Publications by authors named "Jun Wei"

654 Publications

MiR-543 Inhibits the Migration and Epithelial-To-Mesenchymal Transition of TGF-β-Treated Endometrial Stromal Cells via the MAPK and Wnt/β-Catenin Signaling Pathways.

Pathol Oncol Res 2021 29;27:1609761. Epub 2021 Apr 29.

Department of Gynecology, General Hospital of Ningxia Medical University, Yinchuan, China.

Intrauterine adhesion (IUA) is one of the most prevalent reproductive system diseases in females. MicroRNAs (miRNAs) are reported to be master regulators in a variety of diseases, including IUA, but the role of microRNA-543 (miR-543) in IUA remains to be elucidated. In this study, we observed that miR-543 was downregulated in transforming growth factor-beta (TGF-β)-treated endometrial stromal cells (ESCs). Functionally, we observed that miR-543 suppressed the migration, epithelial-to-mesenchymal transition (EMT), and inhibited expression of extracellular matrix (ECM) proteins in TGF-β-treated ESCs. Mechanistically, MAPK1 is targeted by miR-543 after prediction and screening. A luciferase reporter assay demonstrated that miR-543 complementarily binds with the 3' untranslated region of mitogen-activated protein kinase 1 (MAPK1), and western blot analysis indicated that miR-543 negatively regulates MAPK1 protein levels. In addition, results from rescue assays showed that miR-543 inhibits the migration and EMT of TGF-β-treated ESCs by targeting MAPK1. In addition, we observed that miR-543 inactivates the Wnt/β-catenin signaling pathway through inhibiting the phosphorylation of MAPK1 and β-catenin. Finally, we confirmed that miR-543 represses migration, EMT and inhibits levels of ECM proteins in TGF-β-treated ESCs by targeting the Wnt/β-catenin signaling pathway. Our results demonstrated that miR-543 suppresses migration and EMT of TGF-β-treated ESCs by targeting the MAPK and Wnt/β-catenin pathways.
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http://dx.doi.org/10.3389/pore.2021.1609761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262167PMC
April 2021

Observed evidence for guideline-recommended genes in predicting prostate cancer risk from a large population-based cohort.

Prostate 2021 Jul 12. Epub 2021 Jul 12.

Program for Personalized Cancer Care, NorthShore University HealthSystem, Evanston, Illinois, USA.

Background: Germline testing for prostate cancer (PCa) is now recommended by the National Comprehensive Cancer Network. While multi-gene testing has been proposed, evidence for their association with PCa risk is not well established.

Methods: We tested associations of pathogenic/likely pathogenic mutations in 10 guideline-recommended genes (ATM, BRCA1, BRCA2, CHEK2, PALB2, MLH1, MSH2, MSH6, PMS2, and HOXB13) with PCa risk in the UK Biobank, a population-based cohort. Mutations were annotated based on prostate-specific transcripts using the American College of Medical Genetics and Genomics standards. Associations were tested in 4399 PCa cases and 85,403 unaffected male controls using logistic regression adjusting for age and genetic background. p < .005 was considered significant based on Bonferroni correction.

Results: Among the 10 tested genes, significantly higher mutation carrier rates in PCa cases versus controls were found for four genes at p < .005; HOXB13, BRCA2, ATM, and CHEK2, with odds ratios (95% confidence interval) estimated at 4.96 (3.62-6.69), 3.23 (2.23-4.56), 2.95 (2.01-4.22), 1.94 (1.43-2.58), respectively. No significant association was found between mutation carrier status and age at PCa diagnosis or family history of PCa. Despite the large sample size of this study, statistical power remains limited, especially for genes where pathogenic mutation carrier rates are extremely rare (<0.03%).

Conclusion: Observed evidence for PCa risk was found for four of the 10 guideline-recommended genes in this large population-based study. Mutations in these four genes can be interpreted with confidence in genetic counseling for PCa risk assessment. Evidence for the remaining six genes needs to be further evaluated in larger studies.
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http://dx.doi.org/10.1002/pros.24195DOI Listing
July 2021

Metabolic control of T cells and humoral immunity by phosphatidylethanolamine.

Nature 2021 Jul 7. Epub 2021 Jul 7.

Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.

T follicular helper (T) cells are crucial for B cell-mediated humoral immunity. Although transcription factors such as BCL6 drive the differentiation of T cells, it is unclear whether and how post-transcriptional and metabolic programs enforce T cell programming. Here we show that the cytidine diphosphate (CDP)-ethanolamine pathway co-ordinates the expression and localization of CXCR5 with the responses of T cells and humoral immunity. Using in vivo CRISPR-Cas9 screening and functional validation in mice, we identify ETNK1, PCYT2, and SELENOI-enzymes in the CDP-ethanolamine pathway for de novo synthesis of phosphatidylethanolamine (PE)-as selective post-transcriptional regulators of T cell differentiation that act by promoting the surface expression and functional effects of CXCR5. T cells exhibit unique lipid metabolic programs and PE is distributed to the outer layer of the plasma membrane, where it colocalizes with CXCR5. De novo synthesis of PE through the CDP-ethanolamine pathway co-ordinates these events to prevent the internalization and degradation of CXCR5. Genetic deletion of Pcyt2, but not of Pcyt1a (which mediates the CDP-choline pathway), in activated T cells impairs the differentiation of T cells, and this is associated with reduced humoral immune responses. Surface levels of PE and CXCR5 expression on B cells also depend on Pcyt2. Our results reveal that phospholipid metabolism orchestrates post-transcriptional mechanisms for T cell differentiation and humoral immunity, highlighting the metabolic control of context-dependent immune signalling and effector programs.
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http://dx.doi.org/10.1038/s41586-021-03692-zDOI Listing
July 2021

A Reduction Active Theranostic Nanoparticle for Enhanced Near-Infrared Imaging and Phototherapy by Reducing Glutathione Level in Cancer Cells.

J Nanosci Nanotechnol 2021 12;21(12):5965-5971

Key Laboratory for Green Chemical Process of Ministry of Education, Hubei Key Laboratory for Novel Reactor and Green Chemistry Technology, Hubei Engineering Research Center for Advanced Fine Chemicals , School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan, 430205, P. R. China.

Facile preparation of a tumoral-stimuli-activated theranostic nanoparticle with simple constituents remains a challenge for tumor theranostic nanosystems. Herein we design a simple reductionresponsive turn-on theranostic nanoparticle for achieving fluorescent imaging and phototherapy combination. The theranostic nanoparticle is prepared by a simple one-step dialysis method of reduction active amphiphilic hyperbranched poly(-amidoamines) and a near-infrared (NIR) dye indocyanine green (ICG). The fluorescence of ICG is quenched by the aggregation-caused quenching (ACQ) effect. The fluorescent intensity of free ICG at 816 nm was ∼40 times as high as that of particulate ICG. After reductive nanoparticles incubated with dithiothreitol (DTT), the size of the nanoparticles increased from 160 nm to 610 nm by Dynamic light scattering (DLS). As nanoparticles were internalized by cancer cells, the disulfide bonds would be cleaved by intracellular reduction agents like glutathione (GSH), leading to the release of entrapped ICG. The released ICG regained its fluorescence for self-monitoring the release and therapeutic effect of ICG by fluorescence spectra and the quantitative evaluation of NIR fluorescence intensity. Remarkably, nanoparticles can also reinforce antitumor efficacy through photodynamic therapy and GSH depletion property. This study provides new insights into designing turn-on theranostic systems.
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http://dx.doi.org/10.1166/jnn.2021.19514DOI Listing
December 2021

Evaluation of fluoride adsorption in solution by synthetic Al O /CeO : a fixed-bed column study.

Water Environ Res 2021 Jul 2. Epub 2021 Jul 2.

Key Laboratory of Integrated Regulation and Resource Development on Shallow Lakes of Ministry of Education, College of Environment, Hohai University, Nanjing, China.

A highly efficient fluoride adsorbent Al O /CeO was synthesized in this work, and used it to fluoride removal in the fixed-bed adsorption through changing the different experimental conditions (influent F concentration, flow velocity and bed heights). The adsorption capacity was 9.72 mg/g. In addition, Adams-Bohart and Thomas models were used to fit and evaluate the column breakthrough curve of fluoride removal process by Al O /CeO , and the correlation coefficients (R ) of Thomas model were close to 1 under all experimental conditions. The structure of Al O /CeO and the adsorption mechanism were confirmed by XRD, FT-IR, N adsorption and desorption isotherm, SEM, TEM and XPS. Moreover, the adsorption of fluoride (F ) was mainly through metal binding (MF) and hydroxyl binding (Al-OH⋯F) on the surface of the Al O /CeO . Furthermore, the regeneration and co-existing anions studies of Al O /CeO were carried out, and the efficiency of adsorption was still above 70% after five cycles.
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http://dx.doi.org/10.1002/wer.1601DOI Listing
July 2021

Quantitative Evaluation of the Trauma of CT Navigation PELD and OD in the Treatment of HLDH: A Randomized, Controlled Study.

Pain Physician 2021 Jul;24(4):E433-E441

First Affiliated Hospital of GanNan Medical UniversityCollege, GanZhou, China.

Background: More evidence is required to support that computerized tomography navigation percutaneous spinal endoscopy in the treatment of highly migrated lumbar disc herniation is a more minimally invasive surgery than open discectomy .

Objective: To quantitatively evaluate the efficacy and minimal invasiveness of computerized tomography navigation percutaneous spinal endoscopy and open discectomy in highly migrated lumbar disc herniation.

Study Design: A prospective randomized study.

Setting: First Affiliated Hospital of Gannan Medical College.

Methods: From August 2016 to February 2020, 68 patients with highly migrated lumbar disc herniation had undergone discectomy. Thirty-five of them randomly received computerized tomography (CT) navigation percutaneous spinal endoscopy at the pain department (CT navigation percutaneous spinal endoscopy group), and 33 patients received open discectomy at the orthopedics department (open discectomy group). The Visual Analog Scale (VAS) score, Japanese Orthopaedic Association (JOA) score, and modified MacNab criteria were applied to evaluate the clinical situations pre- and post-operation. The serum concentrations of IL-6, TNF-alpha, creatine phosphokina (CPK), and C-reactive protein (CRP) in the 2 groups were quantitatively measured.

Results: The postoperative VAS scores of the back and lower extremity were lower than those pre-operation in both groups, while the VAS score of back pain in the open discectomy group was significantly higher than that in the CT navigation percutaneous spinal endoscopy group at one week post-operation (P < 0.01). The postoperative JOA scores were significantly higher than those pre-operation in both groups. The serum concentrations of IL-6, TNF-alpha, CPK, and CRP in the open discectomy group were higher than those in the computerized tomography navigation percutaneous spinal endoscopy group postoperatively (P < 0.01).

Limitations: This is a single-center randomized study and with the limitation of the sample size.

Conclusion: CT navigation percutaneous spinal endoscopy is a more minimally invasive surgery than open discectomy.Certificate number for the medical institution conducting the clinical trials for humans in China: 934.
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July 2021

A Self-Healing Crease-Free Supramolecular All-Polymer Supercapacitor.

Adv Sci (Weinh) 2021 Jun 1;8(12):2100072. Epub 2021 May 1.

Department of Materials Science and Engineering City University of Hong Kong 83 Dachi Road Kowloon Hong Kong SAR 999077 China.

While traditional three-layer structure supercapacitors are under mechanical manipulations, the high-stress region concentrates, inevitably causing persistent structural problems including interlayer slippage, crease formation, and delamination of the electrode-electrolyte interface. Toward this, an all-polymeric, all-elastic and non-laminated supercapacitor with high mechanical reliability and excellent electrochemical performance is developed. Specifically, a polypyrrole electrode layer is in situ integrated into a silk fibroin-based elastic supramolecular hydrogel film with extensive hydrogen and covalent bonds, where a non-laminate device is realized with structural elasticity at the device level. The non-laminate configuration can avoid slippage and delamination, while the elasticity can preclude crease formation. Furthermore, under more severe mechanical damage, the supercapacitors can restore the electrochemical performance through non-autonomous self-healing capabilities, where the supramolecular design of host-guest interactions in the hydrogel matrix results in a superior self-healing efficiency approaching ≈95.8% even after 30 cutting/healing cycles. The all-elastic supercapacitor delivers an areal capacitance of 0.37 F cm and a volumetric energy density of 0.082 mW h cm, which can well-maintain the specific capacitance even at -20 °C with over 85.2% retention after five cut/healing cycles.
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http://dx.doi.org/10.1002/advs.202100072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224449PMC
June 2021

Genomic Classification and Clinical Outcome in Rhabdomyosarcoma: A Report From an International Consortium.

J Clin Oncol 2021 Jun 24:JCO2003060. Epub 2021 Jun 24.

Department of Pediatrics, Seattle Children's Hospital, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA.

Purpose: Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood. Despite aggressive therapy, the 5-year survival rate for patients with metastatic or recurrent disease remains poor, and beyond fusion status, no genomic markers are available for risk stratification. We present an international consortium study designed to determine the incidence of driver mutations and their association with clinical outcome.

Patients And Methods: Tumor samples collected from patients enrolled on Children's Oncology Group trials (1998-2017) and UK patients enrolled on malignant mesenchymal tumor and RMS2005 (1995-2016) trials were subjected to custom-capture sequencing. Mutations, indels, gene deletions, and amplifications were identified, and survival analysis was performed.

Results: DNA from 641 patients was suitable for analyses. A median of one mutation was found per tumor. In fusion-negative cases, mutation of any RAS pathway member was found in > 50% of cases, and 21% had no putative driver mutation identified. (15%), (15%), and (13%) mutations were found at a higher incidence than previously reported and mutations were associated with worse outcomes in both fusion-negative and fusion-positive cases. Interestingly, mutations in isoforms predominated in infants < 1 year (64% of cases). Mutation of was associated with histologic patterns beyond those previously described, older age, head and neck primary site, and a dismal survival. Finally, we provide a searchable companion database (ClinOmics), containing all genomic variants, and clinical annotation including survival data.

Conclusion: This is the largest genomic characterization of clinically annotated rhabdomyosarcoma tumors to date and provides prognostic genetic features that refine risk stratification and will be incorporated into prospective trials.
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http://dx.doi.org/10.1200/JCO.20.03060DOI Listing
June 2021

Notch signaling and efficacy of PD-1/PD-L1 blockade in relapsed small cell lung cancer.

Nat Commun 2021 06 23;12(1):3880. Epub 2021 Jun 23.

Developmental Therapeutics Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD, USA.

Immune checkpoint blockade (ICB) benefits only a small subset of patients with small cell lung cancer (SCLC), yet the mechanisms driving benefit are poorly understood. To identify predictors of clinical benefit to ICB, we performed immunogenomic profiling of tumor samples from patients with relapsed SCLC. Tumors of patients who derive clinical benefit from ICB exhibit cytotoxic T-cell infiltration, high expression of antigen processing and presentation machinery (APM) genes, and low neuroendocrine (NE) differentiation. However, elevated Notch signaling, which positively correlates with low NE differentiation, most significantly predicts clinical benefit to ICB. Activation of Notch signaling in a NE human SCLC cell line induces a low NE phenotype, marked by increased expression of APM genes, demonstrating a mechanistic link between Notch activation, low NE differentiation and increased intrinsic tumor immunity. Our findings suggest Notch signaling as a determinant of response to ICB in SCLC.
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http://dx.doi.org/10.1038/s41467-021-24164-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222224PMC
June 2021

Targeting the αv integrin/TGF-β axis improves natural killer cell function against glioblastoma stem cells.

J Clin Invest 2021 Jul;131(14)

Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Glioblastoma multiforme (GBM), the most aggressive brain cancer, recurs because glioblastoma stem cells (GSCs) are resistant to all standard therapies. We showed that GSCs, but not normal astrocytes, are sensitive to lysis by healthy allogeneic natural killer (NK) cells in vitro. Mass cytometry and single-cell RNA sequencing of primary tumor samples revealed that GBM tumor-infiltrating NK cells acquired an altered phenotype associated with impaired lytic function relative to matched peripheral blood NK cells from patients with GBM or healthy donors. We attributed this immune evasion tactic to direct cell-to-cell contact between GSCs and NK cells via αv integrin-mediated TGF-β activation. Treatment of GSC-engrafted mice with allogeneic NK cells in combination with inhibitors of integrin or TGF-β signaling or with TGFBR2 gene-edited allogeneic NK cells prevented GSC-induced NK cell dysfunction and tumor growth. These findings reveal an important mechanism of NK cell immune evasion by GSCs and suggest the αv integrin/TGF-β axis as a potentially useful therapeutic target in GBM.
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http://dx.doi.org/10.1172/JCI142116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279586PMC
July 2021

Association of Sickle Cell Trait with Risk and Mortality of COVID-19: Results from the United Kingdom Biobank.

Am J Trop Med Hyg 2021 Jun 15. Epub 2021 Jun 15.

Program for Personalized Cancer Care, NorthShore University HealthSystem, Evanston, Illinois.

Sickle cell trait (SCT) carriers inherit one copy of the Glu6Val mutation in the hemoglobin gene and is particularly common in Black individuals (5-10%). Considering the roles of hemoglobin in immune responses and the higher risk for coronavirus disease (COVID-19) among Black individuals, we tested whether Black SCT carriers were at increased risk for COVID-19 infection and mortality according to the United Kingdom Biobank. Among Black individuals who were tested for COVID-19, we found similar infection rates among SCT carriers (14/72; 19.7%) and noncarriers (167/791; 21.1%), but higher COVID-19 mortality rates among SCT carriers (4/14; 28.6%) than among noncarriers (21/167; 12.6%) (odds ratio [OR], 3.04; 95% confidence interval [CI], 0.69-11.82; P = 0.12). Notably, SCT carriers with preexisting diabetes had significantly higher COVID-19 mortality (4/4; 100%) than those without diabetes (0/10; 0%; (OR, 90.71; 95% CI, 5.66-infinite; P = 0.0005). These findings suggest that Black SCT carriers with preexisting diabetes are at disproportionally higher risk for COVID-19 mortality. Confirmation by larger studies is warranted.
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http://dx.doi.org/10.4269/ajtmh.20-1657DOI Listing
June 2021

Pathogenic Germline Variants in Cancer Susceptibility Genes in Children and Young Adults With Rhabdomyosarcoma.

JCO Precis Oncol 2021 11;5. Epub 2021 Jan 11.

Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.

Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue sarcoma and accounts for 3% of all pediatric cancer. In this study, we investigated germline sequence and structural variation in a broad set of genes in two large, independent RMS cohorts.

Materials And Methods: Genome sequencing of the discovery cohort (n = 273) and exome sequencing of the secondary cohort (n = 121) were conducted on germline DNA. Analyses were performed on 130 cancer susceptibility genes (CSG). Pathogenic or likely pathogenic (P/LP) variants were predicted using the American College of Medical Genetics and Genomics (ACMG) criteria. Structural variation and survival analyses were performed on the discovery cohort.

Results: We found that 6.6%-7.7% of patients with RMS harbored P/LP variants in dominant-acting CSG. An additional approximately 1% have structural variants (, ) in CSGs. CSG variants did not influence survival, although there was a significant correlation with an earlier age of tumor onset. There was a nonsignificant excess of P/LP variants in dominant inheritance genes in the patients with fusion-negative RMS patients versus the patients with fusion-positive RMS. We identified pathogenic germline variants in CSGs previously (, , , mismatch repair genes), rarely (, , , ), or never () reported in RMS. Numerous genes (, , mismatch repair) were on the ACMG Secondary Findings 2.0 list.

Conclusion: In two cohorts of patients with RMS, we identified pathogenic germline variants for which gene-specific therapies and surveillance guidelines may be beneficial. In families with a proband with an RMS-risk P/LP variant, genetic counseling and cascade testing should be considered, especially for ACMG Secondary Findings genes and/or with gene-specific surveillance guidelines.
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http://dx.doi.org/10.1200/PO.20.00218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169077PMC
January 2021

Transcriptome and Metabolome Analyses Provide Insights into the Watercore Disorder on "Akibae" Pear Fruit.

Int J Mol Sci 2021 May 6;22(9). Epub 2021 May 6.

School of Horticulture and Plant Protection, International Research Laboratory of Agriculture and Agri-Product Safety, Key Laboratory of Plant Functional Genomics of the Ministry of Education, Yangzhou University, 48 Wenhui East Road, Yangzhou 225009, China.

Watercore is a physiological disorder that commonly occurs in sand pear cultivars. The typical symptom of watercore tissue is transparency, and it is often accompanied by browning, breakdown and a bitter taste during fruit ripening. To better understand the molecular mechanisms of watercore affecting fruit quality, this study performed transcriptome and metabolome analyses on watercore pulp from "Akibae" fruit 125 days after flowering. The present study found that the "Akibae" pear watercore pulp contained higher sorbitol and sucrose than healthy fruit. Moreover, the structure of the cell wall was destroyed, and the content of pectin, cellulose and hemicellulose was significantly decreased. In addition, the content of ethanol and acetaldehyde was significantly increased, and the content of polyphenol was significantly decreased. Watercore induced up-regulated expression levels of sorbitol synthesis-related (sorbitol-6-phosphate dehydrogenase, S6PDH) and sucrose synthesis-related genes (sucrose synthesis, SS), whereas it inhibited the expression of sorbitol decomposition-related genes (sorbitol dehydrogenase, SDH) and sorbitol transport genes (sorbitol transporter, SOT). Watercore also strongly induced increased expression levels of cell wall-degrading enzymes (polygalactosidase, PG; ellulase, CX; pectin methylesterase, PME), as well as ethanol synthesis-related (alcohol dehydrogenase, ADH), acetaldehyde synthesis-related (pyruvate decarboxylase, PDC) and polyphenol decomposition-related genes (polyphenol oxidase, PPO). Moreover, the genes that are involved in ethylene (1-aminocyclopropane- 1-carboxylate oxidase, ACO; 1-aminocyclopropane- 1-carboxylate synthase, ACS) and abscisic acid (short-chain alcohol dehydrogenase, SDR; aldehyde oxidase, AAO) synthesis were significantly up-regulated. In addition, the bitter tasting amino acids, alkaloids and polyphenols were significantly increased in watercore tissue. Above all, these findings suggested that the metabolic disorder of sorbitol and sucrose can lead to an increase in plant hormones (abscisic acid and ethylene) and anaerobic respiration, resulting in aggravated fruit rot and the formation of bitter substances.
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http://dx.doi.org/10.3390/ijms22094911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124519PMC
May 2021

Integrated RNA and miRNA sequencing analysis reveals a complex regulatory network of Magnolia sieboldii seed germination.

Sci Rep 2021 May 25;11(1):10842. Epub 2021 May 25.

Department of Forestry, Shenyang Agricultural University, Shenyang, China.

Magnolia sieboldii K. Koch (M. sieboldii) is a deciduous Chinese tree species of the Magnoliaceae family with high ornamental, medicinal, and economic benefits. The germination of M. sieboldii seeds under natural conditions is extremely difficult, thereby hindering the cultivation and breeding of this important species. The molecular mechanisms underlying M. sieboldii seed germination remain unclear due to the lack of genomic and transcriptomic resources. Here, we integrated both mRNA and miRNA sequencing to identify the genes and pathways related to M. sieboldii germination. A comprehensive full-length transcriptome containing 158,083 high-quality unigenes was obtained by single-molecule real-time (SMRT) sequencing technology. We identified a total of 13,877 genes that were differentially expressed between non-germinated and germinated seeds. These genes were mainly involved in plant hormone signal transduction and diverse metabolic pathways such as those involving lipids, sugars, and amino acids. Our results also identified a complex regulatory network between miRNAs and their target genes. Taken together, we present the first transcriptome of M. sieboldii and provide key genes and pathways associated with seed germination for further characterization. Future studies of the molecular basis of seed germination will facilitate the genetic improvement M. sieboldii.
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http://dx.doi.org/10.1038/s41598-021-90270-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149418PMC
May 2021

Opening of the Blood-Brain Barrier Using Low-Intensity Pulsed Ultrasound Enhances Responses to Immunotherapy in Preclinical Glioma Models.

Clin Cancer Res 2021 May 24. Epub 2021 May 24.

Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Purpose: The blood-brain barrier (BBB) inhibits adequate dosing/penetration of therapeutic agents to malignancies in the brain. Low-intensity pulsed ultrasound (LIPU) is a safe therapeutic method of temporary BBB disruption (BBBD) to enhance chemotherapeutic delivery to the tumor and surrounding brain parenchyma for treatment of glioblastoma.

Experimental Design: We investigated if LIPU could enhance therapeutic efficacy of anti-PD-1 in C57BL/6 mice bearing intracranial GL261 gliomas, epidermal growth factor receptor variant III (EGFRvIII) chimeric antigen receptor (CAR) T cells in NSG mice with EGFRvIII-U87 gliomas, and a genetically engineered antigen-presenting cell (APC)-based therapy producing the T-cell attracting chemokine CXCL10 in the GL261-bearing mice.

Results: Mice treated with anti-PD-1 and LIPU-induced BBBD had a median survival duration of 58 days compared with 39 days for mice treated with anti-PD-1, and long-term survivors all remained alive after contralateral hemisphere rechallenge. CAR T-cell administration with LIPU-induced BBBD resulted in significant increases in CAR T-cell delivery to the CNS after 24 ( < 0.005) and 72 ( < 0.001) hours and increased median survival by greater than 129%, in comparison with CAR T cells alone. Local deposition of CXCL10-secreting APCs in the glioma microenvironment with LIPU enhanced T-cell glioma infiltration during the therapeutic window ( = 0.004) and markedly enhanced survival ( < 0.05).

Conclusions: LIPU increases immune therapeutic delivery to the tumor microenvironment with an associated increase in survival and is an emerging technique for enhancing novel therapies in the brain.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-3760DOI Listing
May 2021

Application of intravoxel incoherent motion diffusion-weighted imaging in differential diagnosis and molecular subtype analysis of breast cancer.

Am J Transl Res 2021 15;13(4):3034-3043. Epub 2021 Apr 15.

Department of Radiology, The First Affiliated Hospital of Bengbu Medical College Bengbu, Anhui Province, China.

Objective: To explore the application of incoherent motion diffusion-weighted imaging (IVIM-DWI) in the differential diagnosis and molecular subtype analysis of breast cancer.

Methods: The clinical data of 225 patients with breast masses were selected, including breast cancers (n = 135) and benign breast tumors (n = 90). According to pathological results, breast cancers were divided into four subtypes: Luminal A (n = 24), Luminal B (n = 57), HER-2-overexpression (n = 27) and triple-negative breast cancers (n = 27). The patients were detected by IVIM-DWI, and then the average diffusion coefficient (ADC), perfusion fraction (f) value, true dispersion coefficient (D) value and false dispersion coefficient (D*) value were compared and analyzed. The above index were used to identify breast cancer and its molecular subtypes by using the receiver operating characteristic (ROC) curve.

Results: The ADC, D and D*-value in breast cancer group were significantly lower than those in benign tumor group, while the f-value in breast cancer group was higher than that in benign tumor group (P<0.001); The ADC, D, D*, f-value and the combination of four have high diagnostic value in breast cancer; The D-value in PR-positive group was higher than that in the PR-negative group, while it was lower in PR-positive group (P<0.05), and the ADC, D and D*-value in the ER-positive group were significantly lower than those in the ER-negative group (P<0.001); The f-value in HER-2 positive group was higher than that in human epidermal growth factor receptor-2 (HER-2) negative group (P<0.001); The ADC and D-value of Ki-67 high-expression was lower than those of Ki-67 low-expression, while the D-value of Ki-67 high-expression was higher than that of Ki-67 low expression group (P<0.05); The ADC, D, D*, f-value and the combination of four have high diagnostic value in triple negative breast cancer.

Conclusion: IVIM-DWI technology has a significant value in differential diagnosis of benign and malignant breast tumors, and the relevant parameters of IVIM-DWI technology have definite value in the differential diagnosis of breast cancer molecular typing.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129298PMC
April 2021

TAT-modified tetramethylpyrazine-loaded nanoparticles for targeted treatment of spinal cord injury.

J Control Release 2021 Jul 17;335:103-116. Epub 2021 May 17.

Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China. Electronic address:

Tetramethylpyrazine (TMP) has been effectively used for treating spinal cord injury (SCI) due to its anti-inflammatory, antioxidant, and neuroprotective activity. However, its clinical application is limited due to poor water solubility and insufficient spinal cord targeting through the traditional dosage forms. Given that intravascular neutrophils are quickly recruited to the injury site as part of the inflammatory response in SCI, we conjugated the cell-penetrating HIV trans-activator of transcription (TAT) peptide to human serum albumin nanoparticles (NPs) to make a TMP delivery system (TAT-TMP-NPs) that could be internalized by neutrophils and delivered to SCI lesions. Results found that in SCI rats TAT-TMP-NPs promoted the recovery of locomotor function and the lesion area, while reducing the levels of inflammatory cytokines and oxidative stress-related factors. Safety evaluation and in vivo small-animal imaging showed that the cell-penetrating peptide TAT could enhance the uptake of TAT-TMP-NPs by neutrophils without being toxic to the body. TAT-TMP-NPs may overcome the poor water solubility and low bioavailability of TMP, showing promise for the clinical treatment of SCI.
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http://dx.doi.org/10.1016/j.jconrel.2021.05.016DOI Listing
July 2021

NFIB promotes the migration and progression of kidney renal clear cell carcinoma by regulating PINK1 transcription.

PeerJ 2021 23;9:e10848. Epub 2021 Apr 23.

Department of Urology, Hanyang Hospital, Wuhan, Hubei, China.

Kidney renal clear cell carcinoma (KIRC) is the most common and aggressive type of renal cell carcinoma. Due to high mortality rate, high metastasis rate and chemical resistance, the prognosis of KIRC patients is poor. Therefore, it is necessary to study the mechanisms of KIRC development and to develop more effective prognostic molecular biomarkers to help clinical patients. In our study, we used The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to investigate that the expression of nuclear factor I B (NFIB) is significantly higher in KIRC than in adjacent tissues. Moreover, NFIB expression levels are associated with multiple clinical pathological parameters of KIRC, and KIRC patients with high NFIB expression have poor prognosis, suggesting that NFIB may play vital roles in the malignant development of KIRC. Further studies demonstrated that NFIB could promote the progression and metastasis of KIRC and participate in the regulation of PTEN induced kinase 1 (PINK1). Furthermore, we used chromatin immunoprecipitation (ChIP) experiments to confirm that NFIB binds to the PINK1 promoter and regulates its expression at the transcriptional level. Further experiments also confirmed the important roles of PINK1 in promoting the development of tumors by NFIB. Hence, our data provide a new NFIB-mediated regulatory mechanism for the tumor progression of KIRC and suggest that NFIB can be applied as a new predictor and therapeutic target for KIRC.
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http://dx.doi.org/10.7717/peerj.10848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074839PMC
April 2021

[Research Advances in Idiopathic Intracranial Hypertention].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2021 Apr;43(2):288-292

Department of Neurosurgery,PUMC Hospital,CAMS and PUMC,Beijing 100730,China.

Idiopathic intracranial hypertension,also known as pseudotumor cerebri,is a syndrome characterized by raised intracranial pressure of unknown cause.These patients present normal neuroimaging and cerebrospinal fluid analysis while increased intracranial pressure and associated symptoms and signs.Delay of treatment can cause severe visual impairment.There are some new understandings of this disease,and we will review the pathogenesis,diagnosis,and treatment of idiopathic intracranial hypertension.
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http://dx.doi.org/10.3881/j.issn.1000-503X.12693DOI Listing
April 2021

Association of prostate cancer polygenic risk score with number and laterality of tumor cores in active surveillance patients.

Prostate 2021 Jul 6;81(10):703-709. Epub 2021 May 6.

The Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA.

Background: Prostate cancer (PCa) is characterized by its tendency to be multifocal. However, few studies have investigated the endogenous factors that explain the multifocal disease. The primary objective of the current study is to test whether inherited PCa risk is associated with multifocal tumors in PCa patients.

Methods: Subjects in this study were PCa patients of European ancestry undergoing active surveillance at Johns Hopkins Hospital (N = 805) and NorthShore University HealthSystem (N = 432). The inherited risk was measured by genetic risk score (GRS), an odds ratio-weighted and population-standardized polygenic risk score based on known risk-associated single nucleotide polymorphisms. PCa multifocality was indirectly measured by the number and laterality of positive tumor cores from a 12-core systematic biopsy.

Results: In the combined cohort, 35.7% and 66.3% of patients had ≥2 tumor cores at the initial diagnostic biopsy and on at least one subsequent surveillance biopsy, respectively. For tumor laterality, 7.8% and 47.8% of patients had bilateral tumor cores at diagnostic and surveillance biopsies, respectively. We found, for the first time, that patients with higher numbers of positive cores at diagnostic and surveillance biopsies, respectively, had significantly higher mean GRS values; p = .01 and p = 5.94E-04. Additionally, patients with bilateral tumors at diagnostic and surveillance biopsies, respectively, had significantly higher mean GRS values than those with unilateral tumors; p = .04 and p = .01. In contrast, no association was found between GRS and maximum core length of tumor or tumor grade at diagnostic/surveillance biopsies (all p > .05). Finally, we observed a modest trend that patients with higher GRS quartiles had a higher risk for tumor upgrading on surveillance biopsies. The trend, however, was not statistically significant (p > .05).

Conclusions: The associations of GRS with two measurements of PCa multifocality (core numbers and laterality) provide novel and consistent evidence for the link between inherited PCa risk and multifocal tumors.
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http://dx.doi.org/10.1002/pros.24140DOI Listing
July 2021

Variable Effects of PD-Risk Associated SNPs and Variants in Parkinsonism-Associated Genes on Disease Phenotype in a Community-Based Cohort.

Front Neurol 2021 14;12:662278. Epub 2021 Apr 14.

Department of Neurology, Tulane University, New Orleans, LA, United States.

Genetic risk factors for Parkinson's disease (PD) risk and progression have been identified from genome-wide association studies (GWAS), as well as studies of familial forms of PD, implicating common variants at more than 90 loci and pathogenic or likely pathogenic variants at 16 loci. With the goal of understanding whether genetic variants at these PD-risk loci/genes differentially contribute to individual clinical phenotypic characteristics of PD, we used structured clinical documentation tools within the electronic medical record in an effort to provide a standardized and detailed clinical phenotypic characterization at the point of care in a cohort of 856 PD patients. We analyzed common SNPs identified in previous GWAS studies, as well as low-frequency and rare variants at parkinsonism-associated genes in the MDSgene database for their association with individual clinical characteristics and test scores at baseline assessment in our community-based PD patient cohort: age at onset, disease duration, Unified Parkinson's Disease Rating Scale I-VI, cognitive status, initial and baseline motor and non-motor symptoms, complications of levodopa therapy, comorbidities and family history of neurological disease with one or more than one affected family members. We find that in most cases an individual common PD-risk SNP identified in GWAS is associated with only a single clinical feature or test score, while gene-level tests assessing low-frequency and rare variants reveal genes associated in either a unique or partially overlapping manner with the different clinical features and test scores. Protein-protein interaction network analysis of the identified genes reveals that while some of these genes are members of already identified protein networks others are not. These findings indicate that genetic risk factors for PD differentially affect the phenotypic presentation and that genes associated with PD risk are also differentially associated with individual disease phenotypic characteristics at baseline. These findings raise the intriguing possibility that different SNPs/gene effects impact discrete phenotypic characteristics. Furthermore, they support the hypothesis that different gene and protein-protein interaction networks that underlie PD risk, the PD phenotype, and the neurodegenerative process leading to the disease phenotype, and point to the significance of the genetic background on disease phenotype.
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http://dx.doi.org/10.3389/fneur.2021.662278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079937PMC
April 2021

Prognostic Modeling of Patients Undergoing Surgery Alone for Esophageal Squamous Cell Carcinoma: A Histopathological and Computed Tomography Based Quantitative Analysis.

Front Oncol 2021 12;11:565755. Epub 2021 Apr 12.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, China.

Objective: To evaluate the effectiveness of a novel computerized quantitative analysis based on histopathological and computed tomography (CT) images for predicting the postoperative prognosis of esophageal squamous cell carcinoma (ESCC) patients.

Methods: We retrospectively reviewed the medical records of 153 ESCC patients who underwent esophagectomy alone and quantitatively analyzed digital histological specimens and diagnostic CT images. We cut pathological images (6000 × 6000) into 50 × 50 patches; each patient had 14,400 patches. Cluster analysis was used to process these patches. We used the pathological clusters to all patches ratio (PCPR) of each case for pathological features and we obtained 20 PCPR quantitative features. Totally, 125 computerized quantitative (20 PCPR and 105 CT) features were extracted. We used a recursive feature elimination approach to select features. A Cox hazard model with L1 penalization was used for prognostic indexing. We compared the following prognostic models: Model A: clinical features; Model B: quantitative CT and clinical features; Model C: quantitative histopathological and clinical features; and Model D: combined information of clinical, CT, and histopathology. Indices of concordance (C-index) and leave-one-out cross-validation (LOOCV) were used to assess prognostic model accuracy.

Results: Five PCPR and eight CT features were treated as significant indicators in ESCC prognosis. C-indices adjusted for LOOCV were comparable among four models, 0.596 (Model A) vs. 0.658 (Model B) vs. 0.651 (Model C), and improved to 0.711with Model D combining information of clinical, CT, and histopathology (all p<0.05). Using Model D, we stratified patients into low- and high-risk groups. The 3-year overall survival rates of low- and high-risk patients were 38.0% and 25.0%, respectively (p<0.001).

Conclusion: Quantitative prognostic modeling using a combination of clinical data, histopathological, and CT images can stratify ESCC patients with surgery alone into high-risk and low-risk groups.
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http://dx.doi.org/10.3389/fonc.2021.565755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072145PMC
April 2021

Asymmetric Pnictogen-Bonding Catalysis: Transfer Hydrogenation by a Chiral Antimony(V) Cation/Anion Pair.

J Am Chem Soc 2021 May 27;143(17):6382-6387. Epub 2021 Apr 27.

Shenzhen Grubbs Institute, Department of Chemistry, Southern University of Science and Technology, Shenzhen 518055, China.

Pnictogen-bonding catalysis based on σ-hole interactions has recently attracted the attention of synthetic chemists. As a proof-of-concept for asymmetric pnictogen-bonding catalysis, we report herein an enantioselective transfer hydrogenation of benzoxazines catalyzed by a novel chiral antimony cation/anion pair. The chiral pnictogen catalyst library could be rapidly accessed from triarylstibine with readily available mandelic acid analogues, and the catalyst displays remarkable efficiency and enantiocontrol potency even at 0.05 mol % loading. Moreover, the properties of the catalyst and the mechanistic insights have been investigated by nonlinear effect studies, H NMR, LC-MS, and control experiments.
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http://dx.doi.org/10.1021/jacs.1c02808DOI Listing
May 2021

Paper Information Recording and Security Protection Using Invisible Ink and Artificial Intelligence.

ACS Appl Mater Interfaces 2021 Apr 20;13(16):19443-19449. Epub 2021 Apr 20.

Key Laboratory of Micro-systems and Micro-structures Manufacturing of Ministry of Education, Institution Harbin Institute of Technology, Harbin 150001, China.

Conventional paper information protection mainly relies on stimuli-responsive functional materials that can display color or luminescence under external stimuli; however, this method is rather predictable and can be easily cracked. In this work, a paper information protection scheme combining fluorescent invisible ink and artificial intelligence was proposed. The ink was prepared by dissolving carbon nanoparticles in water, which has a high quantum yield and outstanding light stability and salt stability, thus ensuring the integrity of information in complex environments. A five-layer convolutional neural network (one of the two mainstream architectures in today's artificial intelligence fields) was specially trained based on ultraviolet light excited symbols printed by invisible ink. Using this scheme, the correct information could only be read with the specially trained neural network after ultraviolet (UV) irradiation. Without this trained neural network or UV irradiation, misleading messages will be presented. Moreover, it was possible to design unpredictable and highly complex password books to further increase information security. This smart strategy provides new opportunities for high-level paper information encryption and also proposes new ideas for the applications of carbon nanoparticles and artificial intelligence.
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http://dx.doi.org/10.1021/acsami.1c01179DOI Listing
April 2021

Therapeutic targeting of ATR yields durable regressions in small cell lung cancers with high replication stress.

Cancer Cell 2021 Apr;39(4):566-579.e7

Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Small cell neuroendocrine cancers (SCNCs) are recalcitrant cancers arising from diverse primary sites that lack effective treatments. Using chemical genetic screens, we identified inhibition of ataxia telangiectasia and rad3 related (ATR), the primary activator of the replication stress response, and topoisomerase I (TOP1), nuclear enzyme that suppresses genomic instability, as synergistically cytotoxic in small cell lung cancer (SCLC). In a proof-of-concept study, we combined M6620 (berzosertib), first-in-class ATR inhibitor, and TOP1 inhibitor topotecan in patients with relapsed SCNCs. Objective response rate among patients with SCLC was 36% (9/25), achieving the primary efficacy endpoint. Durable tumor regressions were observed in patients with platinum-resistant SCNCs, typically fatal within weeks of recurrence. SCNCs with high neuroendocrine differentiation, characterized by enhanced replication stress, were more likely to respond. These findings highlight replication stress as a potentially transformative vulnerability of SCNCs, paving the way for rational patient selection in these cancers, now treated as a single disease.
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http://dx.doi.org/10.1016/j.ccell.2021.02.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048383PMC
April 2021

Ataxia telangiectasia mutated germline pathogenic variant in adrenocortical carcinoma.

Cancer Genet 2021 Aug 24;256-257:21-25. Epub 2021 Mar 24.

Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, United States. Electronic address:

Background: Adrenocortical carcinoma (ACC) is a rare malignancy arising from the adrenal cortex. ACC carries a dismal prognosis and surgery offers the only chance for a cure. Germline pathogenic variants among certain oncogenes have been implicated in ACC. Here, we report the first case of ACC in a patient with a pathogenic variant in the Ataxia Telangiectasia Mutated (ATM) gene.

Patients And Methods: A 56-year-old Caucasian woman with biopsy proven ACC deemed unresectable and treated with etoposide, doxorubicin and cisplatin (EDP), and mitotane presented to our institution for evaluation. The tumor specimen was examined pathologically, and genetic analyses were performed on the tumor and germline using next-generation sequencing.

Results: Pathologic evaluation revealed an 18.0 × 14.0 × 9.0 cm low-grade ACC with tumor free resection margins. Immunohistochemistry stained for inhibin, melan-A, and chromogranin. ClinOmics analysis revealed a germline pathogenic deletion mutation of one nucleotide in ATM is denoted as c.1215delT at the cDNA level and p.Asn405LysfsX15 (N405KfsX15) at the protein level. Genomic analysis of the tumor showed loss of heterozygosity (LOH) of chromosome 11 on which the ATM resides.

Conclusion: ACC is an aggressive malignancy for which surgical resection currently offers the only curative option. Here we report a heterozygous loss-of-function mutation in germline DNA and LOH of ATM in tumor in an ACC patient, a classic two-hit scenario in a well-known cancer suppresser gene, suggesting a pathogenic role of the ATM gene in certain ACC cases.
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http://dx.doi.org/10.1016/j.cancergen.2021.03.003DOI Listing
August 2021

Synthesis of Mammogram from Digital Breast Tomosynthesis using Deep Convolutional Neural Network with Gradient Guided cGANs.

IEEE Trans Med Imaging 2021 Apr 7;PP. Epub 2021 Apr 7.

Synthetic digital mammography (SDM), a 2D image generated from digital breast tomosynthesis (DBT), is used as a potential substitute for full-field digital mammography (FFDM) in clinic to reduce the radiation dose for breast cancer screening. Previous studies exploited projection geometry and fused projection data and DBT volume, with different post-processing techniques applied on re-projection data which may generate different image appearance compared to FFDM. To alleviate this issue, one possible solution to generate an SDM image is using a learning-based method to model the transformation from the DBT volume to the FFDM image using current DBT/FFDM combo images. In this study, we proposed to use a deep convolutional neural network (DCNN) to learn the transformation to generate SDM using current DBT/FFDM combo images. Gradient guided conditional generative adversarial networks (GGGAN) objective function was designed to preserve subtle MCs and the perceptual loss was exploited to improve the performance of the proposed DCNN on perceptual quality. We used various image quality criteria for evaluation, including preserving masses and MCs which are important in mammogram. Experiment results demonstrated progressive performance improvement of network using different objective functions in terms of those image quality criteria. The methodology we exploited in the SDM generation task to analyze and progressively improve image quality by designing objective functions may be helpful to other image generation tasks.
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http://dx.doi.org/10.1109/TMI.2021.3071544DOI Listing
April 2021

Decoupling convolution network for characterizing the metastatic lymph nodes of breast cancer patients.

Med Phys 2021 Jul 19;48(7):3679-3690. Epub 2021 May 19.

Guangdong Province Key Laboratory of Computational Science, Sun Yat-sen University, Guangzhou, 510275, P.R. China.

Purpose: The dual-energy computed tomography (DECT) technique is an emerging imaging tool that can better characterize material features and has the potential to be a noninvasive means of predicting lymph node metastasis. The purpose of this study was to establish a DECT-specified quantitative approach based on a neural network to characterize the sentinel lymph node (SLN).

Methods: With IRB approval, we retrospectively collected a total of 229 patients (100/229 metastasis) with biopsy proven breast cancer in this study. The chest and axillary spectral CT examinations were performed prior to the axillary lymph node (ALN) surgery. A decoupling convolution network with 11 ROIs from sequential keV (40 to 140 keV with 10 keV increment) was proposed to explicitly extract the spectral and spatial features in a DECT to predict the lymph node status. Focal loss was introduced as the loss function. The metric of the slope of the spectral Hounsfield unit curve measured at the venous phase was used as the baseline approach in comparison to our approach. In additional, a logistic model with radiomic features was also compared to our approach. The area under ROC curve (AUC) was used as the figure of merit to evaluate the classification performance.

Results: By introducing spectral convolution and focal loss, AUC on test set could be improved by 0.15 and 0.01 separately. Compared to the slope of the spectral curve with the average AUC of 0.611 and radiomic model with AUC of 0.825, the proposed approach demonstrates a considerably better performance, with test set AUC value of 0.837, by using decoupling spectral and spatial convolution together with focal loss function.

Conclusions: We presented a new decoupling neural network based quantification method for DECT analysis, which might have potential as a noninvasive tool to predict metastasis lymph node status for breast cancer in clinical practice.
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http://dx.doi.org/10.1002/mp.14876DOI Listing
July 2021

LncRNA MIR503HG promotes hypertrophic scar progression via miR-143-3p-mediated Smad3 expression.

Wound Repair Regen 2021 Apr 5. Epub 2021 Apr 5.

Shanghai Burns Institute, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Hypertrophic scars (HSs) form due to unchecked proliferation of fibrous tissue after an injury to the skin. Recently, lncRNA MIR503HG was shown to be involved in HS. However, the mechanism by which MIR503HG affects the formation and progression of HS still needs further study. qRT-PCR was applied to examine the levels of MIR503HG and miR-143-3p in HS tissues and human hypertrophic scar fibroblasts (hHSFs). The relationships of MIR503HG, miR-143-3p and Smad3 were explored with a dual-luciferase reporter assay. Cell proliferation, apoptosis, and invasion were measured by CCK-8 assay, flow cytometry and transwell assay, respectively. The protein level of Smad3 was tested via Western blotting. MIR503HG was upregulated and miR-143-3p was downregulated in HS versus normal skin tissues. The knockdown of MIR503HG and the overexpression of miR-143-3p suppressed the proliferation and invasion of hHSF, and promoted cell apoptosis. MIR503HG bound to miR-143-3p while miR-143-3p directly targeted Smad3 to inhibit its expression. Suppression of miR-143-3p and overexpression of Smad3, respectively, reversed these effects of knockdown of MIR503HG and overexpression of miR-143-3p on hHSFs. Our research supports a model in which the MIR503HG/miR-143-3p/Smad3 axis serves as a critical regulator of HS, highlighting a promising therapeutic option for HS.
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http://dx.doi.org/10.1111/wrr.12913DOI Listing
April 2021

CT-Guided Posterolateral Full-Endoscopic Ventral Decompression for Single-Level Cervical Spondylotic Myelopathy.

Pain Physician 2021 03;24(2):E203-E210

The First Affiliated Hospital of GanNan Medical College, GanZhou, China.

Background: Percutaneous full-endoscopic surgery was recently developed for the treatment of cervical foraminal stenosis and posterolateral disc herniation. However, there are no studies involving endoscopic surgery to treat cervical spondylotic myelopathy (CSM).

Objectives: To observe the safety, feasibility, and efficacy of posterolateral full-endoscopic ventral decompression (PLEVD) via computed tomography (CT)-guided surgery in patients with single-level CSM.

Study Design: A prospective cohort study.

Setting: The First Affiliated Hospital of Gannan Medical College.

Methods: From May 2018 to August 2019, 21 patients with single-level CSM underwent CT-guided PLEVD. The posterolateral angle was measured during surgery. The neurologic condition was evaluated via the Japanese Orthopaedic Association (JOA) score and recovery rate, and a Visual Analog Scale (VAS) was used to measure pain relief. The maximum spinal canal diameter (MSCD) was measured on pre- and postoperative CT images.

Results: The mean length of follow-up was 11.3 ± 5.3 months. The average posterolateral angle was 36.0° ± 5.6°. The mean VAS score of limbs significantly decreased after surgery. The mean JOA score improved during the follow-up period. Nineteen of the 21 patients achieved good or excellent outcomes, and 2 patients had fair outcomes according to the JOA score 6 months after surgery. The average MSCD was enlarged from 0.55 ± 0.15 cm preoperatively to 1.02 ± 0.18 cm postoperatively.

Limitations: This study was nonrandomized and provides only preliminary clinical results for single-level CSM.

Conclusion: Under appropriate indications, PLEVD under CT guidance is an available and safe technique for treating single-level CSM.
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March 2021
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