Downregulation of NEBL promotes migration and invasion of clear cell renal cell carcinoma by inducing epithelial-mesenchymal transition.

As a member of the nebulin protein family and a structural protein of cytoskeleton, NEBL plays an important role in cardiac diseases. Recently, literature have reported the involvement of NEBL in the occurrence and development of various cancers except clear cell renal cell carcinoma (ccRCC). In this study, we found that mRNA and protein of NEBL are downregulated remarkably in ccRCC tissues based on both the TCGA database and clinical samples we collected. The areas under curve values of NEBL analyzed based on the TCGA database, qRT-PCR and IHC results were 0.9376, 0.9733 and 0.9807, respectively. The lower mRNA level of NEBL was associated with worse outcomes in ccRCC patients. When overexpressing NEBL in ccRCC cell lines, the proliferation, migration and invasion of ccRCC cells were suppressed significantly, suggesting a tumor suppressor role of NEBL. In addition, we identified that NEBL is closely related to epithelial-mesenchymal transition (EMT), thereby reducing the motility of ccRCC cells. Furthermore, the lower expression of NEBL was correlated with ccRCC patients with distant organ metastasis. In summary, we firstly described the aberrant expression of NEBL and revealed its tumor suppressor role in ccRCC. Our data support that NEBL could serve as a valuable diagnostic and prognostic biomarker in ccRCC, as well as a promising therapeutic target.

Prognostic significance of HLA-G in patients with colorectal cancer: a meta-analysis and bioinformatics analysis.

PURPOSE: Human leukocyte antigen-G (HLA-G) has been reported to be aberrantly expressed in colorectal cancer (CRC); however, its prognostic value remains controversial. Hence, our meta-analysis aims to assess the prognostic value of HLA-G in CRC patients based on published literature and The Cancer Genome Atlas (TCGA) datasets. METHODS: A systematic search was conducted on relevant studies retrieved from four electronic databases including PubMed, Embase, Web of Science and Cochrane Library. Hazard ratios (HRs) with 95% confidence intervals (CIs) were recorded to be applied as effective values. Fixed-effects models or random-effects models were applied on the basis of the value of heterogeneity (I 2). Publication bias was analyzed by Begg's and Egger's tests. In addition, the results were validated by using TCGA datasets. RESULTS: Thirteen studies comprising 3896 patients were incorporated into this meta-analysis. The pooled results showed that HLA-G expression was significantly associated with poor overall survival (OS) in both the univariate analysis (HR = 1.44, 95% CI: 1.14-1.83, P = 0.002) and the multivariate analysis (HR = 1.55, 95% CI: 1.23-1.95, P < 0.001). Nevertheless, the expression of HLA-G is not related to age, sex, tumor type, tumor differentiation, TNM stage, or distant metastasis but lymph node metastasis. Notably, the prognosis of colorectal cancer was not consistent with the analysis result from TCGA data. CONCLUSION: HLA-G expression was significantly related to poor OS in CRC according to the results of our meta-analysis. However, we found that the prognostic significance was inconsistent with our results according to the TCGA data in CRC. Hence, more research is still needed to further illustrate the prognostic role of HLA-G in CRC.

The Emerging Role of Ferroptosis in Various Chronic Liver Diseases: Opportunity or Challenge.

Ferroptosis is a recently identified iron-dependent form of intracellular lipid peroxide accumulation-mediated cell death. Different from other types of cell death mechanisms, it exhibits distinct biological and morphological features characterized by the loss of lipid peroxidase repair activity caused by glutathione peroxidase 4, the presence of redox-active iron, and the oxidation of phospholipids-containing polyunsaturated fatty acids. In recent years, studies have shown that ferroptosis plays a key role in various liver diseases such as alcoholic liver injury, non-alcoholic steatohepatitis, liver cirrhosis, and liver cancer. However, the mechanism of ferroptosis and its regulation on chronic liver disease are controversial among different types of cells in the liver. Herein, we summarize the current studies on mechanism of ferroptosis in chronic liver disease, aiming to outline the blueprint of ferroptosis as an effective option for chronic liver disease therapy.

Integrating Low-Temperature-Resistant Two-Dimensional Elastic-Bending and Reconfigurable Plastic-Twisting Deformations into an Organic Crystal.

Integrating plasticity and elasticity in anisotropic molecular crystals is theoretically possible and is beneficial in enabling rich and complex deformations; however, it is much harder to implement in practice. Herein, we report a centimeter-long organic crystal that is two-dimensionally (2D) elastically bendable not only at room temperature but also at ultralow temperatures (-196 °C). The straight crystal can also be manually twisted and reconfigured to form arbitrary right-handed or left-handed helical structures. The integration of low-temperature-resistant (LTR) 2D elastic-bending and reconfigurable plastic-twisting deformations into one organic crystal expands the perspectives of the emerging crystal flexibility. Taking advantage of the unique multiple flexibility characteristics, spatial controllability of optical transmission for cryogenic applications and reusability of light-polarization rotations have been implemented simultaneously in an organic crystal.

Enhanced biostimulation coupled with a dynamic groundwater recirculation system for Cr(VI) removal from groundwater: A field-scale study.

A large gap exists between laboratory findings and successful implementation of bioremediation technologies for the treatment of chromium (Cr)-contaminated sites. This work conducted the enhanced bioremediation of Cr(VI) in situ via the addition of organic carbon (ethanol) coupled with a dynamic groundwater recirculation (DGR)-based system in a field-scale study. The DGR system was applied to successfully (1) remove Cr(VI) from groundwater via enhanced flushing by the recirculation system and (2) deliver the biostimulant to the heterogeneous subsurface environment, including a sand/cobble aquifer and a fractured bedrock aquifer. The results showed that the combined extraction and bioreduction of Cr(VI) were able to reduce Cr(VI) concentrations from 1000 to 2000 mg/L to below the clean-up goal of 0.1 mg/L within the operation period of 52 days. The effectiveness of Cr(VI) bioremediation and the relationship between microbial communities and geochemical parameters were evaluated. Multiple-line of evidence demonstrated that the introduction of ethanol significantly stimulated a variety of bacteria, including those responsible for denitrification, sulfate reduction and reduction of Cr(VI), which contributed to the establishment of reducing conditions in both aquifers. Cr(VI) was removed from groundwater via combined mechanisms of physical removal through the DGR system and the bioreduction of Cr(VI) followed by precipitation. In particular, it was found competitive growth among Cr(VI)-reducing bacteria (such as the enrichment of Geobacter, along with the reduced relative abundance of Acinetobacter and Pseudomonas) was induced by ethanol injection. Furthermore, Cr(VI), total organic carbon, NO2-, and SO42- played important roles in shaping the composition of the microbial community and its functions.

Tim-3 suppresses autoimmune hepatitis via the p38/MKP-1 pathway in Th17 cells.

T-cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) mediates T-cell suppression in various autoimmune diseases, such as chronic inflammatory liver disease. However, the regulatory effect of Tim-3 on Th17 cells in autoimmune hepatitis (AIH) is incompletely understood. Here, we studied the expression and function of Tim-3 in T cells in AIH patients and in a Con A (concanavalin A)-induced mouse AIH model. We report that the frequency of CD4+ Tim-3+ T cells in peripheral blood samples of AIH patients was lower than that in the control group. The p38/MKP-1 and p-JNK pathways were activated, and the expression of interleukin-17A protein was elevated in patients with AIH. Furthermore, the extent of pathological damage in the livers of mice with a blocked Tim-3 signaling pathway (anti-Tim-3 group) was markedly increased and correlated with elevated alanine aminotransferase and aspartate aminotransferase levels. In addition, the frequency of CD4+ IL-17+ T (Th17) cells in the anti-Tim-3 group was increased, while that in mice with blocked p38 activity was decreased. Finally, the expression of MKP-1 (p-p38) gradually increased in the control, Con A, and anti-Tim-3 groups, but the levels of interleukin-17A were decreased in the p38-blocked group. In summary, our results suggest that Tim-3 suppresses AIH by regulating Th17 cells through the p38/MKP-1 pathway.

Effects of two surfactants on microbial diversity of a PCE-degrading microbial consortium.

The effects of two representative surfactants, Rhamnolipids and Tween 80, on the microbial diversity of a PCE-degrading consortium during surfactant-enhanced biodegradation, were explored. The biodegradation efficiency was increased from 47.25% to 73.44%, and 47.25%-66.69%, with the addition of Rhamnolipid at 10 mg/L and Tween 80 at 50 mg/L, respectively. PCE biodegradation kinetics can be described by the pseudo-first-order reaction model for both scenarios. Analyses of alpha and beta indices of the microbial consortium showed that the microbial diversity of both groups exposed to either surfactant was not significantly different from the PCE only group. However, the bacterial abundance in the consortium changed significantly at both the phylum and genus levels. The results demonstrated that the composition of the PCE-degrading consortium is relatively stable, but the exposure to both surfactants results in the enrichment of some genera, which could contribute to the increased biodegradation efficiency.

Enhanced removal of tetrachloroethylene from aqueous solutions by biodegradation coupled with nZVI modified by layered double hydroxide.

Chlorinated volatile organic compounds, such as tetrachloroethylene (PCE), are the most commonly detected toxic contaminants in groundwater. In this study, the performance of PCE removal by a microbial consortium combined with nZVI modified by layered double hydroxide (nZVI-LDH) was evaluated. The enriched PCE-degrading consortium consisted of 44.49% Clostridium and other potential PCE degraders, and 0.5-2.5 mg/L PCE was completely biodegraded within 4 days. The characterization of nZVI-LDH indicated that LDH was coated on the surfaces of nZVI particles with an increased surface area. The PCE removal kinetics by nZVI-LDH was well described by a second-order model, and the removal rate constant of nZVI-LDH was 0.12 L h/mg, higher than that of native nZVI (0.02 L h/mg). Interestingly, the presence of Cu2+ improved the removal efficiency of PCE by nZVI-LDH, owing to its role as a catalyst or medium for charge transfer during reduction. Removal of PCE was enhanced by coupling the PCE-degrading consortium and nZVI-LDH. The initial removal of PCE was mainly dominated by the abiotic degradation and adsorption of nZVI-LDH, and biodegradation then played a major role in the exhaustion of nZVI-LDH. These results suggest that biodegradation coupled with nZVI-LDH has a great potential for applications in the remediation of chlorinated-solvent contaminated groundwater.

Aerobic and Anaerobic Biodegradation of 1,2-Dibromoethane by a Microbial Consortium under Simulated Groundwater Conditions.

This study was conducted to explore the potential for 1,2-Dibromoethane (EDB) biodegradation by an acclimated microbial consortium under simulated dynamic groundwater conditions. The enriched EDB-degrading consortium consisted of anaerobic bacteria Desulfovibrio, facultative anaerobe Chromobacterium, and other potential EDB degraders. The results showed that the biodegradation efficiency of EDB was more than 61% at 15 °C, and the EDB biodegradation can be best described by the apparent pseudo-first-order kinetics. EDB biodegradation occurred at a relatively broad range of initial dissolved oxygen (DO) from 1.2 to 5.1 mg/L, indicating that the microbial consortium had a strong ability to adapt. The addition of 40 mg/L of rhamnolipid and 0.3 mM of sodium lactate increased the biodegradation. A two-phase biodegradation scheme was proposed for the EDB biodegradation in this study: an aerobic biodegradation to carbon dioxide and an anaerobic biodegradation via a two-electron transfer pathway of dihaloelimination. To our knowledge, this is the first study that reported EDB biodegradation by an acclimated consortium under both aerobic and anaerobic conditions, a dynamic DO condition often encountered during enhanced biodegradation of EDB in the field.