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2025
AbstractHair follicle neural crest stem cells reside in the bulge region of the outer root sheath of hair follicles, originate from the ectoderm, and have multidirectional differentiation potential, making them ideal candidates for tissue engineering applications. These cells mainly reside in a hypoxic microenvironment that favors the maintenance of stemness. Recently, many studies have elucidated the involvement of the Hippo pathway in the regulation of stem cell fate. However, few studies have investigated whether the Hippo signaling pathway regulates the growth of hair follicle neural crest stem cells in hypoxic environments. In the present study, we investigated the role of the Hippo pathway in the regulation of hair follicle neural crest stem cells under hypoxic conditions. We identified neural crest‐derived stem cells from single‐cell RNA‐seq data of skin organoids in a public database, and reported that the Hippo pathway was activated in the cell population. Hair follicle neural crest stem cells were isolated from rat hair follicles and cultured under hypoxic (3% oxygen) and normoxic (20% oxygen) conditions. Cell viability was assessed via the CCK8 assay. The expression levels of several key genes, including Hif2α, Nestin, Sox10, Oct4, Nanog, Sox2, and Klf4, were evaluated via quantitative real‐time PCR, after which we treated the cells with verteporfin, a small molecule inhibitor of the Hippo pathway. Changes in the subcellular localization of the hair follicle neural crest stem cell‐specific marker SOX10 were assessed via immunofluorescence. Western blotting was used to analyze the expression levels of proteins associated with stemness and hypoxia responses, including HIF2α, SOX10, OCT4, NANOG, SOX2, and KLF4. The results showed that hypoxic conditions facilitated the maintenance of stemness in hair follicle neural crest stem cells, including the promotion of proliferation and the expression of multipotential markers. Inhibition of the Hippo pathway results in a significant decrease in cell proliferation. The protein expression of HIF2α, SOX10, OCT4, NANOG, SOX2, and KLF4 was also reduced under hypoxic conditions.- Book : ()
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2025
Background: The registry-based collection of detailed cancer and late effect (LE) data in childhood and adolescent cancer (CAC) is rarely explored. Aim: We aimed to provide an overview of CAC registration practices in Europe and share a Slovenian example. Methods: We distributed a questionnaire among European cancer registries on disease, treatment and LE registration and present the system at the Slovenian Cancer Registry along with an example of retrospectively collected LE data from a cohort of central nervous system tumour survivors from 1983 to 2000. Kaplan–Meier and Cox regression were used to calculate the LE incidence. Results: Out of 27 responding registries, over 80% registered cancer type, vital status, death and second primary cancer data. Less than 20% registered cumulative doses of radiation and systemic therapy or progressions. Only three registered LEs. The obstacles in setting up LE collection in registries are a lack of standardization in the variable sets, definitions and methods of collection. In the retrospective cohort, neurological and endocrine LEs were most common. Females had a higher risk of endocrine LEs (HR of 1.89; 95% CI of 1.08–3.31), while patients treated with radiotherapy had higher risks of endocrine (3.47; 1.80–6.69), musculoskeletal and skin LEs (3.16; 1.60–6.26) and second primary cancers (2.85; 1.18–6.75). Conclusions: Standardization and harmonization are necessary to promote detailed CAC and LE registration.- Book : 17(4)
- Pub. Date : 2025
- Page : pp.580-580
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2025
Abstract
Acute ionizing radiation (IR) causes severe DNA damage, leading to cell cycle arrest, cell death, and activation of the innate immune system. The role and signaling pathway of stimulator of interferon genes (STING) in IR-induced tissue damage and cell death are not well understood. This study revealed that STING is crucial for promoting apoptosis in response to DNA damage caused by acute IR both in vitro and in vivo. STING binds to poly (ADP‒ribose) (PAR) produced by activated poly (ADP‒ribose) polymerase-1 (PARP1) upon IR. Compared with that in WT cells, apoptosis was suppressed in Sting
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cells. Excessive PAR production by PARP1 due to DNA damage enhances STING phosphorylation, and inhibiting PARP1 reduces cell apoptosis after IR. In vivo, IR-induced crypt cell death was significantly lower in Sting
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mice or with low-dose PARP1 inhibitor, PJ34, resulting in substantial resistance to abdominal irradiation. STING deficiency or inhibition of PARP1 function can reduce the expression of the proapoptotic gene PUMA, decrease the localization of Bax on the mitochondrial membrane, and thus reduce cell apoptosis. Our findings highlight crucial roles for STING and PAR in the IR-mediated induction of apoptosis, which may have therapeutic implications for controlling radiation-induced apoptosis or acute radiation symptoms.- Book : ()
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2025
Abstract
A new, simple and robust design for a gas proportional scintillation counter (GPSC) is studied. One sole electrode, the anode, is used to define the electric field in the drift and scintillation regions of the detector volume. The anode has an annular shape aligned with the photosensor axis. Such design allows to keep constant the solid angle subtended by the photosensor relative to the different positions of the scintillation region. Having an oblong anode with a 10 cm inner diameter and a 5 cm photomultiplier tube placed 5 cm below the anode, an energy resolution of 12.0 % FWHM has been achieved for a 10 kV anode bias, the maximum voltage that could be applied to the anode in the present prototype. According to simulations, energy resolutions of ~10 % can be achieved for anode voltages of ~13 kV, a value comparable to the 9–10 % achieved in GPSC using solid angle variation compensation. Independently of having a constant solid angle, the absolute value of the solid angle must be considered, a lower number of EL photons detected at the photosensor due to a reduced solid angle may contribute to the GPSC energy resolution degradation. In addition, non-uniformities present in the photosensor or in the GPSC must be taken into account, since they will contribute to a dependence of the pulse amplitude on the radiation interaction position despite the constant solid angle subtended by the photosensor relative to the scintillation region.- Book : 20(02)
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- Page : pp.C02021-C02021
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2025
Abstract
Terrestrial exoplanets around M- and K-type stars are important targets for atmospheric characterization. Such planets are likely tidally locked with the order of spin–orbit resonances (SORs) depending on eccentricity. We explore the impact of SORs on 3D atmospheric dynamics and chemistry, employing a 3D coupled climate-chemistry model to simulate Proxima Centauri b in 1:1 and 3:2 SORs. For a 1:1 SOR, Proxima Centauri b is in the Rhines rotator circulation regime with dominant zonal gradients (global mean surface temperature 229 K). An eccentric 3:2 SOR warms Proxima Centauri b to 262 K with gradients in the meridional direction. We show how a complex interplay between stellar radiation, orbit, atmospheric circulation, and (photo)chemistry determines the 3D ozone distribution. Spatial variations in ozone column densities align with the temperature distribution and are driven by stratospheric circulation mechanisms. Proxima Centauri b in a 3:2 SOR demonstrates additional atmospheric variability, including daytime–nighttime cycles in water vapor of +55% to −34% and ozone (±5.2%) column densities and periastron–apastron water vapor cycles of +17% to −10%. Synthetic emission spectra for the spectral range of the Large Interferometer For Exoplanets fluctuate by up to 36 ppm with the orbital phase angle for a 1:1 SOR due to 3D spatial and temporal asymmetries. The homogeneous atmosphere for the 3:2 SOR results in relatively constant emission spectra and provides an observational discriminant from the 1:1 SOR. Our work emphasizes the importance of understanding the 3D nature of exoplanet atmospheres and associated spectral variations to determine habitability and interpret atmospheric spectra.- Book : 6(1)
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