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Transient chemical-mediated epigenetic modulation confers unrestricted lineage potential on human primed pluripotent stem cells

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science China Life sciences 2025年

作者： Shi Chen Yuanyuan He Lejun Lv Bei Liu Cheng Li Hongkui Deng Jun Xu Department of Cell Biology School of Basic Medical Sciences Peking University Stem Cell Research Center Peking University Health Science Center Peking University Academy of Advanced Interdisciplinary Studies Peking University BeiCell Therapeutics School of Life sciences Center for Bioinformatics Center for Statistical Science Peking University MOE Engineering Research center of Regenerative Medicine School of Basic Medical Sciences State Key Laboratory of Natural and Biomimetic Drugs Peking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and Differentiation College of Life Sciences Peking-Tsinghua Center for Life Sciences Peking University

Human primed pluripotent stem cells are capable of generating all the embryonic ***,their extraembryonic trophectoderm potentials are *** remains unclear how to expand their developmental potential to trophectoderm *** we show that transient treatment with a cocktail of small molecule epigenetic modulators imparts trophectoderm lineage potentials to human primed pluripotent stem cells while preserving their embryonic *** chemically treated cells can generate trophectoderm-like cells and downstream trophoblast stem cells,diverging into syncytiotrophoblast and extravillous trophoblast *** and CUT&Tag analyses reveal that these induced cells share transcriptional profiles with in vivo trophectoderm and cytotrophoblast,and exhibit reduced H3K27me3 modification at gene loci specific to trophoblast lineages compared with primed pluripotent *** exploration highlighted the critical roles of epigenetic modulators HDAC2,EZH1/2,and KDM5s in the activation of trophoblast lineage *** findings demonstrate that transient epigenetic resetting activates unrestricted lineage potential in human primed pluripotent stem cells,and offer new mechanistic insights into human trophoblast lineage specification and in vitro models for studying placental development and related disorders.

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Simulations of electron zebra stripes in the inner radiation belt using a composite empirical electric field model

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science China Earth sciences 2025年第1期68卷 27-38页

作者： Ziyang WANG Ying LIU Qiugang ZONG Hong ZOU Yuguang YE Xuzhi ZHOU Chao YUE Shan WANG Institute of Space Physics and Applied Technology Peking University State Key Laboratory of Lunar and Planetary science Macau University of Science and Technology

The phenomenon termed “zebra stripes” manifests as regular patterns in the energy-space(L shell) spectrum of energetic electrons(ranging from tens to hundreds ke V) within the inner radiation belt. These structures exhibit drift-periodic behavior and commonly arise from large-scale electric field perturbations near the substorm onsets. In this study, we introduce a composite electric field model and replicate the formation, structure, and evolution of zebra stripes using a bounce-averaged test particle code under this electric field model. High-resolution measurements of energetic electrons obtained from the Van Allen Probes and the recently launched Macao science Satellites-1 are used as initial conditions and served to validate our test particle simulations. Comparative analyses between observed data and simulations demonstrate our test particle method's efficacy in capturing zebra stripes' general behavior. Moreover, the composite model proves capable of reproducing realistic variations in the electric field within the inner radiation belt to a certain extent. Nevertheless, subtle differences emerge in the flux strength and the positions of stripes. These disparities primarily stem from limitations inherent in the electric field model and the initial conditions of the simulation. Acknowledging that the model represents an average case, it is conceivable that real-world scenarios may deviate from the average, thereby introducing variations in the observed phenomena.

关键词： Zebra stripes Inner radiation belt Large-scale electric fields Van Allen Probes Macao science Satellite

Cortical hem signaling center: functions, development, and potential implications for evolution and brain disorders

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Neural Regeneration Research 2025年第4期20卷 1079-1080页

作者： Victor V.Chizhikov Igor Y.Iskusnykh Department of Anatomy and Neurobiology University of Tennessee Health Science CenterMemphisTNUSA

Development of the telencephalon relies upon several signaling centers-localized cellular populations that supply secreted factors to pattern the cortical *** such signaling center is the cortical hem,which arises during embryonic development at the telencephalic dorsal midline,adjacent to the choroid plexus and hippocampal primordium(Figure 1A).While the cortical hem has also been described in reptiles and birds,most of our knowledge about the developmental roles of the cortical hem is derived from the analysis in *** cortical hem produces several types of secreted molecules,including wingless-related integration site(Wnt)and bone morphogenetic(Bmp)*** cortical hem is particularly important for the development of the hippocampus,which is involved in learning and memory,and the neocortex,which is the most complex brain region that mediates multiple types of behavior and higher cognitive functions(Mangale et al.,2008;Dal-Valle-Anton and Borrell,2022).

关键词： epithelium Figure center

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Toward Analytical Homogenized Relaxation Modulus for Fibrous Composite Material with Reduced Order Homogenization Method

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Computers, Materials & Continua 2025年第1期82卷 193-222页

作者： Huilin Jia Shanqiao Huang Zifeng Yuan HEDPS Center for Applied Physics and Technology(CAPT)Department of Mechanics and Engineering SciencePeking UniversityBeijing100871China State Key Laboratory for Turbulence and Complex Systems Peking UniversityBeijing100871China

In this manuscript,we propose an analytical equivalent linear viscoelastic constitutive model for fiber-reinforced composites,bypassing general computational *** method is based on the reduced-order homogenization(ROH)*** ROH method typically involves solving multiple finite element problems under periodic conditions to evaluate elastic strain and eigenstrain influence functions in an‘off-line’stage,which offers substantial cost savings compared to direct computational homogenization *** to the unique structure of the fibrous unit cell,“off-line”stage calculation can be eliminated by influence functions obtained *** the standard solid model to the ROH method enables the creation of a comprehensive analytical homogeneous viscoelastic constitutive *** method treats fibrous composite materials as homogeneous,anisotropic viscoelastic materials,significantly reducing computational time due to its analytical *** approach also enables precise determination of a homogenized anisotropic relaxation modulus and accurate capture of various viscoelastic responses under different loading *** sets of numerical examples,including unit cell tests,three-point beam bending tests,and torsion tests,are given to demonstrate the predictive performance of the homogenized viscoelastic ***,the model is validated against experimental measurements,confirming its accuracy and reliability.

关键词： Homogenized relaxation modulus viscoelastic standard solid model reduced order homogenization fibrous composite material

GPS: graph contrastive learning via multi-scale augmented views from adversarial pooling

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science China(Information sciences) 2025年第1期68卷 145-158页

作者： Wei JU Yiyang GU Zhengyang MAO Ziyue QIAO Yifang QIN Xiao LUO Hui XIONG Ming ZHANG School of Computer science National Key Laboratory for Multimedia Information ProcessingPeking University Artificial Intelligence Thrust The Hong Kong University of Science and Technology Department of Computer science University of California

Self-supervised graph representation learning has recently shown considerable promise in a range of fields, including bioinformatics and social networks. A large number of graph contrastive learning approaches have shown promising performance for representation learning on graphs, which train models by maximizing agreement between original graphs and their augmented views(i.e., positive views). Unfortunately, these methods usually involve pre-defined augmentation strategies based on the knowledge of human experts. Moreover, these strategies may fail to generate challenging positive views to provide sufficient supervision signals. In this paper, we present a novel approach named graph pooling contrast(GPS) to address these *** by the fact that graph pooling can adaptively coarsen the graph with the removal of redundancy, we rethink graph pooling and leverage it to automatically generate multi-scale positive views with varying emphasis on providing challenging positives and preserving semantics, i.e., strongly-augmented view and weakly-augmented view. Then, we incorporate both views into a joint contrastive learning framework with similarity learning and consistency learning, where our pooling module is adversarially trained with respect to the encoder for adversarial robustness. Experiments on twelve datasets on both graph classification and transfer learning tasks verify the superiority of the proposed method over its counterparts.

关键词： graph representation learning graph neural networks graph contrastive learning graph augmentations graph pooling

Peficitinib suppresses diffuse-type tenosynovial giant cell tumor by targeting TYK2 and JAK/STAT signaling

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science China Life sciences 2025年

作者： Shan Lu Chenxi Cao Wenjia Zhang Jiayi Li Jingli Yang Zisheng Huang Zhijun Wu Baitao Liu Hongjie Huang Haijun Wang Yongjian Wang Dingge Liu Zhihua Zhang Kaiping Liu Gang Yang Xi Gong Hui Dai Yingjia Li Erdan Dong Xin Zhang Yan Zhang Haihe Laboratory of Cell Ecosystem Institute of Cardiovascular Diseases The First Affiliated Hospital of Dalian Medical University Institute of Cardiovascular sciences School of Basic Medical Sciences Peking University Health Science Center Department of Cardiology and Institute of Vascular Medicine Peking University Third HospitalState Key Laboratory of Vascular Homeostasis and Remodeling Peking University Department of Sports Medicine Peking University Third Hospital Institute of Sports Medicine of Peking University Beijing Key Laboratory of Sports Injuries Engineering Research center of Sports Trauma Treatment Technology and Devices Ministry of Education State Key Laboratory of Membrane Biology Institute of Molecular Medicine College of Future Technology Peking University peking university health science Centre Peking University Department of Immunology School of Basic Medical Sciences NHC Key Laboratory of Medical Immunology Peking University Research center for Cardiopulmonary Rehabilitation University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital) School of Health and Life Sciences University of Health and Rehabilitation Sciences Research Unit of Medical science Research Management/Basic and Clinical Research of Metabolic Cardiovascular Diseases Chinese Academy of Medical Sciences

Diffuse-type tenosynovial giant cell tumor(dTGCT) is a destructive but rare benign proliferative synovial neoplasm. Although surgery is currently the main treatment modality for dTGCT, the recurrence risk is up to 50%. Therefore, there is a great need for effective drugs against dTGCT with minor side effects. The Janus kinase(JAK)/signal transducer and activator of transcription(STAT) signaling plays a central role in rheumatoid arthritis(RA), a disease with similar characteristics as dTGCT, but its function in dTGCT remains *** fibroblast-like synoviocytes(FLS) and macrophages were isolated from 10 synovial tissue samples from dTGCT patients for the screening and validation of the five clinically approved JAK inhibitors to treat RA against dTGCT. Cell viability, cell death, inflammation and the activity of the JAK family members of cultured dTGCT FLS(both 2-D and 3-D) and macrophages were investigated for the efficacy of the JAK inhibitors. Here, we found that similar to RA, JAK/STAT signaling was markedly activated in the dTGCT synovium. Of the 5 JAK inhibitors, peficitinib was shown to have the most potency in addressing some of the pathological responses of dTGCT FLS and *** potency of peficitinib was much higher than pexidartinib, which is the only FDA-approved drug for dTGCT. Mechanistically, peficitinib inhibited tyrosine kinase 2(TYK2), a JAK family member necessary for the pathological progression of dTGCT FLS and macrophages. In summary, we not only revealed JAK/STAT(especially TYK2) signaling as the major mechanism underlying dTGCT, but also identified peficitinib as a promising drug against dTGCT.

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Treadmill exercise in combination with acousto-optic and olfactory stimulation improves cognitive function in APP/PS1 mice through the brain-derived neurotrophic factor-and Cygb-associated signaling pathways

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Neural Regeneration Research 2025年第9期20卷 2706-2726页

作者： Biao Xiao Chaoyang Chu Zhicheng Lin Tianyuan Fang Yuyu Zhou Chuxia Zhang Jianghui Shan Shiyu Chen Liping Li Department of Physiology and Pharmacology Health Science CenterNingbo UniversityNingboZhejiang ProvinceChina Ningbo Key Laboratory of Behavioral Neuroscience Health Science CenterNingbo UniversityNingboZhejiang ProvinceChina Key Laboratory of Addiction Research of Zhejiang Province NingboZhejiang ProvinceChina

A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's ***,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and ***,nonpharmacological interventions aimed at inducing adult neurogenesis are currently *** individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully *** this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 *** deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease ***,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus *** findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 ***,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice

关键词： acousto-optic stimulation adult neurogenesis Alzheimer's disease amyloid precursor protein/presenilin 1 mice amyloid-beta deposition brain cell apoptosis cognitive impairment depression-like behavior involuntary treadmill exercise olfactory stimulation serum metabolites

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Molecular dynamics simulations of helium transport through inorganic mineral nanopores

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science China Earth sciences 2025年第1期68卷 237-252页

作者： Dandan SONG Ping GUAN Chi ZHANG Jiahao REN School of Earth and Space sciences Peking University

Helium transport through nanoscale inorganic mineral pores and pore throats is essential for its overall migration. To elucidate helium's transport dynamics within nanopores, we employed equilibrium and non-equilibrium molecular dynamics simulations to investigate helium's static self-diffusion and pressure-driven flow in quartz slit-shaped nanopores. We also introduced water and various gases, including hydrogen, methane, ethane, nitrogen, and carbon dioxide, into the nanopores to assess their influence on helium transport. Our findings indicate minimal helium adsorption on quartz pore surfaces. Under conditions where the pore size is less than 5 nm and the pressure under 10 MPa, environmental factors markedly influence helium diffusion. Large pore sizes, high temperatures, and low gas pressures enhance helium desorption and facilitate faster diffusion. We observed a positive correlation between helium flow velocity and factors such as pore size, pressure gradient, and surface smoothness of the pores. Notably, the presence of pore water and carrier gases in quartz nanopores, which diffuse more slowly than helium, tends to reduce helium surface adsorption and slow its diffusion. Among the carrier gases studied, nitrogen showed similar adsorption capacity, diffusivity, and stability to helium, while carbon dioxide displayed the highest adsorption capacity and the slowest diffusion rate, markedly differing from helium. Based on the simulation results, we concluded that water and carrier gases primarily function as transport mediums in helium migration, moving together with helium. Nitrogen, which shares similar properties with helium, effectively assists in this co-migration process. Conversely, carbon dioxide, due to its high adsorption capacity and slow diffusion, tends to be lost during co-migration. As a result, gas reservoirs with high nitrogen levels and low carbon dioxide levels are more likely to have higher helium concentrations. Additionally, the smaller por

关键词： Helium transport Slit nanopores Molecular dynamics simulations Diffusion Flow carriers

An NIR-Ⅱ-emissive Ru(Ⅱ) metallacycle for efficient and safe immunotherapy

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science China Chemistry 2025年第1期68卷 5-7页

作者： Chonglu Li Jianbo Zhan Biao Dong Institute of health Inspection and Testing Hubei Provincial Center for Disease Control and Prevention State Key Laboratory on Integrated Optoelectronics College of Electronic Science and Engineering Jilin University

Immunotherapy, as a groundbreaking cancer treatment, has gained considerable attention for its utilization of the body’s immune system to combat tumors [1]. This therapy induces tumor cell apoptosis, triggering a sustained anti-tumor immune response and effectively preventing tumor recurrence and metastasis [2]. The fundamental principle lies in inducing tumor cell death through specific treatment modalities, leading to the release of a cascade of signaling molecules and antigens, thereby mobilizing the immune system to actively identify and attack tumor cells [3].

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