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.     

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.     

An investigation of the drivers,barriers, and incentives for environmental management systems in the Malaysian food and beverage industry

Clean Technologies and Environmental Policy - Food production and consumption is one of the major causes of global environmental degradation. One way to address environmental impacts in the food...     

A numerical study on the soot and combustion performance of a diesel engine with pip shape

Journal of Mechanical Science and Technology - The shape of the combustion chamber plays an important role in the formation of the air-fuel mixture in the chamber, which has a great influence on...     

Multimedia content recommendation in social networks using mood tags and synonyms

Multimedia Systems - The preferences of Web information purchasers are changing. Cost-effectiveness (i.e., an emphasis on performance with respect to price) is becoming less regarded than...     

Effect of garbage collection in iterative algorithms on Spark: an experimental analysis

The Journal of Supercomputing - Spark is one of the most widely used systems for the distributed processing of big data. Its performance bottlenecks are mainly due to the network I/O, disk I/O, and...     

Affective matches of fabric and lighting chromaticity

This study investigates the impact of lighting colors on subjective judgments of fabric: in particular, whether the influence of lighting varies depending on fabric types and color combinations. We conducted two visual assessments. In Study 1 (N = 44), eight illuminants and six types of fabric were presented as cloth stimuli. Derived from the literature review, four sets of adjectives (humble-luxurious, cool-warm, old-new, and not preferred-preferred) were used as metrics. In Study 2 (N = 41), five sets of fabric color combination swatches were assessed under lighting conditions that were identical to those of Study 1. Three bipolar scales (ordinary-characterful, classic-modern, and soft-rigid), were employed from factor analysis along with three unipolar scales (luxurious, preferred, harmonious with lighting). The results showed that hue characteristics of lighting and cloth types influenced participants' perceptions of the fabric. Overall, white lighting with 4000 K was the most preferred and luxurious lighting across various types of clothes, while a pinkish white with 4700 K (duv = −0.0127) was the best matched in every color combination. In addition, there were interaction effects between lighting colors, clothes types, and fabric color combinations with regard to each of the perceptual qualities. This study provides empirical evidence for optimally match lighting colors with fabric in the presentation of fabric goods.