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Boron-enhanced proton therapy has recently appeared as a promising approach to increase the efficiency of proton therapy on tumor cells, and this modality can further be improved by the use of boron nanoparticles (B NPs) as local sensitizers to achieve enhanced and targeted therapeutic outcomes. However, the mechanisms of tumor cell elimination under boron-enhanced proton therapy still require clarification. Here, we explore possible molecular mechanisms responsible for the enhancement of therapeutic outcomes under boron NP-enhanced proton therapy. Spherical B NPs with a mode size of 25 nm were prepared by methods of pulsed laser ablation in water, followed by their coating by polyethylene glycol to improve their colloidal stability in buffers. Then, we assessed the efficiency of B NPs as sensitizers of cancer cell killing under irradiation with a 160.5 MeV proton beam. Our experiments showed that the combined effect of B NPs and proton irradiation induces an increased level of superoxide anion radical generation, which leads to the depolarization of mitochondria, a drop in their membrane mitochondrial potential, and the development of apoptosis. A comprehensive gene expression analysis (via RT-PCR) confirmed increased overexpression of 52 genes (out of 87 studied) involved in the cell redox status and oxidative stress, compared to 12 genes in the cells irradiated without B NPs. Other possible mechanisms responsible for the B NPs-induced radiosensitizing effect, including one related to the generation of alpha particles, are discussed. The obtained results give a better insight into the processes involved in the boron-induced enhancement of proton therapy and enable one to optimize parameters of proton therapy in order to maximize therapeutic outcomes. [ABSTRACT FROM AUTHOR]

The article describes in detail the equipment and method for measuring the Doppler frequency shift (DFS) on an inclined radio path, based on the principle of the phase-locked loop using an SDR receiver for the investigation of seismogenic and man-made disturbances in the ionosphere. During the two M7.8 earthquakes in Nepal (25 April 2015) and Turkey (6 February 2023), a Doppler ionosonde detected co-seismic and pre-seismic effects in the ionosphere, the appearances of which are connected with the various propagation mechanisms of seismogenic disturbance from the lithosphere up to the ionosphere. One day before the earthquake in Nepal and 90 min prior to the main shock, an increase in the intensity of Doppler bursts was detected, which reflected the disturbance of the ionosphere. A channel of geophysical interaction in the system of lithosphere–atmosphere–ionosphere coupling was traced based on the comprehensive monitoring of the DFS of the ionospheric signal, as well as of the flux of gamma rays in subsoil layers of rocks and in the ground-level atmosphere. The concept of lithosphere–atmosphere–ionosphere coupling, where the key role is assigned to ionization of the atmospheric boundary layer, was confirmed by a retrospective analysis of the DFS records of an ionospheric signal made during underground nuclear explosions at the Semipalatinsk test site. A simple formula for reconstructing the velocity profile of the acoustic pulse from a Dopplerogram was obtained, which depends on only two parameters, one of which is the dimension of length and the other the dimension of time. The reconstructed profiles of the acoustic pulses from the two underground nuclear explosions, which reached the height of the reflection point of the sounding radio wave, are presented. [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy (BNCT) is one of the most appealing radiotherapy modalities, whose localization can be further improved by the employment of boron-containing nanoformulations, but the fabrication of biologically friendly, water-dispersible nanoparticles (NPs) with high boron content and favorable physicochemical characteristics still presents a great challenge. Here, we explore the use of elemental boron (B) NPs (BNPs) fabricated using the methods of pulsed laser ablation in liquids as sensitizers of BNCT. Depending on the conditions of laser-ablative synthesis, the used NPs were amorphous (a-BNPs) or partially crystallized (pc-BNPs) with a mean size of 20 nm or 50 nm, respectively. Both types of BNPs were functionalized with polyethylene glycol polymer to improve colloidal stability and biocompatibility. The NPs did not initiate any toxicity effects up to concentrations of 500 µg/mL, based on the results of MTT and clonogenic assay tests. The cells with BNPs incubated at a 10B concentration of 40 µg/mL were then irradiated with a thermal neutron beam for 30 min. We found that the presence of BNPs led to a radical enhancement in cancer cell death, namely a drop in colony forming capacity of SW-620 cells down to 12.6% and 1.6% for a-BNPs and pc-BNPs, respectively, while the relevant colony-forming capacity for U87 cells dropped down to 17%. The effect of cell irradiation by neutron beam uniquely was negligible under these conditions. Finally, to estimate the dose and regimes of irradiation for future BNCT in vivo tests, we studied the biodistribution of boron under intratumoral administration of BNPs in immunodeficient SCID mice and recorded excellent retention of boron in tumors. The obtained data unambiguously evidenced the effect of a neutron therapy enhancement, which can be attributed to efficient BNP-mediated generation of α-particles. [ABSTRACT FROM AUTHOR]

During the catastrophic M7.8 earthquake in Turkey on 6 February 2023, anomalous effects were revealed in the ionosphere associated with various propagation mechanisms of seismogenic disturbance from the lithosphere up to the height of the ionosphere. Seventeen minutes after the main shock, a co-seismic disturbance was detected by a Doppler ionosonde on an inclined, 3010 km long, two-hop radio path "Kuwait—Institute of Ionosphere (Almaty)". An appearance of acoustic waves at the height of 232 km in the ionosphere was fixed 568 s after arrival of the surface Rayleigh wave to the sub-ionospheric point, and such a delay agrees with the calculated propagation time of a vertically moving acoustic wave. The disturbance lasted 160 s, and its double amplitude was above 2 Hz, which noticeably exceeds the background fluctuation of Doppler frequency. The best coincidence between the waveforms of the Doppler signal and of the surface seismic wave was observed over the duration of the two leading periods, with correlation coefficients of 0.86 and 0.79, correspondingly. Pre-seismic effects in the ionosphere were revealed 8 days before the main shock both in the variations of the Doppler frequency and of the critical frequency f 0 F 2 . The probable origination mechanism of the pre-seismic ionospheric disturbances above the region of the earthquake preparation determined by the Dobrovolsky radius may be considered in accordance with the concept of lithospheric–atmospheric–ionospheric coupling. [ABSTRACT FROM AUTHOR]

This paper presents an assessment of nuclear reaction yields of protons, α -particles, and neutrons in human tissue-equivalentmaterial in proton therapy using a simulation with Geant 4. In this study, we also check an enhancement of nuclear reactions due to the presence of Bi, Au, 11 B, and 10 B radiosensitizer nanoparticles. We demonstrate that a proton beam induces a noticeable amount of nuclear reactions in the tissue. Nevertheless, the enhancement of nuclear reaction products due to radiosensitizer nanoparticles is found to be negligible. [ABSTRACT FROM AUTHOR]

Proton therapy is one of the promising radiotherapy modalities for the treatment of deep-seated and unresectable tumors, and its efficiency can further be enhanced by using boron-containing substances. Here, we explore the use of elemental boron (B) nanoparticles (NPs) as sensitizers for proton therapy enhancement. Prepared by methods of pulsed laser ablation in water, the used B NPs had a mean size of 50 nm, while a subsequent functionalization of the NPs by polyethylene glycol improved their colloidal stability in buffers. Laser-synthesized B NPs were efficiently absorbed by MNNG/Hos human osteosarcoma cells and did not demonstrate any remarkable toxicity effects up to concentrations of 100 ppm, as followed from the results of the MTT and clonogenic assay tests. Then, we assessed the efficiency of B NPs as sensitizers of cancer cell death under irradiation by a 160.5 MeV proton beam. The irradiation of MNNG/Hos cells at a dose of 3 Gy in the presence of 80 and 100 ppm of B NPs led to a 2- and 2.7-fold decrease in the number of formed cell colonies compared to control samples irradiated in the absence of NPs. The obtained data unambiguously evidenced the effect of a strong proton therapy enhancement mediated by B NPs. We also found that the proton beam irradiation of B NPs leads to the generation of reactive oxygen species (ROS), which evidences a possible involvement of the non-nuclear mechanism of cancer cell death related to oxidative stress. Offering a series of advantages, including a passive targeting option and the possibility of additional theranostic functionalities based on the intrinsic properties of B NPs (e.g., photothermal therapy or neutron boron capture therapy), the proposed concept promises a major advancement in proton beam-based cancer treatment. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is a widespread oncological disease that proceeds in the indolent form in most patients. However, in some cases, the indolent form can transform into aggressive metastatic incurable cancer. The most important task of PCa diagnostics is to search for early markers that can be used for predicting the transition of indolent cancer into its aggressive form. Currently, there are two effective preclinical models to study PCa pathogenesis: patients derived xenografts (PDXs) and patients derived organoids (PDOs). Both models have limitations that restrict their use in research. In this work, we investigated the ability of the primary 2D prostate cell cultures (PCCs) from PCa patients to express epithelial and cancer markers. Early PCCs were formed by epithelial cells that were progressively replaced with the fibroblast-like cells. Early PCCs contained tissue-specific stem cells that could grow in a 3D culture and form PDOs similar to those produced from the prostate tissue. Early PCCs and PDOs derived from the tissues of PCa patients expressed prostate basal and luminal epithelial markers, as well as cancer markers AMACR, TMPRSS2-ERG, and EZH2, the latter being a promising candidate to mark the transition from the indolent to aggressive PCa. We also identified various TMPRSS2-ERG fusion transcripts in PCCs and PDOs, including new chimeric variants resulting from the intra- and interchromosomal translocations. The results suggest that early PCCs derived from cancerous and normal prostate tissues sustain the phenotype of prostate cells and can be used as a preclinical model to study the pathogenesis of PCa. [ABSTRACT FROM AUTHOR]

After the explosive eruption of the Hunga Tonga volcano on 15 January 2022, disturbances were observed at a distance of about 12,000 km in Northern Tien Shan and regarded variations in the atmospheric pressure, in telluric current, and in the Doppler frequency shift of ionospheric signal. At 16:00:55 UTC, a pulse of atmospheric pressure was detected there, with peak amplitude of 1.3 hPa and propagation speed of 0.3056 km/s, equal to the velocity of Lamb waves. In the variations in the Doppler frequency shift, disturbances of two types were registered on the 3212 km and 2969 km long inclined radio paths, one of which arose as a response to the passage of a Lamb wave (0.3059 km/s) through the reflection point of the radio wave and another as reaction to an acoustic-gravity wave (0.2602 km/s). Two successive perturbations were also detected in the records of telluric current at the arrival times of the Lamb and acoustic-gravity waves at the registration point. According to the parameters of the Lamb wave, the energy transfer into the atmosphere upon the explosion of the Hunga Tonga volcano was roughly estimated to be 2000 Mt of TNT equivalent. [ABSTRACT FROM AUTHOR]

Monitoring radiation background in the near-surface atmosphere and gamma rays, geoacoustic emission, and temperature in a borehole at 40 m depth, as well as Doppler sounding on a low-inclined radio pass, proceeded at the Tien Shan mountain station (3340 m a.s.l.) in northern Tien Shan with the common goal of searching for seismogenic effects preceding earthquakes. The flux of gamma rays in the borehole varied negligibly between the days, and it was not influenced by precipitation. Characteristic bay-like drops of the gamma ray flux were found (2–8) days before the M5.0–M6.2 earthquakes. In an M4.2 earthquake event with a 5.3 km epicenter distance, anomalies were detected (7–10) days before the earthquake in variation of the gamma ray flux, geoacoustic emission, and temperature. Simultaneously with gamma rays, a disturbance was detected in the Doppler shift of the ionospheric signal. Similarly, ionosphere disturbances triggered by the growth of radioactivity in the near-surface atmosphere were found in a retrospective analysis of the Doppler shift data acquired after underground nuclear explosions at the Semipalatinsk testing site. This effect is considered from the viewpoint of the lithosphere-atmosphere-ionosphere coupling concept. [ABSTRACT FROM AUTHOR]

Conventional X-ray therapy (XRT) is commonly applied to suppress cancerous tumors; however, it often inflicts collateral damage to nearby healthy tissue. In order to provide a better conformity of the dose distribution in the irradiated tumor, proton therapy (PT) is increasingly being used to treat solid tumors. Furthermore, radiosensitization with gold nanoparticles (GNPs) has been extensively studied to increase the therapeutic ratio. The mechanism of radiosensitization is assumed to be connected to an enhancement of the absorbed dose due to huge photoelectric cross-sections with gold. Nevertheless, numerous theoretical studies, mostly based on Monte Carlo (MC) simulations, did not provide a consistent and thorough picture of dose enhancement and, therefore, the radiosensitization effect. Radiosensitization by nanoparticles in PT is even less studied than in XRT. Therefore, we investigate the physics picture of GNP-enhanced RT using an MC simulation with Geant4 equipped with the most recent physics models, taking into account a wide range of physics processes relevant for realistic PT and XRT. Namely, we measured dose enhancement factors in the vicinity of GNP, with diameters ranging from 10 nm to 80 nm. The dose enhancement in the vicinity of GNP reaches high values for XRT, while it is very modest for PT. The macroscopic dose enhancement factors for realistic therapeutic GNP concentrations are rather low for all RT scenarios; therefore, other physico-chemical and biological mechanisms should be additionally invoked for an explanation of the radiosensitization effect observed in many experiments. [ABSTRACT FROM AUTHOR]