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Dehydroabietic acid chemosensitizes drug-resistant acute lymphoblastic leukemia cells by downregulating survivin expression

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Asian Pacific Journal of Tropical Biomedicine 2022年第9期12卷 383-390页

作者： Li-Li Shen wei-Hua Huang Hui-Jun Zhao xue-wei yuan Department of Pediatrics Suzhou Kowloon HospitalShanghai Jiao Tong University School of MedicineSuzhouJiangsuChina

Objective:To explore the mechanism of drug resistance in acute lymphoblastic leukemia and the anti-tumor effect of combination therapy of dehydroabietic acid and vincristine against acute lymphoblastic leukemia ***:Acute lymphoblastic leukemia cells REH and CCRFCEM were employed to detect the anti-tumor effect of vincristine and doxorubicin on proliferation and apoptosis using EdU assay,human active caspase-3 Quantikine ELISA kit,and flow ***-resistant REH cells(REH-R),survivin knockdown and overexpressing REH cells were established to verify the role of survivin in drug ***,in vitro and in vivo assays were performed to determine the effect of dehydroabietic acid on the cytotoxicity of ***:Vincristine and doxorubicin markedly suppressed proliferation and induced apoptosis of REH and CCRF-CEM *** expression was upregulated in REH-R cells compared with REH *** of survivin expression obviously restored the sensitivity of REH-R cells to *** phosphorylation was also increased in REH-R cells compared to REH *** addition,LY294002,a PI3k/Akt pathway blocker,inhibited survivin expression and enhanced cytotoxicity of vincristine to REH-R *** acid effectively reduced survivin expression in REH-R cells,thereby enhancing the therapeutic effect of vincristine on drug-resistant *** overexpression markedly reduced the effect of dehydroabietic acid on enhancing the anti-proliferation and inducing apoptosis effect of ***,the combination of dehydroabietic acid with vincristine significantly extended the survival rate in a mouse xenograft model of acute lymphoblastic leukemia,compared with vincristine treatment ***:Dehydroabietic acid may be used as a potential candidate for the treatment of acute lymphoblastic leukemia in combination with vincristine.

关键词： Acute lymphoblastic leukemia Drug resistance Survivin Dehydroabietic acid REH cells Vincristine

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Flurbiprofen microneedle patches for the management of acute postoperative pain

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Nano Research 2024年第8期17卷 7493-7503页

作者： Huaqing Chu Yanyan Zhang yuan Yang Jiangtao xue Cong Li wei Zhang Zhou Li Hui Zheng National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Beijing Institute of Nanoenergy and Nanosystems Chinese Academy of SciencesBeijing 101400China Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases School of Integrated Chinese and Western MedicineHunan University of Chinese MedicineChangsha 410208China School of Life Science Institute of Engineering MedicineBeijing Institute of TechnologyBeijing 100081China Institute of Process Engineering Chinese Academy of SciencesBeijing 100190China

Acute postoperative pain is commonly treated with flurbiprofen(FBP),but conventional delivery methods are *** study prepared a new non-burst release microneedles(MNs)using genipin cross-linked gelatin(cGel).By adding varying amounts of genipin to modulate the crosslinking degree of cGel,the drug release behavior of the drug-loaded MNs in the skin can be *** crosslinking parameters that meet therapeutic requirements are selected,thus providing rapid and longlasting analgesic *** solutions were successfully cross-linked,altering matrix material microstructure,confirmed by scanning electron microscope imaging and fourier transform infrared *** demonstrated increasing mechanical strength with higher *** release rates were rapid initially,then slowed,exhibiting a characteristic of decreased release rates with increasing degrees of *** vivo,FBP/cGel MNs significantly reduced allodynia and hyperalgesia post-surgery,with the greatest effect observed at 2–3 h post-surgery,and can maintain analgesia for up to 6 *** tests confirmed good ***/cGel MNs effectively penetrate the stratum corneum,safely delivering drugs with significant analgesic effects,excellent mechanical properties,and good biocompatibility,representing a promising strategy for managing acute postoperative pain.

关键词： microneedle postoperative pain flurbiprofen non-steroid anti-inflammatory drug cross-linked gelatin

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Combatting Pathogenic Bacteria with Synthetic Immunotherapeutics from Chitosan:Antibody Recruiting at Engineered Bacterial Surface with Peptidoglycan Analogs

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CCS Chemistry 2024年第6期6卷 1448-1457页

作者： yuan Xu Shihao Song Hongwei Duan Yinyue Deng xue-wei Liu School of Chemistry Chemical Engineering and BiotechnologyNanyang Technological UniversitySingapore 637371 Key Laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan UniversityHaikou 570228 School of Pharmaceutical Sciences(Shenzhen) Shenzhen Campus of Sun Yat-sen UniversitySun Yat-sen UniversityShenzhen 518107

The emergence of microbial drug resistance,coupled with the paucity of new antibiotics poses an impending threat to public *** this work,we drew inspiration from synthetic peptidoglycan oligomers and successfully constructed antibody-recruiting peptidoglycan analogs,2a-d,with excellent safety profiles and high efficiencies in recruiting antibodies across different ***,we demonstrated that these peptidoglycan analogs could be readily incorporated into bacteria cell walls,whereby both simple monoclonal and pooled human serum antibodies effectively congregated to the surfaceengineered bacteria,leading to the complete extermination of the engineered bacterial cells both in vitro and in *** peptidoglycan analog agents for recruiting endogenous antibodies to combat pathogenic bacteria enable further development of promising broad-spectrum immunotherapeutics.

关键词： chitosan bacterial infection endogenous antibodies bacterial surface engineering peptidoglycan analogs

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Development of component stiffness equations for thread-fixed one-side bolt connections to an enclosed rectangular hollow section column under tension

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Frontiers of Structural and Civil Engineering 2024年第4期18卷 568-586页

作者： Fu-wei WU yuan-Qi LI Department of Structural Engineering Tongji UniversityShanghai 200092China State Key Laboratory of Disaster Reduction in Civil Engineering Tongji UniversityShanghai 200092China

The derivation and validation of analytical equations for predicting the tensile initial stiffness of threadfixed one-side bolts(TOBs),connected to enclosed rectangular hollow section(RHS)columns,is presented in this *** unknown stiffness components are considered:the TOBs connection and the enclosed RHS ***,the trapezoidal thread of TOB,as an equivalent cantilevered beam subjected to uniformly distributed loads,is analyzed to determine the associated *** on the findings,the thread-shank serial-parallel stiffness model of TOB connection is *** analysis of the tensile stiffness of the enclosed RHS face due to two bolt forces,the four sidewalls are treated as rotation constraints,thus reducing the problem to a two-dimensional plate *** to the load superposition method,the deflection of the face plate is resolved into three components under various boundary and load *** to the plate deflection theory of Timoshenko,the analytical solutions for the three deflections are derived in terms of the variables of bolt spacing,RHS thickness,height to width ratio,***,the validity of the above stiffness equations is verified by a series of finite element(FE)models of T-stub *** proposed component stiffness equations are an effective supplement to the component-based method.

关键词： initial stiffness component based method thread-fixed one-side bolt rectangular hollow sections analytical equation

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Pharmacological regulation of tissue fibrosis by targeting the mechanical contraction of myofibroblasts

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Fundamental Research 2022年第1期2卷 37-47页

作者： Zheng-Quan He xue-wei yuan Zong-Bao Lu Yu-Huan Li Yu-Fei Li Xin Liu Liu Wang Ying Zhang Qi Zhou wei Li State Key Laboratory of Stem Cell and Reproductive Biology Insttute of ZoologyChinese Academy of SciencesBeijing 100101China Institute for Stem Cell and Regenerative Medicine Chinese Academy of SciencesBeijing 100101China Bejig Insitute for Stem Cell and Regenerative Medicine Chinese Academy of SciencesBeljing 100101China University of Chinese Academy of Sciences Beljing 100049China The First Hospitad of Jilin Universiy Changchun Jilin 130021China

Fibrosis can occur in almost all tissues and organs and affects normal physiological function,which may have serious consequences,such as organ ***,there are currently no effective,broad-spectmm drugs suitable for clinical *** the process of fibrosis is an important prerequisite for the development of new therapeutic targets and *** have shown that the limiting of myofibroblast activation or the promoting of their elimination can ameliorate ***,it has not been reported whether a direct decrease in cell contraction can inhibit fibrosis in ***,we have shown that(-)-blebbistatin(Ble),a non-muscle myosin II inhibitor,displayed significant inhibition of liver fibrosis in different chronic injury mouse models in *** found that Ble reduced the stiffness of fibrotic tissues from the early stage,which reduced the extent of myofibroblast activation induced by a stiffer extracellular matrix(ECM).Moreover,Ble also reduced the activation of myofibroblasts induced by TGF-β1,which is the most potent pro-fibrotic ***,Ble reduced mechanical contraction,which inhibited the assembly of stress fibers,decreased the F/G-actin ratio,and led to the exnucleation of YAPJ and ***,we verified its broad-spectrum antifibrotic effect in multiple models of organ *** results highlighted the important role of mechanical contraction in myofibroblast activation and maintenance,rather than just a characteristic of activation,suggesting that it may be a potential target to explore broad-spectrum drugs for the treatment of fibrotic diseases.

关键词： Fibrosis Myofibroblasts Contraction Inhibitor Biomechanics Regeneration

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Pyrolysis Empirical Modeling of Polyester Glass Fiber Reinforced Plastics Using Sestak-Berggren Model Method

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Journal of Thermal Science 2024年第2期33卷 725-738页

作者： NAN wei JI Wenhui yuan Yanping yuan Zhongyuan SUN Yong School of Mechanical Engineering Southwest Jiaotong UniversityChengdu610031China CRRC Changchun Railway Vehicles Co. LtdChangchun130062China

Polyester Glass Fiber Reinforced Plastic(Polyester GFRP),a thermosetting plastic comprised of glass fiber and polyester polymer compounds,is extensively utilized in high-speed *** its pyrolysis mechanism is crucial as it significantly influences the combustion characteristics and fire safety ***,kinetic research on polyester GFRP primarily focuses on employing the Coats-Redfern method to derive a theoretical kinetic ***,the pyrolysis process of polyester GFRP is complex and the aforementioned theoretical model fails to accurately describe the pyrolysis ***,this study seeks to utilize the Sestak and Berggren(SB) model as a methodological approach to reveal the complex reaction mechanism during the pyrolysis *** on thermogravimetric analysis,the entire pyrolysis process of polyester GFRP is divided into two primary ***,model-free methods are employed to ascertain the activation energy and pre-exponential *** results show that the fitted empirical models of the two main pyrolysis stages are f(α)=(1-α)^(1.47)[-ln(1-α)]^(1.50) and f(α)=(1-α)^(1.77)[-ln(1-α)]^(1.72),*** predicted results are in good agreement with experimental data under different heating rates,which indicates that the empirical model can sufficiently describe the pyrolysis process of polyester GFRP.

关键词： polyester GFRP model-fitting methods empirical models pyrolysis

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Tailoring sulfur-doped and nitrogen-defective carbon nitride nanosheets for efficient photo-controlled radical polymerizations

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Science China Chemistry 2024年第7期67卷 2325-2334页

作者： xue Li Meng Kai Xu yuan Huang Tao Cai Key Laboratory of Biomedical Polymers of Ministry of Education College of Chemistry and Molecular SciencesWuhan UniversityWuhan 430072China Wuhan University Shenzhen Research Institute Shenzhen 518057China

Despite the challenges that remain,the synergistic adjustment of various microstructures and photochemical parameters of graphitic carbon nitride(g-C_(3)N_(4))in photocatalytic reactions holds promises for improving catalytic efficiency and reducing energy ***,sulfur-doped and nitrogen-defective g-C_(3)N_(4)(n-SC_(3)N_(x))nanosheets were designed and elaborately *** resultant n-SC_(3)N_(x)possessed a precisely defined 2D layer structure with extensive porosity and incremental specific surface *** photoinduced electron transfer-reversible addition-fragmentation chain transfer(PET-RAFT)polymerization of vinyl monomers with low dispersity,excellent temporal control and high chain-end fidelity was achieved under mild blue light irradiation in a nondegassed *** to their ultrathin nanostructures with nitrogen defects and sulfur dopants,n-SC_(3)N_(x)was capable of catalyzing RAFT polymerization in aqueous solutions at significantly accelerated rates,which were nearly 8 times faster compared to bulk g-C_(3)N_(4).The ease of separation and efficient reusability in subsequent polymerizations was enabled by the heterogeneous nature of n-SC_(3)N_(x).The appeal of this approach was illustrated by the fact that utilizing a reusable and metal-free photocatalyst in aqueous environments allowed for the synthesis of polymers with molecular weight up to 300 kg mol^(-1) and a dispersity of 1.32.

关键词： graphitic carbon nitride nitrogen defects sulfur dopants PET-RAFT polymerization recyclability

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Lipid metabolism dysfunction induced by age-dependent DNA methylation accelerates aging

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Signal Transduction and Targeted Therapy 2022年第6期7卷 2105-2116页

作者： Xin Li Jiaqiang Wang LeYun Wang yuanxu Gao Guihai Feng Gen Li Jun Zou Meixin Yu Yu Fei Li Chao Liu xue wei yuan Ling Zhao Hong Ouyang Jian-Kang Zhu wei Li Qi Zhou Kang Zhang State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of Sciences100101 BeijingChina Institute for Genomic Medicine University of California San DiegoLa JollaCA 92037USA Faculty of Medicine Macao University of Science and TechnologyTapaiMacao 999078China State Key Laboratory of Lunar and Planetary Sciences Macao University of Science and TechnologyTapaiMacao 999078China Clinical Translational Innovation Center West China HospitalSichuan UniversityChengdu 610041China Guangzhou Women and Children Medical Center Guangzhou Medical UniversityGuangzhou 510623China Zhongshan Ophthalmic Center Sun Yat-sen UniversityGuangzhou 510060China Institute of Advanced Biotechnology and School of Life Sciences Southern University of Science and TechnologyShenzhen 518055China

Epigenetic alterations and metabolic dysfunction are two hallmarks of ***,the mechanism of how their interaction regulates aging,particularly in mammals,remains largely *** we show ELOVL fatty acid elongase 2(Elovl2),a gene whose epigenetic alterations are most highly correlated with age prediction,contributes to aging by regulating lipid *** applied artificial intelligence to predict the protein structure of ELOVL2 and the interaction with its *** Elovl2 function disturbs lipid synthesis with increased endoplasmic reticulum stress and mitochondrial dysfunction,leading to key aging phenotypes at both cellular and physiological ***,restoration of mitochondrial activity can rescue age-related macular degeneration(AMD)phenotypes induced by Elovl2 deficiency in human retinal pigmental epithelial(RPE)cells;this indicates a conservative mechanism in both human and *** together,we revealed an epigenetic-metabolism axis contributing to aging and illustrate the power of an AI-based approach in structure-function studies.

关键词： metabolism alterations dysfunction

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Pretreatment and analysis techniques development of TKIs in biological samples for pharmacokinetic studies and therapeutic drug monitoring

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JOURNAL OF PHARMACEUTICAL ANALYSIS 2024年第4期14卷 100899页

作者： Chen, Lan Zhang, yuan Zhang, Yi-Xin Wang, wei-Lai Sun, De-Mei Li, Peng-Yun Feng, xue-Song Tan, Yue China Med Univ Sch Pharm Shenyang 110122 Peoples R China Natl Engn Res Ctr Strateg Drugs Inst Pharmacol & Toxicol Inst Beijing 100850 Peoples R China China Med Univ Dept Gastroenterol Shengjing Hosp Shenyang 110022 Peoples R China

Tyrosine kinase inhibitors (TKIs) have emerged as the first-line small molecule drugs in many cancer therapies, exerting their effects by impeding aberrant cell growth and proliferation through the modulation of tyrosine kinase-mediated signaling pathways. However, there exists a substantial interindividual variability in the concentrations of certain TKIs and their metabolites, which may render patients with compromised immune function susceptible to diverse infections despite receiving theoretically efficacious anticancer treatments, alongside other potential side effects or adverse reactions. Therefore, an urgent need exists for an up-to-date review concerning the biological matrices relevant to bioanalysis and the sampling methods, clinical pharmacokinetics, and therapeutic drug monitoring of different TKIs. This paper provides a comprehensive overview of the advancements in pretreatment methods, such as protein precipitation (PPT), liquid-liquid extraction (LLE), solid-phase extraction (SPE), micro-SPE (m-SPE), magnetic SPE (MSPE), and vortex-assisted dispersive SPE (VA-DSPE) achieved since 2017. It also highlights the latest analysis techniques such as newly developed high performance liquid chromatography (HPLC) and high-resolution mass spectrometry (HRMS) methods, capillary electrophoresis (CE), gas chromatography (GC), supercritical fluid chromatography (SFC) procedures, surface plasmon resonance (SPR) assays as well as novel nanoprobes-based biosensing techniques. In addition, a comparison is made between the advantages and disadvantages of different approaches while presenting critical challenges and prospects in pharmacokinetic studies and therapeutic drug monitoring. (c) 2023 The Author(s). Published by Elsevier B.V. on behalf of Xi'an Jiaotong University. This is an open access article under the CC BY-NC-ND license (http://***/licenses/by-nc-nd/4.0/).

关键词： TKIs Microextraction technique HRMS methods Pharmacokinetic studies Therapeutic drug monitoring TYROSINE KINASE INHIBITORS SOLID-PHASE EXTRACTION PERFORMANCE LIQUID-CHROMATOGRAPHY RP-HPLC METHOD TANDEM MASS-SPECTROMETRY CHRONIC MYELOID-LEUKEMIA WALLED CARBON NANOTUBE UPLC-MS/MS METHOD CLINICAL PHARMACOKINETICS SIMULTANEOUS QUANTIFICATION

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Numerical Analysis of Heat Transfer Characteristics to Supercritical CO_(2) in a Vertical Mini-Channel:Transition and Pseudo-Boiling

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Journal of Thermal Science 2024年第1期33卷 101-113页

作者： yuan Baoqiang WANG wei XIN Gongming DU Wenjing School of Energy and Power Engineering Shandong UniversityJi'nan 250061China

Large eddy simulations have been conducted to study upward transitional flows and heat transfer characteristics of supercritical CO_(2) in a vertical *** numerical simulation was carried out on a modified buoyantPimpleFOAM solver in OpenFOAM 7,and was verified using experiment *** results indicate that increasing the Grashof numbers can reduce the flow stability and make the flow transition *** are four stages of heat transfer in the transition process,i.e.,weakened,improved,recovered and normal heat *** heat transfer phenomena in the transition process were explained from three perspectives:thermal boundary layer theory,turbulent transport and pseudo-boiling *** transfer enhancement during transition is related to the transport of supercritical molecular clusters,and these molecular clusters are regarded as pseudo-bubbles in pseudo-boiling *** flow pattern of the pseudo-phases in the dia-Widom process contains single-phase flow,steady pseudo-film flow,unsteady pseudo-film flow,partial pseudo-bubbles flow and flocculent pseudo-film ***-bubbles have similar behaviors to subcritical bubbles,i.e.,break-up,deformation,condensation and *** researches in this work are favorable for understanding the heat transfer mechanism of supercritical fluids during flow transition.

关键词： supercritical heat transfer large eddy simulation transition pseudo-boiling

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