HK2 in microglia and macrophages contribute to the development of neuropathic pain.

Neuropathic pain is a complex pain condition accompanied by prominent neuroinflammation involving activation of both central and peripheral immune cells. Metabolic switch to glycolysis is an important feature of activated immune cells. Hexokinase 2 (HK2), a key glycolytic enzyme enriched in microglia, has recently been shown important in regulating microglial functions.

Microglia modulate general anesthesia through P2Y receptor.

General anesthesia (GA) is an unconscious state produced by anesthetic drugs, which act on neurons to cause overall suppression of neuronal activity in the brain. Recent studies have revealed that GA also substantially enhances the dynamics of microglia, the primary brain immune cells, with increased process motility and territory surveillance. However, whether microglia are actively involved in GA modulation remains unknown.

Dual roles of hexokinase 2 in shaping microglial function by gating glycolytic flux and mitochondrial activity.

Microglia continuously survey the brain parenchyma and actively shift status following stimulation. These processes demand a unique bioenergetic programme; however, little is known about the metabolic determinants in microglia. By mining large datasets and generating transgenic tools, here we show that hexokinase 2 (HK2), the most active isozyme associated with mitochondrial membrane, is selectively expressed in microglia in the brain.

mTOR-neuropeptide Y signaling sensitizes nociceptors to drive neuropathic pain.

Neuropathic pain is a refractory condition that involves de novo protein synthesis in the nociceptive pathway. The mTOR is a master regulator of protein translation; however, mechanisms underlying its role in neuropathic pain remain elusive. Using the spared nerve injury-induced neuropathic pain model, we found that mTOR was preferentially activated in large-diameter dorsal root ganglion (DRG) neurons and spinal microglia.

Microglia and macrophages contribute to the development and maintenance of sciatica in lumbar disc herniation.

Lumbar disc herniation (LDH) is a major cause of sciatica. Emerging evidence indicated that inflammation induced by the herniated nucleus pulposus (NP) tissues plays a major role in the pathogenesis of sciatica. However, the underlying mechanisms are still elusive.

Analyzing the Noise Robustness of Deep Neural Networks.

Adversarial examples, generated by adding small but intentionally imperceptible perturbations to normal examples, can mislead deep neural networks (DNNs) to make incorrect predictions. Although much work has been done on both adversarial attack and defense, a fine-grained understanding of adversarial examples is still lacking. To address this issue, we present a visual analysis method to explain why adversarial examples are misclassified.

mTOR-mediated metabolic reprogramming shapes distinct microglia functions in response to lipopolysaccharide and ATP.

Microglia constantly survey the brain microenvironment and rapidly adopt different phenotypes in response to environmental stimuli. Such dynamic functions require a unique metabolism and bioenergetics. However, little is known about the basic metabolism of microglia and how metabolic changes regulate microglia function.

Sphingosine kinase 2 cooperating with Fyn promotes kidney fibroblast activation and fibrosis via STAT3 and AKT.

Sphingosine kinases (Sphks) are the rate-limiting enzymes in the conversion of sphingosine to biologically active sphingosine-1-phosphate. The present study aimed to determine the role of Sphk2 and its downstream targets in renal fibroblast activation and interstitial fibrosis. In the kidney interstitium of patients with renal fibrosis, Sphk2-expressing cells (mainly interstitial fibroblasts) were significantly elevated and highly correlated with disease progression in patients.

IL-33/ST2 plays a critical role in endothelial cell activation and microglia-mediated neuroinflammation modulation.

Background: Interleukin-33 (IL-33) is increasingly being recognized as a key immunomodulatory cytokine in many neurological diseases.

Methods: In the present study, wild-type (WT) and IL-33 mice received intracerebroventricular (i.c.

FTY720 attenuates behavioral deficits in a murine model of systemic lupus erythematosus.

Neuropsychiatric (NP) involvement in systemic lupus erythematosus (SLE) severely impacts patients' quality of life and leads to a poor prognosis. The current therapeutic protocol, corticosteroid administration, can also induce neuropsychiatric disorders. FTY720 is an immunomodulator that selectively confines lymphocytes in lymph nodes and reduces autoreactive T cell recruitment to the central nervous system (CNS).

Fingolimod targets cerebral endothelial activation to block leukocyte recruitment in the central nervous system.

Fingolimod (FTY720), an immunomodulator, is approved as an oral treatment for patients with relapsing forms of multiple sclerosis. Its effects are largely attributed to its mechanism of selectively retaining lymphocytes in the lymph nodes to reduce autoreactive T-cell recruitment in the CNS. In this study, we investigated the therapeutic effect of FTY720 on an animal model of CNS inflammation induced by intracerebral ventricle LPS injection.

Analyzing the Training Processes of Deep Generative Models.

Among the many types of deep models, deep generative models (DGMs) provide a solution to the important problem of unsupervised and semi-supervised learning. However, training DGMs requires more skill, experience, and know-how because their training is more complex than other types of deep models such as convolutional neural networks (CNNs). We develop a visual analytics approach for better understanding and diagnosing the training process of a DGM.

Online Visual Analytics of Text Streams.

We present an online visual analytics approach to helping users explore and understand hierarchical topic evolution in high-volume text streams. The key idea behind this approach is to identify representative topics in incoming documents and align them with the existing representative topics that they immediately follow (in time). To this end, we learn a set of streaming tree cuts from topic trees based on user-selected focus nodes.