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nflammasomes in cancer： a double-edgecl sword

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Protein & Cell 2014年第1期5卷 12-20页

作者： Ryan Kolb guang-hui liu Ann M. Janowski Fayyaz S. Sutterwala Weizhou Zhang Department of Pathology Carver College of Medicine University of Iowa Iowa City IA 52242 USA National Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China Gene Expression Laboratory Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Graduate Program in Immunology Carver College Of Medicine University of Iowa iowa City IA 52242 USA Department of Internal Medicine Carver College of Medicine University of Iowa Iowa City IA 52242 USA Veterans Affairs Medical Center Iowa City IA 52241 USA

Chronic inflammatory responses have long been observed to be associated with various types of cancer and play decisive roles at different stages of cancer development. Inflammasomes, which are potent induc- ers of interleukin （IL）-I~ and IL-18 during infammation, are large protein complexes typically consisting of a Nod-like receptor （NLR）, the adapter protein ASC, and Caspase-1. During malignant transformation or cancer therapy, the inflammasomes are postulated to become activated in response to danger signals arising from the tumors or from therapy-induced damage to the tumor or healthy tissue. The activation of inflammasomes plays diverse and sometimes contrasting roles in cancer promotion and therapy depending on the specific con- text. Here we summarize the role of different inflamma- some complexes in cancer progression and therapy. Inflammasome components and pathways may provide novel targets to treat certain types of cancer; however, using such agents should be cautiously evaluated due to the complex roles that inflammasomes and pro- inflammatory cytokines play in immunity.

关键词： inflammasome cancer inflammation

Epigenetic regulation of aging:implications for interventions of aging and diseases

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Signal Transduction and Targeted Therapy 2022年第12期7卷 4283-4304页

作者： Kang Wang huicong liu Qinchao Hu Lingna Wang Jiaqing liu Zikai Zheng Weiqi Zhang Jie Ren Fangfang Zhu guang-hui liu State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of Sciences100101 BeijingChina State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of Sciences100101 BeijingChina University of Chinese Academy of Sciences 100049 BeijingChina School of Biomedical Engineering Shanghai Jiao Tong University200030 ShanghaiChina CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for Bioinformation100101 BeijingChina Hospital of Stomatology Sun Yat-sen University510060 GuangzhouChina guangdong Provincial Key Laboratory of Stomatology Guanghua School of StomatologySun Yat-sen University510060 GuangzhouChina Institute for Stem Cell and Regeneration Chinese Academy of Sciences100101 BeijingChina Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu HospitalCapital Medical University100053 BeijingChina Beijing Institute for Stem Cell and Regenerative Medicine 100101 BeijingChina

Aging is accompanied by the decline of organismal functions and a series of prominent hallmarks,including genetic and epigenetic *** aging-associated epigenetic changes include DNA methylation,histone modification,chromatin remodeling,non-coding RNA(ncRNA)regulation,and RNA modification,all of which participate in the regulation of the aging process,and hence contribute to aging-related ***,understanding the epigenetic mechanisms in aging will provide new avenues to develop strategies to delay ***,aging interventions based on manipulating epigenetic mechanisms have led to the alleviation of aging or the extension of the lifespan in animal *** molecule-based therapies and reprogramming strategies that enable epigenetic rejuvenation have been developed for ameliorating or reversing aging-related *** addition,adopting health-promoting activities,such as caloric restriction,exercise,and calibrating circadian rhythm,has been demonstrated to delay ***,various clinical trials for aging intervention are ongoing,providing more evidence of the safety and efficacy of these ***,we review recent work on the epigenetic regulation of aging and outline the advances in intervention strategies for aging and age-associated diseases.A better understanding of the critical roles of epigenetics in the aging process will lead to more clinical advances in the prevention of human aging and therapy of aging-related diseases.

关键词： aging prevention hence

CRISPR/Cas9 and TALE： beyond cut and paste

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Protein & Cell 2015年第3期6卷 157-159页

作者： Liping Deng Ruotong Ren Jun Wu Keiichiro Suzuki Juan Carlos Izpisua Belmote guang-hui liu National Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China Gene Expression Laboratory Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Beijing Institute for Brain Disorders Beijing 100069 China Center for Molecular and Translational Medicine CMTM Beijing 100101 China

Nuclease-based genome editing has proven to be a powerful and promising tool for disease modeling and gene therapy. Recent advances in CRISPR/Cas and TALE indicate that they could also be used as a targeted regulator ... 详细信息

关键词： TALE CRISPR/Cas9 genome editing,gene expression transcription regulation

SIRT7 antagonizes human stem cell aging as a heterochromatin stabilizer

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Protein & Cell 2020年第7期11卷 483-504页

作者： Shijia Bi Zunpeng liu Zeming Wu Zehua Wang Xiaoqian liu Si Wang Jie Ren Yan Yao Weiqi Zhang Moshi Song guang-hui liu Jing Qu State Key Laboratory of Stem Cell and Reproductive Biology Instiute of ZoologyChinese Academy of SciencesBejing 100101China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBejing 100101China Beiing Institute for Brain Disorders Advanced Innovation Center for Human Brain ProtectionNational Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China CAS Key Laboratory of Genomic and Precision Medicine Beiing Institute of GenomicsChinese Academy of SciencesBeijing 100101China China National Center for Bioinformation Bejing 100101China Institute for Stem cell and Regeneration Chinese Academy of SciencesBeiing 100101China University of Chinese Academy of Sciences Beijing 100049China Department of Cardiology Bejing Anzhen HospitalCapital Medical UniversityBeijing 100029China

SIRT7,a sirtuin family member implicated in aging and disease,is a regulator of metabolism and stress *** remains elusive how human somatic stem cell populations might be impacted by ***,we found that SIRT7 expression declines during human mesenchymal stem cell(hMSC)aging and that SIRT7 deficiency accelerates ***,SIRT7 forms a complex with nuclear lamina proteins and heterochromatin proteins,thus maintaining the repressive state of heterochromatin at nuclear ***,deficiency of SIRT7 results in loss of heterochromatin,derepression of the LINE1 retrotransposon(LINE1),and activation of innate immune signaling via the cGAS-STING *** agingassociated cellular defects were reversed by overexpression of heterochromatin proteins or treatment with a LINE1 targeted reverse-transcriptase ***,these findings highlight how SIRT7 safeguards chromatin architecture to control innate immune regulation and ensure geroprotection during stem cell aging.

关键词： SIRT7 stem cell aging LINE1 cGAS STING

Resolution Enhancement of SOHO/MDI Magnetograms

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Research in Astronomy and Astrophysics 2024年第6期24卷 358-367页

作者： Ying Qin Kai-Fan Ji hui liu Xiao-guang Yu Yunnan Observatories Chinese Academy of SciencesKunming 650011China University of Chinese Academy of Sciences Beijing 100049China Yunnan Key Laboratory of Solar Physics and Space Science Kunming 650216China Key Laboratory for the Structure and Evolution of Celestial Objects Chinese Academy of SciencesKunming 650216China

Research on the solar magnetic field and its effects on solar dynamo mechanisms and space weather events has benefited from the continual improvements in instrument resolution and measurement *** augmentation and assimilation of historical observational data timelines also play a significant role in understanding the patterns of solar magnetic field *** the realm of astronomical data processing,super-resolution(SR)reconstruction refers to the process of using a substantial corpus of training data to learn the nonlinear mapping between low-resolution(LR)and high-resolution(HR)images,thereby achieving higherresolution astronomical *** paper is an application study in high-dimensional nonlinear *** learning models were employed to perform SR modeling on SOHO/MDI magnetograms and SDO/HMI magnetograms,thus reliably achieving resolution enhancement of full-disk SOHO/MDI magnetograms and enhancing the image resolution to obtain more detailed *** this study,a data set comprising 9717pairs of data from 2010 April to 2011 February was used as the training set,1332 pairs from 2011 March were used as the validation set and 1034 pairs from 2011 April were used as the test *** data preprocessing,we randomly cropped 128×128 sub-images as the LR cases from the full-disk MDI magnetograms,and the corresponding 512×512 sub-images as HR ones from the HMI full-disk magnetograms for model *** tests conducted have shown that the study successfully produced reliable 4×SR reconstruction of full-disk MDI *** MESR model's results(0.911)were highly correlated with the target HMI magnetographs as indicated by the correlation coefficient ***,the method achieved the best PSNR,SSIM,MAE and RMSE values,indicating that the MESR model can effectively reconstruct magnetograms.

关键词： magnetic fields techniques:image processing virtual observatory tools Sun:magnetic fields

Focal choroidal excavation: a preliminary interpretation based on clinic and review

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International Journal of Ophthalmology(English edition) 2015年第3期8卷 513-521页

作者： guang-hui liu Bing Lin Xin-Quan Sun Zi-Fang He Ji-Rong Li Rong Zhou Xiao-Ling liu School of Optometry and Ophthalmology and Eye Hospital Wenzhou Medical University Department of Ophthalmology Affiliated People's Hospital to Fujian University of Traditional Chinese Medicine Department of Ophthalmology China-Japan Friendship Hospital

AIM: To describe the clinical and imaging characteristics associated with focal choroidal excavation(FCE), analyze the possible complication, and interpret its probable ***: Retrospective descriptive case series of 37 eyes of 32 patients with FCE. Findings of spectral-domain optical coherence tomography(SD-OCT),fluorescein angiography, indocyanine green angiography,and clinical features were analyzed. RESULTS: All patients were Chinese. Five patients(15.6%) were bilaterally involved. Patients’ ages ranged from 7 to 66 y. Refractive error ranged between +2.0 D and 11.0 D. Mean best-corrected visual acuity was 0.6(range, 0.1 to 1.2). Fundus examinations exhibited mild-moderate localized pigmentary disturbances in the corresponding area of 17 eyes. Fluorescein angiography performed in 18 patients showed varying degrees of hyperfluorescence and hypofluorescence related to a range of retinal pigment epithelium(RPE) *** green angiography performed in 7 patients showed hypofluorescence at the excavation. SD-OCT demonstrated choroidal excavation in all 37 ***-nine eyes showed a single lesion of FCE, and three eyes showed 2-3 separated lesions. Fifteen eyes showed separation between the photoreceptor tips andRPE consistent with nonconforming FCE. Central serous chorioretinopathy(CSC, n =1) and choroidal neovascularization(CNV, n =1) developed during ***: FCE could be interpreted as congenital focal choroidal dysplasia involving the RPE,choriocapillaris, and photoreceptor associated with the faulty anatomy. The abnormal anatomy of FCE was similar to anatomy at risk of CSC and CNV.

关键词： focal choroidal excavation dysplasia optical coherence tomography etiology

Direct conversion of human fibroblasts into retinal pigment epithelium-like cells by defined factors

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Protein & Cell 2014年第1期5卷 48-58页

作者： Kejing Zhang guang-hui liu Fei Yi Nuria Montserrat Tomoaki Hishida Concepcion Rodriguez Esteban Juan Carlos Izpisua Belmonte] Gene Expression Laboratory Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA National Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China Department of Molecular and Cellular Physiology Stanford University School of Medicine 265 Campus Drive StanfordCA 94305 USA Center for Regenerative Medicine in Barcelona Dr. Aiguader 88 08003 Barcelona Spain Biomedical Research Networking Center in Bioengineering Biomaterials and Nanomedicine (CIBER-BBN) BarcelonaSpain

The generation of functional retinal pigment epithelium （RPE） is of great therapeutic interest to the field of regenerative medicine and may provide possible cures for retinal degenerative diseases, including age-related macular degeneration （AMD）. Although RPE cells can be produced from either embryonic stem cells or induced pluripotent stem cells, direct cell reprogramming driven by lineage-determining transcription factors provides an immediate route to their generation. By monitoring a human RPE specific Bestl：：GFP reporter, we report the conversion of human fibroblasts into RPE lineage using defined sets of transcription factors. We found that Bestl：：GFP positive cells formed colonies and exhibited morphological and molecular features of early stage RPE cells. Moreover, they were able to obtain pigmen- tation upon activation of Retinoic acid （RA） and Sonic Hedgehog （SHH） signaling pathways. Our study not only established an ideal platform to investigate the tran- scriptional network regulating the RPE cell fate deter- mination, but also provided an alternative strategy to generate functional RPE cells that complement the useof pluripotent stem cells for disease modeling, drug screening, and cell therapy of retinal degeneration.

关键词： retinal pigment epithelium fibroblasts,direct conversion

Protein quality control of cell stemness

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Cell Regeneration 2020年第1期9卷 259-269页

作者： Pengze Yan Jie Ren Weiqi Zhang Jing Qu guang-hui liu State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China China National Center for Bioinformation Beijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Collaborative Innovation Center of Genetics and DevelopmentBeijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China Institute for Stem cell and Regeneration Chinese Academy of SciencesBeijing 100101China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Beijing Institute for Brain Disorders Advanced Innovation Center for Human Brain ProtectionNational Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China.

Protein quality control(PQC)systems play essential roles in the recognition,refolding and clearance of aberrant proteins,thus ensuring cellular protein homeostasis,or ***,continued proliferation and differentiation of stem cells require a high rate of translation;therefore,accurate PQC systems are essential to maintain stem cell *** evidence suggested crucial roles of PQC systems in regulating the stemness and differentiation of stem *** review focuses on current knowledge regarding the components of the proteostasis network in stem cells,and the importance of proteostasis in maintaining stem cell identity and regenerative functions.A complete understanding of this process might uncover potential applications in aging intervention and aging-related diseases.

关键词： Protein quality control Stem cells Stemness Chaperones Unfolded protein response Ubiquitinproteasome system Autophagy

Establishment of hepatic and neural differentiation platforms of Wilson’s disease specific induced pluripotent stem cells

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Protein & Cell 2012年第11期3卷 855-863页

作者： Fei Yi Jing Qu Mo Li Keiichiro Suzuki Na Young Kim guang-hui liu Juan Carlos Izpisua Belmonte Gene Expression Laboratory Salk Institute for Biological Studies10010 North Torrey Pines RoadLa JollaCA 92037USA National Laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of SciencesBeijing 100101China Center for Regenerative Medicine in Barcelona Dr.Aiguader 8808003 BarcelonaSpain

The combination of disease-specific human induced pluripotent stem cells(iPSC)and directed cell differentiation offers an ideal platform for modeling and studying many inherited human ***’s disease(WD)is a monogenic disorder of toxic copper accumulation caused by pathologic mutations of the ATP7B *** affects multiple organs with primary manifestations in the liver and central nervous system(CNS).In order to better investigate the cellular pathogenesis of WD and to develop novel therapies against various WD syndromes,we sought to establish a comprehensive platform to differentiate WD patient iPSC into both hepatic and neural *** we report the generation of patient iPSC bearing a Caucasian population hotspot mutation of *** with directed cell differentiation strategies,we successfully differentiated WD iPSC into hepatocyte-like cells,neural stem cells and *** expression analysis and cDNA sequencing confirmed the expression of the mutant ATP7B gene in all differentiated *** we established a platform for studying both hepatic and neural abnormalities of WD,which may provide a new tool for tissue-specific disease modeling and drug screening in the future.

关键词： induced pluripotent stem cell Wilson’s disease hepatocyte neural stem cell neuron