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CCS Chemistry 2024年第1期6卷 177-195页

作者： Lang Zhao Shao-Hua Zhuo Tian-Yang Wang Jun-Jun Wu Jing-Yun Su wen-hao li Bo-Dou Zhang Yan-Mei li Key Lab of Bioorganic Phosphorus Chemistry&Chemical Biology Department of ChemistryTsinghua UniversityBeijing 100084 Beijing Institute for Brain Disorders Beijing 100069 Center for Synthetic and Systems Biology Tsinghua UniversityBeijing 100084

Cyclic dinucleotides(CDNs)are natural agonists of the stimulator of interferon genes(STING),which is an attractive immunotherapy target.Currently,CDNs and their derivatives are being investigated clinically.However,the poor bioavailability of exogenous CDNs has limited their application in immunotherapy.Although nanocarriers are widely used for cytosolic delivery of CDNs,their loading capacity is insufficient,and their complicated composition and purification process raises bio-compatibility concerns.Herein,we report a super-simplified CDN self-assembly strategy for carrier-free delivery of CDNs.In the presence of excess K^(+),CDNs form oligomers which further self-assemble with divalent metal ions(such as Mn^(2+))to form nanoparticles(NPs)in aqueous solution.We demonstrate that the self-assembled CDN NPs promote cellular uptake of CDNs and enhance tumor immunogenicity by remodeling the tumor microenvironment,inducing immunogenic tumor cell death and increasing tumorinfiltrating lymphocytes,which is conducive to the generation of tumor neoantigen-specific T-cell responses.We also demonstrate that the use of CDN NPs alone or in combination with immune checkpoint blockades inhibits tumor growth,highlighting the fact that CDN NPs are a potent platform for cancer immunotherapy.

关键词： cyclic dinucleotide STING carrierfree delivery tumor immunogenicity cancer immunotherapy

Experimental Investigation on the Vibration Attenuation of Tensegrity Prisms Integrated with Particle Dampers

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Acta Mechanica Solida Sinica 2022年第4期35卷 672-681页

作者： Si-Qi An hao-Ran Zou wen-hao li Zi-Chen Deng School of Mechanics Civil Engineering and ArchitectureNorthwestern Polytechnical UniversityXi’an710072China

Tensegrities made of tensile strings and compressed struts possess large strength-to-mass ratio values but tend to experience non-negligible vibration in dynamic environments because of poor structural damping.Here,we introduce particle dampers into a tensegrity prism to attenuate vibration,with the goal of establishing a lightweight and efficient approach of vibration suppression.To integrate the particle dampers and the tensegrity,a novel strut structure formed by assembling a solid strut and a hollow strut is devised,in which granular materials are inserted to develop a particle damper.The vibration attenuation performance of the tensegrity prism is investigated through exciter tests.According to the experimental parametric study,the influences of system parameters including excitation magnitude,the filling height of particles,particle size and the configuration of tensegrity prism on the vibration attenuation performance is analyzed.In addition,the experimental results regarding the dependence of the vibration attenuation on the system parameters are interpreted by the mechanism of collisions and frictions between particles and between particles and struts.The maximal vibration attenuation ratio of 76%can be achieved in the experiments.Thus,this research can provide insights into the design of lightweight tensegrity structures where vibration suppression is important,particularly in some dynamic environments.

关键词： Tensegrity structures Particle dampers Vibration suppression Assembling struts

A chitosan-mediated inhalable nanovaccine against SARS-CoV-2

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Nano Research 2022年第5期15卷 4191-4200页

作者： Shao-Hua Zhuo Jun-Jun Wu Lang Zhao wen-hao li Yu-Fen Zhao Yan-Mei li Key Lab of Bioorganic Phosphorus Chemistry&Chemical Biology Department of ChemistryTsinghua UniversityBeijing 100084China Beijing Institute for Brain Disorders Beijing 100069China Center for Synthetic and Systems Biology Tsinghua UniversityBeijing 100084China Institute of Drug Discovery Technology Ningbo UniversityNingbo 315221China

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),with several antigenic variants,has grown into a global challenge,and the rapid establishment of an immune barrier is crucial to achieving long-term control of the virus.This has led to a great demand for easy preparation and scalable vaccines,especially in low-income countries.Here,we present an inhalable nanovaccine comprising chitosan and SARS-CoV-2 spike protein.The chitosan-mediated nanovaccine enabled a strong spike-specific antibody immune response and augmented local mucosal immunity in bronchoalveolar lavage and lungs,which might be capable of protecting the host from infection without systemic toxicity.In addition,the enhanced adaptive immunity stimulated by chitosan showed potential protection against SARS-CoV-2.Furthermore,inhalation of the nanovaccine induced a comparable antibody response compared to intramuscular injection.This inhalable nanovaccine against SARS-CoV-2 offers a convenient and compliant strategy to reduce the use of needles and the need for medical staff.

关键词： severe acute respiratory syndrome coronavirus 2(SASR-CoV-2) inhalation nanovaccine chitosan

Inherent relationship between process parameters,crystallization and mechanical properties of continuous carbon fiber reinforced PEEK composites

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Defence Technology（防务技术） 2023年第6期24卷 269-284页

作者： Xiao-long Ma li-hua wen Shi-yu Wang Jin-you Xiao wen-hao li Xiao Hou School of Astronautics Northwestern Polytechnical UniversityXi'an710072China China Aerospace Science and Technology Corporation Beijing100048China

High-performance thermoplastic composites have been developed as significant structural materials for cutting-edge equipment in the aerospace and defence fields.However,the internal mechanism of processing parameters on mechanical properties in the manufacturing process of thermoplastic composite structures is still a serious challenge.The purpose of this study is to investigate the process/crystallization/property relationships for continuous carbon fiber(CF)reinforced polyether-ether-ketone(PEEK)composites.The composite laminates are fabricated according to orthogonal experiments via the thermoforming method.The mechanical performance is investigated in terms of crystallization properties and fracture morphology characterizations.Experimental results show that the mechanical performance and crystallization properties of thermoplastic composites are significantly affected by the coupling of processing parameters.The increased molding temperature,pressure,and holding time improve the degree of fiber/matrix infiltration and affect the crystallinity and crystalline morphology of the matrix,which further influences the mechanical properties of the composites.This is reflected in the test results that crystallinity has an approximately linear effect on mode-I interlaminar fracture toughness and transverse flexural modulus.As well as the higher molding temperature can destroy the pre-existent crystals to improve the toughness of the matrix,and the well-defined crystalline structures can be observed when fabricated at higher temperatures and longer periods of holding time.

关键词： Polymer matrix composites Thermoplastic Processing parameters Mechanical properties Crystallization

Pore and fracture characteristics of Cretaceous tight reservoir and its control effect on hydrocarbon accumulation in the liuhe Basin

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Petroleum Science 2022年第5期19卷 1939-1949页

作者： wen-hao li Er-Qiang Yang Min Wang Yan-Ran Huang Laboratory of Deep Oil and Gas China University of Petroleum(East China)QingdaoShandong266580China School of Geosciences China University of Petroleum(East China)QingdaoShandong266580China Hunan Provincial Key Laboratory of Shale Gas Resource Utilization Hunan University of Science and TechnologyXiangtanHunan411201China

Tight oil and gas in the Cretaceous has been found in the liuhe Basin,but the rules of tight reservoir and oil and gas accumulation are not clear.This paper discusses the developmental characteristics and evolution law of pores and fractures in the Cretaceous tight reservoir in the liuhe Basin,and reveals its controlling effect on tight oil and gas accumulation.The results show that intercrystalline pores,intergranular pores and dissolution pores are scattered and only developed in shallow tight reservoirs,while microfractures are developed in both shallow and deep layers,which are the main type of reservoir space in the study area.The results of mercury intrusion porosimetry and nitrogen gas adsorption show that with the increase of depth,the proportion of macropores(microcracks)increases,while the proportion of micropores decreases.There are two stages of microfractures developed in the study area,corresponding to the initial fault depression stage from late Jurassic to early late Cretaceous and compressional uplift at the end of late Cretaceous.According to the principle of“inversion and back-stripping method”,combined with the data of optical microscopy and inclusions,the time of each key diagenesis and its contribution to porosity are revealed,and the porosity evolution history of reservoirs in different diagenetic stages is quantitatively restored.The porosity reduction rate of compaction can reach more than 80%,which is the main reason for reservoir densification.The relationship between pore evolution history and oil and gas accumulation history reveals that during the oil and gas filling period of the Xiahuapidianzi Formation(90-85 Ma),the reservoir porosity is only 1.15%,but the development of microfractures in the first stage of the reservoir is conducive to oil and gas accumulation.

关键词： Tight reservoir Microscopic pore structure Microfracture Porosity evolution Hydrocarbon accumulation the liuhe Basin

STING and TLR7/8 agonists-based nanovaccines for synergistic antitumor immune activation

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Nano Research 2022年第7期15卷 6328-6339页

作者： Bo-Dou Zhang Jun-Jun Wu wen-hao li Hong-Guo Hu Lang Zhao Pei-Yang He Yu-Fen Zhao Yan-Mei li Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology(Ministry of Education) Department of ChemistryCenter for Synthetic and Systems BiologyTsinghua UniversityBeijing 100084China Beijing Institute for Brain Disorders Beijing 100069China Institute of Drug Discovery Technology Ningbo UniversityNingbo 315201China

Immunostimulatory therapies based on pattern recognition receptors(PRRs)have emerged as an effective approach in the fight against cancer,with the ability to recruit tumor-specific lymphocytes in a low-immunogenicity tumor environment.The agonist cyclic dinucleotides(CDNs)of the stimulator of interferon gene(STING)are a group of very promising anticancer molecules that increase tumor immunogenicity by activating innate immunity.However,the tumor immune efficacy of CDNs is limited by several factors,including relatively narrow cytokine production,inefficient delivery to STING,and rapid clearance.In addition,a single adjuvant molecule is unable to elicit a broad cytokine response and thus cannot further amplify the anticancer effect.To address this problem,two or more agonist molecules are often used together to synergistically enhance immune efficacy.In this work,we found that a combination of the STING agonist CDGSF and the Toll-like receptor 7/8(TLR7/8)agonist 522 produced a broader cytokine response.Subsequently,we developed multicomponent nanovaccines(MCNVs)consisting of a PC7A polymer as a nanocarrier encapsulating the antigen OVA and adjuvant molecules.These MCNVs activate bone marrow-derived dendritic cells(BMDCs)to produce multiple proinflammatory factors that promote antigen cross-presentation to stimulate specific antitumor Tcell responses.In in vivo experiments,we observed that MCNVs triggered a strong T-cell response in tumor-infiltrating lymphocytes,resulting in significant tumor regression and,notably,a 100%survival rate in mice through 25 days without other partnering therapies.These data suggest that our nanovaccines have great potential to advance cancer immunotherapy with increased durability and potency.

关键词： nanovaccines stimulator of interferon gene(STING) Toll-like receptor 7/8 synergistic immune activation lymph node targeting

Vascular endothelial growth factor B improves impaired glucose tolerance through insulin-mediated inhibition of glucagon secretion

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World Journal of Diabetes 2023年第11期14卷 1643-1658页

作者： Yu-Qi li Lu-Yang Zhang Yu-Chi Zhao Fang Xu Zhi-Yong Hu Qi-hao Wu wen-hao li Ya-Nuo li Department of Pathophysiology School of Basic MedicineBinzhou Medical UniversityYantai 264000Shandong ProvinceChina Department of Rheumatology and Immunology Yantaishan HospitalYantai 264000Shandong ProvinceChina Department of Surgery Yantaishan HospitalYantai 264000Shandong ProvinceChina School of Public Health and Management Binzhou Medical UniversityYantai 264000Shandong ProvinceChina The First School of Clinical Medicine Binzhou Medical UniversityYantai 264000Shandong ProvinceChina

BACKGROUND Impaired glucose tolerance(IGT)is a homeostatic state between euglycemia and hyperglycemia and is considered an early high-risk state of diabetes.When IGT occurs,insulin sensitivity decreases,causing a reduction in insulin secretion and an increase in glucagon secretion.Recently,vascular endothelial growth factor B(VEGFB)has been demonstrated to play a positive role in improving glucose metabolism and insulin sensitivity.Therefore,we constructed a mouse model of IGT through high-fat diet feeding and speculated that VEGFB can regulate hyperglycemia in IGT by influencing insulin-mediated glucagon secretion,thus contributing to the prevention and cure of prediabetes.AIM To explore the potential molecular mechanism and regulatory effects of VEGFB on insulin-mediated glucagon in mice with IGT.METHODS We conducted in vivo experiments through systematic VEGFB knockout and pancreatic-specific VEGFB overexpression.Insulin and glucagon secretions were detected via enzyme-linked immunosorbent assay,and the protein expression of phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)was determined using western blot.Further,mRNA expression of forkhead box protein O1,phosphoenolpyruvate carboxykinase,and glucose-6 phosphatase was detected via quantitative polymerase chain reaction,and the correlation between the expression of proteins was analyzed via bioinformatics.RESULTS In mice with IGT and VEGFB knockout,glucagon secretion increased,and the protein expression of PI3K/AKT decreased dramatically.Further,in mice with VEGFB overexpression,glucagon levels declined,with the activation of the PI3K/AKT signaling pathway.CONCLUSION VEGFB/vascular endothelial growth factor receptor 1 can promote insulin-mediated glucagon secretion by activating the PI3K/AKT signaling pathway to regulate glucose metabolism disorders in mice with IGT.

关键词： Vascular endothelial growth factor B Insulin-mediated Glucagon secretion Prediabetes Impaired glucose tolerance

OCT6 inhibits differentiation of porcine-induced pluripotent stem cells through MAPK and PI3K signaling regulation

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Zoological Research 2022年第6期43卷 911-922页

作者： Xin-Chun Yang Xiao-Long Wu wen-hao li Xiao-Jie Wu Qiao-Yan Shen Yun-Xiang li Sha Peng Jin-lian Hua College of Veterinary Medicine Shaanxi Centre of Stem Cells Engineering&TechnologyNorthwest A&F UniversityYanglingShaanxi 712100China

As a transcription factor of the Pit-Oct-Unc(POU)domain family,octamer-binding transcription factor 6(OCT6)participates in various aspects of stem cell development and differentiation.At present,however,its role in porcine-induced pluripotent stem cells(piPSCs)remains unclear.Here,we explored the function of OCT6 in piPSCs.We found that piPSCs overexpressing OCT6 maintained colony morphology and pluripotency under differentiation conditions,with a similar gene expression pattern to that of non-differentiated piPSCs.Functional analysis revealed that OCT6 attenuated the adverse effects of extracellular signal-regulated kinase(ERK)signaling pathway inhibition on piPSC pluripotency by activating phosphatidylinositol 3-kinase-protein kinase B(PI3K-AKT)signaling activity.Our research sheds new light on the mechanism by which OCT6 promotes PSC maintenance.

关键词： OCT6 piPSCs MAPK/ERK PI3K/AKT Pluripotency

Lack of evolutionary convergence in multiple primary lung cancer suggests insufficient specificity of personalized therapy

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Journal of Genetics and Genomics 2023年第5期50卷 330-340页

作者： Hua Cheng Ziyan Guo Xiaoyu Zhang Xiao-Jin Wang Zizhang li wen-wen Huo Hong-Cheng Zhong Xiao-Jian li Xiang-wen Wu wen-hao li Zhuo-wen Chen Tian-Chi Wu Xiang-Feng Gan Bei-Long Zhong Vassily ALyubetsky Leonid Yu Rusin Junnan Yang Qiyi Zhao Qing-Dong Cao Jian-Rong Yang Department of Thoracic Surgery The Fifth Affiliated HospitalSun Yat-Sen UniversityZhuhaiGuangdong 519000China Department of Genetics and Biomedical Informatics Zhongshan School of MedicineSun Yat-sen UniversityGuangzhouGuangdong 510080China Program in Cancer Research Zhongshan School of MedicineThe Fifth Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510080China Kharkevich Institute for Information Transmission Problems Russian Academy Sciences Moscow 127051Russia Department of Mathematical Logic and Theory of Algorithms Faculty of Mechanics and MathematicsLomonosov Moscow State UniversityMoscow 119991Russia Department of Infectious Diseases Third Affiliated HospitalSun Yat-Sen UniversityGuangzhouGuangdong 510630China Guangdong Provincial Key Laboratory of liver Disease Research the Third Affiliated Hospital Sun Yat-sen UniversityGuangzhouGuangdong 510630China Key Laboratory of Tropical Disease Control Ministry of EducationSun Yat-sen UniversityGuangzhouGuangdong 510080China

Multiple primary lung cancer(MPLC)is an increasingly prevalent subtype of lung cancer.According to recent genomic studies,the different lesions of a single MPLC patient exhibit functional similarities that may reflect evolutionary convergence.We perform whole-exome sequencing for a unique cohort of MPLC patients with multiple samples from each lesion found.Using our own and other relevant public data,evolutionary tree reconstruction reveals that cancer driver gene mutations occurred at the early trunk,indicating evolutionary contingency rather than adaptive convergence.Additionally,tumors from the same MPLC patient are as genetically diverse as those from different patients,while within-tumor genetic heterogeneity is significantly lower.Furthermore,the aberrant molecular functions enriched in mutated genes for a sample show a strong overlap with other samples from the same tumor,but not with samples from other tumors or other patients.Overall,there is no evidence of adaptive convergence during the evolution of MPLC.Most importantly,the similar between-tumor diversity and between-patient diversity suggest that personalized therapies may not adequately account for the genetic diversity among different tumors in an MPLC patient.To fully exploit the strategic value of precision medicine,targeted therapies should be designed and delivered on a per-lesion basis.

关键词： Multiple primary lung cancer Cancer evolution Convergent evolution

Concurrent recycling chemistry for cathode/anode in spent graphite/liFePO_(4) batteries:Designing a unique cation/anion-co-workable dual-ion battery

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Journal of Energy Chemistry 2022年第1期31卷 166-171,I0005页

作者： Yun-Feng Meng hao-Jie liang Chen-De Zhao wen-hao li Zhen-Yi Gu Meng-Xuan Yu Bo Zhao Xian-Kun Hou Xing-Long Wu Faculty of Chemistry Northeast Normal UniversityChangchun 130024JilinChina MOE Key Laboratory for UV light-Emitting Materials and Technology Northeast Normal UniversityChangchun 130024JilinChina

With the increasing popularity of new en ergy electric vehicles,the dema nd for lithium-ion batteries(liBs)has been growing rapidly,which will produce a large number of spent liBs.Therefore,recycling of spe nt liBs has become an urge nt task to be solved,otherwise it will inevitably lead to serious environmental pollution.Herein,a unique recycling strategy is proposed to achieve the concurrent reuse of cathode and anode in the spent graphite/liFePO_(4) batteries.Along with such recycling process,a unique cathode composed of recycled LFP/graphite(RLFPG)with cation/anion-co-storage ability is designed for new-type dual-ion battery(DIB).As a result,the recycle-derived DIB of li/RLFPG is established with good electrochemical performance,such as an initial discharge capacity of 117.4 mA h g^(-1) at 25 mA g^(-1) and 78% capacity retention after 1000 cycles at 100 mA g^(-1).The working mechanism of li/RLFPG DIB is also revealed via in situ X-ray diffraction and electrode kinetics studies.This work not only presents a farreaching significance for large-scale recycling of spent liBs in the future,but also proposed a sustainable and econo mical method to design n ew-type sec on dary batteries as recycling of spe nt liBs.

关键词： Dual-ion batteries liFePO_(4) Graphite Spenr lithium-ion batteries Recycle