Objective:To investigate the effects of different doses of whole abdominal ultra‐high dose rate (FLASH) irradiation on the intestinal microbiota of mice.Methods:A total of 25 healthy male C57BL/6J mice were randomly divided into the control ( n=5) and FLASH irradiation groups ( n=20) by simple randomization method, and the FLASH irradiation group was further divided into different radiation dose subgroups of 10, 15, 20, 25 Gy, 5 in each group. The mice were irradiated with a single whole abdomen at a dose rate of 100 Gy/s, then sacrificed 3.5 d after irradiation. Fresh fecal specimens and intestinal tissues of mice were collected for 16S rRNA sequencing, microbiota analysis, hematoxylin eosin (HE) staining and injury severity score analysis. Two-group comparison was performed by independent sample t-test. Multi-group comparison was conducted by one-way ANOVA. Results:HE staining revealed that the whole abdomen FLASH irradiation caused varying degree of intestinal injury in mice, and the intestinal injury reaction was aggravated with the increase of irradiation dose. β‐diversity analyses showed that there were differences in the composition of intestinal microbiota between FLASH irradiation group and control group ( P=0.001), but the differences in the relative abundance of the species between the irradiation groups at different doses were relatively small, and there were their own dominant genera of bacteria. Comparison of different doses of FLASH irradiation groups with control group screened out 16 species of bacteria with shared differences at the genus level, in which Lactobacillus, Ligilactobacillus and unclassified Lactobacillus were more abundant in the control group, while Escherichia, Allobaculum, and Muribaculum were more abundant in the FLASH irradiation groups. Conclusions:The whole‐abdominal FLASH irradiation induces intestinal damage in mice, and the intestinal damage response is worsened with the increase of irradiation dose. Different doses of whole abdominal FLASH irradiation alter the intestinal microbiota composition of mice. Sixteen species of common intestinal differential microbiota at the genus level are screened out in the different doses of FLASH irradiation groups compared with the control group, which may serve as a marker for measuring intestinal injury in mice irradiated with whole‐abdominal FLASH.

Renal cell carcinoma(RCC)is the most common type of malignant kidney tumors,originating from re-nal tubular epithelial cells.The primary treatment options for RCC include surgery and targeted therapy.Despite the notable advancements in RCC research,significant challenges persist,including the high risk of metastasis and recur-rence post-surgery,as well as the low sensitivity to radiotherapy and chemotherapy.Ferroptosis,a form of regulated cell death first identified in 2012,has garnered significant attention due to its involvement in several cellular processes,including redox balance,iron metabolism,and various signaling pathways related to cancer progression.Given its po-tential to be modulated,ferroptosis offers significant promise for the treatment of cancers,ischemic organ damage,and other degenerative diseases associated with lipid peroxidation.This review discusses recent developments in ferroptosis research,with a particular focus on its role in RCC,and explores future research directions in this area.

Ultra-high dose rate radiotherapy (dose rate ≥40 Gy/s), spearheading a revolution in radiation oncology through its unique " FLASH effect", demonstrates remarkable efficacy in eradicating tumors while concomitantly mitigating damage to normal tissues. This special issue compiles cutting-edge research, offering multi-dimensional insights into its biological mechanisms. At the molecular level, FLASH achieves targeted tumor killing by differentially regulating endoplasmic reticulum stress, cell cycle arrest patterns, programmed cell death, and energy metabolism reprogramming. FLASH irradiation may induce a transient oxygen depletion, creating a hypoxic window that facilitates the efficient scavenging of free radicals within normal tissues. Various animal studies have consistently validated FLASH's capacity to significantly alleviate both acute and long-term radiation injuries while potently suppressing tumor growth. Concurrently, advancements in physics and dosimetry have addressed the core challenges of precise delivery and measurement of ultra-high dose rates, in order to clear critical hurdles for clinical translation. In summary, FLASH radiotherapy has established a solid foundation, spanning from mechanistic elucidation to technological innovation. Its clinical translation now urgently demands the advancement of high-quality, standardized research, with the ultimate goal of safely and precisely harnessing the highly promising FLASH effect for patient benefit, thereby achieving a transformative leap in both therapeutic efficacy and quality of life for cancer patients undergoing radiotherapy.

Objective:To explore the effects of proton FLASH irradiation (FLASH-IR) and conventional irradiation (CONV-IR) on the cell cycle, apoptosis, and pyroptosis of renal cancer cells.Methods:Renal cancer cells (769-P) were irradiated with 8 Gy of protons at a dose rate of 40 Gy/s for FLASH-IR and 0.4 Gy/s for CONV-IR, Ctrl group was treated without irradiation. Cells were collected 24 h after irradiation. The changes in the cell cycle were measured using flow cytometry. The expression of genes and proteins related to the cell cycle, apoptosis, and pyroptosis signaling pathways in renal cancer cells was measured using quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot.Results:Proton FLASH-IR increased the proportion of renal cancer cells in the G 0/G 1 phase [FLASH-IR group vs. Ctrl group, (67.01±0.44)% vs. (38.68±0.63)%, t = -63.99, P<0.05], while CONV-IR increased the proportion of renal cancer cells in the G 2/M phase [CONV-IR group vs. Ctrl group, (56.65±1.52)% vs. (23.67±0.51)%, t = -29.17, P<0.05]. Both proton FLASH-IR and CONV-IR caused apoptosis of renal cancer cells ( tFLASH= -16.24 to -5.01, P <0.05; tCONV=-20.08 to 6.11, P < 0.05) and CONV-IR activated the P53/P21 pathway ( t = -16.86 to -9.74, P < 0.05). Both proton FLASH-IR and CONV-IR induced pyroptosis of renal cancer cells ( tFLASH= -23.36 to 20.18, P <0.05; tCONV=-41.62 to 13.95, P <0.05), and the former exhibited a greater effect (FLASH-IR group vs. CONV-IR group, 0.96±0.01 vs. 0.68±0.44, t = -10.46, P <0.05). Conclusions:Both proton FLASH-IR and CONV-IR bring about changes in the cell cycle of renal cancer, promoting apoptosis and pyroptosis. However, there are differences between the two mechanisms that require further exploration. Proton FLASH-IR holds promise for the treatment of renal cancer.

Objective To explore the differential diagnostic value of three-dimensional CT values in active pulmonary tuberculosis(APTB)and inactive pulmonary tuberculosis(IPTB).Methods A retrospective analysis was conducted on 96 patients with pulmonary tuberculosis.According to whether the pulmonary tuberculosis lesions were active,the patients were divided into APTB group(n=61)and IPTB group(n=35).The baseline data,CT signs,and three-dimensional CT values were compared between two groups.Additionally,the results of three-dimensional CT values and conventional CT reading method in evaluating the activity of pulmonary tuberculosis were compared,and the accuracy,sensitivity and specificity of using three-dimensional CT values and conventional CT reading method to evaluate the activity of pulmonary tuberculosis were further analyzed.Results APTB group showed a higher incidence of bilateral pulmonary lesions than IPTB group(P<0.05).Compared with IPTB group,APTB group had higher proportions of blurred boundaries,parenchymal cavities,ground-glass opacities,and tree-in-bud signs(P<0.05),but lower proportions of parenchymal bronchiectasis,parenchymal calcifications,and fibrous strip shadows(P<0.05).The three-dimensional CT values in APTB group were lower than those in IPTB group(P<0.05).Significant differences were observed between conventional CT reading method and three-dimensional CT values in evaluating the activities of pulmonary parenchymal calcifications and thick-wall cavities(P<0.05).Specifically,three-dimensional CT values correctly identified 92 cases of tuberculosis lesions,including 59 cases of APTB and 33 cases of IPTB,and the remaining 4 misidentified lesions were calcified,consolidated and nodular lesions.Conventional CT reading method correctly identified 68 cases of tuberculosis lesions,including 43 cases of APTB and 25 cases of IPTB.The sensitivity,specificity,and accuracy of three-dimensional CT values were all higher than those of conventional CT reading method(P<0.05).Conclusion Three-dimensional CT values can effectively determine the activity of pulmonary tuberculosis,exhibiting high sensitivity,specificity,and accuracy.

Objective To explore the differential diagnostic value of three-dimensional CT values in active pulmonary tuberculosis(APTB)and inactive pulmonary tuberculosis(IPTB).Methods A retrospective analysis was conducted on 96 patients with pulmonary tuberculosis.According to whether the pulmonary tuberculosis lesions were active,the patients were divided into APTB group(n=61)and IPTB group(n=35).The baseline data,CT signs,and three-dimensional CT values were compared between two groups.Additionally,the results of three-dimensional CT values and conventional CT reading method in evaluating the activity of pulmonary tuberculosis were compared,and the accuracy,sensitivity and specificity of using three-dimensional CT values and conventional CT reading method to evaluate the activity of pulmonary tuberculosis were further analyzed.Results APTB group showed a higher incidence of bilateral pulmonary lesions than IPTB group(P<0.05).Compared with IPTB group,APTB group had higher proportions of blurred boundaries,parenchymal cavities,ground-glass opacities,and tree-in-bud signs(P<0.05),but lower proportions of parenchymal bronchiectasis,parenchymal calcifications,and fibrous strip shadows(P<0.05).The three-dimensional CT values in APTB group were lower than those in IPTB group(P<0.05).Significant differences were observed between conventional CT reading method and three-dimensional CT values in evaluating the activities of pulmonary parenchymal calcifications and thick-wall cavities(P<0.05).Specifically,three-dimensional CT values correctly identified 92 cases of tuberculosis lesions,including 59 cases of APTB and 33 cases of IPTB,and the remaining 4 misidentified lesions were calcified,consolidated and nodular lesions.Conventional CT reading method correctly identified 68 cases of tuberculosis lesions,including 43 cases of APTB and 25 cases of IPTB.The sensitivity,specificity,and accuracy of three-dimensional CT values were all higher than those of conventional CT reading method(P<0.05).Conclusion Three-dimensional CT values can effectively determine the activity of pulmonary tuberculosis,exhibiting high sensitivity,specificity,and accuracy.

Ultra-high dose rate radiotherapy (dose rate ≥40 Gy/s), spearheading a revolution in radiation oncology through its unique " FLASH effect", demonstrates remarkable efficacy in eradicating tumors while concomitantly mitigating damage to normal tissues. This special issue compiles cutting-edge research, offering multi-dimensional insights into its biological mechanisms. At the molecular level, FLASH achieves targeted tumor killing by differentially regulating endoplasmic reticulum stress, cell cycle arrest patterns, programmed cell death, and energy metabolism reprogramming. FLASH irradiation may induce a transient oxygen depletion, creating a hypoxic window that facilitates the efficient scavenging of free radicals within normal tissues. Various animal studies have consistently validated FLASH's capacity to significantly alleviate both acute and long-term radiation injuries while potently suppressing tumor growth. Concurrently, advancements in physics and dosimetry have addressed the core challenges of precise delivery and measurement of ultra-high dose rates, in order to clear critical hurdles for clinical translation. In summary, FLASH radiotherapy has established a solid foundation, spanning from mechanistic elucidation to technological innovation. Its clinical translation now urgently demands the advancement of high-quality, standardized research, with the ultimate goal of safely and precisely harnessing the highly promising FLASH effect for patient benefit, thereby achieving a transformative leap in both therapeutic efficacy and quality of life for cancer patients undergoing radiotherapy.

Objective:To explore the effects of proton FLASH irradiation (FLASH-IR) and conventional irradiation (CONV-IR) on the cell cycle, apoptosis, and pyroptosis of renal cancer cells.Methods:Renal cancer cells (769-P) were irradiated with 8 Gy of protons at a dose rate of 40 Gy/s for FLASH-IR and 0.4 Gy/s for CONV-IR, Ctrl group was treated without irradiation. Cells were collected 24 h after irradiation. The changes in the cell cycle were measured using flow cytometry. The expression of genes and proteins related to the cell cycle, apoptosis, and pyroptosis signaling pathways in renal cancer cells was measured using quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot.Results:Proton FLASH-IR increased the proportion of renal cancer cells in the G 0/G 1 phase [FLASH-IR group vs. Ctrl group, (67.01±0.44)% vs. (38.68±0.63)%, t = -63.99, P<0.05], while CONV-IR increased the proportion of renal cancer cells in the G 2/M phase [CONV-IR group vs. Ctrl group, (56.65±1.52)% vs. (23.67±0.51)%, t = -29.17, P<0.05]. Both proton FLASH-IR and CONV-IR caused apoptosis of renal cancer cells ( tFLASH= -16.24 to -5.01, P <0.05; tCONV=-20.08 to 6.11, P < 0.05) and CONV-IR activated the P53/P21 pathway ( t = -16.86 to -9.74, P < 0.05). Both proton FLASH-IR and CONV-IR induced pyroptosis of renal cancer cells ( tFLASH= -23.36 to 20.18, P <0.05; tCONV=-41.62 to 13.95, P <0.05), and the former exhibited a greater effect (FLASH-IR group vs. CONV-IR group, 0.96±0.01 vs. 0.68±0.44, t = -10.46, P <0.05). Conclusions:Both proton FLASH-IR and CONV-IR bring about changes in the cell cycle of renal cancer, promoting apoptosis and pyroptosis. However, there are differences between the two mechanisms that require further exploration. Proton FLASH-IR holds promise for the treatment of renal cancer.

Renal cell carcinoma(RCC)is the most common type of malignant kidney tumors,originating from re-nal tubular epithelial cells.The primary treatment options for RCC include surgery and targeted therapy.Despite the notable advancements in RCC research,significant challenges persist,including the high risk of metastasis and recur-rence post-surgery,as well as the low sensitivity to radiotherapy and chemotherapy.Ferroptosis,a form of regulated cell death first identified in 2012,has garnered significant attention due to its involvement in several cellular processes,including redox balance,iron metabolism,and various signaling pathways related to cancer progression.Given its po-tential to be modulated,ferroptosis offers significant promise for the treatment of cancers,ischemic organ damage,and other degenerative diseases associated with lipid peroxidation.This review discusses recent developments in ferroptosis research,with a particular focus on its role in RCC,and explores future research directions in this area.

Objective:To investigate the effects of different doses of whole abdominal ultra‐high dose rate (FLASH) irradiation on the intestinal microbiota of mice.Methods:A total of 25 healthy male C57BL/6J mice were randomly divided into the control ( n=5) and FLASH irradiation groups ( n=20) by simple randomization method, and the FLASH irradiation group was further divided into different radiation dose subgroups of 10, 15, 20, 25 Gy, 5 in each group. The mice were irradiated with a single whole abdomen at a dose rate of 100 Gy/s, then sacrificed 3.5 d after irradiation. Fresh fecal specimens and intestinal tissues of mice were collected for 16S rRNA sequencing, microbiota analysis, hematoxylin eosin (HE) staining and injury severity score analysis. Two-group comparison was performed by independent sample t-test. Multi-group comparison was conducted by one-way ANOVA. Results:HE staining revealed that the whole abdomen FLASH irradiation caused varying degree of intestinal injury in mice, and the intestinal injury reaction was aggravated with the increase of irradiation dose. β‐diversity analyses showed that there were differences in the composition of intestinal microbiota between FLASH irradiation group and control group ( P=0.001), but the differences in the relative abundance of the species between the irradiation groups at different doses were relatively small, and there were their own dominant genera of bacteria. Comparison of different doses of FLASH irradiation groups with control group screened out 16 species of bacteria with shared differences at the genus level, in which Lactobacillus, Ligilactobacillus and unclassified Lactobacillus were more abundant in the control group, while Escherichia, Allobaculum, and Muribaculum were more abundant in the FLASH irradiation groups. Conclusions:The whole‐abdominal FLASH irradiation induces intestinal damage in mice, and the intestinal damage response is worsened with the increase of irradiation dose. Different doses of whole abdominal FLASH irradiation alter the intestinal microbiota composition of mice. Sixteen species of common intestinal differential microbiota at the genus level are screened out in the different doses of FLASH irradiation groups compared with the control group, which may serve as a marker for measuring intestinal injury in mice irradiated with whole‐abdominal FLASH.