Publications by authors named "Jie Lin"

817 Publications

Exercise alleviates cardiac remodelling in diabetic cardiomyopathy via the miR-486a-5p-Mst1 pathway.

Iran J Basic Med Sci 2021 Feb;24(2):150-159

Department of Cardiology, Xijing Hospital, Air Force Medical University of PLA, Xi'an 710032, P.R. China.

Objectives: Physical exercise has emerged as an effective therapy to mitigate cardiac remodelling in diabetic cardiomyopathy (DCM). The results of our previous studies revealed mammalian sterile 20-like kinase 1 (Mst1) is a key regulator of the progression of DCM. However, the precise molecular mechanism of physical exercise-induced cardiac protection and its association with Mst1 inhibition remain unclear.

Materials And Methods: Wildtype and Mst1 transgenic mice were challenged with streptozotocin (STZ) to induce experimental diabetes and were divided into sedentary and exercise groups. The DCM phenotype was evaluated by echocardiography, Masson's trichrome staining, TUNEL and immunoblotting analyses. The exercise-regulated miRNAs targeting Mst1 were predicted by bioinformatic analysis and later confirmed by RT-qPCR, immunoblotting, and dual-luciferase reporter assays. In addition, cultured neonatal mouse cardiomyocytes were subjected to simulate diabetes to elucidate the underlying mechanisms.

Results: Compared to the sedentary diabetic control, physical exercise inhibited Mst1 and alleviated cardiac remodelling in mice with DCM, as evidenced by decreases in the left ventricular end-systolic internal dimension (LVESD) and left ventricular end-diastolic internal dimension (LVEDD), increases in the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), attenuation of collagen deposition, and the suppression of apoptosis. Bioinformatic analysis and apoptosis assessments revealed exercise exerted protective effects against DCM through miR-486a-5p release. Moreover, luciferase reporter assays confirmed miR-486a-5p directly suppressed the expression of Mst1, thereby inhibiting the apoptosis of cardiomyocytes subjected to high glucose treatment.

Conclusion: Physical exercise inhibits cardiac remodelling in DCM, and the mechanism is associated with miR-486a-5p release-induced Mst1 inhibition.
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http://dx.doi.org/10.22038/IJBMS.2020.50808.11564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061331PMC
February 2021

Tryptanthrin Regulates Vascular Smooth Muscle Cell Phenotypic Switching in Atherosclerosis by AMP-Activated Protein Kinase/Acetyl-CoA Carboxylase Signaling Pathway.

J Cardiovasc Pharmacol 2021 May;77(5):642-649

Departments of Pharmacy; and.

Abstract: Atherosclerosis (AS) is one of the most severe cardiovascular diseases involved in the phenotypic switching of vascular smooth muscle cells (VSMCs). Tryptanthrin is a natural product with broad biological activities. However, the effect of tryptanthrin on atherosclerotic progression is unclear. The aim of this study was to determine the role of tryptanthrin in AS and explore the potential mechanism. In vitro, primary VSMCs were stimulated with platelet-derived growth factor-BB (PDGF) to induce cell dedifferentiation. Treatment with tryptanthrin (5 μM or 10 μM) suppressed the proliferation and recovered the contractility of VSMCs in the presence of PDGF. The contractile proteins (α-smooth muscle actin, calponin, and SM22α) were increased, and the synthetic protein vimentin was decreased by tryptanthrin in PDGF-induced VSMCs. ApoE-/- mice fed with high-fat diet were used as an in vivo model of AS. Similarly, gavage administration of tryptanthrin (50 mg/kg or 100 mg/kg) attenuated VSMC phenotypic changes from a contractile to a synthetic state in aortic tissues of AS mice. The serum lipid level, atherosclerotic plaque formation, and arterial intimal hyperplasia were attenuated by tryptanthrin. Furthermore, tryptanthrin increased the expression levels of phosphorylated AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) both in vitro and in vivo. Administration of compound C, an AMPK inhibitor, reversed the inhibitory effect of tryptanthrin on VSMC dedifferentiation in vitro. Thus, we demonstrate that tryptanthrin protects against AS progression through the inhibition of VSMC switching from a contractile to a pathological synthetic phenotype by the activation of AMPK/ACC pathway. It provides novel insights into AS prevention and treatment.
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http://dx.doi.org/10.1097/FJC.0000000000001008DOI Listing
May 2021

Melatonin attenuates hepatic ischemia-reperfusion injury in rats by inhibiting NF-κB signaling pathway.

Hepatobiliary Pancreat Dis Int 2021 Apr 18. Epub 2021 Apr 18.

Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China. Electronic address:

Background: The sterile inflammatory response is one of the key mechanisms leading to hepatic ischemia-reperfusion injury. Melatonin has been shown to prevent organ injuries, but its roles in the inflammatory response after hepatic ischemia-reperfusion injury have not been fully explored, especially in late ischemia-reperfusion injury. The present study aimed to investigate the roles and possible mechanisms of melatonin in the inflammatory response after hepatic ischemia-reperfusion injury.

Methods: Sixty Sprague-Dawley rats were randomly divided into a sham group, ischemia-reperfusion injury group (I/R group), and melatonin-treated group (M + I/R group). The rats in the I/R group were subjected to 70% hepatic ischemia for 45 min, followed by 5 or 24 h of reperfusion. The rats in the M + I/R group were injected with melatonin (10 mg/kg, intravenous injection) 15 min prior to ischemia and immediately before reperfusion. Serum and samples of ischemic liver lobes were harvested for future analysis, and the 7-day survival rate was assessed after hepatic ischemia-reperfusion surgery.

Results: In comparison with the I/R group, the M + I/R group showed markedly decreased expression levels of inflammatory cytokines (IL-6 and TNF-α) and numbers of apoptotic hepatocytes (P < 0.05). Immunoblotting showed that the expression levels of IL-6, p-NF-κBp65/t-NF-κBp65 and p-IκB-α/t-IκB-α in the M + I/R group were significantly lower than those in the I/R group, and immunofluorescence staining showed that the expression level of p-NF-κBp65 in the M + I/R group was lower than that in the I/R group (P < 0.05). The 7-day survival rates were 20% in the I/R group and 50% in the M + I/R group (P < 0.05).

Conclusions: Melatonin downregulated the activity of the NF-κB signaling pathway in the early and late stages of hepatic ischemia-reperfusion injury, alleviated the inflammatory response, protected the liver from ischemia-reperfusion injury, and increased the survival rate.
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http://dx.doi.org/10.1016/j.hbpd.2021.04.001DOI Listing
April 2021

Resistance Profiles and Biological Characteristics of Rifampicin-Resistant Small-Colony Variants.

Infect Drug Resist 2021 21;14:1527-1536. Epub 2021 Apr 21.

Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, People's Republic of China.

Background: () is a major contributor to nosocomial and community-acquired infections. small colony variants (SCVs) which changed in relevant phenotype have made more limited and difficult for therapeutic options against infections increasingly. Rifampicin is considered as the "last-resort" antibiotic against . Our study investigated resistance profiles and biological characteristics of rifampicin-resistant SCVs.

Methods: We collected SCVs that were selected from 41 rifampicin-resistant clinical isolates. Then, biological characteristics, resistance spectrum, and rifampicin resistance mechanisms of tested SCVs and corresponding parental strains were investigated by classic microbiological methods, agar dilution method, polymerase chain reaction (PCR). Moreover, the fitness cost of SCVs, including growth, biofilm formation ability, and virulence profile, was also determined by bacterial growth curve assay, biofilm formation assay, and infection model.

Results: There were three SCVs (JP310 SCVs, JP1450 SCVs, JP1486 SCVs) that were selected from 41 rifampicin-resistant SCVs colonies were tiny, with decreased pigmentation, and the hemolysis circle was not obvious compared with corresponding parental strains. And SCVs could not be restored to normal-colony phenotype after hemin, menaquinone, or thymidine supplementation. Different mutations occurred in JP1486 SCVs. Antimicrobial susceptibility testing revealed MICs of SCVs were higher than corresponding parental strains. Besides, the growth ability and virulence of SCVs were lower, and biofilm formation ability of which increased compared with parental strains.

Conclusion: SCVs share the rifampicin resistance mechanisms with parental strains, although there were some differences in the position of mutations. Moreover, we found that the biological characteristics of SCVs were significantly different from corresponding parental strains. In contrast, decreased susceptibility to other antibiotics of SCVs was observed during phenotype switch. Furthermore, SCVs incur the fitness cost.
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http://dx.doi.org/10.2147/IDR.S301863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071703PMC
April 2021

Usefulness of New Shear Wave Elastography Technique for Noninvasive Assessment of Liver Fibrosis in Patients with Chronic Hepatitis B: A Prospective Multicenter Study.

Ultraschall Med 2021 Apr 28. Epub 2021 Apr 28.

Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Purpose:  To explore the usefulness of liver stiffness measurements (LSMs) by sound touch elastography (STE) and sound touch quantification (STQ) in chronic hepatitis B (CHB) patients for staging fibrosis.

Methods:  This prospective multicenter study recruited normal volunteers and CHB patients between May 2018 and October 2019. The volunteers underwent LSM by STE and supersonic shear imaging (SSI) or by STQ and acoustic radiation force impulse imaging (ARFI). CHB patients underwent liver biopsy and LSM by both STE/STQ. The areas under the receiver operating characteristic curves (AUCs) for staging fibrosis were calculated.

Results:  Overall, 97 volunteers and 524 CHB patients were finally eligible for the study. The successful STE and STQ measurement rates were both 100 % in volunteers and 99.4 % in CHB patients. The intraclass correlation coefficients (ICCs) for the intra-observer stability of STE and STQ (0.94; 0.90) were similar to those of SSI and ARFI (0.95; 0.87), respectively. STE and STQ showed better accuracy than the aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) (AUC: 0.87 vs 0.86 vs 0.73 vs 0.77) in staging cirrhosis. However, both STE and STQ were not superior to APRI and FIB-4 in staging significant fibrosis (AUC: 0.76 vs 0.73 vs 0.70 vs 0.71, all P-values > 0.05).

Conclusion:  STE and STQ are convenient techniques with a reliable LSM value. They have a similar diagnostic performance and are superior to serum biomarkers in staging cirrhosis in CHB patients.
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http://dx.doi.org/10.1055/a-1376-6734DOI Listing
April 2021

Natural killer cell receptors regulate responses of HLA-E-restricted T cells.

Sci Immunol 2021 Apr;6(58)

Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute, Parkville, Victoria 3010, Australia.

Human cytomegalovirus (CMV) infection can stimulate robust human leukocyte antigen (HLA)-E-restricted CD8 T cell responses. These T cells recognize a peptide from UL40, which differs by as little as a single methyl group from self-peptides that also bind HLA-E, challenging their capacity to avoid self-reactivity. Unexpectedly, we showed that the UL40/HLA-E T cell receptor (TCR) repertoire included TCRs that had high affinities for HLA-E/self-peptide. However, paradoxically, lower cytokine responses were observed from UL40/HLA-E T cells bearing TCRs with high affinity for HLA-E. RNA sequencing and flow cytometric analysis revealed that these T cells were marked by the expression of inhibitory natural killer cell receptors (NKRs) KIR2DL1 and KIR2DL2/L3. On the other hand, UL40/HLA-E T cells bearing lower-affinity TCRs expressed the activating receptor NKG2C. Activation of T cells bearing higher-affinity TCRs was regulated by the interaction between KIR2D receptors and HLA-C. These findings identify a role for NKR signaling in regulating self/non-self discrimination by HLA-E-restricted T cells, allowing for antiviral responses while avoiding contemporaneous self-reactivity.
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http://dx.doi.org/10.1126/sciimmunol.abe9057DOI Listing
April 2021

An intelligent T-T switchable MRI contrast agent for the non-invasive identification of vulnerable atherosclerotic plaques.

Nanoscale 2021 Apr 23;13(13):6461-6474. Epub 2021 Mar 23.

Department of Radiology, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, 315010, China.

Unlike stable atherosclerotic plaques, vulnerable plaques are very likely to cause serious cardio-cerebrovascular diseases. Meanwhile, how to non-invasively identify vulnerable plaques at early stages has been an urgent but challenging problem in clinical practices. Here, we propose a macrophage-targeted and in situ stimuli-triggered T-T switchable magnetic resonance imaging (MRI) nanoprobe for the non-invasive diagnosis of vulnerable plaques. Precisely, single-dispersed iron oxide nanoparticles (IONPs) modified with hyaluronic acid (HA), denoted as IONP-HP, show macrophage targetability and T MRI enhancement (r/r = 3.415). Triggered by the low pH environment of macrophage lysosomes, the single-dispersed IONP-HP transforms into a cluster analogue, which exhibits T MRI enhancement (r/r = 13.326). Furthermore, an in vivo switch of T-T enhancement modes shows that the vulnerable plaques exhibit strong T enhancement after intravenous administration of the nanoprobe, followed by a switch to T enhancement after 9 h. In contrast, stable plaques show only slight T enhancement but without T enhancement. It is therefore imperative that the intelligent and novel nanoplatform proposed in this study achieves a substantial non-invasive diagnosis of vulnerable plaques by means of a facile but effective T-T switchable process, which will significantly contribute to the application of materials science in solving clinical problems.
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http://dx.doi.org/10.1039/d0nr08039jDOI Listing
April 2021

CT-guided microcoil localization for pulmonary nodules in the scapula-shadowed area before Video-Assisted Thoracic Surgery.

Clin Respir J 2021 Apr 18. Epub 2021 Apr 18.

Department of Thoracic Surgery, China-Japan Friendship Hospital, Beijing, China.

Purpose: To evaluate the feasibility and safety of CT-guided microcoil localization for pulmonary nodules in the scapula-shadowed area before video-assisted thoracic surgery (VATS).

Materials And Methods: Forty-seven patients (18 males, 19 females; mean age 57.5 years) with 48 pulmonary nodules covered by the scapulae were consecutively enrolled in this study. Successful targeting, localization, and VATS were defined as implantation of microcoil at the target site on CT image obtained immediately after the marking procedure, visualization of nodule location during VATS, and complete resection of the target nodule with adequate margin, respectively. Meanwhile, the procedure-related complication rate was also recorded.

Results: The rates of successful targeting and localization were 95.8% (46/48) and 89.6% (43/48), respectively. Of all nodules, 47 were successfully resected with VATS (30 wedge resections; 17 anatomic resections) and 1 nodule was converted to open thoracotomy for diffuse pleural adhesion, thus the successful VATS rate was 97.9% (47/48). With respect to procedure-related complications, only minor complications (including localized pneumothorax and intrapulmonary hemorrhage) were developed and the rate of overall procedure-related complications was 37.5% (18/48), including minor pneumothorax developed in 15 of 48 nodules (31.3%) and intrapulmonary hemorrhage in 6 of 48 nodules (12.5%).

Conclusions: CT-guided microcoil technique is a safe and effective localization method prior to VATS for the nodules in the scapula-shadowed area.
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http://dx.doi.org/10.1111/crj.13379DOI Listing
April 2021

The mechanisms of action of WeiChang'An Pill (WCAP) treat diarrhoea-predominant irritable bowel syndrome (IBS-D) using network pharmacology approach and in vivo studies.

J Ethnopharmacol 2021 Apr 20;275:114119. Epub 2021 Apr 20.

Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China; School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China. Electronic address:

Ethnopharmacological Relevance: WeiChang'An Pill (WCAP) is used in Traditional Chinese Medicine (TCM) to clinically treat diarrhoea-predominant irritable bowel syndrome (IBS-D); however, the underlying pharmacological mechanisms are unclear to date.

Aim Of The Study: To explore the mechanism underlying the therapeutic action of WCAP in IBS-D using a network pharmacology approach and in vivo experiments.

Materials And Methods: The active compounds of WCAP were selected from the TCM Systems Pharmacology Database and TCM Integrated Database, and the potential targets were identified using the Swiss Target Prediction and Similarity Ensemble Approach (SEA) databases. The targets related to IBS-D were mined from the Therapeutic Target Database (TTD), National Center for Biotechnology Information Search database (NCBI), DrugBank database, and DisGeNET database. The intersecting protein-protein interactions (PPIs) of the drug-disease crossover genes were analysed, and the central PPI network was constructed using the String database, version 11.0, and Cytoscape version 3.7.2. Following Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes pathway analyses, the gene-pathway network was constructed for identifying the key target genes and pathways. Based on the results and existing evidence, it was selected the cyclic adenosine monophosphate (cAMP) signalling pathway for further validation using in vivo experiments.

Results: A total of 872 targets were identified from the 77 active compounds in WCAP, which shared 78 targets that were predicted to be related to IBS-D. Twenty-one core targets were identified from the PPI network, which was constructed from the common targets. The results of enrichment analysis revealed that HRT2B, ADRA1A, ADRA1D, and CHRM2 could be the key targets of WCAP in IBS-D, and 11 signalling pathways, including the neuroactive ligand-receptor interaction, calcium signalling, and cAMP signalling pathways, were identified as crucial for the therapeutic activity of WCAP in IBS-D. We also identified the possibility of several interactions and crosstalk between the different pathways. Subsequent molecular biology experiments revealed that the expression levels of cAMP, phospho-(Ser/Thr) protein kinase A substrates (p-PKA), 5-hydroxytryptamine, and proteins in the cAMP signalling pathway, including G protein-coupled receptor (GPCR), adenylyl cyclase 5 (AC5), and cAMP-response element binding protein (CREB), were significantly upregulated in rat models of IBS-D following treatment with WCAP (P < 0.05). However, a reverse trend was observed in the expression of nuclear factor kappa-B (NF-κB) (P < 0.05), which could be attributed to the low-grade inflammation that occurs in IBS-D.

Conclusion: We demonstrated that WCAP may alleviate the symptoms of diarrhoea and visceral sensitivity in IBS-D by regulating the cAMP signalling pathway.
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http://dx.doi.org/10.1016/j.jep.2021.114119DOI Listing
April 2021

Real-World Verification of Artificial Intelligence Algorithm-Assisted Auscultation of Breath Sounds in Children.

Front Pediatr 2021 23;9:627337. Epub 2021 Mar 23.

Department of Respiratory Medicine, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Lung auscultation plays an important role in the diagnosis of pulmonary diseases in children. The objective of this study was to evaluate the use of an artificial intelligence (AI) algorithm for the detection of breath sounds in a real clinical environment among children with pulmonary diseases. The auscultations of breath sounds were collected in the respiratory department of Shanghai Children's Medical Center (SCMC) by using an electronic stethoscope. The discrimination results for all chest locations with respect to a gold standard (GS) established by 2 experienced pediatric pulmonologists from SCMC and 6 general pediatricians were recorded. The accuracy, sensitivity, specificity, precision, and F1-score of the AI algorithm and general pediatricians with respect to the GS were evaluated. Meanwhile, the performance of the AI algorithm for different patient ages and recording locations was evaluated. A total of 112 hospitalized children with pulmonary diseases were recruited for the study from May to December 2019. A total of 672 breath sounds were collected, and 627 (93.3%) breath sounds, including 159 crackles (23.1%), 264 wheeze (38.4%), and 264 normal breath sounds (38.4%), were fully analyzed by the AI algorithm. The accuracy of the detection of adventitious breath sounds by the AI algorithm and general pediatricians with respect to the GS were 77.7% and 59.9% ( < 0.001), respectively. The sensitivity, specificity, and F1-score in the detection of crackles and wheeze from the AI algorithm were higher than those from the general pediatricians (crackles 81.1 vs. 47.8%, 94.1 vs. 77.1%, and 80.9 vs. 42.74%, respectively; wheeze 86.4 vs. 82.2%, 83.0 vs. 72.1%, and 80.9 vs. 72.5%, respectively; < 0.001). Performance varied according to the age of the patient, with patients younger than 12 months yielding the highest accuracy (81.3%, < 0.001) among the age groups. In a real clinical environment, children's breath sounds were collected and transmitted remotely by an electronic stethoscope; these breath sounds could be recognized by both pediatricians and an AI algorithm. The ability of the AI algorithm to analyze adventitious breath sounds was better than that of the general pediatricians.
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http://dx.doi.org/10.3389/fped.2021.627337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023046PMC
March 2021

Characterization of F-fluorodeoxyglucose metabolic spatial distribution improves the differential diagnosis of indeterminate pulmonary nodules and masses with high fluorodeoxyglucose uptake.

Quant Imaging Med Surg 2021 Apr;11(4):1543-1553

Department of PET/CT, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Background: The aim of this study was to investigate the value of visual assessment of F-fluorodeoxyglucose (F-FDG) metabolic spatial distribution (V-FMSD) in the diagnosis of indeterminate pulmonary nodules and masses with high F-FDG uptake.

Methods: A total of 301 patients with indeterminate pulmonary nodules or masses who underwent F-FDG positron emission tomography/computed tomography (PET/CT) imaging were retrospectively studied. The characteristics of F-FDG metabolic spatial distribution (FMSD) in the proximal and distal regions of the lesions were visually analyzed using a 5-point scoring system. The sensitivity, specificity, accuracy, and area under receiver operating characteristic curve (AUC) were compared between V-FMSD and conventional PET/CT methods for the diagnosis of hypermetabolic indeterminate pulmonary nodules and masses.

Results: The V-FMSD results showed that 180 (92.8%) malignant lesions had a score of ≥3 and 78 (72.9%) benign lesions had a score of ≤2. This indicated that the FMSD in the proximal region of malignant lesions was significantly higher than that of the distal region, and the FMSD in the proximal region of benign lesions was significantly lower than that of the distal region. V-FMSD had a specificity of 72.9%, which was markedly higher than those of the maximum standard uptake value (SUV; 0%, P<0.001) and the retention index (RI; 26.2%, P<0.001). The AUC of V-FMSD was 0.886, which was significantly larger than those of the SUV (0.626, P<0.001), RI (0.670, P<0.001), and PET/CT (0.788, P<0.05).

Conclusions: Our study found that pulmonary benign and malignant lesions have distinct FMSD characteristics. V-FMSD can therefore be used as a novel auxiliary marker to improve the diagnostic accuracy of hypermetabolic indeterminate pulmonary nodules and masses.
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http://dx.doi.org/10.21037/qims-20-768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930690PMC
April 2021

ReCiter: An open source, identity-driven, authorship prediction algorithm optimized for academic institutions.

PLoS One 2021 1;16(4):e0244641. Epub 2021 Apr 1.

Information Technologies & Services, Weill Cornell Medicine, New York, New York, United States of America.

Academic institutions need to maintain publication lists for thousands of faculty and other scholars. Automated tools are essential to minimize the need for direct feedback from the scholars themselves who are practically unable to commit necessary effort to keep the data accurate. In relying exclusively on clustering techniques, author disambiguation applications fail to satisfy key use cases of academic institutions. Algorithms can perfectly group together a set of publications authored by a common individual, but, for them to be useful to an academic institution, they need to programmatically and recurrently map articles to thousands of scholars of interest en masse. Consistent with a savvy librarian's approach for generating a scholar's list of publications, identity-driven authorship prediction is the process of using information about a scholar to quantify the likelihood that person wrote certain articles. ReCiter is an application that attempts to do exactly that. ReCiter uses institutionally-maintained identity data such as name of department and year of terminal degree to predict which articles a given scholar has authored. To compute the overall score for a given candidate article from PubMed (and, optionally, Scopus), ReCiter uses: up to 12 types of commonly available, identity data; whether other members of a cluster have been accepted or rejected by a user; and the average score of a cluster. In addition, ReCiter provides scoring and qualitative evidence supporting why particular articles are suggested. This context and confidence scoring allows curators to more accurately provide feedback on behalf of scholars. To help users to more efficiently curate publication lists, we used a support vector machine analysis to optimize the scoring of the ReCiter algorithm. In our analysis of a diverse test group of 500 scholars at an academic private medical center, ReCiter correctly predicted 98% of their publications in PubMed.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244641PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016248PMC
April 2021

18F-PSMA-1007 Uptake in Pulmonary Lymphangitic Carcinomatosis Metastasis From Prostate Cancer.

Clin Nucl Med 2021 Mar 16. Epub 2021 Mar 16.

From the Department of PET/CT, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Abstract: A 55-year-old man with cough, bone pain, and cervical lymphadenopathy underwent both 18F-FDG and 18F-PSMA-1007 PET/CT scans with clinical suspicion of malignant disease. Compared with 18F-FDG PET/CT, 18F-PSMA PET/CT showed intense tracer uptake in the prostate gland, lungs, osteogenic lesions, and multiple lymph nodes. Interestingly, we also found the high tracer concentration of pulmonary lymphangitic carcinomatosis, a very rare form of prostate cancer metastasis to the lung, on 18F-PSMA-1007 PET/CT images.
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http://dx.doi.org/10.1097/RLU.0000000000003582DOI Listing
March 2021

MiR-490 alleviates sepsis-induced acute lung injury by targeting MRP4 in new-born mice.

Acta Biochim Pol 2021 Mar 22. Epub 2021 Mar 22.

Department of Paediatrics, Ruian People's Hospital, Ruian Ciy, Wenzhou City, Zhejiang Province, 325200, China.

The aim of this study was to investigate whether the effects of miR-490 on acute lung injury (ALI) induced by sepsis in vitro and in vivo were through targeting multi-drug resistance-associated protein 4 (MRP4). MiR-490 agomir/NC agomir was injected into mice before cecal ligation and puncture (CLP). Pulmonary microvascular endothelial cells (PMVECs) were transfected with or without miR-490 agomir/NC agomir/MRP4/empty vector before lipopolysaccharide (LPS) stimulation. Histopathology, injure score, and Wet/Dry (W/D) of lung tissues were assessed. The number of neutrophils, macrophages and total cells, total protein concentration, TNF-α and IL-1β level in bronchoalveolar lavage fluid (BALF) were measured. The levels of caspase-3, Bcl-2, TNF-α, and IL-1β were measured in MPVECs. Dual-luciferase reporter assay was used to analyze the relationship between MRP4 and miR-490. When compared to the sham group, in CLP mice, the alveolar lung tissue showed significantly hyperemic, alveolar collapse, the W/D ratio was increased, and the injury index was increased. The number of neutrophils, macrophages and total cells, total protein concentration, TNF-α and IL-1β levels were significantly increased in BALF from CLP mice. The levels of TNF-α and IL-1β were significantly increased in lung tissue from CLP mice. Overexpression of miR-490 alleviated lung injury caused by CLP and inhibited inflammation in mice. The levels of TNF-α, IL-1β and caspase-3 were significantly increased, but the level of Bcl-2 was significantly decreased in MPVECs treated with LPS compared to the control group. Overexpression of miR-490 also reversed the increase of TNF-α, IL-1β, cleaved caspase-3 and Bcl-2 caused by LPS in MPVECs. Dual-luciferase reporter assay confirmed that the target gene of miR-490 was MRP4. Besides, overexpression of MRP4 upregulated TNF-α, IL-1β, and cleaved caspase-3, but downregulated the increase of Bcl-2 induced by miR-490 agomir transfection. These data suggested that miR-490 could relieve sepsis-induced acute lung injury in neonatal mice via targeting MRP4.
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http://dx.doi.org/10.18388/abp.2020_5397DOI Listing
March 2021

A commentary on "A meta-analysis on surgery with or without postoperative radiotherapy to treat squamous cell esophageal carcinoma" (Int J Surg 2020;80:184 -191).

Int J Surg 2021 Apr 18;88:105925. Epub 2021 Mar 18.

Wuhan Hospital of Integrated Traditional Chinese and Western Medicine, Wuhan, 430022, Hubei, China. Electronic address:

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http://dx.doi.org/10.1016/j.ijsu.2021.105925DOI Listing
April 2021

Short-term effect of low-dose rituximab on myasthenia gravis with muscle-specific tyrosine kinase antibody.

Muscle Nerve 2021 Mar 21. Epub 2021 Mar 21.

Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.

Introduction/aims: The study aims to investigate the short-term efficacy of low-dose rituximab and its effect on immunological biomarker levels in myasthenia gravis (MG) patients with antibodies against muscle-specific tyrosine kinase (MuSK-MG).

Methods: Twelve MuSK-MG patients were enrolled in this prospective, open-label, self-controlled pilot study. Clinical severity was evaluated at baseline and 6 mo after a single rituximab treatment (600 mg). B lymphocyte subtypes, MuSK antibody titers, together with levels of immunoglobulins, serum B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), soluble CD40L, and four exosomal microRNAs were evaluated. A correlation matrix to reveal pairwise relationships among above variables was also generated.

Results: The single rituximab treatment significantly lowered the clinical severity scores and reduced daily dosage of prednisone (P = .032) at 6 mo. MuSK antibody titers decreased (P = .035) without significant changes in immunoglobulin levels. Serum BAFF level increased (P = .010), which negatively correlated with the percentages of B cells in lymphocytes as well as clinical severity. Additionally, serum exosomal miR-151a-3p showed a reduction of 28.1% (P = .031).

Discussion: We confirmed the clinical efficacy of low-dose rituximab in MuSK-MG, accompanied by a decrease in MuSK antibody titers and an increase in serum BAFF. Serum BAFF levels negatively correlated with B-cell counts as well as clinical severity.
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http://dx.doi.org/10.1002/mus.27233DOI Listing
March 2021

Cycle-Consistent Generative Adversarial Network: Effect on Radiation Dose Reduction and Image Quality Improvement in Ultralow-Dose CT for Evaluation of Pulmonary Tuberculosis.

Korean J Radiol 2021 Mar 9. Epub 2021 Mar 9.

The D-Lab, Department of Precision Medicine, GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht, The The Netherlands.

Objective: To investigate the image quality of ultralow-dose CT (ULDCT) of the chest reconstructed using a cycle-consistent generative adversarial network (CycleGAN)-based deep learning method in the evaluation of pulmonary tuberculosis.

Materials And Methods: Between June 2019 and November 2019, 103 patients (mean age, 40.8 ± 13.6 years; 61 men and 42 women) with pulmonary tuberculosis were prospectively enrolled to undergo standard-dose CT (120 kVp with automated exposure control), followed immediately by ULDCT (80 kVp and 10 mAs). The images of the two successive scans were used to train the CycleGAN framework for image-to-image translation. The denoising efficacy of the CycleGAN algorithm was compared with that of hybrid and model-based iterative reconstruction. Repeated-measures analysis of variance and Wilcoxon signed-rank test were performed to compare the objective measurements and the subjective image quality scores, respectively.

Results: With the optimized CycleGAN denoising model, using the ULDCT images as input, the peak signal-to-noise ratio and structural similarity index improved by 2.0 dB and 0.21, respectively. The CycleGAN-generated denoised ULDCT images typically provided satisfactory image quality for optimal visibility of anatomic structures and pathological findings, with a lower level of image noise (mean ± standard deviation [SD], 19.5 ± 3.0 Hounsfield unit [HU]) than that of the hybrid (66.3 ± 10.5 HU, < 0.001) and a similar noise level to model-based iterative reconstruction (19.6 ± 2.6 HU, > 0.908). The CycleGAN-generated images showed the highest contrast-to-noise ratios for the pulmonary lesions, followed by the model-based and hybrid iterative reconstruction. The mean effective radiation dose of ULDCT was 0.12 mSv with a mean 93.9% reduction compared to standard-dose CT.

Conclusion: The optimized CycleGAN technique may allow the synthesis of diagnostically acceptable images from ULDCT of the chest for the evaluation of pulmonary tuberculosis.
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http://dx.doi.org/10.3348/kjr.2020.0988DOI Listing
March 2021

Adaptive Mechanisms of Tumor Therapy Resistance Driven by Tumor Microenvironment.

Front Cell Dev Biol 2021 1;9:641469. Epub 2021 Mar 1.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China.

Cancer is a disease which frequently has a poor prognosis. Although multiple therapeutic strategies have been developed for various cancers, including chemotherapy, radiotherapy, and immunotherapy, resistance to these treatments frequently impedes the clinical outcomes. Besides the active resistance driven by genetic and epigenetic alterations in tumor cells, the tumor microenvironment (TME) has also been reported to be a crucial regulator in tumorigenesis, progression, and resistance. Here, we propose that the adaptive mechanisms of tumor resistance are closely connected with the TME rather than depending on non-cell-autonomous changes in response to clinical treatment. Although the comprehensive understanding of adaptive mechanisms driven by the TME need further investigation to fully elucidate the mechanisms of tumor therapeutic resistance, many clinical treatments targeting the TME have been successful. In this review, we report on recent advances concerning the molecular events and important factors involved in the TME, particularly focusing on the contributions of the TME to adaptive resistance, and provide insights into potential therapeutic methods or translational medicine targeting the TME to overcome resistance to therapy in clinical treatment.
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http://dx.doi.org/10.3389/fcell.2021.641469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957022PMC
March 2021

Simplified plasmid cloning with a universal MCS design and bacterial in vivo assembly.

BMC Biotechnol 2021 Mar 15;21(1):24. Epub 2021 Mar 15.

School of Biological Science and Biotechnology, Minnan Normal University, Zhangzhou, 363000, P.R. China.

Background: The ability to clone DNA sequences quickly and precisely into plasmids is essential for molecular biology studies. The recent development of seamless cloning technologies has made significant improvements in plasmid construction, but simple and reliable tools are always desirable for time- and labor-saving purposes.

Results: We developed and standardized a plasmid cloning protocol based on a universal MCS (Multiple Cloning Site) design and bacterial in vivo assembly. With this method, the vector is linearized first by PCR (Polymerase Chain Reaction) or restriction digestion. Then a small amount (10 ~ 20 ng) of this linear vector can be mixed with a PCR-amplified insert (5× molar ratio against vector) and transformed directly into competent E. coli cells to obtain the desired clones through in vivo assembly. Since we used a 36-bp universal MCS as the homologous linker, any PCR-amplified insert with ~ 15 bp compatible termini can be cloned into the vector with high fidelity and efficiency. Thus, the need for redesigning insert-amplifying primers according to various vector sequences and the following PCR procedures was eliminated.

Conclusions: Our protocol significantly reduced hands-on time for preparing transformation reactions, had excellent reliability, and was confirmed to be a rapid and versatile plasmid cloning technique. The protocol contains mostly mixing steps, making it an extremely automation-friendly and promising tool in modern biology studies.
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http://dx.doi.org/10.1186/s12896-021-00679-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962268PMC
March 2021

Prolactin Is Associated With Insulin Resistance and Beta-Cell Dysfunction in Infertile Women With Polycystic Ovary Syndrome.

Front Endocrinol (Lausanne) 2021 25;12:571229. Epub 2021 Feb 25.

Reproductive Medicine Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Background: Our study aimed to investigate if serum prolactin (PRL) levels associated with insulin resistance and beta-cell dysfunction in infertile patients with polycystic ovary syndrome (PCOS).

Methods: This was a retrospective cross-sectional study performed in the reproductive medicine center of the first affiliated hospital of Wenzhou Medical University. From January 2007 to August 2018, a total of 792 PCOS and 700 non-PCOS infertile women were included. All patients' prolactin levels were in the normal range. PCOS was diagnosed according to the Rotterdam Criteria. Anthropometric parameters, blood pressure, serum prolactin levels, sex hormones, fasting lipids, fasting plasma glucose (FPG), fasting insulin (FINS) and hepatic biological parameters were measured in all subjects.

Results: Serum prolactin levels in PCOS women were significantly decreased compared with levels in non-PCOS women after adjusting for age and BMI ( < 0.05). Moreover, we found that prolactin levels were positively associated with high-density lipoprotein cholesterol (HDL-C) and negatively associated with age, BMI, waist circumference (WC), hip circumference (HC), luteinizing hormone/follicle stimulating hormone (LH/FSH), estradiol (E), FINS, homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of β (HOMA-β), triglyceride (TG) and alanine aminotransferase (ALT) ( < 0.05). After adjusting for age and BMI, multiple linear regression analysis revealed that LH, LH/FSH, E, FINS, HOMA-IR, and HOMA-β were negatively associated with serum PRL ( < 0.05).

Conclusions: Low serum PRL levels within the normal range associates with a higher incidence of insulin resistance and beta-cell dysfunction in infertile women with PCOS.
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http://dx.doi.org/10.3389/fendo.2021.571229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947819PMC
February 2021

Organic solvent-based tissue clearing techniques and their applications.

J Biophotonics 2021 Mar 14:e202000413. Epub 2021 Mar 14.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Revealing the true structure of tissues and organs with tissue slicing technology is difficult since images reconstructed in three dimensions are easily distorted. To address the limitations in tissue slicing technology, tissue clearing has been invented and has recently achieved significant progress in three-dimensional imaging. Currently, this technology can mainly be divided into two types: aqueous clearing methods and solvent-based clearing methods. As one of the important parts of this technology, organic solvent-based tissue clearing techniques have been widely applied because of their efficient clearing speed and high clearing intensity. This review introduces the primary organic solvent-based tissue clearing techniques and their applications.
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http://dx.doi.org/10.1002/jbio.202000413DOI Listing
March 2021

Disentangling Intrinsic and Extrinsic Gene Expression Noise in Growing Cells.

Authors:
Jie Lin Ariel Amir

Phys Rev Lett 2021 Feb;126(7):078101

John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA.

Gene expression is a stochastic process. Despite the increase of protein numbers in growing cells, the protein concentrations are often found to be confined within small ranges throughout the cell cycle. Generally, the noise in protein concentration can be decomposed into an intrinsic and an extrinsic component, where the former vanishes for high expression levels. Considering the time trajectory of protein concentration as a random walker in the concentration space, an effective restoring force (with a corresponding "spring constant") must exist to prevent the divergence of concentration due to random fluctuations. In this work, we prove that the magnitude of the effective spring constant is directly related to the fraction of intrinsic noise in the total protein concentration noise. We show that one can infer the magnitude of intrinsic, extrinsic, and measurement noises of gene expression solely based on time-resolved data of protein concentration, without any a priori knowledge of the underlying gene expression dynamics. We apply this method to experimental data of single-cell bacterial gene expression. The results allow us to estimate the average copy numbers and the translation burst parameters of the studied proteins.
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http://dx.doi.org/10.1103/PhysRevLett.126.078101DOI Listing
February 2021

ATAD3B is a mitophagy receptor mediating clearance of oxidative stress-induced damaged mitochondrial DNA.

EMBO J 2021 Apr 5;40(8):e106283. Epub 2021 Mar 5.

Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, China.

Mitochondrial DNA (mtDNA) encodes several key components of respiratory chain complexes that produce cellular energy through oxidative phosphorylation. mtDNA is vulnerable to damage under various physiological stresses, especially oxidative stress. mtDNA damage leads to mitochondrial dysfunction, and dysfunctional mitochondria can be removed by mitophagy, an essential process in cellular homeostasis. However, how damaged mtDNA is selectively cleared from the cell, and how damaged mtDNA triggers mitophagy, remain mostly unknown. Here, we identified a novel mitophagy receptor, ATAD3B, which is specifically expressed in primates. ATAD3B contains a LIR motif that binds to LC3 and promotes oxidative stress-induced mitophagy in a PINK1-independent manner, thus promoting the clearance of damaged mtDNA induced by oxidative stress. Under normal conditions, ATAD3B hetero-oligomerizes with ATAD3A, thus promoting the targeting of the C-terminal region of ATAD3B to the mitochondrial intermembrane space. Oxidative stress-induced mtDNA damage or mtDNA depletion reduces ATAD3B-ATAD3A hetero-oligomerization and leads to exposure of the ATAD3B C-terminus at the mitochondrial outer membrane and subsequent recruitment of LC3 for initiating mitophagy. Furthermore, ATAD3B is little expressed in m.3243A > G mutated cells and MELAS patient fibroblasts showing endogenous oxidative stress, and ATAD3B re-expression promotes the clearance of m.3243A > G mutated mtDNA. Our findings uncover a new pathway to selectively remove damaged mtDNA and reveal that increasing ATAD3B activity is a potential therapeutic approach for mitochondrial diseases.
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http://dx.doi.org/10.15252/embj.2020106283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047441PMC
April 2021

Convallatoxin Promotes M2 Macrophage Polarization to Attenuate Atherosclerosis Through PPARγ-Integrin αβ Signaling Pathway.

Drug Des Devel Ther 2021 23;15:803-812. Epub 2021 Feb 23.

Department of Pharmacy, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, People's Republic of China.

Introduction: As the primary immune cells, macrophages play a key role in atherosclerotic progression. M2 macrophage polarization has been reported to promote tissue repair and attenuate plaque formation upon the expression of anti-inflammatory factors. Convallatoxin (CNT) is a natural cardiac glycoside with anti-inflammatory pharmacological properties. However, whether CNT protects against atherosclerosis (AS) and underlying mechanisms is unknown. This work was designed to explore the potential effects of CNT on atherosclerosis.

Methods: In this study, Apolipoprotein E deficiency (ApoE) mice fed with high-fat diet were established, and CNT (50 or 100 μg/kg) were intragastrically administrated for 12 weeks every day. In vitro, RAW264.7 macrophages stimulated with ox-LDL were treated with CNT (50 or 100 nM) for 24 h. The specific PPARγ antagonist, GW9662, was used to block the PPARγ signaling pathway in vitro. Then, the atherosclerotic lesions, macrophage polarization markers, inflammatory cytokines and PPARγ signaling pathway were examined in further examinations.

Results: Our results showed that the atherosclerotic lesions were reduced by CNT, as demonstrated by the downregulation of serum lipid level and aortic plaque area in AS mice. Furthermore, we found that CNT treatment promoted the expression of M2 macrophage markers (Arg1, Mrc1, Retnla and Chi3l3), and decreased the levels of pro-inflammatory cytokines (IL-6 and TNF-α), accompanied by the increase of anti-inflammatory factor (IL-10) in aortic vessels of AS mice. In ox-LDL-induced RAW264.7 cells, CNT administration also facilitated macrophages polarizing towards M2 subtype and inhibited inflammatory responses. Furthermore, both the in vivo and in vitro experiments showed CNT could increase the expression of PPARγ, Integrin α and Integrin β, and GW9662 could block CNT-induced M2 macrophage polarization.

Conclusion: Taken together, these data suggest that CNT may promote M2 macrophage polarization to exert an anti-atherosclerotic effect, partially through activating PPARγ-Integrin αβ signaling pathway.
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http://dx.doi.org/10.2147/DDDT.S288728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914072PMC
February 2021

Uncontrollable Hemoptysis Due to Pseudoangiosarcomatous Carcinoma of the Lung.

Am J Respir Crit Care Med 2021 Feb 24. Epub 2021 Feb 24.

China-Japan Friendship Hospital, 36635, Radiology, Beijing, China.

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http://dx.doi.org/10.1164/rccm.202004-1307IMDOI Listing
February 2021

Reply to Josef Finsterer's letter referring to "Connectivity on fMRI in the MELAS brain may strongly depend on heteroplasmy and extension or dynamics of stroke-like lesions".

Neuroimage Clin 2021 Feb 15:102596. Epub 2021 Feb 15.

Department of Radiology, HuaShan Hospital, Fudan University, Shanghai, China; Institute of Functional and Molecular Medical Imaging, Fudan University, Shanghai, China. Electronic address:

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http://dx.doi.org/10.1016/j.nicl.2021.102596DOI Listing
February 2021

Oncogenic ZEB2/miR-637/HMGA1 signaling axis targeting vimentin promotes the malignant phenotype of glioma.

Mol Ther Nucleic Acids 2021 Mar 5;23:769-782. Epub 2021 Jan 5.

Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510375, People's Republic of China.

Glioma is the most common primary tumor of the central nervous system. We previously confirmed that zinc finger E-box binding homeobox (ZEB) 2 promotes the malignant progression of glioma, while microRNA-637 (miR-637) is associated with favorable prognosis in glioma. This study aimed to investigate the potential interaction between ZEB2 and miR-637 and its downstream signaling pathway in glioma. The results revealed that ZEB2 could directly bind to the E-box elements in the miR-637 promoter and promote cell proliferation, migration, and invasion via miR-637 downregulation. Subsequent screening confirmed that HMGA1 was a direct target of miR-637, while miR-637 could drive the malignant phenotype of glioma by suppressing HMGA1 both and . Furthermore, interaction between cytoplasmic HMGA1 and vimentin was observed, and vimentin inhibition could abolish increased migration and invasion induced by HMGA1 overexpression. Both HMGA1 and vimentin were associated with an unfavorable prognosis in glioma. Additionally, upregulated HMGA1 and vimentin were found in isocitrate dehydrogenase (IDH) wild-type and 1p/19q non-codeletion diffusely infiltrating glioma. In conclusion, we identified an oncogenic ZEB2/miR-637/HMGA1 signaling axis targeting vimentin that promotes both migration and invasion in glioma.
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http://dx.doi.org/10.1016/j.omtn.2020.12.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868719PMC
March 2021

Para-aortic lymph node metastasis in lower Thoracic Esophageal Squamous Cell Carcinoma after Radical Esophagectomy: a CT-based atlas and its clinical implications for Adjuvant Radiotherapy.

J Cancer 2021 18;12(6):1734-1741. Epub 2021 Jan 18.

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

Our previous work showed that para-aortic lymph node (PALN) metastasis was the major failure pattern in lower thoracic esophageal squamous cell carcinoma (LTESCC) patients who presented abdominal LN failure after curative surgery. We thereby aim to generate a computerized tomography (CT)-based documentation of PALNs and to propose a clinical target volume (CTV) for this region. Sixty-five patients were enrolled. The epicentre of each PALN was drawn onto an axial CT image of a standard patient with reference to the surrounding anatomical landmarks. A CTV for PALN was generated based on the final result of node distribution, and was evaluated for dosimetric performance in three simulated patients. All the studied 248 LNs were below the level of 1.0 cm above the celiac artery (CA), and 94.76% were above the bottom of vertebra L3. Horizontally, 93.33% of the LNs in the celiac level were located within an expansion of 1.5 cm on the CA, and 94.12% of the LNs in the superior mesenteric artery (SMA) level were within 1.5 cm on the left side of the SMA. Below the SMA, all the LNs were behind the left renal vein, left to the right border of the inferior vena cava, and 98.51% of the LNs were medial to the lateral surface of the left psoas major. The proposed CTV could cover 92.74% of the LNs and was dosimetrically feasible. The proposed CTV is the first one to focus on the high-risk area of abdominal failure in LTESCC patients after surgery and can serve as a reference in the adjuvant radiotherapy for LTESCC patients.
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http://dx.doi.org/10.7150/jca.51212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890317PMC
January 2021

Li-Zn Overlayer to Facilitate Uniform Lithium Deposition for Lithium Metal Batteries.

ACS Appl Mater Interfaces 2021 Mar 16;13(8):9985-9993. Epub 2021 Feb 16.

McKetta Department of Chemical Engineering, The University of Texas at Austin, Austin, Texas 78712, United States.

The highly reactive nature and rough surface of Li foil can lead to the uncontrollable formation of Li dendrites when employed as an anode in a lithium metal battery. Thus, it could be of great practical utility to create uniform, electrochemically stable, and "lithiophilic" surfaces to realize homogeneous deposition of Li. Herein, a LiZn alloy layer is deposited on the surface of Li foil by e-beam evaporation. The idea is to introduce a uniform alloy surface to increase the active area and make use of the Zn sites to induce homogeneous nucleation of Li. The results show that the alloy film protected the Li metal anode, allowing for a longer cycling life with a lower deposition overpotential over a pure-Li metal anode in symmetric Li cells. Furthermore, full cells pairing the modified lithium anode with a LiFePO cathode showed an incremental increase in Coulombic efficiency compared with pure-Li. The concept of using only an alloy modifying layer by an in-situ e-beam deposition synthesis method offers a potential method for enabling lithium metal anodes for next-generation lithium batteries.
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http://dx.doi.org/10.1021/acsami.0c21195DOI Listing
March 2021

Characterization of evolution trajectory and immune profiling of brain metastasis in lung adenocarcinoma.

NPJ Precis Oncol 2021 Feb 12;5(1). Epub 2021 Feb 12.

Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, Tongji University School of Medicine, 200433, Shanghai, China.

Characterizing the evolutionary trajectory and immune profiling of brain metastasis (BM) may provide insights in the development of novel therapeutic strategies. Here, we performed whole-exome sequencing and multiplex immunofluorescence (MIF) of 40 samples from 12 lung adenocarcinoma (LUAD) patients with BM and compared to their paired primary tumors. We observed significantly higher intertumor heterogeneity between paired primary tumors and BMs, with only a median of 8.3% of genetic mutations identified as shared. Phylogenetic analysis revealed that BM-competent clones genetically diverged from their primary tumors at relatively early stage, suggesting that the parallel progression model is dominant. In cases with synchronous lymph node metastasis (LNM), phylogenetic analysis suggested that BM is a later event than LNM. MIF analysis found that BMs exhibited significantly lower CD8 T cell infiltration (P = 0.048), and elevated CD4Foxp3 T cell infiltration (P = 0.036) and PD-1 expression (P = 0.047) in comparison to the matched primary tumors, indicating an immunosuppressive microenvironment in BMs. The current study revealed the discrepancy of mutational landscape as well as tumor immune microenvironment between BM and its primary tumor - such findings shall help us better understand the unique biological features of BM and develop innovative strategies accordingly for our patients with LUAD.
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http://dx.doi.org/10.1038/s41698-021-00151-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881241PMC
February 2021