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Hsp90-associated DNA replication checkpoint protein and proteasome-subunit components are involved in the age-related macular degeneration

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Chinese Medical Journal 2021年第19期134卷 2322-2332页

作者： Chen Xing Xiao-feng liu Chun-feng Zhang liu yang Department of Ophthalmology Peking University First HospitalBeijing 100034China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Hepatopancreatobiliary Surgery Department IPeking University Cancer Hospital&InstituteBeijing 100142China Department of Medical Genetics School of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China

Background:Age-related macular degeneration(AMD)is the leading cause of vision loss worldwide.However,the mechanisms involved in the development and progression of AMD are poorly delineated.We aimed to explore the critical genes involved in the progression of AMD.Methods:The differentially expressed genes(DEGs)in AMD retinal pigment epithelial(RPE)/choroid tissues were identified using the microarray datasets GSE99248 and GSE125564,which were downloaded from the gene expression omnibus database.The overlapping DEGs from the two datasets were screened to identify DEG-related biological pathways using gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.The hub genes were identified from these DEGs through protein-protein interaction network analyses.The expression levels of hub genes were evaluated by quantitative real-time polymerase chain reaction following the induction of senescence in ARPE-19 with FK866.Following the identification of AMD-related key genes,the potential small molecule compounds targeting the key genes were predicted by PharmacoDB.Finally,a microRNA-gene interaction network was constructed.Results:Microarray analyses identified 174 DEGs in the AMD RPE compared to the healthy RPE samples.These DEGs were primarily enriched in the pathways involved in the regulation of DNA replication,cell cycle,and proteasome-mediated protein polyubiquitination.Among the top ten hub genes,HSP90AA1,CHEK1,PSMA4,PSMD4,and PSMD8 were upregulated in the senescent ARPE-19 cells.Additionally,the drugs targeting HSP90AA1,CHEK1,and PSMA4 were identified.We hypothesize that Hsa-miR-16-5p might target four out of the five key DEGs in the AMD RPE.Conclusions:Based on our findings,HSP90AA1 is likely to be a central gene controlling the DNA replication and proteasome-mediated polyubiquitination during the RPE senescence observed in the progression of AMD.Targeting HSP90AA1,CHEK1,PSMA4,PSMD4,and/or PSMD8 genes through specific miRNAs or small molecules might potentially alleviate the progression of AMD

关键词： Age-related macular degeneration Retinal pigment epithelium Cell senescence HSP90AA1 DNA damage checkpoint Proteasomal subunit components

Synovial fluid-inspired biomimetic lubricating microspheres:Zwitterionic polyelectrolyte brushes-grafted microgels

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Friction 2023年第6期11卷 938-948页

作者： Guoqiang liu yang feng Xiaohua GAO Zhuo CHEN Nan ZHAO feng ZHOU Weimin liu Center of Advanced Lubrication and Seal Materials State Key Laboratory of Solidification ProcessingNorthwestern Polytechnical UniversityXi’an710072China State Key Laboratory of Solid Lubrication Lanzhou Institute of Chemical PhysicsChinese Academy of SciencesLanzhou730000China

Synovial fluid is made up of various biomacromolecules,including hyaluronic acid,aggrecans,lubricins,and phosphatidylcholine lipid,which are assembled onto the surface of articular cartilage in a gel state.Among them,brush-like biomacromolecules or assemblies have a vital effect on human joint lubrication.Inspired by this,the combination of brush-like molecular structures and gel-like assembly may be an efficient approach for the synthesis of biomimetic lubricating matters.Learning from the lubrication system of human joints,poly(2-methacryloyloxyethyl phosphorylcholine)(PMPC)brushes grafted poly(N-isopropylacrylamide-co-acrylic acid)(poly(NIPAAm-co-AA))microgels,abbreviated as MBs-g-MGs,were synthesized as one kind of biomimetic lubricating additives.It is worth noting that this bionic strategy considered both molecular structure and assembled form,which enabled this hairy microgel to achieve low friction in aqueous medium.Meanwhile,the effective lubrication was still achieved when using MBs-g-MGs at high temperature,indicating that this microgel maintains a good lubricating effect over a wide range of temperature.In addition,this kind of microgel possessed good biocompatibility,which laid the foundation for potential biomedical applications.Looking beyond,these biomimetic microgels may provide an effective lubricating effect for water-based sliding interfaces,especially in biomedical systems.

关键词： biomimetic design zwitterionic polyelectrolyte brushes polymeric microgels aqueous lubrication

Formation mechanism of partial stacking faults by incompletemixed-mode phase transformation: A case study of Fe-Ga alloys

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Journal of Materials Science & Technology 2022年第22期117卷 59-64页

作者： Tianzi yang Tianyu Ma feng liu Xiaobing Ren Frontier Institute of Science and Technology State Key Laboratory for Mechanical Behavior of Materialsand MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed MatterXi’an Jiaotong UniversityXi’an 710049China State Key Laboratory of Solidification Processing and Analytical and Testing Center Northwestern Polytechnical UniversityXi’an 710072China Center for Functional Materials National Institute for Materials ScienceTsukuba 305-0047IbarakiJapan

Partial stacking faults(PSFs) formed by incomplete mixed-mode phase transformation have been found to exhibit unfixed slip distance of closely-packed planes unlike those of the deformation-induced stacking faults(SFs) with fixed distance. Though engineering PSFs can yield appealing properties, such as the enhanced damping capacity, understanding of the interaction between lattice distortion and atomic diffusion and their influences on forming PSFs is still far from being clear. Herein we performed a case study on aged Fe-Ga alloy that undergoes a mixed-mode phase transformation from body-centered cubic(BCC)to ordered face-centered cubic(FCC). The TEM investigations showed that the faulted {111}-FCC distance of the PSFs is shorter than a/6 of the typical {111}- SFs in deformed FCC materials and the PSFs have disordered Fe and Ga arrangements. Further studies revealed that such PSFs will not be completely dissociated at FCC twin boundaries(TBs) even after long term isothermal aging. Consequently,the formation of PSFs can be ascribed to the transformation-dependent atomic ordering and lattice shear strain of the parent BCC lattice, where the diffusion-controlled glides of the PSFs-associated dislocations will accelerate atomic diffusions due to the dislocation-pipe effect along -FCC direction, but may hinder the atomic diffusions across the {111}-FCC TBs due to the retarding effect. This study may add important insight into the defects process during mixed-mode phase transformation and broaden the knowledge of the interaction between concurrently-happened lattice distortion and atomic diffusion.

关键词： Stacking faults Mixed-mode phase transformation Diffusion Lattice distortion Fe-Ga alloy

Spectroscopic data de-noising via training-set-free deep learning method

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Science China(Physics,Mechanics & Astronomy) 2023年第6期66卷 191-199页

作者： Dongchen Huang Junde liu Tian Qian Yi-feng yang Beijing National Laboratoryfor Condensed Matter Physics Institute of PhysicsChinese Academy of SciencesBeijing 100190China School of Physical Sciences University of Chinese Academy of SciencesBeijing 100190China Songshan Lake Materials Laboratory Dongguan 523808China

De-noising plays a crucial role in the post-processing of spectra.Machine learning-based methods show good performance in extracting intrinsic information from noisy data,but often require a high-quality training set that is typically inaccessible in real experimental measurements.Here,using spectra in angle-resolved photoemission spectroscopy(ARPES)as an example,we develop a de-noising method for extracting intrinsic spectral information without the need for a training set.This is possible as our method leverages the self-correlation information of the spectra themselves.It preserves the intrinsic energy band features and thus facilitates further analysis and processing.Moreover,since our method is not limited by specific properties of the training set compared with previous ones,it may well be extended to other fields and application scenarios where obtaining high-quality multidimensional training data is challenging.

关键词： de-noising deep learning spectroscopic data

Dynamic prediction of moving trajectory in pipe jacking: GRU-based deep learning framework

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Frontiers of Structural and Civil Engineering 2023年第7期17卷 994-1010页

作者： Yi-feng yang Shao-Ming LIAO Meng-Bo liu Department of Geotechnical Engineering College of Civil EngineeringTongji UniversityShanghai 200092China Key Laboratory of Road and Traffic Engineering of Ministry of Education Tongji UniversityShanghai 201804China

The moving trajectory of the pipe-jacking machine(PJM),which primarily determines the end quality of jacked tunnels,must be controlled strictly during the entire jacking process.Developing prediction models to support drivers in performing rectifications in advance can effectively avoid considerable trajectory deviations from the designed jacking axis.Hence,a gated recurrent unit(GRU)-based deep learning framework is proposed herein to dynamically predict the moving trajectory of the PJM.In this framework,operational data are first extracted from a data acquisition system;subsequently,they are preprocessed and used to establish GRU-based multivariate multistep-ahead direct prediction models.To verify the performance of the proposed framework,a case study of a large pipe-jacking project in Shanghai and comparisons with other conventional models(i.e.,long short-term memory(LSTM)network and recurrent neural network(RNN))are conducted.In addition,the effects of the activation function and input time-step length on the prediction performance of the proposed framework are investigated and discussed.The results show that the proposed framework can dynamically and precisely predict the PJM moving trajectory during the pipe-jacking process,with a minimum mean absolute error and root mean squared error(RMSE)of 0.1904 and 0.5011 mm,respectively.The RMSE of the GRU-based models is lower than those of the LSTM-and RNN-based models by 21.46%and 46.40%at the maximum,respectively.The proposed framework is expected to provide an effective decision support for moving trajectory control and serve as a foundation for the application of deep learning in the automatic control of pipe jacking.

关键词： dynamic prediction moving trajectory pipe jacking GRU deep learning

Decreased expression of gap junction delta-2 (GJD2) messenger RNA and connexin 36 protein in form-deprivation myopia of guinea pigs

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Chinese Medical Journal 2019年第14期132卷 1700-1705页

作者： Guo-Yuan yang Feng-Yang Liu Xia Li Qiu-Rong Zhu Bing-Jie Chen Long-Qian liu Department of Opthalmology West China HospitalSichuan UniversityChengduSichuan 610041China Department of Ophthalmology First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China

Background:More than ten genome-wide association studies have identified the significant association between the gap junction delta-2 (GJD2) gene and myopia.However,no functional studies have been performed to confirm that this gene is correlated with myopia.This study aimed to observe how this gene changed in mRNA and protein level in the form-deprivation myopia (FDM) animal model.Methods:Four-week-old guinea pigs were randomly divided into two groups:control and FDM groups (n =12 for each group).The right eyes of the FDM group were covered with opaque hemispherical plastic lenses for 3 weeks.For all the animals,refractive status,axial length (AL),and corneal radius of curvature were measured at baseline and 3 weeks later by streak retinoscope,A-scan ultrasonography,and keratometer,respectively.Retinal GJD2 mRNA expression and connexin 36 (Cx36) levels in FDM and control groups were measured by quantitative real-time PCR and Western blot analyses,respectively.Those results were compared using independent t test,Mann-Whitney U test,or paired t test.A significance level of P < 0.05 was used.Results:Three weeks later,the FDM group (form-deprived eyes) showed about a myopic shift of approximately-6.75 (-7.94 to -6.31) D,while the control group remained hyperopic with only a shift of-0.50 (-0.75 to 0.25) D (Z =-3.38,P < 0.01).The AL increased by 0.74 (0.61-0.76) and 0.10 (0.05-0.21) mm in FDM and control groups,respectively (Z =-3.37,P < 0.01).The relative mRNA expression of GJD2 in the FDM group decreased 31.58% more than the control group (t =11.44,P < 0.01).The relative protein expression of CX36 on the retina was lowered by 37.72% in form-deprivation eyes as compared to the controls (t=17.74,P < 0.01).Conclusion:Both the mRNA expression of GJD2 and Cx36 protein amount were significantly decreased in the retina of FDM guinea pigs.This indicates that Cx36 is involved in FDM development,providing compensating evidence for the results obtained from genome-wide association studies.

关键词： Connexin 36 Myopia Guinea pigs Gap junction

Advances in immunotherapy for biliary tract cancers

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Chinese Medical Journal 2024年第5期137卷 524-532页

作者： Yuhao Zhao Mao yang Jiayi feng Xu’an Wang Yingbin liu Department of Biliary–Pancreatic Surgery Renji Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200127China Shanghai Cancer Institute State Key Laboratory of Oncogenes and Related GenesShanghai 200127China Shanghai Key Laboratory of Biliary Tract Disease Shanghai 200082China

Biliary tract cancers(BTC),a heterogeneous disease with poor prognosis,including gallbladder cancer(GBC),intrahepatic cholangiocarcinoma(ICC),and extrahepatic cholangiocarcinoma(ECC).Although surgery is currently the primary regimen to treat BTC,most BTC patients are diagnosed at an advanced stage and miss the opportunity of surgical eradication.As a result,non-surgical therapy serves as the main intervention for advanced BTC.In recent years,immunotherapy has emerged as one of the most promising therapies in a number of solid cancers,and it includes immune checkpoint inhibitors(ICIs)monotherapy or combined therapy,tumor vaccines,oncolytic virus immunotherapy,adoptive cell therapy(ACT),and cytokine therapy.However,these therapies have been practiced in limited clinical settings in patients with BTC.In this review,we focus on the discussion of latest advances of immunotherapy in BTC and update the progress of multiple current clinical trials with different immunotherapies.

关键词： Immunotherapy Biliary tract cancers Immune checkpoint inhibitors Cholangiocarcinoma Gallbladder cancer

Multi-UAVs Collaborative Path Planning in the Cramped Environment

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IEEE/CAA Journal of Automatica Sinica 2024年第2期11卷 529-538页

作者： Siyuan feng Linzhi Zeng Jining liu Yi yang Wenjie Song School of Automation Beijing Institute of TechnologyNanjing 210039China Nanjing Research Institute of Electronics Technology Nanjing 210039China Yichang Testing Technique Research Institute Yichang 443003China IEEE

Due to its flexibility and complementarity, the multiUAVs system is well adapted to complex and cramped workspaces, with great application potential in the search and rescue(SAR) and indoor goods delivery fields. However, safe and effective path planning of multiple unmanned aerial vehicles(UAVs)in the cramped environment is always challenging: conflicts with each other are frequent because of high-density flight paths, collision probability increases because of space constraints, and the search space increases significantly, including time scale, 3D scale and model scale. Thus, this paper proposes a hierarchical collaborative planning framework with a conflict avoidance module at the high level and a path generation module at the low level. The enhanced conflict-base search(ECBS) in our framework is improved to handle the conflicts in the global path planning and avoid the occurrence of local deadlock. And both the collision and kinematic models of UAVs are considered to improve path smoothness and flight safety. Moreover, we specifically designed and published the cramped environment test set containing various unique obstacles to evaluating our framework performance thoroughly. Experiments are carried out relying on Rviz, with multiple flight missions: random, opposite, and staggered, which showed that the proposed method can generate smooth cooperative paths without conflict for at least 60 UAVs in a few minutes.The benchmark and source code are released in https://***/inin-xingtian/multi-UAVs-path-planner.

关键词： Collision avoidance conflict resolution multi-unmanned aerial vehicles(UAVs)system path planning

Research on numerical simulation of transient pressure for high-speed train passing through the most unfavourable length tunnel

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Transportation Safety and Environment 2023年第3期5卷 78-91页

作者： Zhao liu feng liu Shuanbao Yao Dawei Chen Mingzhi yang College of Mechanical Engineering Taiyuan University of TechnologyTaiyuan 030024China CRRC Qingdao Sifang Co.Ltd Qingdao 266111China Key Laboratory of Traffic Safety on Track of Ministry of Education Central South UniversityChangsha 410075China

The length of high-speed railway tunnel is an important factor affecting transient pressure of high-speed train.When the tunnel length is the most unfavourable,the transient pressure changes in the tunnel and on the surface of the train are the most severe,which may affect the safe operation of the train or damage the structure in the tunnel.Based on the three-dimensional,compressible,unsteady N-S equation and finite volume method,this paper uses the CFD numerical simulation method to study the change and amplitude distribution of the transient pressure on the train surface and the tunnel when a high-speed train passes through the most unfavourable length tunnel.A fast calculation method is proposed to save the cost of calculation;it has great applicability of pressure amplitude.The results show that the pressure distribution in the tunnel and on the surface of the train is affected by the train speed,the length of the train and the position of the measuring point.The minimum negative peak value in the tunnel appears at the position where the superposition phenomenon is the most severe,and the position will change with the speed of the train.There are two negative peak waveforms of the train surface pressure,and the first waveformn is greatly affected by the train speed.It improves a reference for studying the strength requirement of the most unfavourable length tunnels and trains,and ensures the safe operation of trains in tunnels of different lengths.

关键词： transient pressure high-speed train most unfavourable tunnel length