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A strategy for mechanically integrating robust hydrogeltissue hybrid to promote the anti-calcification and endothelialization of bioprosthetic heart valve

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Regenerative Biomaterials 2024年第2期3卷 123-136页

作者： Haoshuang Wu Nuoya Chen Tiantian Zheng Li Li Mengyue Hu Yumei Qin Gaoyang Guo Li Yang Yunbing Wang National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610065China Institute of Clinical Pathology West China Hospital of Sichuan UniversityChengdu 610041China College of Polymer Science and Engineering Sichuan UniversityChengdu 610065China

Bioprosthetic heart valve(BHV)replacement has been the predo-minant treatment for severe heart valve diseases over *** clinically available BHVs are crosslinked by glutaraldehyde(GLUT),while the high toxicity of residual GLUT could initiate calcification,severe thrombosis,and delayed ***,we construed a mechanically integrating robust hydrogel-tissue hybrid to improve the performance of *** particular,recombinant humanized coilagen type Ⅲ(rhCOLⅢ),which was precisely customized with anti-coagulant and pro-endothelialization bioactivity,was first incorporated into the polyvinyl alcohol(PVA)-based hydrogel via hydrogen bond ***,tannic acid was introduced to enhance the mechanicalperfo of PVA-based hvdrogel and interfacial bonding between the hydrogel layer and bio-derived tissue due to the strong affinity for a wide range of *** vitro and in vivo experimental results confirmed that the GLUT-crosslinked BHVs modified by the robust PVA-based hydrogel embedded rhCOLII and TA possessed long-term anti-coagulant,accelerated endothelialization,mild inflammatory response and anti-calcification ***,our mechanically integrating robust hydrogel-tissue hybrid strategy showed the potential to enhance the service function and prolong the service life of the BHVs after implantation.

关键词： bioprosthetic heart valves recombinant humanized collagen typeⅢ endothelialization anti-calcification anti-coagulation

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M2 macrophage-related molecular subtypes and prognostic index for prostate cancer patients through integrating single-cell and bulk RNA sequencing analysis

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Genes & Diseases 2024年第4期11卷 131-133页

作者： Dechao Feng Xu Shi Dengxiong Li Ruicheng Wu Jie Wang Wuran Wei Ping Han Department of Urology Institute of UrologyWest China HospitalSichuan UniversityChengduSichuan 610041China

Prostate cancer(PCa)is considered as an age-related disease and accounts for the most prevalence of urinary malignancies in men.1 We previously analyzed the cellular landscape of tumor microenvironment in PCa patients,where we found that cancer-related fibroblasts might play an important role in tumorigenesis and the development of PCa and tumor-associated macrophage(TAM)could function synergistically with them.2 Thus,we further integrated single-cell and bulk RNA sequencing with meta-analysis to specify the prognostic effect of TAM on PCa and construct molecular subgroups and predictive index to guide clinical practice.

关键词： patients macrophage cancer

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NLRP3 and autophagy in retinal ganglion cell inflammation in age-related macular degeneration:potential therapeutic implications

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International Journal of Ophthalmology(English edition) 2024年第8期17卷 1531-1544页

作者： Xiao-Li Wang Yun-Xia Gao Qiong-Zhen Yuan Ming Zhang Department of Ophthalmology West China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina

Retinal degenerative diseases were a large group of diseases characterized by the primary death of retinal ganglion cells(RGCs).Recent studies had shown an interaction between autophagy and nucleotide-binding oligomerization domain-like receptor 3(NLRP3)inflammasomes,which may affect RGCs in retinal degenerative *** NLRP3 inflammasome was a protein complex that,upon activation,produces caspase-1,mediating the apoptosis of retinal cells and promoting the occurrence and development of retinal degenerative *** autophagy could inhibit NLRP3 inflammasome activation,while inhibited autophagy can promote NLRP3 inflammasome activation,which leaded to the accelerated emergence of drusen and lipofuscin deposition under the neurosensory *** activated NLRP3 inflammasome could further inhibit autophagy,thus forming a vicious cycle that accelerated the damage and death of *** review discussed the relationship between NLRP3 inflammasome and autophagy and its effects on RGCs in age-related macular degeneration,providing a new perspective and direction for the treatment of retinal diseases.

关键词： autophagy age-related macular degeneration NLRP3 inflammasome retinal degeneration retinal ganglion cells

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Protective effects of CY-09 and astaxanthin on NaIO_(3)-induced photoreceptor inflammation via the NLRP3/autophagy pathway

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1217-1231页

作者： Xiao-Li Wang Yun-Xia Gao Qiong-Zhen Yuan Ming Zhang Department of Ophthalmology West China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina

AIM:To study the effect of the NLRP3/autophagy pathway on the photoreceptor inflammatory response and the protective mechanism of CY-09 and astaxanthin(AST).METHODS:ICR mice were intraperitoneally injected NaIO_(3),CY-09,AST successively and divided into 5 groups,including the control,NaIO_(3),NaIO_(3)+CY-09,NaIO_(3)+AST,and NaIO_(3)+CY-09+AST *** domain optical coherence tomography and flash electroretinogram were examined and the retina tissues were harvested for immunohistochemistry,enzyme linked immunosorbent assay(ELISA),and Western *** pigment epithelium cell line(ARPE-19 cells)and mouse photoreceptor cells line(661W cells)were also treated with NaIO_(3),CY-09,and AST *** proliferation was assessed by cell counting kit-8(CCK-8)*** was analyzed by flow *** in autophagosome morphology were observed by transmission electron *** polymerase chain reaction(qPCR)was used to detect NLRP3 and ***3,caspase-1,cleaved caspase-1,p62,Beclin-1,and LC3 protein levels were measured by Western ***-1βand IL-18 were measured by ***:Compared with the control group,the activity of NaIO_(3)-treated 661W cells decreased within 24 and 48h,apoptosis increased,NLRP3,caspase-1,IL-1βand IL-18 levels increased,and autophagy-related protein levels increased(P<0.05).Compared with NaIO_(3) group,CY-09 and AST inhibited apoptosis(P<0.05),reduced NLRP3,caspase-1,IL-1βand IL-18 expression(P<0.05),and inhibited *** with the other groups,CY-09 combined with AST significantly decreased NLRP3 expression and inhibited the expression of the autophagy-related proteins p62,Beclin-1,and LC3 in vitro and in vivo(P<0.05).CONCLUSION:CY-09 and AST inhibit NaIO_(3)-induced inflammatory damage through the NLRP3/autophagy pathway in vitro and in ***-09 and AST may protect retina from inflammatory injury.

关键词： CY-09 astaxanthin retinal degeneration photoreceptor cells inflammation NLRP3

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Genes & Diseases 2024年第1期11卷 367-381页

作者： Yunchao Zhang Jiayu Tang Cheng Wang Qinxiu Zhang Anqi Zeng Linjiang Song School of Medical and Life Sciences Chengdu University of Traditional Chinese MedicineChengduSichuan 611137China Institute of Translational Pharmacology and Clinical Application Sichuan Academy of Chinese Medical ScienceChengduSichuan 610041China School of Pharmacy Chengdu University of Traditional Chinese MedicineChengduSichuan 611137China

The incidence and mortality rates of cancer are increasing every year worldwide but the survival rate of cancer patients is still ***,it is necessary to further elucidate the molecular mechanisms involved in tumor development and drug resis-tance to improve cancer cure or survival *** recent years,autophagy has become a hot topic in the field of oncology research,which plays a double-edged role in tumorigenesis,pro-gression,and drug ***,long non-coding RNA(lncRNA)has also been shown to regulate autophagy,and the two-sided nature of autophagy determines the dual regulatory role of autophagy-related IncRNAs(ARlncRNAs).Therefore,ARlncRNAs can be effective ther-apeutic targets for various ***,the high abundance and stability of ARlncR-NAs in tumor tissues make them promising *** this review,we summarized the roles and mechanisms of ARlncRNAs in tumor cell proliferation,apoptosis,migration,invasion,drug resistance,angiogenesis,radiation resistance,and immune *** addition,we described the clinical significance of these ARlncRNAs,including as biomarkers/therapeutic targets and their association with clinical drugs.

关键词： Apoptosis Autophagy Biomarker Cancer Drug resistance LncRNA

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NFHP-RN:AMethod of Few-Shot Network Attack Detection Based on the Network Flow Holographic Picture-ResNet

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Computer Modeling in Engineering & Sciences 2024年第7期140卷 929-955页

作者： Tao Yi Xingshu Chen Mingdong Yang Qindong Li Yi Zhu School of Cyber Science and Engineering Sichuan UniversityChengdu610065China CyberScience Research Institute Sichuan UniversityChengdu610065China chengdu Fengwei Technology Co. Ltd.Chengdu610041China

Due to the rapid evolution of Advanced Persistent Threats(APTs)attacks,the emergence of new and rare attack samples,and even those never seen before,make it challenging for traditional rule-based detection methods to extract universal rules for effective *** the progress in techniques such as transfer learning and meta-learning,few-shot network attack detection has ***,challenges in few-shot network attack detection arise from the inability of time sequence flow features to adapt to the fixed length input requirement of deep learning,difficulties in capturing rich information from original flow in the case of insufficient samples,and the challenge of high-level abstract *** address these challenges,a few-shot network attack detection based on NFHP(Network Flow Holographic Picture)-RN(ResNet)is ***,leveraging inherent properties of images such as translation invariance,rotation invariance,scale invariance,and illumination invariance,network attack traffic features and contextual relationships are intuitively represented in *** addition,an improved RN network model is employed for high-level abstract feature extraction,ensuring that the extracted high-level abstract features maintain the detailed characteristics of the original traffic behavior,regardless of changes in background ***,a meta-learning model based on the self-attention mechanism is constructed,achieving the detection of novel APT few-shot network attacks through the empirical generalization of high-level abstract feature representations of known-class network attack *** results demonstrate that the proposed method can learn high-level abstract features of network attacks across different traffic detail *** state-of-the-artmethods,it achieves favorable accuracy,precision,recall,and F1 scores for the identification of unknown-class network attacks through cross-validation onmultiple datasets.

关键词： APT attacks spatial pyramid pooling NFHP(network flow holo-graphic picture) ResNet self-attention mechanism meta-learning

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Traveling Wave Characteristics Based Pilot Protection Scheme for Hybrid Cascaded HVDC Transmission Line

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Journal of Modern Power Systems and Clean Energy 2024年第3期12卷 971-980页

作者： Dalin Mu Sheng Lin Xiaopeng Li the School of Electrical Engineering Southwest Jiaotong UniversityChengdu 611756China the State Grid sichuan Electric Power Research Institute Chengdu 610041China

The hybrid cascaded high-voltage direct current(HVDC)transmission system has various operation modes,and some operation modes have sharply increasing requirements for protection rapidity,while the traditional pilot differential protection(PDP)has poor rapidity,and even refuses to operate when faults occur on the DC ***,a novel pilot protection scheme based on traveling wave characteristics is ***,the adaptability of the traditional PDP applied in engineering is analyzed for different operation ***,the expressions of the forward traveling wave(FTW)and backward traveling wave(BTW)on the rectifier side and the inverter side are derived for different fault *** the theoretical derivation,the difference between the BTW and FTW on the rectifier side is less than zero,and the same is true on the inverter ***,in the event of an external fault of DC line,the difference between the BTW and FTW at nearfault terminal protection installation point is greater than ***,by summing over the product of the difference between BTW and FTW of the rectifier side and that of the inverter side,the fault identification criterion is *** simulation results show that the proposed pilot protection scheme can quickly and reliably identify the short-circuit faults of DC line in different operation modes.

关键词： Hybrid cascaded high-voltage direct current(HVDC)transmission system DC line operation mode pilot protection

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Development of a cell adhesion-based prognostic model for multiple myeloma:Insights into chemotherapy response and potential reversal of adhesion effects

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Oncology Research 2024年第4期32卷 753-768页

作者： QIAN HU MENGYAO WANG JINJIN WANG YALI TAO TING NIU Department of Hematology West China HospitalSichuan UniversityChengdu610041China

Multiple myeloma(MM)is a hematologic malignancy notorious for its high relapse rate and development of drug resistance,in which cell adhesion-mediated drug resistance plays a critical *** study integrated four RNA sequencing datasets(CoMMpass,GSE136337,GSE9782,and GSE2658)and focused on analyzing 1706 adhesionrelated *** univariate Cox regression analysis identified 18 key prognosis-related genes,including KIF14,TROAP,FLNA,MSN,LGALS1,PECAM1,and ALCAM,which demonstrated the strongest associations with poor overall survival(OS)in MM *** comprehensively evaluate the impact of cell adhesion on MM prognosis,an adhesion-related risk score(ARRS)model was constructed using Lasso Cox regression *** ARRS model emerged as an independent prognostic factor for predicting ***,our findings revealed that a heightened cell adhesion effect correlated with tumor resistance to DNA-damaging drugs,protein kinase inhibitors,and drugs targeting the PI3K/Akt/mTOR signaling ***,we identified promising drug candidates,such as tirofiban,pirenzepine,erlotinib,and bosutinib,which exhibit potential in reversing this *** vitro,experiments employing NCIH929,RPMI8226,and AMO1 cell lines confirmed that MM cell lines with high ARRS exhibited poor sensitivity to the aforementioned candidate *** employing siRNA-mediated knockdown of the key ARRS model gene KIF14,we observed suppressed proliferation of NCIH929 cells,along with decreased adhesion to BMSCs and *** study presents compelling evidence establishing cell adhesion as a significant prognostic factor in ***,potential molecular mechanisms underlying adhesion-related resistance are proposed,along with viable strategies to overcome such *** findings provide a solid scientific foundation for facilitating clinically stratified treatment of MM.

关键词： Cell adhesion Bioinformatics Prognosis Multiple myeloma CAM-DR

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Tumor biomarkers for diagnosis,prognosis and targeted therapy

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2391-2476页

作者： Yue Zhou Lei Tao Jiahao Qiu Jing Xu Xinyu Yang Yu Zhang Xinyu Tian Xinqi Guan Xiaobo Cen Yinglan Zhao Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China West China School of Pharmacy Sichuan UniversityChengdu 610041China School of Medicine Tibet UniversityLhasa 850000China National chengdu Center for Safety Evaluation of Drugs State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

Tumor biomarkers,the substances which are produced by tumors or the body’s responses to tumors during tumorigenesis and progression,have been demonstrated to possess critical and encouraging value in screening and early diagnosis,prognosis prediction,recurrence detection,and therapeutic efficacy monitoring of *** the past decades,continuous progress has been made in exploring and discovering novel,sensitive,specific,and accurate tumor biomarkers,which has significantly promoted personalized medicine and improved the outcomes of cancer patients,especially advances in molecular biology technologies developed for the detection of tumor ***,we summarize the discovery and development of tumor biomarkers,including the history of tumor biomarkers,the conventional and innovative technologies used for biomarker discovery and detection,the classification of tumor biomarkers based on tissue origins,and the application of tumor biomarkers in clinical cancer *** particular,we highlight the recent advancements in biomarker-based anticancer-targeted therapies which are emerging as breakthroughs and promising cancer therapeutic *** also discuss limitations and challenges that need to be addressed and provide insights and perspectives to turn challenges into opportunities in this ***,the discovery and application of multiple tumor biomarkers emphasized in this review may provide guidance on improved precision medicine,broaden horizons in future research directions,and expedite the clinical classification of cancer patients according to their molecular biomarkers rather than organs of origin.

关键词： diagnosis breakthrough biomarkers

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Red blood cell membrane-coated FLT3 inhibitor nanoparticles to enhance FLT3-ITD acute myeloid leukemia treatment

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Chinese Chemical Letters 2024年第9期35卷 303-308页

作者： Jisheng Liu Junli Chen Xifeng Zhang Yin Wu Xin Qi Jie Wang Xiang Gao Department of Neurosurgery and Institute of Neurosurgery State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalWest China Medical SchoolSichuan UniversityChengdu 610041China West China School of Basic Medical Sciences&Forensic Medicine Sichuan UniversityChengdu 610041China Department of Hematology West China HospitalSichuan UniversityChengdu 610041China

FMS-like tyrosine kinase 3(FLT3)is a viable and important therapeutic target for acute myeloid leukemia(AML).FLT3 internal tandem duplication(FLT3-ITD)mutations have been identified in approximately 30%of AML patients,and are associated with unfavorable prognosis,higher risk of relapse,drug resistance,and poor clinical *** FLT3 inhibitors have demonstrated promising efficacy,they cannot cure AML or even significantly extend the lives of patients with FLT3-ITD *** is partly because of poor water solubility,insufficient membrane penetration and short half-life of small molecule ***,the presence of enzymes like CYP3A4 in bone marrow accelerate the elimination and metabolism of FLT3 inhibitors,resulting in low plasma concentrations and side *** we report the erythrocyte membrane-camouflaged FLT3 inhibitor nanoparticles to enhance FLT3-ITD AML ***,we physically coextruded red blood cell(RBC)membrane vesicles with nanoparticles derived from FLT3 inhibitor F30 to obtain F30@RBC-M,which exhibited comparable potent FLT3-ITD inhibitory effects compared to free F30 in vitro,while displaying a higher potent antitumor efficacy in xenograft models due to the prolonged circulation ***,administration of F30@RBC-M significantly extended the survival of mice in a transplanted mouse model than F30 free *** findings suggest that RBC membrane-coated nanoparticles derived from FLT3 inhibitors hold promise as a tool to enhance the therapeutic efficacy to treat FLT3-ITD AML.

关键词： FLT3-ITD Acute myeloid leukemia AML Red blood cell membrane Biomimetics

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