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Objective: Half of the patients with acute large artery occlusion (LAO) have poor outcomes after endovascular treatment (EVT). Early complications such as cerebral edema and symptomatic intracranial hemorrhage (sICH) can lead to early neurological deterioration (END), which correlates with hemodynamics. This study aimed to identify the hemodynamic predictors of END and outcomes in LAO patients after EVT. Methods: A total of 76 patients with anterior circulation LAO who underwent EVT and received transcranial Doppler (TCD) monitoring were included. Bilateral middle cerebral artery (MCA) blood flow velocities (BFVs) were measured repeatedly within 1 week. Mean flow velocities (MFV) and MFV index (ipsilateral MFV/contralateral MFV) were calculated. The primary outcome was the incidence of END within 72 h. The secondary outcome was the functional outcome at 90 days-a good outcome was defined as a modified Rankin scale (mRS) score of 0-2, while a poor outcome was defined as an mRS score of 3-6. Results: A total of 13 patients (17.1 %) experienced END within 72 h, including 5 (38.5 %) with cerebral edema, 5 (38.5 %) with sICH, and 3 (23.0 %) with infarct progression. Multivariable logistic regression analysis showed that a higher 24 h MFV index was independently associated with END (aOR 10.5; 95 % CI 2.28-48.30, p = 0.003) and a poor 90-day outcome (aOR 5.10; 95 % CI 1.38-18.78, p = 0.014). The area under the receiver operating characteristic (ROC) curve (AUC) of the 24 h MFV index for predicting END was 0.807 (95 % CI 0.700-0.915, p = 0.0005), the sensitivity was 84.6 %, and the specificity was 66.7 %. At the 1-week TCD follow-up, patients who had poor 90-day outcomes showed significantly higher 1-week iMFV [73.5 (58.4-99.0) vs. 57.7 (45.3-76.3), p = 0.004] and MFV index [1.24 (0.98-1.57) vs.1.0 (0.87-1.15) p = 0.007]. A persistent high MFV index (PHMI) was independently associated with a poor outcome (aOR 7.77, 95 % CI 1.81-33.3, p = 0.006). Conclusion: TCD monitoring within 24 h after EVT in LAO patients can help predict END, while dynamic follow-up within 1 week is valuable in predicting clinical outcomes.
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Background: Psychological distress is reported to be associated with academic burnout in students while the mediation and moderation effect of resilience and personality are less explored. Purpose: The current study was designed to estimate the mediating effect of resilience and the moderation effect of personality between psychological distress and academic burnout. Participants and methods: A total of 613 students were enrolled from two medical universities between December 2020 and January 2021. They were administered with Academic Burnout Scale, 10-item Kessler Psychological Distress Scale (K10), Connor-Davidson Resilience Scale (CD-RISC-10) and NEO Five-Factor Inventory (NEO-FFI). Latent profile analysis and moderated mediation analysis were performed. Results: Three personalities were identified and named as resilient (13.4%), over-controlled (50.2%) and under-controlled (36.4%). Resilience significantly mediated the relationship between psychological distress and academic burnout while personality significantly moderated the relationship between psychological distress and resilience. Conclusion: Resilience and personality may be two important mediators between psychological distress and academic burnout. More attentions should be paid to students with under-controlled personality and resilience-enhancing interventions could be developed to prevent or alleviate academic burnout in future research.
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This study was designed to estimate the associations between self-efficacy and professional identity. A total of 1,051 freshmen nursing students (FNSs) from the Be Resilient to Nursing Career (BRNC) program were recruited from four universities between September and November 2020. A latent profile and moderated meditation analysis were performed. Four profiles of self-efficacy were identified and named as Lowest (15.6%), Med-low (45.0%), Med-high (32.7%), and Highest (6.7%). The mediating role of resilience and the moderating effect of role models were also identified. Therefore, self-efficacy, resilience, and role models may be three important factors to professional identity in FNSs and these relationships should be further validated in longitudinal or interventional studies.
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Background: Psychological resilience is important to mental health and professional development in newly graduated nursing students (NGNSs). However, the association between psychological resilience and mental health in NGNSs is less explored. Purpose: The current study was designed to determine mental health profiles measured by the Kessler 10 scale (K10) and evaluate the non-linear association between psychological resilience and mental health in NGNSs. Methods: A total of 472 NGNSs from the Be Resilient to Nursing Career program were assessed using the K10 and ten-item Connor-Davidson Resilience Scale (CD-RISC 10). Latent profile analysis and generalized additive model analysis were performed. Results: A four-class model based on the K10 was identified: lowest (28.0%), lower-middle (36.4%), upper-middle (26.1%), and highest (9.5%) subgroups. Academic degree and psychological resilience were significant indicators of mental health profiles. Psychological resilience was negatively and nonlinearly correlated with mental health when the CD-RISC 10 score was >17. Conclusion: There exists heterogeneity in NGNSs' mental health. The negative and nonlinear association between psychological resilience and mental health can only be confirmed in NGNSs with moderate and high resilience levels.
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The high-temperature superplastic deformation behavior of rolled Mg-8Al-2Sn (AT82) and Mg-8Al-1Sn-1Zn (ATZ811) alloys were investigated in this study. During tensile deformation at 573 K, no obvious grain growth occurred in both alloys, because of the high-volume fraction of second phases located at grain boundaries. Meanwhile, texture weakening was observed, suggesting that grain boundary sliding (GBS) is the dominant superplastic deformation mechanism, which agreed well with the strain rate sensitivity (m) and the activation energy (Q) calculations. The microstructural evolution during tensile deformation manifested that there were more and larger cavities in AT82 than ATZ811 during high-temperature tensile deformation. Therefore, superior superplasticity was found in the ATZ811 alloy that presented a tensile elongation of ~510% under a strain rate of 10-3 s-1 at 573 K, in contrast to the relatively inferior elongation of ~380% for the AT82 alloy. Meanwhile, good tensile properties at ambient temperature were also obtained in ATZ811 alloy, showing the ultimate tensile strength (UTS) of ~355 MPa, yield strength (YS) of ~250 MPa and elongation of ~18%. Excellent mechanical performance at both ambient and elevated temperatures can be realized by using economical elements and conventional rolling process, which is desirable for the industrial application of Mg alloy sheets.
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Effects of deformation texture and grain size on mechanical properties and corrosion behavior of the Mg-3Al-1Zn (AZ31) alloys were systematically investigated. The results revealed that the ultimate tensile strength (UTS) and fracture elongation (FE) significantly increased from 232 to 273 MPa and 12.5 to 26.4%, respectively. According to the immersion and electrochemical measurements, the results indicated that the corrosion resistance of the alloy was improved obviously. Via electron backscattered diffraction (EBSD), corrosion morphology showed that the propagation of local pitting corrosion was suppressed, which is ascribed to grain refinement, higher texture intensity, and lower dislocation density after rolling and subsequent annealing.
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TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), also known as APO2L, belongs to the tumor necrosis factor family. By binding to the death receptor 4 (DR4) or DR5, TRAIL induces apoptosis of tumor cells without causing side toxicity in normal tissues. In recent years TRAIL-based therapy has attracted great attention for its promise of serving as a cancer drug candidate. However, the treatment efficacy of TRAIL protein was under expectation in the clinical trials because of the short half-life and the resistance of cancer cells. TRAIL gene transfection can produce a "bystander effect" of tumor cell killing and provide a potential solution to TRAIL-based cancer therapy. In this review we focus on TRAIL gene therapy and various design strategies of TRAIL DNA delivery including non-viral vectors and cell-based TRAIL therapy. In order to sensitize the tumor cells to TRAIL-induced apoptosis, combination therapy of TRAIL DNA with other drugs by the codelivery methods for yielding a synergistic antitumor efficacy is summarized. The opportunities and challenges of TRAIL-based gene delivery and therapy are discussed.
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ADN/uso terapéutico , Técnicas de Transferencia de Gen , Neoplasias/terapia , Ligando Inductor de Apoptosis Relacionado con TNF/genética , Animales , Antineoplásicos/uso terapéutico , Apoptosis/fisiología , Línea Celular Tumoral , Dendrímeros/química , Sinergismo Farmacológico , Terapia Genética/métodos , Humanos , Liposomas/química , Neoplasias/tratamiento farmacológico , Péptidos Cíclicos/químicaRESUMEN
The field of circular non-coding RNAs have been gradually attracted wide attention with the developments of high-throughput sequencing. In this review, we systematically summarize three driving models for circRNAs biogenesis: intron-pairing-driven, RNA binding protein-driven and lariat-driven. In addition, we also briefly introduce the current research methods of circRNAs, which include high-throughput library construction methods, identification through bioinformatics and common experimental verification. Here, we also systematically summarize the functions of circRNAs, including microRNA (miRNA) or protein sponges, regulating the alternative splicing (AS) and expression of host genes, and extensive translation. Finally, we provide a systematic characterization and the latest research progress of circRNAs, which provide a new perspective for further studies of circRNAs in plants.
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Empalme Alternativo , ARN/genética , Intrones , MicroARNs , Modelos Genéticos , Plantas/genética , ARN Circular , Proteínas de Unión al ARNRESUMEN
The microstructure, mechanical properties and corrosion behavior of hotâ»rolled Mgâ»xSnâ»1Znâ»0.5Ca (x = 1, 3 and 5 wt.%) alloys were investigated for possible application as biodegradable implants. The hotâ»rolled Mgâ»xSnâ»1Znâ»0.5Ca alloys consisted of α-Mg matrix and Mg2Sn phase. The number of the Mg2Sn particles significantly increased and the grains were gradually refined (14.2 ± 1.5, ~10.7 ± 0.7 and ~6.6 ± 1.1 µm), while the recrystallized fraction significantly decreased with the increase in the Sn content, the Mgâ»1Snâ»1Znâ»0.5Ca alloy was almost completely recrystallized. Ultimate tensile strength (UTS) and tensile yield strength (TYS) increased slightly, reaching maximum values of 247 MPa and 116 MPa, respectively, for the Mgâ»5Snâ»1Znâ»0.5Ca alloy, and the elongation decreased with the increase in the Sn content; the Mgâ»1Snâ»1Znâ»0.5Ca alloy showed the highest elongation (15.3%). In addition, immersion tests and electrochemical measurements in Hank's solution revealed that the corrosion rates of Mgâ»xSnâ»1Znâ»0.5Ca alloys increased with the increase in the Sn content. A model of the corrosion behavior was discussed for hotâ»rolled Mgâ»xSnâ»1Znâ»0.5Ca alloys in Hank's solution. Among the Mgâ»xSnâ»1Znâ»0.5Ca (x = 1, 3 and 5 wt.%) alloys, Mgâ»1Snâ»1Znâ»0.5Ca alloy exhibits optimal corrosion resistance and appropriate mechanical properties.
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A high extrusion ratio of 166:1 was applied to commercial AZ61 alloy in one step with an extrusion speed of 2.1 m·min-1. The effects of DA (direct aging) treatment on the microstructure and tensile properties of extruded alloy were investigated. The extruded alloy exhibits fine DRXed grains and the average grain size is ~11 µm. After DA treatment at 170 °C, the tensile strength and 0.2% offset yield strength is enhanced from 314 to 336 MPa and from 169 to 191 MPa respectively, sacrificing elongation from 26.5% to 23.3%. The grain size and texture distribution of extruded AZ61 scarcely evolve during the post aging treatment. However, the enhanced strength in peak-aged alloy is mainly caused by the high-density elliptical Mg17Al12 precipitates distributing uniformly along the grain boundaries or within the grains, by precipitation and dispersion hardening. Furthermore, the nano-sized precipitates effectively inhibit grains from coarsening by triggering pinning effects along the grain boundaries at elevated temperature. As a result, the peak-aged alloy exhibits a better superplasticity of 306.5% compared with that of 231.8% of extruded sample. This work provides a practical one-step method for mass-producing Mg alloy sheets with excellent tensile strength and ductility compared with those fabricated by conventional extrusion methods.
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OBJECTIVE: To assess the safety and efficacy of transcutaneous electrical acupoint stimulation (TEAS) for depression in late pregnancy and impacts on inflammatory cytokines. METHODS: A total of 150 pregnant women with depression in late pregnancy were randomized into a high intensity group (nï¼52), a low intensity group (nï¼49) and a control group (nï¼49). TEAS was applied at bilateral Neiguan (PC 6) and Shenmen (HT 7) for 6 weeks. The intensities of TEAS in the high intensity group, the low intensity group and the control group were 10, 5 and 0 mA, respectively. During the process of TEAS, the blood pressure, pulse, uterine contraction and the fetal heart rate were recorded. Depression was evaluated by 24-item Hamilton depression scale (HAMD) before TEAS and after 2-week, 4-week, 6-week treatment. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-1 ß (IL-1 ß) and IL-6 were detected by enzyme-linked immunosorbent assay (ELISA) before and after 6-week treatment. Delivery outcomes were observed. The correlation was analyzed between HAMD difference value and the diffe-rence values of TNF-αï¼ IL-1 ß and IL-6, respectively. RESULTS: The blood pressure, pulse and fetal heart rate had no statistical significance before and after treatment in the three groups (P>0.05). The HAMD scores at all the time points were lower than that before treatment in the high intensity group (P<0.05), which were lower compared with those in the low intensity group and the control group (P<0.05). The HAMD score in the low intensity group decreased after 6-week treatment compared with that before treatment and was lower than that in the control group (P<0.05). The serum levels of IL-1 ß and IL-6 in the high intensity group decreased compared with those before treatment and were lower compared with those in the low intensity group and the control group after 6-week treatment (P<0.05). There was no significant difference in the deliver outcomes among the three groups (P>0.05). The variation of HAMD score did not have significant correlation with those of TNF-αï¼ IL-1 ß and IL-6 (P>0.05). CONCLUSION: TEAS is safe and effective for depression in late pregnancy and can regulate the serum levels of IL-1 ß and IL-6 without influencing on delivery outcome.
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Puntos de Acupuntura , Estimulación Eléctrica Transcutánea del Nervio , Citocinas , Depresión , Electroacupuntura , Femenino , Humanos , Interleucina-1beta , EmbarazoRESUMEN
Multidrug resistance (MDR) is a major hurdle in cancer chemotherapy and makes the treatment benefits unsustainable. Combination therapy is a commonly used method for overcoming MDR. In this study we investigated the anti-MDR effect of dihydroartemisinin (DHA), a derivative of artemisinin, in combination with doxorubicin (Dox) in drug-resistant human colon tumor HCT8/ADR cells. We developed a tumor-targeting codelivery system, in which the two drugs were co-encapsulated into the mannosylated liposomes (Man-liposomes). The Man-liposomes had a mean diameter of 158.8 nm and zeta potential of -15.8 mV. In the HCT8/ADR cells that overexpress the mannose receptors, the Man-liposomes altered the intracellular distribution of Dox, resulting in a high accumulation of Dox in the nuclei and thus displaying the highest cytotoxicity (IC50=0.073 µg/mL) among all the groups. In a subcutaneous HCT8/ADR tumor xenograft model, administration of the Man-liposomes resulted in a tumor inhibition rate of 88.59%, compared to that of 47.46% or 70.54%, respectively, for the treatment with free Dox or free Dox+DHA. The mechanisms underlying the anti-MDR effect of the Man-liposomes involved preferential nuclear accumulation of the therapeutic agents, enhanced cancer cell apoptosis, downregulation of Bcl-xl, and the induction of autophagy.
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Antineoplásicos/farmacología , Artemisininas/farmacología , Neoplasias del Colon/tratamiento farmacológico , Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos , Resistencia a Antineoplásicos/efectos de los fármacos , Animales , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Artemisininas/administración & dosificación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Neoplasias del Colon/patología , Relación Dosis-Respuesta a Droga , Doxorrubicina/administración & dosificación , Portadores de Fármacos/química , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Liposomas/química , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Relación Estructura-ActividadRESUMEN
AIM: Drug efflux-associated multidrug resistance (MDR) is a main obstacle to effective cancer chemotherapy. Large molecule drugs are not the substrates of P-glycoprotein, and can circumvent drug efflux and be retained inside cells. In this article we report a polymer-drug conjugate nanoparticulate system that can overcome MDR based on size-related exclusion effect. METHODS: Doxorubicin was coupled with the triblock polymeric material cell-penetrating TAT-PEG-poly(aspartic acid). The amphiphilic macromolecules (termed TAT-PEG-Asp8-Dox) could self-assemble into nanoparticles (NPs) in water. The antitumor activity was evaluated in drug-resistant human colon cancer HCT8/ADR cells in vitro and in nude mice bearing HCT8/ADR tumor. RESULTS: The self-assembling TAT-PEG-Asp8-Dox NPs were approximately 150 nm with a narrow particle size distribution, which not only increased the cellular uptake efficiency, but also bypassed P-glycoprotein-mediated drug efflux and improved the intracellular drug retention, thus yielding an enhanced efficacy for killing drug-resistant HCT8/ADR colon cancer cells in vitro. Importantly, the TAT-PEG-Asp8-Dox NPs enhanced the intranuclear disposition of drugs for grater inhibition of DNA/RNA biosynthesis. In nude mice bearing xenografted HCT8/ADR colon cancers, intravenous or peritumoral injection of TAT-PEG-Asp8-Dox NPs for 22 d effectively inhibited tumor growth. CONCLUSION: TAT-PEG-Asp8-Dox NPs can increase cellular drug uptake and intranuclear drug delivery and retain effective drug accumulation inside the cells, thus exhibiting enhanced anticancer activity toward the drug-resistant human colon cancer HCT8/ADR cells.
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Antineoplásicos/administración & dosificación , Doxorrubicina/farmacología , Doxorrubicina/farmacocinética , Portadores de Fármacos/administración & dosificación , Resistencia a Antineoplásicos/efectos de los fármacos , Nanopartículas/administración & dosificación , Animales , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Péptidos de Penetración Celular/química , ADN/biosíntesis , Doxorrubicina/administración & dosificación , Portadores de Fármacos/farmacocinética , Humanos , Ratones , Ratones Desnudos , Nanopartículas/química , Tamaño de la Partícula , Péptidos/química , Polietilenglicoles/química , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Hierarchical TiO2 micron spheres assembled by nano-plates were prepared through a facile hydrothermal route. Chemical tuning of the TiO2 through hydrogen reduction (H-TiO2) is shown to increase oxygen-vacancy density and thereby modifies the electronic properties. H-TiO2 spheres with a polar surface serve as the surface-bound intermediates for strong polysulfides binding. Under the restricting and recapturing effect, the sulfur cathode could deliver a high reversible capacity of 928.1 mA h g(-1) after 50 charge-discharge cycles at a current density of 200 mA g(-1). The H-TiO2 additive developed here is practical for restricting and recapturing the polysulfide from the electrolyte.
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Damage to carbon nanotubes (CNTs) during the fabrication process of CNT reinforced composites has great influence on their mechanical properties. In this study, the 2014 Al with powder sizes of 20, 9 and 5 µm was selected to study the effect of initial particle size on the damage to carbon nanotubes (CNTs) during ball milling. The result shows that for CNTs in the ball milled CNT/Al (with powder size of 20 and 9 µm) mixtures, the intensity ratio of the D band and the G band (ID/IG) first increased and then reached a plateau, mainly because most of the CNTs are embedded, to a certain extent, in the aluminum powder after milling, which could protect the CNTs from damage during further milling. While for CNTs in the ball milled CNT/Al (with powder size of 5 µm) mixture, the ID/IG ratio continues to climb from 1.31 to 2.33 with time, indicating continuous damage to the CNTs occurs during the milling. Differential scanning calorimetry (DSC) analysis demonstrates that the chemical instability increased with an increase in the damage level of CNTs, resulting in the formation of aluminum carbide (Al4C3) at a lower temperature before the melting of aluminum, which is detrimental to their mechanical properties.
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It is found that Li2Sb compound can act as the nucleus of primary Mg2Si during solidification, by which the particle size of primary Mg2Si decreased from ~300 to ~15-25 µm. Owing to the synergistic effect of the Li2Sb nucleus and adsorption-poisoning of Li atoms, the effect of complex modification of Li-Sb on primary Mg2Si was better than that of single modification of Li or Sb. When Li-Sb content increased from 0 to 0.2 and further to 0.5 wt.%, coarse dendrite changed to defective truncated octahedron and finally to perfect truncated octahedral shape. With the addition of Li and Sb, ultimate compression strength (UCS) of Al-20Mg2Si alloys increased from ~283 to ~341 MPa and the yield strength (YS) at 0.2% offset increased from ~112 to ~179 MPa while almost no change was seen in the uniform elongation. Our study offers a simple method to control the morphology and size of primary Mg2Si, which will inspire developing new Al-Mg-Si alloys with improved mechanical properties.
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Twin-roll casting AZ31 Mg alloy sheets have been fabricated by normal unidirectional-rolling, head-to-tail rolling, and clock-rolling, respectively. It has been demonstrated that head-to-tail rolling is the most effective to refine the microstructure and weaken the basal texture among the three rolling routes. Excellent integrated tensile properties can be obtained by the head-to-tail rolling. The yield strength, ultimate tensile strength, and plastic elongation are 196 MPa, 301 MPa, and 28.9%, respectively. The strength can benefit from the fine grains (average value of 4.0 µm) of the AZ31 alloy processed by the head-to-tail rolling route, while the excellent plastic elongation is achieved owing to the weakened basal texture besides the fine grains. Results obtained here can be used as a basis for further study of some simple rolling methods, which is critical to the development of Mg alloys with high strength and plasticity.
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Nano-SiC particulates (n-SiCp) reinforced Mg-8Al-1Sn (AT81) composites with different pre-oxidation parameters were fabricated by powder metallurgy (P/M) process combined with hot extrusion. The effects of pre-oxidization treatment of n-SiCp on the microstructure and tensile properties of 0.5 vol % n-SiCp/AT81 composites were investigated accordingly. The distribution of n-SiCp with different pre-oxidation parameters was homogeneous in the composites. Moreover, it was found that a thin MgAl2O4 layer formed at the interface when the n-SiCp were pre-oxidized at 1073 K for 2 h, while the MgAl2O4 layer became much thicker with pre-oxidization temperature increasing to 1273 K for 2 h. After an appropriate pre-oxidization treatment of n-SiCp at 1073 K for 2 h, the as-extruded 0.5 vol % n-SiCp/AT81 composites exhibited an enhanced strength. It was found that the yield strength (YS) and ultimate tensile strength (UTS) increased from 168 MPa and 311 MPa to 255 MPa and 393 MPa compared with the as-extruded AT81 alloy, reflecting 51.8% and 26.4% increments, respectively. The improvement of mechanical properties should be mainly attributed to the grain refinement and homogeneous distribution of n-SiCp in the composites. Moreover, a well-bonded interface and the formation of an appropriate amount of interfacial product (MgAl2O4) benefited the material's mechanical properties.
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Magnesium alloys are highly desirable for a wide range of lightweight structural components. However, rolling Mg alloys can be difficult due to their poor plasticity, and the strong texture yielded from rolling often results in poor plate forming ability, which limits their further engineering applications. Here we report a new hard-plate rolling (HPR) route which achieves a large reduction during a single rolling pass. The Mg-9Al-1Zn (AZ91) plates processed by HPR consist of coarse grains of 30-60 µm, exhibiting a typical basal texture, fine grains of 1-5 µm and ultrafine (sub) grains of 200-500 nm, both of the latter two having a weakened texture. More importantly, the HPR was efficient in gaining a simultaneous high strength and uniform ductility, i.e., ~371 MPa and ~23%, respectively. The superior properties should be mainly attributed to the cooperation effect of the multimodal grain structure and weakened texture, where the former facilitates a strong work hardening while the latter promotes the basal slip. The HPR methodology is facile and effective, and can avoid plate cracking that is prone to occur during conventional rolling processes. This strategy is applicable to hard-to-deform materials like Mg alloys, and thus has a promising prospect for industrial application.