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Introduction: Previously, we demonstrated that patients with full-term singletons and preterm twins require similar dose of intrathecal hyperbaric ropivacaine. However, these findings may be attributable to enrolled patients with preterm twin pregnancies. In this study, we aimed to determine the intrathecal dose requirements of hyperbaric ropivacaine for twins and singletons at equal gestational ages. Methods: We enrolled 75 patients with preterm singletons and 75 patients with preterm twins scheduled for cesarean delivery under combined spinal-epidural anesthesia in this two-arm parallel, randomized, double-blind, dose-response study. Patients with singletons and twins were randomly assigned to receive one of five different doses of hyperbaric ropivacaine: 10, 12, 14, 16, or 18 mg. A probit regression model was used to determine the dose effective in 50% of patients (ED50) and dose effective in 90% of patients (ED90) values. The relative median potency was calculated to compare the ED50 between patients with twins and singletons. Results: Intrathecal ropivacaine ED50 and ED90 (with 95% CI) in patients with preterm singletons were 9.9 (7.2 to 11.5) mg and 16.8 (14.5 to 22.9) mg, respectively. In patients with preterm twins, these values were 9.2 (95% CI 6.4 to 10.8) mg and 15.6 (95% CI 13.6 to 20.6) mg. Between patients with preterm twins and preterm singletons, the relative potency (ED50 ratios) was 0.933 (95% CI 0.72 to 1.15). Conclusions: During preterm gestation, intrathecal hyperbaric ropivacaine dose requirements for scheduled cesarean delivery were not different between patients with twins and singletons. [ABSTRACT FROM AUTHOR]

Purple-leafed plants not only have a higher resistance to biotic and abiotic stresses, but also have higher ornamental value. Anthocyanins are vital for leaf color formation, growth and development of purple leaves. However, the molecular mechanism underlying purple leaf formation in Lagerstroemia indica remains unclear. Metabolomic and transcriptomic analysis of purple-leafed cultivar 'Ebony Embers' and greenleafed cultivar 'Arapahoe' showed that the high expression of anthocyanin structure genes induced hyperaccumulation of cyanidin and pelargonidin derivatives, making the leaves purple. LfiHY5, LfiMYB75 and LfibHLH1 were identified using correlation analysis and weighted gene co-expression network analysis. In 'Arapahoe' x 'Ebony Embers' population, LfiHY5 and LfiMYB75 showed significant positive correlation with leaf anthocyanin content. Transient expression of LfiMYB75 and LfiHY5 in tobacco and purple-leafed crape myrtle indicated that the two genes activated anthocyanin synthesis. Yeast two-hybrid analysis showed that LfiMYB75 and LfibHLH1 could form a complex that enhanced anthocyanin synthesis. Yeast monohybrid and dual-luciferase assays confirmed that LfiHY5 activated the expression of LfiMYB75, to activate the transcription of anthocyanin structural genes LfiCHS and LfiANS. Moreover, there were three alleles of LfiHY5 in crape myrtle, and the different sequences had different activation effects on LfiMYB75. In conclusion, the results showed that LfiHY5 led to upregulate the transcription of LfiMYB75, and LfiMYB75 formed a complex with LfibHLH1, which increased the transcription level of LfiCHS and LfiANS to affect anthocyanin synthesis in crape myrtle. [ABSTRACT FROM AUTHOR]

Abstract Background 4-Hydroxyphenylacetic acid (4HPAA) is an important raw material for the synthesis of drugs, pesticides and biochemicals. Microbial biotechnology would be an attractive approach for 4HPAA production, and cofactors play an important role in biosynthesis. Results We developed a novel strategy called cofactor engineering based on clustered regularly interspaced short palindromic repeat interference (CRISPRi) screening (CECRiS) for improving NADPH and/or ATP availability, enhancing the production of 4HPAA. All NADPH-consuming and ATP-consuming enzyme-encoding genes of E. coli were repressed through CRISPRi. After CRISPRi screening, 6 NADPH-consuming and 19 ATP-consuming enzyme-encoding genes were identified. The deletion of the NADPH-consuming enzyme-encoding gene yahK and the ATP-consuming enzyme-encoding gene fecE increased the production of 4HPAA from 6.32 to 7.76 g/L. Automatically downregulating the expression of the pabA gene using the Esa-PesaS quorum-sensing-repressing system further improved the production of 4HPAA. The final strain E. coli 4HPAA-∆yfp produced 28.57 g/L of 4HPAA with a yield of 27.64% (mol/mol) in 2-L bioreactor fed-batch fermentations. The titer and yield are the highest values to date. Conclusion This CECRiS strategy will be useful in engineering microorganisms for the high-level production of bioproducts.

Abstract Background Ursolic acid (UA) is an anti-cancer herbal compound. In the present study, we observed the effects of UA on anchorage-dependent and -independent growth of human colorectal cancer (CRC) RKO cells. Methods RKO cells were cultured in conventional and detached condition and treated with UA. Cell viability was evaluated by CCK-8 assay. Cell cycle was analyzed by flow cytometry. Apoptosis was identified by Hoechst 33258 staining and flow cytometry analysis. Activities of caspases were measured by commercial kits. Reactive oxygen species (ROS) was recognized by DCFH-DA fluorescent staining. Anoikis was identified by EthD-1 fluorescent staining and flow cytometry analysis. Expression and phosphorylation of proteins were analyzed by western blot. Results UA inhibited RKO cell viability in both a dose- and time-dependent manner. UA arrested the cell cycle at the G0/G1 phase, and induced caspase-dependent apoptosis. UA inhibited Bcl-2 expression and increased Bax expression. In addition, UA up-regulated the level of ROS that contributed to UA activated caspase-3, − 8 and − 9, and induced apoptosis. Furthermore, UA inhibited cell growth in a detached condition and induced anoikis in RKO cells that was accompanied by dampened phosphorylation of FAK, PI3K and AKT. UA also inhibited epithelial-mesenchymal transition (EMT) as indicated by the down-regulation of N-Cad expression and up-regulation of E-Cad expression. Conclusions UA induced caspase-dependent apoptosis, and FAK/PI3K/AKT singling and EMT related anoikis in RKO cells. UA was an effective anti-cancer compound against both anchorage-dependent and -independent growth of RKO cells.

Since the Anyue Gasfield, located in the central Sichuan paleo-uplift of the Sichuan Basin, was discovered, great efforts have been made to work on natural gas exploration and discovery in the Sinian–Lower Paleozoic in the north slope of present paleo-uplift which has similar depositional settings. It is verified by the breakthrough of natural gas exploration in the second Member of Upper Sinian Dengying Formation in the north slope of central Sichuan paleo-uplift by wildcat well PT1 and the new sign of natural gas exploration in the Canglangpu Formation of Lower Cambrian and the fourth Member of Dengying Formation by Well JT1 that there are also favorable conditions for the formation of large-scale gas province in the north slope. In order to determine the natural gas exploration potential of Sinian–Lower Paleozoic in the central Sichuan paleo-uplift and provide the guidance for the following exploration deployment, this paper analyzed the petroleum geological conditions of Sinian–Lower Paleozoic in the north slope. And the following research results were obtained. First, the marginal platform belts in the second and the fourth Member of Sinian Dengying Formation in the north slope are basically separated areally, and they are superior to the Gaoshiti–Moxi area in terms of marginal platform width and sedimentary thickness and are intrinsically advantageous in sedimentation. Second, compared with the Gaoshiti–Moxi area, the reservoirs of Sinian Dengying Formation in the north slope are better in reservoir conditions, and many sets of quality reservoirs are developed vertically in Sinian–Cambrian. Third, hydrocarbon accumulation elements of Sinian Dengying Formation are better allocated in the north slope. Lithological traps are developed with a larger cumulative area. Wells JT1 and PT1 verify that there is gas in the lithological trap of the fourth and the second Member of Dengying Formation and large-scale lithological gas reservoirs are developed in the slope setting. In conclusion, compared with the Gaoshiti–Moxi area, the Sinian–Lower Paleozoic in the north slope is superior in petroleum geological conditions and has the advantage of multi-layer stereoscopic exploration vertically, presenting a great natural gas exploration potential and promising exploration prospects, so it is a new important strategic zone of conventional natural gas exploration in the Sichuan Basin.

ObjectivesThe current study evaluates the performance of dual-energy computed tomography (DECT) derived extracellular volume (ECV) fraction based on dual-layer spectral detector CT for diagnosing cervical lymph nodes (LNs) metastasis from papillary thyroid cancer (PTC) and compares it with the value of ECV derived from conventional single-energy CT (SECT).MethodsOne hundred and fifty-seven cervical LNs (81 non-metastatic and 76 metastatic) were recruited. Among them, 59 cervical LNs (27 non-metastatic and 32 metastatic) were affected by cervical root artifact on the contrast-enhanced CT images in the arterial phase. Both the SECT-derived ECV fraction (ECVS) and the DECT-derived ECV fraction (ECVD) were calculated. A Pearson correlation coefficient and a Bland–Altman analysis were performed to evaluate the correlations between ECVD and ECVS. Receiver operator characteristic curves analysis and the Delong method were performed to assess and compare the diagnostic performance.ResultsECVD correlated significantly with ECVS (r = 0.925; p

Aztreonam/avibactam (AZA), as one of the novel β-lactamases and β-lactamase inhibitor combinations, is considered to be a promising option for bloodstream infection (BSI) of carbapenem-resistant Klebsiella pneumoniae (CR-Kp). However, decreased susceptibility of AZA activity in Enterobacterales has been reported. The aim of this study was to identify the mechanisms of BSI CR-Kp with decreased susceptibility of AZA (minimal inhibitory concentration above 16/4 mg/L) (AZAH-Kp). Nine BSI AZAH-Kp isolates were screened from 317 CR-Kp isolates in Blood Bacterial Resistant Investigation Collaborative System (BRICS) program. Whole genome sequencing, bioinformatics analysis, and the relative expression of blaKPC, ompK35, and ompK37 were explored for CR-Kp with decreased susceptibility to AZA. The results revealed that elevated inhibitory concentration of AZA has emerged in CR-Kp before previous clinical exposure. In addition, decreased AZA susceptibility was associated with higher KPC expression and changes in OmpK35-37.

Blood vessels are ubiquitous in the human body and play essential roles not only in the delivery of vital oxygen and nutrients but also in many disease implications and drug transportation. Although fabricating in vitro blood vessels has been greatly facilitated through various microfluidic organ-on-chip systems, most platforms that are used in the laboratories suffer from a series of laborious processes ranging from chip fabrication, optimization, and control of physiologic flows in micro-channels. These issues have thus limited the implementation of the technique to broader scientific communities that are not ready to fabricate microfluidic systems in-house. Therefore, we aimed to identify a commercially available microfluidic solution that supports user custom protocol developed for microvasculature-on-a-chip (MVOC). The custom protocol was validated to reliably form a smooth and functional blood vessel using a viscous fingering (VF) technique. Using VF technique, the unpolymerized collagen gel in the media channels was extruded by less viscous fluid through VF passive flow pumping, whereby the fluid volume at the inlet and outlet ports are different. The different diameters of hollow tubes produced by VF technique were carefully investigated by varying the ambient temperature, the pressure of the passive pump, the pre-polymerization time, and the concentration of collagen type I. Subsequently, culturing human umbilical vein endothelial cells inside the hollow structure to form blood vessels validated that the VF-created structure revealed a much greater permeability reduction than the vessel formed without VF patterns, highlighting that a more functional vessel tube can be formed in the proposed methodology. We believe the current protocol is timely and will offer new opportunities in the field of in vitro MVOC.

ST59 is the predominant pathotype of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in China. As a variant of ST59, there is relatively little known about the detailed information of ST338. To address this issue, here, we described thirteen ST338 CA-MRSA strains isolated from severe bloodstream infection cases, and focused on their epidemiology, genetic features and virulence potential. Phylogenetic analysis showed the earliest isolated strain of this study is likely a predecessor of recent ST338 lineage (after year of 2014). Furthermore, the phylogenetic reconstruction and time estimation suggested that ST338 evolved from ST59 in 1991. Notably, the carrying patten of virulence factors of all ST338 strains were similar, and the genomic islands νSaα, νSaγ and SaPI and the core virulence factors like hla and psm were detected in ST338 isolates. However, all ST338 isolates lacked some adhesion factors such as clfA, clfB, eap, cna and icaD. Additionally, among these ST338 strains, one PVL-negative ST338 isolate was detected. Experiment on mice nose and human alveolar epithelial cell showed that the nasal colonization ability of ST338 was weaker than that of CA-MRSA MW2. In a mouse bloodstream infection model and skin infection model, PVL+ and PVL− strains had the similar virulence, which was dependent on upregulation of toxin genes rather than the presence of mobile genetic elements such as ΦSa2 carrying PVL. Our findings provide important insight into the epidemiology and pathogenicity of the novel and highly virulent ST338-SCCmec Vb clone.

Clostridioides difficile is the most common pathogen causing antibiotic-associated diarrhea. Previous studies showed that diverse sources, aside from C. difficile infection (CDI) patients, played a major role in C. difficile hospital transmission. This study aimed to investigate relationships and transmission potential of C. difficile strains from different sources. A prospective study was conducted both in the intensive care unit (ICU) and six livestock farms in China in 2018–2019. Ninety-eight strains from CDI patients (10 isolates), asymptomatic hospitalized carriers (55), the ICU environment (12), animals (14), soil (4), and farmers (3) were collected. Sequence type (ST) 3/ribotype (RT) 001, ST35/RT046, and ST48/RT596 were dominant types, distributed widely in multiple sources. Core-genome single-nucleotide polymorphism (cgSNP) analysis showed that hospital and farm strains shared several common clonal groups (CGs, strains separated by ≤ 2 cgSNPs) (CG4/ST3/RT001, CG7/ST35/RT046, CG11/ST48/RT596). CDI patients, asymptomatic carriers, and the ICU environment strains also shared several common CGs. The number of virulence genes was not statistically different between strains from different sources. Multi-source strains in the same CG carried identical virulence gene sequences, including pathogenicity genes at the pathogenicity locus and adhesion-related genes at S-layer cassette. Resistance genes (ermB, tetM, etc.) were widespread in multiple sources, and multi-source strains in the same CG had similar resistance phenotypes and carried consistent transposons and plasmid types. The study indicated that interspecies and cross-regional transmission of C. difficile occurs between animals, the environment, and humans. Community-associated strains from both farms and asymptomatic hospitalized carriers were important reservoirs of CDI in hospitals.

Spinal cord injury has long been a prominent challenge in the trauma repair process. Spinal cord injury is a research hotspot by virtue of its difficulty to treat and its escalating morbidity. Furthermore, spinal cord injury has a long period of disease progression and leads to complications that exert a lot of mental and economic pressure on patients. There are currently a large number of therapeutic strategies for treating spinal cord injury, which range from pharmacological and surgical methods to cell therapy and rehabilitation training. All of these strategies have positive effects in the course of spinal cord injury treatment. This review mainly discusses the problems regarding stem cell therapy for spinal cord injury, including the characteristics and action modes of all relevant cell types. Induced pluripotent stem cells, which represent a special kind of stem cell population, have gained impetus in cell therapy development because of a range of advantages. Induced pluripotent stem cells can be developed into the precursor cells of each neural cell type at the site of spinal cord injury, and have great potential for application in spinal cord injury therapy.

Metro is an important form of public transport in Shanghai. Based on the metro card data, we conduct the cluster analysis of Shanghai metro stations according to the pattern of passenger flow changing with time. Then the characteristics of travel time and surrounding land use are investigated for different types of stations to explore the relationship between urban land-use characteristics and travel activities reflected by passenger flow at metro stations. It is found that the passenger flow pattern of metro stations is closely related to the location conditions of stations and its surrounding land-use patterns. Based on various characteristics, 285 metro stations are classified into four types, including residential-oriented stations, employment-oriented stations, employment-residence-oriented stations, and integrated functional-oriented stations, reflecting the interaction between spontaneous travel behavior and urban land-use characteristics and providing a reference for optimizing the urban functional structure and the spatial allocation of facilities.

Abstract Background Radiation-induced oral mucositis (OM) is one of the most common acute complications for head and neck cancer. Severe OM is associated with radiation treatment breaks, which harms successful tumor management. Radiogenomics studies have indicated that genetic variants are associated with adverse effects of radiotherapy. Methods A large-scale genome-wide scan was performed in 1467 nasopharyngeal carcinoma patients, including 753 treated with 2D-CRT from Genetic Architecture of the Radiotherapy Toxicity and Prognosis (GARTP) cohort and 714 treated with IMRT (192 from the GARTP and 522 newly recruited). Subgroup analysis by radiotherapy technique was further performed in the top associations. We also performed physical and regulatory mapping of the risk loci and gene set enrichment analysis of the candidate target genes. Results We identified 50 associated genomic loci and 64 genes via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping and gene-based analysis, and 36 of these loci were replicated in subgroup analysis. Interestingly, one of the top loci located in TNKS, a gene relevant to radiation toxicity, was associated with increased OM risk with OR = 3.72 of the lead SNP rs117157809 (95% CI 2.10–6.57; P = 6.33 × 10−6). Gene set analyses showed that the 64 candidate target genes were enriched in the biological processes of regulating telomere capping and maintenance and telomerase activity (Top P = 7.73 × 10−7). Conclusions These results enhance the biological understanding of radiotherapy toxicity. The association signals enriched in telomere function regulation implicate the potential underlying mechanism and warrant further functional investigation and potential individual radiotherapy applications.

Abstract Background The purpose of the study is to discuss the correlation between the resistance rate of gram negative bacteria to fluoroquinolones (FQ) and antibiotic consumption intensity of 145 China tertiary hospitals in 2014. Methods This retrospective study adopted national monitoring data from 2014. Each participating hospital required to report annual consumption of each antibiotic, and the resistance rate of gram negative bacteria to FQ. Then the correlation between antibiotic usage and fluoroquinolones –resistant (FQR) rate was consequently investigated. Results One hundred forty-five hospitals were included in the study, and the median antibiotic consumption intensity was 46.30 (23.93–115.39) defined daily dosages (DDDs) per 100 patient-days. Cephalosporins ranks first in the antibiotics consumption, followed by fluoroquinolones, penicillins, and carbapenems. Fluoroquinolones resistance rate varied from hospital to hospital. The correlation analysis showed significant relationship between the percentage of FQR Escherichia coli and the consumption of FQs (r = 0.308, p

Abstract. Objective:. To evaluate the clinical utility of noninvasive prenatal screening (NIPS) for fetuses with congenital heart disease (CHD) and impact of NIPS results on pregnancy outcome. Methods:. This was a retrospective study of pregnant women with fetuses diagnosed with CHDs by sonographic examination, who willing to underwent NIPS as a side-test for fetal aneuploidies. From August 2016 to October 2017, in the sonographic examination center of Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region. NIPS was offered to 117 women who carried fetuses with CHD diagnosed by fetal ultrasound (mean gestational age = 24 weeks). The pregnancy outcomes were followed-up. Results:. NIPS positive rate in our pregnancies with CHD fetuses’ cohort is 11.1% (13/117), and the positive predictive value for aneuploidies is 85.7% (6/7). In the NIPS positive group (n = 13), all pregnancies terminated, 76.9% (10/13) of those decisions were made on ultrasound finding alone. In the NIPS negative group (n = 104), 2 lost follow-up, 79 pregnancies terminated, among which 77.2% (61/79) of the decision was made by ultrasound results alone. Twenty-three pregnancies continued and 78.3% of those fetuses carried single type CHD. In terminated pregnancies that did not considered NIPS results (71/115), 73.2% (52/71) of those carried fetuses with two or more types of CHDs. Conclusion:. NIPS can detect common aneuploidy associated with CHD with high positive predictive value and screening yield. The NIPS result played certain meaningful roles in determining pregnancy outcomes, particularly for fetus with simplex CHD; yet the parents’ decision of pregnancy was mainly made based on ultrasound findings.

Glioblastoma (GBM) is the most common and fatal primary adult brain tumor. To date,various promising chemotherapeutic regimens have been trialed for use in GBM; however, temozolomide(TMZ) therapy remains the only first ⁃ line chemotherapeutic option for newly diagnosed GBM. Despitemaximal therapy with surgery and combined concurrent radiotherapy and chemotherapy, and adjuvant TMZtherapy, the median overall survival (OS) remains approximately 14.6 months. Given the failure ofconventional chemotherapeutic strategies in GBM, there has been renewed interest in the role ofimmunotherapy in GBM. Dendritic cells (DC) are immune antigen⁃presenting cell (APC) that play a role inboth the innate and adaptive immune system, thereby making them prime vehicles for immunotherapy viaDC vaccinations in various cancers. There is great enthusiasm surrounding the use of vaccinations for GBMwith multiple ongoing trials. In this review, we summarize the progress, prospects and challenges of DCvaccine in the treatment of GBM. DOI：10.3969/j.issn.1672⁃6731.2020.02.008

We aimed to clarify the epidemiologic and clinical importance of evolutionary events that occurred in carbapenem-resistant Klebsiella pneumoniae (CRKP). We collected 203 CRKP causing bloodstream infections in a tertiary hospital in China during 2013–2017. We detected a subclonal shift in the dominant clone sequence type (ST) 11 CRKP in which the previously prevalent capsular loci (KL) 47 had been replaced by KL64 since 2016. Patients infected with ST11-KL64 CRKP had a significantly higher 30-day mortality rate than other CRKP-infected patients. Enhanced virulence was further evidenced by phenotypic tests. Phylogenetic reconstruction demonstrated that ST11-KL64 is derived from an ST11-KL47–like ancestor through recombination. We identified a pLVPK-like virulence plasmid carrying rmpA and peg-344 in ST11-KL64 exclusively from 2016 onward. The pLVPK-like–positive ST11-KL64 isolates exhibited enhanced environmental survival. Retrospective screening of a national collection identified ST11-KL64 in multiple regions. Targeted surveillance of this high-risk CRKP clone is urgently needed.

Digestive system pan-cancer is a general term for digestive system tumors including colorectal carcinoma (CRC), esophageal carcinoma (ESCA), stomach adenocarcinoma (STAD), and liver hepatocellular carcinoma (LIHC). Since the anatomical location, function and metabolism are closely related, there may be similarities in development and progression of these tumors. Hypoxia is the consequence of an imbalance between oxygen demand and supply, and intracellular hypoxia is associated with malignant progression, treatment resistance, and poor prognosis in tumors. Therefore, an urgent and challenging task is to investigate the molecular mechanisms associated with hypoxia in digestive system pan-cancer for the prognosis and treatment of digestive tract tumors. In this study, we identified 18 hypoxia-related lncRNAs (HRlncRNAs) by co-expression analysis between hypoxia genes and lncRNAs from digestive system pan-cancer. Six HRlncRNAs were then obtained using lasso regression and multivariate cox analysis to construct a prognostic model. Next, the Akaike information criterion (AIC) values for 3-year receiver operating curve (ROC) were counted to determine the cut-off point and establish an optimal model to distinguish between high- or low-risk groups among patients with digestive system pan-cancer. To evaluate the stability of the prognosis model, we validated it in terms of survival outcomes, clinicopathological stage, tumor-infiltrating immune cells, immune checkpoint inhibitors (ICIs) and anticancer drugs sensitivity. The results suggested that high- risk group had a worse prognosis and a more positive association with tumor-infiltrating immune cells such as B cells, cancer-associated fibroblasts, endothelial cells, monocytes, macrophages and bone marrow dendritic cells in digestive system pan-cancer. Immune checkpoint inhibitors (ICIs) related biomarkers discovered that high-risk group was positively correlated with high expression of HAVCR2 in digestive system pan-cancer. The anticancer drugs sensitivity analysis showed that the high-risk group was associated with the lower half-inhibitory centration (IC50) of Imatinib in digestive system pan-cancer. In conclusion, the prognostic model of HRlncRNAs showed a promising clinical prediction value and may provide a useful reference for the diagnosis and treatment of the digestive system tumors.

In this study, one G2c-subtype strain of porcine epidemic diarrhea virus (PEDV) (SHXX1902 strain) was isolated from clinical samples in suspended Vero cells, which was different from the genotype of the commercial AJ1102 vaccine. As a result, we determined the pathogenicity of different passages’ isolates (SHXX1902 strain) and compared the immunogenicity of G2c-subtype strain (SHXX1902 strain) with the commercial AJ1102 vaccine. The viral titer reached 107 50% tissue culture infectious dose (TCID50)/ml, which met the requirement for seed virus replication during vaccine development. Five-day-old piglets were orally infected with viruses from passages P5 and P35 to determine the pathogenicity and immunogenicity of different passages. Pregnant sows were immunized with inactivated SHXX1902-P5 or the commercial AJ1102 vaccine (first immunized with an attenuated vaccine and then boosted with an inactivated vaccine) to study the influence of the culture method on the immunogenicity of the strain. The median pig diarrhea dose (PDD50) and the median lethal dose (LD50) of the P5 virus were 102.00 and 102.84 TCID50/ml, respectively. All five piglets infected with the SHXX1902-P5 virus shed the virus 24 h after vaccination, whereas only two of the five piglets treated with the SHXX1902-P35 virus shed the virus 48 h after vaccination. The SHXX1902-P35 virus was partially attenuated in the 5-day-old piglets. Inactivated SHXX1902-P5 induced PEDV-specific immunoglobulin G (IgG) antibody responses equivalent to those induced by AJ1102 after infection in sow serum. However, the IgA titer induced by AJ1102 was much higher than that induced by inactivated SHXX1902-P5 since the boost immunization. On days 5 and 7 after farrowing, the IgA titers were similar among the immunized groups. Our study highlights that serial passage can lead to the attenuation of G2c-subtype strain. The immunogenicity of the inactivated strain was similar to the commercial vaccine. Our observation helped conceptualize appropriate study designs for the PEDV vaccine.

BackgroundCarbapenem-resistant Acinetobacter baumannii (CRAB) is a common cause of ventilator-associated pneumonia (VAP) in intensive care unit (ICU) patients, but its infection and colonization state are difficult to distinguish. If the judgment is wrong, it may aggravate the abuse of antibiotics and further accelerate the evolution of drug resistance. We sought to provide new clues for the diagnosis, pathogenesis and treatment of CRAB VAP based on lower respiratory tract (LRT) microbiota.MethodsA prospective study was conducted on patients with mechanical ventilation from July 2018 to December 2019 in a tertiary hospital. Multi-genomics studies (16S rRNA amplicon, metagenomics, and whole-genome sequencing [WGS]) of endotracheal deep aspirate (ETA) were performed.ResultsFifty-two ICU patients were enrolled, including 24 with CRAB VAP (CRAB-I), 22 with CRAB colonization (CRAB-C), and six CRAB-negative patients (infection-free) (CRAB-N). Diversity of pulmonary microbiota was significantly lower in CRAB-I than in CRAB-C or CRAB-N (mean Shannon index, 1.79 vs. 2.73 vs. 4.81, P < 0.05). Abundances of 11 key genera differed between the groups. Acinetobacter was most abundant in CRAB-I (76.19%), moderately abundant in CRAB-C (59.14%), and least abundant in CRAB-N (11.25%), but its interactions with other genera increased in turn. Metagenomics and WGS analysis showed that virulence genes were more abundant in CRAB-I than in CRAB-C. Multi-locus sequence typing (MLST) of 46 CRAB isolates revealed that the main types were ST208 (30.43%) and ST938 (15.22%), with no difference between CRAB-I and CRAB-C.ConclusionLower respiratory tract microbiota dysbiosis including elevated relative abundance of Acinetobacter and reduced bacterial interactions, and virulence enrichment may lead to CRAB VAP.

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) sequence type (ST) 22, especially the epidemic MRSA-15 (EMRSA-15), has been one of the most important disease-causing clones transmitting rapidly within and between hospitals globally. However, the genetic features and evolution of Chinese MRSA ST22 remain to be determined. Herein, we performed comparative genomics analysis of 12 ST22 community-associated (CA) MRSA isolates from China with 9 Chinese ST22 CA-MSSA isolates and 284 ST22 genomes from global sources, to clarify the genotypic features and potential transmission of MRSA ST22 strains isolated in China. Phylogenetic reconstruction and time estimation suggested that the Chinese subclade emerged around 2006, and the ST22-SCCmec V clone may have evolved from the native ST22-MSSA clone rather than spread from other regions, indicating that the Chinese ST22-MRSA-V clone is independent of the EMRSA-15 and Gaza clone, with differences in lukSF-PV and tsst-1 carriage. Virulence assays suggested that the ST22-MRSA clone was highly virulent, displaying higher or similar virulence potential as MSSA ST22 predecessors and the epidemic USA300 and ST22-MSSA. However, two nonsense mutations caused by a frameshift in agrC were identified in two ST22-MSSA isolates, resulting in a significant attenuation of virulence. RT-qPCR also demonstrated that the high virulence potential of these ST22 strains may be attributed to elevated expression of agr. This study provides insight into the epidemiology of the novel and highly virulent CA-MRSA ST22 clones. IMPORTANCE Staphylococcus aureus sequence type 22 (ST22) is the main HA-MRSA clone spreading in Europe. It has strong capacity to supplant and replace other formerly epidemic MRSA clones. Previous work has described genotypic characteristics of ST22 belonging to EMRSA-15 and Gaza clone; however, the genetic feature and virulence potential of Chinese spread of ST22 strains are still limited. We conducted a detailed analysis of genomic evolution of global ST22 strains, to clarify the genotypic features and potential transmission of MRSA ST22 strains isolated from China. Our results suggested that the Chinese subclade is highly virulent, and emerged around 2006. We also demonstrated that the ST22-SCCmec V may have evolved from the native ST22-MSSA clone rather than spread from other regions, and the high virulence potential of these ST22 strains may be attributed to the high expression of agr based on the results of virulence assays of Chinese ST22 clones. Our findings are of great importance for providing insights into the epidemiology and pathogenicity of global and Chinese ST22 clones.

The gut microbiota has an important role in the pathogenesis of hepatic encephalopathy(HE). Rifaximin, an intestinal non-absorbable antibacterial agent, is effective in the treatment of HE. However, whether long-term prophylactic use induces antibacterial resistance and its mechanism for treating HE remains unclear. This prospective study assessed the impact of 12 weeks rifaximin administration on the gut microbiota and resistome in cirrhotic patients. Fecal sampling was conducted 1 day before the first rifaximin administration and at Weeks 1, 2, 4, 6, 8, 10, 12 of the study. Thirty cirrhotic patients who were in remission from recurrent HE was enrolled to receive rifaximin (400mg TID for 12 weeks). Rifaximin improved hyperammonemia and cognitive function in the 21 patients who completed rifaximin treatment. The dynamic observations showed the gut microbiota diversity, composition and the number of resistance genes, plasmids, insertion sequences did not change significantly during the period(P>0.05). Metabolic pathways such as aromatic amino acids, tryptophan synthesis, urea cycle, and LPS synthesis reduced. No new antimicrobial resistance genes was emergenced. However, the number of aminoglycosides, rifamycin and phenolic resistance genes increased, whereas tetracycline, fosfomycin and cephamycin decreased (P

ObjectiveCurrently, the prevalence of CF (Cognitive Frailty) is not very clear, and the relationship between CF and its associated risk factors has not been accurately evaluated. Therefore, it is necessary to conduct a systematic review and meta-analysis further to understand CF's prevalence and associated factors.MethodsEmbase, PubMed, Web of Science, Ovid, and Cochrane were systematically searched for articles exploring the prevalence of CF, the deadline of searching date was up to March 2021. For the prevalence of CF, the events of CF and the total number of patients in every included study were extracted to estimate the prevalence of CF. For associated factors of CF, Odds Ratios (ORs) with (corresponding) 95% confidence intervals (CIs) were used for estimations.ResultsFirstly, the estimated prevalence of CF I (Cognitive Frailty in the model I) was 16%, 95% CI (0.13–0.19), and the estimated prevalence of CF II (Cognitive Frailty in model II) was 6%, 95% CI (0.05–0.07). Secondly, both lower engagement in activities and age were calculated to be independent risk factors of CF, and the OR (95% CI) was 3.31 (2.28–4.81) and 1.10 (1.04–1.16), respectively. Finally, depression was also a prominent risk factor of CF, with the overall OR (95% CI) as 1.57 (1.32–1.87).ConclusionCF was a high prevalence in community older. The various assessment scales and the different cutoff values of diagnostic criteria would affect the prevalence of CF. Lower engagement in activities, age, and depression was the risky factor of CF.Systematic Review Registrationhttp://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42019121369.

ObjectiveThe multicenter literature review and case studies of 3 patients were undertaken to provide an updated understanding of nocardiosis, an opportunistic bacterial infection affecting immunosuppressed nephrotic syndrome (NS) patients receiving long-term glucocorticoid and immunosuppressant treatment. The results provided clinical and microbiological data to assist physicians in managing nocardiosis patients.MethodsThree cases between 2017 and 2018 from a single center were reported. Additionally, a systematic review of multicenter cases described in the NCBI PubMed, Web of Science, and Embase in English between January 1, 2001 and May 10, 2021 was conducted.ResultsThis study described three cases of Nocardia infection in NS patients. The systematic literature review identified 24 cases with sufficient individual patient data. A total of 27 cases extracted from the literature review showed that most patients were > 50 years of age and 70.4% were male. Furthermore, the glucocorticoid or corticosteroid mean dose was 30.9 ± 13.7 mg per day. The average time between hormone therapy and Nocardia infection was 8.5 ± 9.7 months. Pulmonary (85.2%) and skin (44.4%) infections were the most common manifestations in NS patients, with disseminated infections in 77.8% of patients. Nodule/masses and consolidations were the major radiological manifestations. Most patients showed elevated inflammatory biomarkers levels, including white blood cell counts, neutrophils percentage, and C-reactive protein. Twenty-five patients received trimethoprim-sulfamethoxazole monotherapy (18.5%) or trimethoprim-sulfamethoxazole-based multidrug therapy (74.1%), and the remaining two patients (7.4%) received biapenem monotherapy. All patients, except the two who were lost to follow-up, survived without relapse after antibiotic therapy.ConclusionsNephrotic syndrome patients are at high risk of Nocardia infection even if receiving low-dose glucocorticoid during the maintenance therapy. The most common manifestations of nocardiosis in NS patients include abnormal lungs revealing nodules and consolidations, skin and subcutaneous abscesses. The NS patients have a high rate of disseminated and cutaneous infections but a low mortality rate. Accurate and prompt microbiological diagnosis is critical for early treatment, besides the combination of appropriate antibiotic therapy and surgical drainage when needed for an improved prognosis.

Visualization and manipulation of defined motoneurons have provided significant insights into how motor circuits are assembled in Drosophila . A conventional approach for molecular and cellular analyses of subsets of motoneurons involves the expression of a wide range of UAS transgenes using available GAL4 drivers (eg, eve promoter-fused GAL4 ). However, a more powerful toolkit could be one that enables a single-cell characterization of interactions between neurites from neurons of interest. Here we show the development of a UAS > LexA > QF expression system to generate randomly selected neurons expressing one of the 2 binary expression systems. As a demonstration, we apply it to visualize dendrite-dendrite interactions by genetically labeling eve + neurons with distinct fluorescent reporters.

Objectives: This work was to investigate the activity and optimal treatments of ceftazidime-avibactam (CZA) and aztreonam-avibactam (AZA) against bloodstream infections caused by carbapenem resistant Klebsiella pneumoniae (BSIs-CRKP).Methods: A total of 318 nonduplicate BSIs-CRKP isolates were collected from Blood Bacterial Resistant Investigation Collaborative System (BRICS) program. The minimum inhibitory concentration (MIC) of CZA and AZA were determined by agar dilution method. Carbapenemase genes and multilocus sequence typing were amplified by PCR. Monte Carlo simulation (MCS) was conducted to calculate cumulative fraction of response (CFR) of different CZA or AZA administrations.Results: The MIC90 of CZA and AZA were 128/4 and 1/4 mg/L, respectively. There are 87.4 and 3.5% isolates carried blaKPC-2 and blaNDM-1. A total of 68 ST types were identified and 29 novel ST types. ST11 accounted for 66.6%. Further MCS showed CFR of CZA using two-step infusion therapy (rapid first-step 0.5 h infusion and slow second-step 3 h infusion, TSIT) (2.5 g 0.5 h, 3.75 g every 8 h with 3 h infusion and 3.75 g 0.5 h, 2.5 g every 8 h with 3 h infusion) was above 89%. The CFR of AZA with TSIT was above 96%.Conclusion: TSIT with sufficient pharmacokinetic conditions could be useful for enhancing the therapeutic efficacy of CZA and AZA against BSIs-CRKP.

ABSTRACT Since 2010, methicillin-resistant Staphylococcus aureus (MRSA) ST59 began to increase in prevalence in China, gradually replacing ST239 and has become the dominant clone in most hospitals in China. Here, we investigated the changing epidemiology, phylogenetic reconstruction, and genomic characterization of MRSA clones in China to identify the genomic driving factors in the prevalence of ST59. Most MRSA isolates were identified as ST59 (36.98%; 277/749), which increased from 25.09% in 2014 to 35.53% in 2019. The phylogenetic analysis of the 749 MRSA isolates showed a high level of diversity and the copresence of hospital-associated, community-associated, livestock-associated, and hypervirulent clones. Furthermore, minimum spanning trees revealed that ST59 MRSA clones from different hospitals and regions were integrated, suggesting that frequent exchanges had occurred between regions and hospitals. ST59 clones displayed higher susceptibility to antimicrobials than did ST239 and ST5 MRSA clones, indicating that resistance to non-β-lactam and fluoroquinolone antibiotics may be not critical for the epidemic success of ST59 clones. Virulence factors detection showed that sak and chp genes enriched in MRSA ST59 may be associated with the enhanced spreading success of ST59, whereas qacA may have contributed to the predominance of ST5 in East China. Our refined analysis of different clones among ST239, ST5, ST59, and ST398 demonstrated the existence of potential driving factors for the evolution of nosocomial MRSA populations and diversity of the evolutionary events surrounding clonal replacement. IMPORTANCE As a developing country, China has an unbalanced health care system due to regional differences in economic development. However, China is also a country worthy of study with regard to the population dynamics of MRSA within the more resource-rich health care systems. In this study, we carried out genomic analysis to investigate the genomic epidemiology and characterization of MRSA isolated from bloodstream infections over a timespan of 6 years. Our refined analysis of different MRSA clones among ST59, ST5, ST239, and ST398 demonstrated the existence of driving factors for the evolution of nosocomial MRSA populations and diversity of the evolutionary events surrounding clonal replacement.

ObjectInterstitial lung disease (ILD) is a specific form of chronic fibrosing interstitial pneumonia with various etiology. The severity and progression of ILD usually predict the poor outcomes of ILD. Otherwise, Krebs von den Lungen-6 (KL-6) is a potential immunological biomarker reflecting the severity and progression of ILD. This meta-analysis is to clarify the predictive value of elevated KL-6 levels in ILD.MethodEBSCO, PubMed, and Cochrane were systematically searched for articles exploring the prognosis of ILD published between January 1980 and April 2021. The Weighted Mean Difference (WMD) and 95% Confidence Interval (CI) were computed as the effect sizes for comparisons between groups. For the relationship between adverse outcome and elevated KL-6 concentration, Hazard Ratio (HR), and its 95%CI were used to estimate the risk factor of ILD.ResultOur result showed that ILD patients in severe and progressive groups had higher KL-6 levels, and the KL-6 level of patients in the severe ILD was 703.41 (U/ml) than in mild ILD. The KL-6 level in progressive ILD group was 325.98 (U/ml) higher than that in the non-progressive ILD group. Secondly, the KL-6 level of patients in acute exacerbation (AE) of ILD was 545.44 (U/ml) higher than stable ILD. Lastly, the higher KL-6 level in ILD patients predicted poor outcomes. The KL-6 level in death of ILD was 383.53 (U/ml) higher than in survivors of ILD. The pooled HR (95%CI) about elevated KL-6 level predicting the mortality of ILD was 2.05 (1.50–2.78), and the HR (95%CI) for progression of ILD was 1.98 (1.07–3.67).ConclusionThe elevated KL-6 level indicated more severe, more progressive, and predicted the higher mortality and poor outcomes of ILD.

Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or 10 × 109/L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future.

The defect of mixed-grain structure with millimeter-grade coarse grains (MCGs) is frequently found in heavy forgings, such as nuclear main pipes manufactured from 316LN steel. Renovation of such kind forgings can only be conducted through recrystallization. However, the allowed deformation is limited because the geometric size of forgings should be maintained during the renovation. For this purpose, the deformation heterogeneity of 316LN steel with mixed-grain structures were studied experimentally, which demonstrated that the MCGs were more inclined to deform than fine grains even if MCGs are with hard orientations. Therefore, a two-stage method was studied to refine MCGs, which takes the advantage of this deformation heterogeneity. The first stage was to impose a limited deformation to the steel at room temperature, suppressing the dynamic recovery and leading the preferentially deformed MCGs to accumulate enough deformation energy storage. The second stage was rapidly heating the deformed materials to realize static recrystallization (SRX). The results showed that the MCGs were completely refined by SRX even if the reduction rate is only 8%. The SRX mechanisms and refining assessments of MCGs under different deformation conditions were discussed. This work, thus, provides an effective method to salvage the heavy structures in engineering.

We review the recent results from the Belle experiment on the measurements of branching fractions and decay asymmetry parameters (α) for the hadronic weak decays of charmed baryons, including Λc+→B+P: Λc+→(Λ,Σ0)h+ (h=π,K) and Λc+→Σ+(π0,η,η′); Ξc0→B+P: Ξc0→Ξ−π+; Ξc0→B+V: Ξc0→ΛK¯*0, Ξc0→Σ0K¯*0, and Ξc0→Σ+K*−. In addition, we present an overview of the searches for CP violation via the α-induced CP asymmetry for Λc+→(Λ,Σ0)h+ and Ξc0→Ξ−π+. Finally, we discuss the promising decay modes of Ωc0 which can be measured in the near future and are indispensable in searching for CP violation in the charm sector.

The primary ovarian carcinoid tumor is a very rare ovarian tumor, which accounts for approximately 0.5% to 1.7% of all carcinoids and 1% of ovarian cancer. According to its histopathological features, it can be divided into four categories: insular, trabecular, strumal, and mucinous, among which insular carcinoid is common in Western countries. By comparison, the chain-typed and trabecular carcinoid seem to be common in Asian countries. To date, about 150 cases have been reported in the world, and 40% of them are strumal carcinoid tumor of the ovary (SCTO), which is a highly specialized teratoma differentiated from the monomer, and often characterized by the coexistence of thyroid follicular tissue and carcinoid tissue with the neuroendocrine function. Preoperative diagnosis may be difficult due to the very insidious nature of the disease and its multiple imaging manifestations. We reported the case of a 39-year-old woman with a 5-year clinical history. Gynecologic examination and ultrasonic testing revealed an enlarged ovary with a diameter of about 60 mm, accompanied by a hypoechoic area, which was suspected to be a benign teratoma. Ca-125, AFP, free T4, TSH, and other diagnostic indicators were normal. During the laparoscopic oophorocystectomy of the left ovary, a smooth and solid tumor with the size of 6 × 6 × 5 cm was found in the right ovary. During the operation, a mature cystic teratoma containing a struma was frozen, then the oophorocystectomy of the left ovary was performed. According to the Federation International of Gynecology and Obstetrics (FIGO) in 2014, histopathological examination showed a mature teratoma with thyroid carcinoid stage Ic, and Douglas’s cystic hygroma cytopathology was negative. One year after the operation, the patient was tumor-free, with Ca-125, FT4, and TSH being within the normal range. Specific diagnostic tools and serological monitoring of malignant tumors of the ovary have low specificity and sensitivity in the diagnosis of this rare malignant tumor of the ovary. Female patients with habitual constipation, chronic abdominal colic, diarrhea, and endocrine dysfunction also need to be alert to this rare malignant tumor of the ovary.

Pterostilbene is a derivative of resveratrol with a higher bioavailability and biological activity, which shows antioxidant, anti-inflammatory, antitumor, and antiaging activities. Here, directed evolution and host strain engineering were used to improve the production of pterostilbene in Escherichia coli. First, the heterologous biosynthetic pathway enzymes of pterostilbene, including tyrosine ammonia lyase, p-coumarate: CoA ligase, stilbene synthase, and resveratrol O-methyltransferase, were successively directly evolved through error-prone polymerase chain reaction (PCR). Four mutant enzymes with higher activities of in vivo and in vitro were obtained. The directed evolution of the pathway enzymes increased the pterostilbene production by 13.7-fold. Then, a biosensor-guided genome shuffling strategy was used to improve the availability of the precursor L-tyrosine of the host strain E. coli TYR-30 used for the production of pterostilbene. A shuffled E. coli strain with higher L-tyrosine production was obtained. The shuffled strain harboring the evolved pathway produced 80.04 ± 5.58 mg/l pterostilbene, which is about 2.3-fold the highest titer reported in literatures.

Most animal spinal cord injury models involve a laminectomy, such as the weight drop model or the transection model. However, in clinical practice, many patients undergo spinal cord injury while maintaining a relatively complete spinal canal. Thus, open spinal cord injury models often do not simulate real injuries, and few previous studies have investigated whether having a closed spinal canal after a primary spinal cord injury may influence secondary processes. Therefore, we aimed to assess the differences in neurological dysfunction and pathological changes between rat spinal cord injury models with closed and open spinal canals. Sprague-Dawley rats were randomly divided into three groups. In the sham group, the tunnel was expanded only, without inserting a screw into the spinal canal. In the spinal cord injury with open canal group, a screw was inserted into the spinal canal to cause spinal cord injury for 5 minutes, and then the screw was pulled out, leaving a hole in the vertebral plate. In the spinal cord injury with closed canal group, after inserting a screw into the spinal canal for 5 minutes, the screw was pulled out by approximately 1.5 mm and the flat end of the screw remained in the hole in the vertebral plate so that the spinal canal remained closed; this group was the modified model, which used a screw both to compress the spinal cord and to seal the spinal canal. At 7 days post-operation, the Basso-Beattie-Bresnahan scale was used to measure changes in neurological outcomes. Hematoxylin-eosin staining was used to assess histopathology. To evaluate the degree of local secondary hypoxia, immunohistochemical staining and western blot assays were applied to detect the expression of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF). Compared with the spinal cord injury with open canal group, in the closed canal group the Basso-Beattie-Bresnahan scores were lower, cell morphology was more irregular, the percentage of morphologically normal neurons was lower, the percentages of HIF-1α- and VEGF-immunoreactive cells were higher, and HIF-1α and VEGF protein expression was also higher. In conclusion, we successfully established a rat spinal cord injury model with closed canal. This model could result in more serious neurological dysfunction and histopathological changes than in open canal models. All experimental procedures were approved by the Institutional Animal Care Committee of Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, China (approval No. HKDL201810) on January 30, 2018.

Purpose. The study aims to investigate the formation composition and structural-formation zoning of the Late Paleozoic continental volcanic and volcano-sedimentary formations of the Junggar-Balkhash fold system (JBFS). It also seeks to define the geological-geophysical characteristics and metallogenic specialization of the volcanic-plutonic belts (VPB) in the region. Methods. The research utilizes data from detailed mapping and analysis of Late Paleozoic magmatites in JBFS over the past 10-40 years. Structural-formation zoning of the region was performed from an actualistic perspective, along with the formation typification of stratified and intrusive ore formations. The study of metallogenic specialization was conducted considering modern geophysical research methods. Findings. Two main volcanic-plutonic belts have been identified: the Carboniferous marginal-continental Tasty-KusakKotyryasan-Altunemel Belt and the Carboniferous-Permian intracontinental Balkhash-Ili Belt, which together cover about 80% of the JBFS territory. The geological-geophysical characteristics and metallogenic specialization of these belts have been defined. In particular, the findings highlight significant prospects for epithermal gold-silver and copper-porphyry mineralization. Originality. For the first time, a structural-formation zoning of JBFS has been conducted, and the typification of volcanic Plutonic Belts has been substantiated. Additionally, their metallogenic specialization has been determined, revealing patterns of localization for epithermal gold-silver and copper-porphyry deposits. Practical implications. The study’s results are of great importance for exploration geology, contributing to the improved efficiency of searching for ore deposits in the region, particularly epithermal gold-silver and copper-porphyry targets. [ABSTRACT FROM AUTHOR]

Abstract Background Escherichia coli is one of the most common strains of extended-spectrum β-lactam (ESBL)-producing bacteria, and the prevention and treatment of ESBL-producing E. coli infections is an ongoing challenge. The clinical characteristics and outcomes of ESBL-producing E. coli bacteremia in non-transplant patients remain to be elucidated. Methods This retrospective study included 491 non-transplant patients with E. coli bloodstream infections (BSIs) from January 2013 to December 2016 and was conducted to investigate the risk factors, clinical features, and outcomes of these infections. Results Of the 491 E. coli BSI patients, 57.6% suffered from infections with ESBL-producing strains. A multivariate analysis showed that urinary tract infection, prior use of cephalosporin, and treatment with β-lactam-β-lactamase inhibitor (BLBLI) combination antibiotics were independent risk factors for the development of ESBL-producing E. coli BSIs. The overall mortality rate in E. coli BSI patients was 14.46%, and there was no significant difference in the 28 day mortality rate between ESBL-producing E. coli and non-ESBL-producing E. coli BSI patients (14.8% vs. 14.0%, respectively; P = 0.953). Similarly, there was no difference between the community-acquired infection group and the nosocomial infection group. Hepatobiliary disease, carbapenem exposure, high APACHE II score, and hypoproteinemia were independent risk factors for death in E. coli BSI patients. Multivariate analysis showed that hypoproteinemia and severe disease were independent risk factors for death from ESBL-producing E. coli BSIs. Furthermore, there was no significant difference in the 28 day mortality between patients with ESBL-producing E. coli BSIs treated with carbapenem monotherapy versus those treated with BLBLI combination antibiotics (12.8% vs. 17.9%, respectively; P = 0.384). Conclusions Prior use of cephalosporin or BLBLI combination antibiotics increased the risk ratio for ESBL-producing E. coli infection. Hypoproteinemia and severe disease are independent risk factors for death in patients with E. coli BSIs. There was no significant difference in the 28 day prognosis of patients with ESBL-producing E. coli and those with non-ESBL-producing E. coli BSIs. These data do not support the conclusion that carbapenems might be more effective than BLBLI antibiotics for treatment of patients with BSIs caused by ESBL-producing E. coli.

The aim of this study is to discuss the non-catechin flavonoids (NCF) from Camellia sinensis (L.) O. Kuntze seed improving TNF-α impaired insulin stimulated glucose uptake and insulin signaling. Flavonoids had anti-metabolic syndrome and anti-inflammatory properties. It had widely been known for biological activity of catechins in tea, but very few research reports discussed the biological activity of non-catechin flavonoids in tea seed. We used HepG2 cell to treat with 5 μM insulin or with 5 μM insulin + 30 ng/ml TNF-α. Detecting the glucose concentration of medium, insulin decreased the glucose levels of medium meant that insulin promoted glucose uptake into cells, but TNF-α inhibited the glucose uptake effect of insulin. Furthermore, insulin increased the protein expressions of IR, IRS-1, IRS-2, PI3K-α, Akt/PKB, GLUT-2, AMPK, GCK, pyruvate kinase, and PPAR-γ. TNF-α activated p65 and MAPKs (p38, JNK1/2 and ERK1/2), iNOS and COX-2 which worsened the insulin signaling expressions of IR, IRS-1, IRS-2, PI3K-α, Akt/PKB, GLUT-2, AMPK, GCK, pyruvate kinase, and PPAR-γ. We added NCF (500, 1000, 2000 ppm) to cell with insulin and TNF-α. Not only glucose levels of medium were lowered, and the protein expressions of insulin signaling were increased, but p38, JNK1/2, iNOS and COX-2 were also reduced. NCF could ameliorate TNF-α induced insulin resistance through inhibiting p38, JNK1/2, iNOS and COX-2, and suggested that it might be used in the future to help control insulin resistance. This finding is the first report to present the discovery. Keywords: Flavonoids, Camellia sinensis (L.) O. Kuntze seed, TNF-α, Insulin resistance

Adult Chrysoperla sinica Tjeder is a common pollen feeder in maize fields. They are thus directly exposed to insecticidal proteins by consumption of genetically engineered maize pollen containing Bacillus thuringiensis (Bt) proteins. Here we assessed the potential effects of Cry1Ab/2Aj- or Cry1Ac-containing Bt maize pollen on the fitness of adult C. sinica via a dietary-exposure assay under laboratory conditions. Survival, pre-oviposition, fecundity and adult dry weight did not differ between adult C. sinica consuming Bt or the corresponding non-Bt maize pollen. The stability of the Cry protein in the food sources and uptake of the Cry protein by adult C. sinica during the feeding experiment were confirmed by ELISA. These results demonstrate that adult C. sinica are not affected by the consumption of Cry1Ab/2Aj- or Cry1Ac-containing maize pollen, suggesting that production of Bt maize expressing cry1Ab/2Aj or cry1Ac genes will pose a negligible risk to adult C. sinica.