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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

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

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.

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.

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