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.     

An active balancer with rapid bidirectional charge shuttling and adaptive equalization current control for lithium-ion battery strings

This article proposes an active balancer, which features bidirectional charge shuttling and adaptive equalization current control, to fast counterbalance the state of charge (SOC) of cells in a lithium-ion battery (LIB) string. The power circuit consists of certain bidirectional buck-boost converters to transfer energy among the different cells back and forth. Owing to the characterization of the open-circuit voltage (OCV) vs SOC in LIB being relatively smooth near the SOC middle range, the SOC-inspected balance strategy can achieve more precise and efficient equilibrium than the voltage-based control. Accordingly, a compensated OCV-based SOC estimation is put forward to take into account the discrepancy of SOC estimation. Besides, the varied-duty-cycle (VDC) and curve-fitting modulation (CFM) methods are devised herein to tackle the problems of slow equalization rate and low balance efficacy, which arise from the diminution in balancing current as the SOC difference between the cells decreases in the later duration of equalization especially. The proposed strategies have taken the battery nonlinear characteristic and circuit parameter nonideality into account and can adaptively modulate the duty cycle with the SOC difference to keep balancing current constant throughout the balancing cycle. Simulated and experimental results are given to demonstrate the feasibility and effectiveness of the same prototype constructed. Compared with the fixed duty cycle and the VDC methods, the proposed CFM has the best balancing efficiency of 81.4%, and the balance time is shortened by 27.1% and 18.6%, respectively.     

Synthesis of nanopowders with low agglomeration by elaborating Φ values for producing Gd2O3-MgO nanocomposites with extremely fine grain sizes and high mid-infrared transparency

Refining ceramic microstructures to the nanometric range to minimize light scattering provides an interesting methodology for developing novel optical ceramic materials. In this work, we reported the fabrication and properties of a new nanocomposite optical ceramic of Gd₂O₃-MgO. The citric acid sol-gel combustion method was adopted to fabricate Gd₂O₃-MgO nanocomposites with fine-grain sizes, dense microstructures and homogeneous phase domains. Nanopowders with low agglomeration and improved sinterability can be obtained by elaborating Φ values. Further refining of the microstructure of the nanocomposites was achieved by elaborating the hot-pressing conditions. The sample sintered at 65 MPa and 1300 °C showed a quite high hardness value of 14.3 ± 0.2 GPa, a high transmittance of 80.3 %–84.7 % over the 3?6 μm wavelength range, due mainly to its extremely fine-grain size of Gd₂O₃ and MgO (93 and 78 nm, respectively) and high density.     

Magnetically Guidable Proteinaceous Adhesive Microbots for Targeted Locoregional Therapeutics Delivery in the Highly Dynamic Environment of the Esophagus

The esophagus is a tubular-shaped muscular organ where swallowed fluids and muscular contractions constitute a highly dynamic environment. The turbulent, coordinated processes that occur through the oropharyngeal conduit can often compromise targeted administration of therapeutic drugs to a lesion, significantly reducing therapeutic efficacy. Here, magnetically guidable drug vehicles capable of strongly adhering to target sites using a bioengineered mussel adhesive protein (MAP) to achieve localized delivery of therapeutic drugs against the hydrodynamic physiological conditions are proposed. A suite of highly uniform microparticles embedded with iron oxide (IO) nanoparticles (MAP@IO MPs) is microfluidically fabricated using the genipin-mediated covalent cross-linking of bioengineered MAP. The MAP@IO MPs are successfully targeted to a specific region and prolongedly retained in the tubular-structured passageway. In particular, orally administered MAP@IO MPs are effectively captured in the esophagus in vivo in a magnetically guidable manner. Moreover, doxorubicin (DOX)-loaded MAP@IO MPs exhibit a sustainable DOX release profile, effective anticancer therapeutic activity, and excellent biocompatibility. Thus, the magnetically guidable locomotion and robust underwater adhesive properties of the proteinaceous soft microbots can provide an intelligent modular approach for targeted locoregional therapeutics delivery to a specific lesion site in dynamic fluid-associated tubular organs such as the esophagus.     

Optimized Biocatalytic Synthesis of 2-Selenopyrimidine Nucleosides by Transglycosylation**

Selenium-modified nucleosides are powerful tools to study the structure and function of nucleic acids and their protein interactions. The widespread application of 2-selenopyrimidine nucleosides is currently limited by low yields in established synthetic routes. Herein, we describe the optimization of the synthesis of 2-Se-uridine and 2-Se-thymidine derivatives by thermostable nucleoside phosphorylases in transglycosylation reactions using natural uridine or thymidine as sugar donors. Reactions were performed at 60 or 80 °C and at pH 9 under hypoxic conditions to improve the solubility and stability of the 2-Se-nucleobases in aqueous media. To optimize the conversion, the reaction equilibria in analytical transglycosylation reactions were studied. The equilibrium constants of phosphorolysis of the 2-Se-pyrimidines were between 5 and 10, and therefore differ by an order of magnitude from the equilibrium constants of any other known case. Hence, the thermodynamic properties of the target nucleosides are inherently unfavorable, and this complicates their synthesis significantly. A tenfold excess of sugar donor was needed to achieve 40−48 % conversion to the target nucleoside. Scale-up of the optimized conditions provided four Se-containing nucleosides in 6–40 % isolated yield, which compares favorably to established chemical routes.     

Generating Questions Based on Semi-Automated and End-to-End Neural Network

With the emergence of large-scale knowledge base, how to use triple information to generate natural questions is a key technology in question answering systems. The traditional way of generating questions require a lot of manual intervention and produce lots of noise. To solve these problems, we propose a joint model based on semi-automated model and End-to-End neural network to automatically generate questions. The semi-automated model can generate question templates and real questions combining the knowledge base and center graph. The End-to-End neural network directly sends the knowledge base and real questions to BiLSTM network. Meanwhile, the attention mechanism is utilized in the decoding layer, which makes the triples and generated questions more relevant. Finally, the experimental results on SimpleQuestions demonstrate the effectiveness of the proposed approach.     

Characterizations of friction welding joint interface for AISI 316

Because of heat amount is different from peripheral to central of friction welding interface, which is leaded to vary the characterizations along that interface. Current study, respectively, focused on the effect of different friction pressure on micro-structural and mechanical properties of that friction welding joint interface. Presently, these friction pressures are 110, 130, 150 and 170 MPa while kept all other conditions constant. The effects of different friction pressure on welding interface characterization were investigated by EDX, SEM, tensile, compression, impact and hardness tests. The tensile tests carried out on the standardized test piece with diameter 6 mm and 8 mm, thus, compression tests were extracted from the positions of 0°, 45° 90° with test specimen of 4 mm diameter and 6.5 mm length at weld center. Whereas, the impact test pieces were picked up in two positions, the first one is symmetrical, which it obtained to the respect of the rotation axis and the interface, on the other hand, the second one is non-symmetrical with the axis of rotation and symmetrical to the interface, for making the notch head coincide with the center of the welded joint, The obtained results showed that with reducing of friction pressure will present lack of bonding increasing from peripheral toward the welding center, which will responsible on reducing of the mechanical properties such as tensile, compression and impact strength.     

Increasing Volumetric CO2 Uptake of Hypercrosslinked Polymers through Composite Formation

To overcome the drawbacks of solid microporous materials for CO₂ capture, this proof‐of‐concept study demonstrates a low‐cost and rapid method for producing composites consisting of hypercrosslinked polymers (HCP) with a polyethyleneimine (PEI) binder. The resulting materials capture CO₂ through physical and chemical absorption simultaneously. Compared with HCP, the composites exhibit higher CO₂ uptake, higher volumetric density, and improved tolerance to water which is attributed to the PEI binder.