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TERC suppresses PD-L1 expression by downregulating RNA binding protein HuR

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Science China(Life Sciences) 2022年第12期65卷 2505-2516页

作者： Heping Jin yanlian chen Jian Ren Junjiu Huang Yong Zhao Haiying Liu MOE Key Laboratory of Gene Function and Regulation School of Life SciencesSun Yat-sen UniversityGuangzhou 510006China

TERC is the RNA component of telomerase,and provides a template for TERT to synthesize telomere repeats at chromosome ends.Increasing evidence has revealed that TERC is involved in other biological processes beyond telomerase.Here,we found that the expression level of TERC is negatively correlated with PD-L1 and that ectopic expression of TERC but not TERT in ALT cells significantly inhibits PD-L1,suggesting that TERC suppresses PD-L1 expression in a telomerase-independent manner.Mechanistically,instead of regulating PD-L1 m RNA directly,TERC accelerates PD-L1 m RNA degradation by inhibiting the expression of Hu R,which binds to the 3′UTR of PD-L1 m RNA and maintains its stability.We also found that the small molecule AS1842856,a Fox O1 inhibitor,promotes TERC expression and reverses the PD-L1 upregulation caused by chemotherapy,providing a potential combination cancer therapy that avoids cancer immune escape during chemotherapy.

关键词： TERC PD-L1 HuR FoxO1 inhibitor

Nanoparticles for the treatment of spinal cord injury

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Neural Regeneration Research 2025年第6期 1665-1680页

作者： Qiwei Yang Di Lu Jiuping Wu Fuming Liang Huayi Wang Junjie Yang Ganggang Zhang chen Wang yanlian Yang Ling Zhu Xinzhi Sun Department of Orthopedic Surgery The First Affiliated Hospital of Zhengzhou University CAS Key Laboratory of Standardization and Measurement for Nanotechnology CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology University of Chinese Academy of Sciences Department of Neurosurgery The First Affiliated Hospital of Chongqing Medical University

Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.

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旋转水力提升多金属结核运动特性数值模拟

矿冶工程 2024年第2期44卷 13-17页

作者：陈云杜燕连李萌梁栋沈义俊海南大学南海海洋资源利用国家重点实验室海南海口570228 海南大学机电工程学院海南海口570228 海南大学信息与通信工程学院海南海口570228

采用CFD-DEM耦合方法对多金属结核提升进行模拟,研究了垂直管道中不同旋转流场旋流比对水力提升多金属结核输运特性的影响。结果表明,随着旋转流场旋流比增大,旋转强度显著增强,流体流速最大值增大,颗粒群轴向平均速度增大。旋转流场的... 详细信息

采用CFD-DEM耦合方法对多金属结核提升进行模拟,研究了垂直管道中不同旋转流场旋流比对水力提升多金属结核输运特性的影响。结果表明,随着旋转流场旋流比增大,旋转强度显著增强,流体流速最大值增大,颗粒群轴向平均速度增大。旋转流场的旋转强度明显影响管道内颗粒的速度分布:速度大的颗粒逐步分布在管壁周围,速度较小的颗粒分布在管道中心处。旋转流场可降低颗粒群局部浓度,有利于降低因颗粒滞留效应引起局部浓度升高造成的输送管堵塞风险。

关键词：深海采矿多金属结核液固双相流水力提升管道输送旋流比 CFD-DEM耦合

Therapeutic potential of C1632 by inhibition of SARS-CoV-2 replication and viral-induced inflammation through upregulating let-7

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Signal Transduction and Targeted Therapy 2021年第3期6卷 605-607页

作者： chen Xie yanlian chen Dongling Luo Zhen Zhuang Heping Jin Haoxian Zhou Xiaocui Li Haijun Lin Xiaohui Zheng Jing Zhang Peihui Wang Jincun Zhao Yong Zhao Hui Huang Key Laboratory of Gene Engineering of the Ministry of Education School of Life SciencesSun Yat-sen UniversityGuangzhouGuangdongChina Cardiovascular Department The Eighth Affiliated HospitalSun Yat-sen UniversityShenzhenGuangdongChina State Key Laboratory of Respiratory Disease Guangzhou Institute of Respiratory DiseaseThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdongChina Xiamen Innodx Biotech Co. Ltd.XiamenFujianChina School of Pharmaceutical Sciences Wenzhou Medical UniversityWenzhouZhejiangChina Advanced Medical Research Institute Cheeloo College of MedicineShandong UniversityJinanShandongChina

Dear Editor,The COVID-19 pandemic caused by SARS-CoV-2 has led to acute respiratory distress syndrome(ARDS)with a high rate of death.An excessive inflammatory response,caused by virus infection,is associated with severe clinical manifestations that may lead to death of patients.1 Therefore,the blockage of virus replication and suppression of hyper-inflammatory response are beneficial for COVID-19 treatment.However,the drug targeting both virus and hyper-inflammation,as far as we know,is not available yet.

关键词： inflammation distress acute

Formulated nano-liposomes for reversal of cisplatin resistance in NSCLC with nucleus-targeting peptide

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Nano Research 2023年第11期16卷 12864-12879页

作者： Minxian Li Mei Jiang Mengting chen Lilusi Ma Xiaocui Fang yanlian Yang chen Wang Key Laboratory for Biological Effects of Nanomaterials and Nanosafety(Chinese Academy of Sciences) Key Laboratory of Standardization and Measurement for Nanotechnology(Chinese Academy of Sciences)and CAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China Sino-Danish Center for Education and Research Sino-Danish CollegeBeijing 101499China Central Laboratory Beijing Obstetrics and Gynecology HospitalCapital Medical UniversityBeijing 100026China

Cell membrane-engineered nano-delivery systems have evolved as a promising strategy to enhance drug bioavailability,offering an alternative for reversing drug resistance in cancer therapy.Herein,a formulated nano-liposome that fabricated by hybridizing cisplatin-resistant A549 cell line(A549/cis)cancer cell membrane and phospholipids for co-delivery of cisplatin and nuclear protein zeste homolog 2(EZH2)-targeting peptide EIP103,referred to as cLCE,was developed.In vitro results indicated that the formulated nano-liposome can efficiently inhibit A549/cis cancer cell invasion and metastasis through the down-regulation of Ncadherin and vimentin proteins.Mechanistic studies demonstrated that the reduction of nerve growth factor receptor(NGFR)levels and the increase of peroxisome proliferator-activated receptorγ(PPARγ)levels achieved by EIP103 may contribute to the reversal of cisplatin resistance.In vivo results demonstrated that the encapsulation of both cisplatin and EIP103 within cLCE leads to increased intratumoral accumulation and prolonged survival in A549/cis cancer-bearing mice as compared to the individual drugs alone.This can be attributed to the enhanced tumor homing capability of cLCE achieved through the presence of inherited membrane proteins derived from A549/cis cells.Taken together,this study may provide a highly promising therapeutic strategy to improve clinical treatments for cisplatin-resistance non-small-cell lung cancer(NSCLC)as well as other malignant cancers.

关键词： formulated liposome tumor homing cisplatin resistance nucleus-peptide cancer therapy

Dual-functional extracellular vesicles enable synergistic treatment via m^(6)A reader YTHDF1-targeting epigenetic regulation and chemotherapy

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Nano Research 2023年第12期16卷 13309-13321页

作者： Rong Du Qing You Jingyi Liu chen Wang Ling Zhu yanlian Yang CAS Key Laboratory of Standardization and Measurement for Nanotechnology CAS Key Laboratory of Biological Effects of Nanomaterials and NanosafetyNational Center for Nanoscience and TechnologyBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China

Chemotherapy remains one of the most prevailing strategies for cancer treatment.However,its treatment effect is hampered by drug resistance,nonspecific tumor targeting,and severe toxic side effects.Combination chemotherapy with synergistic effect has become an attractive tumor therapy.N6-methyladenosine(m6A)regulators determine the fate of m6A-modified transcripts and play vital roles in cancer development and drug resistance.Gene therapy such as small interfering RNA(siRNA)is a promising strategy to reduce the abnormal gene expression of m6A regulators.However,its poor selectivity and high systemic toxicity necessitate the use of delivery vectors to target specific cells and tissues.Here,we constructed a dual-functional targeted nanodrug platform for the synergetic m6A-associated epigenetic regulation and chemotherapy of ovarian cancer.We encapsulated siRNA targeting the m6A reader YT521-B homology(YTH)N6-methyladenosine RNA-binding protein 1(YTHDF1)and docetaxel(DTX),the first-line chemotherapeutic agent of ovarian cancer,into mesenchymal stem cell-derived small extracellular vesicles(MsEVs).This nanosystem exhibits significant tumor targeting and endo/lysosomal escape of siYTHDF1.It effectively depletes YTHDF1 and suppresses the protein translation of eukaryotic translation initiation factor 3 subunit C(EIF3C)in an m6A-dependent manner.The combination of YTHDF1-targeting epigenetic regulation significantly enhances the anti-tumor effect of DTX and effectively inhibits ovarian cancer progression without causing significant systemic toxicity.This co-delivery nanoplatform offers a promising approach for combinational cancer treatment,showing improved anti-tumor efficacy through the synergistic effects of epigenetic regulation and chemotherapeutic inhibition.

关键词： extracellular vesicles N6-methyladenosine(m6A)modulators docetaxel small interfering RNA(siRNA)delivery ovarian cancer

Terminus-immobilization effect on peptide conformations and peptide–peptide interactions

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Nano Research 2023年第12期16卷 13498-13508页

作者： Wendi Luo Xiaocui Fang chen Wang yanlian Yang Bin Tu Qiaojun Fang Laboratory of Theoretical and Computational Nanoscience CAS Key Laboratory for Biological Effects of Nanomaterials&NanosafetyCAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China Sino-Danish Center for Education and Research Beijing 101408China

Peptide-modified delivery systems are enabling the improvement of the targeting specificity,biocompatibility,stability,etc.However,the precise design of a peptide-decorated surface for a designated function has remained to be challenging due to a lack of mechanistic understanding of the interactions between surface-bound peptide ligands and their receptors.Enlightened by the recent report on pairwise interactions between peptides in the solution state and surface-immobilized state,we used computational simulations to explore the contributing mechanisms underlining the observed binding affinity characteristics.Molecular dynamics simulations were performed to sample and compare conformations of homo-octapeptides free in solution(mobile peptides)and bound to the surface(N-terminal fixed peptides).We found that peptides converged to more extended and rigid conformations when immobilized to the surface and confirmed that the extended structures could increase the space available to counter-interacting peptides during the peptide–peptide interactions.In addition,studies on interactions between stationary and mobile peptides revealed that main-chain/side-chain and side-chain/side-chain hydrogen bonds play an important role.The presented efforts in this work may provide supportive references for peptide design and modification on the nanoparticle surface as well as guidance for analyzing peptide–receptor interactions through an emphasis on hydrogen bonds during peptide design and an understanding of the influence on the binding affinity by the sequence-dependant conformational changes after peptide immobilization.

关键词： terminus-immobilization peptide conformations peptide–peptide interactions molecular dynamics peptide design

Principles of amino-acid–ribonucleotide interaction revealed by binding affinities between homogeneous oligopeptides and singlestranded RNA molecules

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Nano Research 2023年第12期16卷 13294-13300页

作者： Pengyu Wang Xiaocui Fang Ping Li Minxian Li yanlian Yang chen Wang Key Laboratory for Biological Effects of Nanomaterials and Nanosafety(Chinese Academy of Sciences(CAS)) Key Laboratory of Standardization and Measurement for Nanotechnology(CAS)CAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China

We have determined the binding strengths between ribonucleotides of adenine(A),guanine(G),uracil(U),and cytosine(C)in homogeneous single-stranded ribonucleic acids(ssRNAs)and homo-decapeptides consisting of 20 common amino acids.We use a bead-based fluorescence assay for these measurements in which decapeptides are immobilized on the bead surface and ssRNAs are in solutions.The results provide a molecular basis for analyzing selectivity,specificity,and polymorphisms of amino-acid–ribonucleotide interactions.Comparative analyses of the distribution of the binding energies reveal unique binding strength patterns assignable to each pair of amino acid and ribonucleotide originating from the chemical structures.Pronounced favorable(such as Arg–G)and unfavorable(such as Met–U)binding interactions can be identified in selected groups of amino acid and ribonucleotide pairs that could provide basis to elucidate energetics of amino-acid–ribonucleotide interactions.Such interaction selectivity,specificity,and polymorphism manifest the contributions from RNA backbone,RNA bases,as well as main chain and side chain of the amino acids.Such characteristics in peptide–RNA interactions might be helpful for understanding the mechanism of protein–RNA specific recognition and the design of RNA nano-delivery systems based on peptides and their derivatives.

关键词： peptides single-stranded ribonucleic acid(ssRNA) binding affinity flow cytometry

Nano-imaging agents for brain diseases: Environmentally responsive imaging and therapy

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Nano Research 2023年第12期16卷 13134-13163页

作者： Fuming Liang Qing You Xiaopeng Ma Huayi Wang chen Wang Zhaohui He yanlian Yang Ling Zhu CAS Key Laboratory of Standardization and Measurement for Nanotechnology CAS Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyCAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijing 100190China Department of Neurosurgery The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China National Center for Nanoscience and Technology University of Chinese Academy of SciencesBeijing 100049China The First Affiliated Hospital University of Science and Technology of China Anhui Provincial HospitalHefei 230000China

Precise imaging is essential for the accurate diagnosis and surgical guidance of brain diseases but it is challenging due to the difficulties in crossing the blood-brain barrier(BBB),the difficulties in disease lesion targeting,and the limited contrast in the brain environment.Nano-imaging agents were characterized by functionalized modifications,high contrast,small size,and high biocompatibility,thus providing advantages in BBB crossing,brain targeting,imaging resolution,and real-time monitoring,holding great potential in brain disease imaging.Specific characteristics in brain environment and brain diseases(e.g.,marker proteins on the BBB,the pathogenic proteins in the neurodegenerative diseases or brain tumors,and the tumor and inflammatory microenvironment)provide opportunities for the functionalized nano-imaging agents to improve BBB crossing and disease targeting.Moreover,the versatile nano-imaging agents are endowed with therapeutic agents to facilitate the theranostics of brain diseases.Here,we summarized the common materials and imaging techniques of nano-imaging agents and their imaging treatment applications.We discussed their BBB penetration,environmental response for disease targeting,and therapeutic effects.We also provided insights on the advantages,challenges,and application of nano-imaging agents in detecting and treating brain diseases such as neurodegenerative diseases,brain tumors,stroke,and traumatic brain injury.These discussions will help develop nano-imaging agents-based theranostic platforms for the precise diagnosis and treatment of brain diseases.

关键词： brain disease nano-imaging agent blood-brain barrier environmentally responsive imaging treatment