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As a type of novel surface engineering technology, the application of cold spraying in the manufacturing and remanufacturing of high-end precision parts is very suitable. However, the disadvantage of low interface bonding strength can easily induce coating peeling at the coating/substrate interface under the effect of applied loads. Therefore, finding a suitable nondestructive testing method is significant to evaluate the cold-sprayed coating peeling process and provide prediction results. To achieve this aim, magnetic Barkhausen noise (MBN) testing was used in this paper because of its high sensitivity to microstructure variation. The Ni-Zn-Al2O3 ferromagnetic coating deposited on the ductile cast iron substrate was prepared by cold spraying. Based on the wavelet coherence analysis, the frequency of MBN signals induced by magnetic domain movement was mainly concentrated in the range of 1–4 kHz. The spectrum power between 1 kHz and 4 kHz was extracted as the characteristic value, and the linear fitting relationship between the characteristic value and applied load was established. When the power reaches the threshold value range of 3.106×10−8–3.557×10−8 W, the probability that the interfacial stress exceeds the coating/substrate bonding strength and that Ni-Zn-Al2O3 coating peeling occurs is 95%. Combined with the microstructure and morphology analysis, the mechanism of cold-sprayed coating peeling was revealed, and the underlying reason for MBN signal variation was explained. This research can accurately evaluate the ferromagnetic cold-sprayed coating peeling process and the interface bonding strength.

Background As a sequel of ischemic stroke, selective neuronal loss (SNL) mediated by activated microglia and consequential neuroinflammation affects the salvageable peri-infarct area (PIA) and hampers the functional recovery following reperfusion therapy. Recent evidence indicates that inhibition of sulfonylurea receptor 1-transient receptor potential M4 (SUR1-TRPM4) exerts a robust protective effect against inflammation. Hence, we hypothesized that blocking SUR1-TRPM4 channels reduced SNL after brain ischemia in the PIA. Methods Mice subjected to temporary middle cerebral artery occlusion (tMCAO) for 1 h and reperfusion for 24 h were adopted to mimic the pathophysiological changes of ischemic stroke. Gene expression, neuronal apoptosis, and protein content were tested by RNA-sequencing, TUNEL staining, Western blot, respectively. Results After tMCAO, abundant neuronal apoptosis appeared in the PIA, with remarkable up-regulation and co-localization of SUR1 and TRPM4. Blocking the SUR1-TRPM4 channel by glibenclamide (GLB, a SUR inhibitor) and Trpm4 gene deletion (Trpm4−/−) distinctly alleviated apoptotic neurons in the PIA. To explore the potential mechanism of blocking SUR1-TRPM4, we compared gene expression in brain tissues of Trpm4−/− and wild-type mice after tMCAO modeling using RNA-sequencing and identified 217 differentially expressed genes. Among them, the expression of Tgfα was significantly higher in Trpm4−/− mice compared with that in wild-type mice after tMCAO. GLB treatment significantly increased the expression of TGFα in microglia, as validated by Western Blot and immunofluorescence staining. Moreover, intracerebroventricular injection of recombinant TGFα significantly alleviated the neuronal loss in the PIA and improved neurological outcome after tMCAO. In vitro, we subjected BV-2 microglia cells to oxygen-glucose deprivation or lipopolysaccharide stimulation and found significant up-regulation and co-localization of SUR1 and TRPM4, while blocking SUR1-TRPM4 with GLB and 9-phenanthrol (9-Phe, a TRPM4 inhibitor) increased the expression and release of TGFα by activating the CaMKII/CREB pathway. BV-2 microglia derived conditioned medium after oxygen-glucose deprivation or lipopolysaccharide stimulation induced apoptosis of SH-SY5Y cells, which could be inhibited by applying GLB and 9-Phe on BV-2. Furthermore, direct application of recombinant TGFα alleviated neuronal apoptosis mediated by BV-2 microglia conditioned medium. Conclusions Collectively, our findings indicate that blocking SUR1-TRPM4 in microglia alleviates SNL, probably by up-regulating the expression and release of TGFα.

Background Glibenclamide (GLB) reduces brain edema and improves neurological outcome in animal experiments and preliminary clinical studies. Recent studies also suggested a strong anti-inflammatory effect of GLB, via inhibiting Nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome activation. However, it remains unknown whether the anti-inflammatory effect of GLB is independent of its role in preventing brain edema, and how GLB inhibits the NLRP3 inflammasome is not fully understood. Methods Sprague-Dawley male rats underwent 10-min asphyxial cardiac arrest and cardiopulmonary resuscitation or sham-operation. Wild type and Trpm4−/− C57BL/6 male mice underwent radiation-induced brain injury or sham-operation. The Trpm4 siRNA and GLB were injected to block sulfonylurea receptor 1-transient receptor potential M4 (SUR1-TRPM4) channel in rats and mice. Western blotting, quantitative real-time polymerase chain reaction, behavioral analysis, histological examination, and MRI Scanning were used to evaluate the role of GLB in preventing NLRP3-mediated neuroinflammation through inhibiting SUR1-TRPM4, and corresponding neuroprotective effect. To further explore the underlying mechanism, BV2 cells were subjected to lipopolysaccharides, oxygen-glucose deprivation/reperfusion, or radiation. Results Here, in mice model of radiation-induced brain injury with minimal brain edema, GLB significantly alleviated neurocognitive deficit and neuropathological damage, via the inhibition of radiation-induced microglial NLRP3 inflammasome activation by blocking SUR1-TRPM4. Likewise, above neuroprotective effects were also confirmed in rat model of cardiac arrest with brain edema combined with neuroinflammation, through preventing SUR1-TRPM4-mediated NLRP3 activation. Of note, the above effects of GLB could be achieved by gene silencing or knockdown of Trpm4. In vitro, SUR1-TRPM4 and NLRP3 inflammasome were also activated in BV2 cells subjected to lipopolysaccharides, oxygen-glucose deprivation/reperfusion, or radiation, which could be blocked by GLB or 9-phenanthrol, a TRPM4 inhibitor. Importantly, activation of SUR1-TRPM4 in BV2 cells required the P2X7 receptor-mediated Ca2+ influx, which in turn magnified the K+ efflux via the Na+ influx-driven opening of K+ channels, leading to the NLRP3 inflammasome activation. Conclusions These findings suggest that GLB has a direct anti-inflammatory neuroprotective effect independent of its role in preventing brain edema, through inhibition of SUR1-TRPM4 which amplifies K+ efflux and promotes NLRP3 inflammasome activation.

The breakdown of the blood‐brain barrier (BBB) is related to the occurrence and deterioration of neurological dysfunction in ischemic stroke, which leads to the extravasation of blood‐borne substances, resulting in vasogenic edema and increased mortality. However, a limited understanding of the molecular mechanisms that control the restrictive properties of the BBB hinders the manipulation of the BBB in disease and treatment. Here, we found that the glycocalyx (GCX) is a critical factor in the regulation of brain endothelial barrier integrity. First, endothelial GCX displayed a biphasic change pattern, of which the timescale matched well with the biphasic evolution of BBB permeability to tracers within the first week after t‐MCAO. Moreover, GCX destruction with hyaluronidase increased BBB permeability in healthy mice and aggravated BBB leakage in transient middle cerebral artery occlusion (t‐MCAO) mice. Surprisingly, ultrastructural observation showed that GCX destruction was accompanied by increased endothelial transcytosis at the ischemic BBB, while the tight junctions remained morphologically and functionally intact. Knockdown of caveolin1 (Cav1) suppressed endothelial transcytosis, leading to reduced BBB permeability, and brain edema. Lastly, a coimmunoprecipitation assay showed that GCX degradation enhanced the interaction between syndecan1 and Src by promoting the binding of phosphorylated syndecan1 to the Src SH2 domain, which led to rapid modulation of cytoskeletal proteins to promote caveolae‐mediated endocytosis. Overall, these findings demonstrate that the dynamic degradation and reconstruction of GCX may account for the biphasic changes in BBB permeability in ischemic stroke, and reveal an essential role of GCX in suppressing transcellular transport in brain endothelial cells to maintain BBB integrity. Targeting GCX may provide a novel strategy for managing BBB dysfunction and central nervous system drug delivery., Glycocalyx‐regulated transcellular transport across the BBB contributes significantly to the barrier function of the BBB in both normal and diseased conditions. GCX may be an essential target for manipulating BBB permeability to help with drug delivery to the brain or to protect against BBB injury under diseased conditions.

Radiation-induced brain injury (RBI) is a common complication of radiotherapy for head and neck tumors while its mechanism is not fully understood. Animal whole-brain radiation (WBR) models are of key importance in experimental radiation research, and an appropriate radiation source is essential. Previous animal WBR models were administered by clinical linear accelerator to induce the pathophysiological changes of RBI. In the current study, we adopted Faxitron MultiRad 225 X-ray irradiation system to construct a mouse WBR model with a single dose of 30 Gy. In the acute phase of this mouse WBR model, brain edema and blood–brain barrier (BBB) damage were found mild. However, two months later, the results of immunofluorescence showed that astrocytes and microglia were activated continuously, and the number of immature neurons in dentate gyrus (DG) area of hippocampus was significantly reduced, in accordance with the features of chronic pathophysiological changes. Besides, data of MRI scans and behavior tests illustrated the structural changes of brain tissue and cognitive impairment in the chronic phase. To sum up, this mouse WBR model using the Faxitron MultiRad 225 irradiation system with a single dose of 30 Gy is feasible to simulate the RBI-related chronic pathophysiological changes.

The Hilbert transform method has its own particular superiority in phase difference estimation, but endpoint effect limits its precision when data record is short. We firstly analyze endpoint effect of Hilbert transform and point out its reason is spectrum leakage. Then, an all phase Hilbert transform method is proposed to solve this problem. In this method, a pretreatment is carried out at the first place that data record is recomposed with all cases of truncation been considered. In succession, Hilbert transform of the pretreated data is calculated. Phase difference is estimated by triangle operation of the pretreated data and its Hilbert transform. Comparative analysis of phase difference estimation methods based on Hilbert transform with or without endpoint effect is carried out. Theoretical analysis, simulation and experimental results collaborate to prove the validity of the proposed method. Comparative studies demonstrate that the proposed method suppresses endpoint effect effectively and improves the precision significantly when calculational points are deficiency.

Background Brain injury is the leading cause of death and disability in survivors of cardiac arrest, where neuroinflammation is believed to play a pivotal role, but the underlying mechanism remains unclear. Pyroptosis is a pro-inflammatory form of programmed cell death that triggers inflammatory response upon infection or other stimuli. This study aims to understand the role of microglial pyroptosis in post-cardiac arrest brain injury. Methods Sprague-Dawley male rats underwent 10-min asphyxial cardiac arrest and cardiopulmonary resuscitation or sham-operation. Flow cytometry analysis, Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), co-immunoprecipitation, and immunofluorescence were used to evaluate activated microglia and CD11b-positive leukocytes after cardiac arrest and assess inflammasome activation and pyroptosis of specific cellular populations. To further explore the underlying mechanism, MCC950 or Ac-YVAD-cmk was administered to block nod-like receptor family protein 3 (NLRP3) or caspase-1, respectively. Results Our results showed that, in a rat model, successful resuscitation from cardiac arrest resulted in microglial pyroptosis and consequential inflammatory infiltration which was mediated by the activation of NLRP3 inflammasome. Targeting NLRP3 and caspase-1, the executor of pyroptosis, with selective inhibitors MCC950 and Ac-YVAD-cmk treatment significantly prevented microglial pyroptosis, reduced infiltration of leukocytes, improved neurologic outcome, and alleviated neuro-pathological damages after cardiac arrest in modeling rats. Conclusions This study demonstrates that microglial pyroptosis mediated by NLRP3 inflammasome is critically involved in the pathogenesis of post-cardiac arrest brain injury and provides a new therapeutic strategy.

Background: The toll-like receptor (TLR) genes were shown to be involved in the pathogenesis of RA. We aimed to investigate the genetic associations between the TLR-1, -2, -4, and -6 genes polymorphisms and RA susceptibility in a Chinese Han population. Methods : Six polymorphisms (TLR-1 (rs5743610, rs5743618), -2 (rs5743708), -4 (rs4986790, rs4986791), and -6 (rs5743810)) in TLRs genes were genotyped in 360 patients with RA and 560 matched healthy controls by using direct sequencing method. The ORs and 95% CIs were evaluated using a standard logistic regression analysis. Results : No significant association between the allelic, dominant and recessive models of TLR-1 rs5743618, TLR-2 rs5743708, TLR-4 rs4986790 and rs4986791, and TLR-6 rs5743810 polymorphisms and RA risk was observed (p>0.05). However, significant associations were detected between the allelic, dominant and recessive models of TLR-1 rs5743618 and RA risk (allelic: OR[95%CI]= 2.21 [1.73, 2.81], p

A novel porous structure of hexagonal WO3/oriented TiO2 nanorods arrays (h-WO3/TiO2 NRAs) hybrid film was successfully prepared by a facile hydrothermal method. Benefiting from elaborately structure engineering, the hybrid film exhibited large transmittance modulation (ΔT633nm = 73.45%), high coloration efficiency (69.2 cm2·C-1), fast Li+ ions insertion kinetics (6.6 s/2.0 s for tc/tb), stable cyclic stability (maintains 92.9% of initial ΔT after 2000 cycles) as well as areal specific capacitance of 10.93 mF·cm−2 at the current density of 0.1 mA·cm−2. An electrochromic energy storage device (EESD) with six multi-color modulation modes (light gray, dark olive green, yellow green, lime green, dark green and dark blue) was successfully assembled by h-WO3/TiO2 NRAs hybrid film and electrodeposited-V2O5 film. Based on the excellent electrochromic and pseudocapacitive properties, the EESD promised a smart visual monitoring of the energy storage level and can light up a LED after charging, indicating a good energy storage application prospect.

BACKGROUND The IRF5 and TYK2 gene polymorphisms are associated with autoimmune diseases. However, the relationship between the IRF5 and TYK2 gene polymorphisms and RA risk in the Chinese Han population was inconsistent. MATERIAL AND METHODS A total of 578 RA patients (case group) and 578 healthy controls (control group) were assessed in a case-control study. Genotyping of IRF5 (Exon 6 insertion/deletion (in/de), rs2004640, rs2070197, rs10954213) and TYK2 (rs280500, rs280519, rs280521, rs8108236, rs12720253) was performed by direct sequencing method. Data analysis was performed by SHEsis. RESULTS The rs2004640T allele (P=0.0003) and the dominant (P=0.001) and recessive (P=0.01) models of rs2004640 were associated with RA risk after stringent Bonferroni correction (0.05/4). The IRF5 exon 6 (in), rs2070197 and rs10954213 were not associated with RA (P>0.05). Two haplotypes of IRF5 (DTAT and DTGG) were associated with RA susceptibility (P

Osteoporosis is a common skeletal disorder in eldest people, especially in postmenopausal women. The osteoprotegerin (OPG) gene has been reported to be associated with the BMD and pathogenesis of osteoporosis. However, the results were inconsistent and inconclusive in previous studies.A meta-analysis was performed to investigate the effect of four common OPG gene polymorphisms (A163G, G1181C, T245G, and T950C) on BMD in postmenopausal women.A total of 23 eligible studies with 12,973 postmenopausal women were enrolled in present study. Individuals who with AA genotype of A163G were found to have slightly higher femoral hip (P = .03, SMD = 0.49, [95% CI] = [0.06, 0.91]) and total hip BMD (P = .002, SMD = -0.25, [95% CI] = [-0.42, -0.09]) than those with AG genotype. Subjects with GG genotype of G1181C was found to have lower BMD than those with CC or GC genotypes in lumbar spine (GG vs GC: P = .0002, SMD = -0.85, [95% CI] = [-1.29, -0.41]; GG vs CC: P = .02, SMD = -0.21, [-0.39, -0.03]) and total hip BMD (GG vs GC: P = .002, SMD = -0.25, [95% CI] = [-0.42, -0.09]; GG vs CC: P = .01, SMD = -0.15, [95% CI] = [-0.26, -0.03]). In addition, the subjects with GC genotype of G1181C was detected to have lower BMD than those with CC genotype in lumbar spine BMD (P .05). Furthermore, individuals with TT genotype of T950C were shown to have significant lower lumbar spine BMD compared with those with genotype CC in Caucasian (P .05). The lumbar spine BMD was lower for subjects with TC genotype of T950C than those with CC genotype in both Caucasian and Asian populations (P .05). In contrast to A163G, G1181C, and T950G, no association was detected between T245G polymorphism and BMD (P .05).The present meta-analysis demonstrated the OPG A163G, G1181C, and T950G, but not T245G, might influence the BMD in postmenopausal women.

BACKGROUND Ankylosing spondylitis (AS) is one of the most common chronic inflammatory disorders affecting the sacroiliac joints, spine, and peripheral joints. Apart from HLA-B27, the LMP2 gene has been shown to play a role in the pathogenesis of AS as well as AAU in AS. However, genetic associations between LMP2 CfoI polymorphism and AS and AAU were inconclusive. We aimed to investigate the correlation of LMP2 CfoI polymorphism and AS and AAU using meta-analysis. METHODS An exhaustive search was conducted using the PubMed, Embase, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI) electronic databases. The strength association was assessed by crude ORs with 95% CI. RESULTS Eight eligible records with 449 AS patients and 317 healthy controls were included in the present study. The allelic model of the LMP2 CfoI polymorphism is associated with AS risk (OR = 0.60, 95%CI = [0.32, 1.11], P = .003). A stratified analysis based on ethnicity has shown that the allelic model of LMP2 CfoI was associated with AS in the Caucasian population (OR = 0.72, 95%CI = [0.55, 0.93], P = .01) but not in the Asian population (P > .05). Furthermore, no association was detected between LMP2 CfoI polymorphism and AS complication (AAU). CONCLUSION Our combined results revealed that the allelic model of LMP2 CfoI might be a protective factor for AS in the Caucasian population. Nevertheless, future studies on different ethnicities with larger sample sizes are needed to obtain a more convincing result.

The involvement of melanocortin 4 receptor gene (MC4R) in food intake and body weight regulation is well characterized. MC4R mutations are the most frequent monogenic cause of human obesity. Significant associations have been revealed between MC4R mutations and productive traits in pigs, cattle and poultry. Herein, fluorescence-based conformation sensitive gel electrophoresis was used to identify two single nucleotide polymorphisms (SNPs) in the coding region (93G>A and 292G>A) and two SNPs in the 3′-UTR area (1016G>A and 1240T>C) of MC4R gene in 132 German Merino sheep. We found that the 1016G>A mutation in the 3′-UTR was significantly associated with body weight at 120 and 180 days, average daily gain, back fat thickness and loin-eye area. Allele A located at the 292th position of MC4R gene representing Arg98 was associated with significantly higher loin-eye area in sheep. For the synonymous 93G>A mutation, A allele carrier animals had higher back fat thickness. Our results provide evidence that the MC4R gene may be a candidate gene for growth and meat quality traits with MC4R SNPs being potentially valuable as genetic markers for economic traits in German Merino sheep.