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Sensitive and Specific Y-Shaped Ratio Biosensor for Detecting Serum mi R-18a:Potential Early Scanning Tool for Non-Small Cell Lung Cancer

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Journal of Analysis and Testing 2024年第2期8卷 237-244页

作者： Fei Yu Yue Wang Caiyuan Yu Wei Zhang Xuefeng Bai State Key Laboratory of Quality research in Chinese medicines Macao Institute for Applied Research in Medicine and HealthMacao University of Science and TechnologyTaipaMacao999078China Baotou Cancer Hospital Baotou014040Inner MongoliaChina

miR-18a has been identified as a significantly expressed microRNA(miRNA)in non-small cell lung cancer(NSCLC)and plays a vital role in cancer cell transformation,metastasis,and ***,a pair of binary probes from numerous probe pairs based on single nucleotide polymorphism analyses of miR-18a and miR-18b was first designed and screened to develop a Y-shaped ratio biosensor for accurate detection of serum miR-18a in *** special structure of the binary probes combined with the hairpin showed strong specificity for miR-18a,which was confirmed by polyacrylamide gel electrophoresis assay and square wave voltammetry ***,it is beneficial to immobilize single-stranded DNA(ssDNA)probes due to the large specific surface area of nanoporous gold,thereby improving the sensitivity of the *** Y-shaped ratio biosensor exhibited a wide detection range and can quantify the concentration of miR-18a in the range of 10 fmol/L–100 pmol/L,with a limit of detection of 0.211 fmol/L(S/N=3).Moreover,it exhibits excellent detection capabilities in serum samples since the biosensor showed a high selectivity toward the coexistence of miR-18a and ***,the prepared Y-shaped ratio biosensor is a highly sensitive and specific miR-18a detection tool,capable of identifying microscopic amounts of miR-18a in serum samples,providing great potential for early screening of NSCLC.

关键词： Nanoporous gold Y-shaped biosensor miR-18a NSCLC

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

Bioinspired synthesis of cochlearol B and ganocin A

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Chinese Chemical Letters 2024年第7期35卷 242-246页

作者： Zhenhao Wang Yuliang Tang Ruyu Li Shuai Tian Yu Tang Dehai Li Key Laboratory of Marine drugs Chinese Ministry of Education/Sanya Oceanographic institute Ocean University of ChinaQingdao 266003/Sanya 572025China Laboratory for Marine drugs and Bioproducts Pilot National Laboratory for Marine Science and TechnologyQingdao 266237China Marine Biomedical research institute of Qingdao Ocean University of ChinaQingdao 266071China

Described here is a divergent,biosynthetically inspired synthesis of cochlearol B and ganocin *** steps of the synthesis include the chromene unit construction through a biomimetic acid-catalyzed[4+2]ring cyclization.A photochemical[2+2]cycloaddition was featured to construct the cyclobutane core of cochlearol *** skeletal rearrangements of cochlearol B afforded ganocin A,that one of them was Lewis acid mediated epoxide rearrangement and another was DDQ induced cyclobutane formed tetrahydrofuran *** described syntheses not only achieved these natural products in an efficient manner,but also provided insight into the biosynthetic relationship between the two different skeletons.

关键词： Biomimetic rearrangement Avarane skeleton Cascade reactions Lewis acid Total synthesis

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The Wnt-dependent and Wnt-independent functions of BCL9 in development,tumorigenesis,and immunity:Implications in therapeutic opportunities

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Genes & Diseases 2024年第2期11卷 701-710页

作者： Minjie Wu Heng Dong Chao Xu Mengqing Sun Haojin Gao Fangtian Bu Jianxiang Chen College of Pharmacy and Department of Hepatology Institute of Hepatology and Metabolic DiseasesThe Affiliated Hospital of Hangzhou Normal UniversityHangzhou Normal UniversityHangzhouZhejiang 311121China Laboratory of Cancer Genomics Division of Cellular and Molecular ResearchNational Cancer CentreSingapore 169610Singapore Key Laboratory of Elemene Class Anti-Cancer Chinese medicines Engineering Laboratory of Development and Application of Traditional Chinese MedicinesCollaborative Innovation Center of Traditional Chinese Medicines of Zhejiang ProvinceHangzhou Normal UniversityHangzhouZhejiang 311121China

B-cell CLL/lymphoma 9(BCL9)is considered a key developmental regulator and a well-established oncogenic driver in multiple cancer types,mainly through potentiating the Wnt/β-catenin ***,increasing evidences indicate that BCL9 also plays multiple Wnt-independent ***,we summarized the updates of the canonical and non-canonical functions of BCL9 in cellular,physiological,or pathological ***,we also concluded that the targeted inhibitors disrupt the interaction ofβ-catenin with BCL9 reported recently.

关键词： BCL9 Development Immunity Multifaceted functions Therapeutic target Tumorigenesis

A kinetic resolution accompanied chirality transformation process for asymmetric synthesis of chiral phenol,oxaziridine,andα-hydroxyl cyclic ketone

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Science China Chemistry 2024年第9期67卷 2989-2997页

作者： Pengxin Wang Xiaoyong Zhang Lingqing Wang Rui Wang Dongxu Yang Key Laboratory of Preclinical Study for New drugs of Gansu Province School of Basic Medical Sciences&Research Unit of Peptide ScienceChinese Academy of Medical SciencesLanzhou UniversityLanzhou 730000China State Key Laboratory of Bioactive Substance and Function of Natural medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China School of Sciences Great Bay UniversityDongguan 523000China institute of Systems and Physical Biology Shenzhen Bay LaboratoryShenzhen 518055China

Chirality transformation is a basic,attractive,and important strategy for obtaining enantioenriched products with desired chiral *** reported chirality conversion reaction often involves the process from one type of chirality to another *** better utilize the chirality transformation strategy for obtaining two or more products with different chiral elements in a single reaction,a new method of kinetic resolution accompanied by a chirality transformation protocol is proposed and successfully realized in this *** process is used for the asymmetric oxidation of phenol compounds along with the kinetic resolution of oxaziridines.A wide scope of products,including axially chiral phenols,oxaziridines,andα-hydroxyl cyclic ketones were smoothly obtained in high levels of yields and enantioselectivities in the developed *** products can be readily used for the synthesis of various types of chiral ligands,which are potential choices for other catalytic asymmetric reactions.

关键词： chirality transformation kinetic resolution accompanied axially chiral phenols chiral oxaziridines

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The roles and mechanisms of SREBP1 in cancer development and drug response

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Genes & Diseases 2024年第4期11卷 258-269页

作者： Ying He Shasha Qi Lu Chen Jinyu Zhu Linda Liang Xudong Chen Hao Zhang Lvjia Zhuo Shujuan Zhao Shuiping Liu Tian Xie School of Pharmacy Hangzhou Normal UniversityHangzhouZhejiang 311121China Key Laboratory of Elemene Class Anti-Cancer Chinese medicines Engineering Laboratory of Development and Application of Traditional Chinese MedicinesCollaborative Innovation Center of Traditional Chinese Medicines of Zhejiang ProvinceHangzhou Normal UniversityHangzhouZhejiang 311121China Laboratory of Cancer Genomics Division of Cellular and Molecular ResearchNational Cancer Centre SingaporeSingapore 169610Singapore

Cancer occurrence and development are closely related to increased lipid produc-tion and glucose *** are the basic component of the cell membrane and play a significant role in cancer cell processes such as cell-to-cell recognition,signal transduction,and energy supply,which are vital for cancer cell rapid proliferation,invasion,and *** regulatory element-binding transcription factor 1(SREBP1)is a key transcription factor regulating the expression of genes related to cholesterol biosynthesis,lipid homeostasis,and fatty acid *** addition,SREBP1 and its upstream or downstream target genes are implicated in various metabolic diseases,particularly ***,no review of sREBP1 in cancer biology has yet been ***,we summarized the roles and mechanisms of SREBP1 biological processes in cancer cells,including SREBP1 modification,lipid metabolism and reprogramming,glucose and mitochondrial metabolism,immunity,and tumor microenvi-ronment,epithelial-mesenchymal transition,cell cycle,apoptosis,and ***-ally,we discussed the potential role of SREBP1 in cancer prognosis,drug response such as drug sensitivity to chemotherapy and radiotherapy,and the potential drugs targeting SREBP1 and its corresponding pathway,elucidating the potential clinical application based on SREBP1 and its corresponding signal pathway.

关键词： Cancer Drug Lipid metabolism reprogramming Resistance SREBP1

Notoginsenoside Ft1 inhibits colorectal cancer growth by increasing CD8^(+)T cell proportion in tumor-bearing mice through the USP9X signaling pathway

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Chinese Journal of Natural medicines 2024年第4期22卷 329-340页

作者： FENG Yutao LI Yuan MA Fen WU Enjiang CHENG Zewei ZHOU Shiling WANG Zhengtao YANG Li SUN Xun ZHANG Jiwei Shanghai Key Laboratory of Compound Chinese medicines The MOE Key Laboratory for Standardization of Chinese MedicinesInstitute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineShanghai 201203China Gastrointestinal surgery Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China

The management of colorectal cancer(CRC)poses a significant challenge,necessitating the development of innovative and effective *** research has shown that notoginsenoside Ft1(Ng-Ft1),a small molecule,markedly inhibits subcutaneous tumor formation in CRC and enhances the proportion of CD8^(+)T cells in tumor-bearing mice,thus restraining tumor *** into the mechanism revealed that Ng-Ft1 selectively targets the deubiquitination enzyme USP9X,undermining its role in shieldingβ-*** leads to a reduction in the expression of downstream effectors in the Wnt signaling *** findings indicate that Ng-Ft1 could be a promising small-molecule treatment for CRC,working by blocking tumor progression via the Wnt signaling pathway and augmenting CD8^(+)T cell prevalence within the tumor environment.

关键词： Notoginsenoside Ft1 Colorectal cancer CD8^(+)T cell Ubiquitin-specific peptidase 9 X-linked β-Catenin Wnt

Citrinsorbicillin A,a novel homotrimeric sorbicillinoid isolated by LC-MS-guided with cytotoxic activity from the fungus Trichoderma citrinoviride HT-9

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Chinese Chemical Letters 2024年第8期35卷 299-303页

作者： Guo-Ping Yin Ya-Juan Li Li Zhang Ling-Gao Zeng Xue-Mei Liu Chang-Hua Hu Engineering research Center of Coptis Development and Utilization(Ministry of Education) College of Pharmaceutical Sciences and Chinese MedicineSouthwest UniversityChongqing 400715China State Key Laboratory of Natural medicines China Pharmaceutical UniversityNanjing 211198China NMPA Key Laboratory for Quality Monitoring of Narcotic drugs and Psychotropic Substances Chongqing Institute for Food and Drug ControlChongqing 401121China

Citrinsorbicillin A(1),a novel homotrimeric sorbicillinoid,along with two new monomers citrinsor-bicillins B(2)and C(3),were isolated from the Coptis chinensis endophyte Trichoderma citrinoviride HT-9 by liquid chromatograph mass spectrometer(LC-MS)-guided strategy.1 was the first trimeric-example from terrestrial fungi,which possessed a unique carbon skeleton with two bicyclo[2.2.2]octanedione ring connected through an enolated carbon forming by[4+2]*** structures were elucidated by spectroscopic analysis and X-ray diffraction.1 exhibited moderate cytotoxicity against human colon cancer HT29 cells,and it induced significant cell cycle arrest by reducing the protein expression of cyclin D1.

关键词： Citrinsorbicillin A Trimeric sorbicillinoid Coptis chinensis endophyte Trichoderma citrinoviride [4+2]Cycloaddition Cytotoxic activity

Two types of coumarins-specific enzymes complete the last missing steps in pyran- and furanocoumarins biosynthesis

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Acta Pharmaceutica Sinica B 2024年第2期14卷 869-880页

作者： Yucheng Zhao Yuedong He Liangliang Han Libo Zhang Yuanzheng Xia Fucheng Yin Xiaobing Wang Deqing Zhao Sheng Xu Fei Qiao Yibei Xiao Lingyi Kong Department of Resources Science of Traditional Chinese medicines School of Traditional Chinese Pharmacyand State Key Laboratory of Natural MedicinesChina Pharmaceutical UniversityNanjing 210009China College of Bioscience and Biotechnology Hunan Agricultural UniversityChangsha 410128China Jiangsu Key Laboratory of Bioactive Natural Product research and State Key Laboratory of Natural medicines Department of Natural Medicinal ChemistryChina Pharmaceutical UniversityNanjing 210009China Key Laboratory of Crop Gene Resources and Germplasm Enhancement in Southern China Ministry of AgricultureTropical Crops Genetic Resources InstituteChinese Academy of Tropical Agricultural SciencesHaikou 517317China institute of Botany Jiangsu Province and Chinese Academy of SciencesNanjing 210014China Department of Pharmacology School of Pharmacyand State Key Laboratory of Natural MedicinesChina Pharmaceutical UniversityNanjing 210009China

Pyran-and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans,respectively,exhibiting diverse physiological and medical ***,the biosynthetic mechanisms for their core structures remain poorly *** we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in *** included three distinct *** prenyltransferases(PpPT1e3)responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors,and two novel CYP450 cyclases(PpDC and PpOC)crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran *** analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme-catalyzed tetrahydropyran and tetrahydrofuran ring *** possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site-specific *** identified two possible acidic amino acids Glu303 in PpDC and Asp301 in PpOC as vital in the catalytic *** study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chemically diverse in terms of enzyme function and catalytic process.

关键词： Tetrahydropyrans Tetrahydrofurans Baldwin rules Coumarins CYP450cyclase