CRL4DCAF13 E3 ubiquitin ligase targets MeCP2 for degradation to prevent DNA hypermethylation and ensure normal transcription in growing oocytes.

The DNA methylation is gradually acquired during oogenesis, a process sustained by successful follicle development. However, the functional roles of methyl-CpG-binding protein 2 (MeCP2), an epigenetic regulator displaying specifical binding with methylated DNA, remains unknown in oogenesis. In this study, we found MeCP2 protein was highly expressed in primordial and primary follicle, but was almost undetectable in secondary follicles. However, in aged ovary, MeCP2 protein is significantly increased in both oocyte and granulosa cells. Overexpression of MeCP2 in growing oocyte caused transcription dysregulation, DNA hypermethylation, and genome instability, ultimately leading to follicle growth arrest and apoptosis. MeCP2 is targeted by DCAF13, a substrate recognition adaptor of the Cullin 4-RING (CRL4) E3 ligase, and polyubiquitinated for degradation in both cells and oocytes. Dcaf13-null oocyte exhibited an accumulation of MeCP2 protein, and the partial rescue of follicle growth arrest induced by Dcaf13 deletion was observed following MeCP2 knockdown. The RNA-seq results revealed that large amounts of genes were regulated by the DCAF13-MeCP2 axis in growing oocytes. Our study demonstrated that CRL4DCAF13 E3 ubiquitin ligase targets MeCP2 for degradation to ensure normal DNA methylome and transcription in growing oocytes. Moreover, in aged ovarian follicles, deceased DCAF13 and DDB1 protein were observed, indicating a potential novel mechanism that regulates ovary aging.

Synthesis of Azepino[4,5-b]indole via Ring Expansion of Tetrahydro-ß-carbolines Ammonium Ylide.

The formal cyclization strategy was generally used to construct azepino[4,5-b]indole. Herein, we reported a novel and expeditious protocol for the synthesis of quaternary carbon azepino[4,5-b]indole via ring expansion of ammonium ylide, which was formed by the reaction of tetrahydro-ß-carbolines with the diazo compound. The easily available substrates, mild reaction conditions, and broad functional tolerance rendered this method a practical strategy that may significantly afford an efficient method of scaffold hopping in drug discovery.

Water quality drives the reconfiguration of riverine planktonic microbial food webs.

The food web is a cycle of matter and energy within river ecosystems. River environmental changes resulting from human activities are increasingly threatening the composition and diversity of global aquatic organisms and the multi-trophic networks. How multiple environmental factors influence food web patterns among multi-trophic microbial communities in rivers remains largely unknown. Using water quality evaluation and meta-omics techniques, we investigated the composition, structure and interaction characteristics, and drivers of food webs of microorganisms (archaea, bacteria, fungi, protists, metazoa, viridiplantae and viruses) at multiple trophic levels in different water quality environments (Classes II, III, and IV). First, water quality deterioration led to significant changes in the composition of the microbial community at multiple trophic levels, which were represented by the enrichment of Euryarchaeota in the archaeal community, the increase of r-strategists in the bacterial community, and the increase of the proportion of predators in the protist community. Second, deteriorating water quality resulted in a significant reduction in the dissimilarity of community structure (homogenization of community structure in Class III and IV waters). Of the symbiotic, parasitic, and predatory networks, the community networks in Class II water all showed the most stable symbiotic, parasitic, and predatory correlations (higher levels of modularity in the networks). In Class III and IV waters, nutrient inputs have led to increased reciprocal symbiosis and decreased competition between communities, which may have the risk of a positive feedback loop driving a system collapse. Finally, inputs of phosphorus and organic matter could be the main drivers of changes in the planktonic microbial food web in the Fen River. Overall, the results indicated the potential ecological risks of exogenous nutrient inputs, which were important for aquatic ecosystem conservation.

Toxicity factors to assess the ecological risk for soil microbial communities.

The toxicity factor (TF), a critical parameter within the potential ecological risk index (RI), is determined without accounting for microbial factors. It is considerable uncertainty exists concerning its validity for quantitatively assessing the influence of metal(loid)s on microorganisms. To evaluate the suitability of TF, we constructed microcosm experiments with varying RI levels (RI = 100, 200, 300, 500, and 700) by externally adding zinc (Zn), chromium (Cr), copper (Cu), lead (Pb), nickel (Ni), cadmium (Cd), and mercury (Hg) to uncontaminated soil (CK). Quantitative real-time PCR (qPCR) and high-throughput sequencing techniques were employed to measure the abundance and community of bacteria and fungi, and high-throughput qPCR was utilised to quantify functional genes associated with CNPS cycles. The results demonstrated that microbial diversity and function exhibited significant alterations (p < 0.05) in response to increasing RI levels, and the influences on microbial community structure, enzyme activity, and functional gene abundances were different due to the types of metal(loid)s treatments. At the same RI level, significant differences (p < 0.05) were discerned in microbial diversity and function across metal(loid) treatments, and these differences became more pronounced (p < 0.001) at higher levels. These findings suggest that TF may not be suitable for the quantitative assessment of microbial ecological risk. Therefore, we adjusted the TF by following three steps (1) determining the adjustment criteria, (2) deriving the initial TF, and (3) adjusting and optimizing the TF. Ultimately, the optimal adjusted TF was established as Zn = 1.5, Cr = 4.5, Cu = 6, Pb = 4.5, Ni = 5, Cd = 22, and Hg = 34. Our results provide a new reference for quantitatively assessing the ecological risks caused by metal(loid)s to microorganisms.

Evaluating effects of tetrabromobisphenol A and microplastics on anaerobic granular sludge: Physicochemical properties, microbial metabolism, and underlying mechanisms.

Tetrabromobisphenol A (TBBPA) and microplastics are emerging contaminants of widespread concern. However, little is known about the effects of combined exposure to TBBPA and microplastics on the physicochemical properties and microbial metabolism of anaerobic granular sludge. This study investigated the effects of TBBPA, polystyrene microplastics (PS MP) and polybutylene succinate microplastics (PBS MP) on the physicochemical properties, microbial communities and microbial metabolic levels of anaerobic granular sludge. The results showed that chemical oxygen demand (COD) removal of sludge was lowest in the presence of TBBPA alone and PS MP alone with 33.21% and 30.06%, respectively. The microorganisms promoted the secretion of humic substances under the influence of TBBPA, PS MP and PBS MP. The lowest proportion of genes controlling glycolytic metabolism in sludge was 1.52% when both TBBPA and PS MP were added. Microbial reactive oxygen species were increased in anaerobic granular sludge exposed to MPS. In addition, TBBPA treatment decreased electron transfer of the anaerobic granular sludge and disrupted the pathway of anaerobic microorganisms in acquiring adenosine triphosphate, and MPs attenuated the negative effects of TBBPA on the acetate methanogenesis process of the anaerobic granular sludge. This study provides a reference for evaluating the impact of multiple pollutants on anaerobic granular sludge.

Mass cytometry-based peripheral blood analysis as a novel tool for early detection of solid tumours: a multicentre study.

OBJECTIVE: Early detection of a tumour remains an unmet medical need, and approaches with high sensitivity and specificity are urgently required. Mass cytometry time-of-flight (CyTOF) is a powerful technique to profile immune cells and could be applied to tumour detection. We attempted to establish diagnostic models for hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC). DESIGN: We performed CyTOF analysis for 2348 participants from 15 centres, including 1131 participants with hepatic diseases, 584 participants with pancreatic diseases and 633 healthy volunteers. Diagnostic models were constructed through random forest algorithm and validated in subgroups. RESULTS: We determined the disturbance of systemic immunity caused by HCC and PDAC, and calculated a peripheral blood immune score (PBIScore) based on the constructed model. The PBIScore exhibited good performance in detecting HCC and PDAC, with both sensitivity and specificity being around 80% in the validation cohorts. We further established an integrated PBIScore (iPBIScore) by combining PBIScore and alpha-fetoprotein or carbohydrate antigen 19-9. The iPBIScore for HCC had an area under the curve (AUC) of 0.99, 0.97 and 0.96 in training, internal validation and external validation cohorts, respectively. Similarly, the iPBIScore for PDAC showed an AUC of 0.99, 0.98 and 0.97 in the training, internal validation and external validation cohorts, respectively. In early-stage and tumour-marker-negative patients, our iPBIScore-based models also showed an AUC of 0.95-0.96 and 0.81-0.92, respectively. CONCLUSION: Our study proved that the alterations of peripheral immune cell subsets could assist tumour detection, and provide a ready-to-use detection model for HCC and PDAC.

Exposure to bisphenol A alternatives bisphenol AF and fluorene-9-bisphenol induces gonadal injuries in male zebrafish.

Bisphenol A (BPA), present in many household products, can damage the male reproductive system. Accordingly, we summarized urine samples from 6921 human in National Health and Nutrition Examination Survey and found urinary BPA levels were inversely linked with blood testosterone in the children group. Currently, BPA replacements, such as fluorene-9-bisphenol (BHPF) and Bisphenol AF (BPAF), have been introduced to produce "BPA-free" products. Here we demonstrated that BPAF and BHPF could induce delayed gonadal migration and reduce the number of progenitors of germ cell lineage in zebrafish larvae. A close receptor analysis study reveals that BHPF and BPAF can strongly bind to androgen receptors, leading to the downregulation of meiosis-related genes and the overexpression of inflammatory markers. Furthermore, BPAF and BPHF can induce activation of the gonadal axis via negative feedback, leading to the hypersecretion of some upstream hormones and an increase in the expression of upstream hormone receptors. Our findings call for further research on the toxicological effects of BHPF and BPAF on human health and recommend that BPA replacements be investigated for anti-estrogenic action.

Anti-Herpes Simplex Virus Type 1 Activity Evaluation of Natural Derived Phloroglucinol Derivatives and Their Molecular Mechanisms Study.

HSV-1 is a common infection that can cause cold sores. In this study, the anti-HSV-1 virus activity of three series compounds A1-A9, B1-B12, C1-C22 was screened by MTT assay, qRT-PCR assay, Western blot assay and viruses' plaque assays. The results of MTT assay disclosed that phloroglucinol derivatives C2 and C3 effectively inhibited the death of HSV-1 infected vero cells with the CC50 values of C2 and C3 were 72.64 µmol/L and 32.62 µmol/L in HaCaT cells, 137.6 µmol/L and 48.55 µmol/L in Hela cells. The IC50 values of C3 in vero cells and Hela cells were 19.26 µmol/L and 22.98 µmol/L, respectively. In the qRT-PCR experiments, it showed that C2 and C3 effectively reduced the synthesis of HSV-1 early viral gene VP16 and late viral gene gD. The Western blot results showed that both C2 and C3 inhibited the expression of HSV-1 gD protein in a concentration-dependent manner. Lastly, viruses' plaque assay results showed that C2 and C3 inhibited the production of HSV-1 progeny virus in Hela cells and HaCaT cells in a concentration-dependent manner. Taken together, these results suggest that C2 and C3 are promising candidate that warrants further attention in the development of anti-HSV-1 drugs.

Genome-Wide Analysis of bHLH Family Genes and Identification of Members Associated with Cold/Drought-Induced Photoinhibition in Kandelia obovata.

Plant basic helix-loop-helix (bHLH) transcription factors play pivotal roles in responding to stress, including cold and drought. However, it remains unclear how bHLH family genes respond to these stresses in Kandelia obovata. In this study, we identified 75 bHLH members in K. obovata, classified into 11 subfamilies and unevenly distributed across its 18 chromosomes. Collineation analysis revealed that segmental duplication primarily drove the expansion of KobHLH genes. The KobHLH promoters were enriched with elements associated with light response. Through RNA-seq, we identified several cold/drought-associated KobHLH genes. This correlated with decreased net photosynthetic rates (Pn) in the leaves of cold/drought-treated plants. Weighted gene co-expression network analysis (WGCNA) confirmed that 11 KobHLH genes were closely linked to photoinhibition in photosystem II (PS II). Among them, four Phytochrome Interacting Factors (PIFs) involved in chlorophyll metabolism were significantly down-regulated. Subcellular localization showed that KobHLH52 and KobHLH30 were located in the nucleus. Overall, we have comprehensively analyzed the KobHLH family and identified several members associated with photoinhibition under cold or drought stress, which may be helpfulfor further cold/drought-tolerance enhancement and molecular breeding through genetic engineering in K. obovata.

Fetal neurodevelopmental spatio-temporal dynamic transcriptional landscape of maternal insult-induce autism spectrum disorder risk.

Maternal insults during pregnancy induces an increased risk of autism spectrum disorders (ASD) in offspring, but the neuropathological changes in this process remains not to be established. To shed light on this, the transcriptome datasets of maternal blood samples with children later diagnosed with ASD and typical development, and tissue samples of multiple brain regions from ASD patients and human neurodevelopment were conducted to identify the non-chasm differentially expressed genes (DEGs) to generate the spatio-temporal dynamic change. Combined enrichment and interaction network analysis revealed that non-chasm DEGs with similar expression trajectories in the same brain regions, were involved in neural, immune and metabolic GO functions and KEGG pathways, respectively, suggesting that did not performed exactly the same functions. Interestingly, our results found that non-chasm DEGs in frontal cortex and temporal cortex were associated with COVID-19, suggesting that as an environmental risk factor COVID-19 affects an increased risk of ASD.

Bacillus sp. DU-106 ameliorates type 2 diabetes by modulating gut microbiota in high-fat-fed and streptozotocin-induced mice.

AIMS: Type 2 diabetes (T2D) is a chronic disease that manifests as endocrine and metabolic disorders that seriously threatening public health. This study aimed to investigate the effects of Bacillus sp. DU-106 on anti-diabetic effects and gut microbiota in C57BL/6J mice fed a high-fat diet and streptozotocin-induced T2D. METHODS AND RESULTS: Bacillus sp. DU-106 was administered to model mice for eight consecutive weeks. Oral administration of Bacillus sp. DU-106 decreased food and water intake and alleviated body weight loss. Moreover, Bacillus sp. DU-106 imparted several health benefits to mice, including balanced blood glucose, alleviation of insulin resistance in T2D mice and an improvement in lipid metabolism. Furthermore, Bacillus sp. DU-106 protected against liver and pancreatic impairment. Additionally, Bacillus sp. DU-106 treatment reshaped intestinal flora by enhancing gut microbial diversity and enriching the abundance of certain functional bacteria. CONCLUSION: Collectively, these findings suggest that Bacillus sp. DU-106 can ameliorate T2D by regulating the gut microbiota. SIGNIFICANCE AND IMPACT OF STUDY: Therefore, a novel probiotic, Bacillus sp. DU-106 may be a promising therapeutic agent for improving and alleviating T2D in mice.

Virulence and biofilm inhibition of 3-methoxycinnamic acid against Agrobacterium tumefaciens.

AIMS: In the current study the anti-virulence and anti-biofilm activities of the cinnamic acid derivative, 3-methoxycinnamic acid, was investigated against Agrobacterium tumefaciens. METHODS AND RESULTS: Based on the disc diffusion test and ß-galactosidase activity assay, 3-methoxycinnamic acid was shown to interfere with the quorum sensing (QS) system of A. tumefaciens. Crystal violet staining assay, phenol-sulfuric acid method, Bradford protein assay and confocal laser scanning microscopy (CLSM) revealed that the biofilm formation of A. tumefaciens was inhibited after the treatment of 3-methoxycinnamic acid. Employing high-performance liquid chromatography (HPLC) analysis of culture supernatant revealed that the production of 3-oxo-octanoylhomoserine lactone (3-oxo-C8-HSL) decreased concentration-dependently after treatment with 3-methoxycinnamic acid. Swimming and chemotaxis assays also indicated that 3-methoxycinnamic acid had a good effect on reducing the motility and chemotaxis of A. tumefaciens. In addition, the RT-qPCR, molecular docking and simulations further demonstrated that 3-methoxycinnamic acid could competitively inhibit the binding of 3-oxo-C8-HSL to TraR and down-regulate virulence-related genes. CONCLUSIONS: 3-Methoxycinnamic acid is proved to have good anti-virulence and anti-biofilm activities against A. tumefaciens. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study that investigates the anti-virulence and anti-biofilm activities of 3-methoxycinnamic acid against A. tumefaciens. With its potential QS-related virulence and biofilm inhibitory activities, 3-methoxycinnamic acid is expected to be developed as a potent pesticide or adjuvant for the prevention and treatment of crown gall caused by A. tumefaciens.

Identifying the Active Sites of Heteroatom Graphene as a Conductive Membrane for the Electrochemical Filtration of Organic Contaminants.

The dopants of sulfur, nitrogen, or both, serving as the active sites, into the graphitic framework of graphene is an efficient strategy to improve the electrochemical performance of electrochemical membrane filtration. However, the covalent bonds between the doped atoms and the substrate that form different functional groups have a significant role in the specific activity for pollutant degradation. Herein, we found that the singly doped heteroatom graphene (NG and SG) achieved superior removal efficiency of pollutants as compared with that of the double doped heteroatom graphene (SNG). Mechanism studies showed that the doped N of NG presented as graphitic N and substantially increased electron transfer, whereas the doped S of SG posed as -C-SOx-C- provided more adsorption sites to improve electrochemical performance. However, in the case of SNG, the co-doped S and N cannot form the efficient graphitic N and -C-SOx-C- for electrochemical degradation, resulting in a low degradation efficiency. Through the fundamental insights into the bonding of the doped heteroatom on graphene, this work furnishes further directives for the design of desirable heteroatom graphene for membrane filtration.

The Anisotropic Chemical Reaction Mechanism of 1,3,3-trinitroazetidine (TNAZ) under Different Shock Wave Directions by ReaxFF Reactive Molecular Dynamics Simulations.

1,3,3-Trinitroazetidine (TNAZ) has good thermal stability and low shock sensitivity, among other properties, and it has broad prospects in insensitive ammunition applications. In this study, a molecular dynamics calculation based on the ReaxFF-lg force field and multiscale shock technique (MSST) was used to simulate the shock-induced chemical reaction of TNAZ with different shock wave directions. The results showed that the shock sensitivity of TNAZ was in the order of [100] > [010] > [001]. There were significant differences in molecular arrangements in different shock directions, which affected the reaction rate and reaction path in different directions. The molecular arrangement in the [010] and [001] directions formed a "buffer" effect. The formation and cleavage of bonds, formation of small molecules and growth of clusters were analyzed to show the effect of the "buffer". The polymerization reactions in the [010] and [001] directions appeared later than that in the [100] direction, and the cluster growth in the [010] and [001] directions was slower than that in the [100] direction. In different shock loading directions, the formation and cleavage mechanisms of the N-O bonds of the TNAZ molecules were different, which resulted in differences in the initial reaction path and reaction rate in the three directions

ATP citrate lyase inhibitor triggers endoplasmic reticulum stress to induce hepatocellular carcinoma cell apoptosis via p-eIF2α/ATF4/CHOP axis.

ATP citrate lyase (ACLY), a key enzyme in the metabolic reprogramming of many cancers, is widely expressed in various mammalian tissues. This study aimed to evaluate the effects and mechanisms of ACLY and its inhibitor BMS-303141 on hepatocellular carcinoma (HCC). In this study, ACLY was highly expressed in HCC tissues, especially in HepG2 and Huh7 cells, but was down-regulated in Hep3B and HCC-LM3 cells. Besides, ACLY knockdown inhibited HepG2 proliferation and clone formation, while opposite result was noticed in HCC-LM3 cells with ACLY overexpression. Moreover, ACLY knockdown impeded the migration and invasion abilities of HepG2 cells. Similarly, BMS-303141 suppressed HepG2 and Huh-7 cell proliferation. The p-eIF2α, ATF4, CHOP p-IRE1α, sXBP1 and p-PERK were activated in HepG2 cells stimulated by BMS-303141. In cells where ER stress was induced, ATF4 was involved in BMS-303141-mediated cell death procession, and ATF4 knockdown reduced HCC cell apoptosis stimulated by BMS-303141. In a mouse xenograft model, combined treatment with BMS-303141 and sorafenib reduced HepG2 tumour volume and weight. In addition, ACLY expression was associated with HCC metastasis and tumour-node-metastases staging. Survival analysis and Cox proportional hazards regression model showed that overall survival was lower in HCC patients with high ACLY expression; AFP level, TNM staging, tumour size and ACLY expression level were independent risk factors affecting their overall survival. In conclusion, ACLY might represent a promising target in which BMS-303141 could induce ER stress and activate p-eIF2α/ATF4/CHOP axis to promote apoptosis of HCC cells, and synergized with sorafenib to enhance the efficacy of HCC treatment.

A near-infrared fluorescent probe for highly specific and ultrasensitive detection of hypochlorite ions in living cells.

Hypochlorite (ClO-) is an important reactive oxygen species (ROS) in organisms. In this work, a fluorescent probe DBTM based on triphenylamine was synthesized successfully and characterized by spectral methods. The designed probe can rapidly respond to ClO- in just 1 min, followed by the apparent color change from red to yellow. The colorimetric and ratiometric absorbance change of DBTM was attributed to the strong oxidation of ClO-, which broke the connected double bonds and destroyed the conjugate system. The probe DBTM showed an excellent selectivity towards ClO- in comparison with other ROS probes. Besides, the DBTM probe exhibited a highly sensitive response to ClO-, with the detection limits calculated to be 3.3 nM. The probe can be applied in the form of cotton swabs and test strips that could detect ClO- easily, suggesting its potential use as imaging agents for realistic ClO- detection. In particular, DBTM exhibited very low background fluorescence in living cells and was able to detect the minor variation of endogenous hypochlorite in L929 cells. Based on these advantages, the probe DBTM could be a good candidate for detecting ClO- in biological systems.

Chondroitin polymerizing factor (CHPF) contributes to malignant proliferation and migration of hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the human digestive system, and has been recognized as a serious threat to public health worldwide. This study explored the role of chondroitin polymerizing factor (CHPF) in the development and metastasis of HCC. Immunohistochemistry analysis was performed to detect CHPF expression in HCC tissues and para-carcinoma tissues. qRT-PCR and Western blot analysis were used to determine the mRNA and protein expression of CHPF. MTT assays, colony formation assays, and flow cytometry were used to evaluate the cell proliferation, colony formation, and cell apoptosis, respectively. Wound-healing and Transwell assays were performed to evaluate cell migration. The results show that CHPF was not only up-regulated in HCC tissues compared with para-carcinoma tissues, but was also related with more advanced stages of HCC. Further studies revealed that CHPF knockdown significantly inhibited cell proliferation and colony formation, and induce cell apoptosis of HCC cells. Moreover, suppressing the expression of CHPF reduced the migration and invasiveness of HCC cells. In conclusion, we demonstrated that CHPF plays important roles in the development and progression of HCC, and high expression levels of HCC may be related with poorer prognosis. The results from this study may provide a potential therapeutic target for HCC treatment.

High extinction ratio terahertz broadband polarizer based on the aligned Ni nanowire arrays.

We present a broadband terahertz (THz) polarizer based on the stacks of aligned Ni nanowire (NW) arrays. We demonstrated that the polarizer has an extinction ratio of 58.8 dB and an average extinction ratio of 46.6 dB throughout a frequency range of 0.3-2.3 THz. Compared to carbon-nanotube and metallic wire-grid polarizers, our Ni-NW polarizers with rapid, reliable, low-cost fabrication processes are ideal candidates for emerging THz technologies.

Quorum sensing inhibition and tobramycin acceleration in Chromobacterium violaceum by two natural cinnamic acid derivatives.

Chromobacterium violaceum, one free-living Gram-negative bacterium, is abundantly presented in tropics and sub-tropics soil and aquatic environment; it is also an opportunistic human pathogen. Here, two cinnamic acid derivatives, i.e., 4-dimethylaminocinnamic acid (DCA) and 4-methoxycinnamic acid (MCA), were identified as potential quorum sensing (QS) and biofilm inhibitors in C. violaceum ATCC12472. Both DCA (100 µg/mL) and MCA (200 µg/mL) inhibited the levels of N-decanoyl-homoserine lactone (C10-HSL) and reduced the production of certain virulence factors in C. violaceum, including violacein, hemolysin, and chitinase. Metabolomics analysis indicated that QS-related metabolites, such as ethanolamine and L-methionine, were down-regulated after treatment with DCA and MCA. Quantitative real-time polymerase chain reaction (qRT-PCR) demonstrated that DCA and MCA markedly suppressed the expression of two QS-related genes (cviI and cviR). In addition, DCA and MCA also inhibited biofilm formation and enhanced the susceptibility of biofilms to tobramycin, which was evidenced by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Our results indicated that DCA and MCA can serve as QS-based agent for controlling pathogens.Key Points • DCA and MCA inhibited QS and biofilm formation in C. violaceum.• The combination of DCA or MCA and tobramycin removed the preformed biofilm of C. violaceum. • DCA or MCA inhibited virulence factors and expressions of cviI and cviR of C. violaceum.• DCA or MCA are potential antibiotic accelerants for treating C. violaceum infection.

Rosiglitazone Inhibits Activation of Hepatic Stellate Cells via Up-Regulating Micro-RNA-124-3p to Alleviate Hepatic Fibrosis.

BACKGROUND: The activation of hepatic stellate cells (HSCs) is involved in hepatic fibrogenesis and is regulated by the decreased expression of peroxisome proliferator-activated receptor γ (PPARγ). Rosiglitazone (RGZ) is a highly potent agonist of PPARγ. AIMS: To clarify molecular regulatory mechanism of RGZ in the activation of HSCs in hepatic fibrosis. METHODS: A mouse model of hepatic fibrosis was established by carbon tetrachloride with or without RGZ intervention. A vector carrying pcDNA-HOTAIR was constructed and injected into a mouse model. HSCs were isolated from liver tissue and activated by transforming growth factor-ß. The expression of miR-124-3p, HOTAIR, Col1A1, α-SMA, and PPARγ mRNAs was measured by quantitative real-time PCR. The level of PPARγ was measured by Western blotting. The interaction between HOTAIR and PPARγ was assessed by RNA immunoprecipitation (RIP) and RNA pull-down. The target gene of miR-124-3p was determined by luciferase reporter assay and RNA interference approaches. RESULTS: The expression of Col1A1 and α-SMA was reduced after RGZ intervention. Different expressions of HOTAIR and miR-124-3p were observed in liver tissue and HSCs. The luciferase reporter assay and RNA interference approaches indicated that miR-124-3p negatively regulated HOTAIR expression. RIP and RNA pull-down results revealed that PPARγ was interacted by HOTAIR. The therapeutic effect of RGZ on hepatic fibrosis was reversed by overexpression of HOTAIR. CONCLUSIONS: RGZ inhibits the activation of HSCs by up-regulating miR-124-3p. The silencing of HOTAIR by miR-124-3p in HSC activation provided the foundation to understand interactions of ncRNAs and potential treatment target in hepatic fibrosis.