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MAVS Antagonizes Human Stem Cell Senescence as a Mitochondrial Stabilizer

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Research 2024年第2期2023卷 239-257页

作者： Cui Wang Kuan Yang Xiaoqian Liu Si Wang Moshi Song Juan Carlos Izpisua Belimonte Jing Qu Guang-Hui Liu Weiqi Zhang CAS Key Laboratory of Genomic and Precision Medicine Beijng Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Institute for Stem Cell and regeneration Chinese Academy of Sciences Beijing 100101China beijing Institute for Stem Cell and Regenerative Medicine Bejing 100101China Advanced Innovation center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Altos Labs Inc.San DiegoCA 94022USA

Mitochondrial dysfunction is a hallmark feature of cellular senescence and organ ***,we asked whether the mitochondrial antiviral signaling protein(MAVS),which is essential for driving antiviral response,also regulates human stem cell *** answer this question,we used CRISPR/Cas9-mediated gene editing and directed differentiation techniques to generate various MAVS-knockout human stem cell *** found that human mesenchymal stem cells(hMSCs)were sensitive to MAVS deficiency,as manifested by accelerated senescence *** uncovered that the role of MAVS in maintaining mitochondrial structural integrity and functional homeostasis depends on its interaction with the guanosine triphosphatase optic atrophy type 1(OPA1).Depletion of MAVS or OPA1 led to the dysfunction of mitochondria and cellular senescence,whereas replenishment of MAVS or OPA1 in MAVS-knockout hMSCs alleviated mitochondrial defects and premature senescence *** together,our data underscore an uncanonical role of MAVS in safeguarding mitochondrial homeostasis and antagonizing human stem cell senescence.

关键词： CRISPR/Cas9 homeostasis Mitochondrial

CRL2^(APPBP2)-mediated TSPYL2 degradation counteracts human mesenchymal stem cell senescence

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Science China(Life Sciences) 2024年第3期67卷 460-474页

作者： Daoyuan Huang Qian Zhao Kuan Yang Jinghui Lei Ying Jing Hongyu Li Chen Zhang Shuai Ma Shuhui Sun Yusheng Cai Guibin Wang Jing Qu Weiqi Zhang Si Wang Guang-Hui Liu Advanced Innovation centerfor Human Brain Protection National Clinical Research Centerfor Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Translational Medicinecenter International Centerfor Aging and CancerBejing Municipal GeriatricMedical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China beijing Institute for Stem Cell and Regenerative Medicine Beijing100101China CAS Key Laboratory of Genomic and Precision Medicine Bejing Institute of Genomics and China National Center for BioinformationChinese Academy of SciencesBeijing 100101China Institute for Stem Cell and regeneration CASBeijing 100101China The Fifth People's Hospital of Chongqing Chongqing 400062China Sino-Danish Cllege University of Chinese Academy of SciencesBeijing101408China National Laboratory of Biomacromolecules CAS Center for Excelence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing100101China State Key Laboratory of Proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of LifeomicsBeijing 102206China

Cullin-RING E3 ubiquitin ligases(CRLs),the largest family of multi-subunit E3 ubiquitin ligases in eukaryotic cells,represent core cellular machinery for executing protein degradation and maintaining ***,we asked what roles Cullin proteins play in human mesenchymal stem cell(hMSC)homeostasis and *** this end,we conducted a comparative aging phenotype analysis by individually knocking down Cullin members in three senescence models:replicative senescent hMSCs,Hutchinson-Gilford Progeria Syndrome hMSCs,and Werner syndrome *** all family members,we found that CUL2 deficiency rendered hMSCs the most susceptible to *** investigate CUL2-specific underlying mechanisms,we then applied CRISPR/Cas9-mediated gene editing technology to generate CUL2-deficient human embryonic stem cells(hESCs).When we differentiated these into h MSCs,we found that CUL2 deletion markedly accelerates hMSC ***,we identified that CUL2 targets and promotes ubiquitin proteasome-mediated degradation of TSPYL2(a known negative regulator of proliferation)through the substrate receptor protein APPBP2,which in turn downregulates one of the canonical aging marker-P21^(waf1/cip1),and thereby delays *** work provides important insights into how CRL2^(APPBP2)-mediated TSPYL2 degradation counteracts hMSC senescence,providing a molecular basis for directing intervention strategies against aging and aging-related diseases.

关键词： Cullins stem cell senescence aging proteostasis ubiquitination APPBP2 TSPYL2

Dynamic transcriptional programs define distinct mammalian cortical lineages

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neural regeneration Research 2024年第2期19卷 387-389页

作者： Tanzila Mukhtar Verdon Taylor Department of Biomedicine University of BaselBaselSwitzerland Eli and Edythe Broad center of regeneration Medicine and Stem Cell Research University of CaliforniaSan FranciscoCAUSA

The cerebral cortex is composed of billions of neurons and glia that are generated sequentially during *** cells are generated in an organized fashion during *** early stages of brain development,neural stem cells(NSC... 详细信息

关键词： cortex cerebral development

Advances in neuromorphic computing:Expanding horizons for AI development through novel artificial neurons and in-sensor computing

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Chinese Physics B 2024年第3期33卷 1-23页

作者：杨玉波赵吉哲刘胤洁华夏扬王天睿郑纪元郝智彪熊兵孙长征韩彦军王健李洪涛汪莱罗毅 Department of Electronic Engineering Tsinghua UniversityBeijing 100084China beijing National Research center for Information Science and Technology Tsinghua UniversityBeijing 100084China

AI development has brought great success to upgrading the information *** the same time,the large-scale artificial neural network for building AI systems is thirsty for computing power,which is barely satisfied by the conventional computing *** the post-Moore era,the increase in computing power brought about by the size reduction of CMOS in very large-scale integrated circuits(VLSIC)is challenging to meet the growing demand for AI computing *** address the issue,technical approaches like neuromorphic computing attract great attention because of their feature of breaking Von-Neumann architecture,and dealing with AI algorithms much more parallelly and energy *** by the human neural network architecture,neuromorphic computing hardware is brought to life based on novel artificial neurons constructed by new materials or *** it is relatively difficult to deploy a training process in the neuromorphic architecture like spiking neural network(SNN),the development in this field has incubated promising technologies like in-sensor computing,which brings new opportunities for multidisciplinary research,including the field of optoelectronic materials and devices,artificial neural networks,and microelectronics integration *** vision chips based on the architectures could reduce unnecessary data transfer and realize fast and energy-efficient visual cognitive *** paper reviews firstly the architectures and algorithms of SNN,and artificial neuron devices supporting neuromorphic computing,then the recent progress of in-sensor computing vision chips,which all will promote the development of AI.

关键词： neuromorphic computing spiking neural network(SNN) in-sensor computing artificial intelligence

Super-resolution diffractive neural network for alloptical direction of arrival estimation beyond diffraction limits

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Light(Science & Applications) 2024年第8期13卷 1602-1614页

作者： Sheng Gao Hang Chen Yichen Wang Zhengyang Duan Haiou Zhang Zhi Sun Yuan Shen Xing Lin Department of Electronic Engineering Tsinghua UniversityBeijing 100084China beijing National Research center for Information Science and Technology Tsinghua UniversityBeijing 100084China

Wireless sensing of the wave propagation direction from radio sources lays the foundation for communication,radar,navigation,***,the existing signal processing paradigm for the direction of arrival estimation requires the radio frequency electronic circuit to demodulate and sample the multichannel baseband signals followed by a complicated computing process,which places the fundamental limit on its sensing speed and energy ***,we propose the super-resolution diffractive neural networks(S-DNN)to process electromagnetic(EM)waves directly for the DOA estimation at the speed of *** multilayer meta-structures of S-DNN generate super-oscillatory angular responses in local angular regions that can perform the all-optical DOA estimation with angular resolutions beyond the diffraction *** spatial-temporal multiplexing of passive and reconfigurable S-DNNs is utilized to achieve high-resolution DOA estimation over a wide field of *** S-DNN is validated for the DOA estimation of multiple radio sources over 5 GHz frequency bandwidth with estimation latency over two to four orders of magnitude lower than the state-of-the-art commercial devices in *** results achieve the angular resolution over an order of magnitude,experimentally demonstrated with four times,higher than diffraction-limited *** also apply S-DNN’s edge computing capability,assisted by reconfigurable intelligent surfaces,for extremely low-latency integrated sensing and communication with low power *** work is a significant step towards utilizing photonic computing processors to facilitate various wireless sensing and communication tasks with advantages in both computing paradigms and performance over electronic computing.

关键词： beyond optical network

Improving lipid production by Rhodotorula glutinis for renewable fuel production based on machine learning

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Frontiers of Chemical Science and Engineering 2024年第5期18卷 23-35页

作者： Lihe Zhang Changwei Zhang Xi Zhao Changliu He Xu Zhang National Energy R&D center for Biorefinery Beijing University of Chemical TechnologyBeijing 100029China Collage of Life Science and Technology Beijing University of Chemical TechnologyBeijing 100029China beijing Key Laboratory of Bioprocess Beijing University of Chemical TechnologyBeijing 10029China

Microbial lipid fermentation encompasses intricate complex cell growth processes and heavily relies on expert experience for optimal *** modeling of the fermentation process assists researchers in making intelligent decisions,employing logical reasoning and strategic planning to optimize lipid *** this study,the effects of medium components and concen-trations on lipid fermentation were investigated,*** then,leveraging the collated data,a variety of machine learning algorithms were used to model and optimize the lipid fermentation *** models,based on artificial neural networks and support vector machines,achieved R?values all higher than 0.93,ensuring accurate predictions of the fermentation *** linear regression was used to evaluate the respective target parameter,which were affected by the medium components of lipid ***,single and multi-objective optimiza-tion were conducted for lipid fermentation using the genetic *** results demonstrated the maximum biomass of 50.3 g·L^(-1) and maximum lipid concentration of 14.1 g:L^(-1) with the error between the experimental and predicted values less than 5%.The results of the multi-objective optimization reveal the synergistic and competitive relationship between biomass,lipid concentration,and conversion rate,which lay a basis for in-depth optimization and amplification.

关键词： microbial lipid machine learning artificial neural network support vector machine genetic algorithm

Association of DNA methylation/demethylation with the functional outcome of stroke in a hyperinflammatory state

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neural regeneration Research 2024年第10期19卷 2229-2239页

作者： Yubo Wang Ling Zhang Tianjie Lyu Lu Cui Shunying Zhao Xuechun Wang Meng Wang Yongjun Wang Zixiao Li Vascular Neurology Department of NeurologyBeijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina National center for Healthcare Quality Management in Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Chinese Institute for Brain Research BeijingChina Research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina beijing Engineering Research center of Digital Healthcare for Neurological Diseases BeijingChina

Inflammation is closely related to stroke prognosis, and high inflammation status leads to poor functional outcome in stroke. DNA methylation is involved in the pathogenesis and prognosis of stroke. However, the effect of DNA methylation on stroke at high levels of inflammation is unclear. In this study, we constructed a hyperinflammatory cerebral ischemia mouse model and investigated the effect of hypomethylation and hypermethylation on the functional outcome. We constructed a mouse model of transient middle cerebral artery occlusion and treated the mice with lipopolysaccharide to induce a hyperinflammatory state. To investigate the effect of DNA methylation on stroke, we used small molecule inhibitors to restrain the function of key DNA methylation and demethylation enzymes. 2,3,5-Triphenyltetrazolium chloride staining, neurological function scores, neurobehavioral tests, enzyme-linked immunosorbent assay, quantitative reverse transcription PCR and western blot assay were used to evaluate the effects after stroke in mice. We assessed changes in the global methylation status by measuring DNA 5-mc and DNA 5-hmc levels in peripheral blood after the use of the inhibitor. In the group treated with the DNA methylation inhibitor, brain tissue 2,3,5-triphenyltetrazolium chloride staining showed an increase in infarct volume, which was accompanied by a decrease in neurological scores and worsening of neurobehavioral performance. The levels of inflammatory factors interleukin 6 and interleukin-1 beta in ischemic brain tissue and plasma were elevated, indicating increased inflammation. Related inflammatory pathway exploration showed significant overactivation of nuclear factor kappa B. These results suggested that inhibiting DNA methylation led to poor functional outcome in mice with high inflammation following stroke. Further, the effects were reversed by inhibition of DNA demethylation. Our findings suggest that DNA methylation regulates the inflammatory response in stroke

关键词： DNA demethylation DNA methylation DNMT3A functional outcome hyperinflammatory state interleukin neuroinflammation stroke TET2

MAL2 DNA methylation serves as a biomarker for the diagnosis and prognosis of glioma

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Genes & Diseases 2024年第5期11卷 36-39页

作者： Hao Luo Xing Xiao Weiliang Hou Jing Cai Ming Chen Qisheng Tang Yusheng Tong Zengxin Qi Kaicheng Li Liang Chen Department of Neurosurgery Huashan HospitalShanghai Medical CollegeState Key Laboratory of Medical NeurobiologyMOE Frontiers Center for Brain Science and Institutes of Brain ScienceFudan UniversityShanghai 200040China National center for Neurological Disorders Shanghai 200040China Shanghai Key Laboratory of Brain Function and Restoration and neural regeneration Shanghai 200040China Tianqiao and Chrissy Chen Institute Clinical Translational Research center Shanghai 200040China Shanghai QuietD Biotechnology Co. Ltd.Shanghai 201210China

Glioma is a common and malignant brain tumor,and molecular diagnostics for glioma have received increasing attention.1,2 Previous studies have suggested that the MAL2 gene may be involved in the transcytosis of various cancers.3 This study aimed to investigate the potential of MAL2 as a biomarker for *** candidate MAL2 CpG sites were validated by pyrosequencing and used to construct a diagnostic model for *** analysis was also conducted to determine the relationship between highly methylated MAL2-specific CpG sites and the prognosis of *** findings also showed that MAL2 was more highly methylated in glioma than in other *** constructed diagnostic model can distinguish glioma from other cancers with high sensitivity(93.3%)and specificity(86.5%).Additionally,a risk score model was built based on MAL2 methylation to assess the prognosis of glioma。

关键词： glioma diagnosis MAL

NSNO:Neumann Series neural Operator for Solving Helmholtz Equations in Inhomogeneous Medium

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Journal of Systems Science & Complexity 2024年第2期37卷 413-440页

作者： CHEN Fukai LIU Ziyang LIN Guochang CHEN Junqing SHI Zuoqiang Department of Mathematical Sciences Tsinghua UniversityBeijing 100084China Yau Mathematical Sciences center Tsinghua UniversityBeijing 100084China Yanqi Lake beijing Institute of Mathematical Sciences and Applications Beijing 101408China

In this paper,the authors propose Neumann series neural operator(NSNO)to learn the solution operator of Helmholtz equation from inhomogeneity coefficients and source terms to *** equation is a crucial partial differential equation(PDE)with applications in various scientific and engineering ***,efficient solver of Helmholtz equation is still a big challenge especially in the case of high ***,deep learning has shown great potential in solving PDEs especially in learning solution *** by Neumann series in Helmholtz equation,the authors design a novel network architecture in which U-Net is embedded inside to capture the multiscale *** experiments show that the proposed NSNO significantly outperforms the state-of-the-art FNO with at least 60%lower relative L^(2)-error,especially in the large wavenumber case,and has 50%lower computational cost and less data ***,NSNO can be used as the surrogate model in inverse scattering *** tests show that NSNO is able to give comparable results with traditional finite difference forward solver while the computational cost is reduced tremendously.

关键词： Helmholtz equation inverse problem neumann series neural network solution operator