{"title":"NPC1L1 on pancreatic adenocarcinoma cell functions as a two-pronged checkpoint against antitumor activity.","authors":"Ruiyang Zi, Kaicheng Shen, Pengfei Zheng, Xingxing Su, Yishi Yang, Yanrong Chen, Haisu Dai, Chengyi Mao, Yongling Lu, Liting Wang, Hongbo Ma, Wei Wang, Qingyun Li, Wei Lu, Chengtao Li, Shuangjia Zheng, Hui Shi, Xiaohong Liu, Zhiyu Chen, Houjie Liang, Juanjuan Ou","doi":"10.1016/j.xinn.2024.100783","DOIUrl":"10.1016/j.xinn.2024.100783","url":null,"abstract":"<p><p>Pancreatic adenocarcinoma (PAAD) is a highly lethal malignancy with an immunosuppressive microenvironment and a limited immunotherapy response<b>.</b> Cholesterol is necessary for rapid growth of cancer cells, and cholesterol metabolism reprogramming is a hallmark of PAAD. How PAAD cells initiate cholesterol reprogramming to sustain their growth demand and suppressive immunomicroenvironment remains elusive. In this study, we for the first time revealed that PAAD cells overcome cholesterol shortage and immune surveillance via ectopically overexpressing NPC1L1, a cholesterol transporter<b>,</b> but function as a two-pronged checkpoint, which not only directly suppresses TCR activation of CD8<sup>+</sup>T cells but also hijacks the intracellular cholesterol from CD8<sup>+</sup>T cells. <i>In vivo</i>, we showed that ezetimibe, an NPC1L1 inhibitor usually for hypercholesterolemia, efficiently prevented PAAD cells from depriving cholesterol of CD8<sup>+</sup>T cells, and improved the anti-tumor immunity of PAAD to synergize with PD-1 blockade, suggesting NPC1L1 as a promising target to rescue the anti-tumor activity in PAAD.</p>","PeriodicalId":36121,"journal":{"name":"The Innovation","volume":"6 3","pages":"100783"},"PeriodicalIF":33.2,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The InnovationPub Date : 2025-01-18eCollection Date: 2025-02-03DOI: 10.1016/j.xinn.2024.100773
Lei-Yun Wang, Bing Yu, Ying Peng, Kai Mou, Yan Zhan, Yi-Min Wang, Wei Ji, Chun Xu, Le-Dong Xiao, Yan Chen, Hua Wang, Zhi-Hua She, Peng Dai, Gan-Ye Zhao, Yang Wang, Lu-Lu Yu, Miao Yu, Ke Liu, Jia-Jia Cui, Rong Liu, Xi Li, Yuan-Fei Huang, Zhao-Qian Liu, Dong-Sheng Ouyang, Wei Zhang, Qing Li, Xing-Liang Xiong, Cheng-Xian Guo, Jin-Gao Li, Qiao-Li Lv, Qing-He Xing, Hai-Jian Wang, Zhi-Ling Li, Ji-Chu Wu, Long-Jian Huang, Jian He, Li-Ming Tan, Wen-Xu Hong, Xue-Chang Wang, Chao-Peng Li, Qin Lu, Long Zhang, Xiang-Dong Kong, Hong-Hao Zhou, Ji-Ye Yin
{"title":"The pharmacogenomic landscape in the Chinese: An analytics of pharmacogenetic variants in 206,640 individuals.","authors":"Lei-Yun Wang, Bing Yu, Ying Peng, Kai Mou, Yan Zhan, Yi-Min Wang, Wei Ji, Chun Xu, Le-Dong Xiao, Yan Chen, Hua Wang, Zhi-Hua She, Peng Dai, Gan-Ye Zhao, Yang Wang, Lu-Lu Yu, Miao Yu, Ke Liu, Jia-Jia Cui, Rong Liu, Xi Li, Yuan-Fei Huang, Zhao-Qian Liu, Dong-Sheng Ouyang, Wei Zhang, Qing Li, Xing-Liang Xiong, Cheng-Xian Guo, Jin-Gao Li, Qiao-Li Lv, Qing-He Xing, Hai-Jian Wang, Zhi-Ling Li, Ji-Chu Wu, Long-Jian Huang, Jian He, Li-Ming Tan, Wen-Xu Hong, Xue-Chang Wang, Chao-Peng Li, Qin Lu, Long Zhang, Xiang-Dong Kong, Hong-Hao Zhou, Ji-Ye Yin","doi":"10.1016/j.xinn.2024.100773","DOIUrl":"10.1016/j.xinn.2024.100773","url":null,"abstract":"<p><p>Pharmacogenomic landscapes and related databases are important for identifying the biomarkers of drug response and toxicity. However, these data are still lacking for the Chinese population. In this study, we constructed a pharmacogenomic landscape and an associated database using whole-genome sequencing data generated by non-invasive prenatal testing in 206,640 Chinese individuals. In total, 1,577,513 variants (including 331,610 novel variants) were identified among 3,538 pharmacogenes related to 2,086 drugs. We found that the variant spectrum in the Chinese population differed among the seven major regions. Regional differences also exist among provinces in China. The average numbers of drug enzyme, transporter, and receptor variants were 258, 557, and 632, respectively. Subsequent correlation analysis indicated that the pharmacogenes affecting multiple drugs had fewer variants. Among the 16 categories of drugs, we found that nervous system, cardiovascular system, and genitourinary system/sex hormone drugs were more likely to be affected by variants of pharmacogenes. Characteristics of the variants in the enzyme, transporter, and receptor subfamilies showed specificity. To explore the clinical utility of these data, a genetic association study was conducted on 1,019 lung cancer patients. Two novel variants, <i>AKT2</i> chr19:40770621 C>G and <i>SLC19A1</i> chr21:46934171 A>C, were identified as novel platinum response biomarkers. Finally, a pharmacogenomic database, named the Chinese Pharmacogenomic Knowledge Base (CNPKB: http://www.cnpkb.com.cn/), was constructed to collect all the data. In summary, a pharmacogenomic landscape and database for the Chinese population were constructed in this study, which could support personalized Chinese medicine in the future.</p>","PeriodicalId":36121,"journal":{"name":"The Innovation","volume":"6 2","pages":"100773"},"PeriodicalIF":33.2,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The InnovationPub Date : 2025-01-18eCollection Date: 2025-02-03DOI: 10.1016/j.xinn.2024.100777
Zhijie Wang, Chutian Wang, Ying Ji, Mingxin Yang, Chan Li, Mengyao Li, Jingru Yang, Hongyu Tang, Xianwei Luo, Haoyang Hao, Zhicai Liu, Kui Chen, Yanan Chang, Hui Yuan, Lin Feng, Gengmei Xing, Juan Li
{"title":"Magnetically driven bionic nanorobots enhance chemotherapeutic efficacy and the tumor immune response via precise targeting.","authors":"Zhijie Wang, Chutian Wang, Ying Ji, Mingxin Yang, Chan Li, Mengyao Li, Jingru Yang, Hongyu Tang, Xianwei Luo, Haoyang Hao, Zhicai Liu, Kui Chen, Yanan Chang, Hui Yuan, Lin Feng, Gengmei Xing, Juan Li","doi":"10.1016/j.xinn.2024.100777","DOIUrl":"10.1016/j.xinn.2024.100777","url":null,"abstract":"<p><p>We developed magnetically driven bionic drug-loaded nanorobots (MDNs) to accurately target tumors and deliver chemotherapy agents using a customized three-dimensional (3D) magnetic manipulation platform (MMP) system to precisely control their movement mode. MDNs were based on polyethylene glycol-modified homogeneous ultrasmall iron oxide nanoparticles (7.02 ± 0.18 nm). Doxorubicin (12% ± 2% [w/w]) was encapsulated in MDNs by an imide bond. MDNs could imitate the movement mode of a school of wild herrings (e.g., re-dispersion/arrangement/vortex/directional movement) to adapt to the changing and complex physiological environment through the 3D MMP system. MDNs overcame blood flow resistance and biological barriers using optimized magnetic driving properties according to <i>in vivo</i> imaging (magnetic resonance imaging and fluorescence) and histopathology. The performance of fabricated MDNs was verified through cells and tumor-bearing mouse models. The MDNs showed high efficiency of drug delivery and targeting at the tumor site (>10-fold), lower toxicity than free doxorubicin (5 mg/kg body weight), activated immune response in the tumor site, and significantly lengthened survival for mice. The synergistic interaction between MDNs and the 3D MMP system underscores the immense potential of this drug delivery system, indicating a potential revolution in the field of tumor chemotherapy.</p>","PeriodicalId":36121,"journal":{"name":"The Innovation","volume":"6 2","pages":"100777"},"PeriodicalIF":33.2,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The InnovationPub Date : 2025-01-18eCollection Date: 2025-03-03DOI: 10.1016/j.xinn.2024.100784
Juhua Luo, Hongtao Duan, Ying Xu, Ming Shen, Yunlin Zhang, Qitao Xiao, Guigao Ni, Kang Wang, Yihao Xin, Tianci Qi, Lian Feng, Yinguo Qiu, Erik Jeppesen, R Iestyn Woolway
{"title":"Global trends and regime state shifts of lacustrine aquatic vegetation.","authors":"Juhua Luo, Hongtao Duan, Ying Xu, Ming Shen, Yunlin Zhang, Qitao Xiao, Guigao Ni, Kang Wang, Yihao Xin, Tianci Qi, Lian Feng, Yinguo Qiu, Erik Jeppesen, R Iestyn Woolway","doi":"10.1016/j.xinn.2024.100784","DOIUrl":"10.1016/j.xinn.2024.100784","url":null,"abstract":"<p><p>Aquatic vegetation (AV) is vital for maintaining the health of lake ecosystems, with submerged aquatic vegetation (SAV) and floating/emergent aquatic vegetation (FEAV) representing clear and shaded states, respectively. However, global SAV and FEAV dynamics are poorly understood due to data scarcity. To address this gap, we developed an innovative AV mapping algorithm and workflow using satellite imagery (1.4 million Landsat images) from 1989 to 2021 and created a global database of AV across 5,587 shallow lakes. Our findings suggest that AV covers 108,186 km<sup>2</sup> on average globally, accounting for 28.9% (FEAV, 15.8%; SAV, 13.1%) of the total lake area. Over two decades, we observed a notable transition: SAV decreased by 30.4%, while FEAV increased by 15.6%, leading to a substantial net loss of AV. This global trend indicates a shift from clear to shaded conditions, increasingly progressing toward turbid states dominated by phytoplankton. We found that human-induced eutrophication was the primary driver of change until the early 2010s, after which global warming and rising lake temperatures became the dominant drivers. These trends serve as a warning sign of deteriorating lake health worldwide. With future climate warming and intensified eutrophication, these ongoing trends pose a significant risk of disrupting lake ecosystems.</p>","PeriodicalId":36121,"journal":{"name":"The Innovation","volume":"6 3","pages":"100784"},"PeriodicalIF":33.2,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Emerging MOFs, COFs, and their derivatives for energy and environmental applications.","authors":"Xinyue Zhang, Minjia Yan, Pei Chen, Jiaqi Li, Yuxuan Li, Hong Li, Xiaolu Liu, Zhongshan Chen, Hui Yang, Suhua Wang, Jianjun Wang, Zhenwu Tang, Qifei Huang, Jiehong Lei, Tasawar Hayat, Zhijian Liu, Liang Mao, Tao Duan, Xiangke Wang","doi":"10.1016/j.xinn.2024.100778","DOIUrl":"10.1016/j.xinn.2024.100778","url":null,"abstract":"<p><p>Traditional fossil fuels significantly contribute to energy supply, economic development, and advancements in science and technology. However, prolonged and extensive use of fossil fuels has resulted in increasingly severe environmental pollution. Consequently, it is imperative to develop new, clean, and pollution-free energy sources with high energy density and versatility as substitutes for conventional fossil fuels, although this remains a considerable challenge. Simultaneously, addressing water pollution is a critical concern. The development, design, and optimization of functional nanomaterials are pivotal to advancing new energy solutions and pollutant remediation. Emerging porous framework materials such as metal-organic frameworks (MOFs) and covalent organic frameworks (COFs), recognized as exemplary crystalline porous materials, exhibit potential in energy and environmental applications due to their high specific surface area, adjustable pore sizes and structures, permanent porosity, and customizable functionalities. This work provides a comprehensive and systematic review of the applications of MOFs, COFs, and their derivatives in emerging energy technologies, including the oxygen reduction reaction, oxygen evolution reaction, hydrogen evolution reaction, lithium-ion batteries, and environmental pollution remediation such as the carbon dioxide reduction reaction and environmental pollution management. In addition, strategies for performance adjustment and the structure-effect relationships of MOFs, COFs, and their derivatives for these applications are explored. Interaction mechanisms are summarized based on experimental discussions, theoretical calculations, and advanced spectroscopy analyses. The challenges, future prospects, and opportunities for tailoring these materials for energy and environmental applications are presented.</p>","PeriodicalId":36121,"journal":{"name":"The Innovation","volume":"6 2","pages":"100778"},"PeriodicalIF":33.2,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The InnovationPub Date : 2025-01-17eCollection Date: 2025-03-03DOI: 10.1016/j.xinn.2025.100807
Xueying Li, Woojong Kang, Xinyi Fan, Xinyi Tan, Justus Masa, Alex W Robertson, Yousung Jung, Buxing Han, John Texter, Yuanfu Cheng, Bin Dai, Zhenyu Sun
{"title":"Electrochemical CO<sub>2</sub> reduction to liquid fuels: Mechanistic pathways and surface/interface engineering of catalysts and electrolytes.","authors":"Xueying Li, Woojong Kang, Xinyi Fan, Xinyi Tan, Justus Masa, Alex W Robertson, Yousung Jung, Buxing Han, John Texter, Yuanfu Cheng, Bin Dai, Zhenyu Sun","doi":"10.1016/j.xinn.2025.100807","DOIUrl":"10.1016/j.xinn.2025.100807","url":null,"abstract":"<p><p>The high energy density of green synthetic liquid chemicals and fuels makes them ideal for sustainable energy storage and transportation applications. Electroreduction of carbon dioxide (CO<sub>2</sub>) directly into such high value-added chemicals can help us achieve a renewable C cycle. Such electrochemical reduction typically suffers from low faradaic efficiencies (FEs) and generates a mixture of products due to the complexity of controlling the reaction selectivity. This perspective summarizes recent advances in the mechanistic understanding of CO<sub>2</sub> reduction reaction pathways toward liquid products and the state-of-the-art catalytic materials for conversion of CO<sub>2</sub> to liquid C<sub>1</sub> (e.g., formic acid, methanol) and C<sub>2+</sub> products (e.g., acetic acid, ethanol, <i>n</i>-propanol). Many liquid fuels are being produced with FEs between 80% and 100%. We discuss the use of structure-binding energy relationships, computational screening, and machine learning to identify promising candidates for experimental validation. Finally, we classify strategies for controlling catalyst selectivity and summarize breakthroughs, prospects, and challenges in electrocatalytic CO<sub>2</sub> reduction to guide future developments.</p>","PeriodicalId":36121,"journal":{"name":"The Innovation","volume":"6 3","pages":"100807"},"PeriodicalIF":33.2,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The InnovationPub Date : 2025-01-17eCollection Date: 2025-04-07DOI: 10.1016/j.xinn.2024.100767
Shan Jiang, Hao Yu, Ting Zhao, Yao Lu, Xuesong Li, Lei Gao, Jie Mi, Wenzhe Xia, Lanjun Geng, Panpan Li, Mingyue Chen, Mengyao Kang, Jiang Liu, Yuwen Ke
{"title":"A high-definition spatiotemporal transcriptomic atlas of mammalian kidney development.","authors":"Shan Jiang, Hao Yu, Ting Zhao, Yao Lu, Xuesong Li, Lei Gao, Jie Mi, Wenzhe Xia, Lanjun Geng, Panpan Li, Mingyue Chen, Mengyao Kang, Jiang Liu, Yuwen Ke","doi":"10.1016/j.xinn.2024.100767","DOIUrl":"10.1016/j.xinn.2024.100767","url":null,"abstract":"<p><p>The structural composition of organs undergoes significant transformations during organogenesis, laying the foundation for their eventual functional architecture. In contrast, adult organs maintain structural homeostasis. However, the dynamics of organ structure during the organogenesis and homeostasis stages remain poorly understood. Here, we present a spatially resolved transcriptome atlas at single-cell resolution to explore the establishment and maintenance of kidney structure in mice. Our analysis reveals 40 migration-related cell-cell communication events during kidney organogenesis. Contrary to the traditional two-layer model (cortex and medulla), we demonstrate that the kidney develops a five-layer structure over time. Mechanistically, migration-related cell-cell communication drives this structural formation, with ephrin-A5 (Efna5) playing a key role in forming three distinct layers within the medulla. The spatial distribution of specific cell types and their gene expression patterns within these five layers likely enhances renal adaptation to hypoxic and hyperosmotic environments. Furthermore, Frizzled 4 receptor (Fzd4) is critical for the morphogenesis of the U-shaped loop of Henle (LoH). In the adult stage, when structural homeostasis prevails, only three migration-related ligand-receptor pairs are observed, and a stable four-layer structure is maintained due to the absence of progenitor cells. Overall, our findings illustrate the role of intercellular communication in driving the transition from structural establishment during organogenesis to stable maintenance in homeostasis. These insights provide new avenues for advancing organ regeneration strategies.</p>","PeriodicalId":36121,"journal":{"name":"The Innovation","volume":"6 4","pages":"100767"},"PeriodicalIF":33.2,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12131032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The InnovationPub Date : 2025-01-17eCollection Date: 2025-04-07DOI: 10.1016/j.xinn.2024.100769
Jieming Sheng, Le Wang, Wenrui Jiang, Han Ge, Nan Zhao, Tiantian Li, Maiko Kofu, Dehong Yu, Wei Zhu, Jia-Wei Mei, Zhentao Wang, Liusuo Wu
{"title":"Continuum of spin excitations in an ordered magnet.","authors":"Jieming Sheng, Le Wang, Wenrui Jiang, Han Ge, Nan Zhao, Tiantian Li, Maiko Kofu, Dehong Yu, Wei Zhu, Jia-Wei Mei, Zhentao Wang, Liusuo Wu","doi":"10.1016/j.xinn.2024.100769","DOIUrl":"10.1016/j.xinn.2024.100769","url":null,"abstract":"<p><p>Spin excitation continua observed in neutron scattering studies are often considered to be strong evidence of quantum spin liquid formation. In a disorder-free magnetic compound with a quantum spin liquid ground state, the elementary excitation is no longer the conventional spin waves (magnons). Instead, the magnons fractionalize into spinons, producing a characteristic two-spinon continuum. However, it remained uncertain whether a clean, ordered antiferromagnet could exhibit a continuous spectrum similar to that of a quantum spin liquid. This paper presents evidence of a spin excitation continuum in the magnetically ordered state of Na<sub>2</sub>BaCo(PO<sub>4</sub>)<sub>2</sub>, where free spinons are absent. This challenges the interpretation of such a continuum as a definitive signature of a quantum spin liquid in new material studies.</p>","PeriodicalId":36121,"journal":{"name":"The Innovation","volume":"6 4","pages":"100769"},"PeriodicalIF":33.2,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12131017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Emerging paradigms for target discovery of traditional medicines: A genome-wide pan-GPCR perspective.","authors":"Zenghao Bi, Huan Li, Yuting Liang, Dan Sun, Songxin Liu, Wei Chen, Liang Leng, Chi Song, Sanyin Zhang, Zhaotong Cong, Shilin Chen","doi":"10.1016/j.xinn.2024.100774","DOIUrl":"10.1016/j.xinn.2024.100774","url":null,"abstract":"<p><p>Traditional medicines serve not only as an integral part of medical treatments prescribed by healthcare providers but also as a fundamental reservoir for novel molecular scaffolds. However, gaps remain in our understanding of the mechanisms underlying their activity. A superfamily of membrane proteins, G protein-coupled receptors (GPCRs), have been demonstrated to be potential targets for several compounds isolated from traditional medicines. Given that GPCRs serve as targets for approximately one-third of all marketed drugs, they may be compelling targets for repurposing traditional medicines. Despite this potential, research investigating their activity or potential ligands across GPCRome, the library of human GPCRs, is scarce. Drawing on the functional and structural knowledge presently available, this review contemplates prospective trends in GPCR drug discovery, proposes innovative strategies for investigating traditional medicines, and highlights ligand screening approaches for identifying novel drug-like molecules. To discover bioactive molecules from traditional medicines that either directly bind to GPCRs or indirectly modify their function, a genome-wide pan-GPCR drug discovery platform was designed for the identification of bioactive components and targets, and the evaluation of their pharmacological profiles. This platform aims to aid the exploration of all-sided relations between traditional medicines and GPCRome using advanced high-throughput screening techniques. We present various approaches used by many, including ourselves, to illuminate the previously unexplored aspects of traditional medicines and GPCRs.</p>","PeriodicalId":36121,"journal":{"name":"The Innovation","volume":"6 3","pages":"100774"},"PeriodicalIF":33.2,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The InnovationPub Date : 2025-01-16eCollection Date: 2025-05-05DOI: 10.1016/j.xinn.2025.100805
Zhiqi Lao, Xiaoxue Ren, Dehua Zhuang, Lingxia Xie, Yucong Zhang, Wei Li, Yue Chen, Penghui Li, Liping Tong, Paul K Chu, Huaiyu Wang
{"title":"A phenotype-independent \"label-capture-release\" process for isolating viable circulating tumor cells in real-time drug susceptibility testing.","authors":"Zhiqi Lao, Xiaoxue Ren, Dehua Zhuang, Lingxia Xie, Yucong Zhang, Wei Li, Yue Chen, Penghui Li, Liping Tong, Paul K Chu, Huaiyu Wang","doi":"10.1016/j.xinn.2025.100805","DOIUrl":"10.1016/j.xinn.2025.100805","url":null,"abstract":"<p><p>Although various strategies have been proposed for enrichment of circulating tumor cells (CTCs), the clinical outcomes of CTC detection are far from satisfactory. The prevailing methodologies for CTC detection are generally oriented toward naturally occurring targets; however, misdetection and interference are prevalent due to the diverse phenotypes and subpopulations of CTCs, which are highly heterogeneous. Here, a CTC isolation system based on the \"label-capture-release\" process is demonstrated for the precise and highly efficient enrichment of CTCs from clinical blood samples. On the basis of the abnormal glycometabolism of tumor cells, the surface of CTCs can be decorated with artificial azido groups. By utilizing bio-orthogonal plates designed with dibenzocyclooctane (DBCO) and disulfide groups, with the aid of anti-fouling effects, CTCs labeled with azido groups can be captured through a copper-free click reaction and subsequently released via disulfide reduction. The technique has been shown to label tumor cells with the epithelial cell adhesion molecule (EpCAM)+ and EpCAM- phenotypes in both adherent and suspended states. Moreover, it effectively isolates all epithelial, interstitial, and hybrid phenotypes of CTCs from clinical blood samples collected from dozens of patients across more than 10 cancer types. Compared to the clinically approved CTC detection system, our strategy demonstrates superior performance from the perspective of broad-spectrum and accurate recognition of heterogeneous CTCs. More importantly, most of the captured CTCs can be released with the retention of living activity, making this technique well suited for downstream applications such as drug susceptibility tests involving viable CTCs.</p>","PeriodicalId":36121,"journal":{"name":"The Innovation","volume":"6 5","pages":"100805"},"PeriodicalIF":33.2,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144162542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}