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2025
AbstractBackgroundRadiotherapy (RT) is a key treatment modality in cancer therapy, utilizing high‐energy radiation to directly kill tumor cells. Recent research has increasingly highlighted RT's potential to indirectly enhance antitumor immunity. However, this immune activation alone often fails to generate sustained systemic antitumor responses. In this study, we aimed to investigate the antitumor effects of combining cholesterolized toll‐like receptor 7 (TLR7) agonist liposomes, specifically 1V209‐Cho‐Lip, with RT.MethodsMouse tumor models were used to assess the impact of combining 1V209‐Cho‐Lip with RT on tumor progression and modification of the tumor microenvironment. In vitro, primary mouse bone marrow‐derived dendritic cells (BMDCs) were utilized to investigate changes in function and the activated pathways through RNA sequencing. Additionally, we explored the role of oxidized mitochondrial DNA (ox‐mtDNA) released from irradiated tumor cells as a damage‐associated molecular pattern in modulating immune responses. The involvement of interleukin‐1β (IL‐1β) and the inflammasome pathway in the antitumor efficacy of the combined treatment was evaluated using Il‐1β−/− and cysteinyl aspartate specific proteinase 1 knockout (Casp1−/−) mouse models.ResultsThe combination of 1V209‐Cho‐Lip and RT significantly inhibited tumor growth and induced antitumor immunity in tumor models. This combination therapy enhanced maturation, antigen presentation and IL‐1β secretion of dendritic cells (DCs) in vitro. Ox‐mtDNA released from irradiated tumor cells synergized with 1V209‐Cho‐Lip to activate the inflammasome pathway in DCs. The antitumor effect of the combined therapy was significantly reduced in Il‐1β−/− and Casp1−/− mice.ConclusionsThis study suggests that the combination of 1V209‐Cho‐Lip with RT might be a promising antitumor strategy and further studies are warranted to explore the clinical relevance of this combination therapy.- Book : ()
- Pub. Date : 2025
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2025
Hyperparathyroidism disrupts the balance of physiological bone formation and resorption by upregulating osteoclast activity. This leads to hypercalcemia, resulting in osteoporosis and eventually the formation of “brown tumors.” Currently used radiological and nuclear medicine imaging for primary hyperparathyroidism face challenges in accurately diagnosing bone-related complications. Molecular bone imaging techniques routinely consist of bone scintigraphy, with possible addition of bone-SPECT/CT. Recently, renewed interest has emerged in the use of Na[18F]F-PET/CT. Both applications are highly sensitive to in vivo osteoblast activity. However, the latter technique offers improved spatial resolution and sensitivity, as well as shorter incubation and faster scanning. This article summarizes current limitations and potential improvements in bone-SPECT/CT and Na[18F]F-PET/CT imaging in selected patients with hyperparathyroidism, compared to other relevant techniques and clinical parameters.- Book : 5()
- Pub. Date : 2025
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2025
Abstract
This study investigates the response of Timepix3 semiconductor pixel detectors in proton
beams of varying intensities, with a focus on FLASH proton therapy. Using the Timepix3
application-specific integrated circuit (ASIC) chip, we measured the spatial and spectral
characteristics of 220 MeV proton beams delivered in short pulses. The experimental setup involved
Minipix readout electronics integrated with a Timepix3 chipboard in a flexible architecture, and
an Advapix Timepix3 with a silicon sensor. Measurements were carried out with Timepix3 detectors
equipped with experimental gallium arsenide (GaAs) and silicon (Si) sensors. We also investigated
the response of a bare Timepix3 ASIC chip (without sensor). The detectors were placed within a
waterproof holder attached to the positioning system of the IBA Blue water phantom, with
additional measurements performed in air behind a 2 cm-thick polymethyl methacrylate (PMMA)
phantom. The results demonstrated the capability of the Timepix3 detectors to measure
time-over-threshold (ToT, deposited energy) and event counts (number of events in a pixel) in both
conventional and ultra-high-dose-rates (UHDR) proton beams. The bare ASIC chip configuration
sustained up to a dose rate (DR) of 270 Gy/s, the maximum tested intensity, although it exhibited
limited spatial resolution due to low detection efficiency. In contrast, Minipix Timepix3 with
experimental GaAs sensors showed saturation at low DR∼5 Gy/s. Furthermore, the Advapix Timepix3
detector was used in both standard and customized configurations. In the standard configuration
(Ikrum = 5), the detector showed saturation at DR∼5 Gy/s. But, in the customized configuration when
the per-pixel discharging signal (called “Ikrum”) was increased (Ikrum = 80), the detector
demonstrated enhanced performance by reducing the duration of the ToT signal, allowing beam spot
imaging up to DR=∼28 Gy/s in the plateau region of the Bragg curve. For such DR or higher, the
frame acquisition time was reduced to the order of microseconds, meaning only a fraction of the
pulse (with pulse lengths on the order of milliseconds) was captured.- Book : 20(04)
- Pub. Date : 2025
- Page : pp.C04030-C04030
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2025
AbstractPurposeDue to the tight curvature in their design, ring applicators are usually associated with large positioning errors. The standard practice to correct for these deviations based on global offsets may not be sufficient to comply with the recommended tolerance. In this work, we investigate two methods for applicator reconstruction that implement position‐dependent source offset corrections.MethodsMeasurements were performed using the Varian Interstitial PEEK Ring 60° and a Varian BRAVOS afterloader. Source positioning was characterized by means of autoradiographs acquired for three different loading patterns and three 192Ir sources over a period of 5 months. Additionally, the actual source path was determined by means of a series of planar kV images for different dummy cable positions. The first position‐dependent correction method consists of locally modifying the radius of the reconstructed source path according to the measured offsets. The second method, recommended by Varian, simulates a bidirectional movement of the source during applicator reconstruction to compensate for positioning errors.ResultsAutoradiographs showed a quasi‐linear increase of the dwell position offsets, with a negligible error at the tip and a value close to 3 mm at the end of the ring. This result, consistent with a circular wire movement with an effective radius 0.5 mm larger than the nominal value, was in agreement with the observations from the kV images. After implementation of the position‐dependent correction methods, residual positioning errors for the two methods resulted in a mean value (±1 SD) of 0.0 (±0.3) mm, and a range of [−0.7 mm, 0.7 mm].ConclusionThe two tested methods for applicator reconstruction with position‐dependent source offset corrections were able to successfully correct the positioning errors. The method recommended by the manufacturer had the additional advantages of a more straightforward implementation and the potential for use in other applicator types.- Book : ()
- Pub. Date : 2025
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2025
- Book : ()
- Pub. Date : 2025
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2025
The mitochondrial proteome arises from dual genetic origin. Nuclear-encoded proteins need to be transported across or inserted into two distinguished membranes, and the TOM complex represents the main translocase in the outer mitochondrial membrane. Its composition and regulations have been extensively investigated within yeast cells. However, we have little knowledge of the TOM complex composition within human cells. Here, we have defined the TOM interactome in a comprehensive manner using biochemical approaches to isolate the TOM complex in combination with quantitative mass spectrometry analyses. Within these studies, we defined the pleiotropic nature of the human TOM complex, including new interactors, such as TRABD. Our studies provide a framework to understand the various biogenesis pathways that merge at the TOM complex within human cells.- Book : ()
- Pub. Date : 2025
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2025
- Book : ()
- Pub. Date : 2025
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2025
An electrically injected vertical-cavity surface-emitting laser (VCSEL) with quantum-well-embedded InGaN quantum dots (QDs) as the active region was designed. The InGaN QD size and cavity length were optimized using PICS3D simulation software to achieve a high-performance InGaN QD-embedded VCSEL. A comparative analysis between the InGaN QD VCSEL and the traditional InGaN quantum well VCSEL was conducted, and the results demonstrated that the InGaN QD VCSEL achieved higher stimulated recombination radiation and internal quantum efficiency. The threshold current was reduced to 4 mA, corresponding to a threshold current density of 5.1 kA/cm², and the output power reached 4.4 mW at an injection current of 20 mA. A stable single-longitudinal-mode output was also achieved with an output wavelength of 436 nm. The proposed novel quantum-well-embedded QD active-region VCSEL was validated through theoretical simulations, confirming its feasibility. This study provides theoretical guidance and key epitaxial structural parameters for preparing high-performance VCSEL epitaxial materials.- Book : 12(3)
- Pub. Date : 2025
- Page : pp.276-276
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2025
- Book : 1075()
- Pub. Date : 2025
- Page : pp.170423-170423
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2025
Abstract
Radioresistance is a major challenge in tumor radiotherapy and involves in a mixture of cellular events, including ferroptosis, a new type of programmed cell death characterized by the excess accumulation of iron-dependent lipid peroxides. In the present study, we observed that surviving cancer tissues and cells after radiotherapy had significantly greater glutathione to oxidized glutathione (GSH/GSSG) ratios and lower lipid reactive oxygen species (ROS) and malondialdehyde (MDA) levels than nonirradiated tumors and cells. Untargeted lipidomic analyses revealed that oleic acid (OA) and palmitoleic acid (POA) were the most significantly upregulated unsaturated fatty acids in irradiated surviving cancer cells compared with those in control cancer cells irradiated with IR. Both OA and POA could protect cancer cells from the killing effects of the ferroptosis inducer erastin and RSL3, and OA had a stronger protective effect than POA, resulting in lower lipid ROS production than POA. Mechanistically, OA protected cells from ferroptosis caused by the accumulation of polyunsaturated fatty acid-containing phospholipids in an ACSL3-dependent manner. A mouse model demonstrated that ACSL3 knockdown combined with imidazole ketone erastin synergistically enhanced antitumor effects in radiation-resistant tumors in vivo. Our study reveals previously undiscovered associations between radiation and fatty acid metabolism and ferroptosis, providing a novel treatment strategy for overcoming cancer radioresistance.- Book : 16(1)
- Pub. Date : 2025
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