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In the present study, two lanthanoid coordination polymers (Ln-CPs) with the chemical formulae of {[Pr(HL)2(H2O)3]·(H2O)4·Cl}n (1) and [Ho(HL)(CH3COO)2(H2O)3]n (2, H2L = 2-(hydroxymethyl)-1H-benzo[d]imidazole-5-carboxylic acid) using Ln3+ ions along with asymmetric carboxylic acid ligand H2L within solvothermal circumstance in success. Complexes' 1–2 contractions were discovered via single-crystal X-ray diffraction and shaped in-depth by EA, IR spectroscopy, PXRD along with TGA. Their application values on the sports fasciitis along with corresponding mechanism were studied. Enzyme-linked immunosorbent assay (ELISA) was conducted to measure the content of IL-1β along with IL-18 released into muscle tissue. Then, NF-κb activation in muscle tissue was also determined with real-time reverse transcription-polymerase chain reaction (RT-PCR) assay. [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]

Abstract: This work used in-situ scanning electron microscopy method to investigate the small fatigue crack behavior of the aluminum alloy 2024 laminated structure produced by ultrasonic consolidation process. The influence of local microstructure on the crack propagation of the laminates after different heat treatments (T4 and T62) has been compared and discussed. It was found that both the precipitations and the interfaces of the layers could retard crack growth and alter the growth direction, and the effect of interfaces was much stronger. Due to the higher ratio of the toughness to bond strength, the barrier effect of the interfaces on impeding the fatigue crack growth in specimens after the T4 heat treatment was more evident. [Copyright &y& Elsevier]

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]

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]

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]

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]

Abstract: The transient receptor potential vanilloid 1(TRPV1) channels are members of the transient receptor potential (TRP) superfamily. Members of this family are expressed in primary sensory neurons and are best known for their role in nociception and sensory transmission. Multiple painful stimuli can activate these channels. In this review, we discussed the mechanisms of different types of venoms that target TRPV1, such as scorpion venom, botulinum neurotoxin, spider toxin, ciguatera fish poisoning (CFP) and neurotoxic shellfish poisoning (NSP). Some of these toxins activate TRPV1; however, some do not. Regardless of TRPV1 inhibition or activation, they occur through different pathways. For example, BoNT/A decreases TRPV1 expression levels by blocking TRPV1 trafficking to the plasma membrane, although the exact mechanism is still under debate. Vanillotoxins from tarantula (Psalmopoeus cambridgei) are proposed to activate TRPV1 via interaction with a region of TRPV1 that is homologous to voltage-dependent ion channels. Here, we offer a description of the present state of knowledge for this complex subject. [Copyright &y& Elsevier]

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]

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]

• Intergranular fracture along 〈 1 2 - 1 0 〉 and 〈 1 0 1 - 0 〉 oriented twin boundaries (TBs) show directional anisotropy. • Crack initially propagates in a brittle manner along most of the studied TBs. • 〈 1 2 - 1 0 〉 oriented TBs may show higher crack resistance than 〈 1 0 1 - 0 〉 oriented TBs. • Brittle-ductile transition occurs with the increased strain rate and temperature. 〈 1 2 - 1 0 〉 and 〈 1 0 1 - 0 〉 oriented twin boundaries (TBs) have important roles in the modification of strength and ductility of HCP metallic materials. As microcracks may be prone to initiated from TBs, their intrinsic brittleness and ductility need to be studied. Combing atomistic simulations and theoretical calculations, it is demonstrated that the incipient crack propagation behavior along most of the two sets of TBs in HCP titanium is dominated by brittle mode at very low temperature. Nevertheless, significant dislocation activities in the later stage can hinder the crack propagation along 〈 1 2 - 1 0 〉 oriented TBs. Consequently, the ductility of 〈 1 2 - 1 0 〉 oriented TBs is generally superior to that of 〈 1 0 1 - 0 〉 oriented TBs. Furthermore, brittle-ductile transition occurs with the increase of strain rate and temperature due to dislocations emitted from the crack tip and TB site. [ABSTRACT FROM AUTHOR]

• Effects of load ratio and overload ratio on mechanical behavior of crack tip are discussed by finite element method. • Mechanism of overload effect is explained by residual stress and variation of plastic zone. • Effect of compressive load on overload retardation are revealed. In present study, the fatigue crack growth (FCG) behavior of commercial pure titanium (CP-Ti) at negative load ratio with a single tensile overload was investigated through the combination of experiment and finite element method (FEM). The influence of load ratio and overload ratio was considered to investigate the overload retardation effect of FCG with compact-tensile-shear (CTS) specimens. Changes of the fatigue crack growth rate (FCGR) and crack opening force before and after overload were obtained experimentally under different loading conditions. The mechanical behaviors of stress–strain distribution and evolution of plastic zone size ahead of crack tip were explored by FEM for revealing the mechanism of overload at negative load ratios. The results demonstrate that retardation effect of FCG increases with overload ratio, and decreases with load ratio. The retardation effect of overload occurs after a transient acceleration of FCGR. The excessive residual compressive stress induced within the unloading stage of overload cycle ahead of crack tip, causes a shielding effect, which is one of the main factors of overload retardation effect. The difference of plastic strain at crack tip before and after overload makes the monotonic plastic zone (MPZ) and reverse plastic zone (RPZ) compete with each other, resulting in an increase of residual plastic strain, which hinders the crack propagation. At negative load ratios, the overload retardation effect will be weakened by the compressive load because of the decreasing residual plastic strain. [ABSTRACT FROM AUTHOR]

To explore potential critical genes and identify circular RNAs (circRNAs) that act as the competitive endogenous RNA (ceRNA) in a hypoxic pulmonary hypertension (HPH) rat model. Constructed rat model, and a bioinformatics method was used to analyse differentially expressed (DE) genes and construct a circRNA-miRNA-mRNA ceRNA regulatory network. Then, qRT-PCR was used to verify. The significant DEcircRNAs/DEmiRNAs/DEmRNAs was showed, and a ceRNA network with 8 DEcircRNAs, 9 DEmiRNAs and 46 DEmRNAs were constructed. The functional enrichment suggested the inflammatory response, NF-κB signalling, MAPK cascade and Toll-like receptor were associated with HPH. Further assessment confirmed that circ_002723, circ_008021, circ_016925 and circ_020581 could have a potential ceRNA mechanism by sponging miR-23a or miR-21 to control downstream target gene and be involved in the pathophysiology of HPH. The qRT-PCR validation results were consistent with the RNA-Seq results. This study revealed potentially important genes, pathways and ceRNA regulatory networks in HPH. • The HPH rat model was successfully constructed. • Dysregulated circRNAs/miRNAs/mRNAs of HPH from rat lung tissues were integrated, and a circRNA-miRNA-mRNA ceRNA regulatory network was constructed. • A variety of novel genes (including circRNAs/miRNAs/mRNAs) and pathways (including KEGG pathway and ceRNA network) were possibly involved in the occurrence and development of HPH. • The qRT-PCR validation results were consistent with the RNA-Seq results. [ABSTRACT FROM AUTHOR]

• For CP-Ti, the threshold value for ratcheting strain accumulation of the axial stress amplitude is closer to 287 MPa. • Rate Surface Ratio is proposed to represent the difference in velocity during ratcheting accumulation. • The brand-new KBM-PH model with mean stress correction is the best overall among all models. Asymmetrical multiaxial fatigue tests were performed. A new quantification parameter is proposed to represent the difference in velocity during ratcheting accumulation. Although the stress–strain response under asymmetric loading is similar to that under symmetric loading, substantial deteriorations of life are observed. The threshold value for ratcheting strain accumulation of axial stress amplitude is closer to 287 MPa. The brand-new stress parameters-based KBM-PH model with mean stress correction is the best overall among a series of models based on strain and stress parameters with or without mean strain and stress corrections with the best accuracy and ease of use. [ABSTRACT FROM AUTHOR]

Highlights • The effect of load ratio and temperature on FCG rates for base metal and weldment are investigated. • The FCG rate of base metal is quicker than that of weldment, which is mainly due to microstructure. • The monotone plastic zone is larger than that of cyclic plastic zone. Abstract In this paper, the effects of load ratio and temperature on fatigue crack growth (FCG) rates for commercial titanium alloy (CP-Ti) base metal and its weldment are investigated by experiments. Results show that the fatigue crack growth (FCG) rate of weldment is slower than that of base metal, which is mainly due to the difference of the microstructures between them. The microstructures at the weld are coarse grains and acicular martensite, which can reduce the FCG rate of weldment. The effect of load ratio on FCG rate will gradually weaken or even disappear with the increase of temperature. Also, the effect of temperature on FCG rate will gradually weaken or disappear with the increase of secondary cracks on the fracture surface. The results of finite element simulation show the FCG rate will be increased with the increase of plastic zone size and plastic strain, the increase of load ratio and temperature will reduce the FCG rate difference between weldment and base metal. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • More plastic strain energy will be consumed in the high load amplitude. • Δ J ac and Δ J ′ are suitable to describe phenomena in the fracture surface. • The crack growth resistance is higher under high load ratio. • The fracture morphologies are all dimples at the late stage of crack growth. • The data obey the Paris' law mode in the rapid growth stage using Δ J ′. Abstract In this work, fatigue crack growth behavior of commercial pure titanium (CP-Ti) under different load levels is carried out considering the degree of plastic deformation of crack tip. Results show that there are great differences in the stage of crack stable growth in different loading conditions. In the same crack growth rate, strain energy and plastic zone in high load ratio are much higher than those in low load ratio, when crack growth rate is low. However, when crack growth rate is high, the differences of strain energy and plastic zone between these two loading conditions are much smaller. More plastic strain energy will be consumed and a wider range of plastic deformation in crack tip will be required in the high load amplitude. It seems that Δ K and Δ J cannot describe these phenomena, while Δ J ac and Δ J ac ′ proposed in this paper may be more suitable to describe these phenomena in the fracture surface. In different loading conditions, at the late stage of crack growth, the fracture morphologies are all dimples. The data in all the conditions obey the Paris' law mode, with the same coefficient and index in the rapid growth stage using the parameter Δ J ac ′. [ABSTRACT FROM AUTHOR]

Highlights • The global tensile and creep properties of TA2 and its welded joint determined by use of extensometer and DIC technique separately are consistent with each other very well. • The local tensile and creep behaviours of TA2 welded joint including BM, HAZ and WM based on DIC technique can be measured with high precision. • The full-field creep strain of welded joint described by a partition method is proposed in present paper. Then, by the constitutive parameters related with creep stress and distance from the welding centerline, the creep strain at a certain time and position of welded joint can be obtained by modified power law constitutive model. Abstract The tensile properties and creep behaviours of a pure titanium (TA2) welded joint are discussed based on the digital image correlation technique. The mechanical properties of welded, heat-affected, and base metals were evaluated separately and demonstrated significant differences. The global creep constitutive models for a TA2 welded joint were determined considering the influence of stress and the threshold stress of local regions. Subsequently, the full-field creep strain of the welded joint is described using a partition method. A modified power law constitutive model for full-field creep, related to creep stress and distance from the welding centreline, is proposed to predict the creep strain with high precision at any local position. The tensile and creep tests prove that the global deformation and mechanical properties of the TA2 welded joint are significantly different from those of TA2 and the local region. To design welded components, the effects of the difference between local properties and global properties, as well as the global response of the welded joint, must be considered. [ABSTRACT FROM AUTHOR]

Abstract Low cycle fatigue (LCF) behavior of CP-Ti along transverse direction under symmetrical strain and stress-controlled modes was compared systematically. For the strain-controlled tests, tension-compression asymmetry (TCA) has little effect on LCF behavior due to the negligible compressive mean stress. For the stress-controlled tests, TCA is detrimental to LCF resistance. The microstructure evolution during cycling deformation was characterized by EBSD and TEM to identify different deformation mechanisms. It was found that strain cycling deformation was dominated by dislocation slip and exhibited the transition from planar slip to wavy slip with the increase of strain amplitude. For the stress-controlled tests, tensile twinning together with dislocation slip accommodated the increased ratcheting deformation. The strain-life curve under stress-controlled tests is lower than that at strain-controlled tests due to the heterogeneous plastic deformation caused by ratcheting deformation. In order to obtain a unified fatigue life prediction model for different control modes, a novel effective strain range related model was proposed by introducing the TCA factor into the original Manson–Coffin relation. Furthermore, the application of this effective strain range related model was extended to the condition of asymmetrical stress cycling by correcting fatigue ductility coefficient and exponent. [ABSTRACT FROM AUTHOR]

Abstract In order to understand the effects of cyclic asymmetry and control mode on low cycle fatigue (LCF) behavior of CP-Ti along rolling direction (RD), symmetrical strain and stress-controlled fatigue tests were conducted in this paper. LCF behavior of CP-Ti along RD under different control modes was systematically compared from the aspects of cyclic response, microstructure evolution and fatigue life with the technique of electron backscatter diffraction (EBSD) and scanning electron microscope (SEM). It was found that cyclic softening resulted by dislocation slip dominates strain-controlled fatigue. On the contrary, cyclic hardening dominates stress-controlled fatigue at high stress amplitude, leading to a higher cyclic stress-strain curve. Owing to asymmetrical hysteresis loop, compressive ratcheting strain is accumulated in stress-controlled LCF test despite of the fully reversed stress cycling. EBSD results show there is a transition of deformation mechanism from dislocation slip to dislocation slip and twinning dominated cyclic deformation with the increase of compressive ratcheting strain. Meanwhile, GOS analysis and SEM observation indicate that the appearance of massive twins results in the heterogeneous plastic deformation and micro-cracks are favorable to be initiated in the twin abundant area. Besides, compressive ratcheting strain has significant effects on fatigue crack growth as the fracture surface presents the serious abrasion of cleavage facets and fatigue striations. Finally, strain-life curves under different control modes are identical, indicating that fatigue life along RD is insensitive to compressive ratcheting strain under the interaction of these factors. [ABSTRACT FROM AUTHOR]

Highlights • The analytical solution for limit load of orthotropic pressure pipe with constant-depth internal circumferential crack under combined pressure, axial force and bending has been obtained. • It is necessary to consider three directional stress for limit load of thick-walled pressure pipe with internal circumferential crack. • The limit load of pipe under pure bending is only related to axial yield strength. The limit load of pipe under pure internal pressure is mainly determined by circumferential yield strength. Abstract Based on the Hill yield criterion, considering three directional stress (r, θ, z) of pressure pipe, the analytical solution for limit load of orthotropic pressure pipe with constant-depth internal circumferential crack under combined pressure, axial force and bending has been derived. The effect of crack size, anisotropy of pipe material, load (pressure, moment), and pipe size on the limit load of orthotropic pressure pipe is discussed. The results show that it is necessary to consider three directional stress for thick-walled pipe, and the influence of radial stress on the limit load cannot be ignored for thick-walled pipe. The limit load of pipe with constant-depth internal circumferential crack decreases with crack size. The limit load of pipe under pure bending is only related to axial yield strength. The limit load of pipe under pure internal pressure is mainly determined by circumferential yield strength. Graphical abstract Image, graphical abstract [ABSTRACT FROM AUTHOR]

Abstract Experimental and numerical investigations are both performed to study the fracture behavior of CTS specimen of CP-Ti under I-II mixed mode loading. The results show that crack growth path and loading capability of CTS specimen are dependent on both loading angle and crack length. Or rather, crack length effect of CTS specimen on the loading capability and crack growth path (except for pure mode I) becomes more remarkable, as the component of mode I increases. Opening stress from mode I loading is the main reason, the applied mode (tensile and bending opening stress) of which is associated with the crack length of CTS specimen. It is due to the opening stress applied on the specimen, crack length effects on the transition from ductile to brittle fracture and plastic zone (except for pure mode I) ahead of crack tip are more obvious when the component of mode I is dominant, which also explain the results of loading capability and crack growth path (except for pure mode I) respectively. In addition, critical J -integrals J c are analyzed, the results show that constraint effect on J c of mode I dominant crack is much more remarkable than that of mode II dominant crack, which is also because of the applied style of opening stress on the specimen. Graphical abstract Image 1 Highlights • Crack length effect is more obvious for mode I dominant crack. • Constraint is due to the style of mode I tensile loading. • Constraint effectis more obvious for mode I dominant crack. [ABSTRACT FROM AUTHOR]

Highlights • A process of inhibiting and promoting crack growth is performed. • The dimples and striations cover up the facet creep fracture characteristic. • The fatigue-creep interaction diagram based on the analyses is depicted. Abstract In this paper, the effect of the cold creep on fatigue crack growth rate are investigated by experiment considering wide ranges of load amplitudes and load ratios with or without certain degrees of dwell time. To further illustrate the cold creep influence, a series of finite element results are carried out. Finally fracture morphology analyses are also made to explain related crack growth behavior. Results show that fatigue crack growth rate either increases or decreases with certain degrees of hold load and dwell time imposed, depending on the values of the load amplitude and load ratio. This finding is the same as that in the fatigue life. Discussion shows that the effect of creep on fatigue crack growth can be attributed to the competition of the creep stress relaxation and creep strain. A process of inhibiting and promoting crack growth is performed. The fatigue-creep interaction diagram based on the analyses is depicted, by which the interaction between cold creep and fatigue can be well understood. Finally further studies and discussion are carried out by fracture morphology analyses from the dislocation pile-ups, which is in accordance with the finite element results from local creep behavior. This research will provide support to the clear understanding of the cold creep effects on the fatigue crack growth behavior. [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]

Multiple cracks have been widely observed in pressure vessels and structure components. When multiple cracks approach each other, the interaction between them could affect the stress field around the cracks. So multiple cracks should be taken into account simultaneously because the interaction could change the stress intensity factor (SIF) of the cracks. In ASME Boiler and Pressure Vessel Code Section XI, a flaw combination criterion is provided for interacting parallel surface cracks. However, the criterion for the offset distance does not consider the influence of crack size on the magnitude of the interaction and is only given by an absolute value. In present paper, firstly, SIF for parallel surface cracks is evaluated as a function of the crack front position, relative position, aspect ratio and relative size by numerical analysis based on M -integral. And the influence of the interaction on SIF is quantified. It is shown that the crack front position, relative position between two cracks, aspect ratio and relative size are important parameters to determine the interaction between parallel surface cracks. Secondly, the new combination criteria for the offset distance are proposed for the fracture evaluation based on analysis results. [ABSTRACT FROM AUTHOR]

Both experimental and numerical investigations are performed to study the fracture behaviors of I-II mixed mode crack for commercially pure Titanium (CP-Ti). Three different types of specimens are considered in this paper, including Compact tension shear specimen (CTS specimen), Four point bending specimen (FPB specimen) and Cracked central plate (CCP). Results show that there exist two fracture modes of these specimens, including tensile-type fracture mode and shear-type fracture mode. For single edge notched specimen, the failure mode is determined by plastic mixity parameter M p , and the critical values of M p distinguishing the fracture modes are dependent on the specimen geometry (CTS or FPB specimen). For central cracked plate, specimens are all in a tensile-type fracture mode. Furthermore, specimen in a shear-type fracture mode has a higher loading capability than that in a tensile-type fracture mode. And the loading capability of specimen in tensile-type fracture decreases almost linearly with M p . Finally, constraints of these specimens are analyzed. Discrepancies of constraint between specimens increase with the component of mode I increasing. And the difference of constraint resulted from specimen type is much greater than that from crack length. [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]

Molecular dynamics was used to simulate tensile behavior of nanocrystalline titanium with ultra-small grain size ranging from 2.8 nm to 10.2 nm at the strain rate ranging from 10 8  s −1 to 10 10  s −1 . Three dimensional samples with random oriented grains containing no textures were developed by Voronoi tessellation. For all the samples, the yielding is solely controlled by GB mediated process. The inverse Hall-Petch relation between grain size and flow stress was found. The strain rate sensitivity shows increase with the decrease of grain size due to the enhancement of grain boundary (GB) mediated process. Meanwhile, it increases with the applied strain rate due to the local disorder around GBs. Remakeable grain coarsening observed in the 2.8 nm sample causes the slight increase of flow stress. Both GB mediated process and partial dislocation slips play an important role in the plastic deformation of nanocrystalline Ti. With the increase of grain size, rare twins initiated from GBs can be observed. From the size dependent dislocation density analysis, it is concluded that with the increase of grain size, dislocation related deformation contributes more to the plastic strain. [ABSTRACT FROM AUTHOR]

Tensile deformation of single crystal titanium nanowires (NWs) with size ranging from 3 nm to 20 nm along [0001] orientation is investigated by molecular dynamics (MD) simulations. For all NWs, the initial yielding at different strain rates is induced by the nucleation of 10 1 ¯ 2 twinning. Following the saturation of twin volume fraction, the size dependent transition of deformation mechanisms in twinned regions is observed. At the strain rate from 10 8 s − 1 to 10 9 s − 1 , following the deformation twinning, the phase transformation from HCP to FCC dominates the plastic deformation of Ti NWs. By increasing sample size to 20 nm, phase transformation can be replaced by prismatic dislocation slip. At the strain rate from 10 9 s − 1 to 10 10 s − 1 , the critical size for the transition from phase transformation to full dislocation slip decreases with the applied strain rate. With further increasing sample size, after the saturation of 10 1 ¯ 2 twins, the initial single crystal NW transforms to nanocrystalline NW. Subsequent plastic deformation mechanism in the nanocrystalline Ti NW with large size is transferred from grain boundary dominate deformation to the cooperation of grain boundary deformation and dislocation activity. Furthermore, deformation mechanism map is proposed to provide a deep understanding of the plastic deformation of Ti NWs. [ABSTRACT FROM AUTHOR]

Due to the non-negligible role of T -stress on fracture parameter, T -stresses of three typical specimens, including central cracked plate (CCP), compact tension specimen (CTS) and four point bending specimen (FPB), are calculated using 3D finite element method. From the results, the tensile dominant specimen like CCP is in a lower-constraint state when the component of mode I is significant, and in a higher-constraint state when the component of mode II is significant, compared with bending dominant specimen like CTS and FPB specimens. Further, the crack initiation angles and plastic zones are assessed for the three specimens based on modified maximum tangential stress (MMTS) and modified R-criterion (MR). From the comparison, the effect of T -stresses or constraints induced by specimen geometries and loading modes play a significant role on crack initiation angle and plastic zone around the crack tip, which in turn can affect the fracture of specimen. [ABSTRACT FROM AUTHOR]

The effect of bend angle on plastic limit loads of pipe bends under different load conditions is presented using three-dimensional non-linear finite element analyses. Based on finite element analysis, the characteristics of deformation, stress and strain were studied and effect of bend angle on the limit load was discussed. The results show that the effect of bend angle on limit load is great both at 0°∼120° range under internal pressure, torsion moment and in-plane bending moment and at 0°∼90° under out-of-plane moment. Then existing expressions of limit load and the finite element results were compared, and the solutions of limit load under single load condition were made. The proposed unified load solutions were obtained by fitting the finite element data under internal pressure, in-plane bending moment, out-of-plane bending moment and torsion moment. The results show that the proposed unified load solutions are consistent and in good agreement with the current finite element results. [ABSTRACT FROM AUTHOR]

This paper is dedicated to providing a detailed plastic collapse load analysis for un-cracked and circumferential through-wall cracked pipe bends under torsion moment by three dimensional FE methods considering geometric nonlinearity. For un-cracked pipe bends results show that radius-to-thickness is the main factors affecting the plastic collapse load. For cracked pipe bends the weakening factor decreases with increasing crack length, and the decreasing rate exhibits three typical stages which performs a similar trend with that in bending case. Although the weakening factor in plastic collapse load shows the similar variation based on geometric nonlinearity with that based on geometric linearity change, the limit load solutions based on geometric linearity fail to be used in prediction for torsion load based on geometric nonlinearity. So estimating limit load solutions by FE method are proposed, which shows a better choice compared with the past solutions. Furthermore the effect of yield strain is considered with the normalized parameter proposed to represent this weakening effect of yield strain on torsion moment. Results show that pipe parameters bend radius-to-radius and crack length have little impact on the weakening parameter, however radius-to-thickness have an obvious impact on the weakening parameter, which increases with decreasing weakening parameter. Results also show that radius-to-thickness has a great impact on the ovality deformation, while bend radius-to-radius hasn't. Therefore geometry effect is significant for a high yield strain value and a high radius-to-thickness value. [ABSTRACT FROM AUTHOR]

Hypoxia-ischemia brain damage (HIBD) is one of prevalent causes of neonatal mortality and morbidity. Our data demonstrated that hypoxia-ischemia (HI) induced Na + -K + -Cl − -co-transporter 1 (NKCC1) increasing in hippocampus. Previous studies demonstrated that NKCC1 regulates various stages of neurogenesis. In this study, we studied the role of increased NKCC1 in regulating of HI-induced neurogenesis. HIBD model was established in 7 days old Sprague-Dawley rat pup, and the expression of NKCC1 was detected by western blot and qPCR. Brain electrical activity in freely rats was monitored by electroencephalography (EEG) recordings. HI-induced neurogenesis was detected by immunofluorescence staining. Neurobehavioral test was to investigate the neuro-protective role of bumetanide, an inhibitor of NKCC1, on neonatal rats after HI. The results showed that bumetanide treatment significantly reduced brain electrical activity and the seizure stage of epilepsy induced by pentylenetetrazol (PTZ) in vivo after HI. In addition, bumetanide restored aberrant hippocampal neurogenesis and associated cognitive function. Our data demonstrated that bumetanide reduces the susceptibility of epilepsy induced by PTZ in rats suffering from HI injury during neonatal period via restoring the ectopic newborn neurons in dentate gyrus (DG) and cognitive function. [ABSTRACT FROM AUTHOR]

Molecular dynamics simulations were performed to study the tensile behaviors of single crystal titanium nanowire along [0 0 0 1] direction under different strain rates using the Finnis-Sinclair many-body potential. The applied strain rate is ranging from 10 8 s −1 to 10 11 s −1 (0.0001–0.1 ps −1 ). At strain rates below 0.01 ps −1 , the stress-strain curves can be divided into four distinct stages: initial linear stage, sharp drop stage, rapid rise stage and wavelike decrease stage. Structural analysis reveals that the growth of { 1 0 1 ¯ 2 } tensile twin leads to the rapid rise stage in stress-strain curves. The evolution of twinning variants indicates that the number of nucleated twin variants increases with the applied strain rate and the overall twin volume fraction decreases with strain rate. At strain rates above 0.01 ps −1 , three distinct stages are observed in the stress-strain curves. At these strain rates, a rapid transformation to an amorphous state was observed leading to superplastic behavior of nanowire. Besides, deformation mechanism map was constructed for nanowire during tension process at different strain rates. [ABSTRACT FROM AUTHOR]

Vitexin and isovitexin are active components of many traditional Chinese medicines, and were found in various medicinal plants. Vitexin (apigenin-8-C-glucoside) has recently received increased attention due to its wide range of pharmacological effects, including but not limited to anti-oxidant, anti-cancer, anti-inflammatory, anti-hyperalgesic, and neuroprotective effects. Isovitexin (apigenin-6-C-glucoside), an isomer of vitexin, generally purified together with vitexin, also exhibits diverse biological activities. Latest research has suggested that vitexin and isovitexin could be potential substitute medicines for diversity diseases, and may be adjuvants for stubborn diseases or health products. This review summarized recent findings on various pharmacological activities and associative signalling pathways of vitexin and isovitexin to provide a reference for future research and clinical applications. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated that the early suppression of HIF-1α after hypoxia–ischemia (HI) injury provides neuroprotection. Vitexin (5, 7, 4-trihydroxyflavone-8-glucoside), an HIF-1α inhibitor, is a c-glycosylated flavone that has been identified in medicinal plants. Therefore, we hypothesized that treatment with vitexin would protect against HI brain injury. Newborn rat pups were subjected to unilateral carotid artery ligation followed by 2.5 h of hypoxia (8% O 2 at 37 °C). Vitexin (30, 45 or 60 mg/kg) was administered intraperitoneally at 5 min or 3 h after HI. Vitexin, administered 5 min after HI, was neuroprotective as seen by decreased infarct volume evaluated at 48 h post-HI. This neuroprotection was removed when vitexin was administered 3 h after HI. Neuronal cell death, blood–brain barrier (BBB) integrity, brain edema, HIF-1α and VEGF protein levels were evaluated using a combination of Nissl staining, IgG staining, brain water content, immunohistochemistry and Western blot at 24 and 48 h after HI. The long-term effects of vitexin were evaluated by brain atrophy measurement, Nissl staining and neurobehavioral tests. Vitexin (45 mg/kg) ameliorated brain edema, BBB disruption and neuronal cell death; Upregulation of HIF-1α by dimethyloxalylglycine (DMOG) increased the BBB permeability and brain edema compared to HI alone. Vitexin attenuated the increase in HIF-1α and VEGF. Vitexin also had long-term effects of protecting against the loss of ipsilateral brain and improveing neurobehavioral outcomes. In conclusion, our data indicate early HIF-1α inhibition with vitexin provides both acute and long-term neuroprotection in the developing brain after neonatal HI injury. [ABSTRACT FROM AUTHOR]

• The critical plane of CP-Ti under load-controlled mode is aligned with the maximum principal stress plane proved by OM observation. • A new KBMSS-P model with stress parameters is proposed to overcome the variability of strain plane under load-controlled mode. • Stress parameters KBMSS-P and strain parameters KBM-P models are combined to accommodate different control modes. MLCF tests were performed on CP-Ti under load-controlled mode. Both axial and torsional strain responses show three softening stages. CP-Ti shows a significant asymmetric strain response with obvious ratcheting phenomena under symmetric multiaxial stress loading. The critical plane of CP-Ti under load-controlled mode is more closely aligned with the maximum principal stress plane proved by OM observation. Based on this, a new KBMSS-P stress parameters model is proposed to overcome the variability of strain plane under stress loading. It can be further combined with strain parameters KBM-P model by use of the Heaviside function to accommodate different control modes. [ABSTRACT FROM AUTHOR]

In this work, finite element (FE) method is used to determine plastic limit load solutions for pipe bends with circumferential through-wall crack under torsion moment. Both extrados and intrados crack are considered regarding of crack location. Based on FE results estimated solutions are proposed for application, and are also compared with corresponding solutions in previous literatures showing that existing solutions are unfit for prediction of torsion load. The weakening factor W decreases with crack length increasing, and the decreasing rate exhibits three typical stages which performs a similar trend to that with bending moment. Finally a detailed analysis for the mechanical behavior of pipe bends has been conducted which provides some evidence to explain the weaken effect caused by the presence of crack. In torsion mode results show that the non-uniform distributed shear stress is performing symmetric to the profile plane and may have a crucial influence on the weakening factor, while in bending mode the distribution in axial stress and circumferential stress is symmetric to the profile plane and has a decisive influence. Therefore crack is pulled open by in-plane bending load while torn open by torsion load. Some evidence also can be obtained from the Mises stress distribution, where similar variation rule will provide another argument to support such description. [ABSTRACT FROM AUTHOR]

Febrile seizure (FS) is the most common seizure disorder in children, and children with FS are regarded as a high risk for the eventual development of epilepsy. Brain inflammation may be implicated in the mechanism of FS. Transient receptor potential vanilloid 1 (TRPV1) is believed to act as a monitor and regulator of body temperature. The role of inflammation in synaptic plasticity mediation indicates that TRPV1 is relevant to several nervous system diseases, such as epilepsy. Here, we report a critical role for TRPV1 in a febrile seizure mouse model and reveal increased levels of pro-inflammatory factors in the immature brain. Animals were subjected to hyperthermia for 30 min, which generates seizures lasting approximately 20 min, and then were used for experiments. To invoke frequently repetitive febrile seizures, mice are exposed to hyperthermia for three times daily at an interval of 4 h between every time induced seizure, and a total of 4 days to induce. Behavioral testing for febrile seizures revealed that a TRPV1 knock-out mouse model demonstrated a prolonged onset latency and a shortened duration and seizure grade of febrile seizure when compared with wild type (WT) mice. The expression levels of both TRPV1 mRNA and protein increased after a hyperthermia-induced febrile seizure in WT mice. Notably, TRPV1 activation resulted in a significant elevation in the expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α and HMGB1) in the hippocampus and cortex. These data indicate that the reduction of TRPV1 expression parallels a decreased susceptibility to febrile seizures. Thus, preventative strategies might be developed for use during febrile seizures. [ABSTRACT FROM AUTHOR]

The influences of stress and hold time on cycle deformation and failure life of CP-Ti dwell fatigue were systematically investigated. Two dwell fatigue regions were divided by dwell fatigue parameters. At high stress region, creep and ratcheting behaviors are significant, and the failure mechanism is the ductile fracture caused by large deformation. But at low stress region, creep and ratcheting behaviors are tempered, and the failure mechanism is the classical fatigue fracture. It is worth noting that, the influences of hold time on dwell fatigue parameters are different at different dwell fatigue regions. Moreover, the creep and ratcheting interaction was discussed, and the dwell fatigue strain changes from ratcheting strain controlled to creep strain controlled with hold time increasing. At last, since the dwell fatigue life debits are different at different dwell fatigue regions, the dwell fatigue life prediction model considering fatigue, creep and ratcheting was proposed for the dwell fatigue behavior of CP-Ti at ambient temperature. [ABSTRACT FROM AUTHOR]

In present paper, 3D finite element (FE) method is used to determine plastic limit load solutions for pipe bends under combined bending and torsion moment. With a detailed analysis and comparison, a common awareness for loading effect is showing which will raise researchers concern. By the way, past solutions are not appropriate to estimate FE results. In this respect of finite element analysis, overall yielding considering the spread process of yield region from crown to the straight pipe shows these promising finite element results. A wide range of non-dimensional parameters for pipe bends are considered and plastic limit load solutions are suggested. The results show that r / t is the main factor affecting the limit loads. Plastic limit load is independent on the loading path and material constants by normalizing. Results show that the circular interaction rule is a great approximation for pipe bends under combined bending and torsion moment. A series of approaches are confirmed in order to validate our finite element method on plastic limit analysis. Based on the finite element results, approximate plastic limit load solutions are proposed. Present work will further improve the limit load solution for pipe bends under complex loading conditions. [ABSTRACT FROM AUTHOR]

In present work, limit loads for pipe bends under combined internal pressure and out-of-plane bending moment have been investigated systematically via finite element simulation based on both small displacement analysis and large displacement analysis. By normalized methods, a wide range of non-dimensional parameters were considered and limit bending moment expression has been suggested which shows that r / t is the main factor affecting the limit bending moment. In addition, the effect of internal pressure on the limit loads was studied in detail which is significant for thin walled pipe bends. It is found that yield strain ε 0 has an obvious effect on limit load based on large displacement analysis. According to the finite element results, practicable engineering assessment equations of limit loads have been proposed for pipe bends under combined loads. These proposed equations are validated with experiment data and also justified to be a good choice for limit loads assessment. [ABSTRACT FROM AUTHOR]

• Mechanism of overload effect of mixed mode I-II crack growth at negative load ratio is revealed. • Effect of loading angle and loading ratio on crack growth with overload loading is discussed. • Stress–strain field and plastic deformation at crack tip are revealed by finite element method. Fatigue crack growth (FCG) behavior under mixed mode loading has been received extensive attention, including overload condition. The mixed mode I-II fatigue crack growth behavior of commercial pure titanium (CP-Ti) with tensile overload at negative load ratios was investigated by experiment and finite element method (FEM). The effects of loading angle, load ratio and overload on mixed mode I-II fatigue crack growth were discussed with a modified compact-tensile-shear (CTS) specimen. The mechanism of mixed mode crack growth with overload was revealed. Fatigue crack growth path and fatigue crack growth rate (FCGR) with/without overload were compared experimentally, and overload retardation effect was investigated. The variation of plastic zone and the distribution of stress and strain were simulated through finite element method. The mechanism of overload retardation effect of mixed mode I-II crack growth under compressive load was illustrated by microscopic perspective, crack closure and residual compressive stress at crack tip, and the weakening effect of mode II shear component and compressive load effect on overload retardation effect was demonstrated. [ABSTRACT FROM AUTHOR]

Prenatal nicotine exposure causes adverse birth outcome. However, the corresponding metabonomic alterations and underlying mechanisms of nicotine-induced developmental toxicity remain unclear. The aims of this study were to characterize the metabolic alterations in biofluids in nicotine-induced intrauterine growth retardation (IUGR) rat model. In the present study, pregnant Wistar rats were intragastrically administered with different doses of nicotine (0.5, 1.0 and 2.0 mg/kg d) from gestational day (GD) 11–20. The metabolic profiles of the biofluids, including maternal plasma, fetal plasma and amniotic fluid, were analyzed using 1 H nuclear magnetic resonance (NMR)-based metabonomic techniques. Prenatal nicotine exposure caused noticeably lower body weights, higher IUGR rates of fetal rats, and elevated maternal and fetal corticosterone (CORT) levels compared to the controls. The correlation analysis among maternal, fetal serum CORT levels and fetal bodyweight suggested that the levels of maternal and fetal serum CORT presented a positive correlation ( r = 0.356, n = 32, P < 0.05), while there was a negative correlation between fetal ( r = −0.639, n = 32, P < 0.01) and maternal ( r = −0.530, n = 32, P < 0.01) serum CORT level and fetal bodyweight. The fetal metabonome alterations included the stimulation of lipogenesis and the decreased levels of glucose and amino acids. The maternal metabonome alterations involved the enhanced blood glucose levels, fatty acid oxygenolysis, proteolysis and amino acid accumulation. These results suggested that prenatal nicotine exposure is associated with an altered maternal and fetal metabonome, which may be related to maternal increased glucocorticoid level induced by nicotine. [ABSTRACT FROM AUTHOR]

Abstract: This study was designed to investigate the role of experimental febrile seizures in the induction of generalized clonic seizures and the involvement of heat-sensitive channel TRPV1. Pentylenetetrazol-induced clonic seizure was used as the seizure model, and Trpv1 gene knock-out and wild-type C57/BL6 mice were used as experimental subjects. Electroencephalograph and seizure behavior were recorded for the evaluation of the severity of seizures. Increased frequency of the experimental febrile seizures facilitated PTZ-induced generalized clonic seizures. Trpv1 gene deficiency decreased the properties of generalized clonic seizure. The intensity of experimental febrile seizures reduced the threshold to generalized clonic seizure, and Trpv1 gene deficiency decreased the susceptibility to PTZ-induced seizures following early-life hyperthermia challenges in mice. [Copyright &y& Elsevier]

Abstract: Based on the careful analyses of the stress controlled fatigue behavior of commercially pure titanium (CP-Ti) at room temperature, two stress regions can be evidently identified by cycle strain range, ratcheting strain, min ratcheting strain rate, ratcheting failure strain and fracture morphologies. In the high stress region, the ratcheting behavior is significant, and the failure is caused by the large ratcheting deformation. However, in the low stress region, the ratcheting behavior is weak, and the failure is the typical fatigue fracture, with fatigue crack initiation, fatigue extension, and instant rupture. In the high stress region, for both ratcheting and fatigue behaviors, the influence of max stress is greater than stress amplitude. On the contrary, in the low stress region, the influence of stress amplitude on the fatigue behavior is greater than max stress. But the ratcheting behavior in the low stress region is still max stress controlled. Based on the discussion on the fatigue life prediction model, traditional Basquin model and energy based model cannot supply precise fatigue life in the wide stress range, since the ratcheting behavior is not considered. The coupled fatigue damage and ratcheting damage model is proved to make a robust prediction. [Copyright &y& Elsevier]