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Dual human iPSC-derived cardiac lineage cell-seeding extracellular matrix patches promote regeneration and long-term repair of infarcted hearts

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bioactive Materials 2023年第10期28卷 206-226页

作者： Yun Jiang Ling-Ling Zhang Fan Zhang Wei bi Peng Zhang Xiu-Jian Yu sen-Le Rao Shi-Hui Wang Qiang Li Chen ding Ying Jin Zhong-Min Liu Huang-Tian Yang Translational Medical Center for Stem Cell Therapy&Institute for Heart Failure and Regenerative Medicine Shanghai East HospitalSchool of MedicineTongji UniversityShanghai200092China CAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and HealthUniversity of Chinese Academy of Sciences(CAS)CASShanghai200031PR China State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development School of Life SciencesInstitute of Biomedical SciencesHuman Phenome InstituteZhongshan HospitalFudan UniversityShanghai200433China Institute for Stem Cell and Regeneration CASBeijing100101PR China

Human pluripotent stem cell-derived cardiovascular progenitor cells (hCVPCs) and cardiomyocytes (hCMs) possess therapeutic potential for infarcted hearts;however, their efficacy needs to be enhanced. Here we tested the hypotheses that the combination of decellularized porcine small intestinal submucosal extracellular matrix (SIS-ECM) with hCVPCs, hCMs, or dual of them (Mix, 1:1) could provide better therapeutic effects than the SIS alone, and dual hCVPCs with hCMs would exert synergic effects in cardiac repair. The data showed that the SIS patch well supported the growth of hCVPCs and hCMs. Epicardially implanted SIS-hCVPC, SIS-hCM, or SIS-Mix patches at 7-day post-myocardial infarction significantly ameliorated functional worsening, ventricular dilation and scar formation at 28- and 90-day post-implantation in C57/B6 mice, whereas the SIS only mildly improved function at 90-day post-implantation. Moreover, the SIS and SIS-cell patches improved vascularization and suppressed MI-induced cardiomyocyte hypertrophy and expression of Col1 and Col3, but only the SIS-hCM and the SIS-Mix patches increased the ratio of collagen III/I fibers in the infarcted hearts. Further, the SIS-cell patches stimulated cardiomyocyte proliferation via paracrine action. Notably, the SIS-Mix had better improvements in cardiac function and structure, engraftments, and cardiomyocyte proliferation. Proteomic analysis showed distinct biological functions of exclusive proteins secreted from hCVPCs and hCMs, and more exclusive proteins secreted from co-cultivated hCVPCs and hCMs than mono-cells involving in various functional processes essential for infarct repair. These findings are the first to demonstrate the efficacy and mechanisms of mono- and dual-hCVPC- and hCM-seeding SIS-ECM for repair of infarcted hearts based on the side-by-side comparison.

关键词： Induced human pluripotent stem cells Cardiac lineage cells Extracellular matrix patch Cardiomyocyte regeneration Infarcted heart repair

MicroRNA-34c-5p provokes isoprenaline-induced cardiac hypertrophy by modulating autophagy via targeting ATG4B

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Acta Pharmaceutica Sinica B 2022年第5期12卷 2374-2390页

作者： Yuhong Zhang Yanqing ding Min Li Jing Yuan Youhui Yu Xueying bi Huiqi Hong Jiantao Ye Peiqing Liu Department of Pharmacology and Toxicology School of Pharmaceutical SciencesNational and Local United Engineering Lab of Druggability and New Drugs EvaluationSun Yat-sen UniversityGuangzhou 510006China State Key Laboratory of Oncology in Southern China Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhou 510006China

Pathological cardiac hypertrophy serves as a significant foundation for cardiac dysfunction and heart failure. Recently, growing evidence has revealed that microRNAs(miRNAs) play multiple roles in biological processes and participate in cardiovascular diseases. In the present research, we investigate the impact of miRNA-34 c-5 p on cardiac hypertrophy and the mechanism involved. The expression of miR-34 c-5 p was proved to be elevated in heart tissues from isoprenaline(ISO)-infused mice. ISO also promoted miR-34 c-5 p level in primary cultures of neonatal rat cardiomyocytes(NRCMs). Transfection with miR-34 c-5 p mimic enhanced cell surface area and expression levels of foetal-type genes atrial natriuretic factor(Anf) and β-myosin heavy chain(β-Mhc) in NRCMs. In contrast, treatment with miR-34 c-5 p inhibitor attenuated ISO-induced hypertrophic responses. Enforced expression of miR-34 c-5 p by tail intravenous injection of its agomir led to cardiac dysfunction and hypertrophy in mice, whereas inhibiting miR-34 c-5 p by specific antagomir could protect the animals against ISO-triggered hypertrophic abnormalities. Mechanistically, miR-34 c-5 p suppressed autophagic flux in cardiomyocytes, which contributed to the development of hypertrophy. Furthermore, the autophagy-related gene 4 B(ATG4 B) was identified as a direct target of miR-34 c-5 p, and miR-34 c-5 p was certified to interact with 3’untranslated region of Atg4 b mRNA by dual-luciferase reporter assay. miR-34 c-5 p reduced the expression of ATG4 B, thereby resulting in decreased autophagy activity and induction of hypertrophy. Inhibition of miR-34 c-5 p abolished the detrimental effects of ISO by restoring ATG4 B and increasing autophagy. In conclusion, our findings illuminate that miR-34 c-5 p participates in ISO-induced cardiac hypertrophy, at least partly through suppressing ATG4 B and autophagy. It suggests that regulation of miR-34 c-5 p may offer a new way for handling hypertrophy-related cardiac dysfunction.

关键词： Pathological cardiac hypertrophy Isoprenaline miR-34c-5p ATG4B LC3 Autophagy Autophagic flux Neonatal rat cardiomyocytes Mice

Real-time recognition of human lower-limb locomotion based on exponential coordinates of relative rotations

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Science China(Technological Sciences) 2021年第7期64卷 1423-1435页

作者： XU sen ding Ye State Key Laboratory of Mechanical System and Vibration School of Mechanical EngineeringShanghai Jiao Tong UniversityShanghai200240China

This paper proposes a data-driven method using a parametric representation of relative rotations to classify human lower-limb locomotion, which is designed for wearable robots. Three Inertial measurement units(IMUs) are mounted on the subject's waist,left knee, and right knee, respectively. Features for classification comprise relative rotations, angular velocities, and waist acceleration. Those relative rotations are represented by the exponential coordinates. The rotation matrices are normalized by Karcher mean and then the Support Vector Machine(SVM) method is used to train the data. Experiments are conducted with a time-window size of less than 40 ms. Three SVM classifiers telling 3, 5 and 6 rough lower-limb locomotion types respectively are trained, and the average accuracies are all over 98%. With the combination of those rough SVM classifiers, an easy SVMbased ensembled-system is proposed to classify 16 fine locomotion types, achieving the average accuracy of 98.22%, and its latency is 18 ms when deployed to an onboard computer.

关键词： locomotion recognition exponential coordinate relative rotation support vector machine

Metastatic renal cell carcinoma to vagina and review of literature

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Chinese Medical Journal 2013年第9期126卷 1793-1793页

作者： SUN ding-qi LU Jia-ju CAO Qing-wei ZHANG Hui TIAN Yong-jie bi Dong-bin ding sen-tai Deparment of Urology Deparment of Gynaccology and Obstetrics Provincial Hospital Affiliatcd to Shandong University Jinan Shandong 250021 China

To the editor： Renal cell carcinoma （RCC） is a malignant kidney tumor that originates fiom renal tubular epithelialsystem, and 30% of patients with RCC have metastasis at the time of initial diagnosis.1 Frequent sites of RCC metastases include lung, regional lymphatic nodes, liver, bone, and brain,2 while vaginal metastasis of RCC was extremely rare and mostly occurred in the left kidney. We reported a rare case of a patient with metastatic RCC to vagina and investigated the symptoms, diagnosis, therapies, and possible metastatic mechanisms.

关键词：癌肾细胞肺肝骨和骨组织肾胰岛素阴道综述

Large-scale computational screening of metal–organic frameworks for D_(2)/H_(2) separation

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Chinese Journal of Chemical Engineering 2023年第2期54卷 323-330页

作者： Fei Wang Zhiyuan bi Lifeng ding Qingyuan Yang State Key Laboratory of Organic-Inorganic Composites Beijing University of Chemical TechnologyBeijing 100029China College of Information Science and Technology Beijing University of Chemical TechnologyBeijing 100029China Department of Chemistry Xi'an Jiaotong-Liverpool UniversitySuzhou 215123China

Deuterium(D_(2)) is one of the important fuel sources that power nuclear fusion reactors. The existing D_(2)/H_(2) separation technologies that obtain high-purity D_(2) are cost-intensive. Recent research has shown that metal-organic frameworks(MOFs) are of good potential for D_(2)/H_(2) separation application. In this work, a high-throughput computational screening of 12020 computation-ready experimental MOFs is carried out to determine the best MOFs for hydrogen isotope separation application. Meanwhile, the detailed structure-performance correlation is systematically investigated with the aid of machine learning. The results indicate that the ideal D_(2)/H_(2) adsorption selectivity calculated based on Henry coefficient is strongly correlated with the 1/ΔAD feature descriptor;that is, inverse of the adsorbility difference of the two adsorbates. Meanwhile, the machine learning(ML) results show that the prediction accuracy of all the four ML methods is significantly improved after the addition of this feature descriptor. In addition, the ML results based on extreme gradient boosting model also revealed that the 1/ΔAD descriptor has the highest relative importance compared to other commonly-used descriptors. To further explore the effect of hydrogen isotope separation in binary mixture, 1548 MOFs with ideal adsorption selectivity greater than 1.5 are simulated at equimolar conditions. The structure-performance relationship shows that high adsorption selectivity MOFs generally have smaller pore size(0.3-0.5 nm) and lower surface area. Among the top 200 performers, the materials mainly have the sql, pcu, cds, hxl, and ins topologies.Finally, three MOFs with high D_(2)/H_(2) selectivity and good D_(2) uptake are identified as the best candidates,of all which had one-dimensional channel pore. The findings obtained in this work may be helpful for the identification of potentially promising candidates for hydrogen isotope separation.

关键词： Metal–organic frameworks Computational screening Hydrogen isotope separation

An alternative surgical technique for varicoceles:a preliminary experience of the microsurgical spermatic(distal end)-inferior or superficial epigastric vein anastomosis in symptomatic varicoceles associated with perineal pain

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Asian Journal of Andrology 2022年第6期24卷 624-627页

作者： Zi Wan Hai-Ming Cao bi-Cheng Yang Yong Gao Li ding Peng Luo Guang-Wen Yang Lin Ma Chun-Hua Deng The Andrology Department The First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China The Andrology Department The Reproductive Medicine CenterThe Seventh Affiliated HospitalSun Yat-sen UniversityShenzhen 518107China The Reproductive Medicine Center The Key Laboratory for Reproductive Medicine of Guangdong ProvinceThe First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China The Pathology Department The First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China The Urology Department Tongren Municipal People's HospitalTongren 554399China The Reproductive Medicine Center The Seventh Affiliated HospitalSun Yat-sen UniversityShenzhen 518107China

Many therapies are effective in treating varicoceles,including dilation of the pampiniform plexus in males.The most common method of treatment is varicocelectomy.We aimed to assess an alternative technique(microsurgical spermatic[distal end]-superficial or inferior epigastric vein anastomosis)that preserves the normal blood flow pattern for varicocele treatment.We retrospectively analyzed 27 men with varicocele between October 2019 and July 2020.All patients underwent microsurgical spermatic(distal end)-superficial or inferior epigastric vein anastomosis.The prognosis was reviewed retrospectively with an additional survey conducted 3 months after surgery.The mean±standard deviation of the age was 26.1±7.3 years in patients with microsurgical spermatic(distal end)-superficial or inferior epigastric vein anastomosis.The maximum diameter of the varicocele vein,perineal pain score,sperm density,and forward movement of sperm improved over 3 months after surgery.Microsurgical spermatic(distal end)-superficial or inferior epigastric vein anastomosis is a safe and efficient surgical treatment for varicoceles.

关键词： microsurgery pain varicocele vein anastomosis

Formation mechanism of Fe-based amorphous powders produced by spark erosion

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Journal of Materials Science & Technology 2024年第3期170卷 33-46页

作者： Chekai Liu Ran Li Jiazi bi ding Ma Xiaobin Liu Tao Zhang School of Materials Science and Engineering Key Laboratory of Aerospace Materials and Performance(Ministry of Education)Beihang UniversityBeijing 100191China

Spark erosion is a convenient,flexible,and low-cost method to quickly produce fine powders of metals,alloys,and semiconductors in size ranging from nearly a hundred micrometers to submicrometer by repetitive spark discharges.Due to the complexity of the powder-forming journey,normally accompanied by high temperature,high pressure,decomposition,diffusion and rapid quenching caused by discharge plasma,the mechanisms of powder formation and possible contaminant infiltration are still controversial,posing a significant challenge to control particle size and chemical composition of the powder produced by this method.In this study,Fe-based amorphous powders in different particle-size distributions with high sphericity were fabricated by spark erosion under different discharge-energy conditions.The max-imum particle size of the resultant powders can be correlated with discharge parameters,crater depth,and crater radius,respectively.A multi-ring-breakup model is proposed to reveal the particle-size distribution of the powder formed from the electrode melt under a single-pulse discharge.Furthermore,a dielectric-element infiltration model is provided to quantitatively evaluate the infiltration mass ratio of the contaminant elements,stemming from the decomposed products of dielectric liquid,in the resultant powder with different particle sizes.The models verified through the experimental data are significant for the development of high-performance fine Fe-based amorphous powder with controlled particle size and chemical composition.

关键词： Amorphous alloy Particle Spark erosion Infiltration Modeling

Multipoint Heave Motion Prediction Method for Ships Based on the PSO-TGCN Model

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China Ocean Engineering 2023年第6期37卷 1022-1031页

作者： ding Shi-feng MA Qun ZHOU Li HAN sen DONG Wen-bo School of Naval Architecture and Ocean Engineering Jiangsu University of Science and TechnologyZhenjiang 212003China School of Naval Architecture Ocean and Civil EngineeringShanghai Jiao Tong UniversityShanghai 200240China

During ship operations,frequent heave movements can pose significant challenges to the overall safety of the ship and completion of cargo loading.The existing heave compensation systems suffer from issues such as dead zones and control system time lags,which necessitate the development of reasonable prediction models for ship heave movements.In this paper,a novel model based on a time graph convolutional neural network algorithm and particle swarm optimization algorithm(PSO-TGCN)is proposed for the first time to predict the multipoint heave movements of ships under different sea conditions.To enhance the dataset's suitability for training and reduce interference,various filter algorithms are employed to optimize the dataset.The training process utilizes simulated heave data under different sea conditions and measured heave data from multiple points.The results show that the PSO-TGCN model predicts the ship swaying motion in different sea states after 2 s with 84.7%accuracy,while predicting the swaying motion in three different positions.By performing a comparative study,it was also found that the present method achieves better performance that other popular methods.This model can provide technical support for intelligent ship control,improve the control accuracy of intelligent ships,and promote the development of intelligent ships.

关键词： ship motion prediction time delay multipoint forecast time-graph convolutional neural network particle swarm optimization

Prognosis of hepatocellular carcinoma with bile duct tumor thrombus after R0 resection:a matched study

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Hepatobiliary & Pancreatic Diseases International 2016年第6期15卷 626-632页

作者： ding-ding Wang Li-Qun Wu Zu-sen Wang Division of Hepatobiliary Pancreatic Surgery The Affiliated Hospital of Qingdao University

BACKGROUND： Hepatocellular carcinoma （HCC） with bile duct tumor thrombus （BDTT） is rare. The present study aimed to determine post-surgical prognoses in HCC patients with BDTT, as outcomes are currently unclear. METHODS： We compared the prognoses of 110 HCC patients without BDTT （group A） to 22 cases with BDTT （group B）. The two groups were matched in age, gender, tumor etiology, size, number, portal vascular invasion, and TNM stage. Additionally, 28 HCC patients with BDTT were analyzed to identify prognostic risk factors. RESULTS： The 1-, 3-, and 5-year overall survival rates were 90.9%, 66.9%, and 55.9% for group A and 81.8%, 50.0%, and 37.5% for group B, respectively. The median survival time in groups A and B was 68.8 and 31.4 months, respectively （P=0.043）. The patients for group B showed higher levels of serum total bilirubin, alanine aminotransferase and gammaglutamyl transferase, a larger hepatectomy range, and a higher rate of anatomical resection. In subgroup analyses of patients with BDTT who underwent R0 resection, TNM stage Ⅲ-Ⅳ was an independent risk factor for overall survival; these patients had worse prognoses than those with TNM stage Ⅰ-Ⅱ after R0 resection （hazard ratio=6.056, P=0.014）. Besides, univariate and multivariate analyses revealed that non-R0 resection and TNM stage Ⅲ-Ⅳ were independent risk factors for both disease-free survival and overall survival of 28 HCC patients with BDTT. The median overall survival time of patients with BDTT who underwent R0 resection was longer than that of patients who did not undergo R0 resection （31.0 vs 4.0 months, P=0.007）.CONCLUSIONS： R0 resection prolonged survival time in HCC patients with BDTT, although prognosis remains poor. For such patients, R0 resection is an important treatment that determines long-term survival.

关键词： hepatocellular carcinoma bile duct tumor thrombus prognosis recurrence R0 resection