Publications by authors named "Song Xiang"

174 Publications

Enantioselective recognition of chiral acids by supramolecular interactions with chiral AIEgens.

Chem Commun (Camb) 2021 Nov 23. Epub 2021 Nov 23.

Shenzhen Institute of Aggregate Science and Technology, School of Science and Engineering, The Chinese University of Hong Kong, Shenzhen, Guangdong 518172, China.

Novel chiral AIEgens bearing optically pure amino groups were synthesized and showed excellent discrimination for a series of chiral acidic compounds and amino acids. Interestingly, after supramolecular assembly with 4-sulfocalix[4]arene, the obtained complexes showed enhanced enantioselectivity for chiral acids.
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http://dx.doi.org/10.1039/d1cc05618bDOI Listing
November 2021

Elucidating the Effect of the Dopant Ionic Radius on the Structure and Electrochemical Performance of Ni-Rich Layered Oxides for Lithium-Ion Batteries.

ACS Appl Mater Interfaces 2021 Nov 17. Epub 2021 Nov 17.

Institute of New Energy Material Chemistry, School of Materials Science and Engineering, Nankai University, Tianjin 300350, China.

The merits of Ni-rich layered oxide cathodes in specific capacity and material cost accelerate their practical applications in electric vehicles and grid energy storage. However, detrimental structural deterioration occurs inevitably during long-term cycling, leading to potential instability and capacity decay of the cathodes. In this work, we investigate the effect of the doped cation radius on the electrochemical performance and structural stability of Ni-rich cathode materials by doping with Mg and Ca ions in LiNiCoMnO. The results reveal that an increase in the doping ion radius can enlarge the interlayer spacing but lead to the collapse of the layered structure if the ion radius is too large, which undermines the cycling stability of the cathode material. Compared with the Ca-doped sample and the pristine material, Mg-doped LiNiCoMnO presents improved structural stability and superior thermal stability due to the pillar and glue roles of medium-sized Mg ions in the lithium layer. The results of this study suggest that a suitable ionic radius of the dopant is critical for stabilizing the structure and improving the electrochemical properties of Ni-rich layered oxide cathode materials.
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http://dx.doi.org/10.1021/acsami.1c17991DOI Listing
November 2021

Crystal structures of glycogen-debranching enzyme mutants in complex with oligosaccharides.

Acta Crystallogr F Struct Biol Commun 2021 Nov 29;77(Pt 11):420-426. Epub 2021 Oct 29.

Department of Biochemistry and Molecular Biology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, People's Republic of China.

Debranching is a critical step in the mobilization of the important energy store glycogen. In eukaryotes, including fungi and animals, the highly conserved glycogen-debranching enzyme (GDE) debranches glycogen by a glucanotransferase (GT) reaction followed by a glucosidase (GC) reaction. Previous work indicated that these reactions are catalyzed by two active sites located more than 50 Å apart and provided insights into their catalytic mechanisms and substrate recognition. Here, five crystal structures of GDE in complex with oligosaccharides with 4-9 glucose residues are presented. The data suggest that the glycogen main chain plays a critical role in binding to the GT and GC active sites of GDE and that a minimum of five main-chain residues are required for optimal binding.
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http://dx.doi.org/10.1107/S2053230X21010918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8561817PMC
November 2021

1-MNA Ameliorates High Fat Diet-Induced Heart Injury by Upregulating Nrf2 Expression and Inhibiting NF-κB and .

Front Cardiovasc Med 2021 12;8:721814. Epub 2021 Oct 12.

Cardiovascular Center, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, China.

High levels of free fatty acids (FFA) are closely associated with obesity and the development of cardiovascular diseases. Recently, nicotinamide adenine dinucleotide (NAD) metabolism has emerged as a potential target for several modern diseases including diabetes. Herein, we explored the underlying mechanisms of NAD metabolism associated with the risk of cardiovascular disease. Our study found that nicotinamide N-methyltransferase (NNMT) mRNA levels were significantly increased in the hearts of FFA-bound-albumin-overloaded mice and in H9C2 cells treated with palmitic acid (PA). We studied the mechanisms underlining the anti-inflammatory and anti-oxidant activities of 1-methylnicotinamide (1-MNA), a metabolite of NNMT. We found a significantly higher level of reactive oxygen species, inflammation, apoptosis, and cell hypertrophy in PA-treated H9C2 cells and this effect was inhibited by 1-MNA treatment. , 1-MNA improved inflammation, apoptosis, and fibrosis damage in mice and this inhibition was associated with inhibited NF-κB activity. In conclusion, our study revealed that 1-MNA may prevent high fatty diet and PA-induced heart injury by regulating Nrf2 and NF-κB pathways.
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http://dx.doi.org/10.3389/fcvm.2021.721814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8545986PMC
October 2021

Exosomes loaded with programmed death ligand-1 promote tumor growth by immunosuppression in osteosarcoma.

Bioengineered 2021 Oct 26. Epub 2021 Oct 26.

Oncology Department, The second hospital of Shanxi Medical University, China.

Osteosarcoma (OS) is a malignant tumor commonly observed in adolescents, who experience relapse and metastasis (30% of the total cases). Its progression is attributed to immune escape mediated by immune checkpoints. However, the intercellular connection between tumor cells and T cells remain unclear. This study was conducted to explore the effects of PD-L1-loaded exosomes on the tumor growth of OS. The exosomes were extracted from cells and tissues through ultracentrifugation. IFN-γ production was determined to evaluate the activity of Jurkat cells. The in vivo growth of OS cells was examined using a C3H xenograft model in mice, tumor volumes were monitored, and the proportion of CD3+ T cells in tumor tissues was detected. Results revealed that PD-L1 was significantly upregulated in the OS cell lines. MG63 and Saos-2 cells were the most abundant in PD-L1, so they were selected as investigation targets. PD-L1 was found to be also highly expressed in the exosomes isolated from MG63 and Saos-2 cells. The exosomes elicited significant inhibitory effects on IFN-γ secretion in Jurkat cells, which were abolished by the PD-L1 antibody or siRNAs. The in vivo growth of C3H cells was significantly facilitated by the overexpression of mPD-L1 or by the administration of mPD-L1-overloaded exosomes. The infiltration of CD3+ T cells was also decreased. The exosomes extracted from clinical PD-L1-positive OS tissues showed a promising inhibitory property against activated T cells. Therefore, PD-L1-loaded exosomes extracted from OS cells aggravated OS progression by suppressing T cell activities.
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http://dx.doi.org/10.1080/21655979.2021.1996509DOI Listing
October 2021

Effectiveness and safety of pyrotinib-based therapy in patients with HER2-positive metastatic breast cancer: A real-world retrospective study.

Cancer Med 2021 Oct 21. Epub 2021 Oct 21.

Breast Cancer Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.

The previous studies had demonstrated the promising effectiveness and acceptable safety of pyrotinib in patients with HER2-positive metastatic breast cancer. We aimed to investigate the real-world data of pyrotinib in complex clinical practice and complement the findings of clinical trials. Two hundred and eighteen patients were included for effectiveness analysis. A total of 62.0% had received two or more lines of systematic therapy, and 95.4% had been exposed to prior anti-HER2 therapy, with 95.4% receiving trastuzumab, 5.0% receiving pertuzumab, and 40.8% receiving lapatinib. The median progression-free survival (PFS) was 9.3 months and the objective response rate (ORR) was 44.0%. Patients treated with pyrotinib-based therapy as first, second, or later line had a median PFS of 15.0, 10.3, and 6.8 months, respectively. Patients treated with pyrotinib and trastuzumab received significant benefit in terms of median PFS compared with pyrotinib alone (10.7 (9.1-12.3) vs. 8.8 (8.1-9.5), p = 0.016). Patients pretreated with lapatinib had a median PFS of 6.9 months. The median PFS time was 7.0 months in patients with brain metastasis. Multivariate Cox regression analyses showed that lines of pyrotinib-based therapy (1 vs. 2 vs. ≥3), prior treatment with lapatinib, and combination treatments with trastuzumab proved to be independent predictors of PFS. Two hundred and forty-eight patients were included in the safety analysis, and the results showed that the toxicity of pyrotinib was tolerable, with the most common grade 3/4 adverse event being diarrhea (19.8%). Pyrotinib-based therapy demonstrated promising efficacy and tolerable toxicity in first-, second-, and later-line treatments and in lapatinib-treated patients. The combination of pyrotinib and trastuzumab showed advantages in PFS, even for patients resisting trastuzumab. Pyrotinib-based therapy could be the preferred choice for brain metastasis patients, especially when combined with brain radiotherapy.
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http://dx.doi.org/10.1002/cam4.4335DOI Listing
October 2021

lncRNA PSMA3-AS1 promotes the progression of non-small cell lung cancer through targeting miR-17-5p/PD-L1.

Adv Clin Exp Med 2021 Oct;30(10):1043-1050

Department of Oncology, Second Hospital of Shanxi Medical University, Taiyuan, China.

Background: A growing number of studies have shown that long-chain non-coding RNA (lncRNA) plays an important role in the progression of non-small cell lung cancer (NSCLC).

Objectives: To explore the role and potential molecular mechanism of lncRNA PSMA3-AS1 in promoting the proliferation, migration and invasion of NSCLC.

Material And Methods: The expression of PSMA3-AS1, miR-17-5p and PD-L1 in a human bronchial epithelial cell line, BEAS-2B, and NSCLC cell lines, H226 and A549, were detected with quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. The PSMA3-AS1 shRNA transfection was used to reduce the expression of PSMA3-AS1. Double fluorescent enzyme reporting was used to detect the relationship between PSMA3-AS1, miR-17-5p and PD-L1. Cell Counting Kit-8 (CCK-8), wound-healing and transwell assays, as well as western blot, were used to detect the expression of proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT)-related proteins in lung cancer cells.

Results: The expression of PSMA3-AS1 in NSCLC cells was significantly higher than in human bronchial epithelial cells. The PSMA3-AS1 knockdown significantly reduced the proliferation, migration and invasion of lung cancer cells. In addition, double fluorescent enzyme results showed that PSMA3-AS1 could competitively bind miR-17-5p to PD-L1. The expression of miR-17-5p is low in lung cancer cells, while the expression of PD-L1 in them is high. Overexpression of PD-L1 reversed the inhibitory effect of PSMA3-AS1 knockdown on the proliferation, migration and invasion of lung cancer cells.

Conclusions: Generally speaking, PSMA3-AS1 is highly expressed in NSCLC. The PSMA3-AS1 can promote the proliferation, migration and invasion of NSCLC cells by regulating miR-17-5p/PD-L1.
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http://dx.doi.org/10.17219/acem/138624DOI Listing
October 2021

Deep Inference Networks for Reliable Vehicle Lateral Position Estimation in Congested Urban Environments.

IEEE Trans Image Process 2021 5;30:8368-8383. Epub 2021 Oct 5.

Reliable estimation of vehicle lateral position plays an essential role in enhancing the safety of autonomous vehicles. However, it remains a challenging problem due to the frequently occurred road occlusion and the unreliability of employed reference objects (e.g., lane markings, curbs, etc.). Most existing works can only solve part of the problem, resulting in unsatisfactory performance. This paper proposes a novel deep inference network (DINet) to estimate vehicle lateral position, which can adequately address the challenges. DINet integrates three deep neural network (DNN)-based components in a human-like manner. A road area detection and occluding object segmentation (RADOOS) model focuses on detecting road areas and segmenting occluding objects on the road. A road area reconstruction (RAR) model tries to reconstruct the corrupted road area to a complete one as realistic as possible, by inferring missing road regions conditioned on the occluding objects segmented before. A lateral position estimator (LPE) model estimates the position from the reconstructed road area. To verify the effectiveness of DINet, road-test experiments were carried out in the scenarios with different degrees of occlusion. The experimental results demonstrate that DINet can obtain reliable and accurate (centimeter-level) lateral position even in severe road occlusion.
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http://dx.doi.org/10.1109/TIP.2021.3115454DOI Listing
October 2021

Thrombomodulin-mediated Inhibition of Neutrophil Extracellular Trap Formation Alleviates Hepatic Ischemia/Reperfusion Injury by Blocking TLR4 in Rats Subjected to Liver Transplantation.

Transplantation 2021 Sep 16. Epub 2021 Sep 16.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China. West China School of Medicine, Sichuan University, Chongqing, People's Republic of China.

Background: Hepatic ischemia/reperfusion injury (IRI) is an unavoidable outcome of liver transplantation, during which neutrophil extracellular traps (NETs) may play a critical role in the IRI-induced immune response to inflammation. The purpose of this study was to identify the function of recombinant human thrombomodulin (rTM) in the remission of hepatic IRI after liver transplantation and elucidate the specific mechanism.

Methods: NET formation was detected in the serum of liver transplantation patients and rats following liver transplantation. Hematoxylin-eosin (HE) staining, terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) staining, immunohistochemistry and immunofluorescence were used to assess the effect of rTM on NET formation in vitro and in vivo.

Results: We found that rTM markedly inhibited neutrophil formation in NETs, reduced apoptosis in hepatocytes, alleviated rat hepatic IRI and improved liver function. In vitro, rTM inhibited neutrophil formation in NETs, and lipopolysaccharide (LPS) (a Toll-like receptor (TLR)-4 agonist) reversed the inhibitory effect of rTM on NET formation. rTM blocked TLR-4 and the downstream extracellular signal-regulated kinase (ERK)/c-Jun NH2 terminal kinase (JNK) and nicotinamide adenine dinucleotide phosphate (NADPH)/ROS/peptidylarginine deiminase 4 (PAD4) signaling pathways to protect against hepatic IRI and inhibit NET formation. In addition, we demonstrated that combined treatment with rTM and an NADPH oxidative inhibitor had a better effect than either treatment alone.

Conclusions: NETs are a potential therapeutic target in hepatic IRI, and rTM could be used to prevent IR-induced hepatic injury. In addition, cotargeting NETosis-related signaling pathways might be a novel therapeutic strategy for hepatic IRI treatment.
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http://dx.doi.org/10.1097/TP.0000000000003954DOI Listing
September 2021

Glycopeptide-Conjugated Aggregation-Induced Emission Luminogen: A pH-Responsive Fluorescence Probe with Tunable Self-Assembly Morphologies for Cell Imaging.

J Phys Chem B 2021 09 8;125(36):10224-10231. Epub 2021 Sep 8.

CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), University of Chinese Academy of Sciences, No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China.

pH values play an important role in various cell biological processes. Abnormal pH values in living systems are frequently associated with the development of diseases such as cancers, infection, and other diseases. Real-time monitoring of the changes of pH values will give us the significant indication for these diseases' progression. Within those pH-sensitive imaging probes, aggregation-induced emission (AIE) molecules exhibit great potential in aqueous imaging environment due to their high fluorescence quantum yield and stability. However, the modulation of the AIE probe with pH sensitivity and light-up property face challenges. Here, we introduced a new glycopeptide-modified AIE probe () based on the optimized solid-phase peptide synthesis approach. The response to pH of the peptide: DDDD progression changed hydrophobicity and hydrophilicity, resulting in the change of the amphipathicity balance. When modulating the pH from 5.5 to 8.0, the adverse protonation of the peptide induced assembled nanostructure transformation from nanolamellae to nanomicelles. Meanwhile, the pH-induced charge change in peptides can greatly influence the microenvironment of the AIEgen, resulting in the increase of fluorescence intensity.
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http://dx.doi.org/10.1021/acs.jpcb.1c06443DOI Listing
September 2021

Phenylacetylglutamine is associated with the degree of coronary atherosclerotic severity assessed by coronary computed tomographic angiography in patients with suspected coronary artery disease.

Atherosclerosis 2021 09 13;333:75-82. Epub 2021 Aug 13.

Medical School of Chinese People's Liberation Army, Beijing, China; Department of Cardiology, The 2nd Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China; National Clinical Research Center for Geriatric Diseases, Beijing, China; Beijing Key Laboratory of Chronic Heart Failure Precision Medicine, Beijing, China. Electronic address:

Background And Aims: Phenylacetylglutamine (PAG), a gut microbiota metabolite, has recently been found to be associated with major adverse cardiovascular events. In this study, we analyzed the relationship between plasma PAG and coronary atherosclerotic severity assessed by coronary computed tomographic angiography (CCTA).

Methods: We enrolled consecutive patients with suspected coronary artery disease (CAD) who underwent CCTA. Plasma PAG was measured by mass spectrometry. Coronary atherosclerotic severity was evaluated based on plaque burden and plaque vulnerability. Plaque burden was quantified as percent atheroma volume (PAV), CCTA-derived SYNTAX score (CT-SYNTAX) and CAD reporting and data system score (CAD-RADS). Plaque vulnerability was evaluated by the presence of adverse characteristics.

Results: A total of 686 patients were enrolled. The patients were divided into two groups based on median plasma PAG (3.25 μM). A correlation was found between plasma PAG and PAV (r = 0.499, p < 0.01). Patients with obstructive CAD (CAD-RADS>3) and high coronary lesion complexity (CT-SYNTAX≥23) had higher plasma PAG (2.04 vs. 3.8 μM and 2.85 vs. 4.49 μM, respectively; p < 0.01 for all). After adjustment for confounding factors, plasma PAG remained associated with PAV (β: 0.98, p < 0.01), and patients in the higher PAG group had higher risks of obstructive CAD (odds ratio [OR]: 1.88, p < 0.01) and high coronary lesion complexity (OR: 1.47; p < 0.01). In addition, a high plasma PAG level (≥3.25 μM) was not an independent predictor of the presence of high-risk plaques.

Conclusions: There was an independent association between plasma PAG levels and the coronary atherosclerotic burden among patients with suspected CAD.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.08.029DOI Listing
September 2021

Further comments on the role of ACE-2 positive macrophages in human lung.

Cytometry A 2021 Aug 6. Epub 2021 Aug 6.

Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey, USA.

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http://dx.doi.org/10.1002/cyto.a.24484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426751PMC
August 2021

Phylogenetic relationship and characterization of the complete mitochondrial genome of (Lepidoptera: Papilionoidea: Pieridae).

Mitochondrial DNA B Resour 2021 28;6(8):2146-2148. Epub 2021 Jun 28.

School of Life Sciences, Gannan Normal University, Ganzhou, China.

is a common seen diurnal butterflies in the fields and widely distributed in many provinces of China. In this study, we sequenced and analyzed the complete mitochondrial genome (mitogenome) of . This mitogenome was 15,150 bp long and encoded 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), and two ribosomal RNA unit genes (rRNAs). The overall base composition of the mitogenome was estimated to be A 39.8%, T 41.2%, C 11.4% and G 7.6%, with a high A + T content of 81.0%. Except for started with CGA, all other PCGs started with the standard ATN codons (seven ATG, four ATT and one ATC). Most of the PCGs terminated with the stop codon TAA or TAG, whereas , , and end with the incomplete codon T--. Phylogenetic analysis showed that is indeed the sister species of with a high support value. All seven Coliadinae species formed one clade and was sister to Pierinae butterflies. Within Coliadinae, the relationships ( + ( + ( + ))) were highly supported.
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http://dx.doi.org/10.1080/23802359.2021.1944379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245105PMC
June 2021

Inhibition of Long Noncoding RNA Improves Angiotensin II-Induced Cardiac Fibrosis and Hypertrophy by Regulating the MicroRNA 335/ Axis.

Mol Cell Biol 2021 08 24;41(9):e0058020. Epub 2021 Aug 24.

Shanghai University of Medicine & Health Sciences, Zhoupu Hospital, Shanghai, China.

Cardiac fibrosis is a hallmark of various heart diseases and ultimately leads to heart failure. Although long noncoding RNA (lncRNA) has been reported to play important roles in various cancers, its function in cardiac fibrosis remains unclear. The expression of and microRNA 335 (miR-335) in heart tissues of angiotensin II-induced mice and angiotensin II-stimulated mouse cardiomyocyte cell line HL-1 were detected by quantitative real-time PCR (qRT-PCR). Cell viability was evaluated by cell counting kit-8 assay. The expression of galectin-3, fibrosis-related proteins (fibronectin, collagen IaI, and α-SMA), and apoptosis-related proteins [cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP)] was detected by Western blotting. Bioinformatics prediction, luciferase reporter assay, and RNA pulldown assay were performed to determine the relationship between and miR-335 as well as miR-335 and . Gain- and loss-function assays were performed to determine the role of /miR-335/ in cardiac fibrosis. was significantly upregulated and miR-335 was downregulated in heart tissues of angiotensin II-treated mice and angiotensin II-stimulated HL-1 cells. Downregulation of effectively enhanced cell viability and decreased cell size of HL-1 cells and the expression levels of fibrosis-related proteins (fibronectin, collagen IaI, and α-SMA) and apoptosis-related proteins (cleaved caspase-3 and cleaved PARP), which were induced by angiotensin II treatment. Furthermore, elevated the expression levels of by directly regulating miR-335. Our study revealed that downregulation of improved angiotensin II-induced cardiac fibrosis by targeting the miR-335/ axis, suggesting that is a therapeutic target for cardiac fibrosis and hypertrophy.
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http://dx.doi.org/10.1128/MCB.00580-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384070PMC
August 2021

Investigation of Candidate Genes and Pathways in Basal/TNBC Patients by Integrated Analysis.

Technol Cancer Res Treat 2021 Jan-Dec;20:15330338211019506

Department of Breast Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People's Republic of China.

Purpose: This study aims to identify the key pathway and related genes and to further explore the potential molecular mechanisms of triple negative breast cancer (TNBC).

Methods: The transcriptome data and clinical information of breast cancer patients were downloaded from the TCGA database, including 94 cases of paracancerous tissue, 225 cases of Basal like type, 151 cases of Her2 type, 318 cases of Luminal type A, 281 cases of Luminal type B, and 89 cases of Normal Like type. The differentially expressed genes (DEGs) were identified based on the criteria of |logFC|≥1.5 and adjust < 0.001.Their functions were annotated by gene ontology (GO) analysis and Kyoto Encyclopedia of differentially expressed genes & Genomes (KEGG) pathway analysis. Cox regression univariate analysis and Kaplan-Meier survival curves (Log-rank method) were used for survival analysis. FOXD1, DLL3 and LY6D were silenced in breast cancer cell lines, and cell viability was assessed by CCK-8 assay. Further, the expression of FOXD1, DLL3 and LY6D were explored by immunohistochemistry on triple negative breast tumor tissue and normal breast tissue.

Results: A total of 533 DEGs were identified. Functional annotation showed that DEGs were significantly enriched in intermediate filament cytoskeleton, DNA-binding transcription activator activity, epidermis development, and Neuroactive ligand-receptor interaction. Survival analysis found that FOXD1, DLL3, and LY6D showed significant correlation with the prognosis of patients with the Basal-like type ( < 0.05). CCK-8 assay showed that compared with Doxorubicin alone group, the cytotoxicity of Doxorubicin combined with siRNA-knockdown of FOXD1, DLL3, or LY6D was much significant.

Conclusion: The DEGs and their enriched functions and pathways identified in this study contribute to the understanding of the molecular mechanisms of TNBC. In addition, FOXD1, DLL3, and LY6D may be defined as the prognostic markers and potential therapeutic targets for TNBC patients.
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http://dx.doi.org/10.1177/15330338211019506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246569PMC
June 2021

Real-World Data on Apatinib Efficacy - Results of a Retrospective Study in Metastatic Breast Cancer Patients Pretreated With Multiline Treatment.

Front Oncol 2021 10;11:643654. Epub 2021 Jun 10.

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Cheeloo College of Medicine, Shandong University, Jinan, China.

Objectives: The NCCN guidelines recommend that the addition of bevacizumab should be considered in metastatic breast cancers in some circumstances, but there are no recommendations for the similar antiangiogenic drug apatinib. The aim of this study was to evaluate the safety and efficacy of apatinib in metastatic breast cancer patients pretreated with multiline treatment in a real-world setting.

Materials And Methods: Metastatic breast cancer patients pretreated with multiline treatment who had apatinib treatment initiated from September 2015 to August 2019 at Shandong Cancer Hospital and Institute were included. The primary endpoints included PFS and OS, and the secondary endpoint was treatment-related toxicity.

Results: A total of 66 patients with metastatic breast cancer received apatinib treatment after failure of multiline chemotherapy in this study. The median PFS and OS of all 66 patients were 6.0 months and 10.0 months, respectively. The clinical beneficial rate was 40.9%. All patients tolerated treatment well, and no patients died of toxicity. The common toxicities of apatinib were hand and foot syndrome, secondary hypertension and fatigue events. The number of prior chemotherapy regimens was significantly associated with DFS and OS. Capecitabine may be a better choice for combination with a longer median OS of 19 months, while apatinib combined with other drugs was 9 months, and the apatinib monotherapy was 10 months.

Conclusion: Apatinib produced moderate efficacy in metastatic breast cancer patients pretreated with multiline treatment with no significant treatment-related adverse events. Apatinib might be a choice for women as a maintenance salvage therapy following multiline chemotherapy failure.
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http://dx.doi.org/10.3389/fonc.2021.643654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224527PMC
June 2021

A Novel Graph-Based Trajectory Predictor With Pseudo-Oracle.

IEEE Trans Neural Netw Learn Syst 2021 Jun 4;PP. Epub 2021 Jun 4.

Pedestrian trajectory prediction in dynamic scenes remains a challenging and critical problem in numerous applications, such as self-driving cars and socially aware robots. Challenges concentrate on capturing pedestrians' motion patterns and social interactions, as well as handling the future uncertainties. Recent studies focus on modeling pedestrians' motion patterns with recurrent neural networks, capturing social interactions with pooling- or graph-based methods, and handling future uncertainties by using the random Gaussian noise as the latent variable. However, they do not integrate specific obstacle avoidance experiences (OAEs) that may improve prediction performance. For example, pedestrians' future trajectories are always influenced by others in front. Here, we propose the Graph-based Trajectory Predictor with Pseudo-Oracle (GTPPO), an encoder-decoder-based method conditioned on pedestrians' future behaviors. Pedestrians' motion patterns are encoded with a long short-term memory unit, which introduces temporal attention to highlight specific time steps. Their interactions are captured by a graph-based attention mechanism, which draws OAE into the data-driven learning process of graph attention. Future uncertainties are handled by generating multimodal outputs with an informative latent variable. Such a variable is generated by a novel pseudo-oracle predictor, which minimizes the knowledge gap between historical and ground-truth trajectories. Finally, the GTPPO is evaluated on ETH, UCY, and Stanford Drone datasets, and the results demonstrate state-of-the-art performance. Besides, the qualitative evaluations show successful cases of handling sudden motion changes in the future. Such findings indicate that GTPPO can peek into the future.
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http://dx.doi.org/10.1109/TNNLS.2021.3084143DOI Listing
June 2021

Study on the Dynamic Recrystallization Behavior of 47Zr-45Ti-5Al-3V Alloy by CA-FE Simulation.

Materials (Basel) 2021 May 14;14(10). Epub 2021 May 14.

Guizhou Key Laboratory of Materials Mechanical Behavior and Microstructure, College of Materials and Metallurgy, Guizhou University, Guiyang 550025, China.

The dynamic recrystallization (DRX) behavior of 47Zr-45Ti-5Al-3V alloy was studied by using the experiment and numerical simulation method based on DEFORM-3D software and cellular automata (CA) over a range of deformation temperatures (850 to 1050 °C) and strain rates (10 to 10 s). The results reveal that the DRX behavior of 47Zr-45Ti-5Al-3V alloy strongly depends on hot-working parameters. With rising deformation temperature () and decreasing strain rate (ε˙), the grain size (dDRX) and volume fraction (XDRX) of DRX dramatically boost. The kinetics models of the dDRX and XDRX of DRX grains were established. According to the developed kinetics models for DRX of 47Zr-45Ti-5Al-3V alloy, the distributions of the dDRX and XDRX for DRX grains were predicted by DEFORM-3D. DRX microstructure evolution is simulated by CA. The correlation of the kinetics model is verified by comparing the dDRX and XDRX between the experimental and finite element simulation (FEM) results. The nucleation and growth of dynamic recrystallization grains in 47Zr-45Ti-5Al-3V alloy during hot-working can be simulated accurately by CA simulation, comparing with FEM.
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http://dx.doi.org/10.3390/ma14102562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156880PMC
May 2021

Influence of Aging on Corrosion Behaviour of the 6061 Cast Aluminium Alloy.

Materials (Basel) 2021 Apr 7;14(8). Epub 2021 Apr 7.

H.H. Uhlig Corrosion Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

The influence of AlFeSi and MgSi phases on corrosion behaviour of the cast 6061 aluminium alloy was investigated. Scanning Kelvin probe force microscopy (SKPFM), electron probe microanalysis (EPMA), and in situ observations by confocal laser scanning microscopy (CLSM) were used. It was found that MgSi phases were anodic relative to the matrix and dissolved preferentially without significantly affecting corrosion propagation. The AlFeSi phases' influence on 6061 aluminium alloy local corrosion was greater than that of the MgSi phases. The corroded region width reached five times that of the AlFeSi phase, and the accelerating effect was terminated as the AlFeSi dissolved.
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http://dx.doi.org/10.3390/ma14081821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067747PMC
April 2021

Structure of Rad5 provides insights into its role in tolerance to replication stress.

Mol Cell Oncol 2021 4;8(2):1889348. Epub 2021 Mar 4.

Department of Biochemistry and Molecular Biology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), the Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin, P. R. China.

The Rad5 family of proteins are critical genome maintenance factors, with helicase-like transcription factor (HLTF) and SNF2 histone linker PHD RING helicase (SHRPH) in humans implicated in several types of cancer. How their multiple activities coordinate has been unclear. Our recent study on Rad5 shed light on this question.
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http://dx.doi.org/10.1080/23723556.2021.1889348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018420PMC
March 2021

Inhibition of NADPH oxidase 4 attenuates lymphangiogenesis and tumor metastasis in breast cancer.

FASEB J 2021 04;35(4):e21531

Breast Cancer Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People's Republic of China.

Lymphangiogenesis is thought to contribute to promote tumor cells to enter lymphatic vessels and plant at a secondary site. Endothelial cells are the cornerstone of the generation of new lymphatic vessels. NADPH oxidase 4 (Nox4) is the most abundant one of NADPH oxidases in endothelial cells and the most studied one in relevance with cancer. Our purpose is to analyze the relationship between Nox4 and lymphangiogenesis and find out whether the newborn lymphatic vessels lead to cancer metastasis. We first explored the expression of Nox4 in lymphatic endothelial cells of primary invasive breast tumors and human normal mammary glands using GEO databases and found that Nox4 was upregulated in primary invasive breast tumors samples. In addition, its high expression correlated with lymph node metastasis in breast cancer patients. Nox4 could increase the tube formation and lymphatic vessel sprouting in a three-dimensional setting. In vivo, inhibition of Nox4 in 4T1 tumor-bearing mice could significantly decrease the tumor lymphangiogenesis and metastasis. Nox4 may increase tumor lymphangiogenesis via ROS/ERK/CCL21 pathway and attract CCR7-positive breast cancer cells to entry lymphatic vessels and distant organs. In conclusion, our results show that Nox4 is a factor that promotes lymphangiogenesis and is a potential target of antitumor metastasis.
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http://dx.doi.org/10.1096/fj.202002533RDOI Listing
April 2021

gene as a novel pathogenic mutation occurring during the transformation of colorectal adenoma into colorectal cancer.

J Gastrointest Oncol 2021 Feb;12(1):69-78

Department of Oncology, The Second Hospital of Shanxi Medical University, Taiyuan, China.

Background: Polyps may develop into colorectal cancer (CRC) after 10-20 years. The occurrence of polyps and tumors caused by somatic gene mutations is considered a main pathogenesis of CRC. Among all general patients with polyps or CRC, some had adenoma of varying degrees that were consistent with familial colorectal adenomas. A patient with CRC (the propositus) and his brothers and sister, all of whom had varying degrees of colorectal polyps showed different adenomas with different members in a family.

Methods: In the present study, a total of 9 family members were investigated, and a family tree was drawn. Genomic DNA was extracted from peripheral venous blood samples from family members, and whole-exome sequencing (WES) and Sanger sequencing were performed on the DNA samples. The result of WES was compared with compared directly to the reference genome (hg19) with Burrows-Wheeler Aligner, which is as control group from.

Results: We identified a base substitution in the gene (c.68415368T>G, chromosome 9 q13), predicted the target gene of miR-4477b through the biologic website, and analyzed the Gene Ontology (GO) and signal pathway of the target gene. The GO functional annotation analysis of the target gene of mir4477b revealed that these genes are involved mainly in the G1/S transition of the mitotic cell cycle, activation of mitogen-activated protein kinase activity, protein phosphorylation, and membrane, centrosome, cytoplasm, zinc ion-binding, protein-binding, and ligase activity. Kyoto Encyclopedia of Gene and Genomes pathway analysis revealed that miR-4477b regulates target genes mainly involved in the phosphoinositide 3-kinase/Akt signaling pathway, regulation of the actin cytoskeleton, proteoglycans in cancer, pathways in cancer, and renal cell carcinoma.

Conclusions: The mutation of the gene likely leads to the occurrence of adenoma and CRC. In-depth studies of patients from the same family with different stages of adenoma can avoid errors caused by gene diversity, incomplete clinical data, and uncertain disease development. The gene may represent a key gene mutation in colorectal carcinogenesis and a multiyear cancer risk for patients that requires further attention.
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http://dx.doi.org/10.21037/jgo-20-600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944151PMC
February 2021

Characterization and phylogenetic analysis of the complete mitochondrial genome of (Odonata: Anisoptera: Libellulidae).

Mitochondrial DNA B Resour 2021 Feb 17;6(2):620-621. Epub 2021 Feb 17.

School of Life Sciences, Gannan Normal University, Ganzhou, PR China.

is a dragonfly of wet forests and usually perches on fallen logs and shrubs. In this study, we sequenced and analyzed the complete mitochondrial genome (mitogenome) of . This mitogenome was 15,459 bp long and encoded 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), and 2 ribosomal RNA unit genes (rRNAs). The nucleotide composition of the mitogenome was biased toward A and T, with 70.5% of A + T content (A 38.8%, T 31.7%, C 16.6%, and G 12.9%). Gene order was conserved and identical to most other previously sequenced Libellulidae dragonflies. Most PCGs of have the conventional start codons ATN (six ATG, three ATT, and two ATC), with the exception of and (TTG). Except for four PCGs (, , , and ) end with the incomplete stop codon T--, all other PCGs terminated with the stop codon TAA or TAG. Phylogenetic analysis showed that got together with with high support value. Libellulidae had a close relationship with Corduliidae, the relationships (( + ) + ( + ( + ( + )))) were supported in Libellulidae.
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http://dx.doi.org/10.1080/23802359.2021.1875924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894433PMC
February 2021

Pentraxin 3 acts as a functional effector of Akt/NF-κB signaling to modulate the progression and cisplatin-resistance in non-small cell lung cancer.

Arch Biochem Biophys 2021 04 19;701:108818. Epub 2021 Feb 19.

Department of Thoracic Surgery, Cangzhou Central Hospital, Cangzhou, Hebei, China.

Pentraxin 3 (PTX3) has been documented to be involved in the development of chemoresistance, however, the mechanisms by which it regulates cisplatin (DDP) resistance in non-small cell lung cancer (NSCLC) have never been elucidated. Quantitative reverse transcriptase polymerase chain reaction and Western blot were carried to determine the expression of PTX3, ATP-binding cassette sub-family B member 1 (ABCB1)/P-glycoprotein 1 (p-gp), protein kinase B (Akt), phosphorylated Akt and nuclear factor-kappa B (NF-кB) p65. The biological roles of PTX3 in NSCLC progression and NSCLC cell resistance to DDP were evaluated using enzyme-linked immunosorbent assay, cell count kit-8, colony formation assay, flow cytometry, as well as xenograft tumor assay. The expression of PTX3 was increased in the serum of NSCLC patients as well as in NSCLC cell lines. Lower PTX3 level was associated with longer overall survival in lung adenocarcinoma and lung squamous cell carcinoma patients. Furthermore, PTX3 expression was greatly higher in DDP-resistant NSCLC cells than that in NSCLC cells. Silencing of PTX3 restrained the proliferation and promoted the apoptosis of NSCLC cells, as well as sensitized DDP-resistant NSCLC cells to DDP. Additionally, knockdown of PTX3 inhibited the growth of NSCLC tumors in vivo. Upregulation of PTX3 expression was dependent on the activation of Akt/NF-κB signaling. The induction of apoptosis by PTX3 knockdown was enhanced by MK-2206 or JSH-23. In conclusion, knockdown of PTX3 restrained the progression of NSCLC and sensitized NSCLC cells towards DDP, which provides a potential target to restore DDP chemoresponse.
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http://dx.doi.org/10.1016/j.abb.2021.108818DOI Listing
April 2021

Cardioprotective Effect of Echinatin Against Ischemia/Reperfusion Injury: Involvement of Hippo/Yes-Associated Protein Signaling.

Front Pharmacol 2020 11;11:593225. Epub 2021 Jan 11.

Department of Cardiology, Cangzhou Central Hospital, Cangzhou, China.

Echinatin (Ech) has been reported to exert antioxidant and anti-inflammatory activities. In this study, we aimed to characterize the functional role of Ech in myocardial ischemic/reperfusion (MI/R) injury and elucidate its underlying mechanism of action. We established and models of MI/R injury to determine the effect of Ech on MI/R injury. Gene expression was examined using quantitative real-time polymerase chain reaction and western blotting. Myocardial infarction was assessed using tetrazolium chloride staining and the degree of myocardial injury was evaluated by measuring lactate dehydrogenase (LDH) and creatine kinase-myocardial band (CK-MB) levels. Cell apoptosis was detected using the terminal deoxynucleotidyl transfer-mediated dUTP nick end-labeling (TUNEL) assay. The viability of H9c2 cells was determined using Cell Counting Kit-8 assay. MI/R induced myocardial infarction, which was mitigated by Ech treatment. Moreover, Ech treatment resulted in a marked decline of LDH and CK-MB levels in the serum and myocardium of MI/R rats. Ech treatment also restrained cardiomyocyte apoptosis and , as evidenced by reduction in LDH release, the number of TUNEL-positive cells, and caspase-3 activity. Furthermore, Ech administration inhibited MI/R-induced activation of Hippo/Yes-associated protein signaling and , as indicated by inhibition of mammalian sterile 20-like protein kinase 1, large tumor suppressor one, and YAP phosphorylation and promotion of YAP nuclear translocation. However, silencing of YAP counteracted the protective effect of Ech on hypoxia/reoxygenation-induced myocardial injury . Ech exerted its protective effect against MI/R injury at least partially by suppressing the Hippo/YAP signaling pathway, providing novel insights into the remission of MI/R injury.
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http://dx.doi.org/10.3389/fphar.2020.593225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874120PMC
January 2021

Clinicopathological characteristics and prognostic factors of pulmonary sarcomatoid carcinoma: a large population analysis.

Ann Transl Med 2021 Jan;9(2):121

Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, China.

Background: This study was conducted to identify the clinicopathological characteristics and survival outcomes of pulmonary sarcomatoid carcinoma (PSC), and to compare prognostic factors between elderly (≥65 years) and non-elderly (<65 years) patients.

Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients diagnosed with PSC between 2004 and 2016. The Kaplan-Meier method was used for overall survival (OS) and cancer-specific survival (CSS) analysis. The Cox proportional hazards model was used to detect independent prognostic factors. A propensity score matched (PSM) analysis was conducted to compare OS and CSS in elderly versus non-elderly PSC patients.

Results: A total of 1,039 eligible cases were identified, with a median follow-up of 6 months. The 5-year OS and CSS rates were 12.3% and 18.7%, respectively, and the median survival was 6 months. Multivariate analysis revealed that female (HR =0.750, P<0.004), surgery (HR =0.484, P<0.001), chemotherapy (HR =0.504, P<0.001), and radiation (HR =0.801, P=0.041) were independent favorable prognostic factors. There was a significant difference in the OS and CSS rates between elderly and non-elderly patients after PSM (P=0.007 and P=0.017, respectively). In multivariate analysis, the predictors for OS in the elderly patients were gender, tumor stage, and chemotherapy, whereas in the non-elderly patients, the predictors were tumor stage, chemotherapy, and surgery.

Conclusions: The PSC patients in our study had poor survival outcomes. Comprehensive treatment, including surgery, chemotherapy, and radiotherapy, could improve patient prognosis. Elderly patients had different clinicopathological characteristics, compared to non-elderly patients.
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http://dx.doi.org/10.21037/atm-20-6213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867907PMC
January 2021

Structural Insights into the Interaction Between CRTCs and 14-3-3.

J Mol Biol 2021 04 5;433(7):166874. Epub 2021 Feb 5.

Department of Biochemistry and Molecular Biology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, 300070 Tianjin, PR China. Electronic address:

The CREB-Regulated Transcriptional Coactivators (CRTCs) regulate the transcription of CREB target genes and have important functions in many biological processes. At the basal state, they are phosphorylated at multiple residues, which promotes their association with 14-3-3 that sequesters them in the cytoplasm. Upon dephosphorylation, they translocate into the nuclei and associate with CREB to activate the target gene transcription. Although three conserved serine residues in CRTCs have been implicated in their phosphorylation regulation, whether and how they mediate interactions with 14-3-3 is unclear. Here, we provide direct evidence that these residues and flanking regions interact with 14-3-3 and the structural basis of the interaction. Our study also identified a novel salt bridge in CRTC1 with an important function in binding 14-3-3, expanding the understanding of the interaction between 14-3-3 and its ligands.
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http://dx.doi.org/10.1016/j.jmb.2021.166874DOI Listing
April 2021

Mitochondrial genome of (Coleoptera: Chrysomeloidea: Cerambycidae) and phylogenetic analysis.

Mitochondrial DNA B Resour 2021 Jan 13;6(1):71-72. Epub 2021 Jan 13.

School of Life Sciences, Gannan Normal University, Ganzhou, China.

The red-necked longhorn beetle is a major pest of peach orchards. In this study, we sequenced and analyzed the complete mitochondrial genome (mitogenome) of . This mitogenome was 15,760 bp long and encoded 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs) and two ribosomal RNA unit genes (rRNAs). Gene order was conserved and identical to most other previously sequenced Cerambycidae. Most PCGs of have the conventional start codons ATN (six ATT, five ATG and one ATC), with the exception of (TTG). Except for three genes (, and ) end with the incomplete stop codon T-, all other PCGs terminated with the stop codon TAA or TAG. The whole mitogenome exhibited heavy AT nucleotide bias (74.3%). Phylogenetic analysis positioned in a well-supported clade within the subfamily Cerambycinae with (tribe Xystrocerini). These results support the currently accepted taxonomy and provide a better understanding of the phylogenetic analysis of the Cerambycidae.
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http://dx.doi.org/10.1080/23802359.2020.1846475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819112PMC
January 2021

Characterization and phylogenetic analysis of the complete mitochondrial genome of (Odonata: Anisoptera: Libellulidae).

Mitochondrial DNA B Resour 2021 Jan 8;6(1):24-25. Epub 2021 Jan 8.

School of Life Sciences, Gannan Normal University, Ganzhou, PR China.

is a commonly seen dragonfly with a big yellow or white ringlike spot on the third and fourth segments of its abdomen. In this study, we sequenced and analyzed the complete mitochondrial genome (mitogenome) of . This mitogenome was 15,434 bp long and encoded 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), and 2 ribosomal RNA unit genes (rRNAs). Gene order was conserved and identical to most other previously sequenced Libellulidae dragonflies. The whole mitogenome exhibited heavy AT nucleotide bias (74.6%). Most PCGs of have the conventional start codons ATN (six ATG, three ATT, and two ATC), with the exception of and (TTG). Except for four genes (, , , and ) end with the incomplete stop codon T-, all other PCGs terminated with the stop codon TAA or TAG. Phylogenetic analysis showed that got together with with high support value, and the relationships (( + ) + (( + ) + ( + ))) were supported in Libellulidae.
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http://dx.doi.org/10.1080/23802359.2020.1839369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808373PMC
January 2021

Corrigendum to Matrix stiffening induces endothelial dysfunction via the TRPV4/microRNA-6740/endothelin-1 mechanotransduction pathway Acta Biomaterialia, Volume 100, December 2019, Pages 52-60.

Acta Biomater 2021 Mar 23;122:387-388. Epub 2021 Jan 23.

Institute of Health Service and Transfusion Medicine, Academy of Military Medical Sciences, Beijing 100039, P.R.China.

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http://dx.doi.org/10.1016/j.actbio.2021.01.009DOI Listing
March 2021
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