Hemodynamic Shear Stress Regulates the Survival of Circulating Tumour Cells Through Piezo1-Actomyosin-Mediated YAP/TAZ Nuclear Translocation

It is critical to combat tumor metastasis by eradicating disseminated tumor cells in any step during the metastasis process.After entering the blood circulation system,tumor cells are in suspension and experience considerable levels of fluid shear stress.However,the influence of hemodynamic shear stress on the survival of CTCs and the underlying mechanotransduction mechanisms remain unclear.This study shows that fluid shear stress can eliminate the majority of CTCs and the viability of suspended tumor cells depends on the stress magnitude,indicating that tumor cells can sense and respond to fluid shear stress.Mechanistically,the expression of Piezo1 but not Piezo2 is greatly upregulated in suspended tumor cells after shear stress treatment.Inhibiting/activating Piezo1 increases/decreases the viability of suspended tumor cells in shear flow,which depends on Piezo1-mediated calcium entry.These findings suggest that Piezo1 may be the major mechanosensor by which suspended tumor cells sense fluid shear stress.As the downstream effector of Piezo1,actomyosin in tumor cells is significantly activated under increasing shear stress.Its activity influences the survival of CTCs in shear flow and rescues the effects of Piezo1 on tumor cell survival,suggesting that hemodynamic shear stress regulates the survival of CTCs through Piezo1 mediated actomyosin activity.Importantly,fluid shear stress considerably up-regulates YAP/TAZ activity of suspended tumor cells and promotes their nuclear translocation in a magnitude-dependent manner.Inhibiting YAP/TAZ enhances the viability of suspended tumor cells in shear stress,while activating their activity decreases tumor cell survival,suggesting that YAP/TAZ activation promotes the apoptosis of suspended tumor cells,which is different from the findings that YAP/TAZ facilitates the survival of adherent cells to shear flow.Further,blocking the nuclear import of YAP/TAZ inactivates the sensation of suspended tumor cells to fluid shear flow and attenuates the dependence of tumor cell survival on different magnitudes of hemodynamic shear stress.The influence of Piezo1-actomyosin pathway on suspended tumor cells can be rescued by YAP/TAZ activity,suggesting that Piezo1-mediated signaling induces tumor cell apoptosis via nuclear translocation of YAP/TAZ.In addition,fluid shear stress can also activate the expressions of LATS1/2 and MST1/2 in Hippo pathway through Piezo1,which is known to inhibit YAP/TAZ activity.Silencing/activating LATS1/2 or MST1/2 inhibits/enhances the viability of CTCs under shear stress,the effects of which can be further rescued by YAP/TAZ.These findings suggest that the responses of suspended tumor cells to hemodynamic shear stress are partially mediated by Hippo signaling.After nuclear translocation,YAP/TAZ directly bind p73/PUMA,which further promotes the transcription of pro-apoptotic genes and induces the apoptosis of suspended tumor cells.In summary,these findings show that hemodynamic shear stress considerably influences the survival of CTCs in blood circulation.We have identified the calcium channel Piezo1 as a novel mechanosensor for the response of CTCs to fluid shear stress.Hemodynamic shear stress induces the apoptosis of suspended tumor cells through Piezo1-actomyosin-YAP/TAZ-p73/PUMA signaling,which is different from the mechanotranduction mechanisms for tumor cells in adherent.Therefore,this study has unveiled the novel mechanosensor of suspended CTCs in response to fluid shear stress and the subsequent mechanisms and identified Piezo1 and YAP/TAZ as the potential therapeutic targets,through which CTCs may be effectively eradicated in the vasculature to prohibit tumor metastasis.

An interactive tool for visualization and prediction of solar radiation and photovoltaic generation in Colombia

This paper presents the building process of an interactive instrument called the Colombian Solar Atlas able to easily visualize meteorological data but also assess the current and future potentials of solar photovoltaic generation throughout the whole territory of Colombia,South America.This new tool is based on two different meteorological databases.The first one is done with historical data extracted from satellite imagery information,and the other one corresponds to data issues from regional-scale climate change projection models.The satellite database was validated with different in-situ measurements.The Colombian Solar Atlas uses basic and advanced photovoltaic generation models to estimate the generation of a custom solar installation.With this tool,a user selects a point on the map and can have directly pertinent information to search for an optimal location with a spatial resolution of 4 km2.This tool is the first open interactive online tool particularly adapted to study the photovoltaic power potential in Colombia,considering the country’s needs and native language.

单侧纹状体外损伤患者的运动整合和分离缺陷

Functional neuroimaging in human subjects and single cell recordings in monkeys show that several extra-striate visual areas are activated by visual motion. However, the extent to which different types of motion are processed in different regions remains unclear, although neuropsychological studies of patients with circumscribed lesions hint at regional specialization. We, therefore, studied four patients with unilateral damage to different regions of extrastriate visual cortex on a series of visual discrimination tasks that required them, to a different extent, to integrate local motion signals in order to correctly perceive the direction of global motion. Performance was assessed psychophysically and compared with that of control subjects and with the patients’performance with stimuli presented in the visual field ipsilateral to the lesion. The results indicate considerable regional specialization in extra-striate regions for different aspects of motion processing, namely the largest displacement from frame to frame (D-max) that can sustain perception of coherent motion; perception of relative speed; the amount of coherent motion needed to sustain a percept of global motion in a particular direction; the detection of discontinuities within a moving display; the extraction of form from motion. It was also clear that a defect in local motion, i.e. D-max, can be overcome by integrating local motion signals over a longer period of time. Although no patient suffered from only one defect, the overall pattern of results strongly supports the notion of regional specialization for different aspects of motion processing.

Citric Acid-Based Intrinsic Band-Shifting Photoluminescent Materials

Citric acid,an important metabolite with abundant reactive groups,has been demonstrated as a promising starting material to synthesize diverse photoluminescent materials including small molecules,polymers,and carbon dots.The unique citrate chemistry enables the development of a series of citric acid-based molecules and nanomaterials with intriguing intrinsic band-shifting behavior,where the emission wavelength shifts as the excitation wavelength increases,ideal for chromatic imaging and many other applications.In this review,we discuss the concept of“intrinsic band-shifting photoluminescent materials”,introduce the recent advances in citric acid-based intrinsic band-shifting materials,and discuss their potential applications such as chromatic imaging and multimodal sensing.It is our hope that the insightful and forward-thinking discussion in this review will spur the innovation and applications of the unique band-shifting photoluminescent materials.