المؤلفون: Gao, Jiayu, Zhao, Yahui, Wang, Ziwei, Liu, Fei, Chen, Xuan, Mo, Jialin, Jiang, Yifei, Liu, Yongqiang, Tian, Peiyi, Li, Yanong, Deng, Kaiwen, Qi, Xueling, Han, Dongming, Liu, Zijia, Yang, Zhengtao, Chen, Yixi, Tang, Yujie, Li, Chunde, Liu, Hailong, Li, Jiankang, Jiang, Tao

المساهمون: National Key Research and Development Program of China, National Natural Science Foundation of China

المصدر: Animal Models and Experimental Medicine ; ISSN 2576-2095 2576-2095

الوصف: Background Medulloblastoma (MB) is one of the most common malignant brain tumors that mainly affect children. Various approaches have been used to model MB to facilitate investigating tumorigenesis. This study aims to compare the recapitulation of MB between subcutaneous patient‐derived xenograft (sPDX), intracranial patient‐derived xenograft (iPDX), and genetically engineered mouse models (GEMM) at the single‐cell level. Methods We obtained primary human sonic hedgehog (SHH) and group 3 (G3) MB samples from six patients. For each patient specimen, we developed two sPDX and iPDX models, respectively. Three Patch+/− GEMM models were also included for sequencing. Single‐cell RNA sequencing was performed to compare gene expression profiles, cellular composition, and functional pathway enrichment. Bulk RNA‐seq deconvolution was performed to compare cellular composition across models and human samples. Results Our results showed that the sPDX tumor model demonstrated the highest correlation to the overall transcriptomic profiles of primary human tumors at the single‐cell level within the SHH and G3 subgroups, followed by the GEMM model and iPDX. The GEMM tumor model was able to recapitulate all subpopulations of tumor microenvironment (TME) cells that can be clustered in human SHH tumors, including a higher proportion of tumor‐associated astrocytes and immune cells, and an additional cluster of vascular endothelia when compared to human SHH tumors. Conclusions This study was the first to compare experimental models for MB at the single‐cell level, providing value insights into model selection for different research purposes. sPDX and iPDX are suitable for drug testing and personalized therapy screenings, whereas GEMM models are valuable for investigating the interaction between tumor and TME cells.

الإتاحة: https://doi.org/10.1002/ame2.12399Test

المؤلفون: Chen, Yixi

المساهمون: Kunath, Tilo, Rosser, Susan

مصطلحات موضوعية: 573.8, Parkinson’s disease, cell replacement therapy, midbrain dopaminergic progenitors, mDA, Lewy body, a-Synuclein, a-Syn

الوصف: An experimental treatment for Parkinson’s disease (PD) involved the transplantation of fetal midbrain tissue, a source of midbrain dopaminergic (mDA) progenitors, into the striatum of patients to restore dopaminergic innervation. Although clinical benefits were experienced by some patients, this heterogeneous and scarce source of tissue is not sustainable. Recently, mDA progenitors differentiated from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) are comparably potent and efficient as fetal midbrain tissue in rescuing dopaminergic deficits in PD animal models and clinical trials using this cell product are progressing. However, the hESC/hiPSC-derived mDA grafts are still susceptible to the development of Lewy body pathology, as found in clinical trials using fetal tissues. The clinical benefits of the fetal grafts reduced in correlation with the accumulation of Lewy body pathology, therefore, a pathology-resistant graft would be longer-lasting and beneficial to patients. For in vitro modelling of Lewy body pathology, which is an inclusion pathology mainly consist of misfolded α-Synuclein (α-Syn) aggregates, I treated hESC-derived mDA neurons with α-Syn pre-formed fibrils (PFFs). PFFs recruit endogenous α-Syn to form Lewy body-like aggregates which are positive for phospho-serine 129 α-Syn (pS129-αSyn), ubiquitin and p62. The PFF models also recapitulate other aspects of PD, such as synaptic and mitochondrial dysfunction, neuroinflammation and neurodegeneration. Since endogenous α-Syn is essential for the development of aggregates, I attempted to produce pathology-resistant neurons by knocking out α-Syn (SNCA) in hESCs with CRISPR/Cas9n and subsequently differentiating the SNCA+/– and SNCA–/– hESCs into mDA neurons. As α-Syn might play physiological roles which are not yet fully elucidated, I created a single amino acid (S87E) mutation in α-Syn, aiming to reduce α-Syn aggregation without disruption of α-Syn physiological functions. Half of the resulting CRISPR-engineered SNCA+/–, SNCA–/– and SNCAS87E/S87E hESC clones exhibited normal genomic integrity, free from detectable copy number variations (CNVs), large copy-neutral loss of heterozygosity (CN-LOH), off-target events and integration of targeting plasmids. Subsequently, mDA neurons were differentiated from SNCA+/–, SNCA–/– and SNCAS87E/S87E hESCs and they highly resembled mDA neurons derived from WT parental hESCs based on marker analysis and RNAseq. This data suggested that the α-Syn mutations, as well as the selection and cloning process, did not impair mDA differentiation. Synapse formation, spontaneous activities and dopamine secretion were readily observed in mDA neurons of all tested genotypes. The WT mDA neurons treated with PFFs recapitulated pS129-αSyn pathology, but did not result in detectable cell death or significant impairment of synapse formation, mitochondrial morphology or spontaneous neuronal activities within the timeframe of the current study. SNCA+/–, SNCA–/– and SNCAS87E/S87E mDA neurons treated with PFFs revealed that SNCA+/– exhibited significantly less, while SNCA–/– showed no pS129-αSyn pathology and SNCAS87E/S87E exhibited a reduced level of pathology compared to WT mDA neurons. The PFF-treated hESC-derived mDA neuron model established in this study could be used as an effective platform for drug screening. In addition, SNCA+/– and SNCA–/– hESC-derived cells could be valuable cell models for studying the physiological role of α-Syn. On the condition of satisfactory validation in animal models, SNCA+/– and SNCA–/– hESC-derived mDA progenitors would have significant potential in cell replacement therapy for PD.

الوصول الحر: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.818618Test

المؤلفون: Wang‐Chen, Yixi, Kellow, Nicole J., Choi, Tammie S. T.

المصدر: Journal of Human Nutrition and Dietetics ; volume 36, issue 4, page 1576-1588 ; ISSN 0952-3871 1365-277X

الوصف: Background The present study aimed to qualitatively explore the food choice determinants of both Chinese immigrants living in Australia and Chinese people living in mainland China. Methods Eight Chinese Australian participants (female, n = 5; male, n = 3) and ten mainland Chinese participants (female, n = 5; male, n = 5) were recruited from Australia (primarily in Melbourne, Victoria) and China (predominantly in Zhengzhou, Henan province) between June 2021 and March 2022. Participants were diverse in age, socio‐economic background, occupation and health status. Semi‐structured in‐depth interviews were conducted in Mandarin either face‐to‐face or using online video/voice calls. Interviews were audio‐recorded and transcribed verbatim. Investigator triangulation was used to enhance scientific rigour. Results Four themes were identified: (1) food choice determinants were shaped by traditional and modern nutrition perceptions and personal food philosophy; (2) physiological responses to food provide direct feedback that impacts future food choices; (3) consideration of convenience was a predominant influencer of food choice; and (4) the differences in food environments between China and Australia promoted distinctive food choice determinants for Chinese people. Conclusions Chinese Australian and mainland Chinese participants' food choices are shaped by traditional Chinese nutrition philosophy, modern Western nutrition science and the contemporary food environment. There are clear cultural characteristics in their food choice determinants that should be considered by health educators, nutrition professionals and nutrition policymakers when developing culturally appropriate health interventions for Chinese people.

الإتاحة: https://doi.org/10.1111/jhn.13147Test

المؤلفون: Yang, Mengfang, Jiao, Yuzhou, Yan, Yuanyuan, Li, Lisha, Hu, Xiaoshuai, Jiao, Zhe, Li, Mengxia, Chen, Yixi, Shi, Yuejun, Shen, Zhou, Peng, Guiqing

المساهمون: National Science Fund for Distinguished Young Scholars, Joint Fund of the National Natural Science Foundation of China and the Karst Science Research Center of Guizhou Province, National Natural Science Foundation of China, China National Funds for Distinguished Young Scientists

المصدر: Veterinary Microbiology ; volume 281, page 109728 ; ISSN 0378-1135

مصطلحات موضوعية: General Veterinary, General Medicine, Microbiology

الإتاحة: https://doi.org/10.1016/j.vetmic.2023.109728Test
https://api.elsevier.com/content/article/PII:S0378113523000809?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0378113523000809?httpAccept=text/plainTest

المؤلفون: Xie, Yunfei, Chen, Chener, Zhang, Ding, Jiao, Zhe, Chen, Yixi, Wang, Gang, Tan, Yubei, Zhang, Wanpo, Xiao, Shaobo, Peng, Guiqing, Shi, Yuejun

المساهمون: He, Biao, MOST | National Key Research and Development Program of China, MOST | NSFC | National Science Fund for Distinguished Young Scholars

المصدر: Microbiology Spectrum ; volume 11, issue 6 ; ISSN 2165-0497

الوصف: Endoribonuclease non-structural protein 15 (nsp15) (EndoU) is conserved among coronaviruses (CoVs) and is crucial for viral replication, evasion of the innate immune system, and virulence. EndoU-deficient CoVs can activate the interferon (IFN) response and attenuate their virulence, and nsp15 is considered the target of attenuated vaccine development. Among alpha-CoVs, transmissible gastroenteritis virus (TGEV) and feline infectious peritonitis virus (FIPV) cause lethal diseases in piglets and cats, but the role of EndoU in viral propagation and virulence remains unclear. Here, we verified the TGEV and FIPV EndoU active sites His226 and His241 and found that the antagonization of SeV-induced IFN-β production by nsp15 depends on its EndoU activity. Furthermore, we constructed infectious clones of wild-type (WT) and EndoU-deficient (EnUmt) TGEV and FIPV. Unexpectedly, we found that both the WT and EnUmt viruses propagated efficiently in multiple types of immunocompetent (PK-15, IPI-2I, ST, CRFK, F81, and Fcwf-4) cells. Moreover, the results of infection experiments showed that compared with piglets and cats infected with the WT, the EnUmt virus-infected piglets and cats did not exhibit significantly reduced mortality, tissue injury, or viral shedding. Specially, the death of cats infected with EnUmt-FIPV occurred earlier than that of cats infected with WT. Hence, our results suggest that the function of EndoU is conserved, but nsp15-mediated regulation of the propagation and pathogenesis of CoVs are diverse. Our findings provide a reference for an in-depth understanding of EndoU-mediated immune escape and pathogenicity in CoVs. IMPORTANCE Understanding the role of the endoribonuclease non-structural protein 15 (nsp15) (EndoU) in coronavirus (CoV) infection and pathogenesis is essential for vaccine target discovery. Whether the EndoU activity of CoV nsp15, as a virulence-related protein, has a diverse effect on viral virulence needs to be further explored. Here, we found that the transmissible ...

الإتاحة: https://doi.org/10.1128/spectrum.02209-23Test

المؤلفون: Ma, Yuting, Guo, Sicheng, Chen, Yixi, Peng, Yushan, Su, Xi, Jiang, Hui, Lin, Xiumei, Zhang, Jianguo

المصدر: Scientific Data; 6/12/2024, Vol. 11 Issue 1, p1-11, 11p

مصطلحات موضوعية: NEURAL development, CHROMATIN, AGING, OLFACTORY bulb, REGULATOR genes, OLFACTORY receptors

مستخلص: The development and aging of the brain constitute a lifelong dynamic process, marked by structural and functional changes that entail highly coordinated cellular differentiation and epigenetic regulatory mechanisms. Chromatin accessibility serves as the foundational basis for genetic activity. However, the holistic and dynamic chromatin landscape that spans various brain regions throughout development and ageing remains predominantly unexplored. In this study, we employed single-nucleus ATAC-seq to generate comprehensive chromatin accessibility maps, incorporating data from 69,178 cells obtained from four distinct brain regions – namely, the olfactory bulb (OB), cerebellum (CB), prefrontal cortex (PFC), and hippocampus (HP) – across key developmental time points at 7 P, 3 M, 12 M, and 18 M. We delineated the distribution of cell types across different age stages and brain regions, providing insight into chromatin accessible regions and key transcription factors specific to different cell types. Our data contribute to understanding the epigenetic basis of the formation of different brain regions, providing a dynamic landscape and comprehensive resource for revealing gene regulatory programs during brain development and aging. [ABSTRACT FROM AUTHOR]

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المؤلفون: Ma, Yongjie, Chen, Yixi, Lin, Shengru, Guan, Jian, Lin, Liangguang

المساهمون: China Southern Power Grid

المصدر: 2024 4th International Conference on Neural Networks, Information and Communication (NNICE)

الإتاحة: https://doi.org/10.1109/nnice61279.2024.10499008Test
http://xplorestaging.ieee.org/ielx7/10498130/10498125/10499008.pdf?arnumber=10499008Test

المؤلفون: Chen, Yixi, Zhu, Jizhong, Liu, Yun, Zhang, Le, Zhou, Jialin

المساهمون: Basic and Applied Basic Research Foundation of Guangdong Province, High-end Foreign Experts

المصدر: IEEE Transactions on Power Systems ; volume 39, issue 2, page 4446-4458 ; ISSN 0885-8950 1558-0679

مصطلحات موضوعية: Electrical and Electronic Engineering, Energy Engineering and Power Technology

الإتاحة: https://doi.org/10.1109/tpwrs.2023.3298486Test
http://xplorestaging.ieee.org/ielx7/59/10443973/10192371.pdf?arnumber=10192371Test

المؤلفون: Zhang, Wenlong, Chen, Yixi, Ma, Zhiwei, Sun, Zhongxu, Wang, Jiahui, Feng, Jiangtao, Yan, Wei, Wang, Hongjie

المصدر: Fuel ; volume 369, page 131741 ; ISSN 0016-2361

الإتاحة: https://doi.org/10.1016/j.fuel.2024.131741Test
https://api.elsevier.com/content/article/PII:S0016236124008895?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0016236124008895?httpAccept=text/plainTest

المؤلفون: Jiao, Zhe, Wang, Pengpeng, Hu, Xiaoshuai, Chen, Yixi, Xu, Juan, Zhang, Jintao, Wu, Benyuan, Luo, Ruxue, Shi, Yuejun, Peng, Guiqing

المساهمون: National Science Fund for Distinguished Young Scholars, Fundamental Research Funds for the Central Universities, National Natural Science Foundation of China

المصدر: Antiviral Research ; volume 222, page 105794 ; ISSN 0166-3542

مصطلحات موضوعية: Virology, Pharmacology

الإتاحة: https://doi.org/10.1016/j.antiviral.2024.105794Test
https://api.elsevier.com/content/article/PII:S0166354224000020?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0166354224000020?httpAccept=text/plainTest