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A distinction of gliomas at cellular and tissue level by surface-enhanced Raman scattering spectroscopy

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Chinese Chemical Letters 2024年第5期35卷 423-427页

作者： Chengde Wang Liping huang shanshan Wang Lihao Wu Yi Wang Jun Dong Department of Neurosurgery The Second Affiliated Hospital of Soochow UniversitySuzhou 215004China Department of Neurosurgery The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325000China School of Ophthalmology and Optometry Eye HospitalSchool of Biomedical EngineeringWenzhou Medical UniversityWenzhou 325001China Department of Chemistry School of Science and Research Center for Industries of the FutureWestlake UniversityHangzhou 310030China

Glioblastoma multiforme(GBM)is the most common malignant primary brain tumor in adults.The precise identification and distinction of GBM heterogeneity from surrounding brain parenchyma at the cellular level and even at the tissue level are important for GBM therapy.In this study,GBM cells are distinguished from normal astrocytes and non-central nervous system(CNS)tumor cells by surface-enhanced Raman scattering(SERS)based on gold nanoshell(SiO_(2)@Au)particles and support vector machine(SVM)algorithm.In addition,the gold nanoisland(AuNI)SERS substrates are further developed and explored for accurate detection of GBM at the tissue level.The distinction between glioma and trauma tissues,identification of different tumor grades,and IDH mutation are realized with the assistance of orthogonal partial least squares discriminant analysis(OPLS-DA)in a rapid,non-invasive,and convenient method.The results show that the developed SERS-based analytical method has the potential for practical application for the detection of GBM at the single-cell and tissue levels and even for real-time intraoperative diagnosis.

关键词： Glioblastoma multiforme(GBM) Surface-enhanced Raman scattering(SERS) Nanoparticle Nanoisland Machine learning

Sucrose-associated SnRK1a1-mediated phosphorylation of Opaque2 modulates endosperm filling in maize

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Molecular Plant 2024年第5期17卷 788-806页

作者： Tao Yang Yunqin huang Longyu Liao shanshan Wang Haoyu Zhang Jingying Pan Yongcai huang Xiaoling Li Di Chen Tao Liu Xiaoduo Lu Yongrui Wu State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China Sichuan Agricultural UniversityChengdu 611130SichuanChina National Key Laboratory of Plant Molecular Genetics CAS Center for Excellence in Molecular Plant SciencesShanghai lnstitute of Plant Physiology and EcologyChinese Academy of SciencesShanghai 200032China Institute of Molecular Breeding for Maize Qilu Normal UniversityJinanChina

During maize endosperm filling,sucrose not only serves as a source of carbon skeletons for storage-reserve synthesis but also acts as a stimulus to promote this process.However,the molecular mechanisms underlying sucrose and endosperm filling are poorly understood.In this study,we found that sucrose promotes the expression of endosperm-filling hub gene Opaque2(O2),coordinating with storage-reserve accumulation.We showed that the protein kinase SnRK1a1 can attenuate O2-mediated transactivation,but sucrose can release this suppression.Biochemical assays revealed that SnRK1a1 phosphorylates O2 at serine 41(S41),negatively affecting its protein stability and transactivation ability.We observed that mutation of SnRK1a1 results in larger seeds with increased kernel weight and storage reserves,while overexpression of SnRK1a1 causes the opposite effect.Overexpression of the native O2(O2-OE),phospho-dead(O2-SA),and phospho-mimetic(O2-SD)variants all increased 100-kernel weight.Although O2-SA seeds exhibit smaller kernel size,they have higher accumulation of starch and proteins,resulting in larger vitreous endosperm and increased test weight.O2-SD seeds display larger kernel size but unchanged levels of storage reserves and test weight.O2-OE seeds show elevated kernel dimensions and nutrient storage,like a mixture of O2-SA and O2-SD seeds.Collectively,our study discovers a novel regulatory mechanism of maize endosperm filling.Identification of S41 as a SnRK1-mediated phosphorylation site in O2 offers a potential engineering target for enhancing storage-reserve accumulation and yield in maize.

关键词： maize Opaque2 SnRK1 endosperm phosphorylation sucrose

Role of adhesion molecules in cancer and targeted therapy

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Science China(Life Sciences) 2024年第5期67卷 940-957页

作者： Chunmei Fan Fang Xiong shanshan Zhang Zhaojian Gong Qianjin Liao Guiyuan Li Can Guo Wei Xiong He huang Zhaoyang Zeng NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410000China Department of Histology and Embryology Xiangya School of MedicineCentral South UniversityChangsha410013China Department of Stomatology Xiangya HospitalCentral South UniversityChangsha 410078China Department of Oral and Maxillofacial Surgery The Second Xiangya HospitalCentral South UniversityChangsha 410011China Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education Cancer Research InstituteCentral South UniversityChangsha 410078China

Adhesion molecules mediate cell-to-cell and cell-to-extracellular matrix interactions and transmit mechanical and chemical signals among them.Various mechanisms deregulate adhesion molecules in cancer,enabling tumor cells to proliferate without restraint,invade through tissue boundaries,escape from immune surveillance,and survive in the tumor microenvironment.Recent studies have revealed that adhesion molecules also drive angiogenesis,reshape metabolism,and are involved in stem cell self-renewal.In this review,we summarize the functions and mechanisms of adhesion molecules in cancer and the tumor microenvironment,as well as the therapeutic strategies targeting adhesion molecules.These studies have implications for furthering our understanding of adhesion molecules in cancer and providing a paradigm for exploring novel therapeutic approaches.

关键词： adhesion molecules tumor microenvironment invasion and metastasis reshaping metabolism angiogenesis immune evasion tumor stemness therapeutic strategy

Modeling drug-induced mitochondrial toxicity with human primary cardiomyocytes

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Science China(Life Sciences) 2024年第2期67卷 301-319页

作者： Xiaoli Tang Hong Liu Rongjia Rao Yafei huang Mengqi Dong Miaomiao Xu shanshan Feng Xun Shi Li Wang Zengwu Wang Bingying Zhou State Key Laboratory of Cardiovascular Disease Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100037China Department of Epidemiology Cardiovascular Institute and Fuwai HospitalChinese Academy of Medical Science&Peking Union Medical CollegeBeijing 100037China Shenzhen Key Laboratory of Cardiovascular Disease Fuwai Hospital Chinese Academy of Medical SciencesShenzhenShenzhen 518020China

Mitochondrial toxicity induced by therapeutic drugs is a major contributor for cardiotoxicity,posing a serious threat to pharmaceutical industries and patients’lives.However,mitochondrial toxicity testing is not incorporated into routine cardiac safety screening procedures.To accurately model native human cardiomyocytes,we comprehensively evaluated mitochondrial responses of adult human primary cardiomyocytes(h PCMs)to a nucleoside analog,remdesivir(RDV).Comparison of their response to human pluripotent stem cell-derived cardiomyocytes revealed that the latter utilized a mitophagy-based mitochondrial recovery response that was absent in h PCMs.Accordingly,action potential duration was elongated in h PCMs,reflecting clinical incidences of RDV-induced QT prolongation.In a screen for mitochondrial protectants,we identified mitochondrial ROS as a primary mediator of RDV-induced cardiotoxicity.Our study demonstrates the utility of h PCMs in the detection of clinically relevant cardiac toxicities,and offers a framework for h PCM-based high-throughput screening of cardioprotective agents.

关键词： remdesivir mitochondrial toxicity cardiotoxicity human primary cardiomyocytes high-throughput screening

Human ESC-derived vascular cells promote vascular regeneration in a HIF-1α dependent manner

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Protein & Cell 2024年第1期15卷 36-51页

作者： Jinghui Lei Xiaoyu Jiang Daoyuan huang Ying Jing shanshan Yang Lingling Geng Yupeng Yan Fangshuo Zheng Fang Cheng Weiqi Zhang Juan Carlos Izpisua Belmonte Guang-Hui Liu Si Wang Jing Qu Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Translational Medicine Center Intermational Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China University of Chinese Academy of Sciences Beijing 100049China Institute for Stem Cell and Regeneration CASBeijing 100101China The Fifth People's Hospital of Chongqing Chongqing 400062China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China National Laboratory of Biomacromolecules CAs Center for Excellence in BiomacromoleculesInstitute of BiophysicsBeijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China China National Center for Bioinformation Beijing 100101China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China Sino-Danish Center for Education and Research Beijing 101408China Aging Biomarker Consortium China Altos Labs San DiegoCA 92121United State

Hypoxia-inducible factor(HIF-1α),a core transcription factor responding to changes in cellular oxygen levels,is closely associated with a wide range of physiological and pathological conditions.However,its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive.Here,we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-ia-deficient human vascular cells including vascular endothelial cells,vascular smooth muscle cells,and mesenchymal stem cells(MsCs),as a platform for discovering cell type-specific hypox-ia-induced response mechanisms.Through comparative molecular profiling across cell types under normoxic and hypoxic conditions,we provide insight into the indispensable role of HIF-1αin the promotion of ischemic vascular regeneration.We found human MSCs to be the vascular cell type most susceptible to HIF-1a deficiency,and that transcriptional inactivation of ANKZF1,an effector of HIF-1a,impaired pro-angiogenic processes.Altogether,our findings deepen the understanding of HIF-ia in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.

关键词： HIF-1 human ESC vascular cell regeneration

Effects of long-term blood pressure variability on renal function in community population

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Chronic Diseases and Translational Medicine 2024年第2期10卷 149-152页

作者： Zhao Feng Zhiquan Jing Zeya Li Gang Wang shanshan Wu Dan Li Jing Hao Chunlei Yang Jiashu Song Xianzhong Gu Rongchong huang Department of medical service Yongshun Community Health Service CenterYongshun TownBeijingChina Department of Cardiology Beijing Friendship HospitalCapital Medical UniversityBeijingChina Department of Cardiology Weihai Municipal HospitalWeihaiShandongChina National Clinical Research Center for Digestive Diseases Beijing Friendship HospitalCapital Medical UniversityBeijingChina

High blood pressure is a significant contributor to premature mortality,resulting in nearly 10 million deaths and over 200 million disabilities worldwide.1 In recent years,hypertension treatment has shifted focus not only to average blood pressure but also to blood pressure variability(BPV),categorized into very short-term,short-term,and long-term BPV based on the time period of occurrence.2,3 Long-term BPV has emerged as clinically significant,with studies demonstrating its superiority in predicting long-term cardiovascular events,stroke,and mortality compared to short-term variability.Given its association with pre-renal function decline,reducing blood pressure fluctuations is imperative.

关键词： mortality cardiovascular function

A NIR fluorescent probe for Vanin-1 and its applications in imaging, kidney injury diagnosis,and the development of inhibitor

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Acta Pharmaceutica Sinica B 2022年第1期12卷 316-325页

作者： Zhenhao Tian Fei Yan Xiangge Tian Lei Feng Jingnan Cui Sa Deng Baojing Zhang Tian Xie shanshan huang Xiaochi Ma Dalian Key Laboratory of Metabolic Target Characterization and Traditional Chinese Medicine Intervention The Second Affiliated HospitalCollege of Integrative MedicineCollege of PharmacyDalian Medical UniversityDalian 116044China Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical UniversityXuzhou 221004China School of Life Sciences Northwestern Polytechnical UniversityXi'an 710072China School of Chemistry and Chemical Engineering Henan Normal UniversityXinxiang 453007China State Key Laboratory of Fine Chemicals Dalian University of TechnologyDalian 116024China College of Pharmacy Key Laboratory of Elemene Class Anti-Cancer Chinese MedicinesHangzhou Normal UniversityHangzhou 311121China

Vanin-1 is an amidohydrolase that catalyses the conversion of pantetheine into the aminothiol cysteamine and pantothenic acid(coenzyme A precursor), which plays a vital role in multiple physiological and pathological processes. In this study, an enzyme-activated near-infrared(NIR) fluorescent probe(DDAV) has been constructed for sensitively detecting Vanin-1 activity in complicated biosamples on the basis of its catalytic characteristics. DDAV exhibited a high selectivity and sensitivity toward Vanin-1 and was successfully applied to the early diagnosis of kidney injury in cisplatin-induced kidney injury model. In addition, DDAV could serve as a visual tool for in situ imaging endogenous Vanin-1 in vivo. More importantly, Enterococcus faecalis 20247 which possessed high expression of Vanin-1 was screened out from intestinal bacteria using DDAV, provided useful guidance for the rational use of NSAIDs in clinic. Finally, oleuropein as a potent natural inhibitor for Vanin-1 was discovered fromherbal medicines library using a high-throughput screening method using DDAV, which held great promise for clinical therapy of inflammatory bowel disease.

关键词： Vanin-1 NIR fluorescent probe Kidney injury diagnosis Fluorescence imaging Oleuropein

Serum exosomal microRNA-144-3p:a promising biomarker for monitoring Crohn’s disease

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Gastroenterology Report 2022年第1期10卷 313-321页

作者： Peng Chen shanshan huang Qiao Yu Kang Chao Ying Wang Gaoshi Zhou Xiaojun Zhuang Zhirong Zeng Minhu Chen Shenghong Zhang Department of Gastroenterology The First Affiliated HospitalSun Yat-sen UniversityGuangzhouP.R.China Department of Gastroenterology The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouP.R.China Department of Gastroenterology The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouP.R.China

Background:Crohn’s disease(CD)has a tendency for recurrence and requires adequate monitoring and personalized treatment.Since endoscopy is considerably invasive,serum biomarkers are required as alternatives for CD monitoring.Toward this,exosomal microRNAs(miRNAs)may serve as promising candidates.In this study,we aimed to assess the role of serum exosomal microRNA-144-3p(miR-144-3p)as a biomarker for CD monitoring.Methods:We prospectively recruited 154 patients without a history of surgery(Cohort 1)and 75 patients who were to undergo intestinal resection(Cohort 2).Serum samples were collected from Cohort 1 before colonoscopy and from Cohort 2 before surgery and during post-operative colonoscopic examination.The serum levels of exosomal miR-144-3p were measured using quantitative reverse-transcription polymerase chain reaction(PCR).Correlations between relative exosomal miR-144-3p levels,disease activity,and disease behavior were analysed.The area under the receiver-operating characteristic curve(AUC)was used to assess the predictive value of exosomal miR-144-3p regarding mucosal activity and postoperative recurrence.Results:A 3.33-fold increase in serum exosomal miR-144-3p levels was recorded in patients with CD compared with those in healthy controls(P<0.001).The exosomalmiR-144-3p levels were positively correlated with the simple endoscopic score of CD(q=0.547,P<0.001)as well as the Rutgeerts score(q=0.478,P<0.001).Elevated exosomalmiR-144-3p levels were correlated with the penetrating disease with high specificity(100%[95%confidence interval,95.1%–100%]).The accuracy of exosomalmiR-144-3p for identifying post-operative recurrence was higher than that of C-reactive protein(CRP)(AUC,0.775 vs 0.639;P<0.001).Conclusions:Serum exosomal miR-144-3p is a reliable biomarker of mucosal inflammation and penetrating CD.It may identify endoscopic CD recurrence after intestinal resection with higher accuracy than CRP testing.

关键词： Crohn’s disease microRNA-144-3p serum biomarker exosome

Real-time quantification for sulfite using a turn-on NIR fluorescent probe equipped with a portable fluorescence detector

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Chinese Chemical Letters 2022年第9期33卷 4219-4222页

作者： Fei Yan Jingnan Cui Chao Wang Xiangge Tian Dawei Li Yan Wang Baojing Zhang Lei Feng shanshan huang Xiaochi Ma College of Pharmacy Dalian Key Laboratory of Metabolic Target Characterization and Traditional Chinese Medicine InterventionAcademy of Integrative MedicineDalian Medical UniversityDalian 116044China Second Affiliated Hospital Dalian Medical UniversityDalian 116044China State Key Laboratory of Fine Chemicals Dalian University of TechnologyDalian 116024China School of Chemistry and Chemical Engineering Henan Normal UniversityXinxiang 453007China

Sulfur dioxide and its derivative sulfite widely existed in air,water as the environment pollutant.Sulfite is also commonly used as preservative and additive in fresh fruits,vegetables,wines and pharmaceutical materials.Due to sulfite is closely related with human diseases,it is very urgent for the sensitive and rapid quantification of sulfite in various samples.In our study,a turn-on near infrared(NIR)fluorescent probe(MDQ)was developed for sulfite detection based on a Michael addition reaction,with high sensitivity(LOD 4.16 nmol/L),selectivity and fast response time(400 s).Using MDQ,a quantify method for sulfite in traditional Chinese medicines(TCMs)was developed with the advantages of high precision,accuracy and convenient operation.Furthermore,according to the photophysical property of MDQ,a portable fluorescence detector is designed to quantify sulfite for TCMs and surface water in Dalian city of China.Therefore,the developed fluorescent probe MDQ and portable fluorescent detector as a rapid inspection instrument were successfully used to real-time monitor the sulfite in various complex samples.

关键词： Sulfite Fluorescent probe Portable fluorescence detector Traditional Chinese medicine Surface water