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Formulation of lyotropic liquid crystal emulsion based on natural sucrose ester and its tribological behavior as novel lubricant

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Friction 2022年第11期10卷 1879-1892页

作者： Yumei GUO Jiusheng LI Xiaojie ZHOU Yuzhao TANG Xiangqiong ZENG Laboratory for Advanced Lubricating Materials Shanghai Advanced Research InstituteChinese Academy of SciencesShanghai 201210China University of Chinese Academy of sciences Beijing 100049China National Facility for Protein science in Shanghai Shanghai Advanced Research InstituteChinese Academy of SciencesShanghai 201210China

The tribological behavior of oil-in-water emulsions formulated with natural lyotropic liquid crystal(LLC)emulsifiers based on natural sucrose ester was studied for the first time.Polarized optical microscopy,synchrotron radiation small-angle X-ray scattering,wide-angle X-ray scattering,and synchrotron radiation infrared microspectroscopy demonstrated that LLC emulsifiers were tightly ordered at the oil–water interface with a distinct nematic texture.The viscosity of emulsion was observed to change over time.Moreover,the zeta potential and laser particle size distribution verified the emulsion’s satisfactory stability.The frictional shearing test proved that the coefficient of friction of the emulsion versus pure oil decreased by 34.2%.The coefficient of friction of the emulsion with liquid crystal decreased 10.1%versus that without liquid crystal.Although liquid crystal emulsion did not exhibit outstanding anti-wear performance compared with pure oil,its wear volume was 29.4%less than the emulsion without liquid crystal.X-ray photoelectron spectroscopy and scanning electron microscope–energy dispersive X-ray spectroscopy(SEM–EDS)proved that the tribo-film of the emulsion with liquid crystal was formed synergistically by the liquid crystal phase with the base oil.The formulation affecting the lubricant quality was further studied by orthogonal experiments.The resulting Stribeck curve behavior suggested that proper composition with a slightly higher viscosity can better reduce friction in both boundary lubrication and mixed lubrication regimes.The lubrication mechanism indicated that the periodically ordered liquid crystal was transported to the sliding asperity in the form of emulsion droplets,which bored the pressure and released the oil to form a tribo-film.This LLC emulsion is environmentally friendly and potentially non-irritant to the skin.Thus,it has promising application prospects as novel water-based and biological lubricants.

关键词： lyotropic liquid crystal(LLC) emulsion aqueous lubrication tribological behavior

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PRPS2 mutations drive acute lymphoblastic leukemia relapse through influencing PRPS1/2 hexamer stability

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Blood science 2023年第1期5卷 39-50页

作者： Lili Song Peifeng Li Huiying Sun Lixia Ding Jing Wang Benshang Li Bin-Bing S.Zhou Haizhong Feng Yanxin Li Pediatric Translational Medicine Institute Key Laboratory of Pediatric Hematology and Oncology Ministry of HealthState Key Laboratory of Oncogenes and Related GenesDepartment of Hematology&OncologyShanghai Children’s Medical CenterShanghai Jiao Tong University School of MedicineShanghaiChina State Key Laboratory of Bioorganic and Natural Products Chemistry Center for Excellence in Molecular SynthesisShanghai Institute of Organic ChemistryChinese Academy of SciencesShanghaiChina State Key Laboratory of Oncogenes and Related Genes Renji-Med X Clinical Stem Cell Research CenterRen Ji HospitalShanghai Cancer InstituteShanghai Jiao Tong University School of MedicineShanghaiChina

Tumor relapse is the major cause of treatment failure in childhood acute lymphoblastic leukemia(ALL),yet the underlying mechanisms are still elusive.Here,we demonstrate that phosphoribosyl pyrophosphate synthetase 2(PRPS2)mutations drive ALL relapse through influencing PRPS1/2 hexamer stability.Ultra-deep sequencing was performed to identify PRPS2 mutations in ALL samples.The effects of PRPS2 mutations on cell survival,cell apoptosis,and drug resistance were evaluated.In vitro PRPS2 enzyme activity and ADP/GDP feedback inhibition of PRPS enzyme activity were assessed.Purine metabolites were analyzed by ultra-performance liquid-chromatography tandem mass spectrometry(UPLC–MS/MS).Integrating sequencing data with clinical information,we identified PRPS2 mutations only in relapsed childhood ALL with thiopurine therapy.Functional PRPS2 mutations mediated purine metabolism specifically on thiopurine treatment by influencing PRPS1/2 hexamer stability,leading to reduced nucleotide feedback inhibition of PRPS activity and enhanced thiopurine resistance.The 3-amino acid V103-G104-E105,the key difference between PRPS1 and PRPS2,insertion in PRPS2 caused severe steric clash to the interface of PRPS hexamer,leading to its low enzyme activity.In addition,we demonstrated that PRPS2 P173R increased thiopurine resistance in xenograft models.Our work describes a novel mechanism by which PRPS2 mutants drive childhood ALL relapse and highlights PRPS2 mutations as biomarkers for relapsed childhood ALL.

关键词： Drug resistance Childhood acute lymphoblastic leukemia PRPS2 Purine metabolism Tumor relapse

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Carbon ion radiotherapy boost in the treatment of glioblastoma:a randomized phase Ⅰ/Ⅲ clinical trial

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Cancer Communications 2019年第1期39卷 39-50页

作者： Lin Kong Jing Gao Jiyi Hu Rong Lu Jing Yang Xianxin Qiu weixu Hu Jiade J.Lu Department of Radiation Oncology Shanghai Proton and Heavy Ion CenterFudan University Shanghai Cancer CenterShanghai 201321P.R.China Department of Radiation Oncology Shanghai Proton and Heavy Ion CenterPudong4365 Kangxin RoadShanghai 201321P.R.China

Background: Glioblastoma (GBM) is a highly virulent tumor of the central nervous system, with a median survival < 15 months. Clearly, an improvement in treatment outcomes is needed. However, the emergence of these mal... 详细信息

Background: Glioblastoma (GBM) is a highly virulent tumor of the central nervous system, with a median survival wever, the emergence of these malignancies within the delicate brain parenchyma and their infiltrative growth pattern severely limit the use of aggressive local therapies. The particle therapy represents a new promising therapeutic approach to circumvent these prohibitive conditions with improved treatment efficacy. Methods and design: Patients with newly diagnosed malignant gliomas will have their tumor tissue samples submitted for the analysis of the status of O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation. In Phase I, the patients will undergo an induction carbon ion radiotherapy (CIRT) boost followed by 60 GyE of proton irradiation with concurrent temozolomide (TMZ) at 75 mg/m2. To determine the maximal dose of safe induction boost, the tolerance, and acute toxicity rates in a dose-escalation manner from 9 to 18 GyE in three fractions will be used. In Phase III, GBM-only patients will be randomized to receive either 60 GyE (2 GyE per fraction) of proton irradia-tion with concurrent TMZ (control arm) or a CIRT boost (dose determined in Phase I of this trial) followed by 60 GyE of proton irradiation with concurrent TMZ. The primary endpoints are overall survival (OS) and toxicity rates (acute and long-term). Secondary endpoints are progression-free survival (PFS), and tumor response (based upon assess-ment with C-methionine/fluoro-ethyl-tyrosine positron emission tomography [MET/FET PET] or magnetic resonance imaging [MRI] and detection of serologic immune markers). we hypothesize that the induction CIRT boost will result in a greater initial tumor-killing ability and prime the tumor microenvironment for enhanced immunologic tumor clearance, resulting in an expected 33% improvement in OS rates. Discussion: The prognosis of GBM remains grim. The mechanism underpinning the poor prognosis of this malig-nancy is i

关键词： Glioblastoma Anaplastic astrocytoma Carbon ion radiotherapy Proton radiotherapy Temozolomide Overall survival Progression-free survival Toxicity Serologic immune response O-6-methylguanine-DNA methyltransferase

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