AMPK exerts dual regulatory effects on the PI3K pathway

BACKGROUND AMP-activated protein kinase (AMPK) is a fuel-sensing enzyme that is activated when cells experience energy deficiency and conversely suppressed in surfeit of energy supply. AMPK activation improves insulin sensitivity via multiple mechanisms, among which AMPK suppresses mTOR/S6K-mediated negative feedback regulation of insulin signaling. RESULTS In the present study we further investigated the mechanism of AMPK-regulated insulin signaling. Our results showed that 5-aminoimidazole-4-carboxamide-1 ribonucleoside (AICAR) greatly enhanced the ability of insulin to stimulate the insulin receptor substrate-1 (IRS1)-associated PI3K activity in differentiated 3T3-F442a adipocytes, leading to increased Akt phosphorylation at S473, whereas insulin-stimulated activation of mTOR was diminished. In 3T3-F442a preadipocytes, these effects were attenuated by expression of a dominant negative mutant of AMPK α1 subunit. The enhancing effect of ACIAR on Akt phosphorylation was also observed when the cells were treated with EGF, suggesting that it is regulated at a step beyond IR/IRS1. Indeed, when the cells were chronically treated with AICAR in the absence of insulin, Akt phosphorylation was progressively increased. This event was associated with an increase in levels of phosphatidylinositol -3,4,5-trisphosphate (PIP3) and blocked by Wortmannin. We then expressed the dominant negative mutant of PTEN (C124S) and found that the inhibition of endogenous PTEN per se did not affect phosphorylation of Akt at basal levels or upon treatment with AICAR or insulin. Thus, this result suggests that AMPK activation of Akt is not mediated by regulating phosphatase and tensin homologue (PTEN). CONCLUSION Our present study demonstrates that AMPK exerts dual effects on the PI3K pathway, stimulating PI3K/Akt and inhibiting mTOR/S6K.National Institutes of Health (CA118918, GM057959

A multimodal fusion method for Alzheimer’s disease based on DCT convolutional sparse representation

IntroductionThe medical information contained in magnetic resonance imaging (MRI) and positron emission tomography (PET) has driven the development of intelligent diagnosis of Alzheimer’s disease (AD) and multimodal medical imaging. To solve the problems of severe energy loss, low contrast of fused images and spatial inconsistency in the traditional multimodal medical image fusion methods based on sparse representation. A multimodal fusion algorithm for Alzheimer’ s disease based on the discrete cosine transform (DCT) convolutional sparse representation is proposed.MethodsThe algorithm first performs a multi-scale DCT decomposition of the source medical images and uses the sub-images of different scales as training images, respectively. Different sparse coefficients are obtained by optimally solving the sub-dictionaries at different scales using alternating directional multiplication method (ADMM). Secondly, the coefficients of high-frequency and low-frequency subimages are inverse DCTed using an improved L1 parametric rule combined with improved spatial frequency novel sum-modified SF (NMSF) to obtain the final fused images.Results and discussionThrough extensive experimental results, we show that our proposed method has good performance in contrast enhancement, texture and contour information retention

Clinical characteristics and related influencing factors of common rheumatic diseases concomitant with tuberculosis

ObjectiveTo explore the clinical characteristics and risk factors of common systemic rheumatism concomitant with tuberculosis (TB).MethodsA total of 3,906 patients of RA, SLE, and SS diagnosed in the People's Hospital of Sichuan Province from January 2007 to January 2017 were collected. One hundred and five patients with TB were included as TB group, including 42 RA, 41 SLE, and 22 SS patients. In the non-TB group, 84 RA, 82 SLE, and 44 SS patients were randomly selected during the same period.ResultsFever was the most common symptom among RA, SLE, and SS patients with TB, accounting for 83.3%, 92.7%, and 68.2%, respectively. Cough, weight loss or fatigue were the next common. RA patients with TB were mostly pulmonary TB (PTB), accounting for 64.3%. The proportion of PTB for SLE and SS were 46.3%, 59.01%, respectively. In TB group, 59% RA, 57% SLE, and 62% SS with PTB had two or more chest CT findings. There were 48 TB cases received both Interferon Gamma Release Assay (IGRA) and Tuberculin skin test (TST) with positive rates of 91.8%, 45.8%, respectively. The daily average dose of glucocorticoids within 1 year in TB group was higher than that in non-TB group of SLE patients, lower counts of CD4+ T cell count were found in TB group (P < 0.05), while no such differences were found in RA and SS patients.ConclusionRA patients with TB are mainly pulmonary TB. For SLE and SS patients, the chance of PTB and extrapulmonary tuberculosis is similar. Daily average dose of glucocorticoids within 1 year may be a common risk factor for RA, SLE and SS patients developing TB. Decreased CD4+ T cell count may also be a risk factor for SLE patients with TB. Symptoms of RA, SLE, SS with TB, are similar with the primary disease or other infection. It is recommended to conduct both TST and IGRA to help diagnose TB

Regulation Mechanism of Processed Cheese Stretchability

In this work, the regulation mechanism of processed cheese stretchability was studied by adjusting the amount of added emulsifying salt (0.6%–3.0%) and potato acetate starch (0.125%–2%) and pH (5.4–5.8). The results showed that as the emulsifying salt increased from 0.6% to 3.0%, the content of bound calcium in processed cheese decreased from (4.42 ± 0.05) to (0.02 ± 0.04) g/kg, the average fat globule size D(4,3) decreased from (73.08 ± 3.16) to (27.90 ± 2.55) μm, and the bound water content increased from (9.57 ± 0.25)% to (10.40 ± 0.25)%, indicating that the calcium crosslinking effect gradually decreased, the emulsifying effect and hydration degree increased, the interaction between protein molecules changed from strong to weak, so the stretchability of processed cheese initially increased and then decreased. As pH increased from 5.4 to 5.8, the content of bound calcium increased from (2.01 ± 0.08) to (2.74 ± 0.05) g/kg, and the average fat globule size D(4,3) decreased from (36.36 ± 2.68) to (21.37 ± 2.39) μm. Fourier transform infrared spectroscopy showed that the bending vibration absorption peaks of O–H and N–H moved to lower wavenumbers, and the bound water content increased from (9.85 ± 0.16)% to (10.74 ± 0.12)%, indicating that the calcium crosslinking effect, emulsifying effect and hydration degree increased, the interaction between protein molecules changed from strong to weak, so the stretchability of processed cheese increased first and then decreased. As potato acetate starch concentration increased from 0.125% to 2%, the average fat globule size D(4,3) decreased from (54.17 ± 2.74) to (29.92 ± 2.71) μm, and the bound water content increased from (9.90 ± 0.38)% to (11.00 ± 0.21)%, indicating that the emulsifying effect and hydration degree increased, and the stretchability increased first and then decreased. At a potato acetate starch concentration of 2%, starch and protein were separated, so the stretchability became worse. In conclusion, the stretchability of processed cheese is comprehensively regulated by the degree of calcium ion chelation, emulsifying effect, electrostatic interaction between protein molecules, water distribution state and protein-polysaccharide phase behavior

Microbiome and Metabolomics Reveal the Effects of Different Feeding Systems on the Growth and Ruminal Development of Yaks

The change in the feeding system can greatly improve the growth performance of the yak (Bos grunniens), an important livestock species in the plateau region. Here, we comprehensively compared the effects of different feeding systems on the growth performance and ruminal development of yaks, and investigated the effects of ruminal microorganisms and metabolites using the 16S rRNA gene sequencing and liquid chromatograph–mass spectrometer (LC-MS) technologies. We found that compared to traditional grazing feeding, house feeding significantly improved the growth performance (such as average daily gain and net meat weight) and rumen development of the yaks. At the genus level, the abundance of Rikenellaceae RC9 Gut group, Christensenellaceae R-7 group, Lachnospiraceae NK3A20 group, Ruminococcaceae UCG-014, and Prevotellaceae UCG-003 showed significant differences and was closely related to rumen development in the two distinct feeding systems. Also, metabolomics revealed that the change in the feeding system significantly affected the concentration and metabolic pathways of the related rumen metabolites. The metabolites with significant differences were significantly enriched in purine metabolism (xanthine, adenine, inosine, etc.), tyrosine metabolism (L-tyrosine, dopaquinone, etc.), phenylalanine metabolism (dihydro-3-caumaric acid, hippuric acid, etc.), and cAMP signaling pathway [acetylcholine, (-)-epinephrine, etc.]. This study scientifically support the house fattening feeding system for yaks. Also, our results provide new insights into the composition and function of microbial communities that promote ruminal development and in general growth of the yaks

B Cell-Related Circulating MicroRNAs With the Potential Value of Biomarkers in the Differential Diagnosis, and Distinguishment Between the Disease Activity and Lupus Nephritis for Systemic Lupus Erythematosus

Our understanding of circulating microRNAs (miRNAs) related to systemic lupus erythematosus (SLE) remains very limited. In this study, we screened SLE-specific miRNAs in plasma from 42 B cell-related miRNAs by using miRNA PCR Array. The selected miRNAs were first confirmed in plasma samples from 50 SLE patients, 16 rheumatoid arthritis (RA) patients, and 20 healthy donors using qRT-PCR. We then investigated the relationship between expressions of the selected miRNAs and SLE clinical indicators. As a result, 14 miRNAs (miR-103, miR-150, miR-20a, miR-223, miR-27a, miR-15b, miR-16, miR-181a, miR-19b, miR-22, miR-23a, miR-25, miR-92a, and miR-93) were significantly decreased in the plasma of SLE patients compared with healthy controls (P < 0.05) and could act as the diagnostic signature to distinguish SLE patients from healthy donors. Six miRNAs (miR-92a, miR-27a, miR-19b, miR-23a, miR-223, and miR-16) expressed in plasma were significantly lower in SLE patients than in RA patients (P < 0.05), revealing the potentially diagnostic signature to distinguish SLE patients from RA patients. Furthermore, the downregulated expression of miR-19b, miR-25, miR-93, and miR-15b was associated with SLE disease activity (P < 0.05) while miR-15b and miR-22 expressions were significantly lower in SLE patients with low estimate glomerular filtration rate (eGFR < 60 ml/min/1.73 m2) (P < 0.05). The diagnostic potential of miR-15b for SLE disease activity and lupus nephritis (LN) with low eGFR was validated on an independent validation set with 69 SLE patients and a cross-validation set with 80 SLE patients. In summary, the signature of circulating miRNAs will provide novel biomarkers for the diagnosis of SLE and evaluation of disease activity and LN

Prevalence and related factors of epilepsy in children and adolescents with cerebral palsy: a systematic review and meta-analysis

Objective: To study the worldwide prevalence and associated factors of epilepsy in children and adolescents with Cerebral Palsy (CP) and to analyze the differences between various subgroups. Method: We identified all potential studies on the prevalence of epilepsy in children and adolescents with CP from PubMed, Web of Science, and Embase. The search time was from the establishment of the database to November 2022. Randomized effects meta-analysis models were used to calculate the prevalence of epilepsy in CP. Subgroup analysis and meta-regression were utilized to further explore heterogeneity between articles and prevalence disparities between subgroups. The funnel plot and Egger’s test were used to investigate potential publication bias. Results: Seventy-two articles, comprising 53,969 children and adolescents with CP, were included in this study. The results indicated a total epilepsy prevalence of 38.0% (95% CI: 34.8%–41.2%) in CP. The prevalence of epilepsy was 46.4% (95% CI: 41.4%–51.5%) in clinical sample-based studies and 31.6% (95% CI: 28.7%–34.5%) in population-based studies. Meta-regression demonstrated that the sample source, neonatal seizure, family history of epilepsy, EEG or cranial imaging abnormalities, intellectual/cognitive impairment, and topographical types of CP were heterogeneous contributors to the epilepsy prevalence in CP. Conclusion: Approximately one-third of children and adolescents with CP have epilepsy, and the sample source can significantly impact the total prevalence of epilepsy. Neonatal seizures, family history of epilepsy, EEG abnormalities, cranial imaging abnormalities, severe intellectual disability, and quadriplegia may be contributing factors to epilepsy comorbid in CP. Further study is required to verify the strength of these associations with epilepsy. This study aids in identifying the clinical characteristics of young people with CP at risk of developing epilepsy, which may assist clinicians in the early prevention and diagnosis of epilepsy within this population