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Ischemic stroke is a kind of neurological dysfunction caused by cerebral ischemia. Astrocytes, as the most abundant type of glial cells in the central nervous system, are activated into reactive astrocytes after cerebral ischemia, and this process involves the activation or change of a series of cell surface receptors, ion channels and ion transporters, GTPases, signaling pathways, and so on. The role of reactive astrocytes in the development of ischemic stroke is time-dependent. In the early stage of ischemia, reactive astrocytes proliferate moderately and surround the ischemic tissue to prevent the spread of the lesion. At the same time, reactive astrocytes release neuroprotective factors, ultimately relieving brain injury. In the late stage of ischemia, reactive astrocytes excessively proliferate and migrate to form dense glial scar tissue, which hinders the repair of damaged tissue. At the same time, reactive astrocytes in the glial scar release a large number of neurotoxic factors, ultimately aggravating ischemic stroke. In this paper, we focus on the molecular mechanism of astrogliosis and glial scar formation after cerebral ischemia, and explore the relevant studies using glial scar as a therapeutic target, providing a reference for the selection of therapeutic strategies for ischemic stroke and further research directions., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Microglia/macrophages, as pivotal immune cells in the central nervous system (CNS), play a critical role in neuroinflammation associated with ischemic brain injury. Targeting their activation through pharmacological interventions represents a promising strategy to alleviate neurological deficits, thereby harboring significant implications for the prevention and treatment of ischemic stroke. Ligusticum cycloprolactam (LIGc), a novel monomeric derivative of traditional Chinese medicine, has shown potential as a therapeutic agent; however, its specific role in cerebral ischemic injury remains unclear., Methods: In vitro experiments utilized lipopolysaccharide (LPS)-induced inflammation models of RAW264.7 cells and primary mouse microglia. In vivo studies employed LPS-induced neuroinflammation models in mice and a transient middle cerebral artery occlusion (tMCAO) mouse model to evaluate the impact of LIGc on neuroinflammation and microglia/macrophage phenotypic alterations. Further elucidation of the molecular mechanisms underlying these effects was achieved through RNA-Seq analyses., Results: LIGc exhibited the capacity to attenuate LPS-induced production of pro-inflammatory markers in macrophages and microglia, facilitating their transition to an anti-inflammatory phenotype. In models of LPS-induced neuroinflammation and tMCAO, LIGc ameliorated pathological behaviors and neurological deficits while mitigating brain inflammation. RNA-seq analyses revealed formyl peptide receptor 1 (FPR1) as a critical mediator of LIGc's effects. Specifically, FPR1 enhances the pro-inflammatory phenotype of microglia/macrophages and inhibits their anti-inflammatory response by upregulating NLR family pyrin domain protein 3 (NLRP3) inflammasomes, thus aggravating inflammatory processes. Conversely, LIGc exerts anti-inflammatory effects by downregulating the FPR1/NLRP3 signaling axis. Furthermore, FPR1 overexpression or NLRP3 agonists reversed the effects of LIGc observed in this study., Conclusion: Our findings suggest that LIGc holds promise in improving ischemic brain injury and neuroinflammation through modulation of microglia/macrophage polarization. Mechanistically, LIGc attenuates the pro-inflammatory phenotype and promotes the anti-inflammatory phenotype by targeting the FPR1/NLRP3 signaling pathway, ultimately reducing inflammatory responses and mitigating neurological damage., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Secondary neurological impairment mediated by neuroinflammation is recognized as a crucial pathological factor in central nervous system (CNS) diseases. Currently, there exists a lack of specific therapies targeting neuroinflammation. Given that microglia constitute the primary immune cells involved in the neuroinflammatory response, a thorough comprehension of their role in CNS diseases is imperative for the development of efficacious treatments. Recent investigations have unveiled the significance of formyl peptide receptors (FPRs) in various neuroinflammatory diseases associated with microglial overactivation. Consequently, FPRs emerge as promising targets for modulating the neuroinflammatory response. This review aims to comprehensively explore the therapeutic potential of targeting FPRs in the management of microglia-mediated neuroinflammation. It delineates the molecular characteristics and functions of FPRs, elucidates their involvement in the inflammatory response linked to microglial overactivation, and synthesizes therapeutic strategies for regulating microglia-mediated neuroinflammation via FPR modulation, thereby charting a novel course for the treatment of neuroinflammatory diseases., (© 2024 Federation of American Societies for Experimental Biology.)

Central nervous system (CNS) diseases are one of the diseases that threaten human health. The delivery of drugs targeting the CNS has always been a significant challenge; the blood-brain barrier (BBB) is the main obstacle that must be overcome. The rise of bone marrow mesenchymal stem cell (BMSC) therapy has brought hope for the treatment of CNS diseases. However, the problems of low homing rate, susceptibility differentiation into astrocytes, immune rejection, and formation of iatrogenic tumors of transplanted BMSCs limit their clinical application. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) have become a hot research topic in the treatment of CNS diseases in recent years because of their excellent histocompatibility, low immunogenicity, ease of crossing the BBB, and their ability to serve as natural carriers for treatment. This article reviews the mechanisms of BMSC-Exos in CNS diseases and provides direction for further research., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Residual heavy metals in soils will destroy microbial community stability and influence its aggregation. However, exploring microbial ecology under heavy-metal stress still requires a conjoint analysis of bacterial interspecies communication and the community diversity maintenance mechanism. In this study, soil samples were collected from a heavy-metal-contaminated site in China to investigate the ecological response of indigenous microbial communities through high-throughput sequencing. Results showed that bacterial taxa and functions generated unusual decoupling phenomena. There were no significant differences in the diversity of species with the increase in concentration of heavy metals (Hg, Se, and Cr), but the functional diversity was lost. Also, the average niche breadth of bacterial species increased from 1.70 to 2.28, but community stability declined and the species assembly was always a deterministic process (NST <0.5). After the bacterial functional assembly changed from a stochastic process to a deterministic process (NST <0.5), it was transformed into a stochastic process (NST >0.5) again under the stress of high-concentration heavy metals, indicating that the collective stress resistance of bacterial communities changed from positive mutation into passive functional propagation. The research results can provide new insight into understanding the adaptive evolution of communities and ecosystem restoration under the stress of soil heavy metals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: New daily persistent headache (NDPH) is a rare primary headache with unclear pathogenesis. Neuroimaging studies of NDPH are limited, and controversy still exists. Diffusion tensor imaging (DTI) is commonly used to study the white matter. However, lacking specificity, the potential pathological mechanisms of white matter microstructural changes remain poorly understood. In addition, the intricacy of gray matter structures impedes the application of the DTI model. Here, we applied an advanced diffusion model of neurite orientation dispersion and density imaging (NODDI) to study the white matter and cortical gray matter microstructure in patients with NDPH., Methods: This study assessed brain microstructure, including 27 patients with NDPH, and matched 28 healthy controls (HCs) by NODDI. The differences between the two groups were assessed by tract-based spatial statistics (TBSS) and surface-based analysis (SBA), focusing on the NODDI metrics (neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISOVF)). Furthermore, we performed Pearson's correlation analysis between the NODDI indicators and clinical characteristics., Results: Compared to HCs, patients with NDPH had a reduction of density and complexity in several fiber tracts. For robust results, the fiber tracts were defined as comprising more than 100 voxels, including bilateral inferior fronto-occipital fasciculus (IFOF), left superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF), as well as right corticospinal tract (CST). Moreover, the reduction of neurite density was uncovered in the left superior and middle frontal cortex, left precentral cortex, and right lateral orbitofrontal cortex and insula. There was no correlation between the NODDI metrics of these brain regions and clinical variables or scales of relevance after the Bonferroni correction., Conclusions: Our research indicated that neurite loss was detected in both white matter and cortical gray matter of patients with NDPH., (© 2024. The Author(s).)

Background: Chronic migraine (CM) is a debilitating neurofunctional disorder primarily affecting females, characterized by central sensitization. Central sensitization refers to the enhanced response to sensory stimulation, which involves changes in neuronal excitability, synaptic plasticity, and neurotransmitter release. Environmental enrichment (EE) can increase the movement, exploration, socialization and other behaviors of mice. EE has shown promising effects in various neurological disorders, but its impact on CM and the underlying mechanism remains poorly understood. Therefore, the purpose of this study was to determine whether EE has the potential to serve as a cost-effective intervention strategy for CM., Methods: A mouse CM model was successfully established by repeated administration of nitroglycerin (NTG). We selected adult female mice around 8 weeks old, exposed them to EE for 2 months, and then induced the CM model. Nociceptive threshold tests were measured using Von Frey filaments and a hot plate. The expression of c-Fos, calcitonin gene-related peptide (CGRP) and inflammatory response were measured using WB and immunofluorescence to evaluate central sensitization. RNA sequencing was used to find differentially expressed genes and signaling pathways. Finally, the expression of the target differential gene was investigated., Results: Repeated administration of NTG can induce hyperalgesia in female mice and increase the expression of c-Fos and CGRP in the trigeminal nucleus caudalis (TNC). Early exposure of mice to EE reduced NTG-induced hyperalgesia in CM mice. WB and immunofluorescence revealed that EE inhibited the overexpression of c-Fos and CGRP in the TNC of CM mice and alleviated the inflammatory response of microglia activation. RNA sequencing analysis identified that several central sensitization-related signaling pathways were altered by EE. VGluT1, a key gene involved in behavior, internal stimulus response, and ion channel activity, was found to be downregulated in mice exposed to EE., Conclusion: EE can significantly ameliorate hyperalgesia in the NTG-induced CM model. The mechanisms may be to modulate central sensitization by reducing the expression of CGRP, attenuating the inflammatory response, and downregulating the expression of VGluT1, etc., suggesting that EE can serve as an effective preventive strategy for CM., (© 2024. The Author(s).)

Gliomas, the most common malignant brain tumor, present a grim prognosis despite available treatments such as surgical resection, temozolomide (TMZ) therapy, and radiation therapy. This is due to their aggressive growth, high level of immunosuppression, and the blood-brain barrier (BBB), which obstruct the effective exchange of therapeutic drugs. Gliomas can significantly affect differentiation and function of immune cells by releasing extracellular vesicles (EVs), resulting in a systemic immunosuppressive state and a highly immunosuppressive microenvironment. In the tumor immune microenvironment (TIME), the primary immune cells are regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs). In particular, glioma-associated TAMs are chiefly composed of monocyte-derived macrophages and brain-resident microglia. These cells partially exhibit characteristics of a pro-tumorigenic, anti-inflammatory M2-type. Glioma-derived EVs can hijack TAMs to differentiate into tumor-supporting phenotypes or directly affect the maturation of peripheral blood monocytes (PBMCs) and promote the activation of MDSCs. In addition, EVs impair the ability of dendritic cells (DCs) to process antigens, subsequently hindering the activation of lymphocytes. EVs also impact the proliferation, differentiation, and activation of lymphocytes. This is primarily evident in the overall reduction of CD4 + helper T cells and CD8 + T cells, coupled with a relative increase in Tregs, which possess immunosuppressive characteristics. This study investigates thoroughly how tumor-derived EVs impair the function of immune cells and enhance immunosuppression in gliomas, shedding light on their potential implications for immunotherapy strategies in glioma treatment., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Microglia, as the intrinsic immune cells in the brain, are activated following ischemic stroke. Activated microglia participate in the pathological processes after stroke through polarization, autophagy, phagocytosis, pyroptosis, ferroptosis, apoptosis, and necrosis, thereby influencing the injury and repair following stroke. It has been established that polarized M1 and M2 microglia exhibit pro-inflammatory and anti-inflammatory effects, respectively. Autophagy and phagocytosis in microglia following ischemia are dynamic processes, where moderate levels promote cell survival, while excessive responses may exacerbate neurofunctional deficits following stroke. Additionally, pyroptosis and ferroptosis in microglia after ischemic stroke contribute to the release of harmful cytokines, further aggravating the damage to brain tissue due to ischemia. This article discusses the different functional states of microglia in ischemic stroke research, highlighting current research trends and gaps, and provides insights and guidance for further study of ischemic stroke., Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the authors., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Knowledge distillation (KD) is a well-established technique for compressing neural networks and has gained increasing attention in object detection tasks. However, typical object detection distillation methods use fixed-level semantic features for distillation, which might not be best for all training stages and samples. In this paper, a multilayer semantic feature adaptive distillation (MSFAD) method is proposed that uses a routing network composed of a teacher and a student detector, along with an agent network for decision making. Specifically, the inputs to the proxy network consist of the features output by the neck structures of the teacher and student detectors, and the output is a decision on which features to choose for distillation. The MSFAD method improves the distillation training process by enabling the student detector to automatically select valuable semantic-level features from the teacher detector. Experimental results demonstrated that the proposed method increased the mAP 50 of YOLOv5s by 3.4% and the mAP 50-90 by 3.3%. Additionally, YOLOv5n with only 1.9 M parameters achieved detection performance comparable to that of YOLOv5s.

Ischemic stroke (IS) is characterized by high incidence, high recurrence, and high mortality and places a heavy burden on society and families. The pathological mechanisms of IS are complex, among which secondary neurological impairment mediated by neuroinflammation is considered to be the main factor in cerebral ischemic injury. At present, there is still a lack of specific therapies to treat neuroinflammation. The tumor suppressor protein p53 has long been regarded as a key substance in the regulation of the cell cycle and apoptosis in the past. Recently, studies have found that p53 also plays an important role in neuroinflammatory diseases, such as IS. Therefore, p53 may be a crucial target for the regulation of the neuroinflammatory response. Here, we provide a comprehensive review of the potential of targeting p53 in the treatment of neuroinflammation after IS. We describe the function of p53, the major immune cells involved in neuroinflammation, and the role of p53 in inflammatory responses mediated by these cells. Finally, we summarize the therapeutic strategies of targeting p53 in regulating the neuroinflammatory response after IS to provide new directions and ideas for the treatment of ischemic brain injury., (© 2023 Wiley Periodicals LLC.)

Ligustilide, a natural phthalide mainly derived from chuanxiong rhizomes and Angelica Sinensis roots, possesses anti-inflammatory activity, particularly in the context of the nervous system. However, its application is limited because of its unstable chemical properties. To overcome this limitation, ligusticum cycloprolactam (LIGc) was synthesized through structural modification of ligustilide. In this study, we combined network pharmacological methods with experimental verification to investigate the anti-neuroinflammatory effects and mechanisms of ligustilide and LIGc. Based on our network pharmacology analysis, we identified four key targets of ligustilide involved in exerting an anti-inflammatory effect, with the nuclear factor (NF)-κB signal pathway suggested as the main signalling pathway. To verify these results, we examined the expression of inflammatory cytokines and inflammation-related proteins, analysed the phosphorylation level of NF-κB, inhibitor of κBα (IκBα) and inhibitor of κB kinase α and β (IKKα+β), and evaluated the effect of BV2 cell-conditioned medium on HT22 cells in vitro. Our results, demonstrate for the first time that LIGc can downregulate the activation of the NF-κB signal pathway in BV2 cells induced by lipopolysaccharide, suppress the production of inflammatory cytokines and reduce nerve injury in HT22 cells mediated by BV2 cells. These findings suggest that LIGc inhibits the neuroinflammatory response mediated by BV2 cells, providing strong scientific support for the development of anti-inflammatory drugs based on natural ligustilide or its derivatives. However, there are some limitations to our current study. In the future, further experiments using in vivo models may provide additional evidence to support our findings., (© 2023 John Wiley & Sons Australia, Ltd.)

Semi-supervised learning is a learning pattern that can utilize labeled data and unlabeled data to train deep neural networks. In semi-supervised learning methods, self-training-based methods do not depend on a data augmentation strategy and have better generalization ability. However, their performance is limited by the accuracy of predicted pseudo-labels. In this paper, we propose to reduce the noise in the pseudo-labels from two aspects: the accuracy of predictions and the confidence of the predictions. For the first aspect, we propose a similarity graph structure learning (SGSL) model that considers the correlation between unlabeled and labeled samples, which facilitates the learning of more discriminative features and, thus, obtains more accurate predictions. For the second aspect, we propose an uncertainty-based graph convolutional network (UGCN), which can aggregate similar features based on the learned graph structure in the training phase, making the features more discriminative. It can also output the uncertainty of predictions in the pseudo-label generation phase, generating pseudo-labels only for unlabeled samples with low uncertainty; thus, reducing the noise in the pseudo-labels. Further, a positive and negative self-training framework is proposed, which combines the proposed SGSL model and UGCN into the self-training framework for end-to-end training. In addition, in order to introduce more supervised signals in the self-training process, negative pseudo-labels are generated for unlabeled samples with low prediction confidence, and then the positive and negative pseudo-labeled samples are trained together with a small number of labeled samples to improve the performance of semi-supervised learning. The code is available upon request.

Due to the rapid artificial intelligence technology progress and innovation in various fields, this research aims to use science mapping tools to comprehensively and objectively analyze recent advances, hot-spots, and challenges in artificial intelligence-based microplastic-imaging field from the Web of Science (2019-2022). By text mining and visualization in the scientific literature we emphasized some opportunities to bring forward further explication and analysis by (i) exploring efficient and low-cost automatic quantification methods in the appearance properties of microplastics, such as shape, size, volume, and topology, (ii) investigating microplastics water-soluble synthetic polymers and interaction with other soil and water ecology environments via artificial intelligence technologies, (iii) advancing efficient artificial intelligence algorithms and models, even including intelligent robot technology, (iv) seeking to create and share robust data sets, such as spectral libraries and toxicity database and co-operation mechanism, (v) optimizing the existing deep learning models based on the readily available data set to balance the related algorithm performance and interpretability, (vi) facilitating Unmanned Aerial Vehicle technology coupled with artificial intelligence technologies and data sets in the mass quantities of microplastics. Our major findings were that the research of artificial intelligence methods to revolutionize environmental science was progressing toward multiple cross-cutting areas, dramatically increasing aspects of the ecology of plastisphere, microplastics toxicity, rapid identification, and volume assessment of microplastics. The above findings can not only determine the characteristics and track of scientific development, but also help to find suitable research opportunities to carry out more in-depth research with many problems remaining.

Microglia, as innate immune cells in the brain, closely monitor changes in the internal environment and participate in the maintenance of homeostasis in the central nervous system (CNS). Microglia can be polarized to the M1 or M2 phenotype in response to various stimuli in vivo or in vitro, affecting the functions of peripheral neurons. M2 microglia have attracted increasing attention in recent years owing to their beneficial effects on various diseases and injuries of the CNS, such as traumatic brain injury, stroke, Alzheimer's disease and multiple sclerosis. They exert neuroprotective effects by various mechanisms, e.g., suppressing inflammation, promoting the degradation of misfolded and aggregated proteins, promoting neurite growth, enhancing neurogenesis, inhibiting autophagy and apoptosis, promoting myelination, maintaining blood-brain barrier integrity, and enhancing phagocytic activity.This review summarizes the molecular mechanisms by which M2 microglia exert protective effects on neurons and provides a reference for the selection of therapeutic targets for CNS diseases., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Study: Membrane trafficking process is significant for the complex and precise regulatory of the nervous system. Rab11, as a small GTPase of the Rab superfamily, controls endocytic vesicular trafficking to the cell surface after sorting in recycling endosome (RE), coordinating with its receptors to maintain neurological function., Materials and Methods: This article reviewed the literature of Rab11 in nervous system., Results: Rab11-positive vesicles targeted transport growth-related molecules, such as integrins, protrudin, tropomyosin receptor kinase (Trk) A/B receptor and AMPA receptor (AMPAR) to membrane surface to promote the regeneration capacity of axon and dendrites and maintain synaptic plasticity. In addition, many studies have shown that the expression of Rab11 is decreased in multiple neurodegenerative diseases, which is highly correlated with the process of production, transport and clearance of disease-related pathological proteins. And overexpression or increased activity of Rab11 can greatly improve the defect of membrane trafficking and slow down the disease process., Conclusion: With increasing research efforts on Rab11-dependent membrane trafficking mechanisms, a potential target for nerve regeneration and neurodegenerative diseases will be provided.

Annexin, a calcium-dependent phospholipid-binding protein, can affect tumor cell adhesion, proliferation, apoptosis, invasion and metastasis, as well as tumor neovascularization in different ways. Recent studies have shown that annexin exists not only as an intracellular protein in tumor cells, but also in different ways to be secret outside the cell as a "cross-talk" tool for tumor cells and tumor microenvironment, thus playing an important role in the development of tumors, such as participating in epithelial-mesenchymal transition, regulating immune cell behavior, promoting neovascularization and so on. The mechanism of annexin secretion in the form of extracellular vesicles and its specific role is still unclear. This paper summarizes the main role of annexin secreted into the extracellular space in the form of extracellular vesicles in tumorigenesis and drug resistance and analyzes its possible mechanism., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To evaluate the efficacy of scalp-acupuncture on subjects with hemiplegic paralysis of acute ischaemic stroke (AIS)., Methods: One hundred and twenty patients with hemiplegic paralysis of 1 to 7 d post stroke, aged 40 to 75 years, were randomly allocated to receive either standard care (control group) or standard care plus 30 min of scalp-acupuncture applied to the bilateral anterior oblique line of the vertex-temporal (MS6) for 14 d (6 d/week) (trial group). The outcome measures included the National Institutes of Health Stroke scale (NIHSS) for neurological deficits, the Fugl-Meyer assessment (FMA) for limb impairment, and Barthel index (BI) for activities of daily living before and after intervention. The manual muscle test (MMT) was assessed at pre-intervention, at the first post-intervention immediately, and at the 14th day after intervention commencement. Measurements were recorded by a blinded investigator at different time points after initiating the intervention., Results: The trial group had a greater increase in MMT (P < 0.05), FMA, and BI scores (P < 0.01), and a greater decrease in NIHSS scores (P < 0.01) from pre-intervention to post-intervention, and the control group had a greater increase in MMT scores (P < 0.05), and a greater decrease in NIHSS scores(P < 0.01) from pre-intervention to post-intervention. The improvement in MMT (P < 0.01), FMA, BI (P < 0.05), and NIHSS (P < 0.01) scores in the trial group was superior to that of the control group. Meanwhile, scalp-acupuncture intervention had an immediate effect on myodynamia of patients with hemiplegic paralysis after acute ischaemic stroke in this randomized controlled trial., Conclusion: The early scalp-acupuncture intervention after stroke effectively increased myodynamia of the affected limbs, improved neurological deficit degrees, and daily living ability.

As the innate immune cells that permanently reside in the central nervous system (CNS), microglia play an increasingly important role in maintaining brain function. Normally, microglia act as resting phenotype, which can be activated by various types of stimuli and release a variety of inflammatory mediators. Melatonin is an endogenous rhythmic hormone secreted principally by the pineal gland. Increasing evidence suggests that melatonin can detoxify reactive oxygen species (ROS) and prevent microglia from over-activation. This review summarizes the mechanisms of melatonin in inhibiting excessive activation of microglia and demonstrates the feasibility of melatonin in the treatment of diseases related to microglial over-activation.

Ligustilide (LIG) is the main active ingredient of Angelica sinensis (Oliv.) Diels and has a neuroprotective effect against ischemic stroke. However, owing to its multi-conjugated unstable structure, the compound has poor drug-forming properties. Therefore, we synthesized highly stable colorless needle crystals (known as ligusticum cycloprolactam, LIGc) through the structural modification of LIG. After a stability experiment was conducted at room temperature for four months, no impurity peaks were found by HPLC-DAD analysis, which indicated that LIGc resolved the stability issues of LIG. LIGc was absorbed and eliminated rapidly after intravenous administration (C max  = 6.42 ± 1.65 mg/L at a dose of 20 mg/kg) and oral administration (T max  = 0.5 h, C max  = 9.89 ± 1.62 mg/L at a dose of 90 mg/kg, t 1/2z approximately 2.5 h). The absolute oral bioavailability (F) of LIGc was clearly higher than the F of LIG reported in the literature (F, 83.97 % versus 2.6 %). Linear dose-dependent pharmacokinetics were observed after oral administration, with a higher area under the curve (AUC 0-t , 22.31 ± 2.88 mg/L*h) observed at 90 mg/kg than that at 45 mg/kg (AUC 0-t , 13.673 ± 0.666 mg/L*h). Tissue distribution results indicated that LIGc easily crossed the blood-brain barrier (BBB) and was distributed widely to the main tissues and organs of rats. We also conducted a preliminary safety assessment of LIGc by means of an acute toxicity test in KM mice. All mice had excellent health status (ig, dosage of 5.0 g/kg), with no histopathological changes observed in the main organs., Competing Interests: Declaration of competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Oxidative stress and neuroinflammation are closely related to the pathological processes of neurological disorders. Peroxiredoxin 2 (Prdx2) is an abundant antioxidant enzyme in the central nervous system. Prdx2 reduces the production of reactive oxygen species and participates in regulating various signaling pathways in neurons by catalyzing hydrogen peroxide (H 2 O 2 ), thereby protecting neurons against oxidative stress and an inflammatory injury. However, the spillage of Prdx2, as damage-associated molecular patterns, accelerates brain damage after stroke by activating an inflammatory response. The post-translational modifications of Prdx2 also affect its enzyme activity. This review focuses on the effects of Prdx2 and its molecular mechanisms in various neurological disorders.

Rationale: The typical symptoms of stress cardiomyopathy include sudden-onset chest pain and breathlessness or collapse as well as classical symptoms of cardiovascular disease; however, rare reports have described nervous system symptoms as the initial manifestation. Here, we report the case of a young man who presented with a large cerebral infarction as the main clinical symptom of stress cardiomyopathy to increase recognition of the disease., Patient Concerns: A 28-year-old man was admitted to our hospital for sudden-onset weakness of the right limbs and unconsciousness for 1 day. Ten days prior, he began consuming copious amounts of alcohol (500 mL/day) secondary to reactive depression., Diagnoses: Imaging revealed a left internal carotid artery occlusion as assessed by carotid artery ultrasonography. Brain magnetic resonance imaging/magnetic resonance angiography showed new large left cerebral infarction complicated by a reperfusion injury. Moreover, cardiac ultrasonography showed decreased motion of the left ventricular apex, a 3.7 cm mural thrombus in the ventricular apex. The results of coronary and renal artery angiography did not reveal any significant epicardial coronary disease with thrombolysis in the myocardial infarction grade 3 in any of the coronary arteries., Interventions: The patient was administered antiplatelet, anticoagulation, antihypertension, antibiotic, and neurotrophic therapies., Outcomes: The symptoms of cerebral infarction improved significantly after 12 days of admission. Cardiac ultrasonography showed that the wall movement of the left ventricular apex had recovered fully and the mural thrombus resolved completely., Lessons: Patients with stress cardiomyopathy exhibit various clinical manifestations and characteristics. On the basis of our in-depth understanding of stress cardiomyopathy, clinicians should diagnose early and develop reasonable and effective therapies to prevent the harmful effects of related complications.

Methylene Tetrahydrofolate Reductase (MTHFR) catalyzes the conversion of methylene tetrahydrofolate to methylte trahydrofolate. The 677th nucleotide of the MTHFR gene is often regarded as a risk factor of cardiovascular disease. Previous studies demonstrated an elevated risk of ischemic stroke with the MTHFR677TT genotype. In this study, we employed a plasma proteomics method to investigate the connection between the polymorphism of the target nucleotide and stroke. In total, 28 protein spots were differentially expressed between the two groups, and of which, 25 protein spots were up-regulated and 3 were down-regulated. Five randomly selected spots were successfully identified as Haptoglobin (HPT) and Transferrin (TRFE). A functional analysis indicated that most of the differential expressed proteins (DEPs) were related to the inflammatory immune response. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these DEPs were involved in the complement cascade reaction. Meanwhile, protein-protein interactions (PPIs) analysis highlighted the novel association between the C677T MTHFR genotype and Vitamin D binding protein (DBP), which was confirmed by a molecular genetic analysis. The results suggested that the phenotype of the MTHFR might be associated with multiple proteins that have a synergistic effect, which might be related to the mechanism of ischemic stroke.

Objective: To compare the efficacy differences between manual acupuncture (MA) and electroacupuncture (EA) in the treatment of hemiplegia after acute ischemic stroke., Methods: Sixty-eight patients of hemiplegia after acute ischemic stroke were randomized into a MA group (34 cases) and an EA group (34 cases). The routine western medication and bilateral Dingnieqianxiexian (MS 6) were adopted in the two groups. The needles were retained for 30 min. In the MA group, the even-needling technique was used for 3 times during the needle retaining, 1 min each time. In the EA group, on the basis of manual stimulation, EA therapy was added, with disperse-dense wave, 5 Hz/20 Hz. The treatment was given once every day, 6 treatments a week, totally for 2 weeks. US National Institutes of Health stroke scale (NIHSS) score, the simplified Fugl-Meyer motor function (FMA) score and Barthel index (BI) were observed before and after treatment in the two groups. The clinical efficacy was compared between the two groups., Results: NIHSS score was reduced apparently after treatment in the two groups (both P <0.01). The score in the EA group was lower than that in the MA group ( P <0.05). After treatment, FMA score and BI score were all increased apparently in the two groups (all P <0.01) and the scores in the EA group were higher than those in the MA group (both P <0.01). The total effective rate was 94.1% (32/34) in the EA group and was 85.3% (29/34) in the MA group. The efficacy in the EA group was better than that in the MA group ( P <0.05)., Conclusions: EA acts on the rehabilitative effect on nerve defect function in the patients of hemiplegia after acute ischemic stroke. It improves limb motor function and the ability ofdaily life activity. The efficacy is better than that of MA.

Up to date, series of studies on ischemic stroke had resulted in inconsistent conclusion. In this study, we aimed to evaluate which specific genes were associated with increased predisposition to stroke in a Chinese population. To identify the specific genes and polymorphisms associated with predisposition to ischemic stroke, we performed high throughput sequenom based next-generation sequencing from 743 patient with history of ischemic stroke. Variants SNPs in nNOS, renalase, MTHFR, CELSR1 and XYLB genes were found significantly associated with IS, thus suggesting involvement of these loci to IS in Chinese patients. Because of different locations on chromosomes, haplotype analyses were not feasible. Our results demonstrate the top level genes that are related to normal vascular physiology, viz. genes of nitric oxide synthesis, endothelial health and smooth muscle biology. Further validation studies are awaited., (© 2015 International Union of Biochemistry and Molecular Biology.)

Background: Clinical practice guidelines (CPGs) are systematically developed statements to assist practitioners in making decisions about appropriate healthcare in specific clinical circumstances. The methodological quality of CPGs for myasthenia gravis (MG) are unclear., Objective: To critically evaluate the methodological quality of CPGs for MG using AGREE II instrument., Method: A systematical search strategy on PubMed, EMBASE, DynaMed, the National Guideline Clearinghouse (NGC) and the Chinese Biomedical Literature database (CBM) was performed on September 20th 2013. All guidelines related to MG were evaluated with AGREE II. The software used for analysis was SPSS 17.0., Results: A total of 15 CPGs for MG met the inclusion criteria (12 CPGs in English, 3 CPGs in Chinese). The overall agreement among reviews was moderate or high (ICC >0.70). The mean scores (mean ± SD) for al six domains were presented as follows: scope and purpose (60.93% ± 16.62%), stakeholder involvement (40.93% ± 20.04%), rigor of development (37.22% ± 30.46%), clarity of presentation (64.26% ± 16.36%), applicability (28.19% ± 20.56%) and editorial independence (27.78% ± 28.28%). Compared with non-evidence-based CPGs, evidence-based CPGs had statistically significant higher quality scores for all AGREE II domains (P<0.05). All domain scores appear slightly higher for CPGs published after AGREE II instrument development and validation (P>0.05). The quality scores of CPGs developed by NGC/AAN were higher than the quality scores of CPGs developed by other organizations for all domains. The difference was statistically significant for all domains with the exception of clarity of presentation (P = 0.07)., Conclusions: The qualities of CPGs on MG were generally acceptable with several flaws. The AGREE II instrument should be adopted by guideline developers, particularly in China.