A hyaluronic acid hydrogel as a mild photothermal antibacterial, antioxidant, and nitric oxide release platform for diabetic wound healing.

Hyaluronic acid (HA)-based biopolymer hydrogels are promising therapeutic dressings for various wounds but still underperform in treating diabetic wounds. These wounds are extremely difficult to heal and undergo a prolonged and severe inflammatory process due to bacterial infection, overexpression of reactive oxygen species (ROS), and insufficient synthesis of NO. In this study, a dynamic crosslinked hyaluronic acid (HA) hydrogel dressing (Gel-HAB) loaded with allomelanin (AMNP)-N, N'-dis-sec-butyl-N, N'-dinitroso-1, 4-phenylenediamine (BNN6) nanoparticles (AMNP-BNN6) was developed for healing diabetic wounds. The dynamic acylhydrazone bond formed between hydrazide-modified HA (HA-ADH) and oxidized HA (OHA) makes the hydrogel injectable, self-healing, and biocompatible. The hydrogel, loaded with AMNP-BNN6 nanoparticles, exhibits promising ROS scavenging ability and on-demand release of nitric oxide (NO) under near-infrared (NIR) laser irradiation to achieve mild photothermal antibacterial therapy (PTAT) (∼ 48 °C). Notably, the Gel-HAB hydrogel effectively reduced the oxidative stress level, controlled infections, accelerated vascular regeneration, and promoted angiogenesis, thereby achieving rapid healing of diabetic wounds. The injectable self-healing nanocomposite hydrogel could serve as a mild photothermal-enhanced antibacterial, antioxidant, and nitric oxide release platform for the treatment of diabetic wounds.

Mussel-inspired PDA@PEDOT nanocomposite hydrogel with excellent mechanical strength, self-adhesive, and self-healing properties for a flexible strain sensor.

Conductive hydrogel sensors have attracted attention for use in human motion monitoring detection, but integrating excellent biocompatibility, mechanical, self-adhesive, and self-healing properties, and high sensitivity into a hydrogel remains a challenge. In this work, a novel multifunctional conductive particle was designed and added to a polyacrylamide (PAM) matrix to prepare the hydrogel. It is worth noting that with the addition of polydopamine@poly(3,4-ethylenedioxythiophene) (PDA@PEDOT), the PAM/PDA@PEDOT hydrogel (PAPP hydrogel) showed excellent mechanical properties and high adhesion strength on different substrate surfaces. Meanwhile, the PAPP hydrogel shows outstanding self-healing properties, the mechanical properties of PAPP hydrogel broken from the middle recovered 92% tensile strength and 95% elongation at break after 12 h, respectively. Furthermore, assembled as strain wireless sensors, the PAPP sensor displays high sensitivity, where the gauge factor (GF) is 2.82, which can be used to accurately detect human facial micro-expressions and movements. Overall, the PAPP hydrogel with excellent mechanical, self-adhesive, and self-healing properties, and high sensitivity, demonstrated promise for use in wearable devices and bionic skins.

Regulatory role of RGMb in lung injury promoted by the combination of carbon ion irradiation and anti-PD-1 antibody through Erk1/2 and p38 MAPK pathways.

The combination of carbon ion radiotherapy and anti-PD-1 antibody represents a new approach to treating thoracic tumors. However, the lung damage caused by this combination therapy may limit its use, and the potential mechanisms for this are worthy of investigation. The objective of this research was to examine the potential involvement of repulsive guidance molecule b (RGMb) in lung damage promoted by the utilization of carbon ion irradiation combined with an anti-PD-1 antibody. The C57BL/6 mice have been randomly separated into four distinct groups: control, anti-PD-1, whole thorax carbon ion irradiation, and irradiation in combination with anti-PD-1 treatment groups (combination group). Detection of pathological changes in lung tissue using HE staining. Detection of pulmonary fibrosis by Masson staining and the hydroxyproline assay. ELISA to detect TNF-α, TGF-ß, IL-6, and IL-1ß expression levels within lung homogenates. The expression of RGMb, p38 MAPK, and Erk1/2 pathways was detected using a fully automated digital Western blotting system WES (ProteinSimple, USA). Flow cytometry was employed to analyze tissue-resident memory T cells (TRM) within the lung. Subsequently, the siRNA gene was employed to induce the downregulation of RGMb in mice in order to validate the involvement of RGMb in radiation-immune lung injury. The present study observed a significant increase in both inflammatory and fibrotic indicators within the mice group's lung tissue that received the combination treatment. The combination group exhibited elevated levels of TGF-ß, TNF-α, IL-6, and IL-1ß in lung homogenates. Anti-PD-1 antibody and carbon ion irradiation, upregulated RGMb, phospho-p38 MAPK and phospho-Erk1/2. The results obtained from the flow cytometry analysis indicated that the combination group was significantly higher in the number of clonal expansion TRMs, which were predominantly characterized by the expression of CD8+CD103+CD69-TRMs. The downregulate of RGMb via siRNA in mice resulted in a decrease in phospho-p38 MAPK and phospho-Erk1/2. The combination group exhibited a reduction in TNF-α, TGF-ß, IL-6, and IL-1ß in their lung tissues, and the number of CD8+CD103+CD69-TRM was significantly reduced. The combination group exhibited a significant improvement in inflammatory and fibrotic indicators within the lung tissues. Anti-PD-1 antibody and carbon ion irradiation synergistically regulate RGMb, leading to strong clonal expansion of lung TRM through the p38 MAPK and Erk1/2 pathways. The present study offers valuable insights into the treatment of lung injury due to the combined administration of carbon ion radiotherapy and anti-PD-1 antibody therapy.

Multi-MSIProcessor: Data Visualizing and Analysis Software for Spatial Metabolomics Research.

Mass spectrometry imaging (MSI) has emerged as a revolutionary analytical strategy in biomedical research for molecular visualization. By linking the characterization of functional metabolites with tissue architecture, it is now possible to reveal unknown biological functions of tissues. However, due to the complexity and high dimensionality of MSI data, mining bioinformatics-related peaks from batch MSI data sets and achieving complete spatially resolved metabolomics analysis remain a great challenge. Here, we propose novel MSI data processing software, Multi-MSIProcessor (MMP), which integrates the data read-in, MSI visualization, processed data preservation, and biomarker discovery functions. The MMP focuses on the AFADESI-MSI data platform but also supports mzXML and imzmL data input formats for compatibility with data generated by other MSI platforms such as MALDI/SIMS-MSI. MMP enables deep mining of batch MSI data and has flexible adaptability with the source code opened that welcomes new functions and personalized analysis strategies. Using multiple clinical biosamples with complex heterogeneity, we demonstrated that MMP can rapidly establish complete MSI analysis workflows, assess batch sample data quality, screen and annotate differential MS peaks, and obtain abnormal metabolic pathways. MMP provides a novel platform for spatial metabolomics analysis of multiple samples that could meet the diverse analysis requirements of scholars.

Colchicine in atrial fibrillation: are old trees in bloom?

Colchicine is a widely used drug that was originally used to treat gout and rheumatic diseases. In recent years, colchicine has shown high potential in the cardiovascular field. Atrial fibrillation (AF) is a cardiovascular disease with a high incidence. One of the most frequent complications following cardiovascular surgery is postoperative atrial fibrillation (POAF), which affects patient health and disease burden. This article reviews the research status of colchicine in AF and summarizes the relevant progress.

Sleep cycle in children with severe acute bronchopneumonia during mechanical ventilation at different depths of sedation.

BACKGROUND: To investigate the characteristics of sleep cycle in children with severe acute bronchopneumonia treated with invasive mechanical ventilation at different sedation depths. METHODS: We included 35 pediatric patients with severe acute bronchopneumonia treated using mechanical ventilation in Pediatric Intensive Care Unit of Shengjing Hospital of China Medical University. They were divided into deep sedation group (n = 21; ramsay score 5-6) and light sedation group (n = 14; ramsay score3-4) based on sedation depth achieved during mechanical ventilation. Long-term video electroencephalography (EEG) monitoring was performed within the first 24 h after starting mechanical ventilation and after weaning from mechanical ventilation and discontinuing sedatives and analgesics. The results were analyzed and compared with those of normal children to analyze changes in sleep cycle characteristics at different sedation depths and mechanical ventilation stages. RESULTS: There were 29 cases altered sleep architecture. The deep sedation group had a significantly higher incidence of sleep architecture altered, total sleep duration, and non-rapid eye movement sleep-1 (NREM-1) loss incidence than the light sedation group. Moreover, the deep sedation group had a significantly lower awakening number and rapid eye movement sleep (REM) percentage than the light sedation group. The sleep cycle returned to normal in 27 (77%) patients without NREM-1 or REM sleep loss. CONCLUSIONS: Deep sedation during mechanical ventilation allows longer total sleep duration, fewer awakenings, and an increased deep sleep proportion, but sleep architecture is severely altered. After weaning from mechanical ventilation and sedative discontinuation, lightly sedated children exhibit better sleep recovery.

Mussel-inspired adhesive zwitterionic composite hydrogel with antioxidant and antibacterial properties for wound healing.

The skin can be easily injured and attacked by external pathogens, leading to wound infection and wound healing delay. Traditional dressings adhere to wounds only and can cause secondary damage to the new epithelium and bleeding. Herein, a highly adhesive zwitterionic composite hydrogel wound dressing (PDA/PSBMA/NFC/Zn2+ [PSNZn]) with outstanding antibacterial properties, good biocompatibility and excellent rheological properties was prepared by introducing zinc ion-loaded polydopamine (PDA)-coated nanofibrillated cellulose into a covalently-crosslinked sulfobetaine methacrylate (SBMA) network. In vitro and in vivo experiments showed the broad-spectrum and lasting antibacterial activity of the PSNZn composite hydrogel against Escherichia coli and Staphylococcus aureus. In summary, the PSNZn composite hydrogel is an excellent wound dressing candidate with efficient antibacterial properties, high adhesion, excellent biocompatibility and good rheological properties.

Bevacizumab is an effective treatment for symptomatic cerebral necrosis after carbon ion therapy for recurrent intracranial malignant tumours: A case report.

Carbon ion therapy (CIT) is a form of particle therapy, which not only spares normal tissues but may also improve local control of recurrent intracranial tumours. Cerebral radiation necrosis (RN) is one of the most serious adverse reactions of recurrent brain tumours following reirradiation, which may lead to neurological decline or even death. Bevacizumab is an anti-vascular endothelial growth factor antibody, which has been used to treat symptomatic RN. However, studies on bevacizumab for the treatment of CIT-induced RN are sparse. The present study described two cases that were successfully treated with bevacizumab for symptomatic RN following CIT for recurrent intracranial malignant tumours. The two recurrent intracranial malignant tumours, a chondrosarcoma in the right cavernous sinus and an anaplastic meningioma in the right frontal lobe, were enrolled in a clinical trial of CIT. Both cases were treated intravenously with bevacizumab when deterioration that appeared to be symptomatic brain RN was observed. Just before CIT, enhanced magnetic resonance imaging (MRI) was performed in each case to confirm tumour recurrence. Both cases exhibited a deterioration in symptoms, as well as on MRI, at 12-month intervals following CIT. The first case underwent positron emission tomography/computed tomography to confirm no increase in fluorodeoxyglucose uptake in lesion areas. Both cases were diagnosed as having symptomatic brain RN and began intravenous administration of four cycles of 5 mg/kg bevacizumab biweekly. The patients responded well, with rapid and marked improvements on MRI, and in clinical symptoms. No tumour progression was observed 24 months after CIT. In conclusion, bevacizumab was revealed to exert marked effects on symptomatic brain RN following CIT. Notably, cycles of bevacizumab should be administered specifically based on the aim of treating brain necrosis, and long-term or prophylactic applications are not recommended.

Curcumin, novel application in reversing myocardial fibrosis in the treatment for atrial fibrillation from the perspective of transcriptomics in rat model.

In order to explore the possible mechanism of curcumin in the treatment of AF, we focused on the myocardial fibrosis in the pathogenesis of atrial fibrillation to explore whether curcumin could play a role in the treatment of AF by reducing myocardial fibrosis.Rats were given daily gavage of saline (control and AF groups) or curcumin (4 mL/kg, concentration: 50 mg/mL, curcumin groups) during days 4-28. The rat model of AF was induced by Ach - CaCl2, and evaluate the therapeutic effect of curcumin on the duration of AF rhythm, the degree of myocardial fibrosis and the secretion of inflammatory factors in serum. RNA-seq to explore the possible mechanism of curcumin alleviating myocardial fibrosis of AF. curcumin significantly inhibits the duration of AF and reduces the degree of left atrial fibrosis. ELISA results showed curcumin could significantly reduce the secretion of IL-17A, IL-1ß, IL -6 and TGF-ß1. Bioinformatics analyses revealed that the IL-17 signaling pathway are involved in the therapeutic mechanism of curcumin. Furthermore, The genes encoding Col1a1, Fasn, Pck1, Bmp10, IL33 and Figf were pivotal and possible key genes for the therapeutic mechanisms of curcumin.Curcumin can reduce the degree of left atrial fibrosis of AF and the secretion of inflammatory factors. The therapeutic effect of curcumin on AF was attributed to its effect on the IL-17 signaling pathway. Besides, COL1A1, FASN, PCK1, BMP10, IL33 and FIGF were the pivotal genes associated with mechanisms of action of curcumin on AF.

Silencing of the lncRNA H19 enhances sensitivity to X-ray and carbon-ions through the miR-130a-3p /WNK3 signaling axis in NSCLC cells.

BACKGROUND: The lncRNA H19 is believed to act as an oncogene in various types of tumors and is considered to be a therapeutic target and diagnostic marker. However, the role of the lncRNA H19 in regulating the radiosensitivity of non-small cell lung cancer (NSCLC) cells is unknown. METHODS: The expression profiles of lncRNAs in NSCLC were explored via transcriptome sequencing. CCK-8, EdU incorporation and clonogenic survival assays were conducted to evaluate the proliferation and radiosensitivity of NSCLC cells. Flow cytometry and Western blotting were conducted to measure the level of apoptosis. The binding relationship between the lncRNA H19 and miR-130a-3p was determined by a dual-luciferase reporter assay. A binding relationship was also identified between miR-130a-3p and With-No-Lysine Kinase 3 (WNK3). RESULTS: Expression patterns of lncRNAs revealed that the lncRNA H19 was upregulated in radioresistant NSCLC (A549-R11) cells compared with A549 cells. Knockdown of the lncRNA H19 enhanced the sensitivity of NSCLC cell lines to X-ray and carbon ion irradiation. Mechanistically, the lncRNA H19 serves as a sponge of miR-130a-3p, which downregulates WNK3 expression. The lncRNA H19-miR-130a-3p-WNK3 axis modulates radiosensitivity by regulating apoptosis in NSCLC cell lines. CONCLUSION: Knockdown of the lncRNA H19 promotes the sensitivity of NSCLC cells to X-ray and carbon ion irradiation. Hence, the lncRNA H19 might function as a potential therapeutic target that enhances the antitumor effects of radiotherapy in NSCLC.

Corrigendum: Effect of Carbon Ion Radiation Induce Bystander Effect on Metastasis of A549 Cells and Metabonomic Correlation Analysis.

[This corrects the article DOI: 10.3389/fonc.2020.601620.].

The impact of pelvic radiotherapy on the gut microbiome and its role in radiation-induced diarrhoea: a systematic review.

Pelvic radiotherapy is the key treatment for pelvic malignancies, usually including pelvic primary tumour lesions and lymphatic drainage areas in the pelvic region. Therefore, the intestinal tract in the radiation field is inevitably damaged, a phenomenon clinically referred to as radiation enteritis, and diarrhoea is the most common clinical symptom of radiation enteritis. Therefore, it is necessary to study the mechanism of radiation-induced diarrhoea. It has been found that the gut microbiome plays an important role in the development of diarrhoea in response to pelvic radiotherapy, and the species and distribution of intestinal microbiota are significantly altered in patients after pelvic radiotherapy. In this study, we searched for articles indexed in the Cochrane Library, Web of Science, EMBASE and PubMed databases in English and CNKI, Wanfang data and SINOMED in Chinese from their inception dates through 13 March 2020 to collect studies on the gut microbiome in pelvic radiotherapy patients. Eventually, we included eight studies: one study report on prostatic carcinoma, five studies on gynaecological carcinoma and two papers on pelvic carcinomas. All studies were designed as self-controlled studies, except for one that compared toxicity to nontoxicity. The results from all the studies showed that the diversity of intestinal flora decreased during and after pelvic radiotherapy, and the diversity of intestinal flora decreased significantly in patients with diarrhoea after radiotherapy. Five studies observed that the community composition of the gut microbiota changed at the phylum, order or genus level before, during, and after pelvic radiotherapy at different time points. In addition, the composition of the gut microbiota before radiotherapy was different between patients with postradiotherapy diarrhoea and those without diarrhoea in five studies. However, relevant studies have not reached consistent results regarding the changes in microbiota composition. Changes in the intestinal flora induced by pelvic radiotherapy and their relationship between changes in intestinal flora and the occurrence of radiation-induced diarrhoea (RID) are discussed in this study, providing a theoretical basis for the causes of RID after pelvic radiotherapy.

Stubbornly preserving native leaflets is not always right: a case of tricuspid valve re-operation.

Tricuspid valve replacement is becoming more and more popular at various medical centres due to the increase in numbers of patients with tricuspid regurgitation. We report on a case of a 59-year-old man who had undergone tricuspid valve replacement with preservation of the native leaflets two years earlier, and developed early prosthetic dysfunction, which may have been caused by fusion of the native valve leaflets with the prosthetic valve leaflets. The experience of this case informs us that preserving the subvalvular apparatus may impede the motion of the prosthesis, and that adapting the individual morphology of the native tricuspid valve during tricuspid valve replacement could benefit the patient and avoid re-operation.

CircZNF208 enhances the sensitivity to X-rays instead of carbon-ions through the miR-7-5p /SNCA signal axis in non-small-cell lung cancer cells.

BACKGROUND: Mounting evidence suggests that circular RNAs (circRNAs) are closely related to the regulation of gene expression during tumour development. However, the role of circRNAs in modulating the radiosensitivity of non-small cell lung cancer (NSCLC) cells has not been explored. METHODS: Transcriptome sequencing was used to explore the expression profiles of circRNAs in NSCLC. The expression level of circRNAs was changed by inducing instantaneous knockdown or overexpression. Changes in proliferation and radiosensitivity of NSCLC cells were investigated using CCK-8, EDU, and clonal survivals. RESULTS: By analysing the circRNA expression profile of NSCLC cells, we found that circRNA ZNF208 (circZNF208) was significantly upregulated in a radioresistant NSCLC cell line (A549-R11), which was acquired from the parental NSCLC cell line A549. Knockout experiments indicated that circZNF208 enhanced the radiosensitivity of A549 and A549-R11 cells to X-rays. Mechanistically, circZNF208 upregulated SNCA expression by acting as a sponge of miR-7-5p and subsequently promoted the resistance of NSCLC cells to low linear energy transfer (LET) X-rays. However, this effect was not observed in NSCLC cells exposed to high-LET carbon ions. CONCLUSIONS: Knockdown of circZNF208 altered the radiosensitivity of patients with NSCLC to X-rays but did not significantly change the sensitivity to carbon ions. Therefore, circZNF208 might serve as a potential biomarker and therapeutic target for NSCLC treatment with radiotherapy of different modalities.

A Giant Ruptured Noncoronary Sinus of Valsalva Aneurysm: A Case Report.

The occurrence of a giant ruptured aneurysm originating from the noncoronary sinus of Valsalva in the right atrium is extremely rare. Herein, a case is presented of a giant ruptured noncoronary sinus of Valsalva aneurysm (SVA) that was protruding into the right atrium, which was almost completely occupied by an aneurysm. A 61-year-old female was referred to the hospital for exertional palpitation and dyspnea. While a surgical repair was performed by resection of the aneurysm and a sinus remodeling with a patch of fresh bovine pericardium, a very rare case was observed. It was a giant ruptured noncoronary sinus of aneurysm that completely occupied the right atrium, which was difficult to distinguish from the coronary aneurysm. It is also believed that various imaging examinations, such as cardiac computed tomography angiogram (CCTA) and transthoracic echocardiogram (TTE), were useful for the diagnosis.

Cygnus X-1 contains a 21-solar mass black hole-Implications for massive star winds.

The evolution of massive stars is influenced by the mass lost to stellar winds over their lifetimes. These winds limit the masses of the stellar remnants (such as black holes) that the stars ultimately produce. We used radio astrometry to refine the distance to the black hole x-ray binary Cygnus X-1, which we found to be [Formula: see text] kiloparsecs. When combined with archival optical data, this implies a black hole mass of 21.2 ± 2.2 solar masses, which is higher than previous measurements. The formation of such a high-mass black hole in a high-metallicity system (within the Milky Way) constrains wind mass loss from massive stars.

Multiple functions of p21 in cancer radiotherapy.

BACKGROUND: Greater than half of cancer patients experience radiation therapy, for both radical and palliative objectives. It is well known that researches on radiation response mechanisms are conducive to improve the efficacy of cancer radiotherapy. p21 was initially identified as a widespread inhibitor of cyclin-dependent kinases, transcriptionally modulated by p53 and a marker of cellular senescence. It was once considered that p21 acts as a tumour suppressor mainly to restrain cell cycle progression, thereby resulting in growth suppression. With the deepening researches on p21, p21 has been found to regulate radiation responses via participating in multiple cellular processes, including cell cycle arrest, apoptosis, DNA repair, senescence and autophagy. Hence, a comprehensive summary of the p21's functions in radiation response will provide a new perspective for radiotherapy against cancer. METHODS: We summarize the recent pertinent literature from various electronic databases, including PubMed and analyzed several datasets from Gene Expression Omnibus database. This review discusses how p21 influences the effect of cancer radiotherapy via involving in multiple signaling pathways and expounds the feasibility, barrier and risks of using p21 as a biomarker as well as a therapeutic target of radiotherapy. CONCLUSION: p21's complicated and important functions in cancer radiotherapy make it a promising therapeutic target. Besides, more thorough insights of p21 are needed to make it a safe therapeutic target.

Safety and Efficacy of PD-1/PD-L1 inhibitors combined with radiotherapy in patients with non-small-cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: A combination of programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors and radiotherapy (RT) is increasingly being used to treat non-small-cell lung cancer (NSCLC). However, the safety and efficacy of this approach remains controversial. We performed a systematic review and meta-analysis to summarize the related research. METHODS: We searched the China Biology Medicine, EMBASE, Cochrane Library, and PubMed databases for all the relevant studies. The Stata software, version 12.0 was used for the meta-analysis. RESULTS: The study included 20 clinical trials that enrolled 2027 patients with NSCLC. Compared with non-combination therapy, combination therapy using PD-1/PD-L1 inhibitors and RT was associated with prolonged overall survival (OS) (1-year OS: odds ratio [OR] 1.77, 95% confidence interval [CI] 1.35-2.33, p = 0.000; 2-year OS: OR 1.77, 95% CI 1.35-2.33, p = 0.000) and progression-free survival (PFS) (0.5-year PFS: OR 1.83, 95% CI 1.13-2.98, p = 0.014; 1-year PFS: OR 2.09, 95% CI 1.29-3.38, p = 0.003; 2-year PFS: OR 2.47, 95% CI 1.13-5.37, p = 0.023). Combination therapy also improved the objective response rate (OR 2.76, 95% CI 1.06-7.19, p = 0.038) and disease control rate (OR 1.80, 95% CI 1.21-2.68, p = 0.004). This meta-analysis showed that compared with non-combination therapy, combination therapy using PD-1/PD-L1 inhibitors and RT did not increase the serious adverse event rates (≥grade 3); however, this approach increased the rate of grade 1-2 immune-related or radiation pneumonitis. Subgroup analyses revealed that the sequence of PD-1/PD-L1 inhibitors followed RT outperformed in which concurrent PD-1/PD-L1 inhibitor and RT followed PD-1/PD-L1 inhibitor. Combination of stereotactic body RT or stereotactic radiosurgery with PD-1/PD-L1 inhibitors may be more effective than a combination of conventional RT with PD-1/PD-L1 inhibitors in patients with advanced NSCLC. CONCLUSION: Combination therapy using PD-1/PD-L1 inhibitors and RT may improve OS, PFS, and tumor response rates without an increase in serious adverse events in patients with advanced NSCLC. However, combination therapy was shown to increase the incidence of mild pneumonitis.

Integrated analysis of circRNA-miRNA-mRNA network reveals potential prognostic biomarkers for radiotherapies with X-rays and carbon ions in non-small cell lung cancer.

BACKGROUND: This work was aimed at exploring the regulatory network of non-coding RNA (ncRNA) especially circular RNA (circRNA) and microRNA (miRNA), in the sensitivity of non-small cell lung cancer (NSCLC) cells to low linear energy transfer (LET) X-ray and high-LET carbon ion irradiations. METHODS: The radioresistant NSCLC cell line A549-R11 was obtained from its parental cell line A549 through irradiation with X-rays of 2.0 Gy per fraction for 30 times. The sensitivities of A549, A549-R11 and H1299 cells exposed to X-rays and carbon ions were verified using the colony formation assay. A comprehensive circRNA-miRNA-mRNA network was constructed through the sequencing data in parental A549, acquired radioresistant A549-R11 and intrinsic radioresistant H1299 cells, and the network was further optimized according to the prognostic results from the TCGA and GEO databases. RESULTS: Based on high-throughput sequencing of circRNAs, we found that 40 circRNAs were up-regulated while 184 circRNAs were down-regulated in the intersection of the sets of A549-R11 and H1299 cells. Subsequently, a circRNA- miRNA-mRNA network, including 14 interactive pairs and 8 circRNAs, 4 overall survival-associated miRNAs, and 4 mRNAs, was constructed through the high-throughput data screening and bioinformatics methods. CONCLUSIONS: Our results provide a complete understanding to the regulatory mechanism of the sensitivities to low-LET X-ray and high-LET carbon ion irradiations, and might be helpful to screen potential biomarkers for predicting the Carbon-ion radiotherapy (CIRT) and X-ray radiotherapy responses in NSCLC.