Safety assessment of transgenic maize CC-2 by 90-day feeding study in Sprague-Dawley rats.

Objective: The purpose of this study was to assess the safety of transgenic maize CC-2 through a 90-day feeding study in Sprague-Dawley rats. Methods: Transgenic maize CC-2 and its parental counterpart maize Zhengdan 958 were respectively incorporated into diets at levels of 70%, 35% or 17.5% (w/w) and were administrated to rats (n = 10/sex/group) for 90 days. An additional control group of rats (n = 10/sex/group) were fed with the AIN93 breeding diet. All formulated diets were nutritionally balanced. Results: There was no death and obvious toxic symptom in all rats. Food consumption, body weight, total food consumption rate, hematology, urinalysis, organ weight and organ coefficient were comparable between transgenic groups and the corresponding dose parental groups. There were significant differences of food consumption rate on some timepoint between high dose transgenic group and high dose parental group; male rats in high dose transgenic group showed significantly higher ALT/AST than high dose parental group on the middle or end of the experiment; but the differences showed no biological significance. There were no significant differences of other serum biochemistry parameters and pathological changes. Conclusion: The results in this study demonstrated that the transgenic maize CC-2 didn't cause any related toxicity in rats.

[Repairing effects of Lactobacillus acidophilus on ceftriaxone-induced intestinal dysbacteriosis in mice].

OBJECTIVE: To investigate the repairing effect of Lactobacillus acidophilus LA11-Only on ceftriaxone induced intestinal micronbiota imbalance in mice and its alleviating effect on lipid metabolism. METHODS: A total of 30 SPF BALB/c male mice were randomly divided into control group(10) and model group(20). The model group was given ceftriaxone sodium solution by gavage for a week to create a mouse model of antibiotic flora disorder. The natural recovery group(10) was given 10% skimmed milk solution by gavage, and the LA11-Onlly group was given Lactobacillus acidophilus skimmed milk solution(1.0×10~9CFU/mL). Two weeks later, the feces were collected aseptically.16S rRNA sequencing technology and ultra-high-performance liquid chromatography combined with mass spectrometry(UPLC-MS) were used to analyze the repair effect of LA11-Onlly on antibiotic induced bacterial flora disorder and lipid metabolism in mice. RESULTS: After ceftriaxone treatment, the diversity of intestinal microbiota in mice decreased, and there was a significant difference in the composition of flora compared with the control group; After treatment with LA11-Onlly, the Alpha diversity increased, the abundance of beneficial bacteria such as Lactobacillus and Butyricicoccus increased, and the composition of flora was closer to the control group; At the same time, the concentration of short chain fatty acids(SCFAs) increased in varying degrees. Compared with the natural recovery group, the levels of butyric acid and valeric acid in LA11-Onlly group increased significantly, close to the same level as the control group. CONCLUSION: Lactobacillus acidophilus LA11-Onlly probiotics can inhibit the growth of harmful bacteria by regulating the diversity and community composition of intestinal microbiota, promote the increase of the concentration of SCFAs, and alleviate the damage of antibiotics to the body.

[Prediction equation of physical activity level based on step counts for Chinese adults: development and validation].

OBJECTIVE: To develop a prediction equation for estimation physical activity level(PAL) based on the average daily steps in Chinese adults and to verify its prediction power. METHODS: A total of 800 adults with no restriction on physical activity were recruited. Excluding those who wore Actigragh WGT3X-BT accelerometer continuously for less than 3 days, 743 subjects(324 males, 419 females, mean age 31.4 years) were finally included. Daily steps, time of low intensity physical activity(LPA), moderate physical activity(MPA) and vigorous physical activity(VPA) and physical activity energy expenditure(PAEE) were measured by the accelerometer. The method of external validation was adopted. The measured PAL calculated by basal metabolic rate(BMR) measured by indirect thermography(IC) and total energy expenditure(TEE) measured by doubly labeled water method was used as the gold standard. The consistency of the prediction formula was verified by Bland-Altman analysis and the accuracy was verified by the accurate. RESULTS: The prediction equation was developed: PAL=1.17 + 0.000028 Steps. In the external verification, the mean difference was 0.05, the 95% consistency limit was(-0.26, 0.36), and the accuracy was 73%, indicating a good consistency. CONCLUSION: The prediction formula of PAL for Chinese adults based on the steps has good performance and can be applied to the management of physical activity and the prevention of obesity in Chinese adults.

Analysis of Metabolite Distribution in Rat Liver of High-Fat Model by Mass Spectrometry Imaging.

Hyperlipidemia is a medical condition characterized by elevated levels of blood lipids, especially triglycerides (TG). However, it remains unclear whether TG levels remain consistently elevated throughout the entire developmental stage of the high-lipid state. In our animal experiment, we found that TG levels were significantly higher in the early stage of the high-lipid model but significantly decreased at the 14th week of the late stage, reaching levels similar to those of the control group. This suggests that TG levels in the high-lipid model are not always higher than those of the control group. To determine the reason for this observation, we used in situ mass spectrometry imaging (MSI) to detect the distribution of metabolites in the liver of rats. The metabolite distribution of the control rats at different stages was significantly different from that of the model rats, and the high-lipid model differed significantly from the control rats. We identified nine functional metabolites that showed differences throughout the period, namely, PA(20:3-OH/i-21:0), PA(20:4-OH/22:6), PG(20:5-OH/i-16:0), PG(22:6-2OH/i-13:0), PG(O-18:0/20:4), PGP(18:3-OH/i-12:0), PGP(PGJ2/i-15:0), SM(d18:0/18:1-2OH), and TG(14:0/14:0/16:0), among which TG was most significantly correlated with hyperlipidemia and high lipid. This study is unique in that it used MSI to reveal the changes in metabolites in situ, showing the distribution of different metabolites or the same metabolite in liver tissue. The findings highlight the importance of considering the animal's age when using TG as a biomarker for hyperlipidemia. Additionally, the MSI images of the liver in the high-lipid model clearly indicated the distribution and differences of more significant metabolites, providing valuable data for further research into new biomarkers and mechanisms of hyperlipidemia. This new pathway of in situ, visualized, and data-rich metabolomics research provides a more comprehensive understanding of the characteristics of high lipid and its implications for disease prevention and treatment.

Trajectories of 24-Hour Physical Activity Distribution and Relationship with Dyslipidemia.

The association between physical activity (PA) and dyslipidemia is well known, but the relationship between a temporal pattern of PA and dyslipidemia remain unknown. Here, we aimed to identify the intensity and temporal patterns of PA clustered by the trajectory model and their relationship with dyslipidemia. The participants were 701 adults (305 males) aged 18−60 years undergoing continuous measurement of PA with Actigraph GT3X+ accelerometers for at least 3 days. A trajectory analysis was applied based on moderate-to-vigorous intensity physical activity (MVPA) accumulated values over every period per day. The association between PA and dyslipidemia was estimated using a logistic regression model. Four distinct PA trajectory groups in the population were identified (continued low, stable and moderate, late increasing, and early increasing). Specifically, the "moderate and stable group" was associated with a decreased rate of high TG (p < 0.05) and the "moderate and stable group" and "late increasing group" were associated with decreased rates of low HDL-C (p < 0.05). In conclusion, there were four activity trajectory groups in this population and the continued low PA trajectory was associated with a high prevalent rate of an abnormal lipid profile, and continued and moderate activity or late afternoon increasing activity might have lower HDL-C distribution.

Neddylation Regulation of Immune Responses.

Neddylation plays a vital role in post-translational modification, intricately shaping the regulation of diverse biological processes, including those related to cellular immune responses. In fact, neddylation exerts control over both innate and adaptive immune systems via various mechanisms. Specifically, neddylation influences the function and survival of innate immune cells, activation of pattern recognition receptors and GMP-AMP synthase-stimulator of interferon genes pathways, as well as the release of various cytokines in innate immune reactions. Moreover, neddylation also governs the function and survival of antigen-presenting cells, which are crucial for initiating adaptive immune reactions. In addition, neddylation regulates T cell activation, proliferation, differentiation, survival, and their effector functions, thereby ensuring an appropriate adaptive immune response. In this review, we summarize the most recent findings in these aspects and delve into the connection between dysregulated neddylation events and immunological disorders, especially inflammatory diseases. Lastly, we propose future directions and potential treatments for these diseases by targeting neddylation.

Analytical Model of Piezoresistivity for an Inner-Adhesive-Type Carbon Fibre Reinforced Plastic Tunnel Reinforcement.

Cracks in a tunnel lining often emerge under the coupling action of earth and water pressures in a complex stratum environment, and accidents often occur in the process of repairing cracks. In this study, we used the force-sensitive properties of embedded carbon fibre to conduct early-warning research on lining reinforcement to prevent secondary damage during tunnel lining reinforcement. According to the earth load characteristics, a bond stress-slip model of the embedded carbon fibre under bidirectional earth pressure was established on the basis of the thick-walled cylinder theory and the semi-inverse method in elastic theory. The length change of a single fibre was obtained on the basis of the principle that the volume of a single carbon fibre is constant during the deformation process. The resistance and strain model of the single carbon fibre under the action of an external force was then established following the relationship between the resistance, the length change and the volume change of the single carbon fibre. The resistance of carbon fibre composite materials, according to their production technology and unidirectional force properties, was assumed to be a mixture of the series and parallel resistances of the single carbon fibre, and a piezoresistive model of carbon fibre composite materials was formed by using the multidimensional Taylor series expansion and the idea of the average equivalent. The comparison between the theoretical and monitoring values of the piezoresistive model in a tunnel project in Tibet, China revealed that the resistance of various types of carbon fibres increases with the radius of the lining reinforcement and earth pressure and decreases with an increase in the lining reinforcement thickness. Meanwhile, the angles at different positions of the lining reinforcement also have certain effects on the resistance value of the carbon fibre. The variation curve of the piezoresistive model was exponential in both deeply and shallowly buried tunnels, which verifies the rationality of the model.

Lipidomics Reveals That Rice or Flour as a Single Source of Carbohydrates Cause Adverse Health Effects in Rats.

The type of diet is very important for the maintenance of health and nutrition. How the sole source of carbohydrates from rice- or flour-based diet affect blood sugar has not been elucidated for a long time. In order to explore the effects of these diets, sixty SD rats were randomly divided into three groups: control group (C group, AIN-93, standard diet), rice diet group (R group), and flour diet group (F group). All the rats were fed for 7 weeks in total by the assigned diets for 4 weeks (stage 1, S1) and all by the AIN-93 diet for 3 weeks (stage 2, S2). The body weights of all the rats were monitored and serum samples were taken for testing blood glucose, biochemical indicators and untargeted lipidome. It was found that both rice and flour-based diets caused weight gain, but the flour diet had a significant increase in blood sugar and low-density lipoprotein (LDL), while a significant decrease in albumin (ALB) and triglycerides (TG). Twenty-three and 148 lipids were changed by lipidomics in the rice diet group and flour diet group, respectively, and two lipids showed the same changes in the two groups, all belonging to TGs, namely TG (16:0/16:0/16:1) and TG (16:0/16:1/18:2), which showed that a single diet source had a significant effect on the health of rats. Fortunately, we can recover this effect through the subsequent standard diet, allowing the rats to return to normal blood sugar, weight and biochemical indicators. A model can predict the diet types through the logistic regression method. Finally, we proposed that a single diet increased blood sugar and weight through a decrease in TGs, and blood sugar and weight returned to normal after a standard diet. Taken together, the short-term negative effects caused by a single diet can be recovered by a standard diet and further proves the importance of diet types.

[Effects of rice wheat intervention on intestinal microflora of rats based on metagenomics].

OBJECTIVE: To investigate the effects of rice on intestinal microflora in rats. METHODS: Thirty 4-week-old male SD rats were randomly divided into control group, rice group and wheat group according to body weight. The control group was fed with AIN-93 diet, the rice group and the wheat group was fed with the AIN-93 diet which the carbohydrate was replaced with rice and wheat, respectively, for 4 weeks. At the end of the experiment, lipid related biochemical indexes were determined, and the contents of the distal colon(feces) of rats were collected for macro factor detection. RESULTS: From the beginning to the end of feeding, there was no difference in weight gain among the groups. After the end of the experiment, there was no difference among lipid-related indicators and blood glucose. α diversity showed that there was no difference in the diversity of intestinal microbiota between the rice and wheat groups, and the gene abundance analysis of intestinal microbiota in the wheat group showed that the gene abundance of intestinal microbiota was lower. The difference analysis of intestinal microbiota result showed that compared with the rice group, the wheat group was composed of higher proportion of verrucomicrophyla and lower proportion of Bacteroidetes. Lefse analysis showed that the surface group was enriched with Akkermansia Muciniphila, Bifidobacterium animalis, and a variety of beneficial bacteria such as Faecalibaculum rodentium and Intestinimonas butyriciproducens, while Prevotella copri was rich in the rice group. Glycoside hydrolases 8, glycoside hydrolases 16, glycoside hydrolases 99 and glycosyl transferase family 56. CONCLUSION: Rice or wheat as different carbohydrate sources have different effects on the composition of intestinal microflora and carbohydrate-related active enzymes in rats.

Treatment during a developmental window prevents NF1-associated optic pathway gliomas by targeting Erk-dependent migrating glial progenitors.

The mechanism of vulnerability to pediatric low-grade gliomas (pLGGs)-the most common brain tumor in children-during development remains largely unknown. Using mouse models of neurofibromatosis type 1 (NF1)-associated pLGGs in the optic pathway (NF1-OPG), we demonstrate that NF1-OPG arose from the vulnerability to the dependency of Mek-Erk/MAPK signaling during gliogenesis of one of the two developmentally transient precursor populations in the optic nerve, brain-derived migrating glial progenitors (GPs), but not local progenitors. Hyperactive Erk/MAPK signaling by Nf1 loss overproduced GPs by disrupting the balance between stem-cell maintenance and gliogenesis of hypothalamic ventricular zone radial glia (RG). Persistence of RG-like GPs initiated NF1-OPG, causing Bax-dependent apoptosis in retinal ganglion cells. Removal of three Mek1/Mek2 alleles or transient post-natal treatment with a low-dose MEK inhibitor normalized differentiation of Nf1-/- RG-like GPs, preventing NF1-OPG formation and neuronal degeneration. We provide the proof-of-concept evidence for preventing pLGGs before tumor-associated neurological damage enters an irreversible phase.

Metabolomics and physiological analysis of the effect of calcium supplements on reducing bone loss in ovariectomized rats by increasing estradiol levels.

BACKGROUND: Data from the 2010-2012 Chinese National Nutrition and Health Survey showed that the vast majority of postmenopausal women in China had dual deficiencies in calcium and estrogen. OBJECTIVE: This study aimed to clarify whether calcium supplementation alleviated bone loss caused by calcium restriction combined with estrogen deficiency in rats. METHODS: Forty-eight female rats aged 9 weeks were assigned to 4 groups and fed a low-calcium diet: sham-operated (SHAM-LC), ovariectomized (OVX-LC), and ovariectomized rats treated with 750 mg/kg (OVX-LC-M) or 2800 mg/kg CaCO3 (OVX-LC-H). CaCO3 or distilled water was administered orally for 13 weeks. Bone mineral density (BMD) and histomorphometry of the femur, serum biochemical parameters, and serum metabolites were analyzed. RESULTS: The OVX-LC rats showed a significant increase in body weight and serum levels of lipid markers, a significant decrease in serum estradiol, calcium, phosphorus, and 25(OH)D levels, and deterioration of the femur. At 750 mg/kg and 2800 mg/kg, CaCO3 reduced the deterioration of trabecular bone and increased the trabecular area percentage (Tb.Ar %) and BMD of the femur. Serum estradiol levels increased in a dose-dependent manner after CaCO3 supplementation (p < 0.01). The administration of 2800 mg/kg CaCO3 decreased serum triglyceride and high-density lipoprotein levels (p < 0.05) and decreased the levels of the bone turnover markers osteocalcin, N-telopeptide of type I collagen and ß-crosslaps. The results of the metabolomics analysis showed that the glycerophospholipid metabolism pathway was closely related to calcium supplementation, and more DG (44:6 n3), LysoPC (22:2) and PE (P-34:3) and less Cer (d43:0) and PE-NMe2 (46:3) were produced. CONCLUSIONS: The results clearly indicated that calcium supplementation was beneficial for decreasing bone loss in OVX-LC rats. The present study is the first to show that calcium supplementation increased the estradiol content in OVX-LC rats, and the effect of calcium on bone loss may be partially attributed to the increase in the estrogen level that subsequently induced the changes in metabolite levels, eventually increasing the bone mineral density to a relatively higher level to reduce bone deterioration.

[Validity of the international physical activity questionnaire and bouchard diary in Chinese adults].

OBJECTIVE: Based on the accelerometer, the validity of the international physical activity questionnaire long version(IPAQ-L) and Bouchard diary were evaluated to measure the daily physical activity of Chinese adults aged 18-59 years old. METHODS: A total of 200 Chinese adults were recruited in Yinzhou District of Ningbo City in 2019, including 78 males and 122 females, the three age groups 18-29, 30-49, 50 and above accounted for 19. 5%, 61. 5% and 18. 0%, respectively. The volunteers wore Actigraph WGT3 x-BT three-dimensional accelerometer for 3 days, and completed the 3 consecutive days& apos; Bouchard diary and the IPAQ-L. The physical activity energy expenditure(PAEE), sedentary inactivity time, light physical activity time(LPA) and moderate-to-vigorous physical activity time(MVPA) measured by the three tools were estimated respectively. Spearman analysis was used to analyze the correlation, the Friedman test and the Bland-Altman plot were used to test the homogeneity of the three method. RESULTS: 196 volunteers were included in this study. The correlation coefficients of PAEE between IPAQ and diary and accelerometer were 0. 32 and 0. 58, respectively, the correlation coefficients of sedentary behavior were 0. 17, 0. 25, and LPA time was 0. 33, and the estimated IPAQ for MVPA time better than diary. The difference test result showed that, except for IPAQ in the measurement of MVPA, there was no statistical difference from the accelerometer measurement result(P=0. 684), and the difference between other estimated values and the accelerometer measurement result was statistically significant(P& lt; 0. 01), Bland-Altman plot result showed that the diary and IPAQ had good consistency in the measurement of PAEE and IPAQ in the estimation of MVPA time, but there was an overestimation in PAEE. In addition, IPAQ had poor validity in measuring sedentary behavior and LPA. CONCLUSION: IPAQ and Bouchard diary have better validity in evaluating PAEE, and the diary is better than IPAQ. IPAQ has better validity in evaluating MVPA time, but has poor validity in estimating sedentary behavior and LPA time.

Primary cilium and its role in tumorigenesis.

The primary cilium, a sensory organelle that protrudes from the surface of most eukaryotic cells, receives and transduces various critical signals that are essential for normal development and homeostasis. Structural or functional disruption of primary cilia causes a number of human diseases, including cancer. Primary cilia has cross talks with cell cycle and it may act as a cell cycle checkpoint to suppress cancer development. Moreover, primary cilia has cross-regulation with autophagy, which may affect tumor progression. We then discuss the association of the primary cilia with several oncogenic signaling pathways, including Shh, Wnt, Notch and platelet-derived growth factor receptor (PDGFR). Since these signaling pathways are often over-activated in many types of human cancers, primary cilia are likely to play a role in the tumorigenesis by modulating these pathways. Finally, we summarize current progress on the role of cilia during tumorigenesis and the challenges that the cilia-cancer field faces.

[Effects of calcium on the structure of intestinal microbiota in ovariectomized rats].

OBJECTIVE: To study the effect of calcium content on bone mineral density and intestinal microbiota in ovariectomized rats. METHODS: A total of 30 Wistar rats were randomly divided into 3 groups, namely the sham operation group, the model group and the calcium carbonate supplement group. Postmenopausal osteoporosis rats were established by ovariectomy(OVX). After the first week of modeling, each group was intragastric separately. The calcium carbonate solution was given to the calcium carbonate supplement group, and the same amount of sterile water was given to the other two groups. The animals were executed at the end of the 12 weeks. Left femur was taken and bone mineral density(BMD) was detected by dual-energy X-ray absorptiometry. The total DNA of fecal samples was aseptically extracted and the Illumina Miseq platform was to carry out high-throughput sequencing. RESULTS: Compared with the sham operation group, the body mass increment of rats in the model group was significantly increased, the level of BMD was significantly reduced(P<0. 05), the intestinal microbiota diversity was not significantly changed, the Firmicutes abundance was decreased, and the Bacteroidetes abundance was increased. Compared with the model group, the body mass increment of rats in the calcium carbonate supplementation group was significantly reduced and BMD was significantly increased(P<0. 05). There was no significant change in the intestinal microbiota diversity, Firmicutes were increased, and Bacteroidetes were decreased. CONCLUSION: Calcium supplementation can improve bone mineral density and inhibit the increase of body mass during the experiment period, and its mechanism may be related to regulating the structure of intestinal microbiota.

[Comparative study of the detection of serum folate with improved microbial assay and electrochemiluminescence method].

OBJECTIVE: To compare the result of serum folate determined by improved microbial assay and electrochemiluminescence method, and to look for the relationship between them, so as to provide basis for the assessment of nutrition status of folate in population. METHODS: A total of 258 serum samples were examined by improved microbial assay and electrochemiluminescence method. The correlation and consistence of the two method were analyzed. RESULTS: The result showed that the correlation coefficient of the two method was 0. 885, which indicated that the result of two method were highly correlated. Results of Bland-Altman method showed that 94. 5% of the values were within the consistency limit, and the Kappa value of Kappa test was 0. 665. The result of consistency analysis showed that there were some differences between the two methods, and the result of serum folate tested by improved microbial assay were higher than that of electrochemiluminescence method in general. CONCLUSION: The result of serum folate tested by electrochemiluminescence were highly correlated with the improved microbial assay, yet there are some differences in the consistency result between the two methods. Evaluating the nutrition status of folate by electrochemiluminescence may lead to a higher number of folate deficiency.

[Immune function effect of F3 rats fed with genetically modified maize harboring Cry1Ab and epsps genes].

OBJECTIVE: To evaluate the effects of genetically modified maize with Cry1Ab and epsps genes on immune function in F3 rats. METHODS: A total of 180 weaning SD rats for F0 generation were randomly divided into three groups, which were treated with AIN-93 G feed control diet, parental maize diet and genetically modified maize diet respectively. After three generations of breeding, antibody producing cells determination, concanavalin A(ConA)-induced lymphocyte transformation test, natural killer(NK)cells activities assay, whole blood lymphocyte subtype detection, delayed type hypersensitivity test and immunity organ index were performed. RESULTS: There were no significant differences between parental maize diet and genetically modified maize diet in terms of the number of antibody-producing cells, ConA-induced spleen lymphocyte proliferation, NK cell activity, whole blood lymphocyte subsets, delayed type hypersensitivity and thymus index(P>0. 05). CONCLUSION: Under the conditions of this experiment, no significant effects were found on immune function of F3 SD rats through the three generation development study of genetically modified maize with CrylAb and epsps genes.

Three-Generation Reproductive Toxicity of Genetically Modified Maize with Cry1Ab and epsps Genes in Rats.

The genetically modified maize carrying an insect-resistant gene and herbicide-tolerant gene has substantial benefits for crop production. The three-generation reproductive toxicity of the maize was studied in this paper. One hundred and eighty Sprague-Dawley (SD) rats were divided into three groups, which were fed with a genetically modified maize (GM) diet, receptor maize (RM) diet, and AIN-93G (AIN) diet (used as control), respectively. The body weight, food consumption, reproductive parameters, hematological parameters, serum chemistry, organ weight, and histopathology for the three generations were examined, respectively. Minor differences were found between the GM group and the RM group or the AIN control group in terms of reproductive data, hematology, blood chemistry parameters, and organ index, but no macroscopic or histological adverse effects were found or considered as treatment-related. In conclusion, the three-generation study of genetically modified maize DBN9936 with Cry1Ab and epsps genes at a high level showed no unintended adverse effects on rats' reproductive system.

Neddylation-Independent Activities of MLN4924.

MLN4924, also known as pevonedistat, is a highly selective small-molecule inhibitor of NEDD8 (neuronal precursor cell-expressed developmentally downregulated protein 8)-activating enzyme (NAE) to block the entire neddylation modification cascade, leading to inactivation of cullin-RING ligases (CRLs), since activation of CRLs requires cullin neddylation. MLN4924 showed impressive anticancer activity in many preclinical studies and is currently in several Phase I/II clinical trials for anticancer therapy as a single agent or in combination with chemotherapeutic drugs.In addition to well-characterized anti-neddylation activity, recent studies showed that MLN4924 has several neddylation-independent activities. First, MLN4924 triggers EGFR dimerization to activate EGFR and its downstream RAS/MAPK and PI3K/AKT1 signals, leading to enhanced tumor sphere formation, accelerated EGF-mediated wound healing, and inhibited ciliogenesis. Second, MLN4924 induces PKM2 tetramerization to promote glycolysis, thus affecting energy metabolism. Third, MLN4924 inhibits the interaction between ACT1 (NF-κB activator 1) and TRAF6 (tumor necrosis factor receptor-associated factor 6) and attenuates IL-17A-mediated activation of NF-κB to reduce pulmonary inflammation. Fourth, MLN4924 inhibits IRF3 binding to the IFN-ß promoter to inhibit IFN-ß production. And finally, MLN4924 activates the JNK signaling pathway to reduce c-FLIP levels, thus enhancing TRAIL-induced apoptosis. This chapter will summarize these neddylation-independent activities of MLN4924 and discuss the underlying mechanisms and potential therapeutic applications.

[A cohort study of serum leptin level in Zhejiang Province middle and old age residents on blood pressure and hypertension from 2014 to 2017].

OBJECTIVE: To investigate the association between serum leptin concentration with blood pressure and hypertension in different gender. METHODS: A total of 343 non-hypertensive residents aged 30 to 65 were randomly selected from Zhejiang Province in 2014. Parameters including height, weight, waist, blood pressure, serum lipid and serum leptin concentration of participants were measured and determined by physical examination and laboratory detection in 2014 and 2017. The differences in serum leptin levels between the new hypertensive and non-hypertensive people were compared after three years. The relationship between serum leptin levels and hypertension was analyzed by Logistic regression. RESULTS: In 2014 and 2017, concentration of serum leptin in females was significantly higher than that in males, and the blood pressure in males was higher than that in females. At the end of follow-up, 26 new cases of hypertension were found. Serum leptin levels were higher in the female hypertensive group than in the non-hypertensive group(P=0. 0289), whereas there was no statistical difference in males(P>0. 01). Regardless of gender, serum leptin was significantly positively correlated with body mass index(BMI) and waist-to-height ratio(WHtR)(P<0. 0001), and also had correlation with blood pressure. However, after adjusting for BMI or WHtR, the correlation between serum leptin and blood pressure disappeared(P>0. 01). Logistic regression also showed the similar result. CONCLUSION: Serum leptin is not directly related to blood pressure and hypertension, and the positive correlation between them may be explained largely by BMI and WHtR.