Publications by authors named "Lixin Wang"

529 Publications

Tumor-Derived Autophagosomes (DRibbles) Activate Human B Cells to Induce Efficient Antigen-Specific Human Memory T-Cell Responses.

Front Immunol 2021 26;12:675822. Epub 2021 May 26.

Department of Microbiology and Immunology, Medical School, Southeast University, Nanjing, China.

We have reported that tumor-derived autophagosomes (DRibbles) were efficient carriers of tumor antigens and DRibbles antigens could be present by DRibbles-activated B cells to stimulate effect and naïve T cells in mice. However, the effect of DRibbles on human B cells remains unclear. Herein, we found that DRibbles can also efficiently induce proliferation and activation of human B cells and lead to the production of chemokines, cytokines and hematopoietic growth factors. We further demonstrated human B cells can effectively phagocytose DRibbles directly and cross-present DRibbles antigens to stimulate antigen-specific memory T cells. Furthermore, we found that membrane-bound high-mobility group B1 (HMGB1) on DRibbles was crucial for inducing human B cells activation. Therefore, these findings provide further evidence to promote the clinical application of B-DRibbles vaccines.
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http://dx.doi.org/10.3389/fimmu.2021.675822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187759PMC
May 2021

Altered DNA methylation pattern reveals epigenetic regulation of Hox genes in thoracic aortic dissection and serves as a biomarker in disease diagnosis.

Clin Epigenetics 2021 Jun 8;13(1):124. Epub 2021 Jun 8.

Vascular Surgery Department, Zhongshan Xiamen Hospital, Fudan University, Xiamen, People's Republic of China.

Background: Thoracic aortic dissection (TAD) is a severe disease with limited understandings in its pathogenesis. Altered DNA methylation has been revealed to be involved in many diseases etiology. Few studies have examined the role of DNA methylation in the development of TAD. This study explored alterations of the DNA methylation landscape in TAD and examined the potential role of cell-free DNA (cfDNA) methylation as a biomarker in TAD diagnosis.

Results: Ascending aortic tissues from TAD patients (Stanford type A; n = 6) and healthy controls (n = 6) were first examined via whole-genome bisulfite sequencing (WGBS). While no obvious global methylation shift was observed, numerous differentially methylated regions (DMRs) were identified, with associated genes enriched in the areas of vasculature and heart development. We further confirmed the methylation and expression changes in homeobox (Hox) clusters with 10 independent samples using bisulfite pyrosequencing and quantitative real-time PCR (qPCR). Among these, HOXA5, HOXB6 and HOXC6 were significantly down-regulated in TAD samples relative to controls. To evaluate cfDNA methylation pattern as a biomarker in TAD diagnosis, cfDNA from TAD patients (Stanford type A; n = 7) and healthy controls (n = 4) were examined by WGBS. A prediction model was built using DMRs identified previously from aortic tissues on methylation data from cfDNA. Both high sensitivity (86%) and specificity (75%) were achieved in patient classification (AUC = 0.96).

Conclusions: These findings showed an altered epigenetic regulation in TAD patients. This altered epigenetic regulation and subsequent altered expression of genes associated with vasculature and heart development, such as Hox family genes, may contribute to the loss of aortic integrity and TAD pathogenesis. Additionally, the cfDNA methylation in TAD was highly disease specific, which can be used as a non-invasive biomarker for disease prediction.
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http://dx.doi.org/10.1186/s13148-021-01110-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186232PMC
June 2021

A Systematic Review of Antiaging Effects of 23 Traditional Chinese Medicines.

Evid Based Complement Alternat Med 2021 15;2021:5591573. Epub 2021 May 15.

Department of Pathogeny Biology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.

Background: Aging is an inevitable stage of body development. At the same time, aging is a major cause of cancer, cardiovascular disease, and neurodegenerative diseases. Chinese herbal medicine is a natural substance that can effectively delay aging and is expected to be developed as antiaging drugs in the future. . This paper reviews the antiaging effects of 23 traditional Chinese herbal medicines or their active components. . We reviewed the literature published in the last five years on Chinese herbal medicines or their active ingredients and their antiaging role obtained through the following databases: PubMed, EMBASE, Scopus, and Web of Science.

Results: A total of 2485 papers were found, and 212 papers were screened after removing the duplicates and reading the titles. Twenty-three studies met the requirements of this review and were included. Among these studies, 13 articles used as the animal model, and 10 articles used other animal models or cell lines.

Conclusion: Chinese herbal medicines or their active components play an antiaging role by regulating genes related to aging through a variety of signaling pathways. Chinese herbal medicines are expected to be developed as antiaging drugs or used in the medical cosmetology industry.
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http://dx.doi.org/10.1155/2021/5591573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143881PMC
May 2021

Microbiome-Metabolomics Analysis Reveals the Protection Mechanism of -Ketoacid on Adenine-Induced Chronic Kidney Disease in Rats.

Front Pharmacol 2021 11;12:657827. Epub 2021 May 11.

The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, China.

As nitrogen-free precursors of corresponding essential amino, -ketoacid have been widely prescribed to end-stage renal disease patients together with a low protein diet However, the impact of -ketoacid on intestinal microbiota in chronic kidney disease (CKD) individuals is unknown. The study aims at investigating the variation in the intestinal microbiota and metabolic profile in response to -ketoacid treatment in an adenine-induced CKD rat model. Rats in the treatment groups were given solution of compound -ketoacid tablets. At the end of the study, blood, feces, colon tissues and kidney tissues were collected and processed for biochemical analyses, histological and western blot analyses, 16S rRNA sequence and untargeted metabolomic analyses. -Ketoacid treatment reduced serum creatinine, blood urea nitrogen and 24 h urine protein, and alleviated tubular atrophy, glomerulosclerosis and interstitial fibrosis in adenine-induced CKD rats. Moreover, -ketoacid significantly improved intestinal barrier and increased the abundance of , while reduced the abundance of and  at the genus level. In addition, our results also demonstrated that -ketoacid significantly reduced the concentrations of indoxyl sulfate, betaine, choline and cholesterol. Spearman's correlation analysis revealed that the abundance of Coprococcus_3 was positively correlated with serum level of betaine, trimethylamine N-oxide, indoxyl sulfate, cholic acid and deoxycholic acid. -Ketoacid has a reno-protective effect against adenine-induced CKD, which may be mediated regulation of serum metabolic profiles via affecting intestinal microbial community.
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http://dx.doi.org/10.3389/fphar.2021.657827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144710PMC
May 2021

Prognostic value of microRNA-378 in esophageal cancer and its regulatory effect on tumor progression.

Exp Ther Med 2021 Jul 2;22(1):704. Epub 2021 May 2.

Department of Cardiology, Yidu Central Hospital of Weifang, Weifang, Shandong 262500, P.R. China.

The incidence and mortality rates of esophageal squamous cell carcinoma (ESCC) are high in China, which has increased the clinical and economic burden. The present study aimed to investigate the role of microRNA (miRNA/miR)-378 in ESCC. Reverse transcription-quantitative polymerase chain reaction analysis was performed to detect miR-378 expression in ESCC tissues and cell lines. Survival analysis was performed using the Kaplan-Meier method, while Cox regression analysis was performed to determine the prognostic value of miR-378 in ESCC. miR-378 mimic and miR-378 inhibitor was transfected into ESCC cells to overexpress or knockdown miR-378 expression levels in ESCC cells. The Cell Counting Kit-8 assay was performed to assess the proliferative ability of ESCC cells, while the Transwell assay was conducted to assess the effect of miR-378 on the migratory and invasive abilities of ESCC cells. The results demonstrated that miR-378 displayed significantly lower expression both in ESCC cells and tissues by comparison with those in normal cells and adjacent tissues. In addition, patients with low miR-378 expression had a worse prognosis and a shorter overall survival time than those with high miR-378 expression. Furthermore, low miR-378 expression promoted ESCC cell proliferation, migration and invasion. Taken together, the results of the present study suggest that miR-378 may act as a tumor suppressor in the occurrence and development of ESCC.
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http://dx.doi.org/10.3892/etm.2021.10136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120653PMC
July 2021

Changes in Home Blood Pressure Monitored Among Elderly Patients With Hypertension During the COVID-19 Outbreak: A Longitudinal Study in China Leveraging a Smartphone-Based Application.

Circ Cardiovasc Qual Outcomes 2021 05 18;14(5):e007098. Epub 2021 May 18.

State Key Laboratory of Cardiovascular Disease, Hypertension Center, FuWai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China (S.Z., J.B., W.Z., J.C.).

Background: The coronavirus disease 2019 (COVID-19) pandemic has impacted clinical care worldwide. Evidence of how this health crisis affected common conditions like blood pressure (BP) control is uncertain.

Methods: We used longitudinal BP data from an ongoing randomized clinical trial to examine variations in home BP monitored via a smartphone-based application (app) in a total of 7394 elderly patients with hypertension aged 60 to 80 years stratified by their location in Wuhan (n=283) compared with other provinces of China (n=7111). Change in morning systolic BP (SBP) was analyzed for 5 30-day phases during the pandemic, including preepidemic (October 21 to November 20, 2019), incubation (November 21 to December 20, 2019), developing (December 21, 2019 to January 20, 2020), outbreak (January 21 to February 20, 2020), and plateau (February 21 to March 21, 2020).

Results: Compared with non-Wuhan areas of China, average morning SBP (adjusted for age, sex, body mass index) in Wuhan patients was significantly higher during the epidemic growth phases, which returned to normal at the plateau. Between-group differences in ΔSBP were +2.5, +3.0, and +2.1 mm Hg at the incubation, developing, and outbreak phases of COVID-19 (<0.001), respectively. Sensitivity analysis showed a similar trend in trajectory pattern of SBP in both the intensive and standard BP control groups of the trial. Patients in Wuhan also had an increased regimen change in antihypertensive drugs during the outbreak compared with non-Wuhan patients. Expectedly, Wuhan patients were more likely to check their BP via the app, while doctors were less likely to monitor the app for BP control during the pandemic.

Conclusions: Our data demonstrate that the COVID-19 pandemic was associated with a short-term increase in morning SBP among elderly patients with hypertension in Wuhan but not other parts of China. Further study will be needed to understand if these findings extended to other parts of the world substantially affected by the virus. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03015311.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.120.007098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136456PMC
May 2021

Genetic fate-mapping reveals surface accumulation but not deep organ invasion of pleural and peritoneal cavity macrophages following injury.

Nat Commun 2021 05 17;12(1):2863. Epub 2021 May 17.

State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.

During injury, monocytes are recruited from the circulation to inflamed tissues and differentiate locally into mature macrophages, with prior reports showing that cavity macrophages of the peritoneum and pericardium invade deeply into the respective organs to promote repair. Here we report a dual recombinase-mediated genetic system designed to trace cavity macrophages in vivo by intersectional detection of two characteristic markers. Lineage tracing with this method shows accumulation of cavity macrophages during lung and liver injury on the surface of visceral organs without penetration into the parenchyma. Additional data suggest that these peritoneal or pleural cavity macrophages do not contribute to tissue repair and regeneration. Our in vivo genetic targeting approach thus provides a reliable method to identify and characterize cavity macrophages during their development and in tissue repair and regeneration, and distinguishes these cells from other lineages.
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http://dx.doi.org/10.1038/s41467-021-23197-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129080PMC
May 2021

A Deep Learning Prediction Model for Structural Deformation Based on Temporal Convolutional Networks.

Comput Intell Neurosci 2021 20;2021:8829639. Epub 2021 Apr 20.

School of Highway, Chang'an University, Xi'an 710064, China.

The structural engineering is subject to various subjective and objective factors, the deformation is usually inevitable, the deformation monitoring data usually are nonstationary and nonlinear, and the deformation prediction is a difficult problem in the field of structural monitoring. Aiming at the problems of the traditional structural deformation prediction methods, a structural deformation prediction model is proposed based on temporal convolutional networks (TCNs) in this study. The proposed model uses a one-dimensional dilated causal convolution to reduce the model parameters, expand the receptive field, and prevent future information leakage. By obtaining the long-term memory of time series, the internal time characteristics of structural deformation data can be effectively mined. The network hyperparameters of the TCN model are optimized by the orthogonal experiment, which determines the optimal combination of model parameters. The experimental results show that the predicted values of the proposed model are highly consistent with the actual monitored values. The average RMSE, MAPE, and MAE with the optimized model parameters reduce 44.15%, 82.03%, and 66.48%, respectively, and the average running time is reduced by 45.41% compared with the results without optimization parameters. The average RMSE, MAE, and MAPE reduce by 26.88%, 62.16%, and 40.83%, respectively, compared with WNN, DBN-SVR, GRU, and LSTM models.
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http://dx.doi.org/10.1155/2021/8829639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079221PMC
April 2021

A systematic review and meta-analysis on endovascular treatment as an attractive alternative for acute superior mesenteric venous thrombosis.

Vascular 2021 May 4:1708538121991270. Epub 2021 May 4.

Department of Vascular Surgery, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, China.

Objective: This systematic review and meta-analysis evaluated the published data on the efficacy and safety of therapies for superior mesenteric venous thrombosis (SMVT), aiming to provide a reference and set of recommendations for clinical treatment.

Methods: Relevant databases were searched for studies published from 2000 to June 2020 on SMVT treated with conservative treatment, surgical treatment, or endovascular approach. Different treatment types were grouped for analysis and comparison, and odds ratios with corresponding 95% confidence intervals were calculated. The outcomes were pooled using meta-analytic methods and presented by forest plots.

Results: Eighteen articles, including eight on SMVT patients treated with endovascular therapies, were enrolled. The treatment effectiveness was compared between different groups according to the change of symptoms, the occurrence of complications, and mortality as well. The conservative treatment group had better efficacy compared to the surgery group (89.0% vs. 78.6%, <0.05), and the one-year survival rate was also higher (94.4% vs. 80.0%, 0.05), but without statistical significance. As for endovascular treatment, the effectiveness was significantly higher than the surgery group (94.8% vs. 75.2%, <0.05), and the conservative treatment group as well (93.3% vs. 86.3%, 0.05), which still requires further research for the lack of statistical significance.

Conclusions: Present findings indicate that anticoagulation, as conservative treatment should be the preferred clinical option in the clinic for SMVT, due to its better curative effect compared to other treatment options, including lower mortality, fewer complications, and better prognosis. Moreover, endovascular treatment is a feasible and promising approach that is worth in-depth research, for it is less invasive than surgery and has relatively better effectiveness, thus can provide an alternative option for SMVT treatment and may be considered as a reliable method in clinical.
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http://dx.doi.org/10.1177/1708538121991270DOI Listing
May 2021

Tanshinone IIA enhances susceptibility of non-small cell lung cancer cells to NK cell-mediated lysis by up-regulating ULBP1 and DR5.

J Leukoc Biol 2021 Apr 28. Epub 2021 Apr 28.

Center for Traditional Chinese Medicine and Immunology Research, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.

Natural killer (NK) cells have a great potential in cancer immunotherapy. However, their therapeutic efficacy is clinically limited owing to cancer cell immune escape. Therefore, it is urgently necessary to develop novel method to improve the antitumor immunity of NK cells. In the present study, it was found that the natural product tanshinone IIA (TIIA) enhanced NK cell-mediated killing of non-small cell lung cancer (NSCLC) cells. TIIA in combination with adoptive transfer of NK cells synergistically suppressed the tumor growth of NSCLC cells in an immune-incompetent mouse model. Furthermore, TIIA significantly inhibited the tumor growth of Lewis lung cancer (LLC) in an immune-competent syngeneic mouse model, and such inhibitory effect was reversed by the depletion of NK cells. Moreover, TIIA increased expressions of ULBP1 and DR5 in NSCLC cells, and inhibition of DR5 and ULBP1 reduced the enhancement of NK cell-mediated lysis by TIIA. Besides, TIIA increased the levels of p-PERK, ATF4 and CHOP. Knockdown of ATF4 completely reversed the up-regulation of ULBP1 and DR5 by TIIA in all detected NSCLC cells, while knockdown of CHOP only partly reduced these enhanced expressions in small parts of NSCLC cells. These results demonstrated that TIIA could increase the susceptibility of NSCLC cells to NK cell-mediated lysis by up-regulating ULBP1 and DR5, suggesting that TIIA had a promising potential in cancer immunotherapy, especially in NK cell-based cancer immunotherapy.
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http://dx.doi.org/10.1002/JLB.5MA1120-776RRDOI Listing
April 2021

The role of urine IgG in the progression of IgA nephropathy with a high proportion of global glomerulosclerosis.

Int Urol Nephrol 2021 Apr 19. Epub 2021 Apr 19.

Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, Guangdong, China.

Background: IgA nephropathy (IgAN), the most common glomerulonephritis in the world, is an important cause of end-stage renal disease (ESRD). It is necessary to explore new prognostic markers for predicting the activity and progress of IgAN. There are few studies on new prognostic markers in IgAN patients with high proportion of glomerulosclerosis. This study aims to explore the value of urine IgG in predicting the prognosis of IgAN patients.

Methods: The primary end point of this retrospective study was a composite event with a reduction in estimated glomerular filtration rate (eGFR) of  ≥ 50% or ESRD or death. This study assessed the association between urinary IgG and clinicopathological parameters, as well as the prognosis of a high proportion of patients with global glomerulosclerotic IgAN.

Results: This study included 105 IgAN patients with high proportion of global glomerulosclerotic. The level of urinary protein IgG was significantly correlated with clinical prognostic factors. The level of urinary protein IgG was positively correlated with urinary protein excretion (rs = 0.834, P < 0.001), CRP (rs = 0.375, P < 0.001), and C4 (rs = 0.228, P = 0.019), and negatively correlated with eGFR (rs =  - 0.307, P = 0.001). In addition, the level of urinary IgG increased with the increase of tubulointerstitial injury rate, which was positively correlated with endothelial cell proliferation and crescent (all P < 0.05). Prognostic analysis using the Cox proportional hazard regression model and Kaplan-Meier survival curve further determined that urine IgG is an independent risk factor for the prognosis of IgAN with high proportion of global glomerulosclerosis.

Conclusions: This study determined that urine IgG can be used as a useful predictor of the prognosis of IgAN patients with high proportion global glomerulosclerosis. The mechanism of urine IgG trends in IgAN with high proportion of glomerulosclerosis needs further study.
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http://dx.doi.org/10.1007/s11255-021-02858-yDOI Listing
April 2021

Autonomous apomixis in (Asteraceae: Eupatorieae), an invasive alien plant.

AoB Plants 2021 Apr 29;13(2):plab007. Epub 2021 Jan 29.

School of Biology and Food Engineering, Changshu Institute of Technology, Nansanhuanlu 99, Changshu 215500, Jiangsu Province, China.

Understanding the reproductive mechanisms of invasive alien species can lay the foundation for effective control measures. is a triploid neotropical Asteraceae species that is invasive in China and other countries. However, few studies have focused on its reproductive biology. In this study, flow cytometric seed screening (FCSS) was used to identify and confirm the reproductive mode of the species. The development of ovules, anthers, and mega- and microgametophytes was observed using a clearing method and differential interference contrast microscopy. Pollen viability was measured using the Benzidine test and Alexander's stain. Pollen morphology was observed via fluorescence microscopy after sectioning the disk florets and staining with water-soluble aniline blue or 4'6-diamidino-2-phenylindole nuclei dyes. Controlled pollination experiments were conducted on four populations in China to examine the breeding system and to confirm autonomous apomixis. The reproductive mode was found to be autonomous apomixis without pseudogamy, according to FCSS. Megaspore mother cells developed directly into eight-nucleate megagametophytes without meiosis, conforming to -type diplospory. The unreduced egg cells developed into embryos through parthenogenesis, while the endosperm was formed by the fusion of two unreduced polar nuclei. Pollen viability was very low (0.82 ± 0.57 % and 0.36 ± 0.44 %) as measured by the Benzidine test and Alexander's stain, respectively. The majority of the pollen grains were empty and had neither cytoplasm nor nuclei. The seed set was >90 % for all treatments of open pollination, bagging and emasculated capitula. Mature cypselae developed in capitula that were emasculated before flowering, which confirmed that the breeding system of was autonomous apomixis. The present study is the first report of autonomous apomixis in in China. -type autonomous apomixis in greatly increases the probability of successful colonisation and dispersal of into new areas, which likely contributes to its high invasion potential. Effective control measures should be implemented to prevent autonomous (pollen-independent) seed production.
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http://dx.doi.org/10.1093/aobpla/plab007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035972PMC
April 2021

Effectiveness of Chinese herbal medicine combined with Western medicine on deferring dialysis initiation for nondialysis chronic kidney disease stage 5 patients: a multicenter prospective nonrandomized controlled study.

Ann Transl Med 2021 Mar;9(6):490

Department of Nephrology, First Affiliated Hospital of Guiyang College of Traditional Chinese Medicine, Guiyang, China.

Background: In clinical practice, Chinese herbal medicine (CHM) purportedly has beneficial therapeutic effects for chronic kidney disease (CKD), which include delaying disease progression and dialysis initiation. However, there is a lack of high-quality evidence-based results to support this. Therefore, this study aimed to evaluate the efficacy of CHM combined with Western medicine in the treatment of stage 5 CKD.

Methods: This was a prospective nonrandomized controlled study. Stage 5 CKD (nondialysis) patients were recruited form 29 AAA class hospitals across China from July 2014 to April 2019. According to doctors' advice and the patients' wishes, patients were assigned to the CHM group (Western medicine + CHM) and the non-CHM group (Western medicine). Patient demographic data, primary disease, blood pressure, Chinese and Western medical drugs, clinical test results, and time of dialysis initiation were collected during follow-up.

Results: A total of 908 patients were recruited in this study, and 814 patients were finally included for further analysis, including 747 patients in the CHM group and 67 patients in the non-CHM group. 482 patients in the CHM group and 52 patients in the non-CHM group initiated dialysis. The median time of initiating dialysis was 9 (7.90, 10.10) and 3 (0.98,5.02) months in the CHM group and non-CHM group, respectively. The multivariate Cox regression analysis showed that patients in the CHM group had a significantly lower risk of dialysis [adjusted hazard ratio (aHR): 0.38; 95% confidence interval (CI): 0.28, 0.53] compared to those in the non-CHM group. After 1:2 matching, the outcomes of 160 patients were analyzed. The multivariate Cox regression analysis showed that patients in the CHM group had a significantly lower risk of dialysis (aHR: 0.32; 95% CI: 0.21, 0.48) compared to patients in the non-CHM group. Also, the Kaplan-Meier analysis demonstrated that the cumulative incidence of dialysis in the CHM group was significantly lower than that in the non-CHM group (log-rank test, P<0.001) before and after matching.

Conclusions: This study suggest that the combination of CHM and Western medicine could effectively reduce the incidence of dialysis and delay the time of dialysis initiation in stage 5 CKD patients.
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http://dx.doi.org/10.21037/atm-21-871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039672PMC
March 2021

Seven interferon gamma response genes serve as a prognostic risk signature that correlates with immune infiltration in lung adenocarcinoma.

Aging (Albany NY) 2021 04 4;13(8):11381-11410. Epub 2021 Apr 4.

Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou 325000, Zhejiang, China.

Interferon-gamma (IFN-γ) plays a complex role in modulating tumor microenvironment during lung adenocarcinoma (LUAD) development. In order to define the role of IFN-γ response genes in LUAD progression, we characterized the gene expression, mutation profile, protein-protein interaction of 24 IFN-γ response genes, which exhibited significant hazard ratio in overall survival. Two subgroups of LUAD from the TCGA cohort, which showed significant difference in the survival rate, were identified based on the expression of these genes. Furthermore, LASSO penalized cox regression model was used to derive a risk signature comprising seven IFN-γ response genes, including CD74, CSF2RB, PTPN6, MT2A, NMI, LATS2, and PFKP, which can serve as an independent prognostic predictor of LUAD. The risk signature was validated in an independent LUAD cohort. The high risk group is enriched with genes regulating cell cycle and DNA replication, as well as a high level of pro-tumor immune cells. In addition, the risk score is negatively correlated with the expression of immune metagenes, but positively correlated with DNA damage repair genes. Our findings reveal that seven-gene risk signature can be a valuable prognostic predictor for LUAD, and they are crucial participants in tumor microenvironment of LUAD.
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http://dx.doi.org/10.18632/aging.202831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109098PMC
April 2021

Transcollateral Recanalization of an Occluded Superior Mesenteric Artery.

Ann Vasc Surg 2021 Apr 8. Epub 2021 Apr 8.

Department of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Vascular Surgery Institute of Fudan University, Shanghai, China; Department of Vascular Surgery, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, China.

Objective: To report the technique of transcollateral retrograde recanalization of a superior mesenteric artery flush occlusion.

Methods: The technique of a patient undergoing transcollateral retrograde recanalization for acute symptomatic superior mesenteric artery flush occlusion was reviewed and presented. Other adjunctive methods to facilitate the endovascular treatment of the superior mesenteric artery total occlusion lesion were also compared and discussed.

Results: The patient was a 47-year-old woman, acute onset of symptomatic chronic mesenteric ischemia with flush occlusion of the superior mesenteric artery which was unable to be revascularized in a routine operation. A collateral was found to connect celiac artery and superior mesenteric artery (gastroduodenal arch). The guidewire was retrograde crossed the occluded lesion via this collateral and recaptured by the catheter from the same single brachial sheath followed by balloon angioplasty and stent implantation. The patient recovered well and the symptoms completely disappeared after the procedure.

Conclusion: The technique of retrograde recanalization through collateral pathway is an applicable alternative option for patients with superior mesenteric artery flush occlusion who have failed attempts by conventional antegrade approaches.
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http://dx.doi.org/10.1016/j.avsg.2021.02.034DOI Listing
April 2021

Vegetation Dynamic Assessment by NDVI and Field Observations for Sustainability of China's Wulagai River Basin.

Int J Environ Res Public Health 2021 03 4;18(5). Epub 2021 Mar 4.

College of Ecology and Environment, Inner Mongolia University, Hohhot 010021, China.

Accurate monitoring of grassland vegetation dynamics is essential for ecosystem restoration and the implementation of integrated management policies. A lack of information on vegetation changes in the Wulagai River Basin restricts regional development. Therefore, in this study, we integrated remote sensing, meteorological, and field plant community survey data in order to characterize vegetation and ecosystem changes from 1997 to 2018. The residual trend (RESTREND) method was utilized to detect vegetation changes caused by human factors, as well as to evaluate the impact of the management of pastures. Our results reveal that the normalized difference vegetation index (NDVI) of each examined ecosystem type showed an increasing trend, in which anthropogenic impact was the primary driving force of vegetation change. Our field survey confirmed that the meadow steppe ecosystem increased in species diversity and aboveground biomass; however, the typical steppe and riparian wet meadow ecosystems experienced species diversity and biomass degradation, therefore suggesting that an increase in NDVI may not directly reflect ecosystem improvement. Selecting an optimal indicator or indicator system is necessary in order to formulate reasonable grassland management policies for increasing the sustainability of grassland ecosystems.
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http://dx.doi.org/10.3390/ijerph18052528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967379PMC
March 2021

Nano-delivery systems focused on tumor microenvironment regulation and biomimetic strategies for treatment of breast cancer metastasis.

J Control Release 2021 May 30;333:374-390. Epub 2021 Mar 30.

School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address:

Breast cancer metastasis and recurrence accounts for vast majority of breast cancer-induced mortality. Tumor microenvironment (TME) plays an important role at each step of metastasis, evasion of immunosurveillance, and therapeutic resistance. Consequently, TME-targeting alternatives to traditional therapies focused on breast cancer cells are gaining increasing attention. These new therapies involve the use of tumor cells, and key TME components or secreted bioactive molecules as therapeutic targets, alone or in combination. Recently, TME-related nanoparticles have been developed to deliver various agents, such as bioactive ingredients extracted from natural sources or chemotherapeutic agents, genes, proteins, small interfering RNAs, and vaccines; they have shown great therapeutic potential against breast cancer metastasis. Among various types of nanoparticles, biomimetic nanovesicles are a promising means of addressing the limitations of conventional nanocarriers. This review highlights various nanoparticles related to or mediated by TME according to the key TME components responsible for metastasis. Furthermore, TME-related biomimetic nanoparticles against breast cancer metastasis have garnered attention owing to their promising efficiency, especially in payload delivery and therapeutic action. Here, we summarize recent representative studies on nanoparticles related to cancer-associated fibroblasts, extracellular matrix, endothelial cells, angiogenesis, and immune cells, as well as advanced biomimetic nanoparticles. Future challenges and opportunities in the field are also discussed.
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http://dx.doi.org/10.1016/j.jconrel.2021.03.039DOI Listing
May 2021

PepT1-knockout mice harbor a protective metabolome beneficial for intestinal wound healing.

Am J Physiol Gastrointest Liver Physiol 2021 May 24;320(5):G888-G896. Epub 2021 Mar 24.

Institute for Biomedical Sciences, Digestive Diseases Research Group, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia.

Genetic knockout (KO) of peptide transporter-1 (PepT1) protein is known to provide resistance to acute colitis and colitis-associated cancer (CAC) in mouse models. However, it was unclear which molecule(s) or pathway(s) formed the basis for these protective effects. Recently, we demonstrated that the PepT1 microbiota is sufficient to protect against colitis and CAC. Given that PepT1 KO alters the gut microbiome and thereby changes the intestinal metabolites that are ultimately reflected in the feces, we investigated the fecal metabolites of our PepT1 KO mice. Using a liquid chromatography-mass spectrometry (LC-MS)-based untargeted-metabolomics technique, we found that the fecal metabolites were significantly different between the KO and normal wild-type (WT) mice. Among the altered fecal metabolites, tuberonic acid (TA) was sevenfold higher in KO mouse feces than in WT mouse feces. Accordingly, we studied whether the increased TA could direct an anti-inflammatory effect. Using in vitro models, we discovered that TA not only prevented lipopolysaccharide (LPS)-induced inflammation in macrophages but also improved the epithelial cell healing processes. Our results suggest that TA, and possibly other fecal metabolites, play a crucial role in the pathway(s) associated with the anticolitis effects of PepT1 KO. Fecal metabolites were significantly different between the KO and normal wild-type (WT) mice. One fecal metabolite, tuberonic acid (TA), was sevenfold higher in KO mouse feces than in WT mouse feces. TA prevented lipopolysaccharide (LPS)-induced inflammation in macrophages and improved the epithelial cell healing process.
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http://dx.doi.org/10.1152/ajpgi.00299.2020DOI Listing
May 2021

Characteristics of dust-phase phthalates in dormitory, classroom, and home and non-dietary exposure in Beijing, China.

Environ Sci Pollut Res Int 2021 Mar 16. Epub 2021 Mar 16.

Beijing Key Laboratory of Heating, Gas Supply, Ventilation and Air Conditioning Engineering, Beijing University of Civil Engineering and Architecture, Beijing, 100044, China.

The phthalate concentrations in dust from undergraduate dormitories, classrooms, and homes in Beijing, China, were measured in April 2017. We analyzed the characteristics of phthalates in dust from three environments. In addition, we estimated the daily intake of phthalates via three pathways using Monte Carlo simulations. The detection frequency of eight phthalates in dust ranges from 74.5 to 100%. Di (2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DnBP), and di-isobutyl phthalate (DiBP) are the most abundant phthalates. The median proportion of DEHP in dust is the highest, ranging from 67.1 to 72.9%. The PMF results indicated that two, four, and three types of phthalate sources exist in home, dormitory, and classroom, respectively. The differences in the phthalate concentrations between sunny and shaded rooms and urban and suburban classrooms are insignificant, whereas that between male and female dormitories is significant. The total daily intake of DEHP, DnBP, and DiBP ranges from 97.3 to 336 ng/ (kg·day). The oral intake for DEHP in classrooms and the dermal intake of DnBP and DiBP in homes are the highest. The carcinogenic risk of DEHP to university students is the highest in classrooms and the total carcinogenic risk of the three environments is 4.70 × 10.
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http://dx.doi.org/10.1007/s11356-021-13347-1DOI Listing
March 2021

Correlations between Serum P2X7, Vitamin A, 25-hydroxy Vitamin D, and Mycoplasma Pneumoniae Pneumonia.

J Clin Lab Anal 2021 May 16;35(5):e23760. Epub 2021 Mar 16.

Medical Experiment Center, General Hospital of Ningxia Medical University, Yinchuan, China.

Background: Identifying new molecular diagnostic markers for Mycoplasma Pneumoniae Pneumonia (MPP) has always been an essential topic since MPP cases have increased every year, especially among children. Here, we examined the correlation between serum level of Purinergic receptor P2X7, vitamin A, and 25-hydroxy vitamin D (25(OH)D) and the severity of MPP, aiming to identify molecules that have the potential to become diagnostic markers.

Methods: This study was conducted on 186 cases aged 1-14 (136 MPP and 50 non-MPP patients). Serum levels of Purinergic receptor P2X7, vitamin A, 25(OH)D, and multiple inflammatory and immune factors were measured, compared, and tested for statistical significance.

Results: Serum P2X7, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) levels were significantly increased in severe MPP patients, while serum vitamin A, 25(OH)D, IgA, and IgG levels were significantly decreased.

Conclusion: Our results demonstrated a positive correlation between serum P2X7 level and the severity of MPP, and negative correlations between serum levels of vitamin A and 25(OH)D and the severity of MPP, suggesting that high serum levels of P2X7 and low serum levels of vitamin A and 25(OH)D may indicate relatively severer MPP.
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http://dx.doi.org/10.1002/jcla.23760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128307PMC
May 2021

Bupi Yishen Formula Versus Losartan for Non-Diabetic Stage 4 Chronic Kidney Disease: A Randomized Controlled Trial.

Front Pharmacol 2020 29;11:627185. Epub 2021 Jan 29.

Guangzhou Hospital of Traditional Chinese Medicine, Guangzhou, China.

Chinese herbal medicine (CHM) might have benefits in patients with non-diabetic chronic kidney disease (CKD), but there is a lack of high-quality evidence, especially in CKD4. This study aimed to assess the efficacy and safety of Bupi Yishen Formula (BYF) vs. losartan in patients with non-diabetic CKD4. This trial was a multicenter, double-blind, double-dummy, randomized controlled trial that was carried out from 11-08-2011 to 07-20-2015. Patients were assigned (1:1) to receive either BYF or losartan for 48 weeks. The primary outcome was the change in the slope of the estimated glomerular filtration rate (eGFR) over 48 weeks. The secondary outcomes were the composite of end-stage kidney disease, death, doubling of serum creatinine, stroke, and cardiovascular events. A total of 567 patients were randomized to BYF ( = 283) or losartan ( = 284); of these, 549 (97%) patients were included in the final analysis. The BYF group had a slower renal function decline particularly prior to 12 weeks over the 48-week duration (between-group mean difference of eGFR slopes: -2.25 ml/min/1.73 m/year, 95% confidence interval [CI]: -4.03,-0.47), and a lower risk of composite outcome of death from any cause, doubling of serum creatinine level, end-stage kidney disease (ESKD), stroke, or cardiovascular events (adjusted hazard ratio = 0.61, 95%CI: 0.44,0.85). No significant between-group differences were observed in the incidence of adverse events. We conclude that BYF might have renoprotective effects among non-diabetic patients with CKD4 in the first 12 weeks and over 48 weeks, but longer follow-up is required to evaluate the long-term effects. http://www.chictr.org.cn, identifier ChiCTR-TRC-10001518.
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http://dx.doi.org/10.3389/fphar.2020.627185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941267PMC
January 2021

Evaluation of Microbial Assemblages in Various Saline-Alkaline Soils Driven by Soluble Salt Ion Components.

J Agric Food Chem 2021 Mar 11;69(11):3390-3400. Epub 2021 Mar 11.

Inner Mongolia Key Laboratory of Environmental Pollution Control and Waste Resource Recycle, Ministry of Education Key Laboratory of Ecology and Resource Use of the Mongolian Plateau, School of Ecology and Environment, Inner Mongolia University, Hohhot 010021, China.

Land degraded by salinization and alkalization is widely distributed globally and involves a wide range of ecosystem types. However, the knowledge of the indigenous microbial assemblages and their roles in various saline-alkaline soils is limited. This study demonstrated microbial assemblages in various saline-alkaline soils from different regions of Inner Mongolia and revealed the key driving factors to influence microbiome. The correlation network analysis indicates the difference in adaptability of bacterial and fungal communities under stimulation by saline-alkaline stress: fungal community shows higher tolerance, stability, and resilience to various saline-alkaline soils than a bacterial community. The keystone bacteria and fungi that have potential adaptability to various saline-alkaline environments are further identified, and they may confer benefits in restoring saline-alkaline soils by their own effects or assisting plants. For salt-rich soils in different regions, the soluble salt ion components are the major determinant to drive microbial assemblages of different saline-alkaline soils, rather than salinity. Thus, these saline-alkaline soils are clustered into sulfated, chlorinated, and soda-type saline-alkaline soils. Multivariate analysis reveals unique, dominant, and common microbial taxa in three saline-alkaline soils. This result of the conceptual mode indicates that potential roles of unique and dominant microbial taxa on regulating saline-alkaline functions are more vital.
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http://dx.doi.org/10.1021/acs.jafc.1c00210DOI Listing
March 2021

Reversible leukoencephalopathy caused by 2 rodenticides bromadiolone and fluoroacetate: A case report and literature review.

Medicine (Baltimore) 2021 Mar;100(9):e25053

The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

Rationale: With the easy access, rodenticide poisoning has been a public health problem in many countries. Characteristics of central nervous system (CNS) lesions induced by rodenticides are scarcely reported.

Patient Concerns: We presented a case of a 40-year-old man with seizure and consciousness disorder, coagulation dysfunction, and symmetric lesions in white matter and corpus callosum.

Diagnosis: He was diagnosed with rodenticide poisoning due to bromadiolone and fluoroacetamide.

Interventions: He was treated with vitamin K, hemoperfusion, acetamide, and calcium gluconate.

Outcomes: His leukoencephalopathy was reversed rapidly with the improvement of clinical symptoms.

Lessons: This report presented the impact of rodenticide poisoning on CNS and the dynamic changes of brain lesions, and highlighted the importance of timely targeted treatments.
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http://dx.doi.org/10.1097/MD.0000000000025053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939157PMC
March 2021

Prospective study: Aldehyde dehydrogenase 2 gene is associated with cardio-cerebrovascular complications in type 2 diabetes patients.

J Diabetes Investig 2021 Mar 2. Epub 2021 Mar 2.

Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China.

Aims/introduction: Most studies have shown that aldehyde dehydrogenase 2 (ALDH2) mutations were associated with cardio-cerebrovascular complications of diabetes based on cross-sectional investigations, but few studies based on cohorts were carried out. The aim of this study was to explore the correlation between the ALDH2 gene and the occurrence of and death from cardio-cerebrovascular complications in type 2 diabetes patients through a prospective cohort study.

Materials And Methods: According to a community-based and disease-based prospective cohort study design, a baseline cohort of 10,339 persons with type 2 diabetes was established in 2016, and the occurrence of and death from cardio-cerebrovascular complications were followed up until December 2018. A total of 2,500 diabetes patients without cardio-cerebrovascular complications were randomly selected from the baseline cohort to detect the rs671 polymorphism of the ALDH2 gene. Cox regression analysis was carried out on the effect of different ALDH2 rs671 single-nucleotide polymorphisms on the risk and survival time of cardio-cerebrovascular complications among diabetes patients.

Results: There were 215 cardio-cerebrovascular complications, including 10 deaths, that occurred in the 2,500 diabetes patients during the follow-up period. Cox regression analysis showed that rs671 GA/AA genotype, sex (male), poor control of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, blood pressure and glycated were risk factors, whereas drinking alcohol was a protective factor for cardio-cerebrovascular complications (P < 0.05). After adjusting for age and sex, the risk of the rs671 GA/AA genotype was 1.314-fold (95% confidence interval 1.000-1.727) that of the GG genotype.

Conclusion: The G-A mutation of ALDH2 rs671 is a risk factor for the occurrence of and death from cardio-cerebrovascular complications in type 2 diabetes patients. Further studies with larger cohorts and longer follow up will be necessary to reveal a consensus.
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http://dx.doi.org/10.1111/jdi.13538DOI Listing
March 2021

Pain Relief Dependent on IL-17-CD4 T Cell-β-Endorphin Axis in Rat Model of Brachial Plexus Root Avulsion After Electroacupuncture Therapy.

Front Neurosci 2020 9;14:596780. Epub 2021 Feb 9.

School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Background And Purpose: Neuropathic pain is the typical symptom of brachial plexus root avulsion (BPRA), and no effective therapy is currently available. Electroacupuncture (EA), as a complementary and alternative therapy, plays a critical role in the management of pain-associated diseases. In the present study, we aimed to reveal the peripheral immunological mechanism of EA in relieving the pain of BPRA through the IL-17-CD4 T lymphocyte-β-endorphin axis.

Methods: After receiving repeated EA treatment, the pain of BPRA in rats along with the expressions of a range of neurotransmitters, the contents of inflammatory cytokines, and the population of lymphocytes associated were investigated. CD4 T lymphocytes were either isolated or depleted with anti-CD4 monoclonal antibody. The titers of IL-17A, interferon-γ (IFN-γ), and β-endorphin were examined. The markers of T lymphocytes, myeloid-derived suppressor cells (MDSCs), dendritic cells (DCs), macrophages, and natural killer (NK) cells were assessed. The activation of the nuclear transcription factor κB (NF-κB) signaling pathway was tested.

Results: The pain of BPRA was significantly relieved, and the amount of CD4 T lymphocytes was increased after EA treatment. The release of β-endorphin was up-regulated with the up-regulation of IL-17A in CD4 T lymphocytes. The titer of IL-17A was enhanced, leading to an activated NF-κB signaling pathway. The release of β-endorphin and the analgesic effect were almost completely abolished when CD4 T lymphocytes were depleted.

Conclusion: We, for the first time, showed that the neuropathic pain caused by BPRA was effectively relieved by EA treatment via IL-17-CD4 T lymphocyte-β-endorphin mediated peripheral analgesic effect, providing scientific support for EA clinical application.
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http://dx.doi.org/10.3389/fnins.2020.596780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901907PMC
February 2021

Shear stress inhibits cardiac microvascular endothelial cells apoptosis to protect against myocardial ischemia reperfusion injury via YAP/miR-206/PDCD4 signaling pathway.

Biochem Pharmacol 2021 Apr 18;186:114466. Epub 2021 Feb 18.

Department of Pharmacology, Harbin Medical University-Daqing, Daqing 163319, China. Electronic address:

Cardiac microvascular endothelial cells (CMECs), derived from coronary circulation microvessel, are the main barrier for the exchange of energy and nutrients between myocardium and blood. However, microvascular I/R injury is a severely neglected topic, and few strategies can reverse this pathology. In this study, we investigated the mechanism of shear stress in microvascular I/R injury, and try to elucidate the downstream signaling pathways that inhibit CMECs apoptosis to reduce I/R injury. Our results demonstrated that shear stress inhibited the apoptosis protein, increased PECAM-1 expression and eNOS phosphorylation in hypoxia reoxygenated (H/R) CMECs. The mechanism of shear stress was related to up-regulated expression of YAP, the increased number of YAP entering the nucleus by dephosphorylation, the reduced number of TUNEL positive cells, increased miR-206 and inhibited protein level of PDCD4 in CMECs. However, siRNA-mediated knockdown of YAP abolished the protective effects of shear stress on CMECs apoptosis, similar results obtained from administration with AMO-miR-206, and also prevented PDCD4 (target gene of miR-206) increasing when treatment with both AMO-miR-206 and mimics-miR-206. In vivo, restoring the blood fluid with nitroglycerin (NTG) to mimic in vitro shear stress levels, which subsequently improved cardiac function, reduced infarcted area, lowered microvascular perfusion defects. Functional investigations clearly illustrated that increased the protein expression of PECAM-1 and eNOS phosphorylation, activated YAP, strengthened miR-206 expression, and suppressed PDCD4 expression. In summary, this study confirmed that shear stress reversed CMECs apoptosis, relieved microvascular I/R injury, the mechanism of which involving through YAP/miR-206/PDCD4 signaling pathway to finally suppress myocardial I/R injury.
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http://dx.doi.org/10.1016/j.bcp.2021.114466DOI Listing
April 2021

Review: Microtubules monitor calcium and reactive oxygen species signatures in signal transduction.

Plant Sci 2021 Mar 1;304:110589. Epub 2020 Jul 1.

Key Laboratory of Genetics and Fruit Development, College of Horticulture, Nanjing Agricultural University, Nanjing, China.

Signal transductions require calcium (Ca) or reactive oxygen species (ROS) signatures, which act as chemical and electrical signals in response to various biotic and abiotic stresses. Calcium as an ion or second messenger affects the membrane potential and microtubules (MTs) dynamicity, while MTs can modulate auto-propagating waves of calcium and ROS signatures in collaboration with ion channels depending on the stimulus type. Thus, in the current review, we highlight advances in research focused on the relationship between dynamic MTs and calcium and ROS signatures in short-distance transmission. The challenges of Ca-MTs-ROS crosstalk in cold sensing are addressed, which could suggest the prioritization of ROS or Ca in signalling.
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http://dx.doi.org/10.1016/j.plantsci.2020.110589DOI Listing
March 2021

A suite of new Dre recombinase drivers markedly expands the ability to perform intersectional genetic targeting.

Cell Stem Cell 2021 Jun 9;28(6):1160-1176.e7. Epub 2021 Feb 9.

State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai 201210, China; School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China. Electronic address:

The use of the dual recombinase-mediated intersectional genetic approach involving Cre-loxP and Dre-rox has significantly enhanced the precision of in vivo lineage tracing, as well as gene manipulation. However, this approach is limited by the small number of Dre recombinase driver constructs available. Here, we developed more than 70 new intersectional drivers to better target diverse cell lineages. To highlight their applicability, we used these new tools to study the in vivo adipogenic fate of perivascular progenitors, which revealed that PDGFRa but not PDGFRaPDGFRb perivascular cells are the endogenous progenitors of adult adipocytes. In addition to lineage tracing, we used members of this new suite of drivers to more specifically knock out genes in complex tissues, such as white adipocytes and lymphatic vessels, that heretofore cannot be selectively targeted by conventional Cre drivers alone. In summary, these new transgenic tools expand the intersectional genetic approach while enhancing its precision.
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http://dx.doi.org/10.1016/j.stem.2021.01.007DOI Listing
June 2021

Surgical outcomes and factors associated with malignancy in carotid body tumors.

J Vasc Surg 2021 Feb 4. Epub 2021 Feb 4.

Department of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Department of Vascular Surgery, Vascular Surgery Institute of Fudan University, Shanghai, China; Department of Vascular Surgery, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, China.

Objective: To compare the surgical outcomes of benign and malignant carotid body tumor (CBT), and to evaluate the associated factors of malignant CBT.

Methods: Patients who underwent surgical resection of CBT from 2005 to 2018 in a tertiary center were reviewed retrospectively. The common study follow-up end date was December 31, 2019. The tumor size was measured as the maximum transverse diameter on computed tomography scan. Surgical outcomes of benign and malignant CBT were compared. Associated factors of malignancy were analyzed by multivariate logistic analysis.

Results: There were 229 patients undergoing CBT resection. Sixteen patients were diagnosed with malignant CBT. The median follow-up time was 66 months (range, 6-142 months). Basic information including age, sex, course of disease, family history, lesion side, tumor size, and Shamblin classification showed no significant differences between the benign and malignant CBT groups. Patients with malignant CBTs showed a higher rate of preoperative symptoms (31.3% vs 12.2%; P < .05). The rates of vascular reconstruction or repair (P < .01) and neurologic complications (P < .05) were significantly higher in the malignant CBT group. In addition, a significantly longer average procedural time was required for malignant CBTs (P < .05). However, the estimated blood loss and length of hospital stay showed no significant difference. Multivariate logistic regression analysis revealed that the malignant odds of CBT with bilateral lesions (P = .0042; odds ratio, 8.30; 95% confidence interval, 1.84-35.88) or CBT with preoperative symptoms (P = .0016; odds ratio, 7.59; 95% confidence interval, 2.13-27.89) were high.

Conclusions: Compared with benign CBT, malignant CBT is prone to invasive clinical behaviors, resulting in an increased possibility of vascular reconstruction or repair during the surgery as well as postoperative neurologic complications. In addition, the malignant odds of CBT with bilateral lesions or CBT with preoperative symptoms are high.
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http://dx.doi.org/10.1016/j.jvs.2020.12.097DOI Listing
February 2021

Premalignant Oligodendrocyte Precursor Cells Stall in a Heterogeneous State of Replication Stress Prior to Gliomagenesis.

Cancer Res 2021 Apr 2;81(7):1868-1882. Epub 2021 Feb 2.

Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia.

Cancer evolves from premalignant clones that adopt unusual cell states to achieve transformation. We previously pinpointed the oligodendrocyte precursor cell (OPC) as a cell of origin for glioma, but the early changes of mutant OPCs during premalignancy remained unknown. Using mice engineered for inducible - loss in OPCs, we acutely isolated labeled mutant OPCs by laser-capture microdissection, determined global gene-expression changes by bulk RNA sequencing, and compared with cell-state fluctuations at the single-cell level by stochastic profiling, which uses RNA-sequencing measurements from random pools of 10 mutant cells. At 12 days after - deletion, bulk differences were mostly limited to mitotic hallmarks and genes for ribosome biosynthesis, and stochastic profiling revealed a spectrum of stem-progenitor (), proneural, and mesenchymal states as potential starting points for gliomagenesis. At 90 days, bulk sequencing detected few differentially expressed transcripts, whereas stochastic profiling revealed cell states for neurons and mural cells that do not give rise to glial tumors, suggesting cellular dead-ends for gliomagenesis. Importantly, mutant OPCs that strongly expressed key effectors of nonsense-mediated decay () and homology-dependent DNA repair () were identified along with DNA-damage markers, suggesting transcription-associated replication stress. Analysis of 10-cell transcriptomes at 90 days identified a locus of elevated gene expression containing an additional repair endonuclease () and , a Ras-Raf antagonist and possible counterbalance to loss, which was microdeleted or downregulated in gliomas at 150 days. These hidden cell-state variations uncover replication stress as a potential bottleneck that must be resolved for glioma initiation. SIGNIFICANCE: Profiling premalignant cell states in a mouse model of glioma uncovers regulatory heterogeneity in glioma cells-of-origin and defines a state of replication stress that precedes tumor initiation..
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http://dx.doi.org/10.1158/0008-5472.CAN-20-1037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137536PMC
April 2021