1,721,948 research outputs found
Editing flagellin derivatives for exploration of potent radioprotective agents
No full textExploration of medical radiation countermeasures (MRCs) has great implications in protection of mammals from radiation damages. While flagellin has been recently reported to show radioprotective effects, the relationships between flagellin structure and radioprotective activity are rarely explored. Herein, we deliberately edited the amino acid sequence of flagellin in its binding domain with toll-like receptor 5 (TLR5) for exploration of potent flagellin derivatives (Fds). An in vitro screening paradigm was developed to examine the radioprotective effects of six engineered Fds. Notably, mutation of 103 threonine on flagellin into asparagine resulted in a potent MRC candidate (Fd-T103N) displaying 1.28-fold increment of interactions with TLR5. Fd-T103N was able to further activate NF-κB pathway, induce immune protective cytokine (e.g. G-CSF) release, and significantly ameliorate γ-irradiation induced cell death. The protection effects of Fd-T103N were further validated in mice exposed to 10 Gray γ-irradiations. Compared to parent flagellin, Fd-T103N treatment showed higher G-CSF release in mouse blood, lower intestine damages, and 13% increments of mouse survival rates. In short, the established predictive paradigm could greatly reduce the labor-, time- and animal-costs in exploration of MRC candidates. Fd-T103N is a promising candidate of investigational new drug for radioprotection
Nano-enabled Photosynthesis in Tumor to Activate Lipid Peroxidation for Overcome of Cancer Resistances
No full textApoptosis dysregulation is an important mechanism responsible for the intrinsic and acquired resistances of melanoma, which necessitates the exploration of oncological treatments to activate non-apoptotic cell deaths. Herein, we engineered a lipid peroxidation reaction in hyperoxia tumor microenvironment for induction of ferroptosis and overcome of melanoma resistances. The hyperoxia microenvironment was deliberately constructed by implants of photosynthetic microcapsules (PMCs) consisting of cyanobacteria and upconversion nanoparticles for photosynthesis in chloroplast driven by external near infrared photons. Combination of PMCs and X rays evoked a lipid peroxidation reaction and ferroptosis in melanoma cells and xenografts. Consequently, the intrinsic and acquired resistances in melanoma could be overcome by the engineered reaction, which further contributed to the amelioration of tumor metastases and improvement of survival rates in melanoma-bearing mice. Overall, our findings provide opportunities to overcome melanoma resistances by engineered biochemical reactions and will inspire the exploration of oncological treatments
Synthetic Vectors for Activating the Driving Axis of Ferroptosis
No full textFerroptosis is a promising strategy for cancer therapy, with numerous inhibitors of its braking axes under investigation as potential drugs. However, few studies have explored the potential of activating the driving axes to induce ferroptosis. Herein, phosphatidylcholine peroxide decorating liposomes (LIPPCPO) were synthesized to induce ferroptosis by targeting divalent metal transporter 1 (DMT1). LIPPCPO was found to boost lysosomal Fe2+ efflux by inducing cysteinylation of lysosomal DMT1, resulting in glutathione peroxidase 4 (GPX4) suppression, glutathione depletion and ferroptosis in breast cancer cells and xenografts. Importantly, LIPPCPO induced ferroptotic cell death was independent of acquired resistance to radiation, chemotherapy, or targeted agents in 11 cancer cell lines. Furthermore, a strong synergistic ferroptosis effect was observed between LIPPCPO and an FDA-approved drug, artesunate. The formula of LIPPCPO encapsulating artesunate significantly inhibited tumor growth and metastasis and improved the survival rate of breast cancer-bearing mice. These findings provide a distinct strategy for inducing ferroptosis and highlight the potential of LIPPCPO as a vector to synergize the therapeutic effects of conventional ferroptosis inducers
AI3SD Video: The Application of Machine Learning in Molecular Spectroscopy Study
No full textOptical-spectroscopy provides powerful toolkits to decipher molecular structures and their configuration evolutions. However, the theoretical analysis of spectroscopic signals and connecting them with structural detail is a challenging task. Moreover, the intrinsic complexity of spectroscopic signals of molecular systems makes it difficult to correlate spectral characteristics with the underlying molecular structure and dynamics. Herein, we have developed data-driven machine learning (ML) protocols that can predict infrared (IR), ultraviolet/visible (UV/Vis) and Raman spectra of molecule systems with 3 to 5 orders of magnitude reduced computation cost compared to direct quantum chemistry calculations. A convolutional neural network (CNN) model was trained and tested on a dataset consisting 87993 spectra computed from protein peptide segments with α-helical, β-sheet, and other typical secondary structures. The secondary structure classification accuracy reached near 100% and over 98.7% on spectra sets of new segments extracted from the same and homologous proteins, respectively. Importantly, we demonstrate the ML protocol to realize cost-effective relations between spectra, structure, and chemical properties, i.e. spectra determination/prediction from structural information, and configuration or chemical properties determination/recognition from spectroscopic signals.1. S. Ye, K. Zhong, J.X. Zhang, W. Hu, J. Hirst, G.Z. Zhang, S. Mukamel, J. Jiang*, A Machine Learning Protocol for Predicting Protein Infrared Spectra, J. Am. Chem. Soc. 142 (2020) 19071-19077.2. X.J. Wang, S. Ye, W. Hu, E. Sharman, R. Liu, Y. Liu, Y. Luo, J. Jiang*, Electric Dipole Descriptor for Machine Learning Prediction of Catalyst Surface-Molecular Adsorbate Interactions, J. Am. Chem. Soc. 142 (2020) 7737-7743.3. S. Ye, W. Hu, X. Li, J.X. Zhang, K. Zhong, G.Z. Zhang, Y. Luo, S. Mukamel*, J. Jiang*, A Neural Network Protocol for Electronic excitations of N-Methylacetamide, Proc Natl Acad Sci USA. 116 (2019) 11612-11617.4. W. Hu, S. Ye, Y.J Zhang, T.D. Li, G.Z. Zhang, Y. Luo, S. Mukamel, J. Jiang*, Machine Learning Protocol for Surface-Enhanced Raman Spectroscopy, J. Phys. Chem. Lett. 10 (2019) 6026-6031
Large bright blue-glazed general's helmet jar (jiang jun guan)
No full textThis is a large general's helmet jar (jiang jun guan) with a short and straight neck, slanting shoulders, a bulging body tapering to the bottom and a splayed foot. The jar is named for its cover which, with its pearl-shaped finial, resembles an army general's helmet. This type of jar was first seen in the Jiajing (1522-1566) and Wanli (1573-1620) reigns of the Ming dynasty. It became very popular in the Kangxi reign of the Qing dynasty (1662-1722). The exterior of the cover and the large jar itself is glazed in bright blue with numerous tiny bronze-colored mottles. The base of the splayed foot, the interior of the cover, and the jar are mostly white glazed. The bottom rim of the foot, the wide borders of the cover and the upper mouth are unglazed, exposing the white body. A double-circled ring in underglaze blue is seen on the base of the foot.
The shape of this general's helmet jar is typically after the Kangxi model; however, this piece was not made during the Kangxi period. The glaze on it appears exceedingly bright when observed against the light, which is an indication of later copies according to a book titled gu wan zhi nan (Guide of Chinese Antiques) written in 1942 by Zhao Ruzhen, a prestigious modern connoisseur. As such, this bright blue-glazed general's helmet jar is a recent replica of the Kangxi product.Qing dynasty; Republican perio
Lie theory and cohomology of relative Rota–Baxter operators
No full textAbstract
In this paper, we establish a local Lie theory for relative Rota–Baxter operators of weight 1. First we recall the category of relative Rota–Baxter operators of weight 1 on Lie algebras and construct a cohomology theory for them. We use the second cohomology group to study infinitesimal deformations of relative Rota–Baxter operators and modified ‐matrices. Then we introduce a cohomology theory of relative Rota–Baxter operators on a Lie group. We construct the differentiation functor from the category of relative Rota–Baxter operators on Lie groups to that on Lie algebras, and extend it to the cohomology level by proving the Van Est theorem between the two cohomology theories. We integrate a relative Rota–Baxter operator of weight 1 on a Lie algebra to a local relative Rota–Baxter operator on the corresponding Lie group, and show that the local integration and differentiation are adjoint to each other. Finally, we give two applications of our integration of Rota–Baxter operators: one is to give an explicit formula for the factorization problem, and the other is to provide an integration for matched pairs.National Natural Science Foundation of China https://doi.org/10.13039/501100001809China Postdoctoral Science Foundation https://doi.org/10.13039/501100002858Deutsche Forschungsgemeinschaft https://doi.org/10.13039/50110000165
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