Clinical PET Imaging of Microglial Activation: Implications for Microglial Therapeutics in Alzheimer’s Disease

In addition to extracellular β-amyloid plaques and intracellular neurofibrillary tangles, neuroinflammation has been identified as a key pathological characteristic of Alzheimer’s disease (AD). Once activated, neuroinflammatory cells called microglia acquire different activation phenotypes. At the early stage of AD, activated microglia are mainly dominated by the neuroprotective and anti-inflammatory M2 phenotype. Conversely, in the later stage of AD, the excessive activation of microglia is considered detrimental and pro-inflammatory, turning into the M1 phenotype. Therapeutic strategies targeting the modulation of microglia may regulate their specific phenotype. Fortunately, with the rapid development of in vivo imaging methodologies, visualization of microglial activation has been well-explored. In this review, we summarize the critical role of activated microglia during the pathogenesis of AD and current studies concerning imaging of microglial activation in AD patients. We explore the possibilities for identifying activated microglial phenotypes with imaging techniques and highlight promising therapies that regulate the microglial phenotype in AD mice

Management of Refractory/Aggressive Pituitary Adenomas Review of Current Treatment Options

Tumors of central nervous system (CNS) account for a small portion of tumors of human body, which includes tumors occurring in the parenchyma of brain and spinal cord as well as their coverings. This chapter covers some new development in some major brain tumors in both pediatric and adult populations, as well as some uncommon but diagnostic and management challenging tumors

Challenges in QCD matter physics - The Compressed Baryonic Matter experiment at FAIR

Substantial experimental and theoretical efforts worldwide are devoted to explore the phase diagram of strongly interacting matter. At LHC and top RHIC energies, QCD matter is studied at very high temperatures and nearly vanishing net-baryon densities. There is evidence that a Quark-Gluon-Plasma (QGP) was created at experiments at RHIC and LHC. The transition from the QGP back to the hadron gas is found to be a smooth cross over. For larger net-baryon densities and lower temperatures, it is expected that the QCD phase diagram exhibits a rich structure, such as a first-order phase transition between hadronic and partonic matter which terminates in a critical point, or exotic phases like quarkyonic matter. The discovery of these landmarks would be a breakthrough in our understanding of the strong interaction and is therefore in the focus of various high-energy heavy-ion research programs. The Compressed Baryonic Matter (CBM) experiment at FAIR will play a unique role in the exploration of the QCD phase diagram in the region of high net-baryon densities, because it is designed to run at unprecedented interaction rates. High-rate operation is the key prerequisite for high-precision measurements of multi-differential observables and of rare diagnostic probes which are sensitive to the dense phase of the nuclear fireball. The goal of the CBM experiment at SIS100 (sqrt(s_NN) = 2.7 - 4.9 GeV) is to discover fundamental properties of QCD matter: the phase structure at large baryon-chemical potentials (mu_B > 500 MeV), effects of chiral symmetry, and the equation-of-state at high density as it is expected to occur in the core of neutron stars. In this article, we review the motivation for and the physics programme of CBM, including activities before the start of data taking in 2022, in the context of the worldwide efforts to explore high-density QCD matter.Comment: 15 pages, 11 figures. Published in European Physical Journal

Role of matrix Metalloproteinases in pituitary adenoma invasion

Abstract Though pituitary adenomas are benign tumors in most cases, a considerable fraction of PAs behave in a malignant-like manner and invade to the adjacent structures in sellar region, especially the cavernous sinuses. Cancer-cell invasion and metastasis remain a great challenge for physicians and surgeons in spite of emerging advances in drug therapy and surgical Treatment. matrix metalloproteinases, as a family of zinc-dependent endopeptidases, have long been known to be associated with tumor invasion and metastasis mainly via breaking down basement membrane in different tissues. Aberrant expression and activation of matrix metalloproteinases have been detected in invasive pituitary adenomas as in malignancy and correlated to tumor invasion. Therefore, matrix metalloproteinases are considered as promising biomarkers for predicting tumor behavior and even drug targets for novel therapeutic strategies. In this review, we give an overview of the expression, function, regulation and clinical prospects of matrix metalloproteinases, especially focusing on the biological network in which matrix metalloproteinases may be abnormally activated in promoting pituitary adenoma invasion

Investigation on spray cooling heat transfer performance with different nanoparticles and surfactants

Funding Information: This work is supported by the National Natural Science Foundation of China (Grant No. 51806096), China Postdoctoral Science Foundation (No. 2019M661812), Postgraduate Research & Practice Innovation Program of Jiangsu Province (Grant No. SJCX20_0332), Natural Science Foundation of the Jiangsu Higher Education Institutions of China (Grant No. 18KJB560007), and the Research Fund of Key Laboratory of Aircraft Environment Control and Life Support, MIIT, Nanjing University of Aeronautics and Astronautics(Grant No. KLAECLS-E-201902). Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.The spray cooling enhancement method has consistently been the focus area for research as a highly effective cooling method that can alter the properties of spray media by allowing the addition of different types of additives. In this study, an open spray cooling system was established for experimental purposes. Firstly, the effects of nozzles on the spray cooling characteristics were investigated through four kinds of nozzle experiments. Al2O3-H2O, TiO2-H2O, ZrO2-H2O, and SiO2-H2O nanofluids were chosen as cooling substances based on the optimal nozzles, and the effects of the type and concentration of nanoparticles on cooling performance were studied. Based on the performance of the nanoparticles, sodium dodecyl benzenesulfonate(SDBS) was selected as the surfactant for Al2O3 and TiO2 nanoparticles, while cetyltrimethyl ammonium bromide(CTAB) was selected as the surfactant for ZrO2 and SiO2 nanoparticles. The effects of surfactants with different concentrations on the heat transfer performance of nanofluids were studied. The results showed that when the mass fraction of SiO2 nanoparticles was 0.2% and CTAB was 0.005%, an optimal cooling effect was achieved; which was 5.9% higher than that of water and 1.7% higher than that obtained without CTAB.Peer reviewe

The advantages of multi-level omics research on stem cell-based therapies for ischemic stroke

Stem cell transplantation is a potential therapeutic strategy for ischemic stroke. However, despite many years of preclinical research, the application of stem cells is still limited to the clinical trial stage. Although stem cell therapy can be highly beneficial in promoting functional recovery, the precise mechanisms of action that are responsible for this effect have yet to be fully elucidated. Omics analysis provides us with a new perspective to investigate the physiological mechanisms and multiple functions of stem cells in ischemic stroke. Transcriptomic, proteomic, and metabolomic analyses have become important tools for discovering biomarkers and analyzing molecular changes under pathological conditions. Omics analysis could help us to identify new pathways mediated by stem cells for the treatment of ischemic stroke via stem cell therapy, thereby facilitating the translation of stem cell therapies into clinical use. In this review, we summarize the pathophysiology of ischemic stroke and discuss recent progress in the development of stem cell therapies for the treatment of ischemic stroke by applying multi-level omics. We also discuss changes in RNAs, proteins, and metabolites in the cerebral tissues and body fluids under stroke conditions and following stem cell treatment, and summarize the regulatory factors that play a key role in stem cell therapy. The exploration of stem cell therapy at the molecular level will facilitate the clinical application of stem cells and provide new treatment possibilities for the complete recovery of neurological function in patients with ischemic stroke

Prediction of plant secondary metabolic pathways using deep transfer learning

Abstract Background Plant secondary metabolites are highly valued for their applications in pharmaceuticals, nutrition, flavors, and aesthetics. It is of great importance to elucidate plant secondary metabolic pathways due to their crucial roles in biological processes during plant growth and development. However, understanding plant biosynthesis and degradation pathways remains a challenge due to the lack of sufficient information in current databases. To address this issue, we proposed a transfer learning approach using a pre-trained hybrid deep learning architecture that combines Graph Transformer and convolutional neural network (GTC) to predict plant metabolic pathways. Results GTC provides comprehensive molecular representation by extracting both structural features from the molecular graph and textual information from the SMILES string. GTC is pre-trained on the KEGG datasets to acquire general features, followed by fine-tuning on plant-derived datasets. Four metrics were chosen for model performance evaluation. The results show that GTC outperforms six other models, including three previously reported machine learning models, on the KEGG dataset. GTC yields an accuracy of 96.75%, precision of 85.14%, recall of 83.03%, and F1_score of 84.06%. Furthermore, an ablation study confirms the indispensability of all the components of the hybrid GTC model. Transfer learning is then employed to leverage the shared knowledge acquired from the KEGG metabolic pathways. As a result, the transferred GTC exhibits outstanding accuracy in predicting plant secondary metabolic pathways with an average accuracy of 98.30% in fivefold cross-validation and 97.82% on the final test. In addition, GTC is employed to classify natural products. It achieves a perfect accuracy score of 100.00% for alkaloids, while the lowest accuracy score of 98.42% for shikimates and phenylpropanoids. Conclusions The proposed GTC effectively captures molecular features, and achieves high performance in classifying KEGG metabolic pathways and predicting plant secondary metabolic pathways via transfer learning. Furthermore, GTC demonstrates its generalization ability by accurately classifying natural products. A user-friendly executable program has been developed, which only requires the input of the SMILES string of the query compound in a graphical interface

Human neural stem cell transplantation rescues cognitive defects in APP/PS1 model of Alzheimer's disease by enhancing neuronal connectivity and metabolic activity

Alzheimer’s disease (AD), the most frequent type of dementia, is featured by Aβ pathology, neural degeneration and cognitive decline. To date, there is no cure for this disease. Neural stem cell (NSC) transplantation provides new promise for treating AD. Many studies report that intra-hippocampal transplantation of murine NSCs improved cognition in rodents with AD by alleviating neurodegeneration via neuronal complement or replacement. However, few reports examined the potential of human NSC transplantation for AD. In this study, we implanted human brain-derived NSCs (hNSCs) into bilateral hippocampus of an APP/PS1 transgenic mouse model of AD to test the effects of hNSC transplantation on Alzheimer’s behavior and neuropathology. Six weeks later, transplanted hNSCs engrafted into the brains of AD mice, migrated dispersedly in broad brain regions, and some of them differentiated into neural cell types of central nervous system. The hNSC transplantation restored the recognition, learning and memory deficits but not anxiety tasks in AD mice. Although Aβ plaques were not significantly reduced, the neuronal, synaptic and nerve fiber density was significantly increased in the frontal cortex and hippocampus of hNSC-treated AD mice, suggesting of improved neuronal connectivity in AD brains after hNSC transplantation. Ultrastructural analysis confirmed that synapses and nerve fibers maintained relatively well-structured shapes in these mice. Furthermore, in-vivo magnetic resonance spectroscopy showed that hNSC-treated mice had notably increased levels of NAA and Glu in the frontal cortex and hippocampus, suggesting that neuronal metabolic activity was improved in AD brains after hNSC transplantation. These results suggest that transplanted hNSCs rescued Alzheimer’s cognition by enhancing neuronal connectivity and metabolic activity through a compensation mechanism in APP/PS1 mice. This study provides preclinical evidence that hNSC transplantation can be a possible and feasible strategy for treating patients with AD