Publications by authors named "Bo Deng"

232 Publications

Mechanosensitive Piezo1 in endothelial cells promotes angiogenesis to support bone fracture repair.

Cell Calcium 2021 Jun 7;97:102431. Epub 2021 Jun 7.

The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, LS2 9JT, UK. Electronic address:

Piezo1, a calcium-permeable non-selective cationic channel that senses mechanical stimulation in multicellular organisms, mediates various biological processes, including angiogenesis. The supply of nutrients and oxygen through newly formed blood vessels at the fractured lesion is critical for bone fracture repair. The elucidation of the underlying mechanisms involved in angiogenesis and bone repair can aid in improving fracture healing. Here, mice with endothelial cell-specific deletion of Piezo1 channels were used to examine the role of Piezo1 in the initiation of fracture healing. The expression and distribution of Piezo1 was explored in the vasculature of the bone. The deletion of endothelial Piezo1 resulted in impaired bone fracture repair, downregulation of calcium-activated proteolytic calpain activity during vascularization, inhibition of osteoblast maturation and ossification, downregulation of phosphorylated PI3K-AKT, and impaired Notch signaling during bone fracture union. These findings indicated that Piezo1 protein is a potential target for enhancing bone regeneration and treating delayed or nonunion bone fractures.
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http://dx.doi.org/10.1016/j.ceca.2021.102431DOI Listing
June 2021

expression closely correlates with muscle fiber types in porcine muscle and regulates myosin heavy chains mRNA expression in C2C12 cells.

PeerJ 2021 19;9:e11065. Epub 2021 Apr 19.

Institute of Animal Husbandry and Veterinary Science, Zhejiang Academy of Agricultural Science, Hangzhou, Zhejiang, China.

Background: Irisin (a glycosylated protein) is cleaved from fibronectin type III domain-containing protein 5 (FNDC5), which is expressed mainly in animal muscle tissues and has multiple metabolic regulatory activities. However, their roles in controlling myofiber types in skeletal muscle remain unclear.

Methodology: Two different commercial hybridized pigs, LJH (a crossed pig containing Chinese native pig genotypes) and DLY (Duroc × Landrace × Yorkshire) were selected to analyze mRNA expression and the mRNA composition of four adult myosin heavy chain () isoforms (IIIaIIxIIb) in the (LD) muscle. C2C12 myoblasts were cultured to investigate the effects of on the four MyHCs mRNA expressive levels, using small interfering RNA for depletion and a eukaryotic expression vector carrying for overexpression. ZLN005 (a small molecule activator of FNDC5's upstream control gene ) or recombinant human irisin protein were also used.

Results: In LD muscle, LJH pigs had the higher mRNA level, and proportion than DLY pigs (). For C2C12 cells in vitro, small interfering RNA (si-592) silencing of expression markedly reduced mRNA levels (), while overexpression significantly increased mRNA levels (). Exogenous irisin increased the mRNA levels of (peroxisome proliferator-activated receptor gamma coactivator 1-alpha), , , , (nuclear respiratory factor 1), (vascular endothelial growth factor), and (mitochondrial transcription factor A,) (), and the enzyme activities of SDH (succinate dehydrogenase), CK (creatine kinase), and MDH (malate dehydrogenase) in C2C12 myotubes (). These results showed that mRNA expression had a significant association with the characteristics of myofiber types in porcine muscle, and participated in regulating mRNA expression of C2C12 myogenic differentiation cells in vitro. could be an important factor to control muscle fiber types, which provides a new direction to investigate pork quality via muscle fiber characteristics.
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http://dx.doi.org/10.7717/peerj.11065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061570PMC
April 2021

Knockout RAGE alleviates cardiac fibrosis through repressing endothelial-to-mesenchymal transition (EndMT) mediated by autophagy.

Cell Death Dis 2021 May 11;12(5):470. Epub 2021 May 11.

The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.

Endothelial-to-mesenchymal transition (EndMT) has been shown to contribute to cardiac fibrosis and heart failure (HF). Recent studies have demonstrated that EndMT is regulated by autophagy, and we previously showed suppression of excessive autophagy and alleviation of cardiac fibrosis in HF mice with inactivated receptor for advanced glycation end products (RAGE). Thus, we investigated whether reduced cardiac fibrosis due to RAGE knockout occurred by inhibiting EndMT mediated by excessive autophagy. We found a decrease in endothelial cells (CD31/VE-Cadherin) and an increase in cells co-expressing CD31 and α-smooth muscle actin (α-SMA, myofibroblast marker) at 8 weeks in heart tissue of mice subjected to transverse aortic constriction (TAC), which implied EndMT. Knockout RAGE decreased EndMT accompanied by decreased expression of autophagy-related proteins (LC3BII/I and Beclin 1), and alleviated cardiac fibrosis and improved cardiac function in TAC mice. Moreover, 3-methyladenine (3-MA) and chloroquine (CQ), inhibitors of autophagy, attenuated EndMT, and cardiac fibrosis in TAC mice. Importantly, EndMT induced by AGEs could be blocked by autophagy inhibitor in vivo and in vitro. These results suggested that AGEs/RAGE-autophagy-EndMT axis involved in the development of cardiac fibrosis and knockout RAGE ameliorated cardiac fibrosis through decreasing EndMT regulated by autophagy, which could be a promising therapeutic strategy for HF.
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http://dx.doi.org/10.1038/s41419-021-03750-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113558PMC
May 2021

Circulating tumor cells with epithelial-mesenchymal transition markers as potential biomarkers for the diagnosis of lung cancer.

World J Clin Cases 2021 Apr;9(12):2721-2730

Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing 400042, China.

Background: Circulating tumor cells (CTCs) can be clustered into three subtypes according to epithelial-mesenchymal transition (EMT) markers: CTCs with epithelial markers (E-CTCs), CTCs with mesenchymal markers (M-CTCs), and CTCs with both markers (E&M-CTCs). CTC detection has clinical implications in the diagnosis of lung cancer (LC).

Aim: To clarify the diagnostic value of CTCs categorized by EMT markers in LC.

Methods: The study included 106 patients with lung adenocarcinoma, including 42 ground-glass opacities (GGO) and 64 solid lesions, who underwent surgery between July 2015 and December 2019. Eleven patients with benign tumors and seventeen healthy controls were included. CTCs in peripheral blood and associated EMT markers were detected preoperatively using the CanPatrol technique. The diagnostic power of CTCs for discriminating LC cases from controls was analyzed by the receiver operating characteristic (ROC) curve. The CytoploRare technique was used in 20 cases and 18 controls for validation, and Kappa values were calculated to evaluate consistency between techniques.

Results: Of the 106 LC cases, 94 (89.6%) had at least one CTC. CTCs were detectable in 35 (83.3%) of 42 GGO cases. Total CTCs and E&M-CTCs were significantly more frequent in LC cases than in benign or healthy controls. The proportion of M-CTCs plus E&M-CTCs increased gradually from healthy controls, to benign controls, to LC cases. The area under the ROC curve of total CTCs and E&M-CTCs was > 0.8 and > 10.75, respectively. The combined sensitivity of total-CTCs and E&M-CTCs was 85.85% for LC patients (80.95% for GGO patients) and the specificity was 78.57%. The Kappa value was 0.415, indicating relative consistency between CanPatrol and CytoploRare.

Conclusion: CTC detection is valuable for distinguishing LC from controls, and particularly E&M-CTC detection warrants further study.
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http://dx.doi.org/10.12998/wjcc.v9.i12.2721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058682PMC
April 2021

The Human Cytomegalovirus US31 Gene Predicts Favorable Survival and Regulates the Tumor Microenvironment in Gastric Cancer.

Front Oncol 2021 20;11:614925. Epub 2021 Apr 20.

Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Zhejiang Chinese Medical University, Wenzhou, China.

Human cytomegalovirus (HCMV) is an oncogenic virus associated with tumorigenesis. Our previous study revealed that the HCMV US31 gene interacted with NF-κB2 and mediated inflammation through macrophages. However, there are few reports on the role of US31 in gastric cancer (GC). The aim of this study was to investigate the expression of the US31 gene in GC tissue and assess its role in the occurrence and development of GC. US31 expression in 573 cancer tissues was analyzed using immunohistochemistry. Results showed that US31 was significantly associated with tumor size ( = 0.005) and distant metastasis ( < 0.001). Higher US31 expression indicated better overall survival in GC patients. Overexpression of US31 significantly inhibited the proliferation, migration, and invasion of GC cells ( < 0.05). Furthermore, expression levels of CD4, CD66b, and CD166 were positively correlated with US31, suggesting that it was involved in regulating the tumor immune microenvironment of GC. RNA sequencing, along with quantitative real-time polymerase chain reaction, confirmed that the expression of US31 promoted immune activation and secretion of inflammatory cytokines. Overall, US31 inhibited the malignant phenotype and regulated tumor immune cell infiltration in GC; these results suggest that US31 could be a potential prognostic factor for GC and may open the door for a new immunotherapy strategy.
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http://dx.doi.org/10.3389/fonc.2021.614925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093799PMC
April 2021

The Relationship Between Metabolic Parameters, Age, and Thyroid Status: A Cross-Sectional Study-Based National Survey of Iodine Nutrition, Thyroid Disease.

Risk Manag Healthc Policy 2021 23;14:1723-1730. Epub 2021 Apr 23.

Department of Rehabilitation, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People's Republic of China.

Aim: The relationship between thyroid status and metabolic factors was investigated as well as iodine nutrition in the general population and among the elderly population.

Methods: We performed a cross-sectional survey of 2483 subjects to assess the status of national iodine nutrition and incidence of thyroid disease. The general and elderly populations were divided into normal thyroid function (NTF) and subclinical hypothyroidism (SCH) groups. The anthropometric parameters and biochemical indicators were then analyzed.

Results: Overall, 327 participants were diagnosed with thyroid diseases, 73 (22.32%) of whom were 65 years or older. For the general population, compared with the NTF group, individuals in the SCH group were older, presented with higher systolic blood pressure, fasting blood glucose, serum cholesterol, and urinary iodine concentration (all p<0.05) but lower blood uric acid (UA) (p<0.05). Linear regression analysis further revealed that age and triglyceride (TG) serum levels positively correlated with serum thyroid-stimulating hormone (TSH) levels. Multiple regression analyses revealed that age, TG, waist circumference (WC), and body mass index were independent predictors for abnormal TSH serum levels. For the elderly population, compared with NTF group, individuals in the SCH group were substantially older (p<0.05) but presented with lower UA (p<0.05). Pearson linear regression analysis revealed a positive correlation between age (p=0.003) as well as TG levels (p<0.001) and serum TSH levels. In contrast, WC (p=0.003) was negatively related to TSH serum levels. Further multiple regression analysis revealed that age, TG, WC and heart rate were independent predictors of blood TSH.

Conclusion: The large-scale national study of iodine nutrition, thyroid disease has shown a vital relationship between metabolic indicators and serum TSH levels. Age and metabolic diseases increase the likelihood of developing thyroid diseases, both the general population and among the elderly.
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http://dx.doi.org/10.2147/RMHP.S306122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079349PMC
April 2021

Enhanced Antitumor Immune Responses via a Self-Assembled Carrier-Free Nanovaccine.

Nano Lett 2021 05 22;21(9):3965-3973. Epub 2021 Apr 22.

The Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Peking Union Medical College & Chinese Academy of Medical Sciences, Tianjin 300192, China.

Nanovaccines have emerged as promising agents for cancer immunotherapy. However, insufficient antitumor immunity caused by inefficient antigen/adjuvant loading and complicated preparation processes are the major obstacles that limit their clinical application. Herein, two adjuvants, monophosphatidyl A (MPLA) and CpG ODN, with antigens were designed into a nanovaccine to overcome the above obstacles. This nanovaccine was constructed with adjuvants (without additional materials) through facile self-assembly, which not only ensured a high loading efficacy and desirable safety but also facilitated clinical translation for convenient fabrication. More importantly, the selected adjuvants could achieve a notable immune response through synergistic activation of Toll-like receptor 4 (TLR4) and TLR9 signaling pathways, and the resulting nanovaccine remarkably inhibited the tumor growth and prolonged the survival of tumor-implanted mice. This nanovaccine system provides an effective strategy to construct vaccines for cancer immunotherapy.
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http://dx.doi.org/10.1021/acs.nanolett.1c00648DOI Listing
May 2021

Xinyang Tablet inhibits MLK3-mediated pyroptosis to attenuate inflammation and cardiac dysfunction in pressure overload.

J Ethnopharmacol 2021 Jun 30;274:114078. Epub 2021 Mar 30.

The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. Electronic address:

Ethnopharmacological Relevance: Xinyang tablet (XYT) has been traditionally used in the treatment of cardiovascular diseases (CVDs). Our previous study indicated that XYT exhibited protective effects in heart failure (HF).

Aim Of The Study: The aim of the present study was to determine the protective effects of XYT in pressure overload induced HF and to elucidate its underlying mechanisms of action.

Materials And Methods: We analyzed XYT content using high-performance liquid chromatography (HPLC.). Mice were subjected to transverse aortic constriction (TAC) to generate pressure overload-induced cardiac remodeling and were then orally administered XYT or URMC-099 for 1 week after the operation. HL1 mouse cardiomyoblasts were induced by lipopolysaccharides (LPS) to trigger pyroptosis and were then treated with XYT or URMC-099. We used echocardiography (ECG), hematoxylin and eosin (H&E) staining, Masson's trichrome staining and a terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay to evaluate the effects of XYT. Messenger ribonucleic acid (mRNA) levels of collagen metabolism biomarkers and inflammation-related factors were detected. We determined protein levels of inflammation- and pyroptosis-related signaling pathway members via Western blot (WB). Caspase-1 activity was measured in cell lysate using a Caspase-1 Activity Assay Kit. Subsequently, to define the candidate ingredients in XYT that regulate mixed-lineage kinase-3 (MLK3), we used molecular docking (MD) to predict and evaluate binding affinity with MLK3. Finally, we screened 24 active potential compounds that regulate MLK3 via MD.

Results: ECG, H&E staining, Masson's trichrome staining and TUNEL assay results showed that XYT remarkably improved heart function, amelorated myocardial fibrosis and inhibited apoptosis in vivo. Moreover, it reduced expression of proteins or mRNAs related to collagen metabolism, including collagen type 1 (COL1), fibronectin (FN), alpha smooth-muscle actin (α-SMA), and matrix metalloproteinases-2 and -9 (MMP-2, MMP-9). XYT also inhibited inflammation and the induction of pyroptosis at an early stage, as well as attenuated inflammation and pyroptosis levels in vitro.

Conclusion: Our data indicated that XYT exerted protective effects against pressure overload induced myocardial fibrosis (MF), which might be associated with the induction of pyroptosis-mediated MLK3 signaling.
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http://dx.doi.org/10.1016/j.jep.2021.114078DOI Listing
June 2021

Dauricine inhibits proliferation and promotes death of melanoma cells via inhibition of Src/STAT3 signaling.

Phytother Res 2021 Apr 1. Epub 2021 Apr 1.

Department of Traditional Chinese Medicine, Guangzhou Institute of Cardiovascular Disease, State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.

Melanoma is the most common type of skin cancer. Signal transducer and activator of transcription 3 (STAT3) signaling has been demonstrated to be a therapeutic target for melanoma. Dauricine (Dau), an alkaloid compound isolated from the root of Menispermum dauricum DC., has shown tumor-suppressing effects in multiple human cancers, but its potential in melanoma remains unexplored. In this study, we demonstrated that Dau significantly inhibited the viability and proliferation of A375 and A2058 melanoma cells. Death of melanoma cells was also markedly promoted by Dau. Moreover, Dau inhibited phosphorylation-mediated activation of STAT3 and Src in a dose-dependent manner. Notably, constitutive activation of Src partially abolished the antiproliferative and cytotoxic activities of Dau on melanoma cells. Molecular docking showed that Dau could dock on the kinase domain of Src with a binding energy of -10.42 kcal/mol. Molecular dynamics simulations showed that Src-Dau binding was stable. Surface plasmon resonance imaging analysis also showed that Dau has a strong binding affinity to Src. In addition, Dau suppressed the growth of melanoma cells and downregulated the activation of Src/STAT3 in a xenograft model in vivo. These data demonstrated that Dau inhibits proliferation and promotes cell death in melanoma cells by inhibiting the Src/STAT3 pathways.
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http://dx.doi.org/10.1002/ptr.7089DOI Listing
April 2021

Distinct cerebral F-FDG PET metabolic patterns in anti-N-methyl-D-aspartate receptor encephalitis patients with different trigger factors.

Ther Adv Neurol Disord 2021 24;14:1756286421995635. Epub 2021 Feb 24.

PET Center, Huashan Hospital, Fudan University, 518 East Wuzhong Road, Shanghai 200235, China.

Aim: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a subgroup of treatable autoimmune encephalitis, characterized by rapid development of psychosis, cognitive impairments and seizures. Etiologically, anti-NMDAR encephalitis could be divided into three subgroups, which are paraneoplastic (especially associated with ovarian teratoma), viral encephalitis-related and cryptogenic. Each type is different in clinical course, treatment strategies and prognosis. In this study, we aim to investigate whether anti-NMDAR encephalitis patients with different trigger factors exhibit distinct cerebral metabolic patterns detected by F-fluorodeoxyglucose positron emission tomography imaging.

Methods: 24 patients with anti-NMDAR encephalitis in acute phase from Huashan Hospital, Fudan University (Shanghai, China) were recruited in this study. Each patient was classified into one of etiological subgroups. Positron emission tomography images of individual patients were analyzed with both routine visual reading and computer-supported reading by comparison with those of the same 10 healthy controls using a voxel-wise statistical parametric mapping analysis.

Results: Patients in both the cryptogenic (13 patients) and paraneoplastic (five patients) subgroups showed hypermetabolism in the frontal-temporal lobes and basal ganglia, covarying with hypometabolism in the occipital regions. Notably, the abnormal metabolism was usually asymmetric in the cryptogenic subgroup, but relatively symmetric in the paraneoplastic subgroup. Moreover, the other six patients secondary to viral encephalitis presented with significant hypometabolism in the bilateral occipital regions, as well as in the unilateral temporal lobes and part of basal ganglia (also is virus infection side), but hypermetabolism in the contralateral temporal areas.

Conclusion: This study revealed that patients with anti-NMDAR encephalitis triggered by different factors presented distinct cerebral metabolic patterns. Awareness of these patterns may help to better understand the varying occurrence and development of anti-NMDAR encephalitis in each subgroup, and could offer valuable information to the early diagnosis, treatment and prognosis of this disorder.

Trial Registration Number: ChiCTR2000029115 (Chinese clinical trial registry site, http://www.chictr.org).
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http://dx.doi.org/10.1177/1756286421995635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919218PMC
February 2021

Piezo1 impairs hepatocellular tumor growth via deregulation of the MAPK-mediated YAP signaling pathway.

Cell Calcium 2021 May 13;95:102367. Epub 2021 Feb 13.

Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, China; The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.; Faculty of Biological Sciences, University of Leeds, United Kingdom. Electronic address:

Accumulating evidence has revealed the mechanosensitive ion channel protein Piezo1 is contributing to tumorigenesis. However, its role in hepatocellular carcinoma (HCC) remains unexplored. In this study, we demonstrated that Piezo1 was expressed in the HepG2 cell line and depletion of Piezo1 impaired proliferation and migration, as well as increased apoptosis in these cells. Using a Piezo1-specific activator, Yoda1, we identified that calcium entry induced by Yoda1 resulted in phosphorylation of JNK, p38, and ERK, thereby activating the mitogen-activated protein kinase (MAPK) pathway, in a dose- and time-dependent manner. More strikingly, Piezo1 activation integrated with YAP signaling to control the nuclear translocation of YAP and regulation of its target genes. JNK, p38, and ERK (MAPK signaling) regulated Yoda1-induced YAP activation. Consistent with the association of calpain with Piezo1, we also found that calpain activity was decreased by siRNA-mediated knockdown of Piezo1. In addition, the growth of HCC tumors was inhibited in Piezo1 haploinsufficient mice. Together, our findings establish that the Piezo1/MAPK/YAP signaling cascade is essential for HepG2 cell function. These results highlight the importance of Piezo1 in HCC and the potential utility of Piezo1 as a biomarker and therapeutic target.
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http://dx.doi.org/10.1016/j.ceca.2021.102367DOI Listing
May 2021

Taohong siwu decoction attenuates myocardial fibrosis by inhibiting fibrosis proliferation and collagen deposition via TGFBR1 signaling pathway.

J Ethnopharmacol 2021 Apr 16;270:113838. Epub 2021 Jan 16.

Department of Traditional Chinese Medicine (Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, State Key Laboratory of Respiratory Disease), The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510260, China. Electronic address:

Ethnopharmacological Relevance: Myocardial fibrosis after myocardial infarction (MI) leads to cardiac remodeling and loss of function. Taohong siwu decoction (THSWD), a well-known traditional Chinese medicinal prescription, has been clinically used to treat various cardiovascular and cerebrovascular diseases, but its potential functions in myocardial fibrosis after MI remain uncharacterized.

Aim Of The Study: The purpose of current study was to explore the potential mechanism action and anti-myocardial fibrosis effects of treatment with THSWD in vivo and in vitro.

Materials And Methods: Mouse underwent ligation of coronary artery to induce MI and divided equally into the sham group, model group and THSWD treatment groups. After 4 weeks, the effects of THSWD treatment on cardiac function were estimated by echocardiography. HE staining was used to detect the pathologic changes and Masson trichrome staining was used to estimate tissue fibrosis. To further explore the regulatory molecular mechanisms of THSWD, transcriptome analysis was performed. Furthermore, in vitro, we investigated the effect of THSWD on cell proliferation and collagen deposition in primary cardiac fibrosis cells and its possible mechanism of action. Overexpression of TGFBR1 was achieved by infection with an adenovirus vector encoding TGFBR1.

Results: Treatment with THSWD significantly decreased myocardial fibrosis and recovered cardiac function in the post-MI mouse. The transcriptomics data imply that the TGF-β pathway might be a target in the anti-fibrosis effect of THSWD. THSWD inhibits TGF-β1-induced proliferation of primary cardiac fibroblasts. THSWD decreased collagen expression and TGFBR1 and Smad2/3 phosphorylation. Moreover, the inhibitory effect of THSWD on CFs proliferation and collagen deposition, as well as TGFBR1 signaling pathway-associated proteins expression was partially abrogated by overexpression of TGFBR1.

Conclusion: Collectively, the results implicate that THSWD attenuates myocardial fibrosis by inhibiting fibrosis proliferation and collagen deposition via inhibiting TGFBR1, and might be a potential therapeutic agent for treatment of myocardial fibrosis post-MI.
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http://dx.doi.org/10.1016/j.jep.2021.113838DOI Listing
April 2021

High Expression of BCAR1 by Circulating Tumor Cells and Tumor Tissues Is Predictive of a Poor Prognosis of Early-Stage Lung Adenocarcinoma Potentially Due to Regulation of Epithelial-Mesenchymal Transition.

Technol Cancer Res Treat 2020 Jan-Dec;19:1533033820983086

Department of Thoracic Surgery, Daping Hospital, Army Medical University, Chongqing City, China.

Objective: To clarify the clinical significance of breast cancer anti-estrogen resistance protein 1 (BCAR1) expression in circulating tumor cells (CTCs) in the peripheral blood and tumor tissues in patients with early stage lung adenocarcinoma (ES-LUAD).

Methods: The study cohort included 60 patients with stage I LUAD (50 IA and 10 IB) who underwent surgery from November 2015 to November 2018 and 31 healthy controls. The expression levels of BCAR1 and markers of epithelial-mesenchymal transition (EMT) in peripheral blood CTCs were detected using CanPatrol technology before surgery, and immunohistochemical analysis was used to detect BCAR1 expression in tumor tissues collected from 40 patients. The predictive power of BCAR1 expression in CTCs and tumor tissues on disease-free survival (DFS) was analyzed. The Cancer Genome Atlas (TCGA) database was used to study BCAR1 expression and overall survival as validation. The Gene Expression Profiling Interactive Analysis online tool was used to analyze the correlations between the expression levels of BCAR1 and EMT molecular markers.

Results: Both the number and detection rates of BCAR1-negative CTCs and BCAR1-positive CTCs in peripheral blood of lung cancer patients were significantly higher as compared with healthy controls ( < 0.05). BCAR1-positive CTCs more commonly co-expressed both epithelial and mesenchymal markers. Kaplan-Meier analysis demonstrated that patients with BCAR1(++) CTCs in peripheral blood before surgery were more prone to recurrence or metastasis after 2 years. COX analysis showed that patients with higher abundance of BCAR1(++) CTCs had a poorer prognosis (hazard ratio [HR] = 1.712, 95% confidence interval [CI] = 1.077-2.272, = 0.023). Furthermore, high BCAR1 expression in tumor tissues was predictive of a poor prognosis (HR = 2.654, 95% CI = 1.239-5.686, = 0.012), as validated by TCGA database (HR = 2.217, 95% CI = 1.069-4.595, = 0.032). In addition, BCAR1 expression in LUAD tissues from TCGA was significantly positively correlated with the expression of both epithelial markers (e.g., ck8/18/19) and mesenchymal markers (e.g., vimentin and twist).

Conclusion: BCAR1 may have a "dual impact" on EMT markers in tumor tissues and CTCs due to micro-environmental disparities, resulting in important clinical significance, which can potentially guide accurate treatment of LUAD.
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http://dx.doi.org/10.1177/1533033820983086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758864PMC
December 2020

Effects of Bacillus subtilis on growth performance, serum parameters, digestive enzyme, intestinal morphology, and colonic microbiota in piglets.

AMB Express 2020 Dec 2;10(1):212. Epub 2020 Dec 2.

Institute of Animal Husbandry and Veterinary Science, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, Zhejiang, China.

The present study was conducted to investigate effects of Bacillus subtilis on growth performance, serum parameters, digestive enzymes, intestinal morphology, and colonic microbiota in piglets. A total of 72 piglets were weighed and randomly allotted into three treatments (four replication pens per treatment with six piglets/pen) for a 28-day experiment. The dietary treatments were as follows: basal diet (control group, CTR), basal diet supplementation with antibiotic (antibiotic group, ABT), and basal diet supplementation with 0.1% Bacillus subtilis (probiotic group, PBT). The average daily gain of body weight increased in both the ABT and PBT groups, and dietary antibiotics decreased the feed:gain ratio (F:G), as compared to the CTR group (P < 0.05). Both ABT and PBT piglets had increased serum triglycerides and lipase, amylase, maltase activities and villus height:crypt depth ratio (V/C) in ileum (P < 0.05). The PBT group also showed an increase in serum glucose and villus height in the ileum (P < 0.05). Dietary antibiotics increased Lactobacillus johnsonii, as compared to the CTR group, but decreased bacterial diversity and increased Escherichia coli, as compared to the PBT group (P < 0.05). Piglets dietary with B. subtilis modulated the microbiota by increasing the abundance of Firmicutes (L. johnsonii, L. reuteri) and decreasing the abundance of E. coli, as compared to the control group (P < 0.05). These results indicate that dietary of B. subtilis improves growth performance and intestinal health and can be a promising alternative to antibiotics in piglets diet.
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http://dx.doi.org/10.1186/s13568-020-01150-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710768PMC
December 2020

Psoas hematoma as a rare complication of posterior lumbar interbody fusion: a case report.

BMC Surg 2020 Nov 11;20(1):279. Epub 2020 Nov 11.

Department of Orthopedics, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, 317000, China.

Background: Psoas hematoma rarely occurs in patients with spondylolisthesis who undergo posterior lumbar interbody fusion (PLIF) surgery.

Case Presentation: Here we reported a case of a 57-year-old male patient diagnosed with spondylolisthesis who underwent PLIF at the local hospital. Seven days post-surgery, abdominal pain occurred, and the pain in the right lower limb gradually increased. The computerized tomography (CT) indicated a formation of hematoma around the psoas muscle. Digital-subtraction angiography (DSA) suggested a vascular injury, a rupture of the right segmental artery of the lumbar vertebral level 4. The patient then received DSA vascular embolization, after which the lower lumbar segmental artery active bleeding was stopped. One month after discharge, the abdominal hematoma was gradually absorbed, and the pain in the waist, leg, and abdomen disappeared.

Conclusion: Symptoms such as abdominal pain, abdominal distension, and exacerbation of lower limb pain, may suggest the occurrence of psoas hematoma after PLIF. DSA vascular embolization is suggested as the first treatment approach for this type of complication.
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http://dx.doi.org/10.1186/s12893-020-00942-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661274PMC
November 2020

Digraph Energy of Directed Polygons.

Comb Chem High Throughput Screen 2020 Nov 11. Epub 2020 Nov 11.

School of Mathematics and Statistics, Qinghai Normal University, Xining, 810001. China.

Background: The energy E(G) of G is defined as the sum the absolute values of the eigenvalues of its adjacency matrix. In theoretical chemistry, within the Hu ̈ckel molecular orbital (HMO) approximation, the energy levels of the π-electrons in molecules of conjugated hydrocarbons are related to the energy of the molecular graphs.

Objective: Generally, the energy to digraphs was proposed.

Methodology: Let Δ_n be the set consisting of digraphs with n vertices and each cycle having length≡2 mod(4). The set of all the n-order directed hollow k-polygons in Δ_n based on a k-polygon G is denoted by H_k (G).

Results: In this research, by using the quasi-order relation over Δ_n and the characteristic polynomials of digraphs, we describe the directed hollow k-polygon with the maximum digraph energy in H_k (G).

Conclusion: The n-order oriented hollow k-polygon with the maximum digraph energy among Hk(G) only contains a cycle. Moreover, such a cycle is the longest one produced in G.
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http://dx.doi.org/10.2174/1386207323666201111125732DOI Listing
November 2020

FOXO1 and FOXO3a sensitize non-small-cell lung cancer cells to cisplatin-induced apoptosis independent of Bim.

Acta Biochim Biophys Sin (Shanghai) 2020 Dec;52(12):1348-1359

Department of Thoracic Surgery, Daping Hospital, Army Medical University, Chongqing 400042, China.

Low sensitivity to chemotherapy has been a major challenge in the treatment of non-small-cell lung cancer (NSCLC). It is of great clinical significance to discover its mechanisms to improve cell sensitivity to chemotherapeutic drugs. The forkhead box subfamily O (FOXO) transcriptional factors are downstream factors of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway and are reported to play pro-apoptotic roles in a variety of cells including NSCLC cells. But their roles and mechanisms in mediating cell response to chemotherapy remain to be discovered. We proposed that FOXO1 and FOXO3a may increase the sensitivity of NSCLC cells to cisplatin. Moreover, we presumed that LY294002, an inhibitor of the PI3K/AKT pathway, may enhance the cytotoxic effects of cisplatin through upregulating FOXO1 and FOXO3a. In the present study, we found that cisplatin initially increased the expressions and nuclear accumulation of FOXO1 and FOXO3a in NSCLC. Knockdown of FOXO1 and FOXO3a significantly decreased the cell sensitivity to cisplatin in vitro and in vivo. Moreover, inhibition of FOXO1 and FOXO3a attenuated cisplatin-induced cell apoptosis independent of Bim, a pro-apoptotic protein downstream of the FOXOs. Moreover, LY294002 synergistically increased the cytotoxic effects of cisplatin. Mechanistically, LY294002 increased the expressions and nuclear accumulation of FOXO1 and FOXO3a. Knockdown of FOXO1 and FOXO3a abrogated the enhancing effect of LY294002 on cisplatin. Taken together, our results suggested that FOXO1 and FOXO3a sensitize NSCLC cells to cisplatin and mediate the enhancing effects of LY294002 on cisplatin.
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http://dx.doi.org/10.1093/abbs/gmaa129DOI Listing
December 2020

HLA-A and HLA-DRB1 may play a unique role in ovarian teratoma-associated anti-N-methyl-D-aspartate receptor encephalitis.

Reprod Biol Endocrinol 2020 Nov 7;18(1):107. Epub 2020 Nov 7.

Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, No. 910, Hengshan Rd, Shanghai, 200030, China.

Background: Ovarian teratoma-associated anti-N-methyl-D-aspartate receptor encephalitis (NMDAR-E) is a severe autoimmune neurological disorder, and the influence of teratoma-induced autoantibodies on the pathogenesis remains unclear.

Methods: Ovarian teratoma tissues were collected from teratoma patients with and without NMDAR-E. Proteins were extracted and then analyzed using iTRAQ-coupled LC-MS/MS, which was followed by bioinformatics analysis. Candidate proteins were verified by Western blotting and immunohistochemistry.

Results: In total, 36 differentially expressed proteins (DEPs) were identified between the control group and NMDAR-E group, and the bioinformatics analysis revealed that the DEPs were mainly involved in immune-related pathways, especially HLA-A and HLA-DRB1. The western blotting results for HLA-A and HLA-DRB1 were consistent with the results of the iTRAQ analysis. Additionally, the immunohistochemical data revealed that the aggregation of HLA-A (+) and HLA-DRB1 (+) cells was more apparent in the teratoma tissues of NMDAR-E patients compared with that in the tissues of controls.

Conclusion: Our investigation indicated that HLA-A and HLA-DRB1 might be involved in mediating ovarian teratoma-associated NMDAR-E. These findings provide new insights into the pathophysiological mechanisms and provide information for the functional exploration of proteins in the future.
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http://dx.doi.org/10.1186/s12958-020-00661-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648266PMC
November 2020

Catch-up growth in intrauterine growth-restricted piglets associated with the restore of pancreatic and intestinal functions via porcine glucagon-like peptide-2 microspheres.

Arch Anim Nutr 2020 Dec 20;74(6):462-475. Epub 2020 Oct 20.

Institute of Animal Science, Zhejiang Academy of Agricultural Sciences , Hangzhou, China.

Intrauterine growth restriction (IUGR) results in abnormal morphology and gastrointestinal function, such as reduced villi height and crypt depth, thinner mucosa and muscle layers, and reduced brush border enzyme activities, delayed gastric emptying, increased stress response. As a gastrointestinal growth factor, the manner by which the porcine glucagon-like peptide-2 (pGLP-2) microsphere administration restored the gastrointestinal function and growth performance of IUGR piglets was investigated. Fourteen newborn Duroc × (Yorkshire × Landrace) IUGR piglets (0.92 ± 0.113 kg) were assigned into the IUGR (negative control group) and pGLP-2 microsphere groups. The piglets in group pGLP-2 were intraperitoneally administered with 100 mg pGLP-2 microspheres on day 1 after birth. From days 15 to 26 of trial, the body weight of the pGLP-2 group was significantly higher than that of the control. IUGR piglets of group pGLP-2 showed a significantly increased pancreas weight, serum insulin content and activity of lipase and amylase. Injection of pGLP-2 microspheres restored the intestinal absorptive capacity by significantly increasing the mRNA expression of the sodium-glucose cotransporter 1 in the jejunum and the peptide transporter 1 in the jejunum. It also restored the redox balance by increasing the catalase mRNA expression and decreasing the heat shock protein 70 mRNA expression. In addition, this improvement was associated with the significant increase in gut diameter, length and weight. Therefore, it was concluded that the injection of pGLP-2 microspheres was a suitable therapeutic strategy for compensatory growth in low birth weight IUGR piglets.
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http://dx.doi.org/10.1080/1745039X.2020.1833598DOI Listing
December 2020

A simple self-adjuvanting biomimetic nanovaccine self-assembled with the conjugate of phospholipids and nucleotides can induce a strong cancer immunotherapeutic effect.

Biomater Sci 2021 Jan;9(1):84-92

The Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Peking Union Medical College & Chinese Academy of Medical Sciences, Tianjin 300192, China.

Biomimetic nanoparticles have potential applications in many fields due to their favorable properties. Here, we developed a self-adjuvanting biomimetic anti-tumor nanovaccine, which was self-assembled with an amphiphilic conjugate synthesized with the phospholipids of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and hydrophilic Toll-like receptor (TLR9) agonist CpG ODN. The nanovaccine could not only provide effective initial antigen stimulation and sustained long-term antigen supply with a controlled release, but also induce antigen cross-presentation via the MHC-I pathway initiating CD8+ T-cell responses. Moreover, the dense nucleotide shell around the nanovaccine could promote antigen endocytosis via various receptor-mediated pathways into dendritic cells. CpG ODN interacted with TLR9 triggering the cytokine secretion of TNF-α and IL-10, which further boosted the anti-tumor humoral and cellular immune responses, which led to a significant tumor suppressive effect and remarkable survival prolongation. So, this nanovaccine self-assembled with phospholipid-nucleotide amphiphiles can serve as a safe, simple and efficient approach for anti-tumor immunotherapy.
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http://dx.doi.org/10.1039/d0bm01333aDOI Listing
January 2021

BCAR1 promotes proliferation and cell growth in lung adenocarcinoma via upregulation of POLR2A.

Thorac Cancer 2020 11 1;11(11):3326-3336. Epub 2020 Oct 1.

Thoracic Surgery Department, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, China.

Background: This study was designed to investigate the effects of a novel carcinogenetic molecule, p130cas (breast cancer antiestrogen resistance protein 1 or BCAR1) on proliferation and cell growth in lung adenocarcinoma. The study also aimed to identify the possible underlying signal networks of BCAR1.

Methods: First, we evaluated proliferation, cell colony formation, apoptosis, and cell cycle after BCAR1 was knocked out (KO) using CRISPR-Cas9 technology in H1975 and H1299 human lung adenocarcinoma cells. Subsequently, BCAR1 was upregulated in 293T cells and immunoprecipitation-mass spectrometry (IP-MS) was used with bioinformatics analysis to screen for potential networks of BCAR1 interacting proteins. Ultimately, we validated the correlated expressions of BCAR1 and a selected hub gene, RNA polymerase II subunit A (POLR2A), in 54 lung adenocarcinoma tissues, as well as in H1975 and H1299 cells.

Results: Cell proliferation of H1975 and H1299 was significantly inhibited following BCAR1-KO. Colony formation of H1975 cells was also significantly decreased following BCAR1-KO. IP-MS demonstrated 419 potential proteins that may interact with BCAR1. Among them, 68 genes were significantly positively correlated to BCAR1 expression, as verified by TCGA. Six hub genes were revealed by PPI String. High expression of POLR2A, MAPK3, MOV10, and XAB2 predicted poor prognosis in lung adenocarcinoma, as verified by the K-M plotter database. POLR2A and MAPK3 are involved in both catalytic activity and transferase activity. POLR2A and BCAR1 were significantly increased in lung cancer tissues as compared with matched normal tissues. High expression of POLR2A was significantly positively correlated to BCAR1 overexpression and predicted poor prognosis in 54 lung cancer cases. POLR2A expression was significantly decreased following BCAR1-KO in H1975 and H1299 cells.

Conclusions: BCAR1 promotes proliferation and cell growth, probably via upregulation of POLR2A and subsequent enhancement of catalytic and transferase activities. However, additional robust studies are required to elucidate the mechanisms involved.
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http://dx.doi.org/10.1111/1759-7714.13676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606008PMC
November 2020

Influence Mechanism and Optimization Analysis of Technological Parameters for the Composite Prepreg Tape Winding Process.

Polymers (Basel) 2020 Aug 17;12(8). Epub 2020 Aug 17.

Laboratory of Aero-engine High Performance Manufacturing, School of Mechanical Engineering, Northwestern Polytechnical University, Xi'an 710072, China.

Composite prepreg tape winding technology has proven to be an effective method for manufacturing revolving body composite structures in aerospace field. Process parameters including heating temperature, tape tension and roller pressure have an important impact on the winding products' mechanical property such as tensile strength. The aim of this study is to investigate the influence mechanism and optimization analysis of parameters for the composite prepreg tape winding process. Firstly, the sensitivity analysis for single parameter had be employed to reveal the influence mechanism of each winding parameter change on tensile strength. Secondly, iso-surfaces analysis for parameter range had be applied to describe the distribution law of parameter with continuous distribution characteristics. Then the coupling analysis for process parameters was carried out employing response surface methodology. The analysis results showed that tape tension has the most significant effect on the winding products' tensile strength. And the outstanding parameter combination with the heating temperature of 72 °C, tape tension of 307 N and roller pressure of 1263 N was provided by response surface design software via desirability function method. The validation experiments showed that the optimal parameter combination has a positive guiding significance for improving the quality of winding products.
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http://dx.doi.org/10.3390/polym12081843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466006PMC
August 2020

Antibacterial activity of a scorpion-derived peptide and its derivatives in vitro and in vivo.

Toxicon 2020 Oct 5;186:35-41. Epub 2020 Aug 5.

Medical College, Henan University of Science and Technology, Luoyang, 471003, China.

Antimicrobial peptides have recently become extremely popular as a novel class of antimicrobial agents. AMP MK049518 (FLGLLGSVLGSVLPSIFK), identified from the crab-scorpion Didymocentrus krausi, only possesses significant antibacterial activity against Gram-positive bacteria. In this study, a derivative G2K-S3K was designed with an excellent antibacterial spectrum and significantly higher antibacterial activity compared to the natural peptide. G2K-S3K also demonstrated excellent serum- and thermal-stability and did not induce bacterial resistance. In the Staphylococcus aureus and Pseudomonas aeruginosa -induced skin infection in mice, G2K-S3K significantly decreased bacterial counts in the wound by topical application. Thus, G2K-S3K could be a potent topical anti-infective agent against the skin infection caused by S. aureus and P. aeruginosa.
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http://dx.doi.org/10.1016/j.toxicon.2020.07.028DOI Listing
October 2020

miR-223-3p reduces high glucose and high fat-induced endothelial cell injury in diabetic mice by regulating NLRP3 expression.

Exp Ther Med 2020 Aug 10;20(2):1514-1520. Epub 2020 Jun 10.

Department of Endocrinology, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi 330006, P.R. China.

Expression levels of miR-223-3p and NLRP3 in high glucose and high fat (HGHF)-induced diabetic mice, and the mechanism on the injury of mouse cardiac microvascular endothelial cells (MCMECs) were investigated. Four-week C57BL/6J laboratory mice were selected and randomized into a control group and a model group (n=10 each). Mice in the model group were fed with HGHF diet to establish a mouse model of diabetes. Further MCMECs were purchased to construct carriers through transient transfection, and were separated into a normal group (cultured in the normal environment), a model group (not transfected), a blank carrier group (transfected with miR-NC), a miR-223-3p-mimics group, and a miR-223-3p-inhibitor group. RT-qPCR was used to detect the expression levels of miR-223-3p and NLRP3, and western blot analysis to detect the expression levels of NLRP3, apoptosis-related proteins Bax and caspase-3, and anti-apoptotic protein Bcl-2. Flow cytometry was used to observe apoptosis and TargetScan to predict the target relationship between miR-223-3p and NLRP3. Dual-luciferase reporter gene assay was used to detect the relationship between miR-223-3p and NLRP3. Compared with those in the control group, the mice in the model group had significantly lower expression of miR-223-3p. However, significantly higher mRNA and protein expression levels of NLRP3 were observed (P<0.05). After modeling, miR-223-3p overexpression downregulated the expression levels of NLRP3 mRNA, Bax and NLRP3 protein, as well as inhibited endothelial cell apoptosis (P<0.05), while the inhibition of miR-223-3p expression upregulated the expression levels and promoted apoptosis. In conclusion, miR-223-3p expression is low, however, NLRP3 is highly expressed in the heart tissue of HGHF-induced diabetic mice. miR-223-3p reduces the injury of MCMECs and inhibits endothelial cell apoptosis in mice by regulating the expression of NLRP3.
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http://dx.doi.org/10.3892/etm.2020.8864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388564PMC
August 2020

Glycerin/NaOH Aqueous Solution as a Green Solvent System for Dissolution of Cellulose.

Polymers (Basel) 2020 Aug 3;12(8). Epub 2020 Aug 3.

State Key Laboratory of New Textile Materials and Advanced Processing Technologies, Wuhan Textile University, Wuhan 430200, China.

Dissolving cellulose in water-based green solvent systems is highly desired for further industrial applications. The green solvent glycerin-which contains hydrogen-bonding acceptors-was used together with NaOH and water to dissolve cellulose. This mixed aqueous solution of NaOH and glycerin was employed as the new green solvent system for three celluloses with different degree of polymerization. FTIR (Fourier-transform infrared), XRD (X-ray diffractometer) and TGA (thermogravimetric analysis) were used to characterize the difference between cellulose before and after regenerated by HCl. A UbbeloHde viscometer was used to measure the molecule weight of three different kinds of cellulose with the polymerization degree of 550, 600 and 1120. This solvent system is useful to dissolve cellulose with averaged molecule weight up to 2.08 × 10 g/mol.
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http://dx.doi.org/10.3390/polym12081735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465933PMC
August 2020

Theoretical study on temporal and spatial performance of magnetic solenoid used in dilation x-ray imager.

Rev Sci Instrum 2020 Jul;91(7):073302

Research Center of Laser Fusion, China Academy of Engineering Physics, Mianyang, Sichuan 621900, China.

In the Dilation X-ray Imager (DIXI), which is characterized by an ultra-short gating time, a magnetic solenoid is used to keep the photoelectrons from defocusing during the drift process. The performance of the magnetic solenoid has an important influence on the performance of the DIXI. We present in this paper the efforts on studying the spatial and temporal performance of the magnetic solenoid used in the DIXI by tracking the photoelectrons with the particle-in-cell method. The initial parameters of the photoelectrons of the Au cathode were sampled with a Monte Carlo code. A novel magnetic solenoid with a shielding shell made of soft iron was proposed. We compared the performance of this solenoid with a normal solenoid. The simulation results of magnetic field distribution, spatial resolution, transit time spread, and temporal distortion were presented in detail to demonstrate that the performance of the DIXI can be significantly improved by using the magnetic solenoid with the proposed iron shell.
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http://dx.doi.org/10.1063/1.5133395DOI Listing
July 2020

Pyroptosis and ferroptosis induced by mixed lineage kinase 3 (MLK3) signaling in cardiomyocytes are essential for myocardial fibrosis in response to pressure overload.

Cell Death Dis 2020 07 24;11(7):574. Epub 2020 Jul 24.

The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.

Chronic heart failure (CHF) is the final outcome of many cardiovascular diseases, and is a severe health issue faced by the elderly population. Mixed lineage kinase 3 (MLK3), a member of MAP3K family, is associated with aging, inflammation, oxidative stress, and related diseases, such as CHF. MLK3 has also been reported to play an important role in protecting against cardiomyocyte injury; however, its function in myocardial fibrosis is unknown. To investigate the role of MLK3 in myocardial fibrosis, we inhibited the expression of MLK3, and examined cardiac function and remodeling in TAC mice. In addition, we assessed the expression of MLK3 protein in ventricular cells and its downstream associated protein. We found that MLK3 mainly regulates NF-κB/NLRP3 signaling pathway-mediated inflammation and that pyroptosis causes myocardial fibrosis in the early stages of CHF. Similarly, MLK3 mainly regulates the JNK/p53 signaling pathway-mediated oxidative stress and that ferroptosis causes myocardial fibrosis in the advanced stages of CHF. We also found that promoting the expression of miR-351 can inhibit the expression of MLK3, and significantly improve cardiac function in mice subjected to TAC. These results suggest the pyroptosis and ferroptosis induced by MLK3 signaling in cardiomyocytes are essential for adverse myocardial fibrosis, in response to pressure overload. Furthermore, miR-351, which has a protective effect on ventricular remodeling in heart failure caused by pressure overload, may be a key target for the regulation of MLK3.
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http://dx.doi.org/10.1038/s41419-020-02777-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382480PMC
July 2020

circRNA-UBAP2 promotes the proliferation and inhibits apoptosis of ovarian cancer though miR-382-5p/PRPF8 axis.

J Ovarian Res 2020 Jul 20;13(1):81. Epub 2020 Jul 20.

Department of Reproductive Medicine, Reproductive Medical Centre, The First People's Hospital of Yunnan Province, No. 157 Jin Bi Road, Kunming, People's Republic of China.

Objective: circular RNAs (circRNAs) have been reported to be essential regulators of multiple malignant cancers. However, the functions of circRNAs in ovarian cancer need to be further explored. The aim of our study is to explore the role of circRNA-UBAP2 in ovarian cancer and its mechanism.

Results: circRNA-UBAP2 was upregulated in ovarian cancer tissues and cell lines. Knockdown of circRNA-UBAP2 inhibited cell proliferation and promoted cell apoptosis, but circRNA-UBAP2 overexpressed got opposite results. In addition, circRNA-UBAP2 targeted miR-382-5p and downregulated its expression, PRPF8 was a target gene of miR-382-5p. Furthemore, circRNA-UBAP2/miR-382-5p/PRPF8 axis affected the proliferation, apoptosis and cell cycle of ovarian cancer through the mechanism of competing endogenous RNAs (ceRNA).

Conclusion: circRNA-UBAP2 acted as a ceRNA to sponged miR-382-5p, increased the expression level of PRPF8, and prompted proliferation and inhibited apoptosis in ovarian cancer cells.
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http://dx.doi.org/10.1186/s13048-020-00685-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372761PMC
July 2020

Comparison of the fecal microbiomes of healthy and diarrheic captive wild boar.

Microb Pathog 2020 Oct 10;147:104377. Epub 2020 Jul 10.

Liaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, College of Life Science and Bioengineering, Shenyang University, Shenyang, China; Institute of Herpetology, Shenyang Normal University, Shenyang, China. Electronic address:

Diarrhea caused by Enterotoxigenic Escherichia coli (ETEC) is one of the most common clinical diseases observed in captive wild boars, is usually caused by an imbalance in the gut microbiome, and is responsible for piglets significant mortality. However, little research has been undertaken into the structure and function of the intestinal microbial communities in wild boar with diarrhea influenced by enterotoxigenic E. coli. In this study, fecal samples were collected and 16S-rRNA gene sequencing was used to compare the intestinal microbiome of healthy captive wild boar and wild boar with diarrhea on the same farm. We found that the intestinal microbial diversity of healthy wild boar (HWB) was relatively high, while that of diarrheic wild boar (DWB) was significantly lower. Line Discriminant Analysis Effect Size showed that at the genus level, the abundance of Escherichia-Shigella and Fusobacterium was significantly higher in DWB. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States analysis showed that the expression of genes in pathways including infectious diseases: bacterial, metabolism of amino acids, membrane transport, and signal transduction was significantly higher in DWB. In summary, this study provides a theoretical basis for the design of appropriate means of diarrhea treatment in captive wild boar.
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http://dx.doi.org/10.1016/j.micpath.2020.104377DOI Listing
October 2020

The transcriptome analysis of the whole-body of the gastropod mollusk Limax flavus and screening of putative antimicrobial peptide and protein genes.

Genomics 2020 11 7;112(6):3991-3999. Epub 2020 Jul 7.

Medical College, Henan University of Science and Technology, Luoyang 471023, PR China.

The gastropod mollusk Limax flavus, one of the most widespread pests in China, is used to treat infectious diseases in traditional Chinese medicine. However, little genomic information is available for this non-model species. In this study, the whole-body transcriptome of L. flavus was sequenced using next generation sequencing technology. A total of 6.81 Gb clean reads were obtained, which were assembled into 150,766 transcripts with 132,206 annotated unigenes. Functionally classification assigned 30,542 unigenes to 56 Gene Ontology terms, 16,745 unigenes were divided into 26 euKaryotic Ortholog Groups of proteins categories, and 13,854 unigenes were assigned to 230 Kyoto Encyclopedia of Genes and Genomes pathways. Furthermore, we identified 17,251 simple sequence repeats and several kinds of antimicrobial peptide and protein (AMPs) genes. The transcriptome data of L. flavus will provide a valuable genomic resource for further studies on this species, and the AMPs identified in L. flavus will support its medical potential.
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http://dx.doi.org/10.1016/j.ygeno.2020.06.046DOI Listing
November 2020