Abstract Previous data demonstrate that traumatic brain injury (TBI) activates autophagy, and increases microtubule-associated protein 1 light chain 3 (LC3) immunostaining mainly in neurons. However, ...the role of autophagy in traumatic brain damage remains elusive. The aim of the present study was to investigate the autophagic mechanisms participating in traumatic brain injury. The autophagy inhibitors 3-methyladenine (3-MA) and bafliomycin A1 (BFA) were administered with a single i.c.v. injection before TBI. We first examined the protein levels of Beclin-1 and LC3 II, which have been found to promote autophagy previously. Immunoblotting analysis showed that 3-MA pretreatment reduced post-TBI Beclin-1 and LC3-II levels, and maintained p62/SQSTM1 (p62) levels. In addition, double immunolabeling showed that the increased punctate LC3-II dots colocalizing with Propidium Iodide (PI)-stained nuclei at 24 h after injury, were partially inhibited by 3-MA pretreatment. Furthermore, inhibition of autophagy could reduce TBI-induced cell injury assessed with i.p. injection of PI and lesion volume, and attenuate behavioral outcome evaluated by motor test and Morris water maze. The neuroprotective effects were associated with an inhibition on TBI-induced up-regulation of LC3, Beclin-1, cathepsin B, caspase-3 and the Beclin-1/Bcl-2 ratio. Taken together, these data imply that the autophagy pathway is involved in the pathophysiologic responses after TBI, and inhibition of this pathway may help attenuate traumatic damage and functional outcome deficits.
The unique thermal history of different metal additive manufacturing processes would have profound impacts on the resulting microstructure and material properties. However, few have conducted ...benchmark research on the impacts. This work provides a comprehensive benchmark comparison on microstructure, mechanical properties, and their underlying mechanisms in selective laser melting (SLM), electron beam melting (EBM), and mill-annealing of Ti–6Al–4V alloys. The results have shown that the SLMed and EBMed samples possess very fine acicular α′ martensite while the conventional mill-annealed ones have granular α phase. The SLMed samples exhibit the highest tensile and yield strength resulted from the combined effects of refined α’ martensite and high microscale residual stress. The lowest tensile and yield strength and intermediate elongation of the EBMed samples are attributed to the relatively high number of type-II pores and in-situ annealing for residual stress relief during the printing process. The mill-annealed samples have the highest elongation due to the fully dense structure, the negligible microscale residual stress, and favorable grain orientation. It is expected to improve the ductility of SLMed samples via appropriate post-annealing and enhance the strength of EBMed samples by reducing the number of type-II pores through process optimization. The fundamental differences in microstructure and properties are attributed to the unique thermal histories of the concerned processes.
•EBMed samples possess more type- II pores and uncertain mechanical properties.•SLMed samples have the highest strength due to refined α′ and residual micro stress.•Mill-annealed have the largest elongation due to dense structure and favorable texture.
In this study, aluminum matrix composites reinforced with micro-TiN were fabricated using selective laser melting (SLM) technique. The study investigates the effects of TiN content on densification, ...microstructure evolution, crystal textures, and mechanical properties. The results show that the relative density of composite samples containing 0?3 wt. % TiN exceeds 98%. However, further increase in TiN content leads to a decrease in relative density. The TiN particles are uniformly distributed and wetted by the AlSi10Mg matrix, forming a graded interfacial layer. The TiN particles refine the matrix grains and significantly reduce the prevalence (001) texture by promoting a heterogeneous nucleation process. In comparison to the AlSi10Mg alloy, the TiN/AlSi10Mg composite exhibits improved microhardness, tensile strength, and wear resistance. The exceptional mechanical properties of the Al matrix composites are attributed to the dispersion strengthening of the TiN particles and the fine-grain strengthening of the matrix. The optimal TiN content is found to be 3 wt. %, resulting in excellent mechanical performance of the fabricated samples (132.4?4.1 HV for hardness and 379.7?4.6 MPa for tensile strength) with a low friction coefficient of 0.49.
Natural convection flows of an electrically conducting fluid under a uniform magnetic field at different angles θ with respect to horizontal plane are investigated numerically in rectangular ...cavities. A new compact finite difference algorithm, involving a second-order compact scheme for the streamfunction-velocity (ψ−u) form of Navier–Stokes equations and a fourth-order compact scheme for the energy equation, is employed to solve the steady-state laminar magnetohydrodynamic (MHD) natural convection problems. Numerical simulations are carried out in a wide range of Rayleigh number (Ra) and Hartmann number (Ha) at the Prandtl number Pr=0.025. The computed results show that the heat transfer is not only determined by the strength of the magnetic field, but also influenced by the inclination angle. Especially, when the aspect ratio (A) is less or more than 1, it is found that the inclination angle plays a great role on flow and heat transfer.
Solder joints are generally regarded as the weakest part in packaging systems and electronic assemblies in modern electronic products and devices. In this study, both experimental and finite element ...methods were used to characterize the mechanical behavior of micro-scale Ni/Sn3.0Ag0.5Cu/Ni sandwich-structured joints with different thickness-to-diameter ratios (R varying from 1/3 to 1/12) under quasi-static tension loading using a dynamic mechanical analyzer (DMA). Experimental results show that crack initiation and propagation in the solder matrix occur in a typical ductile manner. Compared with Cu/Sn3.0Ag0.5Cu/Cu sandwich-structured solder joints, Ni/Sn3.0Ag0.5Cu/Ni solder joints have much higher tensile strengths due to the dispersion strengthening effect through the fine Ag3Sn particles. With decreasing R, both stiffness and tensile strength of solder joints increase obviously with decreasing coefficient of stress state and damage equivalent stress. Moreover, results of quantitative fractographic analysis by SEM and EDS display three fracture modes with decreasing R. Joints with R≥1/4 all fail by ductile fracture, those with R=1/6 fail by either ductile fracture or mixed ductile and brittle fractures, and for joints with R=1/12, brittle fracture is dominant. Furthermore, results obtained have also shown that the crack growth driving forces, KI and KII, as well as the strain energy release rate, GI, in the Ni3Sn4 layer and at the Ni3Sn4/Ni interface, increase significantly with decreasing R. Hence, under tensile loading the fracture mode of solder joints changes from ductile to brittle as R is decreased.
Discontinuities of the shear force, bending moment, slope, and deflection can be caused by span supports, valves, and cracks etc. For arbitrary discontinuities appearing in the oil-conveying pipe ...resting on Pasternak foundation, the general analytical solution for vibrations of this structure is presented in this paper. To deal with discontinuity terms, generalized functions are employed to express the model displacement of the entire pipe as a single function. This function is then solved by Laplace transform. Continuity conditions at discontinuity points are also given. In addition, the generalized boundary condition (BC), which can be degenerated to many classical BCs, is considered. Numerical section testifies the feasibility and the validity of present solutions, and discusses the effects of some physical parameters on natural frequencies. It is shown that the closer the cracks are to the nearest nodes of mode shapes, the less effects they have on the corresponding natural frequencies; locations of support springs change effects of cracks on natural frequencies by affecting positions of structural nodes; foundation parameters have different effects on natural frequencies. The present method can be applied in maintaining safety and integrity of structures of pipes.
Summary
Background
The relationship of osteoporosis and stroke is still not fully clarified. Apart from the well-known risk factors for stroke, bone mineral density (BMD) has gained more interest in ...recent years.
Aim
To further elucidate the relationship between BMD and stroke risk, a prospective cohort study in the Chinese rural population was conducted.
Design
Retrospective analysis of a family osteoporosis cohort.
Methods
Our subjects were selected from an osteoporosis cohort conducted in Anqing, China. All participants underwent a questionnaire assessment, clinical examinations and laboratory assessments. During the follow-up period, the number of people who had a stroke was recorded. Generalized estimating equation regression analysis was performed to determine the significance of the association between BMD and stroke.
Results
A total of 17868 people were included. A two-way interaction test of sex and BMD on stroke was significant (P = 0.002). There was a significant difference in BMD and stroke morbidity in the male group (P = 0.003). When BMD was assessed as quartiles and the lowest quartile was used as reference, a significantly lower risk for stroke was observed in Q2–4. Notably, no significant difference was observed in female participants with adjusted odds ratio (P > 0.05). The P-value for interaction was calculated. The body mass index (P = 0.014) and waist-to-hip ratio (P = 0.027) were found to be significantly associated with BMD and stroke risk in female participants.
Conclusions
In Chinese rural areas, total BMD may negatively correlated with stroke, especially in men.
Background
Although visceral hypersensitivity is a major pathophysiological feature of irritable bowel syndrome (IBS), its underlying mechanisms remain elusive. Toll‐like receptor 4 (TLR4) is a ...critical pattern recognition molecule of the innate immune system. In this study, we investigated whether the TLR4/myeloid differentiation factor 88 (MyD88)/nuclear factor‐kappa B (NF‐κB) signalling pathway in the spinal cord contributed to the visceral hypersensitivity induced by neonatal colonic irritation (CI) in rats.
Methods
The Sprague‐Dawley rat model of IBS was induced by colon irritation on post‐natal day (PND) 8, PND10 and PND12. Experiments were conducted in adult rats. TLR4 mRNA and protein, and its downstream signalling molecules, MyD88, inhibitory nuclear factor‐kappa B (IκB) and NF‐κB protein expressions in L2‐S4 spinal segments were detected by quantitative real‐time reverse transcription‐polymerase chain reaction as well as Western blotting. TLR4 co‐localization was determined by immunohistochemistry. Levels of tumour necrosis factor‐alpha (TNF‐α) and interleukin 1β (IL‐1β) were measured with enzyme‐linked immunosorbent assay.
Results
We found that neonatal CI treatment induced long‐lasting visceral hypersensitivity without identifiable structural abnormalities in descending colons of adult rats. Neonatal CI treatment evoked a significant up‐regulation of the expressions of TLR4 in glia, MyD88, p‐IκB‐α and NF‐κB in adult rats. Neonatal CI treatment also increased the levels of its downstream inflammatory agents TNF‐α and IL‐1β in the L2–S4 regions of the spinal cord of adult rats.
Conclusions
These results suggest that neonatal CI stimulates the production of IL‐1β and TNF‐α through the TLR4/MyD88/NF‐κB signalling pathway in the spinal cord, which contributed to visceral hypersensitivity induced by neonatal CI in rats.
(a and c) The experimental εxx and εyy strain distribution with overlaid circles with radii of 3Å and 6Å, from which line profiles are obtained. (b and d) The simulated εxx and εyy strain ...distributions. All the figures have the same color scale as inserted in (a). (e and f) Comparison of the circular line profiles taken from the experimental strain distribution (red lines) and simulated strain distribution (green lines) for εxx and εyy with different radii (solid lines for r=3Å and dash lines for r=6Å).
It can be seen from the figure that the simulated results are in good agreement with the experimental results, which proves that the Foreman model with a=2 best describes the strain fields of the misfit dislocations. Display omitted
The complex misfit dislocations with two extra half planes at α-Fe2O3/α-Al2O3 interfaces were investigated by high-resolution transmission electron microscopy. Strain distributions around dislocation core were mapped using geometric phase analysis. Accurate Burgers vectors were determined by dislocation density tensor analysis to simulate strain distributions. By comparing experimental strain distributions with theoretical models, we found that all the dislocations follow the Foreman model (a=2), which indicates they have the same spatial extension of strain field.
The mammalian Y chromosome gene families in the ampliconic region are expressed predominantly or exclusively in the testis, and their copy number variations (CNV) are significantly associated with ...male reproductive traits, suggesting they have important roles in spermatogenesis and testicular development. ZNF280AY (zinc finger protein 280A, Y-linked) is a member of the zinc finger protein family and has been identified as a bovid-specific Y-chromosome gene. The current study applied a reliable quantitative real-time PCR method to estimate the CNV of ZNF280AY in 715 bulls across 21 cattle breeds and to further investigate the association of the CNV of ZNF280AY with bull reproductive traits and ZNF280AY mRNA expression levels in adult testis. The results revealed that the median copy number of ZNF280AY was 47, and the copy number varied from 11 to 154, showing significant CNV between and within the investigated cattle breeds. In addition, all 715 bulls were classified into Y1, Y2, and Y3 lineage groups based on a rapid genotyping method described previously. Pairwise comparisons indicated that bulls belonging to the Y1 lineage had a significantly lower median copy number (40) than bulls belonging to the Y2 (52) and Y3 lineages (57). Association analysis revealed that the CNV of ZNF280AY was correlated negatively with the percentage of normal sperm and sperm concentration in Holstein bulls, whereas no significant correlation was observed with ejaculation volume, total sperm count, sperm motility, postthaw motility (PTM), and scrotal circumference in Holstein and Simmental bulls. Furthermore, no correlation was observed between ZNF280AY copy number and ZNF280AY mRNA expression levels in the testis. The current study suggests that the CNV of the ZNF280AY gene family is associated with male reproductive traits and may serve as a valuable marker for early bull fertility selection in Holstein breeding programs.
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