Solution Structures of Engineered Vault Particles

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Adipocyte-derived IL-6 and leptin promote breast Cancer metastasis via upregulation of Lysyl Hydroxylase-2 expression

Background

Adipocytes make up the major component of breast tissue, accounting for 90% of stromal tissue. Thus, the crosstalk between adipocytes and breast cancer cells may play a critical role in cancer progression. Adipocyte-breast cancer interactions have been considered important for the promotion of breast cancer metastasis. However, the specific mechanisms underlying these interactions are unclear. In this study, we investigated the mechanisms of adipocyte-mediated breast cancer metastasis.

Methods

Breast cancer cells were cocultured with mature adipocytes for migration and 3D matrix invasion assays. Next, lentivirus-mediated loss-of-function experiments were used to explore the function of lysyl hydroxylase (PLOD2) in breast cancer migration and adipocyte-dependent migration of breast cancer cells. The role of PLOD2 in breast cancer metastasis was further confirmed using orthotopic mammary fat pad xenografts in vivo. Clinical samples were used to confirm that PLOD2 expression is increased in tumor tissue and is associated with poor prognosis of breast cancer patients. Cells were treated with cytokines and pharmacological inhibitors in order to verify which adipokines were responsible for activation of PLOD2 expression and which signaling pathways were activated in vitro.

Results

Gene expression profiling and Western blotting analyses revealed that PLOD2 was upregulated in breast cancer cells following coculture with adipocytes; this process was accompanied by enhanced breast cancer cell migration and invasion. Loss-of-function studies indicated that PLOD2 knockdown suppressed cell migration and disrupted the formation of actin stress fibers in breast cancer cells and abrogated the migration induced by following coculture with adipocytes. Moreover, experiments performed in orthotopic mammary fat pad xenografts showed that PLOD2 knockdown could reduce metastasis to the lung and liver. Further, high PLOD2 expression correlated with poor prognosis of breast cancer patients. Mechanistically, adipocyte-derived interleukin-6 (IL-6) and leptin may facilitate PLOD2 upregulation in breast cancer cells and promote breast cancer metastasis in tail vein metastasis assays. Further investigation revealed that adipocyte-derived IL-6 and leptin promoted PLOD2 expression through activation of the JAK/STAT3 and PI3K/AKT signaling pathways.

Conclusions

Our study reveals that adipocyte-derived IL-6 and leptin promote PLOD2 expression by activating the JAK/STAT3 and PI3K/AKT signaling pathways, thus promoting breast cancer metastasis.

     

Dynamic ejection behaviour of water molecules passing through a nano-aperture nozzle

This study used molecular dynamics (MD) simulation to investigate the passage of water molecules through a composite graphene/Au nano-nozzle. Our focus was on the degree to which system temperature, extrusion speed, and nozzle diameter affect jet dynamics and the associated transient phenomena. Our findings show that high pressure and spatial confinement cause the nanojet from a small nozzle diameter (1.0?nm) to bend and twist, whereas the jets from a nozzle with a diameter of 1.5?nm present columns of greater stability. At 100?K, the H₂O nanojet froze at the outlet of the nozzle in the form of condensed icicles. At 500?K, the H₂O nanojet formed a loose spray and gaseous clusters. High extrusion speed of 55.824?m/s produced recirculating flow downstream from the nanojet with the appearance of an erupting volcano, which further prompted the jet column to thicken. Lower extrusion speeds produced jets with flow velocity insufficient to overcome the capillary force at the outlet of the nozzle, which subsequently manifests as unstable fluctuations in the flow rate.

• HIGHLIGHTS

• Water molecules through a composite graphene/Au nano-nozzle forming a nanojet is investigated.

• High pressure and spatial confinement cause the nanojet from a small nozzle diameter (≤1.0?nm) to bend and twist.

• High extrusion speed (≧55.824?m/s) produced recirculating flow downstream from the nanojet.

• Figure abstract: Schematic of the H₂O nano-jet through a nano-nozzle of graphene/Au

     

Investigation into the intracellular fates,speciation and mode of action of selenium-containing neuroprotective agents using XAS and XFM

Background

A variety of selenium compounds have been observed to provide protection against oxidative stress, presumably by mimicking the mechanism of action of the glutathione peroxidases. However, the selenium chemistry that underpins the action of these compounds has not been unequivocally established.

Novel strategy for expression of authentic and bioactive human basic fibroblast growth factor in Bacillus subtilis

Applied Microbiology and Biotechnology - Inteins, also known as “protein introns,” have been found to be present in many microbial species and widely employed for the expression and...     

Sesquiterpene Lactones with COX‐2 Inhibition Activity from Artemisia lavandulaefolia

Two new sesquiterpene lactones, artelavanolides A ( 1 ) and B ( 2 ), and four known sesquiterpene lactones ( 3 – 6 ) were isolated from the leaves of Artemisia lavandulaefolia. Their structures were elucidated based on the analysis of spectroscopic data (1D, 2D‐NMR and HR‐ESI‐MS). The absolute configuration of 1 was determined by the analysis of single‐crystal X‐ray diffraction data. Artelavanolide A ( 1 ) is a rare sesquiterpene lactone possessing an unusual skeleton with the linkage of Me(14)–C(1) that is probably formed through a rearrangement of the guaiane‐type sesquiterpenoids. Artelavanolide B ( 2 ) is a new highly unsaturated guaianolide. Compounds 1 – 6 were tested for activities on the inhibition of COX‐2 enzyme in vitro. All of compounds exhibited inhibitory activity against COX‐2 with IC₅₀ values ranging from 43.29 to 287.07 μm compared with the positive control, celecoxib (IC₅₀ = 18.10 μm ). Among them, 3 showed the best COX‐2 inhibitory activity with an IC₅₀ value of 43.29 μm .     

A Novel Graphene Oxide Wrapped Na2Fe2(SO4)3/C Cathode Composite for Long Life and High Energy Density Sodium‐Ion Batteries

The cathode materials in the Na‐ion battery system are always the key issue obstructing wider application because of their relatively low specific capacity and low energy density. A graphene oxide (GO) wrapped composite, Na₂Fe₂(SO₄)₃@C@GO, is fabricated via a simple freeze‐drying method. The as‐prepared material can deliver a 3.8 V platform with discharge capacity of 107.9 mAh g^?1 at 0.1 C (1 C = 120 mA g^?1) as well as offering capacity retention above 90% at a discharge rate of 0.2 C after 300 cycles. The well‐constructed carbon network provides fast electron transfer rates, and thus, higher power density also can be achieved (75.1 mAh g^?1 at 10 C). The interface contribution of GO and Na₂Fe₂(SO₄)₃ is recognized and studied via density function theory calculation. The Na storage mechanism is also investigated through in situ synchrotron X‐ray diffraction, and pseudocapacitance contributions are also demonstrated. The diffusion coefficient of Na⁺ ions is around 10^?12–10^?10.8 cm² s^?1 during cycling. The higher working voltage of this composite is mainly ascribed to the larger electronegativity of the element S. The research indicates that this well‐constructed composite would be a competitive candidate as a cathode material for Na‐ion batteries.     

Dual Strategies for Argonaute2-Mediated Biogenesis of Erythroid miRNAs Underlie Conserved Requirements for Slicing in Mammals

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