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A Critical Role for γCaMKII in Decoding NMDA Signaling to Regulate AMPA Receptors in Putative Inhibitory Interneurons

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Neuroscience Bulletin 2022年第8期38卷 916-926页

作者： Xingzhi He Yang Wang Guangjun Zhou Jing Yang Jiarui Li Tao li Hailan Hu Huan Ma Department of Neurobiology Affiliated Mental Health Center and Hangzhou Seventh People’s HospitalZhejiang University School of MedicineHangzhou310058China NHC and CAMS Key Laboratory of Medical Neurobiology MOE Frontier Science Center for Brain Research and Brain–Machine IntegrationSchool of Brain Science and Brain MedicineZhejiang UniversityHangzhou310058China Research Units for Emotion and Emotion disorders Chinese Academy of Medical SciencesBeijing100730China

CaMKII is essential for long-term potentiation(LTP),a process in which synaptic strength is increased following the acquisition of information.Among the four CaMKII isoforms,γCaMKII is the one that mediates the LTP of excitatory synapses onto inhibitory interneurons(LTPE→I).However,the molecular mechanism underlying howγCaMKII mediates LTPE→I remains unclear.Here,we show thatγCaMKII is highly enriched in cultured hippocampal inhibitory interneurons and opts to be activated by higher stimulating frequencies in the 10–30 Hz range.Following stimulation,γCaMKII is translocated to the synapse and becomes co-localized with the postsynaptic protein PSD-95.Knocking downγCaMKII prevents the chemical LTP-induced phosphorylation and trafficking of AMPA receptors(AMPARs)in putative inhibitory interneurons,which are restored by overexpression ofγCaMKII but not its kinase-dead form.Taken together,these data suggest thatγCaMKII decodes NMDAR-mediated signaling and in turn regulates AMPARs for expressing LTP in inhibitory interneurons.

关键词： Synaptic plasticity LTP Inhibitory interneurons γCaMKII AMPAR NMDAR

Gut Microbiota Modulation:A Viable Strategy to Address Medical Needs in Hepatocellular Carcinoma and liver Transplantation

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Engineering 2023年第10期29卷 59-72页

作者： Ze Xiang Jian Wu Jiarui Li Shusen Zheng Xuyong Wei Xiao Xu Department of Hepatobiliary and Pancreatic Surgery Affiliated Hangzhou First People’s HospitalSchool of MedicineZhejiang UniversityHangzhou 310006China School of Medicine Zhejiang UniversityHangzhou 310058China Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Affiliated Hangzhou First People’s HospitalSchool of MedicineZhejiang UniversityHangzhou 310006China Department of Clinical Laboratory The Affiliated Suzhou Hospital of Nanjing Medical University&Suzhou Municipal HospitalGusu SchoolNanjing Medical UniversitySuzhou 215008China Shulan(Hangzhou)Hospital Zhejiang Shuren University School of MedicineHangzhou 310022China National Health Commission(NHC)Key Laboratory of Combined Multi-organ Transplantation the First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310003China

Hepatocellular carcinoma(HCC)is the most common malignancy of the liver,posing a significant threat to public health.Although liver transplantation(LT)is an effective treatment for HCC,ischemia–reperfusion(I/R)injury,transplant rejection,and complications after LT can greatly reduce its effectiveness.In recent years,transplant oncology has come into being,a comprehensive discipline formed by the intersection and integration of surgery,oncology,immunology,and other related disciplines.Gut microbiota,an emerging field of research,also plays a crucial role.Through the microbiome–gut–liver axis,the gut microbiota has an impact on the onset and progression of HCC as well as LT.This review summarizes the mechanisms by which the gut microbiota affects HCC and its bidirectional interactions with chronic liver disease that can develop into HCC as well as the diagnostic and prognostic value of the gut microbiota in HCC.In addition,gut microbiota alterations after LT were reviewed,and the relationship between the gut microbiota and liver I/R injury,the efficacy of immunosuppressive drugs used,and complications after LT were discussed.In the era of LT oncology,the role of the gut microbiota in HCC and LT should be emphasized,which can provide new insights into the management of HCC and LT via gut microbiota modulation.

关键词： Gut microbiota Hepatocellular carcinoma(HCC) liver transplantation(LT) Clinical value Mediating mechanism

Cell polarization in ischemic stroke: molecular mechanisms and advances

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Neural Regeneration Research 2025年第3期20卷 632-645页

作者： Yuanwei li Xiaoxiao Xu Xuan Wu Jiarui Li Shiling Chen Danyang Chen Gaigai li Zhouping Tang Department of Neurology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

Ischemic stroke is a cerebrovascular disease associated with high mortality and disability rates. Since the inflammation and immune response play a central role in driving ischemic damage, it becomes essential to modulate excessive inflammatory reactions to promote cell survival and facilitate tissue repair around the injury site. Various cell types are involved in the inflammatory response, including microglia, astrocytes, and neutrophils, each exhibiting distinct phenotypic profiles upon stimulation. They display either proinflammatory or anti-inflammatory states, a phenomenon known as ‘cell polarization.’ There are two cell polarization therapy strategies. The first involves inducing cells into a neuroprotective phenotype in vitro, then reintroducing them autologously. The second approach utilizes small molecular substances to directly affect cells in vivo. In this review, we elucidate the polarization dynamics of the three reactive cell populations(microglia, astrocytes, and neutrophils) in the context of ischemic stroke, and provide a comprehensive summary of the molecular mechanisms involved in their phenotypic switching. By unraveling the complexity of cell polarization, we hope to offer insights for future research on neuroinflammation and novel therapeutic strategies for ischemic stroke.

关键词： astrocyte polarization immune regulation inflammation ischemic injury microglia polarization neutrophil polarization signaling pathways stroke

An effective pharmacological hydrogel induces optic nerve repair and improves visual function

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Science China(life Sciences) 2024年第3期67卷 529-542页

作者： lipeng Wang Shan Zhang Yawen Han Shuo Tang Jiarui Li lina Bu Dongyu Zhao Hongkui Deng Department of Cell Biology Schoolof Basic Medical SciencesPeking University Stem Cell Research CenterStateKey Laboratoryof Naturaland Biomimetic DrugsPeking University Health Science Center Beijing 100191China MOE Key Laboratory of Cell Proliferation and Differentiation College of Life SciencesPeking-Tsinghua Center for Life SciencesPeking UniversityBeijing 100871China Academy for Advanced Interdisciplinary Studies Peking UniversityBeijing 100871China Changping Laboratory Beijing 102206China Department of Ophthalmology Peking University People's Hospital Eye Diseases and Optometry InstituteBeijing 100871China Department of Biomedical Informatics School of Basic Medical SciencesPeking UniversityBeijing 100191China

Irreversible eye lesions, such as glaucoma and traumatic optic neuropathy, can cause blindness;however, no effective treatments exist. The optic nerve, in particular, lacks the capacity to spontaneously regenerate, requiring the development of an effective approach for optic nerve repair, which has proven challenging. Here, we demonstrate that a combination of the small molecules 3BDO and trichostatin A(TSA)—which regulate mTOR and HDAC, respectively—packaged in thermosensitive hydrogel for 4-week-sustained release after intravitreal injection, effectively induced optic nerve regeneration in a mouse model of optic nerve crush injury. Moreover, this combination of 3BDO and TSA also protected axon projections and improved visual responses in an old mouse model(11 months old) of glaucoma. Taken together, our data provide a new, local small molecule-based treatment for the effective induction of optic nerve repair, which may represent a foundation for the development of pharmacological methods to treat irreversible eye diseases.

关键词： retinal ganglion cell axon regeneration old-age glaucoma small molecules pharmacological hydrogel visual function repair

A Novel Bidirectional Interaction Model and Electric Energy Measuring Scheme of EVs for V2G with Distorted Power Loads

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Computer Modeling in Engineering & Sciences 2022年第3期130卷 1789-1806页

作者： jiarui Cui Qing li Bin Cao Xiangquan li Qun Yan School of Automation and Electrical Engineering University of Science and Technology BeijingBeijing100083China Guiyang Aluminum Magnesium Design and Research Institute Co. Ltd.Guiyang550081China Chinalco Intelligent Technology Development Co. Ltd.Hangzhou311199China

With the increasing demand for petroleum resources and environmental issues,new energy electric vehicles are increasingly being used.However,the large number of electric vehicles connected to the grid has brought new challenges to the operation of the grid.Firstly,A novel bidirectional interaction model is established based on modulation theory with nonlinear loads.Then,the electric energy measuring scheme of EVs for V2G is derived under the conditions of distorted power loads.The scheme is composed of fundamental electric energy,fundamental-distorted electric energy,distorted-fundamental electric energy and distorted electric energy.And the characteristics of each electric energy are analyzed.Finally,the correctness of the model and energy measurement method is verified by three simulation cases:the impact signals,the fluctuating signals,and the harmonic signals.

关键词： Electric vehicles V2G energy metering bidirectional interaction model electric energy measuring scheme

High-speed impulsive stimulated Brillouin microscopy

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Photonics Research 2024年第4期12卷 730-739页

作者： Jiarui Li TAORAN LE HONGYUAN ZHANG HAOYUN WEI YAN li State Key Laboratory of Precision Measurement Technology and Instruments Department of Precision InstrumentTsinghua University Cole Eye Institute Cleveland Clinic

Brillouin microscopy, which maps the elastic modulus from the frequency shift of scattered light, has evolved to a faster speed for the investigation of rapid biomechanical changes. Impulsive stimulated Brillouin scattering (ISBS)spectroscopy has the potential to speed up measurement through the resonant amplification interaction from pulsed excitation and time-domain continuous detection. However, significant progress has not been achieved due to the limitation in signal-to-noise ratio (SNR) and the corresponding need for excessive averaging to maintain high spectral precision. Moreover, the limited spatial resolution also hinders its application in mechanical imaging. Here, by scrutinizing the SNR model, we design a high-speed ISBS microscope through multi-parameter optimization including phase, reference power, and acquisition time. Leveraging this, with the further assistance of the Matrix Pencil method for data processing, three-dimensional mechanical images are mapped under multiple contrast mechanisms for a millimeter-scale polydimethylsiloxane pattern immersed in methanol, enabling the identification of these two transparent materials without any contact or labeling. Our experimental results demonstrate the capability to maintain high spectral precision and resolution at a sub-millisecond integration time for one pixel. With a two-order improvement in the speed and a tenfold improvement in the spatial resolution over the state-of-the-art systems, this method makes it possible for ISBS microscopes to sensitively investigate rapid mechanical changes in time and space.

关键词： Biomedical imaging Matrix methods Spatial resolution Stimulated Brillouin scattering Three dimensional imaging Wave propagation

Bandgap engineering of high mobility two-dimensional semiconductors toward optoelectronic devices

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Journal of Materiomics 2023年第3期9卷 527-540页

作者： Qiaoyan Hao Peng li Jidong liu jiarui Huang Wenjing Zhang International Collaborative Laboratory of 2D Materials for Optoelectronics Science and Technology of Ministry of Education Institute of Microscale OptoelectronicsShenzhen UniversityShenzhen518060China Shenzhen Institute of Advanced Electronic Materials Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen518103China

Over the last few years,great advances have been achieved in exploration of high-mobility two-dimensional(2D)semiconductors such as metal chalcogenide InSe and noble-transition-metal dichal-cogenide PdSe_(2).These materials are competitive candidates for constructing next-generation optoelec-tronic devices owing to their unique crystalline and electronic structures.Moreover,the optical and electronic properties of 2D materials can be efficiently modified via precisely engineering their band structures,which is critical for widening specific applications ranging from high-performance opto-electronics to catalysis and energy harvesting.In this review,we focus on the progress in bandgaps engineering of newly emerging high-mobility 2D semiconductors and their applications in optoelec-tronic devices,incorporating our recent study in the InSe and PdSe_(2)systems.First of all,we discuss the structure-property relationship of typical high-mobility 2D semiconductors(InSe and PdSe 2).Next,we analyze several viable strategies for bandgap engineering,including thickness,strain or pressure,alloying,heterostructure,surface modification,intercalation,and so on.Furthermore,we summarize the optoelectronic devices fabricated with such high-mobility 2D semiconductors.The conclusion and outlook in this topic are finally presented.This review aims to provide valuable insights in bandgap engineering of newly emerging 2D semiconductors and explore their potential in future optoelectronic applications.

关键词： High mobility 2D semiconductors Bandgap engineering Alloying Heterostructure

Influence of topography on the fine structures of stratospheric gravity waves:An analysis using COSMIC-2 temperature data

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Earth and Planetary Physics 2024年第3期8卷 497-513页

作者： jiarui Wei Xiao liu JiYao Xu QinZeng li Hong Gao State Key Laboratory of Space Weather National Space Science CenterChinese Academy of SciencesBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China Institute of Electromagnetic Wave School of PhysicsHenan Normal UniversityXinxiang Henan 453000China

We derive the potential energy of gravity waves(GWs)in the upper troposphere and stratosphere at 45°S-45°N from December 2019 to November 2022 by using temperature profiles retrieved from the Constellation Observing System for Meteorology,Ionosphere,and Climate-2(COSMIC-2)satellite.Owing to the dense sampling of COSMIC-2,in addition to the strong peaks of gravity wave potential energy(GWPE)above the Andes and Tibetan Plateau,we found weak peaks above the Rocky,Atlas,Caucasus,and Tianshan Mountains.The land-sea contrast is responsible for the longitudinal variations of the GWPE in the lower and upper stratosphere.At 40°N/S,the peaks were mainly above the topographic regions during the winter.At 20°N/S,the peaks were a slight distance away from the topographic regions and might be the combined effect of nontopographic GWs and mountain waves.Near the Equator,the peaks were mainly above the regions with the lowest sea level altitude and may have resulted from convection.Our results indicate that even above the local regions with lower sea level altitudes compared with the Andes and Tibetan Plateau,the GWPE also exhibits fine structures in geographic distributions.We found that dissipation layers above the tropopause jet provide the body force to generate secondary waves in the upper stratosphere,especially during the winter months of each hemisphere and at latitudes of greater than 20°N/S.

关键词： topography fine structures stratospheric gravity waves Constellation Observing System for Meteorology Ionosphere and Climate-2(COSMIC-2) dissipation layers

Suboptimal adaptive tracking control for FIR systems with binary-valued observations

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Science China(Information Sciences) 2021年第7期64卷 37-47页

作者： Xiangquan li Zhengguang XU jiarui CUI lixin ZHANG School of Automation and Electrical Engineering University of Science and Technology Beijing Key Laboratory of Knowledge Automation for Industrial Processes Ministry of Education

In this paper, we investigate and analyze the suboptimal adaptive control for finite impulse response(FIR) systems with binary-valued observations. As the parameters of FIR systems are unknown and the measurable observations can only provide limited information, we propose and analyze a two-segment design method of an adaptive control law. First, we divide the system running time axis into many sections;each of these sections is divided into two segments. During the short segment, we design the system inputs for estimating parameters. Thus, we employ the empirical-measure-based technique for designing the identification algorithm. Second, we introduce a tracking control law to track a given target based on the system parameter estimates obtained in the short segment. We achieve this using the certainty equivalent principle in the long segment. As the length of short segments tends to infinity, we observe that the parameter estimation algorithm is consistent. However, when the length of segments tends to infinity, we find that the adaptive tracking control law is asymptotically suboptimal. Finally, we demonstrate the efficiency of the two-segment design method using the simulation results.

关键词： parameter identification FIR systems binary-valued observations asymptotically suboptimal tracking adaptive control