TNFAIP3 Derived from Skeletal Stem Cells Alleviated Rat Osteoarthritis by Inhibiting the Necroptosis of Subchondral Osteoblasts.

Recent investigations have shown that the necroptosis of tissue cells in joints is important in the development of osteoarthritis (OA). This study aimed to investigate the potential effects of exogenous skeletal stem cells (SSCs) on the necroptosis of subchondral osteoblasts in OA. Human SSCs and subchondral osteoblasts isolated from human tibia plateaus were used for Western blotting, real-time PCR, RNA sequencing, gene editing, and necroptosis detection assays. In addition, the rat anterior cruciate ligament transection OA model was used to evaluate the effects of SSCs on osteoblast necroptosis in vivo. The micro-CT and pathological data showed that intra-articular injections of SSCs significantly improved the microarchitecture of subchondral trabecular bones in OA rats. Additionally, SSCs inhibited the necroptosis of subchondral osteoblasts in OA rats and necroptotic cell models. The results of bulk RNA sequencing of SSCs stimulated or not by tumor necrosis factor α suggested a correlation of SSCs-derived tumor necrosis factor α-induced protein 3 (TNFAIP3) and cell necroptosis. Furthermore, TNFAIP3-derived from SSCs contributed to the inhibition of the subchondral osteoblast necroptosis in vivo and in vitro. Moreover, the intra-articular injections of TNFAIP3-overexpressing SSCs further improved the subchondral trabecular bone remodeling of OA rats. Thus, we report that TNFAIP3 from SSCs contributed to the suppression of the subchondral osteoblast necroptosis, which suggests that necroptotic subchondral osteoblasts in joints may be possible targets to treat OA by stem cell therapy.

Genome-Centric Metatranscriptomic Characterization of a Humin-Facilitated Anaerobic Tetrabromobisphenol A-Dehalogenating Consortium.

Tetrabromobisphenol A (TBBPA), a widely used brominated flame retardant in electronics manufacturing, has caused global contamination due to improper e-waste disposal. Its persistence, bioaccumulation, and potential carcinogenicity drive studies of its transformation and underlying (a)biotic interactions. This study achieved an anaerobic enrichment culture capable of reductively dehalogenating TBBPA to the more bioavailable bisphenol A. 16S rRNA gene amplicon sequencing and quantitative PCR confirmed that successive dehalogenation of four bromide ions from TBBPA was coupled with the growth of both Dehalobacter sp. and Dehalococcoides sp. with growth yields of 5.0 ± 0.4 × 108 and 8.6 ± 4.6 × 108 cells per µmol Br- released (N = 3), respectively. TBBPA dehalogenation was facilitated by solid humin and reduced humin, which possessed the highest organic radical signal intensity and reducing groups -NH2, and maintained the highest dehalogenation rate and dehalogenator copies. Genome-centric metatranscriptomic analyses revealed upregulated putative TBBPA-dehalogenating rdhA (reductive dehalogenase) genes with humin amendment, cprA-like Dhb_rdhA1 gene in Dehalobacter species, and Dhc_rdhA1/Dhc_rdhA2 genes in Dehalococcoides species. The upregulated genes of lactate fermentation, de novo corrinoid biosynthesis, and extracellular electron transport in the humin amended treatment also stimulated TBBPA dehalogenation. This study provided a comprehensive understanding of humin-facilitated organohalide respiration.

Exploring efficient strategies for air quality improvement in China based on its regional characteristics and interannual evolution of PM2.5 pollution.

Fine particulate matter (PM2.5) harms human health and hinders normal human life. Considering the serious complexity and obvious regional characteristics of PM2.5 pollution, it is urgent to fill in the comprehensive overview of regional characteristics and interannual evolution of PM2.5. This review studied the PM2.5 pollution in six typical areas between 2014 and 2022 based on the data published by the Chinese government and nearly 120 relevant literature. We analyzed and compared the characteristics of interannual and quarterly changes of PM2.5 concentration. The Beijing-Tianjin-Hebei region (BTH), Yangtze River Delta (YRD) and Pearl River Delta (PRD) made remarkable progress in improving PM2.5 pollution, while Fenwei Plain (FWP), Sichuan Basin (SCB) and Northeast Plain (NEP) were slightly inferior mainly due to the relatively lower level of economic development. It was found that the annual average PM2.5 concentration change versus year curves in the three areas with better pollution control conditions can be merged into a smooth curve. Importantly, this can be fitted for the accurate evaluation of each area and provide reliable prediction of its future evolution. In addition, we analyzed the factors affecting the PM2.5 in each area and summarize the causes of air pollution in China. They included primary emission, secondary generation, regional transmission, as well as unfavorable air dispersion conditions. We also suggested that the PM2.5 pollution control should target specific industries and periods, and further research need to be carried out on the process of secondary production. The results provided useful assistance such as effect prediction and strategy guidance for PM2.5 pollution control in Chinese backward areas.

Suppressive stroma-immune prognostic signature impedes immunotherapy in ovarian cancer and can be reversed by PDGFRB inhibitors.

BACKGROUND: As the most lethal gynecologic cancer, ovarian cancer (OV) holds the potential of being immunotherapy-responsive. However, only modest therapeutic effects have been achieved by immunotherapies such as immune checkpoint blockade. This study aims to propose a generalized stroma-immune prognostic signature (SIPS) to identify OV patients who may benefit from immunotherapy. METHODS: The 2097 OV patients included in the study were significant with high-grade serous ovarian cancer in the III/IV stage. The 470 immune-related signatures were collected and analyzed by the Cox regression and Lasso algorithm to generalize a credible SIPS. Correlations between the SIPS signature and tumor microenvironment were further analyzed. The critical immunosuppressive role of stroma indicated by the SIPS was further validated by targeting the major suppressive stroma component (CAFs, Cancer-associated fibroblasts) in vitro and in vivo. With four machine-learning methods predicting tumor immune subtypes, the stroma-immune signature was upgraded to a 23-gene signature. RESULTS: The SIPS effectively discriminated the high-risk individuals in the training and validating cohorts, where the high SIPS succeeded in predicting worse survival in several immunotherapy cohorts. The SIPS signature was positively correlated with stroma components, especially CAFs and immunosuppressive cells in the tumor microenvironment, indicating the critical suppressive stroma-immune network. The combination of CAFs' marker PDGFRB inhibitors and frontline PARP inhibitors substantially inhibited tumor growth and promoted the survival of OV-bearing mice. The stroma-immune signature was upgraded to a 23-gene signature to improve clinical utility. Several drug types that suppress stroma-immune signatures, such as EGFR inhibitors, could be candidates for potential immunotherapeutic combinations in ovarian cancer. CONCLUSIONS: The stroma-immune signature could efficiently predict the immunotherapeutic sensitivity of OV patients. Immunotherapy and auxiliary drugs targeting stroma could enhance immunotherapeutic efficacy in ovarian cancer.

Cost-effectiveness analysis of dinutuximab ß for the treatment of high-risk neuroblastoma in China.

BACKGROUND: Dinutuximab ß can be used to treat children with high-risk neuroblastoma (NB). Due to its high price, whether dinutuximab ß is cost-effective for the treatment of high-risk NB remains uncertain. Therefore, assessing the cost-effectiveness of dinutuximab ß in children with high-risk NB is of high importance. METHODS: The health utilities and economic outcomes in children with high-risk NB were projected using a partitioned survival model. The individual patient data (IPD) of add-on treatment with dinutuximab ß (GD2 group) were derived from the literature, while the IPD of traditional therapy (TT group) were obtained from retrospective data of Shanghai Children's Medical Center. Treatment costs included drugs, adverse event-related expenses, and medical resource use. Utility values were obtained from the literature. Costs and quality-adjusted life-years (QALYs) were measured over a 10-year time horizon. Deterministic sensitivity analyses (DSA) and probabilistic sensitivity analyses (PSA) were also conducted. RESULTS: Compared with the TT group, QALY increased in the GD2 group by 0.72 with an increased cost of $171,269.70, leading to an incremental cost-effectiveness ratio of 236,462.75$/QALY. DSA showed that the price of dinutuximab ß was the main factor on the results than other parameters. Compared with the TT group, the GD2 group could not be cost-effective in the PSA at the $37,920/QALY threshold. CONCLUSION: Results found that dinutuximab ß is not a cost-effective treatment option for children with high-risk NB unless its price is significantly reduced.

Characteristics of groundwater microbial communities' structure under the impact of elevated nitrate concentrations in north China plain.

In groundwater environments, the interaction between microbial communities and the hydrogeochemical parameters have been investigated extensively in the past years. However, little is known whether the maximum contamination level (MCL) is a threshold value that dictates the microbial composition. In this study, we analyzed 10 groundwater samples for their nitrate, nitrite, COD and sulfate concentrations, and characterized their microbial compositions using 16 S rRNA based high-throughput sequencing methods. All the 10 samples had oxygen demands higher than the corresponding MCL of China (10 mg L-1); moreover, 4 out of 10 samples also had nitrate concentrations higher than the corresponding MCL, which indicated that the groundwater quality was negatively impacted by anthropogenic activities. Comparing the microbial composition of groundwater that had higher-than-MCL nitrate concentrations to those that had lower-than-MCL nitrate concentrations, no significant differences were detected in communities' richness and diversity. However, the non-metric multi-dimensional analysis suggested that the 4 groundwater samples whose nitrate concentration exceed MCL are distinctly different from those of the rest 6 samples, indicating that MCL does have a significant impact on microbial structures. Pearson's correlation analysis suggested that none of the four analyzed hydrochemical parameters had significant impact on microbial communities' richness and diversity; however, at the genus level, the correlation results suggested that JG30-KM-CM45, Sphingomonas and Rhodococcus are closely correlated with nitrate concentration. The findings of this study deepened our understanding with respect to the relationships between the environmental quality indices and the microbial compositions of groundwater.

A critical review on graphene oxide membrane for industrial wastewater treatment.

An important way to promote the environmental industry's goal of carbon reduction is to promote the recycling of resources. Membrane separation technology has unique advantages in resource recovery and advanced treatment of industrial wastewater. However, the great promise of traditional organic membrane is hampered by challenges associated with organic solvent tolerance, lack of oxidation resistance, and serious membrane fouling control. Moreover, the high concentrations of organic matter and inorganic salts in the membrane filtration concentrate also hinder the wider application of the membrane separation technology. The emerging cost-effective graphene oxide (GO)-based membrane with excellent resistance to organic solvents and oxidants, more hydrophilicity, lower membrane fouling, better separation performance has been expected to contribute more in industrial wastewater treatment. Herein, we provide comprehensive insights into the preparation and characteristic of GO membranes, as well as current research status and problems related to its future application in industrial wastewater treatment. Finally, concluding remarks and future perspectives have been deduced and recommended for the GO membrane separation technology application for industrial wastewater treatment, which leads to realizing sustainable wastewater recycling and a nearly "zero discharge" water treatment process.

Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) do not Increase the Risk of Hepatic Impairment in Patients with Non-Valvular Atrial Fibrillation: Insights from Multi-Source Medical Data.

BACKGROUND: There is controversy over whether non-vitamin K antagonist oral anticoagulants (NOACs) use increase the risk of hepatic impairment in patients with non-valvular atrial fibrillation (NVAF). We conducted a comprehensive assessment using multi-source medical data. METHODS: We first performed a systematic search of the PubMed, Embase, and Cochrane Library databases (through 11 August 2021) for randomised controlled trials (RCTs) and real-world studies (RWSs) that reported hepatic impairment events in patients with NVAF administered NOACs or vitamin K antagonists (VKAs) therapy. The primary outcomes were hepatic impairment identified by diagnostic liver injury (DLI) or abnormal liver enzyme (ALE). The secondary outcome was hepatic failure. Relative risks (RRs) for RCTs and adjusted hazard ratios (aHRs) for RWSs were calculated separately using random-effects models. We also conducted a disproportionality analysis by extracting reports of hepatic impairment associated with NOACs from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Reporting odds ratios (RORs) were calculated to identify the statistical associations between NOACs and hepatic impairment. Scenario analyses were further performed to eliminate event- and drug-related competition bias. RESULTS: A total of 559,873 patients from five RCTs and four RWSs were included in the pooled analysis. For RCTs, NOACs use was not associated with an increased risk of DLI (RR: 0.96, 95% confidence intervals (CI): 0.73-1.28) or ALE (RR: 0.91, 95% CI: 0.69-1.19) compared with VKAs. The merged results of RWSs also showed a similar risk of DLI (aHR: 0.88, 95% CI: 0.72-1.09) or ALE (aHR: 0.91, 95% CI: 0.82-1.00) between NOACs and VKAs. The results of hepatic failure were in accordance with the primacy outcomes. Analyses of individual NOACs did not significantly affect the results. Insights from the FAERS database failed to detect hepatic impairment signals for overall NOACs agents (ROR: 0.34, 95% CI: 0.32-0.37). Scenario analyses confirmed the primary results. CONCLUSIONS: Insights from multi-source medical data confirmed that NOACs use was not associated with an increased risk of hepatic impairment in patients with NVAF.

Microplastics contamination in groundwater of a drinking-water source area, northern China.

Although the contamination of microplastics (MPs) in groundwater has been anticipated, their occurrence, distribution, and composition require further understanding. In this study, the occurrence and distributions of MPs were investigated in shallow groundwater from an important water source district in Tianjin city of northern China. The abundance, the physical morphology, the chemical composition, and the potential correlations of the determined MPs with human activities were thoroughly characterized. MPs were determined from all ten sampling sites with the abundance ranged between 17.0 ± 2.16 to 44.0 ± 1.63 n/L, revealing the ubiquitous existed MPs contamination. Based on the physical categorization, fiber (44.74%) was the most abundant shape, while blue (31.02%) and transparent (26.09%) were the most prevalent colors. The dominant size of MPs was smaller than 200 µm which accounted for 73.10%. A total of seven types of MPs were determined with polyethylene, polyethylene terephthalate, and polystyrene as the main types, of which, polypropylene showed strong positive correlations with polystyrene, indicating the possible similar sources of them. Besides, the determined MPs in groundwater were greater in areas with the high population density and strong population activity, indicating their high correlation with human activity. The study highlighted the presence of MPs in groundwater of drinking water source in northern China and provided useful information for evaluating the potential ecological effects on water quality safety and human health brought by MPs.

Influence on denitrifying community performance by the long-term exposure to sulfamethoxazole and chlortetracycline in the continuous-flow EGSB reactors.

The response of the denitrification community to long-term antibiotic exposure requires further investigation. Here, the significantly altered denitrifying community structure and function were observed by continuous exposure to 1 mg/L sulfamethoxazole (SMZ) or chlortetracycline (CTC) for 180 d in the expanded granular sludge bed reactors. Thaurea, positively correlated with SMZ and NO3- removal efficiency (NrE), was highly enriched in the SMZ-added reactor, while, Comamons and Acinetobacter were largely inhibited. The acute inhibited and then gradual-recovered NrE (87.17-90.38 %) was observed with highly expressed narG, indicating the adaptability of Thaurea to SMZ. However, the abundance of Thaurea and Comamonas greatly decreased, while Melioribacter and Acinetobacter were largely enriched in the CTC-added reactor. CTC created more serious and continuous inhibition of NO3- reduction (NrE of 64.53-66.95 %), with lowly expressed narG. Improved NO2- reduction capacity was observed in both reactors (70.16-95.42 %) with highly expressed nirS and nosZ, revealing the adaptability of NO2- reduction populations to antibiotics.

Chemical constituents from the stems of Acanthopanax senticosus with their cytotoxic activities.

A new coumestan named 7,5'-dihydroxy-4'-(3''-hydroxy-3''-methyl-trans-isobut-1''-enyl) coumestan (1), together with five known compounds (2-6), was isolated from the EtOAc-soluble extract of the stems of Acanthopanax senticosus. Their structures were elucidated based on extensive spectroscopic analyses. All the isolates were evaluated for in vitro cytotoxic activities against four human cancer cells including HepG2, A549, HeLa and MCF-7. Among them, the new compound 1 was found to exhibit significant cytotoxic activity on HeLa cells with IC50 value of 6.5 µM.

Enhanced low-temperature denitrification by microbial consortium using solid-phase humin.

Reducing the use of liquid organic carbon electron donors during biostimulation of heterotrophic denitrification is critical for sustainable groundwater remediation. Solid-phase humin isolated from natural sources can provide a cost-effective alternative to classical electron donors. In this study, the low-temperature denitrification capacity of an acetate-fed microbial community was enhanced using humin at 20 °C and 10 °C. These enhancements were not caused by faster acetate consumption and greater bacterial growth with the addition of humin. Estimation of the electron balance and first-order kinetics suggested that the enhancement in denitrification occurred mainly after acetate exhaustion. Humin may therefore have acted as an additional electron donor for the denitrifying microbial community, with the reduced quinone group in humin potentially responsible for electron donation. The addition of humin increased the richness and diversity of the denitrifying microbial community, in which Dechloromonas spp. played a critical role. Given the prevalence of humin and denitrifiers using humic substances, our results have important implications in the bioremediation of nitrate-contaminated groundwater using less liquid organic carbon electron donors.

Influence of microbial spatial distribution and activity in an EGSB reactor under high- and low-loading denitrification desulfurization.

To characterize the impact of reactor configuration and influent loading on elemental sulphur (S0) recovery during denitrification desulfurization, a laboratory-scale expanded granular sludge bed (EGSB) reactor was established under two influent acetate/nitrate/sulphide loadings; the water flow velocity, microbial community, and functional genes at different heights were investigated. There was no S0 generated when acetate/nitrate/sulphide loadings were set to 0.95/0.60/1.05 kg/m3.d (low-loading). Furthermore, there were no typical denitrifying sulphide oxidizing bacteria under this condition, and Syntrophobacter, Anaerolineaceae genera were predominant in the reactor. As the influent loading was doubled (high-loading), S0 recovery increased to 87%; the bacterial distribution was relatively homogeneous with sulphide oxidation genera (Thauera) being predominant. Neither nirK nor sqr genes were detected in the low-loading sample at a height of 50 cm. The sqr/sox ratios of low-loading stage were 2.50 (10 cm), 0.94 (30 cm), and 0 (50 cm), and the ratios of the high-loading stage were 1.38 (10 cm), 1.33 (30 cm), and 1.08 (50 cm). A hydrodynamics analysis indicated that the water flow velocity was homogenous throughout the reactor. Appropriate reactor configuration and operation parameters play an important role in the efficient regulation of S0 recovery during denitrification desulfurization.

Microbial fuel cell-upflow biofilter coupling system for deep denitrification and power recovery: Efficiencies, bacterial succession and interactions.

The excess organic carbon is often added to meet denitrification requirements during municipal wastewater treatment, resulting in the carbon waste and increased risk of secondary pollution. In this study, microbial fuel cell (MFC) was coupled with an up-flow denitrification biofilter (BF), and the long-term performances of denitrification and power output were investigated under the different carbon source concentration. With sodium acetate (NaAc) of 600 mg/L and 300 mg/L, the favorable denitrification efficiencies were obtained (98.60%) and the stable current output was maintained (0.44 mÃ0.48 mA). By supplying NaAc of 150 mg/L, the high denitrification efficiency remained in a high range (89.31%) and the current output maintained at 0.12 mA, while, the denitrification efficiency dropped to 71.34% without coupling MFC. Electron balance analysis indicated that both nitrate removal and electron recovery efficiencies were higher in MFC-BF than that in BF, verifying the improved denitrification and carbon utilization performance. Coupling MFC significantly altered the bacterial community structure and composition, and while, the diversified abundance and distribution of bacterial genera were observed at the different locations. Compared with BF, the more exoelectrogenic genera (Desulfobacterium, Trichococcus) and genera holding both denitrifying and electrogenic functions (Dechloromonas, Geobacter) were found dominated in MFC-BF. Instead, the dominating genera in BF were Dechloromonas, Desulfomicrobium, Acidovorax and etc. By coupling MFC, the more complex and diversified network and the closer interaction relationships between the dominant potential functional genera were found. The study provides a feasible approach to effectively improve the denitrification efficiency and organic carbon recovery for deep denitrification process.

Disruption of super-enhancer-driven tumor suppressor gene RCAN1.4 expression promotes the malignancy of breast carcinoma.

BACKGROUND: Super-enhancers (SEs) play a crucial role in cancer, which is often associate with activated oncogenes. However, little is known about how SEs facilitate tumour suppression. Individuals with Down syndrome exhibit a remarkably reduced incidence of breast cancer (BC), moving the search for tumor suppressor genes on human chromosome 21 (HSA21). In this study, we aim to identify and explore potential mechanisms by which SEs are established for tumor suppressor RCAN1.4 on HSA21 in BC. METHODS: In silico analysis and immunohistochemical staining were used to assess the expression and clinical relevance of RCAN1.4 and RUNX3 in BC. Function experiments were performed to evaluate the effects of RCAN1.4 on the malignancy of breast carcinoma in vitro and in vivo. ChIP-seq data analysis, ChIP-qPCR, double-CRISPR genome editing, and luciferase reporter assay were utilized to confirm RUNX3 was involved in regulating RCAN1.4-associated SE in BC. The clinical value of co-expression of RCAN1.4 and RUNX3 was evaluated in BC patients. RESULTS: Here, we characterized RCAN1.4 as a potential tumour suppressor in BC. RCAN1.4 loss promoted tumour metastasis to bone and brain, and its overexpression inhibited tumour growth by blocking the calcineurin-NFATc1 pathway. Unexpectedly, we found RCAN1.4 expression was driven by a ~ 23 kb-long SE. RCAN1.4-SEdistal was sensitive to BRD4 inhibition, and its deletion decreased RCAN1.4 expression by over 90% and induced the malignant phenotype of BC cells. We also discovered that the binding sites in the SE region of RCAN1.4 were enriched for consensus sequences of transcription factor RUNX3. Knockdown of RUNX3 repressed the luciferase activity and also decreased H3K27ac enrichment binding at the SE region of RCAN1.4. Furthermore, abnormal SE-driven RCAN1.4 expression mediated by RUNX3 loss could be physiologically significant and clinically relevant in BC patients. Notably, we established a prognostic model based on RCAN1.4 and RUNX3 co-expression that effectively predicted the overall survival in BC patients. CONCLUSIONS: These findings reveal an important role of SEs in facilitating tumour suppression in BC. Considering that the combination of low RCAN1.4 and low RUNX3 expression has worse prognosis, RUNX3-RCAN1.4 axis maybe a novel prognostic biomarker and therapeutic target for BC patients.

Clinical significance and function of RDH16 as a tumor-suppressing gene in hepatocellular carcinoma.

AIM: Our previous transcriptome sequencing analysis detected that retinol dehydrogenase 16 (RDH16) was dramatically downregulated in hepatocellular carcinoma (HCC). RDH16 belongs to the short-chain dehydrogenases/reductases super family, and its role in HCC remains unknown. This study aimed to investigate the expression and function of RDH16 in HCC. METHODS: The mRNA and protein level of RDH16 in HCC samples were detected by quantitative real-time polymerase chain reaction and immunohistochemistry analyses, respectively. The role of RDH16 in HCC was determined by in vitro and in vivo functional studies. RESULTS: Downregulation of RDH16 has been detected in approximately 90% of primary HCCs, which was significantly associated with high serum alpha-fetoprotein level, tumor size, microsatellite formation, thrombus, and poor overall survival of HCC patients. Compared with non-tumor tissues, higher density of methylation was identified in HCC samples. In addition, RDH16 increases the level of retinoic acid and blocks the de novo synthesis of fatty acid in HCC cells. Functional study shows that ectopic expression of RDH16 in HCC cells suppresses cell growth, clonogenicity, and cell motility. CONCLUSIONS: RDH16 might be a prognostic biomarker and intervention point for new therapeutic strategies in HCC.

Efficient treatment of alizarin yellow R contained wastewater in an electrostimulated anaerobic-oxic integrated system.

An electrostimulated anaerobic-oxic integrated system was constructed for treating alizarin yellow R (AYR) containing wastewater. In electro-stimulated anaerobic unit, AYR decolorization efficiency improved from 51.2% to 96.6%. Two amination metabolites, p-phenylenediamine and 5-aminosalicylic acid, went through oxidation, ammonification and mineralization in oxic unit. Electro-stimulation promoted denitrification and COD removal efficiencies by 15.5% and 8.6%, respectively. A 20% improved nitrification efficiency was observed in oxic unit, due to elimination of AYR toxicity inhibition. No corrosion of heat-treated stainless steel occurred during the 60 days of continuous operation. Electrons sunk in denitrification and decolorization accounted for 34.4-36.8% of those released from COD removal, and 7.3% increase of removed nitrogen in nitrogenous compounds (AYR, nitrate and ammonia) was found. Electro-stimulated anaerobic unit predominated with fermentation and denitrification genera (Propionispira, Rhodocyclus, etc.) and aboundance of electro-active decolorization genus (Desulfovibrio, etc.) increased. Ammonia-oxidizing genus, Comamonas, was the most abundant in aerobic unit. Compared to the suspension, the electrostimulation could increased the abundance of electro-active genera in cathodic biofilm. This study revealed the feasibility of applying electro-stimulation and the conversion laws of nitrogenous organics in secondary bio-treatment system for treating toxic nitrogenous organics-contained wastewater.

Recirculation ratio regulates denitrifying sulfide removal and elemental sulfur recovery by altering sludge characteristics and microbial community composition in an EGSB reactor.

Expanded granular sludge blanket (EGSB) is regarded as a promising reactor to carry out denitrifying sulfide removal (DSR) and elemental sulfur (S0) recovery. Although the recirculation ratio is an essential parameter for EGSB reactors, how it impacts the DSR process remains poorly understood. Here, three lab-scale DSR-EGSB reactors were established with the different recirculation ratios (3:1, 6:1 and 9:1) to evaluate the corresponding variations in pollutant removal, S0 recovery, anaerobic granular sludge (AGS) characteristics and microbial community composition. It was found that an intermediate recirculation ratio (6:1) could facilitate long-term reactor stability. Adequate recirculation ratio could enhance S0 recovery, but an excessive recirculation ratio (9:1) was likely to cause AGS fragmentation and biomass loss. The S0 desorbed more from sludge at higher recirculation ratios, probably due to the enhanced hydraulic disturbance caused by the increased recirculation ratios. At the low recirculation ratio (3:1), S0 accumulation as inorganic suspended solids in AGS led to a decrease in VSS/TSS ratio and mass transfer efficiency. Although typical denitrifying and sulfide-oxidizing bacteria (e.g., Azoarcus, Thauera and Arcobacter) were predominant in all conditions, facultative and heterotrophic functional bacteria (e.g., Azoarcus and Thauera) were more adaptable to higher recirculation ratios than autotrophs (e.g., Arcobacter, Thiobacillus and Vulcanibacillus), which was conducive to the formation of bacterial aggregates to response to the increased recirculation ratio. The study revealed recirculation ratio regulation significantly impacted the DSR-EGSB reactor performance by altering AGS characteristics and microbial community composition, which provides a novel strategy to improve DSR performance and S0 recovery.

Sesamin attenuates intestinal injury in sepsis via the HMGB1/TLR4/IL-33 signalling pathway.

CONTEXT: Sepsis is currently one of the leading causes of death in intensive care units (ICUs). Sesamin was previously reported to inhibit inflammation. However, no studies have revealed the impact of sesamin on sepsis. OBJECTIVE: We studied the mechanism underlying the effect of sesamin on the pathophysiology of sepsis through the HMGB1/TLR4/IL-33 signalling pathway. MATERIALS AND METHODS: Fifty male BALB/c mice (n = 10 per group) were used to establish a caecal ligation and puncture (CLP) mouse model, and given daily injections of sesamin at a low, middle, or high concentration (25, 50, or 100 µM) during the seven-day study period; survival curves were generated by the Kaplan-Meier method. H&E staining and TUNEL staining were performed to assess changes in intestinal morphology intestinal damage in the mouse intestinal epithelium. Molecules related to the HMGB1/TLR4/IL-33 pathway were assessed by RT-qPCR and Western blotting. RESULTS: We found mice in the sepsis group survived for only 4 days, while those treated with sesamin survived for 6-7 days. In addition, sesamin significantly relieved the increase in the levels of MPO (21%, 33.3%), MDA (40.5% and 31.6%), DAO (1.24-fold and 2.31-fold), and pro-inflammatory cytokines such as TNF-α (75% and 79%) and IL-6 (1-fold and 1.67-fold) 24 and 48 h after sepsis induction and downregulated the expression of HMGB1, TLR4, and IL-33 while upregulating the expression of ZO-1 and occludin. DISCUSSION AND CONCLUSIONS: Sesamin improved the 7-day survival rate of septic mice, suppressed the inflammatory response in sepsis through the HMGB-1/TLR4/IL-33 signalling pathway, and further alleviated intestinal injury.

An update on the pharmacokinetics and pharmacodynamics of alisertib, a selective Aurora kinase A inhibitor.

Human Aurora kinases, including Aurora kinase A (AURKA), B (AURKB), and C (AURKC), play an essential role in mitotic events such as monitoring of the mitotic checkpoint, creation of bipolar mitotic spindle and alignment of centrosomes on it, also regulating centrosome separation, bio-orientation of chromosomes and cytokinesis. AURKA and AURKB are key regulators of mitosis and centrosome via polymerizing microfilaments and controlling chromatid segregation. In particular, AURKA plays critical roles in the regulation of mitotic entry, centrosome function, bipolar spindle assembly, and chromosome segregation. AURKA has been found to be overexpressed in various solid and haematological cancers and has been linked with poor prognosis. Its important role in cancer initiation, growth, and metastasis has brought the focus to search for potent and selective AURKA inhibitors for cancer treatment. MLN8237, also known as alisertib, is one selective AURKA inhibitor that has shown remarkable anticancer effects in preclinical studies. Alisertib exhibits favourable pharmacokinetic properties. Alisertib has generally showed good partial response rates of 4-52% and good safety profiles in Phase I and II trials when it is solely administered as well as combined with cytotoxic chemotherapeutic drugs. Recently, the multicentre, randomized Phase III study of alisertib in patients with relapsed or refractory peripheral T-cell lymphoma has been discontinued due to unsatisfactory efficacy. The low risk of side effects, accessibility, and effectiveness of alisertib makes it a new promising anticancer therapy and further mechanistic and clinical studies are warranted.