Electron beam irradiation developed cinnamon oil- (polyvinyl alcohol/gum tragacanth)/graphene oxide dressing hydrogels: Antimicrobial and healing assessments.

This study aimed to develop hydrogel dressings for wound healing composed of gum tragacanth (TG) and polyvinyl alcohol (PVA) loaded with Graphene oxide (GO) and Cinnamon oil (CMO) using electron beam irradiation. The impact of the preparation conditions and the incorporation of GO and CMO on the characteristic properties of the prepared CMO-(PVA/TG)-GO wound dressings was evaluated. The healing-related characteristics were assessed, including fluid absorption and retention, water vapor transmission rate (WVTR), hemolytic assay, and antimicrobial potential. Wound healing efficacy was evaluated using a scratch wound healing assay. FTIR analysis verified the chemical structure, whereas scanning electron microscopy demonstrated an appropriate porosity structure necessary for optimal wound healing. The gel content increases with the initial total polymer concentration and the irradiation dose increases. Higher GO and CMO content improve the gel content and decreases swelling. WVTR decreases with the rise in CMO content. In vitro, cytotoxicity and hemolytic potency assessments confirmed their biocompatibility. The incorporation of GO and CMO enhances the antimicrobial activity and wound-healing capability. Based on the above findings, CMO-(PVA/TG)-GO dressings show promising potential as candidates for wound care.

Cardiac doses with deep inspiration breath hold in breast cancer radiotherapy: direct comparison between WBI, PBI, and interstitial APBI.

Background: The optimal radiotherapy technique for cardiac sparing in left-sided early breast cancer (EBC) is not clear. In this context, the aim of our dosimetric study was to compare cardiac and lung doses according to the type of radiotherapy - whole breast irradiation (WBI), external partial breast irradiation (PBI), and multicatheter interstitial brachytherapy-accelerated partial breast irradiation (MIB-APBI). The dosimetric results with the WBI and PBI were calculated with and without DIBH. Materials and methods: Dosimetric study of 23 patients treated with WBI, PBI, with and without DIBH, or MIB-APBI. The prescribed dose was 40 Gy in 15 fractions for WBI and PBI and 34 Gy in 10 fractions (bid) for MIB-APBI. Doses to the organs-at-risk (OAR) - heart, left anterior descending coronary artery (LAD), left ventricle (LV), and left lung - were recalculated to the equivalent dose in 2-Gy fractions (EQD2). Results: The addition of DIBH significantly reduced EQD2 doses to all OARs (except for the left lung maximal dose) in WBI and PBI. MHD values were 0.72 Gy for DIBH-WBI, 1.01 Gy for MIB-APBI and 0.24 Gy for DIBH-PBI. There were no significant differences in cardiac doses between WBI with DIBH and PBI without DIBH. DIBH-PBI resulted in significantly lower mean doses to all OARs (except for maximum lung dose) compared to MIB-APBI. Conclusions: These results show that the use of DIBH significantly reduces cardiac doses in patients with left EBC. Partial irradiation techniques (PBI, MIB-APBI) significantly reduced cardiac doses due to the smaller clinical target volume. The best results were obtained with DIBH-PBI.

Dynamics and predictors of hematologic toxicity during cranio-spinal irradiation.

Background: Craniospinal irradiation (CSI) is a complex radiotherapy (RT) technique required for treating specific brain tumors and some hematologic malignancies. With large volumes of hematogenous bone marrow (BM) being irradiated, CSI could cause acute hematologic toxicity, leading to treatment interruptions or severe complications. We report on the dynamics and dose/volume predictors of hematologic toxicity during CSI. Materials and methods: Pediatric patients (≤ 18years) undergoing CSI in a tertiary cancer center were included. Medical records were retrospectively reviewed for clinical data and blood parameters were collected at baseline and weekly, until four weeks after the end of RT. The BM substructures were contoured, and dose-volume parameters were extracted. We used Wilcoxon rank-sum test to compare quantitative data, Chi square test for qualitative data and receiver operating characteristics (ROC) curves for dose/volume thresholds. Results: Fifty-one patients were included. Severe toxicities (grade 3-4) were recorded as follows: 2% anemia, 8% thrombocytopenia, 25% leukopenia, 24% neutropenia. Ninety-eight percent of patients had lymphopenia (grade 1-4) at some point. Twenty-nine percent required granulocyte-colony stimulating factor, 50% had an infection and 8% required a blood transfusion. Dmean > 3.6 Gy and V15 Gy > 10.6% for Pelvic Bones were associated with a higher risk of developing any ≥ G3 toxicities. Dmean > 30-35 Gy to the thoracic and lumbar spine was predictive for G3-4 anemia and thrombocytopenia, and Cervical Spine Dmean > 30 Gy was associated with ≥ G3 neutropenia. Conclusion: CSI was well tolerated, without life-threatening complications in our cohort, but hematologic toxicity was frequent, with severity increasing with higher mean doses delivered to the hematogenous BM and larger volumes of BM receiving 30-35 Gy.

Ultrasonic-driven chemical reduction synthesis of alizarin complexone-modified gold nanoparticles for dual-signal colorimetric and fluorometric sensing of histamine in seafood products.

Alizarin complexone-modified gold nanoparticles (Au0-NPsALz) were synthesized using a proposed ultrasonic irradiation-assisted chemical reduction method. Ultrasonic irradiation powers, reaction time and alizarin complexone concentration had been proven to be the main parameters for controlling the nucleation and growth of Au0-NPsALz. In the synthesized ultrasonic irradiation-assisted chemical reduction conditions, Au0-NPsALz had a spherical oriented morphology with a uniform size of 17.84 ± 1.37 nm and are shiny red with a surface plasmon resonance (SPR) of 535 nm. A rapid colorimetric and fluorometric dual-mode detection strategy for selective detection of histamine in seafood was developed based on the self-assembly of Au0-NPsALz-Ni (II) complexes. Ni (II) can capture the histamine molecules close to Au0-NPsALz surfaces, making changes in the colorimetric and fluorometric responses of the solution. The quantitative analysis of histamine was realized through the variation of dual-signal colorimetric and fluorometric responses. Such Au0-NPsALz sensor offered good detection sensitivity for histamine with a detection limit (LOD) of 59.32 µmol L-1 and 116.20 µmol L-1 and wide linear response within the range of 10-10000 µmol L-1 (R2 = 0.9952) and 100-5000 µmol L-1 (R2 = 0.9947) for colorimetric and fluorometric measurement, respectively. Recoveries ranging from 94.99 to 103.29 % and 97.67-106.88 % for colorimetric and fluorometric assay were obtained, showing low levels of matrix effects. Particularly, the results of the dual-mode sensor were also validated by comparing with the HPLC method for improving the assay accuracy and dependability. Ultimately, the developed Au0-NPsALz colorimetric and fluorometric probe performs excellently in practical applications, with promising results for detecting histamine in seafood products.

Current dilemma and future directions over prophylactic cranial irradiation in SCLC: a systematic review in MRI and immunotherapy era.

Small cell lung cancer (SCLC) is the most malignant pathological type of lung cancer with the highest mortality, and the incidence of brain metastasis (BM) is in high frequency. So far, prophylactic cranial irradiation (PCI) has been suggested as an effective treatment for preventing brain metastasis of SCLC. PCI has long been applied to limited-stage SCLC (LS-SCLC) patients who have achieved complete remission after radiotherapy and chemotherapy as a standard treatment. However, the neurocognitive decline is a major concern surrounding PCI. New therapeutic approaches targeting PCI-induced neurotoxicity, including hippocampal protection or memantine, have been increasingly incorporated into the therapeutic interventions of PCI. Helical tomotherapy, RapidArc, and Volumetric-modulated arc therapy (VMAT) with a head-tilting baseplate are recommended for hippocampal protection. Besides, in the MRI and immunotherapy era, the significance of PCI in SCLC patients is controversial. SCLC patients with PCI should be recruited in clinical trials since this is the only way to improve the existing standard of care. This review summarizes the current therapeutic strategy and dilemma over PCI for SCLC, providing a theoretical basis for clinical decision-making and suggestions for PCI practice in clinical.

Pencil Beam Scanning Proton Therapy as Single Vocal Cord Irradiation for Early-Stage Glottic Cancer.

Purpose: Single vocal cord irradiation (SVCI) is a promising technique to maintain excellent oncologic control and potentially improve upon toxicities for treatment of early-stage glottic squamous cell carcinomas. We sought to investigate whether pencil beam scanning (PBS) proton therapy could improve upon the already favorable dose gradients demonstrated with volumetric modulated arc therapy (VMAT) SVCI. Patients and Methods: A 64-year-old gentleman was treated in our department with 6X-flattening filter-free VMAT SVCI to 58.08 Gy in 16 fractions for a T1a well-differentiated squamous cell carcinoma of the left true vocal cord and tolerated it well with good local control. Comparative PBS plans were created in Raystation for the Varian ProBeam with clinical target volume (CTVs) generated to mimic the prescription target volume extent of the VMAT planning target volumes when accounting for PBS plan robustness (±3 mm translational shifts, 3.5% density perturbation). A 3-field single-field optimization plan was selected as dosimetrically preferable. Dosimetric variables were compared. Results: Several organs at risk doses improved with PBS, including the maximum and mean dose to ipsilateral carotids, maximum and mean dose to contralateral carotid, maximum dose to the spinal cord, maximum and mean dose to inferior constrictor/cricopharyngeus, maximum and mean dose to the uninvolved vocal cord, and mean dose to the thyroid gland. There are tradeoffs in skin dose depending on location relative to the target-with the highest and lowest isodoses extending more into the skin with the VMAT plan but with the moderate isodose lines covering a wider area with the PBS plan, but we deemed it tolerable regardless. Conclusion: SVCI is a promising strategy for maintaining the oncologic effectiveness of whole-larynx photon radiation while potentially improving upon the historic toxicity profile. The favorable dose distribution with PBS with respect to organs at risk dosimetry for PBS may allow for further improvements upon VMAT SVCI strategies. Clinical implementation of PBS SVCI may be considered.

Electrical Conductivity Characteristic of Polyimide under Long-Term Combined Electron Irradiation and Thermal Cycle in Vacuum.

During long-term operation, low-earth-orbit spacecraft are exposed to a severe environment of electron irradiation and thermal cycle. This affects the electric properties of polyimide, an essential insulation material for spacecraft electrical transmission equipment, particularly the conductivity characteristic. Therefore, this paper investigates the conductivity and its evolution of polyimide after the combination of 20 keV, 8 nA/cm2 electron irradiation, and 243-343 K, 5 K/min thermal cycle in a vacuum environment for 432 h. The results show that the conductivity increases by about 2 orders of magnitude over 432 h, with the threshold field for electric-field-dependent conductivity decreasing. The conductivity growth rate varies, rising during the first 192 h, then increasing in the midelectric field, and decreasing in the high electric field regions. The thermally stimulated depolarization current method demonstrates that increases in γ, ß1, and ß2 trap densities, associated with enhanced motility of end groups, diamines, and dianhydrides after long-chain breaks, lead to higher conductivity and growth rate. Additionally, increases in ß3 and α trap densities, related to increased C═O bonds and free radicals, reduce the threshold field and the conductivity growth rate in the range of 57.0-100.0 kV/mm after 192 h. These findings provide a reference for the performance evaluation and enhancement of spacecraft polyimide materials.

NDRG2 Deficiency Exacerbates UVB-Induced Skin Inflammation and Oxidative Stress Damage.

UVB radiation induces inflammatory and oxidative stress responses, contributing to skin damage, yet the underlying mechanisms are not fully understood. N-Myc downstream-regulated gene 2 (NDRG2), an emerging stress-associated gene, remains unexplored in UVB-induced skin injury. In this study, we detected skin NDRG2 expression after UVB irradiation for the first time and further used Ndrg2 knockout mice to clarify the role of NDRG2 in UVB-induced skin injury. Three-month-old male Ndrg2+/+ and Ndrg2-/- mice (16-18g) were exposed to UVB to induce acute skin damage, and then dorsal skin samples were collected for subsequent analyses. UVB-induced skin damage was scored. Western Blot Analysis, immunofluorescence (IF) double labeling, and immunohistochemistry (IHC) were employed to assess NDRG2 expression and/or distribution. The concentrations of TNF-α, IL-6, IL-1ß, MPO, MMP8, superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) were quantitatively assessed using enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (HE) staining were employed to determine pathological changes. RNA sequencing and analysis were performed to estimate transcript expression levels and analyze mRNA expression. DESeq2 software was employed to identify differentially expressed genes (DEGs). DEGs were visualized using volcanic and heat maps. Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed to identify primary biological functions, metabolic pathways, or signal transduction pathways associated with DEGs. UVB-challenged Ndrg2-/- mice exhibited significantly exacerbated skin damage (erythema, edema, and erosion), neutrophil infiltration, and apoptosis compared to Ndrg2+/+ mice. Furthermore, UVB-challenged Ndrg2-/- mice displayed significantly elevated pro-inflammatory cytokines, myeloperoxidase (MPO), matrix metalloproteinase-8 (MMP8), and reduced antioxidant expression. RNA sequencing identified 1091 significantly differentially expressed genes enriched in inflammation, immune response, and oxidative stress pathways. In conclusion, the deficiency of Ndrg2 markedly exacerbated UVB-induced skin damage by promoting inflammatory responses and inhibiting antioxidant responses. This suggests that stabilizing NDRG2 expression holds promise as a therapeutic strategy for protecting against UVB-induced skin damage.

Craniospinal irradiation for leptomeningeal metastasis of solid tumors: survival analysis and prognostic factors.

We conducted a study to examine the treatment outcomes and prognostic factors for patients who underwent craniospinal irradiation (CSI) for leptomeningeal metastasis of solid tumors. This retrospective study included patients who received CSI for leptomeningeal metastasis at a single institute between 2010 and 2021. Data from clinical records and the radiation information system were obtained and analyzed. A total of 25 patients were included in the study. Eighteen patients (72%) completed the scheduled CSI. The median overall survival (OS) period was 4.8 months (95% confidence interval (CI): 3.2-10.0 months). Symptom relief was achieved in four out of 23 symptomatic patients (17%). Non-hematological adverse events occurred in 12 patients (48%), with 1 patient (4%) developing Grade 3 bacterial meningitis and the other patients having Grade 1-2 events. Twenty patients (80%) had hematological adverse events of Grade 3 or higher. Grade 4 hematologic toxicities occurred in 3 patients (12%) due to neutropenia and in 11 patients (44%) due to lymphopenia. In multivariate Cox regression analysis, the systemic immune-inflammation index (SII) was identified as the only significant parameter for predicting OS. The median OS periods for patients with SII < 607 and SII ≥ 607 were 6.1 and 2.1 months, respectively (P = 0.003). In conclusion, this study showed the treatment outcomes of CSI for leptomeningeal metastasis of solid tumors. It was shown that a high baseline SII was associated with shorter OS after CSI. The findings will contribute to the evaluation of prognosis after CSI.

Collimation principles of a hollow X-ray microbeam for high-contrast cytoplasm irradiation.

A Monte Carlo simulation was used to assess the performance of a collimated hollow X-ray microbeam for subcellular cytoplasm irradiation. A high-Z coaxial collimation structure with an inner core for nucleus shielding was investigated. Two key performances, the extraction efficiency (cytoplasm dose per unit incident fluence) and the dose contrast (cytoplasm-to-nucleus dose ratio), were evaluated regarding the influences of the material, geometry and physical arrangements of the collimator, target dish and incident beam source. Simulation results demonstrate that a gold coaxial structure with a practical collimation geometry of a 1-mm length, 10-µm inner diameter and 200-µm outer diameter, with the top exit closely attached (with a minimized air gap) to the bottom of a cell dish with a 3-µm thick Mylar film is recommended for cytoplasm irradiation of adherent mammalian cells. For a synchrotron source in the energy range < 10 keV, a dose contrast of approximately 100 can be achieved. For a bremsstrahlung source <30-kV tube voltage, a dose contrast of approximately 50-100 can still be achieved. General principles are summarized with further explanations of the performance of the hollow X-ray microbeam.

Investigation of the beam quality and dose rate dependence of PAKAG polymer gel dosimeter in optical readout technique.

This study aims to evaluate the optical response dependence of the PAKAG polymer gel dosimeter on photon energy and dose rate. The produced gel dosimeters were irradiated using a Varian CL 21EX medical linear accelerator with delivered doses of 0, 2, 4, 6, 8, and 10 Gy. To examine the response dependence on the delivered dose rate, dose rates of 50, 100, 200, and 350 cGy/min were investigated. Additionally, two incident beam qualities of 6 and 18 MV were examined to study the response dependence on the incident beam energy. The irradiated polymer gel dosimeters were readout using a UV Vis spectrophotometer in the 300 to 800 nm scan range. The results reveal that a wide variation in dose rate (50-350 cGy.min-1) influences the absorbance-dose response and the sensitivity of PAKAG polymer gel dosimeter. However, smaller variations did not show a significant effect on the response. Furthermore, the response changed insignificantly with beam quality for investigated energies. It was concluded that the optical reading response of the PAKAG polymer gel dosimeter is satisfactorily independent of external parameters, including dose rate and incident beam quality. .

Combined biological effects of CBCT and therapeutic X-ray dose on chromosomal aberrations of lymphocytes.

BACKGROUND AND PURPOSE: Cone beam computed tomography (CBCT) is routinely used in radiotherapy to localize target volume. The aim of our study was to determine the biological effects of CBCT dose compared to subsequent therapeutic dose by using in vitro chromosome dosimetry. MATERIALS AND METHODS: Peripheral blood samples from five healthy volunteers were irradiated in two phantoms (water filled in-house made cylindrical, and Pure Image CTDI phantoms) with 6 MV FFF X-ray photons, the dose rate was 800 MU/min and the absorbed doses ranged from 0.5 to 8 Gy. Irradiation was performed with a 6 MV linear accelerator (LINAC) to generate a dose-response calibration curve. In the first part of the investigation, 1-5 CBCT imaging was used, in the second, only 2 Gy doses were delivered with a LINAC, and then, in the third part, a combination of CBCT and 2 Gy irradiation was performed mimicking online adapted radiotherapy treatment. Metaphases were prepared from lymphocyte cultures, using standard cytogenetic techniques, and chromosomal aberrations were evaluated. Estimate doses were calculated from chromosome aberrations using dose-response curves. RESULTS: Samples exposed to X-ray from CBCT imaging prior to treatment exhibited higher chromosomal aberrations and Estimate dose than the 2 Gy therapeutic (real) dose, and the magnitude of the increase depended on the number of CBCTs: 1-5 CBCT corresponded to 0.04-0.92 Gy, 1 CBCT + 2 Gy to 2.32 Gy, and 5 CBCTs + 2 Gy to 3.5 Gy. CONCLUSION: The estimated dose based on chromosomal aberrations is 24.8% higher than the physical dose, for the combination of 3 CBCTs and the therapeutic 2 Gy dose, which should be taken into account when calculating the total therapeutic dose that could increase the risk of a second cancer. The clinical implications of the combined radiation effect may require further investigation.

Optimizing UVA and UVC synergy for effective control of harmful cyanobacterial blooms.

Harmful cyanobacterial blooms (HCBs) pose a global ecological threat. Ultraviolet C (UVC) irradiation at 254 nm is a promising method for controlling cyanobacterial proliferation, but the growth suppression is temporary. Resuscitation remains a challenge with UVC application, necessitating alternative strategies for lethal effects. Here, we show synergistic inhibition of Microcystis aeruginosa using ultraviolet A (UVA) pre-irradiation before UVC. We find that low-dosage UVA pre-irradiation (1.5 J cm-2) combined with UVC (0.085 J cm-2) reduces 85% more cell densities compared to UVC alone (0.085 J cm-2) and triggers mazEF-mediated regulated cell death (RCD), which led to cell lysis, while high-dosage UVA pre-irradiations (7.5 and 14.7 J cm-2) increase cell densities by 75-155%. Our oxygen evolution tests and transcriptomic analysis indicate that UVA pre-irradiation damages photosystem I (PSI) and, when combined with UVC-induced PSII damage, synergistically inhibits photosynthesis. However, higher UVA dosages activate the SOS response, facilitating the repair of UVC-induced DNA damage. This study highlights the impact of UVA pre-irradiation on UVC suppression of cyanobacteria and proposes a practical strategy for improved HCBs control.

Incorporating intensity modulated total body irradiation into a Children's Oncology Group trial: Rationale, techniques, and safeguards.

Historically, total body irradiation (TBI) has been delivered using static, parallel opposed photon beams (2D-TBI). Recently, centers have increasingly used intensity-modulated radiation therapy (IMRT) techniques for TBI. Relative to 2D-TBI, IMRT can reduce doses to critical organs (i.e., lungs and kidneys) while delivering myeloablative doses to the rest of the body, so it may decrease the risk of toxicity while maintaining oncologic outcomes. Despite these potential benefits, delivering TBI using IMRT introduces new challenges in treatment planning and delivery. We describe the extensive experience with IMRT-based TBI at Stanford University and City of Hope Cancer Center. These groups, and others, have reported favorable clinical outcomes and have developed methods to optimize treatment planning and delivery. A critical next step is to evaluate the broader adoption of this approach. Therefore, IMRT-based TBI will be incorporated into a prospective, multi-institutional Children's Oncology Group study with careful procedures and safeguards in place.

The effects of carbon-ion beam irradiation on three-dimensional in vitro models of normal oral mucosa and oral cancer: development of a novel tool to evaluate cancer therapy.

Given that the original tumor microenvironment of oral cancer cannot be reproduced, predicting the therapeutic effects of irradiation using monolayer cultures and animal models of ectopic tumors is challenging. Unique properties of carbon-ion irradiation (CIR) characterized by the Bragg peak exert therapeutic effects on tumors and prevent adverse events in surrounding normal tissues. However, the underlying mechanism remains unclear. The biological effects of CIR were evaluated on three-dimensional (3D) in vitro models of normal oral mucosa (NOMM) and oral cancer (OCM3 and OCM4) consisting of HSC-3 and HSC-4 cells. A single 10- or 20-Gy dose of CIR was delivered to NOMM, OCM3, and OCM4 models. Histopathological and histomorphometric analyses and labeling indices for Ki-67, γH2AX, and TUNEL were examined after CIR. The concentrations of high mobility group box 1 (HMGB1) were measured. NOMM exhibited epithelial thinning after CIR, which could be caused by the decreased presence of Ki-67-labeled basal cells. The relative proportion of the thickness of cancer cells to the underlying stroma in cancer models decreased after CIR. This finding appeared to be supported by changes in the three labeling indices, indicating CIR-induced cancer cell death, mostly via apoptosis. Furthermore, the three indices and the HMGB1 release levels significantly differed among the OCM4 that received different doses and with different incubation times after CIR while those of the OCM3 models did not, suggesting more radiosensitivity in the OCM4. The three 3D in vitro models can be a feasible and novel tool to elucidate radiation biology.

Deep Inspiration breath Hold facilitates surgical cavity registration on cone beam imaging for Partial breast irradiation.

BACKGROUND AND PURPOSE: The quality of the Cone Beam Computed Tomography (CBCT) images used for patient set-up is essential to avoid geographical miss when narrower margins or shorter fractionation are used for example in Accelerated Partial Breast Irradiation (APBI). This study evaluates deep inspiration breath hold (DIBH) with skin guided radiotherapy as a tool for image improvement reducing motion artifacts. MATERIALS AND METHODS: Daily CBCT images of left and right breast cancer patients with well-defined surgical cavity on CT simulation were used for this study. Only left sided CBCT were acquired with DIBH. Trained and experienced radiation therapists were asked to evaluate the image quality using a cavity visualization score (CVS), an image quality Likert score, and to perform registration shifts. Images were anonymized and therapists were blinded to the use of DIBH. RESULTS: Images from 21 patients, with 15 CBCT each, were evaluated by 6 radiation therapists, generating 4,015 evaluation points. Statistically significant improvements were observed in CVS and image quality (p < 0.001) with DIBH. Also, the rate of surgical cavity identification increased to 76 % with DIBH compared to 56 % without (p < 0.001). DIBH significantly reduced the inter-observer variability in registration shift corrections (p < 0.001) CONCLUSION: Utilizing DIBH for motion control improves both the image quality and the surgical cavity identification. This results in a decrease in registration variability, which is important for APBI accuracy.

CD47;Rag2;IL-2rγ triple knock-out mice pre-conditioning with busulfan could be a novel platform for generating hematopoietic stem cells engrafted humanized mice.

Introduction: Humanized mouse models to recapitulate human biological systems still have limitations, such as the onset of lethal graft-versus-host disease (GvHD), a variable success rate, and the low accessibility of total body irradiation (TBI). Recently, mice modified with the CD47-SIRPA axis have been studied to improve humanized mouse models. However, such trials have been rarely applied in NOD mice. In this study, we created a novel mouse strain, NOD-CD47nullRag2nullIL-2rγnull (RTKO) mice, and applied it to generate humanized mice. Methods: Four-week-old female NOD-Rag2nullIL-2rγnull (RID) and RTKO mice pre-conditioned with TBI or busulfan (BSF) injection were used for generating human CD34+ hematopoietic stem cell (HSC) engrafted humanized mice. Clinical signs were observed twice a week, and body weight was measured once a week. Flow cytometry for human leukocyte antigens was performed at intervals of four weeks or two weeks, and mice were sacrificed at 48 weeks after HSC injection. Results: For a long period from 16 to 40 weeks post transplantation, the percentage of hCD45 was mostly maintained above 25% in all groups, and it was sustained the longest and highest in the RTKO BSF group. Reconstruction of human leukocytes, including hCD3, was also most prominent in the RTKO BSF group. Only two mice died before 40 weeks post transplantation in all groups, and there were no life-threatening GvHD lesions except in the dead mice. The occurrence of GvHD has been identified as mainly due to human T cells infiltrating tissues and their related cytokines. Discussion: Humanized mouse models under all conditions applied in this study are considered suitable models for long-term experiments based on the improvement of human leukocytes reconstruction and the stable animal health. Especially, RTKO mice pretreated with BSF are expected to be a valuable platform not only for generating humanized mice but also for various immune research fields.

Structural plasticity of pyramidal cell neurons measured after FLASH and conventional dose-rate irradiation.

Evidence shows that ultra-high dose-rate FLASH-radiotherapy (FLASH-RT) protects against normal tissue complications and functional decrements in the irradiated brain. Past work has shown that radiation-induced cognitive impairment, neuroinflammation and reduced structural complexity of granule cell neurons were not observed to the same extent after FLASH-RT (> MGy/s) compared to conventional dose-rate (CONV, 0.1 Gy/s) delivery. To explore the sensitivity of different neuronal populations to cranial irradiation and dose-rate modulation, hippocampal CA1 and medial prefrontal cortex (PFC) pyramidal neurons were analyzed by electron and confocal microscopy. Neuron ultrastructural analyses by electron microscopy after 10 Gy FLASH- or CONV-RT exposures indicated that irradiation had little impact on dendritic complexity and synapse density in the CA1, but did increase length and head diameter of smaller non-perforated synapses. Similarly, irradiation caused no change in PFC prelimbic/infralimbic axospinous synapse density, but reductions in non-perforated synapse diameters. While irradiation resulted in thinner myelin sheaths compared to controls, none of these metrics were dose-rate sensitive. Analysis of fluorescently labeled CA1 neurons revealed no radiation-induced or dose-rate-dependent changes in overall dendritic complexity or spine density, in contrast to our past analysis of granule cell neurons. Super-resolution confocal microscopy following a clinical dosing paradigm (3×10Gy) showed significant reductions in excitatory vesicular glutamate transporter 1 and inhibitory vesicular GABA transporter puncta density within the CA1 that were largely dose-rate independent. Collectively, these data reveal that, compared to granule cell neurons, CA1 and mPFC neurons are more radioresistant irrespective of radiation dose-rate.

Damage Characteristics Analysis of Laser Ablation Triple-Junction Solar Cells Based on Electroluminescence Characteristics.

To study the physical property effects of the laser on GaInP/GaAs/Ge solar cells and their sub-cell layers, a pulsed laser with a wavelength of 532 nm was used to irradiate the solar cells under various energy conditions. The working performance of the cell was measured with a source meter. The electroluminescence (EL) characteristics were assessed using an ordinary and an infrared camera. Based on the detailed balance theory, in the voltage characteristics of an ideal pristine cell, the GaInP layer made the most significant voltage contribution, followed by the GaAs layer, with the Ge layer contributing the least. When a bias voltage was applied to the pristine cell, the top GaInP cell emitted red light at 670 nm, the middle GaAs cell emitted near-infrared light at 926 nm, and the bottom Ge cell emitted infrared light at 1852 nm. In the experiment, the 532 nm laser wavelength within the response spectrum bands of the GaInP layer and the laser passed through the glass cover slip and directly interacted with the GaInP layer. The experimental results indicated that the GaInP layer first exhibited different degrees of damage under laser irradiation, and the cell voltage was substantially attenuated. The GaInP/GaAs/Ge solar cell showed a decrease in electrical and light emission characteristics. As the laser energy increased, the cell's damage intensified, gradually leading to a loss of photoelectric conversion capability, the near-complete disappearance of red light emission, and a gradual degradation of near-infrared emission properties. The EL imaging revealed varying damage states across the triple-junction gallium arsenide solar cell's sub-cells.