Exosome-mediated transduction of mechanical force regulates prostate cancer migration via microRNA

Physical cues in the extracellular microenvironment regulate cancer cell metastasis. Functional microRNA (miRNA) carried by cancer derived exosomes play a critical role in extracellular communication between cells and the extracellular microenvironment. However, little is known about the role of exosomes loaded miRNAs in the mechanical force transmission between cancer cells and extracellular microenvironment. Herein, our results suggest that stiff extracellular matrix (ECM) induced exosomes promote cancer cell migration. The ECM mechanical force regulated the exosome miRNA cargo of prostate cancer cells. Exosome miRNAs regulated by the ECM mechanical force modulated cancer cell metastasis by regulating cell motility, ECM remodeling and the interaction between cancer cells and nerves. Focal adhesion kinase mediated-ECM mechanical force regulated the intracellular miRNA expression, and F-actin mediate-ECM mechanical force regulated miRNA packaging into exosomes. The above results demonstrated that the exosome miRNA cargo promoted cancer metastasis by transmitting the ECM mechanical force. The ECM mechanical force may play multiple roles in maintaining the microenvironment of cancer metastasis through the exosome miRNA cargo.     

Assessing the lethality of ship strikes on whales using simple biophysical models

Studies of ship strikes on whales often focus on large vessels (>20 m), with attention to their speeds and the resulting risk of lethality. Smaller coastal vessels also co-occur with whales, resulting in collisions that merit study. To cast light on injuries caused by vessels of all sizes, we used knowledge of right whale anatomy and Newtonian mechanics to construct simple models that predict the mechanical stresses experienced by whales during collisions. By comparing our predictions with published models and with data from ship strikes on various whale species, we developed a model for lethal injury as a function of several vessel and whale properties, finding that collisions that create stresses in excess of 0.241 MPa were likely to cause lethal injuries to large whales. Furthermore, this model has revealed that (1) vessels of all sizes can yield stresses higher than this critical level, and (2) large vessels produce stresses much larger than this even when travelling at reduced speeds (i.e., 10 knots). The model is fast enough to power an interactive GUI-based tool (in R) and flexible enough to simulate strikes by vessels of different masses and speeds upon whales of different species, sizes, and physical conditions.     

Limited long‐term effectiveness of roller‐chopping for managing woody encroachment

The encroachment of woody plants into grasslands, woodland, and savanna has increased markedly over the past century, prompting the use of different physical methods to remove woody plants and restore grasses. Roller‐chopping is used extensively in the Americas, but little is known about its long‐term effectiveness for restoration, and whether its effectiveness varies with the intensity of encroachment. We compared the effects of roller‐chopping, under three treatment intensities (control, single treatment, double treatment), on woody plant density, ground cover, and groundstorey plants at sites of low, moderate, and high woody plant density in a semi‐arid eastern Australian woodland over 10 years. Both single and double treatment significantly altered the size distribution of Dodonaea viscosa, which comprised more than 85% of woody plants at all sites. Thus, roller‐chopping changed the size distribution of the community from an even‐size distribution to one dominated by shorter plants, irrespective of initial encroachment level. The effectiveness of roller‐chopping was strongly site‐specific, with significant reductions in density at low‐ and high‐density sites, but no clear trend in relation to the intensity of treatment (i.e. single cf. double treatment). The effectiveness of roller‐chopping was unsustained over the long term, with the suppressive effect on woody density diminishing over time. Grass cover increased with increasing intensity of woody removal, but only at the low‐density site and with some ill‐defined, variable, and short‐term effects on plant composition. Managers should consider that the short‐term effects may not adequately reflect the long‐term results of woody plant removal using the roller‐chopper.     

COVID-19 global pandemic planning: Performance and electret charge of N95 respirators after recommended decontamination methods

Shortages of N95 respirators for use by medical personnel have driven consideration of novel conservation strategies, including decontamination for reuse and extended use. Decontamination methods listed as promising by the Centers for Disease Control and Prevention (CDC) (vaporous hydrogen peroxide (VHP), wet heat, ultraviolet irradiation (UVI)) and several methods considered for low resource environments (bleach, isopropyl alcohol and detergent/soap) were studied for two commonly used surgical N95 respirators (3M™ 1860 and 1870+ Aura™). Although N95 filtration performance depends on the electrostatically charged electret filtration layer, the impact of decontamination on this layer is largely unexplored. As such, respirator performance following decontamination was assessed based on the fit, filtration efficiency, and pressure drop, along with the relationship between (1) surface charge of the electret layer, and (2) elastic properties of the straps. Decontamination with VHP, wet heat, UVI, and bleach did not degrade fit and filtration performance or electret charge. Isopropyl alcohol and soap significantly degraded fit, filtration performance, and electret charge. Pressure drop across the respirators was unchanged. Modest degradation of N95 strap elasticity was observed in mechanical fatigue testing, a model for repeated donnings and doffings. CDC recommended decontamination methods including VHP, wet heat, and UV light did not degrade N95 respirator fit or filtration performance in these tests. Extended use of N95 respirators may degrade strap elasticity, but a loss of face seal integrity should be apparent during user seal checks. NIOSH recommends performing user seal checks after every donning to detect loss of appropriate fit. Decontamination methods which degrade electret charge such as alcohols or detergents should not be used on N95 respirators. The loss of N95 performance due to electret degradation would not be apparent to a respirator user or evident during a negative pressure user seal check.     

Local delivery of simvastatin maintains tooth anchorage during mechanical tooth moving via anti-inflammation property and AMPK/MAPK/NF-kB inhibition

Simvastatin (SMV) could increase tooth anchorage during orthodontic tooth movement (OTM). However, previous studies on its bone-specific anabolic and anti-inflammation properties were based on static in vitro and in vivo conditions. AMPK is a stress-activated kinase that protects tissue against serious damage from overloading inflammation. Rat periodontal ligament cells (PDLCs) were subjected to a serial of SMV concentrations to investigate the optimization that promoted osteogenic differentiation. The PDLCs in static and/or tensile culturing conditions then received the proper concentration SMV. Related factors expression was measured by the protein array, real-time PCR and Western blot. The 0.05UM SMV triggered osteogenic differentiation of PDLCs. The inhibition of AMPK activation through a pharmacological approach (Compound C) caused dramatic decrease in osteogenic/angiogenic gene expression and significant increase in inflammatory NF-κB phosphorylation. In contrast, pharmacological activation of AMPK by AICAR significantly inhibited inflammatory factors expression and activated ERK1/2, P38 MAPK phosphorylation. Moreover, AMPK activation induced by SMV delivery significantly attenuated the osteoclastogenesis and decreased the expression of pro-inflammatory TNF-α and NF-κB in a rodent model of OTM. The current studies suggested that SMV could intrigue intrinsic activation of AMPK in PDLCs that promote attenuate the inflammation which occurred under tensile irritation through AMPK/MAPK/NF-kB Inhibition.     

Effect of equilibrium pH on the structure and properties of bleach-damaged human hair fibers

Hair proteins are significantly affected by environmental pH. This impact tends to increase with prior hair damage. To understand how pH affects bleached hair properties, we utilized a number of techniques allowing for the determination of hair thermal properties, swelling and water sorption, and dry and wet tensile properties. At pH 5, hair proteins had the best structural integrity, as determined by differential scanning calorimetry and the highest tensile modulus. At pH 10, protein cross-linking density decreased, water content and hair cross-sectional diameter increased. Alkaline treatment, when compared with pH 5, did not reduce intermediate filament conditions (evaluated via enthalpy measurement) nor mechanical property performance in the wet state. In contrast to alkaline-treated hair, bleached hair equilibrated at pH 3 behaved very differently: it contained two different crosslink density zones, was the least stiff in dry and stiffest in wet conditions. Additionally, it absorbed less water and had the lowest diameter because of reduced water binding by protonated carboxyl groups. The pH 3 to 10 did not affect the mechanical strength of bleached hair in dry or wet conditions.     

Mechanical stretch regulates the expression of specific miRNA in extracellular vesicles released from lung epithelial cells

The underlying mechanism of normal lung organogenesis is not well understood. An increasing number of studies are demonstrating that extracellular vesicles (EVs) play critical roles in organ development by delivering microRNAs (miRNA) to neighboring and distant cells. miRNAs are important for fetal lung growth; however, the role of miRNA–EVs (miRNAs packaged inside the EVs) during fetal lung development is unexplored. The aim of this study was to examine the expression of miRNA–EVs in MLE-12, a murine lung epithelial cell line subjected to mechanical stretch in vitro with the long-term goal to investigate their potential role in the fetal lung development. Both cyclic and continuous mechanical stretch regulate miRNA differentially in EVs released from MLE-12 and intracellularly, demonstrating that mechanical signals regulate the expression of miRNA–EVs in lung epithelial cells. These results provide a proof-of-concept for the potential role that miRNA–EVs could play in the development of fetal lung.