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The article offers information on a study which investigates the localization of Bordetella avium in chickens with bacterial infection through indirect immunoperoxidase technique.

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]

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]

• 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]

• 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]

• 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]

• 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]

• 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]

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]

• Fatigue life of CP-Ti shows non-monotonic variation with stress ratio. • Effects of prestrain on fatigue life under different control modes are clarified. • Current strain-life models including mean stress effects are evaluated. • A new strain-life model with exponential mean stress correction term is proposed. This paper investigates symmetric strain, stress and asymmetric stress-controlled fatigue behavior of prestrained and non-prestrained CP-Ti. The effects of stress ratio, mean stress, prestrain on stress/strain life were carefully analyzed. Stress-life of CP-Ti shows non-monotonic variation with stress ratio, as compressive ratcheting resulted by tension-compression asymmetry accumulates under symmetric stress cycling. Stress-life can be improved by prestrain, regardless of loading condition, due to the decrease of responded strain amplitude. Stress fatigue resistance of the material is actually deteriorated by prestrain at the stress level identical to that of non-prestrained CP-Ti. Strain-life of prestrained sample shows little variation at high strain amplitude due to mean stress relaxation and significant reduction at low strain amplitude. By introducing asymmetry factor, it is further found that strain-life of the material is insensitive to prestrain if the applied mean stress level keeps constant. Finally, current strain-life models with different mean stress correction terms are discussed to evaluate their application ability in fatigue life prediction of CP-Ti under different loading conditions. Though two additional parameters are introduced into the mean stress correction term with power law form, there are still few data points beyond the scatter bounds of two. Therefore, a new strain-life model with exponential mean stress correction term is proposed and verified by fatigue life data of different materials, which has more advantage than existing strain-life models at a wide range of mean stress level. [ABSTRACT FROM AUTHOR]

• New driving force parameter and crack closure models are proposed respectively. • Proposed crack closure model can reflect the variation of crack closure level. • The merits and demerits of models are analyzed by the dispersion of each model. The fatigue crack growth rate (FCGR) is strongly dependent on the load ratio R and most FCGR models are established on the basis of R. At present, there are more FCGR models with positive load ratio. In this paper, fatigue crack growth (FCG) behavior of commercial pure titanium at negative load ratios is studied. The FCGRs at various load ratios are fitted by driving force parameter model and crack closure model. The advantages and disadvantages of different models are analyzed by calculating the dispersion of FCGR curves which are condensed by each model. Improved two-parameter driving force model and proposed crack closure model are proposed by two FCGR modeling methods, respectively. One is to modify the FCGR by improving the stress intensity factor (SIF) K with the two-parameter driving force method. Another is established by correlating the crack closure ratio U and load ratio R , positive SIF range Δ K +, maximum SIF K max based on the variation of crack closure level in stable crack growth stage. It is found that proposed crack closure model is superior to the former in both the condensation effect and the physical significance. Under different loading conditions, proposed crack closure model can reliably and accurately condense the FCGR curves and reflect the variation of crack closure level in the whole stable crack growth stage. The integrity and validity of proposed crack closure model is also further verified by FCGR data of other researchers. [ABSTRACT FROM AUTHOR]

• FCG behavior is explained by compressive load effect and crack closure. • Variation of crack closure level at negative load ratio is obtained by experiment. • Influence of crack closure effect is described to explain anomaly in pre-stage. In this paper, the effect of compressive load and crack closure on mode-I fatigue crack growth (FCG) behavior at negative load ratios is studied with compact-tensile-shear (CTS) specimens made from commercial pure titanium (CP-Ti). The FCG behavior at negative load ratios under constant maximum load controlled has been explained by the interaction of compressive load effect and crack closure. The variation of crack closure level at negative load ratios within stable crack growth stage is obtained by the experiment. The crack closure level keeps constant which makes the crack closure effect dominate the FCG behavior in pre-stage. While in post-stage, the crack closure level drops gradually. The crack closure effect can be neglected currently and the compressive load effect plays a dominate role in post-stage. Meanwhile, the influence of crack closure effect on mechanical behavior at crack tip is described by finite element method (FEM) to explain the anomaly in pre-stage. It is confirmed that there exists a maximum reversed plastic zone induced by the crack closure effect during unloading process in pre-stage at negative load ratios. [ABSTRACT FROM AUTHOR]

In this paper, the distinct influences of pre-strain on low cycle fatigue (LCF) behavior of CP-Ti at different strain amplitudes are clarified from macroscopic and microscopic aspects. At low strain amplitude, the sample of as-received material (AR) shows pronounced secondary cyclic hardening, however, this phenomenon gradually disappears in pre-strained (PS) sample with the increase of pre-strain. As cyclic stress amplitude and mean stress of PS sample increase with the decrease of strain amplitude, the detrimental effect of pre-strain on LCF life becomes more significant at lower strain amplitude, indicating the pre-strain dependent LCF behavior. At high strain amplitude, due to the more significant cyclic softening and mean stress reduction behavior, cyclic stress amplitude and mean stress rapidly decay to the value of AR sample in the initial few cycles, indicating the pre-strain independent LCF behavior. As the reduction of LCF life is related to the increase of mean stress and stress amplitude, the asymmetry coefficient related model can be applied to predict LCF life of CP-Ti. Further TEM observation shows that at low strain amplitude, dislocation structures of AR sample are mainly composed of planar slip structures and the secondary cyclic hardening is caused by corduroy structure. After pre-strain, both planar slip and wavy slip structures are observed in PS sample, indicating that the irreversibility of the dislocation structures inherited from pre-strain causes the decrease of LCF life. At high strain amplitude, the dislocation structures introduced by pre-strain can be erased completely during subsequent cyclic deformation, consequently, dislocation configurations of AR and PS samples are composed of the same wavy slip structures. [ABSTRACT FROM AUTHOR]

Astrocytes are critical regulators of the immune/inflammatory response in several human central nervous system (CNS) diseases. Emerging evidence suggests that dysfunctional astrocytes are crucial players in seizures. The objective of this study was to investigate the role of transient receptor potential vanilloid 4 (TRPV4) in 4-aminopyridine (4-AP)-induced seizures and the underlying mechanism. We also provide evidence for the role of Yes-associated protein (YAP) in seizures. 4-AP was administered to mice or primary cultured astrocytes. YAP-specific small interfering RNA (siRNA) was administered to primary cultured astrocytes. Mouse brain tissue and surgical specimens from epileptic patient brains were examined, and the results showed that TRPV4 was upregulated, while astrocytes were activated and polarized to the A1 phenotype. The levels of glial fibrillary acidic protein (GFAP), cytokine production, YAP, signal transducer activator of transcription 3 (STAT3), intracellular Ca 2+ ([Ca 2+ ] 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 [Ca 2+ ] 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/Ca 2+ /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., (© 2022. The American Society for Experimental NeuroTherapeutics, Inc.)

Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures. Recent studies have shown that complement component 3 (C3) aggravate the neuronal injury in epilepsy. And our previous studies revealed that TRPV1 (transient receptor potential vanilloid type 1) is involved in epilepsy. Whether complement C3 regulation of neuronal injury is related to the activation of TRPV1 during epilepsy is not fully understood. We found that in a mouse model of status epilepticus (SE), complement C3 derived from astrocytes was increased and aggravated neuronal injury, and that TRPV1-knockout rescued neurons from the injury induced by complement C3. Circular RNAs are abundant in the brain, and the reduction of circRad52 caused by complement C3 promoted the expression of TRPV1 and exacerbated neuronal injury. Mechanistically, disorders of neuron-glia interaction mediated by the C3-TRPV1 signaling pathway may be important for the induction of neuronal injury. This study provides support for the hypothesis that the C3-TRPV1 pathway is involved in the prevention and treatment of neuronal injury and cognitive disorders., (© 2021. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences.)

Objective: To observe the effect of acupuncture stimulation of acupoints of the Conception Vessel, Kidney Meridian, Spleen Meridian, and Bladder Meridian on menstrual cycles and duration, and serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estrogen 2 (E(2)) levels in patients with diminished ovarian reserve (DOR)., Methods: A total of 96 patients with DOR of both yin and yang deficiency were randomly divided into medication group and acupuncture group (n = 48 cases in each group). Patients of the medication group were treated by Estradiol Valerate tablets, 2 mg/d on the first 10 days, and Estradiol Cyproterone, 3 mg/d from day 11 to 21, followed by 5 -7 days' rest, and the next therapeutic course, continuously for 6 months. For patients of the acupuncture group, filiform acupuncture needles were separately inserted into every 5 points of the Conceptional Vessel, Kidney, Spleen and Bladder Meridians, manipulated with uniform reinforcing and reducing methods till Deqi, and retained for 40 min. The treatment was conducted once daily for consecutive 10 days in one menstrual cycle, beginning from the 10(th) day on after menstruation, which was repeated for 6 months. The integrative scores (normal = 0, mild=2, moderate=4 and severe=6 points) of menstrual cycle, menstrual duration, amount, color, quality [blood blot or ame- nia, symptoms of traditional Chinese medicine (TCM)] were assessed according to "Guiding Principles for Clinical Trials of New Drugs of Chinese Materia Medica". Serum FSH, LH and E(2) contents were detected by Roche's electrochemical luminescence method., Results: After the treatment, of the two 48 cases in the medication and acupuncture groups, 12 (25.0%) and 20 (4.7) were cured, 11 (22.9 %) and 12 (25.0 %) experienced marked improvement in their symptoms, 20 (41.7%) and 10 (20.8%) were effective, and 5 (10.4%) and 6 (12.5%) failed, with the effective rate being 89.6% and 87.5%, respectively. The integral score of TOM symptoms, menstrual cycle, serum FSH, LH and E2 contents were considerably diminished in both groups after 6 months of treatment (P<0.05), and the TOM symptom score, menstrual cycle, and serum FSH, LH and E2 levels were significantly lower in the acupuncture group than in the medication group 6 months after cease of the treatment (P<0.05), while the menstrual duration in each cycle was notably longer in both groups after the treatment, and evidently longer in the acupuncture group than in the medication group 6 months after cease of the treatment (P<0.05). No significant differences were found between the two groups in the effective rate, score of TOM symptoms, menstrual cycle and duration, and serum FSH, LH and E(2) contents following the treatment (P>0.05)., Conclusion: Acupuncture stimulation of acupoints of the Conception Vessel, Kidney, Spleen, and Bladder Meridians is effective in improving clinical symptoms of DOR patients with deficiency of both yin and yang, and has a longer effect, which may be closely associated with its functions in lowering serum FSH, LH and E(2) levels through regulating the hypothalamic-pituitary-ovarian axis.

Background: Existing literature has shown that patients with coronary artery disease (CAD) can benefit greatly from the strength training; therefore, the strength training should play a more important role in cardiac rehabilitation. However, the medical community may still have conservation to apply the strength training owing to no comprehensive study so far to compare the effectiveness of the strength training to the other trainings, such as aerobic training., Objective: To evaluate the effect of strength training on motor function in patients with CAD., Methods: Published articles from the earliest date available to July 2015 were identified using electronic searches. Two reviewers selected independently relevant randomized controlled trials (RCTs) investigating exercise program with strength training versus control interventions (exercise without strength training, including aerobic training and no exercise group) for the treatment of CAD patients. We examined effects of exercise with strength training versus control interventions on peak oxygen uptake (VO2peak), duration of exercise test and muscle strength. Two reviewers extracted data independently., Results: Twenty seven trials that represented 1151 participants passed the selection criteria and were evaluated for the effects of strength training in CAD patients. For improving VO2peak [SMD (95%CI) = 0.58 (0.11, 1.06)] and muscle strength [upper limb, SMD (95% CI) =0.44 (0.34, 0.55); lower limb, SMD (95% CI) =0.33 (0.16, 0.50)], exercise program with strength training were significantly more effective than one without it. But there is no significantly difference on duration of exercise test [SMD (95%CI) = 0.17 (-0.04, 0.39)] in strength training group than in control group., Conclusions: We conclude strength training is effective in improving muscle strength and VO2peak, in CAD patients, when compared to patients with control group. Furthermore, our evaluations suggest that strength training does not compromise clinical trial completion or safety.

Foamy virus can establish lifelong persistent infection in mammal hosts without inducing diseases. Such special characteristic stimulates the interests of researchers. As reported, the accessory protein Bet of foamy virus could regulate the gene expression and infection cycle of foamy virus and take part in the generation of chronic viral infection. And also, Bet might prevent the host cellular defense factor APO-BEC3 from interfering the replication of virus and play a role in maintaining viral persistent infection. In order to elucidate the roles of Bet in the foamy virus replication and infection, this review summarized the research progress of Bet protein reported in recent years.