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.

Construction of Potential Gene Expression and Regulation Networks in Prostate Cancer Using Bioinformatics Tools.

OBJECTIVE: To identify the key genes involved in prostate cancer and their regulatory network. METHODS: The dataset of mRNA/miRNA transcriptome sequencing was downloaded from The Cancer Genome Atlas/the Gene Expression Omnibus database for analysis. The "edgeR" package in the R environment was used to normalize and analyze differentially expressed genes (DEGs) and miRNAs (DEmiRNAs). First, the PANTHER online tool was used to analyze the function enrichment of DEGs. Next, a protein-protein interaction (PPI) network was constructed using STRING and Cytoscape tools. Finally, miRNA-gene regulatory networks were constructed using the miRTarBase. RESULTS: We identified 4339 important DEGs, of which 2145 were upregulated (Up-DEGs) and 2194 were downregulated (Down-DEGs). Functional enrichment analysis showed that the Up-DEGs were related to the immune system and the cell cycle in prostate cancer, whereas the Down-DEGs were related to the nucleic acid metabolic process and metabolism pathways. Twelve core protein clusters were found in the PPI network. Further, the constructed miRNA-gene interaction network showed that 11 downregulated miRNAs regulated 16 Up-DEGs and 22 upregulated miRNAs regulated 22 Down-DEGs. CONCLUSION: We identified 4339 genes and 70 miRNAs that may be involved in immune response, cell cycle, and other key pathways of the prostate cancer regulatory network. Genes such as BUB1B, ANX1A1, F5, HTR4, and MUC4 can be used as biomarkers to assist in the diagnosis and prognosis of prostate cancer.

Azilsartan ameliorates ventricular hypertrophy in rats suffering from pressure overload-induced cardiac hypertrophy by activating the Keap1-Nrf2 signalling pathway.

OBJECTIVES: Investigate if azilsartan protects against myocardial hypertrophy by upregulating nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated pathways. METHODS: Abdominal aortic constriction (AAC)-induced cardiac hypertrophy in rats was applied. Azilsartan or vehicle was administered daily for 6 weeks in sham or AAC rats. Cardiac morphology and ventricular function were determined. Azilsartan effects upon neonatal rat cardiomyocyte (NRCM) hypertrophy and molecular mechanisms were studied in angiotensin (Ang) II-stimulated NRCMs in vitro. Nrf2-small interfering RNA (siRNA) was used to knockdown Nrf2 expression. Messenger RNA (mRNA)/protein expression of Kelch-like erythroid cell-derived protein (Keap)1 and Nrf2 and its downstream antioxidant enzymes was determined by real-time reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. KEY FINDINGS: Azilsartan treatment ameliorated cardiac hypertrophy/fibrosis significantly in AAC rats. Azilsartan increased expression of Nrf2 protein but decreased expression of Keap1 protein. Upregulation of protein expression of Nrf2's downstream antioxidant enzymes by azilsartan treatment was observed. Azilsartan inhibited Ang II-induced NRCM hypertrophy significantly and similar effects on the Keap1-Nrf2 pathway were observed in vivo. Nrf2 knockdown markedly counteracted the beneficial effects of azilsartan on NRCM hypertrophy and the Keap1-Nrf2 pathway. CONCLUSIONS: Azilsartan restrained pressure overload-induced cardiac remodelling by activating the Keap1-Nrf2 pathway and increasing expression of downstream antioxidant enzymes to alleviate oxidative stress.

One repeated transplantation of allogeneic umbilical cord mesenchymal stromal cells in type 1 diabetes: an open parallel controlled clinical study.

BACKGROUND: The preservation or restoration of ß cell function in type 1 diabetes (T1D) remains as an attractive and challengeable therapeutic target. Mesenchymal stromal cells (MSCs) are multipotent cells with high capacity of immunoregulation, which emerged as a promising cell-based therapy for many immune disorders. The objective of this study was to examine the efficacy and safety of one repeated transplantation of allogeneic MSCs in individuals with T1D. METHODS: This was a nonrandomized, open-label, parallel-armed prospective study. MSCs were isolated from umbilical cord (UC) of healthy donors. Fifty-three participants including 33 adult-onset (≥ 18 years) and 20 juvenile-onset T1D were enrolled. Twenty-seven subjects (MSC-treated group) received an initial systemic infusion of allogeneic UC-MSCs, followed by a repeat course at 3 months, whereas the control group (n = 26) only received standard care based on intensive insulin therapy. Data at 1-year follow-up was reported in this study. The primary endpoint was clinical remission defined as a 10% increase from baseline in the level of fasting and/or postprandial C-peptide. The secondary endpoints included side effects, serum levels of HbA1c, changes in fasting and postprandial C-peptide, and daily insulin doses. RESULTS: After 1-year follow-up, 40.7% subjects in MSC-treated group achieved the primary endpoint, significantly higher than that in the control arm. Three subjects in MSC-treated group, in contrast to none in control group, achieved insulin independence and maintained insulin free for 3 to 12 months. Among the adult-onset T1D, the percent change of postprandial C-peptide was significantly increased in MSC-treated group than in the control group. However, changes in fasting or postprandial C-peptide were not significantly different between groups among the juvenile-onset T1D. Multivariable logistic regression assay indicated that lower fasting C-peptide and higher dose of UC-MSC correlated with achievement of clinical remission after transplantation. No severe side effects were observed. CONCLUSION: One repeated intravenous dose of allogeneic UC-MSCs is safe in people with recent-onset T1D and may result in better islet ß cell preservation during the first year after diagnosis compared to standard treatment alone. TRIAL REGISTRATION: ChiCTR2100045434 . Registered on April 15, 2021-retrospectively registered, http://www.chictr.org.cn/.