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Abstract Background Widespread neuropathic pain usually affects a wide range of body areas and inflicts huge suffering on patients. However, little is known about how it happens and effective therapeutic interventions are lacking. Methods Widespread neuropathic pain was induced by partial infraorbital nerve transection (p-IONX) and evaluated by measuring nociceptive thresholds. In vivo/vitro electrophysiology were used to evaluate neuronal activity. Virus tracing strategies, combined with optogenetics and chemogenetics, were used to clarify the role of remodeling circuit in widespread neuropathic pain. Results We found that in mice receiving p-IONX, along with pain sensitization spreading from the orofacial area to distal body parts, glutamatergic neurons in the ventral posteromedial nucleus of the thalamus (VPMGlu) were hyperactive and more responsive to stimulations applied to the hind paw or tail. Tracing experiments revealed that a remodeling was induced by p-IONX in the afferent circuitry of VPMGlu, notably evidenced by more projections from glutamatergic neurons in the dorsal column nuclei (DCNGlu). Moreover, VPMGlu receiving afferents from the DCN extended projections further to glutamatergic neurons in the posterior insular cortex (pIC). Selective inhibition of the terminals of DCNGlu in the VPM, the soma of VPMGlu or the terminals of VPMGlu in the pIC all alleviated trigeminal and widespread neuropathic pain. Conclusion These results demonstrate that hyperactive VPMGlu recruit new afferents from the DCN and relay the extra-cephalic input to the pIC after p-IONX, thus hold a key position in trigeminal neuropathic pain and its spreading. This study provides novel insights into the circuit mechanism and preclinical evidence for potential therapeutic targets of widespread neuropathic pain.

Developing high strain rate (HSR) forming technologies is significant for efficient and high-quality aerospace sheet metal parts manufacturing. Research on the deformation behaviors and micromechanism of materials under HSRs will contribute to the further application of HSR forming technologies. In this study, the mechanical behavior of AA1060 pure aluminum at low strain rates (LSRs, 0.001 s−1 and 0.1 s−1) and high strain rates (HSRs, 2400 s−1 and 3300 s−1) was tested utilizing quasistatic tensile tests and Hopkinson bar tests at room temperature. The results of the mechanical properties showed that the elongations were 30.01 %, 37.91 %, and 46.61 %, corresponding to strain rates of 0.1 s−1, 2400 s−1, and 3300 s−1, respectively, which were 29.86 % at a strain rate of 0.001 s−1. The maximum amplification of AA1060 elongation reached 56.10 % at the HSR. Microstructure characteristics, including the Schmid factor distribution, geometrically necessary dislocation (GND) distribution, slip band, and dislocation cell, were observed by electron backscattering diffraction (EBSD) and transmission electron microscopy (TEM) under the condition of the same elongation with strain rates of 0.001 s−1 and 3300 s−1. In addition, the reasons for the plastic improvements during HSR loading were also investigated. The hard-oriented grains participate in plastic deformation at HSRs, providing additional space for dislocation multiplication and movement, increased dislocation density, and interaction between dislocations. In addition, the deformed hard-oriented grains also coordinated the strain gradient with soft-oriented grains. This improved the overall deformation uniformity, thus avoiding the premature occurrence of strain localization, namely, the elongation increase.

AA2060-T8 is a relatively new Al–Cu–Li alloy developed in the last few years as a lightweight alternative to conventional Al alloys. Thus, it is essential to characterize the warm flow, fracture, and anisotropic behaviours of this alloy and propose constitutive analysis-based crystal plasticity (CP) modelling to link its mechanical behaviour with the microstructural state. Therefore, in this study, isothermal warm tensile tests were conducted using a Gleeble-3800 thermomechanical simulator and different sample orientations at temperatures and strain rates varying from 373 to 573 K and 0.001–0.1 s−1, respectively. The tensile behaviour of the 2060 Al–Cu–Li alloy sheet depends on the sample orientations, which results in significant anisotropy. The anisotropic degree of the tensile properties of this alloy was significantly reduced by increasing the forming temperature above 473 K. In addition, the fracture behaviours of 2060 Al–Cu–Li sheets were transformed from mixed ductile-brittle fracture mode to ductile fracture mode by decreasing strain rates and increasing the temperatures, respectively. Afterward, a novel crystal plasticity model was proposed to describe the grain behaviour and the deformation mechanism of 2060 Al–Cu–Li alloy under warm forming conditions. The developed constitutive model was implemented using the monolithic time-integration algorithm-based backward Euler method. The results acquired from the proposed constitutive analysis agree well with those obtained from experimentation in all testing conditions. This indicates its ability to accurately predict the warm flow behaviour of 2060 Al–Cu–Li alloy under different strain rates and loading directions.

Micron-size Ni-base alloy (NBA) powders were mixed with both 1.5 wt.% (hereinafter %) micron-size CeO2 (m-CeO2) and also 1.5% and 3.0% nano-size CeO2 (n- CeO2) powders. These mixtures were coated on low-carbon steel (Q235) by 2.0 kW CO2 laser cladding. The effects on the microstructures, phases and electrochemical corrosion of the coatings upon the addition of m- and n- CeO2 powders to NBA (m- and n- CeO2 /NBA) have been investigated. The results showed that a smooth coating was prepared under suitable processing parameters (P= 2.0 kW, V= 180 mm min- 1) by adding 1.5% n- CeO2. In addition to the primary phases of γ-Ni, Cr23 C6 and Ni3 B in the Ni-base alloy coating, CeNi3 was formed in Ni-base alloy coatings with both n- CeO2 and m-CeO2 particles, and CeNi5 appeared in the coating upon decreasing the size of CeO2 particles. Well-developed dendrites were observed in the Ni-base alloy coating; directional dendrites grew at the interface in the coating upon the addition of m-CeO2, whereas fine and multioriented dendrites grew upon decreasing the size of CeO2 particles to the nanoscale. Actinomorphic dendrites and compact equiaxed dendrites grew from the interface to near the surface upon increasing the content of n- CeO2 from 1.5 to 3.0%. In strongly acidic HNO3 solution, the severe corrosion of dendrites occurred and there were many corrosion pits in the Ni-base alloy coating; intercrystalline corrosion also has a dominant role upon the addition of m-CeO2, whereas uniform corrosion occurs in the coating as the size of CeO2 particles is decreased to nanoscale.

A positioning grid is a key clamping structure for fixing the transverse and axial positions of fuel assemblies in nuclear reactors, and it is generally prepared by the transverse stamping of a Zr-4 sheet. However, the texture formed in the processing process of Zr-4 sheets can affect formability, resulting in cracking in the stamping process. Therefore, the relationship between the formability of Zr-4 sheets and the normal Kearns factor (Fn) of basal texture was studied in this paper. The results showed that the Zr-4 sheet with an Fn equaling 0.720, prepared by an isobaric reduction rolling process, would crack in the stamping process. To avoid the cracking during stamping, the formability improvement of Zr-4 sheets based on texture optimization was discussed. By using the finite element model (FEM) and a visco plastic self-consistent (VPSC) model coupled simulation, the relationship between the initial textures and formabilities of Zr-4 sheet is established. It is found that the hardening exponents (n) decreased with increasing Fns in VPSC simulations. Meanwhile, as the Fn increases, cracks are prone to occur at the bottom corner of the stamped sheet in finite element simulation. Given the results from FEM and VPSC simulations, it is proposed that the Fn should be controlled to be less than 0.7 for preventing cracks in the sheet during stamping. Additionally, a new rolling process named non-isobaric reduction rolling was designed in which the Fn of the Zr-4 sheet is successfully reduced to 0.690. The stamping results indicate that the sheet is free of cracks under an Fn of 0.690. Therefore, texture optimization with the proposed rolling process can improve the formability of Zr-4 sheets, which effectively solves the cracking problem of Zr-4 sheets.

A phenomenological model for the prediction of the forming limit curve (FLC) based on basic mechanical properties through a uniaxial tensile test can tremendously shorten the design time of the forming process and reduce the measuring costs. In this paper, a novel phenomenological model named the IMR-Baosteel model (abbreviated as the IB model) is proposed for efficient and accurate FLC prediction of hot-rolled steel sheets featuring distinct variations in thickness and mechanical properties. With a systematic test of the plane strain forming limit (FLC0), it was found that a higher regression correlation exists between the FLC0 and the total elongation under different sheet thicknesses. For accurate assessment of the FLC0 from tensile properties, compared using experiments, the error of FLC0 calculated with the proposed model is within 10%. In the IB model, the left side of FLC can be calculated using a line with a slope of −1 while the right side of the FLC is obtained via a modified Keeler model with the exponent (p) determined as 0.45 for hot-rolled steels. Complete experimental FLCs of hot-rolled steels from measurements and the literature were used to validate the reliability of the proposed model. Resultantly, the prediction of FLCs with the proposed IB model is greatly improved, and agrees much better with the experimental FLCs than the predictions of the well-known Keeler model, Arcelor model and Tata Steel model.

Abstract Background Whether neuroinflammation causes comorbid mood disorders in neuropathic pain remains elusive. Here we investigated the role of high mobility group box 1 protein (HMGB1), a proinflammatory cytokine, in the medial prefrontal cortex (mPFC) in anxiety comorbidity of neuropathic pain. Methods Neuropathic pain was induced by partial transection of the infraorbital nerve (p-IONX) or partial sciatic nerve ligation (PSL) in mice and evaluated by measuring nociceptive thresholds to mechanical and heat stimulation. Anxiety-like behaviors were assessed by elevated plus maze, light dark box and open field tests. Aversive or anti-aversive effect was detected by conditioned place preference test. Neuronal activity was evaluated by single-unit and patch clamp recordings. The contribution of mPFC pyramidal neurons to anxiety was further examined by selectively inhibiting them by optogenetics. HMGB1 expression was measured by immunohistochemistry and western blotting. Antagonism of HMGB1 was achieved by injecting anti-HMGB1 monoclonal antibody (mAb) intracerebrally or intraperitoneally. Results Anxiety-like behaviors were presented earlier after p-IONX than after PSL. HMGB1 expression was upregulated in the mPFC temporally in parallel to anxiety onset, rather than in other regions associated with anxiety. The upregulation of HMGB1 expression and its translocation from the nucleus to cytoplasm in the mPFC occurred predominantly in neurons and were accompanied with activation of microglia and astrocytes. Infusion of anti-HMGB1 mAb into the mPFC during the early and late phases after either p-IONX or PSL alleviated anxiety-like behaviors and aversion without changing pain sensitization, while local infusion of exogenous ds-HMGB1, the proinflammatory form of HMGB1, into the mPFC induced anxiety and aversion but not pain sensitization in naïve mice. In addition to reversing established pain sensitization and anxiety simultaneously, intraperitoneal injection of anti-HMGB1 mAb reduced HMGB1 upregulation and suppressed the hyperexcitability of layer 2/3 pyramidal neurons in the mPFC after p-IONX. Moreover, optogenetic inhibition of mPFC pyramidal neurons alleviated anxiety in p-IONX mice. Conclusion These results demonstrate that HMGB1 in the mPFC drives and maintains anxiety comorbidity in neuropathic pain by increasing the excitability of layer 2/3 pyramidal neurons, and justify antagonism of HMGB1, e.g., neutralization by mAb, as a promising therapeutic strategy for neuropathic pain with anxiety comorbidity.

A series of novel Cu-2Ag-xLa alloys with reinforced mechanical properties and enhanced electrical conductivities are developed. The effects of La addition on the microstructural features and mechanical properties of as-cast and solution treated Cu-2Ag alloys are systematically investigated. The yielding strength of as-cast Cu-2Ag alloys with 0.02La and 0.07La (wt.%) is considerably reinforced by relative amounts of 55.56% and 30.16%, respectively. The strengthening mechanism for such increased yielding strength is mainly related to the shifting of interfacial relation between matrix and Ag-rich phase from original semi-coherent type to non-coherent type with La doping. Consequently, the interface barrier strength is enhanced by the non-coherent interface, and contributes to the increased yielding strength. Meanwhile, the strengthening effect from La addition closely depends on the exact contents of La element. As La content increases from 0.02 to 0.07 (wt.%), the strengthening effect becomes weaker because of the increased space of Ag-rich phases leading to an 16.33% decrease in yield strength. Additionally, La has dual effects on the dissolution of Ag-rich phases and precipitation of new La-rich phase in the as-cast alloys during solution treatment. Simultaneously, the precipitation of the La-rich phase abnormally enhances the electrical conductivity of the solution La-containing alloys when the solution time exceeds 24 h.

Abstract Background Colorectal cancer (CRC) is the leading cause of cancer death worldwide. Screening is a confirmed way to reduce the incidence and mortality rates of CRC. This study aimed to identify a fecal-based, noninvasive, and accurate method for detection of colorectal cancer (CRC) and advanced adenoma (AA). Methods Through detection in tissue (n = 96) and fecal samples (n = 88) and tested in an independent group of fecal samples (n = 294), the methylated DNA marker ITGA4 and bacterial markers Fusobacterium nucleatum (Fn) and Pepetostreptococcusanaerobius (Pa) were identified from the candidate biomarkers for CRC and AA detection. A prediction score (pd-score) was constructed using the selected markers and fecal immunochemical test (FIT) for distinguishing AA and CRC from healthy subjects by logistic regression method. The diagnostic performance of the pd-score was compared with FIT and validated in the external validation cohort (n = 117) and in a large CRC screening cohort. Results The pd-score accurately identified AA and CRC from healthy subjects with an area under the curve (AUC) of 0.958, at a specificity of 91.37%; the pd-score showed sensitivities of 95.38% for CRC and 70.83% for AA, respectively. In the external validation cohort, the sensitivities of the pd-score for CRC and AA detection were 94.03% and 80.00%, respectively. When applied in screening, the pd-score identified 100% (11/11) of CRC and 70.83% (17/24) of AA in participants with both colonoscopy results and qualified fecal samples, showing an improvement by 41.19% compared to FIT. Conclusions The current study developed a noninvasive and well-validated approach for AA and CRC detection, which could be applied widely as a diagnostic and screening test.

Abstract Background The rice blast is a typical fungal disease caused by Magnaporthe oryzae, and the mitochondrial ATP-dependent Lon protease (MAP1) has been proven to be involved in blast development. We previously screened a C3HC type Zinc-finger domain protein (ZFC3), which is interacted with MAP1. The purpose of this research was to study the biological function of ZFC3 protein in M. oryzae. Results We first confirmed that the ZFC3-RFP fusion protein is localized within the mitochondria. The deleted mutant strains of ZFC3 (∆ZFC3) showed the enhanced expression level of mtATP6, particularly mtATP8, and almost unchanged nATP9. ΔZFC3 produces more conidia and more tolerance to multiple stressors. The knock-out strain shows more melanin accumulation suggests the susceptibility to aging. ΔZFC3 displays faster early-stage hypha infiltration involved in MAP1-mediated pathogenicity in host rice. Conclusion These results support the view that ZFC3 is a key regulator involved in gene regulation, stress response, cell wall integrity, longevity, conidiation, infection hypha development and MAP1-mediated pathogenicity in M. oryzae.

The interconversion of CO2 and HCO3− catalyzed by carbonic anhydrases (CAs) is a fundamental biochemical process in organisms. During mammalian–pathogen interaction, both host and pathogen CAs play vital roles in resistance and pathogenesis; during planta–pathogen interaction, however, plant CAs function in host resistance but whether pathogen CAs are involved in pathogenesis is unknown. Here, we biologically characterized the Magnaporthe oryzae CA (MoCA1). Through detecting the DsRED-tagged proteins, we observed the fusion MoCA1 in the mitochondria of M. oryzae. Together with the measurement of CA activity, we confirmed that MoCA1 is a mitochondrial zinc-binding CA. MoCA1 expression, upregulated with H2O2 or NaHCO3 treatment, also showed a drastic upregulation during conidiogenesis and pathogenesis. When MoCA1 was deleted, the mutant ΔMoCA1 was defective in conidiophore development and pathogenicity. 3,3′-Diaminobenzidine (DAB) staining indicated that more H2O2 accumulated in ΔMoCA1; accordingly, ATPase genes were downregulated and ATP content decreased in ΔMoCA1. Summarily, our data proved the involvement of the mitochondrial MoCA1 in conidiogenesis and pathogenesis in the rice blast fungus. Considering the previously reported HCO3− transporter MoAE4, we propose that MoCA1 in cooperation with MoAE4 constitutes a HCO3− homeostasis-mediated disease pathway, in which MoCA1 and MoAE4 can be a drug target for disease control.

ObjectiveRepetitive Transcranial Magnetic Stimulation (rTMS) has been used in cognition impairment due to various neuropsychiatric disorders. However, its optimum parameters and the neuroimaging mechanism are still of uncertainty. In order to simulate a study setting as close to real world as possible, the present study introduces a new orthogonally-designed protocol, consisting of the rTMS intervention with four key parameters (stimulating site, frequency, intensity and pulse number) and three different levels in each one, and aims to investigate the optimum parameters and the brain activity and connectivity in default mode network (DMN), dorsal attention network (DAN), central executive network (CEN) following rTMS intervention to post-stroke cognition impairment (PSCI).MethodsA single-center, orthogonally-designed, triple-blind randomized controlled trial will be conducted and forty-five PSCI patients will be recruited and randomly assigned to one of nine active rTMS groups based on four rTMS paraments: stimulating site, frequency, intensity and pulse number. Neuropsychological, activities of daily living, quality of life and functional magnetic resonance imaging (fMRI) evaluations were be performed pre-, post- and 3 months after rTMS.DiscussionThis study evaluates the optimum parameters of rTMS for patients with post-stroke cognition impairment and explores the alteration of neural function in DMN, DAN, CEN brain network. These results would facilitate the standardized application of rTMS in cognition impairment rehabilitation.

Dihydroxynapthalene-(DHN) and L-dihydroxyphenylalanine (L-DOPA) are two types of dominant melanin in fungi. Fungal melanins with versatile functions are frequently associated with pathogenicity and stress tolerance. In rice blast fungus, Magnaporthe oryzae, DHN melanin is essential to maintain the integrity of the infectious structure, appressoria; but the role of the tyrosinase-derived L-DOPA melanin is still unknown. Here, we have genetically and biologically characterized a tyrosinase gene (MoTyr) in M. oryzae. MoTyr encodes a protein of 719 amino acids that contains the typical CuA and CuB domains of tyrosinase. The deletion mutant of MoTyr (ΔMoTyr) was obtained by using a homologous recombination approach. Phenotypic analysis showed that conidiophore stalks and conidia formation was significantly reduced in ΔMoTyr. Under different concentrations of glycerol and PEG, more appressoria collapsed in the mutant strains than in the wild type, suggesting MoTyr is associated with the integrity of the appressorium wall. Melanin measurement confirmed that MoTyr loss resulted in a significant decrease in melanin synthesis. Accordingly, the loss of MoTyr stunted the conidia germination under stress conditions. Importantly, the MoTyr deletion affected both infection and pathogenesis stages. These results suggest that MoTyr, like DHN pigment synthase, plays a key role in conidiophore stalks formation, appressorium integrity, and pathogenesis of M. oryzae, revealing a potential drug target for blast disease control.

Objective: Postmenopausal osteoporosis (PMOP), a chronic systemic metabolic disease prevalent in middle-aged and elderly women, heavily relies on bone mineral density (BMD) measurement as the diagnostic indicator. In this study, we investigated serum microRNAs (miRNAs) as a possible screening tool for PMOP. Methods: This investigation recruited 83 eligible participants from 795 community-dwelling postmenopausal women between June 2020 and August 2021. The miRNA expression profiles in the serum of PMOP patients were evaluated via miRNA microarray (six PMOP patients and four postmenopausal women without osteoporosis (n-PMOP) as controls). Subsequently, results were verified in independent sample sets (47 PMOP patients and 26 n-PMOP controls) using quantitative real-time PCR. In addition, the target genes and main functions of the differentially expressed miRNAs were explored by bioinformatics analysis. Results: Four highly expressed miRNAs in the serum of patients (hsa-miR-144-5p, hsa-miR-506-3p, hsa-miR-8068, and hsa-miR-6851-3p) showed acceptable disease-independent discrimination performance (area under the curve range: 0.747–0.902) in the training set and verification set, outperforming traditional bone turnover markers. Among four key miRNAs, hsa-miR-144-5p is the only one that can simultaneously predict changes in BMD in lumbar spine 1–4, total hip, and femoral neck (β = −0.265, p = 0.022; β = −0.301, p = 0.005; and β = −0.324, p = 0.003, respectively). Bioinformatics analysis suggested that the differentially expressed miRNAs were targeted mainly to YY1, VIM, and YWHAE genes, which are extensively involved in bone metabolism processes. Conclusions: Bone-metabolism-related serum miRNAs, such as hsa-miR-144-5p, hsa-miR-506-3p, hsa-miR-8068, and hsa-miR-6851-3p, can be used as novel biomarkers for PMOP diagnosis independent of radiological findings and traditional bone turnover markers. Further study of these miRNAs and their target genes may provide new insights into the epigenetic regulatory mechanisms of the onset and progression of the disease.

Human PTEN, a dual-phosphatase tumor suppressor, is frequently dysregulated by alternative splicing. Fungi harbor PTEN homologs, but alternative splicing of fungal PTENs has not been reported as far as we know. Here, we described an alternative splicing case in the PTEN homolog of Magnaporthe oryzae (MoPTEN). Two splice variants of MoPTEN were detected and identified, which are resulted from an intron retention and exclusion (MoPTEN-1/2). Both proteins were different in lipid and protein phosphatase activity and in expression patterns. The MoPTEN deletion mutant (ΔMoPTEN) showed the defects in conidiation, appressorium formation, and pathogenesis. ΔMoPTEN could be completely restored by MoPTEN, but rescued partially by MoPTEN-1 in the defect of conidium and appressorium formation, and by MoPTEN-2 in the defect of invasive development. Assays to assess sensitivity to oxidative stress reveal the involvement of MoPTEN-2 in scavenging exogenous and host-derived H2O2. Taken together, MoPTEN undergoes alternative splicing, and both variants cooperatively contribute to conidium and appressorium development, and invasive hyphae growth in plant cells, revealing a novel disease development pathway in M. oryzae.

Since AA2060-T8 was introduced in the past few years, investigating the mechanical response, fracture mechanisms, and anisotropic behaviour of AA2060-T8 sheets under high strain rate deformation has been crucial. Thus, uniaxial tensile tests were performed under quasi-static, intermediate, and high strain rate conditions using universal testing machines as well as split Hopkinson tensile bars. The experimental results showed that the ductility of AA2060-T8 sheets was improved during high strain rate deformation because of the adiabatic softening and the inertia effect which contribute to slow down the necking development, and these results were verified by the fracture morphologies of high strain rate tensile samples. Furthermore, the strain rate hardening influence of AA2060-T8 was significant. Therefore, the Johnson–Cook constitutive model was modified to consider the effects of both strain and strain rates on the strain hardening coefficient. The results obtained from the improved Johnson–Cook constitutive model are in remarkable accordance with those obtained from experimental work. Thus, the improved Johnson–Cook model can predict the flow behavior of AA2060-T8 sheets at room temperature over a wide range of strain rates. The results of the present study can efficiently be used to develop a new manufacturing route based on impact hydroforming technology (IHF) to manufacture sound thin-walled-complex shape components from AA2060-T8 sheets at room temperature. Keywords: AA2060, High strain rate deformation, Dynamic behavior, Anisotropic response, Phenomenological-based constitutive modelling

ABSTRACT: Mineral potential assessment at the Earth’s surface has been an important research for geoscientists around the world in the past five decades. The fundamental aspects of mineral assessment at different scales can be associated with the following tasks, e.g., mineral potential mapping and estimation of mineral resources. This paper summarized the history and development in terms of theories, methods technologies and software platforms for quantitative assessment of mineral resources in China, e.g. comprehensive information methodology, geological anomaly, three-component quantitative prediction method, 5P ore-finding area, integrated information assessment method, nonlinear process modeling and fractals, three dimensional mineral potential mapping, etc. At last, to discuss the future of quantitative mineral assessment in an era of big data including platform for 3D visualization, analysis and sharing, new methods and protocols for data cleaning, information enhancement, information integration, and uncertainties and multiple explanations of multi-information.© 2019 China Geology Editorial Office.

Since AA2060-T8 was launched the past few years, it was crucial to understand the deformation behavior and to establish a multi-scale model that can link the microstructural state of this alloy with its mechanical behavior. Thus, a computational homogenization-based crystal plasticity modeling was proposed to predict the deformation behavior and capture the anisotropic response of AA2060-T8 at different deformation conditions. Uniaxial tensile tests were accomplished at room temperature and strain rates of 0.001 and 0.1 s−1 using samples with different fiber orientations to experimentally investigate the deformation behavior and anisotropic response of AA2060-T8. Thereafter, to clarify the details of the in-grain deformation features, a representative volume element was established to describe the real microstructure of AA2060-T8 in which each grain was discretized using many finite elements. Afterwards, a dislocation density-based crystal plasticity model was developed to describe the behavior of grains and simulate the plastic deformation of AA2060-T8. The material parameters utilized in the crystal plasticity model was determined from the stress–strain curves of the samples tested at loading direction of 30° with respect to rolling direction and strain rate of 0.001 s−1. Additionally, a periodic boundary condition was modified to consider both geometrical and deformation induced anisotropy. The achieved results from the proposed computational homogenization method are in remarkable agreement with that obtained from experimental work. This means that the proposed computational homogenization method is able to predict the deformation behavior and capture the anisotropic response of AA2060-T8 at various deformation conditions. Keywords: Deformation behavior, Anisotropic response, AA2060, Crystal plasticity finite element modeling, Computational homogenization

The phosphorylation status of proteins, which is determined by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs), governs many cellular actions. In fungal pathogens, phosphorylation-mediated signal transduction has been considered to be one of the most important mechanisms in pathogenicity. Colletotrichum graminicola is an economically important corn pathogen. However, whether phosphorylation is involved in its pathogenicity is unknown. A mitochondrial protein tyrosine phosphatase gene, designated CgPTPM1, was deduced in C. graminicola through the use of bioinformatics and confirmed by enzyme activity assays and observation of its subcellular localization. We then created a CgPTPM1 deletion mutant (ΔCgPTPM1) to analyze its biological function. The results indicated that the loss of CgPTPM1 dramatically affected the formation of conidia and the development and differentiation into appressoria. However, the colony growth and conidial morphology of the ΔCgPTPM1 strains were unaffected. Importantly, the ΔCgPTPM1 mutant strains exhibited an obvious reduction of virulence, and the delayed infected hyphae failed to expand in the host cells. In comparison with the wild-type, ΔCgPTPM1 accumulated a larger amount of H2O2 and was sensitive to exogenous H2O2. Interestingly, the host cells infected by the mutant also exhibited an increased accumulation of H2O2 around the infection sites. Since the expression of the CgHYR1, CgGST1, CgGLR1, CgGSH1 and CgPAP1 genes was upregulated with the H2O2 treatment, our results suggest that the mitochondrial protein tyrosine phosphatase PTPM1 plays an essential role in promoting the pathogenicity of C. graminicola by regulating the excessive in vivo and in vitro production of H2O2.

Fungal sexual development requires the involvement of a large number of functional genes. Fungal genes encoding sexual differentiation process proteins (SDPs), isps, have been known for decades. isp4/SDP and its homologs function as oligopeptide transporters (OPTs), yet their roles in reproduction are unknown. Here, we genetically analyzed all four isp4/SDP homologs in the sexual species Chaetomium thermophilum and asexual species Thermomyces lanuginosus. Using single gene deletion mutants, we found that T. lanuginosus SDP (TlSDP) participated in asexual sporulation, whereas the other homologs participated in sexual morphogenesis. In complementary tests, C. thermophilum SDPs (CtSDP1-3) restored sporulation defects in TlSDP deletion strains (ΔTlSDP), and their translated proteins, which were localized onto the cytomembrane, possessed OPT activity. Interestingly, CtSDP2 accumulated at the top of the hyphae played a distinct role in determining the sexual cycle, glutathione transport, and lifespan shortening. A unique 72nt-insertion fragment (72INS) was discovered in CtSDP2. Biological analysis of the 72INS deletion and DsRED-tagged fusion strains implied the involvement of 72INS in fungal growth and development. In contrast to TlSDP, which only contributes to conidial production, the three CtSDPs play important roles in sexual and asexual reproduction, and CtSDP2 harbors a unique functional 72INS that initiates sexual morphogenesis.

Al-Li alloys are attractive for military and aerospace applications because their properties are superior to those of conventional Al alloys. Their exceptional properties are attributed to the addition of Li into the Al matrix, and the technical reasons for adding Li to the Al matrix are presented. The developmental history and applications of Al-Li alloys over the last few years are reviewed. The main issue of Al-Li alloys is anisotropic behavior, and the main reasons for the anisotropic tensile properties and practical methods to reduce it are also introduced. Additionally, the strengthening mechanisms and deformation behavior of Al-Li alloys are surveyed with reference to the composition, processing, and microstructure interactions. Additionally, the methods for improving the formability, strength, and fracture toughness of Al-Li alloys are investigated. These practical methods have significantly reduced the anisotropic tensile properties and improved the formability, strength, and fracture toughness of Al-Li alloys. However, additional endeavours are required to further enhance the crystallographic texture, control the anisotropic behavior, and improve the formability and damage tolerance of Al-Li alloys.

The TP2 copper tube was prepared with La microalloying by horizontal continuous casting (HCC). The absorptivity of La and its effects on microstructure, tensile and corrosion properties of HCC TP2 copper tube were studied by means of the inductively coupled plasma optical emission spectrometer (ICP-OES), optical microscope (OM), scanning electron microscope (SEM) and potentiodynamic polarization measurements. The results show that the absorptivity of La in the HCC TP2 copper tube is about 15% under antivacuum conditions due to the good chemical activities of La. The impurity elements in copper tube such as O, S, Pb and Si can be significantly reduced, and the average columnar dendrite spacing of the copper tube can also be reduced from 2.21 mm to 0.93 mm by adding La. The ultimate tensile strength and the elongation with and without La addition are almost unchanged. However, the annual corrosion rate of the HCC TP2 copper tube is reduced from 10.18 mm•a-1 to 9.37 mm•a-1 by the purification effect of trace La.

Bicarbonate (HCO3−) transporter family including the anion exchanger (AE) group is involved in multiple physiological processes through regulating acid-base homeostasis. HCO3− transporters have been extensively studied in mammals, but fungal homologues of AE are poorly understood. Here, we characterized the AE group member (MoAE4) in Magnaporthe oryzae. MoAE4 exhibits more sequence and structure homologies with the reported AE4 and BOR1 proteins. In addition to the common sublocalization on cytomembrane, MoAE4 also localizes on tonoplast. Yeast complementation verified that MoAE4 rescues boron sensitivity and endows NaHCO3 tolerance in the BOR1 deleted yeast. MoAE4 gene is bicarbonate induced in M. oryzae; and loss of MoAE4 (ΔMoAE4) resulted in mycelial growth inhibited by NaHCO3. Lucigenin fluorescence quenching assay confirmed that ΔMoAE4 accumulated less HCO3− in vacuole and more HCO3− in cytosol, revealing a real role of MoAE4 in bicarbonate transport. ΔMoAE4 was defective in conidiation, appressorium formation, and pathogenicity. More H2O2 was detected to be accumulated in ΔMoAE4 mycelia and infected rice cells. Summarily, our data delineate a cytomembrane and tonoplast located HCO3− transporter, which is required for development and pathogenicity in M. oryzae, and revealing a potential drug target for blast disease control.

Numerous thermostable enzymes have been reported from the hyperthermophilic archaeon Thermococcus kodakarensis KOD1, which made it an attractive resource for gene cloning. This research reported a glycosyl hydrolase (Tk-ChiA) form T. Kodakarensis with dual hydrolytic activity due to the presence of three binding domains with affinity toward chitin and cellulose. The Tk-ChiA gene was cloned and expressed on Pichia pastoris GS115. The molecular weight of the purified Tk-ChiA is about 130.0 kDa. By using chitosan, CMC-Na and other polysaccharides as substrates, we confirmed that Tk-ChiA with dual hydrolysis activity preferably hydrolyzes both chitosan and CMC-Na. Purified Tk-ChiA showed maximal activity for hydrolyzing CMC-Na at temperature 65°C and pH 7.0. It showed thermal stability on incubation for 4 h at temperatures ranging from 70 to 80°C and remained more than 40% of its maximum activity after pre-incubation at 100°C for 4 h. Particularly, Tk-ChiA is capable of degrading shrimp shell and rice straw through scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR) analysis. The main factors affecting shell and straw degradation were determined to be reaction time and temperature; and both factors were optimized by central composite design (CCD) of response surface methodology (RSM) to enhance the efficiency of degradation. Our findings suggest that Tk-ChiA with dual thermostable hydrolytic activities maybe a promising hydrolase for shell and straw waste treatment, conversion, and utilization.

Annexins (ANXs) are widely expressed and structurally related proteins which play multiple biological roles in animals, plants, and fungi. Although ANXs have been localized to the cytosol and the cell membrane and the molecular basis of the four annexin repeats is well established, the in vivo roles of these proteins are still far from clear, particularly with regard to the filamentous fungi. Thermomyces lanuginosus, a thermophilic fungus, is widely used in the fermentation industry; however, the role of ANX in this organism is unknown. In this study, a single ANX homologue (ANXC7) was identified and characterized in T. lanuginosus. The expression pattern indicated that ANXC7 is closely associated to conidium development, and it accumulated in the mitochondria of the forming conidia. The deletion of ANXC7 (ΔANXC7) resulted in no obvious phenotype related to colony growth on solid CM medium. However, when ΔANXC7 was grown in CM liquid culture, the mycelium masses appeared to be larger and looser compared to the wild-type. Additionally, the dry weight of the mutant mycelia was significantly increased. Under conditions that compromise cell-wall integrity, ΔANXC7 was less vulnerable than the wild-type with regard to such damage. Moreover, based on a surface hydrophobicity test, the ΔANXC7 strain was clearly less hydrophobic. The growth of ΔANXC7 was inhibited when grown under selected stress conditions, particularly with regard to salt stress; however, the oxidative resistance to exogenous H2O2 in ΔANXC7 was increased, and endogenous H2O2 levels within the ΔANXC7 were lower than in the wild-type, thereby suggesting that the ANXC7 specifically controls oxidative resistance. Based on microscopic observation, 4-day-conidia were more prevalent than 5-day conidia on the conidiophore stalk of ΔANXC7, even though the ΔANXC7 demonstrated an increased production of conidia during these days, indicating precocious conidial maturation and shedding from the conidiophore stalk in this strain. Taken together, our data indicate that ANXC7 localizes to the mitochondria and is involved in controlling conidium development and oxidative resistance in T. lanuginosus.

The flow behavior and dynamic globularization of TC11 titanium alloy during subtransus deformation are investigated through hot compression tests. A constitutive model is established based on physical-based hardening model and phenomenological softening model. And based on the recrystallization mechanisms of globularization, the Avrami type kinetics model is established for prediction of globularization fraction and globularized grain size under large strain subtransus deformation of TC11 alloy. As the preliminary application of the previous results, the cogging process of large size TC11 alloy billet is simulated. Based on subroutine development of the DEFORM software, the coupled simulation of one fire cogging process is developed. It shows that the predicted results are in good agreement with the experimental results in forging load and microstructure characteristic, which validates the reliability of the developed FEM subroutine models.