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| 1 | Vitamin B12 modulates Parkinson’s disease LRRK2 kinase activity through allosteric regulation and confers neuroprotection显示文摘Missense mutations in Leucine-Rich Repeat Kinase 2(LRRK2)cause the majority of familial and some sporadic forms of Parkinson’s disease(PD).The hyperactivity of LRRK2 kinase induced by the pathogenic mutations underlies neurotoxicity,promoting the development of LRRK2 kinase inhibitors as therapeutics.Many potent and specific small-molecule LRRK2 inhibitors have been reported with promise.However,nearly all inhibitors are ATP competitive—some with unwanted side effects and unclear clinical outcome—alternative types of LRRK2 inhibitors are lacking.Herein we identify 5′-deoxyadenosylcobalamin(AdoCbl),a physiological form of the essential micronutrient vitamin B12 as a mixed-type allosteric inhibitor of LRRK2 kinase activity.Multiple assays show that AdoCbl directly binds LRRK2,leading to the alterations of protein conformation and ATP binding in LRRK2.STD-NMR analysis of a LRRK2 homologous kinase reveals the contact sites in AdoCbl that interface with the kinase domain.Furthermore,we provide evidence that AdoCbl modulates LRRK2 activity through disrupting LRRK2 dimerization.Treatment with AdoCbl inhibits LRRK2 kinase activity in cultured cells and brain tissue,and prevents neurotoxicity in cultured primary rodent neurons as well as in transgenic C.elegans and D.melanogaster expressing LRRK2 disease variants.Finally,AdoCbl alleviates deficits in dopamine release sustainability caused by LRRK2 disease variants in mouse models.Our study uncovers vitamin B12 as a novel class of LRRK2 kinase modulator with a distinct mechanism,which can be harnessed to develop new LRRK2-based PD therapeutics in the future. | Adam Schaffner Xianting Li Yacob Gomez-Llorente Emmanouela Leandrou Anna Memou Nicolina Clemente Chen Yao Farinaz Afsari Lianteng Zhi Nina Pan Keita Morohashi Xiaoluan Hua Ming-Ming Zhou Chunyu Wang Hui Zhang Shu G.Chen Christopher J.Elliott Hardy Rideout Iban Ubarretxena-Belandia Zhenyu Yue | 2019 | Cell Research2019，29，4： | 7 |
| 2 | Regional Δ~14C patterns and fossil fuel derived CO_2 distribution in the Beijing area using annual plants显示文摘The level of atmosphericΔ14C and the fossil fuel derived CO 2 concentration in the Beijing area from May to September,2009, were systematically analyzed based on radiocarbon(14C)measurements of annual plants by accelerator mass spectrometry(AMS). The results show that the maximumΔ14C in Beijing was 29.6‰±2.2‰,and the minimum was–28.2‰±2.5‰,with a trend of decreasingΔ14C from the outer suburbs to inner suburbs to the urban center.This trend correlates well with increases in fossil fuel derived CO2 caused by human activities such as population density,industrial emissions and traffic,with lower values of atmosphericΔ14C associated with more intensive human activities.The fossil fuel derived CO 2 concentrations from May to September, 2009,ranged from 3.9±1.0 ppm to 25.4±1.0 ppm.It was calculated that each additional 1 ppm of CO2 from fossil fuels depleted the atmosphericΔ14C by approximately 2.70‰.This study suggests that 14C measurements of annual plants by AMS provide an effective method to rapidly trace fossil fuel derived CO2. | XI XianTing DING XingFang FU DongPo ZHOU LiPing LIU KeXin | 2011 | Chinese Science Bulletin2011，56，16： | 7 |
| 3 | Rarefaction and Temperature Gradient Effect on the Performance of the Knudsen Pump显示文摘The prediction of the multiscale flow in the Knudsen pump is important for understanding its pumping mechanism.However,there is little research on such interesting multiscale phenomenon in the Knudsen pumps.In this paper,a novel numerical analysis method combining the direct simulation Monte Carlo(DSMC) method with the smoothed particle hydrodynamics(SPH) method is presented for simulating the multiscale flow,which is often encountered in the application of the Knudsen pumps.Validity and accuracy of the new method are given by comparing its results with that of the previous research.Using the coupled multiscale approach,the rarefaction and the temperature drive are studied,which are two main factors on the performance of the Knudsen pumps.To investigate the effect of rarefaction on the performance of the Knudsen pump,various pump operation pressures are compared.The flow characteristics and pumping ability at different rarefaction are analyzed,and the phenomenon of the multiscale flow is also discussed.Several cases with different linear or nonlinear temperature gradients are set to investigate the effect of temperature gradient on the performance of the Knudsen pump.The flow characteristics of the Knudsen pump such as the velocity,pressure increase,and the mass flowrate are presented.A unique phenomenon,the reverse transpiration effect caused by the nonlinear temperature gradient is studied,and the reason of the significant pressure increase in the pump channel is also analyzed.Since the multiscale gas flow is widely encountered in the microflow systems,the above method and its results can also be greatly beneficial and provide significant insights for the design of the MEMS devices. | YE Jianjun YANG Jian ZHENG Jinyang DING Xianting WONG Ieong LI Weizhong CHEN Cong | 2012 | Chinese Journal of Mechanical Engineering2012，25，4： | 6 |
| 4 | Performance representation of variable-speed compressor for inverter air conditioners based on experimental data显示文摘 | Shuangquan Shao Wenxing Shi Xianting Li Huajun Chen | 2004 | International Journal of Refrigeration2004，，8： | 2 |
| 5 | Performance representation of variable-speed compressor for inverter air conditioners based on experimental data显示文摘 | Shao Shuangquan Shi Wenxing Li Xianting | 2004 | International Journal of Refrigeration2004，27，： | 1 |
| 6 | Numerical research on the scroll compressor with refrigeration injection显示文摘 | B Wang Wenxing Shia Xianting Li | 2008 | Applied thermal engineering2008，28，56： | 1 |
| 7 | Numerical Simulation of Air Distribution in Chair Ventilated Rooms by Simplified Methodology 显示文摘 | ZHAO Bin LI Xianting LU Junjun | 2002 | ASHRAE Trans2002，108，2： | 1 |
| 8 | DNA tetrahedron-mediated immune-sandwich assay for rapid and sensitive detection of PSA through a microfluidic electrochemical detection system显示文摘Prostate-specific antigen(PSA)is the most widely used biomarker for the early diagnosis of prostate cancer.Existing methods for PSA detection are burdened with some limitations and require improvement.Herein,we developed a novel microfluidic–electrochemical(μFEC)detection system for PSA detection.First,we constructed an electrochemical biosensor based on screen-printed electrodes(SPEs)with modification of gold nanoflowers(Au NFs)and DNA tetrahedron structural probes(TSPs),which showed great detection performance.Second,we fabricated microfluidic chips by DNA TSP-Au NF-modified SPEs and a PDMS layer with designed dense meandering microchannels.Finally,theμFEC detection system was achieved based on microfluidic chips integrated with the liquid automatic conveying unit and electrochemical detection platform.TheμFEC system we developed acquired great detection performance for PSA detection in PBS solution.For PSA assays in spiked serum samples of theμFEC system,we obtained a linear dynamic range of 1–100 ng/mL with a limit of detection of 0.2 ng/mL and a total reaction time<25 min.Real serum samples of prostate cancer patients presented a strong correlation between the“gold-standard”chemiluminescence assays and theμFEC system.In terms of operation procedure,cost,and reaction time,our method was superior to the current methods for PSA detection and shows great potential for practical clinical application in the future. | Dezhi Feng Jing Su Yi Xu Guifang He Chenguang Wang Xiao Wang Tingrui Pan Xianting Ding Xianqiang Mi | 2021 | Microsystems & Nanoengineering2021，7，2： | 1 |
| 9 | Per- formance representation of variable-speed compressor for inverter air conditioners based on experimental data 显示文摘 | Shao Shuangquan Shi Wenxing Li Xianting | 2004 | International Journal of Refrigeration2004，27，8： | 1 |
| 10 | Numerical analysis on the effects of refrigerant injection on the scroll compressor显示文摘 | WANG Baolong SHI Wenxing LI Xianting | 2009 | Applied Thermal Engineering2009，29，1： | 1 |
| 11 | Accessibility: a new concept to evaluate the ventilation performance in a finite period of time 显示文摘 | LI XIANTING ZHAO BIN | 2004 | Indoor and Built Environment2004，13，4： | 1 |
| 12 | A general geometrical model of scroll compressors based on discretional initial angles of involute显示文摘 | Wang Baolong Li Xianting Shi Wenxing | 2005 | International Journal of Refrigeration2005，28，6： | 1 |
| 13 | Accessibility:a new concept to evaluate the ventilation performance in a finite period of time显示文摘 | Li Xianting Zhao Bin | 2004 | Indoor and Built Environment2004，13，4： | 1 |
| 14 | An Algoritbaaa to Predict the Transient Moisture Distribution for Wall Condensation Under a Steady Flow Field显示文摘 | Ma Xiaojun Li Xianting Shao Xiaoliang | 2013 | Building and Environment2013，67，： | 1 |
| 15 | Performance of three air distribution systems in VOC removal from an area source显示文摘 | Xudong Yang Jelena Srebric Xianting Li | 2004 | Building and Environment2004，39，： | 1 |
| 16 | A simplified system for indoor airflow simulation 显示文摘 | ZHAO Bin LI Xianting YAN Qisen | 2003 | Build and Envir2003，38，4： | 1 |
| 17 | Numerical Anal- ysis on the Effects of Refrigerant Injection on the Scroll Compressor显示文摘 | Wang Baolong Shi Wenxing Li Xianting | 2009 | Applied Thermal Engineering2009，29，1： | 1 |
| 18 | Performance representation of variable-speed compressor for inverter air conditioners based on experimental data显示文摘 | Shao Shuangquan Shi Wenxing Li Xianting | 2004 | International Journal of Refrigeration2004，27，8： | 1 |
| 19 | Design of experimental bench and internal pressure measurement of scroll compressor with refrigerant injection 显示文摘 | Baolong Wang Xianting Li Wenxing Shi | 2007 | Interna- tional Journal of Refrigeration2007，30，1： | 1 |
| 20 | Energy saving potential of low temperature hot water system based on air source absorption heat pump显示文摘 | Li Xianting Wu Wei Zhang Xiaoling | 2012 | Applied Thermal Engineering2012，48，： | 1 |
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