Erythroblast transformation-specific-related gene promotes metastasis of oral squamous cell carcinoma by transcriptionally upregulating peroxiredoxin 1.

BACKGROUND: Some studies confirmed that erythroblast transformation-specific-related gene (ERG) may be a pathogenic factor of oral squamous cell carcinoma (OSCC). However, the undergoing molecular mechanism has not been elucidated yet. OBJECTIVE: In this study, the investigation will focus on how the transcription factor ERG modulates the biological behaviors of OSCC. METHODS: In this study, cancer tissue specimens and corresponding paracancer tissues were collected from 54 patients. Real-time polymerase chain reaction analysis and Western blots were employed to detect the expression of multiple genes. Cell proliferation assays, Transwell, and flow cytometry assay were utilized to detect the proliferation, invasion, and apoptosis of OSCC cell, respectively. Dual luciferase reporter gene and chromatin immunoprecipitation assays were conducted to verify the regulation of ERG on PRDX1. RESULTS: ERG exhibits high expression levels in OSCC. Inhibition of ERG has been shown to effectively suppress the malignant growth of OSCC cells. Moreover, ERG has been found to transcriptionally upregulate the expression of PRDX1. The knockdown of PRDX1 has demonstrated its ability to inhibit the malignant growth of OSCC cells. Interestingly, when PRDX1 is overexpressed, it attenuates the inhibitory effect of si-ERG on the malignant growth of OSCC cells. This suggests that PRDX1 may play a crucial role in mediating the impact of ERG on malignancy in OSCC cells. CONCLUSION: The transcription factor ERG promotes the expression of PRDX1, which could enhance the proliferation and invasion while inhibiting the apoptosis of OSCC cells.

Exploring the multifaceted role of GCN1: Implications in cellular responses and disease pathogenesis.

GCN1 is a highly conserved protein present widely across eukaryotes. As an upstream activator of protein kinase GCN2, GCN1 plays a pivotal role in integrated stress responses, such as amino acid starvation and oxidative stress. Through interaction with GCN2, GCN1 facilitates the activation of GCN2, thus initiating downstream signaling cascades in response to cellular stressors. In these contexts, the activation of GCN2 necessitates the presence and action of GCN1. Notably, GCN1 also operates as a ribosome collision sensor, contributing significantly to the translation quality control pathway. These discoveries offer valuable insights into cellular responses to internal stresses, vital for maintaining cellular homeostasis. Additionally, GCN1 exhibits the ability to regulate the cell cycle and suppress inflammation, among other processes, independently of GCN2. Our review outlines the structural characteristics and biological functions of GCN1, shedding light on its significant involvement in the onset and progression of various cancer and non-cancer diseases. Our work underscores the role of GCN1 in the context of drug therapeutic effects, hinting at its potential as a promising drug target. Furthermore, our work delves deep into the functional mechanisms of GCN1, promising innovative avenues for the diagnosis and treatment of diseases in the future. The exploration of GCN1's multifaceted roles not only enhances our understanding of its mechanisms but also paves the way for novel therapeutic interventions. The ongoing quest to unveil additional functions of GCN1 holds the promise of further enriching our comprehension of its mode of action.

Bortezomib in previously treated phosphatase and tension homology-deficient patients with advanced intrahepatic cholangiocarcinoma: An open-label, prospective and single-centre phase II trial.

INTRODUCTION: Intrahepatic cholangiocarcinoma (ICC) is characterized by a dismal prognosis with limited therapeutic alternatives. To explore phosphatase and tension homolog (PTEN) as a biomarker for proteasome inhibition in ICC, we conducted a phase II trial to assess the second-line efficacy of bortezomib in PTEN-deficient advanced ICC patients. METHODS: A total of 130 patients with advanced ICC in our centre were screened by PTEN immunohistochemical staining between 1 July 2017, and 31 December 2021, and 16 patients were ultimately enrolled and treated with single-agent bortezomib 1.3 mg/m2 on days 1, 4, 8 and 11 of a 21-day cycle. The primary endpoint was the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors v1.1. RESULTS: The median follow-up was 6.55 months (95% confidence interval [CI]: 0.7-19.9 months). Among the 16 enrolled patients, the ORR was 18.75% (3/16) and the disease control rate was 43.75% (7/16). The median progress-free survival was 2.95 months (95% CI: 2.1-5.1 months) and the median overall survival (mOS) was 7.2 months (95% CI: 0.7-21.6 months) in the intent-to-treat-patients. Treatment-related adverse events of any grade were reported in 16 patients, with thrombopenia being the most common toxicity. Patients with PTEN staining scores of 0 were more likely to benefit from bortezomib than those with staining scores > 0. CONCLUSIONS: Bortezomib yielded an encouraging objective response and a favourable OS as a second-line agent in PTEN-deficient ICC patients. Our findings suggest bortezomib as a promising therapeutic option for patients with PTEN-deficient ICC. HIGHLIGHTS: There is a limited strategy for the second-line option of intrahepatic cholangiocarcinoma (ICC). This investigator-initiated phase 2 study evaluated bortezomib in ICC patients with phosphatase and tension homology deficiency. The overall response rate was 18.75% and the overall survival was 7.2 months in the intent-to-treat cohort. These results justify further developing bortezomib in ICC patients with PTEN deficiency.

IGSF8 is an innate immune checkpoint and cancer immunotherapy target.

Antigen presentation defects in tumors are prevalent mechanisms of adaptive immune evasion and resistance to cancer immunotherapy, whereas how tumors evade innate immunity is less clear. Using CRISPR screens, we discovered that IGSF8 expressed on tumors suppresses NK cell function by interacting with human KIR3DL2 and mouse Klra9 receptors on NK cells. IGSF8 is normally expressed in neuronal tissues and is not required for cell survival in vitro or in vivo. It is overexpressed and associated with low antigen presentation, low immune infiltration, and worse clinical outcomes in many tumors. An antibody that blocks IGSF8-NK receptor interaction enhances NK cell killing of malignant cells in vitro and upregulates antigen presentation, NK cell-mediated cytotoxicity, and T cell signaling in vivo. In syngeneic tumor models, anti-IGSF8 alone, or in combination with anti-PD1, inhibits tumor growth. Our results indicate that IGSF8 is an innate immune checkpoint that could be exploited as a therapeutic target.

Application of System Nursing in the Prevention of Postoperative Nonstructural Scoliosis in Patients With Ear Reconstruction.

OBJECTIVE: To evaluate whether early systematic nursing can reduce the occurrence of postoperative nonstructural scoliosis in patients undergoing ear reconstruction. METHODS: A total of 136 patients with congenital microtia who underwent ear reconstruction surgery at the Department of Plastic Surgery, Chinese Academy of Medical Sciences from, January 2022 to July 2022 were included as study subjects. They were randomly divided into a routine nursing group and a systematic nursing group. After preoperative and postoperative education, as well as continuous follow-up intervention after surgery, spinal CT three-dimensional imaging examination was performed 6 months later to measure the Cobb angle and observe the occurrence of spinal scoliosis. RESULTS: Compared with the routine nursing group, the incidence and severity of postoperative nonstructural scoliosis were significantly reduced in patients who received systematic nursing. CONCLUSIONS: Systematic nursing intervention for patients undergoing ear reconstruction can help prevent the occurrence of postoperative nonstructural scoliosis and has a positive effect on improving patient prognosis. It is worth promoting in clinical treatment.

What Factors Can Affect the Occurrence of Vertigo in Patients After Craniofacial Surgery in China?

Vertigo is a complication of craniomaxillofacial contour plastic surgery characterized by dizziness from hypovolemia in the cerebral hemispheres and brainstem. The authors analyzed the current status and influencing factors of postoperative vertigo in patients who undergo craniomaxillofacial contouring and discussed improvements in nursing strategies. The authors investigated 418 patients admitted to the authors' hospital who underwent craniomaxillofacial contouring between November 2020 and October 2023 and divided them into asymptomatic and symptomatic groups based on syncopal precursors or vertigo. The authors screened the current status of vertigo in patients after craniomaxillofacial contouring and the factors affecting vertigo and determined nursing improvement strategies. After craniomaxillofacial contouring, 125 patients had vertigo symptoms. Postcraniomaxillofacial contouring syncope or vertigo was associated with age, patient vertigo history, family history, depression, weight loss, blood pressure at admission, feeding before getting out of bed, and the level of intraoperative hemorrhage Multifactorial logistic regression analysis revealed the association between postcraniomaxillofacial contouring syncope or vertigo and vertigo history, depression, weight loss, feeding before getting out of bed, and intraoperative bleeding volume. Vertigo precursor incidence after craniomaxillofacial contouring surgery is 29.90%. Its influencing factors are complex, suggesting that nurses need to improve the perioperative health education of craniomaxillofacial contouring surgery and optimize the nursing care, encourage patients to have a reasonable diet or provide parenteral nutritional support preoperatively, help patients get out of bed early postoperatively, encourage them to have multiple meals in little quantity before getting out of bed, and control the intraoperative bleeding, to ensure patient safety postoperatively.

Identification of hub genes in calcific aortic valve disease.

Calcific aortic valve disease (CAVD) is a heart valve disorder characterized primarily by calcification of the aortic valve, resulting in stiffness and dysfunction of the valve. CAVD is prevalent among aging populations and is linked to factors such as hypertension, dyslipidemia, tobacco use, and genetic predisposition, and can result in becoming a growing economic and health burden. Once aortic valve calcification occurs, it will inevitably progress to aortic stenosis. At present, there are no medications available that have demonstrated effectiveness in managing or delaying the progression of the disease. In this study, we mined four publicly available microarray datasets (GSE12644 GSE51472, GSE77287, GSE233819) associated with CAVD from the GEO database with the aim of identifying hub genes associated with the occurrence of CAVD and searching for possible biological targets for the early prevention and diagnosis of CAVD. This study provides preliminary evidence for therapeutic and preventive targets for CAVD and may provide a solid foundation for subsequent biological studies.

Cellular senescence imaging and senolysis monitoring in cancer therapy based on a ß-galactosidase-activated aggregation-induced emission luminogen.

Cellular senescence is a permanent state of cell cycle arrest characterized by increased activity of senescence associated ß-galactosidase (SA-ß-gal). Notably, cancer cells have been also observed to exhibit the senescence response and are being considered for sequential treatment with pro-senescence therapy followed by senolytic therapy. However, there is currently no effective agent targeting ß-galactosidase (ß-Gal) for imaging cellular senescence and monitoring senolysis in cancer therapy. Aggregation-induced emission luminogen (AIEgen) demonstrates strong fluorescence, good photostability, and biocompatibility, making it a potential candidate for imaging cellular senescence and monitoring senolysis in cancer therapy when endowed with ß-Gal-responsive capabilities. In this study, we introduced a ß-Gal-activated AIEgen named QM-ß-gal for cellular senescence imaging and senolysis monitoring in cancer therapy. QM-ß-gal exhibited good amphiphilic properties and formed aggregates that emitted a fluorescence signal upon ß-Gal activation. It showed high specificity towards the activity of ß-Gal in lysosomes and successfully visualized DOX-induced senescent cancer cells with intense fluorescence both in vitro and in vivo. Encouragingly, QM-ß-gal could image senescent cancer cells in vivo for over 14 days with excellent biocompatibility. Moreover, it allowed for the monitoring of senescent cancer cell clearance during senolytic therapy with ABT263. This investigation indicated the potential of the ß-Gal-activated AIEgen, QM-ß-gal, as an in vivo approach for imaging cellular senescence and monitoring senolysis in cancer therapy via highly specific and long-term fluorescence imaging. STATEMENT OF SIGNIFICANCE: This work reported a ß-galactosidase-activated AIEgen called QM-ß-gal, which effectively imaged DOX-induced senescent cancer cells both in vitro and in vivo. QM-ß-gal specifically targeted the increased expression and activity of ß-galactosidase in senescent cancer cells, localized within lysosomes. It was cleared rapidly before activation but maintained stability after activation in the DOX-induced senescent tumor. The AIEgen exhibited a remarkable long-term imaging capability for senescent cancer cells, lasting over 14 days and enabled monitoring of senescent cancer cell clearance through ABT263-induced apoptosis. This approach held promise for researchers seeking to achieve prolonged imaging of senescent cells in vivo.

Enantioselective Construction of C-SCF3 Stereocenters via Nickel Catalyzed Asymmetric Negishi Coupling Reaction.

The construction of the SCF3-containing 1,1-diaryl tertiary carbon stereocenters with high enantioselectivities is reported via a nickel-catalyzed asymmetric C-C coupling strategy. This method demonstrates simple operations, mild conditions and excellent functional group tolerance, with newly designed SCF3-containing synthon, which can be easily obtained from commercially available benzyl bromide and trifluoromethylthio anion in a two-step manner. Further substrate exploration indicated that the reaction system could be extended to diverse perfluoroalkyl sulfide (SC2F5, SC3F7, SC4F9, SCF2CO2Et)-substituted 1,1-diaryl compounds with excellent enantioselectivities. The synthetic utility of this transformation was further demonstrated by convenient derivatization to optical SCF3-containing analogues of bioactive compounds without an apparent decrease in enantioselectivity.

Precise evaluation of batch adsorption kinetics of plant total polyphenols based on a flow-injection online spectrophotometric method.

Efficient evaluation of adsorption kinetics of plant total polyphenols is essential for the design of adsorption separation of bioactive compounds. The conventional method uses manual sampling with poor reproducibility. Here, we developed a new method for on-line determination of total polyphenol content (TPC) in plant extracts by applying the Folin-Ciocalteu method in flow-injection analysis (FIA). The FIA parameters were optimized and a standard curve with excellent linearity was established. Precise determination of TPC with a satisfactory sample throughput of 20 h-1 was achieved for the adsorption kinetic study. The pseudo-second-order kinetic model was found to better describe the kinetic parameters of the batch adsorption/desorption process. The developed method proved to be accurate compared with the conventional method. The FIA method holds significant promise for studying and monitoring adsorption processes, due to its automatic on-line nature, low consumption of reagents and samples, and the ability to generate large quantities of highly accurate adsorption data.

Identification of One O-Methyltransferase Gene Involved in Methylated Flavonoid Biosynthesis Related to the UV-B Irradiation Response in Euphorbia lathyris.

Flavonoids are ubiquitous polyphenolic compounds that play a vital role in plants' defense response and medicinal efficacy. UV-B radiation is a vital environmental regulator governing flavonoid biosynthesis in plants. Many plants rapidly biosynthesize flavonoids as a response to UV-B stress conditions. Here, we investigated the effects of flavonoid biosynthesis via UV-B irradiation in Euphorbia lathyris. We found that exposure of the E. lathyris callus to UV-B radiation sharply increased the level of one O-methyltransferase (ElOMT1) transcript and led to the biosynthesis of several methylated flavonoids. The methyltransferase ElOMT1 was expressed heterologously in E. coli, and we tested the catalytic activity of recombinant ElOMT1 with possible substrates, including caffeic acid, baicalin, and luteolin, in vitro. ElOMT1 could efficiently methylate when the hydroxyl groups were contained in the core nucleus of the flavonoid. This molecular characterization identifies a methyltransferase responsible for the chemical modification of the core flavonoid structure through methylation and helps reveal the mechanism of methylated flavonoid biosynthesis in Euphorbiaceae. This study identifies the O-methyltransferase that responds to UV-B irradiation and helps shed light on the mechanism of flavonoid biosynthesis in Euphorbia lathyris.

Screening radiation-differentially expressed circular RNAs and establishing dose classification models in the human lymphoblastoid cell line AHH-1.

PURPOSE: In the event of a large-scale radiological accident, rapid and high-throughput biodosimetry is the most vital basis in medical resource allocation for the prompt treatment of victims. However, the current biodosimeter is yet to be rapid and high-throughput. Studies have shown that ionizing radiation modulates expressions of circular RNAs (circRNAs) in healthy human cell lines and tumor tissue. circRNA expressions can be quantified rapidly and high-throughput. However, whether circRNAs are suitable for early radiation dose classification remains unclear. METHODS: We employed transcriptome sequencing and bioinformatics analysis to screen for radiation-differentially expressed circRNAs in the human lymphoblastoid cell line AHH-1 at 4 h following exposure to 0, 2, and 5 Gy 60Co γ-rays. The dose-response relationships between differentially expressed circRNA expressions and absorbed doses were investigated using real-time polymerase chain reaction and linear regression analysis at 4 h, 24 h, and 48 h post-exposure to 0, 2, 4, 6, and 8 Gy. Six distinct dose classification models of circRNA panels were established and validated by receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 11 radiation-differentially expressed circRNAs were identified and validated. Based on dose-response effects, those circRNAs changed in a dose-responsive or dose-dependent manner were combined into panels A through F at 4 h, 24 h, and 48 h post-irradiation. ROC curve analysis showed that panels A through C had the potential to effectively classify exposed and non-exposed conditions, which area under the curve (AUC) of these three panels were all 1.000, and the associate p values were .009. Panels D through F excellently distinguished between different dose groups (AUC = 0.963-1.000, p < .05). The validation assay showed that panels A through F demonstrated consistent excellence in sensitivity and specificity in dose classification. CONCLUSIONS: Ionizing radiation can indeed modulate the circRNA expression profile in the human lymphoblastoid cell line AHH-1. The differentially expressed circRNAs exhibit the potential for rapid and high-throughput dose classification.

Intrathecal injection of methotrexate and dexamethasone for vasculitis granuloma of the fourth ventricle: a case report and literature review.

Granulomatosis with polyangiitis (GPA) is a pauci-immune small vessel vasculitis characterised by neutrophil-mediated vasculitis and granuloma. The presence of intracranial parenchymal space-occupying lesions is rarely seen in GPA patients. In this manuscript, we report a case of GPA with granuloma of the fourth ventricle accompanied by obstructive hydrocephalus. Treatment with glucocorticoids (GCs) and multiple immunosuppressants cyclophosphamide (CYC), mycophenolate mofetil (MMF), and rituximab (RTX) showed poor efficacy in this case. After removal of the granuloma by craniotomy, GPA relapsed within 3 months. Under the premise of GC and MMF treatment combined with intrathecal injection of dexamethasone (DXM) and methotrexate (MTX), the intracranial granuloma gradually shrank, and the patient's general condition was alleviated, showing that this is an effective treatment method. Key Points • To date, there are few reports of granulomatous vasculitis combined with granuloma of the fourth ventricle, and our case is the second. • In this case, multiple immunosuppressants and rituximab were ineffective treatments, and the intracranial granuloma was effectively controlled by intrathecal injection of dexamethasone (DXM) and methotrexate (MTX). • Based on this report, it can be suggested that intrathecal injection is effective in treating patients with GPA and central nervous system involvement, but large-scale sample studies are needed.

Exploring the anticancer potential of Actinidia chinensis Planch root extracts (acRoots) on hepatocellular carcinoma: A molecular mechanism study.

Hepatocellular carcinoma (HCC), ranking as the seventh most prevalent cancer worldwide, poses a significant health challenge. Actinidia chinensis Planch Root extracts (acRoots), a traditional Chinese medicine, has exhibited promising inhibitory effects on the proliferation, invasion, and migration of various cancer cell types. Nevertheless, its specific impact and underlying mechanisms concerning HCC remain unclear. This research aimed to elucidate the anticancer properties and potential molecular mechanisms of acRoots in the HepG2 and LM3 cell lines. Our findings demonstrate that acRoots effectively hampers the in vitro proliferation, migration, and invasion of HCC cells. Furthermore, acRoots induces apoptosis and autophagy by impeding the AKT/mTOR signaling pathway, with its inhibitory effects on cells being restored under AKT activator induction. This study, for the first time, elucidates that acRoots can suppress HepG2 and LM3 cell proliferation by blocking the Akt/mTOR pathway, thereby activating apoptosis and autophagy. These results underscore the potential of acRoots as a promising antitumor agent for HCC.

The Comparison of Two Whole-Genome Amplification Approaches for Noninvasive Preimplantation Genetic Testing (ni-PGT) and the Application Scenario of ni-PGT during the Fresh Cycle.

Recently, noninvasive preimplantation genetic testing (ni-PGT) using degenerate oligonucleotide primer PCR (DOP-PCR) and multiple annealing and looping-based amplification cycle (MALBAC)-based whole-genome amplification (WGA) methods has demonstrated predictable results in embryo testing. However, a considerable heterogeneity of results has been reported in numerous studies on these two WGA methods. Our aim was to evaluate the current WGA method for ni-PGT while further clarifying the applicable scenarios of ni-PGT in the fresh cycle. A total of 173 embryos were tested with trophectoderm biopsy and ni-PGT. In the whole preimplantation genetic testing, the clinical concordance rates of the detection results of DOP-PCR and MALBAC with the corresponding trophectoderm biopsy results were 64.12% (84/131) and 68.99% (89/129), respectively (P = 0.405). However, in the detection of abnormal embryos, the detection efficiency of ni-PGT is significantly improved [MALBAC: 96.55% versus 68.99% (P < 0.001); and DOP-PCR: 89.09% versus 64.12% (P < 0.001)]. In addition, the diagnostic efficiency of ni-PGT in low-quality blastocysts was significantly higher than that in high-quality blastocysts [MALBAC: 95.24% versus 51.85% (P = 0.001); and DOP-PCR: 91.30% versus 48.15% (P = 0.001)]. These results contribute to further understanding ni-PGT and to clarifying its application scenario in the fresh cycle.

IL-17 in osteoarthritis: A narrative review.

Osteoarthritis (OA) is a painful joint disease that is common among the middle-aged and elderly populations, with an increasing prevalence. Therapeutic options for OA are limited, and the pathogenic mechanism of OA remains unclear. The roles of cytokines and signaling pathways in the development of OA is a current research hot spot. Interleukin (IL)-17 is a pleiotropic inflammatory cytokine produced mainly by T helper 17 cells that has established roles in host defense, tissue repair, lymphoid tissue metabolism, tumor progression, and pathological processes of immune diseases, and studies in recent years have identified an important role for IL-17 in the progression of OA. This narrative review focuses on the mechanisms by which IL-17 contributes to articular cartilage degeneration and synovial inflammation in OA and discusses how IL-17 and the IL-17 signaling pathway affect the pathological process of OA. Additionally, therapeutic targets that have been proposed in recent years based on IL-17 and its pathway in OA are summarized as well as recent advances in the study of IL-17 pathway inhibitors and the potential challenges of their use for OA treatment.

177 Lu Radiolabelled AIE Dots for Multimodal Imaging Guided Photothermal/Radiopharmaceutical Tumor Therapy.

Aggregation-induced emission luminogens (AIEgens) in the second near-infrared region (NIR-II,1000-1700 nm) have shown tremendous potential as theragnostic probe for tumor multimodal diagnostic imaging and combined treatment owing to their programmable optical, structural and functional properties. Herein, we presented a radionuclide 177 Lu-labeled AIEgen, 177 Lu-2TT-oC6B dots, for NIR-II fluorescence and SPECT/CT imaging-guided tumor photothermal and radiopharmaceutical therapy. Intriguingly, 177 Lu-2TT-oC6B self-assembled into 10 nm dots, exhibited high NIR-II fluorescence quantum yield (QY, 1.34 %) and unprecedented photothermal conversion efficiency (PCE, 70.3 %) in vitro, furtherly performed extremely long blood circulation (T1/2 =52.4 h), persistent tumor accumulation and retention in tumor (NIR-II SNR=5.56; SPECT SNR=36.59) via intravenous administration in vivo. Furthermore, upon NIR light activation and 177 Lu irradiation, 177 Lu-2TT-oC6B demonstrated great application potential in synergistic photothermal/radiopharmaceutical tumor therapy.

Effects of cyclophosphamide and mitomycin C on radiation-induced transcriptional biomarkers in human lymphoblastoid cells.

PURPOSE: Ionizing radiation (IR)-induced transcriptional changes are considered a potential biodosimetry for dose evaluation and health risk monitoring of acute or chronic radiation exposure. It is crucial to understand the impact of confounding factors on the radiation-responsive gene expressions for accurate and reproducible dose assessment. This study aims to explore the potential influence of exposures to chemotherapeutic agents such as cyclophosphamide (CP) and mitomycin C (MMC) on IR-induced transcriptional biomarkers. METHODS: The human B lymphoblastoid cells (AHH-1) were exposed to 0, 20, 50, 100, 200 and 500 µg/ml CP or 0, 0.025, 0.05, 0.1 and 1 µg/ml MMC, respectively. The appropriate concentrations of CP and MMC were added for 1 h before irradiation with 0, 2, 4 and 6 Gy of 60Co γ-rays at a dose rate of 1 Gy/min. Cell viability was evaluated by CCK-8 assay. The gene expression responses of 18 radiation-induced transcriptional biomarkers were examined at 24 h after exposures to CP and MMC, respectively. The expression levels of five crucial DNA interstrand crosslinks (ICLs) repair genes were also evaluated. The biodosimetry models were established based on the specific radiation-responsive gene combinations. RESULTS: The baseline transcriptional levels of the 18 selected genes were slightly affected by CP treatment in the absence of IR, while the transcript responses to IR could be inhibited as the concentration of CP up to 50 µg/ml. MMC treatment up-regulated the background levels in most radiation-responsive gene expressions. Of 18 genes, only the relative mRNA expression levels of CDKN1A and BBC3 were repressed after treatment with IR and MMC in combination. The relative mRNA level of RAD51 was significantly up-regulated after exposure to CP, while the expression of FANCD2, RAD51 and BLM showed an overall increase in response to MMC treatment. After irradiation, the relative mRNA expression levels of FANCD2, BRCA2 and RAD51 exhibited dose-dependent increases in IR alone and MMC treatment groups. In addition, the biodosimetry models were established using 2-4 radiation-responsive genes based on different radiation exposure scenarios. CONCLUSION: Our findings suggested that IR-induced gene expression changes were slightly affected after exposure to a relatively low concentration of CP and MMC. Gene expression combinations might improve the broad applicability of transcriptional biodosimetry across diverse radiation exposures.

Retraction: Radio-photothermal therapy mediated by a single compartment nanoplatform depletes tumor initiating cells and reduces lung metastasis in the orthotopic 4T1 breast tumor model.

Retraction of 'Radio-photothermal therapy mediated by a single compartment nanoplatform depletes tumor initiating cells and reduces lung metastasis in the orthotopic 4T1 breast tumor model' by Min Zhou et al., Nanoscale, 2015, 7, 19438-19447, https://doi.org/10.1039/C5NR04587H.