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AbstractThe structure-activity relationship (SAR) between toxicity and the types of linking ketones of C7 bridged monocarbonyl curcumin analogs (MCAs) was not clear yet. In the pursuit of effective and less cytotoxic chemotherapeutics, we conducted a SAR analysis using various diketene skeletons of C7-bridged MCAs, synthesized cyclic C7-bridged MCAs containing the identified low-toxicity cyclopentanone scaffold and an o-methoxy phenyl group, and assessed their anti-gastric cancer activity and safety profile. Most compounds exhibited potent cytotoxic activities against gastric cancer cells. We developed a quantitative structure-activity relationship model (R2 > 0.82) by random Forest method, providing important information for optimizing structure. An optimized compound 2 exhibited in vitro and in vivo anti-gastric cancer activity partly through inhibiting the AKT and STAT3 pathways, and displayed a favorable in vivo safety profile. In summary, this paper provided a promising class of MCAs and a potential compound for the development of chemotherapeutic drugs.

The aging precipitated phases are of great significance for the strengthening and toughening of Al–Zn–Mg alloys. In this work, pre-precipitating was realized through equal channel angular pressing (ECAP) immediately followed by solid solution treatment at 475 °C for 6 h. Its corresponding strengthening and toughening effect on the room temperature (RT)-rolled Al–6Zn–1Mg alloy was systematically studied. The results indicate that pre-precipitating by ECAP can effectively improve the strength of the RT-rolled Al–6Zn–1Mg alloy and circumvent the strength-ductility trade-off. Microstructure characterization reveals that ECAP induces a large number of microshear bands, which can not only encourage recrystallization but also effectively promote the precipitation of the η′ phase. The synergistic effect of precipitation strengthening and dislocation strengthening contributes to the high strength of Al–6Zn–1Mg alloy, with UTS and YS increasing to ∼522 MPa and ∼400 MPa, respectively. Meanwhile, the ductility remains almost unchanged mainly due to the coordinated grain boundary sliding and the uniform and finely dispersed second phase particles. As a result, the strength-ductility trade-off is effectively avoided. The findings shed some light on optimizing the traditional aging treatment.

The 7046 aluminum alloy possesses a favorable fatigue property, corrosion resistance and weldability, but its moderate strength and plasticity limit its wider application and development. In the present study, severe plastic deformation (SPD) was applied prior to T6 treatment to significantly enhance the strength and toughness of the 7046 aluminum alloy. The results show that the alloy processed by four passes of equal channel angular pressing (ECAP) at 300 °C prior to T6 treatment exhibits an excellent mechanical performance, achieving an ultimate tensile strength (UTS) and elongation (EL) of 485 MPa and 19%, respectively, which are 18.6% and 375% higher than that of the T6 alloy. The mechanical properties of the alloy are further improved by an additional room temperature (RT) rolling process, resulting in a UTS of 508 MPa and EL of 23.4%, respectively. The increased presence of η′ and Al6Mn phases in the 300°C4P-R80%-T6 and 300°C4P-T6 alloys contributes to a strengthening and toughening enhancement in the SPD-processed T6 alloy. The findings from this work may shed new insights into enhancing the 7046 aluminum alloy.

Abstract Background Mucopolysaccharidosis (MPS) II is a rare, X-linked lysosomal storage disease. Approximately two-thirds of patients have central nervous system involvement with some demonstrating progressive cognitive impairment (neuronopathic disease). The natural history of cognitive and adaptive function in patients with MPS II is not well-defined. This 2-year, prospective, observational study evaluated the neurodevelopmental trajectories of boys with MPS II aged ≥ 2 years and 70); between-group differences were nonsignificant. No clear subgroups or patterns were identified for individual changes in VABS-II ABC scores. In total, 49 patients (89.1%) reported ≥ 1 adverse event (AE) and nine patients (16.4%) reported serious AEs. Conclusions Some patients with MPS II had rapid declines in cognitive ability, whereas others remained relatively stable after an initial decline. These insights provide a basis for more detailed analyses of different patient subgroups, which may enhance the definition and understanding of factors that influence cognitive and adaptive function in MPS II. Trial registration ClinicalTrials.gov, NCT01822184. Registered retrospectively: April 2, 2013.

Zinc alloys have great potential to become a new generation of biodegradable implant materials for biomedical applications due to their moderate corrosion rates. However, the poor mechanical properties restrict the application of pure zinc as biomedical materials. In this study, Zn–0.1Mg–0.02Mn alloy was rolled to different reductions at room temperature. The 80% reduction rolled alloy showed the best mechanical performance with ultimate tensile strength and elongation of 397.7 MPa and 15.9%, respectively, which satisfy the requirement of biomedical implant materials. Grain refinement mainly promoted the strength enhancement with increased rolling reductions. The microstructure evolution reveals that the basal-oriented grains and non-basal-oriented grains had different deformation mechanisms to induce DRX process during rolling. DRX could be directly accelerated in basal-oriented grains by basal slip, while twinning and de-twinning process operate to refine the non-basal-oriented grains.

The pivotal role of lithium (Li) in improving the comprehensive mechanical properties of third-generation Al–Li alloys remains significant even at a low content. However, the strengthening contribution of a low dosage lithium and its combination with different processing methods remain largely unknown. This study aimed to investigate the strengthening effects of room-temperature (RT) equal channel angular pressing (ECAP) and rolling on Al–0.6Li alloy. Microstructural evolution during processing was monitored by optical microscope (OM), scanning electron microscope (SEM), electron backscattered diffraction (EBSD), transmission electron microscope (TEM) and X-ray diffraction (XRD). The results revealed that simultaneous high ultimate tensile strength (UTS, 243 MPa) and yield strength (YS, 210 MPa) of the developed Al–0.6Li alloy were specifically achieved with a combination of RT ECAP and rolling, alongside an elongation (EL) of 9.5%. The gained strength improvement was primarily credited to the excellent fine-grain strengthening, as evidenced by a significant reduction in grain size from 101 μm to 1.47 μm, and dislocation strengthening, which, respectively, contributed to an increase of 91 MPa and 100 MPa in YS. Findings from this study demonstrate that with proper processing technology, the mechanical properties of Al–Li alloys with low Li content can be effectively improved, opening new avenues to develop high-performance Al–Li alloys.

Zn–Ag alloys are particularly promising for application as biodegradable implant materials due to their harmless degradation products, suitable degradation rate, and remarkable biocompatibility. Nonetheless, their mechanical properties are generally below the requirements for medical implants. In this work, a bimodal grain structured Zn–0.5Ag–0.2Mg alloy with excellent strength and ductility was achieved through combined equal channel angular pressing (ECAP) and cold rolling (CR), significantly superior to their counterparts obtained through ECAP or CR. Specifically, the ultimate tensile strength (UTS) and elongation (EL) of the alloy are as high as 332 MPa and 63%, respectively, far exceeding the application requirements. In achieving the excellent mechanical properties, a key role is played by hetero-deformation induced (HDI) strengthening. This work may provide practical guidance for developing high-performance Zn alloys.

As the lightest metallic structural materials with excellent damping capacity, good castability, and high specific strength, Mg alloys have huge potential for application in many industries including aircraft, automobile, and rail traffic. However, the strength of Mg alloys generally falls below the application benchmark and the development of high-strength Mg alloys relies on the addition of rare earth (RE) elements, which raises their cost and limits their application. Mg–Sn based alloys are promising age-hardenable RE-free Mg alloys which exhibit the potential of replacing those containing RE elements and becoming heat-resistant high-strength Mg alloys. Microstructure and mechanical properties of Mg–Sn based alloys have attracted enormous research interest over the past two decades. A comprehensive review of recent advances in this field is beneficial for their development, but such a review is still unavailable. This paper reviews recent progress of Mg–Sn based alloys from the perspective of the relationship between aging response and mechanical performance, striving to provide guidance for the development of high-performance Mg–Sn based alloys. Several key aspects are discussed including aging response, room temperature strength and ductility, and tension-compression yield asymmetry.

ABSTRACT Recombinant human parathyroid hormone (1‐84), rhPTH(1‐84), is an approved adjunctive treatment to oral calcium and active vitamin D for adult patients with hypoparathyroidism; however, there is limited information on the effect of twice daily (BID) dosing of rhPTH(1‐84). This was a phase I, open‐label, randomized, crossover, multicenter study conducted in adult patients with chronic hypoparathyroidism. The primary objective was to assess the pharmacokinetic profile and pharmacodynamic effects of 1 day of treatment with rhPTH(1‐84) administered subcutaneously at 25 μg BID, 50 μg BID, and 100 μg once daily (QD) with or without supplemental oral calcium. Safety and tolerability were evaluated as secondary objectives. In total, 33 patients with chronic hypoparathyroidism completed the study. Treatment with rhPTH(1‐84), both BID and QD, over the short‐term maintained serum calcium, lowered serum phosphorus, decreased urinary calcium excretion, and increased urinary phosphorus excretion. The decrease in urinary calcium excretion was numerically greater for BID than QD. Generally, baseline‐adjusted pharmacokinetic parameters including area under the curve and maximum observed concentration increased with increasing rhPTH(1‐84) dose, although this effect was not dose proportional. No new safety findings were observed. Our study revealed no differences thought to be clinically meaningful in pharmacokinetic or pharmacodynamic parameters with BID versus QD rhPTH(1‐84) dosing. Future long‐term studies are warranted to further elucidate the effects of alternative dosing strategies. © 2023 Takeda Development Center Americas, Inc and The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

With a suitable degradation rate, fully bioresorbable degradation products, and excellent biocompatibility, Zn and its alloys are regarded as the most promising biodegradable metallic materials for clinical applications. However, their strength and ductility are generally below the mechanical benchmark for biodegradable implants, such as bone fixtures and stents, which restrict wider applications. Over the past decade, enormous efforts have been dedicated to improving the mechanical performance of Zn alloys, which greatly advance our understanding of Zn alloy development. This review highlights recent progress of biodegradable Zn alloys from the perspective of strengthening and toughening, with an emphasis on the relationship between the microstructure and the mechanical properties of the four major Zn alloy systems: Zn–Mg, Zn–Li, Zn–Mn, and Zn–Cu based alloys. The dominant mechanisms for high strength and high ductility of these alloys are elaborated. Finally, the future challenges and research directions of the field are outlined. This review strives for provide guidance for the future development of high-performance bioresorbable Zn alloys.

In this paper, high-strength ultrafine-grained (UFG) pure aluminum (Al) was successfully achieved via a two-step processing route including room-temperature ECAP process for continuously 16 passes and post liquid nitrogen cryo-rolling for 50% reduction. The two-step processing route was observed to produce ultrafine grains with an average grain size of 0.98 μm and has obvious advantages for the preparation of high-strength pure Al in terms of the strength-ductility synergistic effect, which endows the pure Al excellent UTS value of 180 MPa, good Ef of 17.7% and a very high increase ratio (about 84%) of strength. The high strength was mainly attributed to the outstanding fine-grain strengthening provided by the combination of large-pass ECAP and cryo-rolling. In addition, the better uniform elongation of ECAP-rolled pure Al than ECAPed one was primarily dictated by the enhanced strain hardening capacity and the elongated grain shape.

Flow behavior of three near eutectic Al–Si alloys with the same chemical composition but different average eutectic Si sizes (A1, 1.7 μm; A2, 4.4 μm; A3, 8.2 μm) was investigated by isothermal compression tests conducted on a Gleeble-3500 thermal simulator under four different temperatures (350 °C, 400 °C, 450 °C, and 500 °C) and four different strain rates (0.01 s−1, 0.1 s−1, 1 s−1, and 5 s−1), with a focus on the effect of eutectic Si size. Not only the flow behavior but also the processing map of near eutectic Al–Si alloys are affected by eutectic Si size. The overall trends of the flow stress–strain curves of the three alloys are similar, but their steady flow stresses σs are different: A1 alloy has the largest σs, followed by that of A3. Strain-compensated constitutive equations in the hyperbolic sine form were constructed to describe the flow stress behavior of the three alloys. Materials constants of the constitutive equations depend on eutectic Si size. The processing maps of the three alloys exhibit different characteristics. The instability domain of A2 alloy is restricted to strain rates larger than about 0.4 s−1, in contrast to the case of A1 and A3 alloys in which the instability domain occurs at both low and high strain rates. The results presented in this study indicate that eutectic Si size is an indispensable factor to be considered when dealing with the hot working of Al–Si alloys.

In this paper, the effect of the equal-channel-angular-pressed (ECAPed) substrate on the coating formation and anticorrosion performance of the anodized Al−11Si alloy was systematically investigated. The ECAP process dramatically refines both Al and Si phases of the alloy. The parallel anodizing circuit is designed to enable a comparative study of anodizing process between the cast and the ECAPed alloys by tracking their respective anodizing current quota. The optimum coatings of both alloys were obtained after anodization for 30 min. The ECAPed alloy attained a thicker, more compact, and more uniform coating. Energetic crystal defects in the fine Al grains of the ECAPed substrate promote the anodizing reaction and lead to the thicker coating. Fragmented and uniformly distributed fine Si particles in the ECAPed alloy effectively suppress the coating cracks, enhancing the compactness of the coating. Overall, the ECAP-coated sample exhibits the best anticorrosion performance, which is evidenced by the concurrently enhanced prevention of coating and improved corrosion resistance of the substrate.

This paper investigated the cooperative effects of Li addition and warm Equal Channel Angular Pressing (ECAP) on improving the mechanical properties of an Al-Mg-Li alloy for further weight reduction. The results showed that more Li addition could obviously refine the grains of the as-cast alloy and reduce its density value to only 2.37 g/cm3 when Li content reached 2.5% (about 12.6% lighter than commercial Al alloys). It also had a pronounced influence on the precipitations in the Al-5.5Mg-xLi-0.1Zr alloy, i.e., the number density and size of Al2MgLi and δ’-Al3Li phases. The yield strength of the as-cast alloy was increased with increasing Li, but the elongation deteriorated due to primary network intergranular Al2MgLi and more δ’ particles in the high Li-containing alloy. The warm multi-pass ECAP process was found to simultaneously improve the strength and ductility of the Al-Mg-Li alloys, and greatly alleviate the detrimental effect of Li addition on the elongation, thereby making the ultrafine-grained (UFG) alloys, a good combination of lightweight and high performance, very attractive for aerospace applications for much higher specific strength than both Al matrix composites and Mg alloys.

Mechanical properties usually take precedence for wrought magnesium alloy when it would be used as a structure material. This paper proposed an approach that achieved high strength in AZ91 Mg alloy. The main procedure combined solution heat treatment, equal channel angular pressing (ECAP), and the subsequent low temperature rolling. After solution heat treatment and ECAP, the alloy had fine grains and excellent ductility, which benefited the following rolling at low temperature. By the following rolling (at 150 °C), the strength was further increased to ~432 MPa with a moderate ductility. This approach was proved effective in refining the grains and accumulating dislocations. The ultrahigh strength was attributed to the high density of dislocations and fine structure. The uniformly distributed fine precipitates also supplied precipitate hardening. Recrystallization that happened during rolling and annealing was the main reason for the moderate ductility.

Developing high strength and high ductility magnesium alloys is an important issue for weight-reduction applications. In this work, we explored the feasibility of manipulating nanosized precipitates on LPSO-contained (long period stacking ordered phase) ultra-fine grained (UFG) magnesium alloy to obtain simultaneously improved strength and ductility. The effect of two aging treatments on microstructures and mechanical properties of an UFG Mg-10Y-6Gd-1.5Zn-0.5Zr alloy was systematically investigated and compared by a series of microstructure characterization techniques and tensile test. The results showed that nano γ’’ precipitates were successfully introduced in T5 peak aged alloy with no obvious increase in grain size. While T6 peak aging treatment stimulated the growth of α-Mg grains to 4.3 μm (fine grained, FG), together with the precipitation of γ’’ precipitates. Tensile tests revealed that both aging treatments remarkably improved the strengths but impaired the ductility slightly. The T5 peak aged alloy exhibited the optimum mechanical properties with ultimate strength of 431 MPa and elongation of 13.5%. This work provided a novel strategy to simultaneously improve the strength and ductility of magnesium alloys by integrating the intense precipitation strengthening with ductile LPSO-contained UFG/FG microstructure.

Microstructure evolution of Al-0.2wt.%Mg-0.36wt.%Si-0.3wt.%Ce alloy at three different homogenization temperatures for 6 h was observed by optical microscopy, scanning electron microscopy, and x-ray diffraction. Conductivity and tensile properties of the alloy were tested. Results indicate that homogenization temperature has little effect on the macro-segregation and grain size of the as-cast Al-Mg-Si-Ce alloy; however, it has a significant effect on the conductivity. The conductivity is first improved to a maximum value of about 57.3% IACS with homogenization temperature increasing to 560 °C (2.7% higher than that of the as-cast sample), and then decreased when the temperature continuously increasing. The main contributor is considered to be vacancy concentration, which is directly related to the lattice distortion, thus affects the conductivity. The studied homogenization temperatures almost make no difference among the tensile properties of the alloy. The best homogenization temperature for Al-0.2wt.%Mg-0.36wt.%Si-0.3wt.%Ce alloy is 560 °C with the highest conductivity and no decrement of strength. [ABSTRACT FROM AUTHOR]