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54. Controlling Morphology and Functions of Cardiac Organoids by Two-Dimensional Geometrical Templates.

Author

Hoang, Plansky, Sun, Shiyang, Tarris, Bearett A., and Ma, Zhen

Subjects
*QUADRILATERALS, *PLURIPOTENT stem cells, *ORGANOIDS, *INDUCED pluripotent stem cells
Abstract

Traditionally, tissue-specific organoids are generated as 3D aggregates of stem cells embedded in Matrigel or hydrogels, and the aggregates eventually end up a spherical shape and suspended in the matrix. Lack of geometrical control of organoid formation makes these spherical organoids limited for modeling the tissues with complex shapes. To address this challenge, we developed a new method to generate 3D spatial-organized cardiac organoids from 2D micropatterned human induced pluripotent stem cell (hiPSC) colonies, instead of directly from 3D stem cell aggregates. This new approach opens the possibility to create cardiac organoids that are templated by 2D non-spherical geometries, which potentially provides us a deeper understanding of biophysical controls on developmental organogenesis. Here, we designed 2D geometrical templates with quadrilateral shapes and pentagram shapes that had same total area but different geometrical shapes. Using this templated substrate, we grew cardiac organoids from hiPSCs and collected a series of parameters to characterize morphological and functional properties of the cardiac organoids. In quadrilateral templates, we found that increasing the aspect ratio impaired cardiac tissue 3D self-assembly, but the elongated geometry improved the cardiac contractile functions. However, in pentagram templates, cardiac organoid structure and function were optimized with a specific geometry of an ideal star shape. This study will shed a light on "organogenesis-by-design" by increasing the intricacy of starting templates from external geometrical cues to improve the organoid morphogenesis and functionality. [ABSTRACT FROM AUTHOR]

Published
2023
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62. A neonatal mouse model of Enterovirus D68 infection induces both interstitial pneumonia and acute flaccid myelitis

Author

Sun Shiyang, Ying Fu, Fan Gao, Lianlian Bian, Yao Su, Xing Wu, Yalin Hu, Zhenglun Liang, Ruixiao Du, and Qunying Mao

Subjects
0301 basic medicine, Pathology, medicine.medical_specialty, Necrosis, 030106 microbiology, Antibodies, Viral, Tachypnea, Lethal Dose 50, Pathogenesis, Mice, 03 medical and health sciences, Virology, Enterovirus Infections, medicine, Animals, Tropism, Enterovirus D, Human, Pharmacology, Mice, Inbred BALB C, Lung, business.industry, Immunization, Passive, Neuromuscular Diseases, Myelitis, Viral Load, medicine.disease, Spinal cord, Acute flaccid myelitis, Mice, Inbred C57BL, Disease Models, Animal, Viral Tropism, Pneumonia, 030104 developmental biology, medicine.anatomical_structure, Animals, Newborn, Central Nervous System Viral Diseases, Female, medicine.symptom, Lung Diseases, Interstitial, business
Abstract

Enterovirus D68 (EV-D68) is a causative agent of recent outbreaks of severe respiratory illness, pneumonia and acute flaccid myelitis (AFM) worldwide. The study of the pathogenesis, vaccines and anti-viral drugs for EV-D68 infection has been reported. Given the previously described mouse model of EV-D68, we sought to establish a neonatal mice model inducing both pneumonia and AFM. The neonatal BALB/c mice were inoculated intraperitoneally with the EV-D68 strain (named15296-virus) which was produced by the reverse genetics method. The infected mice displayed limb paralysis, tachypnea and even death, which were similar to the clinical symptoms of human infections. Moreover, the results of histopathologic examination and immunohistochemical staining showed acidophilic necrosis in the muscle, the spinal cord and alveolar wall thickening in the lung, indicating that EV-D68 exhibited strong tropism to the muscles, spinal cord and lung. Furthermore, the results of real-time PCR also suggested that the viral loads in the blood, spinal cord, muscles and lung were higher than those in other tissues at different time points post-infection. Additionally, the neonatal mouse model was used for evaluating the EV-D68 infection. The results of the anti-serum passive and maternal antibody protection indicated that the neonatal mice could be protected against the EV-D68 challenge, and displayed that both the serum of 15296-virus and prototype-virus (Fermon) were performing a certain cross-protective activity against the 15296-virus challenge. In summary, the above results proved that our neonatal mouse model possessed not only the interstitial pneumonia and AFM simultaneously but also a potentiality to evaluate the protective effects of EV-D68 vaccines and anti-viral drugs in the future.

Published
2019

67. Engineering spatial-organized cardiac organoids for developmental toxicity testing

Author

Hoang, Plansky, primary, Kowalczewski, Andrew, additional, Sun, Shiyang, additional, Winston, Tackla S., additional, Archilla, Adriana M., additional, Lemus, Stephanie M., additional, Ercan-Sencicek, A. Gulhan, additional, Gupta, Abha R., additional, Liu, Wenzhong, additional, Kontaridis, Maria I., additional, Amack, Jeffrey D., additional, and Ma, Zhen, additional

Published
2021
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70. A cross-sectional seroepidemiology study of EV-D68 in China

Author

Yao Su, Qunying Mao, Xing Wu, Fan Gao, Fengcai Zhu, Yalin Hu, Sun Shiyang, Lianlian Bian, Zhenglun Liang, Ruixiao Du, and Ying Fu

Subjects
Adult, Male, 0301 basic medicine, China, Pediatrics, medicine.medical_specialty, Adolescent, Epidemiology, Cross-sectional study, Immunology, Prevalence, Antibodies, Viral, Microbiology, Article, Young Adult, 03 medical and health sciences, Blood serum, Pregnancy, Seroepidemiologic Studies, Virology, Drug Discovery, Enterovirus Infections, medicine, Humans, Seroprevalence, Child, Phylogeny, Enterovirus D, Human, Respiratory tract infections, business.industry, Infant, General Medicine, Antibodies, Neutralizing, Acute flaccid myelitis, Vaccination, Cross-Sectional Studies, 030104 developmental biology, Infectious Diseases, Child, Preschool, Female, Parasitology, Pregnant Women, business
Abstract

Enterovirus 68 (EV-D68) is associated with respiratory diseases, such as acute upper respiratory tract infections (URTIs), lower respiratory tract infections (LRTIs), pneumonia, neurological diseases, and acute flaccid myelitis (AFM). In recent years, there have been global outbreaks of EV-D68 epidemics. However, there is no effective vaccine against EV-D68, and the understanding of the seroprevalence characteristics of EV-D68 is limited. To evaluate the epidemiological features of this emerging infection in mainland China, serum samples from 20 pairs of pregnant women and their neonates, 405 infants and children (ages 1 month-15 years), and 50 adults were collected to measure EV-D68 neutralizing antibodies (NtAbs). The results showed that the geometric mean titers (GMTs) of pregnant women and their neonates were 168 (95%CI: 93.6-301.7) and 162.3 (95%CI: 89.9-293.1), respectively. The seroprevalence rate of EV-D68 antibodies was negatively correlated with age in 1-month-old to 12-month-old infants (84% for 1-month-old infants vs 10% for 1-year-old infants), whereas it was positively correlated with age for 1-year-old to 15-year-old children (10% for 1-year-old children vs 92% for 15-year-old children). This study evaluated maternal antibodies against EV-D68 in neonates. Our results showed that if mothers had high levels of anti-EV-D68 NtAbs, the NtAbs titers in their neonates were also high. The GMTs and seroprevalence rates of each age group indicated that EV-D68 infection was very common in China. Periodical EV-D68 seroprevalence surveys and vaccination campaigns should be the top priority for preventing EV-D68 infection.

Published
2018

77. Effect of freezing on recombinant hepatitis E vaccine

Author

Li, Kelei, primary, Dong, Fangyu, additional, Gao, Fan, additional, Bian, Lianlian, additional, Sun, Shiyang, additional, Du, Ruixiao, additional, Hu, Yalin, additional, Mao, Qunying, additional, Zheng, Haifa, additional, Wu, Xing, additional, and Liang, Zhenglun, additional

Published
2019
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78. Hand, foot, and mouth disease associated with coxsackievirus A10: more serious than it seems

Author

Qunying Mao, Zhenglun Liang, Siyuan Liu, Xiao-Ming Yang, Lianlian Bian, Sun Shiyang, Fan Gao, and Xing Wu

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Pediatrics, Genotype, 030106 microbiology, Disease, Coxsackievirus, Microbiology, Antiviral Agents, Hand-foot-and-mouth disease, Disease Outbreaks, 03 medical and health sciences, 0302 clinical medicine, stomatognathic system, Seroepidemiologic Studies, Virology, Epidemiology, medicine, Animals, Humans, 030212 general & internal medicine, Child, biology, business.industry, Public health, Viral Vaccines, medicine.disease, biology.organism_classification, Enterovirus A, Human, Infectious Diseases, business, Hand, Foot and Mouth Disease, Foot (unit)
Abstract

Hand, foot, and mouth disease (HFMD) is a common viral childhood illness, that has been a severe public health concern worldwide, particularly in the Asia-Pacific region. According to epidemiological data of HFMD during the past decade, the most prevalent causal viruses were enterovirus (EV)-A71, coxsackievirus (CV)-A16, CV-A6, and CV-A10. The public health burden of CV-A10-related diseases has been underestimated as their incidence was lower than that of EV-A71 and CV-A16 in most HFMD outbreaks. However, cases of CV-A10 infection are more severe, and its genome is more variable, which has alerted the research community worldwide. Areas covered: In this paper, studies on the epidemiology, laboratory diagnosis, clinical manifestations, molecular epidemiology, seroepidemiology, animal models of CV-A10, and vaccines and antiviral strategies against this genotype are reviewed. In addition, the genetic evolution of circulating strains was analyzed. Expert opinion: Multivalent vaccines against EV-A71, CV-A16, CV-A6, and CV-A10 should be a next-step HFMD vaccine strategy.

Published
2019

79. Design optimization of geometrically confined cardiac organoids enabled by machine learning techniques

Author

Kowalczewski, Andrew, Sun, Shiyang, Mai, Nhu Y., Song, Yuanhui, Hoang, Plansky, Liu, Xiyuan, Yang, Huaxiao, and Ma, Zhen

Abstract

Stem cell organoids are powerful models for studying organ development, disease modeling, drug screening, and regenerative medicine applications. The convergence of organoid technology, tissue engineering, and artificial intelligence (AI) could potentially enhance our understanding of the design principles for organoid engineering. In this study, we utilized micropatterning techniques to create a designer library of 230 cardiac organoids with 7 geometric designs. We employed manifold learning techniques to analyze single organoid heterogeneity based on 10 physiological parameters. We clustered and refined the cardiac organoids based on their functional similarity using unsupervised machine learning approaches, thus elucidating unique functionalities associated with geometric designs. We also highlighted the critical role of calcium transient rising time in distinguishing organoids based on geometric patterns and clustering results. This integration of organoid engineering and machine learning enhances our understanding of structure-function relationships in cardiac organoids, paving the way for more controlled and optimized organoid design.

Published
2024
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80. Seroepidemiology of Coxsackievirus A10 infection in infants and children: A prospective cohort study in Jiangsu, China

Author

Zheng-lun Liang, Lianlian Bian, Xing Wu, Qunying Mao, Fengcai Zhu, Chunlai Jiang, Ying Fu, Fan Gao, and Sun Shiyang

Subjects
0301 basic medicine, Microbiology (medical), Male, China, 030106 microbiology, Coxsackievirus, medicine.disease_cause, Hand-foot-and-mouth disease, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Seroepidemiologic Studies, medicine, Enterovirus 71, Humans, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Cytopathic effect, Enterovirus, biology, business.industry, Infant, Viral Vaccines, Enterovirus a71, biology.organism_classification, medicine.disease, Virology, Enterovirus A, Human, Geometric mean titer, Infectious Diseases, Child, Preschool, Female, business, Hand, Foot and Mouth Disease
Published
2018

81. Seroepidemiology of enterovirus D68 infection in infants and children in Jiangsu, China

Author

Jingxin Li, Zheng-lun Liang, Sun Shiyang, Qunying Mao, Jianwei Wang, Xing Wu, Fengcai Zhu, Lianlian Bian, Yalin Hu, and Fan Gao

Subjects
0301 basic medicine, Microbiology (medical), Male, Pediatrics, medicine.medical_specialty, China, Enterovirus D, 03 medical and health sciences, 0302 clinical medicine, Seroepidemiologic Studies, medicine, Enterovirus 71, Enterovirus Infections, Humans, Enterovirus d68 infection, 030212 general & internal medicine, Prospective Studies, Respiratory Tract Infections, Enterovirus D, Human, Clinical Trials as Topic, Respiratory tract infections, biology, business.industry, Infant, Newborn, Infant, Enterovirus a71, biology.organism_classification, Human enterovirus, Geometric mean titer, 030104 developmental biology, Infectious Diseases, Child, Preschool, Female, business
Published
2018

85. A potential therapeutic neutralization monoclonal antibody specifically against multi-coxsackievirus A16 strains challenge

Author

Du, Ruixiao, primary, Mao, Qunying, additional, Hu, Yalin, additional, Lang, Shuhui, additional, Sun, Shiyang, additional, Li, Kelei, additional, Gao, Fan, additional, Bian, Lianlian, additional, Yang, Ce, additional, Cui, Bopei, additional, Xu, Longfa, additional, Cheng, Tong, additional, and Liang, Zhenglun, additional

Published
2019
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88. First principle calculations study of AlN surface terminal structure evolution under different conditions.

Author

Sun, Shiyang, Sun, Shouye, Ren, Yuan, Tan, Xin, and Xu, Pingping

Subjects
*ALUMINUM nitride, *SURFACE energy, *SURFACE properties, *EVAPORATION (Chemistry), *ADSORPTION (Chemistry)
Abstract

The surface structure and properties of aluminum nitride (AlN) play an important role in many applications. Using the first principle calculations method, we analyzed the surface terminal structure of AlN and its evolution under different conditions by determining the surface energy, adsorption energy, and evaporation energy of the Al and N terminals on the AlN(0001) surface. Our results show that the reason why the N terminal is less stable than the Al terminal is not only because of its high surface energy but also because its adsorption performance is extremely sensitive to the adsorption position. The surface N atoms combine to form N2 molecules that escape during the evaporation process at high temperature. After surface N atoms escape, the AlN surface structure reconstitutes to form a 3×3−R30° hexagonal closest packing (HCP)–like structure, and the energy barrier for the reconstructing process is 3.2 eV. This shows that the structure and form of the AlN(0001) terminals depend on the environmental conditions. [ABSTRACT FROM AUTHOR]

Published
2020
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95. Synonymous codon usage analysis of hand, foot and mouth disease viruses: A comparative study on coxsackievirus A6, A10, A16, and enterovirus 71 from 2008 to 2015

Author

Su, Weiheng, primary, Li, Xue, additional, Chen, Meili, additional, Dai, Wenwen, additional, Sun, Shiyang, additional, Wang, Shuai, additional, Sheng, Xin, additional, Sun, Shixiang, additional, Gao, Chen, additional, Hou, Ali, additional, Zhou, Yan, additional, Sun, Bo, additional, Gao, Feng, additional, Xiao, Jingfa, additional, Zhang, Zhewen, additional, and Jiang, Chunlai, additional

Published
2017
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96. Characterization of human enterovirus71 virus-like particles used for vaccine antigens

Author

Zhao, Dandan, primary, Sun, Bo, additional, Sun, Shiyang, additional, Fu, Bin, additional, Liu, Chuntian, additional, Liu, Dawei, additional, Chu, Yanfei, additional, Ma, Youlei, additional, Bai, Lu, additional, Wu, Yongge, additional, Zhou, Yan, additional, Su, Weiheng, additional, Hou, Ali, additional, Cai, Linjun, additional, Xu, Fei, additional, Kong, Wei, additional, and Jiang, Chunlai, additional

Published
2017
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100. Development a scalable production process for truncated human papillomavirus type-6 L1 protein using WAVE Bioreactor and hollow fiber membrane

Author

Sun, Bo, primary, Zhao, Dandan, additional, Zhang, Xizhen, additional, Gu, Tiejun, additional, Yu, XiangHui, additional, Sun, Shiyang, additional, Zhao, Xinghong, additional, Wei, Liu, additional, Liu, Dawei, additional, Yan, Hui, additional, Meng, Xiangyu, additional, Kong, Wei, additional, Xu, Fei, additional, Yang, Ping, additional, and Jiang, Chunlai, additional

Published
2015
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