Coupled CA-FE simulation for dynamic recrystallization of magnesium alloy during hot extrusion

In the present research,the dynamic recrystallization(DRX) behavior of a newly-developed Mg-Al-Zn-RE alloy with abundant secondphase particles during hot extrusion is investigated by coupling finite element(FE) and cellular automaton(CA) models.A two-dimensional CA model is developed to quantitatively and topologically evaluate the DRX process during deformation with constant forming conditions.Considering the fact that second-phase particles with various sizes extensively exist in the studied Mg-Al-Zn-RE magnesium alloy,models of DRX nucleation and grain growth velocity are modified.The coefficients of the modified CA model are calibrated by isothermal compression experiments of the magnesium alloy.Subsequently,the CA model is coupled with FE analysis to investigate the DRX behavior during the hot extrusions of the Mg-Al-Zn-RE alloy.The DRX behavior of the magnesium alloy at different stages and positions of extruded plates is simulated by the established model.Finer grains near the edge than in the inner of the plates result from higher strain and strain rate.The influence of extrusion conditions on microstructural evolution is explored.Under the employed forming conditions,average grain size decreases 28-62 times from as-cast and solution-treated to as-extruded state due to grain refinement by DRX.With increasing initial billet temperature or extrusion speed,average grain size increases.The finest grains are obtained at the initial billet temperature of 623 K and the extrusion speed of 7.83 mm/s.Low initial billet temperature or high extrusion speed benefits homogeneous grain distribution.The simulated results are in good agreement with experimental ones.

Ultraviolet radiation-induced non-melanoma skin cancer:Regulation of DNA damage repair and inflammation

Exposure to ultraviolet(UV)radiation is associated with approximately 65%of melanoma cases,and 90%of non-melanoma skin cancers(NMSC),including basal cell carcinoma(BCC)and squamous cell carcinoma(SCC).While the incidence of most other malignancies has either stabilized or declined,that of NMSC has increased and is developing even in younger age groups.NMSCs account for nearly 15,000 deaths,3.5 million new cases,and more than 3 billion dollars a year in medical costs in the United States alone,representing a major public health concern.As sun protection efforts have not been proven effective,targeted chemoprevention strategies are much needed.Skin carcinogenesis by DNA damage is considered a predominant paradigm for UV toxicity.Exposure to UV radiation can activate various oncogenes while inactivating tumor suppressor genes,resulting in inappropriate survival and proliferation of keratinocytes that harbor these damages.Moreover,increasing evidence demonstrate that inflammatory responses by the immune cells within the tumor microenvironment also contribute significantly to skin tumorigenesis.Initiation and progression of skin carcinogenesis mediated by UV radiation involve complex pathways,including those of apoptosis,proliferation,autophagy,DNA repair,checkpoint signaling,metabolism,and inflammation.In this review,we highlight the recent advances in two of these key molecular processes that result in UV-mediated skin carcinogenesis.In particular,we discuss 1)pathways that regulate DNA damage repair and 2)the regulation of the inflammatory process its crosstalk with DNA repair potentially leading to non-melanoma skin carcinogenesis.

Mitochondrial dysfunction activates the AMPK signaling and autophagy to promote cell survival

Autophagy is a cellular self-eating process essential for stress response and maintainingtissue homeostasis by lysosomal degradation of unwanted or damaged proteins and organelles.Here, we show that cells with defective mitochondria induce autophagy to promotecell survival through activating the AMPK pathway. Loss of mitochondrial complex III proteincytochrome b activates the AMPK signaling and induced autophagy. Inhibiting mitochondria energeticsby mitochondria-targeted agents activates the AMPK signaling and induced autophagy.Genetic inhibition of AMPK inhibits autophagy induction in cells with defective mitochondria,while genetic inhibition of autophagy has no effect on AMPK activation. Mitochondria dysfunctionhas no effect of DNA repair of UV-induced DNA damage. However, mitochondria dysfunctionsensitizes cells to apoptosis induced by UV radiation. Genetic inhibition of autophagy orAMPK sensitized cells to apoptosis in cells with defective mitochondria. Our results demonstratethat AMPK and autophagy senses mitochondria dysfunction and serves as a mechanismfor survival. Our findings may provide new insights into the interplay between mitochondriafunction and autophagy process in maintaining tissue homeostasis, and suggest that this interactionmay play important roles in diseases such as cancer and neurodegeneration.

Microstructure and mechanical properties of high-strength high-pressure die-cast Mg–4Al–3La–1Ca–0.3Mn alloy

A new high-pressure die-cast(HPDC) Mg–4 Al–3 La–1 Ca–0.3 Mn(ALaX431) alloy with high strength has successfully been fabricated. This HPDC alloy in peakaged state exhibits tensile yield strength(TYS) of 220 MPa at room temperature and TYS of 145 MPa at 250 ℃,higher than the corresponding strength of HPDC Mg alloys reported so far. These high strengths are mainly due to the formation of fine grained structure, semi-continuous reticular structure consisting of stable Al_(3)La and(Mg,Al)2 Ca particles along grain boundaries and numerous nanoscale Al_(2)Ca precipitates within grains. Due to its higher strength than existing HPDC Mg alloys, the new developed alloy has great application potential.

Serum proteomic profiling for autism using magnetic bead-assisted matrix-assisted laser desorption ionization time-of-flight mass spectrometry: a pilot study

Background The pathogenesis of autism spectrum disorders remains elusive and currently there are no diagnostic or pre-dictive biomarkers in autism available. Proteomic profiling has been used in a wide range of neurodevelopmental disorder studies, which could produce deeper perceptions of the molecular bases behind certain disease and potentially becomes useful in discovering biomarkers in autism spectrum disorders. Methods Serum samples were collected from autistic children about 3 years old in age (n = 32) and healthy controls (n = 20) in similar age and gender. The samples were identified specific proteins that are diff erentially expressed by magnetic bead-based pre-fractionation and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-ToF-MS). Results Eight protein peaks were significantly different in autistic children from the healthy controls (P < 0.0001). The two peaks with the most significant diff erences were 6428 and 7758 Da in size. Conclusion According to diff erences in serum protein profiles between the autistic children and healthy controls, this study identified a set of diff erentially expressed proteins those are significant for further evaluation and might function as biomark-ers in autism.