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Ziran Wang,1 Jintu Chen,2 Jingjing Song,3 Lingjun Kong,1 Xuanzhi Wang,4 Tengda Xu,5 Songbai Lin,5 Yaling Dou1 1Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Clinical Laboratory, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian, People’s Republic of China; 3Department of Clinical Laboratory, Anhui Provincial Maternal and Child Health Hospital, Hefei, Anhui, People’s Republic of China; 4Department of Medical Laboratory, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 5Department of Health Management, Peking Union Medical College Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yaling Dou, Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China, Email douyl@pumch.cnObjective: To determine the plasminogen activator inhibitor-1 (PAI-1) 4G/5G (rs1799889) genotype of the subjects in a robust detection method and to explore the association of the PAI-1 4G/5G polymorphism with susceptibility to diabetes mellitus (DM) and hypertension (HTN) as well as clinical characteristics.Methods: This study recruited 208 patients (68 patients were diagnosed with DM, 70 patients with HTN and 70 patients with DM combined with HTN) and 132 healthy controls (HC). A subset of the population was selected to evaluate the accuracy of the Real-time PCR (RT-PCR) method for detecting PAI-1 4G/5G polymorphism by using the sequencing method as the gold standard. Furthermore, the association of the PAI-1 4G/5G polymorphism with genetic susceptibility to DM and HTN was explored. Moreover, variations in clinical characteristics among individuals with various PAI-1 genotypes were also analyzed in the DM group, the HTN group and the DM+HTN group.Results: There was a high concordance between the RT-PCR method and the sequencing method in determining the PAI-1 4G/5G polymorphism. No association was observed between the PAI-1 4G/5G polymorphism and susceptibility to DM, HTN and DM+HTN, respectively. There were no statistical differences in all study indicators among individuals that carrying various genotypes in the HC group. There were several variations in clinical characteristics among individuals harboring different PAI-1 4G/5G genotypes in the DM group, the HTN group and the DM+HTN group.Conclusion: The RT-PCR method can accurately identify the PAI-1 4G/5G genotype in different individuals. The PAI-1 4G/5G polymorphism may not be associated with genetic susceptibility to DM, HTN and DM+HTN, but differences in clinical characteristics among individuals with various genotypes may provide a reference for disease assessment and personalized treatment of patients.Keywords: diabetes mellitus, hypertension, plasminogen activator inhibitor-1, gene polymorphism

There are approximately 2.2 billion people around the world with varying degrees of visual impairments. Among them, individuals with severe visual impairments predominantly rely on hearing and touch to gather external information. At present, there are limited reading materials for the visually impaired, mostly in the form of audio or text, which cannot satisfy the needs for the visually impaired to comprehend graphical content. Although many scholars have devoted their efforts to investigating methods for converting visual images into tactile graphics, tactile graphic translation fails to meet the reading needs of visually impaired individuals due to image type diversity and limitations in image recognition technology. The primary goal of this paper is to enable the visually impaired to gain a greater understanding of the natural sciences by transforming images of mathematical functions into an electronic format for the production of tactile graphics. In an effort to enhance the accuracy and efficiency of graph element recognition and segmentation of function graphs, this paper proposes an MA Mask R-CNN model which utilizes MA ConvNeXt as its improved feature extraction backbone network and MA BiFPN as its improved feature fusion network. The MA ConvNeXt is a novel feature extraction network proposed in this paper, while the MA BiFPN is a novel feature fusion network introduced in this paper. This model combines the information of local relations, global relations and different channels to form an attention mechanism that is able to establish multiple connections, thus increasing the detection capability of the original Mask R-CNN model on slender and multi-type targets by combining a variety of multi-scale features. Finally, the experimental results show that MA Mask R-CNN attains an 89.6% mAP value for target detection and 72.3% mAP value for target segmentation in the instance segmentation of function graphs. This results in a 9% mAP improvement for target detection and 12.8% mAP improvement for target segmentation compared to the original Mask R-CNN.

IRF4 is a master member of the interferon regulatory factor (IRF) family playing vital regulatory roles in immune system development and function. Tetrapods have a single-copy IRF4 gene, while teleosts harbor duplicated IRF4 genes. This work describes three IRF4 paralogs from yellow catfish (Pelteobagrus fulvidraco), designated PfIRF4A, PfIRF4B and PfIRF4B-like. These genes all contain a typical IRF structural architecture. Phylogenic and synteny analyses indicate that they should arise from the teleost-specific whole-genome duplication. PfIRF4 genes are abundantly expressed in the immune-related tissues and upregulated by PolyI:C, LPS, and Edwardsiella ictaluri. Ectopic expression of these genes inhibits the activation of fish type Ⅰ IFN promoters and downregulates the transcription levels of IFN-responsive genes, thus allowing the efficient replication of a fish rhabdovirus, spring viremia of carp virus (SVCV). PfIRF4s possess a repressive effect on MyD88-mediated activation of IFN and NF-κB. Some differences are observed between each individual paralog. PfIRF4B is the main form expressed across the tissues and the most up-regulated one after pathogen induction. It exerts a stronger inhibitory effect on IFN antiviral response than the other two paralogs. PfIRF4A and PfIRF4B-like are primarily present in the nucleus, while PfIRF4B displays colocalization and direct associations with MyD88 in the cytoplasm. Overall, the data demonstrate that three PfIRF4 paralogs show shared and individual functional properties in the negative regulation of type Ⅰ IFN response.

Hollow materials derived from metal-organic frameworks (MOFs) have emerged in the biomedical field due to their unique properties, and different synthesis methods have been proposed. However, so far, the large-scale use of hollow MOFs is mostly limited by the timeliness of synthesis methods. Herein, we propose a new ultrasonic aerosol flow strategy for the instantaneous synthesis of a Zr-MOF-derived hollow sphere complex (ZC-HSC) in only one step. Through rapid transient heating, the coordination between metal salts and organic ligands occurs along with prompt evaporation of the solvent. The whole process lasts for only about 21 s, compared with several steps that take hours or even days for conventional synthesis methods. Based on the ZC-HSC, we designed a nanodrug with the functions of manipulating the tumor microenvironment, which can reshape the tumor microenvironment by improving tumor hypoxia and inflammatory microenvironment and promoting antiangiogenic therapy. Combined with microwave thermo-chemotherapy, the nanodrugs effectively treat triple-negative breast cancer (the tumor cell survival rate was only 34.76 and 31.05% in normoxic and hypoxic states, respectively, and the tumor inhibition rate reached 87.9% at the animal level), providing a new theoretical basis for the treatment of triple-negative breast cancer. This rapid, one-step, and continuous ultrasonic aerosol flow strategy has bright prospects in the synthesis of MOF-derived hollow materials and promotes the further development of large-scale applications of biological nanomaterials.

Microwave hyperthermia is an emerging minimally invasive therapy in which thermal damage and apoptosis of tumor cells are induced by local heating of tissues with microwave radiation. Recently, microwave hyperthermia has been widely used in clinical practice; however, uneven aggregation and dispersion of malignant tumors after microwave hyperthermia are the main problems associated with this method. In this work, a microridged waveguide tumor hyperthermia antenna with an operating frequency of 915 MHz was designed. Although its volume is only 6.6 cm

Background The treatment efficacy of transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) varies widely between individuals. The aim of this study was to identify subtype landscapes and responser related to TACE, and further clarify the regulatory effect and corresponding mechanism of NDRG1 on HCC tumorgenesis and metastasis. Methods The principal component analysis (PCA) algorithm was used to construct a TACE response scoring (TRscore) system. The random forest algorithm was applied to identify the TACE response-related core gene NDRG1 of HCC, and its role in the prognosis of HCC was explored. The role of NDRG1 in the progression and metastasis of HCC and functional mechanism were confirmed using several experimental methods. Results Based on the GSE14520 and GSE104580 cohorts, we identified 2 TACE response-related molecular subtypes for HCC with significant differences in clinical features, and the TACE prognosis of Cluster A was significantly better than that of Cluster B (p p Conclusion The constructed TACE response-related molecular subtypes and TRscores can specifically and accurately predict TACE prognosis for HCC. In addition, the TACE response-related hub gene NDRG1 may act as a guardian against ferroptosis to drive tumorgenesis and metastasis in HCC, which laid a new foundation for the development of new potential targeted therapy strategies to improve disease prognosis in HCC patients.

Shotgun metagenome sequencing provides the opportunity to recover underexplored rare populations and identify difficult-to-elucidate biochemical pathways. However, information on sulfur genes, including their sequences, is scattered in public databases. Here, we introduce SMDB (https://smdb.gxu.edu.cn/)—a manually curated database of sulfur genes based on an in-depth review of the scientific literature and orthology database. The SMDB contained a total of 175 genes and covered 11 sulfur metabolism processes with 395,737 representative sequences affiliated with 110 phyla and 2340 genera of bacteria/archaea. The SMDB was applied to characterize the sulfur cycle from five habitats and compared the microbial diversity of mangrove sediments with that of other habitats. The structure and composition of microorganism communities and sulfur genes were significantly different among the five habitats. Our results show that microorganism alpha diversity in mangrove sediments was significantly higher than in other habitats. Genes involved in dissimilatory sulfate reduction were abundant in subtropical marine mangroves and deep-sea sediments. The neutral community model results showed that microbial dispersal was higher in the marine mangrove ecosystem than in others habitats. The Flavilitoribacter of sulfur-metabolizing microorganism becomes a reliable biomarker in the five habitats. SMDB will assist researchers to analyze genes of sulfur cycle from the metagenomic efficiently.

The coordinated development between industrial agglomeration and regional economic growth is of great significance. Based on the theory, this article constructs a fuzzy multi-criteria evaluation model for the coordination of industrial agglomeration and regional economic growth. The model reveals the impact of industrial agglomeration on economic growth by establishing a regression model. The output value of the secondary industry and the tertiary industry are classified, and the initial value method is used for dimensionless processing. The experimental results show that using the panel unit root test, panel cointegration test, panel regression analysis, and gray correlation analysis to conduct empirical analysis and research, the capital agglomeration and labor agglomeration in regional industries both promote economic growth, and the correlation degree of sustainable agglomeration components reached 89.7%, which significantly and indirectly played a role in promoting the coordinated development of economic growth in regional economic growth.

In the era of big data for exploring attribute reduction/rough set-based feature selection related problems, to design efficient strategies for deriving reducts and then reduce the dimensions of data, two fundamental perspectives of Granular Computing may be taken into account: breaking up the whole into pieces and gathering parts into a whole. From this point of view, a novel strategy named label-specific guidance is introduced into the process of searching reduct. Given a formal description of attribute reduction, by considering the corresponding constraint, we divide it into several label-specific based constraints. Consequently, a sequence of these label-specific based constraints can be obtained, it follows that the reduct related to the previous label-specific based constraint may have guidance on the computation of that related to the subsequent label-specific based constraint. The thinking of this label-specific guidance runs through the whole process of searching reduct until the reduct over the whole universe is derived. Compared with five state-of-the-art algorithms over 20 data sets, the experimental results demonstrate that our proposed acceleration strategy can not only significantly accelerate the process of searching reduct but also offer justifiable performance in the task of classification. This study suggests a new trend concerning the problem of quickly deriving reduct.

To correlate non-invasive quantitative diffusion kurtosis imaging (DKI) and intravoxel incoherent motion-derived (IVIM) parameters with rectal cancer composition assessed by the expression of caudal-type homeobox 2 (CDX-2), Vimentin (VIM), CD34 and Ki-67 on resected tissues, as well as the tumor stroma ratio (TSR) and the results of HE and Masson staining.A prospective study of 26 patients with rectal cancer who underwent magnetic resonance (MR) imaging, including DKI with 4 b values and IVIM at 3.0 T prior to surgery. Primary tumor was harvested and fixed for HE, immunohistochemistry and Masson staining. One-way ANOVA was used to test the differences. Pearson correlation coefficients and multiple linear regression analyses were applied to evaluation the correlations.The apparent diffusion coefficient (ADCADC

Elucidation of the mechanisms of T-cell–mediated antitumor responses will provide information for the rational design and development of cancer immunotherapies. Here, we found that calnexin, an endoplasmic reticulum (ER) chaperone protein, is significantly upregulated in oral squamous cell carcinoma (OSCC). Upregulation of its membranous expression on OSCC cells is associated with inhibited T-cell infiltration in tumor tissues and correlates with poor survival of patients with OSCC. We found that calnexin inhibits the proliferation of CD4+ and CD8+ T cells isolated from the whole blood of healthy donors and patients with OSCC and inhibits the secretion of IFNγ, TNFα, and IL2 from these cells. Furthermore, in a melanoma model, knockdown of calnexin enhanced the infiltration and effector functions of T cells in the tumor microenvironment and conferred better control of tumor growth, whereas treatment with a recombinant calnexin protein impaired the infiltration and effector functions of T cells and promoted tumor growth. We also found that calnexin enhanced the expression of PD-1 on CD4+ and CD8+ T cells by restraining the DNA methylation status of a CpG island in the PD-1 promoter. Thus, this work uncovers a mechanism by which T-cell antitumor responses are regulated by calnexin in tumor cells and suggests that calnexin might serve as a potential target for the improvement of antitumor immunotherapy.

Alphaherpesviruses can establish lifelong infections and cause many diseases in humans and animals, which rely partly on their interaction with IFN-mediated innate immune response. Using alphaherpesviruses PRV and HSV-1 as models, we identified an essential role of DNA methylation regulator UHRF1 in IFN-mediated immunity against virus replication, which unravels a novel mechanism employed by epigenetic factor to control IFN-mediated antiviral immune response and highlight UHRF1, which might be a potential target for antiviral drug development.

Background: Alzheimer's disease (AD) is the most common neurodegenerative disease. Pyroptosis is a new type of programmed cell death, which can lead to the progression of various diseases. The aim of this study was to explore the role of pyroptosis-related genes (PRGs) in Alzheimer's disease and to build the predictive model. Methods: The expression of PRGs in AD was analyzed based on the GSE33000 dataset, and molecular clustering and immune microenvironment analysis were performed on 310 patient samples. The WGCNA algorithm was used to identify the genes that were specifically expressed between different clusters, and then four machine learning models (RF, GLM, SVM and XGB) were used to construct the predictive models for the risk of AD. The prediction capability of the model was verified by nomogram, calibration, decision curve analyses and five external data sets. Results: Multiple PRGs were differentially expressed between AD and normal brain tissue. Based on differentially expressed PRGs, 310 AD patients were divided into two subtypes by consistent clustering. Immune microenvironment analysis showed significant differences in the degree of immune activation among different subtypes. WGCNA algorithm identified the specific genes between AD and normal individuals, Cluster 1 and Cluster 2. The SVM model has the best prediction performance with low residual error and root mean square error, and high area under ROC curve (AUC=0.933). Finally, a prediction model based on five genes (GPR4, STAT3, CASP4, CLIC1 and TNFRSF10B) was constructed and showed satisfactory performance on five externally validated data sets. Nomogram, calibration curve and decision curve analysis proved the prediction performance of the model. Conclusions: This study systematically analyzed the complex relationship between PRGs and AD, and constructed a good prediction model to distinguish AD from normal individuals, which is expected to provide reference for related research.

Chia is an annual crop whose seeds have the highest content of α-linolenic acid (ALA) of any plant species. We generated a high-quality assembly of the chia genome using circular consensus sequencing of PacBio. The assembled six chromosomes are composed of 21 contigs and have a total length of 361.7 Mb. Genome annotation revealed a 53.5% repeat content and 35,850 protein-coding genes. Chia shared a common ancestor with Salvia splendens ~6.1 million years ago. Utilizing the reference genome and two transcriptome datasets, we identified candidate fatty acid desaturases responsible for ALA biosynthesis during chia seed development. Because the seed of S. splendens contains significantly lower proportion of ALA but similar total contents of unsaturated fatty acids, we suggest that strong expression of two ShFAD3 genes are critical for the high ALA content of chia seeds. This genome assembly will serve as a valuable resource for breeding, comparative genomics, and functional genomics studies of chia.

Mangroves are distributed in coastal and estuarine regions and are characterized as a sink for terrestrial pollution. It is believed that complex interactions between environmental factors and microbial communities exist in mangrove swamps. However, little is known about environment-microbe interactions. There is a need to clarify some important environmental factors shaping microbial communities and how environmental factors interact with microbial assemblages in mangrove swamps. In the present study, physicochemical and microbial characteristics in four mangrove reserves (named ZZW, Qin, Bei, and GQ) in the North Beibu Gulf were determined. The interactions between environmental factors and microbial assemblages were analyzed with statistical methods in addition to CCA and RDA. Higher concentrations of sulfate (SO

The aim of the study was to investigate the inhibitory effect of hydroxysaff yellow A (HSYA) on diabetic retinopathy (DR). For this, a total of 27 rats were randomly divided into normal control, model, and HSYA groups. The body weight, blood glucose, and blood–retinal barrier damage of the rats were observed and compared. The pathological change of retinal tissue were measured using H&E staining. The apoptosis of retinal tissue ganglion cells was detected by TUNEL. The interleukin (IL)-1β and tumor necrosis fator (TNF)-α levels were detected using enzyme-linked immunosorbent assay. The level of malondialdehyde (MDA) was detected using thiobarbituric acid method. Superoxide dismutase levels were detected using xanthine oxidase method; Nrf2 and total HO-1 protein expressions were detected using western blot assay; Bcl-2 and P53 protein expression was measured using immunohistochemical staining. The body weight and retinal damage of the HYSA group were significantly improved (p < 0.01, respectively). The apoptosis index of the HYSA group was lower than the model group (p < 0.001). The IL-1β, TNF-α, and MDA levels of the HYSA group were significantly improved in comparison with those of the model group (p < 0.01, respectively). The Nrf-2, HO-1, Bcl-2, and P53 protein expression of HYSA group was significantly improved (p < 0.001, respectively). In conclusion, HYSA can effectively alleviate the apoptosis of retinal ganglion cells in type 2 diabetic rats and improve the progression of DR.

Background & aims Nonalcoholic fatty liver disease (NAFLD) has become a tremendous burden for public health, however, there is no drug for NAFLD therapy at present. Impaired endo-lysosome-mediated protein degradation is observed in a variety of metabolic disorders, such as atherosclerosis, type 2 diabetes mellitus and NAFLD. Small integral membrane protein of lysosome/late endosome (SIMPLE) is a regulator of endosome-to-lysosome trafficking and cell signaling. But the role that SIMPLE plays in NAFLD progression remains unknown. Here we investigated SIMPLE function in NAFLD development and sophisticated mechanism therein. Approach & results This study found in vitro knockdown of SIMPLE significantly aggravated lipid accumulation, inflammation in hepatocytes treated with metabolic stimulation. Consistently, in vivo experiments showed that liver-specific Simple-knockout (Simple-HKO) mice exhibited more severe high-fat diet (HFD)-, high-fat-high-cholesterol diet (HFHC)-, and methionine-choline-deficient diet (MCD)- induced steatosis, glucose intolerance, inflammation, and fibrosis than those fed with normal-chow diet. Meanwhile, RNA-sequencing demonstrated the up-regulated signaling pathways and signature genes involved in lipid metabolism, inflammation and fibrosis in Simple-HKO mice compared to control mice under metabolic stress. Mechanically, we found SIMPLE directly interact with epidermal growth factor receptor (EGFR). SIMPLE deficiency results in dysregulated degradation of EGFR, subsequently hyperactivated EGFR phosphorylation, exaggerating NAFLD development. Moreover, we further demonstrated that using EGFR inhibitor or silencing EGFR expression could ameliorate lipid accumulation induced by the knockdown of SIMPLE. Conclusions SIMPLE ameliorated NASH by prompting EGFR degradation and can also be a potential therapeutic candidate for NASH.

Background Previous research has demonstrated that harsh parenting negatively affects children’s psychological development. This study examined the association between harsh parenting during childhood and life satisfaction of Chinese college students. We further looked at whether this association is explained in part by negative coping styles, and whether peer support lessens the potential effect of harsh parenting on negative coping styles and life satisfaction. Method The sample included 609 Chinese students (aged 17–21 years, M = 18.39, SD = 0.82). The participants responded to questionnaires measuring past experiences with harsh parenting, life satisfaction, negative coping styles, and peer support. Results Regression analysis showed that harsh parenting negatively contributed to students’ life satisfaction via the mediator of negative coping styles, and peer support moderated this negative relationship. Specifically, the negative impact of harsh parenting on life satisfaction was only significant when there was low peer support. The effect of harsh parenting on negative coping styles was higher in individuals with high peer support than in those with low peer support. Conclusion This study highlights the roles of intrinsic (negative coping style) and extrinsic (peer support) factors in understanding the negative effects of harsh parenting on adolescents’ life satisfaction. These results provide insight into how to enhance adolescents’ life satisfaction by reducing harsh parenting and negative coping styles and by promoting peer support.

BackgroundThe prognostic implication of liver fibrosis in acute coronary syndrome (ACS) patients are scarce. We sought to evaluate whether liver fibrosis scores (LFS) were associated with thrombotic or bleeding events in patients with acute coronary syndrome.MethodsWe included 6386 ACS patients who underwent percutaneous coronary intervention (PCI). This study determined liver fibrosis with aspartate aminotransferase to platelet ratio index (APRI), aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT ratio), Forns score, and nonalcoholic fatty liver disease fibrosis score (NFS). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause mortality (ACM), myocardial infarction (MI), and ischemic stroke (IS).ResultsDuring the follow-up, 259 (4.06%) MACCE and 190 (2.98%) bleeding events were recorded. As a continuous variable or a categorical variable stratified by the literature-based cutoff, LFS was positively associated with MACCE (p > 0.05) but not with bleeding events. Compared with subjects with low APRI scores, AST/ALT ratio scores, Forns scores, and NFS scores, subjects with high scores had a 1.57- to 3.73-fold increase risk of MACCE after adjustment (allp ConclusionsIn ACS patients, increased LFS predicted an elevated risk of thrombotic events but not bleeding. LFS may contribute to thrombotic risk stratification after ACS.

ObjectiveThis study aimed to evaluate the current research hotspots and development tendency of Transcranial Direct Current Stimulation (tDCS) in the field of neurobiology from a bibliometric perspective by providing visualized information to scientists and clinicians.Materials and methodsPublications related to tDCS published between 2000 and 2022 were retrieved from the Web of Science Core Collection (WOSCC) on May 5, 2022. Bibliometric features including the number of publications and citations, citation frequency, H-index, journal impact factors, and journal citation reports were summarized using Microsoft Office Excel. Co-authorship, citation, co-citation, and co-occurrence analyses among countries, institutions, authors, co-authors, journals, publications, references, and keywords were analyzed and visualized using CiteSpace (version 6.1.R3).ResultsA total of 4,756 publications on tDCS fulfilled the criteria we designed and then were extracted from the WOSCC. The United States (1,190 publications, 25.02%) and Harvard University (185 publications, 3.89%) were the leading contributors among all the countries and institutions, respectively. NITSCHE MA and FREGNI F, two key researchers, have made great achievements in tDCS. Brain Stimulation (306 publications) had the highest number of publications relevant to tDCS and the highest number of citations (4,042 times). In terms of potential hotspots, we observed through reference co-citation analysis timeline viewer related to tDCS that “depression”#0, “Sensorimotor network”#10, “working memory”#11, and “Transcranial magnetic stimulation”#9 might be the future research hotspots, while keywords with the strong burst and still ongoing were “intensity” (2018–2022), “impairment” (2020–2022), “efficacy” (2020–2022), and “guideline” (2020–2022).ConclusionThis was the first-ever study of peer-reviewed publications relative to tDCS using several scientometric and visual analytic methods to quantitatively and qualitatively reveal the current research status and trends in the field of tDCS. Through the bibliometric method, we gained an in-depth understanding of the current research status and development trend on tDCS. Our research and analysis results might provide some practical sources for academic scholars and clinicians.

BACKGROUND. Drug-eluting bead transarterial chemoembolization (DEB-TACE) has emerged as an alternative to conventional TACE (cTACE) for treatment of hepatocellular carcinoma (HCC), although selecti...

The pressure stimulated currents (PSCs) and acoustic emissions (AEs) simultaneously emitting from rocks during deformation and fracturing are gradually receiving attention for rock dynamic disaster monitoring in underground excavations (mines and tunnels). For the work described in this paper, PSC signals and AE counts were recorded simultaneously during the multi-stage loading of two types of rock samples, sandstone, and gabbro. The PSC’s and AE’s responses to stress changes are studied and compared. The AEs are analyzed to investigate the changes in microcracking and energy dissipation in the two lithologies during uniaxial compression. Using an atomic force microscope, a polarized light microscopy, and a scanning electron microscope, the PSC electrification mechanisms and their correlation with AE responses are discussed. The results show that PSC signals respond more quickly to stress changes than AEs; this is especially true for the sandstone because it has fewer microcracks than the gabbro during the early loading stages. Both the electrification mechanisms and energy dissipation are affected by differences in mineralogy and microcracking, and these differences could account for the different PSC and AE responses observed in the sandstone and gabbro. Both the PSCs and AEs increase as rock damage increases, and the PSC-AE activity can provide warnings before catastrophic rock failures. Microstructural analysis reveals that mobile dislocations and microcrack propagation are joint mechanisms for generating simultaneous PSC and AE signals. This study offers critical insights into simultaneously using PSC and AE responses for geological disaster monitoring and forecasting in deep underground mines.

BackgroundNeuroblastoma is the most common malignant extracranial tumor for children. Molecular mechanisms underpinning the pathogenesis of this disease are yet to be fully clarified. This study aimed to identify a novel oncogene that could be used as a biomarker informing the prognosis of neuroblastoma, and to predict its biological functions, using bioinformatics and molecular biology tools.MethodsThree data sets from the TARGET, GSE62564, and GSE85047 databases were used for analysis. Survivals of patients with high or low expression of bub1 were compared, using the Kaplan-Meier curve and log-rank test. Immune infiltration was evaluated using ESTIMATE and MCP-counter algorithms. Synthetic small interfering RNAs (siRNAs) were employed to silence bub1 expression in neuroblastoma cell lines SH-SY5Y and SK-N-SH, in order to characterize its biological functions. Gene enrichment analyses of bub1 were carried out, using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses.ResultsExpression of bub1 was found to significantly affect overall survival and event-free survival of patients with neuroblastoma, positively correlate with the expressions of tpx2 and the ASPM gene, and negatively correlate with host immune infiltration. Expression of bub1 was elevated in patients with neuroblastoma. Silencing bub1 expression using siRNAs in SH-SY5Y and SK-N-SH resulted in decreased cell growth (p < 0.05), reduced migration (p < 0.05), and increased apoptosis (p < 0.05). Function analysis of bub1 revealed cancer-promoting effects, probably via regulating several important downstream molecules, including that related to the apoptosis process and epithelial-mesenchymal transition.ConclusionWe identified a potential tumor-promoting gene bub1 for neuroblastoma that could also serve as a prognostic biomarker.

This study aimed to evaluate the current research hotspots and development tendency of Transcranial Direct Current Stimulation (tDCS) in the field of neurobiology from a bibliometric perspective by providing visualized information to scientists and clinicians.Publications related to tDCS published between 2000 and 2022 were retrieved from the Web of Science Core Collection (WOSCC) on May 5, 2022. Bibliometric features including the number of publications and citations, citation frequency, H-index, journal impact factors, and journal citation reports were summarized using Microsoft Office Excel. Co-authorship, citation, co-citation, and co-occurrence analyses among countries, institutions, authors, co-authors, journals, publications, references, and keywords were analyzed and visualized using CiteSpace (version 6.1.R3).A total of 4,756 publications on tDCS fulfilled the criteria we designed and then were extracted from the WOSCC. The United States (1,190 publications, 25.02%) and Harvard University (185 publications, 3.89%) were the leading contributors among all the countries and institutions, respectively. NITSCHE MA and FREGNI F, two key researchers, have made great achievements in tDCS.This was the first-ever study of peer-reviewed publications relative to tDCS using several scientometric and visual analytic methods to quantitatively and qualitatively reveal the current research status and trends in the field of tDCS. Through the bibliometric method, we gained an in-depth understanding of the current research status and development trend on tDCS. Our research and analysis results might provide some practical sources for academic scholars and clinicians.

We aim to analyze the effect of liver fibrosis, assessed by the Fibrosis-4 (FIB-4) index, on cardiovascular events in acute coronary syndrome (ACS) patients with and without type 2 diabetes mellitus (T2DM).6563 ACS patients undergoing PCI were analyzed in this study. Patients were divided into three groups according to literature-based FIB-4 cut-offs:1.45, 1.45-3.25, and ≥ 3.25.During the median 2.4-year follow-up, 270 major adverse cardiac and cerebrovascular events (MACCE) and 194 major bleeding were recorded. Intermediate or high FIB-4 scores were significantly associated with an elevated risk of MACCE, mortality, and MI but not associated with ischemic stroke and major bleeding. Further restricted cubic spline analysis showed that FIB-4 as a continuous variable was positively associated with an increased adjusted risk of MACCE. The results were consistent in subgroups with and without T2DM.Liver fibrosis staged by FIB-4 was correlated with an increased risk of MACCE, mortality, and MI in ACS patients who underwent PCI with and without T2DM. FIB-4 index may help risk stratification of ACS patients independent of T2DM status.

Background and aimsEarly detection of mortality after percutaneous coronary intervention (PCI) is crucial, whereas most risk prediction models are based on outdated cohorts before the year 2000. This study aimed to establish a nomogram predicting 30-day mortality after PCI.Materials and methodsIn total, 10,444 patients undergoing PCI in National Center for Cardiovascular Diseases in China were enrolled to establish a nomogram to predict 30-day mortality after PCI. The nomogram was generated by incorporating parameters selected by logistic regression with the stepwise backward method.ResultsFive features were selected to build the nomogram, including age, male sex, cardiac dysfunction, STEMI, and TIMI 0–2 after PCI. The performance of the nomogram was evaluated, and the area under the curves (AUC) was 0.881 (95% CI: 0.8–0.961). Our nomogram exhibited better performance than a previous risk model (AUC = 0.7, 95% CI: 0.586–0.813) established by Brener et al. The survival curve successfully stratified the patients above and below the median score of 4.ConclusionA novel nomogram for predicting 30-day mortality was established in unselected patients undergoing PCI, which may help risk stratification in clinical practice.

Chinese adults’ preference for long-term partners who had a gender-congruent or gender-incongruent occupation were examined. Participants were 442 university students who described themselves as he...

Debate exists on the prognostic significance of spontaneous myocardial infarction (SMI) and periprocedural myocardial infarction (PMI), which could be diagnosed by various definitions.A total of 10,724 patients undergoing percutaneous coronary intervention (PCI) were consecutively enrolled and followed up for a median of 2.4 years. We evaluated outcomes of all-cause death, cardiac death, and major adverse cardiovascular events (MACE). Patients were stratified into three groups, including the No MI group, PMI group, and SMI group. PMI was defined based on different diagnostic criteria, including the third and fourth universal myocardial infarction (MI) definitions, the society for cardiovascular angiography and interventions (SCAI) definition, and the independent biomarker definition. Regardless of these definitions, the PMI groups were all associated with a significantly increased MACE risk at one year or 1000 days (all P0.05), but not all-cause or cardiac death. The SMI group was associated with a markedly elevated risk of death and MACE, but it showed no significant different risk of MACE to PMI using varying definitions.According to various PMI definitions, PMI and SMI were associated with an increased risk of MACE, but not death for PMI. No significantly different risk of MACE was observed between PMI and SMI.

In recent years, marine hypoxia has frequently occurred in global coastal and estuarine waters with detrimental impacts on marine fauna. In this work, we examined the impact of hypoxia on the mortality, growth, reproduction, and enzyme activities of the mysid Neomysis awatschensis. The mortality rate of adult mysids increased by 100% within 4 h under the hypoxia treatment (2 mg/L), while that of juveniles was 53.33 ± 5.77% after 96 h. The long-term low dissolved oxygen (DO) treatment (5 mg/L for 30 d) significantly reduced the fatty acid content of mysids. A significant reproductive inhibition was also observed: the total juvenile productions in the treatment with DO at 4, 5, and 6 mg/L were only 6.5%, 24%, and 60% of the control group (DO at 8.5 mg/L), respectively. The total superoxide dismutase activity increased significantly in low oxygen treatments. Catalase and lactate dehydrogenase activities first increased and then decreased with the dropping DO concentrations. These results suggest that hypoxia has multiple impacts on marine zooplankton. This may adversely affect higher trophic level organisms and the structure and function of marine ecosystems.

Smart contracts are decentralized applications running on Blockchain. A very large number of smart contracts has been deployed on Ethereum. Meanwhile, security flaws of contracts have led to huge pecuniary losses and destroyed the ecological stability of contract layer on Blockchain. It is thus an emerging yet crucial issue to effectively and efficiently detect vulnerabilities in contracts. Existing detection methods like Oyente and Securify are mainly based on symbolic execution or analysis. These methods are very time-consuming, as the symbolic execution requires the exploration of all executable paths or the analysis of dependency graphs in a contract. In this work, we propose ContractWard to detect vulnerabilities in smart contracts with machine learning techniques. First, we extract bigram features from simplified operation codes of smart contracts. Second, we employ five machine learning algorithms and two sampling algorithms to build the models. ContractWard is evaluated with 49502 real-world smart contracts running on Ethereum. The experimental results demonstrate the effectiveness and efficiency of ContractWard. The predictive Micro-F1 and Macro-F1 of ContractWard are over 96% and the average detection time is 4 seconds on each smart contract when we use XGBoost for training the models and SMOTETomek for balancing the training sets. © 2020 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.

L Antigen Family Member 3 (LAGE3) is an important RNA modification-related protein. Whereas few studies have interrogated the LAGE3 protein, there is limited data on its role in tumors. Here, we analyzed and profiled the LAGE3 protein in skin cutaneous melanoma (CM) using TCGA, GTEx, or GEO databases. Our data showed an upregulation of LAGE3 in melanoma cell lines compared to normal skin cell lines. Besides, the Kaplan–Meier curves and Cox proportional hazard model revealed that LAGE3 was an independent survival indicator for CM, especially in metastatic CM. Moreover, LAGE3 was negatively associated with multiple immune cell infiltration levels in CM, especially CD8+ T cells in metastatic CM. Taken together, our study suggests that LAGE3 could be a potential prognostic biomarker and might be a potential target for the development of novel CM treatment strategies.

Human respiratory syncytial virus (HRSV) is a major pathogen of lower respiratory tract infections in children (5 years) and older individuals, with outbreaks mainly reported among infants in hospital pediatric departments and intensive care units (ICUs). An outbreak of severe neonatal pneumonia occurred in a postpartum center in Shenyang city, China, from January to February 2021. In total, 34 respiratory samples were collected from 21 neonates and 13 nursing staff. The samples were screened for 27 pathogens using a TaqMan low-density array, and 20 samples tested positive for HRSV, including 16 neonates and 4 nursing staff samples. Among the 16 hospitalized neonates, seven were admitted to an ICU and nine to general wards. Four of the nursing staff had asymptomatic infections. To investigate the genetic characteristics of the HRSV responsible for this outbreak, the second hypervariable region (HVR2) sequences of the G gene were obtained from six neonates and two nursing staff. Phylogenetic analyses revealed that all eight sequences (SY strains) were identical, belonging to the HRSV BA9 genotype. Our findings highlight the necessity for strict hygiene and disease control measures so as to prevent cross-infection and further avoid potential outbreaks of severe infectious respiratory diseases.

Foot-and-mouth disease virus (FMDV) is an acute, highly contagious, and economically destructive pathogen of vesicular disease that affects domestic and wild cloven-hoofed animals. The FMDV VP1 protein is an important part of the nucleocapsid and plays a significant role during FMDV infection. However, the signal pathways mediated by VP1 in the life cycle of FMDV and the related mechanisms are not yet fully understood. Here, we performed RNA-seq to compare gene expression profiles between pCAGGS-HA-VP1 transfected PK-15 cells and pCAGGS-HA (empty vector) transfected PK-15 cells. The results showed 5,571 genes with significantly different expression levels, of which 2,981 were up-regulated and 2,590 were down-regulated. GO enrichment analysis showed that 51 GO terms were significantly enriched in cell components including protein complex, membrane and organelle part. KEGG enrichment analysis showed 11 KEGG pathways were significantly enriched which were mainly related to the immune system, infectious viral disease, and signal transduction. Among the up-regulated genes, the chemokines such as CCL5, CXCL8, and CXCL10 in turn promoted FMDV replication. In contrast, GBP1, an interferon-stimulated gene that was suppressed by VP1 and FMDV, could effectively inhibit FMDV replication. Our research provides a comprehensive overview of the response of host cells to VP1 protein and a basis for further research to understand the roles of VP1 in FMDV infection including the genes involved in FMDV replication.

In vitro cardiac tissue model holds great potential as a powerful platform for drug screening. Respiratory activity, contraction frequency, and extracellular H

Dendrobium officinale Kimura et Migo is a famous Chinese herb. D. officinale grows on rocks where the available phosphorus is low. The SPX family plays a critical role in maintaining Pi homeostasis in plants. In this paper, 9 SPX family genes were identified in the genome of D. officinale. Bioinformatics and qRT-PCR analysis showed that DoSPXs were involved in response to −Pi stress and had different expression patterns. DoSPX4, which had a unique expression pattern, was clustered with AtSPX4 and OsSPX4. Under −Pi treatment, the expression level of DoSPX4 reached a peak on 5 d in roots, while showing a downward trend in the aboveground parts. DoSPX4 was located on the cell membrane. Overexpression DoSPX4 promoted Pi content in the stem and the expression level of NtPHT1/2 in Nicotiana tabacum. The results of Yeast two-hybrid showed that DoSPX4 could interact with Phosphate High-Affinity Response factor (DoPHR2). These results highlight the role of DoSPX4 in response to low phosphorus, which provides a theoretical basis for further study on the response mechanism of −Pi in D. officinale.

Human respiratory syncytial virus (HRSV) is a major cause of lower respiratory tract infection in infants. The lack of ideal animal models is one of the major obstacles in evaluateing the efficacy of HRSV vaccines. In this study, HRSV-50 was obtained from Hep-2 cells at the 50th passage of the original Long strain (ATCC VR-26). BALB/c mice (6 weeks) were challenged with different titers of HRSV-50. Shockingly, all mice died after 4 days of challenge (6 × 10

Transarterial chemoembolization (TACE) is an important approach for the treatment of unresectable hepatocellular carcinoma (HCC). However, the lactic acid-induced acidic tumor microenvironment (TME) may reduce the therapeutic outcome of TACE. Herein, monodispersed gelatin microspheres loaded with calcium carbonate nanoparticles (CaNPs@Gel-MS) as novel embolic agents were prepared by a simplified microfluidic device. It was found that the particle size and homogeneity of as-prepared CaNPs@Gel-MS were strongly dependent on the flow rates of continuous and dispersed phases, and the inner diameter of syringe needle. The introduction of CaNPs provided the gelatin microspheres with an enhanced ability to encapsulate the chemotherapeutic drug of DOX, as well as a pH-responsive sustained drug release behavior. In vitro results revealed that CaNPs@Gel-MS could largely increase the cellular uptake and chemotoxicity of DOX by neutralizing the lactic acid in the culture medium. In addition, CaNPs@Gel-MS exhibited an excellent and persistent embolic efficiency in a rabbit renal model. Finally, we found that TACE treatment with DOX-loaded CaNPs@Gel-MS (DOX/CaNPs@Gel-MS) had a much stronger ability to inhibit tumor growth than the DOX-loaded gelatin microspheres without CaNPs (DOX@Gel-MS). Overall, CaNPs@Gel-MS could be a promising embolic microsphere that can significantly improve anti-HCC ability by reversing lactic acid-induced chemotherapy resistance during TACE treatment.

Based on the algorithm of Coupled Eulerian Lagrangian (CEL), the processes of the generation of shaped charge jet (SCJ) and the penetration to the inner and outer ship side plates were simulated by the finite element analysis (FEA). Meanwhile, the residual velocity of SCJ after penetrating the side plate could be obtained. In order to compare with the FEA results, the damage caused by the SCJ to the inner and outer plates of the ship side was experimentally studied, and the residual velocity was measured successfully. The comparison demonstrated that the values of the residual velocity obtained by simulation well agreed with the experimental results. The simulation indicated that the velocity of the SCJ decreased after penetrating the inner plate. Moreover, the influences of the ship side structural details, including the inner plate thickness, the distance between the inner and outer plates and the layout of the inner plate, on its protective ability against SCJ were investigated. The research indicated that increasing the thickness of inner plate and the spacing between inner and outer plates can effectively reduce SCJ residual velocity. Replacement of the inner plate with a multilayer plate could obviously reduce the SCJ residual velocity. The simulation method could describe the process of SCJ generation and penetration accurately, and the research results could provide references for the protective structural design of the ship hull attacked by SCJ.