GRP/GRPR enhances alcohol-associated liver injury through the IRF1-mediated Caspase-1 inflammasome and NOX2-dependent ROS pathway.

BACKGROUND AND AIMS: The common characteristics of alcohol-associated liver injury (ALI) include abnormal liver function, infiltration of inflammatory cells, and generation of oxidative stress. The gastrin-releasing peptide receptor (GRPR) is activated by its neuropeptide ligand, gastrin-releasing peptide (GRP). GRP/GRPR appears to induce the production of cytokines in immune cells and promotes neutrophil migration. However, the effects of GRP/GRPR in ALI are unknown. APPROACH AND RESULTS: We found high GRPR expression in the liver of patients with alcohol-associated steatohepatitis and increased pro-GRP levels in peripheral blood mononuclear cells of these patients compared with that of the control. Increased expression of GRP may be associated with histone H3 lysine 27 acetylation induced by alcohol, which promotes the expression of GRP and then GRPR binding. Grpr-/- and Grprflox/floxLysMCre mice alleviated ethanol-induced liver injury with relieved steatosis, lower serum alanine aminotransferase, aspartate aminotransferase, triglycerides, malondialdehyde, and superoxide dismutase levels, reduced neutrophil influx, and decreased expression and release of inflammatory cytokines and chemokines. Conversely, the overexpression of GRPR showed opposite effects. The pro-inflammatory and oxidative stress roles of GRPR might be dependent on IRF1-mediated Caspase-1 inflammasome and NOX2-dependent reactive oxygen species pathway, respectively. In addition, we verified the therapeutic and preventive effects of RH-1402, a novel GRPR antagonist, for ALI. CONCLUSIONS: A knockout or antagonist of GRPR during excess alcohol intake could have anti-inflammatory and antioxidative roles, as well as provide a platform for histone modification-based therapy for ALI.

Heavy metal pollution near an abandoned mercury-bearing waste recovery enterprise in southwestern China: Spatial distribution and its sources in soil and plants.

The contribution of smelting of nonferrous metals to heavy metals in surface soil have become increasingly important over the past decade. In this study, the distribution of heavy metals around an abandoned mercury-bearing waste recovery enterprise were investigated. Soil (14) and plant (18) samples were collected in the surrounding area. The total concentration of heavy metals and methyl mercury content were measured by ICP-MS and HPLC-ICP-MS. The results show that the average contents of Cd, Cr, Pb, Hg and As in all soil samples are higher than the second-level values of Soil environmental quality-Risk control standard for soil contamination of development land (GB 36600-2018). Hg in the leaves ranged from 0.003 to 0.174 mg kg-1. Besides, the Pearson correlation analysis results indicate that Hg has a different environmental behavior compared to the other heavy metal under certain environmental or geographical conditions. But the mantel test statistical analysis results show that the Cr (P < 0.01), Cu, Pb, and Fe (P < 0.05) in the soil may have similar pollution sources with carbonate-bound mercury and iron-manganese oxide-bound mercury. The Hg concentrations show no correlation among plant leaves and soil, but significantly influenced by the distance and wind direction. These findings suggest that Hg in plant leaves may be derived from the deposition of atmospheric mercury from secondary mercury plant. The results will supplement those for relevant policy making for mercury-bearing waste recovery enterprises to improve urban environmental quality and human health.

Retraction notice to "A novel circular RNA circ-ZNF652 promotes hepatocellular carcinoma metastasis through inducing snail-mediated epithelial-mesenchymal transition by sponging miR-203/miR-502-5p" [YBBRC 513(4) (2019) 812-819].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). The authors claim that other members of their lab attempted to repeat the experiments in this study several times and found that the activation ability of snail on circ-znf652 was significantly lower than reported, indicating that this regulation loop does not exist. The authors' incorrect experimental method and lack of reasonable control, coupled with the lack of experimental experience of the first author, led to the mistakes and mean the results cannot be relied upon. In order not to mislead other scientists, they requested to retract their manuscript. The Editor-in-Chief has approved this retraction. The authors apologise to the readership of the journal for these errors.

Effect of ibuprofen (IBU) on the sulfur-based and calcined pyrite-based autotrophic denitrification (SCPAD) systems with two filling modes: Performance and toxic response mechanism.

To investigate the effect of ibuprofen (IBU) on the sulfur-based and calcined pyrite-based autotrophic denitrification (SCPAD) systems, two individual reactors with the layered filling (L-SCPAD) and mixed filling (M-SCPAD) systems were established via sulfur and calcined pyrite. Effluent NO3--N concentration of the L-SCPAD and M-SCPAD systems was first increased to 6.44, 0.93 mg/L under 0.5 mg/L IBU exposure and gradually decreased to 1.66 mg/L, 0 mg/L under 4.0 mg/L IBU exposure, indicating that NO3--N removal performance of the M-SCPAD system was better than that of the L-SCPAD system. The variation of extracellular polymeric substances (EPS) characteristics demonstrated that more EPS was secreted in the M-SCPAD system compared to the L-SCPAD system, which contributed to forming a more stable biofilm structure and protecting microorganisms against the toxicity of IBU in the M-SCPAD system. Moreover, the increased electron transfer impedance and decreased cytochrome c implied that IBU inhibited the electron transfer efficiency of the L-SCPAD and M-SCPAD systems. The decreased adenosine triphosphate (ATP) and electron transfer system activity (ETSA) content showed that IBU inhibited metabolic activity, but the M-SCPAD system exhibited higher metabolic activity compared to the L-SCPAD system. In addition, the analysis of the bacterial community indicated a more stable abundance of nitrogen removal function bacteria (Bacillus) in the M-SCPAD system compared to the L-SCPAD system, which was conducive to maintaining a stable denitrification performance. The toxic response mechanism based on the biogeobattery effect was proposed in the SCPAD systems under IBU exposure. This study provided an important reference for the long-term toxic effect of IBU on the SCPAD systems.

Responses of anammox and sulfur/pyrite autotrophic denitrification in one-stage system to high nitrogen load: Performance, metabolic and bacterial community.

To remove residual nitrate from anammox process and achieve efficient nitrogen removal, a two-stage system (TAS) with the two individual reactors and a one-stage system (OAS) with the spatial functional areas in one reactor were established via anammox coupling sulfur autotrophic denitrification. The total nitrogen removal efficiency (TNRE) of OAS system (97.85 ± 1.92%) was higher than that of TAS system (93.63 ± 1.87%) under the influent NH4+-N and NO2--N of 227 and 300 mg/L. Meanwhile, the responses of microbial metabolism to high nitrogen load were investigated in term of microbial metabolites, electron transfer and metabolic activity. Microbial metabolites characteristics demonstrated that the OAS system secreted more EPS with lower protein (PN)/polysaccharide (PS) ratio than that in the TAS system, which was beneficial to protect bacteria from high nitrogen load. Electrochemical analysis suggested that the secretion of electron conductive substance (such as PN, PS) and redox active substances (such as flavin mononucleotide, the binding of flavins and cytochrome c on the outer membrane) were increased in the OAS system, which promoted the electron transfer efficiency. Moreover, the electron transport system activity (ETSA) values and ATP contents in OAS system were higher than that in the TAS system, which indicated that metabolic activity was improved in OAS system under the stimulation of high nitrogen load. Additionally, the bacterial community analysis indicated that the functional bacteria of Candidatus_Kuenenia and Armatimonadetes_gp5 had higher abundance in the OAS system than that in the TAS system, which was beneficial to realize the stable nitrogen removal performance. Overall, the responses mechanism of the OAS system was established to explain the resistant to high nitrogen load.

[The Role of TGF-ß1/SMAD in Diabetic Nephropathy: Mechanisms and Research Development]. / TGF-ß1/SMADåœ¨ç³–å°¿ç— è‚¾ç— ä¸­çš„ä½œç”¨æœºåˆ¶ä¸Žç ”ç©¶è¿›å±•.

Diabetic nephropathy (DN) is a common complication of diabetes and a leading cause of end-stage renal disease. Transforming growth factor-ß1 (TGF-ß1)/SMAD signaling activation plays an important role in the onset and progression of DN. Reported findings suggest that the activation of TGF-ß1 (including the latent form, the active form, and the receptors) and its downstream signaling proteins (SMAD3, SMAD7, etc.) plays a critical role in DN. In addition, TGF-ß1/SMAD signaling may mediate the pathogenesis and progression of DN via various microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Emerging evidence shows that TGF-ß1, SMAD3, and SMAD7 are the main signaling proteins that contribute to the development of DN, and that they can be potential targets for the treatment of DN. However, recent clinical trials have shown that the anti-TGF-ß1 monoclonal antibody treatment fails to effectively alleviate DN, which suggests that upstream inhibition of TGF-ß1/SMAD signaling does not alleviate clinical symptoms and that this may be related to the fact that TGF-ß1/SMAD has multiple biological effects. Targeted inhibition of the downstream TGF-ß1 signaling (e.g., SMAD3 and SMAD7) may be an effective approach to attenuate DN. This article discussed the current understanding of the molecular mechanisms and potential targets for the treatment and prevention of DN by focusing on TGF-ß1/SMAD signaling.

Discovery and therapeutic implications of bioactive dihydroxylated phenolic acids in patients with severe heart disease and conditions associated with inflammation and hypoxia.

Our initial studies detected elevated levels of 3,4-dihydroxyphenyllactic acid (DHPLA) in urine samples of patients with severe heart disease when compared with healthy subjects. Given the reported anti-inflammatory properties of DHPLA and related dihydroxylated phenolic acids (DPAs), we embarked on an exploratory multi-centre investigation in patients with no urinary tract infections to establish the possible pathophysiological significance and therapeutic implications of these findings. Chinese and Caucasian patients being treated for severe heart disease or those conditions associated with inflammation (WBC ≥ 10 ×109/L or hsCRP ≥ 3.0 mg/L) and/or hypoxia (PaO2 ≤ 75 mmHg) were enrolled; their urine samples were analyzed by HPLC, HPLC-MS, GC-MS and biotransformation assays. DHPLA was detected in urine samples of patients, but undetectable in healthy volunteers. Dynamic monitoring of inpatients undergoing treatment showed their DHPLA levels declined in proportion to their clinical improvement. In DHPLA-positive patients' fecal samples, Proteus vulgaris and P. mirabilis were more abundant than healthy volunteers. In culture, these gut bacteria were capable of reversible interconversion between DOPA and DHPLA. Furthermore, porcine and rodent organs were able to metabolize DOPA to DHPLA and related phenolic acids. The elevated levels of DHPLA in these patients suggest bioactive DPAs are generated de novo as part of a human's defense mechanism against disease. Because DHPLA isolated from Radix Salvia miltiorrhizae has a multitude of pharmacological activities, these data underpin the scientific basis of this medicinal plant's ethnopharmacological applications as well as highlighting the therapeutic potential of endogenous, natural or synthetic DPAs and their derivatives in humans.

Mechanistic Study of the Effects of Agricultural Amendments on Photochemical Processes in Paddy Water during Rice Growth.

The photochemical properties of paddy water might be affected by the commonly used amendments in rice fields owing to the associated changes in water chemistry; however, this important aspect has rarely been explored. We examined the effects of agricultural amendments on the photochemistry of paddy water during rice growth. The amendments significantly influenced the photogenerated reactive intermediates (RIs) in paddy water, such as triplet dissolved organic matter (3DOM*), singlet oxygen, and hydroxyl radicals. Compared with control experiments without amendments, the application of straw and lime increased the RI concentrations by up to 16.8 and 11.1 times, respectively, while biochar addition had limited effects on RI generation from paddy water in in situ experiments under sunlight. Fluorescence emission-excitation matrix spectroscopy, Fourier transform ion cyclotron resonance mass spectrometry, and structural equation modeling revealed that upon the addition of straw and lime amendments, humified DOM substances contained lignins, proteins, and fulvic acids, which could produce more RIs under irradiation. Moreover, the amendments significantly accelerated the degradation rate of 2,4-dichlorophenol but led to the 3DOM*-mediated formation of more toxic and stable dimeric products. This study provides new insights into the effects of amendments on the photochemistry of paddy water and the pathways of abiotic degradation of organic contaminants in paddy fields.

Enhanced simultaneous partial nitrification and denitrification performance of aerobic granular sludge via tapered aeration in sequencing batch reactor for treating low strength and low COD/TN ratio municipal wastewater.

The aerobic granular sludge simultaneous partial nitrification, denitrification and phosphorus removal (AGS-SPNDPR) process was carried out via tapered aeration in sequencing batch reactor (SBR) for treating low strength and low COD/TN ratio municipal wastewater. The results showed that aerobic granular sludge was successfully cultivated with good sedimentation performance when treating the municipal wastewater. Meanwhile, the median granule size increased to 270 (R1) and 257 (R2) µm on day 80. The excellent removal performance of COD (92%) and NH4+-N (95%) were achieved under different aeration modes, while the higher TN removal efficiency (76%) was achieved by tapered aeration. The accumulation of NO2--N in R2 indicated that the tapered aeration was beneficial to achieve simultaneously partial nitrification and denitrification. Meanwhile, the high-efficiency phosphorus (95%) removal was realized via additional carbon source, and SPNDPR process was formed under tapered aeration. The bacterial community analysis indicated denitrifying glycogen-accumulating organisms (DGAOs) Candidatus_Competibacter and ammonia-oxidizing bacteria (AOB) Nitrosomonas were more effectively enriched via tapered aeration, while phosphorus-accumulating organisms (PAOs) Candidatus_Accumulibacter were effectively enriched under additional organic carbon. AOB, denitrifying bacteria and PAOs were simultaneously enriched by tapered aeration and additional carbon source, which was beneficial to nutrients removal. This study might be conducive to the application of AGS-SPNDPR system for treating low strength and low COD/TN ratio municipal wastewater under tapered aeration.

Rational design of biogenic PdxAuy nanoparticles with enhanced catalytic performance for electrocatalysis and azo dyes degradation.

The green biogenic PdAu nanoparticles (bio-PdAu NPs) exhibits remarkable catalytic performance in hydrogenation, which is highly desired. However, the catalytic principles and effectiveness of bio-PdxAuy NPs in response to various catalytic systems (electrocatalysis and suspension-catalysis) are unclear. Herein, a facile synthetic strategy for bio-PdxAuy NPs synthesis with controlled size and the catalytic principles for hydrogen evolution reaction (HER) and azo dye degradation is reported. In the biosynthetic process, the size and composition of the bio-PdxAuy NPs could be precisely controlled by predesigning the precursor mass ratio of Pd/Au, and the Au proportion showed a linear relationship with the size of NPs (R2 = 0.92). The obtained bio-PdxAuy NPs exhibit variable activity in electrocatalysis (HER) and suspension-catalysis (azo dye degradation). For electrocatalysis, the formation of conductive networks that facilitates the extracellular electron transfer is crucial. It was revealed that the bio-Pd2Au8 exhibited superior electrocatalytic performance in HER/toward hydrogen evolution, with a maximum current density of 1.65 mA cm-2, which was 1.54 times higher than that commercial Pd/C (1.07 mA cm-2). The high electrocatalytic activity was attributed to its appropriate size (81.38 ± 6.14 nm) and uniform distribution on the cell surface, which promoted the extracellular electron transfer by constructing a conductive network between catalyst and electrode. However, for suspension-catalysis, the size effect and synergistic effect of bimetallic NPs have a more prominent effect on the degradation of azo dyes. As the increase of Au proportion the particle size decreases, and the catalytic activity of bio-PdxAuy improved significantly. The response principles of bio-PdxAuy proposed in this study provide a reliable reference for the rational design of bio-based bimetallic catalysts with enhanced catalytic performance.

Semi-starvation fluctuation driving rapid partial denitrification granular sludge cultivation in situ by microorganism exudate metabolites feedbacks.

In this study, semi-starvation fluctuation driving PD granules cultivation in situ by microorganism exudate metabolites feedbacks was firstly investigated. The PD granules of high nitrite production were cultivated with an excellent mean nitrate-to-nitrite transformation rate (NTR) of 56.39% in just 30 days. The granules size was improved from the initial size of 0.09 ± 0.01 mm in diameter to a size above 2 mm when the extracellular polymeric substance (EPS) content increased from 80.21 ± 10.20 mg/g MLVSS to 777.00 ± 22.13 mg/g MLVSS. Acyl-homoserine lactone signals (AHLs) ultimately increased ten-fold more than the initially through 30 days of cultivation. Meanwhile, Thauera had been identified as the main function bacteria of PD, which enriched from 0.47% to 10.67%. Results demonstrated that AHLs, EPS, PD bacteria and the PD granules cultivation were closely associated. Semi-starvation fluctuation produced oligotrophic stress on bacterial community, a part of bacteria would be eliminated on starvation for oligotrophic stress and AHLs of bacteria regarded as distress signals resulted in the rapid formation of PD granules. A mechanism for PD granular cultivation with semi-starvation fluctuation was proposed from the aspect of oligotrophic stress. A better strategy for rapid PD granules cultivation was obtained and it could be useful for the mainstream granule-based PD combined with the anammox process application in the future.

Effect of calcinated pyrite on simultaneous ammonia, nitrate and phosphorus removal in the BAF system and the Fe2+ regulatory mechanisms: Electron transfer and biofilm properties.

To efficiently remove nitrogen and phosphorus from secondary effluent with low values of COD/TN, a novel biological aerated filter (BAF) utilizing calcined pyrite with a large specific surface area (SSA) and pore diameter (PD) was designed to address this challenge. From the perspective of nutrients removal performance, and the corresponding effluent total nitrogen (TN) and PO43--P in the calcined pyrite autotrophic denitrification (CPAD) process decreased from 40.21 to 1.07 mg/L to 1.22 and 0.14 mg/L, respectively. Furthermore, the nutrients removal kinetics analysis showed that the CPAD and pyrite autotrophic denitrification (PAD) processes could be fitted with Half-order and Zero-order reactions via kinetics analysis, respectively, indicating that the TN removal performance of CPAD processes was better than that of the PAD process. Moreover, CPAD combined with sulfur autotrophic denitrification (SAD) processes was fitted by First-order reaction, and the TN removal performance was further enhanced over the CPAD process. From the perspective of microregulation, Fe2+ production in the PAD and CPAD processes could accelerate the electron transfer rate by increasing electron transport system activity (ETSA) and reducing electrochemical impedance spectroscopy (EIS). Moreover, Fe2+ stimulated microbes to produce more proteins (PN) and C10-HSL, which improved biofilm stability and interspecific communication processes. Notably, nitrifiers and autotrophic denitrifiers were simultaneously enriched via detection of high-throughput sequencing of 16 S rRNA genes, which verified the feasibility of simultaneous nitrification and autotrophic denitrification. Therefore, BAF with calcined pyrite and sulfur as composite fillers have a considerable advantage in nutrients removal.

Differences in nitrification and ammonium-oxidising prokaryotes in the process of wetland restoration.

Ammonia-oxidising archaea (AOA) and ammonia-oxidising bacteria (AOB) are ammonium oxidising prokaryotes that can drive soil nitrification in wetlands. During the restoration of wetlands, different types of land use soils (agricultural soil [AS], restored wetland soil [RS], and natural wetland soil [NWS]) are present. However, studies on the effects of changes in the types of land use in wetlands during restoration on nitrification and the community composition of AOA and AOB are still not well understood. In this study, the differences in the potential nitrification rate (PNR) and community composition of AOA and AOB in AS, RS, and NWS were compared and discussed. The results indicated that the PNRs in the AS, RS, and NWS were on the same order of magnitude. Nitrification was mainly driven by AOB. High-throughput sequencing results showed that the genus Nitrososphaera of AOA and unclassified_o_Nitrosomonadales of AOB were only detected in the AS. Redundancy analysis (RDA) results indicated that the community composition of AOA was mostly influenced by pH, while TC was the most influential variable on the community composition of AOB. Our study provides a basis for distinguishing the roles of ammonium-oxidising prokaryotes in nitrification and further understanding the changes in nitrifying activity in wetlands during restoration.

Acupuncture for Adults with Diarrhea-Predominant Irritable Bowel Syndrome or Functional Diarrhea: A Systematic Review and Meta-Analysis.

Objective. To evaluate the clinical effectiveness and safety of acupuncture therapy in the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) or functional diarrhea (FD) in adults. Method. Five electronic databases-PubMed, EMBASE, CNKI, VIP, and Wanfang-were searched, respectively, until June 8, 2020. The literature of clinical randomized controlled trials of acupuncture for the treatment of IBS-D or FD in adults were collected. Meta-analysis was conducted by Using Stata 16.0 software, the quality of the included studies was assessed by the RevMan ROB summary and graph, and the results were graded by GRADE. Result. Thirty-one studies with 3234 patients were included. Most of the studies were evaluated as low risk of bias related to selection bias, attrition bias, and reporting bias. Nevertheless, seven studies showed the high risk of bias due to incomplete outcome data. GRADE's assessments were either moderate certainty or low certainty. Compared with loperamide, acupuncture showed more effectiveness in weekly defecation (SMD = -0.29, 95% CI [-0.49, -0.08]), but no significant improvement in the result of the Bristol stool form (SMD = -0.28, 95% CI [-0.68, 0.12]). In terms of the drop-off rate, although the acupuncture group was higher than the bacillus licheniformis plus beanxit group (RR = 2.57, 95% CI [0.24, 27.65]), loperamide group (RR = 1.11, 95% CI [0.57, 2.15]), and trimebutine maleate group (RR = 1.19, 95% CI [0.31, 4.53]), respectively, it was lower than the dicetel group (RR = 0.83, 95% CI [0.56, 1.23]) and affected the overall trend (RR = 0.93, 95% CI [0.67, 1.29]). Besides, acupuncture produced more significant effect than dicetel related to the total symptom score (SMD = -1.17, 95% CI [-1.42, -0.93]), IBS quality of life (SMD = 2.37, 95% CI [1.94, 2.80]), recurrence rate (RR = 0.43, 95% CI [0.28, 0.66]), and IBS Symptom Severity Scale (SMD = -0.75, 95% CI [-1.04, -0.47]). Compared to dicetel (RR = 1.25, 95% CI [1.18, 1.32]) and trimebutine maleate (RR = 1.35, 95% CI [1.13, 1.61]), acupuncture also showed more effective at total efficiency. The more adverse effect occurred in the acupuncture group when comparing with the dicetel group (RR = 11.86, 95% CI [1.58, 89.07]) and loperamide group (RR = 4.42, 95% CI [0.57, 33.97]), but most of the adverse reactions were mild hypodermic hemorrhage. Conclusion. Acupuncture treatment can improve the clinical effectiveness of IBS-D or FD, with great safety, but the above conclusions need to be further verified through the higher quality of evidence.

Development and Evaluation of Cucurbitacin B Microemulsion: the Effect of Oil Phase and Aqueous Phase on Drug Percutaneous Absorption Based on ATR-FTIR Spectroscopy and Molecular Modeling.

The present study aimed to develop a cucurbitacin B microemulsion (CuB-ME) and investigate the mechanism of the enhanced drug skin absorption at the molecular level. Firstly, the pseudo-ternary phase diagrams were developed to evaluate the effect of composition on microemulsion properties systematically. The formulation composition types and ratios of oil phase, surfactant, co-surfactant, and aqueous phase were optimized by an in vitro skin permeation experiment, and the optimized formula was confirmed with the pharmacodynamics study. Furthermore, the molecular mechanism of enhanced skin permeation was investigated using ATR-FTIR and molecular modeling. As a result, the optimized CuB-ME formulation was composed of Azone:Tween 80:ethanol:water = 2.5:16.9:5.6:75.0 (w/w/w/w). The oil phase improved skin permeation by disordering the stratum corneum intercellular liquid, while the aqueous phase impacted the particle size of the microemulsion and permeability coefficient of the drug. Besides, the hydration state of skin lipid also enhanced drug permeation by the interaction of water and the polar head of ceramide. The in vitro skin permeation amount was 45.47 ± 10.39 µg/cm2, and no significant skin irritation was observed. The pharmacodynamics study demonstrated that CuB-ME had a significant therapeutic effect on the animal tumor model. In conclusion, the CuB-ME was developed successfully and the effect of the oil phase and aqueous phase on drug skin permeation was clarified at the molecular level.

LncRNA CCAT1 promotes autophagy via regulating ATG7 by sponging miR-181 in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a significant clinical challenge, and the mechanisms underlying HCC pathogenesis remain incompletely understood. Colon cancer associated transcript 1 (CCAT1), is one novel long noncoding RNA (lncRNA) which is upregulated in HCC. Autophagy is a vital process in HCC progression, and it is unknown whether CCAT1 regulates autophagy in HCC. MATERIALS AND METHODS: Immunofluorescence staining and transmission electron microscopy were used to analyze autophagy activity. Luciferase assay was performed to confirm miRNA-181a-5p (miR-181a-5p) bind CCAT1 and ATG7. RESULTS: CCAT1 levels were higher in tissue and cell lines of HCC. In function research, we found that CCAT1 facilitates HCC cell autophagy and cell proliferation. Our results show that, mechanistically, CCAT1 promotes autophagy through functioning as a sponge for miR-181a-5p, and then regulating ATG7 expression. CONCLUSION: Our findings indicate CCAT1 may play a role in regulating autophagy by sponging miR-181a-5p in HCC.

A novel circular RNA circ-ZNF652 promotes hepatocellular carcinoma metastasis through inducing snail-mediated epithelial-mesenchymal transition by sponging miR-203/miR-502-5p.

Circular RNA (circRNA), a special class of non-coding RNA, is increasingly being realized as a critical regulator in human diseases, including carcinomas. However, its role in hepatocellular carcinoma (HCC) metastasis remains largely unknown. Herein, we enrolled three Gene Expression Omnibus (GEO) databases and screened and identified a novel circRNA, circ-ZNF652 (hsa_circ_0003258), which was significantly upregulated in HCC tissues and cell lines. Importantly, HCC patients with high circ-ZNF652 expression were more prone to vascular invasion, intrahepatic metastasis, distant metastasis, and poor outcome. Subsequent functional experiments showed that depletion of circ-ZNF652 dramatically suppressed the migratory and invasive capabilities of HCC cells in vitro as well as tumor metastasis in vivo by inhibiting the process of epithelial-mesenchymal transition (EMT). Mechanistically, circ-ZNF652 could physically interact with miR-203 and miR-502-5p to increase the expression of their common target gene Snail (a key transcription factor that triggers EMT), thereby promoting the metastasis of HCC. In turn, the upregulated Snail was capable of binding to the E-box motif (CAGGTG) on the promoter of circ-ZNF652 to elevate circ-ZNF652 expression. Collectively, our findings suggest that circ-ZNF652 is a novel driver of EMT and unveil the important regulatory role of circ-ZNF652/miR-203/miR-502-5p/Snail feedback loop in HCC metastasis.

LncRNA TUBA4B functions as a competitive endogenous RNA to inhibit gastric cancer progression by elevating PTEN via sponging miR-214 and miR-216a/b.

BACKGROUND: Emerging evidence demonstrates that long non-coding RNA (lncRNA) is an important regulator in tumorigenesis and development. Tubulin Alpha 4B (TUBA4B), a novel lncRNA, was recently proposed as a tumor suppressor in several human cancers. However, its role in gastric cancer (GC) remains unclear. In this study, we aimed to investigate the expression level, clinical implication, biological function and potential regulatory mechanism of TUBA4B in GC. METHODS: qRT-PCR was employed to detect the expression of TUBA4B in GC tissues, cell lines and plasma. In vitro and in vivo experiments were carried out using colony formation/CCK-8/transwell invasion/cell apoptosis assay and xenograft tumor model, respectively. mRNA sequencing was used to identify the TUBA4B-related downstream genes. RESULTS: TUBA4B was significantly decreased in GC tissues, cells and plasma. Low TUBA4B was positively correlated with larger tumor size, lymph node metastasis and advanced TNM stage. Moreover, TUBA4B was identified as an effective biomarker for the diagnosis and prognosis of patients with GC. Functionally, ectopic expression of TUBA4B inhibited GC cell proliferation, invasion and induced apoptosis in vitro as well as dampened tumor growth and metastasis in vivo. Furthermore, TUBA4B was found to be a competitive endogenous RNA (ceRNA) that could physically bind to and sequester miR-214 and miR-216a/b to increase the expression of their common downstream target PTEN, resulting in inactivation of PI3K/AKT signaling pathway, thereby retarding GC progression. CONCLUSION: Our data highlight the compelling regulatory role of TUBA4B in GC, and reactivation of TUBA4B may be a promising therapeutic avenue for GC patients.

Isolation and Cr(VI) reduction characteristics of quinone respiration in Mangrovibacter plantisponsor strain CR1.

A Cr(VI)-reducing Mangrovibacter plantisponsor strain, CR1, was isolated from tannery effluent sludge and had quinone respiration characteristics. Its chromate (CrO4 (2-) ) resistance, quinone respiration characteristics, and Cr(VI) reduction efficiencies were evaluated in detail. Strain CR1 exhibited a high Cr(VI) resistance with a minimal inhibitory concentration (MIC) of 32 mM in LB medium, and its quinone respiration could occur when an electron donor and strain CR1 both existed in the reaction system. Cr(VI) reduction by strain CR1 was significantly enhanced by a factor of 0.4-4.3 with five different quinone compounds: anthraquinone-2,7-disulfonate, anthraquinone-1-sulfonate, anthraquinone-2-sulfonate (AQS), anthraquinone-2,6-disulfonate, and anthraquinone-1,5-disulfonate. AQS was the best electron shuttle among them, and the greatest enhancement to the Cr(VI) bio-reduction was achieved with 0.96 mM AQS. The correlation between the reaction constant k (mg Cr(VI) g(-1) dry cell weight H(-1) ) and thermodynamic temperature T (K) was expressed as an Arrhenius equation lnk=-7662.9/T+27.931(R2=0.9486); the activation energy Ea was 63.71 kJ mol(-1) , and the pre-exponential factor A was 1.35 × 10(12)  mg Cr(VI) g(-1) dry cell weight H(-1) . During the Cr(VI) reduction process, the pH tended to become neutral, and the oxidation-reduction potential decreased to -440 mV. The efficient reduction of Cr(VI) mediated by a quinone respiration strain shows potential for the rapid anaerobic removal of Cr(VI).