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Acta Pharmaceutica Sinica B 2022年第6期12卷 2658-2671页

作者： Tingting Yang Yuzhu Hu Junming Miao Jing Chen Jiagang Liu Yongzhong Cheng Xiang Gao Department of Neurosurgery and institute of Neurosurgery State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalWest China Medical SchoolSichuan University and Collaborative Innovation Center for BiotherapyChengdu 610041China Department of Medical Oncology State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalWest China Medical SchoolSichuan University and Collaborative Innovation Center for BiotherapyChengdu 610041China

Glioma is a primary aggressive brain tumor with high recurrence *** poor efficiency of chemotherapeutic drugs crossing the blood-brain barrier(BBB) is well-known as one of the main challenges for anti-glioma ***,massive infiltrated tumor-associated macrophages(TAMs) in glioma further thwart the drug ***,a therapeutic nanosystem(SPP-ARV-825) is constructed by incorporating the BRD4-degrading proteolytic targeting chimera(PROTAC) ARV-825 into the complex micelle(SPP) composed of substance P(SP) peptide-modified poly(ethylene glycol)-poly(D,L-lactic acid)(SP-PEG-PDLL A) and methoxy poly(ethylene glycol)-poly(D,L-lac tic acid)(mPEG-PDLL A,PP),which could penetrate BBB and target brain ***,released drug engenders antitumor effect via attenuating cells proliferation,inducing cells apoptosis and suppressing M2 macrophages polarization through the inhibition of IRF4 promoter transcription and phosphorylation of STAT6,STAT3 and *** together,our work demonstrates the versatile role and therapeutic efficacy of SPP-ARV-825 micelle against glioma,which may provide a novel strategy for glioma therapy in future.

关键词： Glioma BRD4 ARV-825 Micelle M2 macrophage

A β-cyclodextrin covalent organic framework used as a chiral stationary phase for chiral separation in gas chromatography

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Chinese Chemical Letters 2022年第2期33卷 898-902页

作者： Bo Tang Wei Wang Huipeng Hou Yiquan Liu Zongkun Liu Lina Geng Liquan Sun Aiqin Luo Key Laboratory of Molecular Medicine and biotherapy School of Life ScienceBeijing Institute of TechnologyBeijing 100081China

Chiral covalent organic frameworks(CCOFs) featuring chirality, stability, and good porosity have attracted a considerable amount of attention due to their important applications, such as asymmetric catalysis, chiral separation, and chiral recognition. In this study, a β-cyclodextrin(β-CD) covalent organic framework(β-CD-COF) diluted with polysiloxane OV-1701 was explored as a novel chiral stationary phase(CSP) for gas chromatography(GC) separation of racemates. The β-CD-COF coated capillary column had excellent selectivity, not only for the separation of linear alkanes, linear alcohols, fatty acid methyl esters mixture, the Grob mixture and positional isomers, but also for the resolution of chiral compounds, including chiral alcohols, aldehydes, ethers, and amino acid derivatives. In addition, the β-CD-COF-coated capillary column presented good repeatability and reproducibility. This work indicated the great potential of the CCOFs coated capillary column for the chromatographic separation of enantiomers.

关键词： β-Cyclodextrin Covalent organic framework Chiral stationary phase Gas chromatography Enantioseparation

生物信息学资源助力蛋白质磷酸化的系统层次理解

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Science Bulletin 2024年第8期69卷 989-992页

作者：彭迪贾大夏宏光张珞颖黄鹏宇薛宇 Department of Bioinformatics and Systems Biology MOE Key Laboratory of Molecular BiophysicsHubei Bioinformatics and Molecular Imaging Key LaboratoryCollege of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan 430074China Key Laboratory of Birth Defects and Related Diseases of Women and Children Department of PaediatricsWest China Second University HospitalState Key Laboratory of BiotherapySichuan UniversityChengdu 610041China Department of Biochemistry&Research Center of Clinical Pharmacy of The First Affiliated Hospital Zhejiang University School of MedicineHangzhou 310058China institute of Biomedical Engineering Chinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300192China Nanjing University institute of Artificial Intelligence Biomedicine Nanjing 210031China

Protein phosphorylation,catalyzed by protein kinases(PKs),is one of the most prevalent post-translational modifications(PTMs)in *** occurring at different positions in a protein sequence can possess distinct functional impacts,and sitespecific phosphorylation may drastically alter a protein’s conformation,activity,and ***,biologists usually focused on studying regulatory mechanisms of phosphorylation in a limited number of proteins,mainly due to a lack of highthroughput *** the past two decades,advances in liquid chromatography coupled with tandem mass spectrometry(LC-MS/MC)have boomed a revolutionary technology named phosphoproteomics,which can simultaneously quantify thousands of phosphorylation sites(p-sites),and provide a great opportunity for a systems-level understanding of *** LCMS/MC,other approaches such as immunohistochemistry(IHC)and immune-detection by sequencing(ID-seq)have also emerged.

关键词： positions catalyzed translational

Co-delivery of doxorubicin and curcumin via cRGD-peptide modified PEG-PLA self-assembly nanomicelles for lung cancer therapy

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Chinese Chemical Letters 2022年第5期33卷 2507-2511页

作者： Yunchu Zhang Tingting Li Yuzhu Hu Jing Chen Yihong He Xiang Gao Yan Zhang Department of Thoracic Oncology Cancer CenterState Key Laboratory of BiotherapyWest China HospitalWest China Medical SchoolSichuan University and Collaborative Innovation Center for BiotherapyChengdu 610041China Department of Neurosurgery and institute of Neurosurgery State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalWest China Medical SchoolSichuan University and Collaborative Innovation Center for BiotherapyChengdu 610041China

Lung cancer is the most common malignancy in the world, with a high mortality rate. Nevertheless,therapies to act effectively against lung cancer remain elusive. So far, chemotherapy is still the frontline treatment of lung cancer. Doxorubicin(DOX) is a broad-spectrum anti-tumor drug. However, DOX often has serious side effects and causes multi-drug resistance, which greatly limits its clinical *** this work, biodegradable methoxy poly(ethylene glycol)-poly(lactic acid)(MPEG-PLA) and cyclo(ArgGly-Asp-D-Phe-Lys)(c RGD) polypeptide modified PEG-PLA(c RGD-PEG-PLA) copolymers were used for the co-delivery of curcumin(CUR) and DOX(CUR-DOX/c RGD-M). The particle size of the self-assembled drugloaded nanomicelle approximately was 27.4 nm and the zeta potential was -2.7mV. Interestingly, CUR can enhance the uptake of DOX by Lewis lung carcinoma(LL/2) cells. The experimental results in vivo and in vitro showed that CUR-DOX/c RGD-M combination therapy could promote apoptosis of lung cancer cells, and conspicuously inhibit the tumor growth. Our data indicate that CUR-DOX/c RGD-M will be biodegradable and sustainable, which may have potential clinical application value in the treatment of lung cancer.

关键词： Doxorubicin Curcumin Lung cancer Nanomicelle Co-delivery

Application of nanotechnology in CAR-T-cell immunotherapy

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Chinese Chemical Letters 2023年第3期34卷 49-65页

作者： Qiang Zeng Zhigang Liu Ting Niu Chuan He Ying Qu Zhiyong Qian Department of Hematology and institute of Hematology State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

It is cellular immunotherapy for the tumor that the in vitro modified immunocytes from patients or donors are reinfused into patients to kill tumor *** antigen receptor T cell(CAR-T)therapy,one of the most successful and representative tumor cellular immunotherapies,is now the weapon for cancer after extensive *** CAR-T immunotherapy achieves success in treating relapsed/refractory hematological tumors,its drawbacks,including the poor effect in solid tumors,cytokine release syndrome(CRS)or CAR-T-related encephalopathy syndrome(CRES),on-target,off-tumor effect,and high cost,cannot be *** is advantageous in the construction of CARs,the transfection of T cells,the expansion,delivery,and antitumor effect of CAR-T cells,and the reduction of CAR-T therapy-associated ***,introducing nanotechnology into CAR-T immunotherapy has already been performed in numerous studies with highly promising *** this review,we summarized the nanotechnologies used in CAR-T immunotherapy and discussed the challenges and directions of CAR-T immunotherapy combined with nanotechnologies in the future.

关键词： CAR-T immunotherapy Nanotechnology Nanobody Nanoparticle

Melphalan-loaded methoxy poly(ethylene glycol)-poly(D,L-lactide)copolymer nanomicelles in the treatment of multiple myeloma

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中国化学快报:英文版 2023年第9期34卷 193-198页

作者： Yingying Chen Qiang Zeng Bingyang Chu Zhigang Liu Xue Wei Mengran Chen Peipei Yang Minghai Tang Ting Niu Yongqian Jia Ying Qu Zhiyong Qian Department of Hematology and institute of Hematology State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

Multiple myeloma(MM)is the second most common hematological tumor characterized by the proliferation of monoclonal plasma ***(MEL)is commonly used in the treatment of MM and is especially essential for patients undergoing autologous stem cell transplantation(ASCT).Although many drugs for MM have been developed in recent years,chemotherapy followed by ASCT remains the optimal ***,the backbone of the conditioning regimen,brings severe toxicities at a high *** delivery systems enable drugs to be highly effective and have low *** this study,methoxy poly(ethylene glycol)-poly(D,L-lactide)copolymer(MPEG-PDLLA)was chosen to encapsulate melphalan,and the characteristics,effectiveness,and safety of MEL/MPEG-PDLLA in vitro and in vivo were ***/MPEG-PDLLA showed slow release and was easily engulfed by MM cells despite a result of the antitumor assay comparable to that of free melphalan in *** in vivo results showed that MEL/MPEG-PDLLA could significantly alleviate tumor burden and prolong survival time without increasing the toxicity to vital *** addition,MEL/MPEG-PDLLA could significantly reduce the damage to the intestinal mucosa caused by *** conclusion,MEL/MPEG-PDLLA shows improved antitumor activity and has the potential to alleviate pains of MM patients undergoing ASCT.

关键词： Melphalan Multiple myeloma MPEG-PDLLA Nanomicelle

Electrochemical Chiral Recognizing Tryptophan Enantiomers Based on Chiral Metal-Organic Framework D-MOF

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Chemical Research in Chinese Universities 2023年第6期39卷 976-984页

作者： HOU Huipeng TANG Shanshan WANG Wei LIU Miao LIANG Axin XIE Bingteng YI Yue LUO Aiqin Key Laboratory of Molecular Medicine and biotherapy School of Life ScienceBeijing Institute of TechnologyBeijing 100081P.R.China

In this work,an electrochemical chiral sensor of a nanowire-like chiral metal-organic framework/multiwalled carbon nanotube-chitosan/glassy carbon electrode(D-MOF/MWCNTs-CS/GCE)was proposed for the enantiorecognition of L/D-tryptophan(L/D-Trp).The asymmetrical spatial structure of D-MOF provides the feasibility for the enantiorecognition of Trp ***,differential pulse voltammetry(DPV)was carried out to be the detection method and the DPV peak potential difference(ΔEp)between L-Trp and D-Trp was referred as the index of the enantiorecognition *** parameters,such as mass ratios and drop-coated volume of MWCNTs-CS,drop-coated volume and concentration of D-MOF,pH and detection temperature of D-MOF/MWCNTs-CS/GCE were optimized for the largestΔEp *** the molecular dynamics(MD)simulation was used to elucidate the enantiorecognition ***,the proportions of D-Trp(D-Trp%)in Trp mixtures were detected in a good linear relationship with the DPV peak potentials(Ep),and the proposed electrochemical chiral sensor exhibited good reproducibility,stability and enantiorecognition ***,the proposed electrochemical chiral sensor(D-MOF/MWCNTs-CS/GCE)has a good application prospect in the fields of biomedicine,clinical diagnosis,chemical production,pharmaceuticals safety and so on.

关键词： Electrochemical chiral sensor Chiral metal-organic framework Multiwalled carbon nanotube-chitosan(MWCNTs-CS) D-MOF Tryptophan(Trp) Potential difference(ΔEp)

A dural substitute based on oxidized quaternized guar gum/porcine peritoneal acellular matrix with improved stability, antibacterial and anti-adhesive properties

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Chinese Chemical Letters 2023年第3期34卷 424-429页

作者： Xiaoshuang Yu Pengfei Yue Xu Peng Hongmei Ding Ningning Lei Xixun Yu College of Polymer Science and Engineering Sichuan UniversityChengdu 610065China West China Hospital of Sichuan University Department of BiotherapyCancer CenterState Key Laboratory of BiotherapyChengdu 610041China Experimental and Research Animal institute Sichuan UniversityChengdu 610065China

Trauma and neurosurgery often result in dural defects and are followed by serious complications or even death, finding suitable dural replacement materials to repair the defective dura has important clinical significance. Porcine peritoneal acellular matrix(PPAM) is a promising alternative material, but its poor stability makes it difficult to meet the various needs of dural reconstruction. In this work, we developed a novel antibacterial cross-linking agent oxidized quaternized guar gum(OQGG) and used it for the first time to stabilize PPAM to construct a dural mater substitute(OQGG-PPAM). The results showed that 1.5%OQGG-PPAM presented suitable mechanical property as well as good thermal stability and resistance to enzymatic degradation. It also exhibited good antibacterial activity and good anti-leakage ability. Furthermore, 1.5% OQGG-PPAM not only exhibited excellent cell compatibility but also significantly stimulated the secretion of b FGF and VEGF from seeded cells which was convenient for dural remodeling. In vivo experiment, it also exhibited the excellent histocompatibility and good anti-adhesion property. This study showed that OQGG can be used as a novel antibacterial cross-linking reagent for crosslinking natural tissues and 1.5% OQGG-PPAM was a potential candidate material for dura mater substitute.

关键词： Oxidized quaternized guar gum Dural substitute Porcine peritoneal acellular matrix Antibacterial

Structural insights into substrate recognition and translocation of human peroxisomal ABC transporter ALDP

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Signal Transduction and Targeted Therapy 2023年第3期8卷 1269-1281页

作者： Chao Xiong Li-Na Jia Wei-Xi Xiong Xin-Tong Wu Liu-Lin Xiong Ting-Hua Wang Dong Zhou Zhen Hong Zheng Liu Lin Tang Department of Neurology State Key Lab of Biotherapy and Cancer CenterWest China HospitalSichuan University and Collaborative Innovation Center for Biotherapy610041 ChengduSichuanChina institute of Brain Science and Brain-inspired Technology of West China Hospital Sichuan UniversityChengduChina institute of Neurological Disease State Key Lab of BiotherapyWest China HospitalSichuan University610041 ChengduSichuanChina School of Life and Health Kobilka Institute of Innovative Drug Discoverythe Chinese University of Hong Kong(Shenzhen)ShenzhenChina

Dysfunctions of ATP-binding cassette,subfamily D,member 1(ABCD1)cause X-linked adrenoleukodystrophy,a rare neurodegenerative disease that affects all human *** in the peroxisome membrane,ABCD1 plays a role in the translocation of very long-chain fatty acids for theirβ-***,the six cryo-electron microscopy structures of ABCD1 in four distinct conformational states were *** the transporter dimer,two transmembrane domains form the substrate translocation pathway,and two nucleotide-binding domains form the ATP-binding site that binds and hydrolyzes *** ABCD1 structures provide a starting point for elucidating the substrate recognition and translocation mechanism of *** of the four inward-facing structures of ABCD1 has a vestibule that opens to the cytosol with variable *** acid(C26:0)-CoA substrate binds to the transmembrane domains(TMDs)and stimulates the ATPase activity of the nucleotide-binding domains(NBDs).W339 from the transmembrane helix 5(TM5)is essential for binding substrate and stimulating ATP hydrolysis by ***1 has a unique C-terminal coiled-coil domain that negatively modulates the ATPase activity of the ***,the structure of ABCD1 in the outward-facing state indicates that ATP molecules pull the two NBDs together and open the TMDs to the peroxisomal lumen for substrate *** five structures provide a view of the substrate transport cycle and mechanistic implication for disease-causing mutations.

关键词： starting hydrolysis insight

Somatic copy number alterations are predictive of progression-free survival in patients with lung adenocarcinoma undergoing radiotherapy

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Cancer Biology & Medicine 2022年第5期19卷 685-695页

作者： Fan Kou Lei Wu Yan Guo Bailu Zhang Baihui Li Ziqi Huang Xiubao Ren Lili Yang Department of Immunology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyKey Laboratory of Cancer Immunology and BiotherapyTianjin 300060China Department of biotherapy Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin 300060China

Objective:Lung cancer is the most common cause of cancer-related deaths *** copy number alterations(SCNAs)have been used to predict responses to therapies in many cancers,including lung ***,little is known about whether they are predictive of radiotherapy *** aimed to understand the prognostic value and biological functions of ***:We analyzed the correlation between SCNAs and clinical outcomes in The Cancer Genome Atlas data for 486 patients with non-small cell lung cancer who received *** set enrichment analyses were performed to investigate the potential mechanisms underlying the roles of SCNAs in the radiotherapy *** results were validated in 20 patients with lung adenocarcinoma(LUAD)receiving ***:SCNAs were a better predictor of progression-free survival(PFS)in LUAD(P=0.024)than in lung squamous carcinoma(P=0.18)in patients treated with *** and multivariate regression analyses revealed the superiority of SCNAs in predicting PFS in patients with *** with stage I cancer and low SCNA levels had longer PFS than those with high SCNA levels(P=0.022).Our prognostic nomogram also showed that combining SCNAs and tumor/node/metastasis provided a better model for predicting long-term ***,high SCNA may activate the cell cycle pathway and induce ***:SCNAs may be used to predict PFS in patients with early-stage LUAD with radiotherapy,in combination with TNM,with the aim of predicting long-term ***,SCNAs are a novel predictive biomarker for radiotherapy in patients with LUAD.

关键词： SCNA radiotherapy lung cancer progression-free survival immune infiltration