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Study on the mechanism of Wuzi-Yanzong-Wan-medicated serum interfering with the mitochondrial permeability transition pore in the GC-2 cell induced by atractyloside

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Chinese Journal of Natural Medicines 2022年第4期20卷 282-289页

作者： WU De-ling WANG Tong-Sheng LIU Hong-Juan ZHANG Wei TONG Xiao-Hui PENG Dai-yin kong ling-yi 无 State Key Laboratory of Natural Medicines Jiangsu Key Laboratory of Bioactive Natural Product ResearchSchool of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 210009China School of Pharmacy Anhui University of Chinese MedicineAnhui Province Key Laboratory of Chinese Medical FormulaHefei 230012China School of Integrated Traditional Chinese and Western Medicine Anhui University of Chinese MedicineHefei 230012China

Wuzi-Yanzong-Wan(WZYZW)is a classic prescription for male infertility.Our previous investigation has demon-strated that it can inhibit sperm apoplosis via afecting mitochondria,but the underlying mechanisms are unclear.The purpose of the present study was to explore the actions of WZYZW on mitochondrial permeability transition pore(mPTP)in mouse spermatocyte cell line(GC-2 cells)opened by atractyloside(ATR).At first,WZYZW-mediated serum was prepared from rats following oral adminis-tration of WZYZW for 7 days.GC-2 cells were divided into control group,model group,positive group,as well as 5%,10%,15%WZYZW-medicated serum group.Cyclosporine A(CsA)was used as a positive control.50 μmol·L^(-1) ATR was added afer drugs in-cubation.Cell viability was asessed using CCK-8.Apoptosis was detected using flow cytometry and TUNEL method.The opening of mPTP and mitochondrial membrane potential(MMP)were dected by Calcein AM and JC-1 fuorescent probe respectively.The mRNA and protein levels of voltage-dependent anion channel I(VDACI),cyelophilin D(CypD),adenine nucleide translocator(ANT),cytochrome C(Cyt C),caspase 3,9 were dected by RT-PCR(real time quantity PCR)and Western blotting respectively.The results demonstrated that mPTP of GC-2 cells was opened alpter 24 hours of ATR treatment,resulting in decreased MMP and increased apoptosis.Pre-protection with WZYZ-medicated serum and CsA inhibited the opening of mPTP of GC-2 cells induced by ATR associ ated with increased MMP and decreased apoptosis.Morcover,the results of RT-qPCR and WB suggested that WZYZW-medicated serum could significantly reduce the mRNA and protein levels of VDACI and CypD,Caspase-3,9 and CylC,as well as a increased ra-tio of BclBax.However,ANT was not significantly ffected.Therefore,these findings indicated that WZYZW inhibited mitochondri-al mediated apoptosis by atenuating the opening of mPTP in GC-2 cells.WZYZW-medicated serum inhibited the expressions of VDACI and CypD and increased the expression of Bcl-2,which afected the opening of mPTP and exerted p

关键词： Wuzi-Yanzong-Wan Mitochondrial permeability transition pore Voltage-dependent anion channel 1 Cyclophilin D Mitochondrial membrane potential

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Sesquiterpenoids from the leaves of Sarcandra glabra

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Chinese Journal of Natural Medicines 2022年第3期20卷 215-220页

作者： WANG Yong-Yue LI Qiu-Rong CHI Jun LI Ji-Xin kong ling-yi LUO Jun Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 210009China

Sarglanoids A-F,six new sesquiterpenoids belonging to eudesmane(1-5)and eremophilane(6)types,were isolated from the leaves of Sarcandra glabra,a famous traditional Chinese medicine(TCM).Their structures including absolute configurations were elucidated through extensive spectroscopic analysis and electronic circular dichroism(ECD)calculations.Compounds 1-2 were rare N-containing eudesmane-type sesquiterpenoids.Compound 3 exhibited inhibitory activity against nitric oxide(NO)production in lipopolysaccharides(LPS)-induced RAW 264.7 cells with IC_(50) values at 20.00±1.30μmol·L^(-1).These findings provide scientific evidence for sesquiterpenoids as the material foundation of S.glabra.

关键词： Sarcandra glabra Sesquiterpenoids N-containing sesquiterpenoids Anti-inflammatory

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The impact of urban planning on land use and land cover in Pudong of Shanghai, China

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Journal of Environmental Sciences 2003年第2期15卷 205-214页

作者： Nobukazu Nakagoshi CHEN Jia-kuan kong ling-yi Graduated School for International Development and Cooperation Hiroshima UniversityMinistry of Education Key Laboratory for Biodiversity Science and Ecological Engineering Institute of Biodiversity Science Fudan UniversitySchool of Environmental Engineering Tongji University Kagamiyama Higashi-Hiroshima 739—8529 JapanShanghai 200433 China Shanghai 200092 China

Functional zones in cities constitute the most conspicuous components of newly developed urban areas, and have been a hot spot for domestic and foreign investors in China, which not only show the expanse of urban space accompanied by the shifts both in landscape (from rural to urban) and land use(from less extensive to extensive), but also display the transformation of regional ecological functions. By using the theories and methods of landscape ecology, the structure of landscapes and landscape ecological planning can be analyzed and evaluated for studying the urban functional zones' layout. In 1990, the Central Government of China declared to develop and open up Pudong New Area so as to promote economic development in Shanghai. Benefited from the advantages of Shanghai's location and economy, the government of Pudong New Area has successively built up 7 different functional zones over the past decade according to their functions and strategic goals. Based on the multi-spectral satellite imageries taken in 1990, 1997 and 2000, a landscape ecology analysis was carried out for Pudong New Area of Shanghai, supported by GIS technology. Green space (including croplands) and built-up areas are the major factors considered in developing urban landscape. This paper was mainly concerned with the different spatial patterns and dynamics of green space, built-up areas and new buildings in different functional zones, as influenced by different functional layouts and development strategies. The rapid urbanization in Pudong New Area resulted in a more homogeneous landscape. Agricultural landscape and suburban landscape were gradually replaced by urban landscape as the degree of urbanization increased. As a consequence of urbanization in Pudong, not only built-up patches, but also newly-built patches and green patches merged into one large patch, which should be attributed to the construction policy of extensive green space as the urban development process in Pudong New Area. The shape of green area of 7 functional zones became

关键词： functional zone landscape ecology Pudong urbanization

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Endless exploration for natural products: dedicated to the 80th birthday of Prof. SUN Han-Dong

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Chinese Journal of Natural Medicines 2019年第12期17卷 881-882页

作者： kong ling-yi Chinese Journal of Natural Medicines Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines Department of Natural Medicinal Chemistry China Pharmaceutical University

Natural Products always exhibit more intellectual bioactivities and atom economy,and it’s also an important source of innovative drugs.Prof.SUN Han-Dong,Academician of Chinese Academy of Sciences from Kunming Institute of Botany,has made outstanding contributions to natural product chemistry,andsetagoodexamplefor ouryounggeneration.Onthe occasion ofProfSun’s 80th birthday,I’d like to express my deep respect to him,and wish Prof.SUN a happy birthday and good health.

关键词： Academician birthday drugs

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Type B polycyclic polyprenylated acylphloroglucinols from the roots of Hypericum beanii

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Chinese Journal of Natural Medicines 2021年第5期19卷 385-390页

作者： LI Wei-Xian XU Wen-Jun LUO Jun YANG Lei kong ling-yi Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 210009China

Two new type B polycyclic polyprenylated acylphloroglucinols(PPAPs)(1 and 2)and a known biogenetic precursor hyperbeanol Q(3)were isolated from the root extract of Hypericum beanii,a medicinal plant widespread in southwest China.Their chemical structures were elucidated by 1 D/2 D NMR and HRESIMS data analysis,and absolute configurations were determined through detailed electric circular dichroism(ECD)analysis including ECD exciton chirality,Mo2(OAc)4-induced ECD,and ECD comparison.Of these compounds,hyperbeone A(1)is a typical[3.3.1]-type B PPAP with an unusual C-1 geranyl side chain,and hyperberin C(2)possesses a rare bicyclo[5.3.1]hendecane core.Taking compound 3 as a starting point,a plausible biosynthetic pathway to the bicyclic type B frameworks of 1 and 2 was proposed.

关键词： Polyprenylated acylphloroglucinol Hypericum beanii Hyperbeone A ECD

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A new Lycopodium alkaloid from Phlegmariurus fargesii

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Chinese Journal of Natural Medicines 2014年第5期12卷 373-376页

作者： PAN Ke LUO Jian-Guang kong ling-yi State Key Laboratory of Natural Medicines Department of Natural Medicinal Chemistry China Pharmaceutical University

AIM: To investigate the chemical constituents from the whole plants of Phlegmariurus fargesii. METHOD: Compounds were isolated by repeated silica gel column chromatography. Their structures were elucidated by spectroscopic methods and chemical correlation. The acetylcholinesterase(AChE) inhibitory activity of the isolated compounds was evaluated. RESULTS: A new Lycopodium alkaloid, lycopodine N-oxide(1), along with lycopodine(2), 8,15-dehydrolycopodine(3), 6α-hydroxylycopodine(4), deacetyllycoclavine(5), N-methylhuperzine B(6), lycodine(7), and phlegmarine(8), was isolated. CONCLUSION: Compound 1 is a new Lycopodium alkaloid, and compound 3 was obtained from nature for the first time. Other alkaloids are isolated from this plant for the first time.

关键词：药理学天然药物性质实验药理学

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Lignans with(N,N-diethyl)methyl amino group from Buxus rugulosa

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Chinese Journal of Natural Medicines 2021年第9期19卷 675-679页

作者： WANG Yu-Huan yiN Yong CUI Le-Tian LI Qiu-Rong kong ling-yi LUO Jun Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 210009China

Buxrugulosides A–E,four lignan glycosides(1–4)and a protocatechuate derivative(5)featuring a rare(N,Ndiethyl)methyl amino group at aromatic rings,were obtained from the aerial parts of Buxus rugulosa,which is famous for treating coronary heart disease.Their structures including absolute configurations were elucidated by HRMS,1 D and 2 D NMR,and by comparing their CD data with previous reports.Compound 1 was a rare sesquilignan,and all of these compounds were the first example of lignans with(N,N-diethyl)methyl amino group.

关键词： Lignan glycoside (N,N-diethyl)methyl amino group Buxus rugulosa

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Polyphyllin I promotes cell death via suppressing UPR-mediated CHOP ubiquitination and degradation in non-small cell lung cancer

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Chinese Journal of Natural Medicines 2021年第4期19卷 255-266页

作者： LIU Ming-Ming ZHU Miao-Lin DONG Rui-Fang ZHANG Chao ZHANG Hao YANG Lei kong ling-yi XIA Yuan-Zheng Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009China Jiangsu Cancer Hospital Nanjing 210009China

Polyphyllin I(PPI)purified from Polyphylla rhizomes displays puissant cytotoxicity in many kinds of cancers.Several researches investigated its anti-cancer activity.But novel mechanisms are still worth investigation.This study aimed to explore PPI-induced endoplasmic reticulum(ER)stress as well as the underlying mechanism in non-small cell lung cancer(NSCLC).Cell viability or colony-forming was detected by MTT or crystal violet respectively.Cell cycle,apoptosis,reactive oxygen species(ROS)and mitochondrial membrane potential were assessed by flow cytometry.Gene and protein levels were evaluated by q RT-PCR and immunoblotting respectively.Protein interaction was determined by immunoprecipitation or immunofluorescence assay.Gene overexpression or silencing was carried out by transient transfection with plasmids or small interfering RNAs.The Cancer Genome Atlas(TCGA)database was used for Gene Set Enrichment Analysis(GSEA),survival analysis,gene expression statistics or pathway enrichment assay.PPI inhibited the propagation of NSCLC cells,increased non-viable apoptotic cells,arrested cell cycle at G2/M phase,induced ROS levels but failed to decrease mitochondrial membrane potential.High levels of GRP78 indicates poor prognosis in NSCLC patients.PPI selectively suppressed unfolded protein response(UPR)-induced GRP78 expression,subsequently protected CHOP from GRP78-mediated ubiquitination and degradation.We demonstrated that the natural product PPI,obtained from traditional herbal medicine,deserves for further study as a valuable candidate for lead compound in the chemotherapy of NSCLC.

关键词： Non-small cell lung cancer Polyphyllin I Endoplasmic reticulum stress C/EBP homologous protein Ubiquitination

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METTL5 promotes cell proliferation,invasion,and migration by up-regulating Toll-like receptor 8 expression in colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2006-2017页

作者： ling-Shang kong Ran Tao yi-Fan Li Wen-Bin Wang Xue Zhao Department of General Surgery The Second Affiliated Hospital of Anhui Medical UniversityHefei 230001Anhui ProvinceChina Department of Vascular Surgery The Second Affiliated Hospital of Anhui Medical UniversityHefei 230002Anhui ProvinceChina Department of General Surgery The First Affiliated Hospital of Anhui Medical UniversityHefei 230001Anhui ProvinceChina Anhui Public Health Clinical Center Hefei 230012Anhui ProvinceChina Department of Scientific Research Anhui Public Health Clinical CenterHefei 230012Anhui ProvinceChina Department of Scientific Research The First Affiliated Hospital of Anhui Medical UniversityHefei 230001Anhui ProvinceChina

BACKGROUND N6-methyladenosine(m6A)modification represents the predominant alteration found in eukaryotic messenger RNA and plays a crucial role in the progression of various tumors.However,despite its significance,the comprehensive investigation of METTL5,a key m6A methyltransferase,in colorectal cancer(CRC)remains limited.AIM To investigate the role of METTL5 in CRC.METHODS We assessed METTL5 expression levels in clinical samples obtained from CRC patients as well as in CRC cell lines.To elucidate the downstream targets of METTL5,we performed RNA-sequencing analysis coupled with correlation analysis,leading us to identify Toll-like receptor 8(TLR8)as a potential downstream target.In vitro functional assessments of METTL5 and TLR8 were conducted using CCK-8 assays,scratch assays,as well as assays measuring cell migration and invasion.RESULTS Our findings reveal a pronounced upregulation of METTL5 expression in both CRC cells and tissues,which correlated significantly with an unfavorable prognosis.In vitro experiments unequivocally demonstrated the oncogenic role of METTL5,as evidenced by its promotion of CRC cell proliferation,invasion,and migration.Notably,we identified TLR8 as a downstream target of METTL5,and subsequent down-regulation of TLR8 led to a significant inhibition of CRC cell proliferation,invasion,and tumor growth.CONCLUSION The heightened expression of METTL5 in CRC is strongly associated with clinicopathological features and a poor prognosis,thereby underscoring its potential utility as a critical marker for facilitating early diagnosis and prognostication in CRC.

关键词： METTL5 Toll-like receptor 8 Colorectal cancer

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Light(Science & Applications) 2024年第2期13卷 333-346页

作者： yifan Sun Qian Li ling-Jun kong Xiangdong Zhang Key Laboratory of advanced optoelectronic quantum architecture and measurements of Ministry of Education Beijing Key Laboratory of Nanophotonics&Ultrafine Optoelectronic SystemsSchool of PhysicsBeijing Institute of Technology100081BeijingChina

Compared with electrical neural networks,optical neural networks(ONNs)have the potentials to break the limit of the bandwidth and reduce the consumption of energy,and therefore draw much attention in recent years.By far,several types of ONNs have been implemented.However,the current ONNs cannot realize the acceleration as powerful as that indicated by the models like quantum neural networks.How to construct and realize an ONN with the quantum speedup is a huge challenge.Here,we propose theoretically and demonstrate experimentally a new type of optical convolutional neural network by introducing the optical correlation.It is called the correlated optical convolutional neural network(COCNN).We show that the COCNN can exhibit“quantum speedup”in the training process.The character is verified from the two aspects.One is the direct illustration of the faster convergence by comparing the loss function curves of the COCNN with that of the traditional convolutional neural network(CNN).Such a result is compatible with the training performance of the recently proposed quantum convolutional neural network(QCNN).The other is the demonstration of the COCNN’s capability to perform the QCNN phase recognition circuit,validating the connection between the COCNN and the QCNN.Furthermore,we take the COCNN analog to the 3-qubit QCNN phase recognition circuit as an example and perform an experiment to show the soundness and the feasibility of it.The results perfectly match the theoretical calculations.Our proposal opens up a new avenue for realizing the ONNs with the quantum speedup,which will benefit the information processing in the era of big data.

关键词： process quantum convolution

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