Research (Washington, D.C.)最新文献_第5页

Lateral Hypothalamus Calcium/Calmodulin-Dependent Protein Kinase II α Neurons Encode Novelty-Seeking Signals to Promote Predatory Eating. 下丘脑外侧钙/钙调素依赖性蛋白激酶II α神经元编码寻求新奇的信号以促进掠夺性进食。

IF 11

Research (Washington, D.C.) Pub Date : 2022-08-05 eCollection Date: 2022-01-01 DOI: 10.34133/2022/9802382

Na Tan, Jiaying Shi, Lingyu Xu, Yanrong Zheng, Xia Wang, Nanxi Lai, Zhuowen Fang, Jialu Chen, Yi Wang, Zhong Chen

{"title":"Lateral Hypothalamus Calcium/Calmodulin-Dependent Protein Kinase II α Neurons Encode Novelty-Seeking Signals to Promote Predatory Eating.","authors":"Na Tan, Jiaying Shi, Lingyu Xu, Yanrong Zheng, Xia Wang, Nanxi Lai, Zhuowen Fang, Jialu Chen, Yi Wang, Zhong Chen","doi":"10.34133/2022/9802382","DOIUrl":"https://doi.org/10.34133/2022/9802382","url":null,"abstract":"Predatory hunting is an innate appetite-driven and evolutionarily conserved behavior essential for animal survival, integrating sequential behaviors including searching, pursuit, attack, retrieval, and ultimately consumption. Nevertheless, neural circuits underlying hunting behavior with different features remain largely unexplored. Here, we deciphered a novel function of lateral hypothalamus (LH) calcium/calmodulin-dependent protein kinase II α (CaMKIIα +) neurons in hunting behavior and uncovered upstream/downstream circuit basis. LH CaMKIIα + neurons bidirectionally modulate novelty-seeking behavior, predatory attack, and eating in hunting behavior. LH CaMKIIα + neurons integrate hunting-related novelty-seeking information from the medial preoptic area (MPOA) and project to the ventral periaqueductal gray (vPAG) to promote predatory eating. Our results demonstrate that LH CaMKIIα + neurons are the key hub that integrate MPOA-conveyed novelty-seeking signals and encode predatory eating in hunting behavior, which enriched the neuronal substrate of hunting behavior.","PeriodicalId":520765,"journal":{"name":"Research (Washington, D.C.)","volume":" ","pages":"9802382"},"PeriodicalIF":11.0,"publicationDate":"2022-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9394055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40347766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

CNS Organoid Surpasses Cell-Laden Microgel Assembly to Promote Spinal Cord Injury Repair. 中枢神经系统类器官超越细胞负载微凝胶组装促进脊髓损伤修复。

IF 11

Research (Washington, D.C.) Pub Date : 2022-08-03 eCollection Date: 2022-01-01 DOI: 10.34133/2022/9832128

Zitian Wang, Haoran Zhao, Xiaowei Tang, Tianyu Meng, Davit Khutsishvili, Bing Xu, Shaohua Ma

{"title":"CNS Organoid Surpasses Cell-Laden Microgel Assembly to Promote Spinal Cord Injury Repair.","authors":"Zitian Wang, Haoran Zhao, Xiaowei Tang, Tianyu Meng, Davit Khutsishvili, Bing Xu, Shaohua Ma","doi":"10.34133/2022/9832128","DOIUrl":"https://doi.org/10.34133/2022/9832128","url":null,"abstract":"The choice of therapeutic agents remains an unsolved issue in the repair of spinal cord injury. In this work, various agents and configurations were investigated and compared for their performance in promoting nerve regeneration, including bead assembly and bulk gel of collagen and Matrigel, under acellular and cell-laden conditions, and cerebral organoid (CO) as the in vitro preorganized agent. First, in Matrigel-based agents and the CO transplantations, the recipient animal gained more axon regeneration and the higher Basso, Beattie, and Bresnahan (BBB) scoring than the grafted collagen gels. Second, new nerves more uniformly infiltrated into the transplants in bead form assembly than the molded chunks. Third, the materials loaded the neural progenitor cells (NPCs) or the CO implantation groups received more regenerated nerve fibers than their acellular counterparts, suggesting the necessity to transplant exogenous cells for large trauma (e.g., a 5 mm long spinal cord transect). In addition, the activated microglial cells might benefit from neural regeneration after receiving CO transplantation in the recipient animals. The organoid augmentation may suggest that in vitro maturation of a microtissue complex is necessary before transplantation and proposes organoids as the premium therapeutic agents for nerve regeneration.","PeriodicalId":520765,"journal":{"name":"Research (Washington, D.C.)","volume":" ","pages":"9832128"},"PeriodicalIF":11.0,"publicationDate":"2022-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9394056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40349843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Advances in the Emerging Gradient Designs of Li Metal Hosts. 新型锂金属载体梯度设计的研究进展。

IF 11

Research (Washington, D.C.) Pub Date : 2022-08-01 eCollection Date: 2022-01-01 DOI: 10.34133/2022/9846537

Wanqing Guan, Xiaoqi Hu, Yuhang Liu, Jinmeng Sun, Chen He, Zhuzhu Du, Jingxuan Bi, Ke Wang, Wei Ai

{"title":"Advances in the Emerging Gradient Designs of Li Metal Hosts.","authors":"Wanqing Guan, Xiaoqi Hu, Yuhang Liu, Jinmeng Sun, Chen He, Zhuzhu Du, Jingxuan Bi, Ke Wang, Wei Ai","doi":"10.34133/2022/9846537","DOIUrl":"https://doi.org/10.34133/2022/9846537","url":null,"abstract":"Developing host has been recognized a potential countermeasure to circumvent the intrinsic drawbacks of Li metal anode (LMA), such as uncontrolled dendrite growth, unstable solid electrolyte interface, and infinite volume fluctuations. To realize proper Li accommodation, particularly bottom-up deposition of Li metal, gradient designs of host materials including lithiophilicity and/or conductivity have attracted a great deal of attention in recent years. However, a critical and specialized review on this quickly evolving topic is still absent. In this review, we attempt to comprehensively summarize and update the related advances in guiding Li nucleation and deposition. First, the fundamentals regarding Li deposition are discussed, with particular attention to the gradient design principles of host materials. Correspondingly, the progress of creating different gradients in terms of lithiophilicity, conductivity, and their hybrid is systematically reviewed. Finally, future challenges and perspective on the gradient design of advanced hosts towards practical LMAs are provided, which would provide a useful guidance for future studies.","PeriodicalId":520765,"journal":{"name":"Research (Washington, D.C.)","volume":" ","pages":"9846537"},"PeriodicalIF":11.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33443276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 10

Surface-Condition-Dependent Deformation Mechanisms in Lead Nanocrystals. 铅纳米晶体中表面条件相关的变形机制。

IF 11

Research (Washington, D.C.) Pub Date : 2022-07-27 eCollection Date: 2022-01-01 DOI: 10.34133/2022/9834636

Hongtao Zhang, Wen Wang, Jun Sun, Li Zhong, Longbing He, Litao Sun

{"title":"Surface-Condition-Dependent Deformation Mechanisms in Lead Nanocrystals.","authors":"Hongtao Zhang, Wen Wang, Jun Sun, Li Zhong, Longbing He, Litao Sun","doi":"10.34133/2022/9834636","DOIUrl":"https://doi.org/10.34133/2022/9834636","url":null,"abstract":"Serving as nanoelectrodes or frame units, small-volume metals may critically affect the performance and reliability of nanodevices, especially with feature sizes down to the nanometer scale. Small-volume metals usually behave extraordinarily in comparison with their bulk counterparts, but the knowledge of how their sizes and surfaces give rise to their extraordinary properties is currently insufficient. In this study, we investigate the influence of surface conditions on mechanical behaviors in nanometer-sized Pb crystals by performing in situ mechanical deformation tests inside an aberration-corrected transmission electron microscope (TEM). Pseudoelastic deformation and plastic deformation processes were observed at atomic precision during deformation of pristine and surface-oxidized Pb particles, respectively. It is found that in most of the pristine Pb particles, surface atom diffusion dominates and leads to a pseudoelastic deformation behavior. In stark contrast, in surface-passivated Pb particles where surface atom diffusion is largely inhibited, deformation proceeds via displacive plasticity including dislocations, stacking faults, and twinning, leading to dominant plastic deformation without any pseudoelasticity. This research directly reveals the dramatic impact of surface conditions on the deformation mechanisms and mechanical behaviors of metallic nanocrystals, which provides significant implications for property tuning of the critical components in advanced nanodevices.","PeriodicalId":520765,"journal":{"name":"Research (Washington, D.C.)","volume":" ","pages":"9834636"},"PeriodicalIF":11.0,"publicationDate":"2022-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9362692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33438008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Design Rules of the Mixing Phase and Impacts on Device Performance in High-Efficiency Organic Photovoltaics. 高效有机光伏混合相设计规律及其对器件性能的影响。

IF 10.7

Research (Washington, D.C.) Pub Date : 2022-07-26 eCollection Date: 2022-01-01 DOI: 10.34133/2022/9817267

Jingnan Song, Ming Zhang, Tianyu Hao, Jun Yan, Lei Zhu, Guanqing Zhou, Rui Zeng, Wenkai Zhong, Jinqiu Xu, Zichun Zhou, Xiaonan Xue, Chun-Chao Chen, Weihua Tang, Haiming Zhu, Zaifei Ma, Zheng Tang, Yongming Zhang, Feng Liu

{"title":"Design Rules of the Mixing Phase and Impacts on Device Performance in High-Efficiency Organic Photovoltaics.","authors":"Jingnan Song, Ming Zhang, Tianyu Hao, Jun Yan, Lei Zhu, Guanqing Zhou, Rui Zeng, Wenkai Zhong, Jinqiu Xu, Zichun Zhou, Xiaonan Xue, Chun-Chao Chen, Weihua Tang, Haiming Zhu, Zaifei Ma, Zheng Tang, Yongming Zhang, Feng Liu","doi":"10.34133/2022/9817267","DOIUrl":"10.34133/2022/9817267","url":null,"abstract":"In nonfullerene acceptor- (NFA-) based solar cells, the exciton splitting takes place at both domain interface and donor/acceptor mixture, which brings in the state of mixing phase into focus. The energetics and morphology are key parameters dictating the charge generation, diffusion, and recombination. It is revealed that tailoringthe electronic properties of the mixing region by doping with larger-bandgap components could reduce the density of state but elevate the filling state level, leading to improved open-circuit voltage (V OC) and reduced recombination. The monomolecular and bimolecular recombinations are shown to be intercorrelated, which show a Gaussian-like relationship with V OC and linear relationship with short-circuit current density (J SC) and fill factor (FF). The kinetics of hole transfer and exciton diffusion scale with J SC similarly, indicating the carrier generation in mixing region and crystalline domain are equally important. From the morphology perspective, the crystalline order could contribute to V OC improvement, and the fibrillar structure strongly affects the FF. These observations highlight the importance of the mixing region and its connection with crystalline domains and point out the design rules to optimize the mixing phase structure, which is an effective approach to further improve device performance.","PeriodicalId":520765,"journal":{"name":"Research (Washington, D.C.)","volume":" ","pages":"9817267"},"PeriodicalIF":10.7,"publicationDate":"2022-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9362714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33438009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular Thermal Motion Modulated Room-Temperature Phosphorescence for Multilevel Encryption. 用于多级加密的分子热运动调制室温磷光。

IF 11

Research (Washington, D.C.) Pub Date : 2022-07-23 eCollection Date: 2022-01-01 DOI: 10.34133/2022/9782713

Jiaqiang Zhao, Guojuan Yan, Wei Wang, Shishi Shao, Binfang Yuan, Yan Jie Li, Xuepeng Zhang, Cheng Zhi Huang, Peng Fei Gao

{"title":"Molecular Thermal Motion Modulated Room-Temperature Phosphorescence for Multilevel Encryption.","authors":"Jiaqiang Zhao, Guojuan Yan, Wei Wang, Shishi Shao, Binfang Yuan, Yan Jie Li, Xuepeng Zhang, Cheng Zhi Huang, Peng Fei Gao","doi":"10.34133/2022/9782713","DOIUrl":"https://doi.org/10.34133/2022/9782713","url":null,"abstract":"The stimulus-responsive room-temperature phosphorescence (RTP) materials have become an increasingly significant topic in the fields of bioimaging, sensing, and anticounterfeiting. However, this kind of materials is scarce to date, especially for the ones with delicate stimulus-responsive behavior. Herein, a universal strategy for multilevel thermal erasure of RTP via chromatographic separation of host-guest doping RTP systems is proposed. The tunable host-guest systems, matrix materials, heating temperature, and time are demonstrated to allow precise six-level data encryption, QR code encryption, and thermochromic phosphorescence encryption. Mechanistic study reveals that the thermal-responsive property might be attributed to molecular thermal motion and the separation effect of the silica gel, which provides expanded applications of host-guest RTP materials such as cold chain break detection. This work offers a simple yet universal way to construct advanced responsive RTP materials.","PeriodicalId":520765,"journal":{"name":"Research (Washington, D.C.)","volume":" ","pages":"9782713"},"PeriodicalIF":11.0,"publicationDate":"2022-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40697391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Distribution- and Metabolism-Based Drug Discovery: A Potassium-Competitive Acid Blocker as a Proof of Concept. 基于分布和代谢的药物发现:一种钾竞争性酸阻滞剂作为概念的证明。

IF 11

Research (Washington, D.C.) Pub Date : 2022-07-22 eCollection Date: 2022-01-01 DOI: 10.34133/2022/9852518

Ming-Shu Wang, Yi Gong, Lin-Sheng Zhuo, Xing-Xing Shi, Yan-Guang Tian, Chang-Kang Huang, Wei Huang, Guang-Fu Yang

{"title":"Distribution- and Metabolism-Based Drug Discovery: A Potassium-Competitive Acid Blocker as a Proof of Concept.","authors":"Ming-Shu Wang, Yi Gong, Lin-Sheng Zhuo, Xing-Xing Shi, Yan-Guang Tian, Chang-Kang Huang, Wei Huang, Guang-Fu Yang","doi":"10.34133/2022/9852518","DOIUrl":"https://doi.org/10.34133/2022/9852518","url":null,"abstract":"Conventional methods of drug design require compromise in the form of side effects to achieve sufficient efficacy because targeting drugs to specific organs remains challenging. Thus, new strategies to design organ-specific drugs that induce little toxicity are needed. Based on characteristic tissue niche-mediated drug distribution (TNMDD) and patterns of drug metabolism into specific intermediates, we propose a strategy of distribution- and metabolism-based drug design (DMBDD); through a physicochemical property-driven distribution optimization cooperated with a well-designed metabolism pathway, SH-337, a candidate potassium-competitive acid blocker (P-CAB), was designed. SH-337 showed specific distribution in the stomach in the long term and was rapidly cleared from the systemic compartment. Therefore, SH-337 exerted a comparable pharmacological effect but a 3.3-fold higher no observed adverse effect level (NOAEL) compared with FDA-approved vonoprazan. This study contributes a proof-of-concept demonstration of DMBDD and provides a new perspective for the development of highly efficient, organ-specific drugs with low toxicity.","PeriodicalId":520765,"journal":{"name":"Research (Washington, D.C.)","volume":" ","pages":"9852518"},"PeriodicalIF":11.0,"publicationDate":"2022-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40690122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Proteome-Wide Profiling of the Covalent-Druggable Cysteines with a Structure-Based Deep Graph Learning Network. 基于结构的深度图学习网络在蛋白质组范围内分析共价可用药半胱氨酸。

IF 11

Research (Washington, D.C.) Pub Date : 2022-07-21 eCollection Date: 2022-01-01 DOI: 10.34133/2022/9873564

Hongyan Du, Dejun Jiang, Junbo Gao, Xujun Zhang, Lingxiao Jiang, Yundian Zeng, Zhenxing Wu, Chao Shen, Lei Xu, Dongsheng Cao, Tingjun Hou, Peichen Pan

{"title":"Proteome-Wide Profiling of the Covalent-Druggable Cysteines with a Structure-Based Deep Graph Learning Network.","authors":"Hongyan Du, Dejun Jiang, Junbo Gao, Xujun Zhang, Lingxiao Jiang, Yundian Zeng, Zhenxing Wu, Chao Shen, Lei Xu, Dongsheng Cao, Tingjun Hou, Peichen Pan","doi":"10.34133/2022/9873564","DOIUrl":"https://doi.org/10.34133/2022/9873564","url":null,"abstract":"Covalent ligands have attracted increasing attention due to their unique advantages, such as long residence time, high selectivity, and strong binding affinity. They also show promise for targets where previous efforts to identify noncovalent small molecule inhibitors have failed. However, our limited knowledge of covalent binding sites has hindered the discovery of novel ligands. Therefore, developing in silico methods to identify covalent binding sites is highly desirable. Here, we propose DeepCoSI, the first structure-based deep graph learning model to identify ligandable covalent sites in the protein. By integrating the characterization of the binding pocket and the interactions between each cysteine and the surrounding environment, DeepCoSI achieves state-of-the-art predictive performances. The validation on two external test sets which mimic the real application scenarios shows that DeepCoSI has strong ability to distinguish ligandable sites from the others. Finally, we profiled the entire set of protein structures in the RCSB Protein Data Bank (PDB) with DeepCoSI to evaluate the ligandability of each cysteine for covalent ligand design, and made the predicted data publicly available on website.","PeriodicalId":520765,"journal":{"name":"Research (Washington, D.C.)","volume":" ","pages":"9873564"},"PeriodicalIF":11.0,"publicationDate":"2022-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40690121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Dip-Printed Microneedle Motors for Oral Macromolecule Delivery. 用于口服大分子输送的浸印微针马达。

IF 11

Research (Washington, D.C.) Pub Date : 2022-07-20 eCollection Date: 2022-01-01 DOI: 10.34133/2022/9797482

Xiaoxuan Zhang, Guopu Chen, Lijun Cai, Lu Fan, Yuanjin Zhao

{"title":"Dip-Printed Microneedle Motors for Oral Macromolecule Delivery.","authors":"Xiaoxuan Zhang, Guopu Chen, Lijun Cai, Lu Fan, Yuanjin Zhao","doi":"10.34133/2022/9797482","DOIUrl":"https://doi.org/10.34133/2022/9797482","url":null,"abstract":"Micromotors have demonstrated values in drug delivery, and recent attempts focus on developing effective approaches to generate functional micromotors to improve this area. Here, with the integration of microfluidic droplet printing and wettability-induced drawing photolithography, we present an innovative spatiotemporal serial multistep dip-printing strategy to generate novel independent microneedle motors (IMNMs) for orally delivering macromolecular drugs. As the strategy combines the advantages of the hydrophilic wettability, extension effects, and capillary effects, the IMNMs with an oblate basement and a needle-shaped head or a core-shell structured multicomponent head can be created by simply printing pregel droplets layer by layer, following with simultaneous wiredrawing and solidification. Owing to the polarized magnetic particles in the bottom basement and the rapidly dissolvable polymers as the middle basement, the resultant IMNMs can respond to magnetic fields, move to desired places under a magnet, penetrate tissue-like substrates, induce head-basement separation, and leave only the needles for cargo release. Based on these features, we have demonstrated that these IMNMs can deliver insulin via intestinal tracts to realize effective blood glucose control of diabetic rabbit models. These results indicate the practical values and bright future of the dip-printing stratagem and these IMNMs in clinical applications.","PeriodicalId":520765,"journal":{"name":"Research (Washington, D.C.)","volume":" ","pages":"9797482"},"PeriodicalIF":11.0,"publicationDate":"2022-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40690120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Programming of Regulatory T Cells In Situ for Nerve Regeneration and Long-Term Patency of Vascular Grafts. 调节性T细胞原位编程用于神经再生和血管移植物长期通畅。

IF 11

Research (Washington, D.C.) Pub Date : 2022-07-19 eCollection Date: 2022-01-01 DOI: 10.34133/2022/9826426

Yanhong Wang, Fangchao Xue, Yanzhao Li, Lin Lin, Yeqin Wang, Shanlan Zhao, Xingli Zhao, Yong Liu, Ju Tan, Gang Li, Haoran Xiao, Juan Yan, Hao Tian, Min Liu, Qiao Zhang, Zhaojing Ba, Lang He, Wenyan Zhao, Chuhong Zhu, Wen Zeng

{"title":"Programming of Regulatory T Cells In Situ for Nerve Regeneration and Long-Term Patency of Vascular Grafts.","authors":"Yanhong Wang, Fangchao Xue, Yanzhao Li, Lin Lin, Yeqin Wang, Shanlan Zhao, Xingli Zhao, Yong Liu, Ju Tan, Gang Li, Haoran Xiao, Juan Yan, Hao Tian, Min Liu, Qiao Zhang, Zhaojing Ba, Lang He, Wenyan Zhao, Chuhong Zhu, Wen Zeng","doi":"10.34133/2022/9826426","DOIUrl":"https://doi.org/10.34133/2022/9826426","url":null,"abstract":"Rapid integration into the host tissue is critical for long-term patency after small diameter tissue engineering vascular grafts (sdTEVGs) transplantation. Neural recognition may be required for host integration and functionalization of the graft. However, immune rejection and inflammation hinder nerve regeneration of sdTEVGs. Here, a CRISPR/dCas9-nanocarrier was used for targeted programming of regulatory T cells (Treg cells) in situ to promote nerve regeneration of sdTEVGs by preventing excessive inflammation. Treg cells and (C-C chemokine receptor) CCR2+ macrophage recruitment occurred after transplantation. The nanodelivery system upregulated ten eleven translocation (TET2) in Treg cells in vitro. Reprogrammed Treg cells upregulated anti-inflammatory cytokines and decreased the proportion of CCR2+ macrophages. IL-6 concentrations decreased to the levels required for nerve regeneration. Implantation of CRISPR/dCas9 nanodelivery system-modified sdTEVGs in rats resulted in Treg cell editing, control of excessive inflammation, and promoted nerve regeneration. After 3 months, nerve regeneration was similar to that observed in normal blood vessels; good immune homeostasis, consistency of hemodynamics, and matrix regeneration were observed. Neural recognition promotes further integration of the graft into the host, with unobstructed blood vessels without intimal hyperplasia. Our findings provide new insights into vascular implant functionalization by the host.","PeriodicalId":520765,"journal":{"name":"Research (Washington, D.C.)","volume":" ","pages":"9826426"},"PeriodicalIF":11.0,"publicationDate":"2022-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40697392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1