Long noncoding RNA C17orf91 is a potential prognostic marker and functions as an oncogene in ovarian cancer

BACKGROUND: This study was aimed to explore the role of long noncoding RNA C17orf91 and its potential mechanisms in ovarian cancer development. RESULTS: To assess its role in ovarian cancer, microarray datasets (GSE14407, GSE30587, and GSE17260) in Gene Expression Omnibus (GEO) were utilized to assess the expression and clinical significance of C17orf91 in ovarian cancer. Next, loss-of-function studies were performed to establish the role of C17orf91 and the underlying mechanisms in ovarian cancer development. It was found that elevated expression of C17orf91 was observed in omental metastases when compared with matched primary ovarian tumors(GSE30587, P = 0.016). Moreover, Log Rank analysis revealed that increased expression of C17orf91 was associated with shorter progression free survival(PFS)(HR = 1.90(1.19-3.03), P = 0.008). Overall survival(OS) also showed a similar trend, but did not reach statistical significance(HR = 1.75(0.97-3.13), P = 0.061). Loss-of-function studies further demonstrated that C17orf91 repression impaired migration, invasion and viability of ovarian cancer cells, and downregulated the pro-metastatic gene, MYC, at both mRNA and protein level. CONCLUSION: Collectively, our findings revealed that C17orf91 was a potential prognostic marker and functioned as an oncogene in ovarian cancer. It remains to be seen whether modulation of C17orf91 expression will cause phenotypic changes in vivo. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13048-016-0258-3) contains supplementary material, which is available to authorized users

Driving toward sustainable cities: The interplay between Chinese emerging corporate ESG performance and climate finance in achieving low-carbon development

Climate finance plays a pivotal role in directing increased capital flow toward climate change mitigation and adaptation activities. Many emerging enterprises have grown rapidly under the influence of climate finance policies, contributing to urban low-carbon transition. Therefore, it is important to explore the interrelationships between climate finance, enterprise low-carbon transformations, and urban carbon emission efficiency. This study delves into the impact of climate finance on urban carbon emission efficiency and its underlying transmission mechanisms, drawing upon comprehensive panel data of 262 Chinese cities and 4125 enterprises from 2009 to 2019. The findings indicate that urban climate finance have significantly positive influences on urban carbon emission efficiency and unveil that enterprise environmental, social and governance (ESG) performance exhibits positive influences on urban carbon emission efficiency, underscoring the critical role of enterprises as the vanguard of climate finance. Moreover, the research presents the mediating effect of enterprise green innovation between the urban climate finance and carbon emission efficiency. The mediating effect manifests distinct threshold effects among different levels of enterprise green innovation. Our results suggest that China should enact tailored climate finance policies for higher urban emission efficiency, including judicious allocation of climate funds and effective guidance on enterprise-driven green technological innovation

Ancient Genomics Reveals the Origin, Dispersal, and Human Management of East Asian Domestic Pigs

Pigs are the most commercially important modern livestock animal in East Asia. Numerous aspects of their domestication history remain unclear, however, including the geographic center of their domestication, their subsequent dispersal routes, and the emergence of phenotypic traits specific to domestic pigs. To address these questions, we generated 21 nuclear genomes and 23 mitogenomes from ancient domestic pigs and wild boar from 5,800 BCE to 1,300 CE across China. Our analyses of newly generated and previously published Eurasian suid genomes confirmed Northern China and eliminated Southwestern China as the domestication origin of modern East Asian pigs. Following their association with people and the first appearance of black coat coloration, Northern Chinese domestic pigs dispersed alongside Yellow River millet farmers to the Yangtze River Basin and Southwestern China, which they admixed with local wild boar. A genome-wide loss of diversity and signatures of inbreeding in ancient Northern pigs may have been the result of intensified human management as early as 3,000 BCE. Our results reveal the geographic and temporal origins and subsequent dispersal and admixture of pigs in China, mirroring human migration and agricultural development history

BlaPSZ-1, a novel AmpC gene identified from a Pantoea isolate

BackgroundPantoea species of the family Erwiniaceae are well-known plant pathogens and animal and human conditional pathogens. Due to the widespread and continuous use of antimicrobials, multidrug-resistant strains continue to emerge, making clinical treatment difficult; therefore, there is an increasing need to clarify the mechanisms of drug resistance.MethodsA rabbit anal fecal sample was collected by a swab and the streak plate method was used to isolate single colonies. The standard agar dilution method was used to determine the minimum inhibitory concentrations (MICs) against antimicrobials. The complete genome sequence of the bacterium was obtained using Next-Generation Sequencing platforms. The potential resistance gene was annotated based on the Comprehensive Antibiotic Resistance Database (CARD) and verified by molecular cloning. The β-lactamase PSZ-1 was expressed via the pCold I expression vector and its enzyme kinetic parameters were analyzed. The genetic environment and evolutionary process of the novel resistance gene-related sequences were analyzed by bioinformatic methods.ResultsThe isolate Pantoea endophytica X85 showed some degree of resistance to penicillins as well as cephalosporins. A novel AmpC resistance gene, designated blaPSZ-1 in this research, was identified to be encoded in the plasmid (pPEX85) of P. endophytica X85. BlaPSZ-1 showed resistance to penicillins and several first-, second-and third-generation cephalosporins as well as aztreonam, but it did not show resistance to the fourth-generation cephalosporins or carbapenems tested. Enzyme kinetic assays revealed that it could hydrolyze amoxicillin, penicillin G, cephalothin, and cefazolin, and its hydrolytic activity could be strongly inhibited by the inhibitor avibactam, which was generally consistent with antimicrobial susceptibility testing results. No hydrolytic activity was observed for third-generation cephalosporins or aztreonam.ConclusionIn this study, a novel AmpC β-lactamase gene, designated blaPSZ-1, was characterized and it was encoded in the plasmid of the bacterium P. endophytica X85. It shows resistance to penicillins and several cephalosporins. The discovery of novel drug resistance mechanisms can help guide the scientific use of drugs in animal husbandry and clinical practice, effectively avoiding the abuse of antimicrobials and thus preventing the further development and spread of bacterial resistance

Identification and characterization of a novel chromosomal aminoglycoside 3’-O-phosphotransferase, APH(3′)-Id, from Kluyvera intermedia DW18 isolated from the sewage of an animal farm

BackgroundAminoglycosides, as important clinical antimicrobials, are used as second-line drugs for treating multidrug-resistant tuberculosis or combined with β-lactam drugs for treating severe infections such as sepsis. Aminoglycoside-modifying enzyme (AME) is the most important mechanism of aminoglycoside resistance and deserves more attention.MethodsThe bacterium Kluyvera intermedia DW18 was isolated from the sewage of an animal farm using the conventional method. The agar dilution method was used to determine the minimum inhibitory concentrations (MICs) of antimicrobials. A novel resistance gene was cloned, and the enzyme was expressed. The kinetic parameters were measured by a SpectraMax M5 multifunctional microplate reader. Bioinformatic analysis was performed to reveal the genetic context of the aph(3′)-Id gene and its phylogenetic relationship with other AMEs.ResultsA novel aminoglycoside 3′-O-phosphotransferase gene designated aph(3′)-Id was identified in K. intermedia DW18 and shared the highest amino acid identity of 77.49% with the functionally characterized aminoglycoside 3′-O-phosphotransferase APH(3′)-Ia. The recombinant plasmid carrying the novel resistance gene (pMD19-aph(3′)-Id/E. coli DH5α) showed 1,024-, 512-, 128- and 16-fold increased MIC levels for kanamycin, ribostamycin, paromomycin and neomycin, respectively, compared with the reference strain DH5α. APH(3′)-Id showed the highest catalytic efficiency for ribostamycin [kcat/Km of (4.96 ± 1.63) × 105 M−1/s−1], followed by paromomycin [kcat/Km of (2.18 ± 0.21) × 105 M−1/s−1], neomycin [kcat/Km of (1.73 ± 0.20) × 105 M−1/s−1], and kanamycin [kcat/Km of (1.10 ± 0.18) × 105 M−1/s−1]. Three conserved functional domains of the aminoglycoside phosphotransferase family and ten amino acid residues responsible for the phosphorylation of kanamycin were found in the amino acid sequence of APH(3′)-Id. No mobile genetic element (MGE) was discovered surrounding the aph(3′)-Id gene.ConclusionIn this work, a novel aminoglycoside 3’-O-phosphotransferase gene designated aph(3′)-Id encoded in the chromosome of the environmental isolate Kluyvera intermedia DW18 was identified and characterized. These findings will help clinicians select effective antimicrobials to treat infections caused by pathogens with this kind of resistance gene

Identification and characterization of a novel β-lactamase gene, blaAMZ–1, from Achromobacter mucicolens

BackgroundAchromobacter is a genus of gram-negative bacteria that can act as opportunistic pathogens. Recent studies have revealed that some species of Achromobacter show inherent resistance to β-lactams, but the resistance mechanisms of Achromobacter mucicolens have rarely been reported.MethodThe bacterium was isolated using standard laboratory procedures. The agar dilution method was used to determine the minimum inhibitory concentrations (MICs). Genome sequencing was performed using the PacBio RS II and Illumina HiSeq 2500 platforms, and the Comprehensive Antibiotic Resistance Database (CARD) was used to annotate the drug resistance genes. The localization of the novel β-lactamase AMZ-1 was determined, and its characteristics were determined via molecular cloning and enzyme kinetic analysis. The phylogenetic relationship and comparative genomic analysis of the resistance gene-related sequences were also analyzed.ResultAchromobacter mucicolens Y3, isolated from a goose on a farm in Wenzhou, showed resistance to multiple antibiotics, including penicillins and cephalosporins. BlaAMZ–1 showed resistance to amoxicillin, penicillin G, ampicillin, cephalothin and cefoxitin, and the resistance activity could be inhibited by β-lactamase inhibitors. Enzyme kinetic analysis results showed that AMZ-1 has hydrolytic activity against a wide range of substrates, including cephalothin, amoxicillin, penicillin G, and cefoxitin but not ampicillin. The hydrolytic activity of AMZ-1 was greatly inhibited by avibactam but much more weakly inhibited by tazobactam. Mobile genetic elements could not be found around the blaAMZ–1-like genes, which are conserved on the chromosomes of bacteria of the genus Achromobacter.ConclusionIn this study, a novel AmpC gene, blaAMZ–1, from the animal-origin bacterium A. mucicolens Y3 was identified and characterized. It conferred resistance to some penicillins and first- and second-generation cephalosporins. The identification of this novel resistance gene will be beneficial for the selection of effective antimicrobials to treat associated infections

Identification of floR Variants Associated With a Novel Tn4371-Like Integrative and Conjugative Element in Clinical Pseudomonas aeruginosa Isolates

Florfenicol is widely used to control respiratory diseases and intestinal infections in food animals. However, there are increasing reports about florfenicol resistance of various clinical pathogens. floR is a key resistance gene that mediates resistance to florfenicol and could spread among different bacteria. Here, we investigated the prevalence of floR in 430 Pseudomonas aeruginosa isolates from human clinical samples and identified three types of floR genes (designated floR, floR-T1 and floR-T2) in these isolates, with floR-T1 the most prevalent (5.3%, 23/430). FloR-T2 was a novel floR variant identified in this study, and exhibited less identity with other FloR proteins than FloRv. Moreover, floR-T1 and floR-T2 identified in P. aeruginosa strain TL1285 were functionally active and located on multi-drug resistance region of a novel incomplete Tn4371-like integrative and conjugative elements (ICE) in the chromosome. The expression of the two floR variants could be induced by florfenicol or chloramphenicol. These results indicated that the two floR variants played an essential role in the host’s resistance to amphenicol and the spreading of these floR variants might be related with the Tn4371 family ICE