ClpXP is a protease involved in DNA damage repair, stationary-phase gene expression, and ssrA-mediated protein quality control. To date, however, only a handful of ClpXP substrates have been identified. Using a tagged and inactive variant of ClpP, substrates of E. coli ClpXP were trapped in vivo, purified, and identified by mass spectrometry. The more than 50 trapped proteins include transcription factors, metabolic enzymes, and proteins involved in the starvation and oxidative stress responses. Analysis of the sequences of the trapped proteins revealed five recurring motifs: two located at the C terminus of proteins, and three N-terminal motifs. Deletion analysis, fusion proteins, and point mutations established that sequences from each motif class targeted proteins for degradation by ClpXP. These results represent a description of general rules governing substrate recognition by a AAA+ family ATPase and suggest strategies for regulation of protein degradation.

Although polycrystalline hexagonal boron nitride (PC-hBN) has been realized, defects and grain boundaries still cause charge scatterings and trap sites, impeding high-performance electronics. Here, we report a method of synthesizing wafer-scale single-crystalline hBN (SC-hBN) monolayer films by chemical vapor deposition. The limited solubility of boron (B) and nitrogen (N) atoms in liquid gold promotes high diffusion of adatoms on the surface of liquid at high temperature to provoke the circular hBN grains. These further evolve into closely packed unimodal grains by means of self-collimation of B and N edges inherited by electrostatic interaction between grains, eventually forming an SC-hBN film on a wafer scale. This SC-hBN film also allows for the synthesis of wafer-scale graphene/hBN heterostructure and single-crystalline tungsten disulfide.

Protection of endothelial integrity has been recognized as a frontline approach to alleviating sepsis progression, yet no effective agent for preserving endothelial integrity is available. Using an unusual anti-angiopoietin 2 (ANG2) antibody, ABTAA (ANG2-binding and TIE2-activating antibody), we show that activation of the endothelial receptor TIE2 protects the vasculature from septic damage and provides survival benefit in three sepsis mouse models. Upon binding to ANG2, ABTAA triggers clustering of ANG2, assembling an ABTAA/ANG2 complex that can subsequently bind and activate TIE2. Compared with a conventional ANG2-blocking antibody, ABTAA was highly effective in augmenting survival from sepsis by strengthening the endothelial glycocalyx, reducing cytokine storms, vascular leakage, and rarefaction, and mitigating organ damage. Together, our data advance the role of TIE2 activation in ameliorating sepsis progression and open a potential therapeutic avenue for sepsis to address the lack of sepsis-specific treatment.

Flexible TiO(2) crossbar memory device arrays were fabricated on plastic substrates using amorphous titanium oxide thin films grown by the low-temperature plasma-enhanced atomic layer deposition method. Al/ TiO(2)/Al memory cells on polyethersulfone (PES) showed an enhanced endurance property (up to 10(4) cycles) and low switching voltages compared to the cells on rigid substrates. The multi-stacked memory arrays were constructed by forming the additional Al/ TiO(2)/Al layer on the first memory device layer. Memory cells on each layer exhibited stable switching characteristics and mechanical robustness without interlayer cell-to-cell interference.

Oxidation can deteriorate the properties of copper that are critical for its use, particularly in the semiconductor industry and electro-optics applications1–7. This has prompted numerous studies exploring copper oxidation and possible passivation strategies8. In situ observations have, for example, shown that oxidation involves stepped surfaces: Cu2O growth occurs on flat surfaces as a result of Cu adatoms detaching from steps and diffusing across terraces9–11. But even though this mechanism explains why single-crystalline copper is more resistant to oxidation than polycrystalline copper, the fact that flat copper surfaces can be free of oxidation has not been explored further. Here we report the fabrication of copper thin films that are semi-permanently oxidation resistant because they consist of flat surfaces with only occasional mono-atomic steps. First-principles calculations confirm that mono-atomic step edges are as impervious to oxygen as flat surfaces and that surface adsorption of O atoms is suppressed once an oxygen face-centred cubic (fcc) surface site coverage of 50% has been reached. These combined effects explain the exceptional oxidation resistance of ultraflat Cu surfaces.

Glycoprotein conformations are complex and heterogeneous. Currently, site-specific characterization of glycopeptides is a challenge. We sought to establish an efficient method of N-glycoprotein characterization using mass spectrometry (MS). Using alpha-1-acid glycoprotein (AGP) as a model N-glycoprotein, we identified its tryptic N-glycopeptides and examined the data reproducibility in seven laboratories running different LC-MS/MS platforms. We used three test samples and one blind sample to evaluate instrument performance with entire sample preparation workflow. 165 site-specific N-glycopeptides representative of all N-glycosylation sites were identified from AGP 1 and AGP 2 isoforms. The glycopeptide fragmentations by collision-induced dissociation or higher-energy collisional dissociation (HCD) varied based on the MS analyzer. Orbitrap Elite identified the greatest number of AGP N-glycopeptides, followed by Triple TOF and Q-Exactive Plus. Reproducible generation of oxonium ions, glycan-cleaved glycopeptide fragment ions, and peptide backbone fragment ions was essential for successful identification. Laboratory proficiency affected the number of identified N-glycopeptides. The relative quantities of the 10 major N-glycopeptide isoforms of AGP detected in four laboratories were compared to assess reproducibility. Quantitative analysis showed that the coefficient of variation was <25% for all test samples. Our analytical protocol yielded identification and quantification of site-specific N-glycopeptide isoforms of AGP from control and disease plasma sample.

The aim of this prospective study was to assess the clinical outcomes of an unstable fracture of the lateral end of the clavicle treated with an arthroscopic-assisted locking compressive plate (LCP) clavicular hook plate. Twenty-three patients underwent arthroscopic assisted LCP clavicular hook plate fixation for these fractures. All patients achieved clinical and radiological union over a mean of 4.2 months (range, 3.4-5 months). Four patients (17%) showed some degree of acromial osteolysis. Three patients (13%) showed radiological signs of arthrosis of the acromioclavicular joint. In one patient, a second fracture (stress) was observed between the medial two screws of the plate without an additional injury. Five patients (22%) showed subacromial bursitis on dynamic ultrasonography. The mean Constant and Murley score was 91 points (range, 81-98). The average level of pain in the shoulder at rest and on abduction was 1 (range, 0-2) and 2.4 (range, 0-4), respectively. Based on our experience, arthroscopic-assisted LCP hook plate fixation for the treatment of unstable fractures of the lateral end of the clavicle is not without complications. However, it is an acceptable alternative method that is easy to apply with good results. Furthermore, it prevents rotator cuff impingement, allows early mobilisation and maintains the acromioclavicular joint biomechanics.

Growth of 2D van der Waals layered single‐crystal (SC) films is highly desired not only to manifest the intrinsic physical and chemical properties of materials, but also to enable the development of unprecedented devices for industrial applications. While wafer‐scale SC hexagonal boron nitride film has been successfully grown, an ideal growth platform for diatomic transition metal dichalcogenide (TMdC) films has not been established to date. Here, the SC growth of TMdC monolayers on a centimeter scale via the atomic sawtooth gold surface as a universal growth template is reported. The atomic tooth‐gullet surface is constructed by the one‐step solidification of liquid gold, evidenced by transmission electron microscopy. The anisotropic adsorption energy of the TMdC cluster, confirmed by density‐functional calculations, prevails at the periodic atomic‐step edge to yield unidirectional epitaxial growth of triangular TMdC grains, eventually forming the SC film, regardless of the Miller indices. Growth using the atomic sawtooth gold surface as a universal growth template is demonstrated for several TMdC monolayer films, including WS2, WSe2, MoS2, the MoSe2/WSe2 heterostructure, and W1−xMoxS2 alloys. This strategy provides a general avenue for the SC growth of diatomic van der Waals heterostructures on a wafer scale, to further facilitate the applications of TMdCs in post‐silicon technology.