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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]

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]

• 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]

• 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]

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]

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]

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]

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]

• The proportion of mode II loading component increases with λ under biaxial compression. • There are crucial differences in variation range and tendency of T z subjected to biaxial tensile and compressive loading. • Stress triaxiality factor h is sensitive to a / W , t / W , β and λ under biaxial compression. • h can be adopted as a unified constraint parameter for long crack under biaxial compressive loading. Crack sizes, geometrical configurations of specimens and structures, as well as loading conditions have significant effect on in-plane and out-of-plane constraint effects. Safety assessment with constraint effects can effectively improve the accuracy. There are prominent discrepancies between compressive fracture and tensile fracture. Most of engineering structures are usually under biaxial loading conditions, so that the influence of biaxial compressive loading on fracture analysis with constraint effects is worth paying attention. The size effect factor (relative crack length a / W , thickness to width ratio t / W and crack inclination angle β) and load factor (lateral pressure coefficient λ) of central cracked plate (CCP) specimens with I-II mixed mode crack on constraint effects under biaxial compressive loading have been investigated through theoretical analysis and finite element analysis. In-plane non-singular T -stress (T 11) and its components (T x , T y , and T xy), out-of-plane non-singular T -stress (T 33), out-of-plane constraint parameter T z and stress triaxiality factor h have been adopted to quantify constraint effects. It demonstrates that λ has remarkable influence on SIF, T 11 and T 33 under biaxial compressive loading. The effect of higher a / W (long cracks) on B 11 is more noticeable when I-II mixed mode crack is closer to pure mode II crack or pure mode I crack. The proportion of shear fracture increases under biaxial compression with λ. With the increase of β , B 33 decreases sharply and then increases rapidly with higher λ. T z can directly reflect stress states and adequately describe the loss of out-of-plane constraint. The stress state of crack tip is more likely to asymptotic plane-strain condition ahead of crack tip under compression. There are crucial differences in variation range and tendency of T z subjected to biaxial tensile and biaxial compressive loading. Moreover, T z is insensitive to λ. Stress triaxiality factor h can illustrate in-plane and out-of-plane constraint effects including size effect and load factor (sensitive to a / W , t / W , β and λ), especially can be adopted as a unified constraint parameter for long cracks under biaxial compressive loading. The in-plane T -stress components can be directly calculated by T 11 under biaxial compression. The empirical equations of K II and T 11 containing size effect and load factor simultaneously are effective and convenient for applications. [ABSTRACT FROM AUTHOR]

Highlights: [•] The deformation behavior of CP-Ti is strain rate sensitive at low temperature. [•] The activation energy is temperature dependent in the temperature range concerned. [•] The quantitative index of the deformation mechanism is proposed. [•] The threshold temperature 438K is determined for CP-Ti. [•] An improved Arrhenius type model is proposed with a wider application scope. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, based on the finite element (FE) simulation and the analytical net-section criterion (NSC) solution, the influences of the off-centered angle and the dimension of local wall thinning (LWT) on limit loads of pipes with LWT are systematically investigated. It is interesting that the off-centered angle commonly affects the limit load for all dimensions of LWT. Moreover, the axial length of LWT also plays an important role in the load capacity, which cannot be considered in the analytical NSC solution. In order to improve the prediction accuracy of the NSC analytical solution of pipes with the off-centered LWT, the effects of the off-centered angle and the axial length are considered together in the establishment of the improved NSC solution. It is confirmed by the statistical analysis that the prediction accuracy of the NSC solution can be significantly improved by addressing the effects of two factors together. [Copyright &y& Elsevier]

Abstract: To determine the immune function of Taishan Robinia pseudoacacia Polysaccharide (TRPPS) on chickens, 240 chickens were selected as experimental animals and treated with various doses of TRPPS by hypodermic injection before immunized NDV inactivated vaccine. The results indicated that any dose of TRPPS could significantly promote the development of the immune organs, increase the quantity of leukocyte and the ratio of lymphocyte, and improve the antibody titers against Newcastle disease. Meanwhile, it also increased the magnitude of SIgA in duodenum. However, the dose of 200mg/ml showed to be the most effective. Therefore, in terms of improving immunologic function and production performance, TRPPS could be used as a vaccine immunopotentiator for immune responses. [Copyright &y& Elsevier]

Abstract: The H-current (I H) regulates membrane electrical activity in many excitable cells. The antiepileptic drug gabapentin (GBP) has been shown to increase I H in hippocampal area CA1 pyramidal neurons, and this has been proposed as an anticonvulsant mechanism of action. I H also regulates excitability in some types of hippocampal interneuron that provide synaptic inhibition to CA1 pyramidal neurons, suggesting that global pharmacological I H enhancement could have more complex effects on the local synaptic network. However, whether I H in CA1 interneurons is modulated by GBP has not been examined. In this study, we tested the effects of GBP on I H on hippocampal area CA1 stratum oriens non-pyramidal neurons, and on spontaneous inhibitory postsynaptic currents (sIPSCs) in CA1 pyramidal neurons in immature rat brain slices. GBP (100μM) increased I H in approximately 67% of interneurons that exhibited I H, with no apparent effect on cell types that did not exhibit I H. GBP also increased the frequency of spontaneous (but not miniature) inhibitory postsynaptic currents in pyramidal neurons without altering amplitudes or rise and decay times. These data indicate that I H in a subset of CA1 interneuron types can be increased by GBP, similarly to its effect on I H in pyramidal neurons, and further, that indirectly increased spontaneous inhibition of pyramidal neurons could contribute to its anticonvulsant effects. [Copyright &y& Elsevier]

• SIF and constraint parameters at the crack tip of CCP specimen under uniaxial compression are illustrated quantitatively. • There is a loss of out-of-plane constraint under compression when t/W ≤ 0.9. • The loss of out-of-plane constraint can be directly and evidently investigated through the analysis of T z than T 33. • The empirical equations for K II , T 11 and T z have been obtained are convenient and effective for application. The crack tip constraint effect should be considered in the fracture assessment of structures with cracks, and the in-plane constraint and out-of-plane constraint should be illustrated simultaneously for the three-dimensional cracks in practical engineering structures. The constraint effect of central cracked plate (CCP) specimens with I-II mixed mode crack under uniaxial compression has been investigated quantitatively in present work. The relationship between T -stress components (T x , T y , T xy) and in-plane constraint parameter T 11 has been established. The effects of a wide range of in-plane and out-of-plane geometrical configurations (including relative crack length a / W and thickness to width ratio t / W), material parameters (including elastic modulus E and Poisson's ratio ν), crack inclination angle β and friction coefficient μ corresponding to stress intensity factors (K), in-plane constraint parameter T 11 and out-of-plane constraint parameters T 33 and T z at the crack tip have been calculated and discussed theoretically and numerically. It demonstrates that the constraint parameters can effectively express the stress-strain field at the crack tip. The relative crack length a / W has an influence on the in-plane and out-of-plane constraint parameters, and the thickness to width ratio t / W mainly affects the out-of-plane constraint parameters T 33 and T z. The out-of-plane constraint parameters should be considered for long cracks. There is a loss of out-of-plane constraint under compression when t / W less than or equal to 0.9, which can be much more directly and evidently investigated through the analysis of T z than T 33. The empirical equations for K II , T 11 and T z have been obtained according to theoretical analysis and simulation results, which are convenient and effective for application. [ABSTRACT FROM AUTHOR]

• The maximum principal strain critical plane is more effective under both IP and OP loading. • FS model and KBM-P model can be applied to both IP and OP loading in a general form. • MLCF life prediction model based on newly defined α N f and α are established. Non-proportional multiaxial low-cycle fatigue (MLCF) tests were performed on CP-Ti at different multiaxial strain ratios. The optical microscopy observations and life prediction models verified that the critical plane of CP-Ti was the maximum principal strain plane and that it was effective under non-proportional loading. A non-proportional life coefficient and strain energy density coefficient are proposed. Typical MLCF life prediction models, such as the ESN, FS, KBM, and KBM-P models, are discussed under non-proportional loading. Finally, by associating the newly defined non-proportional life coefficient with the non-proportional hardening factor, two comprehensive non-proportional MLCF life prediction models are established, which have higher accuracies than those of previous models. [ABSTRACT FROM AUTHOR]

• Anisotropic crack tip behavior in hcp titanium is studied by 2D and 3D atomistic simulations. • The stress triaxiality around the crack tip is lower in 3D simulations. • The activation of the oblique slip mode improves crack tip plasticity in 3D simulations. • The critical stress intensity factor for dislocation emission is lower in free 3D simulations. As three-dimensional (3D) atomistic simulations require much higher computational costs, two-dimensional (2D) atomistic simulations under plane strain condition are widely used to study dislocation emission from the crack tip. In order to study the difference of crack tip behavior in 2D and 3D simulations, both 2D and 3D atomistic simulations of the anisotropic crack tip response in hcp titanium were performed, as well as the comparison of simulation results with linear elastic fracture mechanics (LEFM) predictions. The comparing results find significant discrepancies of the near tip stress fields, incipient crack tip deformation and critical stress intensity factor in 2D and 3D simulations. In consistent with the theoretical predictions, crack tip plasticity is solely contributed by the inclined slip mode with a lower critical stress intensity factor than that for cleavage, otherwise an artificial cleavage behavior may be observed in 2D simulations. In contrast to this, the lower stress triaxiality near the free surface leads to an easier dislocation nucleation in free 3D simulations. Besides, the participation of the oblique slip mode improves crack tip plasticity and facilitates the activation of the inclined slip mode that cannot be activated in 2D simulations. In general, the incipient crack tip behavior observed in 3D simulations shows more consistency with experimental results. [ABSTRACT FROM AUTHOR]

The morphology and ultrastructure of the compound eye of the predatory bug, Montandoniola moraguesi (Puton, 1986) was investigated using scanning and transmission electron microscopy. Its compound eyes, which contain ∼195 ommatidia per eye, have the following characteristics: each ommatidium possesses a laminated corneal lens measuring ∼9 μm in diameter and ∼7 μm in thickness, a tetrapartite eucone crystalline cone, which is approximately 5.5 μm long, like a dumbbell with the distal end larger than the proximal end, eight clustered retinula cells ∼25.6 μm in length, two primary pigment cells and eight secondary primary pigment cells. The rhabdomeres of the eight retinula cells form a circular, tiered rhabdom of two elongated and six peripheral retinula cells. The rhabdomeres of cells R7 and R8 are distributed along the basolateral surface of the cone and form a centrally-fused rhabdom that spans nearly the full length of the ommatidium. The microvilli of the peripheral rhabdom (R1–R6) are radially arranged and form a bilobed, V-like shape in the central rhabdom. Based on the similarity of the compound eye of M. moraguesi to the eyes of other predatory insect species, the evolution and function of eyes in predators are briefly discussed. • This study first provides a morphological and ultrastructural description of the compound eye in the adult form of the predatory bug Montandoniola moraguesi (Hemiptera: Anthocoridae; Puton, 1986) by scanning and transmission electron microscopy. • In M. moraguesi the rhabdomeres are contiguous only halfway through longitudinal section, and diverge continuously toward the proximal region compared with other beetles. • The rhabdomeres of both R7 and R8 are in contact laterally, and a cylindrical structure of microvilli surrounds the centrally placed retinula cells and forms a V-shape structure. • This rhabdom pattern is unique in Heteroptera and mostly closely resembles that of Cimicomorpha and Pentatomomorpha beetles. [ABSTRACT FROM AUTHOR]

Predicting the plastic limit load precisely is crucial for the design and reliability assessment of complicated structures. Cylindrical shell structure with nozzle fabricated with anisotropy material has been widely used in pressurized equipment. This study is devoted to developing a plastic limit load expression to capture the effect of anisotropy of materials on the plastic limit load of cylindrical shell with nozzle under internal pressure. In the proposed expression, the effects of four dimensionless parameters including diameter to thickness ratio, opening ratio, wall thickness ratio and yield strength ratio on the plastic limit load of the orthotropic cylindrical shell with nozzle were comprehensively considered. To verify the predictive ability of the proposed plastic limit load expression, finite element results, traditional Cloud-Rodabaugh expression's results and burst test results were compared with the proposed expression's results. It reveals that the predicted results of the proposed expression are in good agreement with experimental data, indicating the proposed expression is robust in describing the plastic limit load variation under different geometries of cylinder and nozzle. • The effect of four dimensionless parameters was considered. • A novel plastic limit load solution for the orthotropic cylindrical shell with nozzle was proposed. • The proposed plastic limit load solution was validated by experimental results. [ABSTRACT FROM AUTHOR]

• Three-dimensional models of the fractured surface are scanned by OM system. • CP-Ti's critical plane is more in line with maximum principal strain rather than maximum shear strain plane. • A new KBM-U model incorporating the effect of multiaxial strain ratio is proposed. • The established KBM-P model provides a superior life prediction of CP-Ti compared to other mentioned models. • The cleavage characteristics disappear at higher strain ratios with some shear dimples appearing. Multiaxial low cycle fatigue (MLCF) tests were performed on commercial pure titanium (CP-Ti) at different multiaxial strain ratios (λ = 0.865, 1.73, 3.46, 5.19). A higher λ accelerated the initial cyclic hardening for the axial stress. For torsional stress responses, all specimens showed initial cyclic hardening characteristics. Optical microscopy (OM) observations of the fracture surfaces showed that the critical plane of CP-Ti is better aligned with the maximum principal strain plane rather than the maximum shear strain plane. The fatigue-life curves obtained from the tests were constructed using the Zamrik, ESN, SWT, FS, and KBM models. According to the modified critical plane, a KBM-P model based on the maximum principal strain plane is proposed. A unified life prediction KBM-U model incorporating the effect of λ is further proposed. Scanning electron microscopy (SEM) observations of fatigue fractures showed that fatigue cracks initiated from the outer surface of the specimen at all λ. Many small cleavage surfaces of different sizes and heights were observed in the crack propagation zone. At higher λ, these cleavage characteristics were accompanied by shear dimples. [ABSTRACT FROM AUTHOR]

• Changes of fracture criterion and mechanism of I-II mixed mode FCG are revealed. • Competition of crack closure mechanisms of I-II mixed mode FCG is explained. • A new FCGR model is proposed by considering crack closure and fracture criterion. With the increase of design and application parameters for pressurized structures, the mixed mode fatigue crack growth (FCG) behavior has become a concerned problem in the field of structural integrity. In order to understand FCG behavior of I-II mixed mode crack growth at negative load ratios, an improved compact tensile shear (CTS) specimen of commercial pure titanium is taken to study the effects of load ratio and loading angle on I-II mixed mode FCG behavior through experiments and finite element method (FEM), which mechanism is discussed in depth as well. The contribution of mode I and mode II crack growth driving forces to I-II mixed mode FCG is analyzed. The changes of crack fracture criterion and the mechanism of crack growth in I-II mixed mode FCG process are revealed, and the competition relationship between two crack closure mechanisms of I-II mixed mode crack at negative load ratios is explained. An improved fatigue crack growth rate (FCGR) model that can make I-II mixed mode FCGR normalized is proposed by considering both the crack closure and the crack fracture criterion eventually. [ABSTRACT FROM AUTHOR]

• Plastic deformation and stress-strain response of crack tip under mode I and mixed-mode I-II loading are discussed. • Variation of stress-strain field and monotonic plastic zone at crack tip are revealed. • Effects of evolution of strain energy on fatigue crack growth behavior are analyzed. The mechanical behavior of crack tip under mode I and mixed-mode I-II fatigue loading for commercial pure titanium at negative load ratios are carried out by finite element method in this paper. The effects of maximum fatigue load, load ratio, loading angle and normalized crack length on the mechanical behavior of crack tip are discussed. The change of mechanical behavior of crack tip is analyzed through the evolution of strain energy. The results show that the increase of maximum fatigue load and crack length increase the plastic strain accumulation at crack tip in mode I fatigue crack growth (FCG), which causes the crack tip release more fracture energy to drive crack growth and affect the distribution of stress-strain field. The decrease of load ratio also increases the plastic strain accumulation and the plastic energy dissipation at crack tip. In mixed-mode I-II FCG, the larger loading angle increase the resistance of crack deflection and cause more plastic strain accumulation at crack tip. After the crack deflects, the crack growth increases the crack tip plastic zone and the morphology of plastic zone changes continuously, which cause the crack growth path move away from the mode I crack growth direction. Different loading angles produce different crack growth paths, which deviates from mode I crack growth direction with the increase of loading angle. [ABSTRACT FROM AUTHOR]