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Journal of Pharmaceutical Analysis 2024年第2期14卷 287-290页

作者： Chunyan Zhu Xuemin Yao Dandan Liu Guoxin Zhang Yongping Zhu Hongyu Chi Shuangpan Zhang Jun Yang Ying Liu Jigang Wang Na Lin institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing100700China

Nowadays,roughly 603.7 million people are bothered by obesity[1].More seriously,obesity brings inflammation to the peripheral and central nervous system,which compromises the comorbidity of obesity,major depression[2],and cognitive deficits[3].Drug competent in the comorbidity is still *** 2015,Liu et al.[4]reported celastrol(CEL)as a powerful anti-obesity *** our previous study.

关键词： inflammation obesity obese

Advances in regional nodal management of early-stage breast cancer

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Chinese Journal of Cancer Research 2024年第2期36卷 215-225页

作者： Zhao Bi Yongsheng Wang Breast Cancer Center Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinan 250017China

With the continuous improvement of systemic treatment, reasonable local regional control of early-stage breast cancer can be translated into survival benefits. The optimization of regional nodal management in patients with limited sentinel lymph node(SLN) metastasis needs to be weighed by surgical complications, regional recurrence risk, and lymph node status, as well as other escalating treatment(systemic/radiotherapy) that may result from deescalating surgery. With the effective support and supplementation of systemic therapy and radiotherapy, the management of axillary surgery is developing in a de-escalating trend. The widespread application of neoadjuvant therapy has contributed to optimizing the management of patients with clinically node-negative/imaging nodepositive disease. In clinical practice, it is necessary to consider the residual tumor burden of regional lymph nodes when formulating the optimal irradiation fields in patients with limited positive SLN without axillary lymph node dissection. The combined application of genomic tests and American College of Surgeons Oncology Group Z0011/AMAROS criteria could provide patients with a better strategy of dual de-escalation treatment, which includes the de-escalation of both axillary surgery and systemic treatment. In the era of sentinel lymph node biopsy(SLNB), the regional nodal management of breast cancer should adhere to the concept of “updating ideas, making bold assumptions, and carefully seeking proof”, make full use of the benefits of systemic therapy and radiotherapy to reduce the scope of surgery and complications, and expand the “net benefit” of efficacy and quality of life. This review discusses the optimization of regional nodal management in the era of SLNB, in order to provide reference information for clinicians.

关键词： Breast cancer sentinel lymph node biopsy internal mammary lymph node radiotherapy surgery

Turning point of organoid transplantation:first-in-human trial of iPSC-derived retinal organoid grafting in patients with retinitis pigmentosa

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Science China(Life Sciences) 2024年第5期67卷 1082-1084页

作者： Chang-Jun Zhang Zi-Bing Jin Beijing institute of Ophthalmology Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China

The discovery of induced pluripotent stem cells(iPSCs)has revolutionized the field of disease research,providing a promising platform for studying various *** the last decade,significant progress has been made in combining iPSCs with other cutting-edge technologies to investigate disease mechanisms and develop potential treatments.

关键词： conditions patients retinitis

(+)/(-)-Gerbeloid A,a pair of unprecedented coumarin-based polycyclic meroterpenoid enantiomers from Gerbera piloselloides:Structural elucidation,semi-synthesis,and lipid-lowering activity

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2657-2668页

作者： Chenxu Zhao Jingrong Li Yue Hu Lingyu Li Meng Yu Yunfeng Huang Tao Zhang Hai Shang Zhongmei Zou State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Medicinal Plant DevelopmentChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100193China institute of Chinese Medicine Resources Guangxi Institute of Chinese Medicine&Pharmaceutical ScienceNanning 530000China

A pair of coumarin-based polycyclic meroterpenoid enantiomers(+)/(-)-gerbeloid A[(+)-1a and(-)-1b]were isolated from the medicinal plant Gerbera piloselloides,which have a unique caged oxatricyclo[4.***.2.0^(3,8)]decene *** planar and three-dimensional structures were exhaustively characterized by comprehensive spectroscopic data and X-ray diffraction *** by the hypothetical biosynthetic pathway,the biomimetic synthesis of racemic 1 was achieved using 4-hydroxy-5-methylcoumarin and citral as the starting material via oxa-6πelectrocyclization and intramolecular[2+2]***,the results of the biological activity assay demonstrated that both(+)-1a and(-)-1b exhibited potent lipid-lowering effects in 3T3-L1 adipocytes and the high-fat diet zebrafish ***,the lipid-lowering activity of(+)-1a is better than that of(-)-1b at the same concentration,and molecular mechanism study has shown that(+)-1a and(-)-1b impairs adipocyte differentiation and stimulate lipolysis by regulating C/EBPα/PPARγsignaling and Perilipin signaling in vitro and in *** findings provide a promising drug model molecule for the treatment of obesity.

关键词： Gerbera piloselloides Natural products Coumarin meroterpenoid Structural elucidation Biomimetic synthesis Lipid-lowering activity 3T3-L1 adipocytes High-fat diet zebrafish model

Molecular quantification of herbs(Herb-Q):a pyrosequencingbased approach and its application in Pinellia ternata

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Chinese Journal of Natural Medicines 2024年第7期22卷 663-672页

作者： PEI Yifei LIU Ziyi YU Dade ZHANG Xiangyu SUN Wei CHEN Xiaofang FENG Xue LI Xiwen institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing 100700China Bijie institute of Traditional Chinese Medicine Bijie 551700China The Key Laboratory for Health Industry of Bijie Bijie Medical CollegeBijie 551700China

Variations in herb dosage due to species adulteration and dosing inaccuracies can substantially affect clinical safety and *** species quantification remains challenging,as current methods often yield inconsistent *** study introduces a novel pyrosequencing-based technique,termed herb molecular quantification(Herb-Q),designed to precisely quantify herbal *** evaluated its effectiveness using Pinellia ternata and five of its ***,we assessed commonly used DNA barcodes with sequences from a public database,identifying two candidate regions,Maturase K(matK)and internal transcribed spacer 2(ITS2),for screening specific single nucleotide polymorphism(SNP)loci,allowing for species-specific *** loci were validated by amplifying and sequencing genomic material from collected *** validation studies showed that Herb-Q demonstrated excellent linearity,accuracy,repeatability,and detection *** established quantitative standard curves with high R^(2)values(>0.99)to enable precise species quantification,which were combined with external standards to provide clear and accurate visual quantification *** average bias in quantifying the tuber of *** was 2.38%,confirming that Herb-Q can accurately identify and quantify herbal product ***,the entire quantification process took less than 4 *** study presents a novel,rapid method for accurately quantifying species in herbal products and advances the application of DNA barcoding from species identification to quantitative detection.

关键词： Quantification Adulterant DNA barcodes Single nucleotide polymorphism

Dysregulated N6-methyladenosine modification in peripheral immune cells contributes to the pathogenesis of amyotrophic lateral sclerosis

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Frontiers of Medicine 2024年第2期18卷 285-302页

作者： Di He Xunzhe Yang Liyang Liu Dongchao Shen Qing Liu Mingsheng Liu Xue Zhang Liying Cui Department of Neurology Peking Union Medical College Hospital(PUMCH)Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100730China medical Doctor Program Chinese Academy of Medical Science and Peking Union Medical CollegeBeijing100730China McKusick-Zhang Center for Genetic Medicine State Key Laboratory of Medical Molecular BiologyInstitute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijing100730China Neuroscience Center Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100730China

Amyotrophic lateral sclerosis(ALS)is a progressive neurogenerative disorder with uncertain *** evidence implicates N6-methyladenosine(m6A)modification in ALS *** RNA immunoprecipitation sequencing(MeRIP-seq)and liquid chromatography–mass spectrometry were utilized for m6A profiling in peripheral immune cells and serum proteome analysis,respectively,in patients with ALS(n=16)and controls(n=6).The single-cell transcriptomic dataset(GSE174332)of primary motor cortex was further analyzed to illuminate the biological implications of differentially methylated genes and cell communication *** of peripheral immune cells revealed extensive RNA hypermethylation,highlighting candidate genes with differential m6A modification and expression,including C-X3-C motif chemokine receptor 1(CX3CR1).In RAW264.7 macrophages,disrupted CX3CR1 signaling affected chemotaxis,potentially influencing immune cell migration in *** proteome analysis demonstrated the role of dysregulated immune cell migration in *** type-specific expression variations of these genes in the central nervous system(CNS),particularly microglia,were *** communication between neurons and glial cells was selectively altered in ALS *** integrated approach underscores m6A dysregulation in immune cells as a potential ALS contributor.

关键词： amyotrophic lateral sclerosis N^(6)-methyladenosine epi-transcriptome proteome single cell RNA sequencing analysis CX3CR1

Phenylalanine deprivation inhibits multiple myeloma progression by perturbing endoplasmic reticulum homeostasis

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3493-3512页

作者： Longhao Cheng Xiaoxue Wang Aijun Liu Ying Zhu Hu Cheng Jiangling Yu Lili Gong Honglin Liu Guolin Shen Lihong Liu institute of Clinical medical Sciences ChinaeJapan Friendship HospitalCapital Medical UniversityBeijing 100029China Department of Pharmacy ChinaeJapan Friendship HospitalBeijing 100029China Beijing Chao-Yang Hospital Capital Medical UniversityBeijing 100020China institute of Chemicals Safety Chinese Academy of Inspection and QuarantineBeijing 100020China

Amino acid metabolic remodeling is a hallmark of cancer,driving an increased nutritional demand for amino *** acids are pivotal for energetic regulation,biosynthetic support,and homeostatic maintenance to stimulate cancer ***,the role of phenylalanine in multiple myeloma(MM)remains ***,we demonstrate that phenylalanine levels in MM patients are decreased in plasma but elevated in bone marrow(BM)*** the treatment,phenylalanine levels increase in plasma and decrease in *** suggests that changes in phenylalanine have diagnostic value and that phenylalanine in the BM microenvironment is an essential source of nutrients for MM *** requirement for phenylalanine by MM cells exhibits a similar *** phenylalanine utilization suppresses MM cell growth and provides a synergistic effect with Bortezomib(BTZ)treatment in vitro and murine ***,phenylalanine deprivation induces excessive endoplasmic reticulum stress and leads to MM cell apoptosis through the ATF3eCHOPeDR5 *** with ATF3 significantly affects phenylalanine deprivation *** conclusion,we have identified phenylalanine metabolism as a characteristic feature of MM metabolic *** is necessary for MM proliferation,and its aberrant demand highlights the importance of lowphenylalanine diets as an adjuvant treatment for MM.

关键词： Multiple myeloma Phenylalanine Amino acid metabolism Nutrient deprivation Cancer therapy Endoplasmic reticulum stress ATF3 Apoptosis

Colorectal cancer cell dormancy:An insight into pathways

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World Journal of Gastroenterology 2024年第33期30卷 3810-3817页

作者： Anil Kumar Lekha Saha Department of Pharmacology Post Graduate Institute of Medical Education and ResearchChandigarh 160012India

Cancer cell dormancy(CCD)in colorectal cancer(CRC)poses a significant challenge to effective *** CRC,CCD contributes to tumour recurrence,drug resistance,and amplifying the disease's *** molecular mechanisms governing CCD and strategies for eliminating dormant cancer cells remain largely ***,understanding the molecular mechanisms governing dormancy is crucial for improving patient outcomes and developing targeted *** editorial highlights the complex interplay of signalling pathways and factors involved in colorectal CCD,emphasizing the roles of Hippo/YAP,pluripotent transcription factors such as NANOG,HIF-1αsignalling,and Notch signalling ***,ERK/p38α/β/MAPK pathways,AKT signalling pathway,and Extracellular Matrix Metalloproteinase Inducer,along with some potential less explored pathways such as STAT/p53 switch and canonical and non-canonical Wnt and SMAD signalling,are also involved in promoting colorectal *** their clinical significance,these findings may offer the potential for identifying key dormancy regulator pathways,improving treatment strategies,surmounting drug resistance,and advancing personalized medicine ***,insights into dormancy mechanisms could lead to the development of predictive biomarkers for identifying patients at risk of recurrence and the tailoring of targeted therapies based on individual dormancy *** is essential to conduct further research into these pathways and their modulation to fully comprehend CRC dormancy mechanisms and enhance patient outcomes.

关键词： Colorectal cancer Colorectal cancer cell dormancy Cancer cell dormancy Pathways in colorectal cancer dormancy

Simulation and fabrication of in vitro microfluidic microelectrode array chip for patterned culture and electrophysiological detection of neurons

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Nanotechnology and Precision Engineering 2024年第2期7卷 1-10页

作者： Yan Yang Shihong Xu Yu Deng Yaoyao Liu Kui Zhang Shiya Lv Longze Sha Qi Xu Xinxia Cai Jinping Luo State Key Laboratory of Transducer Technology Aerospace Information Research InstituteChinese Academy of SciencesBeijing 100190China School of Electronic Electrical and Communication EngineeringUniversity of Chinese Academy of SciencesBeijing 100049China State Key Laboratory of medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China

To enable the detection and modulation of modularized neural networks in vitro,this study proposes a microfluidic microelectrode array chip for the cultivation,compartmentalization,and control of neural *** chip was designed based on the specific structure of neurons and the requirements for detection and ***-element analysis of the chip’s flow field was conducted using the COMSOL Multiphysics software,and the simulation results show that the liquid within the chip can flow smoothly,ensuring stable flow fields that facilitate the uniform growth of neurons within the microfluidic *** employing MEMS technology in combination with nanomaterial modification techniques,the microfluidic microelectrode array chip was fabricated *** hippocampal neurons were cultured on the chip,forming a well-defined neural *** electrical activity of the detected neurons was recorded,exhibiting a 23.7%increase in amplitude compared to neuronal discharges detected on an open-field microelectrode *** study provides a platform for the precise detection and modulation of patterned neuronal growth in vitro,potentially serving as a novel tool in neuroscience research.

关键词： Microfluidic Microelectrode array In vitro Neural chip

Schisanhenol ameliorates non-alcoholic fatty liver disease via inhibiting miR-802 activation of AMPK-mediated modulation of hepatic lipid metabolism

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Acta Pharmaceutica Sinica B 2024年第9期14卷 3949-3963页

作者： Bin Li Qi Xiao Hongmei Zhao Jianuo Zhang Chunyan Yang Yucen Zou Bengang Zhang Jiushi Liu Haitao Sun Haitao Liu State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Medicinal Plant DevelopmentChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100193China institute of Basic medical Sciences Chinese Academy of Medical SciencesDepartment of PathophysiologyPeking Union Medical CollegeBeijing 100005China

Non-alcoholic fatty liver disease(NAFLD),characterized by hepatic steatosis,is a common metabolic liver disease ***,satisfactory drugs for NAFLD treatment remain *** and diabetes are the leading causes of NAFLD,and compounds with anti-obesity and antidiabetic activities are considered suitable candidates for treating *** this study,biochemical and histological assays revealed that a natural lignan schisanhenol(SAL)effectively decreased lipid accumulation and improved hepatic steatosis in free fatty acid(FFA)-treated HepG2 cells and high-fat diet(HFD)-induced NAFLD ***,molecular analyses,microRNA(miRNA)-seq,and bioinformatics analyses revealed that SAL may improve NAFLD by targeting the miR-802/adenosine monophosphateactivated protein kinase(AMPK)***-specific overexpression of miR-802 in NAFLD mice significantly impaired SAL-mediated liver protection and decreased the protein levels of phosphorylated(p)-AMPK and ***-luciferase assay analysis further confirmed that miR-802 inhibits hepatic AMPK expression by binding to the 3’untranslated region of mouse Prkab1 or human PRKAA1.

关键词： Schisanhenol Non-alcoholic fatty liver disease Hepatic steatosis Lipid metabolism miR-802 AMPK SREBP-1c PPARa