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Chinese Journal of Natural medicines 2024年第4期22卷 291-292页

作者： DU Jinfa LIAO Pan LU Xu State Key Laboratory of Natural medicines School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 210009China department of Biology Hong Kong Baptist UniversityKowloon TongHong KongChina State Key Laboratory of Agrobiotechnology The Chinese University of Hong KongHong KongChina State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Beijing 100700China Medical Botanical Garden China Pharmaceutical UniversityNanjing 210009China

Paclitaxel,a tetracyclic diterpenoid,has garnered attention for its potent anti-cancer properties and intricate molecular structure,making it a significant target for chemical synthesis and biosynthesis[1].However,its natural sources are extremely limited,as it is derived exclusively from the bark of endangered genus Taxus plants,which contain paclitaxel in very low concentrations(0.01%−0.05%)[2-3].Recent advances in synthetic biology present promising opportunities to enhance paclitaxel levels in Taxus cell cultures or to enable the reconstitution of its production in heterologous hosts,such as yeast or tobacco(Nicotiana benthamiana).

关键词： Paclitaxel biosynthesis Baccatin III Cytochrome P450 Taxane oxetanase 1 Heterologous reconstitution

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Decoding m^(6)A mRNA methylation by reader proteins in liver diseases

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Genes & Diseases 2024年第2期11卷 711-726页

作者： Lijiao Sun Xin Chen Sai Zhu Jianan Wang Shaoxi Diao Jinyu Liu Jinjin Xu Xiaofeng Li Yingyin Sun Cheng Huang Xiaoming Meng Xiongwen Lv Jun Li Inflammation and Immune Mediated Diseases Laboratory of Anhui Province Anhui Institute of Innovative DrugsSchool of PharmacyAnhui Medical UniversityHefeiAnhui 230032China The Key Laboratory of Anti-inflammatory and Immune medicines Anhui Medical UniversityMinistry of EducationHefeiAnhui 230032China Institute for Liver Diseases of Anhui Medical University ILD-AMUAnhui Medical UniversityHefeiAnhui 230032China department of Nephropathy The First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230022China department of Oncology The First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230032China

N6-methyladenosine(m^(6)A)is a dynamic and reversible epigenetic *** the most prevalent internal post-transcriptional modification in eukaryotic RNA,it participates in the regulation of gene expression through various mechanisms,such as mRNA splicing,nuclear export,localization,translation efficiency,mRNA stability,and structural *** involvement of m^(6)A in the regulation of gene expression depends on the specific recognition of m^(6)A-modified RNA by reader *** the pathogenesis and treatment of liver disease,studies have found that the expression levels of key genes that promote or inhibit the development of liver disease are regulated by m^(6)A modification,in which abnormal expression of reader proteins determines the fate of these gene *** this review,we introduce m^(6)A readers,summarize the recognition and regulatory mechanisms of m^(6)A readers on mRNA,and focus on the biological functions and mechanisms of m^(6)A readers in liver cancer,viral hepatitis,non-alcoholic fatty liver disease(NAFLD),hepatic fibrosis(HF),acute liver injury(ALI),and other liver *** information is expected to be of high value to researchers deciphering the links between m^(6)A readers and human liver diseases.

关键词： IGF2BPs Liver diseases m^(6)A modification m^(6)A reader mRNA metabolism YTH domain protein

Concise Synthesis of Lactococcus garvieae Lipoteichoic Acids Through an Additive-Modulated Preactivation Protocol and the Immunological Studies

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CCS Chemistry 2024年第2期6卷 403-414页

作者： Tianlu Li Tong Li Yue Yang Haoru Zhuang Jianwu Lv Ning Zhou Miaomiao Zhang Fengshan Wang Yiqun Geng Richard R.Schmidt Peng Peng National Glycoengineering Research Center Shandong Key Laboratory of Carbohydrate Chemistry and GlycobiologyNMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate Based MedicineShandong UniversityQingdao 266237 State Key Laboratory of Bioactive Substance and Function of Natural medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050 department of Chemistry University of KonstanzD-78457 Konstanz

Lipoteichoic acids(LTAs)are macroamphiphiles composed of alditol,lipid,phosphate,and carbohydrate *** to their inherent complexity,it is a severe challenge to access LTAs with structural integrity from natural sources for biological or immunological ***,we describe the first total synthesis of Lactococcus garvieae LTA(type II LTA),containing five distinct 1,2-cis gluco/galactopyranosidic linkages,via a novel additive-modulated O-glycosyl trichloroacetimidate preactivation glycosidation *** strategy features(1)high glycosidation yields and excellent 1,2-cis stereoselectivities independent of the donor anomeric configuration,(2)common and inexpensive reagents as promoters and additives,(3)application to standard glycosyl imidate donors without resorting to participating protection,and(4)general application to reactive and less reactive glycosyl ***,via the precise stereocontrolled construction of three galactopyranosidic and two glucopyranosidic bonds on a multigram scale,a series of structurally well-defined LTA molecules were successfully *** evaluation of these type II synthetic LTAs showed a structure–activity relationship in the stimulation of a proinflammatory response.

关键词： 1,2-cis glycosidation stereoselectivity lipoteichoic acid total synthesis additive-modulated trichloroacetimidate glycosidation immune response

Genetic and immunologic characteristics of colorectal cancer patients with KRAS mutations and predictive significance of tumor immune microenvironment in adjuvant chemotherapy

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Genes & Diseases 2024年第3期11卷 43-46页

作者： Zhengqi Wen Wenliang Li Chengmin Shi Junrui Ma Sihui Zhao Ruize Zhou Xihong Liu Rong Yang Zhiping Zhang Hushan Zhang Bo Li department of Oncology The First Affiliated Hospital of Kunming Medical UniversityKunmingYunnan 650032China The Third Affliated Hospital of Kunming Medical University(Yunnan Cancer Center) KunmingYunnan 650021China Gastrointestinal and Hernia Surgery The First Affiliated Hospital of Kunming Medical UniversityKunmingYunnan 650032China School of Nursing Yunnan University of Chinese MedicineKunmingYunnan 650022China department of General Surgery The First People's Hospital of Yunnan ProvinceKunmingYunnan 650000China department of General Surgery The Affiliated Hospital of Yunnan UniversityYunnan 650011China Medical department 3D Medicines Inc.Shanghai 201114China Zhaotong Health Vocational College ZhaotongYunnan 657000China

Colorectal cancer(CRC)is one of the most common cancers around the world,and it is one of the leading causes of cancer-related death.1 Although anti-EGFR therapy and immune checkpoint inhibitor(ICl)therapy are becoming more and more important for colorectal therapy,however,clinical outcomes of current treatments for metastatic CRC,especially with ICls,have been shown to be affected by the status of ***,KRAS mutation status detection has become a very important diagnostic factor for managing metastatic CRC patients.

关键词： KRAS colorectal patients

A One Health approach to fight antimicrobial resistance in Uganda: Implementation experience, results, and lessons learned

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Biosafety and Health 2024年第2期6卷 125-132页

作者： Reuben Kiggundu J.P.Waswa Niranjan Konduri Hassan Kasuja Marion Murungi Patrick Vudriko Harriet Akello Eric Lugada Cecilia Muiva Esther Were Dinah Tjipura Henry Kajumbula Kate Kikule Emmanuel Nfor Mohan P.Joshi USAID medicines Technologiesand Pharmaceutical Services ProgramManagement Sciences for HealthKampala 256Uganda USAID medicines Technologiesand Pharmaceutical Services ProgramManagement Sciences for HealthArlingtonVA 22203USA College of Veterinary Medicine Animal Resources and BiosecurityMakerere UniversityKampala 256Uganda Ministry of Health Uganda Kampala 256Uganda USAID Strengthening Supply Chain Systems Activity Management Sciences for HealthKampala 256Uganda USAID medicines Technologiesand Pharmaceutical Services ProgramManagement Sciences for HealthNairobi 254Kenya department of Microbiology College of Health SciencesMakerere UniversityKampala 256Uganda

Uganda has been implementing the Global Health Security Agenda(GHSA)since 2015 to build its capacity according to World Health Organization(WHO)Benchmarks on International Health Regulations *** country remains prone to outbreaks,with more than 20 disease outbreaks reported in the past five years,including Ebola virus disease,Crimean-Congo haemorrhagic fever,Marburg haemorrhagic fever,measles,yellow fever,coronavirus disease 2019(COVID-19),and *** resistance(AMR)is an ongoing *** scored capacity level 3 on infection prevention and control(IPC)and antimicrobial stewardship(AMS)in the 2017 Joint External Evaluation(JEE)*** gaps were being addressed after a self-assessment in *** paper describes the technical assistance approaches provided to Uganda by the medicines,Technologies,and Pharmaceutical Services Program,funded by the United States(U.S.)Agency for International Development,and implemented by Management Sciences for *** program,through a One Health approach,supported systematic capacity strengthening based on the JEE's capacity advancement framework for global health security,specifically relating to *** program's interventions impacted 32 WHO benchmark actions(7 for AMR multisectoral coordination,16 for IPC,and 9 for AMS),contributing to Uganda's strengthened GHSA *** success built on the AMR platform,the program trained 745 health workers in IPC for the Ebola virus and provided support for simulation exercises by eight district IPC *** program also worked with the Ministry of Health to coordinate IPC for the COVID-19 response in five health regions,covering 45 districts and reaching 5,452 health workers at 858 health facilities.

关键词： One health Antimicrobial resistance Antibiotic resistance Jointexternal evaluation Global health security Uganda Africa WHO Benchmarks for International Health Regulations Capacities

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Formulation,characterization and in vivo and in vitro evaluation of aloe-emodin-loaded solid dispersions for dissolution enhancement

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Journal of Traditional Chinese Medicine 2024年第1期44卷 54-62页

作者： LI Xiuyan LUO Yuting WANG Jinhui DU Zhimin Key Laboratory of Basic and Application Research of Beiyao Heilongjiang University of Chinese MedicineMinistry of EducationHarbin 150040China College of Pharmacy Harbin Medical UniversityHarbin 150081China Institute of Clinical Pharmacology the Second Affliated Hospital of Harbin Medical University(University Key aboratory of Drug ResearchHeilongjiang Province)Harbin 150086China department of Clinical Pharmacology College of Pharmacy Harbin Medical UniversityHarbin 150081China State Key Laboratory of Quality Research in Chinese medicines Macao University of Science and TechnologyMacao 999078China

OBJECTIVE:To prepare aloe-emodin solid dispersion(AE-SD)and determine the metabolic process of AE and AE-SD in ***:AE-SD was prepared via solvent evaporation or solvent melting using PEG-6000 and PVP-K30 as *** analysis,X-ray diffraction spectroscopy,differential scanning calorimetry,Fourier transform infrared spectroscopy and scanning electron microscopy were used to identify the physical state of *** prescriptions were screened via the dissolution degree determination *** Phoenix software,AE suspension and AE-SD were subjected to a pharmacokinetic comparison study analyzing the alteration of behavior in vivo after AE was prepared as a solid *** toxicity was assessed in mice,and the physiological toxicity was used as the determination criterion for ***:AE-SD showed that AE existed in the carrier in an amorphous *** with polyethylene glycol,polyvinylpyrrolidone(PVP)inhibited AE crystallization,causing the drug to transform from a dense crystalline state to an amorphous form and increasing the degree of drug ***,it was more suitable as a carrier material for *** addition of poloxamer(POL)was more beneficial to the stability of solid dispersions and could reduce the amount of *** dissolution test confirmed that the optimal ratio of AE to the composite vector AE-PVP-POL was 1:2:2,and its dissolution effect was also *** on the pharmacokinetic comparison,the drug absorption was faster and quickly reached the peak of blood drug concentration in AE-SD compared to AE,the Cmax of AE-SD was greater than that of AE,and t1/2 and mean residence time of AE-SD were less than *** results showed that the drug metabolism in AE-SD was better,and the residence time was *** toxicology study showed that both AE and AE-SD had no ***:This paper established that the solubility of the drug could be increased after preparing a solid dispersion,

关键词： aloe-emodin solid dispersion solvent evaporation drug liberation pharmacokinetics

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Dynamic gut microbiome-metabolome in cationic bovine serum albumin induced experimental immune-complex glomerulonephritis and effect of losartan and mycophenolate mofetil on microbiota modulation

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Journal of Pharmaceutical Analysis 2024年第4期14卷 562-577页

作者： Wenying Shi Zhaojun Li Weida Wang Xikun Liu Haijie Wu Xiaoguang Chen Xunrong Zhou Sen Zhang State Key Laboratory of Bioactive Substances and Functions of Natural medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100050China State Key Laboratory of Functions and Applications of Medicinal Plants College of PharmacyGuizhou Provincial Engineering Technology Research Center for Chemical Drug R&DGuizhou Medical UniversityGuiyang550004China department of Medicine Solna Center for Molecular MedicineKarolinska University Hospital and Karolinska InstituteStockholm17176Sweden department of Pharmacy The Second Affiliated Hospital of Guizhou University of Traditional Chinese MedicineGuiyang550001China

Dynamic changes in gut dysbiosis and metabolomic dysregulation are associated with immune-complex glomerulonephritis(ICGN).However,an in-depth study on this topic is currently ***,we report an ICGN model to address this *** was induced via the intravenous injection of cationized bovine serum albumin(c-BSA)into Sprague-Dawley(SD)rats for two weeks,after which mycophenolate mofetil(MMF)and losartan were administered *** and six weeks after ICGN establishment,fecal samples were collected and 16S ribosomal DNA(rDNA)sequencing and untargeted metabolomic were *** microbiota transplantation(FMT)was conducted to determine whether gut normali-zation caused by MMF and losartan contributed to their renal protective effects.A gradual decline in microbial diversity and richness was accompanied by a loss of renal *** 18 genera were found to have significantly different relative abundances between the early and later stages,and Marvinbryantia and Allobaculum were markedly upregulated in both *** metabolomics indicated that the tryptophan metabolism was enhanced in ICGN,characterized by the overproduction of indole and kynurenic acid,while the serotonin pathway was *** of losartan and MMF ameliorated microbial dysbiosis and reduced the accumulation of indoxyl conjugates in *** using feces from animals administered MMF and losartan improved gut dysbiosis by decreasing the Firmicutes/Bacteroidetes(F/B)ratio but did not improve renal *** findings indicate that ICGN induces serous gut dysbiosis,wherein an altered tryptophan metabolism may contribute to its *** and losartan significantly reversed the gut microbial and metabolomic dysbiosis,which partially contributed to their renoprotective effects.

关键词： Immune-complex glomerulonephritis Gut microbiome Metabolomics Fecal microbiota transplant Tryptophan metabolism

Diet restriction and exercise alleviate cognitive reduction of high fat diet(HFD)-induced obese mice by rescuing inflammation-mediated compromised insulin signaling pathway through activating AMPK/SIRT1 signal pathway and suppressing TLR4 signal pathway

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Food Science and Human Wellness 2024年

作者： Hu Zhang Ye Zhang Jiling Liang Jiahang Li Miao He Xin Liu Jielun Huang Minghui Wang Jingjing Fan Ning Chen Tianjiu Research and Development Center for Exercise Nutrition and foods， Hubei Key Laboratory of Exercise Training and Monitoring， College of Sports Medicine， Wuhan Sports University Physical Education Institute， Hubei University of Science and Technology

Obesity， caused by excessive energy， leads to body weight gain and various diseases， including cognitive impairment. Current studies suggest that diet restriction such as optimal fasting and regular exercise are crucial for improving cognitive capacity. However， further exploration is needed to understand the specific mechanisms of high fat diet (HFD)-induced cognitive decline in obesity. In the present study， 4-month-old mice were subjected to HFD feeding for 18 weeks， followed by aerobic exercise and high-intensity intermittent exercise， regular diet feeding， and intermittent fasting for 8 weeks， and then used to evaluate cognitive capacity， inflammation， compromised insulin signaling pathway， oxidative stress， and apoptosis in hippocampal tissue， as well as AMPK/SIRT1 and TLR4 signal pathways. Obese mice revealed impaired cognitive capacity as compared with mice fed with regular diets. In contrast， aerobic exercise， high-intensity intermittent exercise， regular diet， and intermittent fasting could inhibit apoptosis caused by inflammation-mediated compromised insulin signaling pathway in hippocampal tissues through activating the AMPK/SIRT1 signal pathway and suppressing the TLR4 signal pathway， thereby rescuing the cognitive impairment of obese mice. Therefore， diet restriction and exercise interventions may play a positive role in reverting obesity-induced cognitive impairment.

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An Update on the Clinical Pipelines of New Antibacterial Drugs Developed in China

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Engineering 2024年第7期38卷 52-68页

作者： Xinyi Yang Congran Li Xiukun Wang Zhonghui Zheng Peiyi Sun Chunjie Xu Luni Chen Jiandong Jiang Staffan Normark Birgitta Henriques-Normark Xuefu You Beijing Key Laboratory of Antimicrobial Agents/Laboratory of Pharmacology Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Division for Medicinal Microorganism-Related Strains CAMS Collection Center of Pathogenic MicroorganismsChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China State Key Laboratory of Bioactive Substances and Functions of Natural medicines Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Shandong Xinhua Pharmaceutical Co. Ltd.Zibo 255005China department of Microbiology Tumor and Cell BiologyKarolinska InstitutetStockholm SE-17177Sweden State Key Laboratory of Bioactive Substances and Function of Natural medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Clinical Microbiology Karolinska University HospitalBioclinicumStockholm SE-17176Sweden

Antibacterial resistance is a global health threat that requires further concrete action on the part of all *** this context,one of the biggest concerns is whether enough new antibacterial drugs are being discovered and *** several high-quality reviews on clinical antibacterial drug pipelines from a global perspective were published recently,none provides comprehensive information on original antibacterial drugs at clinical stages in *** this review,we summarize the latest progress of novel antibacterial drugs approved for marketing and under clinical evaluation in China since *** was obtained by consulting official websites,searching commercial databases,retrieving literature,asking personnel from institutions or companies,and other means,and a considerable part of the data covered here has not been included in other *** of June 30,2023,a total of 20 antibacterial projects from 17 Chinese pharmaceutical companies or developers were identified and *** them,two new antibacterial drugs that belong to traditional antibiotic classes were approved by the National Medical Products Administration(NMPA)in China in 2019 and 2021,respectively,and 18 antibacterial agents are in clinical development,with one under regulatory evaluation,five in phase-3,six in phase-2,and six in *** of the clinical candidates are new analogs or monocomponents of traditional antibacterial pharmacophore types,including two dual-acting hybrid antibiotics and a recombinant antibacterial ***,despite there being 17 antibacterial clinical candidates,our analysis indicates that there are still relatively few clinically differentiated antibacterial agents in stages of clinical development in ***,Chinese pharmaceutical companies and institutions will develop more innovative and clinically differentiated candidates with good market potential in the future research and development(R&D)of original antibacterial drugs.

关键词： Antimicrobial resistance New antibiotics Clinical pipelines WHO priority pathogens National Mega-Project for Innovative Drugs

COVID-19 Vaccine Acceptance and Hesitancy among Pregnant Women: A Knowledge, Attitude, and Perceived Risks Survey in Lusaka, Zambia

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Pharmacology & Pharmacy 2024年第5期15卷 147-166页

作者： Steward Mudenda Ruth Mbewe Manal Hadi Ghaffoori Kanaan Shafiq Mohamed department of Pharmacy School of Health Sciences University of Zambia Lusaka Zambia department of Agriculture Technical Institute of Suwaria Middle Technical University Baghdad Iraq medicines Management and Pharmacy Services St. James University Hospital Leeds Teaching Hospitals NHS Trust Leeds United Kingdom

Introduction: The coronavirus disease 2019 (COVID-19) is an infectious disease of the respiratory tract caused by SARS-CoV-2. Since its emergence, there have been increased rates of transmission and spread, morbidity and mortality which led to the development of COVID-19 vaccines to address the pandemic. This study assessed acceptance, knowledge, attitude, and perceived risks regarding COVID-19 vaccines among pregnant women attending antenatal care at two First-Level Hospitals in Lusaka, Zambia. Materials and Methods: This was a cross-sectional study that was conducted among 241 pregnant women using a questionnaire from August 2023 to October 2023 in two First-Level Hospitals in Lusaka district, Zambia. The collected data were analyzed using IBM Statistical Package for Social Sciences (SPSS) version 22.0. Statistical analysis was performed using a Chi-square test. The statistical significance was set at a 95% confidence level. Results: Of the 241 participants, 107 (42.7%) were aged between 24 and 34 years. Overall, 64.3% accepted the COVID-19 vaccines, of which 122 (50.6%) were already vaccinated. Further, 203 (84.6%) of the pregnant women had good knowledge, and 199 (82.6%) had positive attitudes towards COVID-19 vaccines. However, 58.5% thought COVID-19 vaccines were not safe and could cause infertility. Alongside this, 70.1% thought that COVID-19 vaccines were harmful during pregnancy. Having good knowledge of COVID-19 vaccines was associated with age (p = 0.049), education status (p = 0.001), and employment status (p = 0.001). Having a positive attitude towards COVID-19 vaccines was associated with education status (p = 0.001) and employment status (p = 0.001). Conclusion: This study found that most pregnant women had good knowledge, and positive attitudes, and the majority accepted the COVID-19 vaccine. Encouragingly, most of the pregnant women who accepted the COVID-19 vaccines were already vaccinated. Most pregnant women thought that COVID-19 vaccines had sid

关键词： COVID-19 Vaccines Pregnant Women Vaccine Acceptance Vaccine Hesitancy Zambia