILI in tumorigenesis.

Piwil2 inhibits keratin 8 degradation through promoting p38-induced phosphorylation to resist Fas-mediated apoptosis.

The piwi-like 2 (piwil2) gene is widely expressed in tumors and protects cells from apoptosis induced by a variety of stress stimuli. However, the role of Piwil2 in Fas-mediated apoptosis remains unknown. Here, we present evidence that Piwil2 inhibits Fas-mediated apoptosis. By a bacterial two-hybrid screening, we identify a new Piwil2-interacting partner, keratin 8 (K8), a major intermediate filament protein protecting the cell from Fas-mediated apoptosis. Our results show that Piwil2 binds to K8 and p38 through its PIWI domain and forms a Piwil2/K8/P38 triple protein-protein complex. Thus, Piwil2 increases the phosphorylation level of K8 Ser-73 and then inhibits ubiquitin-mediated degradation of K8. As a result, the knockdown of Piwil2 increases the Fas protein level at the membrane. In addition to our previous finding that Piwil2 inhibits the expression of p53 through the Src/STAT3 pathway, here we demonstrate that Piwil2 represses p53 phosphorylation through p38. Our present study indicates that Piwil2 plays a role in Fas-mediated apoptosis for the first time and also can affect p53 phosphorylation in tumor cells, revealing a novel mechanism of Piwil2 in apoptosis, and supports that Piwil2 plays an active role in tumorigenesis.

[Effect of nitrogen and phosphorus on growth and competition of M. aeruginosa and S. quadricauda].

In order to disclosure the formation rule of predominant species in different nutrition conditions, three kinds of nutrition concentration were selected for the competition experiments with the common species of blue-green algae bloom Microcystis aeruginosa and the common species of green algae bloom Scenedesmus quadricauda. The competition relation was analysed by the competition parameters. The results indicate, in low nutrition, Scenedesmus quadricauda can stimulate the growth of Microcystis aeruginosa in mixed culture, the simulation becomes evident in low N/P ratio and M. aeruginosa can also stimulate the growth of S. quadricauda; in eutrophic condition, inhibition effect is connected with N/P; in hyper-eutrophic condition, the inhibition effect of S. quadricauda on M. aeruginosa is about three times as that of M. aeruginosa on S. quadricauda, and the effect of N/P ratio on competition inhibition parameters isn't evident. In low concentration N and P water, M. aeruginosa is easy to become predominant species, while in high concentration N and P water, S. quadricanda is easy to become predominant species.