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Simple application of adipose-derived stem cell-derived extracellular vesicles coating enhances cytocompatibility and osteoinductivity of titanium implant

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Regenerative Biomaterials 2021年第1期8卷 64-72页

作者： Lifeng Chen Shan Mou Jinfei Hou Huimin Fang Yuyang Zeng Jiaming Sun Zhenxing Wang Department of Plastic Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Wuhan Clinical Research Center for Superficial Organ Reconstruction Wuhan Union Hos pitalHuazhong University of Science and Technology1277 Jiefang AvenueWuhan 430022China

Surface modification using bioactive molecules is frequently performed to improve the biological properties of medical metal biomaterial titanium(Ti)implants.Developmental evidence suggests that mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)served as potent bioactive component.As a subset of MSC EV,adipose-derived stem cel-derived extracellular vesicles(ADSC-EVs)could be obtained from abundant adipose tissue.Meanwhile,it possesses multiple re-generative properties and might be used to endow biological activities to medical Ti implant.Here,we present a simple ADSC-EV coating strategy based on physisorption of fibronectin.This ADSC-EV functionalized Ti implants(EV-Ti)revealed enhanced osteoblast compatibility and osteoinduc-tive activity.Cell spreading area of EV-Ti group was 1.62-and 1.48-fold larger than that of Ti group after 6 and 12 h of cell seeding,respectively.Moreover,EV-Ti promoted alkaline phosphatase,col-lagen 1 and osteocalcin gene expression in osteoblast by 1.51-,1.68-and 1.82-fold compared with pristine Ti,respectively.Thus,the MSC-EVs modification method reported here provide a clinically translatable strategy to promote the bioactivity of Ti implants.

关键词： adipose-derived stem cll-derived extraellular vesicles titanium surface modification fibronectin osteoinductivity

Average iron isotopic compositions of the upper continental crust：constrained by loess from the Chinese Loess Plateau

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Acta Geochimica 2017年第2期36卷 125-131页

作者： Yingzeng Gong Ying Xia fang Huang huimin Yu CAS Key Laboratory of Crust-Mantle Material and Environments School of Earth and Space Sciences University of Science and Technology of China Hefei 230026 Anhui China

Iron isotopic composition of the upper continental crust(UCC) is critical for understanding Fe mobilization and migration through the Earth. Because rocks exposed at Earth's surface have heterogeneous δ^(56)Fe, finegrained clastic sediments can be used to estimate the average composition of UCC. In this study, we report δ^(56)Fe of loess-paleosol sequences from Yimaguan, Chinese Loess Plateau(CLP), to constrain the average Fe isotopic composition of UCC. The loess-paleosol sequences in this area formed in glacial-interglacial cycles and are characterized by varying degrees of weathering. Our data show that the loess-paleosol layers have extremely homogeneous Fe isotopic compositions with δ^(56)Fe ranging from 0.06‰ to 0.12‰, regardless of variations in the major element composition and weathering intensity. Our study indicates that since Fe isotopes are not significantly fractionated during loess deposition, the loess can be regarded as representative of UCC. It follows that the average δ^(56)Fe of UCC is 0.09‰± 0.03‰(2SD), consistent with previous estimates based on igneous rock data.

关键词：黄土高原地区同位素组成平均黄土-古土壤序列上地壳冰期-间冰期旋回铁风化强度

Discover the Post-Translational Modification Proteome Using Mass Spectrometry

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Chinese Journal of Chemistry 2021年第3期39卷 550-558页

作者： Ying Zhang Caiyun fang huimin Bao Wenjuan Yuan Haojie Lu Shanghai Cancer Center and Institutes of Biomedical Sciences Fudon UniversityShanghai 200032China Department of Chemistry and NHC Key Laboratory of Glycoconjugates Research Fudan UniversityShanghai 200032China

Protein post-translational modifications(PTMs)are chemical modifications on proteins.PTMs play a key role in many cellular processes by influencing the structure of proteins and dynamically regulating their functions.Therefore,characterizing PTMs at proteome level is critical to provide invaluable insight into the functions of proteins underlying different biological processes.Advances in modern proteomics technologies including sample preparation,chromatography separation as well as mass spectrometry have propelled the PTMs proteome to further depths.During the past decade,to better examine the PTMs with high sensitivity and selectivity,our group have developed a series of MS-based novel analytical approaches to study the protein PTMs.Herein,we mainly introduce these approaches developed by our group and discuss how to overcome the technical obstacles of studying various protein PTMs with mass spectrometry.

关键词： Proteome Mass spectrometry Post translational modification Qualitative analysis Quantitative analysis

Super-resolution imaging for in situ monitoring sub-cellular micro-dynamics of small molecule drug

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1864-1877页

作者： huimin Chen Guiqian fang Youxiao Ren Weiwei Zou Kang Ying Zhiwei Yang Qixin Chen School of Pharmaceutical Sciences&Institute of Materia Medica Medical Science and Technology Innovation CenterShandong First Medical University&Shandong Academy of Medical SciencesJinan 250062China MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter School of PhysicsXi'an Jiaotong UniversityXi'an 710049China Reproductive Medicine Center Department of Obstetrics and Gynecologythe First Affiliated Hospital of Anhui Medical UniversityHefei 230022China

Small molecule drugs play a pivotal role in the arsenal of anticancer pharmacological agents. Nonetheless, their small size poses a challenge when directly visualizing their localization, distribution, mechanism of action (MOA), and target engagement at the subcellular level in real time. We propose a strategy for developing triple-functioning drug beacons that seamlessly integrate therapeutically relevant bioactivity, precise subcellular localization, and direct visualization capabilities within a single molecular entity. As a proof of concept, we have meticulously designed and constructed a boronic acid fluorescence drug beacon using coumarin–hemicyanine (CHB). Our CHB design includes three pivotal features: a boronic acid moiety that binds both adenosine triphosphate (ATP) and adenosine diphosphate (ADP), thus depleting their levels and disrupting the energy supply within mitochondria;a positively charged component that targets the drug beacon to mitochondria;and a sizeable conjugated luminophore that emits fluorescence, facilitating the application of structured illumination microscopy (SIM). Our study indicates the exceptional responsiveness of our proof-of-concept drug beacon to ADP and ATP, its efficacy in inhibiting tumor growth, and its ability to facilitate the tracking of ADP and ATP distribution around the mitochondrial cristae. Furthermore, our investigation reveals that the micro-dynamics of CHB induce mitochondrial dysfunction by causing damage to the mitochondrial cristae and mitochondrial DNA. Altogether, our findings highlight the potential of SIM in conjunction with visual drug design as a potent tool for monitoring the in situ MOA of small molecule anticancer compounds. This approach represents a crucial advancement in addressing a current challenge within the field of small molecule drug discovery and validation.

关键词： Mitochondrial Drug beacon Sub-cellular Small molecule Energy supply Anti-tumor

Alendronate loaded graphene oxide functionalized collagen sponge for the dual effects of osteogenesis and anti-osteoclastogenesis in osteoporotic rats

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Bioactive Materials 2020年第4期5卷 859-870页

作者： Yuyang Zeng Muran Zhou Lifeng Chen Huimin Fang Shaokai Liu Chuchao Zhou Jiaming Sun Zhenxing Wang Department of Plastic Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China Wuhan Clinical Research Center for Superficial Organ Reconstruction Wuhan430022China

Graphene Oxide(GO)-related hydrogels have been extensively studied in hard tissue repair,because GO can not only enhance the mechanical properties of polymers but also promote osteogenic differentiation of mesenchymal stem cells.However,simple GO-related hydrogels are not ideal for the repair of osteoporotic bone defects as the overactive osteoclasts in osteoporosis.Alendronate(Aln)is known to inhibit osteoclasts and may bind to GO through covalent connection.Therefore,delivering Aln in GO-related hydrogels may be effective to repair osteoporotic bone defects.Here,we developed a control-released system which is constructed by collagen(Col)-GO sponges loaded with Aln(Col-GO-Aln)for osteoporotic bone defect repair.In vitro,Col-GO-Aln sponges prolonged the release period of Aln,and the sponge containing 0.05%(w/v)GO released Aln faster than sponge with 0.2%GO.Furthermore,tartrate-resistant acid phosphatase(TRAP)and F-actin staining demonstrated that Col-GO-Aln sponges effectively inhibited osteoclastogenesis of monocyte-macrophages.In vivo,micro-CT scan showed that the volume of newborn bone in defect site by 0.05%GO sponge was nearly three times larger than that of other groups.Moreover,the CT and histological examinations of rat femur proved that Col-GO-Aln sponges decreased the number of osteoclasts and suppressed the systemic bone loss in osteoporotic rats.These findings reveal that the application of GO as carriers of anti-osteoporosis drugs is a viable treatment for osteoporosis.The results also underscore the potential of GO-related hydrogels with Aln-releasing capacity for bone regeneration in osteoporosis.

关键词： Osteoporosis Osteoporotic bone defect Graphene oxide Osteoclast Alendronate

Super-resolution imaging reveals the subcellular distribution of dextran at the nanoscale in living cells

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Chinese Chemical Letters 2022年第4期33卷 1865-1869页

作者： huimin Chen Han Wang Yongchun Wei Maomao Hu Bo Dong Hongbao fang Qixin Chen Institute of Materia Medica Shandong First Medical University&Shandong Academy of Medical SciencesJi’nan 250062China Department of Cardiology Shandong Provincial Hospital Affiliated to Shandong UniversityJi’nan 250012China State Key Laboratory of Coordination Chemistry Chemistry and Biomedicine Innovation Center(ChemBIC)School of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210023China

Theranostic visualization of dextran at the nanoscale is beneficial for understanding the bioregulatory mechanisms of this molecule. In this study, we applied structured illumination microscopy(SIM) to capture the distribution of Cy5-Dextran at different incubation periods in living cells. The results showed that Cy5-Dextran could be absorbed by He La cells. In addition, we clarified that Cy5-Dextran exhibited differential organelle distribution(lysosomal or mitochondrial) in a time-dependent manner. Moreover,lysosomal Cy5-Dextran localization was found to be independent of the autophagy process, while Cy5-Dextran localized to the mitochondria triggered a pro-apoptotic event, upregulating the levels of reactive oxygen species(ROS) to accelerate mitochondrial fragmentation. This work uses a visualized strategy to reveal the anti-tumor bioactivity of dextran, which was achieved by regulating apoptosis and autophagy.

关键词： Dextran Subcellular distribution Super-resolution imaging Structured illumination microscopy

Microstructure,elastic/mechanical and thermal properties of CrTaO_(4):A new thermal barrier material?

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Journal of Advanced Ceramics 2024年第3期13卷 373-387页

作者： Shuang Zhang Xiaohui Wang Chao Zhang huimin Xiang Yingwei Li Cheng fang Mingliang Li Hailong Wang Yanchun Zhou School of Materials Science and Engineering Zhengzhou UniversityZhengzhou 450001China Shenyang National Laboratory for Materials Science Institute of Metal ResearchChinese Academy of SciencesShenyang 110016China School of Civil Engineering Wuhan UniversityWuhan 430072China

CrTaO_(4)(or Cr_(0.5)Ta_(0.5)O_(2))has been unexpectedly found to play a decisive role in improving the oxidation resistance of Cr and Ta-containing refractory high-entropy alloys(RHEAs).This rarely encountered complex oxide can effectively prevent the outward diffusion of metal cations from the RHEAs.Moreover,the oxidation kinetics of CrTaO_(4)-forming RHEAs is comparable to that of the well-known oxidation resistant Cr_(2)O_(3)-and Al_(2)O_(3)-forming Ni-based superalloys.However,CrTaO_(4)has been ignored and its mechanical and thermal properties have yet to be studied.To fill this research gap and explore the untapped potential for its applications,here we report for the first time the microstructure,mechanical and thermal properties of CrTaO_(4)prepared by hot-press sintering of solid-state reaction synthesized powders.Using the HAADF and ABF-STEM techniques,rutile crystal structure was confirmed and short range ordering was directly observed.In addition,segregation of Ta and Cr was identified.Intriguingly,CrTaO_(4)exhibits elastic/mechanical properties similar to those of yttria stabilized zirconia(YSZ)with Young’s modulus,shear modulus,and bulk modulus of 268,107,and 181 GPa,respectively,and Vickers hardness,flexural strength,and fracture toughness of 12.2±0.44 GPa,142±14 MPa,and 1.87±0.074 MPa·m^(1/2).The analogous elastic/mechanical properties of CrTaO_(4)to those of YSZ has spurred inquiries to lucrative leverage it as a new thermal barrier material.The measured melting point of CrTaO_(4)is 2103±20 K.The anisotropic thermal expansion coefficients areα_(a)=(5.68±0.10)×10^(-6)K^(-1),α_(c)=(7.81±0.11)×10^(-6)K^(-1),with an average thermal expansion coefficient of(6.39±0.11)×10^(-6)K^(-1).The room temperature thermal conductivity of CrTaO_(4)is 1.31 W·m^(-1)·K^(-1)and declines to 0.66 W·m^(-1)·K^(-1)at 1473 K,which are lower than most of the currently well-known thermal barrier materials.From the perspective of matched thermal expansion coefficient,CrTaO_(4)pertains to an eligible thermal barrier material fo

关键词： microstructure synthesis thermal conductivity thermal expansion coefficient melting point CrTaO_(4) mechanical and thermal properties

Investigation of the characteristics and deactivation of catalytic active center of Cr-Al_2O_3 catalysts for isobutane dehydrogenation

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Journal of Energy Chemistry 2015年第1期24卷 101-107页

作者： Deren fang Jinbo Zhao Wanjun Li Xu fang Xin Yang Wanzhong Ren huimin Zhang Provincial Key Lab of Chemical Manufacture Engineering Yantai University

Deactivation mechanism of Cr-Al2O3catalyst and the interaction of Cr-A1 in the dehydrogenation of isobutane, as well as the nature of the catalytic active center, were studied using XRD, SEM, XPS, H2-TPR, isobutane-TPR and TPO techniques. The results revealed that the deactivation of Cr-Al2O3 catalyst was mainly caused by carbon deposition on its surface. The Cr3＋ ion could not be reduced by hydrogen but could be reduced to Cr2＋ by hydrocarbons and monoxide carbon. The active center for isobutane dehydrogenation could be Cr2＋/Cr3＋ produced from Cr6＋ by the on line reduction of hydrocarbon and carbon monoxide. The binding energy of Al3＋ was strongly affected by the state of chromium cations in the catalysts.

关键词： isobutane dehydrogenation Cr/Al2O3 deactivation active center catalyst

Internal incentives and operations strategies for the watersaving supply chain with cap-and-trade regulation

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Frontiers of Engineering Management 2019年第1期6卷 87-101页

作者： Zhisong CHEN Li fang huimin WANG Business School Nanjing Normal University Nanjing 210023 China Stem School of Business New York University New York NY 10012 USA State Key Laboratory of Hydrology-Water Resources and Hydraulic Engineering Hohai University Nanjing 210098 China Business School Hohai University Nanjing 211100 China College of Management and Economics Tianjin University Tianjin 300072 China

Faced with the rapid development of modem industries of agriculture, manufacturing, and services, water resources are becoming increasingly scarce. Industries with high water consumption are generally regulated by the government's water cap-and-trade (CAT) regulation to solve the contradiction between the limited water supply and the rapid growing water demand. Supply chain equilibrium and coordination models under the benchmark scenario without water saving and CAT regulation, watersaving supply chain equilibrium and coordination models under the scenario without/with CAT regulation are developed, analyzed and compared. The corresponding numerical and sensitivity analyses for all models are conducted and compared, and the managerial insights and policy recommendations are summarized in this article. The results indicate that (1) Conducting water saving could improve effectively the operational performance of the water-saving supply chain under the scenario without/with CAT regulation.(2) The coordination strategy based on the revenue sharing contract could efficiently coordinate the water-saving supply chain, enhance water consumption reduction rate, and improve the operational performance of the water-saving supply chain.(3) The implementation of CAT regulation enhances effectively water-consumptio reduction in the water-saving supply chain and improves the operational performance of water-saving supply chain.(4) Simultaneous implementation of CAT regulation by the government and adopting coordination strategy by the water-saving supply chain would be superior to any other scenarios/strategies.(5) A suitable water cap based on the industrial average water consumption and historical water consumption data are beneficial for constructing reasonable and effective incentive mechanism.(6) A higher marginal trade price could induce more reduction in water consumption and create better operational performance for the manufacturer and water-saving supply chain, both under the equilibrium and coordination strategies.

关键词： water-saving supply chain equilibrium coordination internal incentive cap and trade regulation