{"title":"Facile construction of dual-response super-resolution probes for tracking organelles dynamics","authors":"Daili Liu, Guiqian Fang, Yanfeng Wang, Caicai Meng, Zhidong Liu, Qixin Chen, Xintian Shao","doi":"10.1002/EXP.20230145","DOIUrl":"10.1002/EXP.20230145","url":null,"abstract":"<p>Super-resolution imaging techniques, such as structured illumination microscopy (SIM), have enabled researchers to obtain nanoscale organelle-level outputs in living systems, but they impose additional stringent requirements on fluorescence probes. However, high-performance, custom-designed SIM probes that can explain underlying biological processes remain unavailable. Herein, a customizable engineering toolkit is developed for the facile assembly of SIM probes suitable for subcellular component detection. This toolkit is used to customize a fluorescent molecule, <b>CPC</b> (coumarin–phenylhydrazine–carboxyl), capable of simultaneously monitoring peroxynitrite (ONOO<sup>−</sup>) and polarity distribution in mitochondria and lipid droplets (LDs), respectively, through functional ON–OFF mechanisms. The customized <b>CPC</b> molecule demonstrated excellent imaging capabilities under SIM, enabled the successful localization of multiple organelles, and reliably tracked the distribution of different components, thus facilitating the study of the interplay between organelles. Using <b>CPC</b>, the physical transition of intracellular LDs is demonstrated from heterogeneity to homogeneity. This was specifically observed during ferroptosis where the polarity of the LDs increased and their morphology became more contracted. Furthermore, the loss of LDs functionality could not counteract the accumulation of ONOO<sup>−</sup> within the mitochondria, leading to the decoupling of mitochondrial LDs during ferroptosis. These results confirmed the potential mechanism of LDs dysfunction and decoupling triggered via cumulative mitochondrial oxidative stress during ferroptosis. To summarize, this toolkit will be a powerful tool for examining subtle variations among components during the interplay between different organelles, thus offering novel avenues for understanding and treating related diseases.</p>","PeriodicalId":72997,"journal":{"name":"Exploration (Beijing, China)","volume":"4 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/EXP.20230145","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140251247","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}
Yajie Sun, Yan Hu, Yuanyuan Geng, Chao Wan, Yang Liu, Yifei Liao, Xiujuan Shi, Jonathan F. Lovell, Kunyu Yang, Honglin Jin
{"title":"A self-assembled, genetically engineered, irradiated tumor cell debris vaccine","authors":"Yajie Sun, Yan Hu, Yuanyuan Geng, Chao Wan, Yang Liu, Yifei Liao, Xiujuan Shi, Jonathan F. Lovell, Kunyu Yang, Honglin Jin","doi":"10.1002/EXP.20220170","DOIUrl":"10.1002/EXP.20220170","url":null,"abstract":"<p>Vaccine-based therapeutics for cancers face several challenges including lack of immunogenicity and tumor escape pathways for single antigen targets. It has been reported that radiotherapy has an in situ vaccine effect that provides tumor antigens following irradiation, helping to activate antigen-presenting cells (APCs). Herein, a new vaccine approach is developed by combining genetically engineered irradiated tumor cell debris (RTD) and hyaluronic acid (HA), termed HA@RTD. A cancer cell line is developed that overexpresses granulocyte-macrophage colony-stimulating factor (GM-CSF). A hydrogel was developed by covalent conjugation of HA with RTD proteins that acted as a potent vaccine system, the effects which were probed with T cell receptor sequencing. The engineered vaccine activated antitumor immunity responses and prevented tumor growth in mice even with a single immunization. HA@RTD vaccine efficacy was also assessed in therapeutic settings with established tumors and in combination with immune checkpoint blockade.</p>","PeriodicalId":72997,"journal":{"name":"Exploration (Beijing, China)","volume":"4 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/EXP.20220170","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140078530","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}
Kun Qian, Shu Gao, Zhaoning Jiang, Qihang Ding, Zhen Cheng
{"title":"Recent advances in mitochondria-targeting theranostic agents","authors":"Kun Qian, Shu Gao, Zhaoning Jiang, Qihang Ding, Zhen Cheng","doi":"10.1002/EXP.20230063","DOIUrl":"10.1002/EXP.20230063","url":null,"abstract":"<p>For its vital role in maintaining cellular activity and survival, mitochondrion is highly involved in various diseases, and several strategies to target mitochondria have been developed for specific imaging and treatment. Among these approaches, theranostic may realize both diagnosis and therapy with one integrated material, benefiting the simplification of treatment process and candidate drug evaluation. A variety of mitochondria-targeting theranostic agents have been designed based on the differential structure and composition of mitochondria, which enable more precise localization within cellular mitochondria at disease sites, facilitating the unveiling of pathological information while concurrently performing therapeutic interventions. Here, progress of mitochondria-targeting theranostic materials reported in recent years along with background information on mitochondria-targeting and therapy have been briefly summarized, determining to deliver updated status and design ideas in this field to readers.</p>","PeriodicalId":72997,"journal":{"name":"Exploration (Beijing, China)","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/EXP.20230063","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140264626","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}
{"title":"Recent advances in bacteria-based platforms for inflammatory bowel diseases treatment","authors":"Jiaoying Lu, Xinyuan Shen, Hongjun Li, Juan Du","doi":"10.1002/EXP.20230142","DOIUrl":"10.1002/EXP.20230142","url":null,"abstract":"<p>Inflammatory bowel disease (IBD) is a recurring chronic inflammatory disease. Current treatment strategies are aimed at alleviating clinical symptoms and are associated with gastrointestinal or systemic adverse effects. New delivery strategies are needed for the treatment of IBD. Bacteria are promising biocarriers, which can produce drugs in situ and sense the gut in real time. Herein, we focus on recent studies of engineered bacteria used for IBD treatment and introduce the application of engineered bacteria in the diagnosis. On this basis, the current dilemmas and future developments of bacterial delivery systems are discussed.</p>","PeriodicalId":72997,"journal":{"name":"Exploration (Beijing, China)","volume":"4 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/EXP.20230142","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140265176","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}
Zhaoyang Ye, Linsheng Li, Ling Yang, Li Zhuang, Ashok Aspatwar, Liang Wang, Wenping Gong
{"title":"Impact of diabetes mellitus on tuberculosis prevention, diagnosis, and treatment from an immunologic perspective","authors":"Zhaoyang Ye, Linsheng Li, Ling Yang, Li Zhuang, Ashok Aspatwar, Liang Wang, Wenping Gong","doi":"10.1002/EXP.20230138","DOIUrl":"10.1002/EXP.20230138","url":null,"abstract":"<p>The coexistence of diabetes mellitus (DM) and tuberculosis (TB) presents a significant global burden, with DM being recognized as a major risk factor for TB. This review comprehensively analyzes the immunological aspects of DM-TB comorbidity, shedding light on the impact of DM on TB pathogenesis and immune responses. It reveals that high blood glucose levels in TB patients contribute to reduced innate immune cell count, compromised phagocytic function, and delayed antigen presentation. These factors ultimately impair the clearance of <i>Mycobacterium tuberculosis</i> (MTB) and delay adaptive immune responses. With the interaction between TB and DM, there is an increase in inflammation and elevated secretion of pro-inflammatory cytokines by immune cells. This exacerbates the inflammatory response and contributes to poor treatment outcomes in TB. Moreover, the review explores the effects of DM on TB prevention, diagnosis, and treatment. It highlights how poor glycemic control, insulin resistance (IR), DM complications, and genetic factors increase the risk of MTB infection in individuals with DM. Additionally, DM-related immune suppression adversely affects the sensitivity of traditional diagnostic tests for TB, potentially resulting in underdiagnosis and delayed intervention. To mitigate the burden of TB in DM patients, the review emphasizes the need for further research on the mechanisms underlying DM reactivation in latent TB infection (LTBI). It shows how important it is to find and treat LTBI in DM patients as soon as possible and suggests looking into biomarkers that are specific to DM to make diagnosis more accurate.</p>","PeriodicalId":72997,"journal":{"name":"Exploration (Beijing, China)","volume":"4 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/EXP.20230138","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140265295","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}
{"title":"Research progress and application of high efficiency organic solar cells based on benzodithiophene donor materials","authors":"Congqi Lin, Ruixiang Peng, Jingyu Shi, Ziyi Ge","doi":"10.1002/EXP.20230122","DOIUrl":"10.1002/EXP.20230122","url":null,"abstract":"<p>In recent decades, the demand for clean and renewable energy has grown increasingly urgent due to the irreversible alteration of the global climate change. As a result, organic solar cells (OSCs) have emerged as a promising alternative to address this issue. In this review, we summarize the recent progress in the molecular design strategies of benzodithiophene (BDT)-based polymer and small molecule donor materials since their birth, focusing on the development of main-chain engineering, side-chain engineering and other unique molecular design paths. Up to now, the state-of-the-art power conversion efficiency (<i>PCE</i>) of binary OSCs prepared by BDT-based donor materials has approached 20%. This work discusses the potential relationship between the molecular changes of donor materials and photoelectric performance in corresponding OSC devices in detail, thereby presenting a rational molecular design guidance for stable and efficient donor materials in future.</p>","PeriodicalId":72997,"journal":{"name":"Exploration (Beijing, China)","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/EXP.20230122","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140411057","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}
Guanyi Wang, Xiongmin Mao, Wang Wang, Xiaolong Wang, Sheng Li, Zijian Wang
{"title":"Bioprinted research models of urological malignancy","authors":"Guanyi Wang, Xiongmin Mao, Wang Wang, Xiaolong Wang, Sheng Li, Zijian Wang","doi":"10.1002/EXP.20230126","DOIUrl":"10.1002/EXP.20230126","url":null,"abstract":"<p>Urological malignancy (UM) is among the leading threats to health care worldwide. Recent years have seen much investment in fundamental UM research, including mechanistic investigation, early diagnosis, immunotherapy, and nanomedicine. However, the results are not fully satisfactory. Bioprinted research models (BRMs) with programmed spatial structures and functions can serve as powerful research tools and are likely to disrupt traditional UM research paradigms. Herein, a comprehensive review of BRMs of UM is presented. It begins with a brief introduction and comparison of existing UM research models, emphasizing the advantages of BRMs, such as modeling real tissues and organs. Six kinds of mainstream bioprinting techniques used to fabricate such BRMs are summarized with examples. Thereafter, research advances in the applications of UM BRMs, such as culturing tumor spheroids and organoids, modeling cancer metastasis, mimicking the tumor microenvironment, constructing organ chips for drug screening, and isolating circulating tumor cells, are comprehensively discussed. At the end of this review, current challenges and future development directions of BRMs and UM are highlighted from the perspective of interdisciplinary science.</p>","PeriodicalId":72997,"journal":{"name":"Exploration (Beijing, China)","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/EXP.20230126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140445316","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}
{"title":"Oxygen-carrying semiconducting polymer nanoprodrugs induce sono-pyroptosis for deep-tissue tumor treatment","authors":"Fengshuo Wang, Yongliang Fan, Yue Liu, Xiangxin Lou, Linawati Sutrisno, Shaojun Peng, Jingchao Li","doi":"10.1002/EXP.20230100","DOIUrl":"10.1002/EXP.20230100","url":null,"abstract":"<p>Sonodynamic therapy (SDT) has been explored for cancer therapy, especially for deep tumors due to its low tissue penetration restriction. The therapeutic efficacy of SDT is limited due to the complicated tumor microenvironment. This study reports the construction of oxygen-carrying semiconducting polymer nanoprodrugs (OSPN<sub>pro</sub>) for deep tumor treatment via combining amplified SDT with pyroptosis. An oxygen carrier perfluorohexane, sonodynamic semiconducting polymer as the sonosensitizer, and reactive oxygen species (ROS)-responsive prodrug are co-loaded into a nanoparticle system, leading to the formation of these polymer nanoprodrugs. Such OSPN<sub>pro</sub> show an effective accumulation in tumor tissues after systemic administration, in which they deliver oxygen to relieve tumor hypoxia microenvironment and thus mediate amplified SDT via producing ROS under ultrasound (US) irradiation, even when the tumors are covered with a 2-cm chicken breast tissue. In addition, the ROS-responsive prodrugs are activated by the generated ROS to trigger pyroptosis of tumor cells. Such a sono-pyroptosis induces a strong antitumor immunity with obviously higher level infiltrations of effector immune cells into tumors. Therefore, OSPN<sub>pro</sub>-based combinational therapy can greatly inhibit the growth of 2-cm chicken breast tissue-covered deep tumors and suppress tumor metastasis. This study offers a prodrug nanoplatform for treatment of deep tumor via sono-pyroptosis strategy.</p>","PeriodicalId":72997,"journal":{"name":"Exploration (Beijing, China)","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/EXP.20230100","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139958488","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}
{"title":"Frontispiece: Viscoelastic blood coagulation testing system enabled by a non-contact triboelectric angle sensor (EXP2 1/2024)","authors":"Baocheng Wang, Xuelian Wei, Hanlin Zhou, Xiaole Cao, Enyang Zhang, Zhong Lin Wang, Zhiyi Wu","doi":"10.1002/EXP.20240105","DOIUrl":"https://doi.org/10.1002/EXP.20240105","url":null,"abstract":"<p>Thromboelastography (TEG) remains a convenient and effective viscoelastic coagulation testing device for guiding blood component transfusion and assessing the risk of thrombosis. This work presents a novel TEG that incorporates a miniaturized triboelectric coagulation sensor, enabling a comprehensive assessment of the coagulation system and advancing the miniaturization of traditional TEGs.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":72997,"journal":{"name":"Exploration (Beijing, China)","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/EXP.20240105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139739097","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}
Weidong Cheng, Mengyuan Zhao, Yuecheng Lai, Xin Wang, Huanyan Liu, Peng Xiao, Guang Mo, Bin Liu, Yunpeng Liu
{"title":"Inside Front Cover: Recent advances in battery characterization using in situ XAFS, SAXS, XRD, and their combining techniques: From single scale to multiscale structure detection (EXP2 1/2024)","authors":"Weidong Cheng, Mengyuan Zhao, Yuecheng Lai, Xin Wang, Huanyan Liu, Peng Xiao, Guang Mo, Bin Liu, Yunpeng Liu","doi":"10.1002/EXP.20240102","DOIUrl":"https://doi.org/10.1002/EXP.20240102","url":null,"abstract":"<p>Advanced battery characterization techniques contribute to revealing and clarifying the chemical reaction processes and mechanisms inside the batteries. From atomic scale to nanoscale to long-range periodic scale, from single scale to multiscale structure detection, this review comprehensively overviews the recent advances in battery characterization using in-situ synchrotron XAFS, SAXS, XRD, and their combining techniques.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":72997,"journal":{"name":"Exploration (Beijing, China)","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/EXP.20240102","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139739094","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}