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In this study, a series of 4-[(quinolin-4-yl)amino]benzamide derivatives as the novel anti-influenza agents were designed and synthesized. Cytotoxicity assay, cytopathic effect assay and plaque inhibition assay were performed to evaluate the anti-influenza virus A/WSN/33 (H1N1) activity of the target compounds. The target compound G07 demonstrated significant anti-influenza virus A/WSN/33 (H1N1) activity both in cytopathic effect assay (EC50 = 11.38 ± 1.89 µM) and plaque inhibition assay (IC50 = 0.23 ± 0.15 µM). G07 also exhibited significant anti-influenza virus activities against other three different influenza virus strains A/PR/8 (H1N1), A/HK/68 (H3N2) and influenza B virus. According to the result of ribonucleoprotein reconstitution assay, G07 could interact well with ribonucleoprotein with an inhibition rate of 80.65% at 100 µM. Furthermore, G07 exhibited significant activity target PA−PB1 subunit of RNA polymerase according to the PA−PB1 inhibitory activity prediction by the best pharmacophore Hypo1. In addition, G07 was well drug-likeness based on the results of Lipinski's rule and ADMET prediction. All the results proved that 4-[(quinolin-4-yl)amino]benzamide derivatives could generate potential candidates in discovery of anti-influenza virus agents. [ABSTRACT FROM AUTHOR]

Background: There is on one hand sufficient evidence showing strong association between resilience and self-rated successful aging. On the other hand, strength training could contribute the cultivation of resilience among older adults. Therefore, the current study aims to examine the effectiveness of resistance training on resilience among Chinese older adults in Hong Kong.Methods: This study will apply a three-group, double blinded (outcome assessors and data analysts), randomized controlled trial (RCT) to examine the effectiveness of the interventions on resilience, functional fitness, and health related quality of life immediately after a 16-week intervention, as well as the residual effects 12 weeks after completion of the interventions.Discussion: It is expected that resistance training is promising or even superior to aerobic training in the improvement of resilience. Given the limited evidence on the literature, it is urgently needed to explore the effects of resistance training on the improvement of resilience in older adults. Findings of the current study can contribute to the development of effective resistant training programs for the promotion of resilience among older adults.Trial Registration: The trial is registered at the ClinicalTrials.gov PRS (Trial ID: NCT04690465 ; Date of First Posted: 30/12/2020). [ABSTRACT FROM AUTHOR]

Purpose: Resilience is an important trait for older adults facing adversity. This qualitative study aimed to identify the characteristics that contribute to resilience in a group of community-dwelling older adults in Hong Kong. Methods: Twenty-five Chinese older adults were invited. Interviews were conducted to collect information about the adverse events in their lives, their attitudes towards adversity and the beliefs underlying their approaches to overcoming adversity. The transcripts were analyzed using qualitative content analysis. Results: Seven themes emerged from the interviews: equanimity, positive attitudes towards life; meaningfulness, self-reliance, social support, environmental support, and spirituality and faith. Conclusion: Our qualitative analysis found that resilience among older adults in Hong Kong is characterized by internal, external and existential factors. The results may be useful for the development of proactive interventions aimed at assisting older adults to enhance the positive experiences in their lives. [ABSTRACT FROM AUTHOR]

Antrafenine is a drug initially designed for anti-inflammation uses. In this work we have synthesized a library of its structural analogs and tested the anti-influenza activities. These analogs belong to a group of 2-(quinolin-4-yl)amino benzamides or 2-(quinolin-4-yl)amino benzoate derivatives. Best performers were identified, namely 12 , 34 , 41 , with IC 50 against A/WSN/33 (H1N1) of 5.53, 3.21 and 6.73 μM respectively. These chemicals were also effective against A/PR/8/34 (H1N1), A/HK/1/68 (H3N2) and B/Florida/04/2006 viruses. Time-of-addition study and minigenome luciferase reporter assay both supported that the compounds act on the ribonucleoprotein (RNP) components. Using 34 and 41 as representative compounds, we determined by microscale thermophoresis that this group of compounds bind to both PA C-terminal domain and the nucleoprotein (NP) which is the most abundant subunit of the RNP. Taken together, we have identified a new class of anti-influenza compounds with dual molecular targets and good potential to be further developed. The influenza viruses, especially influenza A and B subtypes, cause many deaths each year. The high mutation rate of the virus renders available therapeutics less effective with time. In this work we identify a new class of compounds, structurally similar to the anti-inflammation drug antrafenine, with good potency against influenza A strains. The IC 50 of the best performers are within low micromolar range and thus have good potential for further development. [Display omitted] • 42 novel compounds that shared structure similarities to the NSAID, antrafenine, were designed and synthesized. • The most potent compounds could inhibit different strains of influenza A and influenza B viruses. • Mechanistic studies revealed that these compounds may dually target the PA and NP proteins of the influenza virus. [ABSTRACT FROM AUTHOR]