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The formation of a halogen-bonded network using four NHX-(CH2)3-NX-(CH2)3-NHX molecules (X = Cl, Br, or I) is investigated using DFT. The self-assembly of the four basic motifs results in a tube-like structure with C4h symmetry, with one halogen-bonded network located at each end of the structure and one at its center. Each halogen-bonded network has four quasi-planar N-X···N interactions with binding energies that increase with the size of X. The structure is found to bind Li+ at each of the halogen-bonded networks, albeit more strongly at its center. The binding of Li+ is driven by halogen atom lone pairs that produce a rich electron density orthogonal to the halogen bond. The presence and strength of the interactions are further examined using AIM and NBO calculations. Lastly, IRC calculations are performed to examine the transitions between the Li+ complex minima and, thus, the potential for transporting the metal ion from one end of the tube to the other. Based on the tetrameric structure, a model intramolecular structure is built and considered as a potential host for Li+. In this case, the central intermolecular N-X···N network is replaced by an intramolecular Si-C≡C-Si network. Interestingly, both intermolecular and intramolecular structures exhibit similar Li+ binding abilities.

Heat shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone which is essential in eukaryotes. It is required for the activation and stabilization of a wide variety of client proteins and many of them are involved in important cellular pathways. Since Hsp90 affects numerous physiological processes such as signal transduction, intracellular transport, and protein degradation, it became an interesting target for cancer therapy. Structurally, Hsp90 is a flexible dimeric protein composed of three different domains which adopt structurally distinct conformations. ATP binding triggers directionality in these conformational changes and leads to a more compact state. To achieve its function, Hsp90 works together with a large group of cofactors, termed co-chaperones. Co-chaperones form defined binary or ternary complexes with Hsp90, which facilitate the maturation of client proteins. In addition, posttranslational modifications of Hsp90, such as phosphorylation and acetylation, provide another level of regulation. They influence the conformational cycle, co-chaperone interaction, and inter-domain communications. In this review, we discuss the recent progress made in understanding the Hsp90 machinery.

The spatiotemporal transition of small GTPase Rab5 to Rab7 is crucial for early-to-late endosome maturation, yet the precise mechanism governing Rab5-to-Rab7 switching remains elusive. USP8, a ubiquitin-specific protease, plays a prominent role in the endosomal sorting of a wide range of transmembrane receptors and is a promising target in cancer therapy. Here, we identified that USP8 is recruited to Rab5-positive carriers by Rabex5, a guanine nucleotide exchange factor (GEF) for Rab5. The recruitment of USP8 dissociates Rabex5 from early endosomes (EEs) and meanwhile promotes the recruitment of the Rab7 GEF SAND-1/Mon1. In USP8-deficient cells, the level of active Rab5 is increased, while the Rab7 signal is decreased. As a result, enlarged EEs with abundant intraluminal vesicles accumulate and digestive lysosomes are rudimentary. Together, our results reveal an important and unexpected role of a deubiquitinating enzyme in endosome maturation.

Understanding the deterioration of the charge generation layer (CGL) is an uprising issue for efficient and stable tandem organic light-emitting diodes. Here, we comprehensively investigated the change in the electrical characteristics of Li-doped CGLs according to different stress conditions and compared the stability of Li diffusion in two phenanthroline-based electron transport materials. Through current density-voltage and capacitance-frequency measurements, it was revealed that electrical stress and thermal stress affect CGL's electrical properties differently. Moreover, the exponential trap distribution model analysis informed that the Li diffusion is expedited toward narrowing depletion width in the CGL. Diffusion of Li and thermal effect to the diffusion was experimentally observed by X-ray photoelectron spectroscopy (XPS) depth profiling. We also evaluated variations in the operating voltage of tandem devices that differed only in nCGL. Overall, Li diffusion occurs more favorably in sparse Bphen film with weak binding energy rather than closely packed BPPB film with strong binding energy, which highlights that atomic geometry and morphological characteristics are crucial for the stability of tandem devices.

Low shear stress (LSS) plays a critical role in the site predilection of atherosclerosis through activation of cellular mechanosensors, such as platelet endothelial cell adhesion molecule 1 (PECAM-1). Poly(ADP-ribose) polymerase 1 (PARP-1) is a nuclear enzyme that regulates the expression of various inflammatory cytokines. The nuclear enzyme high mobility group box 1 (HMGB1) can induce inflammation response by binding to toll-like receptor 4 (TLR4). In the present study, we aimed to investigate the role and mechanism of HMGB1 in LSS induced inflammation in human umbilical vein endothelial cells (HUVECs). HUVECs were stimulated by undisturbed shear stress (USS, 1 Pa) and LSS (0.4 Pa) in our experiments. Gene expression was inhibited by small interfering RNA (siRNA). ICAM-1 expression was regulated by LSS in a time dependent manner. LSS can induce HMGB1 translocation from nucleus to cytoplasm and release. Compared with the USS, LSS could increase the protein expression of PECAM-1 and PARP-1 as well as the secretion of TNF-α and IL-1β. LSS induced the translocation of HMGB1 from nucleus to cytoplasm. Inhibition of HGMB1 reduced LSS-induced inflammatory response. Inhibition of PARP-1 suppressed inflammatory response through inhibiting TLR4 expression and HMGB1 translocation. PECAM-1 inhibition reduced LSS-induced ICAM-1 expression, TNF-α and IL-1β secretion, and monocytes adhesion. LSS can induce inflammatory response via PECAM-1/PARP-1/HMGB1 pathway. PARP-1 plays a fundamental role in HMGB1 translocation and TLR4 expression. Inhibition of PARP-1 may shed light on the treatment of HMGB1 involved inflammation during atherosclerosis.

A simple label-free method uses the electrical properties of cells to detect how ligands bind to membrane proteins.A simple label-free method uses the electrical properties of cells to detect how ligands bind to membrane proteins.