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TRIM21-dependent ultrasmall chiral gold nanoparticles for preventing microglia senescence against Alzheimer's disease

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Science China Chemistry 2024年第4期67卷 1360-1372页

作者： Meiru Lu Changlong Hao liguang xu Feng Yu Jiwei Jiang Yanli Wang Jun xu Hua Kuang Chuanlai xu Maozhong Sun International Joint Research Laboratory for Biointerface and Biodetection State Key Laboratory of Food Science and ResourcesSchool of Food Science and TechnologyJiangnan UniversityWuxi 214122China Institute of Life Sciences Jiangsu UniversityZhenjiang 212013China Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijing 100050China National Clinical Research Center for Neurological Diseases Beijing 100070China

Tripartite motif 21(TRIM21)is an E3 ubiquitin ligase that shows great promise for protein degradation through ***,ultrasmall chiral gold nanoparticles(D-or L-NPs)modified by D-or L-glutathione ligands were *** conjugated with an NLR family pyrin domain-containing protein 3(NLRP3)antibody(D-NP-a NLRP3 or L-NP-a NLRP3),DNP-a NLRP3 showed effective delivery efficiency of the antibody into microglia and prevented Aβ-mediated microglia senescence,and p16^(ink4a),a marker of senescence,in the microglia was reduced by 90.3%±7.8% while L-NP-a NLRP3 decreased by 48.01%±3.1%.Mechanistic investigations revealed that the D-NP-a NLRP3((1.5±0.3)×10^(7)M^(-1))exhibited sixteen-fold larger binding affinity to transmembrane glycoprotein SLC3A2 than L-type((9.5±2.7)×10^(5)M^(-1)),which led to a high efficiency of antibody delivery and TRIM21-dependent NLRP3 ***,the blood-brain barrier(BBB)-crossing ability of chiral NP-a NLRP3 as well as NLRP3 degradation was demonstrated in *** APP/PS1 Alzheimer's disease(AD)model mice experiments exhibited a reduction of 89.7%±6.8% for the NLRP3 protein and 84.2±7.5% for p16^(ink4a)following the intravenous administration of D-NP-a NLRP3 once a week for 60 ***,the levels of the AD markers Aβ and phosphorylatedTau in the brains were reduced by 86.2%±8.2% and 81.6%±9.1%;these were 2.1-fold and 1.9-fold higher than those treated with L-NP-a NLRP3,*** studies provide a method to rescue AD-like pathologies and prevent senescence.

关键词： chiral gold nanoparticles amyloid-β NLRP3 TRIM21 senescence Alzheimer's disease

Development of a broad-specific immunochromatographic assay for the screening of diclofenac and its analogs in health tea and health beverages

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Food Bioscience 2022年第6期50卷 406-414页

作者： Xiaoxin xu Xinxin xu Shanshan Song liguang xu Yingyue Zhu Chuanlai xu Hua Kuang Liqiang Liu State Key Lab of Food Science and Technology School of Food Science and TechnologyJiangnan UniversityWuxiJiangsu214122People's Republic of China School of Biotechnology and Food Engineering Changshu Institute of TechnologyChangshuJiangsu215500China

Diclofenac(DIC)is often mixed into health products by unscrupulous merchants to claim antirheumatic *** this study,A highly sensitive group-selective monoclonal antibody(mAb)was prepared,and an immunochromatographic assay was developed for rapid screening of DIC,diclofenac methyl(DICA)and N-phenylanthranilic acid(PAA)in health teas and health *** our quantitative analysis,the LOQs for the immunochromatographic test strip(ICS)for the detection of DIC(DICA and PAA)in health tea and health beverage were 0.17(1.13 and 1.34)and 0.12(0.25 and 0.53)ng/mL,*** method was compared with LC-MS/MS method to detect the spiked samples,and the results were in good agreement with the LC-MS/MS,to verifying the effectiveness of the new ***,the ICS we have developed appears to be suitable for monitoring in-field residue levels of DIC,DICA and PAA in real samples.

关键词： Diclofenac Diclofenac methyl N-Phenylanthranilic acid Group-selected monoclonal antibody Immunochromatographic assay Health tea and health beverage samples

Rapid and sensitive determination of difenoconazole in cucumber and pear samples using an immunochromatographic assay

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Food Bioscience 2022年第3期47卷 1124-1131页

作者： Jie Liu Xinxin xu Aihong Wu Shanshan Song liguang xu Chuanlai xu Liqiang Liu Hua Kuang State Key Laboratory of Food Science and Technology Jiangnan UniversityWuxiPeople's Republic of China International Joint Research Laboratory for Biointerface and Biodetection and School of Food Science and TechnologyJiangnan UniversityWuxiPeople's Republic of China

Difenoconazole is triazole fungicide,widely used to prevent the growth and reproduction of fungi and to control fungal diseases in fruits and *** this work,we prepared a hapten of difenoconazole and produced a highly-sensitive anti difenoconazole-monoclonal antibody(mAb)with an IC50 of 0.64 ng/*** the mAb,an immunochromatographic assay(ICA)was developed to analyze difenoconazole residues in pear and cucumber *** ICA exhibited LOD values of 2.60 and 2.30 ng/g for difenoconazole in pear and cucumber samples,*** ICA showed average recoveries of difenoconazole ranging from 94.3%±3.6%–105.4%±1.6%,and CVs of 1.5–4.2%in cucumber and pear *** used to measure difenoconazole in samples,the ICA results were compatible with those detected by LC/*** results of this study support the idea that an ICA is a practical and effective tool for high-throughput and rapid analysis of difenoconazole residues in vegetables and fruits.

关键词： Difenoconazole Immunochromatographic assay Monoclonal antibody Pear Cucumber

Development of ic-ELISA and colloidal cold-based immunochromatographic assay for red 2G detection in fruit drinks, red wine, and yoghurts

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Food Bioscience 2023年第2期52卷 865-871页

作者： Xiaoling Li Xinxin xu Lingling Guo Shanshan Song Liqiang Liu Yingyue Zhu Hua Kuang Chuanlai xu liguang xu State Key Laboratory of Food Science and Technology Jiangnan UniversityWuxiJiangsu214122PR China International Joint Research Laboratory for Biointerface and Biodetection And School of Food Science and TechnologyJiangnan UniversityWuxiJiangsu214122PR China School of Biotechnology and Food Engineering Changshu Institute of TechnologyChangshuJiangsu215500PR China

Red 2G(R2G),a cheap industrial colorant,cannot be added to *** anti-R2G monoclonal antibody(mAb)was prepared by immunizing mice with the conjugate of R2G hapten and protein,which based on the 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide(EDC)*** competitive enzyme-linked immunosorbent assay(ic-ELISA)and colloidal gold-based immunochromatographic assay(CG-ICA)methods were used to determine R2G in fruit drinks,red wine,and yoghurts.A standard curve of the developed ic-ELISA showed that the IC50 of the anti-R2G mAb was 1.02 ng/mL,and limit of detection value(LOD)was 0.21 ng/*** the CG-ICA developed,the visual limit of detection values(vLOD)were 2 ng/mL and cut-off values of 100 ng/mL in *** results indicated that these two methods could be used to quickly detect R2G in fruit drinks,red wine,and yoghurts.

关键词： Monoclonal antibody Red 2G Ic-ELISA Hapten Colloidal gold-based immunochromatographic assay

Electromagnetic field-enhanced chiral dimanganese trioxide nanoparticles mitigate Parkinson’s disease

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Science China Chemistry 2022年第10期65卷 1911-1920页

作者： Xiuxiu Wang Jing Zhao Weiwei Wang Meiru Lu Aihua Qu Maozhong Sun Xiaoqing Gao Chen Chen Hua Kuang Chuanlai xu liguang xu International Joint Research Laboratory for Biointerface and Biodetection Jiangnan UniversityWuxi 214122China State Key Laboratory of Food Science and Technology Jiangnan UniversityWuxi 214122China Wenzhou Institute University of Chinese Academy of SciencesOujiang LaboratoryWenzhou 325001China

The misfolding and aggregation ofα-synuclein(α-syn)is closely associated with Parkinson’s disease(PD).Here,chiral dimanganese trioxide(Mn_(2)O_(3))nanoparticles(NPs)were prepared for PD treatment enhanced by a noninvasive electromagnetic field(MF).The affinity constants of D-NPs towardα-syn monomer(mono)orα-syn fibril were 3.5 times or 5.2 times higher,respectively,than those of L-NPs,and the mechanical force generated by NPs under a MF further promoted the interaction between NPs andα-syn to amplify the difference between L-NPs and *** the synergy effect of the preferentially affinity ability and MF-induced mechanical forces,D-NPs exhibited a better inhibitory efficiency onα-syn fibrillization than ***,after differentially cellular uptake of L-/D-NPs via the caveolin-mediated pathway,as reactive oxygen species(ROS)-scavengers,D-NPs possess higher efficiency in decreasing intracellular ROS level than L-NPs to provide higher cytoprotective efficiency to neuron *** vivo data showed that after treatment with D-NPs under a MF for 60 days,α-syn concentration in the cerebrospinal fluid of PD mice decreased 81%,while dopamine level in the brain of PD mice increased *** findings indicated the potential of utilizing the synergic interplay of chiral NPs and MF for treating disease and opened a new path to explore the nanoscale chirality for regulating the biological effect.

关键词： electromagnetic field chiral dimanganese trioxide nanoparticles mitigate Parkinson’s Disease

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Identifying the effective combination of acupuncture and traditional Chinese medicinal herbs for postmenopausal osteoporosis therapy through studies of their molecular regulation of bone homeostasis

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Journal of Traditional Chinese Medicine 2024年第1期44卷 212-219页

作者： REN Ping WANG Quanwu BAI Wei SUN Miao LIU Zheling GAO Ming WANG Liang PENG Bo xu liguang Department of Health Management the Third Affiliated Clinical Hospital of Changchun University of Chinese MedicineChangchun 130117China Department of Dirty Tuina the affiliated Hospital to Changchun University of Chinese MedicineChangchun 130117China Department of Acupuncture the affiliated Hospital to Changchun University of Chinese MedicineChangchun 130117China Department of Rehabilitation Medicine the 924th Hospital of the PLA Joint Logistic Support ForceFoshan 528226China Department of College of Acupuncture and Massage Changchun University of Chinese MedicineChangchun 130117China

Worldwide,as the population age,osteoporosis is becoming increasingly common,and osteoporotic fractures have a significant economic *** women are the most susceptible to developing osteoporosis and the most critical time to prevent it is during the perimenopausal and early menopausal *** this regard,we hypothesize rational combination of acupuncture and Traditional Chinese Medicine(TCM)in the form of herbal extract could prevent osteoporosis in *** deficiency during menopause causes low-level inflammation that stimulates the formation of osteoclasts,the boneresorbing cells,and simultaneously inhibits the viability and function of osteoblasts,the bone-forming *** most potent inflammatory cytokine in skeletal homeostasis is the receptor activator of nuclear factor kappa B ligand(RANKL)that stimulates osteoclast ***,the canonical Wnt pathway is essential for osteoblastogenesis and bone formation,and estrogen deficiency leads to diminished functioning of this *** and acupuncture could target the RANKL and the Wnt pathway in favorable ways to prevent the accelerated bone loss experienced during the early menopausal stage and promote the gain in bone mass in postmenopausal *** this review,we propose a rational combination of specific TCM and acupuncture targeting those signaling molecules/pathways by the drugs that are in clinical use for the treatment of postmenopausal *** rational approach revealed that Danshen(Radix Salviae Miltiorrhizae)could exert a synergistic effect with *** then propose a translational path for developing the putative combination in women with postmenopausal osteoporosis to curtail the risk of osteoporotic fractures.

关键词： medicine traditional osteogenic anti-resorptive review

Chiral Cu_(x)Co_(y)S Supraparticles Ameliorate Parkinson’s Disease

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CCS Chemistry 2022年第7期4卷 2440-2451页

作者： Baimei Shi Aihua Qu Weiwei Wang Meiru Lu Zhuojia xu Chen Chen Changlong Hao Maozhong Sun liguang xu Chuanlai xu Hua Kuang International Joint Research Laboratory for Biointerface and Biodetection Jiangnan UniversityWuxiJiangsu 214122 State Key Laboratory of Food Science and Technology Jiangnan UniversityWuxiJiangsu 214122

Protein aggregation causes alpha-synuclein(α-syn)to change from its original physiological role to a pathological state,which is a potential pathogenic mechanism in Parkinson’s disease(PD).Chiral _(L/D)-Cu_(x)Co_(y)S supraparticles(_(L/D)-SPs)with a circular dichroism value of 35 mdeg at 805 nm were fabricated using a simple wet-chemical *** _(L/D)-SPs prevented the α-syn monomers from forming fibrils and triggered the α-syn fibrils to turn into monomers under 808 nm near-infrared(NIR)*** living MN9D cells,D-SPs reduced cellular damage,neuronal functional deficits,and neuron loss caused by α-syn fibrils after NIR spectroscopy treatment within 10 min to prevent α-syn ***,the reactive oxygen species produced by _(D)-SPs were 1.42 times higher than those produced by _(L)-*** vivo experiments showed that _(D)-SPs had a protective effect on neuron damage caused by α-syn aggregate deposition,reduced the symptoms in a mouse model of PD,and restored cognitive *** NIR light treatment,the amount of α-syn in a mouse model of PD decreased by more than 67.5%.At the same time,_(D)-SPs gradually decomposed into small nanoparticleswithin 60 days and were excreted through the blood-brain *** discovery paves theway for the treatment of neurodegenerative diseases using chiral SPs under NIR light irradiation.

关键词： chirality Cu_(x)Co_(y)S supraparticles α-synuclein Parkinson’s disease

基于频率耦合阻抗的直驱风电机组次同步振荡关键影响因素分析及抑制措施

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电网技术 2023年第4期47卷 1641-1652页

作者：肖仕武徐立光华北电力大学电气与电子工程学院北京市昌平区102206 国网天津市电力公司城西供电分公司天津市南开区300110

直驱风电机组与弱交流电网的动态交互导致次同步振荡现象时有发生,计及频率耦合效应的阻抗分析法是研究该现象的有效方法之一。首先,建立了计及锁相环、直流电容电压及LC滤波器动态的频率耦合序阻抗模型,并结合阻抗扫频验证了模型的正确... 详细信息

直驱风电机组与弱交流电网的动态交互导致次同步振荡现象时有发生,计及频率耦合效应的阻抗分析法是研究该现象的有效方法之一。首先,建立了计及锁相环、直流电容电压及LC滤波器动态的频率耦合序阻抗模型,并结合阻抗扫频验证了模型的正确性;其次,基于修正的序阻抗伯德图判据对并网系统进行稳定判别得出风险频段的负电阻是导致系统失稳的主要原因;进一步,鉴于电压环、锁相环主要影响次/超频带的阻抗特性,采用灵敏度分析法从带宽和阻尼比角度量化了电压环、锁相环参数对风机阻抗的影响,得出初始参数下的电压环阻尼比是造成阻抗在风险频段呈现负电阻的关键原因;最后,设计了串联超前相位校正的改进控制方案,方案可通过阻抗重塑削弱风险频段的负电阻特性,进而使得并网系统的稳定性提升。结合时域仿真验证了灵敏度分析的正确性和改进控制方案对振荡抑制的有效性。

关键词：次同步振荡频率耦合负电阻改进控制方案

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Potential application of biogenic silica as an indicator of paleo-primary productivity in East Antarctic lakes

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Advances in Polar Science 2011年第3期22卷 131-142页

作者： JIANG Shan LIU XiaoDong xu LiQiang SUN liguang Institute of Polar Environment University of Science and Technology of China Hefei 230026 China

We collected two lake sediment cores （MC and DM） from the East Antarctic region for analysis of biogenic silica and other biogeochemical parameters （e.g., organic matter, C, N, S, H）. Based on synthetically comparative research, we focused on the potential application of biogenic silica （BSi） for the reconstruction of paleo-primary productivity in the East Antarctic lakes. Analytical results showed that a large number of diatoms were well preserved in the freshwater lake sediments, and that concentrations of biogenic silica displayed notable fluctuations over different water depths. The content of biogenic silica had a consistent profile over water depth, and this pattern changed with organic matter, reflecting their potential as eco-environmental proxies. Low lev- els of BSi and organic matter indicated reduction of lake algal production, and corresponded to decreased lake primary productivity. Due to the fragile ecosystem state and limited contribution of terrestrinl organic matter in the East Antarctic lakes, the contents of biogenic silica in the lacustrine sediments can sensitively indicate the evolutionary history of paleo-primary productivity. Overall, BSi is an ideal proxy for the reconstruction of past eeo-environmental change recorded in the lacustrine sediments on East Antarctica.

关键词： East Antarctica, lacustrine sediments BSi paleo-primary productivity organic matter