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Generated SecPen_NY-ESO-1_ubiquitin-pulsed dendritic cell cancer vaccine elicits stronger and specific T cell immune responses

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Acta Pharmaceutica Sinica B 2021年第2期11卷 476-487页

作者： Yunkai Yang Xiaohan Guo Bo hu Peng He Xiaowu Jiang Zuohuan Wang huaxing Zhu Lina hu Minghua Yu Meiqing Feng Shanghai Engineering Research Center of ImmunoTherapeutics School of PharmacyFudan UniversityShanghai 201203China Shanghai Novoprotein Biotechnology Co. Ltd.Shanghai 201203China Medical School of Yichun University Yichun 336000China Clinical Research Center 2nd Affiliated HospitalMedical College of Zhejiang UniversityHangzhou 310009China Department of Oncology Shanghai Pudong HospitalFudan University Pudong Medicine CenterShanghai 201399China

Dendritic cell-based cancer vaccines(DC vaccines)have been proved efficient and safe in immunotherapy of various cancers,including melanoma,ovarian and prostate ***,the clinical responses were not always *** we proposed a novel strategy to prepare DC *** the present study,a fusion protein SNU containing a secretin-penetratin(SecPen)peptide,NY-ESO-1 and ubiquitin was designed and *** establish the DC vaccine(DC-SNU),the mouse bone marrowderived DCs(BMDCs)were isolated,pulsed with SNU and maturated with cytokine *** peripheral blood mononuclear cells(PBMCs)from C57 BL/6 mice inoculated intraperitoneally with DCSNU were separated and cocultured with MC38/MC38NY-ESO-1 tumor cells or DC *** results show that SNU was successfully *** strategy made NY-ESO-1 entering cytoplasm of BMDCs more efficiently and degraded mainly by *** we expected,mature BMDCs expressed higher CD40,CD80 and CD86 than immature ***,the PBMCs released more IFN-γand TNF-αwhen stimulated with DC-SNU in vitro ***’s more,the PBMCs induced stronger and specific cytotoxicity towards MC38NY-ESO-1 tumor *** the above,it demonstrated that DC-SNU loaded with SecPen and ubiquitin-fused NY-ESO-1 could elicit stronger and specific T cell immune *** strategy can be used as a platform for DC vaccine preparation and applied to various cancers treatment.

关键词： Dendritic cells Cancer vaccine NY-ESO-1 SecPen Ubiquitin

Structural Characteristics and Molecular Mechanism of Hepatitis B Virus Reverse Transcriptase

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Virologica Sinica 2009年第6期24卷 509-517页

作者： hui FENG Kang-hong hu State Key Laboratory of Virology Wuhan Institute of Virology Chinese Academy of Sciences Wuhan 430071China

Hepatitis B virus (HBV), a typical member of the Hepadnaviridae family, is responsible for infections that cause B-type hepatitis which leads to severe public health problems around the world. The small enveloped DNA-containing virus replicates via reverse transcription, and this unique process is accomplished by the virally encoded reverse transcriptase (RT). This multi-functional protein plays a vital role in the viral life cycle. Here, we provide a summary of current knowledge regarding the structural characteristics and molecular mechanisms of HBV RT. Improved understanding of these processes is of both theoretical and practical significance for fundamental studies of HBV and drug discovery.

关键词： Hepadnavirus Hepatitis B virus (HBV) Reverse transcriptase

Microstructure and Texture Evolution of Fe-33Mn-3Si-3Al TWIP Steel on Strain

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Journal of Wuhan University of Technology(Materials Science) 2019年第1期34卷 176-182页

作者： hu Yangyang SU Yu Schoole of Materials Engineering Shanghai University of Engineering Science

The microstructure and texture evolution of Fe-33Mn-3Si-3Al twinning induced plasticity(TWIP) steel were studied by the scanning electron microscope(SEM) and X-ray diffraction(XRD) at room temperature. After quasi-static tensile, the texture evolution of different strain was observed. It was shown that the Goss and Brass components increased within the strain range of less than 0.6. Whereas, the main components were decreased when the strain levels were greater than 0.6. This behavior was attributed to the low stacking fault energy(SFE) and was related to the strain energy of this high manganese steel. At high strain levels, the high strain energy may contribute to the Brass components transition to the A(rot-Brass) components.

关键词： strain microstructure texture evolution TWIP steel strain energy

Million-scale data integrated deep neural network for phonon properties of heuslers spanning the periodic table

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npj Computational Materials 2023年第1期9卷 2155-2166页

作者： Alejandro Rodriguez Changpeng Lin Hongao Yang Mohammed Al-Fahdi Chen Shen Kamal Choudhary Yong Zhao Jianjun hu Bingyang Cao Hongbin Zhang Ming hu Department of Mechanical Engineering University of South CarolinaColumbiaSC 29208USA Theory and Simulation of Materials(THEOS) École Polytechnique Fédérale de LausanneCH-1015 LausanneSwitzerland Key Laboratory for Thermal Science and Power Engineering of Ministry of Education Department of Engineering MechanicsTsinghua UniversityBeijing 100084China Institute of Materials Science Technical University of DarmstadtDarmstadt 64287Germany Materials Science and Engineering Division National Institute of Standards and TechnologyGaithersburgMD 20899USA Department of Computer Science and Engineering University of South CarolinaColumbiaSC 29208USA

Existing machine learning potentials for predicting phonon properties of crystals are typically limited on a material-to-materialbasis, primarily due to the exponential scaling of model complexity with the number of atomic species. We address this bottleneckwith the developed Elemental Spatial Density Neural Network Force Field, namely Elemental-SDNNFF. The effectiveness andprecision of our Elemental-SDNNFF approach are demonstrated on 11,866 full, half, and quaternary Heusler structures spanning 55elements in the periodic table by prediction of complete phonon properties. Self-improvement schemes including active learningand data augmentation techniques provide an abundant 9.4 million atomic data for training. Deep insight into predicted ultralowlattice thermal conductivity (<1 Wm^(−1) K^(−1)) of 774 Heusler structures is gained by p–d orbital hybridization analysis. Additionally, aclass of two-band charge-2 Weyl points, referred to as “double Weyl points”, are found in 68% and 87% of 1662 half and 1550quaternary Heuslers, respectively.

关键词： properties phonon spanning

ESMD-Flow: An Intelligent Flow Forwarding Scheme with Endogenous Security Based on Mimic Defense in Space-Air-Ground Integrated Network

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China Communications 2022年第1期19卷 40-51页

作者： Ziyong Li Yuxiang hu Di Zhu JiangxingWu Yunjie Gu PLA Strategic Support Force Information Engineering University Zhengzhou 450002China 61660 Unit of PLA Beijing 100089China

The Space-Air-Ground Integrated Network(SAGIN) realizes the integration of space, air,and ground networks, obtaining the global communication ***-Defined Networking(SDN) architecture in SAGIN has become a promising solution to guarantee the Quality of Service(QoS).However, the current routing algorithms mainly focus on the QoS of the service, rarely considering the security requirement of flow. To realize the secure transmission of flows in SAGIN, we propose an intelligent flow forwarding scheme with endogenous security based on Mimic Defense(ESMD-Flow). In this scheme, SDN controller will evaluate the reliability of nodes and links, isolate malicious nodes based on the reliability evaluation value, and adapt multipath routing strategy to ensure that flows are always forwarded along the most reliable multiple paths. In addition, in order to meet the security requirement of flows, we introduce the programming data plane to design a multiprotocol forwarding strategy for realizing the multiprotocol dynamic forwarding of flows. ESMD-Flow can reduce the network attack surface and improve the secure transmission capability of flows by implementing multipath routing and multi-protocol hybrid forwarding mechanism. The extensive simulations demonstrate that ESMD-Flow can significantly improve the average path reliability for routing and increase the difficulty of network eavesdropping while improving the network throughput and reducing the average packet delay.

关键词： space-air-ground integrated network(SAGIN) endogenous security multipath routing multi-protocol forwarding

Transient growth in Poiseuille-Rayleigh-Bénard flows of binary fluids with Soret effect

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Applied Mathematics and Mechanics(English Edition) 2016年第9期37卷 1203-1218页

作者： Jun hu D.HENRY H.BENHADID Xieyuan YIN Institute of Applied Physics and Computational Mathematics Beijing 100088China Laboratoire de Mecanique des Fluides et d'Acoustique CNRS/Universitd de LyonEcole Centrale de Lyon/universite Lyon 1/INSA de LyonECL36 avenue Guy de Collongue69134 Ecully CedexFrance Department of Modern Mechanics University of Science and Technology of ChinaHefei 230027China

The transient growth due to non-normMity is investigated for the Poiseuille- Rayleigh-Benard problem of binary fluids with the Soret effect. For negative separation factors such as ψ = -0.1, it is found that a large transient growth can be obtained by the non-normal interaction of the two least-stable-modes, i.e., the upstream and downstream modes, which determine the linear critical boundary curves for small Reynolds numbers. The transient growth is so strong that the optimal energy amplification factor G（t） is up to 10^2 - 10^3. While for positive separation factors such as ψ = 0.1, the transient growth is weak with the order O（I） of the amplification factor, which can even be computed by the least-stable-mode. However, for both cases, the least-stable-mode can govern the long-term behavior of the amplification factor for large time. The results also show that large Reynolds numbers have stabilization effects for the maximum amplification within moderate wave number regions. Meanwhile, much small negative or large positive separation factors and large Rayleigh numbers can enlarge the maximum transient growth of the pure streamwise disturbance with the wavenumber α= 3.14. Moreover, the initial and evolutionary two-dimensional spatial patterns of the large transient growth for the pure streamwise disturbance are exhibited with a plot of the velocity vector, spanwise vorticity, temperature, and concentration field. The initial three-layer cell vorticity struc- ture is revealed. When the amplification factor reaches the maximum Gmax, it develops into one cell structure with large amplification for the vorticity strength.

关键词： binary fluid Soret effect transient growth Poiseuille-Rayleigh-Benard flow

Short-term memory of danger signals or environmental stimuli in mesenchymal stem cells： implications for therapeutic potential

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Cellular & Molecular Immunology 2016年第3期13卷 369-378页

作者： Guang-Yang Liu Yang Liu Ying Lu Ya-Ru Qin Guo-hu Di Yong-Hong Lei hu-Xian Liu Yan-Qi Li Chutse Wu Xian-Wen hu Hai-Feng Duan Key Laboratory of Systems Bioengineering School of Chemical Engineering and Technology Tianjin University Tianjin China Beijing Institute of Radiation Medicine (BIRM) Beijing China 307 Hospital of the Chinese People's Liberation Army Beijing China 301 Hospital of the Chinese People's Liberation Army Beijing China Beijing Institute of Biotechnology (BIB) Beijing China

Mesenchymal stem/stromal cells （MSCs） possess some characteristics of immune cells, including a pro-inflammatory phenotype, an immunosuppressive phenotype, antibacterial properties and the expression of Toll-like receptor proteins. Here we show that, similar to immune cells, MSCs retain information from danger signals or environmental stimuli for a period of time. When treated with the pro-inflammatory factors lipopolysaccharide （LPS） or tumor necrosis factor-a （TNF-a）, MSCs display increased expression of IL-6, IL-8 and MCP-1. Following re-plating and several rounds of cell division in the absence of stimulating factors, the expression of IL-6, IL-8 and MCP-1 remained higher than in untreated cells for over 7 days. A spike in cytokine secretion occurred when cells were exposed to a second round of stimulation. We primed MSCs with LPS and LPS-primed MSCs had better therapeutic efficacy at promoting skin flap survival in a diabetic rat model than did unprimed MSCs. Finally, we found that several microRNAs, including miR146a, miR150 and miR155, along with the modification of DNA by 5-hydroxymethylcytosine （5hmC）, mediate the MSC response to LPS and TNF-e stimulation. Collectively, our data suggest that MSCs have a short-term memory of environmental signals, which may impact their therapeutic potential.

关键词： environmental stimuli mesenchymal stem cells pre-conditioning short-term memory

Optimization of chemistry and process parameters for control of intermetallic formation in Mg sludges

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Journal of Magnesium and Alloys 2024年第4期12卷 1431-1448页

作者： Y.Fu G.G.Wang A.hu Y.Li K.B.Thacker J.P.Weiler H.hu Department of Mechanical Automotive and Materials EngineeringUniversity of Windsor401 Sunset AveWindsorOntario N9B 3P4Canada Global Technology Centre Meridian Lightweight Technologies25 MacNab AveStrathroyOntario N7G 4H6Canada

Intermetallic formation in sludge during magnesium(Mg)melting,holding and high pressure die casting practices is a very important ***,very often it is overlooked by academia,original equipment manufacturers(OEM),metal ingot producers and even die *** aim of this study was to minimize the intermetallic formation in Mg sludge via the optimization of the chemistry and process *** Al8Mn5 intermetallic particles were identified by the microstructure analysis based on the Al and Mn *** design of experiment(DOE)technique,Taguchi method,was employed to minimize the intermetallic formation in the sludge of Mg alloys with various chemical compositions of Al,Mn,Fe,and different process parameters,holding temperature and holding *** sludge yield(SY)and intermetallic size(IS)was selected as two *** optimum combination of the levels in terms of minimizing the intermetallic formation were 9 wt.%Al,0.15 wt.%Mn,0.001 wt.%(10 ppm)Fe,690℃ for the holding temperature and holding at 30 mins for the holding time,*** best combination for smallest intermetallic size were 9 wt.%Al,0.15 wt.%Mn,0.001 wt.%(10 ppm)Fe,630℃ for the holding temperature and holding at 60 mins for the holding time,*** groups of sludge factors,Chemical Sludge(CSF),Physical Sludge(PSF)and Comprehensive Sludge Factors(and CPSF)were established for prediction of sludge yields and intermetallic sizes in Al-containing Mg *** CPSF with five independent variables including both chemical elements and process parameters gave high accuracy in prediction,as the prediction of the PSF with only the two processing parameters of the melt holding temperature and time showed a relatively large deviation from the experimental *** Chemical Sludge Factor was primarily designed for small ingot producers and die casters with a limited melting and holding capacity,of which process parameters could be fixed *** Physical Sludge Factor could be used f

关键词： Magnesium sludge Al-Mn intermetallic Optimization Taguchi method Sludge factor Chemical composition Process parameter

Genome-wide transcriptome analysis of porcine epidemic diarrhea virus virulent or avirulent strain-infected porcine small intestinal epithelial cells

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Virologica Sinica 2022年第1期37卷 70-81页

作者： Ouyang Peng Xiaona Wei Usama Ashraf Fangyu hu Yongbo Xia Qiuping Xu Guangli hu Chunyi Xue Yongchang Cao Hao Zhang State Key Laboratory of Biocontrol Life Sciences SchoolSun Yat-sen UniversityGuangzhou510006China Wen's Group Academy Wen's Foodstuffs Group CoLtdXinxingGuangdong527400China State Key Laboratory of Agricultural Microbiology Huazhong Agricultural UniversityWuhan430070China Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou510120China

Porcine epidemic diarrhea virus(PEDV)is the main cause of diarrhea,vomiting,and mortality in pigs,which results in devastating economic loss to the pig industry around the *** recent years,the advent of RNAsequencing technologies has led to delineate host responses at late stages of PEDV infection;however,the comparative analysis of host responses to early-stage infection of virulent and avirulent PEDV strains is currently ***,using the BGI DNBSEQ RNA-sequencing,we performed global gene expression profiles of pig intestinal epithelial cells infected with virulent(GDS01)or avirulent(HX)PEDV strains for 3,6,and 12 *** was observed that over half of all significantly dysregulated genes in both infection groups exhibited a down-regulated expression *** enrichment analyses indicated that the differentially expressed genes(DEGs)in the GDS01 group were predominantly related to autophagy and apoptosis,whereas the genes showing the differential expression in the HX group were strongly enriched in immune responses/*** the DEGs,the functional association of TLR3 and IFIT2 genes with the HX and GDS01 strains replication was experimentally validated by TLR3 inhibition and IFIT2 overexpression systems in cultured ***3 expression was found to inhibit HX strain,but not GDS01 strain,replication by enhancing the IFIT2 expression in infected *** conclusion,our study highlights similarities and differences in gene expression patterns and cellular processes/pathways altered at the early-stage infection of PEDV virulent and avirulent *** findings may provide a foundation for establishing novel therapies to control PEDV infection.

关键词： Coronavirus Porcine epidemic diarrhea virus(PEDV) Virulence Transcriptome Apoptosis Autophagy Immunity