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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 | Pancreatitis-associated Protein-1 mRNA expression in mouse pancreasis upregulated by Lipopolysaccharide independent of cerulein-pancreatitis显示文摘 | Xingpeng Wang Bingxian Wang Jianxin Wu | 2001 | J Gast Hepa2001，16，： | 1 |
| 3 | Optimization design of fertilizer apparatus owned arc gears based on discrete element method显示文摘To improve the uniformity of the flow when fertilizer apparatus discharges fertilizer,a kind of fertilizer apparatus owned arc gears was designed.Also,the design and working principle of its general structure and key components were analyzed theoretically.Aiming at exploring the influence of arc structural parameters to the performance of arc gears discharging fertilizer,DEM simulation was used in this study.Fertilizer apparatus owned arc gears was taken as the research object to analyze the influence of two key components including the arc radius of gears’concave-grooves and the minimal length between two mutual meshing gears.The variation coefficient of fertilizer discharging amount stability and the linear determined coefficient of fertilizer discharging amount in unit time as evaluation index were selected.Two factors and five levels quadratic rotation orthogonal experiment was applied,and Design-Expert 8.0 software was used to achieve data processing and analysis.The results of experiment indicated that the arc radius of gears’concave-grooves had significant effect on the linear determined coefficient of fertilizer discharging amount in unit time,and the minimal length between two mutual meshing gears had significant effect on the variation coefficient of fertilizer discharging amount stability.The optimum structural parameters were 8.54 mm as the arc radius of gears’concave-grooves and 5.22 mm as the minimal length between two mutual meshing gears.Upon this circumstance,the variation coefficient was 0.28 and determination coefficient was 0.9972.The optimum apparatus was selected to conduct the bench test and field simulation test.The results indicated that the variation coefficient is 0.27,and the linear determined coefficient of is 0.9980.The results of simulation experiment were anastomotic basically with the real result,which showed that DEM simulation technology was usable to the experiment of testing fertilizer discharging.The results of this research can provide a reference to the improving of performance in discharging fertilizer. | Guoqiang Dun Zhiyong Gao Yuxuan Liu Wenyi Ji Ning Mao Xingpeng Wu Wenhui Liu | 2021 | International Journal of Agricultural and Biological Engineering2021，14，2： | 1 |
| 4 | Rationale and Study Design for Evaluating the Efficacy and Safety of Intracardiac Echocardiography-Guided Minimal-Fluoroscopy Ablation in Patients with Paroxysmal Atrial Fibrillation:A Non-Inferior,Multi-Center,Prospective Randomized Controlled Trial(PAF-ICE Trial)显示文摘The feasibility and safety of intracardiac echocardiography(ICE)-guided catheter ablation for atrial fibrillation(AF)using a minimal/zero-fluoroscopy approach have recently been reported.This approach helps to reduce ionizing radiation exposure and orthopedic complications resulting from using lead aprons.The objectives of this planned prospective,multicenter randomized controlled trial(RCT)(paroxysmal AF(PAF)-ICE trial;ChiCTR2000033624)are to evaluate the efficacy and safety of ICE-guided minimal-fluoroscopy ablation in patients with PAF and the impact on occupational hazards among lab staff.Patients will be randomized in a 1:1 ratio to 2 groups:minimal fluoroscopy group(n=216)and traditional approach group(n=216).In the minimal fluoroscopy group,an ICE catheter will be used for geometry/anatomic construction,transseptal puncture,catheter tracking,and effusion monitoring.Pulmonary vein isolation(PVI)will be performed using an open-irrigated radiofrequency SmartTouch Surround Flow or SmartTouch catheter(Biosense Webster,Diamond Bar,California,USA),and confirmed by a multipolar Lasso or PentaRay catheter(Biosense Webster).In the traditional approach group,an ICE catheter will not be used.Transseptal puncture will be performed under fluoroscopic guidance,with all geometries constructed by mapping the catheters.The primary efficacy endpoint is freedom from AF recurrence(without antiarrhythmic medications)at 12months after ablation.Other endpoints include duration of lead apron use,measures of intra-procedural efficiency,and peri-procedural complications.This RCT will evaluate the efficacy and safety of ICE-guided minimal-fluoroscopy ablation in patients with PAF,also evaluate the benefits to lab staff(regarding reducing occupational hazards)related to this“minimal/zero-fluoroscopy”and“leadless”mode. | Ruhong Jiang Xingpeng Liu Jidong Zhang Yu Chen Rui Wang Mengzuo Wu Deyong Long Jia Li Haixiong Wang Jie Fan Weizhu Ju Weili Ge Xu Liu Hai Deng Weijian Wang Pingzhen Yang Ding Li Xiaobo Huang Xiongtao Liu Hailong Tao Paul CZei Roderick Tung Xunzhang Wang Chenyang Jiang | 2021 | Cardiology Discovery2021，1，4： | 1 |
| 5 | Controllable Bending of Bi-hydrogel Strips with Differ ent ial Swelling显示文摘Bi-hydrogel strips consisting of a highly swelling layer and a non-swelling layer are investigated in this study,in which the differential swelling capabilities and mismatch strain in the composite structure drive the strips into a bending configuration when being exposed to solvents.A modified analytical model originated from Timoshenko theory on bi-material beam is proposed to predict the swelling-induced bending shape of the bi-hydrogel strips,with explicit relations of bending curvature and mid-span deflection versus mismatch strain.Different sets of experiments were performed to verify the analytical model and its solutions,in which the swellinginduced mismatch strain was systematically tuned by the selection of saline concentration.The broad agreements bet ween the t heore tical and experimen tai results indicate that the modified analytical model can be used to guide the design of morphing elements by modulating layer-bylayer mismatches in gel composites to produce precise and complex shape transformations for practical applications. | Yi Wu Xingpeng Hao Rui Xiao Ji Lin Zi Liang Wu Jun Yin Jin Qian | 2019 | Acta Mechanica Solida Sinica2019，32，5： | 0 |
| 6 | Model construction of soybean average diameter and hole parameters of seed-metering wheel based on DEM显示文摘To satisfy the demands of soybean precision sowing,this article starts with statistics of the physical parameters of soybean seeds in Heilongjiang province,China.The filling process of soybean seeds was analyzed,and the ratio relationship between the diameter,depth,chamfer length of seed-metering wheel’s holes and the mean diameter of soybean seeds was determined.EDEM was used to simulate seeding circumstances of hole seed-metering wheel with different holes’sizes.The hole diameter ratio,hole depth ratio,and chamfer length ratio were the test factors,while the percentage of single multiple and the empty seeds were test indexes.The triple quadratic regression orthogonal rotation combination test was designed,and the mathematical model between test indexes and test factors was established.Results showed that the influence of hole diameter ratio and hole depth ratio was significant(p<0.01)in the case of single,multiple and empty seed percentage while chamfer length ratio was only significant in single seed percentage compared to multiple and empty seeds percentage(p>0.05).The chamfer length ratio was 0.15,the hole diameter ratio was 1.63-1.73,the hole depth ratio was 0.81-1.20,the quality of seeding index was more than 90,and multiple and missing indexes were less than 6%and 4%,respectively.The soybean hole wheel seeding device was produced under the optimal parameter combination,to perform a comparative verification test with non-optimized parameters.The test showed anastomotic simulation results,verified the validity of the simulation.The seeding device after optimization expressed the best operating performance,which might satisfy the demands of soybean precision sowing.The study results can provide a theoretical reference for the optimization design of soybean seeding devices. | Guoqiang Dun Ning Mao Zhiyong Gao Xingpeng Wu Wenhui Liu Cheng Zhou | 2022 | International Journal of Agricultural and Biological Engineering2022，15，1： | 0 |
| 7 | Large-scale long terminal repeat insertions produced a significant set of novel transcripts in cotton显示文摘Genomic analysis has revealed that the 1,637-Mb Gossypium arboreum genome contains approximately 81%transposable elements(TEs),while only 57%of the 735-Mb G.raimondii genome is occupied by TEs.In this study,we investigated whether there were unknown transcripts associated with TE or TE fragments and,if so,how these new transcripts were evolved and regulated.As sequence depths increased from 4 to 100 G,a total of 10,284 novel intergenic transcripts(intergenic genes)were discovered.On average,approximately 84%of these intergenic transcripts possibly overlapped with the long terminal repeat(LTR)insertions in the otherwise untranscribed intergenic regions and were expressed at relatively low levels.Most of these intergenic transcripts possessed no transcription activation markers,while the majority of the regular genic genes possessed at least one such marker.Genes without transcription activation markers formed their+1 and-1 nucleosomes more closely(only(117±1.4)bp apart),while twice as big spaces(approximately(403.5±46.0)bp apart)were detected for genes with the activation markers.The analysis of 183 previously assembled genomes across three different kingdoms demonstrated systematically that intergenic transcript numbers in a given genome correlated positively with its LTR content.Evolutionary analysis revealed that genic genes originated during one of the whole-genome duplication events around 137.7million years ago(MYA)for all eudicot genomes or 13.7 MYA for the Gossypium family,respectively,while the intergenic transcripts evolved around 1.6 MYA,resultant of the last LTR insertion.The characterization of these low-transcribed intergenic transcripts can facilitate our understanding of the potential biological roles played by LTRs during speciation and diversifications. | Yan Yang Xingpeng Wen Zhiguo Wu Kun Wang Yuxian Zhu | 2023 | Science China(Life Sciences)2023，66，8： | 0 |
| 8 | 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 |
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