Publications by authors named "Jue Wang"

1,083 Publications

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Pyronaridine induces apoptosis in Non-small cell lung cancer cells by upregulating DR5 expression and inhibiting EGFR.

Chem Biol Drug Des 2021 Jul 21. Epub 2021 Jul 21.

State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Avenida Wai Long, Taipa Macau, China.

Lung cancer is the leading cause of cancer death. Pyronaridine, a synthetic drug of artemisinin has been used in China for over 30 years for the treatment of malaria, but its effect on non-small cell lung cancer (NSCLC) cells is rarely reported. In this study, we determined the efficacy of pyronaridine in four different NSCLC cell lines and explored its mechanism in H1975. The data showed that pyronaridine could upregulate the expression of TRAIL (TNF-related apoptosis-inducing ligand)-mediated DR5 (Death receptor 5) to promote cellular apoptosis. Meanwhile, the JNK (c-Jun N-terminal kinase) level was detected to be significantly increased after treating with pyronaridine. We used JNK inhibitor and found that it could partially inhibit cell apoptosis. The results showed that EGFR (Epidermal growth factor receptor), PI3K and AKT were downregulated after the treatment of pyronaridine. In summary, pyronaridine can selectively kill NSCLC by regulating TRAIL-mediated apoptosis and downregulating the protein level of EGFR. It is a promising anticancer drug for NSCLC.
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http://dx.doi.org/10.1111/cbdd.13926DOI Listing
July 2021

Accurate prediction of protein structures and interactions using a three-track neural network.

Science 2021 Jul 15. Epub 2021 Jul 15.

Molecular Biophysics & Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.

DeepMind presented remarkably accurate predictions at the recent CASP14 protein structure prediction assessment conference. We explored network architectures incorporating related ideas and obtained the best performance with a three-track network in which information at the 1D sequence level, the 2D distance map level, and the 3D coordinate level is successively transformed and integrated. The three-track network produces structure predictions with accuracies approaching those of DeepMind in CASP14, enables the rapid solution of challenging X-ray crystallography and cryo-EM structure modeling problems, and provides insights into the functions of proteins of currently unknown structure. The network also enables rapid generation of accurate protein-protein complex models from sequence information alone, short circuiting traditional approaches which require modeling of individual subunits followed by docking. We make the method available to the scientific community to speed biological research.
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http://dx.doi.org/10.1126/science.abj8754DOI Listing
July 2021

Sequential CD19/22 CAR T-cell immunotherapy following autologous stem cell transplantation for central nervous system lymphoma.

Blood Cancer J 2021 Jul 15;11(7):131. Epub 2021 Jul 15.

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Chimeric antigen receptor (CAR) T-cell immunotherapy following autologous stem cell transplantation (ASCT) is a promising method for refractory or relapsed multiple myeloma, but explicit data for central nervous system lymphoma (CNSL) are lacking. Here, we treated 13 CNSL patients with ASCT sequential CD19/22 CAR T-cell infusion and simultaneously evaluated the clinical efficacy and toxicity. The 13 CNSL patients analyzed included four primary CNSL and nine secondary CNSL patients. Patients 1 and 10, who had complete remission status before enrollment, maintained clinical efficacy without recurrence. Nine of the remaining 11 patients responded to our protocol with a median durable time of 14.03 months, and the overall response and complete remission rate were 81.81% and 54.55%, respectively. No patient suffered grades 3-4 cytokine-release syndrome (CRS), and only patient 10 experienced severe immune effector cell-associated neurotoxicity syndrome (ICANS). In addition, increases in serum ferritin and interleukin-6 levels were often accompanied by CRS and ICANS. After a median follow-up time of 14.20 months, the estimated 1-year progression-free survival and overall survival rates were 74.59% and 82.50%, respectively. Sequential CD19/22 CAR T-cell immunotherapy following ASCT as a novel method for CNSL appears to have encouraging long-term efficacy with relatively manageable side effects.
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http://dx.doi.org/10.1038/s41408-021-00523-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282870PMC
July 2021

Histatin 1 enhanced the speed and quality of wound healing through regulating the behaviour of fibroblast.

Cell Prolif 2021 Jul 13:e13087. Epub 2021 Jul 13.

Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department and 4th Medical Center, PLA General Hospital and PLA Medical College, Beijing, China.

Objectives: Histatin 1(Hst 1) has been proved to promote wound healing. However, there was no specific study on the regulation made by Hst 1 of fibroblasts in the process of wound healing. This research comprehensively studied the regulation of Hst 1 on the function of fibroblasts in the process of wound healing and preliminary mechanism about it.

Materials And Methods: The full-thickness skin wound model was made on the back of C57/BL6 mice. The wound healing, collagen deposition and fibroblast distribution were detected on days 3, 5 and 7 after injury. Fibroblast was cultured in vitro and stimulated with Hst 1, and then, their biological characteristics and functions were detected.

Results: Histatin 1 can effectively promote wound healing, improve collagen deposition during and after healing and increase the number and function of fibroblasts. After healing, the mechanical properties of the skin also improved. In vitro, the migration ability of fibroblasts stimulated by Hst 1 was significantly improved, and the fibroblasts transformed more into myofibroblasts, which improved the function of contraction and collagen secretion. In fibroblasts, mTOR signalling pathway can be activated by Hst 1.

Conclusions: Histatin 1 can accelerate wound healing and improve the mechanical properties of healed skin by promoting the function of fibroblasts. The intermolecular mechanisms need to be further studied, and this study provides a direction about mTOR signalling pathway.
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http://dx.doi.org/10.1111/cpr.13087DOI Listing
July 2021

Ultrasonic characteristics of carotid webs.

Neuroradiology 2021 Jul 12. Epub 2021 Jul 12.

Department of Ultrasound, Hwa Mei Hospital, University of Chinese Academy of Sciences, 41 Northwest Street, Ningbo, 315010, Zhejiang, China.

Purpose: This study aimed to retrospectively analyze the ultrasonographic images of 46 cases of carotid web (CW) and summarize their manifestations to reduce the rate of misdiagnosis.

Methods: For the analysis of ultrasonic manifestations, 46 patients with a confirmed diagnosis of CW by digital subtraction angiography (DSA) and CT angiography (CTA) in our hospital from January 2015 to October 2020 were collected. The location and the morphology of CW, the presence of a plaque at the base and thrombus at the surrounding of the CW, and whether they resulted in arteriostenosis were discussed.

Results: The average age of 46 patients was 43.23 ± 4.89 years old and there were 18 males and 28 females. Fifteen patients were admitted with cerebral infarction. The CW was located at the initial segment of the internal carotid artery in 22 cases, the bifurcation of the carotid artery in 20 cases, and the common carotid artery in 4 cases. CW in 5 patients was longer than half of the artery diameter, two patients with "cliff-like" arteriostenosis, 29 patients with plaques, and 16 patients with thrombi. The CW grew in the direction of the blood flow without obvious fluttering. The CW has a higher display rate on the ultrasound longitudinal section than the transverse section.

Conclusion: We identified some typical ultrasound characteristics of CW. Recognizing them will improve diagnostic accuracy of CW by ultrasonography.
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http://dx.doi.org/10.1007/s00234-021-02757-0DOI Listing
July 2021

Untargeted serum metabolomics and potential biomarkers for Sjögren's syndrome.

Clin Exp Rheumatol 2021 Jun 29. Epub 2021 Jun 29.

Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, and Department of Biomedical Engineering, College of Engineering and Applied Sciences, Nanjing National Laboratory of Microstructures, Jiangsu Key Laboratory of Artificial Functional Materials, Nanjing University, Nanjing, Jiangsu, China.

Objectives: At present, the pathogenesis of Sjögren's syndrome (SS) remains unclear. This research aimed to identify differential metabolites that contribute to SS diagnosis and discover the disturbed metabolic pathways.

Methods: Recent advances in mass spectrometry have allowed the identification of hundreds of unique metabolic signatures and the exploration of altered metabolite profiles in disease. In this study, 505 candidates including healthy controls (HCs) and SS patients were recruited and the serum samples were collected. A non-targeted gas chromatography-mass spectrometry (GC-MS) serum metabolomics method was used to explore the changes in serum metabolites.

Results: We found SS patients and HCs can be distinguished by 21 significant metabolites. The levels of alanine, tryptophan, glycolic acid, pelargonic acid, cis-1-2-dihydro-1-2-naphthalenediol, diglycerol, capric acid, turanose, behenic acid, dehydroabietic acid, stearic acid, linoleic acid, heptadecanoic acid, valine, and lactic acid were increased in serum samples from SS patients, whereas levels of catechol, anabasine, 3-6-anhydro-D-galactose, beta-gentiobiose, 2-ketoisocaproic acid and ethanolamine were decreased. The significantly changed pathways included the following: Linoleic acid metabolism; unsaturated fatty acid biosynthesis; aminoacyl-tRNA biosynthesis; valine, leucine, and isoleucine biosynthesis; glycerolipid metabolism; selenocompound metabolism; galactose metabolism; alanine, aspartate and glutamate metabolism; glyoxylate and dicarboxylate metabolism; glycerophospholipid metabolism; and valine, leucine and isoleucine degradation.

Conclusions: These findings enhance the informative capacity of biochemical analyses through the identification of serum biomarkers and the analysis of metabolic pathways and contribute to an improved understanding of the pathogenesis of SS.
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June 2021

Membrane Feature-Inspired Profiling of Extracellular Vesicles for Pancreatic Cancer Diagnosis.

Anal Chem 2021 Jul 12;93(28):9860-9868. Epub 2021 Jul 12.

Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 211198, China.

Extracellular vesicles (EVs) have recently emerged as a promising tumor biomarker, and EV phenotyping offers many benefits for cancer diagnosis. However, the practicality of EV assays remains a challenge due to macromolecule disturbances, biomarker heterogeneities, and EV abundance limitations. Here, we demonstrate a membrane-based biosensor for precise and sensitive EV identification. The sensor synergistically integrates EV capture and detection by virtue of EV membrane features (membrane protein and lipid bilayer), comprising antibody-conjugated magnetic beads (AbMBs) and duplex-specific nuclease (DSN)-mediated amplification cycles. Bivalent cholesterol (biChol)-modified RNA-DNA duplexes are designed to insert into the EV membrane, transforming EV signals into RNA signals and initiating the signal amplification. The membrane-based signal production pattern eliminates protein interference. By employing four antibodies specific to PCa-related membrane proteins, the AbMB-biChol platform enables the successful differentiation and monitoring of PCa-related EVs and distinguishes PCa patients from healthy donors with improved efficacy, exhibiting superior efficiency over the analyses based on clinically used biomarker CA19-9 and PCa-related proteins. As such, the developed system has great potential for clinical PCa diagnosis.
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http://dx.doi.org/10.1021/acs.analchem.1c01712DOI Listing
July 2021

Mesenchymal Stem Cells (MSCs) in Targeted Drug Delivery: Literature Review and Exploratory Data on Migrating and Differentiation Capacities of Bone MSCs into Hepatic Progenitor Cells.

Curr Top Med Chem 2021 Jul 7. Epub 2021 Jul 7.

Department of Surgical Oncology, Shaanxi Provincial People's Hospital (Third Hospital of Medical College of Xi'an Jiaotong University), Xi'an 710068, China.

Background And Objective: Mesenchymal stem cells (MSCs), particularly bone MSCs (BMSCs) offer great potentials for targeted therapeutic applications due to their migratory and differentiation capacities. Significant advances have been achieved in the differentiation of hepatocyte or hepatocyte-like cells both in vitro and in vivo. However, there is limited knowledge on the differentiation of BMSCs into bipotential hepatic progenitor cells or cholangiocytes. This study reviews the potentials and advances in using MSCs as vehicles for targeted drug delivery and proposes a new method for induction of differentiation in rat BMSCs into hepatic progenitor cells in vitro, and assesses the differential and migratory capacities.

Methods: The BMSCs of Sprague Dawley (SD) rats were harvested from the femur and the tibiae of the rats. After isolation and culturing, BMSCs from Passage 1 were used for the study. The in vitro differentiation of the hepatic progenitor cells was performed using a 2-step induction approach after 5-day serum deprivation from the BMSCs and culturing in Dulbecco's modified eagle medium. Spontaneous in vitro differentiation of BMSCs was examined in the absence of growth factors for 15 days as a control treatment. Hepatocytes differentiation was achieved by exposing the culture to collagen type I-coated plates. Cholangiocytes differentiation was achieved by replating the BMC-HepPCs on a layer of Matrigel. Immunofluorescence was conducted on twelve-well plates to determine cell differentiation. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was used to determine the total RNA extracted using the Trizol LS reagent. In the hepatocyte differentiation group, after periodic acid-schiff (PAS) staining for glycogen, the inverted microscope was used to determine differentiation and undifferentiated BMC-HepPCs served as controls. The amount of low-density lipoprotein (LDL) uptake by the BMSCs-derived hepatocytes were assessed using fluorescence microscopy. The secretion of rat albumin was quantified using a quantitative ELISA kit.

Results: Differentiation induction is indicative of the sequential supplementation of sodium butyrate and cytokines, which are involved in the embryonic development of the mammalian liver. Hepatic progenitor cells, derived from bone marrow, can be differentiated bidirectionally in vitro into both hepatocyte and cholangiocyte cell lines. The differentiated cells, including hepatic progenitor cells, hepatocytes, and bile duct-like cells, were identified and analyzed at mRNA and protein levels.

Conclusion: Our findings show that BMSCs can be utilized as novel bipotential hepatic progenitor cells and thereby for hepatobiliary disease treatment or hepatobiliary tissue engineering.
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http://dx.doi.org/10.2174/1568026621666210708092728DOI Listing
July 2021

Magnetic resonance imaging radiomics predicts preoperative axillary lymph node metastasis to support surgical decisions and is associated with tumor microenvironment in invasive breast cancer: A machine learning, multicenter study.

EBioMedicine 2021 Jul 3;69:103460. Epub 2021 Jul 3.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Medical Oncology, Breast Tumor Centre, Phase I Clinical Trial Centre, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address:

Background: in current clinical practice, the standard evaluation for axillary lymph node (ALN) status in breast cancer has a low efficiency and is based on an invasive procedure that causes operative-associated complications in many patients. Therefore, we aimed to use machine learning techniques to develop an efficient preoperative magnetic resonance imaging (MRI) radiomics evaluation approach of ALN status and explore the association between radiomics and the tumor microenvironment in patients with early-stage invasive breast cancer.

Methods: in this retrospective multicenter study, three independent cohorts of patients with breast cancer (n = 1,088) were used to develop and validate signatures predictive of ALN status. After applying the machine learning random forest algorithm to select the key preoperative MRI radiomic features, we used ALN and tumor radiomic features to develop the ALN-tumor radiomic signature for ALN status prediction by the support vector machine algorithm in 803 patients with breast cancer from Sun Yat-sen Memorial Hospital and Sun Yat-sen University Cancer Center (training cohort). By combining ALN and tumor radiomic features with corresponding clinicopathologic information, the multiomic signature was constructed in the training cohort. Next, the external validation cohort (n = 179) of patients from Shunde Hospital of Southern Medical University and Tungwah Hospital of Sun Yat-Sen University, and the prospective-retrospective validation cohort (n = 106) of patients treated with neoadjuvant chemotherapy in prospective phase 3 trials [NCT01503905], were included to evaluate the predictive value of the two signatures, and their predictive performance was assessed by the area under operating characteristic curve (AUC). This study was registered with ClinicalTrials.gov, number NCT04003558.

Findings: the ALN-tumor radiomic signature for ALN status prediction comprising ALN and tumor radiomic features showed a high prediction quality with AUC of 0·88 in the training cohort, 0·87 in the external validation cohort, and 0·87 in the prospective-retrospective validation cohort. The multiomic signature incorporating tumor and lymph node MRI radiomics, clinical and pathologic characteristics, and molecular subtypes achieved better performance for ALN status prediction with AUCs of 0·90, 0·91, and 0·93 in the training cohort, the external validation cohort, and the prospective-retrospective validation cohort, respectively. Among patients who underwent neoadjuvant chemotherapy in the prospective-retrospective validation cohort, there were significant differences in the key radiomic features before and after neoadjuvant chemotherapy, especially in the gray-level dependence matrix features. Furthermore, there was an association between MRI radiomics and tumor microenvironment features including immune cells, long non-coding RNAs, and types of methylated sites. Interpretation this study presented a multiomic signature that could be preoperatively and conveniently used for identifying patients with ALN metastasis in early-stage invasive breast cancer. The multiomic signature exhibited powerful predictive ability and showed the prospect of extended application to tailor surgical management. Besides, significant changes in key radiomic features after neoadjuvant chemotherapy may be explained by changes in the tumor microenvironment, and the association between MRI radiomic features and tumor microenvironment features may reveal the potential biological underpinning of MRI radiomics.
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http://dx.doi.org/10.1016/j.ebiom.2021.103460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261009PMC
July 2021

OIFlow: Occlusion-Inpainting Optical Flow Estimation by Unsupervised Learning.

IEEE Trans Image Process 2021 14;30:6420-6433. Epub 2021 Jul 14.

Occlusion is an inevitable and critical problem in unsupervised optical flow learning. Existing methods either treat occlusions equally as non-occluded regions or simply remove them to avoid incorrectness. However, the occlusion regions can provide effective information for optical flow learning. In this paper, we present OIFlow, an occlusion-inpainting framework to make full use of occlusion regions. Specifically, a new appearance-flow network is proposed to inpaint occluded flows based on the image content. Moreover, a boundary dilated warp is proposed to deal with occlusions caused by displacement beyond the image border. We conduct experiments on multiple leading flow benchmark datasets such as Flying Chairs, KITTI and MPI-Sintel, which demonstrate that the performance is significantly improved by our proposed occlusion handling framework.
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http://dx.doi.org/10.1109/TIP.2021.3093781DOI Listing
July 2021

Obstruction of the formation of granulation tissue leads to delayed wound healing after scald burn injury in mice.

Burns Trauma 2021 29;9:tkab004. Epub 2021 Apr 29.

State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.

Background: Delayed wound healing remains a common but challenging problem in patients with acute or chronic wound following accidental scald burn injury. However, the systematic and detailed evaluation of the scald burn injury, including second-degree deep scald (SDDS) and third-degree scald (TDS), is still unclear. The present study aims to analyze the wound-healing speed, the formation of granulation tissue, and the healing quality after cutaneous damage.

Methods: In order to assess SDDS and TDS, the models of SDDS and TDS were established using a scald instrument in C57BL/6 mice. Furthermore, an excisional wound was administered on the dorsal surface in mice (Cut group). The wound-healing rate was first analyzed at days 0, 3, 5, 7, 15 and 27, with the Cut group as a control. Then, on the full-thickness wounds, hematoxylin and eosin (H&E) staining, Masson staining, Sirius red staining, Victoria blue staining and immunohistochemistry were performed to examine re-epithelialization, the formation of granulation tissue, vascularization, inflammatory infiltration and the healing quality at different time points in the Cut, SDDS and TDS groups.

Results: The presented data revealed that the wound-healing rate was higher in the Cut group, when compared with the SDDS and TDS groups. H&E staining showed that re-epithelialization, formation of granulation tissue and inflammatory infiltration were greater in the Cut group, when compared with the SDDS and TDS groups. Immunohistochemistry revealed that the number of CD31, vascular endothelial growth factor A, transforming growth factor-β and α-smooth muscle actin reached preferential peak in the Cut group, when compared with other groups. In addition, Masson staining, Sirius red staining, Victoria blue staining, Gordon-Sweets staining and stress analysis indicated that the ratio of collagen I to III, reticular fibers, failure stress, Young's modulus and failure length in the SDDS group were similar to those in the normal group, suggesting that healing quality was better in the SDDS group, when compared with the Cut and TDS groups.

Conclusion: Overall, the investigators first administered a comprehensive analysis in the Cut, SDDS and TDS groups through experiments, which further proved that the obstacle of the formation of granulation tissue leads to delayed wound healing after scald burn injury in mice.
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http://dx.doi.org/10.1093/burnst/tkab004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240558PMC
April 2021

An Integrated Individual Environmental Exposure Assessment System for Real-Time Mobile Sensing in Environmental Health Studies.

Sensors (Basel) 2021 Jun 11;21(12). Epub 2021 Jun 11.

Department of Geography, Planning, and Environment, East Carolina University, Greenville, NC 27858, USA.

The effects of environmental exposure on human health have been widely explored by scholars in health geography for decades. However, recent advances in geospatial technologies, especially the development of mobile approaches to collecting real-time and high-resolution individual data, have enabled sophisticated methods for assessing people's environmental exposure. This study proposes an individual environmental exposure assessment system (IEEAS) that integrates objective real-time monitoring devices and subjective sensing tools to provide a composite way for individual-based environmental exposure data collection. With field test data collected in Chicago and Beijing, we illustrate and discuss the advantages of the proposed IEEAS and the composite analysis that could be applied. Data collected with the proposed IEEAS yield relatively accurate measurements of individual exposure in a composite way, and offer new opportunities for developing more sophisticated ways to measure individual environmental exposure. With the capability to consider both the variations in environmental risks and human mobility in high spatial and temporal resolutions, the IEEAS also helps mitigate some uncertainties in environmental exposure assessment and thus enables a better understanding of the relationship between individual environmental exposure and health outcomes.
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http://dx.doi.org/10.3390/s21124039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230798PMC
June 2021

P4HA2 promotes cell proliferation and migration in glioblastoma.

Oncol Lett 2021 Aug 10;22(2):601. Epub 2021 Jun 10.

Department of Anatomy, Medical School and Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu 226001, P.R. China.

Glioblastoma (GBM) is a primary malignant tumor characterized by high infiltration and angiogenesis in the brain parenchyma. Glioma stem cells (GSCs), a heterogeneous GBM cell type with the potential for self-renewal and differentiation to tumor cells, are responsible for the high malignancy of GBM. The purpose of the present study was to investigate the roles of significantly differentially expressed genes between GSCs and GBM cells in GBM progression. The gene profiles GSE74304 and GSE124145, containing 10 GSC samples and 12 GBM samples in total, were obtained from the Gene Expression Omnibus (GEO) database. The overlapping differentially expressed genes were identified with GEO2R tools and Venn software online. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis was performed on the 41 upregulated and 142 downregulated differentially expressed genes in GSCs compared with in GBM cells via the DAVID website. Protein-protein interaction and module analyses in Cytoscape with the STRING database revealed 21 hub genes that were downregulated in GSCs compared with in GBM cells. Survival analysis conducted via the GEPIA2 website revealed that low expression levels of the hub genes prolyl 4-hydroxylase subunit α2 (P4HA2), TGF-β induced, integrin subunit α3 and thrombospondin 1 were associated with significantly prolonged survival time in patients with GBM. Further experiments were performed focusing on P4HA2. Reverse transcription-quantitative PCR was used to detect P4HA2 gene expression. In agreement with the bioinformatics analysis, P4HA2 expression was higher in U87 cells than in GSCs. Cell Counting Kit-8, EdU incorporation, cell cycle analysis, wound healing and Transwell assays demonstrated that the cell proliferation and migration increased after P4HA2 overexpression and decreased after P4HA2-knockdown. In conclusion, the present study demonstrated that low P4HA2 expression in GSCs promoted GBM cell proliferation and migration, suggesting that P4HA2 may act as a switch in the transition from GSCs to GBM cells.
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http://dx.doi.org/10.3892/ol.2021.12862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228437PMC
August 2021

Developing a novel and simple biosensor for Cystatin C as a fascinating marker of glomerular filtration rate with DNase I-aided recycling amplification strategy.

J Pharm Biomed Anal 2021 Sep 24;203:114230. Epub 2021 Jun 24.

NMPA Key Laboratory for Bioequivalence Research of Generic Drug Evaluation, Shenzhen Institute for Drug Control, Shenzhen 518057, China. Electronic address:

Cystatin C (Cys C) has been proposed as a fascinating glomerular filtration rate (GFR) marker for early detection of acute kidney injury and chronic kidney disease. However, most of traditional methods for Cys C detection are immunoassays, which was tedious to perform and unfriendly for economics. In this work, a novel and simple biosensor for the sensitive measurement of Cys C via DNase I-aided recycling amplification strategy was successfully constructed based on the graphene oxide (GO) and fluorophore-labelled aptamer, which can be used to the early prediction of kidney injury. The fluorescence of fluorophore-labelled aptamer was quenched by GO based on the Fluorescence Resonance Energy Transfer (FRET) and recovered with the existence of Cys C. In addition, the DNase I enzyme would digest the fluorophore-labelled aptamer and dissociate the Cys C to launch the next reaction, resulting in an increase of signal amplification. Hence, the limit of detection is found to be 0.16 ng mL, which is almost 3 times lower than that without DNase I. Consequently, the developed biosensor offers a novel approach towards simple and rapid detection of Cys C based on the integration of GO and aptamer. Conceivably, this strategy holds a wide scope in the application of numerous other analytes if corresponding aptamers are available.
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http://dx.doi.org/10.1016/j.jpba.2021.114230DOI Listing
September 2021

Generalized One-Class Learning Using Pairs of Complementary Classifiers.

IEEE Trans Pattern Anal Mach Intell 2021 Jun 28;PP. Epub 2021 Jun 28.

In this paper, we present novel objectives for one-class learning, which we collectively refer to as Generalized One-class Discriminative Subspaces (GODS). Our key idea is to learn a pair of complementary classifiers to flexibly bound the one-class data distribution, where the data belongs to the positive half-space of one of the classifiers in the complementary pair and to the negative half-space of the other. To avoid redundancy while allowing non-linearity in the classifier decision surfaces, we design each classifier as an orthonormal frame and learn these frames via jointly optimizing for two objectives, namely: i) to minimize the distance between the two frames, and ii) to maximize the margin between the frames and the data. The learned frames will thus characterize a piecewise linear decision surface allowing for efficient inference, while our objectives seek to bound the data within a minimal volume that maximizes the decision margin, thereby robustly capturing the data distribution. We explore several variants of our formulation under different constraints on the constituent classifiers, including kernelized feature maps. We provide experiments on several applications in computer vision, including anomaly detection in video sequences, human poses, and activities, as well as on five UCI datasets, demonstrating state-of-the-art results.
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http://dx.doi.org/10.1109/TPAMI.2021.3092999DOI Listing
June 2021

Fe induction strategy for hollow porous N-doped carbon with superior performance in oxygen reduction.

Chem Commun (Camb) 2021 Jul;57(58):7108-7111

College of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan 410083, P. R. China.

An Fe induction strategy is introduced to achieve template-free synthesis of Co,Fe dual-metal N-codoped hollow porous carbon from zeolitic imidazole frameworks, which is beneficial for the exposure of highly dispersed metal (M)-Nx active sites and enhancement of mass transport, thereby exhibiting a superior electrocatalytic activity (E1/2, 0.86 VRHE).
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http://dx.doi.org/10.1039/d1cc02127cDOI Listing
July 2021

Proteomic analyses identify intracellular targets for Japanese encephalitis virus nonstructural protein 1 (NS1).

Virus Res 2021 Sep 24;302:198495. Epub 2021 Jun 24.

Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, College of Animal Science and Technology, Beijing University of Agriculture, Beijing, 102206, China. Electronic address:

Japanese encephalitis is a zoonotic disease caused by Japanese encephalitis virus (JEV). JEV nonstructural protein 1 (NS1) is involved in many crucial biological events during viral infection and immune suppression. To investigate the role of JEV NS1 in virus-infected cells, the molecules with which it interacts intracellularly were screened with a pull-down assay and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The interaction between heterogeneous nuclear ribonucleoprotein K (hnRNP K), vimentin and NS1 were verified with coimmunoprecipitation and confocal assays. Our results show that JEV NS1 interacts with vimentin, hnRNP K and colocalizes with cellular vimentin and hnRNP K. Furthermore, our results demonstrate that the expression of vimentin and hnRNP K were up-regulated in both NS1-transfected and JEV-infected cells. Knocking down vimentin and hnRNP K reduced viral replication while conversely, over-expression of vimentin and hnRNP K improved viral replication, suggesting an important role for this protein in the viral life cycle. Also, We found that vimentin also interacted with hnRNP K after overexpression of NS1 or JEV infection. These findings provide insight into the molecular mechanism of JEV replication and highlight the key role the NS1 in JEV infection.
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http://dx.doi.org/10.1016/j.virusres.2021.198495DOI Listing
September 2021

Improving the Effect of Transcranial Alternating Current Stimulation (tACS): A Systematic Review.

Front Hum Neurosci 2021 7;15:652393. Epub 2021 Jun 7.

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China.

With the development of electrical stimulation technology, traditional transcranial alternating current stimulation (tACS) technology has been found to have the drawback of not targeting a specific area accurately. Studies have shown that optimizing the number and position of electrodes during electrical stimulation has a very good effect on enhancing brain stimulation accuracy. At present, an increasing number of laboratories have begun to optimize tACS. However, there has been no study summarizing the optimization methods of tACS. Determining whether different optimization methods are effective and the optimization approach could provide information that could guide future tACS research. We describe the results of recent research on tACS optimization and integrate the optimization approaches of tACS in recent research. Optimization approaches can be classified into two groups: high-definition electrical stimulation and interference modulation electrical stimulation. The optimization methods can be divided into five categories: high-definition tACS, phase-shifted tACS, amplitude-modulated tACS, the temporally interfering (TI) method, and the intersectional short pulse (ISP) method. Finally, we summarize the latest research on hardware useful for tACS improvement and outline future directions.
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http://dx.doi.org/10.3389/fnhum.2021.652393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215166PMC
June 2021

Metric learning for image-based flower cultivars identification.

Plant Methods 2021 Jun 22;17(1):65. Epub 2021 Jun 22.

College of Agriculture / College of Tree Peony, Henan University of Science and Technology, Luoyang, 471023, China.

Background: The study of plant phenotype by deep learning has received increased interest in recent years, which impressive progress has been made in the fields of plant breeding. Deep learning extremely relies on a large amount of training data to extract and recognize target features in the field of plant phenotype classification and recognition tasks. However, for some flower cultivars identification tasks with a huge number of cultivars, it is difficult for traditional deep learning methods to achieve better recognition results with limited sample data. Thus, a method based on metric learning for flower cultivars identification is proposed to solve this problem.

Results: We added center loss to the classification network to make inter-class samples disperse and intra-class samples compact, the script of ResNet18, ResNet50, and DenseNet121 were used for feature extraction. To evaluate the effectiveness of the proposed method, a public dataset Oxford 102 Flowers dataset and two novel datasets constructed by us are chosen. For the method of joint supervision of center loss and L-softmax loss, the test accuracy rate is 91.88%, 97.34%, and 99.82% across three datasets, respectively. Feature distribution observed by T-distributed stochastic neighbor embedding (T-SNE) verifies the effectiveness of the method presented above.

Conclusions: An efficient metric learning method has been described for flower cultivars identification task, which not only provides high recognition rates but also makes the feature extracted from the recognition network interpretable. This study demonstrated that the proposed method provides new ideas for the application of a small amount of data in the field of identification, and has important reference significance for the flower cultivars identification research.
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http://dx.doi.org/10.1186/s13007-021-00767-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220695PMC
June 2021

Association of dietary isoflavone consumption with subclinical cardiovascular disease in middle-aged and elderly Chinese people.

Nutr Metab Cardiovasc Dis 2021 Jul 18;31(8):2302-2310. Epub 2021 Apr 18.

Department of Biostatistics, School of Public Health, Southern Medical University(Guangdong Provincial Key Laboratory of Tropical Disease Research), No. 1838 North Guangzhou Avenue, Guangzhou, 510515, People's Republic of China. Electronic address:

Background And Aims: The association between isoflavone (ISF) consumption and cardiovascular disease (CVD) remains controversial because of limited evidence. Carotid atherosclerosis is an established indicator of subclinical CVD. The study aimed to investigate the relationship between dietary ISF intake and subclinical CVD in middle-aged and elderly adults.

Methods And Results: A total of 873 subjects aged 40-70 years without CVD were enrolled in this cross-sectional study. A restricted cubic spline was used to investigate the association between ISF intake and subclinical CVD risk. The odds ratio (OR) and 95% confidence interval of the risk of subclinical CVD for ISF were estimated by two-segmented logistic regression analysis. In Model 2, there was a non-linear association between ISF intake and the risk of subclinical CVD among women (P = 0.002), with an inverse association below the change point. The nadir for the risk of subclinical CVD among women was 7.26 mg/day (energy-adjusted). Below the change point, an increase of 1 mg ISF/day reduced the risk of subclinical CVD by 15%. There was no significant association between ISF intake and subclinical CVD risk above the change point (OR = 1.01 [0.99, 1.04]). ISF intake was not associated with subclinical CVD risk in men (Model 2: P = 0.224).

Conclusions: Below the change point (7.26 mg/day), women with a higher intake of ISF had a significantly lower risk of subclinical CVD. Encouraging the consumption of ISF-rich foods may help to lower CVD risk in middle-aged and elderly women.

Trial Registration: This study is registered at http://www.chictr.org.cn (ChiCTR 1900022445).
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http://dx.doi.org/10.1016/j.numecd.2021.04.003DOI Listing
July 2021

Large-Scale Brain Functional Network Integration for Discrimination of Autism Using a 3-D Deep Learning Model.

Front Hum Neurosci 2021 2;15:687288. Epub 2021 Jun 2.

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Sciences and Technology, Xi'an Jiaotong University, Xi'an, China.

Goal: Brain functional networks (BFNs) constructed using resting-state functional magnetic resonance imaging (fMRI) have proven to be an effective way to understand aberrant functional connectivity in autism spectrum disorder (ASD) patients. It is still challenging to utilize these features as potential biomarkers for discrimination of ASD. The purpose of this work is to classify ASD and normal controls (NCs) using BFNs derived from rs-fMRI.

Methods: A deep learning framework was proposed that integrated convolutional neural network (CNN) and channel-wise attention mechanism to model both intra- and inter-BFN associations simultaneously for ASD diagnosis. We investigate the effects of each BFN on performance and performed inter-network connectivity analysis between each pair of BFNs. We compared the performance of our CNN model with some state-of-the-art algorithms using functional connectivity features.

Results: We collected 79 ASD patients and 105 NCs from the ABIDE-I dataset. The mean accuracy of our classification algorithm was 77.74% for classification of ASD versus NCs.

Conclusion: The proposed model is able to integrate information from multiple BFNs to improve detection accuracy of ASD.

Significance: These findings suggest that large-scale BFNs is promising to serve as reliable biomarkers for diagnosis of ASD.
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http://dx.doi.org/10.3389/fnhum.2021.687288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206477PMC
June 2021

Targeted Micellar Phthalocyanine for Lymph Node Metastasis Homing and Photothermal Therapy in an Orthotopic Colorectal Tumor Model.

Nanomicro Lett 2021 Jun 19;13(1):145. Epub 2021 Jun 19.

Hongqiao International Institute of Medicine, Tongren Hospital and State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200025, People's Republic of China.

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http://dx.doi.org/10.1007/s40820-021-00666-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214644PMC
June 2021

Establishment of a 3D model of tumor-driven angiogenesis to study the effects of anti-angiogenic drugs on pericyte recruitment.

Biomater Sci 2021 Jun 17. Epub 2021 Jun 17.

Laboratory of Stem Cells and Translational Medicine, Institutes for Life Sciences, School of Medicine, South China University of Technology, Guangzhou 510006, P. R. China. and National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, P. R. China and Key Laboratory of Biomedical Engineering of Guangdong Province, South China University of Technology, Guangzhou 510006, P. R. China and Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou 510006, P. R. China and Innovation Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, P. R. China.

Hepatocellular carcinoma (HCC), as a well-vascularized tumor, has attracted increasing attention in antiangiogenic therapies. Notably, emerging studies reveal that the long-term administration of antiangiogenic drugs induces hypoxia in tumors. Pericytes, which play a vital role in vascular stabilization and maturation, have been documented to be associated with antiangiogenic drug-induced tumor hypoxia. However, the role of antiangiogenic agents in regulating pericyte behavior still remains elusive. In this study, by using immunostaining analysis, we first demonstrated that tumors obtained from HCC patients were highly angiogenic, in which vessels were irregularly covered by pericytes. Therefore, we established a new 3D model of tumor-driven angiogenesis by culturing endothelial cells, pericytes, cancer stem cells (CSCs) and mesenchymal stem cells (MSCs) with microcarriers in order to investigate the effects and mechanisms exerted by antiangiogenic agents on pericyte recruitment during tumor angiogenesis. Interestingly, microcarriers, as supporting matrices, enhanced the interactions between tumor cells and the extracellular matrix (ECM), promoted malignancy of tumor cells and increased tumor angiogenesis within the 3D model, as determined by qRT-PCR and immunostaining. More importantly, we showed that zoledronic acid (ZA) reversed the inhibited pericyte recruitment, which was induced by sorafenib (Sora) treatment, through fostering the expression and activation of ErbB1/ErbB2 and PDGFR-β in pericytes, in both an in vitro 3D model and an in vivo xenograft HCC mouse model. Hence, our model provides a more pathophysiologically relevant platform for the assessment of therapeutic effects of antiangiogenic compounds and identification of novel pharmacological targets, which might efficiently improve the benefits of antiangiogenic treatment for HCC patients.
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http://dx.doi.org/10.1039/d0bm02107eDOI Listing
June 2021

The GABA Receptor Influences Pressure Overload-Induced Heart Failure by Modulating Macrophages in Mice.

Front Immunol 2021 31;12:670153. Epub 2021 May 31.

Institution of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Myocardial macrophages have key roles in cardiac remodeling and dysfunction. The gamma-aminobutyric acid subtype A (GABA) receptor was recently found to be distributed in macrophages, allowing regulation of inflammatory responses to various diseases. This study aimed to clarify the role of GABA receptor-mediated macrophage responses in pressure overload-induced heart failure.

Methods And Results: C57BL/6J mice underwent transverse aortic constriction for pressure-overload hypertrophy (POH) and were intraperitoneally treated with a specific GABA receptor agonist (topiramate) or antagonist (bicuculline). Echocardiography, histology, and flow cytometry were performed to evaluate the causes and effects of myocardial hypertrophy and fibrosis. Activation of the GABA receptor by topiramate reduced ejection fraction and fractional shortening, enlarged the end-diastolic and end-systolic left ventricular internal diameter, aggravated myocardial hypertrophy and fibrosis, and accelerated heart failure in response to pressure overload. Mechanistically, topiramate increased the number of Ly6C macrophages in the heart during POH and circulating Ly6C classic monocyte infiltration in late-phase POH. Further, topiramate drove Ly6C macrophages toward MHCII macrophage polarization. As a result, Ly6C macrophages activated the amphiregulin-induced AKT/mTOR signaling pathway, and Ly6CMHCII macrophage polarization increased expression levels of osteopontin and TGF-β, which led to myocardial hypertrophy and fibrosis. Conversely, GABA receptor blockage with bicuculline reversed these effects.

Conclusions: Control of the GABA receptor activity in monocytes/macrophages plays an important role in myocardial hypertrophy and fibrosis after POH. Blockade of the GABA receptor has the potential to improve pressure overload-induced heart failure.
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http://dx.doi.org/10.3389/fimmu.2021.670153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201502PMC
May 2021

The associations of gut microbiota and fecal short-chain fatty acids with bone mass were largely mediated by weight status: a cross-sectional study.

Eur J Nutr 2021 Jun 15. Epub 2021 Jun 15.

Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Nutrition and Food Hygiene, School of Public Health, Southern Medical University, Guangzhou, China.

Purpose: We aimed to investigate whether the gut microbiota and fecal short-chain fatty acids (SCFAs) are associated with bone mass in healthy children aged 6-9 years.

Methods: In this study, 236 healthy children including 145 boys and 91 girls were enrolled. 16S rRNA gene sequencing was used to characterize the composition of their gut microbiota. Total and 10 subtypes of SCFAs in the fecal samples were determined by high-performance liquid chromatography. Dual X-ray absorptiometry was used to measure the bone mineral density (BMD) and bone mineral content (BMC) for total body (TB) and total body less head (TBLH). Z score of TBLH BMD was calculated based on the recommended reference.

Results: Four gut microbiota principal components (PCs) were identified by the compositional principal component analysis at the genus level. After adjustment of covariates and controlling for the false discovery rate, multiple linear regression analysis showed that PC3 score (positive loadings on genera Lachnoclostridium and Blautia) was significantly negatively associated with TBLH BMD/BMC/Z score, TB BMC and pelvic BMD (β: - 0.207 to - 0.108, p: 0.002-0.048), whereas fecal total and several subtypes of SCFAs were correlated positively with TBLH BMD/Z score and pelvic BMD (β: 0.118-0.174, p: 0.038-0.048). However, these associations disappeared after additional adjustment for body weight. Mediation analysis suggested that body weight significantly mediated 60.4% and 78.0% of the estimated association of PC3 score and SCFAs with TBLH BMD Z score, respectively.

Conclusions: The associations of gut microbiota composition and fecal SCFA concentrations with bone mass in children were largely mediated by body weight.
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http://dx.doi.org/10.1007/s00394-021-02597-xDOI Listing
June 2021

Chrysin Inhibits Pseudo-allergic Reaction by Suppressing Mitochondrial STAT3 Activation MAS-Related GPR Family Member X2.

J Agric Food Chem 2021 Jun 8;69(23):6569-6577. Epub 2021 Jun 8.

School of Pharmacy, Xi'an Jiaotong University, Xi'an 710049, China.

Chrysin, one of the most pharmacologically active natural flavonoids, has been extracted from various plants. Mast cells are an important part of innate immunity-mediating anaphylaxis. Pseudo-allergic reactions are currently believed to be associated with the MAS-related GPR family member X2 (MrgX2). In this study, the anti-pseudo allergy effect of chrysin and its underlying mechanisms were studied and . Chrysin inhibited passive cutaneous anaphylaxis and systemic pseudo-allergy . LAD2 cell degranulation, calcium ion (Ca) influx, and adenosine 5'-triphosphate (ATP) content were significantly suppressed in a dose-dependent manner. Chrysin suppressed pseudo-allergic reactions through the PLC/IP3/Ca and ERK/STAT3 serine 727 pathways downstream of MrgX2. Therefore, mitochondrial ATP, but not glycolysis, is vital for pseudo-allergic reactions mediated by MrgX2. This study provides new insights for the treatment of pseudo-allergy.
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http://dx.doi.org/10.1021/acs.jafc.1c02565DOI Listing
June 2021

SARS-CoV-2 infection induces the activation of tissue factor-mediated coagulation by activation of acid sphingomyelinase.

Blood 2021 Jun 1. Epub 2021 Jun 1.

The University of Texas Health Science Center at Tyler, Tyler, Texas, United States.

SARS-CoV-2 infection is associated with the hypercoagulable state. Tissue factor (TF) is the primary cellular initiator of coagulation. Most of the TF expressed on cell surfaces remains cryptic. Sphingomyelin (SM) is responsible for maintaining TF in the encrypted state, and hydrolysis of SM by acid sphingomyelinase (ASMase) increases TF activity. ASMase was shown to play a role in virus infection biology. In the present study, we investigated the role of ASMase in SARS-CoV-2 infection-induced TF procoagulant activity. Infection of human monocyte-derived macrophages (MDMs) with SARs-CoV-2 spike protein pseudovirus (SARS-CoV-2-SP-PV) markedly increased TF procoagulant activity at the cell surface and released TF+ extracellular vesicles (EVs). The pseudovirus infection did not increase either TF protein expression or phosphatidylserine externalization. SARS-CoV-2-SP-PV infection induced the translocation of ASMase to the outer leaflet of the plasma membrane, which led to the hydrolysis of SM in the membrane. Pharmacological inhibitors or genetic silencing of ASMase attenuated SARS-CoV-2-SP-PV-induced increased TF activity. Inhibition of SARS-CoV-2 receptor, angiotensin-converting enzyme-2, attenuated SARS-CoV-2-SP-PV-induced increased TF activity. Overall, our data suggest that SARS-CoV-2 infection activates the coagulation by decrypting TF through activation of ASMase. Our data suggest that the FDA-approved functional inhibitors of ASMase may help treat hypercoagulability in COVID-19 patients.
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http://dx.doi.org/10.1182/blood.2021010685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172270PMC
June 2021

The Role and Mechanism of ATM-Mediated Autophagy in the Transition From Hyper-Radiosensitivity to Induced Radioresistance in Lung Cancer Under Low-Dose Radiation.

Front Cell Dev Biol 2021 12;9:650819. Epub 2021 May 12.

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

This study aimed to investigate the effect of ataxia telangiectasia mutated (ATM)-mediated autophagy on the radiosensitivity of lung cancer cells under low-dose radiation and to further investigate the role of ATM and its specific mechanism in the transition from hyper-radiosensitivity (HRS) to induced radioresistance (IRR). The changes in the HRS/IRR phenomenon in A549 and H460 cells were verified by colony formation assay. Changes to ATM phosphorylation and cell autophagy in A549 and H460 cells under different low doses of radiation were examined by western blot, polymerase chain reaction (PCR), and electron microscopy. ATM expression was knocked down by short interfering RNA (siRNA) transfection, and ATM-regulated molecules related to autophagy pathways were screened by transcriptome sequencing analysis. The detection results were verified by PCR and western blot. The differential metabolites were screened by transcriptome sequencing and verified by colony formation assay and western blot. The nude mouse xenograft model was used to verify the results of the cell experiments. (1) A549 cells with high expression of ATM showed positive HRS/IRR, whereas H460 cells with low expression of ATM showed negative HRS/IRR. After the expression of ATM decreased, the HRS phenomenon in A549 cells increased, and the radiosensitivity of H460 cells also increased. This phenomenon was associated with the increase in the autophagy-related molecules phosphorylated c-Jun N-terminal kinase (p-JNK) and autophagy/Beclin 1 regulator 1 (AMBRA1). (2) DL-Norvaline, a product of carbon metabolism in cells, inhibited autophagy in A549 cells under low-dose radiation. DL-Norvaline increased the expression levels of ATM, JNK, and AMBRA1 in A549 cells. (3) Mouse experiments confirmed the regulatory role of ATM in autophagy and metabolism and its function in HRS/IRR. ATM may influence autophagy through p-JNK and AMBRA1 to participate in the regulation of the HRS/IRR phenomenon. Autophagy interacts with the cellular carbon metabolite DL-Norvaline to participate in regulating the low-dose radiosensitivity of cells.
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http://dx.doi.org/10.3389/fcell.2021.650819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149741PMC
May 2021