AQP3 Increases Intercellular Cohesion in NSCLC A549 Cell Spheroids through Exploratory Cell Protrusions

Tumor cell aggregation is critical for cell survival following the loss of extracellular matrix attachment and dissemination. However, the underlying mechanotransduction of clustering solitary tumor cells is poorly understood, especially in non-small cell lung cancers (NSCLC). Here, we examined whether cell surface protrusions played an important role in facilitating the physical contact between floating cells detached from a substrate. We employed poly-2-hydroxyethyl methacrylate-based 3D culture methods to mimic in vivo tumor cell cluster formation. The suprastructural analysis of human NSCLC A549 cell spheroids showed that finger-like protrusions clung together via the actin cytoskeleton. Time-lapse holotomography demonstrated that the finger-like protrusions of free-floating cells in 3D culture displayed exploratory coalescence. Global gene expression analysis demonstrated that the genes in the organic hydroxyl transport were particularly enriched in the A549 cell spheroids. Particularly, the knockdown of the water channel aquaporin 3 gene (AQP3) impaired multicellular aggregate formation in 3D culture through the rearrangement of the actomyosin cytoskeleton. Moreover, the cells with reduced levels of AQP3 decreased their transmigration. Overall, these data indicate that cell detachment-upregulated AQP3 contributes to cell surface protrusions through actomyosin cytoskeleton remodeling, causing the aggressive aggregation of free-floating cells dependent on the property of the substratum and collective metastasis.     

Diphenyl-Methane Based Thyromimetic Inhibitors for Transthyretin Amyloidosis

Thyromimetics, whose physicochemical characteristics are analog to thyroid hormones (THs) and their derivatives, are promising candidates as novel therapeutics for neurodegenerative and metabolic pathologies. In particular, sobetirome (GC-1), one of the initial halogen-free thyromimetics, and newly synthesized IS25 and TG68, with optimized ADME-Tox profile, have recently attracted attention owing to their superior therapeutic benefits, selectivity, and enhanced permeability. Here, we further explored the functional capabilities of these thyromimetics to inhibit transthyretin (TTR) amyloidosis. TTR is a homotetrameric transporter protein for THs, yet it is also responsible for severe amyloid fibril formation, which is facilitated by tetramer dissociation into non-native monomers. By combining nuclear magnetic resonance (NMR) spectroscopy, computational simulation, and biochemical assays, we found that GC-1 and newly designed diphenyl-methane-based thyromimetics, namely IS25 and TG68, are TTR stabilizers and efficient suppressors of TTR aggregation. Based on these observations, we propose the novel potential of thyromimetics as a multi-functional therapeutic molecule for TTR-related pathologies, including neurodegenerative diseases.     

小型核桃脱壳分选一体机的设计

核桃不仅营养价值极高,而且核桃壳的药用价值也非常高,国内小企业和家庭在核桃硬壳脱壳加工环节,一般采用人工破壳取仁的方式,这种方式劳动强度大,人工成本高且不卫生;针对这个问题设计了一款小型的硬壳脱壳,壳仁分离分选的机器来提高生产效率,减少成本,提高收入。     

Spatiotemporal Magnetocaloric Microenvironment for Guiding the Fate of Biodegradable Polymer Implants

The degradation behavior of implants is significantly important for bone repair. However, it is still unprocurable to spatiotemporally regulate the degradation of the implants to match bone ingrowth. In this paper, a magneto-controlled biodegradation model is established to explore the degradation behavior of magnetic scaffolds in a magnetothermal microenvironment generated by an alternating magnetic field (AMF). The results demonstrate that the scaffolds can be heated by magnetic nanoparticles (NPs) under AMF, which dramatically accelerated scaffold degradation. Especially, magnetic NPs modified by oleic acid with a better interface compatibility exhibit a greater heating efficiency to further facilitate the degradation. Furthermore, the molecular dynamics simulations reveal that the enhanced motion correlation between magnetic NPs and polymer matrix can accelerate the energy transfer. As a proof-of-concept, the feasibility of magneto-controlled degradation for implants is demonstrated, and an optimizing strategy for better heating efficiency of nanomaterials is provided, which may have great instructive significance for clinical medicine.     

Simultaneous fractionation of multiple classes of polyphenols from honeybush tea using solid-phase extraction

The structural diversity of polyphenols and the inherent limitations of current extraction techniques pose a challenge to extract polyphenols using a simple and green method. Hence, in this study, a method was developed to simultaneously fractionate multiple classes of polyphenols by only varying ethanol-water solutions. Honeybush tea, which is rich in polyphenols, was selected as a model for this study. Solvent extraction followed by solid-phase extraction (SPE) was developed to obtain a polyphenol-rich fraction from six honeybush samples. Based on a gradient elution programme (10%, 30%, 50%, 70% and 90% (v/v) ethanol-water solution) of SPE, the Strata X cartridge showed a better recovery of most targeted polyphenols under 0.9 mL of the drying volume and 1 mL min⁻¹ of the dispensing speed. The elution programme for fractionating most polyphenols was as follows: single elution with 50% ethanol, followed by twice elution with 70% ethanol. The antioxidant capacity was used to analyse the differences among the polyphenol-rich fractions from six honeybush samples. Principal component analysis (PCA) revealed that unfermented C. genistoides (GG) has the greatest antioxidant capacity among the honeybush species studied. Additionally, mangiferin, isomangiferin and vicenin-2 were the main contributors to the antioxidant capacity in six honeybush fractions according to the correlation study.     

Progressive NO2 Sensors with Rapid Alarm and Persistent Memory-Type Responses for Wide-Range Sensing Using Antimony Triselenide Nanoflakes

Antimony triselenide (Sb₂Se₃) nanoflake-based nitrogen dioxide (NO₂) sensors exhibit a progressive bifunctional gas-sensing performance, with a rapid alarm for hazardous highly concentrated gases, and an advanced memory-type function for low-concentration (<1 ppm) monitoring repeated under potentially fatal exposure. Rectangular and cuboid shaped Sb₂Se₃ nanoflakes, comprising van der Waals planes with large surface areas and covalent bond planes with small areas, can rapidly detect a wide range of NO₂ gas concentrations from 0.1 to 100 ppm. These Sb₂Se₃ nanoflakes are found to be suitable for physisorption-based gas sensing owing to their anisotropic quasi-2D crystal structure with extremely enlarged van der Waals planes, where they are humidity-insensitive and consequently exhibit an extremely stable baseline current. The Sb₂Se₃ nanoflake sensor exhibits a room-temperature/low-voltage operation, which is noticeable owing to its low energy consumption and rapid response even under a NO₂ gas flow of only 1 ppm. As a result, the Sb₂Se₃ nanoflake sensor is suitable for the development of a rapid alarm system. Furthermore, the persistent gas-sensing conductivity of the sensor with a slow decaying current can enable the development of a progressive memory-type sensor that retains the previous signal under irregular gas injection at low concentrations.     

A Case Report of Germline Compound Heterozygous Mutations in the BRCA1 Gene of an Ovarian and Breast Cancer Patient

The germline carrier of the BRCA1 pathogenic mutation has been well proven to confer an increased risk of breast and ovarian cancer. Despite BRCA1 biallelic pathogenic mutations being extremely rare, they have been reported to be embryonically lethal or to cause Fanconi anemia (FA). Here we describe a patient who was a 48-year-old female identified with biallelic pathogenic mutations of the BRCA1 gene, with no or very subtle FA-features. She was diagnosed with ovarian cancer and breast cancer at the ages of 43 and 44 and had a strong family history of breast and gynecological cancers.