Sex differences in the effects of brown adipocyte CD47 deficiency on age-related weight change and glucose homeostasis.

Our previous studies demonstrated that mice with global CD47 deficiency are lean and resistant to diet or aging-associated obesity and metabolic complications. This protective effect is partially through modulating brown fat function. To definitively determine the role of brown fat CD47 in age-related metabolic homeostasis, inducible brown adipocyte-specific cd47 deficient mice were generated by crossbreeding cd47 floxed mice with UCP1-CreERT2 mice and characterized in this study. Efficient knockdown of CD47 in brown fat was achieved in both male and female mice through tamoxifen administration. Intriguingly, our findings indicated that male mice lacking CD47 in brown fat displayed a notable reduction in body weight starting at 23 weeks of age when housed at a temperature of 22 °C, in comparison to control mice. This reduction in weight was accompanied by improved glucose tolerance. Remarkably, this phenotype persisted even when the male mice were housed under thermoneutral conditions (30 °C). Conversely, female knockout mice did not exhibit significant changes in weight throughout the study. In addition to the enhanced glucose homeostasis, brown fat CD47 deficiency in male mice also prevented age-related hypertriglyceridemia and non-alcoholic fatty liver disease. Furthermore, the brown fat tissue of male knockout mice exhibited reduced whitening, while maintaining comparable levels of thermogenic markers. This suggests the involvement of a thermogenesis-independent mechanism. Altogether, these findings highlight a sex difference in the impact of brown adipocyte CD47 deficiency on age-related weight changes and glucose homeostasis.

Adipocyte-Derived PXR Signaling Is Dispensable for Diet-Induced Obesity and Metabolic Disorders in Mice.

Pregnane X receptor (PXR) is a xenobiotic receptor that can be activated by numerous chemicals including endogenous hormones, dietary steroids, pharmaceutical agents, and environmental chemicals. PXR has been established to function as a xenobiotic sensor to coordinately regulate xenobiotic metabolism by regulating the expression of many enzymes and transporters required for xenobiotic metabolism. Recent studies have implicated a potentially important role for PXR in obesity and metabolic disease beyond xenobiotic metabolism, but how PXR action in different tissues or cell types contributes to obesity and metabolic disorders remains elusive. To investigate the role of adipocyte PXR in obesity, we generated a novel adipocyte-specific PXR deficient mouse model (PXRΔAd). Notably, we found that loss of adipocyte PXR did not affect food intake, energy expenditure, and obesity in high-fat diet-fed male mice. PXRΔAd mice also had similar obesity-associated metabolic disorders including insulin resistance and hepatic steatosis as control littermates. PXR deficiency in adipocytes did not affect expression of key adipose genes in PXRΔAd mice. Our findings suggest that adipocyte PXR signaling may be dispensable in diet-induced obesity and metabolic disorders in mice. Further studies are needed to understand the role of PXR signaling in obesity and metabolic disorders in the future. SIGNIFICANCE STATEMENT: The authors demonstrate that deficiency of adipocyte pregnane X receptor (PXR) does not affect diet-induced obesity or metabolic disorders in mice and infers that adipocyte PXR signaling may not play a key role in diet-induced obesity. More studies are needed to understand the tissue-specific role of PXR in obesity.

Transfer learning-based attenuation correction for static and dynamic cardiac PET using a generative adversarial network.

PURPOSE: The goal of this work is to demonstrate the feasibility of directly generating attenuation-corrected PET images from non-attenuation-corrected (NAC) PET images for both rest and stress-state static or dynamic [13N]ammonia MP PET based on a generative adversarial network. METHODS: We recruited 60 subjects for rest-only scans and 14 subjects for rest-stress scans, all of whom underwent [13N]ammonia cardiac PET/CT examinations to acquire static and dynamic frames with both 3D NAC and CT-based AC (CTAC) PET images. We developed a 3D pix2pix deep learning AC (DLAC) framework via a U-net + ResNet-based generator and a convolutional neural network-based discriminator. Paired static or dynamic NAC and CTAC PET images from 60 rest-only subjects were used as network inputs and labels for static (S-DLAC) and dynamic (D-DLAC) training, respectively. The pre-trained S-DLAC network was then fine-tuned by paired dynamic NAC and CTAC PET frames of 60 rest-only subjects to derive an improved D-DLAC-FT for dynamic PET images. The 14 rest-stress subjects were used as an internal testing dataset and separately tested on different network models without training. The proposed methods were evaluated using visual quality and quantitative metrics. RESULTS: The proposed S-DLAC, D-DLAC, and D-DLAC-FT methods were consistent with clinical CTAC in terms of various images and quantitative metrics. The S-DLAC (slope = 0.9423, R2 = 0.947) showed a higher correlation with the reference static CTAC as compared to static NAC (slope = 0.0992, R2 = 0.654). D-DLAC-FT yielded lower myocardial blood flow (MBF) errors in the whole left ventricular myocardium than D-DLAC, but with no significant difference, both for the 60 rest-state subjects (6.63 ± 5.05% vs. 7.00 ± 6.84%, p = 0.7593) and the 14 stress-state subjects (1.97 ± 2.28% vs. 3.21 ± 3.89%, p = 0.8595). CONCLUSION: The proposed S-DLAC, D-DLAC, and D-DLAC-FT methods achieve comparable performance with clinical CTAC. Transfer learning shows promising potential for dynamic MP PET.

Expert consensus on oncological [18F]FDG total-body PET/CT imaging (version 1).

BACKGROUND: [18F]FDG imaging on total-body PET/CT (TB PET/CT) scanners, with improved sensitivity, offers new potentials for cancer diagnosis, staging, and radiation treatment planning. This consensus provides the protocols for clinical practices with a goal of paving the way for future studies with the total-body scanners in oncological [18F]FDG TB PET/CT imaging. METHODS: The consensus was summarized based on the published guidelines and peer-reviewed articles of TB PET/CT in the literature, along with the opinions of the experts from major research institutions with a total of 40,000 cases performed on the TB PET/CT scanners. RESULTS: This consensus describes the protocols for routine and dynamic [18F]FDG TB PET/CT scanning focusing on the reduction of imaging acquisition time and FDG injected activity, which may serve as a reference for research and clinic oncological PET/CT studies. CONCLUSION: This expert consensus focuses on the reduction of acquisition time and FDG injected activity with a TB PET/CT scanner, which may improve the patient throughput or reduce the radiation exposure in daily clinical oncologic imaging. KEY POINTS: • [18F]FDG-imaging protocols for oncological total-body PET/CT with reduced acquisition time or with different FDG activity levels have been summarized from multicenter studies. • Total-body PET/CT provides better image quality and improved diagnostic insights. • Clinical workflow and patient management have been improved.

First report of successful treatment of chronic pediatric tibial osteomyelitis and fracture using autologous platelet-rich plasma.

Osteomyelitis is a refractory disease caused by microbial invasion of the bone, leading to destruction of the bone tissue. It is more common in children. Osteomyelitis requires long treatment at high cost and is associated with high rates of recurrence and disability. It can also be complicated by sepsis that, if not treated in time, can result in death. Here, we report the first case of a 10-year-old patient who presented with chronic tibial osteomyelitis complicated with fracture. The patient had received traditional treatment for osteomyelitis for over 14 months without success. However, after 4 months of treatment with autologous platelet-rich plasma, the fracture, infection, and osteomyelitis resolved completely. These clinical observations demonstrate the potential for using autologous platelet-rich plasma as a novel treatment for chronic pediatric osteomyelitis.

Association of cognitive impairment and diabetes on survival in Chinese older people with hypertension: a 10-year prospective study.

BACKGROUND: Older people with hypertension may have more complex multisystem problems and a higher risk of morbidity and mortality. We aimed to examine the association of cognitive impairment (CI) and diabetes mellitus (DM) on all-cause mortality in the aged with hypertension (HTN). METHODS: This is a prospective cohort study with a sample of 1017 older people with hypertension aged 60 years or older who completed baseline examinations in 2009-2010 and followed up for ten years in 2020. The endpoint was death from any cause. Subjects were categorized as HTN only, HTN + DM, HTN + CI, and HTN + DM + CI. Cox regression model was used to determine the association of comorbidities on all-cause mortality. RESULTS: During the 10-year follow-up period, 196 deaths occurred. After adjusted for covariates, risk of death from any cause was significantly increased in the older people with increased comorbidities (P = 0.003). Compared with the HTN only, with HTN + CI, and HTN + DM + CI, the HRs (95% confidence intervals) for all-cause mortality were 1.61(1.13-2.30) and 1.79(1.07-2.99), respectively. In stratified analyses, the relationship between comorbidities level and the risk of all-cause mortality persisted. CONCLUSION: All-cause mortality risks increased with increasing the comorbidities. This study emphasizes the importance of comprehensive management of the older people with HTN in clinical practice and public health policy.

[Breast milk intake of Chinese infants aged 0-5 months in 2019-2021].

OBJECTIVE: To describe the breast milk intake of infants aged 0-5 months in China and its trends, and to analyze the effects of feeding mode, gender and regions on breast milk intake. METHODS: Data were extracted from Ministry of Science and Technology's basic resource survey project "China's 0-18-year-old children's nutrition and health system survey and application" project. Caregivers were face to face interviewed to collect the basic information of infants. Weighing method was used to measure 24 hourly breast milk intake of infants aged 0-5 months in China. The rank sum test was used to compare the differences in breast milk intake between groups, the Spearman rank sum test was used to analyze the trend of breast milk intake with increasing age, and the general linear regression model was used to analyze the effects of gender and region on breast milk intake. RESULTS: The mean breast milk intake of exclusively breastfed infants aged 0-5 months was 800.1 g/d, ranging from 696.4 to 937.7 g/d. Breast milk intake increased with age and remained stable at 5 months(ß=29.6, P=0.009). There was a statistically significant difference in breast milk intake among infants in different month age groups(χ~2=17.96, P=0.003). Infants aged 0-5 months who are exclusively breastfed were fed 8 times in 24 hours, the breast milk intake per each time is 103.4-152.5 g, the duration of each feeding is 20.4-24.6 min, and the breast milk intake per minute is 4.4-7.0 g. Except for 5 months of age, there was no gender difference in the 24-hour breast milk intake of exclusively breastfed infants aged 0 to 4 months(P>0.05). Except for 4-month-old exclusively breastfed infants, there was no regional differences in the breast milk intake of others(t=-4.25, P<0.001). In the mixed feeding group, breast milk + complementary feeding group and breast milk + formula powder + complementary feeding group, the breast milk intake of infants aged 0-5 months were 341.1-496.7 g, 239.1-742.7 g and 90.0-508.0 g, respectively. CONCLUSION: In 2019-2021, infants aged 0-5 months in China Breast milk intake increased with age, and remained stable at 5 months. The breast milk intake of infants aged 0-5 months in different regions or genders is similar except for individual months. The introduction of formula or complementary food directly affects the intake of breast milk in infants.

YTHDF3 modulates hematopoietic stem cells by recognizing RNA m6A modification on Ccnd1.

Hematopoietic stem cells (HSC) give rise to the cells of the blood system over the whole lifespan. N6-methyladenosine (m6A), the most prevalent RNA modification, modulates gene expression via the processes of "writing" and "reading". Recent studies showed that m6A "writer" genes (Mettl3 and Mettl14) play an essential role in HSC. However, which reader deciphers the m6A modification to modulate HSC remains unknown. In this study, we observed that dysfunction of Ythdf3 and Ccnd1 severely impaired the reconstitution capacity of HSC, which phenocopies Mettl3-deficient HSC. Dysfunction of Ythdf3 and Mettl3 results in a translational defect of Ccnd1. Ythdf3 and Mettl3 regulate HSC by transmitting m6A RNA methylation on the 5' untranslated region of Ccnd1. Enforced Ccnd1 expression completely rescued the defect of Ythdf3-/- HSC and partially rescued Mettl3-compromised HSC. Taken together, this study identified, for the first time, that Ccnd1 is the target of METTL3 and YTHDF3 to transmit the m6A RNA methylation signal and thereby regulate the reconstitution capacity of HSC.

Anti-CD47 antibody treatment attenuates liver inflammation and fibrosis in experimental non-alcoholic steatohepatitis models.

BACKGROUND & AIMS: With the epidemic burden of obesity and metabolic diseases, nonalcoholic fatty liver disease (NAFLD) including steatohepatitis (NASH) has become the most common chronic liver disease in the western world. NASH may progress to cirrhosis and hepatocellular carcinoma. Currently, no treatment is available for NASH. Therefore, finding a therapy for NAFLD/NASH is in urgent need. Previously we have demonstrated that mice lacking CD47 or its ligand thrombospondin1 (TSP1) are protected from obesity-associated NALFD. This suggests that CD47 blockade might be a novel treatment for obesity-associated metabolic disease. Thus, in this study, the therapeutic potential of an anti-CD47 antibody in NAFLD progression was determined. METHODS: Both diet-induced NASH mouse model and human NASH organoid model were utilized in this study. NASH was induced in mice by feeding with diet enriched with fat, fructose and cholesterol (AMLN diet) for 20 weeks and then treated with anti-CD47 antibody or control IgG for 4 weeks. Body weight, body composition and liver phenotype were analysed. RESULTS: We found that anti-CD47 antibody treatment did not affect mice body weight, fat mass or liver steatosis. However, liver immune cell infiltration, inflammation and fibrosis were significantly reduced by anti-CD47 antibody treatment. In vitro data further showed that CD47 blockade prevented hepatic stellate cell activation and NASH progression in a human NASH organoid model. CONCLUSION: Collectively, these data suggest that anti-CD47 antibody might be a new therapeutic option for obesity-associated NASH and liver fibrosis.

Human milk cholesterol is associated with lactation stage and maternal plasma cholesterol in Chinese populations.

BACKGROUND: Milk cholesterol concentrations throughout lactation were analyzed, and the relationship between maternal plasma cholesterol and milk cholesterol in various Chinese populations was examined. METHODS: A sub-sample of 1138 lactating women was randomly selected from a large cross-sectional study in China (n = 6481). Milk cholesterol concentrations were determined by HPLC, and concentrations of maternal plasma lipids were determined by an automated biochemical analyzer. RESULTS: The mean cholesterol concentrations were 200, 171, and 126 mg/L for colostrum, transitional milk, and mature milk, respectively. Cholesterol concentrations differed significantly between stages of lactation (colostrum vs. transitional milk, colostrum vs. mature milk, transitional milk vs. mature milk, all p < 0.001). Concentrations of maternal plasma total cholesterol (TC) (p = 0.02) and low-density lipoprotein cholesterol (LDL-C) (p = 0.03) were significantly associated with milk cholesterol. Milk cholesterol concentrations varied among different ethnicities (Tibetan vs. Hui: 164 vs. 131 mg/L, p = 0.027) but not among different geographic regions. CONCLUSIONS: The concentration of cholesterol in human milk changes dynamically throughout lactation. Milk cholesterol concentrations are significantly associated with maternal plasma concentrations of TC and LDL-C, and milk cholesterol concentrations vary across ethnicities in China. IMPACT: Concentrations of milk cholesterol were measured in various Chinese populations. Cholesterol concentrations differ significantly between stages of lactation. Maternal plasma total cholesterol and low-density lipoprotein cholesterol are associated with milk cholesterol. Milk cholesterol concentrations vary across ethnicities in China.

Diagnostic challenges in primary cardiac lymphoma, the opportunity of 18F-FDG PET/CT integrated with contrast-enhanced CT.

BACKGROUND: The purpose of this study was to retrospectively evaluate the value of 18F-FDG PET/CT integrated with contrast-enhanced CT (CECT) in the differential diagnosis of primary cardiac lymphomas (PCLs) and primary cardiac angiosarcomas (PCAs). METHODS: Clinical and imaging data of patients with PCLs and PCAs were collected. All patients underwent preoperative 18F-FDG PET/CT and thoracic CECT. The enhancement pattern and tumor morphology were analyzed using CECT images. The intensity- and volume-based PET parameters of cardiac lesions were analyzed. The performance characteristics of all parameters were assessed. RESULTS: Nine patients with PCL and eight patients with PCA were analyzed. There were significant differences in SUVmax (t = 3.790, P = .002), SUVmean (t = 4.273, P = .001), metabolic tumor volume (U = 13.00, P = .027), tumor-to-liver ratio (U = 10.00, P = .011), and total lesion glycolysis (U = 4.0, P = .001) between PCLs and PC18As. There were significant differences in the enhancement pattern of tumors (P = .002) and tumor morphology (P = .015). The combination of F-FDG PET/CT and CECT improved the diagnostic accuracy, and the combination cutoff (SUVmean > 5.17) could reach 100%, but the difference was not statistically significant (P > .05). CONCLUSION: The intensity- and volume-based PET parameters of PCL were significantly higher than those of PCA. The enhancement pattern and tumor morphology were also different. According to these characteristics, the two most common types of primary cardiac malignancies can be differentiated.

Relationship of a new anthropometric index with left ventricular hypertrophy in hypertensive patients among the Han Chinese.

BACKGROUND: This study aimed to assess the relationship of a new anthropometric index with left ventricular hypertrophy (LVH) in hypertensive patients among the Han Chinese. METHODS: The study is a community-based cross-sectional study that included 4639 patients with hypertension and integrated clinical and echocardiographic data. Left ventricular (LV) mass was measured by transthoracic echocardiography. LVH was diagnosed by using the criteria of left ventricular mass indexed (LVMI) over 49.2 g/m2.7 for men and 46.7 g/m2.7 for women. Quartiles of a body shape index (ABSI), body roundness index (BRI), waist circumference (WC), and body mass index (BMI) were used regarding LVH prevalence. The logistic regression model was used to determine the odds ratio (OR) and 95% confidence intervals (CI) of the new anthropometric index and LVH. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive ability of the obesity indices for LVH risk. RESULTS: The prevalence of LVH increased across quartiles for ABSI, BRI, BMI, and WC. Comparing the lowest with the highest quartile, adjusted OR (95% CI) for LVH were significantly different for BRI 3.86 (3.12-4.77), BMI 3.54 (2.90-4.31), and WC 2.29 (1.88-2.78). No association was observed for ABSI. According to ROC analysis, the area under the curve (AUC) of BRI was (AUC: 0.653, 95% CI 0.637-0.669), BMI (AUC: 0.628, 95% CI 0.612-0.644), WC (AUC: 0.576, 95% CI 0.559-0.593), ABSI (AUC: 0.499, 95% CI 0.482-0.516). CONCLUSIONS: This study shows that LVH prevalence increased per quartile across the Han Chinese population with hypertension for ABSI, BRI, BMI, and WC. There is a significant association between BRI and LVH in hypertensive people, while ABSI was not. BRI showed potential for use as an alternative obesity measure in the assessment of LVH.

Conicity-index predicts all-cause mortality in Chinese older people: a 10-year community follow-up.

BACKGROUND: Abdominal obesity (AO) has been regarded as the most dangerous type of obesity. The Conicity-index (C-index) had a high ability to discriminate underlying AO. The purpose of this study was to determine the ability of C-index to predict all-cause mortality among non-cancer Chinese older people. METHODS: The participants were residents of the Wanshou Road community in Beijing, China. Receiver operating curve (ROC) curves were used to determine the sensitivity and specificity of the best cut-off values for different anthropometric measures for predicting all-cause mortality. The area under the curve (AUC) of the ROC curves were calculated to compare the relative ability of various anthropometric measures to correctly identify older people in the community where all-cause mortality occurs. Included subjects were grouped according to C-index tertiles. The association between C-index and all-cause mortality was verified using Kaplan-Meier survival analysis and different Cox regression models. RESULTS: During a mean follow-up period of 9.87 years, 1821 subjects completed follow-up. The average age was 71.21 years, of which 59.4% were female. The ROC curve results showed that the AUC of the C-index in predicting all-cause mortality was 0.633. Kaplan-Meier survival curves showed a clear dose-response relationship between C-index and all-cause mortality. With the increase of C-index, the survival rate of the study population showed a significant downward trend (P < 0.05). Adjusted for age, gender, hip circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose (FBG), 2-h postprandial blood glucose (2hPG), glycosylated hemoglobin, high-density lipids protein (LDL), triglyceride, serum creatinine, serum uric acid, urine albumin-creatinine ratio (UACR), Mini-Mental State Examination (MMSE), smoking history, and drinking history, COX regression analysis showed that in the model adjusted for all covariates, the risk of all-cause mortality in tertile 3 was 1.505 times that in tertile 1, and the difference was statistically significant. CONCLUSIONS: The C-index is an independent risk factor for all-cause mortality in the non-cancer Chinese older people.

The relationship between urinary albumin to creatinine ratio and all-cause mortality in the elderly population in the Chinese community: a 10-year follow-up study.

BACKGROUND: In patients with diabetes and hypertension, proteinuria is independently associated with all-cause death. However, in the general population, urinary albumin to creatinine ratio (UACR) is less used to predict all-cause mortality. When the urinary albumin to creatinine ratio is within the normal range (UACR< 30 mg/g), the clinical relevance of an increased urinary albumin excretion rate is still debated. We studied the relationship between UACR and all-cause mortality in community populations, and compared UACR groups within the normal range. METHODS: The participants were the inhabitants from the Wanshoulu community in Beijing, China. The average age is 71.48 years, and the proportion of women is 60.1%. A total of 2148 people completed random urine samples to determine the urinary albumin to creatinine ratio (UACR). The subjects were divided into three groups according to UACR: Group 1 (UACR< 10 mg/g), Group 2 (10 mg/g < UACR< 30 mg/g), Group 3 (UACR> 30 mg/g). We used Kaplan-Meier survival analysis and Cox regression model to verify the relationship between UACR and all-cause mortality. RESULTS: At an average follow-up of 9.87 years (718,407.3 years), the total mortality rate were 183.4/1000. In the Cox proportional hazards model, after adjusting for possible confounders, those with normal high-value UACR (group 2) showed a higher all-cause mortality than those with normal low-value UACR (group 1) [hazard ratio (HR) 1.289, 95% confidence interval (CI) 1.002 ~ 1.659 for all-cause mortality]. Those with proteinuria (group 3) showed a higher all-cause mortality than those with normal low-value UACR (group 1) [hazard ratio (HR) 1.394, 95% confidence interval (CI) 1.020 ~ 1.905 for all-cause mortality]. CONCLUSION: Urinary albumin to creatinine ratio is an important risk factor for all-cause death in community population. Even if it is within the normal range (UACR< 30 mg/g), it occurs in people with high normal value (10 mg/g < UACR< 30 mg/g), the risk of all-cause death will also increase.

[Meta analysis of the validity of image-based dietary assessment method based on energy and macronutrients].

OBJECTIVE: Meta-analysis was used to study the validity of image-based dietary assessment(IBDA) in evaluating energy and macronutrients intake, and compared with three traditional method: weighed food record(WFR), 24-hour dietary recall(24-HDR) and double-labeled water(DLW). METHODS: Studies were retrieved and collected from various databases including China National Knowledge Infrastructure(CNKI), WanFang Database, VIP Database, PubMed, Web of Science, Cochrane Library and Embase, screened according to the inclusion and exclusion criteria. After extracting the data, all the data were Meta-analyzed through RevMan 5.4. RESULTS: A total of 24 studies were included. Meta-analysis showed that, comparison of IBDA method and traditional method in energy intake assessment[MD=-54.71 kcal/d(95%CI-118.81-9.39), P=0.09], comparison of carbohydrate intake assessment[MD=-2.77 g(95%CI-8.86-3.31), P=0.37], comparison of protein intake assessment[MD=0.00 g(95%CI-2.09-2.09), P>0.05], comparison of fat intake assessment[MD=0.10 g(95%CI-2.06-2.25), P=0.93], these differences were not statistically significant. Subgroup analysis showed that, IBDA method compared with the 24-hour dietary review method in protein intake(P=0.01), the difference was statistically significant. IBDA method overestimated protein intake by about 7.3% on average compared with the 24-hour dietary review method. CONCLUSION: There was no significant difference between IBDA method and traditional method in the assessment of energy and macronutrient intakes.

[Value of three-dimensional speckle-tracking imaging in evaluating left ventricular systolic function and its correlation with peripheral arterial elasticity in children with simple obesity: a prospective study]. / ä¸‰ç»´æ–‘ç‚¹è¿½è¸ªæˆåƒæŠ€æœ¯å¯¹å•çº¯æ€§è‚¥èƒ–å„¿ç«¥å·¦å¿ƒå®¤æ”¶ç¼©åŠŸèƒ½çš„è¯„ä»·åŠå ¶ä¸Žå¤–å‘¨åŠ¨è„‰å¼¹æ€§ç›¸å ³æ€§çš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To study the application of three-dimensional speckle-tracking imaging in evaluating left ventricular systolic function and its correlation with peripheral arterial elasticity in children with simple obesity. METHODS: Random sampling combined with convenience sampling was used to obtain research samples, and then the samples were divided into an obesity group (23 cases), an overweight group (21 cases), and a normal group (24 cases). Three-dimensional speckle-tracking imaging was used to measure the global longitudinal strain (GLS), global radial strain (GRS), and global circumferential strain (GCS) of the left ventricle. An automatic arteriosclerosis tester was used to measure ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV). These parameters were compared among the three groups. The correlation of three-dimensional speckle-tracking parameters with ABI and baPWV was evaluated. RESULTS: There were no significant differences in GLS, GRS, and GCS between the obesity and normal groups (P>0.05). The overweight group had a significantly higher GLS than the normal group [(-24±7) vs (-19±12), P<0.05]. The obesity and overweight groups had a significantly lower ABI than the normal group [(1.00±0.09)/(1.09±0.13) vs (2.25±0.13), P<0.05). The obesity group had a significantly higher baPWV than the normal group [(978±109) vs (905±22), P<0.05]. In the children with obesity, GLS was positively correlated with baPWV (r=0.516, P<0.05) , but not correlated with ABI (P>0.05), and GCS and GRS had no significant correlation with ABI or baPWV (P>0.05). CONCLUSIONS: There are varying degrees of changes in left ventricular systolic function and peripheral arterial elasticity in children with simple obesity, and there is a certain correlation between them.

Absence of CD47 maintains brown fat thermogenic capacity and protects mice from aging-related obesity and metabolic disorder.

Brown and beige adipocytes burn energy to produce heat and could serve as a therapeutic target to counteract metabolic diseases including obesity and type 2 diabetes. Aging is associated with reduced brown fat mass and thermogenic capacity and a risk factor for metabolic diseases. Our previous studies implicated a role for CD47 in regulating brown fat function and energy balance in young adult animals. In this study, we further determined its role in natural aging related metabolic disorders. The results demonstrated that aged CD47 deficient mice (under normal chow diet) had reduced body weight and fat mass, and improved glucose tolerance as compared to aged wild type (WT) mice. Indirect calorimetry result showed that food intake and total activity were comparable between two genotypes. However, CD47 deficient mice had increased energy expenditure and better cold tolerance, accompanied by increased white adipose tissue browning and well-maintained juvenile morphology of brown adipose tissue (BAT). Moreover, transcriptome (RNA-seq) and pathway enrichment analysis revealed that BAT from aged CD47 deficient mice had upregulated genes involving in mitochondria oxidative phosphorylation, thermogenesis, fatty acid metabolism, and valine, leucine and isoleucine (BCAA) degradation, indicating the activated BAT status in aged CD47 deficient mice. Collectively, these data suggest that blocking CD47 signaling protects mice from natural aging-associated obesity and glucose intolerance, partially though activation and expansion of the thermogenic machinery, further supporting that CD47 maybe a potential target for aging related metabolic disorder.

Design, Synthesis, Biological Evaluation, and Molecular Docking of 2,4-Diaminopyrimidine Derivatives Targeting Focal Adhesion Kinase as Tumor Radiotracers.

There are two important topics in the field of cancer research: one is targeted molecular therapy and the other is tumor molecular imaging. Focal adhesion kinase (FAK) is considered as an attractive target for oncologic diagnosis and therapy. A series of 2,4-diaminopyrimidine derivatives were labeled with 18F to study their biological properties and their potential as positron emission tomography tumor imaging agents. They inhibited the activity of FAK with IC50 values in the wide range of 0.6-2164 nM, among which the IC50 of Q6 was 3.2 nM. For the biodistribution in S180-bearing mice, the corresponding [18F]Q6 was relatively good, with the highest uptake of 3.35 ± 0.32 % ID/g at 30 min postinjection, with a tumor/muscle ratio of 2.08 and a tumor/bone ratio of 2.48. Accordingly, [18F]Q6 was considered as a potential PET imaging agent for tumor diagnosis.

Purine-rich element binding protein B attenuates the coactivator function of myocardin by a novel molecular mechanism of smooth muscle gene repression.

Myocardin is a potent transcriptional coactivator protein, which functions as the master regulator of vascular smooth muscle cell differentiation. The cofactor activity of myocardin is mediated by its physical interaction with serum response factor, a ubiquitously expressed transactivator that binds to CArG boxes in genes encoding smooth muscle-restricted proteins. Purine-rich element binding protein B (Purß) represses the transcription of the smooth muscle α-actin gene (Acta2) in fibroblasts and smooth muscle cells by interacting with single-stranded DNA sequences flanking two 5' CArG boxes in the Acta2 promoter. In this study, the ability of Purß to modulate the cofactor activity of myocardin was investigated using a combination of cellular and biochemical approaches. Results of smooth muscle gene promoter-reporter assays indicated that Purß specifically inhibits the coactivator function of myocardin in a manner requiring the presence of all three single-stranded DNA binding domains in the Purß homodimer. DNA binding analyses demonstrated that Purß interacts with CArG-containing DNA elements with a much lower affinity compared to other purine-rich target sequences present in the Acta2 promoter. Co-immunoprecipitation and DNA pull-down assays revealed that Purß associates with myocardin and serum response factor when free or bound to duplex DNA containing one or more CArG boxes. Functional analysis of engineered Purß point mutants identified several amino acid residues essential for suppression of myocardin activity. Collectively, these findings suggest an inhibitory mechanism involving direct protein-protein interaction between the homodimeric Purß repressor and the myocardin-serum response factor-CArG complex.

Evaluation of the diagnostic value of joint PET myocardial perfusion and metabolic imaging for vascular stenosis in patients with obstructive coronary artery disease.

BACKGROUND: To investigate the diagnostic value of joint PET myocardial perfusion and metabolic imaging for vascular stenosis in patients with suspected obstructive coronary artery disease (CAD). METHODS: Eighty-eight patients (53 and 35 applied for training and validation, respectively) with suspected obstructive CAD were referred to 13N-NH3 PET/CT myocardial perfusion imaging (MPI) and 18F-FDG PET/CT myocardial metabolic imaging (MMI) with available coronary angiography for analysis. One semi-quantitative indicator summed rest score (SRS) and five quantitative indicators, namely, perfusion defect extent (EXT), total perfusion deficit (TPD), myocardial blood flow (MBF), scar degree (SCR), and metabolism-perfusion mismatch (MIS), were extracted from the PET rest MPI and MMI scans. Different combinations of indicators and seven machine learning methods were used to construct diagnostic models. Diagnostic performance was evaluated using the sum of four metrics (noted as sumScore), namely, area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. RESULTS: In univariate analysis, MIS outperformed other individual indicators in terms of sumScore (2.816-3.042 vs 2.138-2.908). In multivariate analysis, support vector machine (SVM) consisting of three indicators (MBF, SCR, and MIS) achieved the best performance (AUC 0.856, accuracy 0.810, sensitivity 0.838, specificity 0.757, and sumScore 3.261). This model consistently achieved significantly higher AUC compared with the SRS method for four specific subgroups (0.897, 0.839, 0.875, and 0.949 vs 0.775, 0.606, 0.713, and 0.744; P = 0.041, 0.005, 0.034 0.003, respectively). CONCLUSIONS: The joint evaluation of PET rest MPI and MMI could improve the diagnostic performance for obstructive CAD. The multivariate model (MBF, SCR, and MIS) combined with SVM outperformed other methods.