Low-dose Irradiation Research Articles

Cationic Metal-Organic Layer Delivers siRNAs to Overcome Radioresistance and Potentiate Cancer Radiotherapy.

Radiotherapy plays an important role in modern oncology, but its treatment efficacy is limited by the radioresistance of tumor cells. As a member of the inhibitor of apoptosis protein family, survivin plays a key role in developing radioresistance by mediating apoptosis evasion, promoting epithelial-mesenchymal transition, and modulating cell cycle dynamics. Efficient downregulation of survivin expression presents a promising strategy to enhance the antitumor effects of radiotherapy. Herein, we report the design of a hafnium-porphyrin-based cationic metal-organic layer (CMOL) with quaternary ammonium capping groups to deliver small interfering RNAs (siRNAs) for enhanced radiotherapy. The CMOL@siRNA nanoplatform not only increased energy deposition from X-rays and reactive oxygen species generation via a unique radiotherapy-radiodynamic therapy process, but also effectively delivered siRNAs to downregulate survivin expression and ameliorate radioresistance of cancer cells. Consequently, CMOL@siRNA in combination with low-dose X-ray irradiation demonstrated remarkable antitumor efficacy with 96.9% and 91.4% tumor growth inhibition in murine colorectal carcinoma and triple-negative breast cancer models, respectively.

Irradiation-Induced Microstrain and Dislocation Density in Additively Manufactured 316H Stainless Steel

This study investigated the response of additively manufactured (AM) 316H stainless steel (SS) compared to its conventionally manufactured counterpart under simulated irradiation conditions. We irradiated both types of steels with 0.5 MeV H+ ions at room temperature and analyzed their microstructural and mechanical properties. X-ray diffraction revealed higher initial dislocation densities in AM SS due to its fabrication process. Interestingly, at lower irradiation doses (0.6 dpa), the AM SS showed a decrease in microstrain, while the conventional SS showed an increase. This suggests differing defect annihilation mechanisms. At 6.0 dpa, AM SS exhibited a rise in mi- crostrain and dislocation density, potentially due to saturation effects. Conversely, conventional SS showed a decrease, possibly indicating disordering from the irradiation. Microhardness measure- ments supported these findings, with AM SS displaying a more gradual response compared to the pronounced hardening and softening observed in conventional SS. Tensile testing revealed lower hardening and strength in irradiated AM SS compared to its pristine state. Scanning electron mi- croscopy showed contrasting fracture behavior between the two steel types, with AM SS exhibiting less embrittlement despite its higher initial hardness. Overall, AM SS demonstrated superior mi- crohardness and microstructural integrity after irradiation, suggesting its potential for applications in harsh irradiated environments.

Atomic-scale probing of ion migration dynamics in Na3Ni2SbO6 cathode for sodium ion batteries

Honeycomb-layered phases like Na3Ni2SbO6 have been extensively researched as high-voltage and high-rate capability cathode materials for sodium-ion batteries. However, our understanding of the structural stability and dynamic reaction mechanisms of Na3Ni2SbO6 cathode during cycling, especially at atomic-scale, remains limited. Here, we track the microstructure evolution during extraction of Na+ ions in Na3Ni2SbO6 cathode at atomic scale in an aberration-corrected transmission electron microscope. The electron beam irradiation that can provide a driving force for the Na+ ion migration, allows us to mimic the battery charge process. By controlling the electron beam dose, we study the structure evolution behavior to obtain insights into understanding the work principle and failure mechanism of Na3Ni2SbO6 cathode under different charge rate conditions. We find that the real-time structural evolution and ion migration pathways of Na3Ni2SbO6 cathode are distinct under different electron beam doses. High-dose irradiation reveals Na ion depletion, surface cracks, and phase transformations, mimicking rapid capacity decay. In contrast, low-dose irradiation shows slower ion migration, ordered Na vacancy formation, and maintaining structural integrity, which more closely resembles the electrochemical process of actual battery. This study provides an atomistic understanding of the structural stability and Na ions deintercalation mechanism in Na3Ni2SbO6 cathodes, offering new insights into optimizing electrode materials.

Low-dose neutron irradiation effects on the elastoplastic deformation mechanisms of aluminum-doped gallium nitride under contact loading

The elastoplastic deformation mechanisms of irradiated aluminum (Al)-doped gallium nitride (GaN) under contact loading are investigated in this work using the nanoindentation simulations, which is of great significance for understanding the mechanical properties of the Al-doped GaN and guiding the design of durable and high-performance GaN-based devices. The mechanical behaviors of the Al-doped GaN with different doping concentrations are analyzed, including the indentation hardness, Young's modulus, elastic recovery rates, phase transformations, and stress distribution. It is found that Al doping increases their hardness, Young's modulus, and elastic recovery rates, and leads to an enlargement of the phase transformation regions, which is dominated by the high coordination number (CN) phase transformations. Furthermore, the effects of low-dose neutron irradiation on their elastoplastic deformation mechanisms are studied by triggering cascade collisions within the structure. When subjected to such irradiation, structural changes occur in the Al-doped GaN, their indentation hardness, Young's modulus, and elastic recovery rates increase remarkably, and its phase transformation mechanism is changed remarkably. The dislocation behaviors of the doped and undoped GaN are different under neutron irradiation. This study is important for capturing the mechanical stability and integrity of Al-doped GaN in an irradiation environment, as well as developing GaN-based devices with superior irradiation resistance.

Radiotherapy enhances the anti-tumor effect of CAR-NK cells for hepatocellular carcinoma

BackgroundChimeric antigen receptor (CAR)-NK cell therapy has shown remarkable clinical efficacy and safety in the treatment of hematological malignancies. However, this efficacy was limited in solid tumors owing to hostile tumor microenvironment (TME). Radiotherapy is commonly used for solid tumors and proved to improve the TME. Therefore, the combination with radiotherapy would be a potential strategy to improve therapeutic efficacy of CAR-NK cells for solid tumors.MethodsGlypican-3 (GPC3) was used as a target antigen of CAR-NK cell for hepatocellular carcinoma (HCC). To promote migration towards HCC, CXCR2-armed CAR-NK92 cells targeting GPC3 were first developed, and their cytotoxic and migration activities towards HCC cells were evaluated. Next, the effects of irradiation on the anti-tumor activity of CAR-NK92 cells were assessed in vitro and in HCC-bearing NCG mice. Lastly, to demonstrate the potential mechanism mediating the sensitized effect of irradiation on CAR-NK cells, the differential gene expression profiles induced by irradiation were analyzed and the expression of some important ligands for the NK-cell activating receptors were further determined by qRT-PCR and flow cytometry.ResultsIn this study, we developed CXCR2-armed GPC3-targeting CAR-NK92 cells that exhibited specific and potent killing activity against HCC cells and the enhanced migration towards HCC cells. Pretreating HCC cells with irradiation enhanced in vitro anti-HCC effect and migration activity of CXCR2-armed CAR-NK92 cells. We further found that only high-dose (8 Gy) but not low-dose (2 Gy) irradiation in one fraction could significantly enhanced in vivo anti-HCC activity of CXCR2-armed CAR-NK92 cells. Irradiation with 8 Gy significantly up-regulated the expression of NK cell-activating ligands on HCC cells.ConclusionsOur results indicate the evidence that irradiation could efficiently enhance the anti-tumor effect of CAR-NK cells in solid tumor model. The combination with radiotherapy would be an attractive strategy to improve therapeutic efficacy of CAR-NK cells for solid tumors.

The efect of low-dose gamma radiation on the development of plants from irradiated Pisum sativum sprouts in laboratory experiments

The problem of radiation exposure to organisms is relevant for areas where nuclear industry enterprises are located. Plant biotests are widely used for biotesting of anthropogenic factors affecting the environment, including radiation. The sensitivity of growth and cytogenetic parameters of the biotest based on Pisum sativum to the action of gamma irradiation n has been shown before, but only at high doses. The purpose of this work was to evaluate the influence of low-dose gamma irradiation on the development of Pisum sativum over 6-10 days after irradiating the sprouts. In the experiments, seeds of the Radomir sowing variety from the collection of the pea breeding laboratory of Krasnoyarsk Research Institute of Agriculture - Federal Research Centre Krasnoyarsk Scientific Center SB RAS were used. Pea sprouts were irradiated with a 137Cs source for 24 and 72 hours, with the absorbed dose being 20 and 62 mGy. After irradiation, the sprouts were grown in a climatic chamber on hydroponics for 10 days (240 hours). The control consisted of non-irradiated sprouts grown under identical conditions. The experiments for the first time provided reliable data on the negative effects of gamma irradiation (20 and 62 mGy) on the development of sowing peas 6-10 days after irradiation. A negative effect of gamma irradiation on the growth of the main and lateral roots of young plants was revealed. The experiments with irradiated pea sprouts confirmed the previously known fact that plant roots are more sensitive to irradiation compared to shoots. The pattern of change in the length of the main root of peas over time during germination at a dose of 20 mGy is described by a linear equation, while for a higher dose of irradiation, 62 mGy, the data can be approximated by a logarithmic equation with saturation. The different character of root length dependence on the time of cultivation after irradiation indicates a possible trend in plant growth under various doses of irradiation and cultivation times.

Bifunctional Metal-Organic Framework Synergistically Enhances Radiotherapy and Activates STING for Potent Cancer Radio-Immunotherapy.

The activation of the stimulator of interferon genes (STING) protein by cyclic dinucleotide metabolites plays a critical role in antitumor immunity. However, synthetic STING agonists like 4-(5,6-dimethoxybenzo[b]thiophen-2-yl)-4-oxobutanoic acid (MSA-2) exhibit suboptimal pharmacokinetics and fail to sustain STING activation in tumors for effective antitumor responses. Here, we report the design of MOF/MSA-2, a bifunctional MSA-2 conjugated nanoscale metal-organic framework (MOF) based on Hf6 secondary building units (SBUs) and hexakis(4'-carboxy[1,1'-biphenyl]-4-yl)benzene bridging ligands, for potent cancer radio-immunotherapy. By leveraging the high-Z properties of the Hf6 SBUs, the MOF enhances the therapeutic effect of X-ray radiation and elicits potent immune stimulation in the tumor microenvironment. MOF/MSA-2 further enhances radiotherapeutic effects of X-rays by enabling sustained STING activation and promoting the infiltration and activation of immune cells in the tumors. MOF/MSA-2 plus low-dose X-ray irradiation elicits strong STING activation and potent tumor regression, and when combined with an immune checkpoint inhibitor, effectively suppresses both primary and distant tumors through systemic immune activation.

Superior Survival After Unrelated Allogeneic Stem Cell Transplantation With Low-Dose ATG Compared to Low-Dose TBI in Myeloablative Fludarabine/Busulfan-Based Regimen for MDS on Behalf of the Adult MDS Working Group of the JSTCT

The fludarabine/intravenous busulfan 12.8 mg/kg (FB4) regimen is an effective conditioning regimen in allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome (MDS); however, limited data is available on the prognostic impact of FB4 with low-dose anti-thymoglobulin (ATG ≤ 5 mg/kg) or low-dose total body irradiation (TBI ≤ 4 Gy). Therefore, we retrospectively evaluated the outcomes in 280 adults with de novo MDS who underwent their first transplantation from an unrelated donor between 2009 and 2018. Median age was 61 years (range, 16 to 70 years). In the FB4 alone (FB4), FB4 plus ATG (FB4-ATG), and FB4 plus TBI (FB4-TBI) groups, 3-years overall survival (OS) rates were 39.9%, 64.8%, and 43.7%; 3-years nonrelapse mortality (NRM) were 32.1%, 22.1%, and 27.1%; and 3-years relapse incidences were 34.7%, 21.2%, and 28.9%, respectively. The multivariate analyses showed that FB4-ATG group significantly correlated with better OS (hazard Ratio [HR], 0.51; 95% confidence interval [CI], 0.27 to 0.95; P = .032) than FB4 group. FB4-ATG group tended to correlate with lower NRM (HR, 0.36; 95% CI, 0.13 to 1.06; P = .063) than FB4 group. In comparison with FB4-TBI group, FB4-ATG group showed better OS (HR 0.52, 95% CI 0.27 to 0.99, P = .049) and NRM (HR 0.034, 95% CI 0.11 to 0.92, P = .034). No significant differences were observed in OS and NRM between the FB4-TBI and FB4 groups. The present study demonstrated that the FB4 plus low-dose ATG regimen improved OS and NRM, but FB4 plus low-dose TBI regimen had no clear benefit over FB4 alone, in MDS patients who used unrelated donors.

Low-dose 60Co-γ-ray irradiation promotes the growth of cucumber seedlings by inducing CsSAUR37 expression.

Cucumber (Cucumis sativus L.) is a major vegetable crop grown globally, with a cultivation history of more than 3000years. The limited genetic diversity, low rate of intraspecific variation, and extended periods of traditional breeding have resulted in slow progress in their genetic research and the development of new varieties. Gamma (γ)-ray irradiation potentially accelerates the breeding progress; however, the biological and molecular effects of γ-ray irradiation on cucumbers are unknown. Exposing cucumber seeds to 0, 50, 100, 150, 200, and 250Gy doses of 60Co-γ-ray irradiation, this study aimed to investigate the resulting phenotype and physiological characteristics of seedling treatment to determine the optimal irradiation dose. The results showed that low irradiation doses (50-100Gy) enhanced root growth, hypocotyl elongation, and lateral root numbers, promoting seedling growth. However, high irradiation doses (150-250Gy) significantly inhibited seed germination and growth, decreasing the survival rate of seedlings. More than 100Gy irradiation significantly decreased the total chlorophyll content while increasing the malondialdehyde (MDA) and H2O2 content in cucumber. Transcriptome sequencing analysis at 0, 50, 100, 150, 200, and 250Gy doses showed that gene expression significantly differed between low and high irradiation doses. Gene Ontology enrichment and functional pathway enrichment analyses revealed that the auxin response pathway played a crucial role in seedling growth under low irradiation doses. Further, gene function analysis revealed that small auxin up-regulated gene CsSAUR37 was a key gene that was overexpressed in response to low irradiation doses, promoting primary root elongation and enhancing lateral root numbers by regulating the expression of protein phosphatase 2Cs (PP2Cs) and auxin synthesis genes.

Real-Time Fluorescence Monitoring System for Optimal Light Dosage in Cancer Photoimmunotherapy.

Background/Objectives: Near-infrared photoimmunotherapy (NIR-PIT) was recently approved for the treatment of unresectable locally advanced or recurrent head and neck cancers in Japan; however, only one clinical dose has been validated in clinical trials, potentially resulting in excessive or insufficient dosing. Moreover, IRDye700X (IR700) fluorescence intensity plateaus during treatment, indicating a particular threshold for the antitumor effects. Therefore, we investigated the NIR laser dose across varying tumor sizes and irradiation methods until the antitumor effects of the fluorescence decay rate plateaued. Methods: Mice were subcutaneously transplanted with A431 xenografts and categorized into control, clinical dose (cylindrical irradiation at 100 J/cm², frontal irradiation at 50 J/cm²), and evaluation groups. The rate of tumor IR700 fluorescence intensity decay to reach predefined rates (-0.05%/s or -0.2%/s) until the cessation of light irradiation was calculated using a real-time fluorescence imaging system. Results: The evaluation group exhibited antitumor effects comparable to those of the clinical dose group at a low irradiation dose. Similar results were observed across tumor sizes and irradiation methods. Conclusions: In conclusion, the optimal antitumor effect of NIR-PIT is achieved when the fluorescence decay rate reaches a plateau, indicating the potential to determine the appropriate dose for PIT using a real-time fluorescence monitoring system.

Total Ionizing Dose and Single-Event Effect Response of the AD524CDZ Instrumentation Amplifier

This manuscript focuses on studying the radiation response of the Commercial-off-the-shelf (COTS) AD524CDZ operational amplifier. Total Ionizing Dose (TID) effects were tested using low-dose 60Co irradiation. Single-Event Effect (SEE) sensitivity was studied on this operational amplifier using a 105 MeV proton beam. Additionally, further study of the SEE response was carried out using a Two-photon absorption laser to scan some sensitive sectors of the die. For this laser experiment, different gain setups and laser energies were employed to determine how the Single Event Transient (SET) response of the device was affected based on the test configuration. The results from the TID experiments revealed that the studied device remained functional after 100 krads (Si). Proton experiments revealed the studied device exhibited a high SET response with a maximum DC offset SET of about 1.5 V. Laser experiments demonstrated that there was a clear SET reduction when using 10× and 1000× gain setups.

LBE corrosion behavior of helium pre-irradiated martensitic steel

In the design of the spallation target of CiADS, T91 steel was selected for the most critical component, the beam window. A Si-modified martensitic steel (SIMP) has been currently developed, which has better corrosion resistance and is planning to replace T91 as a material of beam window in the future. In order to assess the effect of irradiation damage on the microstructure evolution and corrosion behavior of the SIMP, the pre-irradiated samples with irradiation doses from 5 × 1015 to 3 × 1017 He/cm2 exposed in static lead-bismuth eutectic (LBE) with saturated oxygen at 350 °C for 4000 h were investigated. Results show that pre-irradiation neither change the double-layer structure of the oxide layer nor significantly affect the corrosion rate. This may be due to the slow diffusion of elements at low temperatures, and the low irradiation dose not reaching the threshold for triggering accelerated corrosion.

Biodegradable copper-iodide clusters modulate mitochondrial function and suppress tumor growth under ultralow-dose X-ray irradiation

Both copper (Cu2+/+) and iodine (I−) are essential elements in all living organisms. Increasing the intracellular concentrations of Cu or I ions may efficiently inhibit tumor growth. However, efficient delivery of Cu and I ions into tumor cells is still a challenge, as Cu chelation and iodide salts are highly water-soluble and can release in untargeted tissue. Here we report mitochondria-targeted Cu-I cluster nanoparticles using the reaction of Cu+ and I− to form stable bovine serum albumin (BSA) radiation-induced phosphors (Cu-I@BSA). These solve the stability issues of Cu+ and I− ions. Cu-I@BSA exhibit bright radioluminescence, and easily conjugate with the emission-matched photosensitizer and targeting molecule using functional groups on the surface of BSA. Investigations in vitro and in vivo demonstrate that radioluminescence under low-dose X-ray irradiation excites the conjugated photosensitizer to generate singlet oxygen, and combines with the radiosensitization mechanism of the heavy atom of iodine, resulting in efficient tumor inhibition in female mice. Furthermore, our study reveals that BSA protection causes the biodegradable Cu-I clusters to release free Cu and I ions and induce cell death by modulating mitochondrial function, damaging DNA, disrupting the tricarboxylic acid cycle, decreasing ATP generation, amplifying oxidative stress, and boosting the Bcl-2 pathway.

Synthesis and Photodynamic Activities of Pyridine- or Pyridinium-Substituted Aza-BODIPY Photosensitizers.

In this work, various novel pyridinyl- and pyridinium-modified Aza-BODIPY PSs were designed and constructed based on monoiodo Aza-BODIPY PSs (BDP-4 and BDP-15) in an attempt to construct "structure-inherent organelles-targeted" PSs to endow potential organelle-targeting ability. Pyridinyl PSs displayed potent photodynamic efficacy, and monorigidified PSs were very effective. The monorigidified PS 20 with meta-pyridinyl moiety displayed the most potent photoactivity and negligible dark toxicity with a favorable dark/phototoxicity ratio (>4800). To our surprise, monorigidified PS with meta-pyridinyl moiety (e.g., 20) was lipid droplet-targeted. 20 showed good cellular uptake and intracellular ROS generation compared with BDP-15. The preliminary cell death process exploration indicated that 20 resulted in lipid peroxidation and induced cell death through an iron-independent ferroptosis-like cell death pathway. In vivo antitumor efficacy experiments manifested that 20 significantly inhibited tumor growth and outperformed BDP-15 and Ce6 even under a single low-dose light irradiation (30 J/cm2).

Digitonin-Loaded Nanoscale Metal-Organic Framework for Mitochondria-Targeted Radiotherapy-Radiodynamic Therapy and Disulfidptosis.

The efficacy of radiotherapy (RT) is limited by inefficient X-ray absorption and reactive oxygen species generation, upregulation of immunosuppressive factors, and a reducing tumor microenvironment (TME). Here, the design of a mitochondria-targeted and digitonin (Dig)-loaded nanoscale metal-organic framework, Th-Ir-DBB/Dig, is reported to overcome these limitations and elicit strong antitumor effects upon low-dose X-ray irradiation. Built from Th6O4(OH)4 secondary building units (SBUs) and photosensitizing Ir(DBB)(ppy)2 2+ (Ir-DBB, DBB=4,4'-di(4-benzoato)-2,2'-bipyridine; ppy=2-phenylpyridine) ligands, Th-Ir-DBB exhibits strong RT-radiodynamic therapy (RDT) effects via potent radiosensitization with high-Z SBUs for hydroxyl radical generation and efficient excitation of Ir-DBB ligands for singlet oxygen production. Th-Ir-DBB/Dig releases digitonin in acidic TMEs to trigger disulfidptosis of cancer cells and sensitize cancer cells to RT-RDT through glucose and glutathione depletion. The released digitonin simultaneously downregulates multiple immune checkpoints in cancer cells and T cells through cholesterol depletion. As a result, Th-Ir-DBB/dig plus X-ray irradiation induces strong antitumor immunity to effectively inhibit tumor growth in mouse models of colon and breast cancer.

Influence of γ-radiation on magnetoelectrical properties of Bi0.85Sb0.15 (0.001≤x≥0.05) solid solution

Abstract The influence of γ-quantum on the magnetoelectric properties of Bi0.85Sb0.15 <Pbx> (0.001≤x≥0.05) thermoelectrics doped with lead atoms at ~77÷300K and magnetic field induction up to 1.0 Tesla has been studied. It was found that at low doses of gamma irradiation of the Bi0.85Sb0.15 <Pb> solid solution, point defects are formed, which lead to an increase in the concentration of free electrons n, specific electrical conductivity σ and a decrease in the absolute value of the thermo EMF coefficients α and RH. As the dose of γ-quanta increases in the process of subsequent restructuring, point defects accumulate, i.e. accumulation of point defects, which leads to a decrease in the concentration of current carriers and a corresponding change in σ, α. and RH.

High Bioavailability of Spinach Folate Evaluated by Functional Biomarkers in a Folate Depletion-Repletion Mouse Model.

The bioavailability of natural folates is 50% lower than that of synthetic folic acid (FA); however, it remains unclear whether this value is universally applicable to all foods. Therefore, the present study investigated the bioavailability of folate from spinach using multiple biomarkers in a folate depletion-repletion mouse model. Mice were fed a folate-deficient diet for 4 wk and subsequently divided into three groups: folate-deficient, FA, and spinach folate. The folate repletion group received either FA or spinach folate at 2 mg/kg diet for 9 d. On the 7th day of repletion, half of each group underwent low-dose total body X-ray irradiation to induce chromosomal damage in bone marrow. Folate bioavailability biomarkers included measurements of folate levels in plasma, liver, and bone marrow along with an analysis of plasma homocysteine levels and chromosome damage, both of which are functional biomarkers of body folate. The consumption of a folate-deficient diet led to decreased tissue folate levels, increased plasma homocysteine levels, and chromosomal damage. Repletion with spinach folate restored folate levels in plasma, liver, and bone marrow to 69, 13, and 68%, respectively, of FA levels. Additionally, spinach folate repletion reduced plasma homocysteine levels and chromosome damage to 83% and 93-117%, respectively, of FA levels. Collectively, the present results demonstrated that the bioavailability of spinach folate exceeded 83% of FA, particularly when assessed using functional biomarkers.

Radiation-induced liver disease mimicking liver metastasis after low-dose hepatic irradiation during radiotherapy for gastric mucosa-assisted lymphoid tissue lymphoma: A case report.

Radiation-induced liver disease (RILD) is an established complication of hepatic irradiation that is typically reported in patients receiving high-dose radiotherapy for hepatocellular carcinoma or liver metastases. However, RILD can also occur after unintentional low-dose liver exposure during radiotherapy for other gastrointestinal malignancies when careful precautions are not taken. We report the case of a 44-year-old woman with gastric mucosa-associated lymphoid tissue lymphoma who underwent salvage radiotherapy administered to the entire stomach. One month after completing this radiotherapy, computed tomography and magnetic resonance imaging of the patient's abdomen revealed a 4 cm lesion in the left lateral liver segment, suggestive of metastasis. An ultrasound-guided biopsy was performed, and the histopathological findings were consistent with those of RILD. Conservative management was pursued with close monitoring of liver function tests. The patient's imaging findings and liver enzyme levels normalized approximately 3 months after the initial diagnosis. This case highlights the importance of considering RILD in the differential diagnosis of new hepatic lesions detected after radiotherapy, even in patients with low-dose liver exposure within generally acceptable limits. Careful correlation with the radiotherapy plan is crucial to avoid misdiagnosing RILD as metastatic disease and to guide appropriate management.

Tumor Microenvironment Reprogrammed Bimetallic Hybrid Nanostimulator for Triggering Radio-Cuproptosis-Immunotherapy.

Radio-immunotherapy driven by radiation-induced immunogenic cell death (ICD) is emerging as a potential opportunity to address conventional radiotherapy (RT) that is only applicable to localized tumor treatment. However, the effective activation of ICD during RT is severely limited by radiation dose, weak tumor immunogenicity, and radio-resistance caused by tumor microenvironment (TME). Herein, a novel bimetallic hybrid nanoscale coordination nanostimulator is first proposed by phosphate backbone doped with copper ions (Cu2+) and hafnium ions (Hf4+), and then modified with polyvinylpyrrolidone (PVP). The PVPylated Cu/Hf-doped phosphate nanostimulator (denoted as CHP) exhibits effective reprogramming of TME, including depletion of tumor endogenous glutathione (GSH), relief of tumor hypoxia and repolarization of M2 phenotypic macrophages, thus achieving tumor radiosensitization at low X-ray irradiation dose, gradually accumulation of tumor endogenous reactive oxygen species (ROS) and augmenting cuproptosis. In addition, cuproptosis can amplify RT-induced anti-tumor immunity through ICD activation, ultimately resulting in a robust anti-tumor immune response and long-term immunity, evidenced by distant tumor growth inhibition of 4T1-tumor-bearing models. More interestingly, it is discovered that CHP-mediated cuproptosis can be intensifiable during X-ray irradiation. Taken together, this work presents a novel radio-cuproptosis-immunotherapy cascade strategy, offering a new perspective for innovation in the treatment field of breast cancer.

Clinical and preclinical evidence on the bioeffects and movement-related implications of photobiomodulation in the orthodontic tooth movement: A systematic review.

Photobiomodulation (PBM) has been demonstrated as a non-invasive and painless technique with great potential to accelerate orthodontic tooth movement (OTM). However, there is a great inconsistency among PBM protocols and reported outcomes, probably due to the poor translatability of preclinical knowledge into early clinical practice. Hence, this review aims to fill this gap by establishing the state-of-the-art on both preclinical and clinical applications of PBM, and by comprehensively discussing the most suitable stimulation protocols described in the literature. This review was conducted according to PRISMA guidelines. A bibliographic search was carried out in the PubMed, Scopus and Cochrane databases using a combination of keywords. Only studies written in English were eligible and no time limit was applied. A total of 69 studies were selected for this review. The revised literature describes that PBM can effectively reduce orthodontic treatment time and produce analgesic and anti-inflammatory effects. We found that PBM of 640 ± 25, 830 ± 20 and 960 ± 20 nm, delivered at a minimum energy density per irradiation point of 5 J/cm2 daily or every other day sessions is robustly associated with increased tooth movement rate. Pain relief seems to be achieved with lower irradiation doses compared to those required for OTM acceleration. For the first time, the bioeffects induced by PBM for the acceleration of OTM are comprehensively discussed from a translational point of view. Collectively, the evidence from preclinical and clinical trials supports the use of PBM as a coadjuvant in orthodontics for enhancing tooth movement and managing treatment-associated discomfort. Overall, the revised studies indicate that optimal PBM parameters to stimulate tissue remodelling are wavelengths of 830 ± 20 nm and energy densities of 5-70 J/cm2 applied daily or every other day can maximize the OTM rate, while lower doses (up to 16 J/cm2 per session) delivered in non-consecutive days seem to be optimal for inducing analgesic effects. Future research should focus on optimizing laser parameters and treatment protocols customized for tooth and movement type. By fine-tuning laser parameters, clinicians can potentially reduce treatment times, improve patient comfort and achieve more predictable outcomes, making orthodontic care more efficient and patient-friendly, thus consolidating PBM usage in orthodontics.