Publications by authors named "Tao Yan"

560 Publications

Identification of autophagy-related long non-coding RNA prognostic and immune signature for clear cell renal cell carcinoma.

Transl Androl Urol 2021 Aug;10(8):3317-3331

Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: Studies over the past decade have shown that long non-coding RNAs (lncRNAs) play an essential role in the tumorigenesis and progression of kidney renal clear cell carcinoma (KIRC). Meanwhile, autophagy has been demonstrated to regulate KIRC pathogenesis and targeting therapy resistance. However, the prognostic value of autophagy-related lncRNAs in KIRC patients has not been reported before.

Methods: In this study, we obtained transcriptome data of 611 KIRC cases from the TCGA database and 258 autophagy-related mRNAs from the HADb database to identify autophagy-related lncRNAs by co-expression network. A prognostic model was then established basing on these autophagy-related lncRNAs, dividing patients into high-risk and low-risk groups. Survival analysis, clinical variables dependent receiver operating characteristic (ROC) analyses, univariate/multivariate Cox analyses, and clinical correlation analysis were performed based on risk signature with R language. Gene set enrichment analysis (GSEA) was then performed to investigate the potential mechanism of the risk signature promoting KIRC progression with GSEA software. CIBERSORT algorithm was performed to assess the impact of these lncRNAs on the infiltration of immune cells.

Results: A total of 17 lncRNAs were screened out and all these lncRNAs were found significantly related to KIRC patients' overall survival in subsequent survival analyses. Besides, the overall survival time in the high-risk group was much poorer than in the low-risk group. The ROC analysis revealed that the prognostic value of risk signature was better than age, gender, grade, and N stage. Univariate/multivariate analyses suggested that the risk signature was an independent predictive factor for KIRC patients. Immune and autophagy related pathways were dramatically enriched in high-risk and low-risk groups, respectively, and lncRNAs related immune cells were identified by CIBERSORT.

Conclusions: In summary, our identified 17 autophagy-related lncRNAs had prognostic value for KIRC patients which may function in immunomodulation.
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http://dx.doi.org/10.21037/tau-21-278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421821PMC
August 2021

Osthole Attenuates Bleomycin-Induced Pulmonary Fibrosis by Modulating NADPH Oxidase 4-Derived Oxidative Stress in Mice.

Oxid Med Cell Longev 2021 4;2021:3309944. Epub 2021 Sep 4.

Department of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, China.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease characterized by the extensive accumulation of myofibroblasts and collagens. However, the exact mechanism that underlies this condition is unclear. Growing evidence suggests that NADPH oxidases (NOXs), especially NOX4-derived oxidative stress, play an important role in the development of lung fibrosis. Bleomycin (BLM) is a tumor chemotherapeutic agent, which has been widely employed to establish IPF animal models. Osthole (OST) is an active constituent of the fruit of . Here, we used an in vivo mouse model and found that OST suppressed BLM-induced body weight loss, lung injury, pulmonary index increase, fibroblast differentiation, and pulmonary fibrosis. OST also significantly downregulated BLM-induced NOX4 expression and oxidative stress in the lungs. In vitro, OST could inhibit TGF-1-induced Smad3 phosphorylation, differentiation, proliferation, collagen synthesis, NOX4 expression, and ROS generation in human lung fibroblasts in a concentration-dependent manner. Moreover, NOX4 overexpression could prevent the above effects of OST. We came to the conclusion that OST could significantly attenuate BLM-induced pulmonary fibrosis in mice, via the mechanism that involved downregulating TGF-1/NOX4-mediated oxidative stress in lung fibroblasts.
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http://dx.doi.org/10.1155/2021/3309944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437590PMC
September 2021

Interface engineering of [email protected](OH) nanoarray heterostucture: Electrodeposition of [email protected](OH) as N and H channels for artificial NH synthesis under mild conditions.

J Colloid Interface Sci 2021 Aug 18;606(Pt 2):1374-1379. Epub 2021 Aug 18.

Key Laboratory of Interfacial Reaction & Sensing Analysis in Universities of Shandong, School of Chemistry and Chemical Engineering, University of Jinan, Jinan, Shandong 250022, China; Collaborative Innovation Center for Green Chemical Manufacturing and Accurate Detection, Jinan, Shandong 250022, China. Electronic address:

The electrocatalytic reduction of nitrogen (N) to ammonia (NH) has broad prospects for green and sustainable NH production. Due to the electrocatalytic nitrogen reduction reaction (eNRR) performance of transition metal compound may be restricted with low yield rate, we develop transition metal interface engineering to improve the eNRR performance. Although the edge of MoS catalyst is active, the MoS(001) surface is inert for N electroreduction. Through the hydrothermal and electrodeposition methods, Fe(OH) as N and H channels coated on MoS nanosheets array ([email protected](OH)/CC) is synthesized. Such catalyst exhibits excellent eNRR performance in 0.1 M NaSO with high Faradaic efficiency (2.76%) and NH yield rate (4.23 × 10 mol s cm) at - 0.45 V (vs. RHE). This work may provide a new electrocatalyst synthesis pathway for artificial N fixation. Density functional theory calculations show that electrodeposition Fe(OH) can accelerate eNRR process rate of MoS.
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http://dx.doi.org/10.1016/j.jcis.2021.08.099DOI Listing
August 2021

Ionic liquid-assisted fabrication of metal-organic framework-derived indium oxide/bismuth oxyiodide p-n junction photocatalysts for robust photocatalysis against phenolic pollutants.

J Colloid Interface Sci 2021 Aug 25;606(Pt 2):1261-1273. Epub 2021 Aug 25.

State Key Laboratory of Photocatalysis on Energy and Environment, Research Institute of Photocatalysis, Fuzhou University, Fuzhou 350116, PR China.

Constructing a p-n heterojunction is a feasible strategy to manipulate the dynamic behaviors of photogenerated carriers through an internal electric field. Herein, a novel highly efficient indium oxide/bismuth oxyiodide (InO/BiOI) p-n junction photocatalyst was fabricated using a facile ionic liquid-assisted precipitation method for the first time. The morphologies were modified by adding different amounts of acetic acid solution. Their hierarchical architecture was beneficial for adsorbing contaminants in wastewater, while the in-situ formed p-n heterojunction between BiOI and InO facilitated interfacial charge transfer and improved the quantum efficiency. Their visible light-responsive photocatalytic activities were systematically investigated by photocatalytic o-phenylphenol (OPP) and 4-tert-butylphenol (PTBP) oxidation. The degradation rate of OPP over InO/BiOI-2 was up to 5.67 times higher than that for BiOI. The excellent activity of InO/BiOI should be attributed to the rapid interfacial charge transfer, depressed carrier recombination, and proper band potentials. Trapping experiments and electron paramagnetic resonance characterizations confirmed the generation of hydroxyl radicals (•OH) and superoxide radicals (•O), which have played a key role in decomposing pollutants. The intermediate products generated during the photocatalytic degradation of OPP were detected and identified by liquid chromatography-mass spectrometry. Meanwhile, their possible molecular structures and degradation pathways have also been inferred.
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http://dx.doi.org/10.1016/j.jcis.2021.08.132DOI Listing
August 2021

Microfluidic Tandem Mechanical Sorting System for Enhanced Cancer Stem Cell Isolation and Ingredient Screening.

Adv Healthc Mater 2021 Sep 5:e2100985. Epub 2021 Sep 5.

Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, 210023, China.

Robust isolation of cancer stem cells (CSCs) in a high-throughput, label-free manner is critical for understanding tumor heterogeneity and developing therapeutic strategies targeting CSCs. Cell-mechanics-based microfluidic sorting systems provide efficient and specific platforms for investigation of stem cell-like characteristics on the basis of cell deformability and cell-substrate adhesion properties. In the present study, a microfluidic tandem mechanical sorting system is developed to enrich CSCs with high flexibility and low adhesive capacity. In the integrated microfluidic system, cancer cells are driven by hydrodynamic forces to flow continuously through two featured devices, which are functionalized with sequentially variable microbarriers and surface-coated fluid mixing microchannels, respectively. Collected deformable and low-adhesive cancer cells exhibit enhanced stem cell-like properties with higher stemness and metastasis capacity both in vitro and in vivo, compared with each single device separation. Using these devices, bioactive natural compound screening targeting CSCs is performed and a potent therapeutic compound isoliquiritigenin from licorice is identified to inhibit the lung cancer stem cell phenotype. Taken together, this microfluidic tandem mechanical sorting system can facilitate drug screening targeting CSCs and the analysis of signals regulating CSC function in drug resistance.
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http://dx.doi.org/10.1002/adhm.202100985DOI Listing
September 2021

Linkages Between Nutrient Resorption and Ecological Stoichiometry and Homeostasis Along a Chronosequence of Mongolian Pine Plantations.

Front Plant Sci 2021 13;12:692683. Epub 2021 Aug 13.

College of Environmental Sciences and Engineering, Liaoning Technical University, Fuxin, China.

Nutrient resorption is an important strategy for nutrient conservation, particularly under conditions of nutrient limitation. However, changes in nutrient resorption efficiency with stand development and the associated correlations with ecological stoichiometry and homeostasis are poorly understood. In the study, the authors measured carbon (C), nitrogen (N), and phosphorus (P) concentrations in soil and in green and senesced needles along a chronosequence of Mongolian pine ( var. ) plantations (12-, 22-, 31-, 42-, 52-, and 59-year-old) in Horqin Sandy Land of China, calculated N and P resorption efficiency (NRE and PRE, respectively), and homeostasis coefficient. The authors found that soil organic C and total N concentrations increased, but soil total P and available P concentrations decreased with stand age. Green needle N concentrations and N:P ratios as well as senesced needle C:N ratios, NRE, and PRE exhibited patterns of initial increase and subsequent decline with stand age, whereas green needle C:N ratios and senesced needle N concentrations, and N:P ratios exhibited the opposite pattern. NRE was positively correlated with N concentration and N:P ratio, but negatively correlated with C:N ratio in green needles, whereas the opposite pattern was observed in senesced needles. PRE was negatively correlated with senesced needle P concentration, soil-available N concentration, and available N:P ratio. The homeostatic coefficient of N:P was greater when including all stand ages than when including only those younger than 42 years. These findings indicate that tree growth may change from tending to be N limited to tending to be P limited along the Mongolian pine plantation chronosequence. Nutrient resorption was coupled strongly to tree growth and development, whereas it played a lesser role in maintaining stoichiometric homeostasis across the plantation chronosequence. Therefore, adaptive fertilization management strategies should be applied for the sustainable development of Mongolian pine plantations.
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http://dx.doi.org/10.3389/fpls.2021.692683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414255PMC
August 2021

Age-associated changes in caecal microbiome and their apparent correlations with growth performances of layer pullets.

Anim Nutr 2021 Sep 10;7(3):841-848. Epub 2021 Jul 10.

College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.

The microbiome in gastrointestinal tracts play an important role in regulating nutrient utilization and absorption, gut immune function, and host growth or development. This study was conducted to investigate the composition and dynamic distribution of caecal microbiota in pullets during the first 16 weeks. Growth performance, immune organs index, and intestinal morphology of pullets were analyzed at 3, 6, 12 and 16 weeks of age. The caecal contents were collected for microbiota analysis by 16S rRNA gene sequencing method. With advancing ages in pullets, the gradually increased average daily feed intake (ADFI), feed conversion ratio (FCR) and intestinal villus height, but the gradually decreased organs index of thymus and bursa were determined. Meanwhile, more abundant caecal bacterial communities were determined from pullets at 12 and 16 weeks of age than those at 3 and 6 weeks of age. Furthermore, the dominant microflora of pullets from different weeks of age were analyzed by using LEfSe: The higher abundance of , , and were found at 6 weeks; , , and were determined at 12 weeks; and the higher abundance of , , and were determined at 16 weeks. Further functional predicted analysis by PICRUSt revealed that the endocrine system and carbohydrate metabolism were significantly developed at 3 weeks. The development of the immune system was predicted to be mainly during 6 to 12 weeks, while cardiovascular diseases and circulatory system were during 12 to 16 weeks. In addition, the significantly negative correlation between and villus height, the significantly negative correlation between growth parameters (ADFI and FCR) and , and ; and the significantly positive relations between growth parameters (ADFI and FCR) and , , and were determined by using Pearson analyses. In conclusion, our data demonstrated that growth performance and intestinal morphology correlate well with caecal microbiota, which could provide new insights to establish or develop nutritional strategies to manage the intestinal health or development of laying pullets.
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http://dx.doi.org/10.1016/j.aninu.2020.11.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379648PMC
September 2021

Reduced activity of intestinal surface Na/H exchanger NHE3 is a key factor for induction of diarrhea after PEDV infection in neonatal piglets.

Virology 2021 Aug 27;563:64-73. Epub 2021 Aug 27.

Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi, Xinjiang, 830052, China. Electronic address:

Porcine epidemic diarrhea virus (PEDV; family Coronaviridae, genus Alphacoronavirus) causes acute diarrhea and vomiting, dehydration, and high mortality in neonatal piglets. Despite extensive research focusing on the pathogenesis of PEDV infection, the molecular pathogenesis of PEDV-induced diarrhea in piglets remains unclear. Na/H exchanger 3 (NHE3), the main exchanger of electroneutral sodium in intestinal epithelial cells, is closely associated with the occurrence of diarrhea. To date, there is no study on whether diarrhea caused by PEDV infection is related to the activity of NHE3. In the present study, it was found that the expression level of cell membrane protein NHE3 significantly decreased after PEDV infection, whereas the total level of protein expression was not significantly changed. The Na/H transport rate and the mRNA abundance of NHE3 decreased; the NHE3 activity decreased gradually with increasing infection time. In vivo, after PEDV infection of newborn piglets, rupture of intestinal villi and interstitial degeneration of intestinal epithelial cells in different intestinal segments were observed by hematoxylin-eosin staining. Immunohistochemical and immunofluorescence methods were used to observe the decreased expression of NHE3 protein on the membrane of intestinal epithelial cells in the jejunum and ileum. Taken together, these data indicate that PEDV infection reduces NHE3 activity in intestinal epithelial cells, hindering Na transport and thus causing diarrhea.
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http://dx.doi.org/10.1016/j.virol.2021.08.011DOI Listing
August 2021

Association of coffee and genetic risk with incident dementia in middle-aged and elderly adults.

Nutr Neurosci 2021 Aug 23:1-10. Epub 2021 Aug 23.

School of Public Health, Tianjin Medical University, Tianjin, People's Republic of China.

Background: Prior evidence suggests that coffee might be related to dementia, however, little is known about coffee and dementia in individuals with elevated genetic susceptibility for dementia. Additionally, most previous studies have focused on total coffee instead of examining coffee types separately.

Methods: This study included 203,776 participants (60-73 years old) from the UK Biobank who were initially free of dementia. Polygenic risk scores for dementia were divided into quintile to stratify individuals into low (lowest quintile), intermediate (quintile 2-4), and high (highest quintile) genetic risk categories. Coffee intake was assessed at baseline and included total, instant, ground, and decaffeinated coffee.

Results: During a median follow-up of 11.4 years, 4405 cases of dementia occurred (1856 Alzheimer's disease [AD], 1105 vascular dementia). Compared to non-coffee drinking, heavy instant coffee drinking (> 6 cups/day) and moderate decaffeinated coffee drinking (1-3 cups/day) were associated with a higher risk of dementia (hazard ratio [HR] 1.19-1.34) and AD (HR 1.41-1.51), while moderate ground coffee drinking was associated with a lower risk of dementia (HR, 0.78; = 0.001) and vascular dementia (HR, 0.58; < 0.001). Among participants at high genetic risk, heavy coffee drinking was associated with a 95% (HR; 1.95, 95% CI, 1.21-3.16) higher risk of AD than non-coffee drinking. We found an interaction between coffee and genetic risk in relation to AD (= 0.038).

Conclusion: The association of dementia and coffee varied by coffee types. Heavy coffee consumption was associated with a higher risk of AD in individuals with high genetic risk for dementia.
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http://dx.doi.org/10.1080/1028415X.2021.1966868DOI Listing
August 2021

Microbiota modulate Doxorubicin induced cardiotoxicity.

Eur J Pharm Sci 2021 Nov 17;166:105977. Epub 2021 Aug 17.

Neurology, Tianjin Medical University General Hospital Tianjin Neurological Institute, Key Laboratory of Post-Neurotrauma Neurorepair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin-300052, China. Electronic address:

Chemotherapy has several adverse effects to patients, some of which are life-threatening. We hypothesized that Doxorubicin induced microbiome imbalance and intestinal damage may contribute to Doxorubicin induced cardiac dysfunction. Male adult (2-3 months) C57BL/6 mice were administered 3 mg/kg, 5 mg/kg, 7.5 mg/kg,15 mg/kg, 20 mg/kg doses of Doxorubicin. Echocardiography was performed at 7 and 14 days after Doxorubicin administration. 16S rRNA amplicon sequencing was used to characterize microbiome changes. Fecal microbiota transplantation (FMT) was performed to evaluate the role of the microbiota on Doxorubicin induced cardiac dysfunction. Doxorubicin dose dependently increases mortality rate and induces cardiac dysfunction. 5 mg/kg-Doxorubicin significantly induces decreased left ventricular ejection fraction (LVEF) and fraction shortening (FS) as well as increased cardiac fibrosis, inflammation and oxidative stress respond without increasing mortality. 5 mg/kg-Doxorubicin induces significant decreased colorectum length, increased loss of goblet cells, numbers of ulcers and infiltration of lymphocyte clusters and decreased tight junction protein ZO-1, as well as increased plasma endotoxin level measured by ELISA assay. 16S rRNA microbiota analysis shows that Doxorubicin-induced microbiota dysbiosis with decreased community richness compared with normal control mice. FMT to Doxorubicin-5 mg treated mice significantly improved cardiac function by increasing LVEF and FS as well as decreased perivascular and interstitial fibrosis; increased colorectum length, decreased the loss of goblet cells,infiltration of lymphocyte clusters,the number of ulcers and plasma endotoxin level; improved microbiota composition, function and diversity with increased abundance of Alloprevotella, Prevotellaceae_UCG-001 and Rikenellaceae_RC9_gut_group. We find that normal fecal transplantation improves cardiac function, decreases gut damage and alter microbiota composition induced by Doxorubicin. The microbiota appears to contribute to heart-gut interaction.
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http://dx.doi.org/10.1016/j.ejps.2021.105977DOI Listing
November 2021

The Immune Heterogeneity Between Pulmonary Adenocarcinoma and Squamous Cell Carcinoma: A Comprehensive Analysis Based on lncRNA Model.

Front Immunol 2021 29;12:547333. Epub 2021 Jul 29.

Institute of Oncology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Adenocarcinoma (AD) and squamous cell carcinoma (SCC) are both classified as major forms of non-small cell lung cancer, but differences in clinical prognoses and molecular mechanisms are remarkable. Recent studies have supported the importance of understanding immune status in that it influences clinical outcomes of cancer, and immunotherapies based on the theory of "immune editing" have had notable clinical success. Our study aimed to identify specific long non-coding (lnc) RNAs that control key immune-related genes and to use them to construct risk models for AD and SCC. Risk scores were used to separate patients into high- and low-risk groups, and we validated the prognostic significance of both risk scores with our own cohorts. A Gene Set Enrichment Analysis suggested that the immune responses of patients in the AD high-risk group and the SCC low-risk group tended to be weakened. Evaluation of immune infiltration revealed that the degree of infiltration of dendritic cells is of particular importance in AD. In addition, prediction of responses to immune checkpoint inhibitor (ICI) treatments, based on the T Cell Immune Dysfunction and Exclusion and immunophenoscore models, indicated that deterioration of the immune microenvironment is due mainly to T cell exclusion in AD patients and T cell dysfunction in SCC patients and that high-risk patients with SCC might benefit from ICI treatment. The prediction of downstream targets The Cancer Proteome Atlas and RNA-seq analyses of a transfected lung cancer cell line indicated that the lncRNA LINC00996 is a potential therapeutic target in AD.
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http://dx.doi.org/10.3389/fimmu.2021.547333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358782PMC
July 2021

Effect of Metabolic Health and Obesity Phenotype on Risk of Diabetes Mellitus: A Population-Based Longitudinal Study.

Diabetes Metab Syndr Obes 2021 5;14:3485-3498. Epub 2021 Aug 5.

Key Laboratory of Environment Medicine Engineering of Ministry of Education, Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, Jiangsu Province, People's Republic of China.

Background: Epidemiologic evidence on body mass index (BMI)-metabolic status phenotypes and diabetes risk remains controversial, especially for metabolically healthy obesity (MHO). We aimed to examine the effect of metabolic health and obesity phenotype on diabetes risk in the Chinese population.

Methods: A population-based cohort study was carried out. The baseline survey was conducted in 2017, with two follow-up visits in 2018 and 2020. Diabetes was defined based on the criteria of the World Health Organization. Robust generalized estimating equation models with a binary distribution using a log link and exchange structure were applied for the pooled analysis sample.

Results: A total sample of 9623 observations was pooled for the longitudinal data analysis. The average follow-up time was 1.64 years per person and the overall incidence density of diabetes was 6.94% person-years. Decreased diabetes risk was found in metabolically healthy overweight phenotype (RR = 0.65; 95% CI = 0.47-0.90) and no significant associations were detected for the MHO individuals (RR = 0.99; 95% CI = 0.63-1.53) compared with those of metabolically healthy normal weight, in contrast to metabolically unhealthy normal weight (MU-NW) (RR = 1.81; 95% CI = 1.28-2.55), metabolically unhealthy overweight (MU-OW) (RR = 2.02; 95% CI = 1.57-2.61) and metabolically unhealthy obesity (MUO) (RR = 2.48; 95% CI = 1.89-3.26) phenotypes. Significant associations between BMI-metabolic status phenotypes and diabetes were found in both males and females.

Conclusion: The MUO phenotype needs to be accorded much more importance. MU-NW and MU-OW are also important component for targeted prevention. Our findings can be targeted for optimizing preventive strategies to mitigate the obviously increased prevalence of diabetes.
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http://dx.doi.org/10.2147/DMSO.S317739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353171PMC
August 2021

PD-1/PD-L1 inhibitors-based treatment for advanced renal cell carcinoma: Mechanisms affecting efficacy and combination therapies.

Cancer Med 2021 Sep 12;10(18):6384-6401. Epub 2021 Aug 12.

Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

With the widespread use of PD-1/PD-L1 monoclonal antibodies (mAbs) in the treatment of multiple malignant tumors, they were also gradually applied to advanced renal cell carcinoma (aRCC). Nowadays, multiple PD-1/PD-L1 mAbs, such as nivolumab, avelumab, and pembrolizumab, have achieved considerable efficacy in clinical trials. However, due to the primary, adaptive, and acquired resistance to these mAbs, the efficacy of this immunotherapy is not satisfactory. Theories also vary as to why the difference in efficacy occurs. The alterations of PD-L1 expression and the interference of cellular immunity may affect the efficacy. These mechanisms demand to be revealed to achieve a sustained and complete objective response in patients with aRCC. Tyrosine kinase inhibitors have been proven to have synergistic mechanisms with PD-1/PD-L1 mAb in the treatment of aRCC, and CTLA-4 mAb has been shown to have a non-redundant effect with PD-1/PD-L1 mAb to enhance efficacy. Although combinations with targeted agents or other checkpoint mAbs have yielded enhanced clinical outcomes in multiple clinical trials nowadays, the potential of PD-1/PD-L1 mAbs still has a large development space. More potential mechanisms that affect the efficacy demand to be developed and transformed into the clinical treatment of aRCC to search for possible combination regimens. We elucidate these mechanisms in RCC and present existing combination therapies applied in clinical trials. This may help physicians' select treatment options for patients with refractory kidney cancer.
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http://dx.doi.org/10.1002/cam4.4190DOI Listing
September 2021

Radiomics-based MRI for predicting Erythropoietin-producing hepatocellular receptor A2 expression and tumor grade in brain diffuse gliomas.

Neuroradiology 2021 Aug 9. Epub 2021 Aug 9.

Department of Diagnostic Radiology, Affiliated Jinling Hospital, Medical School of Nanjing University, 305#, Eastern Zhongshan Rd, Nanjing, 210002, China.

Purpose: EphA2 is a key factor underlying invasive propensity of gliomas, and is associated with poor prognosis of tumors. We aimed to develop a radiomics-based imaging index for predicting EphA2 expression in diffuse gliomas, and further estimating its value for grading of tumors.

Methods: A total of 182 patients with diffuse gliomas were included. All subjects underwent pre-operative MRI and post-operative pathological diagnosis. EphA2 expression of tumors was scored on pathological sections with immunohistochemical staining using monoclonal EphA2 antibody. MRI radiomics features were extracted from three-dimensional contrast-enhanced T1-weighted imaging and diffusion kurtosis imaging. Predictive models were constructed using machine learning-based radiomics features selection and three classifiers for predicting EphA2 expression and tumor grade. Features of best EphA2 expression model were subsequently used to construct another model of tumor grading. For each model, 146 cases (80%) were randomly picked as training and the rest 36 (20%) were testing cohorts. EphA2 expression was further correlated to the radiomics features in both grade models using Spearman's correlation.

Results: Logistic regression model presented highest performance for predicting EphA2 expression (AUC: 0.836/0.724 in training/validation set). Tumor gradings model guided by features from EphA2 expression model demonstrated comparable performance (AUC: 0.930/0.983) to that constructed directly using imaging radiomics features (AUC: 0.960/0.977). Two radiomics features which included in both LR-grade models showed strong correlation (P < 0.05) with EphA2 expression.

Conclusion: The expression of EphA2 in gliomas could be predicted by radiomics features extracted from diffusion kurtosis MRI, which could also be used to assist tumor grading.
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http://dx.doi.org/10.1007/s00234-021-02780-1DOI Listing
August 2021

Oral Spermidine Targets Brown Fat and Skeletal Muscle to Mitigate Diet-Induced Obesity and Metabolic Disorders.

Mol Nutr Food Res 2021 Aug 7:e2100315. Epub 2021 Aug 7.

Key Laboratory of Infection and Immunity of Shandong Province, Shandong Provincial Clinical Research Center for Immune Diseases and Gout, Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.

Introduction: Obesity causes many life-threatening diseases. It is important to develop effective approaches for obesity treatment. Oral supplementation with spermidine retards age-related processes, but its influences on obesity and various metabolic tissues remain largely unknow. This study aims to investigate the effects of oral spermidine on brown adipose tissue (BAT) and skeletal muscle as well as its roles in counteracting obesity and metabolic disorders.

Methods And Results: Spermidine is orally administrated into high-fat diet (HFD)-fed mice. The weight gain, insulin resistance, and hepatic steatosis are attenuated by oral spermidine in HFD-fed mice, accompanied by an alleviation of white adipose tissue inflammation. Oral spermidine promotes BAT activation and metabolic adaptation of skeletal muscle in HFD-fed mice, evidenced by UCP-1 induction and CREB activation in both tissues. Notably, oral spermidine upregulates tyrosine hydroxylase in hypothalamus of HFD-fed mice; spermidine treatment increases tyrosine hydroxylase expression and norepinephrine production in neurocytes, which leads to CREB activation and UCP-1 induction in brown adipocytes and myotubes. Spermidine also directly promotes UCP-1 and PGC-1α expression in brown adipocytes and myotubes.

Conclusion: Spermidine serves as an oral supplement to attenuate obesity and metabolic disorders through hypothalamus-dependent or -independent BAT activation and skeletal muscle adaptation.
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http://dx.doi.org/10.1002/mnfr.202100315DOI Listing
August 2021

Population-based associations between progression of normal-tension glaucoma and Yang-deficient constitution among Chinese persons.

Br J Ophthalmol 2021 Aug 6. Epub 2021 Aug 6.

Eye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, China

Purpose: To explore the association between constitution types as defined by traditional Chinese medicine (TCM) and risk for normal-tension glaucoma (NTG).

Design: Population-based cohort study.

Methods: Persons were identified in a population cohort aged ≥30 years with NTG, defined as having an untreated mean intraocular pressure measurement ≤21 mm Hg over six separate occasions, with no single reading >24 mm Hg (as in the Collaborative Normal Tension Glaucoma Study). The Body Constitution in Traditional Chinese Medicine Questionnaire was used to assess each participant's TCM constitution types. The association between various constitutions and visual field progression according to Early Manifest Glaucoma Trial criteria was assessed using Cox regression HR models.

Results: Among 142 participants (245 eyes), 23 persons (17.6%) and 25 eyes (10.2%) progressed, over a mean (SD) follow-up duration of 3.49 (0.99) years. Progression rates were highest in participants with Yang-deficient constitution (n=19, 13.4%), among whom 7 (36.8%) exhibited worsening fields. After adjusting for sex, age, central corneal thickness, retinal nerve fibre layer thickness and mean deviation on visual field testing, Yang-deficient constitution (HR 4.63, 95% CI 1.77 to 12.1, p=0.002) and higher mean intraocular pressure during follow-up (HR 1.25, 95% CI 1.01 to 1.56, p=0.044) were associated with field progression.

Conclusions: Yang-deficient constitution and higher intraocular pressure are risk factors for visual field progression in NTG patients. Yang deficiency is characterised by abnormal vasoregulation, and these results may be consistent with prior studies linking NTG progression to Raynaud's phenomenon and migraine.
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http://dx.doi.org/10.1136/bjophthalmol-2021-319210DOI Listing
August 2021

Integrated neural network model with pre-RBF kernels.

Sci Prog 2021 Jul-Sep;104(3):368504211026111

Institute of Electromechanical and Information Engineering, Putian University, Putian, Fujian, China.

To improve the network performance of radial basis function (RBF) and back-propagation (BP) networks on complex nonlinear problems, an integrated neural network model with pre-RBF kernels is proposed. The proposed method is based on the framework of a single optimized BP network and an RBF network. By integrating and connecting the RBF kernel mapping layer and BP neural network, the local features of a sample set can be effectively extracted to improve separability; subsequently, the connected BP network can be used to perform learning and classification in the kernel space. Experiments on an artificial dataset and three benchmark datasets show that the proposed model combines the advantages of RBF and BP networks, as well as improves the performances of the two networks. Finally, the effectiveness of the proposed method is verified.
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http://dx.doi.org/10.1177/00368504211026111DOI Listing
August 2021

Expression of microRNA-155-5p in patients with refractory diabetic macular edema and its regulatory mechanism.

Exp Ther Med 2021 Sep 8;22(3):975. Epub 2021 Jul 8.

Department of Retinal and Vitreous Diseases, Aier Eye Hospital of Wuhan University, Wuhan, Hubei 430000, P.R. China.

Diabetic macular edema (DME) is the main cause of visual impairment in diabetic patients, but its pathogenesis remains unclear. The purpose of the present study was to analyze the expression of microRNA (miR)-155-5p in patients with DME and its regulatory mechanism. A total of 72 patients diagnosed with DME and 17 with idiopathic macular hole (MH) were recruited. Among samples from patients with DME, 45 were DME and 27 were refractory DME, whereas patients with idiopathic MH served as the control group. Optical coherence tomography and fundus photograph analysis revealed that part of the retina in the fundus of patients with DME was thickened, with macular edema occurring simultaneously. In refractory patients with DME, macular edema was associated with bleeding and a dark cavity between retinal layers. Through reverse transcription-quantitative PCR analysis, miR-155-5p was highly expressed in the aqueous humor (AH) and plasma of patients with DME compared with that in patients with MH, and this was even higher in the refractory DME group. Upon analyzing patient clinical data, the difference in miR-155-5p expression in the AH and plasma was positively associated with disease course, body mass index, fasting blood-glucose, glycated hemoglobin, proteinuria and glycosuria. The expression of miR-155-5p was not significantly different based on hemoglobin, intraocular pressure and sex. The aforementioned results indicate that miR-155-5p might promote the development of DME. To further study the molecular mechanism, human retinal microvascular endothelial cells (HRMECs) were cultured and treated with high glucose . The results showed that miR-155-5p expression was significantly upregulated in HRMECs induced by high glucose. After inhibiting the expression of miR-155-5p, cell proliferation, angiogenesis and VEGF protein levels were significantly downregulated, whereas miR-155-5p mimics had the opposite effect. In summary, miR-155-5p is closely associated with DME and is a potential target for refractory DME treatment.
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http://dx.doi.org/10.3892/etm.2021.10407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290410PMC
September 2021

Lactulose Improves Neurological Outcomes by Repressing Harmful Bacteria and Regulating Inflammatory Reactions in Mice After Stroke.

Front Cell Infect Microbiol 2021 13;11:644448. Epub 2021 Jul 13.

Department of Neurology, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Key Laboratory of Post-Neurotrauma, Neurorepair, and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China.

Background And Objective: Gut microbiota dysbiosis following stroke affects the recovery of neurological function. Administration of prebiotics to counteract post-stroke dysbiosis may be a potential therapeutic strategy to improve neurological function. We aim to observe the effect of lactulose on neurological function outcomes, gut microbiota composition, and plasma metabolites in mice after stroke.

Methods: Male C57BL/6 mice (20-25 g) were randomly divided into three groups: healthy control, photothrombotic stroke + triple-distilled water, and photothrombotic stroke + lactulose. After 14 consecutive days of lactulose administration, feces, plasma, and organs were collected. 16S rDNA sequencing, plasma untargeted metabolomics, qPCR, flow cytometry and Elisa were performed.

Results: Lactulose supplementation significantly improved the functional outcome of stroke, downregulated inflammatory reaction, and increased anti-inflammatory factors in both the brain and gut. In addition, lactulose supplementation repaired intestinal barrier injury, improved gut microbiota dysbiosis, and partially amended metabolic disorder after stroke.

Conclusion: Lactulose promotes functional outcomes after stroke in mice, which may be attributable to repressing harmful bacteria, and metabolic disorder, repairing gut barrier disruption, and reducing inflammatory reactions after stroke.
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http://dx.doi.org/10.3389/fcimb.2021.644448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313872PMC
August 2021

Nr5a homologues in the ricefield eel Monopterus albus: Alternative splicing, tissue-specific expression, and differential roles on the activation of cyp19a1a promoter in vitro.

Gen Comp Endocrinol 2021 Oct 26;312:113871. Epub 2021 Jul 26.

Institute of Aquatic Economic Animals and Guangdong Province Key Laboratory for Aquatic Economic Animals, School of Life Sciences, Sun Yat-Sen University, Guangzhou, China; Guangdong Provincial Engineering Technology Research Center for Healthy Breeding of Important Economic Fish, Sun Yat-Sen University, Guangzhou, China. Electronic address:

Nr5a (Fushi tarazu factor 1, Ftz-F1) homologues belong to the nuclear receptor superfamily, and are involved in the regulation of reproduction in vertebrates. Four genes encoding Nr5a homologues were present in the genome of ricefield eel, which are designated as nr5a1a, nr5a1b, nr5a2, and nr5a5 in the present study. Alternatively spliced transcripts were identified for nr5a1a and nr5a1b genes. Sequence analysis indicated that nr5a5 is possibly a paralog of nr5a2, and nr5a1b is lost during evolution in some teleosts including tilapia and medaka. Ricefield eel nr5a genes exhibit tissue-specific expression patterns, with nr5a1a and nr5a1b resembling that of the SF-1/Ad4BP (NR5A1) subfamily, and nr5a2 and nr5a5 resembling that of the NR5A2/LRH/FTF subfamily. Transcriptomic analysis revealed parallel expression profiles of nr5a1a, foxl2, and cyp19a1a in ovarian follicles during vitellogenesis, with peak values at the late vitellogenic stage. Real-time PCR indicated that the expression levels of nr5a1a and foxl2 in gonads were decreased significantly during the sexual transition from female to the late intersexual stage. In vitro transient transfection assay showed that Nr5a1a up-regulated ricefield eel cyp19a1a promoter activities synergistically with Foxl2. However, Nr5a1b, Nr5a2, and Nr5a5 could neither activate ricefield eel cyp19a1a promoter alone nor enhance the stimulatory effects of Foxl2 on cyp19a1a promoter activities. Collectively, the above data suggest that Nr5a homologues may have diverse and differential roles in the tissues of ricefield eels. The up-regulation of gonadal nr5a1a and foxl2 during vitellogenesis may be important for the ovarian development whereas their down-regulation during the sexual transition period may be important for the sex change process of ricefield eels, possibly through the regulation of cyp19a1a gene expression.
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http://dx.doi.org/10.1016/j.ygcen.2021.113871DOI Listing
October 2021

Data on performance and variation index for shield tunnelling through soft deposit.

Data Brief 2021 Jun 27;36:107103. Epub 2021 Apr 27.

State Key Laboratory of Internet of Things for Smart City, University of Macau, Macau, China.

The data presented in this article pertain to field records of EPB shield machine in Metro Line No. 5 in Tianjin, China. Field performance of shield machine (cutterhead, screw machine, and shield advancing) are shown in the figures. Specifically, the database consists of the main parameters for shield tunnelling including cutterhead rotation speed, cutterhead torque, screw machine rotation speed, screw machine torque, shield thrust, and shield advance rate. In addition, the calculation process of energy consumption and variation index R during the tunnelling are displayed. The value of the dataset is the consideration of silt or clay soil encountered in the shield tunnelling area including the proportion of soils, grain gradation, and effects on performance and energy consumption of different parts in shield machine. These field data are applied to evaluate the construction efficiency in the article titled "Construction efficiency of shield tunnelling through soft deposit in Tianjin" [1].
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http://dx.doi.org/10.1016/j.dib.2021.107103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257968PMC
June 2021

Disrupting the Interaction of nNOS with CAPON Prevents the Reinstatement of Morphine Conditioned Place Preference.

Cereb Cortex 2021 Jul 23. Epub 2021 Jul 23.

Department of Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.

Drug abuse is a dramatic challenge for the whole society because of high relapse rate. Environmental cues are crucial for the preference memory of drug abuse. Extinction therapy has been developed to inhibit the motivational effect of drug cues to prevent the reinstatement of morphine abuse. However, extinction therapy alone only forms a new kind of unstable inhibitory memory. We found that morphine conditioned place preference (CPP) extinction training increased the association of nitric oxide synthase (nNOS) with its carboxy-terminal PDZ ligand (CAPON) in the dorsal hippocampus (dHPC) significantly and blocking the morphine-induced nNOS-CAPON association using Tat-CAPON-12C during and after extinction training reversed morphine-induced hippocampal neuroplasticity defect and prevented the reinstatement and spontaneous recovery of morphine CPP. Moreover, in the hippocampal selective ERK2 knock-out or nNOS knockout mice, the effect of Tat-CAPON-12C on the reinstatement of morphine CPP and hippocampal neuroplasticity disappeared, suggesting ERK2 is necessary for the effects of Tat-CAPON-12C. Together, our findings suggest that nNOS-CAPON interaction in the dHPC may affect the consolidation of morphine CPP extinction and dissociating nNOS-CAPON prevents the reinstatement and spontaneous recovery of morphine CPP, possibly through ERK2-mediated neuroplasticity and extinction memory consolidation, offering a new target to prevent the reinstatement of drug abuse.
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http://dx.doi.org/10.1093/cercor/bhab234DOI Listing
July 2021

Short-term effects of ambient air pollution and meteorological factors on tuberculosis in semi-arid area, northwest China: a case study in Lanzhou.

Environ Sci Pollut Res Int 2021 Jul 21. Epub 2021 Jul 21.

Gansu Key Laboratory for Environmental Pollution Prediction and Control, College of Earth and Environmental Sciences, Lanzhou University, 222 South Tianshui Road, Chengguan District, Lanzhou, 730000, Gansu Province, People's Republic of China.

To investigate the short-term effects of ambient air pollution and meteorological factors on daily tuberculosis (TB), semi-parametric generalized additive model was used to assess the impacts of ambient air pollutants and meteorological factors on daily TB case from 2005 to 2010 in Chengguan District, Lanzhou, China. Then a non-stratification parametric model and a stratification parametric model were applied to study the interactive effect of air pollutants and meteorological factors on daily TB. The results show that sulfur dioxide (SO), nitrogen dioxide (NO), and particulate matter with aerodynamic diameter less than 10μm (PM) were positively correlated with daily TB case; the excess risk (ER) and 95% confidence interval (CI) were 1.79% (0.40%, 3.20%), 3.86% (1.81%, 5.96%), and 0.32% (0.02%, 0.62%), respectively. Daily TB case was positively correlated with maximum temperature, minimum temperature, average temperature, vapor pressure, and relative humidity, but negatively correlated with atmospheric pressure, wind speed, and sunshine duration. The association with average temperature was the strongest, whose ER and 95% CI were 4.43% (3.15%, 5.72%). In addition, there were significant interaction effects between air pollutants and meteorological factors on daily TB case.
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http://dx.doi.org/10.1007/s11356-021-15445-6DOI Listing
July 2021

Clinical Performance of a Powered Surgical Stapler for Left Atrial Appendage Resection in a Video-Assisted Thoracoscopic Ablation for Patients with Nonvalvular Atrial Fibrillation.

Int Heart J 2021 Jul 17;62(4):764-770. Epub 2021 Jul 17.

Department of Cardiovascular Surgery, Zhongshan Hospital, Fudan University.

Left atrial appendage (LAA) has been found to be associated with the occurrence of thromboembolism in patients with nonvalvular atrial fibrillation (NVAF). Stapling exclusion of LAA during surgical ablation could be an alternative to oral anticoagulation for NVAF patients. However, its safety and efficacy have rarely been examined. Thus, in this study, we aimed to evaluate the safety and efficacy of a powered surgical stapler for LAA resection during ablation for patients with NVAF.Adult patients with NVAF undergoing stapler surgery were included in this study. LAAs of patients were cut off using a powered surgical stapler. Intraoperative transesophageal echocardiogram (TEE) was applied before and after the operation. Each patient received anticoagulant therapy for 2 months after surgery and was regularly followed up by appointment or via telephone call. Patients would undergo physical examinations, echocardiography, and 24-hour dynamic electrocardiogram in a local or in our hospital to determine whether there was a recurrence of atrial fibrillation (AF) or thromboembolism caused by AF.In total, 124 patients were included in this study (male: 88 (71.0%); mean age: 62.3 years). Blood loss was less than 100 mL in all patients with no operative complications or hospital deaths. Moreover, 119 (96.0%) follow-up data were collected, with a mean period of 27.4 months. All patients discontinued oral anticoagulants 2 months after their operation. As per our findings, AF recurred in 23 patients (18.5%), with an average of 9.1 months after surgery. No patients were diagnosed with thromboembolism related to AF.Stapling exclusion of LAA during surgical ablation could safely and completely resect the LAA. The effect of thrombus prevention was deemed satisfactory.
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http://dx.doi.org/10.1536/ihj.20-765DOI Listing
July 2021

Combined prognostic nutritional index and albumin-bilirubin grade to predict the postoperative prognosis of HBV-associated hepatocellular carcinoma patients.

Sci Rep 2021 Jul 16;11(1):14624. Epub 2021 Jul 16.

Department of Liver Surgery, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, China.

This study aims to evaluate the predictive value of the prognostic nutritional index (PNI) and albumin-bilirubin grade (ALBI) for the postoperative prognosis of hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) patients undergoing radical hepatectomy (RH). Besides, we seek to identify novel prognosis indicators for HBV-HCC patients. Between April 2009 and March 2015, this work enrolled 868 patients diagnosed with HBV-HCC and undergoing RH in the Liver Surgery Department, West China Hospital, Sichuan University (WCHSU). The basic information, laboratory examination indicators, pathological reports, and follow-up data of patients were included. SPSS 22.0 statistical software was used for statistical data analyses. Platelet (PLT), alpha-fetoprotein (AFP), maximum diameter (max-D), number of tumors (Number), degree of differentiation (DD), Microvascular invasion situation (MVI), satellite focus situation (SF), PNI, and ALBI were the independent risk factors for both overall survival (OS) and disease-free survival (DFS) of HBV-HCC patients undergoing RH. Taking PNI = 46 and ALBI = - 2.80 as cut-off values, the OS and DFS of the PNI-high group were significantly higher than those of the PNI-low group. Meanwhile, the OS and DFS of the ALBI-low group were significantly higher than those of the ALBI-high group; the OS and DFS of the PNI-high + ALBI-low group were significantly higher than those of the PNI-low + ALBI-high group. Xie prognostic index (XPI) was the independent risk factor for both OS and DFS of HBV-HCC patients undergoing RH. The OS and DFS of the XPI-high group were significantly higher than those of the XPI-low group. This paper reveals that preoperative PNI and ALBI can predict the OS and DFS of HBV-HCC patients undergoing RH. Their impact on the prognosis of HBV-HCC patients is insignificant, however, it cannot be ignored. XPI can precisely predict the prognosis of HBV-HCC patients undergoing RH, nonetheless, its effect requires additional research for validation.
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http://dx.doi.org/10.1038/s41598-021-94035-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285529PMC
July 2021

Controlled CRISPR-Cas9 Ribonucleoprotein Delivery for Sensitized Photothermal Therapy.

Small 2021 Aug 16;17(33):e2101155. Epub 2021 Jul 16.

Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, 210023, China.

Manipulation of CRISPR delivery for stimuli-responsive gene editing is crucial for cancer therapeutics through maximizing efficacy and minimizing side-effects. However, realizing controlled gene editing for synergistic combination therapy remains a key challenge. Here, a near-infrared (NIR) light-triggered thermo-responsive copper sulfide (CuS) multifunctional nanotherapeutic platform is constructed to achieve controlled release of CRISPR-Cas9 ribonucleoprotein (RNP) and doxorubicin for tumor synergistic combination therapy involving in gene therapy, mild-photothermal therapy (PTT), and chemotherapy. The semiconductor CuS serves as a "photothermal converter" and can stably convert NIR light (808 nm) into local thermal effect to provide photothermal stimulation. The double-strand formed between CuS nanoparticle-linked DNA fragments and single-guide RNA is employed as a controlled element in response to photothermal stimulation for controlled gene editing and drug release. Hsp90α, one subunit of heat shock protein 90 (Hsp90), is targeted by Cas9 RNP to reduce tumor heat tolerance for enhanced mild-PTT effects (≈43 °C). Significant synergistic therapy efficacy can be observed by twice NIR light irradiation both in vitro and in vivo, compared to PTT alone. Overall, this exogenously controlled method provides a versatile strategy for controlled gene editing and drug release with potentially synergistic combination therapy.
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http://dx.doi.org/10.1002/smll.202101155DOI Listing
August 2021

Targeting TRAF3IP2 alleviates high glucose-induced cardiomyocyte inflammation and apoptosis.

Drug Dev Res 2021 Jul 14. Epub 2021 Jul 14.

Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong, Guangzhou, China.

To clarify the role of TRAF3IP2 in high glucose (HG)-stimulated cardiomyocyte inflammation and apoptosis and its action mechanism. SiRNA plasmid of TRAF3IP2 was constructed and transfected into HG-stimulated cardiomyocytes to silence TRAF3IP2. The expression of TRAF3IP2 was determined by quantitative polymerase chain reaction (qPCR) and western blot. Cell viability and cytotoxicity were first observed using cell counting kit-8 and lactate dehydrogenase assays. The inflammatory injury of the cardiomyocytes was then examined by real time-qPCR (RT-qPCR) and western blot. The oxidative stress of the cardiomyocytes was evaluated using reactive oxygen species assay kit, RT-qPCR, western blot and enzyme activity assay kit. Next, cell apoptosis was detected employing TUNEL and western blot. Finally, RT-qPCR and western blot were performed to investigate the effects of inhibitors of dipeptidyl peptidase-4, including saxagliptin, empagliflozin and linagliptin, on TRAF3IP2. TRAF3IP2 expression was found to be increased in HG-stimulated cardiomyocytes. TRAF3IP2 interference inhibited HG-induced cell viability loss, cytotoxicity, inflammatory response, oxidative stress and apoptosis of the cardiomyocytes. Moreover, saxagliptin, empagliflozin and linagliptin inhibited the expression of TRAF3IP2. TRAF3IP2 interference alleviates HG-induced inflammation and apoptosis of cardiomyocytes. The result suggests that TRAF3IP2 may be a promising therapeutic target in treating diabetic cardiomyopathy.
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http://dx.doi.org/10.1002/ddr.21856DOI Listing
July 2021

Prevalence and treatment of high cardiovascular disease risk in Inner Mongolia, China.

Rev Cardiovasc Med 2021 Jun;22(2):521-529

School of Public Health, Inner Mongolia Medical University, 010110 Hohhot, Inner Mongolia, China.

Early identification of individuals with high risk is crucial to preventing cardiovascular disease (CVD). We aimed to determine the prevalence of high CVD risk in Inner Mongolia and to analyze the treatment of major risk factors among individuals with high CVD risk. We selected 70,380 participants aged 35-75 years in Inner Mongolia between 2015 and 2017 using multistage stratified sampling. All participants completed a questionnaire and their blood pressure, blood glucose and lipid levels, height, weight and waist circumference were measured. Participants without a history of CVD were defined as high CVD risk if the predicted 10-year risk for CVD exceeded 10%. We assessed rates of high CVD risk and the prevalence and treatment of major risk factors among individuals with high CVD risk. After excluding participants with previous CVD, 68,083 participants remained. The overall prevalence of high CVD risk was 24.96%. The age- and sex-standardized rate of high CVD risk was 22.92%. Among high-risk participants, the prevalence of risk factors was hypertension (91.9%), dyslipidemia (54.1%), obesity (34.6%), diabetes (27.6%), and smoking (24.5%); clustering of these risk factors was common. The percentage of high-risk individuals taking antihypertensive drugs was 45.94% in those with hypertension; 27.99% of those with diabetes took hypoglycemic drugs and only 5.01% of those with dyslipidemia took lipid-lowering drugs. Control rates of hypertension, diabetes, and dyslipidemia were 1.20%, 4.43%, and 2.78%, respectively. Therefore, the prevalence of high CVD risk was elevated in Inner Mongolia, and treatment and control rates were low.
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http://dx.doi.org/10.31083/j.rcm2202060DOI Listing
June 2021

Risk prediction models based on hematological/body parameters for chemotherapy-induced adverse effects in Chinese colorectal cancer patients.

Support Care Cancer 2021 Jul 2. Epub 2021 Jul 2.

Department of Pharmacy, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, China.

Purpose: To determine risk factors and develop novel prediction models for chemotherapy-induced adverse effects (CIAEs) in Chinese colorectal cancer (CRC) patients receiving capecitabine.

Methods: A total of 233 Chinese CRC patients receiving post-operative chemotherapy with capecitabine were randomly divided into a training set (70%) and a validation set (30%). CIAE-related hematological/body parameters were screened by univariate logistic regression. Based on a set of factors selected from LASSO (least absolute shrinkage and selection operator) logistic regression, stepwise multivariate logistic regression was applied to develop prediction models. Area under the receiver operating characteristic (ROC) curve and Hosmer-Lemeshow (HL) test were used to evaluate the discriminatory ability and the goodness of fit of each model.

Results: In total, 35 variables were identified to be associated with CIAEs in univariate analysis. Developed multivariable models had AUCs (area under curve) ranging from 0.625 to 0.888 and 0.428 to 0.760 in the training and validation set, respectively. The grade ≥ 1 anemia multivariable model achieved the best discriminatory ability with AUC of 0.760 (95%CI: 0.609-0.912) and good calibration with HL P value of 0.450. Then, a nomogram was constructed to predict grade ≥ 1 anemia, which included variables of age, pre-operative hemoglobin count, and pre-operative albumin count, with C-indexes of 0.775 and 0.806 in the training and validation set, respectively.

Conclusions: This study identified valuable hematological/body parameters related to CIAEs. A nomogram based on the multivariable model including three hematological/body predictors can accurately predict grade ≥ 1 anemia, facilitating clinicians to implement personalized medicine early for Chinese CRC patients receiving post-operative chemotherapy for better safety treatment. Trial registration This study was registered as a clinical trial at www.clinicaltrials.gov (NCT03030508).
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http://dx.doi.org/10.1007/s00520-021-06337-zDOI Listing
July 2021
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