Approaches to selective and potent inhibition of glioblastoma by vanadyl complexes: Inducing mitotic catastrophe and methuosis.

Drug resistance has been a major problem for cancer chemotherapy, especially for glioblastoma multiforme that is aggressive, heterogeneous and recurrent with <3% of a five-year survival and limited methods of clinical treatment. To overcome the problem, great efforts have recently been put in searching for agents inducing death of tumor cells via various non-apoptotic pathways. In the present work, we report for the first time that vanadyl complexes, i.e. bis(acetylacetonato)oxidovanadium (IV) (VO(acac)2), can cause mitotic catastrophe and methuotic death featured by catastrophic macropinocytic vacuole accumulation particularly in glioblastoma cells (GCs). Hence, VO(acac)2 strongly suppressed growth of GCs with both in vitro (IC50 = 4-6 µM) and in vivo models, and is much more potent than the current standard-of-care drug Temozolomide. The selective index is as high as ∼10 or more on GCs over normal neural cells. Importantly, GCs respond well to vanadium treatment regardless whether they are carrying IDH1 wild type gene that causes drug resistance. VO(acac)2 may induce methuosis via the Rac-Mitogen-activated protein kinase kinase 4 (MKK4)-c-Jun N-terminal kinase (JNK) signaling pathway. Furthermore, VO(acac)2-induced methuosis is not through a immunogenicity mechanism, making vanadyl complexes safe for interventional therapy. Overall, our results may encourage development of novel vanadium complexes promising for treatment of neural malignant tumor cells.

Characterization of microbial community and antibiotic resistome in intra urban water, Wenzhou China.

The present study investigated the water quality index, microbial composition and antimicrobial resistance genes in urban water habitats. Combined chemicals testing, metagenomic analyses and qualitative PCR (qPCR) were conducted on 20 locations, including rivers from hospital surrounds (n = 7), community surrounds (n = 7), and natural wetlands (n = 6). Results showed that the indexes of total nitrogen, phosphorus, and ammonia nitrogen of hospital waters were 2-3 folds high than that of water from wetlands. Bioinformatics analysis revealed a total of 1,594 bacterial species from 479 genera from the three groups of water samples. The hospital-related samples had the greatest number of unique genera, followed by those from wetlands and communities. The hospital-related samples contained a large number of bacteria associated with the gut microbiome, including Alistipes, Prevotella, Klebsiella, Escherichia, Bacteroides, and Faecalibacterium, which were all significantly enriched compared to samples from the wetlands. Nevertheless, the wetland waters enriched bacteria from Nanopelagicus, Mycolicibacterium and Gemmatimonas, which are typically associated with aquatic environments. The presence of antimicrobial resistance genes (ARGs) that were associated with different species origins in each water sample was observed. The majority of ARGs from hospital-related samples were carried by bacteria from Acinetobacter, Aeromonas and various genera from Enterobacteriaceae, which each was associated with multiple ARGs. In contrast, the ARGs that were exclusively in samples from communities and wetlands were carried by species that encoded only 1 to 2 ARGs each and were not normally associated with human infections. The qPCR showed that water samples of hospital surrounds had higher concentrations of intI1 and antimicrobial resistance genes such as tetA, ermA, ermB, qnrB, sul1, sul2 and other beta-lactam genes. Further genes of functional metabolism reported that the enrichment of genes associated with the degradation/utilization of nitrate and organic phosphodiester were detected in water samples around hospitals and communities compared to those from wetlands. Finally, correlations between the water quality indicators and the number of ARGs were evaluated. The presence of total nitrogen, phosphorus, and ammonia nitrogen were significantly correlated with the presence of ermA and sul1. Furthermore, intI1 exhibited a significant correlation with ermB, sul1, and blaSHV, indicating a prevalence of ARGs in urban water environments might be due to the integron intI1's diffusion-promoting effect. However, the high abundance of ARGs was limited to the waters around the hospital, and we did not observe the geographical transfer of ARGs along with the river flow. This may be related to water purifying capacity of natural riverine wetlands. Taken together, continued surveillance is required to assess the risk of bacterial horizontal transmission and its potential impact on public health in the current region.

Degradation of 8:2 fluorotelomer carboxylic acid (8:2 FTCA) by plants and their co-existing microorganisms.

8:2 fluorotelomer carboxylic acid (8:2 FTCA), an important precursor of perfluorocarboxylic acids (PFCAs), is widely detected in environment and biotas. Hydroponic exposures were conducted to investigate the accumulation and metabolism of 8:2 FTCA in wheat (Triticum aestivum L.) and pumpkin (Cucurbita maxima L.). Endophytic and rhizospheric microorganisms co-existing with the plants were isolated to investigate their contributions to degrade 8:2 FTCA. Wheat and pumpkin roots could take up 8:2 FTCA efficiently with the root concentration factor (RCF) as 5.78 and 8.93, respectively. 8:2 FTCA could be biotransformed to 8:2 fluorotelomer unsaturated carboxylic acid (8:2 FTUCA), 7:3 fluorotelomer carboxylic acid (7:3 FTCA), and seven PFCAs with 2-8 carbon chain length in plant roots and shoots. Cytochromes P450 (CYP450) and glutathione-S-transferase (GST) activities in plants were significantly increased, while flavin-dependent monooxygenases (FMOs) activities were not changed, suggesting that CYP 450 and GST were involved in the transformation of 8:2 FTCA in plant tissues. Twelve 8:2 FTCA-degrading endophytic (8 strains) and rhizospheric (4 strains) bacterial strains were isolated from root interior, shoot interior and rhizosphere of plants, respectively. These bacteria were identified as Klebsiella sp. based on the morphology and 16S rDNA sequence, and they could biodegrade 8:2 FTCA to intermediates and stable PFCAs.

Neuroprotection against ischemic stroke requires a specific class of early responder T cells in mice.

Immunomodulation holds therapeutic promise against brain injuries, but leveraging this approach requires a precise understanding of mechanisms. We report that CD8+CD122+CD49dlo T regulatory-like cells (CD8+ TRLs) are among the earliest lymphocytes to infiltrate mouse brains after ischemic stroke and temper inflammation; they also confer neuroprotection. TRL depletion worsened stroke outcomes, an effect reversed by CD8+ TRL reconstitution. The CXCR3/CXCL10 axis served as the brain-homing mechanism for CD8+ TRLs. Upon brain entry, CD8+ TRLs were reprogrammed to upregulate leukemia inhibitory factor (LIF) receptor, epidermal growth factor-like transforming growth factor (ETGF), and interleukin 10 (IL-10). LIF/LIF receptor interactions induced ETGF and IL-10 production in CD8+ TRLs. While IL-10 induction was important for the antiinflammatory effects of CD8+ TRLs, ETGF provided direct neuroprotection. Poststroke intravenous transfer of CD8+ TRLs reduced infarction, promoting long-term neurological recovery in young males or aged mice of both sexes. Thus, these unique CD8+ TRLs serve as early responders to rally defenses against stroke, offering fresh perspectives for clinical translation.

Factors influencing mindfulness among clinical nurses in China: An observational cross-sectional study.

AIM: The aim of this study was to evaluate factors influencing mindfulness among clinical nurses in China. BACKGROUND: Mindfulness has positive effects on nurses' negative emotions and job burnout. However, few studies have explored the antecedent variables of mindfulness. METHODS: A total of 358 clinical nurses in Beijing Aerospace Center Hospital completed a cross-sectional survey between July and September 2020. The study employed self-report questionnaires covering social demographics, mindfulness, anxiety, job burnout, emotion regulation, stress perception, resilience, well-being and loneliness. RESULTS: The mean Mindful Attention Awareness Scale score was 66.82 ± 11.53, which is near the cut-off score between the high and medium mindfulness categories. Anxiety, stress perception, emotional exhaustion and expressive suppression negatively affected the level of mindfulness, while mental resilience and cognitive reappraisal positively influenced the level of mindfulness (all P < .05). CONCLUSION: Hospital nurses have higher-than-normal levels of mindfulness. The mindfulness level of clinical nurses is related to anxiety, stress perception, resilience, cognitive reappraisal, emotional exhaustion and expressive suppression. IMPLICATIONS FOR NURSING MANAGEMENT: Nursing managers should consider the role and mechanism of positive psychology and develop targeted intervention measures to improve nurses' mindfulness, in order to further reduce their negative emotions, improve their sense of professional benefit and thus ensure the quality and safety of nursing.

Identification and Functional Analysis of Apoptotic Protease Activating Factor-1 (Apaf-1) from Spodoptera litura.

Apoptotic protease activating factor-1 (Apaf-1) is an adaptor molecule, essential for activating initiator caspase and downstream effector caspases, which directly cause apoptosis. In fruit flies, nematodes, and mammals, Apaf-1 has been extensively studied. However, the structure and function of Apaf-1 in Lepidoptera remain unclear. This study identified a novel Apaf-1 from Spodoptera litura, named Sl-Apaf-1. Sl-Apaf-1 contains three domains: a CARD domain, as well as NOD and WD motifs, and is very similar to mammalian Apaf-1. Interference of Sl-apaf-1 expression in SL-1 cells blocked apoptosis induced by actinomycin D. Overexpression of Sl-apaf-1 significantly enhances apoptosis induced by actinomycin D in Sf9/SL-1/U2OS cells, suggesting that the function of Sl-Apaf-1 is evolutionarily conserved. Furthermore, Sl-Apaf-1 could interact with Sl-caspase-5 (a homologue of mammalian caspase-9) and yielded a binding affinity of 1.37 × 106 M-1 according isothermal titration calorimetry assay. Initiator caspase (procaspase-5) of S. litura could be activated by Sl-Apaf-1 (without WD motif) in vitro, and the activated Sl-caspase-5 could cleave Sl-procaspase-1 (a homologue of caspase-3 in mammals), which directly caused apoptosis. This study demonstrates the key role of Sl-Apaf-1 in the apoptosis pathway, suggesting that the apoptosis pathway in Lepidopteran insects and mammals is conserved.

Transforming Growth Factor Beta-Activated Kinase 1-Dependent Microglial and Macrophage Responses Aggravate Long-Term Outcomes After Ischemic Stroke.

Background and Purpose- Microglia/macrophages (Mi/MΦ) can profoundly influence stroke outcomes by acquiring functionally dominant phenotypes (proinflammatory or anti-inflammatory; deleterious or salutary). Identification of the molecular mechanisms that dictate the functional status of Mi/MΦ after brain ischemia/reperfusion may reveal novel therapeutic targets for stroke. We hypothesized that activation of TAK1 (transforming growth factor beta-activated kinase 1), a key MAP3K upstream of multiple inflammation-regulating pathways, drives Mi/MΦ toward a proinflammatory phenotype and potentiates ischemia/reperfusion brain injury. Methods- Young adult mice were subjected to 1 hour of middle cerebral artery occlusion (MCAO) followed by reperfusion. TAK1 was targeted by tamoxifen-induced Mi/MΦ-specific knockout or administration of a selective inhibitor 5Z-7-Oxozeaenol after MCAO. Neurobehavioral deficits and long-term gray matter and white matter injury were assessed up to 35 days after MCAO. Mi/MΦ functional status and brain inflammatory profiles were assessed 3 days after MCAO by RNA-seq, flow cytometry, and immunohistochemistry. Results- TAK1 Mi/MΦ-specific knockout markedly ameliorated neurological deficits in the rotarod and cylinder tests for at least 35 days after MCAO. Mechanistically, RNA-seq of purified brain Mi/MΦ demonstrated that proinflammatory genes and their predicted biological functions were downregulated or inhibited in microglia and macrophages from TAK1 Mi/MΦ-specific knockout mice versus WT mice 3 days after MCAO. Consistent with the anti-inflammatory phenotype of Mi/MΦ-specific knockout, oxozeaenol treatment mitigated neuroinflammation 3 days after MCAO, manifested by less Iba1+/CD16+ proinflammatory Mi/MΦ and suppressed brain invasion of various peripheral immune cells. Oxozeaenol treatment beginning 2 hours after MCAO improved long-term sensorimotor and cognitive functions in the foot fault, rotarod, and water maze tests. Furthermore, Oxozeaenol promoted both gray matter and white matter integrity 35 days after MCAO. Conclusions- TAK1 promotes ischemia/reperfusion-induced inflammation, brain injury, and maladaptive behavior by enhancing proinflammatory and deleterious Mi/MΦ responses. Therefore, TAK1 inhibition is a promising therapy to improve long-term stroke outcomes.

TGFα preserves oligodendrocyte lineage cells and improves white matter integrity after cerebral ischemia.

Transforming growth factor α (TGF-α) has been reported to play important roles in neurogenesis and angiogenesis in the injured brain. The present study characterizes a novel role for TGFα in oligodendrocyte lineage cell survival and white matter integrity after ischemic stroke. Three days after transient (60 min) middle cerebral artery occlusion (tMCAO), TGFα expression was significantly increased in microglia/macrophages and neurons. Expression of the receptor of TGFα-epidermal growth factor receptor (EGFR)-was increased in glial cells after ischemia, including in oligodendrocyte lineage cells. TGFα knockout enlarged brain infarct volumes and exacerbated cell death in oligodendrocyte precursor cells (OPCs) and oligodendrocytes three days after tMCAO. TGFα-deficient mice displayed long-term exacerbation of sensorimotor deficits after tMCAO, and these functional impairments were accompanied by loss of white matter integrity and impaired oligodendrocyte replacement. In vitro studies confirmed that 5 or 10 ng/mL TGFα directly protected OPCs and oligodendrocytes against oxygen and glucose deprivation (OGD)-induced cell death, but exerted no effects on OPC differentiation. Further studies identified STAT3 as a key transcription factor mediating the effects of TGFα on OPCs and oligodendrocytes. In conclusion, TGFα provides potent oligodendrocyte protection against cerebral ischemia, thereby maintaining white matter integrity and improving neurological recovery after stroke.

Macrophages reprogram after ischemic stroke and promote efferocytosis and inflammation resolution in the mouse brain.

AIMS: Blood-borne monocytes/macrophages infiltrate the brain in massive numbers after ischemic stroke, but their impact on poststroke brain injury and recovery remains elusive. This study examined the transcriptomic changes in monocytes/macrophages after ischemic stroke and the functional implications of these changes, particularly with regards to the contribution of these cells to the phagocytic clearance of dead/dying cells (efferocytosis) in the poststroke brain. METHODS: We performed whole-genome RNA sequencing on the monocyte/macrophage population sorted from mouse brain and peripheral blood 5 days after permanent focal cerebral ischemia. In addition, the spatial and temporal profiles of macrophage efferocytosis were examined in vivo by immunohistochemistry 3-7 days after brain ischemia. RESULTS: Robust transcriptomic changes occurred in monocytes/macrophages upon infiltrating the poststroke brain. Functional enrichment analysis revealed a transcriptome of brain macrophages that strongly favored efferocytic activity. A large number of efferocytosis-related genes were upregulated in brain macrophages, the products of which are essential components involved in various steps of efferocytosis, such as chemotaxis, recognition of dead cells, engulfment, and processing of phagosomes. The efferocytic activity of brain macrophages were verified by immunohistochemistry, wherein Iba1-labeled microglia/macrophages effectively cleared apoptotic neurons in the infarct during the subacute stage after brain ischemia. We also identified PPARγ and STAT6 as potential upstream regulators that shaped this proefferocytic and inflammation-resolving transcriptome of macrophages in the poststroke brain. CONCLUSION: Macrophages play a crucial role in the phagocytic clearance of dead neurons after ischemic stroke and promote the resolution of inflammation in the brain. Molecular therapies that enhance macrophage efferocytic capability may be promising treatments for ischemic stroke by facilitating inflammation resolution, brain repair, and recovery of neurological functions.

STAT6/Arg1 promotes microglia/macrophage efferocytosis and inflammation resolution in stroke mice.

Efferocytosis, or phagocytic clearance of dead/dying cells by brain-resident microglia and/or infiltrating macrophages, is instrumental for inflammation resolution and restoration of brain homeostasis after stroke. Here, we identify the signal transducer and activator of transcription 6/arginase1 (STAT6/Arg1) signaling axis as a potentially novel mechanism that orchestrates microglia/macrophage responses in the ischemic brain. Activation of STAT6 was observed in microglia/macrophages in the ischemic territory in a mouse model of stroke and in stroke patients. STAT6 deficiency resulted in reduced clearance of dead/dying neurons, increased inflammatory gene signature in microglia/macrophages, and enlarged infarct volume early after experimental stroke. All of these pathological changes culminated in an increased brain tissue loss and exacerbated long-term functional deficits. Combined in vivo analyses using BM chimeras and in vitro experiments using microglia/macrophage-neuron cocultures confirmed that STAT6 activation in both microglia and macrophages was essential for neuroprotection. Adoptive transfer of WT macrophages into STAT6-KO mice reduced accumulation of dead neurons in the ischemic territory and ameliorated brain infarction. Furthermore, decreased expression of Arg1 in STAT6-/- microglia/macrophages was responsible for impairments in efferocytosis and loss of antiinflammatory modality. Our study suggests that efferocytosis via STAT6/Arg1 modulates microglia/macrophage phenotype, accelerates inflammation resolution, and improves stroke outcomes.

Transient selective brain cooling confers neurovascular and functional protection from acute to chronic stages of ischemia/reperfusion brain injury.

Ischemic injury can be alleviated by the judicious use of hypothermia. However, the optimal regimens and the temporal kinetics of post-stroke neurovascular responses to hypothermic intervention have not been systematically studied. These gaps slow the clinical translation of hypothermia as an anti-stroke therapy. Here, we characterized the effects of transient selective brain hypothermia (TSBH) from the hyperacute to chronic stages of focal ischemia/reperfusion brain injury induced by transient middle cerebral artery occlusion in mice. A simple cooling device was used to induce TSBH during cerebral ischemia. This treatment reduced mortality from 31.8% to 0% and improved neurological outcomes for at least 35 days post-injury. TSBH mitigated blood-brain barrier leakage during the hyperacute and acute injury stages (1-23 h post-reperfusion). This early protection of the blood-brain barrier was associated with anti-inflammatory phenotypic polarization of microglia/macrophages, reduced production of pro-inflammatory cytokines, and less brain infiltration of neutrophils and macrophages during the subacute injury stage (three days post-reperfusion). TSBH elicited enduring protective effects on both grey and white matter for at least 35 days post-injury and preserved the long-term electrophysiological function of fiber tracts. In conclusion, TSBH ameliorates ischemia/reperfusion injury in the neurovascular unit from hyperacute to chronic injury stages after experimental stroke.

Brain-selective mild hypothermia promotes long-term white matter integrity after ischemic stroke in mice.

INTRODUCTION: The neuroprotective effects of hypothermia in acute ischemic stroke are well documented. However, the mechanisms involved in the effects remain to be clearly elucidated and the role of hypothermia on long-term white matter integrity after acute ischemic stroke has yet to be investigated. AIMS: To investigate the role of mild focal hypothermia on long-term white matter (WM) integrity after transient cerebral ischemia. RESULTS: Mild focal hypothermia treatment immediately after ischemic stroke significantly promotes WM integrity 28 days after the occlusion of the middle cerebral artery (MCAO) in mice. Higher integrity of white matter, lower activation of total microglia, less infarct volume, and better neurobehavioral function were detected in hypothermia-treated mice compared to normothermia-treated mice. Furthermore, we found that hypothermia could decrease detrimental M1 phenotype microglia and promote healthy M2 phenotype microglia. In vitro, results also indicated that hypothermia promoted oligodendrocytes differentiation and maturation after oxygen glucose deprivation. CONCLUSION: Hypothermia promotes long-term WM integrity and inhibits neuroinflammation in a mouse model of ischemic brain injury.

A new era for stroke therapy: Integrating neurovascular protection with optimal reperfusion.

Recent advances in stroke reperfusion therapies have led to remarkable improvement in clinical outcomes, but many patients remain severely disabled, due in part to the lack of effective neuroprotective strategies. In this review, we show that 95% of published preclinical studies on "neuroprotectants" (1990-2018) reported positive outcomes in animal models of ischemic stroke, while none translated to successful Phase III trials. There are many complex reasons for this failure in translational research, including that the majority of clinical trials did not test early delivery of neuroprotectants in combination with successful reperfusion. In contrast to the clinical trials, >80% of recent preclinical studies examined the neuroprotectant in animal models of transient ischemia with complete reperfusion. Furthermore, only a small fraction of preclinical studies included long-term functional assessments, aged animals of both genders, and models with stroke comorbidities. Recent clinical trials demonstrate that 70%-80% of patients treated with endovascular thrombectomy achieve successful reperfusion. These successes revive the opportunity to retest previously failed approaches, including cocktail drugs that target multiple injury phases and different cell types. It is our hope that neurovascular protectants can be retested in future stroke research studies with specific criteria outlined in this review to increase translational successes.

CMTM6 overexpression is associated with molecular and clinical characteristics of malignancy and predicts poor prognosis in gliomas.

CMTM6, a previously uncharacterized protein, was identified as a critical regulator of PD-L1, which is reported as an immune checkpoint inhibitor, to modulate the T cell activities both in vitro and in vivo of other tumors. However, the role of CMTM6 has so far remained unclear in glioma. To investigate the role of CMTM6 in gliomas, we analyzed the transcriptome level, genomic profiles and its relationship with clinical practice. 1862 glioma samples with transcriptome data were enrolled in this study, including CGGA RNA-seq, TCGA RNA-seq, CGGA-microarray, GSE16011 and IVY GBM databases. Clinical information and genomic profiles containing somatic mutations and DNA copy numbers were also obtained. We found that CMTM6 expression was highly correlated with major clinical and molecular characteristics. Cases with high CMTM6 expression were more likely to be predicted as malignant entities and frequent with genomic aberrations of driver oncogenes. Moreover, gene ontology analysis based on significantly correlated genes of CMTM6 expression exhibited that CMTM6 was associated with immune responses and inflammatory activities. CMTM6 was synthetic with other immune checkpoint inhibitors. Additionally, CMTM6 was involved in immune functions via modulating T-lymphocyte-mediated anti-tumor immunity. Finally, high CMTM6 expression was associated with reduced survival time and may serve as a strong indicator of poor prognosis in gliomas. In brief, High level of CMTM6 expression is closely related to high malignant gliomas. Meanwhile, CMTM6 plays an important role in regulating T cell activation and antitumor responses. Therefore, CMTM6 is a promising target for developing immunotherapy of gliomas.

Screening for Fabry's disease in young patients with ischemic stroke in a Chinese population.

PURPOSE: Fabry disease is an X-linked lysosomal storage disorder frequently associated with cerebrovascular disease. Data regarding Fabry disease and ischemic stroke has been lacking in China. In this study, we investigated the prevalence of Fabry disease and the distribution of the alpha-galactosidase A (α-GalA) gene - GLA mutations in young stroke patients in the Chinese population and its association with stroke subtypes. METHODS: A total of 357 ischemic stroke patients admitted to Xuanwu Hospital of Capital Medical University, aged 18-55 years old, including 293 patients with cerebral infarction and 64 patients with transient ischemic attack, were enrolled in this study. Mutations in the GLA gene were screened by Sanger sequencing. Enzyme levels were measured to further confirm the disease in patients with the gene mutation. The mutation frequency was compared among different stroke subtypes and further compared with the control group individually. RESULTS: No pathogenic mutations in the coding regions of the GLA gene were identified in this group of patients and thus no Fabry disease was found in our study. However, the frequency of an intronic polymorphism c.-10C>T was significantly different among different Trial of Org 10172 in Acute Stroke Treatment subtypes (p < 0.01). The frequency of the c.-10C>T polymorphism in patients with stroke due to other causes and undetermined causes was much higher than that in the control group (OR = 3.18, 95% CI: 1.29-7.83, p < 0.01). CONCLUSIONS: Fabry disease is a rare disease, and it will not benefit to screen all stroke patients. In addition, our results suggested that the c.-10C>T polymorphism may be a risk factor for ischemic stroke of other and undetermined causes. Further study is required to confirm our findings.

Pericytes in Brain Injury and Repair After Ischemic Stroke.

Pericytes are functional components of the neurovascular unit (NVU). They provide support to other NVU components and maintain normal physiological functions of the blood-brain barrier (BBB). The brain ischemia and reperfusion result in pathological alterations in pericytes. The intimate anatomical and functional interactions between pericytes and other NVU components play pivotal roles in the progression of stroke pathology. In this review, we depict the biology and functions of pericytes in the normal brain and discuss their effects in brain injury and repair after ischemia/reperfusion. Since ischemic stroke occurs mostly in elderly people, we also review age-related changes in pericytes and how these changes predispose aged brains to ischemic/reperfusion injury. Strategies targeting pericyte responses after ischemia and reperfusion may provide new therapies for ischemic stroke.

[Meta-analysis of risk factors of Chinese patients with different cerebral artery stenosis locations].

OBJECTIVE: We conducted a Meta-analysis to explore the relationship between different locations of cerebral artery stenosis and the risk factors in Chinese ischemic cerebral artery disease patients. METHODS: We systematically searched electronic literature databases (last search 31 December 2014) for studies reporting the association between cerebral artery stenosis locations and risk factors of ischemic cerebral artery disease. We grouped patients into two groups, only intracranial artery stenosis group and only extracranial artery stenosis group, by the location of cerebral artery stenosis. Meta-analysis was carried out by Review Manager (Version 5.2) provided by Cochrane Collaboration. After the heterogeneity test, the odds ratios (OR) or the mean differences (MD) and 95% confidence interval (95% CI) were combined. The publication bias and sensitivity analysis were tested as while. RESULTS: A total of thirteen studies were identified, which are including 1 672 patients with intracranial artery stenosis and 1 239 patients with extracranial artery stenosis. The only intracranial artery stenosis patients tend to be younger than the patients of the other group. The combined MD (95% CI) of age was -4.57 (-8.22--0.91, P=0.01). Besides, the proportion of smokers in the only intracranial artery stenosis patients was higher than the other group. The combined OR (95% CI) of smoking was 0.08 (0.68-0.93, P=0.005). CONCLUSIONS: As to Chinese ischemic cerebral artery disease patients, visible differences of age and smoking were detected between the only intracranial artery stenosis group and extracranial group. However some risk factors of cerebral artery stenosis which were proved by large scale studies, such as hypertension, diabetes and dyslipidemia, were failed to test the visible difference between the two groups.

The fabrication, nano/micro-structure, heat- and wear-resistance of the superhydrophobic PPS/PTFE composite coatings.

A simple engineering method was used to fabricate stability and wear-resistance of superhydrophobic PPS-based PPS/PTFE surfaces through nano/micro-structure design and modification of the lowest surface energy groups (-CF2-), which was inspired by the biomimic lotus leaves. The hydrophobic properties and wear-resistance of the coatings were measured by a contact angle meter and evaluated on a pin-on-disk friction and wear tester, respectively. Moreover, the surfaces of the PPS/PTFE composite coatings were investigated by means of scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffractometry (XRD), and thermogravimetry (TG) analysis. Results showed that the highest contact angle of the PPS/PTFE surface, with papillae-like randomly distributed double-scale structure, could reach up to 162°. When 1 wt.% PDMS was added, the highest contact angle could hold is 172°. The coatings also retained superhydrophobicity, even under high temperature environment. The investigation also indicated that the coatings were not only superhydrophobic but also oleophobic behavior at room temperature, such as the crude oil, glycerol, and oil-water mixture. The PPS/45%PTFE coatings had more stable friction coefficient and excellent wear-resistance (331,407 cycles) compared with those with less than 45% of PTFE.

Potential influence of Asp in the Ca2+ coordination position 5 of parvalbumin on the calcium-binding affinity: a computational study.

Parvalbumins (PV) are calcium-binding proteins, all sharing the common helix-loop-helix (EF-hand) motif. This motif contains a central twelve-residue Ca(2+)-binding loop with the flanking helices positioned roughly perpendicular to each other. The precise role of these coordination residues has been the subject of intense studies. In this work, we focus on the coordination position 5 in the CD Ca(2+)-binding site of silver hake parvalbumin isoform B (SHPV-B). The most common residue at site 5 of calcium-binding loop in canonical EF-hands is Asp [B.J. Marsden, G.S. Shaw, B.D. Sykes, Biochem. Cell Biol. 68 (1990) 587-601], but in the CD site of PV, this position is almost always serine (Ser). The substitution of Ser with Asp will add the 5th carboxylate residue in the CD coordination sphere. However, as predicted by the acid pair hypothesis, the Ca(2+)-binding affinity would be maximized in an EF-hand motif that has four carboxylate ligands paired along the +/-x, and +/-z-axes [R.E. Reid, R.S. Hodges, J. Theor. Biol. 84 (1980) 401-444]. Molecular dynamics simulations and free energy calculations were employed to investigate the influence of Ser to Asp mutation at position 5 on calcium-binding affinity. We found that the Asp variant exhibited remarkable stability during the entire molecular dynamics simulation, with not only the retention of the Ca(2+)-binding site, but also increased compactness in the coordination sphere. The S55D fragment also accommodated Ca(2+) well. We conclude that the reason why Asp which is the most common residue at site 5 of calcium-binding loop in canonical EF-hands has never been identified at this position experimentally for PVs might be related to its physiological functions.