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Anti-lymphangiogenesis for boosting drug accumulation in tumors

Signal Transduction and Targeted Therapy 2024年第5期9卷 2161-2175页

作者： Chunling Wang Junchao Xu Xiaoyu Cheng Ge Sun Fenfen Li Guangjun Nie Yinlong Zhang CAS Key Laboratory for Biomedical Effects of Nanomaterials&Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijing 100190China sino-danish College University of Chinese Academy of SciencesBeijing 100190China sino-danish center for Education and Research Beijing 100190China Department of Bioengineering University of PennsylvaniaPhiladelphiaPA 19104USA School of Nanoscience and Engineering University of Chinese Academy of SciencesBeijing 100049China

The inadequate tumor accumulation of anti-cancer agents is a major shortcoming of current therapeutic drugs and remains an even more significant concern in the clinical prospects for nanomedicines.Various strategies aiming at regulating the intratumoral permeability of therapeutic drugs have been explored in preclinical studies,with a primary focus on vascular regulation and stromal reduction.However,these methods may trigger or facilitate tumor metastasis as a tradeoff.Therefore,there is an urgent need for innovative strategies that boost intratumoral drug accumulation without compromising treatment outcomes.As another important factor affecting drug tumor accumulation besides vasculature and stroma,the impact of tumor-associated lymphatic vessels(LVs)has not been widely considered.In the current research,we verified that anlotinib,a tyrosine kinase inhibitor with anti-lymphangiogenesis activity,and SAR131675,a selective VEGFR-3 inhibitor,effectively decreased the density of tumor lymphatic vessels in mouse cancer models,further enhancing drug accumulation in tumor tissue.By combining anlotinib with therapeutic drugs,including doxorubicin(Dox),liposomal doxorubicin(Lip-Dox),and anti-PD-L1 antibody,we observed improved anti-tumor efficacy in comparison with monotherapy regimens.Meanwhile,this strategy significantly reduced tumor metastasis and elicited stronger anti-tumor immune responses.Our work describes a new,clinically transferrable approach to augmenting intratumoral drug accumulation,which shows great potential to address the current,unsatisfactory efficacies of therapeutic drugs without introducing metastatic risk.

关键词： drugs angiogenesis metastasis

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Engineering Fe OOH/Ni（OH）2 heterostructures on Ni3S2 surface to enhance seawater splitting

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Rare Metals 2024年第5期43卷 1989-1998页

作者： Chen Yang Ya-Dong Li Li-Juan Cao Xi-Long Wang Han-Pu Liang Qingdao Institute of Bioenergy and Bioprocess Technology Chinese Academy of Sciences center of Materials Science and Optoelectronics Engineering University of Chinese Academy of Sciences sino-danish College University of Chinese Academy of Sciences

The construction of highly stable and efficient electrocatalysts is desirable for seawater splitting but remains challenging due to the high concentration of Cl-in seawater.Herein,Fe OOH/Ni（OH）2heterostructure supported on Ni3S2-covered nickel foam （Fe–Ni/Ni3S2/NF）was fabricated by hydrothermal and etching methods,as well as anodic oxidation process.The electronic structure of Fe OOH and Ni（OH）2could be modulated after depositing Fe OOH nanoparticles on Ni（OH）2nanosheet,which greatly boosted the catalytic activity.When the catalyst used as an electrode for oxygen evolution reaction（OER）,it needed low overpotentials of 266 and 368 m V to achieve current densities of 100 and 800 m A·cm-2,respectively,in 1 mol·L-1KOH+seawater electrolyte.It can operate continuously at 100 m A·cm-2for 400 h without obvious decay.Particularly,in situ generated SO42-from inner Ni3S2during electrolysis process would accumulate on the surface of active sites to form passivation layers to repel Cl-,which seemed to be responsible for superior stability.The study not only synthesizes an OER catalyst for highly selective and stable seawater splitting,but also gives a novel approach for industrial hydrogen production.

关键词： Anodic oxidation Heterostructure Oxygen evolution reaction Seawater splitting

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Perfluorinated iodine alkanes promote the differentiation of mouse embryonic stem cells by regulating estrogen receptor signaling

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Journal of Environmental Sciences 2024年第3期137卷 443-454页

作者： Zhihua Ren Xiaoxi Yang Tingting Ku Qian S.Liu Jiefeng Liang Qunfang Zhou Francesco Faiola Guibin Jiang State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China College of Resources and Environment University of Chinese Academy of SciencesBeijing 100049China College of Environment and Resource Research Center of Environment and HealthShanxi UniversityTaiyuan 030006China College of sino-danish University of Chinese Academy of SciencesBeijing 100049China

Investigating the development toxicity of perfuorinated iodine alkanes(PFIs)is critical,given their estrogenic effects through binding with estrogen receptors(ERs).In the present study,two PFIs,including dodecafuoro-1,6-diiodohexane(PFHx DI)and tridecafuorohexyl iodide(PFHx I),with binding preference to ERαand ERβ,respectively,were selected to evaluate their effects on proliferation and differentiation of the mouse embryonic stem cells(m ESCs).The results revealed that,similar to E_(2),50μmol/L PFHx DI accelerated the cell proliferation of the m ESCs.The PFI stimulation at the exposure concentrations of 2–50μmol/L promoted the differentiation of the m ESCs as characterized by the upregulation of differentiation-related biomarkers(i.e.,Otx2 and Dnmt3β)and downregulation of pluripotency genes(i.e.,Oct4,Nanog,Sox2,Prdm14 and Rex1).Comparatively,PFHx DI exhibited higher induction effect on the differentiation of the m ESCs than did PFHx I.The tests on ER signaling indicated that both PFI compounds induced exposure concentration-dependent expressions of ER signaling-related biomarkers(i.e.,ERα,ERβand Caveolin-1)in the m ESCs,and the downstream ER responsive genes(i.e.,c-fos,c-myc and c-jun)well responded to PFHx I stimulation.The role of ER in PFI-induced effects on the m ESCs was further validated by the antagonistic experiments using an ER inhibitor(ICI).The findings demonstrated that PFIs triggered ER signaling,and perturbed the differentiation program of the m ESCs,causing the potential health risk during early stage of development.

关键词： Perfuorinated iodine alkanes(PFIs) Embryonic stem cells(ESCs) Developmental toxicity Cell differentiation Estrogen receptor-related signaling

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Filtration performance and modeling of granular bed for dust removal from coal pyrolytic vapors

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Chinese Journal of Chemical Engineering 2024年第1期65卷 35-42页

作者： Shuaiqiang Yang Lin Du Guangchao Ding Runguo Liu Wenli Song Songgeng Li State Key Laboratory of Multiphase Complex Systems Institute of Process EngineeringChinese Academy of SciencesBeijing 100190China School of Petrochemical Engineering Yan’an Vocational and Technical CollegeYan’an 716000China sino-danish College University of Chinese Academy of SciencesBeijing 100049China

Dust removal from pyrolytic vapors at high temperatures is an obstacle to the industrialization of the coal pyrolysis process.In this work,a granular bed with expanded perlites as filtration media was designed and integrated into a 10 t·d^(–1)coal pyrolysis facility.The testing results showed that around 97.56%dust collection efficiency was achieved.As a result,dust content in tar was significantly lowered.The pressure drop of the granular bed maintained in the range of 356 Pa to 489 Pa.The dust size in the effluent after filtration exhibited a bimodal distribution,which was attributed to the heterogeneity of the dust components.The effects of filtration bed on pyrolytic product yields were also discussed.A modified filtration model based on the macroscopic phenomenological theory was proposed to describe the performance of the granular bed.The computation results were well agreed with the experimental data.

关键词： Granular bed filtration Dust removal Pyrolysis Filtration Fixed-bed

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Superhydrophobic magnetic Fe_(3)O_(4) polyurethane sponges for oil-water separation and oil-spill recovery

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Journal of Environmental Sciences 2024年第5期139卷 160-169页

作者： Shiyu Wu Yunjie Xiang Yaqi Cai Jingfu Liu sino-danish College University of Chinese Academy of SciencesBeijing 100049China State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China School of Environment Hangzhou Institute for Advanced StudyUCASHangzhou 310024China School of Environmental Science and Engineering Southern University of Science and TechnologyShenzhen 518055China

The effective and affordable separation of oil and water,a crucial process in the safe han dling of environmental disasters such as crude oil spills and recovery of valuable resources is a highly sought-after yet challenging task.Herein,superhydrophobic PU sponge was fab ricated for the fast and cost-effective adsorptive separation of oil and different organic sol vents from water.Octadecyltrichlorosilane(OTS)-functionalized Fe_(3)O_(4)@SiO_(2)core-shell mi crospheres were dip-coated on the surface of porous materials via a dip-coating process thereby endowing them with superhydrophobicity.Owing to the hydrophobic interaction between OTS molecules and oil and increased capillary force in the micropores,the result ing superhydrophobic sponge served as a selective oil-sorbent scaffold for absorbing oil from oil-water mixtures,including oil-water suspensions and emulsions.Remarkably,after the recovery of the adsorbed oil via mechanical extrusion,these superhydrophobic materials could be reused multiple times and maintain their oil-water separation efficacy even afte 10 oil-water separation cycles.

关键词： Fe_(3)O_(4)@SiO_(2)-OTS polyurethane sponge Oil-water separation Adsorption capacity Oil-spill recovery

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Human ESC-derived vascular cells promote vascular regeneration in a HIF-1α dependent manner

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Protein & Cell 2024年第1期15卷 36-51页

作者： Jinghui Lei Xiaoyu Jiang Daoyuan Huang Ying Jing Shanshan Yang Lingling Geng Yupeng Yan Fangshuo Zheng Fang Cheng Weiqi Zhang Juan Carlos Izpisua Belmonte Guang-Hui Liu Si Wang Jing Qu 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 State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Translational Medicine center Intermational Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China University of Chinese Academy of Sciences Beijing 100049China Institute for Stem Cell and Regeneration CASBeijing 100101China The Fifth People's Hospital of Chongqing Chongqing 400062China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China National Laboratory of Biomacromolecules CAs Center for Excellence in BiomacromoleculesInstitute of BiophysicsBeijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China China National center for Bioinformation Beijing 100101China sino-danish College University of Chinese Academy of SciencesBeijing 101408China sino-danish center for Education and Research Beijing 101408China Aging Biomarker Consortium China Altos Labs San DiegoCA 92121United State

Hypoxia-inducible factor(HIF-1α),a core transcription factor responding to changes in cellular oxygen levels,is closely associated with a wide range of physiological and pathological conditions.However,its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive.Here,we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-ia-deficient human vascular cells including vascular endothelial cells,vascular smooth muscle cells,and mesenchymal stem cells(MsCs),as a platform for discovering cell type-specific hypox-ia-induced response mechanisms.Through comparative molecular profiling across cell types under normoxic and hypoxic conditions,we provide insight into the indispensable role of HIF-1αin the promotion of ischemic vascular regeneration.We found human MSCs to be the vascular cell type most susceptible to HIF-1a deficiency,and that transcriptional inactivation of ANKZF1,an effector of HIF-1a,impaired pro-angiogenic processes.Altogether,our findings deepen the understanding of HIF-ia in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.

关键词： HIF-1 human ESC vascular cell regeneration

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Individualized brain mapping for navigated neuromodulation

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Chinese Medical Journal 2024年第5期137卷 508-523页

作者： Chaohong Gao Xia Wu Xinle Cheng Kristoffer Hougaard Madsen Congying Chu Zhengyi Yang Lingzhong Fan sino–danish College University of Chinese Academy of SciencesBeijing 100190China Brainnetome center National Laboratory of Pattern RecognitionInstitute of AutomationChinese Academy of SciencesBeijing 100190China School of Artificial Intelligence University of Chinese Academy of SciencesBeijing 100190China Department of Applied Mathematics and Computer Science Technical University of DenmarkKongens Lyngby 2800Denmark danish Research Centre for Magnetic Resonance Centre for Functional and Diagnostic Imaging and ResearchCopenhagen University Hospital Amager and HvidovreHvidovre 2650Denmark CAS center for Excellence in Brain Science and Intelligence Technology Institute of AutomationChinese Academy of SciencesBeijing 100190China School of Health and Life Sciences University of Health and Rehabilitation SciencesQingdaoShandong 266000China

The brain is a complex organ that requires precise mapping to understand its structure and function.Brain atlases provide a powerful tool for studying brain circuits,discovering biological markers for early diagnosis,and developing personalized treatments for neuropsychiatric disorders.Neuromodulation techniques,such as transcranial magnetic stimulation and deep brain stimulation,have revolutionized clinical therapies for neuropsychiatric disorders.However,the lack of fine-scale brain atlases limits the precision and effectiveness of these techniques.Advances in neuroimaging and machine learning techniques have led to the emergence of stereotactic-assisted neurosurgery and navigation systems.Still,the individual variability among patients and the diversity of brain diseases make it necessary to develop personalized solutions.The article provides an overview of recent advances in individualized brain mapping and navigated neuromodulation and discusses the methodological profiles,advantages,disadvantages,and future trends of these techniques.The article concludes by posing open questions about the future development of individualized brain mapping and navigated neuromodulation.

关键词： Brain atlas Individualization Navigated neuromodulation Multimodal magnetic resonance imaging Transcranial magnetic stimulation Deep brain stimulation

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Comprehensive evaluation of an ionic liquid based deep purification process for NH_(3)-containing industrial gas

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Journal of Environmental Sciences 2024年第2期136卷 698-708页

作者： Guoxiong Zhan Fei Cao Jianjun Chen Zhen Chen Yuanmeng Duan Fei Chang Shaojuan Zeng Yinge Bai Zengxi Li Xiangping Zhang Junhua Li State Key Joint Laboratory of Environment Simulation and Pollution Control School of EnvironmentTsinghua UniversityBeijing 100084China sino-danish College University of Chinese Academy of SciencesBeijing 100049China Institute of Process Engineering Chinese Academy of SciencesBeijing 100190China College of Chemical and Engineering University of Chinese Academy of SciencesBeijing 100049China

Ammonia(NH_(3))emission has caused serious environment issues and aroused worldwide concern.The emerging ionic liquid(IL)provides a greener way to efficiently capture NH_(3).This paper provides rigorous process simulation,optimization and assessment for a novel NH_(3)deep purification process using IL.The process was designed and investigated by simulation and optimization using ionic liquid[C_(4)im][NTF_(2)]as absorbent.Three objective functions,total purification cost(TPC),total process CO_(2)emission(TPCOE)and thermal efficiency(ηeff)were employed to optimize the absorption process.Process simulation and optimization results indicate that at same purification standard and recovery rate,the novel process can achieve lower cost and CO_(2)emission compared to benchmark process.After process optimization,the optimal functions can achieve 0.02726$/Nm~3(TPC),311.27 kg CO_(2)/hr(TP-COE),and 52.21%(ηeff)for enhanced process.Moreover,compared with conventional process,novel process could decrease over$3 million of purification cost and 10000 tons of CO_(2)emission during the life cycle.The results provide a novel strategy and guidance for deep purification of NH_(3)capture.

关键词： NH_(3) Capture Process Ionic Liquid Process Simulation Process Optimization Deep purification

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Decoding human brain functions: Multi-modal, multi-scale insights

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The Innovation 2024年第1期5卷 17-18页

作者： Camilla T.Erichsen Deying Li Lingzhong Fan sino-danish center University of Chinese Academy of SciencesBeijing 100190China Brainnetome center Institute of AutomationChinese Academy of SciencesBeijing 100190China Core Centre for Molecular Morphology Section for Stereology and MicroscopyDepartment of Clinical MedicineAarhus University8200 Aarhus NDenmark School of Health and Life Sciences University of Health and Rehabilitation SciencesQingdao 266000China

Unraveling the intricate relationship between the structure and function of the human brain remains a central and unresolved question in neuroscience.Ethical considerations impose significant constraints on invasive techniques in human neuroscience research.Consequently,knowledge about human brain function often relies on animal models to provide valuable discoveries and insights.However,caution is warranted,as findings from animal studies may not always be directly translatable to humans,especially when investigating higher cognitive functions.

关键词： functions insight modal

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Aging hallmarks of the primate ovary revealed by spatiotemporal transcriptomics

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Protein & Cell 2024年第5期15卷 364-384页

作者： Huifen Lu Ying Jing Chen Zhang Shuai Ma Weiqi Zhang Daoyuan Huang Bin Zhang Yuesheng Zuo Yingying Qin Guang-Hui Liu Yang Yu Jing Qu Si Wang Advanced Innovation center for Human Brain Protection National Clinical Research Center for 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 Medicine center International Center for Aging and CancerBeijing Municipal Geriatric Medical 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 Beijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China Institute for Stem cell and Regeneration CASBeijing 100101China China National center for Bioinformation Beijing 100101China The Fifth People’s Hospital of Chongqing Chongqing 400062China sino-danish College University of Chinese Academy of SciencesBeijing 101408China sino-danish center for Education and Research Beijing 101408China Department of Obstetrics and Gynecology Center for Reproductive MedicinePeking UniversityThird HospitalBeijing 100191China Clinical Stem Cell Research center Peking UniversityThird HospitalBeijing 100191China center for Reproductive Medicine Cheeloo College of MedicineShandong UniversityJinan 250012China Key Laboratory of Reproductive Endocrinology of Ministry of Education National Research Center for Assisted Reproductive Technology and Reproductive GeneticsShandong Key Laboratory of Reproductive MedicineShandong Provincial Clinical Research Center for Reproductive HealthJinan 250012China Key Laboratory of Organ Regeneration and Reconstruction Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Biomarker Consortium Beijing 100101China

The ovary is indispensable for female reproduction,and its age-dependent functional decline is the primary cause of infertility.However,the molecular basis of ovarian aging in higher vertebrates remains poorly understood.Herein,we apply spatiotemporal transcriptomics to benchmark architecture organization as well as cellular and molecular determinants in young primate ovaries and compare these to aged primate ovaries.From a global view,somatic cells within the non-follicle region undergo more pronounced transcriptional fluctuation relative to those in the follicle region,likely constituting a hostile microenvironment that facilitates ovarian aging.Further,we uncovered that inflammation,the senescent-associated secretory phenotype,senescence,and fibrosis are the likely primary contributors to ovarian aging(PCOA).Of note,we identified spatial co-localization between a PCOA-featured spot and an unappreciated MT2(Metallothionein 2)highly expressing spot(MT2^(high))characterized by high levels of inflammation,potentially serving as an aging hotspot in the primate ovary.Moreover,with advanced age,a subpopulation of MT2^(high)accumulates,likely disseminating and amplifying the senescent signal outward.Our study establishes the first primate spatiotemporal transcriptomic atlas,advancing our understanding of mechanistic determinants underpinning primate ovarian aging and unraveling potential biomarkers and therapeutic targets for aging and age-associated human ovarian disorders.

关键词： spatial transcriptome primate ovary aging senescence inflammation

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