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ObjectivesTigecycline is recognized as one of the last-line antibiotics to treat serious bacterial infection caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). The plasmid-borne gene tet(X4) mediates high resistance to tigecycline. However, the prevalence and genetic context of tet(X4) in K. pneumoniae from various sources are not fully understood. Here, we investigated the prevalence of tet(X4)-positive K. pneumoniae and characterized the genetic context of tet(X4)-bearing plasmids in K. pneumoniae isolates.MethodsPolymerase chain reaction (PCR) was used to detect the tet(X4) gene. The transferability of the tet(X4)-carrying plasmids was tested by conjugation assays. The Galleria mellonella infection model was used to test virulence of tet(X4)-positive strains. Whole-genome sequencing and genome-wide analysis were performed to identify the antimicrobial resistance and the virulence genes, and to clarify the genetic characteristics of the tet(X4)-positive isolates.ResultsAmong 921 samples, we identified two tet(X4)-positive K. pneumoniae strains collected from nasal swabs of two pigs (0.22%, 2/921). The two tet(X4)-positive isolates exhibited high minimum inhibitory concentrations to tigecycline (32–256 mg/L) and tetracycline (256 mg/L). The plasmids carrying the tet(X4) gene can transfer from the donor strain K. pneumoniae to the recipient strain Escherichia coli J53. Genetic analysis of the complete sequence of two tet(X4)-carrying plasmids pTKPN_3-186k-tetX4 and pTKPN_8-216k-tetX4 disclosed that the tet(X4) gene was flanked by delta ISCR2 and IS1R, which may mediate the transmission of the tet(X4) gene.ConclusionThe prevalence of tet(X4)-positive K. pneumoniae among different sources was low. ISCR2 and IS1R may contribute to the horizontal transfer of tet(X4) gene. Effective measures should be taken to prevent the transmission of tet(X4)-producing K. pneumoniae in humans or animals.

Bacterial infections, especially those caused by multidrug‐resistant pathogens, pose a significant threat to public health. Vaccines are a crucial tool in fighting these infections; however, no clinically available vaccine exists for the most common bacterial infections, such as those caused by Pseudomonas aeruginosa. Herein, a multiantigenic antibacterial nanovaccine (AuNP@HMV@SPs) is reported to combat P. aeruginosa infections. This nanovaccine utilizes the hybrid membrane vesicles (HMVs) created by fusing macrophage membrane vesicles (MMVs) with bacterial outer membrane vesicles (OMVs). The HMVs mitigate the toxic effects of both OMVs and bacterial secreted toxins (SP) adsorbed on the surface of MMVs, while preserving their stimulating properties. Gold nanoparticles (AuNPs) are utilized as adjuvant to enhance immune response without comprising safety. The nanovaccine AuNP@HMV@SPs induces robust humoral and cellular immune responses, leading to destruction of bacterial cells and neutralization of their secreted toxins. In murine models of septicemia and pneumonia caused by P. aeruginosa, AuNP@HMV@SPs exhibits superior prophylactic efficacy compared to control groups including OMVs, or MMVs@SPs and HMV@SPs, achieving 100% survival in septicemia and > 99.9% reduction in lung bacterial load in pneumonia. This study highlights AuNP@HMV@SPs as a safe and effective antibacterial nanovaccine, targeting both bacteria and their secreted toxins, and offers a promising platform for developing multiantigenic antibacterial vaccines against multidrug‐resistant pathogens. [ABSTRACT FROM AUTHOR]

In this paper, we are interested in propagation dynamics of a nonlocal dispersal Zika transmission model with general incidence. When the threshold R$$ \mathcal{R} $$ is greater than one, we prove that there is a wave speed c∗>0$$ {c}^{\ast }>0 $$ such that the model has a traveling wave solution with speed c>c∗$$ c>{c}^{\ast } $$, and there is no traveling wave solution with speed less than c∗$$ {c}^{\ast } $$. When the threshold R$$ \mathcal{R} $$ is less than or equal to one, we show that there is no nontrivial traveling wave solution. The approaches we use here are Schauder's fixed point theorem with an explicit construction of a pair of upper and lower solutions, the contradictory approach, and the two‐sided Laplace transform. [ABSTRACT FROM AUTHOR]

Secondary flowering is the phenomenon in which a tree blooms twice or more times a year. Along with the development of blueberry (Vaccinium corymbosum L.) fruits in spring, a large number of secondary flowers on the strong upright spring shoots were noticed in blueberries planted in the greenhouse. To reveal the cause and possible regulatory mechanism of the phenomenon, we clarified the phenological characteristics of flower bud differentiation and development on the spring shoots by combining phenological phenotype with anatomical observation. Furthermore, the changes in carbohydrates, trehalose-6-phosphate (Tre6P), and the relationship among the key enzyme regulatory genes for Tre6P metabolism and the key regulatory genes for flower formation during the differentiation process of apical buds and axillary buds were investigated. The results showed that the process of flower bud differentiation and flowering of apical and axillary buds was consistent, accompanied by a large amount of carbohydrate consumption. This process was positively correlated with the expression trends of VcTPS1/2, VcSnRK1, VcFT, VcLFY2, VcSPL43, VcAP1, and VcDAM in general, and negatively correlated with that of VcTPP. In addition, there is a certain difference in the differentiation progress of flower buds between the apical and axillary buds. Compared with axillary buds, apical buds had higher contents of sucrose, fructose, glucose, Tre6P, and higher expression levels of VcTPS2, VcFT, VcSPL43, and VcAP1. Moreover, VcTPS1 and VcTPS2 were more closely related to the physiological substances (sucrose and Tre6P) in axillary bud and apical bud differentiation, respectively. It was suggested that sucrose and trehalose-6-phosphate play a crucial role in promoting flower bud differentiation in strong upright spring shoots, and VcTPS1 and VcTPS2 might play a central role in these activities. Our study provided substantial sight for further study on the mechanism of multiple flowering of blueberries and laid a foundation for the regulation and utilization of the phenomenon of multiple flowering in a growing season of perennial woody plants. [ABSTRACT FROM AUTHOR]

Accurate prediction of individual mobility is crucial for developing intelligent transportation systems. However, while previous models usually focused on predicting individual mobility under ordinary conditions, the models that are applicable to large crowding events are still lacking. Here, we employ the smart card data of 6.5 million subway passengers of the Shenzhen Metro to develop a Markov chain-based individual mobility prediction model (i.e., SCMM) applicable to both ordinary and anomalous passenger flow situations. The proposed SCMM model improves the Markov chain model by incorporating the station-level anomalous passenger flow index and the collective mobility patterns of similar passengers. Compared with the benchmark models, the SCMM model achieves the highest prediction accuracy in both ordinary conditions and large crowding events. Our results highlight the importance of combining an individual's own historical mobility data with collective mobility data and suggest the appropriate weights of individual and collective information considered in individual mobility modeling., Author(s): Bao Guo [1]; Kaipeng Wang [1]; Hu Yang [1]; Fan Zhang [2]; Pu Wang (corresponding author) [1] 1. Introduction An in-depth understanding of individual human mobility is of significant [...]

The shear deformation of rock joints is significant for the safety and stability of rock engineering. In order to study the constitutive relation of shear deformation in jointed rock mass under a normal stress, the direct shear tests under different normal stresses were carried out on the sandstone specimens with irregular joints using the RDS-200 rock direct shear test system. Based on the shear stress−deformation curve of the jointed rock, it can be divided into four stages including pre-peak compaction stage, linear stage, yield stage and post-peak softening stage. The post-peak softening stage can be further divided into three types including platform type, gradual decline type and drop type based on the decreasing magnitude and rate of shear stress at the post-peak period. The shear deformation constitutive model of the sandstone with irregular joints was established using piecewise function based on the shear deformation characteristics at different stages. Compared with the existing constitutive models, the new proposed shear deformation constitutive model of the jointed rock mass has a much higher fitting accuracy for the experimental results, which can better describe the deformation characteristics of the jointed rock in the whole shear process. The shear stress−shear displacement curve of irregular joints with different roughness coefficients under different normal stresses can be predicted after determining the relevant model parameters in the corresponding empirical formula after some direct shear tests. The research is practical for understanding the shear deformation of joints in rocks by numerical simulation and the safety evaluation of engineering.

Abstract Background Carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) causes serious infections with significant morbidity and mortality. However, the epidemiology and transmission mechanisms of CR-hvKP and the corresponding carbapenem-resistant plasmids require further investigation. Herein, we have characterized an ST11 K. pneumoniae strain EBSI041 from the blood sample encoding both hypervirulence and carbapenem resistance phenotypes from a patient in Egypt. Results K. pneumoniae strain EBSI041 showed multidrug-resistance phenotypes, where it was highly resistant to almost all tested antibiotics including carbapenems. And hypervirulence phenotypes of EBSI041 was confirmed by the model of Galleria mellonella infection. Whole-genome sequencing analysis showed that the hybrid plasmid pEBSI041-1 carried a set of virulence factors rmpA, rmpA2, iucABCD and iutA, and six resistance genes aph(3′)-VI, armA, msr(E), mph(E), qnrS, and sul2. Besides, bla OXA-48 and bla SHV-12 were harboured in a novel conjugative IncL-type plasmid pEBSI041-2. The bla KPC-2-carrying plasmid pEBSI041-3, a non-conjugative plasmid lacking the conjugative transfer genes, could be transferred with the help of pEBSI041-2, and the two plasmids could fuse into a new plasmid during co-transfer. Moreover, the emergence of the p16HN-263_KPC-like plasmids is likely due to the integration of pEBSI041-3 and pEBSI041-4 via IS26-mediated rearrangement. Conclusion To the best of our knowledge, this is the first report on the complete genome sequence of KPC-2- and OXA-48-coproducing hypervirulent K. pneumoniae from Egypt. These results give new insights into the adaptation and evolution of K. pneumoniae during nosocomial infections.

Abstract Background Mobile colistin resistance like gene (mcr-like gene) is a new type of polymyxin resistance gene that can be horizontally transferred in the Enterobacteriaceae. This has brought great challenges to the treatment of multidrug-resistant Escherichia coli and K. pneumoniae. Results K. pneumoniae 16BU137 and E. coli 17MR471 were isolated from the bus and subway handrails in Guangzhou, China. K. pneumoniae 19PDR22 and KP20191015 were isolated from patients with urinary tract infection and severe pneumonia in Anhui, China. Sequence analysis indicated that the mcr-1.1 gene was present on the chromosome of E. coli 17MR471, and the gene was in the gene cassette containing pap2 and two copies of ISApl1.The mcr-1.1 was found in the putative IncX4 type plasmid p16BU137_mcr-1.1 of K. pneumoniae 16BU137, but ISApl1 was not found in its flanking sequence. Mcr-8 variants were found in the putative IncFIB/ IncFII plasmid pKP20191015_mcr-8 of K. pneumoniae KP20191015 and flanked by ISEcl1 and ISKpn26. Conclusion This study provides timely information on Enterobacteriaceae bacteria carrying mcr-like genes, and provides a reference for studying the spread of mcr-1 in China and globally.

Summary: The nucleus accumbens (NAc) plays an important role in motivation and reward processing. Recent studies suggest that different NAc subnuclei differentially contribute to reward-related behaviors. However, how reward is encoded in individual NAc neurons remains unclear. Using in vivo single-cell resolution calcium imaging, we find diverse patterns of reward encoding in the medial and lateral shell subdivision of the NAc (NAcMed and NAcLat, respectively). Reward consumption increases NAcLat activity but decreases NAcMed activity, albeit with high variability among neurons. The heterogeneity in reward encoding could be attributed to differences in their synaptic inputs and transcriptional profiles. Specific optogenetic activation of Nts-positive neurons in the NAcLat promotes positive reinforcement, while activation of Cartpt-positive neurons in the NAcMed induces behavior aversion. Collectively, our study shows the organizational and transcriptional differences in NAc subregions and provides a framework for future dissection of NAc subregions in physiological and pathological conditions.

BackgroundCardiac surgery–associated acute kidney injury (CSA-AKI) is a major complication following pediatric cardiac surgery, which is associated with increased morbidity and mortality. The early prediction of CSA-AKI before and immediately after surgery could significantly improve the implementation of preventive and therapeutic strategies during the perioperative periods. However, there is limited clinical information on how to identify pediatric patients at high risk of CSA-AKI. ObjectiveThe study aims to develop and validate machine learning models to predict the development of CSA-AKI in the pediatric population. MethodsThis retrospective cohort study enrolled patients aged 1 month to 18 years who underwent cardiac surgery with cardiopulmonary bypass at 3 medical centers of Central South University in China. CSA-AKI was defined according to the 2012 Kidney Disease: Improving Global Outcomes criteria. Feature selection was applied separately to 2 data sets: the preoperative data set and the combined preoperative and intraoperative data set. Multiple machine learning algorithms were tested, including K-nearest neighbor, naive Bayes, support vector machines, random forest, extreme gradient boosting (XGBoost), and neural networks. The best performing model was identified in cross-validation by using the area under the receiver operating characteristic curve (AUROC). Model interpretations were generated using the Shapley additive explanations (SHAP) method. ResultsA total of 3278 patients from one of the centers were used for model derivation, while 585 patients from another 2 centers served as the external validation cohort. CSA-AKI occurred in 564 (17.2%) patients in the derivation cohort and 51 (8.7%) patients in the external validation cohort. Among the considered machine learning models, the XGBoost models achieved the best predictive performance in cross-validation. The AUROC of the XGBoost model using only the preoperative variables was 0.890 (95% CI 0.876-0.906) in the derivation cohort and 0.857 (95% CI 0.800-0.903) in the external validation cohort. When the intraoperative variables were included, the AUROC increased to 0.912 (95% CI 0.899-0.924) and 0.889 (95% CI 0.844-0.920) in the 2 cohorts, respectively. The SHAP method revealed that baseline serum creatinine level, perfusion time, body length, operation time, and intraoperative blood loss were the top 5 predictors of CSA-AKI. ConclusionsThe interpretable XGBoost models provide practical tools for the early prediction of CSA-AKI, which are valuable for risk stratification and perioperative management of pediatric patients undergoing cardiac surgery.

The fat-related enzymes of whole wheat flour cause the increase in fatty acid value, the tallowiness of whole wheat flour and the higher microbial count. This seriously affects the shelf life of whole wheat flour and restricts the circulation and sales of whole wheat flour. In this study, the key physical and chemical indicators, as well as microbial count of several commercially available whole wheat flours are analyzed and compared. The results show that after 3 months of storage, the fatty acid values of the whole wheat flour are close to or slightly higher than the industry standard requirements. The bran prepared in laboratory was treated with atmospheric steam at different times. The results showed that after 10 minutes of steaming treatment, the total plate count in the bran decreased from 2.2×105 CFU/g to 1.4×102 CFU/g, and the spores count decreased from 1.2 ×103 CFU/g to 1.1×102 CFU/g. After 20 minutes of atmospheric steaming treatment,the total plate count and spores decreased to less than 100 CFU/g. Atmospheric steaming treatment for 10 minutes can inactivate the bran lipase and lipoxygenase by 90% and 80%, respectively. The whole wheat flour was prepared by adding bran that has been steamed for 10 minutes back to the flour. Based on the results of whole wheat flour shelf life test, we therefore conclude that the shelf life of whole wheat flour is at least 16～17 months.

AIM: To compare the differences and agreement in axial length(AL), anterior chamber depth(ACD)flat axial corneal curvature(K1)and steep axial corneal curvature(K2)measured by SW-9000 and IOL Master 500.METHODS: Totally 258 eyes of 129 patients with ametropia were measured with SW-9000 and IOL Master 500. Among them, 159 eyes were low to moderate myopia(-0.75D≤ spherical equivalent 0.05), but there was significant difference in K2(P

PURPOSEHepatocellular carcinoma (HCC) usually occurs accompanied by portal hypertension. Transcatheter arterial chemoembolization (TACE) is recommended as an effective treatment in HCC. Recent studies had conflicting results regarding the effectiveness and safety of TACE for HCC in patients with transjugular intrahepatic portosystemic shunt (TIPS). This meta-analysis aimed to evaluate the influence of TIPS on the effectiveness and safety of TACE for patients with HCC.METHODSA comprehensive search of studies among PubMed, Web of Science and Cochrane Library was conducted, from the earliest publishing date to January 27th, 2020. Statistical analyses were all performed using the Stata 13.0 software. I2 index statistic was used to assess heterogeneity.RESULTSSix studies with a total of 536 patients with HCC were included in the analysis. The pooled response rate was 51% (95% CI: 25% to 77%) with a significant heterogeneity (I2=93.3%, p < 0.001). The TACE + TIPS group had an inferior response rate than the non-TIPS group, but the difference had no statistical significance (p = 0.171) and heterogeneity was low (I2=0.00%, p = 0.490). Pooled hepatic failure rate was 8.8% (95% CI: 5.2% to 12.4%) with low heterogeneity (I2=0.0%, p = 0.747). But the pooled hepatic failure rate increased to 12.7% (95% CI: 5.7% to 19.7%) with low heterogeneity (I2=11.5%, p = 0.323) if the patients who received TIPS after TACE were excluded.CONCLUSIONTIPS does not influence the effectiveness of TACE, but attention should be paid to the risk of hepatic failure.