The mechanistic target of rapamycin complex 1 (mTORC1) controls cell growth and metabolism in response to nutrients, energy levels and growth factors. It contains the atypical kinase mTOR and the RAPTOR subunit that binds to the TOS motif of substrates and regulators. mTORC1 is activated by the small GTPase RHEB and inhibited by PRAS40. Here we present the 3.0 Å cryo-EM structure of mTORC1 and the 3.4 Å structure of activated RHEB-mTORC1. RHEB binds to mTOR distally from the kinase active site, yet causes a global conformational change that allosterically realigns active-site residues, accelerating catalysis. Cancer-associated hyperactivating mutations map to structural elements that maintain the inactive state, and we provide biochemical evidence that they mimic RHEB relieving auto-inhibition. We also present crystal structures of RAPTOR-TOS motif complexes that define the determinants of TOS recognition, of an mTOR FKBP12-rapamycin-binding (FRB) domain–substrate complex that establishes a second substrate-recruitment mechanism, and of a truncated mTOR-PRAS40 complex that reveals PRAS40 inhibits both substrate-recruitment sites.
The environmental pollution has become a serious issue because the pollutants can cause permanent damage to the DNA, nervous system, and circulating system, resulting in various incurable diseases, such as organ failure, malformation, angiocardiopathy, and cancer. The effective detection of environmental pollutants is urgently needed to keep them far away from daily life. Among the reported pollutant sensors, luminescent metal–organic frameworks (LMOFs) with tunable structures have attracted remarkable attention to detect the pollutants because of their excellent selectivity, sensitivity, and recyclability. Although lots of metal–organic framework (MOF)‐based luminescent sensors have been summarized and discussed in previous reviews, the detection of environmental pollutants, especially radioactive ions and heavy metal ions, still have not been systematically presented. Here, the sensing mechanisms and construction principles of luminescent MOFs are discussed, and the state‐of‐the‐art MOF‐based luminescent sensors of environmental pollutants, including pesticides, antibiotics, explosives, VOCs, toxic gas, toxic small molecules, radioactive ions, and heavy metal ions are highlighted. This comprehensive review may further guide the development of luminescent MOFs and promote their practical applications for sensing environmental pollutants.
Two novel anionic In-MOFs V101 and V102 were synthesized and structurally characterized. The structrual transformation from 2-fold interpenetration to noninterpenetration was completed by changing solvent from DMF to DEF. Luminescence investigations reveal that only V102 not V101 can sensitively and selectively detect traces of antibiotics nitrofurazone in water solution via an environmentally friendly manner, and the detection limit can reach to 0.2 ppm. The luminescent difference between V101 and V102 mainly originates from the divergence of interpenetration structures. Namely, through interpenetration-control, the luminescent probe can switch on or off to detect nitrofurazone. This is the first example of interpenetration-dependent MOFs-based luminescent probe.
Cyclization of propargylic alcohols with CO 2 is an important reaction in industry,a nd noble-metal catalysts are often employed to ensure the high product yields under environmentally friendly conditions.H erein ap orous noblemetal-free framework 1 with large 1D channels of 1.66 nm diameter was synthesized for this reaction. Compound 1 exhibits excellent acid/base stability,a nd is even stable in corrosive triethylamine for one month. Catalytic studies indicate that 1 is an effective catalyst for the cyclization of propargylic alcohols and CO 2 without any solvents under mild conditions,a nd the turnover number (TON) can reach to arecord value of 14 400. Furthermore,t his MOF catalyst also has rarely seen catalytic activity when the biological macromolecule ethisterone was used as as ubstrate.M echanistic studies reveal that the synergistic catalytic effect between Cu I and In III plays ak ey role in the conversion of CO 2 .
We studied the effects of status epilepticus (SE) induced by lithium chloride/pilocarpine treatment on gene expression of neurotrophins of the nerve growth factor (NGF) family and of their high-affinity receptors of the tyrosine protein kinase (trk) family in the forebrain. Using in situ hybridization (ISH), we demonstrated an early (3 h after treatment) increase in brain-derived neurotrophic factor (BDNF) and trkB mRNA expression in the dentate gyrus, amygdala, and piriform cortex, as well as widespread increases in the cerebral cortex. NGF mRNA, but not the mRNA of its receptor trkA, was increased in the dentate gyrus. In contrast, 12 h after treatment, neurotrophin-3 (NT-3) decreased, and its receptor trkC mRNA increased. There was no change in NT-4 mRNA levels. All changes were blocked by pretreatment with scopolamine, a muscarinic antagonist. The noncompetitive N-methyl-D-aspartate (NMDA) antagonist ketamine blocked NGF, BDNF, and trkB mRNA increases in the hippocampus and cerebral cortex, but not in the amygdala and piriform cortex. In contrast, ketamine did not affect NT-3 and trkC changes. These results provide a complete description of changes in mRNA levels of neurotrophins and their receptors in the forebrain after SE and supply additional data supporting the view that neurotrophin gene expression is related to abnormal neuronal activity.
pH value is a key parameter in reflecting the health status, reaction process, and water quality. The construction of highly sensitive pH luminescent ratiometric is important but challenging. Herein we designed and synthesized a unique triple-interpenetrated luminescent lanthanide-organic framework {[Eu(PPTA)0.5(NO3)(DMF)2]·H2O} n (V104) based on an amphoteric ligand 4,4′,4′′,4′′′-(1,4-phenylenebis(pyridine-4,2,6-triyl))tetrabenzoic acid (H4PPTA). Compound V104 possesses high solvent and acid/alkaline stabilities. Luminescent investigations reveal that V104 exhibits dual emission peaks at 390 and 480 nm, and these two peaks can separately detect OH– and H+ among various anions and cations. Importantly, V104 can serve as a self-calibrated pH ratiometric to quantitatively detect pH value, and the sensitivity can reach 403.2% per pH for OH–, and 129.5% per pH for H+. Furthermore, by encapsulating magnetic γ-Fe2O3 nanoparticles in V104, the pH sensor can be readily separated from the analyte by external magnet and recycled at least four times, suggesting as-synthesized γ-Fe2O3@V104 has potential for monitoring pH fluctuations in water. To our knowledge, this is the first self-calibrated ratiometric pH-sensor based on two responsive wave bands which can separately detect OH– and H+.
The detection of recorded epileptic seizure activity in electroencephalogram (EEG) segments is crucial for the classification of seizures. Manual recognition is a time-consuming and laborious process that places a heavy burden on neurologists, and hence, the automatic identification of epilepsy has become an important issue. Traditional EEG recognition models largely depend on artificial experience and are of weak generalization ability. To break these limitations, we propose a novel one-dimensional deep neural network for robust detection of seizures, which composes of three convolutional blocks and three fully connected layers. Thereinto, each convolutional block consists of five types of layers: convolutional layer, batch normalization layer, nonlinear activation layer, dropout layer, and max-pooling layer. Model performance is evaluated on the University of Bonn dataset, which achieves the accuracy of 97.63%∼99.52% in the two-class classification problem, 96.73%∼98.06% in the three-class EEG classification problem, and 93.55% in classifying the complicated five-class problem.
Electrocatalytic reduction of CO2 by metal–organic frameworks (MOFs) has been widely investigated, but insufficient conductivity limits application. Herein, a porous 3D In‐MOF {(Me2NH2)[In(BCP)]⋅2 DMF}n (V11) with good stability was constructed with two types of channels (1.6 and 1.2 nm diameter). V11 exhibits moderate catalytic activity in CO2 electroreduction with 76.0 % of Faradaic efficiency for formate (FEHCOO‐). Methylene blue molecules of suitable size and pyrolysis temperature were introduced and transformed into carbon particles (CPs) after calcination. The performance of the obtained CPs@V11 is significantly improved both in FEHCOO‐ (from 76.0 % to 90.1 %) and current density (2.2 times). Control experiments show that introduced CPs serve as accelerant to promote the charges and mass transfer in framework, and benefit to sufficiently expose active sites. This strategy can also work on other In‐MOFs, demonstrating the universality of this method for electroreduction of CO2.
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