Altered spontaneous brain activity during dobutamine challenge in healthy young adults: A resting-state functional magnetic resonance imaging study

IntroductionThere is a growing interest in exploring brain-heart interactions. However, few studies have investigated the brain-heart interactions in healthy populations, especially in healthy young adults. The aim of this study was to explore the association between cardiovascular and spontaneous brain activities during dobutamine infusion in healthy young adults.MethodsForty-eight right-handed healthy participants (43 males and 5 females, range: 22–34 years) underwent vital signs monitoring, cognitive function assessment and brain MRI scans. Cardiovascular function was evaluated using blood pressure and heart rate, while two resting-state functional magnetic resonance imaging (rs-fMRI) methods—regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF)—were used together to reflect the local neural activity of the brain. Logistic regression was used to model the association between brain and heart.ResultsResults showed that blood pressure and heart rate significantly increased after dobutamine infusion, and the performance in brain functional activity was the decrease in ReHo in the left gyrus rectus and in ALFF in the left frontal superior orbital. The results of logistic regression showed that the difference of diastolic blood pressure (DBP) had significant positive relationship with the degree of change of ReHo, while the difference of systolic blood pressure (SBP) had significant negative impact on the degree of change in ALFF.DiscussionThese findings suggest that the brain-heart interactions exist in healthy young adults under acute cardiovascular alterations, and more attention should be paid to blood pressure changes in young adults and assessment of frontal lobe function to provide them with more effective health protection management

Proto-oncogene Src links lipogenesis via lipin-1 to breast cancer malignancy

Src基因是哺乳动物中发现的第一个原癌基因，其编码的蛋白是一个酪氨酸激酶，在促进乳腺癌、肺癌等诸多肿瘤的发生、进展和恶化中起着重要的作用。在研究中，研究团队发现Src能够承接生长因子和肥胖微环境相关的因子如胰岛素和瘦素的信号，通过直接磷酸化lipin-1，增强其催化合成甘油脂的活性，提高细胞摄入的脂肪酸向甘油脂尤其是磷脂转化。进一步实验表明，Src磷酸化lipin-1能够加速乳腺癌细胞生长，促进小鼠模型中肿瘤的进展和转移。这项研究不但做出了对脂肪合成途径的调控机制的又一重要发现，还揭示了原癌基因Src可以承接癌细胞内外的活化信号，通过lipin-1为媒介重塑癌细胞脂代谢，使得肿瘤细胞具有增殖和转移的优势。该论文揭示了臭名昭著的原癌基因Src通过直接结合并磷酸化lipin-1（一种磷脂酸磷酸化酶，在脂质代谢中具有重要作用），以增强其酶活性，从而加速甘油酯的合成速率，进而促进乳腺癌的发生发展。 该研究由厦门大学生命科学学院、广州医科大学第五附属医院、第四军医大学西京医院和中山大学孙逸仙纪念医院等单位合作完成，厦门大学生命科学学院博士后宋林涛和广州医科大学第五附属医院刘志华教授为该论文的共同第一作者。【Abstract】Increased lipogenesis has been linked to an increased cancer risk and poor prognosis; however, the underlying mechanisms remain obscure. Here we show that phosphatidic acid phosphatase (PAP) lipin-1, which generates diglyceride precursors necessary for the synthesis of glycerolipids, interacts with and is a direct substrate of the Src proto-oncogenic tyrosine kinase. Obesity-associated microenvironmental factors and other Src-activating growth factors, including the epidermal growth factor, activate Src and promote Src-mediated lipin-1 phosphorylation on Tyr398, Tyr413 and Tyr795 residues. The tyrosine phosphorylation of lipin-1 markedly increases its PAP activity, accelerating the synthesis of glycerophospholipids and triglyceride. Alteration of the three tyrosine residues to phenylalanine (3YF-lipin-1) disables lipin-1 from mediating Src-enhanced glycerolipid synthesis, cell proliferation and xenograft growth. Re-expression of 3YF-lipin-1 in PyVT;Lpin1−/− mice fails to promote progression and metastasis of mammary tumours. Human breast tumours exhibit increased p-Tyr-lipin-1 levels compared to the adjacent tissues. Importantly, statistical analyses show that levels of p-Tyr-lipin-1 correlate with tumour sizes, lymph node metastasis, time to recurrence and survival of the patients. These results illustrate a direct lipogenesis-promoting role of the pro-oncogenic Src, providing a mechanistic link between obesity-associated mitogenic signaling and breast cancer malignancy.This work was supported by grants from the National Natural Science Foundation of China (#31822027, #31690101, #91854208, #31871168, #82002965), the Fundamental Research Funds for the Central Universities (#20720190084), Project “111” sponsored by the State Bureau of Foreign Experts and Ministry of Education of China (#BP2018017), XMU Training Programme of Innovation and Entrepreneurship for Undergraduates (#2017Y0578, #2018Y1281) and China Postdoctoral Science Foundation (#2019M652254). 该研究也得到了国家自然科学基金，中央高校基础研究项目和中国博士后科学基金等的资助

The roles of ncRNAs and histone-modifiers in regulating breast cancer stem cells

Abstract Cancer stem cells (CSCs), a subpopulation of cancer cells with ability of initiating tumorigenesis, exist in many kinds of tumors including breast cancer. Cancer stem cells contribute to treatment resistance and relapse. Conventional treatments only kill differentiated cancer cells, but spare CSCs. Combining conventional treatments with therapeutic drugs targeting to CSCs will eradicate cancer cells more efficiently. Studying the molecular mechanisms of CSCs regulation is essential for developing new therapeutic strategies. Growing evidences showed CSCs are regulated by non-coding RNA (ncRNA) including microRNAs and long non-coding RNAs (lncRNAs), and histone-modifiers, such as let-7, miR-93, miR-100, HOTAIR, Bmi-1 and EZH2. Herein we review the roles of microRNAs, lncRNAs and histone-modifiers especially Polycomb family proteins in regulating breast cancer stem cells (BCSCs)

Parallelization Techniques in Quantum Chemistry

Probabilistic wind power forecasting has become an important tool for optimal economic dispatch and unit commitment of modern power systems with significant renewable energy penetrations. Ensemble forecasting based on Monte Carlo simulation is commonly used by many grid operators, but other probabilistic approaches, such as multi-step iterative wind power forecasting have not yet been fully explored. The associated uncertainty analysis is an important yet challenging issue in this area. This paper proposes to use an analytic interval forecasting framework to estimate the forecasting uncertainty of a wind farm in Ireland based on the Temporally Local Gaussian Process (TLGP) model and evaluates the probabilistic forecasting metrics of reliability and sharpness. The key findings confirm that TLGP not only has better forecasting accuracy but is also less sensitive to uncertainty propagation than Gaussian Process (GP). This work provides an effective analytical framework for iterative multi-step interval forecasting

<i>Dendrobium officinale</i> Enzyme Changing the Structure and Behaviors of Chitosan/γ-poly(glutamic acid) Hydrogel for Potential Skin Care

Hydrogels have been widespreadly used in various fields. But weak toughness has limited their further applications. In this study, Dendrobium officinale enzyme (DOE) was explored to improve chitosan/γ-poly(glutamic acid) (CS/γ-PGA) hydrogel in the structure and properties. The results indicated that DOE with various sizes of ingredients can make multiple noncovalent crosslinks with the skeleton network of CS/γ-PGA, significantly changing the self-assembly of CS/γ-PGA/DOE hydrogel to form regular protuberance nanostructures, which exhibits stronger toughness and better behaviors for skin care. Particularly, 4% DOE enhanced the toughness of CS/γ-PGA/DOE hydrogel, increasing it by 116%. Meanwhile, water absorption, antioxygenation, antibacterial behavior and air permeability were increased by 39%, 97%, 27% and 52%

Density functional theory (DFT) studies of vanadium-titanium based selective catalytic reduction (SCR) catalysts

Based on density functional theory (DFT) and basic structure models, the chemical reactions on the surface of vanadium-titanium based selective catalytic reduction (SCR) denitrification catalysts were summarized. Reasonable structural models (non-periodic and periodic structural models) are the basis of density functional calculations. A periodic structure model was more appropriate to represent the catalyst surface, and its theoretical calculation results were more comparable with the experimental results than a non-periodic model. It is generally believed that the SCR mechanism where NH3 and NO react to produce N-2 and H2O follows an Eley-Rideal type mechanism. NH2NO was found to be an important intermediate in the SCR reaction, with multiple production routes. Simultaneously, the effects of H2O, SO2 and metal on SCR catalysts were also summarized. (C) 2019 The Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier B.V