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Syrosingopine,an anti-hypertensive drug and lactate transporter(MCT1/4)inhibitor,activates hepatic stellate cells and exacerbates liver fibrosis in a mouse model

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Genes & Diseases 2024年第4期11卷 28-30页

作者： Meichun Guo Yannian Gou Xiangyu Dong Jiamin Zhong Aohua Li Ailing Hao Tongchuan He Jiaming Fan Ministry of Education Key laboratory of Diagnostic medicine and the School of Laboratory Diagnostic MedicineChongqing Medical UniversityChongqing 400016China molecular Oncology laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA

Syrosingopine is an anti-hypertensive drug and can cause high intracellular lactate levels and end-product inhibition of lactate dehydrogenase by inhibiting the lactate transporters MCT1 and MCT4.Previous studies have shown that syrosingopine plays an essential role in the process of glycolytic blockade,ATP depletion,and cell death in cancer due to high intracellular levels of lactate.

关键词： hypertensive MCT1 drug

Solution-processed all-inorganic lead halide perovskite/layered double hydroxides superlattices

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Science China Chemistry 2024年

作者： Deyu Li Mingming Zhang Lulu Wei Shubing Tian Mingze Sun Kang Liu Jixiang Xu Lei Wang Jun Xing Key laboratory of Eco-chemical Engineering Ministry of Education College of Chemistry and Molecular Engineering Qingdao University of Science & Technology College of sino-german Science and Technology Qingdao University of Science & Technology

Quantum wells and superlattices are key building blocks in the semiconductor industry, normally fabricated using epitaxial growth techniques, such as vapor phase epitaxy, metalorganic chemical vapor deposition and molecular beam epitaxy. However,these complicated preparation processes, as well as their high cost, limit their extensive applications. It is essential to develop a simple solution process for building superstructures. Here, we demonstrate an ion exchange strategy for synthesizing an allinorganic superlattice cesium lead bromide/layered double hydroxides(CsPbBr3/LDH) in solution. At room temperature, the perovskite ions diffuse into the interlayer of LDH and assemble into layered perovskite with various thicknesses. Compared with traditional organic-inorganic hybrid perovskite superlattice, the all-inorganic perovskite superlattice CsPbBr3/LDH has weak quantum confinement, which exhibits narrow emission line-widths of 20 nm, high quantum yields of 55%, and radiative lifetimes of several ns. Our findings offer a new route to synthesize novel perovskite superlattices and enrich the perovskite supercrystal platform for electronics, photonics and optoelectronics devices.

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Catalysis by subsurface metal atoms in Al(001) through electron transfer

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National Science Review 2024年第4期11卷 12-13页

作者： Bo Sun Ding Ma Beijing National laboratory for molecular Science New Cornerstone Science Laboratory College of Chemistry and Molecular Engineering Peking University

Heterogeneous catalysis plays a crucial role in the chemical industry, which has evolved from the investigation of chemisorption to an electronic structure[1]. Diverse strategies, such as alloying,doping, and confining, have been applied to enhance the catalytic properties of active sites through electronic modulation. The electron transfer between active sites and substrates profoundly influences catalytic activity [2].

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Meningeal lymphatic vasculature,a general target for glioblastoma therapy?

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Fundamental Research 2024年第2期4卷 267-269页

作者： Changping Zhou Han Xu Jincai Luo laboratory of Vascular Biology Institute of Molecular MedicineCollege of Future TechnologyBeijing Key Laboratory of Cardiometabolic Molecular MedicinePeking UniversityBeijing 100871China

Glioblastoma(GBM)causes nearly universal mortality as a result of the failure of conventional therapies including surgical resection,targeted radiation therapy,and chemotherapy.An increasingly important treatment option is combining immunotherapy with other therapies in both preclinical and clinical studies.The central nervous system(CNS)has been historically considered an immune privileged area,but increasing evidence,including the recent rediscovery of meningeal lymphatic vessels(MLVs),has overturned this notion.MLVs are populated by multiple immune cells and connect the CNS to the periphery by draining cerebrospinal fluid with soluble CNS antigens and immune cells into cervical lymph nodes.In the past few years,more and more studies have indicated that MLVs are involved in the regulation of inflammation and the immune response in the pathogenesis of various CNS diseases including GBM.Here,we explore the critical interlinkages between MLVs and GBM therapies including chemotherapy,radiotherapy and immunotherapy,and propose the meningeal lymphatic vasculature as a general target for GBM therapy.

关键词： Meningeal lymphatic vessels Glioblastoma Immunity Vascular endothelial growth factor C Immune modulation

Enhancement of endogenous midbrain neurogenesis by microneurotrophin BNN-20 after neural progenitor grafting in a mouse model of nigral degeneration

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Neural Regeneration Research 2024年第6期19卷 1318-1324页

作者： Theodora Mourtzi Nasia Antoniou Christina Dimitriou Panagiotis Gkaravelas Georgia Athanasopoulou Panagiota Nti Kostantzo Olga Stathi Efthymia Theodorou Maria Anesti Rebecca Matsas Fevronia Angelatou Georgia Kouroupi Ilias Kazanis laboratory of Developmental Biology Department of Biology University of Patras laboratory of Cellular and molecular Neurobiology-Stem Cells Hellenic Pasteur Institute 3. Department of Physiology School of Medicine University of Patras

We have previously shown the neuroprotective and pro-neurogenic activity of microneurotrophin BNN-20 in the substantia nigra of the “weaver” mouse, a model of progressive nigrostriatal degeneration. Here, we extended our investigation in two clinically-relevant ways. First, we assessed the effects of BNN-20 on human induced pluripotent stem cell-derived neural progenitor cells and neurons derived from healthy and parkinsonian donors. Second, we assessed if BNN-20 can boost the outcome of mouse neural progenitor cell intranigral transplantations in weaver mice, at late stages of degeneration. We found that BNN-20 has limited direct effects on cultured human induced pluripotent stem cell-derived neural progenitor cells, marginally enhancing their differentiation towards neurons and partially reversing the pathological phenotype of dopaminergic neurons generated from parkinsonian donors. In agreement, we found no effects of BNN-20 on the mouse neural progenitor cells grafted in the substantia nigra of weaver mice. However, the graft strongly induced an endogenous neurogenic response throughout the midbrain, which was significantly enhanced by the administration of microneurotrophin BNN-20. Our results provide straightforward evidence of the existence of an endogenous midbrain neurogenic system that can be specifically strengthened by BNN-20. Interestingly, the lack of major similar activity on cultured human induced pluripotent stem cell-derived neural progenitors and their progeny reveals the in vivo specificity of the aforementioned pro-neurogenic effect.

关键词： adult neurogenesis BNN-20 brain-derived neurotrophic factor cell replacement induced pluripotent stem cells (iPSCs) neurotrophic factors Parkinson’s disease substantia

Micelle-directed self-assembly of single-crystal-like mesoporous stoichiometric oxides for high-performance lithium storage

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National Science Review 2024年第4期11卷 195-205页

作者： Yanhua Wan Changyao Wang Xingmiao Zhang Yang Yin Mengmeng Liu Bing Ma Linlin Duan Yuzhu Ma Wei Zhang Changlin Zheng Dongliang Chao Fei Wang Yongyao Xia Wei Li Department of Chemistry Laboratory of Advanced Materials Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials State Key Laboratory of Molecular Engineering of Polymers College of Chemistry and Materials ScienceFudan University State Key laboratory of Surface Physics and Department of Physics Fudan University

Due to their uncontrollable assembly and crystallization process,the synthesis of mesoporous metal oxide single crystals remains a formidable challenge.Herein,we report the synthesis of single-crystal-like mesoporous Li2TiSiO5by using soft micelles as templates.The key lies in the atomic-scale self-assembly and step-crystallization processes,which ensure the formation of single-crystal-like mesoporous Li2TiSiO5microparticles via an oriented attachment growth mechanism under the confinement of an in-situ formed carbon matrix.The mesoporous Li2TiSiO5anode achieves a superior rate capability(148 mAh g-1at5.0 A g-1) and outstanding long-term cycling stability(138 mAh g-1after 3000 cycles at 2.0 A g-1) for lithium storage as a result of the ultrafast Li+diffusion caused by penetrating mesochannels and nanosized crystal frameworks（5-10 nm）.In comparison,bulk Li2TiSiO5exhibits poor rate capability and cycle performance due to micron-scale diffusion lengths.This method is very simple and reproducible,heralding a new way of designing and synthesizing mesoporous single crystals with controllable frameworks and chemical functionalities.

关键词： mesoporous materials micelles single-crystal-like Li2TiSiO5 lithium-ion batteries

Reduced expression of semaphorin 3A in osteoclasts causes lymphatic expansion in a Gorham-Stout disease(GSD)mouse model

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第1期25卷 38-50页

作者： Dongfang ZHANG Hao XU Chi QIN Kangming CAI Jing ZHANG Xinqiu XIA Jingwen BI Li ZHANG Lianping XING Qianqian LIANG Wensheng WANG laboratory of molecular medicine College of Life Science and State Key Laboratory of Cell Differentiation and RegulationHenan Normal UniversityXinxiang453007China Longhua Hospital&Spine Institute Shanghai University of Traditional Chinese MedicineShanghai200032China Key laboratory of Theory and Therapy of Muscles and Bones Ministry of Education(Shanghai University of Traditional Chinese Medicine)Shanghai201203China Department of Pathology and laboratory medicine University of Rochester Medical CenterRochester14642USA

Gorham-Stout disease(GSD)is a sporadic chronic disease characterized by progressive bone dissolution,absorption,and disappearance along with lymphatic vessel infiltration in bone-marrow cavities.Although the osteolytic mechanism of GSD has been widely studied,the cause of lymphatic hyperplasia in GSD is rarely investigated.In this study,by comparing the RNA expression profile of osteoclasts(OCs)with that of OC precursors(OCPs)by RNA sequencing,we identified a new factor,semaphorin 3A(Sema3A),which is an osteoprotective factor involved in the lymphatic expansion of GSD.Compared to OCPs,OCs enhanced the growth,migration,and tube formation of lymphatic endothelial cells(LECs),in which the expression of Sema3A is low compared to that in OCPs.In the presence of recombinant Sema3A,the growth,migration,and tube formation of LECs were inhibited,further confirming the inhibitory effect of Sema3A on LECs in vitro.Using an LEC-induced GSD mouse model,the effect of Sema3A was examined by injecting lentivirus-expressing Sema3A into the tibiae in vivo.We found that the overexpression of Sema3A in tibiae suppressed the expansion of LECs and alleviated bone loss,whereas the injection of lentivirus expressing Sema3A short hairpin RNA(shRNA)into the tibiae caused GSD-like phenotypes.Histological staining further demonstrated that OCs decreased and osteocalcin increased after Sema3A lentiviral treatment,compared with the control.Based on the above results,we propose that reduced Sema3A in OCs is one of the mechanisms contributing to the pathogeneses of GSD and that expressing Sema3A represents a new approach for the treatment of GSD.

关键词： Semaphorin 3A Gorham-Stout disease Osteoclast Osteolysis Lymphatic endothelial cell

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Anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab for first-line treatment in advanced natural killer T cell lymphoma

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1665-1674页

作者： Jie Xiong Shu Cheng Xiao Gao Shan-He Yu Yu-Ting Dai Xin-Yun Huang Hui-Juan Zhong Chao-Fu Wang Hong-Mei Yi Hao Zhang Wei-Guo Cao Rong Li Wei Tang Yan Zhao Peng-Peng Xu Li Wang Wei-Li Zhao Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Nuclear medicine Shanghai Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Pathology Shanghai Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Otolaryngology Shanghai Rujin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Radiation Shanghai Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Hematology Navy Medical Center of PLAShanghaiChina Pole de Recherches sino-Francais en Science du Vivant et Genomique Laboratory of Molecular PathologyShanghaiChina

Natural killer T cell lymphoma(NKTCL)is highly aggressive,with advanced stage patients poorly responding to intensive chemotherapy.To explore effective and safe treatment for newly diagnosed advanced stage NKTCL,we conducted a phase ll study of anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab(NCT04096690).Twenty-two patients with a median age of 51 years(range,24-74)were enrolled and treated with induction treatment of pegaspargase 2500 IU/m2 intramuscularly on day 1 and sintilimab 200 mg intravenously on day 2 for 6 cycles of 21 days,followed by maintenance treatment of sintilimab 200 mg for 28 cycles of 21 days.The complete response and overall response rate after induction treatment were 59%(95%Cl,43-79%)and 68%(95%Cl,47-84%),respectively.With a median follow-up of 30 months,the 2 year progression-free and overall survival rates were 68%(95%Cl,45-83%)and 86%(95%Cl,63-95%),respectively.The most frequently grade 3/4 adverse events were neutropenia(32%,n=7)and hypofibrinogenemia(18%,n=4),which were manageable and led to no discontinuation of treatment.Tumor proportion score of PD-L1,peripheral blood high-density lipoprotein cholesterol,and apolipoprotein A-l correlated with good response,while PD-1 on tumor infiltrating lymphocytes and peripheral Treg cells with poor response to pegaspargase plus sintilimab treatment.In conclusion,the chemo-free regimen pegaspargase plus sintilimab was effective and safe in newly diagnosed,advanced stage NKTCL.Dysregulated lipid profle and immunosuppressive signature contributed to treatment resistance,providing an alternative therapeutic approach dual targeting fatty acid metabolism and CTLA-4 in NKTCL.

关键词： killer metabolism lymphoma

The First-in-Human Whole-Body Dynamic Pharmacokinetics Study of Aptamer

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Research 2024年第1期2023卷 119-130页

作者： Ding Ding Haitao Zhao Dali Wei Qinglai Yang Cai Yang Ruowen Wang Yumei Chen Lianghua Li Shuxian An Qian Xia Gang Huang Jianjun Liu Zeyu Xiao Weihong Tan Institute of molecular medicine(IMM) Renji HospitalState Key Laboratory of Oncogenes and Related GenesShanghai Jiao Tong University School of Medicineand College of Chemistry and Chemical EngineeringShanghai Jiao Tong UniversityShanghai 200240China Department of Nuclear medicine Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China Center for molecular Imaging Probes Cancer Research InstituteUniversity of South ChinaHengyangHunan 421001China The Key laboratory of Zhejiang Province for Aptamers and Theranostics Zhejiang Cancer HospitalHangzhou Institute of Medicine(HIM)Chinese Academy of SciencesHangzhouZhejiang 310022China molecular Science and Biomedicine laboratory(MBL) State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringHunan UniversityChangshaHunan 410082China Shanghai Key laboratory of molecular Imaging Shanghai University of Medicine and Health SciencesShanghai 201318China Department of Pharmacology and Chemical Biology Shanghai Jiao Tong University School of MedicineShanghai200127China

Serving as targeting ligands,aptamers have shown promise in precision medicine.However,the lack of knowledge of the biosafety and metabolism patterns in the human body largely impeded aptamers’clinical translation.To bridge this gap,here we report the first-in-human pharmacokinetics study of protein tyrosine kinase 7 targeted SGC8 aptamer via in vivo PET tracking of gallium-68(^(68)Ga)radiolabeled aptamers.The specificity and binding affinity of a radiolabeled aptamer,named ^(68)Ga[Ga]-NOTA-SGC8,were maintained as proven in vitro.Further preclinical biosafety and biodistribution evaluation confirmed that aptamers have no biotoxicity,potential mutation risks,or genotoxicity at high dosage(40 mg/kg).Based on this result,a first-in-human clinical trial was approved and carried out to evaluate the circulation and metabolism profiles,as well as biosafety,of the radiolabeled SGC8 aptamer in the human body.Taking advantage of the cutting-edge total-body PET,the aptamers’distribution pattern in the human body was acquired in a dynamic fashion.

关键词： metabolism dosage Whole