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Chinese Journal of natural medicines 2024年第1期22卷 75-88页

作者： SONG Jiangzhou ZOU Guiqing ZHAO Zhou ZHU Ya XUE Jiayu AO Lanjia SUN Huiyong HAO Haiping ZHANG Bo XU Xiaowei state key laboratory of natural medicines Key Lab of Drug Metabolism and PharmacokineticsChina Pharmaceutical UniversityNanjing 210009China state key laboratory of natural medicines China Pharmaceutical UniversityNanjing 210009China

NAD(P)H:quinone oxidoreductase 1(NQO1)is a flavin protease highly expressed in various cancer ***1 catalyzes a futile redox cycle in substrates,leading to substantial reactive oxygen species(ROS)*** ROS generation results in extensive DNA damage and elevated poly(ADP-ribose)polymerase 1(PARP1)-mediated consumption of nicotinamide adenine dinucleotide(NAD^(+)),ultimately causing cell *** phosphoribosyltransferase(NAMPT),the rate-limiting enzyme in the NAD^(+)salvage synthesis pathway,emerges as a critical target in cancer *** concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD+*** this study,we designed,synthesized,and assessed a novel series of proqodine A derivatives targeting both NQO1 and *** these,compound T8 demonstrated potent antitumor ***,T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and *** discovery offers a promising new molecular entity for advancing anticancer research.

关键词： NQO1 ROS NAMPT NAD^(+) T8

Progress in approved drugs from natural product resources

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Chinese Journal of natural medicines 2024年第3期22卷 195-211页

作者： LUO Zhongwen YIN Fucheng WANG Xiaobing KONG Lingyi state key laboratory of natural medicines and Jiangsu key laboratory of Bioactive natural Product Research School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 211198China

natural products (NPs) have consistently played a pivotal role in pharmaceutical research, exerting profound impactson the treatment of human diseases. A significant proportion of approved molecular entity drugs are either directly derived from NPs orindirectly through modifications of NPs. This review presents an overview of NP drugs recently approved in China, the United states,and other countries, spanning various disease categories, including cancers, cardiovascular and cerebrovascular diseases, centralnervous system disorders, and infectious diseases. The article provides a succinct introduction to the origin, activity, development process, approval details, and mechanism of action of these NP drugs.

关键词： New drugs natural products Structural modification

Exosomes derived from pulmonary metastatic sites enhance osteosarcoma lung metastasis by transferring the miR-194/215 cluster targeting MARCKS

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2039-2056页

作者： Pei Yu Yubao Han Lulu Meng Yanyuan Tian Zhiwei Jin Jun Luo Chao Han Wenjun Xu Lingyi Kong Chao Zhang state key laboratory of natural medicines Jiangsu Key Laboratory of Bioactive Natural Product ResearchSchool of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 211198China

Osteosarcoma,a prevalent primary malignant bone tumor,often presents with lung metastases,severely impacting patient survival *** vesicles,particularly exosomes,play a pivotal role in the formation and progression of osteosarcoma-related pulmonary ***,the communication between primary osteosarcoma and exosome-mediated pulmonary lesions remains obscure,with the potential impact of pulmonary metastatic foci on osteosarcoma progression largely *** study unveils an innovative mechanism by which exosomes originating from osteosarcoma pulmonary metastatic sites transport the miR-194/215 cluster to the primary tumor *** transportation enhances lung metastatic capability by downregulating myristoylated alanine-rich C-kinase substrate(MARCKS)*** this phenomenon,in this study we employ cationic bovine serum albumin(CBSA)to form nanoparticles(CBSA-anta-194/215)via electrostatic interaction with antagomir-miR-194/*** nanoparticles are loaded into nucleic acid-depleted exosomal membrane vesicles(anta-194/215@Exo)targeting osteosarcoma lung metastatic *** with bioengineered exosome mimetics(anta-194/215@Exo)not only impedes osteosarcoma progression but also significantly prolongs the lifespan of tumor-bearing *** findings suggest that pulmonary metastatic foci-derived exosomes initiate primary osteosarcoma lung metastasis by transferring the miR-194/215 cluster targeting MARCKS,making the miR-194/215 cluster a promising therapeutic target for inhibiting the progression of patients with osteosarcoma lung metastases.

关键词： Lung–bone transmission miR-194/215 cluster Exosome Lung metastasis Epithelial–mesenchymal transition Vasculogenic mimicry Bioengineered exosome mimetics Osteosarcoma

Anti-psoriasis molecular targets and active components discovery of Optimized Yinxieling Formula via affinity-purified strategy

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Chinese Journal of natural medicines 2024年第2期22卷 127-136页

作者： WANG Wei LIU Lijuan YANG Zhuo LU Chuanjian TU Pengfei ZHAO Ruizhi ZENG Kewu state key laboratory of natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China state key laboratory of Dampness Syndrome of Chinese medicine The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510006China

Psoriasis,a prevalent inherited skin condition,involves an inflammatory response as a key pathogenic *** Optimized Yinxieling Formula(OYF),rooted in traditional Chinese medicine,is extensively utilized in clinical settings to treat *** previous studies have demonstrated OYF’s significant anti-inflammatory effects in psoriasis,its potential molecular targets and active components remain *** study aimed to unveil the anti-psoriasis molecular targets and active components of *** findings indicated that OYF extract markedly reduced the production of several inflammatory mediators,including IL-23,nitric oxide,TNF-α,and IL-1β,in LPS-induced RAW264.7 *** synthesized OYF extract-crosslinked beads to isolate pharmacological targets from RAW264.7 lysates using an affinity purification strategy,known as Target *** enriched target proteins were subsequently identified via LC-MS/MS,followed by bioinformatics analysis to map the psoriasis-associated pathway-gene *** identified a total of 76 potential target proteins,which were highly associated with mRNA transcription *** particular,pathway-gene network analysis revealed that the IL-23 inflammatory pathway was involved in the anti-psoriasis effect of OYF *** further utilized a target protein-based affinity capture strategy,combined with LC-MS and SPR analysis,to globally screen OYF’s active components,focusing on the mRNA transcription regulator,fused in sarcoma(FUS).This process led to the identification of umbelliferone,vanillic acid,protocatechuic acid,gentisic acid,and echinacoside as key compounds targeting FUS to inhibit IL-23 ***,we formulated a compound cocktail(CpdC),which significantly reduced psoriasis area and severity index(PASI)scores and the expressions of IL-23 and Ki67 in an imiquimod(IMQ)-induced psoriasis mouse ***,our study elucidates the primary molecular targets and active components of OYF,offeri

关键词： Psoriasis Optimized Yinxieling Formula(OYF) FUS protein Molecular targets Affinity-purified strategy

A multi-enzymatic cascade reaction for the synthesis of bioactive C-oligosaccharides

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Chinese Chemical Letters 2024年第6期35卷 451-455页

作者： Kebo Xie Qian Zhang Fei Ye Jungui Dai state key laboratory of Bioactive Substance and Function of natural medicines CAMS Key Laboratory of Enzyme and Biocatalysis of Natural Drugs and NHC Key Laboratory of Biosynthesis of Natural ProductsInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

C-Oligosaccharides are rare in nature and possess diverse ***,their chemical synthesis faces many *** this work,enzymatic introduction of C-linked sugar chains to target aglycones was successfully achieved by multi-enzymatic cascade reactions.A C-glycosyltransferase from Aloe barbadensis was employed to introduce the first C-linked glucose and then a cyclomaltodextrin glucanotransferase from Bacillus licheniformis was used to extend the sugar chain.A total of twenty C-oligosaccharides with 2-6 sugars were synthesized from scale-up reactions and exhibited good water solubility and sodium-dependent glucose transporter 2(SGLT2)inhibitory ***,a glucoamylase was used to control the length of the sugar chain and the C-maltosides were efficiently *** findings not only expanded the structural diversity of C-oligosaccharides,but also provided a strategy for the modification of C-glycoside drugs to improve the druggability.

关键词： C-Oligosaccharides C-Glycosyltransferase Cyclomaltodextrin glucanotransferase Glucoamylase Enzymatic synthesis SGLT2 inhibitory activity

A fungal CYP from Beauveria bassiana with promiscuous steroid hydroxylation capabilities

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Chinese Chemical Letters 2024年第5期35卷 218-222页

作者： Yu Peng Yue Wang Tian-Jiao Chen Jing-Jing Chen Jin-Ling Yang Ting Gong Ping Zhu state key laboratory of Bioactive Substance and Function of natural medicines NHC Key Laboratory of Biosynthesis of Natural ProductsCAMS Key Laboratory of Enzyme and Biocatalysis of Natural DrugsInstitute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

Hydroxylation of steroid core is critical to the synthesis of steroid *** sp^(3) C-H hydroxylation is challenging through chemical catalysis,alternatively,fungal biotransformation offers a possible solution to this ***,mining and metabolic engineering of cytochrome P450 monooxygenases(CYPs)is usually regarded as a more eco-friendly and efficient ***,we report the mining and identification of a new steroid CYP(CYP68BE1)from Beauveria bassiana by transcriptomics,heterologous expression,in vivo and in vitro functional *** catalytic promiscuity of CYP68BE1 was explored,and CYP68BE1 showed promiscuously and catalytically versatile,which is qualified for monohydroxylation on C11α,C1α,C6βand dihydroxylation on C1β,11αand C6β,11αof six steroids,leading to the production of key steroid intermediates required in the industrial synthesis of some indispensable steroid *** dynamics simulations were performed,revealing the molecular basis of different binding orientations of CYP68BE1 with different *** discovery of CYP68BE1 offers a promising biocatalyst for enriching the steroid structural and functional diversity,which also can be applied to biosynthesize valuable steroid drug intermediates.

关键词： Fungal CYPs Steroid hydroxylase Beauveria bassiana Promiscuous biocatalyst Molecular dynamics

Immunomodulatory Function of Pien Tze Huang in T Cell-Mediated Anti-tumor Activity against B16-F10,MC38 and Hep1-6 Tumor Models

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Chinese Journal of Integrative medicine 2024年第4期30卷 348-358页

作者： FU Yu-bing LIU Chen-feng WANG Jin-jia JI Xiao-lin TANG Rong-han LIAO Kun-yu CHEN Ling-yue HONG Ya-zhen FAN Bin-bin WANG Shi-cong LIU Wen-Hsien state key laboratory of Cellular Stress Biology School of Life SciencesFaculty of Medicine and Life ScienceXiamen UniversityXiamenFujian Province(361102)China Fujian Pien Tze Huang Enterprise key laboratory of natural medicine Research and Development ZhangzhouFujian Province(363000)China

Objective To investigate the anti-tumor effects of Pien Tze Huang(PZH)in mouse models of B16–F10 melanoma,MC38 colorectal cancer,Hep1-6 hepatocellular carcinoma and chemically induced hepatocellular carcinoma *** Various tumor models,including B16–F10,MC38 and Hep1-6 tumor hypodermic inoculation models,B16–F10 and Hep1-6 pulmonary metastasis models,Hep1-6 orthotopic implantation model,and chemically induced hepatocellular carcinoma model,were utilized to evaluate the anti-tumor function of *** growth was assessed by measuring tumor size and weight of solid tumors isolated from C57BL/6 *** cell proliferation and death of tumor cells in vitro,as well as T cell activation markers,cytokine production and immune checkpoints analysis,single-cell suspensions were prepared from mouse spleen,lymph nodes,and tumors after PZH *** PZH demonstrated significant therapeutic efficacy in inhibiting tumor growth(P0.05).Nevertheless,PZH exhibited a remarkable ability to enhance T cell activation and the production of interferon gamma,tumor necrosis factor alpha,and interleukin 2 in CD4^(+)T cells in vitro(P<0.01 or P<0.05).Importantly,PZH substantially inhibited T cell exhaustion and boosted cytokine production by tumor-infiltrating CD8^(+)T cells(P<0.01 or P<0.05).Conclusion This study has confirmed a novel immunomodulatory function of PZH in T cell-mediated anti-tumor immunity,indicating that PZH holds promise as a potential therapeutic agent for cancer treatment.

关键词： Pien Tze Huang metastasis anti-tumor immunity T cell activation T cell exhaustion immune checkpoints Chinese medicine

Potassium isotopic signatures of modern offshore detrital sediments from different climatic regimes and the implications

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Science China Earth Sciences 2024年第2期67卷 405-419页

作者： Jun MU Tianyu CHEN Qian YU Shichao AN Jianfang CHEN Xuefa SHI Weiqiang LI state key laboratory for Mineral Deposits Research School of Earth Sciences and EngineeringNanjing UniversityNanjing210023China Ministry of Education key laboratory for Coast and Island Development School of Geography and Ocean ScienceNanjing UniversityNanjing210023China state key laboratory of Satellite Ocean Environment Dynamics Second Institute of OceanographyMinistry of Natural ResourcesHangzhou310012China key laboratory of Marine Geology and Metallogeny First Institute of OceanographyMinistry of Natural ResourcesQingdao266061China

Potassium isotopes are a novel tracer for continental *** K isotope studies on chemical weathering generally targeted weathering profiles under a particular climate region,yet the effects of chemical weathering on K isotopes under different climatic backgrounds remain ***,little is known about the K isotope signatures of modern unconsolidated detrital ***,we report K isotopic data of surficial seafloor sediments from continental shelves along the east coast of China(ECC),as well as those around the tropical Hainan island in the northern South China *** ECC sediments have a relatively narrow distribution ofδ^(41)K(with reference to NIST3141a)values,which range from(-0.40±0.01)‰to(-0.57±0.04)‰,with an average of(-0.51±0.09)‰.By contrast,δ^(41)K values of Hainan offshore sediments display a larger variation,ranging from(-0.28±0.07)‰to(-0.67±0.02)‰.Theδ^(41)K values of Hainan offshore sediments exhibit negative correlations with the chemical index of alteration(CIA),Al/K,Ti/K,and total iron(FeT),which underlines the control of chemical weathering on K isotopic signatures of detritus inputs into *** also measured Mg isotope compositions for the same samples;interestingly,the variability inδ^(26)Mg of the samples is small(~0.24‰)for all ECC and Hainan offshore sediments,andδ^(26)Mg values do not show clear correlations with indexes of chemical *** study demonstrates the link between K isotopic variability of detrital sediments and climatic conditions including rainfall intensity,which indicates that K isotopes of the detrital component of marine sediments could be applied to study Earth’s climate in deep ***δ^(41)K values of the offshore detrital sediments are significantly less variable than those of pelagic marine sediments,highlighting the importance of distinguishing the effects of diagenesis and neoformation of clay minerals from continental weathering in attempts to study deep-time climate-weathering

关键词： Potassium isotopes Magnesium isotopes Chemical weathering Detrital sediments Climatic regimes Mean annual precipitation

Conversion of a single-layer ANN to photonic SNN for pattern recognition

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Science China(Information Sciences) 2024年第1期67卷 261-270页

作者： Yanan HAN Shuiying XIANG Tianrui ZHANG Yahui ZHANG Xingxing GUO Yuechun SHI state key laboratory of Integrated Service Networks State Key Discipline Laboratory of Wide Bandgap Semiconductor TechnologyXidian University Yongjiang laboratory

This work presents a complete conversion scheme for photonic spiking neural networks(SNNs).We verified that the output of an artificial neural network(ANN) trained with the simulated optical activation function can be directly converted into the spike rate of a photonic spiking neuron *** reveal the feasibility of hardware implementation,we considered the effects of different bit precisions of data and weight,noise level,and bias current mismatch on the converted *** proposed scheme was evaluated using the Deterding vowel,IRIS,TIDIGITS,and MNIST datasets for pattern recognition,and achieved mean accuracies of 95.80%,98.67%,96.19%,and 92.33%,*** proposed scheme can convert an ANN into a photonic SNN with almost no precision loss,and the performance was comparable to that of an ANN trained with the rectified linear unit *** proposed scheme can enable the high-performance implementation of photonic SNNs.

关键词： photonic SNN conversion optical computing pattern recognition artificial neural network

TBAB hydrate formation and growth in a microdevice under static and dynamic conditions

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Petroleum Science 2024年第2期21卷 1396-1404页

作者： Xingxun Li Ming Liu Qingping Li Weixin Pang Guangjin Chen Changyu Sun state key laboratory of Heavy Oil Processing China University of Petroleum BeijingBeijing102249China state key laboratory of natural Gas Hydrate CNOOC Research Institute Co.Ltd.Beijing100027China

The natural gas hydrate has become one of the most promising future green energy sources on the *** natural gas hydrates mostly exist in the sediments with porous structure, so a solid understanding of the hydrate formation and growth processes in the porous medium is of significance for the exploitation of natural gas hydrate. The micro-packed bed device is one of the efficient microfluidic devices in the engineering field, but it has been rarely used for the hydrate-based research. In this study, a transparent micro-packed bed device filled with glass beads was developed to mimic the porous condition of sediments, and used to in-situ visualize the hydrate formation and growth habits in the pore spaces under both static and dynamic conditions. For the static experiment, two types of hydrate growth patterns in porous medium were observed and identified in the micro-packed bed device, which were the graincoating growth and pore-filling growth. For the dynamic condition, the hydrate formation, growth,distribution habits and hydrate blockage phenomena in the pore spaces were in-situ visually *** impacts of flowrate and subcooling on the pressure variation of the micro-packed bed and the duration of the hydrate growth under dynamic flow condition in pores were in-situ monitored and analyzed. The higher flowrate could result in the faster hydrate growth and more severe blockage in pores, but the effect of subcooling condition might be less significant at the high flowrate.

关键词： Hydrate formation Hydrate growth Microdevice In-situ measurement