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Functional aspects of the brain lymphatic drainage system in aging and neurodegenerative diseases

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Journal of Biomedical Research 2024年第3期38卷 206-221页

作者： Yan Chen Xiaoxin he jiachen Cai Qian Li Jiangsu Key Laboratory of Neurodegeneration Nanjing Medical UniversityNanjingJiangsu 211166China Shandong Institute of Brain Science and Brain-inspired Research Shandong First Medical University&Shandong Academy of Medical SciencesJinanShandong 250117China Center for Global health Nanjing Medical UniversityNanjingJiangsu 211166China

The phenomenon of an aging population is advancing at a precipitous rate.Alzheimer's disease(AD)and Parkinson's disease(PD)are two of the most common age-associated neurodegenerative diseases,both of which are primarily characterized by the accumulation of toxic proteins and the progressive demise of neuronal structures.Recent discoveries about the brain lymphatic drainage system have precipitated a growing body of investigations substantiating its novel roles,including the clearance of macromolecular waste and the trafficking of immune cells.Notably,aquaporin 4-mediated glymphatic transport,crucial for maintaining neural homeostasis,becomes disrupted during the aging process and is further compromised in the pathogenesis of AD and PD.Functional meningeal lymphatic vessels,which facilitate the drainage of cerebrospinal fluid into the deep cervical lymph nodes,are integral in bridging the central nervous system with peripheral immune responses.Dysfunction in these meningeal lymphatic vessels exacerbates pathological trajectory of the age-related neurodegenerative disease.This review explores modulatory influence of the glymphatic system and meningeal lymphatic vessels on the aging brain and its associated neurodegenerative disorders.It also encapsulates the insights of potential mechanisms and prospects of the targeted non-pharmacological interventions.

关键词： glymphatic system meningeal lymphatic vessels aging neurodegenerative diseases nonpharmacological therapies

Simultaneous capture of ISG15 conjugating and deconjugating enzymes using a semi-synthetic ISG15-Dha probe

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Science China Chemistry 2023年第3期66卷 837-844页

作者： Chuntong Li Tian Wang Lujun Liang Guochao Chu jiachen Zhang Wei he Lei Liu Jinghong Li Department of Chemistry Key Laboratory of Bioorganic Phosphorus Chemistry&Chemical BiologyCenter for Synthetic and Systems BiologyState Key Laboratory of Chemical Oncogenomics(Shenzhen)Tsinghua UniversityBeijing 100084China School of Pharmaceutical Sciences Tsinghua UniversityBeijing 100084China Center for BioAnalytical Chemistry Hefei National Laboratory of Physical Science at MicroscaleUniversity of Science and Technology of ChinaHefei 230026China

ISG15 is a ubiquitin-like(Ubl) protein attached to substrate proteins by ISG15 conjugating enzymes whose dysregulation is implicated in a multitude of disease processes, but the probing of these enzymes remains to be accomplished. here, we describe the development of a new activity-based probe ISG15-Dha(dehydroalanine) through protein semi-synthesis. In vitro crosslinking and cell lysate proteomic profiling experiments showed that this probe can sequentially capture ISG15 conjugating enzymes including E1 enzyme UBA7, E2 enzyme UBE2L6, E3 enzyme heRC5, the previously known ISG15 deconjugating enzyme(USP18), as well as some other enzymes(USP5 and USP14) which we additionally confirmed to impart deISGylation activity. Collectively, ISG15-Dha provides a new tool that can simultaneously capture ISG15 conjugating and deconjugating enzymes for biochemical or pharmacological studies.

关键词： ISG15-Dha probe semi-synthesis activity based probe proteomics ISGylation

Piezo1-targeted aerosol inhalation nanoparticles for acute lung injury

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Journal of Materials Science & Technology 2023年第10期141卷 21-31页

作者： Xinxin Liu Xuwei Ling Jiachen He Xingzhi Liu Lin Wang Huiling Liu Chang Liu Yi Wang Xiao Lin Chunhua Ling Qin Shi Department of Respiratory Medicine the First Affiliated Hospital of Soochow UniversitySuzhou 215031China Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Gannan Medical University/Gannan Branch of National Clinical Research Center for GeriatricsGanzhou 341000China Department of Orthopedics the First Affiliated Hospital of Soochow UniversityOrthopedic Institute of Soochow UniversitySuzhou 215031China School of Nano-Tech and Nano-Bionics University of Science and Technology of ChinaSuzhou 215123China University of Science and Technology of China Hefei 230026China National Clinical Research Center for hematologic Diseases the First Affiliated Hospital of Soochow UniversitySuzhouJiangsu 215031China

Inhaled drug-containing nanocarriers have been well applied as an important strategy in pulmonary dis-eases.Acute lung injury(ALI)is characterized by abnormal lung tension and complex pathogenesis,with high mortality because of the limitations of targeted intervention.Accordingly,in the present study,we first identified that the mechanosensitive ion channel Piezo1 participated in the ALI-associated processes induced by lipopolysaccharide(LPS)in vitro and in vivo.Then,chitosan-stabilized bovine serum albu-min nanoparticles(NCs)emulsified with the Piezo1 inhibitor GsMTx4(NC-GsMTx4)were generated and exhibited excellent biocompatibility and biological function.Through aerosol inhalation,NC-GsMTx4 im-proved lung injury and inhibited cell apoptosis in LPS-stressed ALI mice and alleviated pulmonary fibrosis during the later stage of ALI.Mechanistically,GsMTx4 could regulate inflammation and apoptosis in lung epithelial cells via NF-κB and ERK1/2 signaling.In summary,our findings provide new insights into the pathological mechanisms of Piezo1 in ALI progression,and nebulized inhalation of NC-GsMTx4 offers a prospective platform for targeting Piezo1 to treat ALI efficiently and conveniently.

关键词： Acute lung injury Piezo1 Nanoparticle carrier NF-κB ERK1/2 GsMTx4

4K-DMDNet:diffraction model-driven network for 4K computer-generated holography

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Opto-Electronic Advances 2023年第5期6卷 17-29页

作者： Kexuan Liu jiachen Wu Zehao he Liangcai Cao State Key Laboratory of Precision Measurement Technology and Instruments Department of Precision InstrumentsTsinghua UniversityBeijing 100084China

Deep learning offers a novel opportunity to achieve both high-quality and high-speed computer-generated holography(CGH).Current data-driven deep learning algorithms face the challenge that the labeled training datasets limit the training performance and generalization.The model-driven deep learning introduces the diffraction model into the neural network.It eliminates the need for the labeled training dataset and has been extensively applied to hologram generation.However,the existing model-driven deep learning algorithms face the problem of insufficient constraints.In this study,we propose a model-driven neural network capable of high-fidelity 4K computer-generated hologram generation,called 4K Diffraction Model-driven Network(4K-DMDNet).The constraint of the reconstructed images in the frequency domain is strengthened.And a network structure that combines the residual method and sub-pixel convolution method is built,which effectively enhances the fitting ability of the network for inverse problems.The generalization of the 4K-DMDNet is demonstrated with binary,grayscale and 3D images.High-quality full-color optical reconstructions of the 4K holograms have been achieved at the wavelengths of 450 nm,520 nm,and 638 nm.

关键词： computer-generated holography deep learning model-driven neural network sub-pixel convolution oversampling

Efficient hydrogenation of ethylene carbonate derived from CO_(2) to synthesize methanol and ethylene glycol over core-shell Cu@GO catalyst

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Green Chemical Engineering 2022年第3期3卷 228-239页

作者： Chanjuan Zhang Liguo Wang Zhuo Han Peng he Yan Cao jiachen Li Huiquan Li CAS Key Laboratory of Green Process and Engineering National Engineering Research Center of Green Recycling for Strategic Metal ResourcesInstitute of Process EngineeringChinese Academy of SciencesBeijing100190China Sino-Danish College University of Chinese Academy of SciencesBeijing100049China Sino-Danish Center for Education and Research University of Chinese Academy of SciencesBeijing100049China School of Chemical Engineering University of Chinese Academy of SciencesBeijing100049China Dalian National Laboratory for Clean Energy Dalian116023China

The synthesis of sustainable methanol and ethylene glycol(EG)via hydrogenation of ethylene carbonate(EC)has caught researchers’growing interests on account of the indirect chemical utilization of CO_(2).Core-shell Cu@GO catalysts with random nanoporous network of graphite oxide(GO)were synthesized via a simple method of ul-trasonic precipitation.Cu@GO catalysts were analyzed systematically by N_(2) physisorption,TGA measurement,XRD,FT-IR,Raman,TEM,SEM,and XPS(XAES).In particular,the mentioned method was confirmed to be effective to fabricate the high dispersity core-shell Cu@GO catalysts through promoting the specific surface area.The as-prepared Cu@GO catalyst was then successfully applied in the hydrogenation of CO_(2)-derived EC to pro-duce methanol and EG.A high TOF of 1526 mg EC g cat^(-1) h^(-1) could be attained in EC hydrogenation at the reaction temperature of 493K.Accordingly,the correlation of catalytic structure and performance disclosed that the synergistic effect between Cu^(+) and Cu^(0) was responsible for achieving high activity of the catalyst.In addition,the reusability of Cu@GO catalyst suggested that graphite oxide shell structure could decrease the aggregation of Cu particles,thus enhance the stability of Cu-based catalysts.DFT calculation results suggested that the involvement of carbon film on Cu was favorable for the stabilization of the active sites.This study is helpful for developing new and stable catalytic system for indirect chemical utilization of CO_(2) to synthesize commodity methanol and EG.

关键词： Ethylene carbonate Selective hydrogenation Methanol Ethylene glycol Cu-based catalyst

Epigenetic regulation of hematopoietic stem cell homeostasis

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Blood Science 2019年第1期1卷 19-28页

作者： Penglei Jiang Hui Wang jiachen Zheng Yingli Han he Huang Pengxu Qian Center of Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated HospitalZhejiang University School of MedicineHangzhouP.R.China Institute of hematology Zhejiang Engineering Laboratory for Stem Cell and ImmunotherapyZhejiang UniversityHangzhouP.R.China

As one of the best characterized adult stem cells,hematopoietic stem cell(HSC)homeostasis is of great importance to hematopoiesis and immunity due to HSC’s abilities of self-renewal and multi-lineage differentiation into functional blood cells.However,excessive self-renewal of HSCs can lead to severe hematopoietic malignancies like leukemia,whereas deficient selfrenewal of HSCs may result in HSC exhaustion and eventually apoptosis of specialized cells,giving rise to abnormalities such as immunodeficiency or anemia.How HSC homeostasis is maintained has been studied for decades and regulatory factors can be generally categorized into two classes:genetic factors and epigenetic factors.Although genetic factors such as signaling pathways or transcription factors have been well explored,recent studies have emerged the indispensable roles of epigenetic factors.In this review,we have summarized regulatory mechanisms of HSC homeostasis by epigenetic factors,including DNA methylation,histone modification,chromatin remodeling,non-coding RNAs,and RNA modification,which will facilitate applications such as HSC ex vivo expansion and exploration of novel therapeutic approaches for many hematological diseases.

关键词： Epigenetics hematopoietic stem cells Homeostasis

Inferring user profiles in social media by joint modeling of text and networks

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Science China(Information Sciences) 2019年第11期62卷 201-203页

作者： Ruifeng XU jiachen DU Zhishan ZHAO Yulan he Qinghong GAO Lin GUI School of Computer Science and Technology Harbin Institute of Technology Shenzhen Graduate School Baidu Inc. Department of Computer Science University of Warwick

Dear editor,With the rapid growth of social media platforms such as Twitter and Chinese Weibo, personalized services, such as recommendation and personalized advertising, provide more engaging experiences for the users. A prerequisite to personalized services is effective user profiling. However, many users do not want to share their profiles online due to

关键词： profile Inferring user profiles in social media by joint modeling of text and networks

A Cost-Effective D-A-D Type Hole-Transport Material Enabling 20% Efficiency Inverted Perovskite Solar Celis

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Chinese Journal of Chemistry 2021年第6期39卷 1545-1552页

作者： jiachen Huang Jie Yang Huiliang Sun Kui Feng Qiaogan Liao Bolin Li he Yan Xugang Guo Department of Materials Science and Engineering Southern University of Science and Technology(SUSTech)No.1088Xueyuan RoodShenzhenGuangdong 518055China Depanment of Chemistry The Hong Kong University of Science and TechnologyClear Water BayHong KongChina School of Materials Science and Engineering Harbin Institute of TechnologyHorbinHeilongjiang 150001China

High-performance,cost-effective hole-transport materials(HTMs)are greatly desired for the commercialization of perovskite solar cells(PVSCs).herein,two new HTMs,TPA-FO and TPA-PDO,are devised and synthesized,which have a donor-acceptor-donor(D-A-D)type molecule design featuring carbonyl group-functionalized arenes as the acceptor(A)units.The carbonyl group at the central core of HTMs can not only tune frontier molecular orbital(FMO)energy levels and surface wettability,but also can enable efficient surface passivation effects,resulting in reduced recombination loss.When employed as HTMs in inverted PVSCs without using dopant,TPA-FO with one carbonyl group yields a high power conversion efficiency(PCE)of 20.24%,which is among the highest values reported in the inverted PVSCs with dopant-free HTMs.More importantly,the facile one-step synthetic process enables a low cost of 30 USD g^(-1) for TPA-FO,much cheaper than the most studied HTMs used for high-efficiency dopant-free PVSCs.These results demonstrate the potential of D-A-D type molecules with carbonyl group-functionalized arene core in developing the low-cost dopant-free HTMs toward highly efficient PVSCs.

关键词： Energy conversion Donor-acceptor systems Interfaces Hole-transport materials Inverted perovskite solar cells

基于强化学习的大跨度桥梁风致振动主动控制研究

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交通科技 2023年第6期 18-24页

作者：何佳琛中铁第四勘察设计院集团有限公司武汉430063

主动控制措施依靠外部能源供给,可有效抑制大跨度桥梁的风致振动。为探究基于强化学习的大跨度桥梁风致振动主动控制,以苏通长江大桥为工程背景,建立风-桥-主动质量阻尼器的时域控制方程,利用深度确定性策略梯度强化学习算法(DDPG)为主... 详细信息

主动控制措施依靠外部能源供给,可有效抑制大跨度桥梁的风致振动。为探究基于强化学习的大跨度桥梁风致振动主动控制,以苏通长江大桥为工程背景,建立风-桥-主动质量阻尼器的时域控制方程,利用深度确定性策略梯度强化学习算法(DDPG)为主动质量阻尼器设计控制律,并与利用LQR算法所设计出的主动控制系统在抑振效果层面进行对比,检验利用强化学习算法所设计的控制系统在面对随机风环境及结构参数不确定时的鲁棒性能,并以一个单自由度非线性涡振主动控制的工况说明了强化学习对非线性系统的适用性。结果表明,利用DDPG算法设计出的主动控制律在实施时仅需要测量桥梁跨中节点的位移响应和加速度响应就能够达到与LQR算法相当的控制效果;当系统产生外部扰动或桥梁结构本身的刚度矩阵发生改变时,利用强化学习设计的ATMD仍具备令人满意的控制性能;强化学习是一个适用范围广泛的通用性框架,可用于线性或非线性系统,由于其本身的理念,其所设计出的主动控制系统,在均方值控制效果方面优于相应的峰值控制效果。

关键词：主动控制措施强化学习深度确定性策略梯度算法鲁棒性非线性系统