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Optimized nanoparticle-mediated delivery of CRISPR- Cas9 system for B cell intervention

nano Research 2018年第12期11卷 6270-6282页

作者： Min Li ya-nan fan Zhi-yao Chen Ying-Li Luo Yu-Cai Wang Zhe-Xiong Lian Cong-Fei Xu Jun Wang School of Life Sciences University of Science and Technology of ChinaHefei230027China Institutes for Life Sciences School of MedicineSouth China University of TechnologyGuangzhou 510006China School of Biomedical Sdence and Engineering South China University of TechnologyGuangzhou 510006China National Engineering Research Center for 7issue Restoration and Reconstruction South China University of TechnologyGuangzhou 570006China Key Laboratory of Biomedical Engineering of Guangdong Province South China University of TechnologyGuangzhou 510006China

B cells exert multiple effector functions, and dysfunctions of B cells often lead to initiation and progression of diseases, including autoimmune and inflammatory diseases. Therefore, B cell intervention may be an effective strategy to treat diseases involving B cells. The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 gene editing system has been widely used for DNA deletion, insertion, and replacement. nanocarriers have been developed as relatively mature systems and may be applied to deliver the CRISPR-Cas9 system to B cells in vivo. In this study, we created a library of nanoparticles (NPs) with different polyethylene glycol densities and zeta potentials and screened an optimal NP for in vivo B cell targeting. The selected NP could deliver the CRISPR-Cas9 system to B cells and induce Cas9 expression inside the cell environment. Injection of the NP encapsulated with Cas9/gB220 (NPCas9/gB220) into mice could disrupt B220 expression in B cells, suggestive of its applications to intervene the expression of the target molecule in B cells. Moreover, the treatment with NPCas9/gBAFFR could decrease the number of B cells and exert therapeutic effect in rheumatoid arthritis, as B-cell activating factor receptor (BAFFR) is vital for the survival and functions of B cells. In conclusion, we developed a carrier for the delivery of the CRISPR-Cas9 gene editing system for B cell intervention that could be used for the treatment of diseases related to B cell dysfunctions.

关键词： B cell gene editing nanoparticle immune intervention autoimmunity

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Highly Efficient DCL, UCL, and TPEF in Hybridized Ln-Complexes from Ir-Metalloligand

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CCS Chemistry 2021年第2期3卷 729-738页

作者： Jun-Ting Mo Zheng Wang Peng-yan Fu Lu-Yin Zhang ya-nan fan Mei Pan Cheng-Yong Su MOE Laboratory of Bioinorganic and Synthetic Chemistry Lehn Institute of Functional MaterialsSchool of ChemistrySun Yat-Sen UniversityGuangzhou 510275 State Key Laboratory of Advanced Processing and Recycling of Nonferrous Metals School of Materials Science and EngineeringLanzhou University of TechnologyLanzhou 730050 State Key Laboratory of Applied Organic Chemistry Lanzhou UniversityLanzhou 730000

In molecular level lanthanide complexes,it is still challenging to achieve near-infrared(NIR)down-conversion luminescence(DCL)and visible up-conversion luminescence(UCL)efficiently under ambient *** delicate design of hybridized iridium−europium−ytterbium(Ir–Eu–Yb)trimetallic complexes from an Ir-metalloligand,DCL and UCL emissions with opposite photon conversion pathways were achieved simultaneously in one integrated *** detail,three different types of energy transfer(ET)and photoluminescence(PL)were detected,as follows:(1)Highly sensitized NIR-DCL from Yb(III)center via ETIr→Eu→Yb,which gave the longest decay lifetime(553μs)at room temperature ever reported in solid-state Yb-complexes.(2)Unprecedented UCL red emission from Eu(III)center via ETYb→Eu using 980 nm continuous wavelength(CW)laser excitation,which required ultralow energy threshold(0.616W/cm2).(3)Two-photon excited fluorescence(TPEF)via ETIr→Eu using femtosecond pulsed laser *** exquisite module of“one stone,three birds”provides a new stimulus in the design and application of multifunctional UCL/DCL/TPEF optical materials under ambient conditions.

关键词： NIR up-conversion down-conversion,two-photon d–f heteronuclear

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Progress in nanoparticle-based regulation of immune cells

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Medical Review 2023年第2期3卷 152-179页

作者： ya-nan fan Gui Zhao Yue Zhang Qian-Ni Ye Yi-Qun Sun Song Shen yang Liu Cong-Fei Xu Jun Wang School of Biomedical Sciences and Engineering South China University of TechnologyGuangzhou International CampusGuangzhouGuangdong ProvinceChina National Engineering Research Center for Tissue Restoration and Reconstruction South China University of TechnologyGuangzhouGuangdong ProvinceChina Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education South China University of TechnologyGuangzhouGuangdong ProvinceChina Department of Biomedical Engineering Wake Forest School of MedicineWinston-SalemNCUSA School of Biomedical Sciences and Engineering South China University of TechnologyGuangzhou International CampusGuangzhou 511442Guangdong ProvinceChina National Engineering Research Center for Tissue Restoration and Reconstruction South China University of TechnologyGuangzhou 510006Guangdong ProvinceChina Guangdong Provincial Key Laboratory of Biomedical Engineering South China University of TechnologyGuangzhou 510006Guangdong ProvinceChina

Immune cells are indispensable defenders of the human body,clearing exogenous pathogens and toxicities or endogenous malignant and aging *** cell dysfunction can cause an inability to recognize,react,and remove these hazards,resulting in cancers,inflammatory diseases,autoimmune diseases,and *** cells regulation has shown great promise in treating disease,and immune agonists are usually used to treat cancers and infections caused by immune *** contrast,immunosuppressants are used to treat inflammatory and autoimmune ***,the key to maintaining health is to restore balance to the immune system,as excessive activation or inhibition of immune cells is a common complication of *** are efficient drug delivery systems widely used to deliver small molecule inhibitors,nucleic acid,and *** nanoparticles for the targeted delivery of drugs to immune cells provides opportunities to regulate immune cell *** this review,we summarize the current progress of nanoparticle-based strategies for regulating immune function and discuss the prospects of future nanoparticle design to improve immunotherapy.

关键词： biomaterial drug delivery immune cell immunotherapy nanoparticle

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Tenofovir disoproxil fumarate in Chinese chronic hepatitis B patients:Results of a multicenter,double-blind,double-dummy,clinical trial at 96 weeks

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World Journal of Clinical Cases 2021年第18期9卷 4690-4699页

作者： Xiao-fan Chen ya-nan fan Chong-Wen Si yan-yan Yu Jia Shang Zu-Jiang Yu Qing Mao Qing Xie Wei Zhao Jun Li Zhi-Liang Gao Shan-Ming Wu Hong Tang Jun Cheng Xin-Yue Chen Wen-Hong Zhang Hao Wang Zhong-nan Xu Ling Wang Jun Dai Jing-Hang Xu Department of Infectious Diseases Center for Liver DiseasesPeking University First HospitalBeijing 100034China Department of Infectious Diseases Henan Provincial People's HospitalZhengzhou 450003Henan ProvinceChina Department of Infectious Diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina Department of Infectious Diseases Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Department of Infectious Diseases Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai 200025China Department of Infectious Diseases The Second Affiliated Hospital of Southeast UniversityNanjing 210011Jiangsu ProvinceChina Department of Infectious Diseases The First Affiliated Hospital with Nanjing Medical UniversityNanjing 210029Jiangsu ProvinceChina Department of Infectious Diseases The Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630Guangdong ProvinceChina Department of Infectious Diseases Shanghai Public Health Clinical CenterFudan UniversityShanghai 201052China Department of Infectious Diseases West China Hospital of Sichuan UniversityChengdu 610041Sichuan ProvinceChina Center of Hepatology Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Department of International Medical Beijing Youan HospitalCapital Medical UniversityBeijing 10069China Department of Infectious Diseases Huashan HospitalFudan UniversityShanghai 200040China Department of Infectious Diseases Peking University People's HospitalBeijing 100044China Clinical Center Jiangsu Chia-tai Tianqing Pharmaceutical Co.LtdNanjing 210000Jiangsu ProvinceChina

BACKGROUND Tenofovir disoproxil fumarate(TDF)is a prodrug of a nucleotide *** an antiviral drug,TDF has been proposed in the first-line treatment of chronic hepatitis B(CHB).Qingzhong,a brand name of TDF,commercialized by Jiangsu Chia-tai Tianqing Pharmaceutical Co Ltd.,and Viread,another brand name of TDF,commercialized by GlaxoSmithKline,have both been approved by the State Food and Drug Administration,*** To investigate the efficacy and safety of the two TDF agents in the treatment of Chinese CHB *** This trial was registered at *** with the identifier number of NCT02287857.A total of 330 Chinese CHB patients,among which 232 were hepatitis B e antigen(HBeAg)-positive,were included in this 5-year-long,multicenter,double-blinded,double-dummy,randomized-controlled,noninferiority phase III *** participants were initially randomized into two groups:Group A(n=161),in which the participants received 300 mg Qingzhong once a day for 48 wk;and Group B,in which the participants received 300 mg Viread once a day for 48 *** from week 49,all the participants in Groups A and B received 300 mg Qingzhong once a day until the 96th *** this study,the primary endpoint was the decrease in plasma level of hepatitis B virus(HBV)DNA at the 96th week,while the secondary endpoints were suppression of HBV replication,alanine aminotransferase(ALT)normalization,HBeAg loss,and HBeAg seroconversion *** For the participants with HBeAg-positive CHB,the decrease in mean HBV DNA level relative to the baseline value was comparable between Groups A and B(5.77 vs 5.73 log10 IU/mL,P>0.05)at the 96th *** addition,similar percentages of HBeAg-positive participants in the two groups exhibited undetectable levels of HBV DNA,HBeAg loss,and HBeAg seroconversion(71.05%vs 77.97%,31.00%vs 27.27%,and 20.22%vs 15.79%,respectively,in Group A vs Group B;P>0.05).For the participants with HBeAg-negative CHB,the decrease in mean HBV DNA level r

关键词： Chronic hepatitis B Hepatitis B virus infection Chronic Tenofovir disoproxil

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Microglia lactylation in relation to central nervous system diseases

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Neural Regeneration Research 2025年第1期20卷 29-40页

作者： Hui yang nan Mo Le Tong Jianhong Dong Ziwei fan Mengxian Jia Juanqing Yue Ying Wang School of Pharmacy Hangzhou Normal UniversityHangzhouZhejiang ProvinceChina Department of Clinical Laboratory The Fourth Clinical Medical College of Zhejiang University of Traditional Chinese Medicine(Hangzhou First People’s Hospital)HangzhouZhejiang ProvinceChina College of Medical Veterinary and Life SciencesUniversity of GlasgowGlasgowUK Department of Orthopedics(Spine Surgery) the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Department of Pathology Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhouZhejiang ProvinceChina Department of Clinical Research Center Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhouZhejiang ProvinceChina

The development of neurodegenerative diseases is closely related to the disruption of central nervous system ***,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative *** has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of *** is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various *** review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting ***,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.

关键词： brain central nervous system glycolysis immune response inflammation lactate metabolism lactate lactylation microglia neurodegenerative diseases

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Effects of water level variations on the water quality of Huayang Lakes, China

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Journal of Geographical Sciences 2025年第1期35卷 173-188页

作者： AN Lesheng LIU Chun fan Zhongya LIAO Kaihua WANG Wencai WANG nan School of Resources and Environment Anqing Normal University South China Institute of Environmental Sciences Ministry of Ecology and Environment The Key Laboratory of Watershed Geographic Sciences Nanjing Institute of Geography and LimnologyCAS

To explore water level variations and their dynamic influence on the water quality of Huayang Lakes, the water level from 1967 to 2023 and water quality from 2015 to 2023 were analyzed using the Mann–Kendall trend test, box plots, and violin plots. The results show a notable hydrological rhythm of water level alternation between dry and flood seasons in Huayang Lakes, with an average water level of 12.82 m and a monthly range of 11.21–17.24m. Since 2017, the water level of Huayang Rivers has shown a decreasing trend of –0.02 m/*** phosphorus(TP) has become the primary pollutant. The TP concentrations in Longgan Lake(the largest lake) during the dry, rising, flood, and retreating seasons from 2015 to 2023were 0.083, 0.061, 0.050, and 0.059 mg/L, respectively. The effect of water level on TP was mainly observed during the low-water period. When the water level in the dry season rose to 12.25 and 13.00 m, the percentage of TP exceeding 0.1 mg/L in Longgan Lake decreased to 55.8% and 33.3%, respectively. During the dry season, wind and wave disturbances caused the release of endogenous phosphorus in Huayang Lakes. This led to drastic fluctuations in TP concentration, reducing the correlation between water level and TP. When external control is limited, the water level during the dry season should be maintained between 12.25 and 13.0 m. Additionally, it is necessary to accelerate the restoration of submerged macrophyte species(such as Hydrilla verticillata and Vallisneria natans) in the Huayang Rivers.

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Tackling the microlensing wave effects of strong lensing gravitational waves with TAAH

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 257-258页

作者： Zuhui fan South-Western Institute for Astronomy Research Yunnan University

The rapid development of gravitational wave（GW） observations since their first detection in 2015 [1] has opened a completely new window for exploring the Universe. Consequently, astronomical research has entered the multimessenger era, allowing us to use different tracers to view the cosmos from various perspectives. Among others, the appealing application of gravitational wave events from compact binary mergers is that they can act as standard sirens to determine absolute cosmic distances entirely independent of standard candles. This approach is one of the most promising means to solve the current H0tension problem.

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Soluble epoxide hydrolase:a next-generation drug target for Alzheimer's disease and related dementias

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Neural Regeneration Research 2025年第9期20卷 2585-2586页

作者： Andrew Gregory Chengyun Tang fan fan Department of Physiology Medical College of GeorgiaAugusta UniversityAugustaGAUSA

Alzheimer's disease(AD)and Alzheimer's diseaserelated dementias(ADRD)represent a significant public health challenge,with projections indicating a substantial increase in affected individuals due to the aging global *** the World Health Organization,AD/ADRD has affected more than 55 million individuals worldwide,with an additional 10 million cases diagnosed each year.

关键词： Alzheimer population drug

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Reconstructing forest and grassland cover changes in China over the past millennium

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Science China Earth Sciences 2025年第1期68卷 94-110页

作者： fanneng HE fan yaNG yafei WANG Key Laboratory of Land Surface Pattern and Simulation Institute of Geographic Sciences and Natural Resources Research Chinese Academy of Sciences Key Research Institute of Yellow River Civilization and Sustainable Development Henan University University of Chinese Academy of Sciences

Historical forest and grassland cover changes not only are critical indicators for quantifying ecological and environmental change processes but also serve as fundamental data for long-term climate change simulations and terrestrial ecosystem carbon emission assessments. However, because of limitations in historical data, quantitative estimations and spatially gridded reconstructions of these changes remain challenging, necessitating further methodological exploration. This study focused on China's present-day land area over the past millennium, objectively capturing the characteristics and drivers of forest and grassland cover changes. On this basis, using the forest transition theory and the space-for-time substitution method, we depicted the historical deforestation process as an inverted “S” curve and developed a model to reconstruct historical forest area changes based on the functional relationship between the forest area and population size dynamics. Subsequently, a gridded forest allocation model was established on the basis of deforestation tendencies. For the grassland cover, we implemented regionspecific methods, such as the cropland area deduction method and the habitat constraint method, to quantitatively reconstruct historical changes. Consequently, we obtained provincial forest and grassland area changes over the past millennium and mapped 10-km-resolution gridded data of forest and grassland cover. The results indicated the following.(1) The methods developed using population data as a proxy objectively reproduced the spatiotemporal evolution of forest and grassland cover in China over the past millennium. These feasible methods offer a novel pathway for the quantitative reconstruction of historical forest and grassland cover changes.(2) The data indicated that China's forest area generally decreased over the past millennium, characterized by a “decrease-then-increase” pattern. The forest area experienced three distinct phases: a slow decline(AD 1000

关键词： Land use and land cover change Forest Grassland Quantitative reconstruction Gridded reconstruction China historical period

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低温胁迫下水稻基因组DNA甲基化的MSAP分析

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安徽农业科学 2017年第4期45卷 135-137,186页

作者：王亚男范思静安徽金培因科技有限公司安徽合肥230088

[目的]研究低温胁迫对水稻幼苗DNA甲基化水平及模式变化。[方法]以水稻幼苗为材料,利用66个不同的引物组合对来自对照(CK)、4℃低温胁迫1 d(T_1)、4℃低温胁迫2 d(T_2)、4℃低温胁迫3 d(T_3)和恢复2 d(T_4)的水稻DNA样品进行甲基化敏感... 详细信息

[目的]研究低温胁迫对水稻幼苗DNA甲基化水平及模式变化。[方法]以水稻幼苗为材料,利用66个不同的引物组合对来自对照(CK)、4℃低温胁迫1 d(T_1)、4℃低温胁迫2 d(T_2)、4℃低温胁迫3 d(T_3)和恢复2 d(T_4)的水稻DNA样品进行甲基化敏感扩增多态性(MSAP)分析,探讨低温胁迫和恢复后,DNA的甲基化水平及模式变化。[结果]甲基化水平分析表明,CK、T_1、T_2、T_3处理样本中总甲基化率分别为37.19%、33.79%、33.67%和32.67%。进一步分析表明低温胁迫处理导致水稻DNA总甲基化水平降低,然而恢复处理组(T_4)减缓了这种趋势。[结论]水稻基因组部分位点的甲基化可能参与了水稻对低温胁迫的响应。

关键词：低温胁迫水稻甲基化敏感扩增多态性 DNA甲基化

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