Search

Stroke is a neurological disease that causes significant disability and death worldwide. Ischemic stroke accounts for 75% of all strokes. The pathophysiological processes underlying ischemic stroke include oxidative stress, the toxicity of excitatory amino acids, ion disorder, enhanced apoptosis, and inflammation. Noncoding RNAs (ncRNAs) may have a vital role in regulating the pathophysiological processes of ischemic stroke, as confirmed by the altered expression of ncRNAs in blood samples from acute ischemic stroke patients, animal models, and oxygen-glucose-deprived (OGD) cell models. Due to specific changes in expression, ncRNAs can potentially be biomarkers for the diagnosis, treatment, and prognosis of ischemic stroke. As an important brain cell component, glial cells mediate the occurrence and progression of oxidative stress after ischemic stroke, and ncRNAs are an irreplaceable part of this mechanism. This review highlights the impact of ncRNAs in the oxidative stress process of ischemic stroke. It focuses on specific ncRNAs that underlie the pathophysiology of ischemic stroke and have potential as diagnostic biomarkers and therapeutic targets.

Subtypes of microglia/macrophage regulate the inflammation in the opposite direction during ischemic stroke. JAK2/STAT3 signaling pathway participates in the development of stroke-related inflammation via ischemic stimulation. However, the relationship between JAK2/STAT3 pathway and microglia/macrophage phenotype transformation is unclear.This study established a transient middle cerebral artery occlusion (tMCAO) model in male STAT3For the conditioned STAT3-KO mice, the infarction was significantly increased after MCAO, accompanied by the aggravation of neurological deficit. Higher expression of iNOS and CD16/32 than Arg-1, Ym-1, and CD206 in vivo and in vitro, and decreased p-STAT3/STAT3 ratio in STAT3Collectively, these results reveal that JAK2/STAT3 signaling pathway regulates the microglia/macrophage polarization (skewing toward the M2 polarization) during the CIRI, thus alleviating brain damage. Therefore, approaches targeting JAK2/STAT3 activation are promising therapies for ischemic stroke.

Liver hepatocellular carcinoma (LIHC) is a malignancy with a high mortality and morbidity rate worldwide. However, the pathogenesis of LIHC has still not been thoroughly studied. Transmembrane and coiled-coil domains 3 (TMCO3) encodes a monovalent cation, a member of the proton transducer 2 (CPA2) family of transporter proteins. In the present study, TMCO3 expression and its relationship with cancer prognosis, as well as its immunological role in LIHC were studied by bioinformatic analysis. We found the significant overexpression of TMCO3 in LIHC in the TCGA, HCCDB, and GEO databases. In LIHC patients, high TMCO3 expression was related to poorer overall survival (OS) and TMCO3 had good predictive accuracy for prognosis. Moreover, TMCO3 was linked to the infiltrates of certain immune cells in LIHC. The correlation of TMCO3 with immune checkpoints was also revealed. Moreover, patients with LIHC with low TMCO3 expression showed a better response to immune checkpoint blockade (ICB) than those with LIHC with high TMCO3 expression. GO and KEGG enrichment analyses indicated that TMCO3 was probably involved in the microtubule cytoskeleton organization involved in mitosis, small GTPase mediated signal transduction, and TGF-β pathway. In conclusion, TMCO3 may be a potential biomarker for LIHC prognosis and immunotherapy.

Glioma is the common, most aggressive and poorest prognostic tumor type in the brain. More and more biomarkers associated with glioma treatment, prognosis, and immunity are being discovered. Here, we aimed to explore the underlying biological functions and prognostic predictive value of Apolipoprotein L4 (APOL4) in glioma. We downloaded the expression data of APOL4 and clinical information from several databases and used R software for preprocessing. The clinical significance of APOL4 in a glioma outcome was explored by the Cox regression analysis and Kaplan–Meier survival analysis. In addition, immune infiltrates and microenvironmental indicators were assessed by CIBERSORT and TIMER. GO and KEGG analyses were used to analyze the potential functions of APOL4 in gliomas. APOL4 expression was increased in glioma specimens compared to normal tissues and correlated dramatically with the WHO grade. A survival analysis showed a shorter overall survival (OS) in glioma patients with APOL4 overexpression, and a Cox regression analysis showed that APOL4 was an independent prognostic factor for the OS of glioma patients. GSEA, GO, and KEGG enrichment analyses showed remarkable enrichment in immune-related pathways. APOL4 expression was positively correlated with immune infiltration (including DC cells, neutrophils, CD8+ T cells, B cells, macrophages, CD4+ T cells, etc.) and microenvironmental parameters (including immune, stromal, and ESTIMATE scores) in gliomas. Glioma patients with a higher expression of APOL4 may be more sensitive to immune checkpoint inhibitors (ICI). In conclusion, these findings suggest that APOL4 is associated with the tumor grade and immune infiltrates; APOL4 may be a new and potential biomarker for therapeutic and prognostic evaluations that may further suggest the therapeutic efficacy of immunotherapy.

Ischemic stroke is an acute cerebrovascular disease characterized by sudden interruption of blood flow in a certain part of the brain, leading to serious disability and death. At present, treatment methods for ischemic stroke are limited to thrombolysis or thrombus removal, but the treatment window is very narrow. However, recovery of cerebral blood circulation further causes cerebral ischemia/reperfusion injury (CIRI). The endoplasmic reticulum (ER) plays an important role in protein secretion, membrane protein folding, transportation, and maintenance of intracellular calcium homeostasis. Endoplasmic reticulum stress (ERS) plays a crucial role in cerebral ischemia pathophysiology. Mild ERS helps improve cell tolerance and restore cell homeostasis; however, excessive or long-term ERS causes apoptotic pathway activation. Specifically, the protein kinase R-like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme 1 (IRE1) pathways are significantly activated following initiation of the unfolded protein response (UPR). CIRI-induced apoptosis leads to nerve cell death, which ultimately aggravates neurological deficits in patients. Therefore, it is necessary and important to comprehensively explore the mechanism of ERS in CIRI to identify methods for preserving brain cells and neuronal function after ischemia.

The role of ferroptosis in ischemic stroke has been hotly debated recently, but the mechanism is not clearly clarified. It has been reported that the NLRP3 inflammasome is essential for the progression of ischemic stroke. Whether the ferroptosis after ischemic stroke mediated by the activation of NLRP3 inflammasome is still not reported. In this study, we investigated the effect of NLRP3 deficiency on ferroptosis following cerebral ischemia-reperfusion injury (CIRI) in vivo and in vitro.In vivo, we used C57BL/6J mice and NLRP3Three days after MCAO, the NLRP3Inhibition of the NLRP3 inflammasome alleviates CIRI by inhibiting ferroptosis and inflammation, possibly through a mechanism of the Keap1-Nrf2 pathway.

Stroke is a disease with high incidence, mortality and disability rates. It is also the main cause of adult disability in developed countries. Stroke is often caused by small emboli on the inner wall of the blood vessels supplying the brain, which can lead to arterial embolism, and can also be caused by cerebrovascular or thrombotic bleeding. With the exception of recombinant tissue plasminogen activator (rt-PA), which is a thrombolytic drug used to recanalize the occluded artery, most treatments have been demonstrated to be ineffective. Stroke can also induce peripheral organ damage. Most stroke patients have different degrees of injury to one or more organs, including the lung, heart, kidney, spleen, gastrointestinal tract and so on. In the acute phase of stroke, severe inflammation occurs in the brain, but there is strong immunosuppression in the peripheral organs, which greatly increases the risk of peripheral organ infection and aggravates organ damage. Nonneurological complications of stroke can affect treatment and prognosis, may cause serious short-term and long-term consequences and are associated with prolonged hospitalization and increased mortality. Many of these complications are preventable, and their adverse effects can be effectively mitigated by early detection and appropriate treatment with various medical measures. This article reviews the pathophysiological mechanism, clinical manifestations and treatment of peripheral organ injury after stroke.

Cyclin-dependent kinase regulatory subunit 2 (CKS2) is a potential prognostic marker and is overexpressed in various cancers. This study analyzed sequencing and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus, with external validation using the Chinese Glioma Genome Atlas (CGGA) data. CKS2 expression in the normal brain and tumor tissue was compared. cBioPortal and MethSurv were utilized to scrutinize the prognostic value of CKS2 methylation. Gene set enrichment examination and single-sample gene set enrichment analysis were employed to explore the potential biological functions of CKS2. Cell viability, colony formation, and transwell assays were conducted to evaluate the influence of CKS2 on glioma cell proliferation and invasion. Compared with normal brain tissue, the expression of CKS2 was upregulated in glioma samples (p < 0.001). Multivariate data analysis from TCGA and CGGA indicated that increased expression of CKS2 was an independent risk factor for the prognosis of overall survival in glioma patients. CKS2 methylation was negatively associated with CKS2 expression. Patients with CKS2 hypomethylation had worse overall survival compared with patients with CKS2 methylation, as suggested by the analysis of both TCGA and CGGA datasets. The expression level of CKS2 is closely related to tumor immunity, including the correlation of tumor immune cell infiltration, immune score, and co-expression of multiple immune-related genes. In addition, CKS2 is associated with several immune checkpoints and responses to the chemotherapy drug cisplatin. CKS2 knockdown impeded the expansion and aggression of glioma cell lines. The changes in CKS2 expression may provide a novel prognostic biomarker that can be used to improve patient overall survival rates.

Background and Purpose. Stroke-associated pneumonia (SAP) is a common complication after stroke that increases the mortality of patients. Although there have been many studies suggesting that stroke can increase patient susceptibility to pneumonia, it is still unknown whether the treatment of stroke can also improve lung injury. We used NLRP3-knockout (NLRP3-KO) mice to verify that an improvement in brain injury would also be beneficial to lung injury and further confirm the relationship between stroke and pneumonia. Methods. C57/BL6 wild-type (WT) and NLRP3-KO mice were used to construct middle cerebral artery occlusion (MCAO) models. 2,3,5-Triphenyltetrazolium chloride (TTC) was used to evaluate brain damage, and neurological deficits were assessed. Then, lung tissue injury was examined in the different groups of mice by hematoxylin-eosin (HE) staining. Inflammation (macrophage and neutrophil infiltration, NLRP3-associated inflammatory molecules) and oxidative stress (reactive oxygen species, ROS) in the lungs were comprehensively examined by immunofluorescence staining and Western blotting. Results. First, our findings demonstrated that NLRP3 knockout had a protective effect against cerebral ischemia–reperfusion injury after MCAO. Second, by reducing brain damage after MCAO, lung inflammation was also alleviated. Immunofluorescence staining showed that NLRP3-KO-MCAO mice had reduced inflammatory effector molecule (caspase-1 and IL-1β) expression and macrophage and neutrophil infiltration in the lung, as well as remissive oxidative stress state in the lung, compared with WT-MCAO mice. We also observed a decrease in phosphorylated p65 (p-p65) (an NF-κB factor) in NLRP3-KO-MCAO mice, suggesting that the NF-κB pathway was involved in the protective effect of NLRP3 gene knockout on stroke-induced lung injury. Conclusions. NLRP3 inflammasome knockout not only is beneficial for cerebral ischemia–reperfusion injury but also reduces the severity of poststroke lung injury by reducing brain damage. It has been confirmed that there is a relationship between central insult and peripheral organ injury, and protecting the brain can prevent peripheral organ damage.

Phosphatidylinositol binding clathrin assembly protein interacting mitotic regulator (PIMREG) localizes to the nucleus and can significantly elevate the nuclear localization of clathrin assembly lymphomedullary leukocythemia gene. Although there is some evidence to support an important action for PIMREG in the occurrence and development of certain cancers, currently no pan-cancer analysis of PIMREG is available. Therefore, we intended to estimate the prognostic predictive value of PIMREG and to explore its potential immune function in 33 cancer types. By using a series of bioinformatics approaches, we extracted and analyzed datasets from Oncomine, The Cancer Genome Atlas, Cancer Cell Lineage Encyclopedia (CCLE) and the Human Protein Atlas (HPA), to explore the underlying carcinogenesis of PIMREG, including relevance of PIMREG to prognosis, microsatellite instability (MSI), tumor mutation burden (TMB), tumor microenvironment (TME) and infiltration of immune cells in various types of cancer. Our findings indicate that PIMREG is highly expressed in at least 24 types of cancer, and is negatively correlated with prognosis in major cancer types. In addition, PIMREG expression was correlated with TMB in 24 cancers and with MSI in 10 cancers. We revealed that PIMREG is co-expressed with genes encoding major histocompatibility complex, immune activation, immune suppression, chemokine and chemokine receptors. We also found that the different roles of PIMREG in the infiltration of different immune cell types in different tumors. PIMREG can potentially influence the etiology or pathogenesis of cancer by acting on immune-related pathways, chemokine signaling pathway, regulation of autophagy, RIG-I like receptor signaling pathway, antigen processing and presentation, FC epsilon RI pathway, complement and coagulation cascades, T cell receptor pathway, NK cell mediated cytotoxicity and other immune-related pathways. Our study suggests that PIMREG can be applied as a prognostic marker in a variety of malignancies because of its role in tumorigenesis and immune infiltration.

BackgroundInflammatory responses play a multiphase role in the pathogenesis of cerebral ischemic stroke (IS). Ruxolitinib (Rux), a selective oral JAK 1/2 inhibitor, reduces inflammatory responses via the JAK2/STAT3 pathway. Based on its anti-inflammatory and immunosuppressive effects, we hypothesized that it may have a protective effect against stroke. The aim of this study was to investigate whether inhibition of JAK2 has a neuroprotective effect on ischemic stroke and to explore the potential molecular mechanisms.MethodsRux, MCC950 or vehicle was applied to middle cerebral artery occlusion (MCAO) mice in vivo and an oxygen-glucose deprivation/reoxygenation (OGD/R) model in vitro. After 3 days of reperfusion, neurological deficit scores, infarct volume and brain water content were assessed. Immunofluorescence staining and western blots were used to measure the expression of NLRP3 inflammasome components. The infiltrating cells were investigated by flow cytometry. Proinflammatory cytokines were assessed by RT-qPCR. The expression of the JAK2/STAT3 pathway was measured by western blots. Local STAT3 deficiency in brain tissue was established with a lentiviral vector carrying STAT3 shRNA, and chromatin immunoprecipitation (ChIP) assays were used to investigate the interplay between NLRP3 and STAT3 signaling.ResultsRux treatment improved neurological scores, decreased the infarct size and ameliorated cerebral edema 3 days after stroke. In addition, immunofluorescence staining and western blots showed that Rux application inhibited the expression of proteins related to the NLRP3 inflammasome and phosphorylated STAT3 (P-STAT3) in neurons and microglia/macrophages. Furthermore, Rux administration inhibited the expression of proinflammatory cytokines, including TNF-α, IFN-γ, HMGB1, IL-1β, IL-2, and IL-6, suggesting that Rux may alleviate IS injury by inhibiting proinflammatory reactions via JAK2/STAT3 signaling pathway regulation. Infiltrating macrophages, B, T, cells were also reduced by Rux. Local STAT3 deficiency in brain tissue decreased histone H3 and H4 acetylation on the NLRP3 promoter and NLRP3 inflammasome component expression, indicating that the NLRP3 inflammasome may be directly regulated by STAT3 signaling. Rux application suppressed lipopolysaccharide (LPS)-induced NLRP3 inflammasome secretion and JAK2/STAT3 pathway activation in the OGD/R model in vitro.ConclusionJAK2 inhibition by Rux in MCAO mice decreased STAT3 phosphorylation, thus inhibiting the expression of downstream proinflammatory cytokines and the acetylation of histones H3 and H4 on the NLRP3 promoter, resulting in the downregulation of NLRP3 inflammasome expression.

Ischemic stroke is one of the main issues threatening human health worldwide, and it is also the main cause of permanent disability in adults. Energy consumption and hypoxia after ischemic stroke leads to the death of nerve cells, activate resident glial cells, and promote the infiltration of peripheral immune cells into the brain, resulting in various immune-mediated effects and even contradictory effects. Immune cell infiltration can mediate neuronal apoptosis and aggravate ischemic injury, but it can also promote neuronal repair, differentiation and regeneration. The central nervous system (CNS), which is one of the most important immune privileged parts of the human body, is separated from the peripheral immune system by the blood-brain barrier (BBB). Under physiological conditions, the infiltration of peripheral immune cells into the CNS is controlled by the BBB and regulated by the interaction between immune cells and vascular endothelial cells. As the immune response plays a key role in regulating the development of ischemic injury, neutrophils have been proven to be involved in many inflammatory diseases, especially acute ischemic stroke (AIS). However, neutrophils may play a dual role in the CNS. Neutrophils are the first group of immune cells to enter the brain from the periphery after ischemic stroke, and their exact role in cerebral ischemia remains to be further explored. Elucidating the characteristics of immune cells and their role in the regulation of the inflammatory response may lead to the identification of new potential therapeutic strategies. Thus, this review will specifically discuss the role of neutrophils in ischemic stroke from production to functional differentiation, emphasizing promising targeted interventions, which may promote the development of ischemic stroke treatments in the future.

The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome is a member of the NLR family of inherent immune cell sensors. The NLRP3 inflammasome can detect tissue damage and pathogen invasion through innate immune cell sensor components commonly known as pattern recognition receptors (PRRs). PRRs promote activation of nuclear factor kappa B (NF-κB) pathways and the mitogen-activated protein kinase (MAPK) pathway, thus increasing the transcription of genes encoding proteins related to the NLRP3 inflammasome. The NLRP3 inflammasome is a complex with multiple components, including an NAIP, CIITA, HET-E, and TP1 (NACHT) domain; apoptosis-associated speck-like protein containing a CARD (ASC); and a leucine-rich repeat (LRR) domain. After ischemic stroke, the NLRP3 inflammasome can produce numerous proinflammatory cytokines, mediating nerve cell dysfunction and brain edema and ultimately leading to nerve cell death once activated. Ischemic stroke is a disease with high rates of mortality and disability worldwide and is being observed in increasingly younger populations. To date, there are no clearly effective therapeutic strategies for the clinical treatment of ischemic stroke. Understanding the NLRP3 inflammasome may provide novel ideas and approaches because targeting of upstream and downstream molecules in the NLRP3 pathway shows promise for ischemic stroke therapy. In this manuscript, we summarize the existing evidence regarding the composition and activation of the NLRP3 inflammasome, the molecules involved in inflammatory pathways, and corresponding drugs or molecules that exert effects after cerebral ischemia. This evidence may provide possible targets or new strategies for ischemic stroke therapy.

Objective: The current study was to explore whether meisoindigo was effective in suppressing proliferation and inducing apoptosis of human glioblastoma multiforme U87 cells and to explore its possible mechanisms. Method: Morphological changes were observed by light microscopy. Cell counting kit-8 (CCK-8) assay was performed to detect cellular proliferation. Apoptosis was monitored by flow cytometry. Akt, phospho-Akt, PI3K, p65, phospho-p65 and apoptosis-related proteins caspase-3 and caspase-9 were examined by Western blotting assays. Immunofluorescence was used to evaluate level of P65 expression in cells. Result: Meisoindigo inhibited the proliferation of U87 cells, and the inhibitory effect increased in a dose dependent manner. Moreover, meisoindigo exposure triggered an increase in the level of caspase-3 and caspase-9, supporting its role in the activation of apoptosis. Furthermore, meisoindigo reduced the expression of PI3K, Akt, phospho-Akt, NF-κB, p65 and phospho-p65 in U87 cells, and displacement of p65 from the nucleus to the cytoplasm. Conclusion: Meisoindigo inhibits proliferation and induces apoptosis of U87 cells, probably through down-regulating the PI3K/Akt pathway and reducing nuclear translocation of NF-κB p65.

Stroke is the leading cause of disability and mortality in the world, but the pathogenesis of ischemic stroke (IS) is not completely clear and treatments are limited. Mounting evidence indicate that neovascularization is a critical defensive reaction to hypoxia that modulates the process of long-term neurologic recovery after IS. Angiogenesis is a complex process in which the original endothelial cells in blood vessels are differentiated, proliferated, migrated, and finally remolded into new blood vessels. Many immune cells and cytokines, as well as growth factors, are directly or indirectly involved in the regulation of angiogenesis. Inflammatory cells can affect endothelial cell proliferation, migration, and activation by secreting a variety of cytokines via various inflammation-relative signaling pathways and thus participate in the process of angiogenesis. However, the mechanism of inflammation-mediated angiogenesis has not been fully elucidated. Hence, this review aimed to discuss the mechanism of inflammation-mediated angiogenesis in IS and to provide new ideas for clinical treatment of IS.

BackgroundEvidence shows that inflammatory responses play multiphasic roles in stroke pathogenesis. Ruxolitinib (Rux), a selective oral JAK 1/2 inhibitor, is efficacious in COVID-19 by reducing inflammation via the JAK2/STAT3 pathway. MethodsHere, we investigated whether JAK2 inhibition has neuroprotective effects against ischemic stroke (IS) in MCAO mice in vivo and in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) model, and explored the potential molecular mechanisms. Rux was applied to MCAO mice. Immunofluorescence staining, RT-qPCR, and western blots were used to measure the expression of NLRP3 inflammation components and proinflammatory cytokines as well as JAK2/STAT3 pathway. Local STAT3 deficiency in brain tissue was established to investigate the interplay between NLRP3 and STAT3 signaling.ResultsRux treatment obviously improved neurological scores, decreased the infarct size and ameliorated cerebral edema 3 days after stroke. In addition, immunofluorescence staining and western blots showed that Rux application inhibited the expression of NLRP3 inflammasome components, proteins related to the NLRP3 inflammasome and phosphorylated STAT3 (p-STAT3) in neurons. Furthermore, Rux administration inhibited the expression of proinflammatory cytokines, including TNF-α, IFN-γ, HMBG1, IL-1β, IL-2, and IL-6 in middle cerebral artery occlusion (MCAO) model mice, suggesting that Rux may alleviate IS injury by inhibiting proinflammatory reactions via JAK2/STAT3 signaling pathway regulation. Local STAT3 deficiency decreased histone H3 and H4 acetylation on the NLRP3 promoter and the NLRP3 inflammasome component expression, indicating that the NLRP3 inflammasome may be directly regulated by STAT3 signaling. Finally, the effect of Rux on the NLRP3 inflammasome was further assessed in a HT22 cell OGD/R model in vitro. Rux application markedly suppressed lipopolysaccharide (LPS)-induced NLRP3 inflammasome secretion and JAK2/STAT3 pathway activation in vitro the in OGD/R HT22 cell model.ConclusionJAK2 inhibition by Rux in MCAO mice decreased STAT3 phosphorylation, thus inhibiting downstream proinflammatory cytokines and H3 and H4 acetylation on the NLRP3 promoter, resulting in downregulation of NLRP3 inflammasome component expression.

As a kind of credit loan business without collateral, credit card business has a high risk. The scale of bank credit card business is growing rapidly, but the credit management of bank for all levels of credit card is not mature, resulting in the risk of credit card business and related business problems. An Australian credit card transaction data is proposed to predict the occurrence of credit card default. The results show that the bank card application is mainly affected by six key factors. The bank could focus on influential factors and consider whether to accept the customer's credit card application according to the fitting model.

Through considerable effort in research and clinical studies, the immune system has been identified as a participant in the onset and progression of brain injury after ischaemic stroke. Due to the involvement of all types of immune cells, the roles of the immune system in stroke pathology and associated effects are complicated. Past research concentrated on the functions of monocytes and neutrophils in the pathogenesis of ischaemic stroke and tried to demonstrate the mechanisms of tissue injury and protection involving these immune cells. Within the past several years, an increasing number of studies have elucidated the vital functions of T cells in the innate and adaptive immune responses in both the acute and chronic phases of ischaemic stroke. Recently, the phenotypes of T cells with proinflammatory or anti-inflammatory function have been demonstrated in detail. T cells with distinctive phenotypes can also influence cerebral inflammation through various pathways, such as regulating the immune response, interacting with brain-resident immune cells and modulating neurogenesis and angiogenesis during different phases following stroke. In view of the limited treatment options available following stroke other than tissue plasminogen activator therapy, understanding the function of immune responses, especially T cell responses, in the post-stroke recovery period can provide a new therapeutic direction. Here, we discuss the different functions and temporal evolution of T cells with different phenotypes during the acute and chronic phases of ischaemic stroke. We suggest that modulating the balance between the proinflammatory and anti-inflammatory functions of T cells with distinct phenotypes may become a potential therapeutic approach that reduces the mortality and improves the functional outcomes and prognosis of patients suffering from ischaemic stroke.

With the rapid growth of the financial market, the management of credit card recipients by financial institute is becoming increasingly significant. In order to retain the valuable customers and prevent churn by providing the right incentives, analysis of customer default payment data are required. A Linear Discrimination Regression (LDA) model is used to analysis of the data of customer default rate in Taiwan. The results of final regression model were shown using scorecard. Discussion of the KS Test results determines improvement in performance that financial institute will get from this risk model.

In this paper, we designed a progressive compression transmission system for 3D models in order to solve the transmission limitation caused by the large data volume of the 3D models. The system built on the basis of an improved quadratic error measurement algorithm based on triangle strips. The system is implemented based on C ++ and OpenGL, using TCP / IP transmission protocol and C / S mode. The system preprocesses the model by storing the progressive transfer hierarchy model file locally. The transmission process uses the DEFLATE algorithm to compress the data, thereby the system can reduce the amount of transmitted data and improving the transmission and display speed of the model. The local model is stored by blind watermarking, the client can only browse and interact with the model. In order to prevent the misappropriation of 3D models, users cannot download the models. The system solves the problems of slow transmission and long display time of 3D models. Experiments prove the effectiveness of this system.

The Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway, a well-conserved and basic intracellular signaling cascade, is mostly inactivated under basal conditions, although it can be phosphorylated under extracellular stimulation; in addition, it can influence the transcription and expression of multiple genes involved in biological processes such as cellular growth, metabolism, differentiation, degradation and angiogenesis. The inflammatory response, apoptosis, oxidative stress and angiogenesis are the main factors involved in the pathogenesis of ischemic stroke. Numerous studies have confirmed that the JAK2/STAT3 axis can be activated rapidly by ischemic stress, which is closely related to the regulation of these important pathological processes. However, different opinions on the specific role of this signaling pathway remain. In this paper, we review and summarize previous studies on the JAK2/STAT3 pathway in ischemic stroke.

Ischemic stroke is a devastating disease with long-term disability. However, the pathogenesis is unclear and treatments are limited. Meisoindigo, a second-generation derivative of indirubin, has general water solubility and is well-tolerated. Previous studies have shown that meisoindigo reduces inflammation by inhibiting leukocyte chemotaxis and migration. In the present study, we investigated the hypothesis that meisoindigo was also protective against ischemic stroke, then evaluated its underlying mechanisms. In vivo, adult male C57BL/6J wild-type mice were used to produce a middle cerebral artery occlusion (MCAO) stroke model. On day three after reperfusion, obvious improvement in neurological scores, infarct volume reduction and cerebral edema amelioration were observed in meisoindigo treatment. Moreover, immunofluorescence staining and western-blot showed that the expression of NLRP3 inflammasome and its associated proteins in neurons and microglia was inhibited by meisoindigo. The effects of Meisoindigo on NLRP3 inflammasome inactivation and increased the M2 phenotype of microglia/macrophage through shifting from a M1 phenotype, which was possibly mediated by inhibition of TLR4/NF-κB. Furthermore, we verified the inhibitory effect of meisoindigo on TLR4/NF-κB signaling pathway, and found that meisoindigo treatment could significantly suppressed the expression of TLR4/NF-κB pathway-associated proteins in a dose-dependent manner, meanwhile, which resulted in downregulation of HMGB1 and IL-1β. Next, we established an in vitro oxygen glucose deprivation/Reperfusion (OGD/R) model in HT-22 and BV2 cells to simulate ischemic conditions. Cytotoxicity assay showed that meisoindigo substantially improved relative cell vitality and in HT-22 and BV2 cells following OGD/R in vitro. After suffering OGD/R, the TLR4/NF-κB pathway was activated, the expression of NLRP3 inflammasome-associated proteins and M1 microglia/macrophage were increased, but meisoindigo could inhibit above changes in both HT-22 and BV2 cells. Additionally, though lipopolysaccharide stimulated the activation of TLR4 signaling in OGD/R models, meisoindigo co-treatment markedly reversed the upregulation of TLR4 and following activation of NLRP3 inflammasome and polarization of M1 microglia/macrophages mediated by TLR4. Overall, we demonstrate for the first time that meisoindigo post-treatment alleviates brain damage induced by ischemic stroke in vivo and in vitro experiments through blocking activation of the NLRP3 inflammasome and regulating the polarization of microglia/macrophages via inhibition of the TLR4/NF-κB signaling pathway.

Ischemia/reperfusion injury (IRI) occurs commonly during renal transplantation. It has been well demonstrated that the inflammatory response has an important role in the pathogenesis and pathological processes of IRI. However, the signaling events that trigger the activation of the inflammatory response are less clear. Accumulated evidence has identified the role of various injury factors released from or exposed in ischemic, damaged, or dying cells, which serve as initiators of the inflammatory response and exacerbate kidney injury after renal IRI. Signaling pathways triggered by these endogenous molecules that activate different pathogen recognition receptors have also been widely investigated. Here, we review the molecular signaling molecules that initiate the inflammatory response during renal IRI and that provide potential therapeutic options for the disease.

The gut-brain-microbiota axis (GBMAx) coordinates bidirectional communication between the gut and brain, and is increasingly recognized as playing a central role in physiology and disease. MicroRNAs are important intracellular components secreted by extracellular vesicles (EVs), which act as vital mediators of intercellular and interspecies communication. This review will present current advances in EV-derived microRNAs and their potential functional link with GBMAx. We propose that EV-derived microRNAs comprise a novel regulatory system for GBMAx, and a potential novel therapeutic target for modifying GBMAx in clinical therapy.

Sodium tanshinone IIA sulfonate (STS) can protect against brain damage induced by stroke. However, the neural protection mechanism of STS remains unclear. We investigated whether STS performs its protective function by suppressing autophagy and inflammatory activity during brain injury. We established a transient middle cerebral artery occlusion and reperfusion (MCAO/R) model by blocking the left middle cerebral artery with a thread inserted through the internal carotid artery for 1 h, followed by reperfusion for 48 h either with or without STS and the autophagy inhibitor 3-methyladenine (3-MA). Neuroprotective effects were determined by evaluating infarction, brain edema, and neurological deficits. The numbers of microglia-derived macrophages, monocyte-derived microglia, T cells, and B cells in the brains were measured, based on the surface marker analyses of CD45, CD11b, B220, CD3, and CD4 using fluorescence-assisted cell sorting. STS (10, 20, 40 mg/kg) was able to significantly reduce infarct volumes, improve neurological deficits, and reduce brain water contents. STS treatment reduced neuroinflammation, as assessed by the infiltration of macrophages and neutrophils, corresponding with reduced numbers of macrophages, T cells, and B cells in ischemia/reperfusion (I/R) brains. In addition, STS treatment also attenuated the upregulation of autophagy associated proteins, such as LC3-II, Beclin-1 and Sirt 6, which was induced by MCAO. These results demonstrated that STS can provide remarkable protection against ischemic stroke, possibly via the inhibition of autophagy and inflammatory activity.

High-mobility group box 1 protein (HMGB1) is a novel, cytokine-like, and ubiquitous, highly conserved, nuclear protein that can be actively secreted by microglia or passively released by necrotic neurons. Ischemic stroke is a leading cause of death and disability worldwide, and the outcome is dependent on the amount of hypoxia-related neuronal death in the cerebral ischemic region. Acting as an endogenous danger-associated molecular pattern (DAMP) protein, HMGB1 mediates cerebral inflammation and brain injury and participates in the pathogenesis of ischemic stroke. It is thought that HMGB1 signals via its presumed receptors, such as toll-like receptors (TLRs), matrix metalloproteinase (MMP) enzymes, and receptor for advanced glycation end products (RAGEs) during ischemic stroke. In addition, the release of HMGB1 from the brain into the bloodstream influences peripheral immune cells. However, the role of HMGB1 in ischemic stroke may be more complex than this and has not yet been clarified. Here, we summarize and review the research into HMGB1 in ischemic stroke.

At present, there are many problems in the core programming curriculums of the specialized computer science such as low coordination with other courses, insufficient fusion and poor integration with the overall development of special discipline. The present study is mainly focused on programming curriculums for specialized computer science and the specific reform scheme is also put forward, with some innovation and