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Objective: The emergence of clinical Klebsiella pneumoniae strains harboring acrAB-tolC genes in the chromosome, along with the presence of two repetitive tandem core structures for bla KPC-2 and bla CTX-M-65 genes on a plasmid, has presented a significant clinical challenge. Methods: In order to study the detailed genetic features of K. pneumoniae strain SC35, both the bacterial chromosome and plasmids were sequenced using Illumina and nanopore platforms. Furthermore, bioinformatics methods were employed to analyze the mobile genetic elements associated with antibiotic resistance genes. Results: K. pneumoniae strain SC35 was found to possess a class A beta-lactamase and demonstrated resistance to all tested antibiotics. This resistance was attributed to the presence of efflux pump genes, specifically acrAB-tolC, on the SC35 chromosome. Additionally, the SC35 plasmid p1 carried the two repetitive tandem core structures for bla KPC-2 and bla CTX-M-65, as well as bla TEM-1 with rmtB, which shared overlapping structures with mobile genetic elements as In413, Tn3, and TnAs3. Through plasmid transfer assays, it was determined that the SC35 plasmid p1 could be successfully transferred with an average conjugation frequency of 6.85 × 10-4. Conclusion: The structure of the SC35 plasmid p1 appears to have evolved in correlation with other plasmids such as pKPC2_130119, pDD01754-2, and F4_plasmid pA. The infectious strain SC35 exhibits no susceptibility to tested antibioticst, thus effective measures should be taken to prevent the spread and epidemic of this strain.

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IMPORTANCE: To our knowledge, this is the first study to report the in vitro activity of two novel antimicrobial drugs, including imipenem-relebactam (IMR) and aztreonam-avibactam (AZA), toward carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-hvKP) strains. Our in vitro activity study revealed that only few antibacterial agents (including several novel agents) exhibit high antimicrobial activity toward carbapenem-resistant Klebsiella pneumoniae (CRKP) and CR-hvKP isolates. IMR and AZA may be promising therapeutic agents for the treatment of infections caused by CRKP and CR-hvKP isolates.

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The RADIALIS-like (RL) proteins are v-myb avian myeloblastosis viral oncogene homolog (MYB)-related transcription factors (TFs), and are involved in many biological processes, including metabolism, development, and response to biotic and abiotic stresses. However, the studies on the RL genes of Camellia sinensis are not comprehensive enough. Therefore, we undertook this study and identified eight CsaRLs based on the typical conserved domain SANT Associated domain (SANT) of RL. These genes have low molecular weights and theoretical pI values ranging from 5.67 to 9.76. Gene structure analysis revealed that six CsaRL genes comprise two exons and one intron, while the other two contain a single exon encompassing motifs 1 and 2, and part of motif 3. The phylogenetic analysis divided one hundred and fifty-eight RL proteins into five primary classes, in which CsaRLs clustered in Group V and were homologous with CssRLs of the Shuchazao variety. In addition, we selected different tissue parts to analyze the expression profile of CsaRLs, and the results show that almost all genes displayed variable expression levels across tissues, with CsaRL1a relatively abundant in all tissues. qRT-PCR (real-time fluorescence quantitative PCR) was used to detect the relative expression levels of the CsaRL genes under various abiotic stimuli, and it was found that CsaRL1a expression levels were substantially higher than other genes, with abscisic acid (ABA) causing the highest expression. The self-activation assay with yeast two-hybrid system showed that CsaRL1a has no transcriptional activity. According to protein functional interaction networks, CsaRL1a was well connected with WIN1-like, lysine histidine transporter-1-like, ß-amylase 3 chloroplastic-like, carbonic anhydrase-2-like (CA2), and carbonic anhydrase dnaJC76 (DJC76). This study adds to our understanding of the RL family and lays the groundwork for further research into the function and regulatory mechanisms of the CsaRLs gene family in Camellia sinensis.

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Objective: To analyze the mortality rate of patients with Klebsiella pneumoniae bacteremia (KPB) and the impact of extended spectrum beta-lactamase (ESBL) producing or carbapenem-resistance (CR) KP on the mortality rate among patients with bacteremia. Methods: EMbase, Web of Science, PubMed, and The Cochrane Library were searched up to September 18th, 2022. Two reviewers independently extracted data and evaluated risk of bias of included studies by ROBINS-I tool. A meta-regression analysis was conducted using a mixed-effects model to explore possible sources of heterogeneity. A random-effects model was used for pooled analysis in case of significant heterogeneity (I2>50%). Otherwise, the fixed-effects model was performed. Results: A total of 157 studies (37,915 enrolled patients) were included in the meta-analysis. The pooled death proportions of KPB were 17% (95% CI=0.14-0.20) at 7-day, 24% (95% CI=0.21-0.28) at 14-day, 29% (95% CI=0.26-0.31) at 30-day, 34% (95% CI=0.26-0.42) at 90-day, and 29% (95% CI=0.26-0.33) in hospital, respectively. Heterogeneity was found from the intensive care unit (ICU), hospital-acquired (HA), CRKP, and ESBL-KP in the meta-regression analysis. More than 50% of ICU, HA, CRKP, and ESBL-KP were associated with a significant higher 30-day mortality rates. The pooled mortality odds ratios (ORs) of CRKP vs. non-CRKP were 3.22 (95% CI 1.18-8.76) at 7-day, 5.66 (95% CI 4.31-7.42) at 14-day, 3.87 (95% CI 3.01-3.49) at 28- or 30-day, and 4.05 (95% CI 3.38-4.85) in hospital, respectively. Conclusions: This meta-analysis indicated that patients with KPB in ICU, HA-KPB, CRKP, and ESBL-KP bacteremia were associated with a higher mortality rate. The high mortality rate caused by CRKP bacteremia has increased over time, challenging the public health.

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OBJECTIVE: We aim to analyze the distribution of Klebsiella pneumoniae in different specimen sources and its antibiotic resistance trends from the Antimicrobial Resistant Investigation Network of Sichuan Province (ARINSP) between 2017 and 2020. METHODS: According to the monitoring scheme, each participating hospital identified the bacteria and performed antimicrobial susceptibility tests using approved procedures. The data of non-repetitive isolates collected from outpatients and inpatients were submitted to ARINSP. The WHONET 5.6 software was used to analyze the results according to the Clinical and Laboratory Standards Institute (CLSI). RESULTS: Between 2017 and 2020, 833,408 non-repetitive clinical isolates of bacteria were isolated in total. The bacterial strains isolated from sputum and broncho-alveolar lavage accounted for 48.7, 56.4, 49.2, and 43.7% from 2017 to 2020 respectively, among all sources. The number of Klebsiella pneumoniae isolates from sputum and broncho-alveolar lavage increased from 18,809 in 2018, 19,742 in 2019, to 19,376 in 2020, playing a predominant role among all specimens. Meropenem-resistant K. pneumoniae occurrences (5.7% in 2017, 7.3% in 2018, 8.0% in 2019, and 7.5% in 2020) remained highest among carbapenems, and increased slightly over time. The resistance rate to tigecycline remained lowest, and declined from 2.4% in 2017, to 0.4% in 2018, and from 0.7% in 2019, to 0.6% in 2020. CONCLUSION: The overall resistance rates of Klebsiella pneumoniae to carbapenems increased in Sichuan Province, giving a significant challenge to control K. pneumoniae related infections. Tigecycline has retained activity to against K. pneumoniae. Ongoing surveillance is essential. It can help for implementing intervention programs to reduce the occurrence of antimicrobial resistance and to provide with a rational use of antimicrobials.

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Objective: To systematically review and compare the efficacy and posttreatment resistance of ceftazidime-avibactam therapy and ceftazidime-avibactam-based combination therapy in patients with Gram-negative pathogens. Methods: PubMed, Embase, Web of Science, CNKI, and Wanfang Data databases were searched from their inception up to March 31, 2021, to obtain studies on ceftazidime-avibactam therapy versus ceftazidime-avibactam-based combination therapy in patients with carbapenem-resistant Gram-negative pathogens. The primary outcome was mortality rate, and the second outcomes were microbiologically negative, clinical success, and the development of resistance after ceftazidime-avibactam treatment. Results: Seventeen studies representing 1,435 patients (837 received ceftazidime-avibactam-based combination therapy and 598 received ceftazidime-avibactam therapy) were included in the meta-analysis. The results of the meta-analysis showed that no statistically significant difference was found on mortality rate (Petos odds ratio (OR) = 1.03, 95% confidence interval (CI) 0.79-1.34), microbiologically negative (OR = 0.99, 95% CI 0.54-1.81), and clinical success (OR =0.95, 95% CI 0.64-1.39) between ceftazidime-avibactam-based combination therapy and ceftazidime-avibactam therapy. Although there was no difference in posttreatment resistance of ceftazidime-avibactam (OR = 0.65, 95% CI 0.34-1.26) in all included studies, a trend favoring the combination therapy was found (according to the pooled three studies, OR = 0.18, 95% CI 0.04-0.78). Conclusions: The current evidence suggests that ceftazidime-avibactam-based combination therapy may not have beneficial effects on mortality, microbiologically negative, and clinical success to patients with carbapenem-resistant Gram-negative pathogens. A trend of posttreatment resistance occurred more likely in ceftazidime-avibactam therapy than the combination therapy. Due to the limited number of studies that can be included, additional high-quality studies are needed to verify the above conclusions.

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OBJECTIVE: To evaluate the value of routine preoperative gastroscopy/colonoscopy in patients with suspected ovarian cancer for differential diagnosis and judgment of bowel resection. METHODS: All women diagnosed with suspected ovarian cancer who underwent gastroscopy/colonoscopy before surgery in our center were retrospectively identified. Gastroscopy/colonoscopy results and clinical pathology, imaging, and surgical findings were analyzed. RESULTS: 389 patients were included. Among them, 40 (including 13 gastric and 9 colonic malignancy) were ovarian metastasis. Compared with imaging, gastrointestinal endoscopy showed no statistical advantage in the specificity and sensitivity (99.4% vs. 99.7%, P=1.0; 55.0% vs. 45.2%, P=0.057; respectively). All patients with gastric/colonic cancer metastasize except for one had indicative imaging or tumor marker abnormalities. Three patients with colonic cancer metastases underwent optimal surgery and alive with no recurrence, the other 19 patients experienced palliative chemotherapy. There is no significant difference in the sensitivity of colonoscopy and imaging in predicting intestinal incision (61.5% vs. 43.8%, P=0.804), whereas the latter had higher specificity (87.8% vs. 74.3%, P=0.001). CONCLUSIONS: For patients with suspected ovarian cancer, the incidence of gastrointestinal metastases is low, routine gastroscopy/colonoscopy before treatment is less efficient. Gastroscopy/colonoscopy has limited power to predict the need for gastrointestinal resection before ovarian cancer surgery.

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Accurately monitoring and effectively controlling the tritium compounds based on their ro-vibrational energy structure are important issues in various nuclear systems. Because of their radioactivity, it is difficult to obtain the corresponding energies directly through experiments. In this paper, the potential energy curves and the corresponding ro-vibrational full spectrum of DT, HT and T2 systems are derived by ab initio methods. However, it is difficult to verify the reliability of the calculated results due to the lack of direct experimental support. Therefore, a data-driven reliability analysis method is proposed, which can confirm the reliability by extracting information from the relevant calculations and multiple experimental data (the vibrational level, rotational level, and molar heat capacity) of similar systems (HD, H2, D2). The results show that: 1) The potential energy curves obtained by the ab initio method can provide the full ro-vibrational energy spectrum with an accuracy of approximately 10 cm-1; 2) Macroscopic heat capacity information can be used to distinguish and calibrate the overall reliability of microscopic ro-vibrational energies; 3) For the isotopic energy level structure of hydrogen, the influence of isotopes is mainly mass effect.

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Molecular spectroscopy plays an important role in the study of physical and chemical phenomena at the atomic level. However, it is difficult to acquire accurate vibrational spectra directly in theory and experiment, especially these vibrational levels near the dissociation energy. In our previous study (Variational Algebraic Method), dissociation energy and low energy level data are employed to predict the ro-vibrational spectra of some diatomic system. In this work, we did the following: 1) We expand the method to a more rigorous combined model-driven and data-driven machine learning approach (Spectroscopy Learning Method). 2) Extracting information from a wide range of existing data can be used in this work, such as heat capacity. 3) Reliable vibrational spectra and dissociation energy can be predicted by using heat capacity and the reliability of this method is verified by the ground states of CO and Br2 system.

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The details of quantum multi-body interactions are so rich and subtle which make it difficult to accurately model for some situations such as the behavior of diatomic long-range vibrations. In recent years, data-driven machine learning has made remarkable achievements in capturing complex relationships that are subtle. Combining the characteristics of these two fields, we propose a joint machine learning method to obtain reliable diatomic vibrational spectra including dissociation energy by using accessible heterogeneous micro/macro information such as low lying vibrational energy levels and heat capacity. Applications of this method to CO and Br2 in the ground state yield their state of the art of vibrational spectra including dissociation limit. The strategy introduced here is an exploration of combining the model-driven and data-driven method to cover subtle physical details that are difficult to study in a single way.

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OBJECTIVE: The objective of this study was to identify risk factors for postoperative infection in Chinese lung cancer patients. METHODS: A comprehensive search was performed in PubMed, EMbase, CNKI, and WanFang Data databases to identify studies investigating risk factors for postoperative infection in Chinese lung cancer patients. Meta-analysis was performed by using Revman 5.2 software. RESULTS: A total of 12 studies were included. The results of meta-analysis showed that old age, male gender, diabetes, cigarette smoking, squamous cell carcinoma, pulmonary diseases, longer of mechanical ventilation, and longer time of surgery procedure were associated with increased risk of postoperative infection. In addition, prophylactic antibiotic was associated with decreased risk of postoperative infection. CONCLUSION: The current meta-analysis suggests that the old age, male gender, diabetes mellitus, cigarette smoking, squamous cell carcinoma, pulmonary diseases, longer of mechanical ventilation, and longer of surgery time are risk factors for postoperative infection in Chinese lung cancer patients. Due to the limited quality and quantity of included studies, more high-quality studies are needed to verify the above results.

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Functional engineered nanoparticles are promising drug delivery carriers. As the construction of a functional nanocarrier always needs the optimization of multiple technical variables, efficient in vitro high-throughput evaluation methods would help to shorten the development cycle. In the present study, we generated a tissue mimic of the colon of inflammatory bowel disease (IBD) patients. Generally, Caco-2 cells and THP-1 cells were grown in a 3-D matrix with different number, spatial distribution and specific extracellular cell matrix (ECM) composition according to real healthy and inflamed animal colon tissues. After interlerukin-1ß/lipopolysaccharide (LPS) stimulation, the artificial model closely resembled the pathological features of IBD patient's colon, including massive cytokines and mucus production, epithelium defect and leukocytic infiltration. The tissue and cellular uptake of three different nanoparticles in the artificial model was similar to that in 2,4,6-trinitrobenzenesulfonic acid (TNBS) colitic mice. Most importantly, our artificial tissue can be placed into 96-well plates for high-throughput screening of drug delivery carriers for the treatment of IBD. Our study suggested a readily achievable way to improve current methodologies for the development of colon targeted drug delivery systems.

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