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Reconstructive phase transitions are characterized by significant changes in the crystal structure of a material, typically accompanied by dramatic changes in its physical properties. In this Letter, via first-principles calculations, we report a reconstructive phase transition between nonlayered and layered tungsten dinitride (WN2) with kinetic energy barriers of 0.19 and 0.61 eV per formula unit depending on the transition direction. The nonlayered-to-layered transition can be triggered when an in-plane biaxial strain reaches 9.3%, while the layered-to-nonlayered transition happens at 53.5% of an out-of-plane uniaxial strain. The nonlayered and layered WN2 phases exhibit distinct structural, bonding, and electronic characteristics. Another intrinsic advantage of the reconstructive transition between layered and nonlayered phases is that it can be easily extended to two-dimensional (2D) nanoscale regions. Our results predict a rich phase diagram for 2D WN2 under strains, appealing for advanced nanoelectronics applications such as phase-change electronics or pressure sensors. [ABSTRACT FROM AUTHOR]

Arabinoside and derived nucleoside analogs, a family of nucleoside analogs, exhibit diverse typically biological activities and are widely used as antibacterial, antiviral, anti-inflammatory, antitumor, and other drugs in clinical and preclinical trials. Although with a long and rich history in the field of medicinal chemistry, the biosynthesis of arabinoside has only been sporadically designed and studied, and it remains a challenge. Here, we constructed an in vitro multi-enzymatic cascade for the biosynthesis of arabinosides. This artificial biosystem was systematically optimized, involving an exquisite pathway design, NADP+ regeneration, meticulous enzyme selection, optimization of the key enzyme dosage, and the concentration of inorganic phosphate. Under the optimized conditions, we achieved 0.37 mM of vidarabine from 5 mM of sucrose and 2 mM of adenine, representing 18.7% of the theoretical yield. Furthermore, this biosystem also has the capability to produce other arabinosides, such as spongouridine, arabinofuranosylguanine, hypoxanthine arabinofuranoside, fludarabine, and 2-methoxyadenine arabinofuranoside, from sucrose, and corresponding nucleobase by introducing different nucleoside phosphorylases. Overall, our biosynthesis approach provides a pathway for the biosynthesis of arabinose-derived nucleoside analogs, offering potential applications in the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

A high sodium (HS) diet is believed to affect bone metabolism processes. Clarifying its impact on osseointegration of titanium (Ti) implants holds significant implications for postoperative dietary management of implanted patients. This investigation probed the impact of sodium ions (Na+) on neovascularization and osteogenesis around Ti implants in vivo , utilizing micro-computed tomography, hematoxylin and eosin staining, and immunohistochemical analyses. Concurrently, in vitro experiments assessed the effects of varied Na+ concentrations and exposure durations on human umbilical vein endothelial cells (HUVECs) and MC3T3-E1 cells. In vivo , increased dietary sodium (0.8%–6.0%) led to a substantial decline in CD34 positive HUVECs and new bone formation around Ti implants, alongside an increase in inflammatory cells. In vitro , an increase in Na+ concentration (140–150 mmol/L) adversely affected the proliferation, angiogenesis, and migration of HUVECs, especially with prolonged exposure. While MC3T3-E1 cells initially exhibited less susceptibility to high Na+ concentrations compared to HUVECs during short-term exposure, prolonged exposure to a HS environment progressively diminished their proliferation, differentiation, and osteogenic capabilities. These findings suggest that HS diet had a negative effect on the early osseointegration of Ti implants by interfering with the process of postoperative vascularized bone regeneration. [ABSTRACT FROM AUTHOR]

In hypertrophied and failing hearts, fuel metabolism is reprogrammed to increase glucose metabolism, especially glycolysis. This metabolic shift favors biosynthetic function at the expense of ATP production. Mechanisms responsible for the switch are poorly understood. We found that inhibitory factor 1 of the mitochondrial [F.sub.0][F.sub.1]-ATP synthase (ATPIF1), a protein known to inhibit ATP hydrolysis by the reverse function of ATP synthase during ischemia, was significantly upregulated in pathological cardiac hypertrophy induced by pressure overload, myocardial infarction, or [alpha]-adrenergic stimulation. Chemical cross-linking mass spectrometry analysis of hearts hypertrophied by pressure overload suggested that increased expression of ATPIF1 promoted the formation of [F.sub.o][F.sub.1]-ATP synthase nonproductive tetramer. Using ATPIF1 gain- and loss-of-function cell models, we demonstrated that stalled electron flow due to impaired ATP synthase activity triggered mitochondrial ROS generation, which stabilized [HIF1.sub.[alpha]], leading to transcriptional activation of glycolysis. Cardiacspecific deletion of ATPIF1 in mice prevented the metabolic switch and protected against the pathological remodeling during chronic stress. These results uncover a function of ATPIF1 in nonischemic hearts, which gives [F.sub.o][F.sub.1]-ATP synthase a critical role in metabolic rewiring during the pathological remodeling of the heart., Introduction Mitochondrial [F.sub.o][F.sub.1]-ATP synthase, or complex V, is composed of a soluble catalytic [F.sub.1] region (main subunit composition [[alpha].sub.3][[beta].sub.3][gamma]) in the mitochondrial matrix and a membrane-embedded [F.sub.o] region (1). The [...]

Two-dimensional (2D) ferromagnets have attracted significant interest for their potential in spintronic device miniaturization, especially since the discovery of ferromagnetic ordering in monolayer materials such as CrI3 and Fe3GeTe2 in 2017. This study presents a detailed investigation into the effects of the Hubbard U parameter, biaxial strain, and structural distortions on the magnetic characteristics of T″-phase VTe2. We demonstrate that setting the Hubbard U to 0 eV provides an accurate representation of the observed structural, magnetic, and electronic features for both bulk and monolayer T″-phase VTe2. The application of strain reveals two distinct ferromagnetic states in the monolayer T″-phase VTe2, each characterized by minor structural differences, but notably different magnetic moments. The T″-1 state, with reduced magnetic moments, emerges under compressive strain, while the T″-2 state, featuring increased magnetic moments, develops under tensile strain. Our analysis also compares the magnetic anisotropy between the T and T″ phases of VTe2, highlighting that the periodic lattice distortion in the T″-phase induces an in-plane anisotropy, which makes it a material with an easy-axis of magnetization. Monte Carlo simulations corroborate our findings, indicating a high Curie temperature of approximately 191 K for the T″-phase VTe2. Our research not only sheds light on the critical aspects of the VTe2 system but also suggests new pathways for enhancing low-dimensional magnetism, contributing to the advancement of spintronics and straintronics. [ABSTRACT FROM AUTHOR]

In this paper, we present the results of proof-of-concept experiments using a novel photocleavable and mass spectrometry identifiable cross-linker pcPIR (photocleavable protein interaction reporter), pcPIR can be dissociated under UV irradiation either off- or online before the introduction to the mass spectrometers. Photo dissociation of cross-linkers is different from either the gas phase or the chemical cleavage of cross-linkers. Different types of cross-links can be identified using the pcPIR mass relationships, where the mass of cross-linked precursor equals the sum of the masses of the released products and reporter. Since pcPIR is cleaved prior to the entrance to the mass spectrometer, the released peptides are available to be sequenced with routine collision-induced dissociation (CID) MS/MS experiments and database search algorithms. In this report, the pcPIR strategy of identifying the cross-linked peptides with on- and off-line photocleavage coupled with novel targeted data dependent LC-MS/MS is demonstrated with the use of standard peptides, bovine serum albumin (BSA), and human hemoglobin tetramer protein complex. 10.1021/ac902615g

One of the challenges in protein interaction studies with chemical cross-linking stems from the complexity of intra-, inter-, and dead-end cross-linked peptide mixtures. We have developed new cross-linkers to study protein--protein interactions with mass spectrometry to improve the ability to deal with this complexity. Even the accurate mass capabilities of FTICR-MS alone cannot unambiguously identify cross-linked peptides from cell-labeling experiments due to the complexity of these mixtures resultant from the enormous number of possible cross-linked species. We have developed novel cross-linkers that have unique fragmentation features in the gas phase. The characteristics of these cross-linkers combined with the accurate mass capability of FTICR-MS can help distinguish cross-linking reaction products and assign protein identities. These cross-linkers that we call protein interaction reporters (PIRs) have been constructed with two reactive groups attached through two bonds that can be preferentially cleaved by low-energy CID of the respective protonated precursor ions. After cleavage of the labile bonds, the middle part of the linker serves as a reporter ion to aid identification of cross-linked peptides. This report highlights three new PIRs with new features that have been developed to improve the efficiency of release of reporter ions. The new cross-linkers reported here were tuned with the addition of an affinity tag, a hydrophilic group, a photocleavable group, and new low-energy MS/ MS cleavable bonds. This report presents our investigation of the MSMS fragmentation behavior of selected protonated ions of the new compounds. The comprehensive fragmentation of these PIRs and PIR-labeled cross-linked peptides with low-energy collisions and an example of electron capture dissociation in FHCR-MS is presented. These new cross-linkers will contribute to current systems biology research by allowing acquisition of global or large-scale data on protein--protein interactions.

Reduced flow rate electrospray ionization has been proven to provide improved sensitivity, less background noise, and improved limits of detections for ESI-MS analysis. Miniaturizing the ESI source from conventional electrospray to microelectrospray and further down to nanoelectrospray has resulted in higher and higher sensitivity; however, when effects of flow rate were investigated for atmospheric pressure ESI-IMS using a nanospray emitter, a striking opposite result was observed. The general tendency we observed in ESI-IMS was that higher flow rate offered higher ion signal intensity throughout a variety of conditions investigated. Thus, further efforts were undertaken to rationalize these contradictory results. It is well accepted that decreased flow rate increases both ionization efficiency and transmission efficiency, thus improving ion signal in ESI-MS. However, our study revealed that decreased flow rate results in decreased ion signal because ion transfer is constant, no matter how flow rate changes in ESI-IMS. Since ion transfer is constant in atmospheric pressure ESI-IMS, ionization efficiency can be studied independently, which otherwise is not possible in ESI-MS in which both ionization efficiency and transmission efficiency vary as conditions alter. In this article, we present a systematic study of signal intensity and ionization efficiency at various experimental conditions using ESI-IMS and demonstrate the ionization efficiency as a function of flow rate, analyte concentration, and solvent composition.

A new mass spectrometry identifiable cross-linking strategy has been developed to study protein--protein interactions. The new cross-linker was designed to have two low-energy MS/MS-cleavable bonds in the spacer chain to provide three primary benefits: First, a reporter tag can be released from cross-link due to cleavage of the two labile bonds in the spacer chain. Second, a relatively simple MS/MS spectrum can be generated owing to favorable cleavage of labile bonds. And finally, the cross-linked peptide chains are dissociated from each other, and each then can be fragmented separately to get sequence information. Therefore, this novel type of cross-linker was named protein interaction reporter (PIR). To this end, two RINK groups were utilized to make our first-generation cross-linker using solid-phase peptide synthesis chemistry. The RINK group contains a bond more labile than peptide bonds during low-energy activation. The new cross-linker was applied to cross-link ribonuclease S (RNase S), a noncovalent complex of S-peptide and S-protein. The results demonstrated that the new cross-linker effectively reacted with RNase S to generate various types of cross-linked products. More importantly, the cross-linked peptides successfully released reporter ions during selective MS/MS conditions, and the dissociated peptide chains remained intact during M[S.sup.2], thus enabling M[S.sup.3] to be performed subsequently. In addition, dead-end, intra-, and inter-cross-linked peptides can be distinguished by analyzing MS/MS spectra.