4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene,a Major Active Metabolite of Bisphenol A,Triggers Pancreatic β-Cell Death via a JNK/AMPKα Activation-Regulated Endoplasmic Reticulum Stress-Mediated Apoptotic Pathway

4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), a major active metabolite of bisphenol A (BPA), is generated in the mammalian liver. Some studies have suggested that MBP exerts greater toxicity than BPA. However, the mechanism underlying MBP-induced pancreatic β-cell cytotoxicity remains largely unclear. This study demonstrated the cytotoxicity of MBP in pancreatic β-cells and elucidated the cellular mechanism involved in MBP-induced β-cell death. Our results showed that MBP exposure significantly reduced cell viability, caused insulin secretion dysfunction, and induced apoptotic events including increased caspase-3 activity and the expression of active forms of caspase-3/-7/-9 and PARP protein. In addition, MBP triggered endoplasmic reticulum (ER) stress, as indicated by the upregulation of GRP 78, CHOP, and cleaved caspase-12 proteins. Pretreatment with 4-phenylbutyric acid (4-PBA; a pharmacological inhibitor of ER stress) markedly reversed MBP-induced ER stress and apoptosis-related signals. Furthermore, exposure to MBP significantly induced the protein phosphorylation of JNK and AMP-activated protein kinase (AMPK)α. Pretreatment of β-cells with pharmacological inhibitors for JNK (SP600125) and AMPK (compound C), respectively, effectively abrogated the MBP-induced apoptosis-related signals. Both JNK and AMPK inhibitors also suppressed the MBP-induced activation of JNK and AMPKα and of each other. In conclusion, these findings suggest that MBP exposure exerts cytotoxicity on β-cells via the interdependent activation of JNK and AMPKα, which regulates the downstream apoptotic signaling pathway.     

Translesion Synthesis or Repair by Specialized DNA Polymerases Limits Excessive Genomic Instability upon Replication Stress

DNA can experience “replication stress”, an important source of genome instability, induced by various external or endogenous impediments that slow down or stall DNA synthesis. While genome instability is largely documented to favor both tumor formation and heterogeneity, as well as drug resistance, conversely, excessive instability appears to suppress tumorigenesis and is associated with improved prognosis. These findings support the view that karyotypic diversity, necessary to adapt to selective pressures, may be limited in tumors so as to reduce the risk of excessive instability. This review aims to highlight the contribution of specialized DNA polymerases in limiting extreme genetic instability by allowing DNA replication to occur even in the presence of DNA damage, to either avoid broken forks or favor their repair after collapse. These mechanisms and their key regulators Rad18 and Polθ not only offer diversity and evolutionary advantage by increasing mutagenic events, but also provide cancer cells with a way to escape anti-cancer therapies that target replication forks.     

Self-Adaptive Control System for Additive Manufacturing Using Double Electrode Micro Plasma Arc Welding

Wire arc additive manufacturing(WAAM)has been investigated to deposit large-scale metal parts due to its high deposition efficiency and low material cost.However,in the process of automatically manufacturing the high-quality metal parts by WAAM,several problems about the heat build-up,the deposit-path optimization,and the stability of the process parameters need to be well addressed.To overcome these issues,a new WAAM method based on the double electrode micro plasma arc welding(DE-MPAW)was designed.The circuit principles of different metal-transfer models in the DE-MPAW deposition process were analyzed theoretically.The effects between the parameters,wire feed rate and torch stand-off distance,in the process of WAAM were investigated experimentally.In addition,a real-time DE-MPAW control system was developed to optimize and stabilize the deposition process by self-adaptively changing the wire feed rate and torch stand-off distance.Finally,a series of tests were performed to evaluate the con-trol system's performance.The results show that the capability against interferences in the process of WAAM has been enhanced by this self-adaptive adjustment system.Further,the deposition paths about the metal part's layer heights in WAAM are simplified.Finally,the appearance of the WAAM-deposited metal layers is also improved with the use of the control system.     

Symmetric and asymmetric membranes based on La0.5Sr0.5Fe0.7Ga0.3O3-δ perovskite with high oxygen semipermeation flux performances and identification of the rate-determining step of oxygen transport

This work focuses on identifying the rate-determining step of oxygen transport through La_0.5Sr_0.5Fe_0.7Ga_0.3O_3-δ membranes with symmetric and asymmetric architectures. The best oxygen semipermeation fluxes are 3.4 10⁻³ mol. m^-2.s^-1 and 6.3 10⁻³ mol. m^-2.s^-1 at 900 °C for the symmetric membrane and asymmetric membrane with a modified surface. The asymmetric membrane with a modified surface leads to an increase of approximately 7 times the oxygen flux compared to that obtained with the La_0.5Sr_0.5Fe_0.7Ga_0.3O_3-δ dense membrane without surface modification. This work also shows that the oxygen flux is mainly governed by gaseous oxygen diffusion through the porous support of asymmetric La_0.5Sr_0.5Fe_0.7Ga_0.3O_3-δ membranes.     

Toward a better understanding of multifunctional cement-based materials: The impact of graphite nanoplatelets (GNPs)

The impact of graphite nanoplatelets (GNPs) on the physical and mechanical properties of cementitious nanocomposites was investigated. A market-available premixed mortar was modified with 0.01% by weight of cement of commercial GNPs characterized by two distinctively different aspect ratios.The rheological behavior of the GNP-modified fresh admixtures was thoroughly evaluated. Hardened cementitious nanocomposites were investigated in terms of density, microstructure (Scanning Electron Microscopy, SEM and micro–Computed Tomography, μ-CT), mechanical properties (three-point bending and compression tests), and physical properties (electrochemical impedance spectroscopy, EIS and thermal conductivity measurements). At 28 days, all GNP-modified mortars showed about 12% increased density. Mortars reinforced with high aspect ratio GNPs exhibited the highest compressive and flexural strength: about 14% and 4% improvements compared to control sample, respectively. Conversely, low aspect ratio GNPs led to cementitious nanocomposites characterized by 36% decreased electrical resistivity combined with 60% increased thermal conductivity with respect to the control sample.     

The origin of interfacial delamination in Au/ceramic cofired LTCC structure

The interfacial delamination of electrode/ceramic multilayer structure will seriously damage the reliability of low temperature co-fired ceramic (LTCC) module in practical applications. In this work, three kinds of glasses employed in Au electrode are designed and prepared to study the abnormal expansion and delamination process in the Au/ceramic LTCC multilayer structure. The interfacial delamination in the co-fired structure is found to be attributed to the abnormal expansion of glass in respect to Au electrode at high temperature, which is originated from the enlarged closed pores during the co-firing process. This conclusion is further confirmed by co-firing the sample in a low-pressure condition. The mechanism and elimination of interfacial delamination here provides a feasible solution for the design of novel glasses in Au electrode for LTCC applications.     

Microstructural,mechanical, and thermal properties of microwave-sintered KLS-1 lunar regolith simulant

KLS-1 Lunar regolith simulant was microwave sintered to explore its potential applicability in future lunar construction. The effects of sintering temperature on linear shrinkage, density, porosity, and microstructural, mechanical, and thermal properties were investigated. As the sintering temperature increased, linear shrinkage and density increased and porosity decreased. Structural evolution in the sintered samples was characterized by scanning electron microscopy and X-ray diffraction. Unconfined compressive strength testing showed that mechanical strength increased significantly with increasing sintering temperature, with 1120 °C giving the highest strength of 37.0 ± 4.8 MPa. The sintered samples exhibited a coefficient of thermal expansion of approximately 5 × 10⁻⁶ °C⁻¹, which was well-maintained even after cyclic temperature stress between −100 and 200 °C. Therefore, this microwave processing appears promising for the fabrication of building material with sufficient mechanical strength and thermal durability for lunar construction.     

Surface modification of cellulose nanocrystals towards new materials development

Cellulose nanocrystals (CNCs) are a kind of sustainable nanoparticle from biomass, which are widely used as reinforcing filler and assembly building block for high-performance composites and function materials including biomaterial, optics, and so forth. Here, their unique advantages in material applications were reviewed based on their rod-like morphology, crystalline structure, dimension-related effects, and multi-level order structure. Then, we focused on the molecular engineering of CNCs, including the structure and physicochemical properties of their surface, along with surface modification methods and steric effects. We further discussed the performance-improvement and functionalization methods based on multi-component complex systems, together with the effects of surface molecular engineering on the performance and functions. Meanwhile, methods of optimizing orientation in uniaxial arrays were discussed along with those of enhancing photoluminescence efficiency via surface chemical modification and substance coordination. In the end, we prospected the design, development, and construction methods of new CNCs materials.     

Mitochondrial and Autophagic Regulation of Adult Neurogenesis in the Healthy and Diseased Brain

Adult neurogenesis is a highly regulated process during which new neurons are generated from neural stem cells in two discrete regions of the adult brain: the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus in the hippocampus. Defects of adult hippocampal neurogenesis have been linked to cognitive decline and dysfunction during natural aging and in neurodegenerative diseases, as well as psychological stress-induced mood disorders. Understanding the mechanisms and pathways that regulate adult neurogenesis is crucial to improving preventative measures and therapies for these conditions. Accumulating evidence shows that mitochondria directly regulate various steps and phases of adult neurogenesis. This review summarizes recent findings on how mitochondrial metabolism, dynamics, and reactive oxygen species control several aspects of adult neural stem cell function and their differentiation to newborn neurons. It also discusses the importance of autophagy for adult neurogenesis, and how mitochondrial and autophagic dysfunction may contribute to cognitive defects and stress-induced mood disorders by compromising adult neurogenesis. Finally, I suggest possible ways to target mitochondrial function as a strategy for stem cell-based interventions and treatments for cognitive and mood disorders.     

Tunable multicolor upconversion luminescence of Yb3+ sensitized Na3La(VO4)2 crystals

Multicolor upconversion luminescence materials show significantly applications in materials science. In this paper, the novel Yb³⁺-sensitized Na₃La(VO₄)₂ upconversion luminescence crystals are synthesized by the solid-state reaction method. Three primary colors upconversion luminescence are successfully achieved in Na₃La(VO₄)₂:Yb³⁺,Tm³⁺, Na₃La(VO₄)₂:Yb³⁺,Er³⁺, and Na₃La(VO₄)₂:Yb³⁺,Ho³⁺ crystals excited by the single 980 nm LD. Multicolor upconversion luminescence can be obtained by simply adjusting the combination ratios of these three samples. Luminescence mechanisms of the Yb³⁺-sensitized system are discussed in detail. In the Na₃La(VO₄)₂ host material, the Yb³⁺/Ho³⁺ codoped system exhibits unusual red upconversion luminescence based on the short decay time of Ho³⁺ ion ⁵I₆ level, which provides the possibility of three primary color luminescence under 980 nm excitation.