AXL is required for hypoxia-mediated hypoxia-inducible factor-1 alpha function in glioblastoma.

Glioblastoma (GBM) is the most aggressive type of central nervous system tumor. Molecular targeting may be important when developing efficient GBM treatment strategies. Sequencing of GBMs revealed that the receptor tyrosine kinase (RTK)/RAS/phosphatidylinositol-3-kinase pathway was altered in 88% of samples. Interestingly, AXL, a member of RTK, was proposed as a promising target in glioma therapy. However, the molecular mechanism of AXL modulation of GBM genesis and proliferation is still unclear. In this study, we investigated the expression and localization of hypoxia-inducible factor-1 alpha (HIF-1α) by AXL in GBM. Both AXL mRNA and protein are overexpressed in GBM. Short-interfering RNA knockdown of AXL in U251-MG cells reduced viability and migration. However, serum withdrawal reduced AXL expression, abolishing the effect on viability. AXL is also involved in hypoxia regulation. In hypoxic conditions, the reduction of AXL decreased the level and nuclear localization of HIF-1α. The co-expression of HIF-1α and AXL was found in human GBM samples but not normal tissue. This finding suggests a mechanism for GBM proliferation and indicates that targeting AXL may be a potential GBM therapeutic. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-023-00195-z.

Exploring scavenger receptor class F member 2 and the importance of scavenger receptor family in prediagnostic diseases.

Scavenger Receptor Class F Member 2 (SCARF2), also known as the Type F Scavenger Receptor Family gene, encodes for Scavenger Receptor Expressed by Endothelial Cells 2 (SREC-II). This protein is a crucial component of the scavenger receptor family and is vital in protecting mammals from infectious diseases. Although research on SCARF2 is limited, mutations in this protein have been shown to cause skeletal abnormalities in both SCARF2-deficient mice and individuals with Van den Ende-Gupta syndrome (VDEGS), which is also associated with SCARF2 mutations. In contrast, other scavenger receptors have demonstrated versatile responses and have been found to aid in pathogen elimination, lipid transportation, intracellular cargo transportation, and work in tandem with various coreceptors. This review will concentrate on recent progress in comprehending SCARF2 and the functions played by members of the Scavenger Receptor Family in pre-diagnostic diseases.

Urban effects on local cloud patterns.

Urbanization extensively modifies surface roughness and properties, impacting regional climate and hydrological cycles. Urban effects on temperature and precipitation have drawn considerable attention. These associated physical processes are also closely linked to clouds' formation and dynamics. Cloud is one of the critical components in regulating urban hydrometeorological cycles but remains less understood in urban-atmospheric systems. We analyzed satellite-derived cloud patterns spanning two decades over 447 US cities and quantified the urban-influenced cloud patterns diurnally and seasonally. The systematic assessment suggests that most cities experience enhanced daytime cloud cover in both summer and winter; nocturnal cloud enhancement prevails in summer by 5.8%, while there is modest cloud suppression in winter nights. Statistically linking the cloud patterns with city properties, geographic locations, and climate backgrounds, we found that larger city size and stronger surface heating are primarily responsible for summer local cloud enhancement diurnally. Moisture and energy background control the urban cloud cover anomalies seasonally. Under strong mesoscale circulations induced by terrains and land-water contrasts, urban clouds exhibit considerable nighttime enhancement during warm seasons, which is relevant to strong urban surface heating interacting with these circulations, but other local and climate impacts remain complicated and inconclusive. Our research unveils extensive urban influences on local cloud patterns, but the effects are diverse depending on time, location, and city properties. The comprehensive observational study on urban-cloud interactions calls for more in-depth research on urban cloud life cycles and their radiative and hydrologic implications under the urban warming context.

Functional characteristics and research trends of PDE11A in human diseases (Review).

cAMP and cGMP are important secondary messengers involved in cell regulation and metabolism driven by the G protein­coupled receptor. cAMP is converted via adenylyl cyclase (AC) and activates protein kinase A to phosphorylate intracellular proteins that mediate specific responses. cAMP signaling serves a role at multiple steps in tumorigenesis. The level of cAMP is increased in association with cancer cell formation through activation of AC­stimulatory G protein by mutation. Phosphodiesterases (PDEs) hydrolyze cAMP and cGMP to AMP and GMP. PDEs are composed of 11 families, and each can hydrolyze cAMP and cGMP or both cAMP and cGMP. PDEs perform various roles depending on their location and expression site, and are involved in several diseases, including male erectile dysfunction, pulmonary hypertension, Alzheimer's disease and schizophrenia. PDE11A is the 11th member of the PDE family and is characterized by four splice variants with varying tissue expression and N­terminal regulatory regions. Among tissues, the expression of PDE11A was highest in the prostate, and it was also expressed in hepatic skeletal muscle, pituitary, pancreas and kidney. PDE11A is the first PDE associated with an adrenocortical tumor associated genetic condition. In several studies, three PDE11A mutations have been reported in patients with Cushing syndrome with primary pigmented nodular adrenocortical disease or isolated micronodular adrenocortical disease without other genetic defects. It has been reported that an increase in PDE11A expression affects the proliferation of glioblastoma and worsens patient prognosis. The present mini­review summarizes the location of PDE11A expression, the impact of structural differences and disease relevance.

Scavenger receptor class F member 2 (SCARF2) as a novel therapeutic target in glioblastoma.

Scavenger receptor class F member 2 (SCARF2) is expressed by endothelial cells with very large cytoplasmic domains and is the second isotype, also known as scavenger receptor expressed by endothelial cells 2 (SREC-2). SREC-1 plays an important role in the binding and endocytosis of various endogenous and exogenous ligands. Many studies have been carried out on modified low-density lipoprotein internalization activity, but there have been few studies on SCARF2. Higher expression of SCARF2 has been found in glioblastoma (GBM) than normal brain tissue. Through analysis of The Cancer Genome Atlas database, it was confirmed that SCARF2 is widely expressed in GBM, and increased SCARF2 expression correlated with a poor prognosis in patients with glioma. The results of this study showed that the expression of SCARF2 is increased in GBM cell lines and patients, suggesting that SCARF2 may be a potential diagnostic marker and therapeutic molecule for cancers including glioma.

Diurnal evolution of urban tree temperature at a city scale.

Despite the importance of urban trees' surface temperature in assessing micro-climate interactions between trees and the surrounding environment, their diurnal evolution has been largely understudied at a city-wide scale due to a lack of effective thermal observations. By downscaling ECOSTRESS land surface temperature imaginary over New York City, we provide the first diurnal analysis of city-scale canopy temperature. Research reveals a remarkable spatial variation of the canopy temperature during daytime up to 5.6 K (standard deviation, STD), while the nighttime STD remains low at 1.7 K. Further, our analysis shows that the greenspace coverage and distance to bluespaces play an important role in cooling the local canopy during daytime, explaining 25.0-41.1% of daytime spatial variation of canopy temperatures while surrounding buildings modulate canopy temperature asymmetrically diurnally: reduced daytime warming and reduced nocturnal cooling. Built on space-borne observations and a flexible yet robust statistical method, our research design can be easily transferable to explore urban trees' response to local climate across cities, highlighting the potentials of advancing the science and technologies for urban forest management.