Global genomic epidemiology and transmission dynamics of plasmid-borne tmexCD-toprJ-carrying Klebsiella pneumoniae in a one health context.

The emergence of tmexCD-toprJ, a novel plasmid-mediated resistance-nodulation-division (RND) type efflux pump gene cluster, poses a significant threat to public health by diminishing bacterial susceptibility to the last-resort antibiotics, including tigecycline. Between 2020 and 2022, 18 Klebsiella pneumoniae strains carrying the tmexCD-toprJ gene were recovered from over 30,000 human stool samples collected from patients across five hospitals in China. Phylogenetic analysis of these 18 strains revealed clonal transmission of tmexCD-toprJ-carrying K. pneumoniae among patients and hospital settings. Comparative analysis of the 18 tmexCD-toprJ-carrying plasmids showed conservation in the genetic backgrounds of tmexCD-toprJ, despite the diverse backbone structures among the plasmids. The inactive suppressor, TNfxB1, is located in front of all tmexCD1-toprJ1, while TNfxB3 is located upstream of tmexCD3-toprJ3. Conjugation experiments demonstrated the transferability of plasmids from three strains to the recipient Escherichia coli J53. Among all 237 globally distributed tmexCD-toprJ-carrying strains, the majority (92.83 %) were from China. These strains encompassed 50 sequence types, with the most prevalent being ST11 (12.66 %), ST37 (11.81 %), and ST15 (11.39 %). Samples originated from various sources: 47.26 % from human, 38.82 % from livestock, and 13.08 % from the environment. The most common tmexCD-toprJ genotype was tmexCD1-toprJ1 (86.92 %, n = 206), followed by tmexCD2-toprJ2 (8.86 %, n = 21) and tmexCD3-toprJ3 (4.22 %, n = 10). The tmexCD1-toprJ1 gene was found in livestock (44.66 %, n = 92), humans (39.81 %, n = 82), and environmental samples (15.05 %, n = 31). In contrast, tmexCD2-toprJ2 and tmexCD3-toprJ3 were only found in human samples. Additionally, tmexCD-toprJ has been detected in 79 strains of K. pneumoniae harboring carbapenem-resistance genes. Given the presence of tmexCD-toprJ across various hosts and environments, establishing a comprehensive surveillance system from a One Health perspective is particularly vital.

The utility of MOF-based materials in direct air capture (DAC) application to ppm-level CO2.

Metal-organic frameworks (MOFs) are well-suited materials for CO2 removal and have robust capture capacity and selectivity. Although the adsorption of CO2 in MOFs has been studied, the implementation of ppm-level CO2 uptake in MOFs and the effects of the pore size and charge have not been fully explored. We performed grand canonical Monte Carlo (GCMC) simulations combined with the Density Functional Theory plus U (DFT + U) charge method to investigate MOF screening for ppm-level CO2 uptake and its application in a direct air capture (DAC) system. Three types of MOFs containing eight members were studied: i.e., ZIF-68, 69, 70; UiO-66, 67, 68; CAU-10; and MIL-125. The pore landscape characterization, electrostatic field-induced enhancement, and preferential binding sites of these MOFs were examined for CO2 capture. MOFs with pore limited diameters (PLD) 1.5 times the size of CO2 molecules and with large cavity diameters (LCD) smaller than 10 Å exhibit robust confinement capacity. Polar functional groups and metal ions dominate the electrostatic contributions and subsequently enhance the surface adhesion of CO2 molecules. For a given framework, favorable CO2 binding occurs in the following order: small pores/cages > polar functional group/metal ions > larger pores/cages. ZIF-69 which comprises smaller pores (7.5 Å) and robust polar functional groups (-Cl) collectively enhances CO2 capture; thus, ZIF-69 outperforms other MOFs; the performance of ZIF-69 is followed by that of CAU-10 which has an optimal pore size of 6 Å. These findings are of fundamental and practical importance for the application of MOFs in DAC technologies for CO2 removal.

Dissecting positive selection events and immunological drives during the evolution of adeno-associated virus lineages.

Adeno-associated virus (AAV) serotypes from primates are being developed and clinically used as vectors for human gene therapy. However, the evolutionary mechanism of AAV variants is far from being understood, except that genetic recombination plays an important role. Furthermore, little is known about the interaction between AAV and its natural hosts, human and nonhuman primates. In this study, natural AAV capsid genes were subjected to systemic evolutionary analysis with a focus on selection drives during the diversification of AAV lineages. A number of positively selected sites were identified from these AAV lineages with functional relevance implied by their localization on the AAV structures. The selection drives of the two AAV2 capsid sites were further investigated in a series of biological experiments. These observations did not support the evolution of the site 410 of the AAV2 capsid driven by selection pressure from the human CD4+ T-cell response. However, positive selection on site 548 of the AAV2 capsid was directly related to host humoral immunity because of the profound effects of mutations at this site on the immune evasion of AAV variants from human neutralizing antibodies at both the individual and population levels. Overall, this work provides a novel interpretation of the genetic diversity and evolution of AAV lineages in their natural hosts, which may contribute to their further engineering and application in human gene therapy.

Global Emergence and Genomic Epidemiology of blaNDM-Carrying Klebsiella variicola.

Purpose: Klebsiella variicola has emerged as a human pathogen in the past decade. Here, we present findings related to a K. variicola strain carrying the blaNDM-1 gene, which was isolated from a urinary tract infection in China. Global transmission dynamics and genomic epidemiology of blaNDM-carrying K. variicola were further investigated. Material and Methods: The complete genome sequence of the strain was determined using the Illumina NovaSeq 6000 and Nanopore MinION sequencer. Genomic features and resistance mechanisms were analyzed through diverse bioinformatics approaches. Additionally, genome sequences of K. variicola strains carrying blaNDM were retrieved from the NCBI database, and a comprehensive analysis of the global dissemination trends of these strains was conducted. Results: K. variicola strain 353 demonstrated resistance to multiple antimicrobials, including carbapenems. Within its genome, we identified fourteen antimicrobial resistance genes associated with ß-lactam, aminoglycoside, fosfomycin, quinolone, trimethoprim, rifamycin, and sulfonamide resistance. The carbapenem-resistant gene blaNDM-1 was located on an IncU-type plasmid spanning 294,608 bp and flanked by ISCR1 and IS26. Downstream of blaNDM-1, we identified an Intl1 element housing numerous antibiotic resistance genes. A comprehensive search of the NCBI database revealed 72 K. variicola strains carrying blaNDM from twelve different countries, predominantly from clinical sources, with the highest prevalence observed in the USA and China. A total of 28 distinct sequence types (STs) were identified, with ST115 being the most prevalent, followed by ST60. Conclusion: In summary, this study presents the genomic characterization of a K. variicola strain carrying blaNDM-1 on an IncU-type plasmid. The research highlights the global dissemination of blaNDM-carrying K. variicola, observed in both healthcare settings and natural environments. Our data have revealed a diverse array of antimicrobial resistance determinants in K. variicola, providing valuable insights that could aid in the development of strategies for the prevention, diagnosis, and treatment of K. variicola infections.

Characterization the microbial diversity and metabolites of four varieties of Dry-Cured ham in western Yunnan of China.

In this study, high-throughput sequencing and metabolomics analysis were conducted to analyze the microbial and metabolites of dry-cured Sanchuan ham, Laowo ham, Nuodeng ham, and Heqing ham that have fermented for two years produced from western Yunnan China. Results showed that at the genus level, the dominant bacteria in the four types of ham were Halomonas and Staphylococcus, while the dominant fungi were Aspergillus and Yamadazyma. A total 422 different metabolites were identified in four types of ham, mainly amino acids, peptides, fatty acids, and their structural analogs, which were involved in pantothenate and coenzyme A biosynthesis, caffeine, and tyrosine metabolism. The dominant microorganisms of the four types of ham were mainly related to the metabolism of fatty acids and amino acids. This research enhances the identification degree of these four types of dry-cured ham and provides a theoretical basis for developing innovative and distinctive ham products.

Association of altitude and frailty in Chinese older adults: using a cumulative frailty index model.

Objective: The population is aging exponentially and the resulting frailty is becoming increasingly evident. We aimed to explore the association between altitude and frailty, and to identify associated factors for frailty. Methods: This is a community-based cross-sectional survey. 1,298 participants aged ≥60 years from three different altitudes were included in the study. To quantify frailty, we constructed a frailty index (FI) and a frailty score (FS). The FI was divided into non-frailty, prefrailty, and frailty. The Odds Ratios and confidence intervals (ORs, 95%CIs) were used to evaluate the association between altitude and FI and FS in multivariate ordinal logistic regression and linear regression. Results: There were 560 (53.1%) participants in the prefrailty and 488 (37.6%) in the frailty group. The FS increased with higher altitude (P for trend <0.001). Multivariate ordinal logistic regression analysis revealed an association between altitude and frailty, OR = 1.91 (95% CI: 1.38-2.64) in mid-high altitude and 2.49 (95% CI:1.40-4.45) in high altitude. The same trend of association was found in the univariate analysis. The FS increased by 1.69 (95% CI: 0.78-2.60) at mid-high altitude and 3.24 (95%CI:1.66-4.81) at high altitude compared to medium altitude. Conclusion: The study indicates that high altitude exposure is an associated factor for frailty in older adults. This association become stronger with higher altitudes. As a result, it is essential to conduct early frailty screening for residents living at high altitudes.

Genomic insights into a blaNDM-5-carrying Escherichia coli ST167 isolate recovered from faecal sample of a healthy individual in China.

OBJECTIVES: Since its discovery, blaNDM-5 has spread widely amongst Escherichia coli strains in clinical patients, causing carbapenem resistance. Here we report the complete genome sequence of an NDM-5-producing E. coli strain isolated from the faecal sample of a healthy individual in Hangzhou, China. METHODS: The whole-genome sequence of E. coli CREC8 was obtained utilising both the Nanopore sequencer and the Illumina NovaSeq 6000 platform. Antimicrobial resistance genes, multilocus sequence typing, and plasmid replicons were identified using the BacWGSTdb server. The phylogenetic relationship between CREC8 and other E. coli strains was investigated using the core genome multilocus sequence typing (cgMLST) strategy. RESULTS: The complete genome sequence of E. coli CREC8 consists of one chromosome and 7 plasmids. CREC8 belongs to ST167 according to the MLST scheme. Seven ARGs were identified, including carbapenem resistance gene blaNDM-5 which was located in an IncFIA/IncFII type plasmid. A total of 164 E. coli ST167 strains related to 25 countries across four continents can be retrieved from the NCBI database, 95 of them carrying the blaNDM gene with blaNDM-5 the most (N = 79). Phylogenetic analysis revealed a worldwide distribution of E. coli ST167 strains, with China having the highest prevalence (37%, 61/165). CONCLUSION: In summary, we reported a blaNDM-5-carrying E. coli ST167 strain isolated from a healthy individual in China. Such strains are more commonly isolated from hospitalised patients but are rarely isolated from healthy individuals. This indicates a further epidemic of carbapenem-resistant E. coli strains in the healthy population which needs our attention.

Genomic characterization of a carbapenem-resistant Citrobacter freundii clinical isolate from China carrying blaNDM-5 on a novel IncC-IncFIB-IncX3 plasmid.

OBJECTIVES: Citrobacter freundii is one of the important pathogens that can cause nosocomial infections. The advent of carbapenem-resistant C. freundii complicates clinical treatment. Here, we reported the genome sequence of a carbapenem-resistant C. freundii strain carrying a novel IncC-IncFIB-IncX3 plasmid in China. METHODS: The genome sequence of C. freundii CRNMS1 was obtained using the Illumina NovaSeq 6000 platform and the long-read Nanopore sequencer. Multilocus sequence typing was identified using MLST (v.2.23.0). The identification of antimicrobial resistance genes (ARGs) and plasmid replicons was performed using the resfinder and plasmidfinder of ABRicate (v.1.0.1). Circular comparisons of plasmids were performed using the BLAST Ring Image Generator (BRIG). RESULTS: CRNMS1 belongs to ST116 in the C. freundii MLST scheme. Thirteen ARGs were predicted in all, including blaNDM-5, which was located in a plasmid. The plasmid pblaNDM5-S1, which carried the blaNDM-5 gene, was discovered to be a novel plasmid including three plasmid replicons (IncC, IncFIB, and IncX3) as well as seven ARGs (sul1, sul2, floR, dfrA17, aadA5, qnrA1, and blaNDM-5). A total of 38 blaNDM-5-bearing C. freundii strains can be retrieved from the NCBI database. Phylogenetic analysis revealed a worldwide distribution of C. freundii strains carrying the blaNDM-5 gene, with China having the highest prevalence (39%, 15/38). However, they were distantly related to CRNMS1 with SNP differences >2545. CONCLUSION: In summary, we reported a novel IncC-IncFIB-IncX3 plasmid carrying blaNDM-5 in a carbapenem-resistant C. freundii strain in China. The development of such hybrid plasmids facilitates the transmission of ARGs.

Symptom clusters and characteristics of cervical cancer patients receiving concurrent chemoradiotherapy: A cross-sectional study.

Background: Cervical cancer patients have a high symptom burden during concurrent chemoradiotherapy (CCRT) and urgently need precise symptom management strategies. Nonetheless, the symptom profile and influencing factors are unclear. Methods: A total of 234 patients with cervical cancer who underwent CCRT in a tertiary care hospital clinical oncology center in Guangxi Zhuang Autonomous Region from March 2022 to March 2023 were included in the study. The general information questionnaire, M.D. Anderson symptom inventory, Fatigue Scale-14, Pittsburgh Sleep Quality Index, and grip strength test were used for the investigation. Symptom clusters were extracted by exploratory factor analysis, and latent profile analysis was performed using Mplus 8.0 software. Multinomial logistic regression was used to explore the factors influencing the potential categories of symptom clusters. Results: Exploratory factor analysis extracted four symptom clusters: a fatigue-related symptom cluster, a gastrointestinal-related symptom cluster, a mood-related symptom cluster, and a physical-related symptom cluster, of which the fatigue-related symptom cluster was more severe and was divided into three potential categories: low fatigue-good muscle fitness type (25.63%), general fatigue-moderate muscle fitness type (68.37%) and high fatigue-low muscle fitness type (6%). Multinomial logistic regression analysis showed that hemoglobin levels, tumor stage, absence of complications, and unemployment were factors influencing the fatigue-related symptom cluster in patients undergoing CCRT for cervical cancer. Conclusions: Cervical cancer patients experience multiple symptom clusters during CCRT. Different characteristics appeared in different clusters. Among them, fatigue-related symptom clusters were more severe and heterogeneous. In clinical practice, we should pay attention to and use high symptom feature predictors, focusing on the core symptoms that play a dominant role, achieving early identification and management, and reducing patients' symptom burden.

Genomic insights into a multidrug-resistant Acinetobacter bereziniae strain co-carrying blaOXA-301 and blaNDM-1 from China.

OBJECTIVES: Acinetobacter bereziniae has been found to cause health care-associated infections, especially in immunocompromised patients. The emergence of two carbapenemase-producing A. bereziniae strains complicates clinical management. Here, we present the genome sequence of a clinical A. bereziniae strain from China co-carrying blaOXA-301 and blaNDM-1. METHODS: The genomic DNA of BZAB1 was subjected to whole-genome sequencing using the Illumina NovaSeq 6000 system and assembled using SPAdes 3.13.0. Using the resfinder database of ABRicate V1.01, antimicrobial resistance genes were identified. The Snippy application was used to carry out the phylogenetic analysis. RESULTS: The genome sequence of A. bereziniae BZAB1 consists of 122 contigs consisting of 4 596 983 bp. A total of nine antimicrobial resistance genes were predicted in BZAB1, including two carbapenemase genes: blaOXA-301 and blaNDM-1. Sixty-nine A. bereziniae strains can be retrieved from the National Centre for Biotechnology Information database, 29 of which possess the blaOXA-301 gene and five of which contain the blaNDM-1 gene. Only three strains carry both blaNDM-1 and blaOXA-301. It is worth noting that all three strains carrying both blaNDM-1 and blaOXA-301 are from China, two of which are clonally related to BZAB1. CONCLUSION: We report the genome sequence of a multidrug-resistant A. bereziniae strain co-carrying blaOXA-301 and blaNDM-1. A. bereziniae strains carrying various beta-lactam resistance genes have been identified sporadically over the world. Our findings could help us aid in understanding the genomic insights of this pathogen. Their future prevalence must be given more consideration.

Global emergence of carbapenem-resistant Klebsiella pneumoniae co-carrying multiple carbapenemases.

The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) co-carrying multiple carbapenemases is complicating clinical treatment. This study aimed to investigate the global dissemination trends of CRKP strains that co-carry multiple carbapenemases. The CRKP isolate KP424 co-carrying blaNDM-1 and blaKPC-2, recovered from a stool specimen, was identified by the NG-Test Carba 5 test, and the genome sequence was further determined by using Nanopore MinION and Illumina NovaSeq 6000 technologies. The genome sequences of the CRKP strains carrying multiple carbapenemase genes were further retrieved from the NCBI GenBank database. Thirteen antimicrobial resistance genes, including blaNDM-1 and blaKPC-2, have been identified in KP424, with blaNDM-1 and blaKPC-2 located on different plasmids. In total, 832 genome sequences of CRKP strains co-carrying two carbapenemase genes were retrieved from the NCBI database. Strains carrying both blaNDM and blaOXA-48-like accounted for 665 (79.9 %) of the total strains, ranking first, and those carrying both blaKPC and blaNDM accounted for 103 (12.4 %), ranking second. The prevalence of CRKP strains co-carrying two carbapenemase genes increased significantly over time, from 0.40 % in 2010 to 9.67 % in 2021. The proportion of strains carrying both blaKPC and blaNDM has also increased, from 0.00 % in 2010 to 4.40 % in 2021. The strains carrying both blaKPC and blaNDM had the highest prevalence (66.7 %, 52/78) in China, while those carrying both blaNDM and blaOXA-48-like had the highest prevalence worldwide. Multiple-carbapenemase producers pose a great threat to public health; further research on the mechanisms underlying multiple carbapenemase gene occurrence is required to prevent their global dissemination.

Combined virome analysis and metagenomic sequencing to reveal the viral communities and risk of virus-associated antibiotic resistance genes during composting.

The issue of antibiotic resistance genes (ARGs) pollution in manure has garnered significant attention, with viruses now being recognized as crucial carriers and disseminators of ARGs. However, the virus-associated ARG profiles and potential health risks in composts are still unclear. In this study, the viral communities and associated ARGs in biogas residue and pig faeces composts were profiled by virome analysis. The viral communities were dominated by Caudovirales, and non-thermophilic viruses were inactivated during composting. The diversity and abundance of ARGs were lower in virome than in metagenome, while ARGs' risk was greater in virome than in metagenome. There were six bacterial genera identified as viral hosts at the genomic level, Pseudomonas and Clostridium carried high-risk ARGs. Virus-associated ARGs in viral hosts had a higher risk rank than non-virus-associated ARGs. Composting reduced the diversity, abundance and risk of viral ARGs. The risk of ARGs in biogas residues was significantly lower than that of pig faeces in the initial period of composting, and the two different substracts equally less harmful after composting. These results revealed that viruses play a non-negligible role in spreading ARGs, posing high risk to environmental and human health.

Diabetes knowledge and training needs among non-endocrinology nurses.

Background: It is necessary to determine the diabetes knowledge level among non-endocrinology nurses in primary care hospitals to develop continuing education strategies. Method: A questionnaire survey was conducted among 6819 non-endocrinology nurses in 70 primary hospitals in the Guangxi Zhuang Autonomous Region to assess their diabetes knowledge level and training needs. Factors affecting knowledge level were analyzed using multiple linear regression models. Results: Diabetes knowledge was low, particularly for diabetes monitoring. Knowledge was higher in nurses who had in-service education and training in diabetes; most believed that training was necessary and hoped to improve their ability to care for diabetic patients. The most suitable training method was considered to be each nurse was taught by an assigned person after centralized specialized education and training. Conclusion: Non-endocrinology nurses in primary care hospitals lack knowledge of diabetes and have a strong need for training. Systematic training is required to ensure that patients receive high-quality and comprehensive care.

Dynamic assessment and system dynamics simulation of safety risk in whole life cycle of coal mine.

Based on the accident causation theory, the mechanism and inducement of construction safety risk in mining enterprises are clarified. The safety risk system of mining enterprises is divided into five subsystems: personnel, material equipment, technology, environment, and management by rough set theory. The comprehensive weight of each risk factor is calculated by network analytic hierarchy process and fuzzy comprehensive evaluation method. Taking a mine in Shanxi Province as the research object, the causal traceability diagram and stock flow diagram of the risk system of mining enterprises are constructed by means of system dynamics model. The influence of various risk factors of the mine on the overall safety risk management level of the enterprise is simulated, and the numerical value of key personnel influence factors is adjusted. The sensitivity changes of safety productivity and safety risk management level of mining enterprises in different situations are analyzed. The results show that: (1) the management and personnel subsystem has the greatest impact on the safety risk management of mining enterprises, followed by the technology, material equipment, and environment subsystem. (2) Increasing safety input can improve the safety level and reduce the expected safety value time, otherwise it will reduce the safety level and delay the expected safety value time. (3) Further simulation of the personnel subsystem, it is found that the factors affecting the safety level of mining enterprises contain six factors, namely, the technical level of construction personnel, the management level of manager, the conduct code of construction personnel, the safety consciousness of practitioners, the basic quality of construction personnel, and the physical and mental state of construction personnel. (4) The conversion rate of personnel safety input to manager's management level and the safety consciousness of practitioners presents a steep decline-slow rise-gradually steady development trend, which mainly because the benefits of safety input have certain time delay and lag.

Homologous booster immunization with an inactivated vaccine induced robust antibody response in healthcare workers: A retrospective study.

Coronavirus Disease 2019 (Covid-19) severely impacted the health, society, and economy around the world. With declining protective efficacy of primary vaccination and the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, a Covid-19 booster vaccination is being fully implemented globally. Many people received three doses of BBIBP-CorV inactivated vaccine in China and other developing countries. However, the antibody response and immune persistence of the homologous BBIBP-CorV booster vaccination is yet to be thoroughly evaluated, as previous studies focused within one month after the third dose. In this study, 97 participants were enrolled to analyze the antibody response and immune persistence within 6 months as well as the safety within 7 days after the third-dose of homologous BBIBP-CorV inactivated vaccine. The seroconversion rate for total antibody against the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein were both 100% at month 1 and month 6 after the third dose. The IgG against the RBD of the SARS-CoV-2 S protein seroconversion rate increased from 42.27% before the third dose to 100% 1 month after the third dose and then slightly decreased to 98.97% 5 months later. Positive IgM against the RBD of the SARS-CoV-2 S protein was rare and was observed in only one participant at month 1 after the third dose. The neutralizing antibody levels at month 1 and month 6 after the third dose increased 63.32-fold and 13.16-fold compared with those before the third dose, and the positive rate for neutralizing antibody was still 100% at month 6 after the third dose. Importantly, the antibody responses induced by the vaccine and immune persistence were not affected by sex or age. No serious adverse reactions were reported. Total antibody and IgG against the RBD of the SARS-CoV-2 S protein were highly correlated with neutralizing antibody, suggesting that total antibody and IgG against the RBD of the SARS-CoV-2 S protein could be used as predictors for neutralizing antibody. In conclusion, the third dose of homologous BBIBP-CorV inactivated vaccine induced a robust antibody response and moderate immune persistence. These finding are of great significance for development future vaccination strategies.

Molecular epidemiology and genomic insights into the transmission of carbapenem-resistant NDM-producing Escherichia coli.

Escherichia coli is a leading cause of nosocomial infections. Carbapenem-resistant E. coli (CREC), which has been frequently isolated in recent years because of the widespread use of carbapenems, poses a significant challenge to clinical anti-infection treatment. In this study, a total of 27 CREC strains were identified from a set of 795 E. coli isolates collected over a two-year period from a tertiary hospital in China. Whole-genome sequencing revealed that 17 strains carried the bla NDM-5 gene, 5 strains carried the bla NDM-1 gene, 1 strain carried the bla NDM-7 gene, and the remaining 4 strains carried the bla KPC-2 gene. All 23 NDM-producing E. coli strains were resistant to all antibiotics except tigecycline, colistin, and cefiderocol. Nine different sequence types (STs) were identified, with ST410 and ST167 being the most prevalent. All of the bla NDM genes were located on conjugatable plasmids. We identified five different plasmid replicon types ranging in size from 20 kb to 200 kb, with the IncX3-type plasmid, 46 kb in size, being a key factor in facilitating the horizontal transmission of the bla NDM gene in E. coli. The structure surrounding the bla NDM gene was relatively conserved and mainly contained the following structures: IS3000-ISAbal25-IS5-bla NDM-ble MBL-trpF-dsbC-IS26. However, the plasmid backbone structure was highly variable, which indicates that the bla NDM gene has already spread horizontally among different types of plasmids. In addition, we discovered two copies of the bla NDM-5 gene in a single plasmid (pEC29-NDM-5), with an identical structure around the gene and the complete sequence of the class 1 integron. Our findings detail the prevalence of CREC in a tertiary hospital in China, and the emergence of multiple copies of the bla NDM-5 gene on a single plasmid needs our attention.

Occurrence, distribution and risk of pharmaceutical and personal care products in the Haihe River sediments, China.

In the aquatic environment, pharmaceuticals and personal care products (PPCPs) detected in sediments are rising health concerns to human and aquatic ecosystem. The migration of PPCPs in the sediments poses a potential risk to surface water and groundwater environment. Insight on the spatial distribution and vertical profile of PPCPs in sediments at the regional scale is valuable for comprehensive prevention of PPCP risk. The Haihe River is one of the major water systems for the rapid development of urbanization, industrialization and agriculture in Northern China. The study aimed to characterize the occurrence, distribution and ecological risks of PPCPs in the sediments of the Haihe River, especially to investigate the vertical distribution of PPCPs using core sediments. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to analyze 24 selected PPCPs in sediment samples. In total, 11 PPCPs were detected, and the detected concentrations (0-1.26 ng g-1) were, lower than in other water bodies in literature (0-24.4 ng g-1). The sediments of the Haihe River located in the Tianjin downtown were most-severely polluted, with the highest cumulative concentration of PPCPs of 9.45 ng g-1, indicating the relatively high contribution of human consumption of PPCPs for the megacity. Spearman correlation analysis shows that both of the TOC contents and particle size distribution can influence the migration and deposition of PPCPs. The risk assessment results showed that the current level of PPCPs has no severe adverse effects on aquatic organisms in the Haihe River. However, special attention should be paid to the environmental risks caused by the migration of PPCPs with high loading and mobility (such as sulfamethoxazole).

Naftopidil enantiomers suppress androgen accumulation and induce cell apoptosis via the UDP-glucuronosyltransferase 2B15 in benign prostate hyperplasia.

Accumulation of androgens mediate alterations in prostate growth and has emerged as an essential factor in benign prostate hyperplasia (BPH). Dihydrotestosterone (DHT), the most potent natural androgen, binds to androgen receptors (AR) and regulates the prostate growth. Many inhibitors of DHT synthesis have been developed to reduce DHT levels and used in the treatment of prostate diseases. However, therapies targeting the elimination of the DHT remain limited. The DHT in prostate is metabolized by UDP-glucuronosyltransferase 2B (UGT2B) and transforms into inactive products. In this study, we analyzed and demonstrated that two enantiomers of naftopidil (NAF), an α1D/1A-adrenoceptor blocker, induced expression and activity of UGT2B in BPH rat prostate models as well as UGT2B15 in human prostate cells, BPH-1. The NAF enantiomers reduced intraprostatic and intracellular DHT levels, thus promoting cell apoptosis. Besides, assays with siRNA UGT2B15 transfection showed that UGT2B15 played an essential role in mediating the effects of the NAF enantiomers. The UGT2B15 mediated the inhibition of AR and PSA expression by NAF enantiomers. The data showed that the mechanism of upregulating UGT2B15 by the NAF enantiomers might differ from that of AR antagonists and 5α-reductase inhibitors. Together, our results demonstrated that NAF enantiomers could be potential and novel UGT2B15 regulators, which accelerated the DHT elimination and promoted apoptosis of BPH-1 cells. This study could help expand the clinical application of NAF and support the development of new therapeutic strategies targeting the elimination of androgens for the treatment of BPH and other androgen-sensitive diseases.

High-efficiency hydrocracking of phenanthrene into BTX aromatics over a Ni-modified lamellar-crystal HY zeolite.

A new Ni-HY zeolite with lamellar-crystals was prepared as a catalyst for phenanthrene hydrocracking. It showed significantly improved reactivity and BTX (benzene, toluene and xylene) selectivity (up to 99.1% and 75.6%, respectively), depending on a reasonable synergistic effect between its excellent internal-diffusion and the high-efficiency concerted catalysis of surface metal-Ni active sites and acid sites. In particular, compared with a conventional Ni-HY with diamond-shaped crystals, its significantly shortened diffusion-reaction path of the micropore system in the lamellar crystals greatly enhanced the diffusion-reaction efficiency of large-molecule phenanthrene and polycyclic intermediates and remarkably improved the utilization of both pores and internal reactive sites, powerfully promoting phenanthrene into benzene series conversion. The much decreased diffusion-residence time of benzene-series products in shortened channels also effectively weakened the further cracking loss of the benzene-ring, leading to enhanced BTX selectivity. Moreover, this shorter-channel Ni-HY catalyst with a higher external surface area and mesoporous volume also exhibited greatly improved catalytic stability attributed to its stronger capabilities of accommodating coke and resisting coke-deposition. The phenanthrene conversion of >76.3% and the BTX yield of >46.3% were obtained during a 60 h on-stream reaction.