Research on the Evaluation System of Scientific Research Ethics Based on AHP-Fuzzy Comprehensive Evaluation

Scientific research ethics is the value concept and code of conduct to be followed in scientific research, technological development and other scientific and technological activities. However, in recent years, some researchers have ignored ethical constraints in scientific research activities, resulting in more prominent ethical issues in scientific research. This study takes China Southern Power Grid Corporation as an example, based on ISO9000 standards, uses AHP-fuzzy comprehensive evaluation theory to establish a scientific research ethics evaluation system, aiming at improving the timeliness and targeting of scientific research ethics management

Study on the Role of SIRT2 in Stem Cell Aging and Chronic Inflammation

Aging is among the top known risk factors for most human diseases. Understanding thebiology of aging holds the promise to prevent or treat a wide range of seeminglyunrelated diseases. Originally being viewed as a passive and irreversible accumulationof changes over time, aging is currently perceived as a progressive biological declinethat succumbs to genetic manipulations. Hallmarks of aging have been identified,including but not limited to, stem cell exhaustion, mitochondrial dysfunction, deregulatednutrient sensing, and genomic instability. However, the molecular mechanismsdetermining the aging process remain elusive. In particular, the cell/tissue specificresponses to aging-associated damages still await investigation. This knowledge ispivotal to understand the molecular basis of the heterogeneous effects of aging ondiverse tissues. The aim of this dissertation work was to gain molecular insights into thisknowledge by studying the two striking aspects of aging: stem cell dysfunction andchronic inflammation.Adult stem cells maintain tissue homeostasis throughout life. It has been known fordecades that adult stem cell function declines with age, however, the exact mechanismscontributing to this degeneration remain tentative. We found that SIRT2, a primarilycytosolic NAD+-dependent deacetylase, is required for hematopoietic stem cell (HSC)maintenance at old age. Mechanistic studies demonstrated that SIRT2 exerts its rolethrough modulating cell death processes in HSCs. SIRT2 expression is significantlyreduced in old HSCs, which is consistent with increased cell death in HSCs duringaging. Enforced SIRT2 expression reverses the increased cell death observed in HSCsduring physiological aging. Further, we show that restoring SIRT2 expression canrejuvenate the functionality of old HSCs, suggesting the reversibility of the functionaldecline in HSCs with age.SIRT2 has been reported to suppress inflammation in multiple inflammation-inducingmouse models. Based on these findings, we investigated SIRT2’s role in chronic sterileinflammation associated with physiological aging. Chronic NLRP3 inflammasomeactivation during aging has a causal role in developing pathological inflammation insterile inflammatory diseases, such as atherosclerosis, Alzheimer’s disease,Parkinson’s disease, obesity, diabetes, multiple sclerosis, and cancer. In light of this, weexplored whether SIRT2 suppresses aging-associated chronic inflammation throughregulating the NLRP3 inflammasome activity. We found that SIRT2 specifically inhibitsNLRP3 inflammasome in macrophages. NLRP3 inflammasome is activated inmacrophages with age, with a concomitant reduction in SIRT2 levels. Enforced SIRT2expression in macrophages from old mice reverses aging-associated NLRP3inflammasome activation, suggesting a potential reversible mechanism for the agingassociatedinflammation phenotype.Our studies demonstrate that down-regulation of SIRT2 levels plays significant roles indifferent cells and tissues during aging. In HSCs, SIRT2 suppresses the activation ofcell death processes and preserves HSC regenerative capacity, while in macrophages,SIRT2 mediated NLRP3 inhibition prevents the development of chronic inflammation.These results not only broaden the physiological relevance of the cytosolic NAD+protein deacetylase SIRT2 to include stem cell homeostasis, but also exemplify theheterogeneity in tissue responses to aging-associated down-regulation of the SIRT2protein expression. Further, from the therapeutic standpoints, these findings also opennovel avenues to explore the potential reversibility of both stem cell aging and systemiclow-grade inflammation associated with aging

Research on the Evaluation System of Scientific Research Ethics Based on AHP-Fuzzy Comprehensive Evaluation

Scientific research ethics is the value concept and code of conduct to be followed in scientific research, technological development and other scientific and technological activities. However, in recent years, some researchers have ignored ethical constraints in scientific research activities, resulting in more prominent ethical issues in scientific research. This study takes China Southern Power Grid Corporation as an example, based on ISO9000 standards, uses AHP-fuzzy comprehensive evaluation theory to establish a scientific research ethics evaluation system, aiming at improving the timeliness and targeting of scientific research ethics management

Nutrient Sensing and the Oxidative Stress Response

The simplicity and effectiveness of calorie restriction (CR) in lifespan and healthspan extension have fascinated generations searching for the Fountain of Youth. CR reduces levels of oxidative stress and damage, which have been postulated in the free radical theory of aging as a major cause of aging and diseases of aging. This reduction has long been viewed as a result of passive slowing of metabolism. Recent advances in nutrient sensing have provided molecular insights into the oxidative stress response and suggest that CR triggers an active defense program involving a cascade of molecular regulators to reduce oxidative stress. Physiological studies have provided strong support for oxidative stress in the development of aging-associated conditions and diseases but have also revealed the surprising requirement for oxidative stress to support normal physiological functions and, in some contexts, even slow aging and prevent the progression of cancer. Deciphering the molecular mechanisms and physiological implications of the oxidative stress response during CR will increase our understanding of the basic biology of aging and pave the way for the design of CR mimetics to improve healthspan

A mitochondrial UPR-mediated metabolic checkpoint regulates hematopoietic stem cell aging

Deterioration of adult stem cells accounts for much of aging-associated compromised tissue maintenance. How stem cells maintain metabolic homeostasis remains elusive. Here, we identified a regulatory branch of the mitochondrial unfolded protein response (UPR(mt)), which is mediated by the interplay of SIRT7 and NRF1 and is coupled to cellular energy metabolism and proliferation. SIRT7 inactivation caused reduced quiescence, increased mitochondrial protein folding stress (PFS(mt)), and compromised regenerative capacity of hematopoietic stem cells (HSCs). SIRT7 expression was reduced in aged HSCs, and SIRT7 up-regulation improved the regenerative capacity of aged HSCs. These findings define the deregulation of a UPR(mt)-mediated metabolic checkpoint as a reversible contributing factor for HSC aging

Mitochondrial Stress-Initiated Aberrant Activation of the NLRP3 Inflammasome Regulates the Functional Deterioration of Hematopoietic Stem Cell Aging

Aging-associated defects in hematopoietic stem cells (HSCs) can manifest in their progeny, leading to aberrant activation of the NLRP3 inflammasome in macrophages and affecting distant tissues and organismal health span. Whether the NLRP3 inflammasome is aberrantly activated in HSCs during physiological aging is unknown. We show here that SIRT2, a cytosolic NAD+-dependent deacetylase, is required for HSC maintenance and regenerative capacity at an old age by repressing the activation of the NLRP3 inflammasome in HSCs cell autonomously. With age, reduced SIRT2 expression and increased mitochondrial stress lead to aberrant activation of the NLRP3 inflammasome in HSCs. SIRT2 overexpression, NLRP3 inactivation, or caspase 1 inactivation improves the maintenance and regenerative capacity of aged HSCs. These results suggest that mitochondrial stress-initiated aberrant activation of the NLRP3 inflammasome is a reversible driver of the functional decline of HSC aging and highlight the importance of inflammatory signaling in regulating HSC aging.ISSN:2666-3864ISSN:2211-124

Reduced fetal telomere length in gestational diabetes.

Gestational diabetes mellitus (GDM) is an important complication of pregnancy that poses significant threats to women and their offspring. Telomere length shortens as cellular damage increases and is associated with metabolic diseases. Telomere length in fetal leucocytes was determined in 82 infants of women with GDM (N = 82) and 65 normal pregnant women (N = 65). Women with preeclampsia (N = 45) and gestational hypertension (N = 23) were also studied. In the GDM group, telomere length was significantly shorter than normal pregnancy (P = 0.028), but there were no significant differences in fetal telomere length between preeclampsia and normal pregnancy (P = 0.841) and between gestational hypertension and normal pregnancy (P = 0.561). Regression analysis revealed that fetal telomere length was significantly associated with intrauterine exposure to GDM (P = 0.027 after adjustment for maternal age, gestational age at delivery, birth weight and fetal gender). Shortened telomere length may increase the risk of metabolic diseases in adulthood of GDM offspring

Mitochondrial Stress-Initiated Aberrant Activation of the NLRP3 Inflammasome Regulates the Functional Deterioration of Hematopoietic Stem Cell Aging.

Aging-associated defects in hematopoietic stem cells (HSCs) can manifest in their progeny, leading to aberrant activation of the NLRP3 inflammasome in macrophages and affecting distant tissues and organismal health span. Whether the NLRP3 inflammasome is aberrantly activated in HSCs during physiological aging is unknown. We show here that SIRT2, a cytosolic NAD+-dependent deacetylase, is required for HSC maintenance and regenerative capacity at an old age by repressing the activation of the NLRP3 inflammasome in HSCs cell autonomously. With age, reduced SIRT2 expression and increased mitochondrial stress lead to aberrant activation of the NLRP3 inflammasome in HSCs. SIRT2 overexpression, NLRP3 inactivation, or caspase 1 inactivation improves the maintenance and regenerative capacity of aged HSCs. These results suggest that mitochondrial stress-initiated aberrant activation of the NLRP3 inflammasome is a reversible driver of the functional decline of HSC aging and highlight the importance of inflammatory signaling in regulating HSC aging