Nano Today
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2024
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IF 13.2
Shiwen Duan,Jianmin Gao,Haoqin Ke,Chengquan Huang,Chaoyue Sun,Yujie Ren,Yixue Zhang,Xiumei Jiang,Yinliang Wang,Gang Liu
Mosquitoes are notorious for transmitting arbovirus diseases. Existing genetic-based control strategies only target one of mosquitoes’ flying, blood-sucking and reproduction behaviors and are technically demanding, limiting their real-world application. Therefore, there is an imperative need to identify novel molecular targets for developing multi-effect, easy-to-deploy mosquito control strategies. We herein identified and characterized the function of mosquito iron-sulfur-cluster assembly protein AalbNFS1. Silencing AalbNFS1 with double-strand RNAs (dsNFS1) caused evident metabolic and enzyme activity abnormalities in mosquito tissues and cells. Further analyses revealed that AalbNFS1 deficiency simultaneously reduced mosquitoes’ flying, blood-sucking and reproductive abilities by inducing muscle cell ferroptosis, confirming AalbNFS1 as a multi-effect molecular target for mosquito control purposes. To facilitate the real-world deployment of dsNFS1, a chitosan-tripolyphosphate-dsNFS1 (CS-TPP-dsNFS1) nanosystem was synthesized, generating satisfactory mosquito control effects. Collectively, our study pioneers the research on iron-sulfur-cluster biosynthesis mechanisms in mosquitoes and develops an effective mosquito control nanosystem with promising real-world applicability.
研究领域:
昆虫学
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分子生物学
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生物技术
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公共卫生
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DOI
高影响因子
Chinese Medicine
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2022
·Vol. 17
·期 1
·1-16
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IF 4.546
Chen Jia-Qian,Chen Yan-Yan,Du Xia,Tao Hui-Juan,Pu Zong-Jin,Shi Xu-Qin,Yue Shi-Jun,Zhou Gui-Sheng,Shang Er-Xin,Tang Yu-Ping,Duan Jin-Ao
Background Rhei Radix et Rhizoma (rhubarb), as one of the typical representatives of multi-effect traditional Chinese medicines (TCMs), has been utilized in the treatment of various diseases due to its multicomponent nature. However, there are few systematic investigations for the corresponding effect of individual components in rhubarb. Hence, we aimed to develop a novel strategy to fuzzily identify bioactive components for different efficacies of rhubarb by the back propagation (BP) neural network association analysis of ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry for every data (UPLC-Q-TOF/MSE) and integrated effects.Methods Through applying the fuzzy chemical identification, most components of rhubarb were classified into different chemical groups. Meanwhile the integration effect values of different efficacies can be determined by animal experiment evaluation and multi-attribute comprehensive indexes. Then the BP neural network was employed for association analysis of components and different efficacies by correlating the component contents determined from UPLC-Q-TOF/MSE profiling and the integration effect values. Finally, the effect contribution of one type of components may be totaled to demonstrate the universal and individual characters for different efficacies of rhubarb.Results It suggested that combined anthraquinones, flavanols and their polymers may be the universal character to the multi-functional properties of rhubarb. Other components contributed to the individuality of rhubarb efficacies, including stilbene glycosides, anthranones and their dimers, free anthraquinones, chromones, gallic acid and gallotannins, butyrylbenzenes and their glycosides.Conclusion sOur findings demonstrated that the bioactive components for different efficacies of rhubarb were not exactly the same and can be systematically differentiated by the network-oriented strategy. These efforts will advance our knowledge and understanding of the bioactive components in rhubarb and provide scientific evidence to support the expansion of its use in clinical applications and the further development of some products based on this medicinal herb.
研究领域:
药理学
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分析化学
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中医药学
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DOI
PubMed
高影响因子
ACS Nano
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2023
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IF 17.1
Chao Li,Yuxing Wu,Qinjun Chen,Yifan Luo,Peixin Liu,Zheng Zhou,Zhenhao Zhao,Tongyu Zhang,Boyu Su,Tao Sun,Chen Jiang
Reperfusion injury presents a significant obstacle to neuronal survival following successful recanalization in ischemic stroke, which is characterized by intricate pathophysiological processes comprising numerous interconnected pathways. Oxidative stress-induced neuronal ferroptosis and the overactivation of glial cells play important roles in this phenomenon. In this study, we developed a targeted cross-linked micelle loaded with idebenone to rescue the ischemic penumbra by inhibiting neuronal ferroptosis and glial overactivation. In rat models, the CREKA peptide-modified micelles accumulate in the damaged brain via binding to microthrombi in the ipsilateral microvessels. Upon reactive oxygen species (ROS) stimulation, diselenide bonds within the micelles are transformed to hydrophilic seleninic acids, enabling synchronized ROS consumption and responsive drug release. The released idebenone scavenges ROS, prevents oxidative stress-induced neuronal ferroptosis, attenuates glial overactivation, and suppresses pro-inflammatory factors secretion, thereby modulating the inflammatory microenvironment. Finally, this micelle significantly reinforces neuronal survival, reduces infarct volume, and improves behavioral function compared to the control groups. This pleiotropic therapeutic micelle provides a proof-of-concept of remodeling the lesion microenvironment by inhibiting neuronal ferroptosis and glial overactivation to treat cerebral ischemia-reperfusion injury.
研究领域:
神经科学
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药学
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生物医学工程
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分子生物学
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DOI
PubMed
高影响因子
APPLIED SURFACE SCIENCE
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2018
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IF 4.439
Wenfei Zhou,Mo Yang,Shaopeng Li,Jinsong Zhu
Systematic and rapid profiling of the interactions between small molecule drugs (or candidates) and target proteins is vital in studying drug promiscuity and drug discovery. However, a label-free and high-throughput method for the detection of small molecules binding on protein microarray is still lacking. In this research, we introduced surface plasmon resonance imaging (SPRi) technology combined with protein microarray on 3D-dextran hydrogel chip surface to realize the detection of small molecule drugs. With the development and optimization of this method, we obtained the ideal binding signals of small molecular drugs versus their target proteins, with good quality and uniformity (CV = 10.3%, n = 48). Then we demonstrated three applications, including in situ mimicking and detecting the formation of FK506-mediated trimer complex (FKBP12-FK506-calcineurin), rapid validation of FK506-FKBP12 recognition via FKBP12 mutant microarray (1 vs n mode), and 3 × 4 orthogonal studying the drug binding specificity on protein microarray (m vs n mode). Fortunately, these trials enable the label-free and kinetic study of drug-protein interactions on SPRi in a high-throughput manner, which could be a promising solution in screening/forecasting side effect of drugs (or candidates), drug repositioning or repurposing, target identification of natural products and personalized medicine, etc.
研究领域:
药学
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生物化学
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生物技术
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药物发现
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蛋白质组学
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Ying Luo,Zhongsheng Xu,Qianying Du,Lian Xu,Yi Wang,Jie Xu,Junrui Wang,Sijin Chen,Wenli Zhang,Bo Liu,Jia Liu,Dajing Guo,Yun Liu
The immune landscape of late-stage liver cancer is featured by severe immunosuppression that is characterized by poor immunogenicity, T-cell exhaustion, and infiltration of a large number of immunosuppressive cells, leading to compromised therapeutic efficacy of mainstream immunotherapies. Herein, we developed a pleiotropic immune cell mobilization strategy to modulate immune systems for immunosuppressive liver cancer therapy. In this study, immunogenic bacteria-derived outer membrane vesicles (OMVs) were exploited as a vector to deposit Cu and Mn with mixed valence states via one-step biomineralization, followed by platelet membrane camouflage, which are denoted as OPCM. Mechanistically, the pleiotropic OPCM possesses POD, CAT, and GPX-like activities, thereby achieving cGAS-STING activation, immunogenic ferroptosis, and tumor hypoxia alleviation, ultimately leading to initiation of the cancer immunity cycle, modulation of both innate and adaptive immune system, and reversion of immunosuppression. Notably, the combination with typical αPD-L1 treatment augmented the tumor suppression effect by amplifying the intensity of ferroptosis due to IFN-γ secretion by activated T cells. Overall, the metal biomineralized OPCMs in combination with αPD-L1 formed a closed-loop therapy that cycles from immunotherapy and ferroptosis therapy, providing new insights for treating immunosuppressive liver cancer.
研究领域:
免疫学
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癌症生物学
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生物技术
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纳米医学
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产品关联
DOI
高影响因子
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