ABSTRACT
BACKGROUND: Vascular calcification is a common vascular lesion associated with high morbidity and mortality from cardiovascular events. Antibiotics can disrupt the gut microbiota (GM) and have been shown to exacerbate or attenuate several human diseases. However, whether antibiotic-induced GM disruption affects vascular calcification remains unclear. METHODS: Antibiotic cocktail (ABX) treatment was utilized to test the potential effects of antibiotics on vascular calcification. The effects of antibiotics on GM and serum short-chain fatty acids (SCFAs) in vascular calcification mice were analyzed using 16 S rRNA gene sequencing and targeted metabolomics, respectively. Further, the effects of acetate, propionate and butyrate on vascular calcification were evaluated. Finally, the potential mechanism by which acetate inhibits osteogenic transformation of VSMCs was explored by proteomics. RESULTS: ABX and vancomycin exacerbated vascular calcification. 16 S rRNA gene sequencing and targeted metabolomics analyses showed that ABX and vancomycin treatments resulted in decreased abundance of Bacteroidetes in the fecal microbiota of the mice and decreased serum levels of SCFAs. In addition, supplementation with acetate was found to reduce calcium salt deposition in the aorta of mice and inhibit osteogenic transformation in VSMCs. Finally, using proteomics, we found that the inhibition of osteogenic transformation of VSMCs by acetate may be related to glutathione metabolism and ubiquitin-mediated proteolysis. After adding the glutathione inhibitor Buthionine sulfoximine (BSO) and the ubiquitination inhibitor MG132, we found that the inhibitory effect of acetate on VSMC osteogenic differentiation was weakened by the intervention of BSO, but MG132 had no effect. CONCLUSION: ABX exacerbates vascular calcification, possibly by depleting the abundance of Bacteroidetes and SCFAs in the intestine. Supplementation with acetate has the potential to alleviate vascular calcification, which may be an important target for future treatment of vascular calcification.
Subject(s)
Acetates , Anti-Bacterial Agents , Fatty Acids, Volatile , Gastrointestinal Microbiome , Vascular Calcification , Animals , Gastrointestinal Microbiome/drug effects , Vascular Calcification/metabolism , Vascular Calcification/etiology , Vascular Calcification/drug therapy , Mice , Fatty Acids, Volatile/metabolism , Acetates/pharmacology , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/pharmacology , Male , Osteogenesis/drug effects , RNA, Ribosomal, 16S/genetics , Disease Models, Animal , Mice, Inbred C57BL , Vancomycin/adverse effects , Vancomycin/pharmacology , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/drug effectsABSTRACT
The taxonomic classification of Picea meyeri and P. mongolica has long been controversial. To investigate the genetic relatedness, evolutionary history, and population history dynamics of these species, genotyping-by-sequencing (GBS) technology was utilized to acquire whole-genome single nucleotide polymorphism (SNP) markers, which were subsequently used to assess population structure, population dynamics, and adaptive differentiation. Phylogenetic and population structural analyses at the genomic level indicated that although the ancestor of P. mongolica was a hybrid of P. meyeri and P. koraiensis, P. mongolica is an independent Picea species. Additionally, P. mongolica is more closely related to P. meyeri than to P. koraiensis, which is consistent with its geographic distribution. There were up to eight instances of interspecific and intraspecific gene flow between P. meyeri and P. mongolica. The P. meyeri and P. mongolica effective population sizes generally decreased, and Maxent modeling revealed that from the Last Glacial Maximum (LGM) to the present, their habitat areas decreased initially and then increased. However, under future climate scenarios, the habitat areas of both species were projected to decrease, especially under high-emission scenarios, which would place P. mongolica at risk of extinction and in urgent need of protection. Local adaptation has promoted differentiation between P. meyeri and P. mongolica. Genotypeâenvironment association analysis revealed 96,543 SNPs associated with environmental factors, mainly related to plant adaptations to moisture and temperature. Selective sweeps revealed that the selected genes among P. meyeri, P. mongolica and P. koraiensis are primarily associated in vascular plants with flowering, fruit development, and stress resistance. This research enhances our understanding of Picea species classification and provides a basis for future genetic improvement and species conservation efforts.
Subject(s)
Genome, Plant , Picea , Polymorphism, Single Nucleotide , Population Dynamics , Picea/genetics , Phylogeny , Gene Flow , Adaptation, Physiological/genetics , EcosystemABSTRACT
The construction of novel structured Prussian blue analogs (PBAs) by chemical etching has attracted the most attention to PBA derivatives with outstanding performance. In this work, the unprecedented PBA orthogonal frustums are first prepared from nanocubes through a selective chemical etching approach using trisodium citrate as an etchant. The citrate ions can chelate with nickel species from the edges/corners of NiCo-PBA nanocubes and then disintegrate NiCo-PBAs resulting in the generation of NiCo-PBA orthogonal frustums. The derived CoNi2S4/Co0.91S composites still inherit the original orthogonal frustum structure and possess outstanding supercapacitor performance. This study develops a popularized method to construct novel structured PBAs and brings inspiration for designing PBA-based electrodes with advanced electrochemical performance.
ABSTRACT
2,2'-Bipyridyl (bpy) is widely used as a chelating unit for metal complexation but is not usually considered as a hydrogen-bonding unit. This is because the metal-free bpy units are usually in a transoid conformation, and the two nitrogen lone pairs are pointed to the opposite sides. We now report a metallomacrocycle whose three metal-free bpy units are in a cisoid conformation and are fixed in the cavity. The complexation of nickel(II) only at the salen units of the triangular bpytrisalen ligand produced this rigid and planar macrocycle. Its cavity is surrounded by hydrogen-bond acceptors (N of bpy and O of salen), and it was found that unique pentagonal prism clusters of water molecules templated by the cavity were formed in the crystal. This study has not only increased the variation of the synthetic methodologies of multinuclear complexes but has also provided the structural platform on which multiple bpy units exert hydrogen-bonding functions.
ABSTRACT
BACKGROUND: Circular RNAs (circRNAs) have been shown to be involved in tumorigenesis and progression. However, the role of circGLIS3 (hsa_circ_0002874) in prostate cancer (PCa) has yet not been reported. METHODS: Candidate circRNA were determined through comprehensive analysis of public datasets, PCa cell lines, and tissues data. A series of cellular functional assays, including CCK-8, colony formation, wound healing, and transwell assays were performed. Subsequently, RNA sequencing, RNA immunoprecipitation, methylated RNA immunoprecipitation, microRNA pulldown, luciferase reporter assay, and western blot were used to explore the underlying molecular mechanisms. Moreover, the xenograft tumor mouse model was established to elucidate the function of circGLIS3. RESULTS: CircGLIS3, derived from exon 2 of the parental GLIS3 gene, was identified as a novel oncogenic circRNA in PCa that was closely associated with the biochemical recurrence. Its expression levels were upregulated in PCa tissues and cell lines as well as enzalutamide high-resistant cells. The cellular functional assays revealed that circGLIS3 promoted PCa cell proliferation, migration, and invasion. METTL3-mediated N6-methyladenosine (m6A) modification maintained its upregulation by enhancing its stability. Mechanically, CircGLIS3 sponged miR-661 to upregulate MDM2, thus regulating the p53 signaling pathway to promote cell proliferation, migration, and invasion. Furthermore, in vitro and in vivo experiments, the knockdown of circGLIS3 improved the response of PCa cells to ARSI therapies such as enzalutamide. CONCLUSIONS: METTL3-mediated m6A modification of circGLIS3 regulates the p53 signaling pathway via the miR-661/MDM2 axis, thereby facilitating PCa progression. Meanwhile, this study unveils a promising potential target for ARSI therapy for PCa.
Subject(s)
Cell Proliferation , Disease Progression , Gene Expression Regulation, Neoplastic , Methyltransferases , Prostatic Neoplasms , RNA, Circular , Male , Humans , RNA, Circular/genetics , RNA, Circular/metabolism , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Prostatic Neoplasms/metabolism , Animals , Methyltransferases/metabolism , Methyltransferases/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Mice , Adenosine/analogs & derivatives , Adenosine/metabolism , Cell Movement/genetics , Mice, Nude , MicroRNAs/genetics , MicroRNAs/metabolism , Phenylthiohydantoin/pharmacology , Phenylthiohydantoin/analogs & derivatives , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/genetics , Proto-Oncogene Proteins c-mdm2/metabolism , Proto-Oncogene Proteins c-mdm2/genetics , Drug Resistance, Neoplasm/genetics , Mice, Inbred BALB C , Benzamides , NitrilesABSTRACT
The role played by activists' sexual orientation and gender identity in their involvement and commitment to LGBT movements is an understudied area in the Chinese context. Using identity and dramaturgical theory, this qualitative study explored how activists' work and commitment toward promoting LGBT rights and services is shaped and influenced by their identities. The study draws on data from life history interviews conducted with 20 long-time LGBT activists in Yunnan, China. The findings indicate that their sexual orientation and gender identities were, in the long run, seen as assets by the activists that shaped their work and commitment in the LGBT movement. Despite initial challenges in establishing identity-based connections with co-workers/clients, the emergence of sense of inclusiveness through recognition of activists' efforts, particularly when working with diverse gender and sexual minorities, stands out as a prominent theme in this context. This dynamic is important in bolstering the longevity of activists' commitment and building the continued momentum of LGBT movements in the region and internationally.
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BACKGROUND: Cuproptosis, an emerging form of programmed cell death, has recently been identified. However, the association between cuproptosis-related long non-coding RNA (lncRNA) signature and the prognosis in prostate carcinoma remains elusive. This study aims to develop the novel cuproptosis-related lncRNA signature in prostate cancer and explore its latent molecular function. METHODS: RNA-seq data and clinical information were downloaded from the TCGA datasets. Then, cuproptosis-related gene was identified from the previous literature and further applied to screen the cuproptosis-related differentially expressed lncRNAs. Patients were randomly assigned to the training cohort or the validation cohort with a 1:1 ratio. Subsequently, the machine learning algorithms (Lasso and stepwise Cox (direction = both)) were used to construct a novel prognostic signature in the training cohorts, which was validated by the validation and the entire TCGA cohorts. The nomogram base on the lncRNA signature and several clinicopathological traits were constructed to predict the prognosis. Functional enrichment and immune analysis were performed to evaluate its potential mechanism. Furthermore, differences in the landscape of gene mutation, tumour mutational burden (TMB), microsatellite instability (MSI), drug sensitivity between both risk groups were also assessed to explicit their relationships. RESULTS: The cuproptosis-related lncRNA signature was constructed based on the differentially expressed cuproptosis-related lncRNAs, including AC005790.1, AC011472.4, AC099791.2, AC144450.1, LIPE-AS1, and STPG3-AS1. Kaplan-Meier survival and ROC curves demonstrate that the prognosis signature as an independent risk indicator had excellent potential to predict the prognosis in prostate cancer. The signature was closely associated with age, T stage, N stage, and the Gleason score. Immune analysis shows that the high-risk group was in an immunosuppressive microenvironment. Additionally, the significant difference in landscape of gene mutation, tumour mutational burden, microsatellite instability, and drug sensitivity between both risk groups was observed. CONCLUSIONS: A novel cuproptosis-related lncRNA signature was constructed using machine learning algorithms to predict the prognosis of prostate cancer. It was closely with associated with several common clinical traits, immune cell infiltration, immune-related functions, immune checkpoints, gene mutation, TMB, MSI, and the drug sensitivity, which may be useful to improve the clinical outcome.
Subject(s)
Apoptosis , Carcinoma , Prostatic Neoplasms , RNA, Long Noncoding , Humans , Male , Microsatellite Instability , Prognosis , Prostate , Prostatic Neoplasms/genetics , RNA, Long Noncoding/genetics , Tumor Microenvironment , CopperABSTRACT
BACKGROUND: RNASET2 has been identified as an oncogene with anti-angiogenic and immunomodulatory effects in a variety of cancers, but its function in clear cell renal cell carcinoma (ccRCC) is still not well understood. METHODS: The RNASET2 expression matrix was extracted from the The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets and analyzed for diagnostic and prognostic value. RNASET2 mRNA expression was detected by quantitative polymerase chain reaction (qPCR) in ccRCC patients and renal cancer cell lines. Wound healing assay, transwell assay, western blotting, and tube formation assays were used to evaluate the function of RNASET2 in renal cancer in vitro. In addition, transcriptome sequencing was performed on knockdown RNASET2 kidney cancer cells to analyze their potential signaling pathways. Moreover, the immune microenvironment and mutational status were evaluated to predict the potential mechanisms of RNASET2 involvement in renal cancer progression. Sensitivity to common chemotherapeutic and targeted agents was assessed according to the Genomics of Drug Sensitivity in Cancer (GDSC) database. RESULTS: RNASET2 expression was significantly upregulated in ccRCC tissues and renal cancer cell lines, predicting poor prognosis for patients. In vitro experiments showed that silencing RNASET2 inhibited the migration and pro-angiogenic ability of renal cancer cells. Transcriptome sequencing suggested its possible involvement in the remodeling of the immune microenvironment in renal cell carcinoma. Furthermore, bioinformatics analysis and immunohistochemical staining showed that RNASET2 was positively correlated with the infiltration abundance of regulatory T cells. Finally, we mapped the mutational landscape of RNASET2 in ccRCC and found its predictive value for drug sensitivity. CONCLUSIONS: Our results suggest that RNASET2 is a promising biomarker and therapeutic target in ccRCC.
Subject(s)
Carcinoma, Renal Cell , Carcinoma , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/genetics , Prognosis , Biomarkers , Kidney Neoplasms/genetics , Tumor Microenvironment , Ribonucleases , Tumor Suppressor ProteinsABSTRACT
PURPOSE: Kidney renal papillary cell carcinoma (KIRP) is a highly heterogeneous malignancy and current systemic therapeutic strategies are difficult to achieve a satisfactory outcome for advanced disease. Meanwhile, there is a lack of effective biomarkers to predict the prognosis of KIRP. METHODS: Using TCGA, GTEx, UALCAN, TIMER, TIMER 2.0 and STRING databases, we analyzed the relationship of SNHG6 with KIRP subtypes, tumor-infiltrating immune cells and potential target mRNAs. Based on TCGA data, ROC curves, Kaplan-Meier survival analysis and COX regression analysis were performed to evaluate the diagnostic and prognostic value of SNHG6 in KIRP. Nomogram was used to predict 3- and 5-year disease-specific survival in KIRP patients. In addition, with the help of Genetic ontology and Gene set enrichment analysis, the biological processes and signalling pathways that SNHG6 may be involved in KIRP were initially explored. RESULTS: In patients with KIRP, SNHG6 was significantly upregulated and associated with a more aggressive subtype (lymph node involvement, pathological stage IV, CIMP phenotype) and poor prognosis. The ROC curve showed good diagnostic efficacy (AUC value: 0.828) and the C-index of the Nomogram for predicting DSS at 3 and 5 years was 0.920 (0.898-0.941). In the immune microenvironment of KIRP, SNHG6 expression levels were negatively correlated with macrophage abundance and positively correlated with cancer-associated fibroblasts. Furthermore, SNHG6 may promote KIRP progression by regulating the expression of molecules such as AURKB, NDC80, UBE2C, NUF2, PTTG1, CENPH, SPC25, CDCA3, CENPM, BIRC5, TROAP, EZH2. Last, GSEA suggests that SNHG6 may be involved in the regulation of the PPAR signalling pathway and the SLIT/ROBO signalling pathway. CONCLUSIONS: Our analysis suggests that a high SNHG6 expression status in KIRP is associated with a poorer prognosis for patients, and also elucidates some potential mechanisms contributing to this poorer outcome. This may provide new insights into the treatment and management of KIRP in the foreseeable future.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Prognosis , Carcinoma, Renal Cell/genetics , Kidney Neoplasms/genetics , Kidney/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Tumor Microenvironment , Cell Cycle ProteinsABSTRACT
BACKGROUND: The response of advanced clear cell renal cell carcinoma (ccRCC) to immunotherapy is still not durable, suggesting that the immune landscape of ccRCC still needs to be refined, especially as some molecules that have synergistic effects with immune checkpoint genes need to be explored. METHODS: The expression levels of CENPM and its relationship with clinicopathological features were explored using the ccRCC dataset from TCGA and GEO databases. Quantitative polymerase chain reaction (qPCR) analysis was performed to validate the expression of CENPM in renal cancer cell lines. Kaplan-Meier analysis, COX regression analysis and Nomogram construction were used to systematically evaluate the prognostic potential of CENPM in ccRCC. Besides, single gene correlation analysis, protein-protein interaction (PPI) network, genetic ontology (GO), kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA) were used to predict the biological behaviour of CENPM and the possible signalling pathways involved. Finally, a comprehensive analysis of the crosstalk between CENPM and immune features in the tumor microenvironment was performed based on the ssGSEA algorithm, the tumor immune dysfunction and exclusion (TIDE) algorithm, the TIMER2.0 database and the TISIDB database. RESULTS: CENPM was significantly upregulated in ccRCC tissues and renal cancer cell lines and was closely associated with poor clinicopathological features and prognosis. Pathway enrichment analysis revealed that CENPM may be involved in the regulation of the cell cycle in ccRCC and may have some crosstalk with the immune microenvironment in tumors. The ssGSEA algorithm, CIBERSOPT algorithm suggests that CENPM is associated with suppressor immune cells in ccRCC such as regulatory T cells. The ssGSEA algorithm, CIBERSOPT algorithm suggests that CENPM is associated with suppressor immune cells in ccRCC such as regulatory T cells. Furthermore, the TISIDB database provides evidence that not only CENPM is positively associated with immune checkpoint genes such as CTLA4, PDCD1, LAG3, TIGIT, but also chemokines and receptors (such as CCL5, CXCL13, CXCR3, CXCR5) may be responsible for the malignant phenotype of CENPM in ccRCC. Meanwhile, predictions based on the TIDE algorithm support that patients with high CENPM expression have a worse response to immunotherapy. CONCLUSIONS: The upregulation of CENPM in ccRCC predicts a poor clinical outcome, and this malignant phenotype may be associated with its exacerbation of the immunosuppressive state in the tumor microenvironment.
Subject(s)
Carcinoma, Renal Cell , Carcinoma , Cell Cycle Proteins , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/genetics , Kidney Neoplasms/genetics , Transcriptional Activation , Tumor Microenvironment/genetics , Up-Regulation , Cell Cycle Proteins/geneticsABSTRACT
OBJECTIVES: To compare the perioperative and oncological outcomes of robotic-assisted tumor enucleation (RATE) and robotic-assisted partial nephrectomy (RAPN) in the treatment of intermediate and high complexity renal cell carcinoma (RCC). METHODS: We retrospectively collected the data of 359 patients with intermediate and high complexity RCC who underwent RATE and RAPN. The perioperative, oncological, and pathological outcomes of the two groups were compared, and univariate and multivariate analyses were used to evaluate the risk factors for warm ischemia time (WIT) > 25 min. RESULTS: Compared with RAPN group, patients in RATE group had shorter operative time (P < 0.001), shorter WIT (P < 0.001), and less estimated blood loss (EBL) (P < 0.001). The decrease rate of estimated glomerular filtration rate (eGFR) in RATE group was better than that in RAPN group (P < 0.001). Multivariable analysis showed that RAPN and higher PADUA score were independent risk factors for WIT > 25 min (both P < 0.001). The rate of positive surgical margin was similar between the two groups, but the local recurrence rate of the RATE group was higher than that of the RAPN group (P = 0.027). CONCLUSIONS: RATE and RAPN have similar oncological outcomes for the treatment of intermediate and high complexity RCC. In addition, RATE was superior to RAPN in perioperative outcomes.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Robotic Surgical Procedures , Humans , Carcinoma, Renal Cell/surgery , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/surgery , Kidney Neoplasms/pathology , Robotic Surgical Procedures/adverse effects , Retrospective Studies , Treatment Outcome , Nephrectomy/adverse effectsABSTRACT
To evaluate the effects of donor ages on growth and stress resistance of 6-year-old seedlings propagated from 5-, 2000-, and 3000-year-old Platycladus orientalis donors with grafting, cutting, and seed sowing, growth indicators and physiological and transcriptomic analyses were performed in 6-year-old seedlings in winter. Results showed that basal stem diameters and plant heights of seedlings of the three propagation methods decreased with the age of the donors, and the sown seedlings were the thickest and tallest. The contents of soluble sugar, chlorophyll, and free fatty acid in apical leaves of the three propagation methods were negatively correlated with donor ages in winter, while the opposite was true for flavonoid and total phenolic. The contents of flavonoid, total phenolic, and free fatty acid in cutting seedlings were highest in the seedlings propagated in the three methods in winter. KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis of differentially expressed genes showed phenylpropanoid biosynthesis and fatty acid metabolism pathways, and their expression levels were up-regulated in apical leaves from 6-year-old seedlings propagated from 3000-year-old P. orientalis donors. In addition, hub genes analysis presented that C4H, OMT1, CCR2, PAL, PRX52, ACP1, AtPDAT2, and FAD3 were up-regulated in cutting seedlings, and the gene expression levels decreased in seedlings propagated from 2000- and 3000-year-old donors. These findings demonstrate the resistance stability of cuttings of P. orientalis and provide insights into the regulatory mechanisms of seedlings of P. orientalis propagated from donors at different ages in different propagation methods against low-temperature stress.
Subject(s)
Seedlings , Thuja , Seedlings/metabolism , Fatty Acids, Nonesterified/metabolism , Gene Expression Profiling , Chlorophyll/metabolism , Thuja/genetics , Gene Expression Regulation, PlantABSTRACT
Pathogenic bacteria experience diverse stresses induced by host cells during infection and have developed intricate systems to trigger appropriate responses. Bacterial stress responses have been reported to defend against these stresses and cross-protect bacteria from antibiotic attack. In this study, we aimed to assess whether oxidative stress affects bacterial susceptibility to fluoroquinolone (FQ) and the underlying mechanism. Stenotrophomonas maltophilia, a species with high genetic diversity, is distributed ubiquitously and is an emerging multidrug-resistant opportunistic pathogen. FQs are among the limited antibiotic treatment options for S. maltophilia infection. The minimum inhibitory concentrations (MICs) of 103 S. maltophilia clinical isolates against ciprofloxacin (CIP) and levofloxacin (LVX) were determined using the agar dilution method in Mueller-Hinton plates with or without menadione (MD), a superoxide generator. The resistance rates for ciprofloxacin and levofloxacin were 40% and 18% in the MD-null group and increased to 91% and 23%, respectively, in the MD-treated group. Of the 103 isolates tested, 54% and 27% had elevated MICs against ciprofloxacin and levofloxacin, respectively, in the presence of MD. The involvement of oxidative stress responses in the MD-mediated FQ resistance was further assessed by mutants construction and viability assay. Among the 16 oxidative stress alleviation systems evaluated, fadACB and smeU1VWU2X contributed to MD-mediated FQ resistance. The antibiotic susceptibility test is an accredited clinical method to evaluate bacterial susceptibility to antibiotics in clinical practice. However, oxidative stress-mediated antibiotic resistance was not detected using this test, which may lead to treatment failure.
Subject(s)
Gram-Negative Bacterial Infections , Stenotrophomonas maltophilia , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Ciprofloxacin/pharmacology , Ciprofloxacin/therapeutic use , Fluoroquinolones/pharmacology , Fluoroquinolones/therapeutic use , Gram-Negative Bacterial Infections/drug therapy , Humans , Levofloxacin/pharmacology , Levofloxacin/therapeutic use , Microbial Sensitivity Tests , Oxidative StressABSTRACT
AIMS: The emerging of drug resistant Pseudomonas aeruginosa is a critical challenge and renders an urgent action to discover innovative antimicrobial interventions. One of these interventions is to disrupt the pseudomonas quinolone signal (pqs) quorum sensing (QS) system, which governs multiple virulence traits and biofilm formation. This study aimed to investigate the QS inhibitory activity of a series of new PqsR inhibitors bearing a quinoline scaffold against Ps. aeruginosa. METHODS AND RESULTS: The results showed that compound 1 suppressed the expression of QS-related genes and showed the best inhibitory activity to the pqs system of wild-type Ps. aeruginosa PAO1 with an IC50 of 20.22 µmol L-1 . The virulence factors including pyocyanin, total protease, elastase and rhamnolipid were significantly suppressed in a concentration-dependent manner with the compound. In addition, compound 1 in combination with tetracycline inhibited synergistically the bacterial growth and suppressed the biofilm formation of PAO1. The molecular docking studies also suggested that compound 1 could potentially interact with the ligand-binding domain of the Lys-R type transcriptional regulator PqsR as a competitive antagonist. CONCLUSIONS: The quinoline-based derivatives were found to interrupt the quorum sensing system via the pqs pathway and thus the production of virulence factors was inhibited and the antimicrobial susceptibility of Ps. aeruginosa was enhanced. SIGNIFICANCE AND IMPACT OF STUDY: The study showed that the quinoline-based derivatives could be used as an anti-virulence agent for treating Ps. aeruginosa infections.
Subject(s)
Pseudomonas aeruginosa , Pyocyanine , Anti-Bacterial Agents/chemistry , Bacterial Proteins/metabolism , Biofilms , Endopeptidases/pharmacology , Ligands , Molecular Docking Simulation , Pancreatic Elastase/metabolism , Pseudomonas aeruginosa/metabolism , Pyocyanine/metabolism , Quorum Sensing , Tetracyclines/pharmacology , Virulence Factors/genetics , Virulence Factors/metabolismABSTRACT
Oxytetracycline hydrochloride is the most widely used veterinary antibiotic in aquaculture. The presence of large amounts of residual antibiotics in aquaculture wastewater harms the ecological environment. In this study, the ternary composite of Zn0.75Mn0.75Fe1.5O4/ZnFe2O4/ZnO (ZMF-ZF-Z) photocatalyst was prepared by the coprecipitation method for degradation of oxytetracycline hydrochloride in marine aquaculture wastewater. The crystal phase, structure, morphology, elemental composition, element content, and optical properties of photogenerated electron-hole pairs of catalyst were characterized by XRD, SEM, EDS, UV-VIS (DRS), PL spectroscopy, and other test methods. The results showed that ZMF-ZF-Z photocatalyst had a larger response range of visible light than pure ZnO, which can absorb more natural light. During the process of the experiment, the photocatalytic effect of Z ZMF-ZF-Z photocatalyst was almost no weakening after 5 times reuse, which means quite good stability of the photocatalyst. Under the visible light irradiation, the degradation rate of oxytetracycline hydrochloride in seawater was 77.11% with ZMF-ZF-Z photocatalyst, which was about 3 times higher than that of pure ZnO, and the photocatalytic activity was significantly improved. This research provides a scientific and effective method for degrading antibiotics in seawater in actual production and life.
Subject(s)
Oxytetracycline , Zinc Oxide , Anti-Bacterial Agents/chemistry , Light , Oxytetracycline/chemistry , Seawater , Wastewater , Zinc Oxide/chemistryABSTRACT
The lanthanum modified multi-walled carbon nanotubes (La-CNTs) prepared by an impregnation method were investigated for the adsorption of chlortetracycline (CTC) in aquaculture wastewater. The adsorbents were characterized by SEM, EDS, XRD and BET. The effects of some factors including La-containing impregnant concentration, adsorbent dosage, CTC adsorbate concentration, adsorption time, pH of the adsorbate solution and additional ions on the CTC adsorption by La-CNTs were investigated in detail, and the optimal adsorption conditions were determined. The adsorption kinetics obeyed the quasi-second-order kinetic model. The adsorption isotherms obeyed the Langmuir model and the fitted maximum capacity of La-CNTs for CTC adsorption was 55.3 mg/g.
Subject(s)
Chlortetracycline , Nanotubes, Carbon , Water Pollutants, Chemical , Water Purification , Adsorption , Aquaculture , Hydrogen-Ion Concentration , Kinetics , Lanthanum/chemistry , Nanotubes, Carbon/chemistry , Thermodynamics , Wastewater/chemistry , Water Pollutants, Chemical/analysisABSTRACT
Recently, Mo-based metal catalysts are widely applied in the electrocatalytic nitrogen reduction reaction (NRR) due to the lower binding energy between the Mo atom and N atom. The design of a Mo-based catalyst@carbon heterostructure and the introduction of anion vacancies are effective measures to improve their NRR performance. In this research, the cross-linked Vo-MoO2@C (Vo means oxygen vacancies) heterostructure nanoparticles with rich oxygen vacancies are first synthesized via pectin assisted hydrothermal reaction followed by calcination and treating with NaBH4 solution. Vo-MoO2@C exhibits good electrocatalytic NRR performance with an ammonia yield rate of 9.75 µg h-1 mg-1 at -0.5 V (RHE) and a Faraday efficiency (FE) of 3.24% at -0.3 V (RHE) under ambient conditions.
ABSTRACT
A simple and practical method for α-ketoamide synthesis via a decarboxylative strategy of isocyanates with α-oxocarboxylic acids is described. The reaction proceeds at room temperature under mild conditions without an oxidant or an additive, showing good substrate scope and functional compatibility. Moreover, the applicability of this method was further demonstrated by the synthesis of various bioactive molecules and different application examples through a two-step one-pot operation.
ABSTRACT
BACKGROUND: To evaluate the feasibility and safety of robot-assisted retroperitoneal laparoscopic adrenalectomy (RARLA) for large pheochromocytomas (PHEOs; size≥6 cm) compared with retroperitoneal laparoscopic adrenalectomy (RLA). METHODS: Fifty-one patients who underwent adrenalectomy for large PHEOs between March 2016 and January 2019 were enrolled and divided into two groups, including 32 RLA cases and 19 RARLA cases. We compared the perioperative efficacy and long-term follow-up results between the two groups. RESULTS: Preoperative data, including demographics, comorbidities and tumour characteristics, were similar between the groups. Intraoperatively, the RARLA group had a lower incidence of haemodynamic instability (26.3% vs. 56.2%, P = 0.038) and less intraoperative blood loss (100 ml vs. Two hundred milliliter, P = 0.042) than the RLA group. The groups showed no significant differences in operative time or transfusion rates. Postoperatively, the time to diet resumption, time to ambulation, time to drainage removal and postoperative hospital stay were shorter in the RARLA group than in the RLA group (1 d vs. 2 d, P = 0.027; 1 d vs. 2 d, P = 0.034; 3 d vs. 5 d, P = 0.002; 5 d vs. 6 d, P = 0.02, respectively). The groups exhibited no significant differences in the duration of anaesthetic use, complications, or long-term follow-up results for the blood pressure (BP) improvement rate. CONCLUSIONS: Compared with RLA, RARLA is a safe, feasible and even optimized procedure for large PHEOs.
Subject(s)
Adrenal Gland Neoplasms , Adrenalectomy , Laparoscopy , Pheochromocytoma , Robotic Surgical Procedures , Adrenal Gland Neoplasms/surgery , Adrenalectomy/methods , Adult , Female , Humans , Male , Middle Aged , Pheochromocytoma/surgery , Retrospective StudiesABSTRACT
Gold nanorods (AuNR) have received significant attention in tumor thermo-chemotherapy. However, insufficient thermal availability limits the in vivo highly efficient applications of AuNR in photothermal therapy. In this study, we have fabricated N-isopropylacrylamide grafted O-carboxymethyl chitosan nanoparticles (NCMC NPs) with thermo-responsive properties for co-encapsulating AuNR and doxorubicin (DOX), forming AuNR@NCMC/DOX nanocomposites (NCs). As a result of the thermo- and photothermal-responsiveness, AuNR@NCMC/DOX NCs exhibited irreversible aggregation at high temperature and under near-infrared (NIR) irradiation with an increase of size to 3 µm. When AuNR@NCMC/DOX NCs reached tumor sites following intravenous administration, they were located in the tumor vessels under NIR irradiation due to an embolization effect. This response enhanced tumor targeting, on-demand release, and the thermal performance of AuNR@NCMC/DOX NCs. We have observed higher tumor accumulation of DOX and AuNR with subsequent stronger inhibition of tumor growth than that achieved without NIR irradiation. The development of AuNR-based NCs with multiple smart responsivenesses at tumors can provide a promising paradigm for solid tumor treatment via the cooperative effects of photothermal therapy and chemoembolization.