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| 1 | Macrophage-mediated tumor-targeted delivery of engineered Salmonella typhimurium VNP20009 in anti-PD1 therapy against melanoma显示文摘Bacterial antitumor therapy has great application potential given its unique characteristics,including genetic manipulation, tumor targeting specificity and immune system modulation. However,the nonnegligible side effects and limited efficacy of clinical treatment limit their biomedical applications. Engineered bacteria for therapeutic applications ideally need to avoid their accumulation in normal organs and possess potent antitumor activity. Here, we show that macrophage-mediated tumor-targeted delivery of Salmonella typhimurium VNP20009 can effectively reduce the toxicity caused by administrating VNP20009 alone in a melanoma mouse model. This benefits from tumor-induced chemotaxis for macrophages combined with their slow release of loaded strains. Inspired by changes in the tumor microenvironment, including a decrease in intratumoral dysfunctional CD8+T cells and an increase in PDL1 on the tumor cell surface, macrophages were loaded with the engineered strain VNP-PD1nb, which can express and secrete anti-PD1 nanoantibodies after they are released from macrophages. This novel triple-combined immunotherapy significantly inhibited melanoma tumors by reactivating the tumor microenvironment by increasing immune cell infiltration, inhibiting tumor cell proliferation, remodeling TAMs to an M1-like phenotype and prominently activating CD8+T cells. These data suggest that novel combination immunotherapy is expected to be a breakthrough relative to single immunotherapy. | Leyang Wu Lin Li Shufeng Li Lina Liu Wenjie Xin Chenyang Li Xingpeng Yin Xuebo Xu Feifei Bao Zichun Hua | 2022 | Acta Pharmaceutica Sinica B2022，12，10： | 3 |
| 2 | Remnant neuromuscular junctions in denervated muscles contribute to functional recovery in delayed peripheral nerve repair显示文摘Schwann cell proliferation in peripheral nerve injury(PNI)enhances axonal regeneration compared to central nerve injury.However,even in PNI,long-term nerve damage without repair induces degeneration of neuromuscular junctions(NMJs),and muscle atrophy results in irreversible dysfunction.The peripheral regeneration of motor axons depends on the duration of skeletal muscle denervation.To overcome this difficulty in nerve regeneration,detailed mechanisms should be determined for not only Schwann cells but also NMJ degeneration after PNI and regeneration after nerve repair.Here,we examined motor axon denervation in the tibialis anterior muscle after peroneal nerve transection in thy1-YFP mice and regeneration with nerve reconstruction using allografts.The number of NMJs in the tibialis anterior muscle was maintained up to 4 weeks and then decreased at 6 weeks after injury.In contrast,the number of Schwann cells showed a stepwise decline and then reached a plateau at 6 weeks after injury.For regeneration,we reconstructed the degenerated nerve with an allograft at 4 and 6 weeks after injury,and evaluated functional and histological outcomes for 10 to 12 weeks after grafting.A higher number of pretzel-shaped NMJs in the tibialis anterior muscle and better functional recovery were observed in mice with a 4-week delay in surgery than in those with a 6-week delay.Nerve repair within 4 weeks after PNI is necessary for successful recovery in mice.Prevention of synaptic acetylcholine receptor degeneration may play a key role in peripheral nerve regeneration.All animal experiments were approved by the Institutional Animal Care and Use Committee of Tokyo Medical and Dental University on 5 July 2017,30 March 2018,and 15 May 2019(A2017-311C,A2018-297A,and A2019-248A),respectively. | Leyang Li Hiroyuki Yokoyama Hidetoshi Kaburagi Takashi Hirai Kunikazu Tsuji Mitsuhiro Enomoto Yoshiaki Wakabayashi Atsushi Okawa | 2020 | Neural Regeneration Research2020，15，4： | 2 |
| 3 | Volunteered remote sensing data generation with air passengers as sensors显示文摘Remote sensing satellites are playing very important roles in diverse earth observation fields.However,long revisit period,high cost and dense cloud cover have been the main limitations of satellite remote sensing for a long time.This paper introduces the novel volunteered passenger aircraft remote sensing(VPARS)concept,which can partly overcome these problems.By obtaining aerial imaging data from passengers using a portable smartphone on a passenger aircraft,it has various advantages including low cost,high revisit,dense coverage,and partial anti-cloud,which can well complement conventional remote sensing data.This paper examines the concept of VPARS and give general data processing framework of VPARS.Several cases were given to validate this processing approach.Two preliminary applications on land cover classification and economic activity monitoring validate the applicability of the VPARS data.Furthermore,we examine the issues about data maintenance,potential applications,limitations and challenges.We conclude the VPARS can benefit both scientific and industrial communities who rely on remote sensing data. | Chisheng Wang Yongquan Wang Leyang Wang Zhongwen Hu Shaobiao Zhang Shuanglong Wang Wenqun Xiu Hongxing Cui Dan Wang Qingquan Li | 2021 | International Journal of Digital Earth2021，14，2： | 1 |
| 4 | Slip distribution inversion of seismic sub-fault dip iteration using gradient based optimizer algorithm显示文摘This paper considers setting different dips for different sub-faults to fit the actual rupture situation based on the fault rupture of the 2013 Lushan M_(S)7.0 earthquake.Meanwhile,combined with the coseismic GNSS data of the Lushan earthquake,the source parameters and sliding distribution of the Lushan earthquake fault are inversed.Firstly,we use the gradient based optimizer(GBO)in nonlinear inversion to obtain the source parameters of this seismic fault.The inversion results indicate that the strike of the fault is 206.52°,the dip is 44.10°,the length is 21.92 km,and the depth is 12.79 km.To refine the sliding distribution of the seismic fault,the seismic fault is divided into 3×3 sub-faults.Then,we fix the central sub-fault dip of 44.10°;the dip of other sub-faults is obtained by iteration.After that,the model is further divided into a fault layer model composed of 23×19 sub fault slices,and using the Matlab fitting function is used to fit the dip of the 23×19 sub faults.Finally,the Lushan seismic fault plane is established as a shovel structure with steep upper and gentle lower,steep south and gentle north.The slip distribution inversion results indicate that the depth of the slip peak is 13 km,the corresponding maximum slip momentum is 0.67 m,the seismic moment is 1.10×10^(19)N·m and the corresponding moment magnitude is MW6.66.The results above are consistent with the research results of seismology. | Leyang Wang Han Li Ming Pang | 2024 | Geodesy and Geodynamics2024，15，2： | 0 |
| 5 | GBO algorithm for seismic source parameters inversion显示文摘The use of geodetic observation data for seismic fault parameters inversion is the research hotspot of geodetic inversion, and it is also the focus of studying the mechanism of earthquake occurrence. Seismic fault parameters inversion has nonlinear characteristics, and the gradient-based optimizer(GBO) has the characteristics of fast convergence speed and falling into local optimum hardly. This paper applies GBO algorithm to simulated earthquakes and real LuShan earthquakes in the nonlinear inversion of the Okada model to obtain the source parameters. The simulated earthquake experiment results show that the algorithm is stable, and the seismic source parameters obtained by GBO are slightly closer to the true value than the multi peak particle swarm optimization(MPSO). In the 2013 LuShan earthquake experiment, the root mean square error between the deformation after forwarding of fault parameters obtained by the introduced GBO algorithm and the surface observation deformation was 3.703 mm, slightly better than 3.708 mm calculated by the MPSO. Moreover, the inversion result of GBO algorithm is better than MPSO algorithm in stability. The above results show that the introduced GBO algorithm has a certain practical application value in seismic fault source parameters inversion. | Leyang Wang Han Li | 2023 | Geodesy and Geodynamics2023，14，2： | 0 |
| 6 | Camouflaging attenuated Salmonella by cryo-shocked macrophages for tumor-targeted therapy显示文摘Live bacteria-mediated antitumor therapies mark a pivotal point in cancer immunotherapy.However,the difficulty in reconciling the safety and efficacy of bacterial therapies has limited their application.Improving bacterial tumor-targeted delivery while maintaining biosafety is a critical hurdle for the clinical translation of live microbial therapy for cancer.Here,we developed“dead”yet“functional”Salmonella-loaded macrophages using liquid nitrogen cold shock of an attenuated Salmonella typhimurium VNP20009-contained macrophage cell line.The obtained“dead”macrophages achieve an average loading of approximately 257 live bacteria per 100 cells.The engineered cells maintain an intact cellular structure but lose their original pathogenicity,while intracellular bacteria retain their original biological activity and are delay freed,followed by proliferation.This“Trojan horse”-like bacterial camouflage strategy avoids bacterial immunogenicity-induced neutrophil recruitment and activation in peripheral blood,reduces the clearance of bacteria by neutrophils and enhances bacterial tumor enrichment efficiently after systemic administration.Furthermore,this strategy also strongly activated the tumor microenvironment,including increasing antitumor effector cells(including M1-like macrophages and CD8+Teffs)and decreasing protumor effector cells(including M2-like macrophages and CD4+Tregs),and ultimately improved antitumor efficacy in a subcutaneous H22 tumor-bearing mouse model.The cryo-shocked macrophage-mediated bacterial delivery strategy holds promise for expanding the therapeutic applications of living bacteria for cancer. | Leyang Wu Zengzheng Du Lin Li Liyuan Qiao Shuhui Zhang Xingpeng Yin Xiaoyao Chang Chenyang Li Zichun Hua | 2024 | Signal Transduction and Targeted Therapy2024，9，2： | 0 |
| 7 | Recent Advances in the Geodesy Data Processing显示文摘Geodetic functional models,stochastic models,and model parameter estimation theory are fundamental for geodetic data processing.In the past five years,through the unremitting efforts of Chinese scholars in the field of geodetic data processing,according to the application and practice of geodesy,they have made significant contributions in the fields of hypothesis testing theory,un-modeled error,outlier detection,and robust estimation,variance component estimation,complex least squares,and ill-posed problems treatment.Many functional models such as the nonlinear adjustment model,EIV model,and mixed additive and multiplicative random error model are also constructed and improved.Geodetic data inversion is an important part of geodetic data processing,and Chinese scholars have done a lot of work in geodetic data inversion in the past five years,such as seismic slide distribution inversion,intelligent inversion algorithm,multi-source data joint inversion,water reserve change and satellite gravity inversion.This paper introduces the achievements of Chinese scholars in the field of geodetic data processing in the past five years,analyzes the methods used by scholars and the problems solved,and looks forward to the unsolved problems in geodetic data processing and the direction that needs further research in the future. | Jianjun ZHU Leyang WANG Jun HU Bofeng LI Haiqiang FU Yibin YAO | 2023 | Journal of Geodesy and Geoinformation Science2023，6，3： | 0 |
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