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Macrophage plays an important role in homeostasis and immunity, and dysfunctional macrophage polarization is believed to be associated with the pathogenesis of tissue fibrosis and tumor progression. Colony stimulating factor-1 (CSF-1), a polypeptide chain cytokine, through its receptor (CSF-1R) regulates the differentiation of macrophages. Recently, the promising therapeutic potential of CSF-1/CSF-1R signaling pathway inhibition in cancer treatment is widely used. Furthermore, inhibition of CSF-1/CSF-1R signaling combined with radiotherapy has been extensively studied to reduce immunosuppression and promote abscopal effect. In addition, cumulative evidence demonstrated that M2 phenotype macrophage is dominant in tissue fibrosis and the inhibition of CSF-1/CSF-1R signaling pathway ameliorated pulmonary fibrosis, including radiation-induced lung fibrosis. Herein, we provide a comprehensive review of the CSF-1/CSF-1R signaling pathway in radiotherapy, with a focus on advances in macrophage-targeted strategies in the treatment of cancer and pulmonary fibrosis.

The glutathione S-transferase P1(GSTP1) is an isoenzyme in the glutathione-S transferases (GSTs) enzyme system, which is the most abundant GSTs expressed in adult lungs. Recent research shows that GSTP1 is closely related to the regulation of cell oxidative stress, inhibition of cell apoptosis and promotion of cytotoxic metabolism. Interestingly, there is evidence that GSTP1 single nucleotide polymorphisms (SNP) 105Ile/Val related to the risk of radiation induced lung injury (RILI) development, which strongly suggests that GSTP1 is closely associated with the occurrence and development of RILI. In this review, we discuss our understanding of the role of GSTP1 in RILI and its possible mechanism.

Background and purpose Radiation-induced lung injury (RILI) limits the efficacy of thoracic radiotherapy. However, the underlying mechanism of RILI remains unclear. cGAS-STING pathway is reported to be involved in the recognization of cytosolic dsDNA and various inflammatory diseases. This study aimed to investigate the role of cGAS-STING pathway in the development of RILI. Materials and methods A pre-clinical mouse model of RILI was established by whole thorax irradiation and confirmed using H&E and Masson’s trichrome staining. STING agonist (DMXAA) and antagonist(C-176) were administrated to modulate cGAS-STING pathway in vivo. Western blot and ELISA were used to determine the expression levels of different proteins. Results Quantitation analysis showed dsDNA accumulation in lung tissue and western blot showed the up-regulation of cGAS and STING protein level post-irradiation, indicating pathway activation. Histological evaluation showed that C-176 administration ameliorated radiation-induced pulmonary inflammation and fibrosis, while DMXAA exhibited contrary effects. In further in vitro study, the release of dsDNA induced by radiation led to the activation of cGAS-STING pathway in RAW 264.7 cells, resulting in the polarization into M1 phenotype and pro-inflammatory production. Conclusion In summary, our data demonstrated a link between cGAS-STING pathway and the development of RILI, indicating its potential application in clinic.

This study compared deep inspiration breath-hold (DIBH) versus free-breathing (FB) techniques in postoperative radiotherapy for left-sided breast cancer. Dosimetric parameters for 94 patients were analyzed. DIBH significantly improved target conformity while reducing cardiac exposure, with mean heart dose decreasing by 2.631 Gy (EQD2). Significant dose reductions were also observed in bilateral lungs, esophagus, and spinal cord. A weak correlation was identified between left lung volume expansion and organ-at-risk dose reduction. Receiver operating characteristic analysis determined that a left lung volume increase of 807.1 cc predicted clinically meaningful cardiac protection. DIBH demonstrates effective organ sparing while only marginally compromising target coverage. Additionally, lung volume expansion could serve as a potential patient selection criterion.

Coal seam permeability is one of the key parameters affecting coalbed methane (CBM), and plays an important role in resource evaluation and regional selection. To fully explore the diffusion/flow potential properties initiated by methane adsorption beneath diverse moisture contents (1–5%) in coal molecules. The pore size distribution and methane adsorption capacities were discussed based on Monte Carlo (MC) and molecular dynamics (MD) methods. The potential properties of diffusion/flow induced by methane adsorption were investigated using the maximum absolute adsorption capacities as benchmark. The variation patterns of the pore structure were analyzed using SEM scanning experiment to verify the results of simulation analysis. It is found that the free pores facilitate methane molecular adsorption and increase adsorption spaces; the skeleton pores restrict the flow and transport of water molecules. Reduction values in surface free energies increase at different temperatures, and released heat diffusion coefficients and permeabilities for methane molecules drop as moisture contents increase. Interestingly, however, enhancements in temperatures increase the methane molecular diffusion coefficients. The lower the activation energies, the easier they are to diffuse. Sufficiently, the optimum conditions for gas drainage of coal seam are at temperature of 293K and moisture content of 5%, indicating greater contributions to gas pressure relief for coal seam. By comparing the results of molecular simulation and SEM scanning, trend of change is basically the same. Moreover, it is explored that hydraulic measure was the most significant to the CBM stimulation technology through field engineering application. This research is expected to provide guidance for facilitating the effectiveness of gas extraction for coal seam.

Background Radiation-induced lung injury (RILI) often occurs during clinical chest radiotherapy and acute irradiation from accidental nuclear leakage. This study explored the role of monophosphoryl lipid A (MPLA) in RILI. Materials and Methods The entire thoracic cavity of C57BL/6N mice was irradiated at 20 Gy with or without pre-intragastric administration of MPLA. HE staining, Masson trichrome staining, and TUNEL assay were used to assess lung tissue injury after treatment. The effect of irradiation on the proliferation of MLE-12 cells was analyzed using the Clonogenic assay. The effect of MPLA on the apoptosis of MLE-12 cells was analyzed using flow cytometry. Expression of γ-H2AX and epithelial-mesenchymal transition (EMT) markers in MLE-12 cells was detected by immunofluorescence and Western blot, respectively. Results MPLA attenuated early pneumonitis and late pulmonary fibrosis after thoracic irradiation and reversed radiation-induced EMT in C57 mice. MPLA further promoted proliferation and inhibited apoptosis of irradiated MLE-12 cells in vitro. Mechanistically, the radioprotective effect of MPLA was mediated by exosomes secreted by stimulated macrophages. Macrophage-derived exosomes modulated DNA damage in MLE-12 cells after irradiation. MPLA promoted the polarization of RAW 264.7 cells to the M1 phenotype. The exosomes secreted by M1 macrophages suppressed EMT in MLE-12 cells after irradiation. Conclusion MPLA is a novel treatment strategy for RILI. Exosomes derived from macrophages are key to the radioprotective role of MPLA in RILI.

Purpose To evaluate the dosimetric characteristics of ZAP-X stereotactic radiosurgery (SRS) for single brain metastasis by comparing with two mature SRS platforms. Methods Thirteen patients with single brain metastasis treated with CyberKnife (CK) G4 were selected retrospectively. The prescription dose for the planning target volume (PTV) was 18–24 Gy for 1–3 fractions. The PTV volume ranged from 0.44 to 11.52 cc.Treatment plans of thirteen patients were replanned using the ZAP-X plan system and the Gamma Knife (GK) ICON plan system with the same prescription dose and organs at risk (OARs) constraints. The prescription dose of PTV was normalized to 70% for both ZAP-X and CK, while it was 50% for GK. The dosimetric parameters of three groups included the plan characteristics (CI, GI, GSI, beams, MUs, treatment time), PTV (D 2 , D 95 , D 98 , D min , D mean , Coverage), brain tissue (volume of 100%-10% prescription dose irradiation V 100% -V 10% , D mean ) and other OARs (D max , D mean ),all of these were compared and evaluated. All data were read and analyzed with MIM Maestro. One-way ANOVA or a multisample Friedman rank sum test was performed, where p  < 0.05 indicated significant differences. Results The CI of GK was significantly lower than that of ZAP-X and CK. Regarding the mean value, ZAP-X had a lower GI and higher GSI, but there was no significant difference among the three groups. The MUs of ZAP-X were significantly lower than those of CK, and the mean value of the treatment time of ZAP-X was significantly shorter than that of CK. For PTV, the D 95 , D 98 , and target coverage of CK were higher, while the mean of D min of GK was significantly lower than that of CK and ZAP-X. For brain tissue, ZAP-X showed a smaller volume from V 100% to V 20% ; the statistical results of V 60% and V 50% showed a difference between ZAP-X and GK, while the V 40% and V 30% showed a significant difference between ZAP-X and the other two groups; V 10% and D mean indicated that GK was better. Excluding the D max of the brainstem, right optic nerve and optic chiasm, the mean value of all other OARs was less than 1 Gy. For the brainstem, GK and ZAP-X had better protection, especially at the maximum dose. Conclusion For the SRS treating single brain metastasis, all three treatment devices, ZAP-X system, CyberKnife G4 system, and GammaKnife system, could meet clinical treatment requirements. The newly platform ZAP-X could provide a high-quality plan equivalent to or even better than CyberKnife and Gamma Knife, with ZAP-X presenting a certain dose advantage, especially with a more conformal dose distribution and better protection for brain tissue. As the ZAP-X systems get continuous improvements and upgrades, they may become a new SRS platform for the treatment of brain metastasis.

Ultra-high dose rate (FLASH) radiotherapy is a novel modality delivering dose rates several orders of magnitude higher than conventional dose rate (CONV) radiotherapy. FLASH radiotherapy has been shown to significantly reduce the damaging effects on normal tissues while achieving similar tumor control, a phenomenon referred to as the FLASH effect. Radiation-induced lung injury (RILI) represents a prevalent complication in thoracic tumor radiotherapy, significantly compromising treatment outcomes and patient quality of life. Emerging preclinical evidence consistently demonstrates that FLASH radiotherapy significantly attenuates radiation-induced lung injury compared to CONV radiotherapy. The observed radioprotection primarily manifests in structural preservation of alveolar epithelium, pulmonary vasculature, and bronchial networks, concomitant with substantial reductions in both radiation pneumonitis and subsequent pulmonary fibrosis. Current evidence suggests that RILI pathogenesis involves multiple mechanisms, including DNA damage and repair, reactive oxygen species (ROS) and oxidative stress, inflammation, and immune response. These mechanistic insights provide a crucial foundation for investigating the radiobiological basis of the FLASH effect. Our review summarizes the preclinical studies of FLASH radiotherapy in mitigating lung injury. Furthermore, it explores the potential mechanisms underlying the FLASH effect from the perspective of the biological mechanism of RILI, aiming to provide a reference and direction for the clinical translation of FLASH radiotherapy.

Radiotherapy is one of the most important treatments for chest tumours. Although there are plenty of strategies to prevent damage to normal lung tissues, it cannot be avoided with the emergence of radiation‐induced lung injury. The purpose of this study was to investigate the potential radioprotective effects of glucosamine, which exerted anti‐inflammatory activity in joint inflammation. In this study, we found glucosamine relieved inflammatory response and structural damages in lung tissues after radiation via HE staining. Then, we detected the level of epithelial‐mesenchymal transition marker in vitro and in vivo, which we could clearly observe that glucosamine treatment inhibited epithelial‐mesenchymal transition. Besides, we found glucosamine could inhibit apoptosis and promote proliferation of normal lung epithelial cells in vitro caused by radiation. In conclusion, our data showed that glucosamine alleviated radiation‐induced lung injury via inhibiting epithelial‐mesenchymal transition, which indicated glucosamine could be a novel potential radioprotector for radiation‐induced lung injury.

Background It is very important to accurately delineate the CTV on the patient’s three-dimensional CT image in the radiotherapy process. Limited to the scarcity of clinical samples and the difficulty of automatic delineation, the research of automatic delineation of cervical cancer CTV based on CT images for new patients is slow. This study aimed to assess the value of Dense-Fully Connected Convolution Network (Dense V-Net) in predicting Clinical Target Volume (CTV) pre-delineation in cervical cancer patients for radiotherapy. Methods In this study, we used Dense V-Net, a dense and fully connected convolutional network with suitable feature learning in small samples to automatically pre-delineate the CTV of cervical cancer patients based on computed tomography (CT) images and then we assessed the outcome. The CT data of 133 patients with stage IB and IIA postoperative cervical cancer with a comparable delineation scope was enrolled in this study. One hundred and thirteen patients were randomly designated as the training set to adjust the model parameters. Twenty cases were used as the test set to assess the network performance. The 8 most representative parameters were also used to assess the pre-sketching accuracy from 3 aspects: sketching similarity, sketching offset, and sketching volume difference. Results The results presented that the DSC, DC/mm, HD/cm, MAD/mm, ∆V, SI, IncI and JD of CTV were 0.82 ± 0.03, 4.28 ± 2.35, 1.86 ± 0.48, 2.52 ± 0.40, 0.09 ± 0.05, 0.84 ± 0.04, 0.80 ± 0.05, and 0.30 ± 0.04, respectively, and the results were greater than those with a single network. Conclusions Dense V-Net can correctly predict CTV pre-delineation of cervical cancer patients and can be applied in clinical practice after completing simple modifications.