Tailored design of NKT-stimulatory glycolipids for polarization of immune responses.

Natural killer T (NKT) cell is a distinct population of T lymphocytes that can rapidly release massive amount of Th1 and Th2 cytokines upon the engagement of their T cell receptor with glycolipids presented by CD1d. The secreted cytokines can promote cell-mediated immunity to kill tumor cells and intracellular pathogens, or suppress autoreactive immune cells in autoimmune diseases. Thus, NKT cell is an attractive target for developing new therapeutics to manipulate immune system. The best-known glycolipid to activate NKT cells is α-galactosylceramide (α-GalCer), which has been used as a prototype for designing new NKT stimulatory glycolipids. Many analogues have been generated by modification of the galactosyl moiety, the acyl chain or the phytosphingosine chain of α-GalCer. Some of the analogues showed greater abilities than α-GalCer in polarizing immune responses toward Th1 or Th2 dominance. Among them, several analogues containing phenyl groups in the lipid tails were more potent in inducing Th1-skewed cytokines and exhibited greater anticancer efficacy than α-GalCer. Analyses of the correlation between structure and activity of various α-GalCer analogues on the activation of iNKT cell revealed that CD1d-glycolipid complexes interacted with the same population of iNKT cell expressing similar T-cell receptor Vβ as α-GalCer. On the other hand, those phenyl glycolipids with propensity for Th1 dominant responses showed greater binding avidity and stability than α-GalCer for iNKT T-cell receptor when complexed with CD1d. Thus, it is the avidity and stability of the ternary complexes of CD1d-glycolipid-iNKT TCR that dictate the polarity and potency of immune responses. These findings provide a key to the rationale design of immune modulating glycolipids with desirable Th1/Th2 polarity for clinical application. In addition, elucidation of α-GalCer-induced anergy, liver damage and accumulation of myeloid derived suppressor cells has offered explanation for its lacklustre anti-cancer activities in clinical trials. On other hand, the lack of such drawbacks in glycolipid analogues containing phenyl groups in the lipid tails of α-GalCer coupled with the greater binding avidity and stability of CD1d-glycolipid complex for iNKT T-cell receptor, account for their superior anti-cancer efficacy in tumor bearing mice. Further clinical development of these phenyl glycolipids is warranted

Effect of Influenza Vaccination on Mortality and Risk of Hospitalization in Elderly Individuals with and without Disabilities: A Nationwide, Population-Based Cohort Study

Purpose: The effects of influenza vaccines are unclear for elderly individuals with disabilities. We use a population-based cohort study to estimate the effects of influenza vaccines in elderly individuals with and without disabilities. Methods: Data were taken from the National Health Insurance Research Database and Disabled Population Profile of Taiwan. A total of 2,741,403 adults aged 65 or older were identified and 394,490 were people with a disability. These two groups were further divided into those who had or had not received an influenza vaccine. Generalized estimating equations (GEE) were used to compare the relative risks (RRs) of death and hospitalization across the four groups. Results: 30.78% elderly individuals without a disability and 34.59% elderly individuals with a disability had vaccinated for influenza. Compared to the unvaccinated elderly without a disability, the vaccinated elderly without a disability had significantly lower risks in all-cause mortality (RR = 0.64) and hospitalization for any of the influenza-related diseases (RR = 0.91). Both the unvaccinated and vaccinated elderly with a disability had significantly higher risks in all-cause mortality (RR = 1.81 and 1.18, respectively) and hospitalization for any of the influenza-related diseases (RR = 1.73 and 1.59, respectively). Conclusions: The elderly with a disability had higher risks in mortality and hospitalization than those without a disability; however, receiving influenza vaccinations could still generate more protection to the disabled elderl

Effects of Quality of Financial Statements and CEO Turnover

The purpose of this study is to explore the effect of CEO turnover and CFO turnover on earnings management. In addition, Taiwan’s authorities will require listed companies to complete the establishment of audit committee replacing supervisors in 2022. Corporate governance is not an overnight phenomenon. It has been existing from a long time. It is only that the beginning of 21st century when colossal enterprises started to fall, government across globe started giving it due credit. The present paper is an attempt to trace the history of corporate governance. It starts with discussing various theories which led to the development of such an important concept and then dwells on various models in which economies employ corporate governance in their structure and finally the evolution of corporate governance across globe. The paper sheds light on important committees and reforms which have been the genesis of corporate governance across globe. It undertakes an extensive literature review on different aspects of corporate governance. Corporate governance is a concept which still debatable among experts in describing it. The purpose of this study is to explore how the implementation and principal problems of good corporate governance in the management of current limited liability company