Global emergence of double and multi-carbapenemase producing organisms: epidemiology, clinical significance, and evolutionary benefits on antimicrobial resistance and virulence.

Redundant carbapenemase-producing (RCP) bacteria, which carry double or multiple carbapenemases, represent a new and concerning phenomenon. The objective of this study is to conduct a comprehensive analysis of the epidemiology and genetic mechanisms of RCP strains to support targeted surveillance and control measures. A retrospective analysis was conducted using surveillance data from 277 articles. Statistical analysis was performed to determine and evaluate species prevalence, proportions of carbapenemases, antibiotic susceptibility profiles, sample information, and patient outcomes. Complete plasmid sequencing data were utilized to investigate potential antimicrobial resistance or virulence advantages that strains may gain from acquiring redundant carbapenemases. RCP bacteria are widely distributed globally, and their prevalence is increasing over time. Several countries, including China, India, Iran, Turkey, and South Korea, have reported more than 100 RCP strains. The most commonly reported RCP species are Klebsiella pneumoniae and Acinetobacter baumannii, which exhibit varying proportions of carbapenemase combinations. Certain species-carbapenemase combinations, such as K. pneumoniae carrying New Delhi metallo-ß-lactamase (NDM) + oxacillinase (OXA) (56.76%) and K. pneumoniae carbapenemase (KPC) + Verona integron-encoded metallo-ß-lactamase (VIM) (50.00%) carbapenemases, are associated with high mortality rates. In patients with RCP strains isolated from the bloodstream and respiratory system, the mortality rates are 58.70% and 69.23%, respectively. Analysis of plasmids from RCP strains suggests that they may acquire additional antibiotic resistance phenotypes and virulence factors. Carbapenem-resistant bacteria carrying redundant carbapenemases pose a significant global health threat. This study provides valuable insights into the epidemiology and genetic mechanisms of these bacteria, supporting the development of effective control and prevention strategies to mitigate their transmission.IMPORTANCEThis study examined the global distribution patterns of 1,780 bacteria with double or multiple carbapenemases from 277 articles and assessed their clinical impact. The presence of multiple carbapenemases increases the chances of co-resistance to other classes of antibiotics and more virulence factors, further complicating the clinical management of infections.

MFTR-Net: A Multi-Level Features Network with Targeted Regularization for Large-Scale Point Cloud Classification.

There are some irregular and disordered noise points in large-scale point clouds, and the accuracy of existing large-scale point cloud classification methods still needs further improvement. This paper proposes a network named MFTR-Net, which considers the local point cloud's eigenvalue calculation. The eigenvalues of 3D point cloud data and the 2D eigenvalues of projected point clouds on different planes are calculated to express the local feature relationship between adjacent point clouds. A regular point cloud feature image is constructed and inputs into the designed convolutional neural network. The network adds TargetDrop to be more robust. The experimental result shows that our methods can learn more high-dimensional feature information, further improving point cloud classification, and our approach can achieve 98.0% accuracy with the Oakland 3D dataset.

Transcription factors TP63 facilitates malignant progression of thyroid cancer by upregulating KRT17 expression and inducing epithelial-mesenchymal transition.

Thyroid cancer (TC) is a relatively prevalent endocrine tumor among women, the incidence of which is rapidly rising. In this present study, we aimed to provide new therapeutic targets from the aspect of transcription factor-target gene interaction. TP63 and KRT17 were both highly expressed in TC tissues and cells. The results of ChIP and dual-luciferase assays confirmed TP63 to bind the KRT17 promoter. Cell function assays revealed that knockdown of TP63 could repress TC cell progression. Furthermore, the rescue assay verified that TP63 could facilitate KRT17 expression to activate the AKT signaling pathway, which in turn stimulated TC cell invasion and migration, and induced EMT. All these results verified that TP63 facilitates TC malignant progression by promoting KRT17 expression and inducing EMT.

SA-FEM: Combined Feature Selection and Feature Fusion for Students' Performance Prediction.

Around the world, the COVID-19 pandemic has created significant obstacles for education, driving people to discover workarounds to maintain education. Because of the excellent benefit of cheap-cost information distribution brought about by the advent of the Internet, some offline instructional activity started to go online in an effort to stop the spread of the disease. How to guarantee the quality of teaching and promote the steady progress of education has become more and more important. Currently, one of the ways to guarantee the quality of online learning is to use independent online learning behavior data to build learning performance predictors, which can provide real-time monitoring and feedback during the learning process. This method, however, ignores the internal correlation between e-learning behaviors. In contrast, the e-learning behavior classification model (EBC model) can reflect the internal correlation between learning behaviors. Therefore, this study proposes an online learning performance prediction model, SA-FEM, based on adaptive feature fusion and feature selection. The proposed method utilizes the relationship among features and fuses features according to the category that achieved better performance. Through the analysis of experimental results, the feature space mined by the fine-grained differential evolution algorithm and the adaptive fusion of features combined with the differential evolution algorithm can better support online learning performance prediction, and it is also verified that the adaptive feature fusion strategy based on the EBC model proposed in this paper outperforms the benchmark method.

Silibinin induces G1 arrest, apoptosis and JNK/SAPK upregulation in SW1990 human pancreatic cancer cells.

The aim of the present study was to investigate the inhibitory effect of silibinin on SW1990 pancreatic cancer cells. An MTT assay following silibinin treatment demonstrated an inhibitory effect on AsPC-1 and SW1990 cells in a dose- and time-dependent manner. Propidium iodide staining analysis identified the cell cycle arrest of G1 phase and western blotting analysis demonstrated that the expression levels of cyclin D1, cyclin E2, cyclin A and cyclin B1 were decreased. The expression of G1-associated cell cycle-dependent kinases, cyclin-dependent kinase (CDK)4 and CDK6, were also decreased, whereas the expression of p15 (p15INK4B) was increased. In addition, after SW1990 cells were incubated with various concentrations of silibinin, early and late apoptotic cells were detected using flow cytometry. Silibinin increased the activities of caspase-9 and caspase-3, and subsequent cleavage of poly (ADP-ribose) polymerase (PARP) was also observed. The expression levels of B-cell lymphoma (Bcl)-2, Bcl-2-like 1 and myeloid cell leukemia 1 were decreased, whereas the expression of Bcl-like protein 4 did not alter and the expression levels of Bcl-2-like 1 small and Bcl-2-like protein 11 were increased. The expression levels of c-Jun N-terminal kinase (JNK) and phospho-JNK were also increased. In conclusion, silibinin inhibited cell proliferation, induced cell cycle G1 arrest via upregulating p15INK4B and induced mitochondrial apoptosis via upregulating JNK/stress-activated protein kinase (SAPK) signaling pathway in human pancreatic cancer SW1990 cells.

Norcantharidin Inhibits SK-N-SH Neuroblastoma Cell Growth by Induction of Autophagy and Apoptosis.

Norcantharidin, a low-toxic analog of the active anticancer compound cantharidin in Mylabris, can inhibit proliferation and induce apoptosis of multiple types of cancer cells. However, the anticancer activities of norcantharidin with respect to neuroblastoma, and its underlying mechanisms, have not been investigated. Therefore, our study was designed to determine the efficacy of norcantharidin on SK-N-SH neuroblastoma cell death and to elucidate detailed mechanisms of activity. In the present study, norcantharidin suppressed the proliferation and cloning ability of SK-N-SH cells in a dose-dependent manner, apparently by reducing the mitochondrial membrane potential and arresting SK-N-SH cells at the G2/M stage, accompanied by elevated expressions of p21 and decreased expressions of cyclin B1 and cell division control 2. Treatment by norcantharidin induced significant mitophagy and autophagy, as demonstrated by a decrease in Translocase Of Outer Mitochondrial Membrane 20 (TOM20), increased beclin1 and LC3-II protein expression, reduced protein SQSTM1/p62 expression, and accumulation of punctate LC3 in the cytoplasm of SK-N-SH cells. In addition, norcantharidin induced apoptosis through regulating the expression of B-cell lymphoma 2-associated X protein/B-cell lymphoma 2 and B-cell lymphoma 2-associated X protein/myeloid cell leukemia 1 and activating caspase-3 and caspase-9-dependent endogenous mitochondrial pathways. We also observed an increase in phosphor-AMP-activated protein kinase accompanied with a decrease in phosphor-protein kinase B and mammalian target of rapamycin expression after treatment with norcantharidin. Subsequent studies indicated that norcantharidin participates in cellular autophagy and apoptosis via activation of the c-Jun NH2-terminal kinases/c-Jun pathway. In conclusion, our results demonstrate that norcantharidin can reduce the mitochondrial membrane potential, induce mitophagy, and subsequently arouse cellular autophagy and apoptosis; the AMP-activated protein kinase, protein kinase B/mammalian target of rapamycin, and c-Jun NH2-terminal kinases/c-Jun signaling pathways are widely involved in these processes. Thus, the traditional Chinese medicine norcantharidin could be a novel therapeutic strategy for treating neuroblastoma.