Notes

Underwater Antithrombotics.
Taken together, these studies provide new insights into the mechanisms underlying GSC-driven niche development, i.e., organization of the self-advantageous niche microenvironments for GSC maintenance and expansion leading to glioma progression and recurrence. A series of such studies can redefine the current concept of anti-GSC niche therapy that targets ligands/receptors supporting GSCs, and have potential to accelerate cancer therapy development.
We aimed at identifying the key genes of prognostic value in clear cell renal cell carcinoma (ccRCC) microenvironment and construct a risk score prognostic model.

Immune and stromal scores were calculated using the ESTIMATE algorithm. A total of 539 ccRCC cases were divided into high- and low-score groups. The differentially expressed genes in immune and stromal cells for the prognosis of ccRCC were screened. The relationship between survival outcome and gene expression was evaluated using univariate and multivariate Cox proportional hazard regression analyses. A risk score prognostic model was constructed based on the immune/stromal scores.

The median survival time of the low immune score group was longer than that of the high immune score group (
= 0.044). Ten tumor microenvironment-related genes were selected by screening, and a predictive model was established, based on which patients were divided into high- and low-risk groups with markedly different overall survival (
< 0.0001). Multivariate Cox analyses showed that the risk score prognostic model was independently associated with overall survival, with a hazard ratio of 1.0437 (confidence interval 1.0237-1.0641,
< 0.0001).

Low immune scores were associated with extended survival time compared to high immune scores. The novel risk predictive model based on tumor microenvironment-related genes may be an independent prognostic biomarker in ccRCC.
Low immune scores were associated with extended survival time compared to high immune scores. The novel risk predictive model based on tumor microenvironment-related genes may be an independent prognostic biomarker in ccRCC.
The spondin-2 (SPON2) gene is overexpressed in multiple malignant tumors and may promote tumor aggressiveness. However, its expression profile and functional roles in clear cell renal cell carcinoma (ccRCC) are still unclear.

SPON2 expression in ccRCC was evaluated using expression data from TCGA and GEO databases, then confirmed by local patient population (94 patients). The clinical significance of SPON2 expression was evaluated. Downregulation of SPON2 was performed using small-interfering RNA (siRNA). The effects of SPON2 silencing on cell proliferation, apoptosis, invasion, and migration
were investigated.

SPON2 was overexpressed in the majority of the ccRCC at both mRNA and protein levels. SPON2 expression was significantly correlated with stage, grade, and recurrence (all
< 0.05) in patients with localized ccRCC. The receiver operating characteristic (ROC) curve showed that SPON2 expression could serve as a predictor of recurrence. SPON2 expression was significantly associated with recurrence-free survival (RFS) in patients with localized ccRCC. Knocking down SPON2 resulted in suppressed cell invasion and migration
.

SPON2 expression might function as a prognostic biomarker in patients with localized ccRCC.
SPON2 expression might function as a prognostic biomarker in patients with localized ccRCC.UVB in sunlight, 290-315 nm, can inactivate SARS CoV and SARS CoV-2 viruses on surfaces and in the air. Laboratory exposure to ultraviolet irradiance in the UVC range inactivates many viruses and bacteria in times less than 30 min. Estimated UVB inactivation doses from sunlight in J/m2 are obtained from UVC measurements and radiative transfer calculations, weighted by a virus inactivation action spectrum, using OMI satellite atmospheric data for ozone, clouds, and aerosols. For SARS CoV, using an assumed UVC dose near the mid-range of measured values, D90 = 40 J/m2, 90% inactivation times T90 are estimated for exposure to midday 1000-1400 direct plus diffuse sunlight and for nearby locations in the shade (diffuse UVB only). For the assumed D90 = 40 J/m2 model applicable to SARS CoV viruses, calculated estimates show that near noon 1100-1300 clear-sky direct sunlight gives values of T90 less then 90 min for mid-latitude sites between March and September and less than 60 min for many equatorial sites for 12 months of the year. Recent direct measurements of UVB sunlight inactivation of the SARS CoV-2 virus that causes COVID-19 show shorter T90 inactivation times less than 10 min depending on latitude, season, and hour. The equivalent UVC 254 nm D90 dose for SARS CoV-2 is estimated as 3.2 ± 0.7 J/m2 for viruses on a steel mesh surface and 6.5 ± 1.4 J/m2 for viruses in a growth medium. For SARS CoV-2 clear-sky T90 on a surface ranges from 4 min in the equatorial zone to less than 30 min in a geographic area forming a near circle with solar zenith angle less then 60O centered on the subsolar point for local solar times from 0900 to 1500 h.On the 23 March 2020, a country-wide COVID-19 lockdown was imposed on the UK. The following 100 days saw anthropogenic movements quickly halt, before slowly easing back to a "new" normality. In this short communication, we use data from official UK air-quality sensors (DEFRA AURN) and the UK Met Office stations to show how lockdown measures affected air quality in the UK. We compare the 100 days post-lockdown (23 March to 30 June 2020) with the same period from the previous 7 years. We find, as shown in numerous studies of other countries, the nitrogen oxides levels across the country dropped substantially (∼ 50%). However, we also find the ozone levels increased (∼ 10%), and the levels of sulphur dioxide more than doubled across the country. These changes, driven by a complex balance in the air chemistry near the surface, may reflect the influence of low humidity as suggested by Met Office data, and potentially, the reduction of nitrogen oxides and their interactions with multiple pollutants.It is often assumed that people with high ability in a domain will be excellent raters of quality within that same domain. This assumption is an underlying principle of using raters for creativity tasks, as in the Consensual Assessment Technique. While several prior studies have examined expert-novice differences in ratings, none have examined whether experts' ability to identify the quality of a creative product is being driven more by their ability to identify high quality work, low quality work, or both. To address this question, a sample of 142 participants completed individual difference measures and rated the quality of several sets of creative captions. Unbeknownst to the participants, the captions had been identified a prior by expert raters as being of particularly high or low quality. Hierarchical regression analyses revealed that after controlling for participants' background and personality, those who scored significantly higher on any of three external measures of creativity also rated low-quality captions significantly lower than their peers; however, they did not rate the high-quality captions significantly higher. These findings support research in other domains suggesting that ratings of quality may be driven more by the lower end of the quality spectrum than the high end.
Pathological flows in patients with severe aortic stenosis are associated with acquired von Willebrand syndrome. This syndrome is characterized by excessive cleavage of von Willebrand factor by its main protease, A Disintegrin and Metalloproteinase with a Thrombospondin Type 1 Motif, Member 13 (ADAMTS13) leading to decreased VWF function and mucocutaneous bleeding. Aortic valve replacement and correction of the flow behavior to physiological levels reverses the syndrome, supporting the association between pathological flow and acquired von Willebrand syndrome. We investigated the effects of shear and elongational rates on von Willebrand factor cleavage in the presence of ADAMTS13.

We identified acquired von Willebrand syndrome in five patients with severe aortic stenosis. Doppler echography values from these patients were used to develop three computational fluid dynamic (CFD) aortic valve models (normal, mild and severe stenosis). Shear, elongational rates and exposure times identified in the CFD simulations were used as parameters for the design of microfluidic devices to test the effects of pathologic shear and elongational rates on the structure and function of von Willebrand factor.

The shear rates (0-10,000s
), elongational rates (0-1000 s
) and exposure times (1-180 ms) tested in our microfluidic designs mimicked the flow features identified in patients with aortic stenosis. The shear and elongational rates tested
did not lead to excessive cleavage or decreased function of von Willebrand factor in the presence of the protease.

High shear and elongational rates in the presence of ADAMTS13 are not sufficient for excessive cleavage of von Willebrand Factor.
High shear and elongational rates in the presence of ADAMTS13 are not sufficient for excessive cleavage of von Willebrand Factor.
Induced pluripotent stem cell (iPSC)-derived endothelial cells (ECs) have the potential for therapeutic application in several cardiovascular diseases. Mechanical strain is known to regulate EC behavior and stem cell differentiation and may play a role in directing EC differentiation of iPSCs.
, a long non-coding RNA (lncRNA), is known to affect ECs in several mechanically relevant pathologies and may play a role in this process as well. Therefore, we investigated expression changes of
resulting from mechanical stimulation during EC differentiation, as well as functional effects on EC tube formation.

iPSCs were subjected to 5% cyclic mechanical strain during EC differentiation. RT-PCR and flow cytometry were used to assess changes in mesoderm differentiation and gene expression in the final ECs as a result of strain. Functional outcomes of mechanically differentiated ECs were assessed with a tube formation assay and changes in
.
was also overexpressed in human umbilical vein endothelial cells (HUVECs) to assess its role in non-
-expressing ECs.

Mechanical strain promoted mesoderm differentiation, marked by increased expression of brachyury 24 h after initiation of differentiation. Strain also increased expression of
,
, VE-cadherin, and
in differentiated ECs. Strain-differentiated ECs formed tube networks with higher junction and endpoint density than statically-differentiated ECs. Overexpression of
in HUVECs resulted in similar patterns of tube formation.

expression is increased by mechanical strain and promotes tube branching in iPSC-derived ECs.
H19 expression is increased by mechanical strain and promotes tube branching in iPSC-derived ECs.
NETosis is an innate immune response elicited by activated neutrophils to fight microbial infections. Activated neutrophils release DNA fibers decorated with anti-microbial proteins called neutrophil extracellular traps (NETs) into the extracellular space to trap and kill surrounding microbes.

Here, we show that tumor-derived IL-8 released by cancer cells also activates the release of NETs. Until now, there have been no existing technologies that leverage NETs as an anti-tumor drug delivery vehicle. In this study, we demonstrate the re-engineering of neutrophils to express an apoptosis-inducing chimeric protein, supercharged eGFP-TRAIL, on NETs that can ensnare and kill tumor cells while retaining their anti-microbial capabilities.

We observed significant TRAIL-induced apoptosis in tumor cells captured by TRAIL-decorated NETs.

This work demonstrates NETs as a promising technology to deliver protein in response to local cytokine signals.
This work demonstrates NETs as a promising technology to deliver protein in response to local cytokine signals.
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