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Background: The astrocytes in the central nervous system (CNS) exhibit morphological and functional diversity in brain region-specific pattern. Functional alterations of reactive astrocytes are commonly present in human temporal lobe epilepsy (TLE) cases, meanwhile the neuroinflammation mediated by reactive astrocytes may advance the development of hippocampal epilepsy in animal models. Nuclear factor I-A (NFIA) may regulate astrocyte diversity in the adult brain. However, whether NFIA endows the astrocytes with regional specificity to be involved in epileptogenesis remains elusive. Methods: Here, we utilize an interference RNA targeting NFIA to explore the characteristics of NFIA expression and its role in astrocyte reactivity in a 4-aminopyridine (4-AP)-induced seizure model in vivo and in vitro. Combined with the employment of a HA-tagged plasmid overexpressing NFIA, we further investigate the precise mechanisms how NIFA facilitates epileptogenesis. Results: 4-AP-induced NFIA upregulation in hippocampal region is astrocyte-specific, and primarily promotes detrimental actions of reactive astrocyte. In line with this phenomenon, both NFIA and vanilloid transient receptor potential 4 (TRPV4) are upregulated in hippocampal astrocytes in human samples from the TLE surgical patients and mouse samples with intraperitoneal 4-AP. NFIA directly regulates mouse astrocytic TRPV4 expression while the quantity and the functional activity of TRPV4 are required for 4-AP-induced astrocyte reactivity and release of proinflammatory cytokines in the charge of NFIA upregulation. NFIA deficiency efficiently inhibits 4-AP-induced TRPV4 upregulation, weakens astrocytic calcium activity and specific astrocyte reactivity, thereby mitigating aberrant neuronal discharges and neuronal damage, and suppressing epileptic seizure. Conclusions: Our results uncover the critical role of NFIA in astrocyte reactivity and illustrate how epileptogenic brain injury initiates cell-specific signaling pathway to dictate the astrocyte responses. [ABSTRACT FROM AUTHOR]

By experimental methods, 26 specimens were designed to conduct elastic and elastic–plastic buckling tests on cylindrical shells containing cracks. This study discusses the influence of factors such as the length–diameter ratio, the diameter–thickness ratio, the crack length, the inclination of the crack, etc., on the buckling load. Additionally, finite element models were established to compare with experimental results. For the PMMA cylindrical shell, the results showed that as the length–diameter ratio of the cylindrical shell increased, the buckling load first decreased and then increased. For the 6063 aluminum alloy cylindrical shell, with increasing length–diameter ratio, diameter–thickness ratio, and crack length of the cylindrical shell, the buckling load decreased accordingly. However, concerning the crack inclination, as the crack inclination increased, the buckling load increased accordingly. This indicates that the larger the crack inclination, the higher the load capacity of the cylindrical shell containing cracks. Through finite element simulations of cylindrical shells with cracks, it was found that through compressive mechanical properties, both elastic and elastic–plastic buckling loads yielded results that are closer to the experimental results. Additionally, the inclusion of contact effects in numerical simulations further improved the agreement with the experimental results, and the variation trend of the buckling load in the finite element simulation was consistent with the experimental results. The research findings provide valuable references for the assessment of load capacity in structures containing cracks. [ABSTRACT FROM AUTHOR]

The effective flood storage volume of flood storage and detention area is the real capability of occupying flood, which is a fundamental basis when formulating and optimizing real-time the flood dispatching plan in flood storage and detention area. The dispatch of inland river flood will occupy the flood storage volume of lakes, polders and swales in the flood storage and detention area, reducing the effective flood storage volume. This paper selects the flood storage and detention area of Longsai Lake, Hanbei River as an example, calculates and analyzes the flood storage volume and its variation characteristics of lakes, polders and swales occupied by the inland river flood dispatching at different frequencies as well as the change rule of the effective flood storage volume after dispatching inland river flood and its influence. The results show that: ➀ When there are lakes, polders and swales in a flood storage and detention area, the flood storage volume of lakes occupied by the dispatching of inland river flood is significantly greater than those of polders and swales, and the greater the inland river flood, the greater the difference in flood storage volume occupied between lakes versus polders and swales. When the 5-year to 50-year occurrence flood happens in the inland river of the Longsai Lake flood storage and detention area, the flood storage volume occupied by lakes are 97.9%~98.1% in all dispatching volume. ➁ The reduction of the effective flood storage volume in flood storage and detention area caused by inland river flood dispatching changes with the frequency of inland river flood. The greater the flood in the inland river, the more significant the reduction of effective flood storage volume in flood storage and detention area. When the 50-year occurrence flood happens in the inland river of the Longsai Lake flood storage and detention area, the effective flood storage volume decreases by about 13.5%, and when the 5-year occurrence flood happens, the effective flood storage volume decreases by 7.81%. ➂ When the inland river flood occurs and is likely to encounter the flood of the mainstream, the reduction of effective flood storage volume will influence the flood dispatching plan obviously, and the effective flood storage volume of the flood storage and detention area shall be calculated and determined in real time according to the incoming flow, and the dispatching plan shall be optimized or adjusted, the personnel and property shall be transferred in advance. [ABSTRACT FROM AUTHOR]

Multiaxial low cycle fatigue tests under non‐proportional stress (NPSS) controlled mode were performed on commercial pure titanium (CP‐Ti). Strain responses of axial and torsional channels under highly applied stress amplitudes show an initial hardening phenomenon. Non‐proportional hardening coefficient of CP‐Ti is independent of the controlled mode. The critical plane of CP‐Ti under NPSS controlled mode is aligned with the maximum principal stress plane proved by optical microscopy observation. Optimized FSM model and KBM‐PM model with mean axial and torsional strain are established. These models are further integrated into equations related to multiaxial stress ratio with high accuracy of life prediction for CP‐Ti under NPSS controlled mode. Highlights: Non‐proportional hardening coefficient of CP‐Ti is independent of the controlled mode.The critical plane of CP‐Ti is aligned with the maximum principal stress plane.Energy and optimized critical plane model with mean strain are established. [ABSTRACT FROM AUTHOR]

In order to evaluate the reliability of cracked cylindrical shell effectively and reasonably, study the load capacity of cracked structures and understand the failure modes of cracked structures, in this paper the finite element method is adopted for cylindrical shells with mixed mode crack. The finite element models of cylindrical shell with an inclined through crack under external pressure were established by finite element method, the elastic and elastic-plastic buckling loads were calculated. The influences of crack length (c), crack angle (θ), cylindrical shell length-radius ratio (L/R), radius-thickness ratio (R/T), boundary conditions on buckling load were explored. The analysis of cracked cylindrical shells with simple support on buckling load shows that the load bearing capacity of cracked cylindrical shells decreases with the increase of length- radius ratio, radius-thickness ratio and crack inclination angle. The increase of crack length can weaken the bearing capacity of cylindrical shell. The variation of elastic-plastic buckling load is consistent with that of elastic buckling load. Under the clamped support, the variation of buckling load is consistent with the buckling load of cracked cylindrical shell with simple support, and the buckling load of cracked cylindrical shell with clamped support is evidently higher than that of simple support. The post-buckling analysis further shows that the changes of crack inclination angle and crack length do not affect the variation modes of pre-buckling and post-buckling deformation of cracked cylindrical shells, but affect the load capacity. The relationship between buckling load of different boundary conditions (simply supported and clamp-supported) and geometrical parameters (length-radius ratio, radius-thickness ratio, crack length and crack Angle) was obtained by nonlinear regression. The results of solution can predict the buckling load of cylindrical shell with an inclined through crack. [ABSTRACT FROM AUTHOR]

Based on fracture mechanics theory, a finite element method was used to determine the stress intensity factors of the inclined crack on the inner surface of the pipe under axial compression load and external pressure. The effects of different influencing factors on the stress intensity factor along the crack front considering crack closure were systematically explored, which were different to those under internal pressure. The effects of high aspect ratio on KII, the crack inclination asymmetry caused by curvature and the effects of the friction coefficient on the stress intensity factors of the pipe with an inclined inner surface crack under axial compression load and external pressure were explored in this paper. To be fit for defect assessment, the solutions for stress intensity factors KII and KIII were derived, and new correction factors fθ and fμ were proposed in the empirical solutions to accommodate the crack inclination asymmetry and the friction coefficient, respectively. [ABSTRACT FROM AUTHOR]

The formation of homopolypeptide vesicles and the identification of their self-assembly mechanism have been challenging issues in the field of polymer self-assembly. Using complementary circular dichroism (CD), Fourier transform infrared (FTIR) and low-field nuclear magnetic resonance (LF-NMR) spectroscopies, in this study we show that the higher hydrophilic ability of side-chains is a key factor for the formation of homopolypeptide vesicles from homo poly(Nε-carbobenzoxy-L-lysine) (PZlys), in which the vesicular structures are confirmed by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and atomic force microscopy (AFM) measurements. Poly(γ-benzyl-L-glutamate-co-Nε-carbobenzoxy-L-lysine) [P(BLG-co-Zlys)] containing different molar ratios of BLG to Zlys units with the same peptide backbone as PZlys are used as the controls. The copolypeptides can only form micelles under the same conditions, due to the more hydrophobic nature of their side-chains. These results show that the specific side-chain structure of the polypeptides plays a fundamental role in the self-assembly of homopolypeptides. These findings can be useful to understand how the hydrophilicity of the side chains of amino acid residues on the surface of a protein affects its structures. [ABSTRACT FROM AUTHOR]

Considering T‐stress components under compression, the crack initiation characteristics of HT200 and PMMA under uniaxial compression have been investigated by theoretical analysis and experimental study for central cracked plate (CCP) and compact tension shear (CTS) specimens with I‐II mixed mode crack. Crack initiation angles of CCP and CTS specimens under compressive load were theoretical predicted according to modified maximum tangential stress (MMTS) criterion and modified maximum shear stress (MMSS) criterion. The influence of material parameters and specimen geometrical configurations on crack initiation characteristics was illustrated through experiments. It demonstrates that the modified fracture criterion considering T‐stress components is more consistent with experiments. Crack initiation angle is related to material properties. Limit load PL is controlled by KII under compression for CCP specimen, and PL of PMMA is less than that of HT200. The closure effect on CTS specimens is less significant than that on CCP specimens. Highlights: Crack initiation angle of closed crack is related to material properties.Limit load PL is controlled by KII under compression for CCP specimens.The closure effect on CTS specimens is less significant than that on CCP specimens. [ABSTRACT FROM AUTHOR]

In‐plane biaxial fatigue tests of commercial pure titanium (CP‐Ti) were performed to investigate the effects of load ratio and phase shift on fatigue and ratcheting behavior. The results show that with the decrease of load ratio or the increase of phase shift, biaxial ratcheting strain effect is more significant, leading to the deterioration of fatigue resistance. Analysis of the crack morphology and fracture characteristic reveals that the crack propagation path becomes complex and the fracture morphology changes due to the enhanced non‐proportional hardening effect. Finally, current multiaxial life prediction models are evaluated to compare the applicability in the biaxial fatigue life prediction. Highlights: Effects of load ratio and phase shift on biaxial ratcheting behavior are discussed.Biaxial fatigue life is more sensitive to the variation of the phase shift.The crack morphology and fracture characteristics are analyzed.The applicability of different multiaxial life prediction models is evaluated. [ABSTRACT FROM AUTHOR]

Astrocytes are critical regulators of the immune/inflammatory response in several human central nervous system (CNS) diseases. Emerging evidence suggests that dysfunctional astrocytes are crucial players in seizures. The objective of this study was to investigate the role of transient receptor potential vanilloid 4 (TRPV4) in 4-aminopyridine (4-AP)-induced seizures and the underlying mechanism. We also provide evidence for the role of Yes-associated protein (YAP) in seizures. 4-AP was administered to mice or primary cultured astrocytes. YAP-specific small interfering RNA (siRNA) was administered to primary cultured astrocytes. Mouse brain tissue and surgical specimens from epileptic patient brains were examined, and the results showed that TRPV4 was upregulated, while astrocytes were activated and polarized to the A1 phenotype. The levels of glial fibrillary acidic protein (GFAP), cytokine production, YAP, signal transducer activator of transcription 3 (STAT3), intracellular Ca2+([Ca2+]i) and the third component of complement (C3) were increased in 4-AP-induced mice and astrocytes. Perturbations in the immune microenvironment in the brain were balanced by TRPV4 inhibition or the manipulation of [Ca2+]i in astrocytes. Knocking down YAP with siRNA significantly inhibited 4-AP-induced pathological changes in astrocytes. Our study demonstrated that astrocytic TRPV4 activation promoted neuroinflammation through the TRPV4/Ca2+/YAP/STAT3 signaling pathway in mice with seizures. Astrocyte TRPV4 inhibition attenuated neuroinflammation, reduced neuronal injury, and improved neurobehavioral function. Targeting astrocytic TRPV4 activation may provide a promising therapeutic approach for managing epilepsy. [ABSTRACT FROM AUTHOR]

Asparaginase/pegaspargase containing regimens combined with radiotherapy are highly effective and considered the cornerstone of localized Natural killer/T-cell lymphoma (NKTL) treatment. However, these chemotherapy regimens inevitably cause relatively high incidence of treatment-related adverse events (TRAEs). Herein we retrospectively evaluated the efficacy and safety of the combined regimen of anti-PD-1 antibody, anlotinib and pegaspargase "sandwich" with radiotherapy in localized NKTL. Anti-PD-1 antibody and pegaspargase at 2500 U/m2 were administered on day 1, while anlotinib (12 mg once a day) was orally administered on days 1-14. The treatment was repeated every 3 weeks. All the eight patients included received 3 cycles of the regimen followed by radiotherapy and an additional 3 cycles. The overall response rate was 100%, and the complete response rate was 87.5%. With a median follow-up time of 35.5 months (range, 34.03-40.90 months), median PFS and OS times were not reached. The 3-year PFS and OS rates were 100% and 100%, respectively. All patients were alive at the last follow-up. No treatment-related death and no grade 4 TRAE was reported. No grade 3/4 hematological toxicity was detected, and half of the patients didn't report any hematological toxicity. This study indicates that anti-PD-1 antibody combined with anlotinib and pegaspargase is a promising chemoradiotherapy regimen for localized NTKL, with mild toxicity and good tolerance. [ABSTRACT FROM AUTHOR]

Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures. Recent studies have shown that complement component 3 (C3) aggravate the neuronal injury in epilepsy. And our previous studies revealed that TRPV1 (transient receptor potential vanilloid type 1) is involved in epilepsy. Whether complement C3 regulation of neuronal injury is related to the activation of TRPV1 during epilepsy is not fully understood. We found that in a mouse model of status epilepticus (SE), complement C3 derived from astrocytes was increased and aggravated neuronal injury, and that TRPV1-knockout rescued neurons from the injury induced by complement C3. Circular RNAs are abundant in the brain, and the reduction of circRad52 caused by complement C3 promoted the expression of TRPV1 and exacerbated neuronal injury. Mechanistically, disorders of neuron–glia interaction mediated by the C3–TRPV1 signaling pathway may be important for the induction of neuronal injury. This study provides support for the hypothesis that the C3–TRPV1 pathway is involved in the prevention and treatment of neuronal injury and cognitive disorders. [ABSTRACT FROM AUTHOR]

Objective Exploring the impact of job demand-oriented training on the core competence and quality of nursing in the radiology department. Methods The 26 nurses from the Department of Radiology at the First Affiliated Hospital of Nanchang University were selected as the research subjects, and the training needs were investigated. The training plan was formulated according to the survey results and job characteristics, and the job demand-oriented training was conducted for one year. The core competence, nursing quality, specialist theory and operational skills of the nurses before and after the training were compared. Results After training, the core competence score, preparation completion rate, puncture success rate, post-training nurse specialized theory, and operational skill scores were significantly higher than those before training (all P <0.05). The contrast leakage rate was significantly lower than that before training (P < 0. 05). Conclusion The implementation of job demand-oriented training will help improve the core competence, specialized theory and operational skills of the radiology nurses and improve the quality of care. [ABSTRACT FROM AUTHOR]

Summary: Aim: Multiple sclerosis (MS) is a neurological autoimmune disorder characterized by mistaken attacks of inflammatory cells against the central nervous system (CNS), resulting in demyelination and axonal damage. Kv1.3 channel blockers can inhibit T‐cell activation and have been designed for MS therapy. However, little is known about the effects of Kv1.3 blockers on protecting myelin sheaths/axons in MS. This study aimed at investigating the neuroprotection efficacy of a selective Kv1.3 channel blocker ImKTx88 (ImK) in MS animal model. Methods: Experimental autoimmune encephalomyelitis (EAE) rat model was established. The neuroprotective effect of ImK was assessed by immunohistochemistry and transmission electron microscopy (TEM). In addition, the antiinflammatory effect of ImK by suppressing T‐cell activation was assessed by flow cytometry and ELISA in vitro. Results: Our results demonstrated that ImK administration ameliorated EAE clinical severity. Moreover, ImK increased oligodendrocytes survival, preserved axons, and myelin integrity and reduced the infiltration of activated T cells into the CNS. This protective effect of the peptide may be related to its suppression of autoantigen‐specific T‐cell activation via calcium influx inhibition. Conclusion: ImK prevents neurological damage by suppressing T‐cell activation, suggesting the applicability of this peptide in MS therapy. [ABSTRACT FROM AUTHOR]

Abstract: Glioblastoma is the most common primary brain tumor in adults and still remains incurable, due to the limited accumulation of drugs in the tumor area. Herein, iRGD‐modified nanoparticles, DOX@MSN‐SS‐iRGD&1MT, are developed for simultaneous delivery of chemotherapeutic agents (doxorubicin, DOX) and immune checkpoint inhibitor (1‐methyltryptophan, 1MT) into orthotopic glioma. The nanoparticles are comprised of mesoporous silica nanoparticles loaded with DOX, combined with Asp‐Glu‐Val‐Asp (DEVD) connected 1MT, and finally modified by iRGD. These nanoparticles show the capability of penetrating through blood brain barrier into the tumor area, and significantly improve accumulation of drugs in orthotopic brain tumors with minimal side effects. The nanoparticles also activate cytotoxic CD8+ T lymphocytes and inhibit CD4+ T cells in both GL261 cells cocultured with splenocytes in vitro and GL261‐luc orthotopic tumors in vivo. Moreover, the expression of antitumor cytokines IFNα/β, IFN‐γ, TNF, IL‐17, STING, and GrzB is upregulated while protumor proteins p‐STAT3 and IL‐10 are downregulated in the brain tumor area. This study demonstrates the advantages of chemo‐immunotherapeutic nanoparticles accumulated in the brain tumor area and their effectively inhibiting tumor proliferation, which establishes a delivery platform to promote antitumor immunity against glioblastoma. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this paper is to investigate the influence of key parameters on the bond strength and failure modes of laminated structures made of different aluminum alloys (i.e. Al 2024 and Al 7075) via the ultrasonic consolidation (UC) process.Design/methodology/approach The UC is used to fabricate laminated structures with various parameters. The push-pin tests were performed on the specimens of different materials and parameters, and the force and displacement were recorded during the tests. The peak punch force was used to represent the bond quality of the laminated structure, and the curves of force versus displacement were used to study the failure modes of the structures.Findings It is found that the lower normal force, the larger vibration amplitude and the lower travel speed can result in stronger bonding. Three different failure modes are observed in the tests, due to the different relations between the toughness of interface and raw materials. The process parameters have influence on the interface toughness of a laminated structure, which further leads to different failure modes.Originality/value The overall mechanical properties of a laminated structure highly depend on the bond quality between laminated layers. The push-pin test can easily and effectively evaluate the bond quality of the laminated structure. This paper not only focuses on the bond strength evaluation, but also analyzes the different failure modes of laminated structures made of different aluminum alloys, which can give an opportunity to optimize the parameters for different materials. [ABSTRACT FROM AUTHOR]

Gamma-amino-butyric acid (GABA)-containing interneurons are crucial to both development and function of the brain. Down-regulation of GABAergic inhibition may result in the generation of epileptiform activity. Loss, axonal sprouting, and dysfunction of interneurons are regarded as mechanisms involved in epileptogenesis. Recent evidence suggests that network connectivity and the properties of interneurons are responsible for excitatory-inhibitory neuronal circuits. The balance between excitation and inhibition in CA1 neuronal circuitry is considerably altered during epileptic changes. This review discusses interneuron diversity, the causes of interneuron dysfunction in epilepsy, and the possibility of using GABAergic neuronal progenitors for the treatment of epilepsy. [ABSTRACT FROM AUTHOR]

Purpose Cerebral hypoxia is a major cause of neonatal seizures, and can lead to epilepsy. Pathologic anatomic and physiologic changes in the dentate gyrus have been associated with epileptogenesis in many experimental models, as this region is widely believed to gate the propagation of limbic seizures. However, the consequences of hypoxia-induced seizures for the immature dentate gyrus have not been extensively examined. Methods Seizures were induced by global hypoxia (5-7% O2 for 15 min) in rat pups on postnatal day 10. Whole-cell voltage-clamp recordings were used to examine A-type potassium currents ( IA) in dentate granule cells in hippocampal slices obtained 1-17 days after hypoxia treatment. Key Findings Seizure-inducing hypoxia resulted in decreased maximum IA amplitude in dentate granule cells recorded within the first week but not at later times after hypoxia treatment. The decreased IA amplitude was not associated with changes in the voltage-dependence of activation or inactivation removal, or in sensitivity to inhibition by 4-aminopyridine (4- AP). However, consistent with the role of IA in shaping firing patterns, we observed in the hypoxia group a significantly decreased latency to first spike with depolarizing current injection from hyperpolarized potentials. These differences were not associated with changes in resting membrane potential or input resistance, and were eliminated by application of 10 m 4- AP. Significance Given the role of IA to slow action potential firing, decreased IA could contribute to long-term hippocampal pathology after neonatal seizure-inducing hypoxia by increasing dentate granule cell excitability during a critical window of activity-dependent hippocampal maturation. [ABSTRACT FROM AUTHOR]

A novel amphiphilic copolymer poly(ethylene glycol)- block-poly( N, N-dimethylamino-2-ethylmethacrylate)- blockpoly[6-(4-methoxy-azobenzene-4′-oxy) hexyl methacrylate] (PEG- b-PDMAEMA- b-PMMAzo) was prepared by ATRP polymerization. The self-assembly and responsive behaviors were investigated by SEM, TEM, LLS and UV-Vis spectra. The results indicated that the copolymers can self-assemble into spherical structures in aqueous media. The aggregate size can be tuned by pH and temperature. The trans- cis isomerization behavior of the formed aggregates was also examined. Upon irradiation with a linear polarized light, the elongation degree of the aggregates was increased with the irradiation time. [ABSTRACT FROM AUTHOR]

Febrile seizures (FSs) are the most common convulsions in childhood. Studies have demonstrated a significant relationship between a history of prolonged FSs during early childhood and temporal sclerosis, which is responsible for intractable mesial temporal lobe epilepsy. It has been shown that interleukin-1β (IL-1β) is intrinsically involved in the febrile response in children and in the generation of FSs. We summarize the gene polymorphisms, changes of IL-1β levels and the putative role of IL-1β in the generation of FSs. IL-1β could play a role either in enhancing or in reducing neural excitability. If the enhancing and reducing effects are balanced, an FS does not occur. When the enhancing effect plays the leading role, an FS is generated. A mild imbalance can cause simple FSs while a severe imbalance can cause complex FSs and febrile status epilepticus. Therefore, anti-IL-1β therapy may help to treat FSs. [ABSTRACT FROM AUTHOR]

From a cDNA library of Chinese scorpion Buthus martensii Karsch, full-length cDNAs of 351 nucleotides encoding precursors (named BmKIM) that contain signal peptides of 21 amino acid residues, a mature toxin of 61 residues with four disulfide bridges, and an extra Gly-Lys-Lys tail, were isolated. The genomic sequence of BmKIM was cloned and sequenced; it consisted of two exons disrupted by an intron of 1622 bp, the largest known in scorpion toxin genomes, inserted in the region encoding the signal peptide. The cDNA was expressed in Escherichia coli . The recombinant BmKIM was toxic to both mammal and insects. This is the first report that a toxin with such high sequence homology with an insect-specific depressant toxin group exhibits toxicity to mammals. Using whole cell patch-clamp recording, it was discovered that the recombinant BmKIM inhibited thesodium current in rat dorsal root ganglion neurons andventricular myocytes and protected against aconitine- induced cardiac arrhythmia. [ABSTRACT FROM AUTHOR]

The in-plane biaxial specimen can well reflect the complex stress state of sheet metal. However, there is no standard for small-sized specimens used in the low-power biaxial fatigue testing machine. The main goal of this paper is to apply the finite element method and orthogonal experiment method to design the cruciform specimen, considering the influence of three main parameters including the diameter of the central semispherical thinning area, the minimum thickness of the center and the arm thickness of the specimen. According to the central strain dispersion coefficient and the strain concentration coefficient proposed in this paper, we ensured that the distribution of strain in the gauge area is uniform and the strain it at its maximum value at the same time. The optimized specimen is verified by a biaxial fatigue test with the digital image correlation (DIC) technique. It is found that the fatigue crack appears in the center region, which proves that the optimized specimen can be effectively used for biaxial fatigue test. [ABSTRACT FROM AUTHOR]

Background: Neonatal hypoxic-ischemic brain damage (HIBD), a leading cause of neonatal mortality, has intractable sequela such as epilepsy that seriously affected the life quality of HIBD survivors. We have previously shown that ion channel dysfunction in the central nervous system played an important role in the process of HIBD-induced epilepsy. Therefore, we continued to validate the underlying mechanisms of TRPV1 as a potential target for epilepsy.Methods: Neonatal hypoxic ischemia and oxygen-glucose deprivation (OGD) were used to simulate HIBD in vivo and in vitro. Primarily cultured astrocytes were used to assess the expression of TRPV1, glial fibrillary acidic protein (GFAP), cytoskeletal rearrangement, and inflammatory cytokines by using Western blot, q-PCR, and immunofluorescence. Furthermore, brain electrical activity in freely moving mice was recorded by electroencephalography (EEG). TRPV1 current and neuronal excitability were detected by whole-cell patch clamp.Results: Astrocytic TRPV1 translocated to the membrane after OGD. Mechanistically, astrocytic TRPV1 activation increased the inflow of Ca2+, which promoted G-actin polymerized to F-actin, thus promoted astrocyte migration after OGD. Moreover, astrocytic TRPV1 deficiency decreased the production and release of pro-inflammatory cytokines (TNF, IL-6, IL-1β, and iNOS) after OGD. It could also dramatically attenuate neuronal excitability after OGD and brain electrical activity in HIBD mice. Behavioral testing for seizures after HIBD revealed that TRPV1 knockout mice demonstrated prolonged onset latency, shortened duration, and decreased seizure severity when compared with wild-type mice.Conclusions: Collectively, TRPV1 promoted astrocyte migration thus helped the infiltration of pro-inflammatory cytokines (TNF, IL-1β, IL-6, and iNOS) from astrocytes into the vicinity of neurons to promote epilepsy. Our study provides a strong rationale for astrocytic TRPV1 to be a therapeutic target for anti-epileptogenesis after HIBD. [ABSTRACT FROM AUTHOR]

Background: Hypoxic-ischemic encephalopathy (HIE) is a serious birth complication with high incidence in both advanced and developing countries. Children surviving from HIE often have severe long-term sequela including cerebral palsy, epilepsy, and cognitive disabilities. The severity of HIE in infants is tightly associated with increased IL-1β expression and astrocyte activation which was regulated by transient receptor potential vanilloid 1 (TRPV1), a non-selective cation channel in the TRP family.Methods: Neonatal hypoxic ischemia (HI) and oxygen-glucose deprivation (OGD) were used to simulate HIE in vivo and in vitro. Primarily cultured astrocytes were used for investigating the expression of glial fibrillary acidic protein (GFAP), IL-1β, Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), and activation of the nucleotide-binding, oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome by using Western blot, q-PCR, and immunofluorescence. Brain atrophy, infarct size, and neurobehavioral disorders were evaluated by Nissl staining, 2,3,5-triphenyltetrazolium chloride monohydrate (TTC) staining and neurobehavioral tests (geotaxis reflex, cliff aversion reaction, and grip test) individually.Results: Astrocytes were overactivated after neonatal HI and OGD challenge. The number of activated astrocytes, the expression level of IL-1β, brain atrophy, and shrinking infarct size were all downregulated in TRPV1 KO mice. TRPV1 deficiency in astrocytes attenuated the expression of GFAP and IL-1β by reducing phosphorylation of JAK2 and STAT3. Meanwhile, IL-1β release was significantly reduced in TRPV1 deficiency astrocytes by inhibiting activation of NLRP3 inflammasome. Additionally, neonatal HI-induced neurobehavioral disorders were significantly improved in the TRPV1 KO mice.Conclusions: TRPV1 promotes activation of astrocytes and release of astrocyte-derived IL-1β mainly via JAK2-STAT3 signaling and activation of the NLRP3 inflammasome. Our findings provide mechanistic insights into TRPV1-mediated brain damage and neurobehavioral disorders caused by neonatal HI and potentially identify astrocytic TRPV1 as a novel therapeutic target for treating HIE in the subacute stages (24 h). [ABSTRACT FROM AUTHOR]

In this paper, the effects of temperature and dwell time on the Fatigue Crack Growth (FCG) behavior of commercial pure titanium were studied under high and low load ratios. Besides, combined with the fracture surface morphology, the specific characteristics of FCG were analyzed under pure fatigue and dwell fatigue conditions. The experiment results show that the FCG rate of commercial pure titanium (CP-Ti) increases with the temperature under low load ratio, and the dwell time increases the FCG rate. Also, the enhancement of the dwell time increases as the temperature rises. The dwell effect tends to be saturated when the temperature rises to 200 °C. Under high load ratio, the FCG rate of CP-Ti also exhibits a temperature-sensitive enhancement. The enhancement effect of the dwell time on the FCG rate under high load ratio is more significant. However, the effect of the hold time on the FCG rate does not increase at 300 °C. The da/dN–ΔK/E FCG curves for CP-Ti have a tendency to approach each other under different load ratios, which indicates that the E-modulus is an important factor for the difference. The effect of dwell time on the FCG behavior of CP-Ti is dominated by the creep deformation mechanism under different load ratios from room temperature to 300 °C. At the same time, the oxidation effect gradually becomes significant as the load ratio increases to 300 °C. The fracture surface morphology shows that the secondary cracks and the roughness increase with temperature or dwell time under low load ratio condition, while, under high load ratio, the effect of creep deformation on the FCG behavior is more obviously enhanced, and plastic deformation is gradually significant with increase of the dimples. [ABSTRACT FROM AUTHOR]

Background: Neonatal hypoxic-ischemic brain damage, characterized by tissue loss and neurologic dysfunction, is a leading cause of mortality and a devastating disease of the central nervous system. We have previously shown that vitexin has been attributed various medicinal properties and has been demonstrated to have neuroprotective roles in neonatal brain injury models. In the present study, we continued to reinforce and validate the basic understanding of vitexin (45 mg/kg) as a potential treatment for epilepsy and explored its possible underlying mechanisms.Methods: P7 Sprague-Dawley (SD) rats that underwent right common carotid artery ligation and rat brain microvascular endothelial cells (RBMECs) were used for the assessment of Na+-K+-Cl- co-transporter1 (NKCC1) expression, BBB permeability, cytokine expression, and neutrophil infiltration by western blot, q-PCR, flow cytometry (FCM), and immunofluorescence respectively. Furthermore, brain electrical activity in freely moving rats was recorded by electroencephalography (EEG).Results: Our data showed that NKCC1 expression was attenuated in vitexin-treated rats compared to the expression in the HI group in vivo. Oxygen glucose deprivation/reoxygenation (OGD) was performed on RBMECs to explore the role of NKCC1 and F-actin in cytoskeleton formation with confocal microscopy, N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide, and FCM. Concomitantly, treatment with vitexin effectively alleviated OGD-induced NKCC1 expression, which downregulated F-actin expression in RBMECs. In addition, vitexin significantly ameliorated BBB leakage and rescued the expression of tight junction-related protein ZO-1. Furthermore, inflammatory cytokine and neutrophil infiltration were concurrently and progressively downregulated with decreasing BBB permeability in rats. Vitexin also significantly suppressed brain electrical activity in neonatal rats.Conclusions: Taken together, these results confirmed that vitexin effectively alleviates epilepsy susceptibility through inhibition of inflammation along with improved BBB integrity. Our study provides a strong rationale for the further development of vitexin as a promising therapeutic candidate treatment for epilepsy in the immature brain. [ABSTRACT FROM AUTHOR]