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CMKLR1 senses chemerin/resolvin E1 to control adipose thermogenesis and modulate metabolic homeostasis

Fundamental Research 2024年第3期4卷 575-588页

作者： Zewei Zhao Siqi Liu Bingxiu Qian Lin Zhou Jianglin Shi Junxi Liu Lin Xu zhonghan Yang Department of Biochemistry Molecular Cancer Research CenterSchool of MedicineSun Yat-sen UniversityShenzhenGuangdong 518107China Department of Biochemistry Zhongshan School of MedicineSun Yat-sen UniversityGuangzhouGuangdong 510080China School of Public Health Sun Yat-sen UniversityGuangzhouGuangdong 510080China

Induction of beige fat for thermogenesis is a potential therapy to improve homeostasis against obesity.β3-adrenoceptor(β3-AR),a type of G protein-coupled receptor(GPCR),is believed to mediate the thermogenesis of brown fat in mice.However,β3-AR has low expression in human adipose tissue,precluding its activation as a standalone clinical modality.This study aimed at identifying a potential GPCR target to induce beige fat.We found that chemerin chemokine-like receptor 1(CMKLR1),one of the novel GPCRs,mediated the development of beige fat via its two ligands,chemerin and resolvin E1(RvE1).The RvE1 levels were decreased in the obese mice,and RvE1 treatment led to a substantial improvement in obese features and augmented beige fat markers.Inversely,despite sharing the same receptor as RvE1,the chemerin levels were increased in obesogenic conditions,and chemerin treatment led to an augmented obese phenotype and a decline of beige fat markers.Moreover,RvE1 and chemerin induced or restrained the development of beige fat,respectively,via the mechanistic target of rapamycin complex 1(mTORC1)signaling pathway.We further showed that RvE1 and chemerin regulated mTORC1 signaling differentially by forming hydrogen bonds with different binding sites of CMKLR1.In conclusion,our study showed that RvE1 and chemerin affected metabolic homeostasis differentially,suggesting that selectively modulating CMKLR1 may be a potential therapeutic target for restoring metabolic homeostasis.

关键词： Obesity Insulin resistance Thermogenesis CMKLR1 Resolvin E1 Chemerin

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The gut microbiome and microbial metabolites in acute myocardial infarction

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Journal of Genetics and Genomics 2022年第6期49卷 569-578页

作者： Chenglin Liu zhonghan sun Shalaimaiti Shali Zhendong Mei Shufu Chang Hanjun Mo Lili Xu Yanni Pu Huihui Guan Guo-Chong Chen Qibin Qi Zhexue Quan Ji Qi Kang Yao Yuxiang Dai Yan Zheng Junbo Ge State Key Laboratory of Genetic Engineering School of Life Sciences and Human Phenome InstituteFudan UniversityShanghai 200433China Ministry of Education Key Laboratory of Contemporary Anthropology Fudan UniversityShanghai 200433China Department of Cardiology Shanghai Institute of Cardiovascular DiseaseZhongshan HospitalFudan University1609 Xietu RoadShanghai 200032China Department of Epidemiology and Population Health Albert Einstein College of MedicineBronxNY 10461USA Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering Institute of Biodiversity ScienceSchool of Life SciencesFudan UniversityShanghai 200433China

Emerging evidence has highlighted the role of gut microbiome in human health.However,the integrative role of gut microbiome and microbial metabolites in acute myocardial infarction(AMI)remains unclear.The current study profiles the microbial community through 16S rRNA gene sequencing and shotgun metagenomic sequencing and measures fecal short-chain fatty acids and circulating choline pathway metabolites among 117 new-onset AMI cases and 78 controls.Significant microbial alternations are observed in AMI patients compared with controls(P=0.001).The abundances of nine species(e.g.,Streptococcus salivarius and Klebsiella pneumoniae)are positively associated,and one species(Roseburia hominis)is inversely associated with AMI status and severity.A gut microbial score at disease onset is associated with the risk of major adverse cardiovascular events in 3.2 years(hazard ratio[95%CI]:2.01[1.04-4.24])in AMI patients.The molar proportions of fecal acetate and butyrate are higher,and the circulating levels of choline and carnitine are lower in AMI patients than in controls.In addition,disease classifiers show that AMI cases and controls have a more distinct pattern in taxonomical composition than in pathways or metabolites.Our findings suggest that microbial composition and functional potentials are associated with AMI status and severity.

关键词： Acute myocardial infarction Atherosclerosis Microbiome Short-chain fatty acids

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Exome sequencing identifies rare mutations of LDLR and QTRT1 conferring risk for early-onset coronary artery disease in Chinese

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National Science Review 2022年第8期9卷 22-25页

作者： Kang Yao Yuxiang Dai Juan Shen Yi Wang Huanjie Yang Runda Wu Qijun Liao Hongyi Wu Xiaodong Fang Shalaimaiti Shali Lili Xu Meng Hao Chenhao Lin zhonghan sun Yilian Liu Mengxin Li Zhen Wang Qiang Gao Shuning Zhang Chenguang Li Wei Gao Lei Ge Yunzeng Zou Aijun sun Juying Qian Li Jin Shangyu Hong Yan Zheng Junbo Ge Department of Cardiology Zhongshan HospitalFudan University Shanghai Institute of Cardiovascular Disease BGI Genomics BGI-Shenzhen State Key Laboratory of Genetic Engineering School of Life Sciences and Human PhenomeInstituteFudan University BGI-Shenzhen State Key Laboratory of Genetic Engineering School of Life Sciences and Human Phenome InstituteFudan University

Despite the advances made over the past decades, the known loci for coronary artery disease(CAD) still only explain<20% of the genetic variation in risk[1,2]. The known loci with the strongest effects usually confer a 20%–37% increased CAD risk and the most loci modulate risk by ≤10% [1]. While most of the current data are from European populations, the use of trans-ethnic analyses could be helpful to identify additional loci. Genetic inheritance may impose a high burden on early-onset coronary artery disease(EOCAD).

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Nanoparticle(NP)-mediated APOC1 silencing to inhibit MAPK/ERK and NF-κB pathway and suppress breast cancer growth and metastasis

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Science China(Life Sciences) 2023年第11期66卷 2451-2465页

作者： Shaomin Liu Fengqian Zhang Yixia Liang Guo Wu Rong Liu Xiuling Li Phei Er Saw zhonghan Yang Department of Biochemistry Molecular Cancer Research CenterSchool of MedicineSun Yat-sen UniversityShenzhen 518107China Nanhai Translational Innovation Center of Precision Immunology Sun Yat-sen Memorial HospitalFoshan 528200China Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study Institute of Pharmacy&PharmacologySchool of Pharmaceutical ScienceUniversity of South ChinaHengyang 421001China

Breast cancer is one of the most common malignant tumors with high mortality and poor prognosis in women.There is an urgent need to discover new therapeutic targets for breast cancer metastasis.Herein,we identified that Apolipoprotein C1(APOC1)was up-regulated in primary tumor of breast cancer patient that recurrence and metastasis by immunohistochemistry(IHC).Kaplan-Meier Plotter database showed that high levels of APOC1 in breast cancer patients were strongly associated with worse overall survival(OS)and relapse-free survival(RFS).Mechanistically,APOC1 silencing significantly inhibits MAPK/ERK kinase pathway and restrains the NF-κB to decrease the transcription of target genes related to growth and metastasis in vitro.Based on this regulatory mechanism,we developed these findings into potential therapeutic drugs,glutathione(GSH)responsive nanoparticles(NPs)were used for systemic APOC1 siRNA delivery,NPs(siAPOC1)silenced APOC1 expression,and subsequently resulted in positive anti-tumor effects in orthotopic and liver metastasis models in vivo.Taken together,GSH responsive NPmediated siAPOC1 delivery was proved to be effective in regulating growth and metastasis in multiple tumor models.These findings show that APOC1 could be a potential biomarker to predict the prognosis of breast cancer patients and NP-mediated APOC1 silencing could be new strategies for exploration of new treatments for breast cancer metastasis.

关键词： cancer metastasis APOC1 nanoparticles siRNA delivery

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Feature Fusion Based Hand Gesture Recognition Method for Automotive Interfaces

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Chinese Journal of Electronics 2020年第6期29卷 1153-1164页

作者： XU Qianyi QIN Guihe sun Minghui YAN Jie JIANG Huiming ZHANG zhonghan College of Computer Science and Technology Jilin University Key Laboratory of Symbolic Computing and Knowledge Engineering Ministry of Education Jilin University College of Software Jilin University

Hand gesture recognition on the depth videos is a promising approach for automotive interfaces because it is less sensitive to light variation and more accurate than other traditional methods.However,video gestures recognition is still a challenging task since lots of interferences are induced by the uncorrelated gesture factors.Considering that if the displays are more relevant,the results will more accurate,so ResNext,a kind of compact and efficient neural network,is firstly used as feature extractor,then an improved weighted frame unification method is adopted to obtain the key frame samples,finally the Discriminant correlation analysis(DCA) is employed to fuse features for static data and dynamic data after conducting Feature embedding branch(FEB) on static data.The public dataset named Depth based gesture recognition database(DGRD) is used in this paper,but the dataset is a little small and the class distribution is largely imbalance,and we find the performance of ResNext degrades badly in the condition of imbalance problem although it achieves excellent result at sufficient training data.In order to conquer the disadvantages of limited dataset,a special loss function scheme combining the soft max loss and dice loss is proposed.Evaluation of the algorithm performances in comparison with other state-of-the-art methods indicates that the proposed method is more practical for gesture recognition and may be widely adopted by automotive interfaces.

关键词： Weighted frame unification Discriminant correlation analysis (DCA) Feature embedding branch (FEB) Gesture recognition Loss function

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Selective laser melting of NiTi alloy with superior tensile property and shape memory effect

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Journal of Materials Science & Technology 2019年第10期35卷 2238-2242页

作者： Zhiwei Xiong zhonghan Li Zhen sun Shijie Hao Ying Yang Meng Li Changhui Song Ping Qiu Lishan Cui State Key Laboratory of Heavy Oil Processing China University of PetroleumBeijing102249China Qian Xuesen Laboratory of Space Technology China Academy of Space TechnologyBeijing100094China School of Mechanical&Automotive Engineering South China University of TechnologyGuangzhou510641China

It is a challenge to develop complex-shaped Ni Ti shape memory alloy parts by traditional processing methods, due to the poor machinability of Ni Ti alloy. It is reported that selective laser melting(SLM) of additive manufacturing could overcome this problem. However, the reported SLM-produced Ni Ti exhibits poor tensile ductility due to the inner defects and adverse unidirectional columnar grains from SLM process. In this work, the defect-less SLM-Ni Ti with nondirective columnar grains was fabricated by optimizing the intraformational laser scanning length and interformational laser scanning direction. The obtained lath-shaped SLM-Ni Ti sample exhibits tensile strain of 15.6%, more than twice of the reported maximum result(7%). Besides, the SLM-Ni Ti part with complex geometry displays a shape memory recovery of 99% under compressive deformation of 50%.

关键词： NiTi shape memory alloy Selective laser melting Tensile ductility Shape memory effect

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冠心病肠道菌群及其代谢产物变化的研究进展

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Science Bulletin 2023年第6期68卷 549-552,M0003页

作者：戴宇翔孙仲汉郑琰葛均波 Department of Cardiology Zhongshan HospitalFudan UniversityShanghai 200032China Shanghai Institute of Cardiovascular Disease Shanghai 200032China State Key Laboratory of Genetic Engineering School of Life Sciences and Human Phenome InstituteFudan UniversityShanghai 200438China

Over the past decades, epidemiological evidence has documented risk factors of coronary artery disease (CAD), leading to extraordinary progress in understanding, preventing, and treating CAD. Nevertheless, CAD remains the top cause of mortality worldwide. The residual cardiovascular risk beyond these established factors has motivated the discovery of novel targets for risk reduction and effective treatment.

关键词：肠道菌群 artery 代谢产物

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An in-situ spectroscopy investigation of alkali metal interaction mechanism with the imide functional group

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Nano Research 2020年第12期13卷 3224-3229页

作者： Xu Lian Zhirui Ma zhonghan Zhang Jinlin Yang Shuo sun Chengding Gu Yuan Liu Honghe Ding Jun Hu Xu Cao Junfa Zhu Shuzhou Li Wei Chen Department of Chemistry National University of SingaporeSingapore117543Singapore Centre for Advanced 2D Materials National University of SingaporeSingapore117546Singapore School of Materials Science and Engineering Nanyang Technological UniversitySingapore639798Singapore National University of Singapore(Suzhou)Research Institute Suzhou215123China Joint School of National University of Singapore and Tianjin University International Campus of Tianjin UniversityFuzhou350207China National Synchrotron Radiation Laboratory Department of Chemical PhysicsUniversity of Science and Technology of ChinaHefei230029China Department of Physics National University of SingaporeSingapore117542Singapore

Organic anode materials have attracted considerable interest owing to their high tunability by adopting various active functional groups.However,the interaction mechanisms between the alkali metals and the active functional groups in host materials have been rarely studied systematically.Here,a widely used organic semiconductor of perylene-3,4,9,10-tetracarboxylic diimide(PTCDI)was selected as a model system to investigate how alkali metals interact with imide functional groups and induce changes in chemical and electronic structures of PTCDI.The interaction at the alkali/PTCDI interface was probed by in-situ X-ray photoelectron spectroscopy(XPS),ultraviolet photoelectron spectroscopy(UPS),synchrotron-based near edge X-ray absorption fine structure(NEXAFS),and corroborated by density functional theory(DFT)calculations.Our results indicate that the alkali metal replaces the hydrogen atoms in the imide group and interact with the imide nitrogen of PTCDI.Electron transfer induced gap states and downward band-bending like effects are identified on the alkali-deposited PTCDI surface.It was found that Na shows a stronger electron transfer effect than Li.Such a model study of alkali insertion/intercalation in PTCDI gives insights for the exploration of the potential host materials for alkali storage applications.

关键词： perylene-3,4,9,10-tetracarboxylic diimide(PTCDI) lithium storage organic anode imide electron transfer

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Preparation of two kinds of superparamagnetic carriers-supported cis-platinum complexes and the compari-son of their characteristics

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Chinese Science Bulletin 2006年第2期51卷 151-157页

作者： XIE Minqiang CHEN Shuaijun XU Xueqing LI zhonghan SHEN Hui XU Jiarui Department of Otorhinolaryngology Head and Neck Surgery The Third Affiliated Hospital Sun Yat Sen University Guangzhou 510630 China School of Physics and Engineering Sun Yat Sen University Guangzhou 510275 China School of Chemistry and Chemical Engineering Sun Yat Sen University Guangzhou 510275 China

The purpose of the research is to ex- plore the effect of different surface modifiers in preparation of magnetic carriers-supported cis-plat- inum (CDDP) complex and their characteristics. So- dium alginate (SA) and N-oleoylsarcosine (NOSARK) were used respectively as linkers between CDDP and magnetic nanometer particles (MNP), and carri- ers-supported CDDP complex of carboxymethyl dex- tran (CM-dex) was used as the control. The physical and chemical characteristics of CDDP-MNP were measured by transmission electron microscope, photon correlation spectrum (PCS), spectrophotome- ter, etc. The advantages and disadvantages of the two linkers were analyzed through comparing the stability and quantity of reversibly bound CDDP. The cis-platinum magnetic nanometer particles were found to have the shape of approximately uniformly pellets under transmission electron microscope. The distribution of PCS diameter was 43―52 nm and the diameter of magnetic nucleus of CDDP- MNP com- plex was about 8.8±1.3 nm. The drug- loading ca- pacity of SA is larger than that of NOSARK, and similar to that of CM-dex. The SA-modified CDDP-MNP solution remained stable after being kept at 4℃ for 40 d. SA is superior to NOSARK as a magnetic nanoparticles surface modifier. Natural SA can supersede CM-dex to serve as linker between CDDP and MNP. In practical application, we should take both the maximal reversible CDDP-bonding capacity and CDDP utilization rate into consideration.

关键词：顺铂磁性纳米粒子 N-油酰基肌氨酸海藻酸钠超顺磁性

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The ACTIVE study protocol:apatinib or placebo plus gefitinib as first-line treatment for patients with EGFR-mutant advanced non-small cell lung cancer(CTONG1706)

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Cancer Communications 2019年第1期39卷 607-614页

作者： zhonghan Zhang Fan Luo Yang Zhang Yuxiang Ma Shaodong Hong Yunpeng Yang Wenfeng Fang Yan Huang Li Zhang Hongyun Zhao State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineGuangzhou 510060GuangdongP.R.China Department of Medical Oncology Sun Yat-sen University Cancer Center651 Dongfeng Road EastGuangzhou 510060GuangdongP.R.China Department of Clinical Research Sun Yat-sen University Cancer Center651 Dongfeng Road EastGuangzhou 510060GuangdongP.R.China

Background:Gefitinib,as the first epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKI)approved for the treatment of advanced non-small cell lung cancer(NSCLC),has been proved to significantly improve the progression-free survival(PFS)in the first-line setting but suffers from resistance 7-10 months after treatment initia-tion.Apatinib(YN968D1),a potent vascular endothelial growth factor receptor(VEGFR)2-TKI,specifically binds to VEGFR2 and leads to anti-angiogenetic and anti-neoplastic effect.Concurrent inhibition of VEGFR and EGFR path-ways represents a rational approach to improve treatment responses and delay the onset of treatment resistance in EGFR-mutant NSCLC.This ACTIVE study aims to assess the combination of apatinib and gefitinib as a new treatment approach for EGFR-mutant NSCLC as a first-line setting.Methods:This multicenter,randomized,double-blind,placebo-controlled phase III study(NCT02824458)has been designed to assess the efficacy and safety of apatinib or placebo combined with gefitinib as a first-line treatment for patients with EGFR-mutant advanced NSCLC.A total of 310 patients with EGFR-mutation(19del or 21L858R),pathological stage IIIB to IV non-squamous NSCLC were to be enrolled.The primary endpoint is investigator assessment of PFS,and the secondary endpoints include independent radiological central(IRC)-confirmed PFS,overall survival(OS),objective response rate(ORR),disease control rate(DCR),time to progressive disease(TTPD),duration of response(DoR),quality of life(QoL)and safety.The patients are randomized in a 1:1 ratio to receive gefitinib(250 mg,p.o.q.d.)plus apatinib(500 mg,p.o.q.d.)or gefitinib plus placebo,given until disease progression or intolerable adverse events.Exploratory biomarker analysis will be performed.This study is being conducted across China and comprises of 30 participating centers.Enrollment commenced in August 2017 and finished in December 2018,most of the patients are in the follow-up period.Anticipated outcomes and significance:The present stud

关键词： NSCLC EGFR VEGFR Tyrosine kinase inhibitors Apatinib Gefitinib Randomized Double-blind Placebo Phase III

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