Gallic acid as biofilm inhibitor can improve transformation efficiency of Ruminiclostridium papyrosolvens.

Ruminiclostridium papyrosolvens is an anaerobic, mesophilic, and cellulolytic clostridia, promising consolidated bioprocessing (CBP) candidate for producing renewable green chemicals from cellulose, but its genetic transformation has been severely impeded by extracellular biofilm. Here, we analyzed the effects of five different inhibitors with gradient concentrations on R. papyrosolvens growth and biofilm formation. Gallic acid was proved to be a potent inhibitor of biofilm synthesis of R. papyrosolvens. Furthermore, the transformation efficiency of R. papyrosolvens was significantly increased when the cells were treated by the gallic acid, and the mutant strain was successfully obtained by the improved transformation method. Thus, inhibition of biofilm formation of R. papyrosolvens by using gallic acid will contribute to its genetic transformation and efficient metabolic engineering.

Development of an efficient ClosTron system for gene disruption in Ruminiclostridium papyrosolvens.

Ruminiclostridium papyrosolvens is an anaerobic, mesophilic, and cellulolytic clostridia, promising consolidated bioprocessing (CBP) candidate for producing renewable green chemicals from cellulose, but its metabolic engineering is limited by lack of genetic tools. Here, we firstly employed the endogenous xylan-inducible promoter to control ClosTron system for gene disruption of R. papyrosolvens. The modified ClosTron can be easily transformed into R. papyrosolvens and specifically disrupt targeting genes. Furthermore, a counter selectable system based on uracil phosphoribosyl-transferase (Upp) was successfully established and introduced into the ClosTron system, which resulted in plasmid curing rapidly. Thus, the combination of xylan-inducible ClosTron and upp-based counter selectable system makes the gene disruption more efficient and convenient for successive gene disruption in R. papyrosolvens. KEY POINTS: • Limiting expression of LtrA enhanced the transformation of ClosTron plasmids in R. papyrosolvens. • DNA targeting specificity can be improved by precise management of the expression of LtrA. • Curing of ClosTron plasmids was achieved by introducing the upp-based counter selectable system.

S1PR1 regulates NDV-induced IL-1ß expression via NLRP3/caspase-1 inflammasome.

Newcastle disease (ND) is an acute, febrile, and highly contagious disease caused by the Newcastle disease virus (NDV), an important pathogen harmful to domestic poultry. Virulent NDV strain infection induces IL-1ß expression and along with strong inflammatory response, ultimately results in death. Inhibition or overexpression of S1PR1, an important target for inflammatory disease treatment, regulates IL-1ß expression, suggesting that S1PR1 may alter the degree of the inflammatory response induced by NDV infection by regulating pro-inflammatory cytokine expression. However, the molecular mechanism by which S1PR1 regulates IL-1ß expression remains unclear. Here, we explore the expression and tissue distribution of S1PR1 after NDV infection and found that S1PR1 expression increased in the lungs, bursa of Fabricius, and DF-1. IL-1ß expression induced by NDV was increased following treatment of cells with the S1PR1-specific agonist, SEW2871. In contrast, IL-1ß expression induced by NDV was decreased after cells were treated with the S1PR1 inhibitor W146, suggesting that S1PR1 promotes NDV-induced IL-1ß expression. Further investigation demonstrated that NDV induced IL-1ß expression through p38, JNK/MAPK, and NLRP3/caspase-1 signaling molecules and S1PR1 affected the expression of IL-1ß by activating the NLRP3/caspase-1 inflammasome but had no significant effect on p38 and JNK/MAPK. Our study shows that NDV infection promotes S1PR1 expression and induces IL-1ß expression through p38, JNK/MAPK, and NLRP3/caspase-1 inflammasomes and that S1PR1 regulates IL-1ß expression mainly through the NLRP3/caspase-1 inflammasome.

Co Nanoparticles Decorated Corncob-Derived Biomass Carbon as an Efficient Electrocatalyst for Nitrate Reduction to Ammonia.

Nitrate (NO3-) is a type of common pollutant in aqueous systems. Electrochemical NO3- reduction is an ecofriendly and sustainable strategy, which can selectively reduce NO3- to highly value-added NH3 and remove NO3- pollutants at the same time. In this work, Co nanoparticles decorated corncob-derived biomass carbon as a highly active electrocatalyst for NO3- to NH3 conversion. Such a catalyst can achieve an amazing Faradaic efficiency of 93.4% and a large NH3 yield of 0.60 mmol h-1 cm-2 in alkaline media. 15N-Labeling experiment proves that the detected NH3 is derived from NO3- electroreduction. In addition, it also displays excellent durability in long-term and cycle-electrolysis tests.

Development of an in vivo methylation system for transformation of Ruminiclostridium cellulolyticum.

AIMS: Ruminiclostridium cellulolyticum, an anaerobic cellulolytic bacterium producing an efficient cellulolytic extracellular complex named cellulosome, is a promising host for biofuel production from lignocellulose. This study aims to develop a rapid transformation method for R. cellulolyticum avoiding its restriction system. METHODS AND RESULTS: The CceI restriction system is a major barrier to introduction of foreign DNA into R. cellulolyticum cells. To improve the transformation efficiency of R. cellulolyticum, the gene encoding CceI methyltransferase (M.CceI) of R. cellulolyticum H10 was functionally expressed in Escherichia coli, resulting in an in vivo methylation system for transformation of R. cellulolyticum. The electrotransformation experiments of R. cellulolyticum H10 with the E. coli-Clostridium shuttle plasmid pMTC6 showed that the transformation efficiency reached up to 2.6 × 103 ±0.23 × 103  CFU per µg plasmid DNA. The results demonstrated that the system is able to confer the M.CceI-specific DNA methylation pattern to its resident plasmid, which makes the plasmid resistant to the CceI restriction and efficiently transferred into R. cellulolyticum. CONCLUSIONS: In this study, we generated an in vivo methylation system of R. cellulolyticum, allowing interspecies DNA transfer and improving transformation efficiency. SIGNIFICANCE AND IMPACT OF THE STUDY: This research result will greatly facilitate the metabolic engineering of R. cellulolyticum for biofuel production directly from cellulose.

Phylogenetic analysis of infectious bronchitis virus circulating in southern China in 2016-2017 and evaluation of an attenuated strain as a vaccine candidate.

Avian infectious bronchitis (IB) is a highly contagious viral respiratory disease, caused by infectious bronchitis virus (IBV), that poses an important economic threat to the poultry industry. In recent years, genotypes GI-7, GI-13, and GI-19 have been the most prevalent IBV strains in China. However, in this study, we found that most IBV strains from southern China in 2016-2017 belonged to genotype GVI-1. This genotype, for which there is no vaccine, has been reported sporadically in the region. The GDTS13 strain, which caused severe IB outbreaks on the farms where it was isolated, was evaluated as a candidate vaccine strain. GDTS13 was serially passaged in specific-pathogen-free embryonated chicken eggs for 100 generations to produce GDTS13-F100. Safety testing indicated that GDTS13-F100 had no pathogenic effect on chickens. Additionally, GDTS13-F100 showed an excellent protective effect against GDTS13, with no clinical signs or virus shedding observed in immunized chickens challenged with the parent strain. These findings indicate that GVI-1 has become the most prevalent IBV genotype in southern China and that GDTS13-F100 may serve as an attenuated vaccine to protect against infection with this genotype.

Photoinduced Radical Emission in a Coassembly System.

Developing radical emission at ambient conditions is a challenging task since radical species are unstable in air. In the present work, we overcome this challenge by coassembling a series of tricarbonyl-substituted benzene molecules with polyvinyl alcohol (PVA). The strong hydrogen bonds between the guest dopants and the PVA host matrix protect the free radicals of carbonyl compounds after light irradiation, leading to strong solid state free radical emission. Changing temperature and peripheral functional groups of the tricarbonyl-substituted benzenes can influence the intensity of the radical emission. Quantum-chemical calculations predict that such free radical fluorescence originates from anti-Kasha D2 →D0 vertical emission by the anion radicals. The photoinduced radical emission by the tricarbonyl-substituted benzenes was successfully utilized for information encryption application.

Newcastle disease virus RNA-induced IL-1ß expression via the NLRP3/caspase-1 inflammasome.

Newcastle disease virus (NDV) infection causes severe inflammation and is a highly contagious disease in poultry. Virulent NDV strains (GM) induce large quantities of interleukin-1ß (IL-1ß), which is the central mediator of the inflammatory reaction. Excessive expression of IL-1ß exacerbates inflammatory damage. Therefore, exploring the mechanisms underlying NDV-induced IL-1ß expression can aid in further understanding the pathogenesis of Newcastle disease. Here, we showed that anti-IL-1ß neutralizing antibody treatment decreased body temperature and mortality following infection with virulent NDV. We further explored the primary molecules involved in NDV-induced IL-1ß expression from the perspective of both the host and virus. This study showed that overexpression of NLRP3 resulted in increased IL-1ß expression, whereas inhibition of NLRP3 or caspase-1 caused a significant reduction in IL-1ß expression, indicating that the NLRP3/caspase-1 axis is involved in NDV-induced IL-1ß expression. Moreover, ultraviolet-inactivated GM (chicken/Guangdong/GM/2014) NDV failed to induce the expression of IL-1ß. We then collected virus from GM-infected cell culture supernatant using ultracentrifugation, extracted the viral RNA, and stimulated the cells further with GM RNA. The results revealed that RNA alone was capable of inducing IL-1ß expression. Moreover, NLRP3/caspase-1 was involved in GM RNA-induced IL-1ß expression. Thus, our study elucidated the critical role of IL-1ß in the pathogenesis of Newcastle disease while also demonstrating that inhibition of IL-1ß via anti-IL-1ß neutralizing antibodies decreased the damage associated with NDV infection; furthermore, GM RNA induced IL-1ß expression via NLRP3/caspase-1.

Immune effect of a Newcastle disease virus DNA vaccine with IL-12 as a molecular adjuvant delivered by electroporation.

Newcastle disease (ND), caused by virulent Newcastle disease virus (NDV) strains, has been one of the most problematic diseases affecting the poultry industry worldwide. Conventional vaccines provide effective protection for birds to survive ND outbreaks, but they may not completely suppress NDV shedding. NDV strains circulate on farms for a long time after the initial infection and cause potential risks. A new vaccine with fast clearance ability and low viral shedding is needed. In this study, we used interleukin-12 (IL-12) as an adjuvant and electroporation (EP) as an advanced delivery system to improve a DNA vaccine candidate. The fusion (F) protein gene from an NDV strain of the prevalent genotype VII.1.1 was cloned to prepare the vaccine. Chickens immunized with the F gene DNA vaccine co-delivered with an IL-12-expressing plasmid DNA showed higher neutralizing antibody levels and stronger concanavalin-A-induced lymphocyte proliferation than those treated with the F gene DNA vaccine alone. The co-delivered vaccine provided 100% protection, and less viral shedding and a shorter release time were observed in challenged chickens than when the F gene DNA vaccine was administered alone. The use of F gene DNA combined with IL-12 delivered by electroporation is a promising approach for vaccination against ND.

Progress on chicken T cell immunity to viruses.

Avian virus infection remains one of the most important threats to the poultry industry. Pathogens such as avian influenza virus (AIV), avian infectious bronchitis virus (IBV), and infectious bursal disease virus (IBDV) are normally controlled by antibodies specific for surface proteins and cellular immune responses. However, standard vaccines aimed at inducing neutralizing antibodies must be administered annually and can be rendered ineffective because immune-selective pressure results in the continuous mutation of viral surface proteins of different strains circulating from year to year. Chicken T cells have been shown to play a crucial role in fighting virus infection, offering lasting and cross-strain protection, and offer the potential for developing universal vaccines. This review provides an overview of our current knowledge of chicken T cell immunity to viruses. More importantly, we point out the limitations and barriers of current research and a potential direction for future studies.

Emergence and Adaptation of a Novel Highly Pathogenic H7N9 Influenza Virus in Birds and Humans from a 2013 Human-Infecting Low-Pathogenic Ancestor.

Since its emergence in 2013, the H7N9 low-pathogenic avian influenza virus (LPAIV) has been circulating in domestic poultry in China, causing five waves of human infections. A novel H7N9 highly pathogenic avian influenza virus (HPAIV) variant possessing multiple basic amino acids at the cleavage site of the hemagglutinin (HA) protein was first reported in two cases of human infection in January 2017. More seriously, those novel H7N9 HPAIV variants have been transmitted and caused outbreaks on poultry farms in eight provinces in China. Herein, we demonstrate the presence of three different amino acid motifs at the cleavage sites of these HPAIV variants which were isolated from chickens and humans and likely evolved from the preexisting LPAIVs. Animal experiments showed that these novel H7N9 HPAIV variants are both highly pathogenic in chickens and lethal to mice. Notably, human-origin viruses were more pathogenic in mice than avian viruses, and the mutations in the PB2 gene associated with adaptation to mammals (E627K, A588V, and D701N) were identified by next-generation sequencing (NGS) and Sanger sequencing of the isolates from infected mice. No polymorphisms in the key amino acid substitutions of PB2 and HA in isolates from infected chicken lungs were detected by NGS. In sum, these results highlight the high degree of pathogenicity and the valid transmissibility of this new H7N9 variant in chickens and the quick adaptation of this new H7N9 variant to mammals, so the risk should be evaluated and more attention should be paid to this variant.IMPORTANCE Due to the recent increased numbers of zoonotic infections in poultry and persistent human infections in China, influenza A(H7N9) virus has remained a public health threat. Most of the influenza A(H7N9) viruses reported previously have been of low pathogenicity. Now, these novel H7N9 HPAIV variants have caused human infections in three provinces and outbreaks on poultry farms in eight provinces in China. We analyzed the molecular features and compared the relative characteristics of one H7N9 LPAIV and two H7N9 HPAIVs isolated from chickens and two human-origin H7N9 HPAIVs in chicken and mouse models. We found that all HPAIVs both are highly pathogenic and have valid transmissibility in chickens. Strikingly, the human-origin viruses were more highly pathogenic than the avian-origin viruses in mice, and dynamic mutations were confirmed by NGS and Sanger sequencing. Our findings offer important insight into the origin, adaptation, pathogenicity, and transmissibility of these viruses to both poultry and mammals.

Chenodeoxycholic Acid from Bile Inhibits Influenza A Virus Replication via Blocking Nuclear Export of Viral Ribonucleoprotein Complexes.

Influenza A virus (IAV) infection is still a major global threat for humans, especially for the risk groups: young children and the elderly. The currently licensed antiviral drugs target viral factors and are prone to viral resistance. In recent years, a few endogenous small molecules from host, such as estradiol and omega-3 polyunsaturated fatty acid (PUFA)-derived lipid mediator protection D1 (PD1), were demonstrated to be capable of inhibiting IAV infection. Chenodeoxycholic acid (CDCA), one of the main primary bile acids, is synthesized from cholesterol in the liver and classically functions in emulsification and absorption of dietary fats. Clinically, CDCA has been used in the treatment of patients with cholesterol gallstones for more than five decades. In this study, we showed that CDCA attenuated the replication of three subtypes of influenza A virus, including a highly pathogenic H5N1 strain, in A549 and MDCK cell cultures with IC50 ranging from 5.5 to 11.5 µM. Mechanistically, CDCA effectively restrained the nuclear export of viral ribonucleoprotein (vRNP) complexes. In conclusion, as an endogenous physiological small molecule, CDCA can inhibit IAV replication in vitro, at least in part, by blocking vRNP nuclear export, and affords further studies for development as a potential antiviral agent against IAV infections.

Tacrolimus improves proteinuria remission in adults with cyclosporine A-resistant or -dependent minimal change disease.

AIMS: Cyclosporin A (CsA) is considered as an effective treatment option for steroid-resistant or-dependent patients with adult-onset minimal change disease (MCD). However, CsA resistance or dependence is also observed in these patients. Tacrolimus (TAC) is a calcineurin inhibitor that is potent in cytokine suppression. The authors aim to evaluate the efficacy and safety of TAC therapy in CsA-resistant and-dependent adult-onset MCD patients. METHODS: Patients with adult-onset MCD were enrolled in our department from 2008 to 2012. All patients were demonstrated to be resistant to or dependent on CsA therapy. Prednisone (0.5 mg/kg per day) combined with TAC (0.05-0.1 mg/kg per day) were prescribed to these patients for at least 6 months. The primary outcome was complete or partial remission of proteinuria. Secondary outcomes included time required for complete or partial remission, adverse events, number of relapses, and TAC dosages. RESULTS: A total of 11 MCD patients were enrolled in this observational study. The numbers of patients who presented with resistance to or dependence on CsA were 7 and 4, respectively. The total remission rate was 90.9% (10/11) with the complete remission rate 72.7% (8/11). Most remission patients achieved remission during the first 2 months of TAC therapy. Patients who presented with dependence on CsA had achieved complete remission with TAC therapy, while outcomes for CsA-resistant patients were four complete remissions, two partial remissions and one resistance. The adverse events were observed in this study included infection, diarrhoea, and worsened hypertension. Five patients who had remission experienced relapse. CONCLUSIONS: Tacrolimus improves proteinuria remission in adults with CsA-resistant or -dependent MCD.

Phenotypic Characteristics and Genetic Diversity of Salmonella enterica Serotype Derby Isolated from Human Patients and Foods of Animal Origin.

Salmonella enterica serotype Derby is among the three most common serotypes of nontyphoidal Salmonella isolated from patients with diarrhea in China. In this study, 133 Salmonella Derby isolates from human patients (n = 74) and foods of animal origin (n = 59) in Shanghai, China, between September 2013 and December 2014, were selected to study its phenotypic characteristics and genetic diversity. The isolates were subjected to antimicrobial susceptibility testing, plasmid replicon typing, virulence profile determination, and molecular subtyping by pulsed-field gel electrophoresis (PFGE). Isolates were frequently resistant to tetracycline (87.22%), sulfisoxazole (74.44%), and streptomycin (62.41%), and a low frequency of resistance was found toward ofloxacin (3.01%), ceftazidime (2.26%), and cefepime (1.50%); in addition, 93 (69.92%) isolates were multidrug resistant. The most common plasmid incompatibility replicon types were the IncF family (FIA, 51.31%; FIC, 27.82%; and FIB, 21.80%) and IncP types (35.34%): these plasmid types may be associated with the spread of antibiotic resistance and virulence genes. All isolates were positive for the Salmonella pathogenicity island (SPI) gene avrA and the fimbrial gene bcfC from among the 10 virulence genes detected, and most of them carried ssaQ (99.25%), mgtC (97.74%), siiD (98.50%), sopB (97.74%), and sopE (96.99%). PFGE showed 68 patterns in nine main clusters at an 85% similarity threshold. Most of the isolates from different sources possessed the same fingerprints or molecular profiles in each cluster, which strongly suggests the possibility that foods of animal origin, especially pork, serve as an important source for human infection. Moreover, this diversity may suggest strains originating from multiple clones. Therefore, surveillance on this serotype should be strengthened to prevent transmission of Salmonella Derby from foods of animal origin, especially pork, to humans.

Cation-Induced Variation of Micromorphology and Luminescence Properties of Tungstate Phosphors by a Hydrothermal Method.

Eu3+-doped MWO4 (M = Zn, Cd, Ca, Sr, or Ba) nanorods and rodlike, spherical, dumbbell-like, and double-tapter-like grains have been obtained via a hydrothermal method. The distinct differences in cationic radius lead to a special morphology, which is attributed to the symmetry of the crystal structure and the differences in the growth rates of various crystals, and it further leads to the variation of luminescence. It was found that the charge transfer band of MWO4:0.04Eu3+ exhibits a blue shift with an increasing cationic radius, and the shift is ascribed to less covalency being caused by an increase in the cationic radius. The emission intensity obviously increases with cationic radius, increasing for the samples with a monoclinic phase; however, it is the opposite for the samples with a tetragonal phase, and CaWO4:0.04Eu3+ exhibits an optimal emission intensity. In addition, the possible reasons for the decay lifetime are also discussed in detail. Our results indicate that cations can effectively control the crystal structure, micromorphology, and luminescence in tungstate phosphors, and thus, our approach is effective for obtaining materials with the desired morphology and crystal structure.

The MYC, TERT, and ZIC1 genes are common targets of viral integration and transcriptional deregulation in avian leukosis virus subgroup J-induced myeloid leukosis.

UNLABELLED: The integration of retroviruses into the host genome following nonrandom genome-wide patterns may lead to the deregulation of gene expression and oncogene activation near the integration sites. Slow-transforming retroviruses have been widely used to perform genetic screens for the identification of genes involved in cancer. To investigate the involvement of avian leukosis virus subgroup J (ALV-J) integration in myeloid leukosis (ML) in chickens, we utilized an ALV-J insertional identification platform based on hybrid capture target enrichment and next-generation sequencing (NGS). Using high-definition mapping of the viral integration sites in the chicken genome, 241 unique insertion sites were obtained from six different ALV-J-induced ML samples. On the basis of previous statistical definitions, MYC, TERT, and ZIC1 genes were identified as common insertion sites (CIS) of provirus integration in tumor cells; these three genes have previously been shown to be involved in the malignant transformation of different human cell types. Compared to control samples, the expression levels of all three CIS genes were significantly upregulated in chicken ML samples. Furthermore, they were frequently, but not in all field ML cases, deregulated at the mRNA level as a result of ALV-J infection. Our findings contribute to the understanding of the relationship between multipathotypes associated with ALV-J infection and the molecular background of tumorigenesis. IMPORTANCE: ALV-Js have been successfully eradicated from chicken breeding flocks in the poultry industries of developed countries, and the control and eradication of ALV-J in China are now progressing steadily. To further study the pathogenesis of ALV-J infections, it will be necessary to elucidate the in vivo viral integration and tumorigenesis mechanism. In this study, 241 unique insertion sites were obtained from six different ALV-J-induced ML samples. In addition, MYC, TERT, and ZIC1 genes were identified as the CIS of ALV-J in tumor cells, which might be a putative "driver" for the activation of the oncogene. In addition, the CIS genes showed deregulated expression compared to nontumor samples. These results have potentially important implications for the mechanism of viral carcinogenesis.

Inhibition of MiR-199a-5p reduced cell proliferation in autosomal dominant polycystic kidney disease through targeting CDKN1C.

BACKGROUND: With a prevalence of about 1:500 to 1:1,000, autosomal dominant polycystic kidney disease (ADPKD) often causes renal failure, with many serious complications. However, there is no Food and Drug Administration (FDA) approved therapy available. MATERIAL/METHODS: MiR-199a-5p level in ADPKD patient samples, rat model, and cell lines were determined with Realtime PCR assay. After miR-199a-5p inhibitor was transfected, we detected the cell proliferation and apoptosis using an MTT assay and an Annexin V-FITC staining kit, respectively. Finally, TargetScan version 5.1 was used to predict the miRNA target and the target gene of miR-199a-5p was proved by a Luciferase assay. RESULTS: We identified a dramatically up-regulated microRNA, miR-199a-5p, in ADPKD tissues and cell lines. Our data show that inhibition of miR-199a-5p suppressed cyst cells proliferation and induced cell apoptosis. We found that miR-199a-5p might exert this effect through targeting CDKN1C/p57. CONCLUSIONS: Up-regulation of miR-199a-5p in ADPKD tissues might promote cell proliferation through suppressing CDKN1C, suggesting miR-199a-5p as a novel target for ADPKD treatment.

Improvement of ClosTron for successive gene disruption in Clostridium cellulolyticum using a pyrF-based screening system.

Clostridium includes a number of species, such as thermophilic Clostridium thermocellum and mesophilic Clostridium cellulolyticum, producing biofuels and chemicals from lignocellulose, while genetic engineering is necessary to improve wild-type strains to fulfill the requirement of industrialization. ClosTron system is widely used in the gene targeting of Clostridium because of its high efficiency and operability. However, the targetron plasmid present in cell hinders the successive gene disruption. To solve this problem, a pyrF-based screening system was developed and implemented in C. cellulolyticum strain H10 in this study for efficient targetron plasmid curing. The screening system was composed of a pyrF-deleted cell chassis (H10ΔpyrF) constructed via homologous recombination and a PyrF expression cassette located in a targetron plasmid containing an erythromycin resistance gene. With the screening system, the gene targeting could be achieved following a two-step procedure, including the first step of gene disruption through targetron transformation and erythromycin selection and the second step of plasmid curing by screening with 5-fluoroorotic acid. To test the developed screening system, successive inactivation of the major cellulosomal exocellulase Cel48F and the scaffoldin protein CipC was achieved in C. cellulolyticum, and the efficient plasmid curing was confirmed. With the assistance of the pyrF-based screening system, the targetron plasmid-cured colonies can be rapidly selected by one-plate screening instead of traditional days' unguaranteed screening, and the successive gene disruption becomes accomplishable with ClosTron system with improved stability and efficiency, which may promote the metabolic engineering of Clostridium species aiming at enhanced production of biofuels and chemicals.

Effects of endothelial nitric oxide synthase gene on end stage renal disease progression in autosomal dominant polycystic kidney disease.

AIM: To investigate whether endothelial nitric oxide synthase (eNOS) gene associate with the progression of autosomal dominant polycystic kidney disease (ADPKD). METHODS: Databases of EMBASE, Pubmed, ISI, Ovid Database, Cochrane library and China National Knowledge Infrastructure were all searched. Associated studies about eNOS polymorphisms and ADPKD were analyzed by meta-analysis. RESULTS: A total of 11 studies with Glu298Asp and 4b/a polymorphisms were included. A allele of the 4b/a polymorphism increased the risk of end stage renal disease (ESRD) in ADPKD (odds ratio (OR) = 1.85, 95% confidence interval (CI) 1.17-2.94, P = 0.009). However, GG phenotype of Glu298Asp polymorphism neither decreased the ESRD risk (OR = 0.77, 95% CI 0.55-1.08, P = 0.13) nor affected the hypertension risk (OR = 1.04, 95% CI 0.66-1.66, P = 0.86). The GG phenotype carriers had later ESRD age compared with the T allele of Glu298Asp polymorphism (WMD = 2.39; 95% CI 1.32-3.46; P < 0.0001). Significant association was also found in Caucasians (WMD = 2.41; 95% CI 1.18-3.64; P = 0.0001). Subgroup analysis by gender indicated GG genotype carriers had older age of ESRD than T allele carriers in males (WMD = 4.51; 95% CI 3.95-5.08; P = 0.00001), but not in females. CONCLUSIONS: GG genotype of the Glu298Asp variant slowed the ESRD progression in ADPKD, while a allele carriers of the 4b/a variant increased the risk of ESRD. Variants of eNOS gene might play different roles in the ESRD progression in ADPKD.

Compensatory evolution of chromosomes and plasmids counteracts the plasmid fitness cost.

Plasmids incur a fitness cost that has the potential to restrict the dissemination of resistance in bacterial pathogens. However, bacteria can overcome this disadvantage by compensatory evolution to maintain their resistance. Compensatory evolution can occur via both chromosomes and plasmids, but there are a few reviews regarding this topic, and most of them focus on plasmids. In this review, we provide a comprehensive overview of the currently reported mechanisms underlying compensatory evolution on chromosomes and plasmids, elucidate key targets regulating plasmid fitness cost, and discuss future challenges in this field. We found that compensatory evolution on chromosomes primarily arises from mutations in transcriptional regulatory factors, whereas compensatory evolution of plasmids predominantly involves three pathways: plasmid copy number regulation, conjugation transfer efficiency, and expression of antimicrobial resistance (AMR) genes. Furthermore, the importance of reasonable selection of research subjects and effective integration of diverse advanced research methods is also emphasized in our future study on compensatory mechanisms. Overall, this review establishes a theoretical framework that aims to provide innovative ideas for minimizing the emergence and spread of AMR genes.