As an important member of crystalline porous polymers, acylhydrazone-linked covalent organic frameworks (COFs) have gained much attention in recent years. However, the low structural stability imparts a limit on their practical applications. To tackle this problem, we report a simple strategy to increase the chemical stability of acylhydrazone-linked COFs by incorporating azobenzene groups in the conjugated framework. Through reinforcing the π-π stacking interactions between the adjacent layers with increased π-surface, it is surprising to find that the resulting materials exhibit extreme stability in harsh environments, such as in strong acid, strong base, aqueous educing agent and boiling water, even exposed to air for one year. As a proof-of-concept, such frameworks have been used to remove various organic micropollutants such as antibiotics, plastic components, endocrine disruptors, and carcinogens from water with high capacity, fast speed and excellent reusability over a wide pH range at environmentally relevant concentrations. The results provide a new avenue to significantly enhance the stability of COFs for practical applications.This work describes the first generalizable method to modify various metal-organic framework (MOF) surfaces with polyimide, polysulfone, polycarbonate, and polymer of intrinsic microporosity-1 (PIM-1). The method first utilizes electrostatic adsorption to rapidly decorate positively charged MOF surfaces with a layer of negatively charged metal-organic nanocapsule, PgC5 Cu. After mixing with the polymer, the copper open metal sites on PgC5 Cu can coordinatively crosslink the polar functional groups on the surface polymer upon thermal activation thereby resulting in the immobilization of a uniform sub-10 nm polymer coating. We quantitatively analyzed the distribution of free path spacing between MOF particles and demonstrated that when the surface polymer matches the matrix polymer, the MOF dispersion was not only visually improved but also found to align perfectly with a theoretically predicted ideal dispersion model where no aggregation driving force was present.Introduction of α-N-methylated non-proteinogenic amino acids into peptides can improve their biological activities, membrane permeability and proteolytic stability. This is commonly achieved, in nature and in the lab, by assembling pre-methylated amino acids. The more appealing route of methylating amide bonds is challenging. Biology has evolved an α-N-automethylating enzyme, OphMA, which acts on the amide bonds of peptides fused to its C-terminus. Due to the ribosomal biosynthesis of its substrate, the activity of this enzyme towards peptides with non-proteinogenic amino acids has not been addressed. An engineered OphMA, intein-mediated protein ligation and solid-phase peptide synthesis have allowed us to demonstrate the methylation of amide bonds in the context of non-natural amides. This approach may have application in the biotechnological production of therapeutic peptides.Receptor activator of nuclear factor-κΒ ligand (RANKL) is necessary and sufficient to promote osteoclastogenesis and a key pathogenic factor in osteoporosis. Failure of periosteal apposition to compensate for bone loss due to endosteal resorption further contributes to bone fragility. Whether these two processes are biologically related, however, remains unknown. Using high-resolution peripheral quantitative computed tomography (HR-pQCT), we first examined cortical bone parameters at distal radius and tibia in postmenopausal women (PMW) as well as in cadaveric human adult humeri. Increases in medullary area were negatively correlated with cortical bone volume but positively with total bone volume, and this relationship was stronger in the dominant arm, suggesting a mechanically driven process. To investigate the role of RANKL in this dual process, we used mice overexpressing huRANKL (huRANKLTg+ ). Trabecular and cortical bone volume (Ct.BV) are reduced in these mice, whereas cortical total volume (Ct.TV) is increased. In these bones, Sost mRNA levels are downregulated and periostin (Postn) mRNA levels upregulated, hence providing a positive message for periosteal bone formation. In turn, genetic deletion of Postn in huRANKLTg+ mice prevented the increase in Ct.TV and aggravated bone fragility. In contrast, cathepsin K (Ctsk) ablation improved Ct.TV in both huRANKLTg+ and wild-type (WT) mice and stimulated periosteal bone formation, while augmenting Postn protein levels. Hydroxyfasudil inhibitor Therefore, bone strength in huRANKLTg+ /Ctsk-/- mice was restored to WT levels. These findings suggest that high levels of RANKL not only induce endosteal bone loss but may somewhat restrict periosteal bone formation by triggering periostin degradation through cathepsin K, hence providing a biological mechanism for the observed limited increase in cortical area in postmenopausal women. © 2021 American Society for Bone and Mineral Research (ASBMR).
Porphyromonas gingivalis is a key pathogen in microbiota associated with periodontitis. The purpose of the present study was to assess the association between salivary counts of red-complex bacteria and clinical periodontal status in a Japanese population.
A total of 977 subjects who visited a general dental clinic in Japan from 2003 to 2006 were enrolled in the study. Stimulated saliva was obtained, and the amounts of major periodontal bacteria were measured using real-time polymerase chain reaction. Probing pocket depth (PPD), bleeding on probing (BOP), and each subject's average proximal bone crest level (BCL) on dental radiographs were measured.
The number of P. gingivalis strongly associated with percentage of 4mm or more PPD sites, BOP positive percentage, and 1.5mm or more BCL sites. The detection of P. gingivalis with Treponema denticola and/or Tannerella forsythia showed a high rate of three positive clinical parameters, whereas the only P. gingivalis detected group and those without P. gingivalis had a low rate of three positive clinical parameters.
Among red-complex bacteria, the amount of P. gingivalis showed the strongest association with the severity of periodontal condition, and co-occurrence of P. gingivalis with T. denticola and/or T. forsythia showed heightened progression of periodontitis.
Among red-complex bacteria, the amount of P. gingivalis showed the strongest association with the severity of periodontal condition, and co-occurrence of P. gingivalis with T. denticola and/or T. forsythia showed heightened progression of periodontitis.Hydroxyfasudil inhibitor
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