Mobile genetic elements affect the dissemination of antibiotic resistance genes (ARGs) of clinical importance in the environment.

The prevalence of antibiotic resistance genes (ARGs) in the environment is a quintessential One Health issue that threats both human and ecosystem health; however, the source and transmission of ARGs, especially clinically important ARGs (CLIARGs), in the environment have not yet been well studied. In the present study, shotgun metagenomic approaches were used to characterize the microbiome, resistome, and mobilome composition in human feces and six different environment sample types in South China. Overall, the resistome harbored 157 CLIARGs, with specific ARG hotspots (e.g., human feces, wastewater treatment plants, livestock manure and wastewater) excreting significantly higher abundance of CLIARGs compared with the natural environment. A redundancy analysis (RDA) was performed and revealed that the bacterial community compositions and mobile genetic elements (MGEs) explained 55.08% and 34.68% of the variations in ARG abundance, respectively, indicating that both bacterial community and MGEs are key contributors to the maintenance and dissemination of CLIARGs in the environment. The network analysis revealed non-random co-occurrence patterns between 200 bacterial genera and 147 CLIARGs, as well as between 135 MGEs and 123 CLIARGs. In addition to numerous co-shared CLIARGs among different sample types, the source tracking program based on the FEAST probabilistic model was used to estimate the relative contributions of the CLIARGs from potential sources to the natural environment. The source tracking analysis results delineated that mobilome, more than microbiome, contributed CLIARG transmission from those ARG hotspots into natural environment, and the MGEs in WWTPs seem to play the most significant role in the spread of CLIARGs to the natural environment (average contribution 32.9%-46.4%). Overall, this study demonstrated the distribution and dissemination of CLIARGs in the environment, and aimed to better inform strategies to control the spread of CLIARGs into the natural environment.

A Crack Segmentation Model Combining Morphological Network and Multiple Loss Mechanism.

With the wide application of computer vision technology and deep-learning theory in engineering, the image-based detection of cracks in structures such as pipelines, pavements and dams has received more and more attention. Aiming at the problems of high cost, low efficiency and poor detection accuracy in traditional crack detection methods, this paper proposes a crack segmentation network by combining a morphological network and a multiple-loss mechanism. First, for improving the identification of cracks with different resolutions, the U-Net network is used to extract multi-scale features from the crack image. Second, for eliminating the effect of polarized light on the cracks under different illuminations, the extracted crack features are further morphologically processed by a white-top hat transform and a black-bottom hat transform. Finally, a multi-loss mechanism is designed to solve the problem of the inaccurate segmentation of cracks on a single scale. Extensive experiments are carried out on five open crack datasets: Crack500, CrackTree200, CFD, AEL and GAPs384. The experimental results showed that the average ODS, OIS, AIU, sODS and sOIS are 75.7%, 73.9%, 36.4%, 52.4% and 52.2%, respectively. Compared with state-of-the-art methods, the proposed method achieves better crack segmentation performance. Ablation experiments also verified the effectiveness of each module in the algorithm.

Global trend of antimicrobial resistance in common bacterial pathogens in response to antibiotic consumption.

The emergence of antimicrobial resistance (AMR) is a growing public health threat worldwide and antibiotic consumption is being increasingly recognized as the main selective pressure driving this resistance. However, global trend in antibiotic resistance in response to antibiotic consumption is not fully understood. In this study, we collected national resistance data on specific resistant pathogens considered by the World Health Organization (WHO) as priority and antibiotic consumption data for 61 countries to assess the global trends in antibiotic resistance of those common bacterial pathogens and their association with antibiotic consumption. The low- and middle-income countries (LMICs) represented the largest hotspots of resistance, which presented relatively higher resistance rates in common bacterial pathogens but lower antibiotic consumption rates compared to high-income countries (HICs). Specifically, we developed the Normalized Antibiotic Resistance/Consumption Index (NARCI) and produced global maps of NARCI to roughly assess the appropriateness of antibiotic consumption across countries and to indicate the potentially inappropriate antibiotic consumption in LMICs compared with HICs. Additionally, we linked antibiotic consumption rates and resistance rates of target pathogens, in conjunction with NARCI and the correlation analysis between antibiotic use and resistance, to inform strategies to alleviate the threat of antibiotic resistance worldwide.

Research progress on source, risk assessment, and management of emerging pollutants in drinking water.

With the extensive production and use of various chemicals, emerging pollutants including environmental endocrine disrupting chemicals, perfluoro chemicals, antibiotics, and microplastics have been continuously entering the environment, and spread to water through multiple pathways. The pollution of these emerging pollutants raised continuous concerns for the safety of drinking water, threating the ecological environment and human health. In combination with international research progress, we discussed in detail about pollution, source, and risk assessment of emerging pollutants in drinking water. We further suggested and prospected the challenge of environmental management of emerging pollutants. This review could promote the public's understanding of emerging pollutants, and provide theoretical support for risk prevention and treatment of emerging pollutants in drinking water.

A Preliminary in vitro and in vivo Evaluation of the Effect and Action Mechanism of 17-AAG Combined With Azoles Against Azole-Resistant Candida spp.

Invasive candidiasis is the primary reason for the increased cases of mortality in a medical environment. The resistance spectra of Candida species to antifungal drugs have gradually expanded. Particularly, the resistance spectra of Candida auris are the most prominent. Hsp90 plays a protective role in the stress response of fungi and facilitates their virulence. In contrast, Hsp90 inhibitors can improve the resistance of fungi to antifungal drugs by regulating the heat resistance of Hsp90, which destroys the integrity of the fungal cell walls. Hsp90 inhibitors thus offer a great potential to reduce or address fungal drug resistance. The drugs tested for the resistance include itraconazole, voriconazole, posaconazole, fluconazole, and 17-AAG. A total of 20 clinical strains of Candida were investigated. The broth microdilution checkerboard technique, as adapted from the CLSI M27-A4 method, was applied in this study. We found that 17-AAG alone exerted limited antifungal activity against all tested strains. The MIC range of 17-AAG was 8 to >32 µg/ml. A synergy was observed among 17-AAG and itraconazole, voriconazole, and posaconazole against 10 (50%), 7 (35%), and 13 (65%) of all isolates, respectively. Moreover, the synergy between 17-AAG and fluconazole was observed against 5 (50%) strains of azole-resistant Candida. However, no antagonism was recorded overall. Our result adequately verifies the influence of 17-AAG on the formation of Candida spp. biofilm. Moreover, we determined that with the use of rhodamine 6G to detect drug efflux and that of dihydrorhodamine-123 to detect intracellular reactive oxygen species (ROS), treatment with 17-AAG combined with azole drugs could inhibit the efflux pump of fungi and promote the accumulation of ROS in the fungal cells, thereby inducing fungal cell apoptosis. Thus, the mechanism of 17-AAG combined with azoles can kill fungi. Our results thus provide a new idea to further explore drugs against drug-resistant Candida spp.

Th17 cell-derived miR-155-5p modulates interleukin-17 and suppressor of cytokines signaling 1 expression during the progression of systemic sclerosis.

BACKGROUND: miR-155-5p is associated with autoimmune diseases. T helper 17 (Th17) cells, interleukin (IL)-17, and suppressor of cytokines signaling 1 (SOCS1) have important roles in the pathogenesis of systemic sclerosis (SSc). The purpose of this study was to explore the role of miR-155-5p in the regulation of IL-17 and SOCS1 expression in Th17 cells and the subsequent effect on SSc disease progression. METHODS: Th17 cells were isolated from peripheral blood mononuclear cells of SSc patients and healthy controls (HCs). RT-qPCR and western blotting were used to examine the expression patterns of miR-155-5p, IL-17, and SOCS1. Luciferase reporter assays were performed to confirm SOCS1 as a target of miR-155-5p. RNA pull-down assays were performed to detect the interaction of IL-17 and SOCS1 with miR-155-5p. In situ hybridization was performed to analyze the co-expression pattern of miR-155-5p and IL17A in Th17 cells. RESULTS: The levels of Th17 cell-derived miR-155-5p were significantly up-regulated in SSc patients compared with HCs, and its levels were negatively correlated with SOCS1 levels. Meanwhile, miR-155-5p positively regulated IL-17 expression levels in Th17 cells isolated from SSc patients as the disease progressed. Using pmirGLO vectors, SOCS1 was confirmed as a target of miR-155-5p. The binding status of IL-17 and SOCS1 to miR-155-5p was related to SSc progression. An increase in the co-localization of miR-155-5p and IL-17 was associated with greater SSc progression. CONCLUSIONS: IL-17 and SOCS1 expression modulated by Th17 cell-derived miR-155-5p are critical for SSc progression, which may provide novel insights into the pathogenesis of SSc.

The Synergistic Effect of Tacrolimus (FK506) or Everolimus and Azoles Against Scedosporium and Lomentospora Species In Vivo and In Vitro.

Scedosporium and Lomentospora infections in humans are generally chronic and stubborn. The use of azoles alone cannot usually inhibit the growth of these fungi. To further explore the combined effect of multiple drugs and potential mechanisms of action, we tested the antifungal effects of tacrolimus (FK506) and everolimus in combination with azoles in vitro and in vivo on 15 clinical strains of Scedosporium/Lomentospora species and detected the level of Rhodamine 6G, ROS activity, and apoptosis. The in vitro results showed that the combinations of tacrolimus with itraconazole, voriconazole, and posaconazole showed synergistic effects on 9 strains (60%), 10 strains (73%), and 7 strains (47%), respectively, and the combinations of everolimus with itraconazole, voriconazole, and posaconazole showed synergistic effects on 8 strains (53%), 8 strains (53%), and 7 strains (47%), respectively. The synergistic effects might correspond to the elevated ROS activity (the tacrolimus + itraconazole group compared to the itraconazole group, (P < 0.05)), early apoptosis (itraconazole (P < 0.05) and voriconazole (P < 0.05) combined with everolimus), and late apoptosis (the tacrolimus + itraconazole group compared to the itraconazole group, (P < 0.01); the tacrolimus + posaconazole group compared to the posaconazole group, (P < 0.05)), but not inhibition of efflux pump activity. Our in vitro results suggested that a combination of tacrolimus or everolimus and azoles have a synergistic effect against Scedosporium/Lomentospora. The synergistic mechanisms of action might be triggering excessive ROS activity and apoptosis. In vivo, the survival rate of G. mellonella (sixth instar larvae) was significantly improved by tacrolimus alone, everolimus alone, azoles alone, and tacrolimus and everolimus combined with azoles separately (P < 0.05 for the tacrolimus group; P < 0.01 for the everolimus group and the itraconazole group; P = 0.0001 for the tacrolimus and posaconazole group; P < 0.0001 for other groups except the everolimus and itraconazole group, everolimus and posaconazole group, and tacrolimus and itraconazole group). From the results, we infer that the combination of tacrolimus or everolimus with azoles has obvious synergistic effect on Scedosporium/Lomentospora, and might enhance the level of apoptosis and necrosis. However, the synergistic effects were not related to the efflux pump. In conclusion, from our in vitro and in vivo study, tacrolimus and everolimus combined with azoles may have a synergistic effect in the treatment against Scedosporium/Lomentospora, improving the drug activity of azoles and promoting a better prognosis for patients.

Long-term spatiotemporal variation of antimicrobial resistance genes within the Serratia marcescens population and transmission of S. marcescens revealed by public whole-genome datasets.

The development of antimicrobial resistance (AMR) is accelerated by the selective pressure exerted by the widespread use of antimicrobial drugs, posing an increasing danger to public health. However, long-term spatiotemporal variation in AMR genes in microorganisms, particularly in bacterial pathogens in response to antibiotic consumption, is not fully understood. Here, we used the NCBI RefSeq database to collect 478 whole-genome sequences for Serratia marcescens ranging from 1961 up to 2019, to document global long-term AMR trends in S. marcescens populations. In total, 100 AMR gene subtypes (16 AMR gene types) were detected in the genomes of S. marcescens populations. We identified 3 core resistance genes in S. marcescens genomes, and a high diversity of AMR genes was observed in S. marcescens genomes after corresponding antibiotics were discovered and introduced into clinical practice, suggesting the adaptation of S. marcescens populations to challenges with therapeutic antibiotics. Our findings indicate spatiotemporal variation of AMR genes in S. marcescens populations in relation to antibiotic consumption and suggest the potential transmission of S. marcescens isolates harboring AMR genes among countries and between the environment and the clinic, representing a public health threat that necessitates international solidarity to overcome.

Seasonal disparities and source tracking of airborne antibiotic resistance genes in Handan, China.

The transmission of airborne antibiotic resistance genes (ARGs) loaded on particle is a significant global public health concern. Up to date, the dispersal pattern of airborne ARGs remains unclear despite their critical role in multiregional transmission. In this study, airborne ARGs loaded on fine particulate matter (PM2.5) and source tracking based on the airflow trajectories were performed by the potential source contribution function (PSCF) and concentration weighted trajectory (CWT) model. The results show that the absolute abundance of ARG subtypes were generally twice times higher in the winter season than that in the summer season, which could be attributable to winter haze events with high particulate matter concentrations in Handan. Exogenous input from serious haze events and local release of ARGs loaded on PM2.5 of air masses may cause higher levels of ARGs in the winter. Moreover, based on the positive correlation between the abundance of ARGs and PM2.5 concentration, a source tracing model of airborne ARGs was proposed to the estimate of ARGs release and dissemination. This study highlights airborne ARGs transmission loaded on PM2.5 of air masses, which facilitating the global spread of antibiotic resistance.

Human Herpesvirus 6B U26 Inhibits the Activation of the RLR/MAVS Signaling Pathway.

U26 is one of the roseolovirus unique genes with unknown function. Human herpesvirus 6B (HHV-6B) pU26 is predicted to be an 8-transmembrane protein containing a mitochondrion location signal. Here, we analyzed U26 function during HHV-6B infection and find that (i) HHV-6B U26 is expressed at a very early stage during HHV-6B infection, and knockdown of it results in a significant decrease of HHV-6B progeny virus production; (ii) U26 inhibits the activation of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR)/mitochondrial antiviral signaling protein (MAVS) signaling pathway, an important anti-HHV-6B infection innate immune response, by targeting MAVS protein for degradation; and (iii) a portion of U26 locates to the mitochondria, which could affect the mitochondrial membrane potential and finally leads to MAVS degradation. These findings indicate that HHV-6B U26 is a novel antagonistic viral factor against host innate antiviral immunity.IMPORTANCE HHV-6B (human herpesvirus 6B) is well known to evade host antiviral responses and establish a lifelong latent infection. How HHV-6B evades RNA recognition is still poorly understood. Our results indicate that HHV-6 U26 plays a vital role in RLR/MAVS signaling pathway activity. Knockout of endogenous MAVS could facilitate HHV-6B replication. The findings in this study could provide new insights into host-virus interactions and help develop a new therapy against HHV-6B infection.

The prevalence of ampicillin-resistant opportunistic pathogenic bacteria undergoing selective stress of heavy metal pollutants in the Xiangjiang River, China.

The emergence of clinically relevant ß-lactam-resistant bacteria poses a serious threat to human health and presents a major challenge for medical treatment. How opportunistic pathogenic bacteria acquire antibiotic resistance and the prevalence of antibiotic-resistant opportunistic pathogenic bacteria in the environment are still unclear. In this study, we further confirmed that the selective pressure of heavy metals contributes to the increase in ampicillin-resistant opportunistic pathogens in the Xiangjiang River. Four ampicillin-resistant opportunistic pathogenic bacteria (Pseudomonas monteilii, Aeromonas hydrophila, Acinetobacter baumannii, and Staphylococcus epidermidis) were isolated on Luria-Bertani (LB) agar plates and identified by 16S rRNA sequencing. The abundance of these opportunistic pathogenic bacteria significantly increased in the sites downstream of the Xiangjiang River that were heavily influenced by metal mining activities. A microcosm experiment showed that the abundance of ß-lactam resistance genes carried by opportunistic pathogenic bacteria in the heavy metal (Cu2+ and Zn2+) treatment group was 2-10 times higher than that in the control. Moreover, heavy metals (Cu2+ and Zn2+) significantly increased the horizontal transfer of plasmids in pathogenic bacteria. Of particular interest is that heavy metals facilitated the horizontal transfer of conjugative plasmids, which may lead to the prevalence of multidrug-resistant pathogenic bacteria in the Xiangjiang River.

Colistin and amoxicillin combinatorial exposure alters the human intestinal microbiota and antibiotic resistome in the simulated human intestinal microbiota.

Antibiotics treatment could cause the dysbiosis of human intestinal microbiota and antibiotic resistome. Fecal microbiota transplantation (FMT) has been an efficacious treatment to restore the dysbiosis of intestinal microbiota in a variety of intestinal diseases. However, to data, the effect of the combinatorial antibiotic treatment on microbiota, antibiotic resistome and the FMT for restoration affected by combinatorial antibiotic exposure in the human intestinal microbiota remain unclear. In this study, we systematically investigated the effect of the colistin and amoxicillin combinatorial exposure in the simulator of the human intestinal microbial ecosystem (SHIME) and found that this combinatorial exposure significantly altered (p < 0.05) the human intestinal microbiota and antibiotic resistome. The shift of bacterial community and antibiotic resistome could incompletely recovery to baseline by FMT treatment after combinatorial antibiotic exposure. Additionally, the variance of antibiotic resistome was dominantly driven by the bacterial community (41.18%-68.03%) after the combinatorial antibiotic exposure. Overall, this study first to investigate the influence of the colistin and amoxicillin combinatorial exposure on the intestinal microbiota and antibiotic resistome, and assess the FMT recovery in the simulated human intestinal microbiota, which may potentially provide a correct administration of antibiotics and application of FMT in the clinic.

A new target for the treatment of inflammatory bowel disease: Interleukin-37.

Interleukin (IL)-37 belongs to the IL-1 cytokine family. It has anti-inflammatory effects on numerous autoimmune diseases such as asthma, psoriasis, inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), multiple sclerosis (MS) and rheumatoid arthritis (RA). Mechanistically, IL-37 plays an anti-inflammatory role by regulating the expression of inflammatory factors in two ways: binding extracellular receptors IL-18R or transferring into the nucleus with Smad3. IBD is a kind of idiopathic intestinal inflammatory disease with unknown etiology and pathogenesis. Recent researches had proved that IL-37 is negatively involved in the pathogenesis and development of IBD. Among various inflammatory diseases, IL-37 has been shown to regulate inflammatory development by acting on various immune cells such as neutrophils, macrophages (Mϕ), dendritic cells (DCs), T cells and intestinal epithelial cells. This review summarizes the biological role of IL-37, and its immunoregulatory effects on the immune cells, especially anti-inflammatory function in both human and experimental models of IBD.

Municipal Solid Waste Treatment System Increases Ambient Airborne Bacteria and Antibiotic Resistance Genes.

Landfill and incineration are the primary disposal practices for municipal solid waste (MSW) and have been considered as the critical reservoir of antibiotic resistance genes (ARGs). However, the possible transmission of ARGs from the municipal solid waste treatment system (MSWT system) to ambient air is still unclear. In this study, we collected inside and ambient air samples (PM10 and PM2.5) and potential source samples (leachate and solid waste) in the MSWT system. The results showed that the MSWT system contributed to the increased ambient airborne bacteria and associated ARGs. Forty-one antibiotic-resistant bacteria (ARB) harboring blaTEM-1 were isolated, and the full-length nucleotide sequences of the blaTEM-1 gene (harbored by identical bacillus) from air (downwind samples) were 100% identical with those in the leachate and solid waste, indicating that the MSWT system was the important source of disperse bacteria and associated ARGs in the ambient air. The daily intake (DI) burden level of ARGs via PM inhalation was comparable with that via ingestion of drinking water but lower than the DI level via ingestion of raw vegetables. The antibiotic-resistant opportunistic pathogen Bacillus cereus was isolated from air, with a relatively high DI level of Bacillus via inhalation (104-106 copies/day) in the MSWT system. This study highlights the key pathway of airborne ARGs to human exposure.

Gut resistomes, microbiota and antibiotic residues in Chinese patients undergoing antibiotic administration and healthy individuals.

Human gut microbiota is an important reservoir of antibiotic resistance genes (ARGs). Although dysbacteriosis after the antibiotic course has been previously observed in the patient guts, a comprehensive comparison of gut resistomes, microbiota and antibiotic residues in healthy individuals and patients undergoing antibiotic administration is little. Using high-throughput qPCR, 16S rRNA gene amplicon sequencing and UPLC-MS/MS, we systematically examined the antibiotic resistome, gut microbiota, and antibiotic residues in fecal samples from both Chinese healthy individuals and patients receiving antibiotic therapy. Compared with healthy individuals, patients' guts harbored lower diverse gut resistome and microbiota, but higher concentrations of antibiotics and ARGs. Antibiotic concentration in human guts was positively correlated with ARG total abundance, but was negatively related to the diversity of both ARGs and bacterial communities, which demonstrated that antibiotic administration could shape the antibiotic resistomes and bacterial communities in the patient guts. Gene cfxA was evaluated as a potential biomarker to distinguish the patients receiving antibiotic therapy from the healthy individuals in China since its wide detection and significant enrichment in the guts of the patients. The detection of some veterinary antibiotics in human guts illustrated the potential transmission of antibiotic from the external environment to human via the food chain. The obtained results could help to better understand the influence of antibiotic therapy in shaping antibiotic reistomes and bacterial communities in Chinese individuals.

Simultaneous removal of antibiotics and antibiotic resistance genes from pharmaceutical wastewater using the combinations of up-flow anaerobic sludge bed, anoxic-oxic tank, and advanced oxidation technologies.

Pharmaceutical wastewater often contains high levels of antibiotic residues and serves as an important reservoir for antibiotic resistance genes (ARGs). However, the current pharmaceutical wastewater treatment plants (PWWTPs) were not sufficiently effective in removing antibiotics and ARGs. Here, we designed a lab-scale simulation reactor, including up-flow anaerobic sludge bed (UASB), anoxic-oxic tank (A/O), and four separate advanced oxidation processes (AOPs) i.e., UV, Ozonation, Fenton, and Fenton/UV, to simultaneously remove 18 antibiotics and 10 ARGs from a real pharmaceutical wastewater. The results showed that all antibiotics were fully eliminated through the reactor during 180 d-operation. Among all treatment units, UASB provided the greatest contribution (85.8 ±â€¯16.1%) for the removal of 18 antibiotics. The mass balance results manifested that degradation was a predominant mechanism for the removal of tetracyclines, sulfamethoxazole, and ampicillin (62.5-80.9%), while sorption to sludge (73.9%) was predominant for enrofloxacin removal in UASB. Meanwhile, the substantial decrease of ARG absolute abundance (log reduction by 0.1-3.1 fold) through the whole reactor was observed although the existence of the partial enrichment (1.2-3.8 log units) from the influent to the A/O unit. Fenton/UV combination was the most effective AOP for the removal of ARGs. Finally, the optimum operating conditions for the removal of ARGs using Fenton was also proposed considering the relatively lower cost and high ARG elimination. Overall, this study provides feasible suggestions for the design of real PWWTPs for simultaneous removal of antibiotics and ARGs.

Arctic antibiotic resistance gene contamination, a result of anthropogenic activities and natural origin.

The increasing global prevalence of antibiotic resistance genes (ARGs) in the environment is attributed to anthropogenic activities, particularly the misuse of antimicrobial drugs in human care and animal production. In the present study, we first examined Arctic/sub-Arctic (polar) sediments for the abundance and diversity of 30 ARGs against sulfonamide, tetracycline, aminoglycoside, quinolone, macrolide, and ß-lactam antibiotics. Polar sediment ARGs were detected by qPCR at relatively low levels (10-9 to 10-5 copies/16S rRNA gene copies) compared to the reference sites, which were heavily impacted regions of China (the Haihe River, the Tianjin Water Park water and the Qilihai Wetland water, at 10-8 to 10-2 copies/16S rRNA gene copies). A human mitochondrial gene target, Hmt, was first used to aid in the identification of ARGs associated with anthropogenic activities, being relatively persistent, in high copy number and a human-specific molecular marker. Hmt was consistently present in easily quantifiable amounts in the polar sediment samples, indicating their relationship with human-impact, and it was also positively correlated with the relative abundance of ARGs and to the concentrations of modern-day antibiotics. Phylogenetic analyses of resistance sequences from both the Arctic marine sediments and a major database of human pathogens indicated that the ARGs in polar region were the result of a mix of human influence and natural origins. To our knowledge, this is the first study to show that ARGs in Arctic marine sediments appear to be a mixture of both natural origins and recent human influence. This study provides a significant reference regarding the global reach of antibiotic resistance, which is associated with anthropogenic activities.

Discharge of KPC-2 genes from the WWTPs contributed to their enriched abundance in the receiving river.

At present, very little is known about the persistence and spread pathway of KPC-2 genes in the environment. Our previous study reported the prevalence and persistence of KPC-2 genes in wastewater treatment plants (WWTPs). In the present work, we investigated the occurrence and fate of KPC-2 genes in a WWTP discharge-receiving river and studied the effect of WWTP discharges on the prevalence of KPC-2 genes and host bacteria in the receiving river. It is observed that a considerable level of KPC-2 genes occurred in the receiving river, and a significant increase of blaKPC-2 abundance in the downstream following WWTP discharge was observed compared to the upstream. Furthermore, opportunistic pathogens with 100% identical blaKPC-2 sequence, like Escherichia coli and Kluyvera georgiana, were isolated from both WWTP and its receiving water, whereas no blaKPC-2 carrying bacteria was detected in the upstream. These findings indicated that the treated wastewater discharges have a considerable influence on blaKPC-2 levels in the receiving river. Interestingly, there is no correlation between concentrations of antibiotics and blaKPC-2 concentrations, demonstrating that the increase of KPC-2 genes in the receiving river is mainly due to WWTP release. This finding is important because it illustrates a significant pathway for KPC-2 gene proliferation to the environment.

mRNA expression of glucocorticoid receptor and serological and virological markers of chronic hepatitis B.

Glucocorticoid receptor (GR) function is essential for glucocorticoid action on various effector cells. The aim of the present study was to investigate the mRNA expression profiles of GRα and GRß in peripheral blood mononuclear cells (PBMC) and examine the association between the expression levels of the GR isoforms and the serological and virological hepatitis B virus (HBV) status in patients with chronic hepatitis B (CHB). A total of 29 CHB patients were examined in the present study, which were divided into subgroups according to serological and virological markers. The levels of GRα and GRß in PBMCs, HBV viral loads, HBV surface antigen (HBsAg), HBV e antigen (HBeAg) and pre­S1Ag were measured. A total of 43 healthy individuals served as controls. GRα was present in the PBMCs of all CHB patients and healthy controls, whereas GRß­specific products were present in only 93.1% of the CHB patients and 86.0% of the healthy controls. The GRα levels were positively correlated with the expression of GRß in the CHB patients (r=0.419; P<0.05) and were significantly lower compared with those observed in the healthy controls (60.51 ± 23.73, vs. 100.00 ± 40.75; P<0.001). Compared with the healthy controls, significant differences were observed in the mRNA expression of GRα in the CHB patients when stratified according to the HBeAg, pre­S1Ag and HBV viral load status (P<0.05), but not in the pre­S1Ag­positive patients. These data demonstrated that the mRNA expression profile of GRα differed between the CHB patients and the healthy controls. In addition, the HBV serological and virological markers were not associated with the mRNA levels of the GR isoforms in the CHB patients.

Reduction of fibrosis in dibutyltin dichloride-induced chronic pancreatitis using rat umbilical mesenchymal stem cells from Wharton's jelly.

OBJECTIVES: The objective of this study was to investigate the effects of rat umbilical cord mesenchymal stem cells (UCMSCs) from Wharton's jelly on dibutyltin dichloride (DBTC)-induced chronic pancreatitis (CP) and subsequent pancreatic fibrosis in rats. METHODS: A rat model of CP induced by DBTC was used. Male Sprague-Dawley rats were randomly divided into 4 groups: the control, DBTC, DBTC + UCMSCs, and control + UCMSC groups. Umbilical cord mesenchymal stem cells were administered intravenously on day 5 after the administration of DBTC. On days 14 and 28, the rats were evaluated morphologically and biochemically. The expression levels of inflammatory cytokines and chemokines in the pancreatic tissues of different groups were evaluated using quantitative real-time polymerase chain reaction. The activation of pancreatic stellate cells was estimated by immunochemistry and Western blot analysis of α-smooth muscle actin. RESULTS: Umbilical cord mesenchymal stem cells were detected in inflamed pancreatic tissues. Umbilical cord mesenchymal stem cell treatment improved the histological scores and alleviated the fibrosis of pancreas samples, The expression of cytokines in the DBTC + UCMSC group was significantly lower than that in the DBTC group. Also, pancreatic stellate cell activation was inhibited by UCMSC treatment. CONCLUSIONS: Xenogeneic transplantation of UCMSCs is a novel approach for the treatment of CP and subsequent fibrosis. Umbilical cord mesenchymal stem cells may be a promising therapeutic intervention for human CP in the future.