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2 per 100 000 persons/year. Using GLM, the increment is statistically significant (P = 0.02). When compared to the last registry, the rate of increment had attenuated, with annual increment in crude incidence in the two periods for T1D less then 15 years changing from 4.3% to 3.5% (P = 0.02). CONCLUSIONS The incidence of T1D children increased significantly in the past two decades in Hong Kong, but the rate of increase had attenuated in recent years. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.AIMS MitraClip therapy for the treatment of functional mitral regurgitation (FMR) is an increasingly used intervention for high-risk surgical patients. The aim of this observational study was to assess the impact of residual mitral regurgitation (rMR) at discharge on long-term outcome after MitraClip therapy in patients with FMR. METHODS AND RESULTS Overall, 458 patients (mean age 73.8 ± 8.9 years) underwent MitraClip implantation between September 2008 and December 2017. The impact of rMR ≤ 1+ at discharge (n = 251) was retrospectively compared to patients graded as rMR 2+ (n = 173) and rMR ≥3+ (n = 34) at discharge. Median follow-up time was 5.09 years (5.00-5.26) with maximum follow-up of 10.02 years. The primary outcome was survival, and Kaplan-Meier analyses revealed significant differences among all rMR subgroups with highest survival rates for rMR ≤ 1+ patients. This was further confirmed by composite outcome analyses (P  less then  0.02). The inferior outcomes of rMR 2+ and rMR ≥ 3+ at discharge were confirmed by increased adjusted hazard ratios when rMR 2+ (1.54, P = 0.0039) and rMR ≥ 3+ (2.16, P = 0.011) were compared to rMR ≤ 1+. Moreover, patients with stable rMR ≤ 1+ grades within 12 months showed significantly higher survival rates compared to patients with rMR ≤ 1+ at discharge and rMR ≥ 2+ at 12-month follow-up or rMR ≥ 2+ at discharge and 12-month follow-up (P = 0.029). CONCLUSIONS Patients with optimal and durable rMR ≤ 1+ at discharge and 12-month follow-up showed better outcome compared to patients with rMR 2+ and rMR ≥ 3+. Treatment success and durability characterized by rMR ≤ 1+ at discharge and 12 months seem to be important factors for long-term outcomes, which has to be further confirmed by prospective randomized trials. © 2020 European Society of Cardiology.Polymerization-induced self-assembly (PISA) enables the scalable synthesis of functional block copolymer nanoparticles with various morphologies. Herein we exploit this versatile technique to produce so-called ‘high χ -low N ‘ diblock copolymers that undergo nanoscale phase separation in the solid state to produce sub-10 nm surface features. By varying the degree of polymerization of the stabilizer and core-forming blocks, PISA provides rapid access to a wide range of diblock copolymers, and enables fundamental thermodynamic parameters to be determined. In addition, the pre-organization of copolymer chains within sterically-stabilized nanoparticles that occurs during PISA leads to enhanced phase separation relative to that achieved using solution-cast molecularly-dissolved copolymer chains. © 2020 WILEY-VCH Verlag GmbH & Co. D609 cost KGaA, Weinheim.The amino-terminal copper and nickel/N-terminal site (ATCUN/NTS) present in proteins and bioactive peptides exhibits high affinity towards Cu II ions and have been implicated in human copper physiology. Little is known, however, about the rate and exact mechanism of formation of such complexes. We used the stopped-flow and microsecond freeze-hyperquenching (MHQ) techniques supported by steady-state spectroscopic and electrochemical data to demonstrate the formation of partially coordinated intermediate Cu II complexes formed by glycyl-glycyl-histidine (GGH) peptide, the simplest ATCUN/NTS model. One of these novel intermediates, characterized by two-nitrogen coordination, t ½ ∼100 ms at pH = 6.0 and the ability to maintain the Cu II /Cu I redox pair is the best candidate for the long-sought reactive species in extracellular copper transport. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Oral squamous cell carcinoma (OSCC) is an extremely aggressive neoplasm, which is usually diagnosed in the advanced stage of the disease. Extensive studies have shown a link between chronic inflammation and various types of cancer, including OSCC. Salicylate is a biotransformation product of aspirin, with similar anti-inflammatory ability to aspirin but lacks aspirin’s inhibitory effect on the isolated cyclooxygenase activity. Our study indicates that salicylate sensitizes OSCC to anti-cancer drugs, but the mechanisms of its action are unclear. Here, OSCC cells were used to evaluate the cytotoxicity of salicylate alone or in combination with cisplatin (CDDP). RPPA proteomic array and Western blotting were employed to determine the signaling pathways affected by salicylate. Salicylate decreased cell survival rate and induced cell apoptosis in OSCC cells but not human normal oral mucosal epithelial cells (hTERT-OME). The use of sodium salicylate (SS) dramatically sensitized OSCC cells to CDDP. RPPA array showed that SS reduced many oncogenes such as PI3K/mTOR signaling and cancer stem cell (CSC)-related genes versus control. Western and transcriptional analyses substantiated that salicylate down-regulated these CSC-associated genes and the mTOR pathway dose dependently. Salicylate preferentially repressed the ability of sorted ALDH1+ cells to form tumor spheres. Finally, salicylate suppressed tumor growth in vivo, and the combination of salicylate and CDDP further synergistically reduced the growth of tumors. Salicylate hinders OSCC cell growth and sensitizes OSCC cells to CDDP through targeting CSCs and the mTOR signaling pathway. We propose that salicylate is beneficial for OSCC patients, and salicylate may be combined with chemotherapies to effectively treat OSCC patients. This article is protected by copyright. All rights reserved.G-Quadruplex (G4)-forming DNA sequences have a tendency to form stable multimeric structures. This can be problematic for studies with synthetic oligodeoxynucleotides. Here, we describe a method that quantitatively converts multimeric intermolecular structures of Pu27 sequence from c-myc promoter into desired monomeric G4 by alkaline treatment and refolding. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.