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In this work, we demonstrate a process having the capability to realize single-digit nanometer lithography using single heavy ions. Piperlongumine research buy By adopting 2.15 GeV 86Kr26+ ions as the exposure source and hydrogen silsesquioxane (HSQ) as a negative-tone inorganic resist, ultrahigh-aspect-ratio nanofilaments with sub-5 nm feature size, following the trajectory of single heavy ions, were reliably obtained. Control experiments and simulation analysis indicate that the high-resolution capabilities of both HSQ resist and the heavy ions contribute the sub-5 nm fabrication result. Our work on the one hand provides a robust evidence that single heavy ions have the potential for single-digit nanometer lithography and on the other hand proves the capability of inorganic resists for reliable sub-5 nm patterning. Along with the further development of heavy-ion technology, their ultimate patterning resolution is supposed to be more accessible for device prototyping and resist evaluation at the single-digit nanometer scale.A cobalt-catalyzed dearomatization of indoles via transfer hydrogenation with HBpin and H2O has been developed. link2 This reaction offered a straightforward platform to access hexahydropyrido[1,2-a]indoles in high regio- and chemoselectivity. A preliminary reaction mechanism was proposed on the basis of deuterium-labeling experiments, and a cobalt hydride species was involved in the reaction.Myocilin-associated glaucoma is a new addition to the list of diseases linked to protein misfolding and amyloid formation. Single point variants of the ∼257-residue myocilin olfactomedin domain (mOLF) lead to mutant myocilin aggregation. Here, we analyze the 12-residue peptide P1 (GAVVYSGSLYFQ), corresponding to residues 326-337 of mOLF, previously shown to form amyloid fibrils in vitro and in silico. We applied solid-state NMR structural measurements to test the hypothesis that P1 fibrils adopt one of three predicted structures. Our data are consistent with a U-shaped fibril arrangement for P1, one that is related to the U-shape predicted previously in silico. Our data are also consistent with an antiparallel fibril arrangement, likely driven by terminal electrostatics. Our proposed structural model is reminiscent of fibrils formed by the Aβ(1-40) Iowa mutant peptide, but with a different arrangement of molecular turn regions. Taken together, our results strengthen the connection between mOLF fibrils and the broader amylome and contribute to our understanding of the fundamental molecular interactions governing fibril architecture and stability.Silver sulfide (Ag2S) has gained widespread attention in second near-infrared (950-1700 nm, NIR-II) window imaging because of its high fluorescence quantum yield and low toxicity. However, its "always on" fluorescence shows inapplicability for targeted molecule-activated biomedical applications. Herein, we first developed a novel silver/silver sulfide Janus nanoparticle (Ag/Ag2S JNP) for specific activatable fluorescence imaging in the NIR-II window. Inner-particle electron compensation from Ag to Ag2S upon laser irradiation endowed JNPs an "off" state of fluorescence, whereas the oxidization of Ag incubated with H2O2, decreasing the electron-transfer effect and illuminating the NIR-II fluorescence of the Ag2S part. In contrast, the absorption of Ag/Ag2S JNPs slightly decreased in an H2O2-dependent manner, showing an activated photoacoustic imaging mechanism. The Ag/Ag2S JNPs were used for noninvasive location and diagnosis of diseases in vivo, such as for liver injury and cancer, with high sensitivity and accuracy.Monitoring the DNA dynamics in solution has great potential to develop new nucleic acid-based sensors and devices. With spectroscopic approaches, both at the ensemble average and single-molecule resolution, this study is directed to differentiate a single nucleotide mismatch (SNM) via a metal ion-stabilized mismatched base-pairing (C-Ag+-C/C-Cu2+-T) (C = cytosine, T = thymine) and site-selective extrinsic fluorophore, specifically, Thioflavin T (ThT). This is the first approach of its kind where dynamic quantities like molecular diffusion coefficients and diffusion times have been utilized to distinguish the least-stable SNM (CC & CT) formed by the most discriminating nucleobase, specifically, cytosine in a 20-mer duplex DNA. Additionally, this work also quantifies metal ions (Ag+ and Cu2+) at lower concentrations using fluorescence correlation spectroscopy. Our results can provide greater molecular-level insights into the mismatch-dependent metal-DNA interactions and also illuminate ThT as a new fluorophore to monitor the dynamics involved in DNA-metal composites.The linear sequence of amino acids in a protein folds into a 3D structure to execute protein activity and function, but it is still challenging to profile the 3D structure at the proteome scale. Here, we present a method of native protein tandem mass tag (TMT) profiling of Lys accessibility and its application to investigate structural alterations in human brain specimens of Alzheimer's disease (AD). In this method, proteins are extracted under a native condition, labeled by TMT reagents, followed by trypsin digestion and peptide analysis using two-dimensional liquid chromatography and tandem mass spectrometry (LC/LC-MS/MS). The method quantifies Lys labeling efficiency to evaluate its accessibility on the protein surface, which may be affected by protein conformations, protein modifications, and/or other molecular interactions. link3 We systematically optimized the amount of TMT reagents, reaction time, and temperature and then analyzed protein samples under multiple conditions, including different labeling time (5 and 30 min), heat treatment, AD and normal human cases. The experiment profiled 15370 TMT-labeled peptides in 4475 proteins. As expected, the heat treatment led to extensive changes in protein conformations, with 17% of the detected proteome displaying differential labeling. Compared to the normal controls, AD brain showed different Lys accessibility of tau and RNA splicing complexes, which are the hallmarks of AD pathology, as well as proteins involved in transcription, mitochondrial, and synaptic functions. To eliminate the possibility that the observed differential Lys labeling was caused by protein level change, the whole proteome was quantified with standard TMT-LC/LC-MS/MS for normalization. Thus, this native protein TMT method enables the proteome-wide measurement of Lys accessibility, representing a straightforward strategy to explore protein structure in any biological system.Electromagnetic interference (EMI) shielding materials with excellent EMI shielding efficiency (SE), lightweight property, and superb mechanical performance are vitally important for modern society, but it is still a challenge to realize these performances simultaneously on one material. Here, we report a sustainable bioinspired double-network structural material with excellent specific strength (146 MPa g-1 cm3) and remarkable EMI SE (100 dB) from cellulose nanofiber (CNF) and carbon nanotubes (CNTs), which demonstrates remarkable and outstanding performance to both typical metal materials and reported polymer composites. In particular, the bioinspired double-network structure design simultaneously achieves an extremely high electrical conductivity and mechanical strength, which makes it a lightweight, high shielding efficiency, and sustainable structural material for real-life electromagnetic wave shielding applications.A dataset is the basis of deep learning model development, and the success of deep learning models heavily relies on the quality and size of the dataset. In this work, we present a new data preparation protocol and build a large fragment-based dataset Frag20, which consists of optimized 3D geometries and calculated molecular properties from Merck molecular force field (MMFF) and DFT at the B3LYP/6-31G* level of theory for more than half a million molecules composed of H, B, C, O, N, F, P, S, Cl, and Br with no larger than 20 heavy atoms. Based on the new dataset, we develop robust molecular energy prediction models using a simplified PhysNet architecture for both DFT-optimized and MMFF-optimized geometries, which achieve better than or close to chemical accuracy (1 kcal/mol) on multiple test sets, including CSD20 and Plati20 based on experimental crystal structures.Quorum sensing is being investigated as an alternative therapeutic strategy in antibacterial drug discovery programs aimed at combatting bacterial resistance. LsrK is an autoinducer-2 kinase (belongs to the sugar kinase family), playing a key role in the phosphorylation of the autoinducer-2 (AI-2) signaling molecules involved in quorum sensing. Inhibiting LsrK could result in reduced pathogenicity by interfering with quorum sensing signaling. Previously, we have generated homology models to employ in structure-based virtual screening and successfully identified the first class of LsrK inhibitors. While conducting these studies, the crystal structure of LsrK was released, providing us with an opportunity to evaluate the reliability and quality of our models. A comparative structural analysis of the crystal structure and homology models revealed consistencies among them in the overall structural fold and binding site. Furthermore, the binding characteristics and conformational changes of LsrK have been investigated using molecular dynamics to inspect whether LsrK undergoes similar conformational changes as that of sugar kinases. These studies revealed the flexibility of the LsrK C-terminal domain (Domain II) attributing to the conformational changes in LsrK resulting in open and closed states during the phosphorylation. Further, simulations provided us with insights into the flexibility of a loop in Domain I that can influence the ligand accessibility to the LsrK binding site.Guttiferone F, a natural polyprenylated polycyclic acylphloroglucinol, was originally assigned as the 30-epimer of garcinol by NMR data analyses. Conversion of guttiferone F in the presence of acid afforded its cyclized form (2a), which was previously assigned as 30-epi-cambogin. However, the absolute configurations of guttiferone F and 2a have not been determined. Reinvestigation of the structures of those two compounds, using X-ray and NMR data analyses and chemical transformation, revealed that the original assignment of the C-30 absolute configuration in guttiferone F and 2a should be inverted. Guttiferone F is indeed garcinol, and 2a, which was previously identified as 30-epi-cambogin, is cambogin.High-resolution tandem mass spectrometry (HR-MS2)-based metabolomic studies of Amycolatopsis saalfeldensis, isolated from the "Saalfelder Feengrotten" caves in Germany, led to the isolation of three ribosomally synthesized and post-translationally modified type II thiopeptides, saalfelduracin B-D (1-3) and the known saalfelduracin A (4). The structures of all four compounds were determined by comparative two-dimensional NMR analysis and high-resolution tandem mass spectrometry.The semiconductor-metal junction is one of the most critical factors for high-performance electronic devices. In two-dimensional (2D) semiconductor devices, minimizing the voltage drop at this junction is particularly challenging and important. Despite numerous studies concerning contact resistance in 2D semiconductors, the exact nature of the buried interface under a three-dimensional (3D) metal remains unclear. Herein, we report the direct measurement of electrical and optical responses of 2D semiconductor-metal buried interfaces using a recently developed metal-assisted transfer technique to expose the buried interface, which is then directly investigated using scanning probe techniques. We characterize the spatially varying electronic and optical properties of this buried interface with less then 20 nm resolution. To be specific, potential, conductance, and photoluminescence at the buried metal/MoS2 interface are correlated as a function of a variety of metal deposition conditions as well as the type of metal contacts.
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