Nitrite reacts with deoxyhemoglobin to form nitric oxide (NO) and methemoglobin. Though this reaction is experimentally associated with NO generation and vasodilation, kinetic analysis suggests that NO should not be able to escape inactivation in the erythrocyte. We have discovered that products of the nitrite-hemoglobin reaction generate dinitrogen trioxide (N2O3) via a novel reaction of NO and nitrite-bound methemoglobin. The oxygen-bound form of nitrite-methemoglobin shows a degree of ferrous nitrogen dioxide (Fe(II)-NO2*) character, so it may rapidly react with NO to form N2O3. N2O3 partitions in lipid, homolyzes to NO and readily nitrosates thiols, all of which are common pathways for NO escape from the erythrocyte. These results reveal a fundamental heme globin- and nitrite-catalyzed chemical reaction pathway to N2O3, NO and S-nitrosothiol that could form the basis of in vivo nitrite-dependent signaling. Because the reaction redox-cycles (that is, regenerates ferrous heme) and the nitrite-methemoglobin intermediate is not observable by electron paramagnetic resonance spectroscopy, this reaction has been 'invisible' to experimentalists over the last 100 years.
BackgroundRapid population ageing in China is increasing the numbers of older people who are likely to require health services in response to higher levels of poor perceived health and chronic diseases. Understanding factors influencing health services use at late life will help to plan for increasing needs for health care, reducing inequalities in health services use and releasing severe pressures on a highly variable health care system that has constrained public resources and increasing reliance on health insurance and user payments.MethodsDrawing on the nationally representative China Health and Retirement Longitudinal Study 2013 data, we apply the Andersen healthcare utilization conceptual model to binary logistic regression multivariate analyses to examine the joint predictors of physical examinations, outpatient and inpatient care among the middle-aged and elderly in China.ResultsThe multivariate analyses find that both physical examinations and inpatient care rates increase significantly by age when health deteriorates. Females are less likely to use inpatient care. Significant socio-economic variations exist in healthcare utilization. Older people with higher education, communist party membership, urban residence, non-agricultural household registration, better financial situation are more likely to have physical examinations or inpatient care. Factors influencing all three types of health care utilization are household expenditure, losing a partner, having multiple chronic diseases or perceiving poor health. With activities of daily living limitations or pain increases the probability of seeing a doctor while with functional loss increases the rates of having physical examinations, but being the ethnic minorities, no social health insurance, with depression, fair or poor memory could be a barrier to having physical examinations or seeing a doctor, which might delay the early diagnose of severe health problems among these groups. Not drinking, not smoking and regular physical exercises are adaptations after having health problems.ConclusionsAs a rapidly ageing society, in order to address the increasing needs and inequalities in health care utilization, China is facing a massive challenge to reform the current health care system, improve equitable access to health insurance and financial affordability for the most disadvantaged, as well as to provide more health education and information to the general public.
M1 macrophage accumulation and excessive inflammation are commonly encountered issues in diabetic wounds and can fail in the healing process. Hence, hydrogel dressings with immunoregulatory capacity have great promise in the clinical practice of diabetic wound healing. However, current immunoregulatory hydrogels are always needed for complex interventions and high‐cost treatments, such as cytokines and cell therapies. In this study, a novel glycyrrhizic acid (GA)‐based hybrid hydrogel dressing with intrinsic immunoregulatory properties is developed to promote rapid diabetic wound healing. This hybrid hydrogel consists of interpenetrating polymer networks composed of inorganic Zn2+‐induced self‐assembled GA and photo‐crosslinked methyl acrylated silk fibroin (SF), realizing both excellent injectability and mechanical strength. Notably, the SF/GA/Zn hybrid hydrogel can regulate macrophage responses in the inflammatory microenvironment, circumventing the use of any additives. The immunomodulatory properties of the hydrogel can be harnessed for safe and efficient therapeutics that accelerate the three phases of wound repair and serve as a promising dressing for the management of diabetic wounds.
PCNS/BHC composites were prepared by grafting PCNSs with high graphitization degree and abundant pores onto BHC surfaces for high-performance supercapacitors.
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