Shining a light on liver health: advancements in fluorescence-enhanced enzyme biosensors for early disease detection.

Early detection of liver diseases holds paramount importance in optimizing treatment outcomes and prognosis, thereby significantly enhancing the likelihood of recovery while mitigating the risk of progression to liver cancer. Liver diseases encompass a spectrum of conditions, each potentially manifesting distinct enzymatic profiles. Monitoring these enzymes in situ facilitates timely intervention and therapeutic management. In recent years, the field of biosensor technology has witnessed remarkable advancement, owing to strides in biomedicine and computational sciences. Biosensors have garnered widespread utility across medical and biological domains, spanning the detection of disease biomarkers, drug release tracking, ion imaging, and fluorescence imaging within living organisms. These applications have markedly enhanced imaging resolution and have the potential to refine disease diagnosis accuracy for clinicians. A pivotal aspect in the successful application of this technology lies in the construction of fluorescence probes adept at swiftly and selectively identifying target enzymes by amalgamating liver disease enzymes with fluorescence probe technology. However, research in this niche area remains relatively scarce. Building upon this foundational understanding, the present review delineates the utilization of biosensors in the early diagnosis of liver disease. Serving as a theoretical framework, this review envisages the development of high-performance biosensors tailored for the early detection of liver cancer. Furthermore, it offers insights into the potential of biosensor technology to progress and broaden its practical applications, thus contributing to the advancement of diagnostic methodologies in liver disease management.

Crosstalk among disulfidptosis-related lncRNAs in lung adenocarcinoma reveals a correlation with immune profile and clinical prognosis.

Disulfidptosis refers to a specific programmed cell death process characterized by the accumulation of disulfides. It has recently been reported in several cancers. However, the impact of disulfidptosis-related long non-coding RNAs (lncRNAs) on malignant tumors has remained largely unknown. In the present work, we screened prognostic disulfidptosis-related lncRNAs and studied their effects on lung adenocarcinoma. Relevant clinical data of lung adenocarcinoma cases were retrieved from The Cancer Genome Atlas (TCGA) database. RNA sequencing was used to identify differentially expressed disulfidptosis-related lncRNAs within lung adenocarcinoma. In addition, prognostic disulfidptosis-related lncRNAs were obtained through univariate Cox regression analysis. LASSO-COX was used to construct new disulfidptosis-related lncRNA signatures. Different statistical approaches were used to validate the practicability and accuracy of the disulfidptosis-related lncRNAs signatures. Furthermore, several bioinformatic approaches were used to study relevant heterogeneities in biological processes and pathways of diverse risk groups. Reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) was conducted to analyze the expression of disulfidptosis-related lncRNAs. Finally, seven disulfidptosis-related lncRNA signatures were identified in lung adenocarcinoma cells. The prognosis prediction model constructed efficiently predicted patient survival. Subgroup analysis revealed significant differences in immune cell proportion, including T follicular helper cells and M0 macrophages. In addition, in vitro experimental results demonstrated significant differences in disulfidptosis-related lncRNAs. Altogether, the six disulfidptosis-related lncRNA signatures could serve as a potential prognostic biomarker for lung adenocarcinoma. Furthermore, these can be used as a prediction model in individualized immunotherapy for lung adenocarcinoma.

Exploring the application and challenges of fNIRS technology in early detection of Parkinson's disease.

Background: Parkinson's disease (PD) is a prevalent neurodegenerative disorder that significantly benefits from early diagnosis for effective disease management and intervention. Despite advancements in medical technology, there remains a critical gap in the early and non-invasive detection of PD. Current diagnostic methods are often invasive, expensive, or late in identifying the disease, leading to missed opportunities for early intervention. Objective: The goal of this study is to explore the efficiency and accuracy of combining fNIRS technology with machine learning algorithms in diagnosing early-stage PD patients and to evaluate the feasibility of this approach in clinical practice. Methods: Using an ETG-4000 type near-infrared brain function imaging instrument, data was collected from 120 PD patients and 60 healthy controls. This cross-sectional study employed a multi-channel mode to monitor cerebral blood oxygen changes. The collected data were processed using a general linear model and ß values were extracted. Subsequently, four types of machine learning models were developed for analysis: Support vector machine (SVM), K-nearest neighbors (K-NN), random forest (RF), and logistic regression (LR). Additionally, SHapley Additive exPlanations (SHAP) technology was applied to enhance model interpretability. Results: The SVM model demonstrated higher accuracy in differentiating between PD patients and control group (accuracy of 85%, f1 score of 0.85, and an area under the ROC curve of 0.95). SHAP analysis identified the four most contributory channels (CH) as CH01, CH04, CH05, and CH08. Conclusion: The model based on the SVM algorithm exhibited good diagnostic performance in the early detection of PD patients. Future early diagnosis of PD should focus on the Frontopolar Cortex (FPC) region.

Comparison of different rhythmic auditory stimuli on prefrontal cortex cortical activation during upper limb movement in patients with Parkinson's disease: a functional near-infrared spectroscopy study.

Background: A large number of literatures show that rhythmic auditory stimulation (RAS) can effectively improve Parkinson's disease (PD) patients' gait speed, frequency and speed. Its application and curative effect on upper limb motor function is relatively few. Objective: By studying the immediate effect of RAS with different rhythms on the prefrontal cortex (PFC) blood oxygen response during upper limb movement in PD patients, this study discusses the potential neurophysiological mechanism of RAS on upper limb movement in PD patients, which is expected to provide guidance for patients with upper limb dysfunction such as Parkinson's disease. Methods: In this study, 31 PD patients with upper limb static tremors were recruited to complete the nail board task on the healthy upper limb under the baseline rhythm, slow rhythm and fast rhythm provided by the therapist. At the same time, fNIRS was used to observe the blood oxygen response of PFC. Results: There was no significant main effect onsidein all brain regions (p > 0.05), and there was no interaction between rhythm and side (p > 0.05); Except lPFC, the main effect of rhythm in other brain regions was significant (p < 0.05), and ΔHbO increased with the change of rhythm. Paired analysis showed that there were significant differences in ΔHbO between slow rhythm and baseline rhythm, between fast rhythm and baseline rhythm, and between slow rhythm and fast rhythm (p < 0.05); The ΔHbO of rPFC, lDLPFC and rDLPFC were significantly different between slow rhythm and fast rhythm (p < 0.05); there were significant differences in the ΔHbO of BA8 between slow rhythm and baseline rhythm, and between slow rhythm and fast rhythm (p < 0.05). Conclusion: RAS may be a useful upper limb rehabilitation strategy for PD patients with upper limb dysfunction. At the same time, RAS with different rhythms also have different responses to PFC blood oxygen during upper limb movement in PD patients, so that we can design interventions for this kind of cortical mechanism. Identifying the neurophysiological mechanism of RAS on upper limb movement in PD patients may help clinicians customize rehabilitation methods for patients according to clues, so as to highly personalize upper limb training and optimize its effect.

Nanotechnology for brain tumor imaging and therapy based on π-conjugated materials: state-of-the-art advances and prospects.

In contemporary biomedical research, the development of nanotechnology has brought forth numerous possibilities for brain tumor imaging and therapy. Among these, π-conjugated materials have garnered significant attention as a special class of nanomaterials in brain tumor-related studies. With their excellent optical and electronic properties, π-conjugated materials can be tailored in structure and nature to facilitate applications in multimodal imaging, nano-drug delivery, photothermal therapy, and other related fields. This review focuses on presenting the cutting-edge advances and application prospects of π-conjugated materials in brain tumor imaging and therapeutic nanotechnology.

A diagnostic model of nerve root compression localization in lower lumbar disc herniation based on random forest algorithm and surface electromyography.

Objective: This study aimed to investigate the muscle activation of patients with lumbar disc herniation (LDH) during walking by surface electromyography (SEMG) and establish a diagnostic model based on SEMG parameters using random forest (RF) algorithm for localization diagnosis of compressed nerve root in LDH patients. Methods: Fifty-eight patients with LDH and thirty healthy subjects were recruited. The SEMG of tibialis anterior (TA) and lateral gastrocnemius (LG) were collected bilaterally during walking. The peak root mean square (RMS-peak), RMS-peak time, mean power frequency (MPF), and median frequency (MF) were analyzed. A diagnostic model based on SEMG parameters using RF algorithm was established to locate compressed nerve root, and repeated reservation experiments were conducted for verification. The study evaluated the diagnostic efficiency of the model using accuracy, precision, recall rate, F1-score, Kappa value, and area under the receiver operating characteristic (ROC) curve. Results: The results showed that delayed activation of TA and decreased activation of LG were observed in the L5 group, while decreased activation of LG and earlier activation of LG were observed in the S1 group. The RF model based on eight SEMG parameters showed an average accuracy of 84%, with an area under the ROC curve of 0.93. The RMS peak time of TA was identified as the most important SEMG parameter. Conclusion: These findings suggest that the RF model can assist in the localization diagnosis of compressed nerve roots in LDH patients, and the SEMG parameters can provide further references for optimizing the diagnosis model in the future.

Study on Chain Extension Blending Modification and Foaming Behavior of Thermoplastic Polyamide Elastomer.

In order to improve the melt foaming properties of thermoplastic polyamide elastomers and reduce the shrinkage rate of foamed materials, acid anhydride chain extenders SMA (styrene maleic anhydride copolymer) are used in this paper to in situ reactive blending thermoplastic polyamide elastomers (TPAE) and polyamide 6 (PA6). The rheological and crystalline properties of the modified samples were characterized by a rotational rheometer and differential scanning calorimeter, and the melt batch foaming experiment with CO2 as the foaming agent was carried out. The results showed that the melting enthalpy of modified TPAE reduced with the addition of content of PA6, which implied that the crystallinity of the hard phase of the system was depressed. Nevertheless, the reduction of crystallinity was beneficial to improve the penetration of gas and reduce the effect of the pressure difference inside and outside the cell on foam shrinkage. Additionally, the microcross-linked structure formed with the increase of PA6 content enhanced the storage modulus of modified TPAE, which could accelerate recovery of strain. The foaming temperature zone and recovery performance of all modified TPAE samples were significantly improved. The overall shrinkage rate was reduced to less than 10%, the maximum expansion ratio could reach 11-13 times with a more complete and uniform cell structure, and the resilience was improved by about 12%.

The Validity and Reliability of a New Intelligent Three-Dimensional Gait Analysis System in Healthy Subjects and Patients with Post-Stroke.

Odonate is a new, intelligent three-dimensional gait analysis system based on binocular depth cameras and neural networks, but its accuracy has not been validated. Twenty-six healthy subjects and sixteen patients with post-stroke were recruited to investigate the validity and reliability of Odonate for gait analysis and examine its ability to discriminate abnormal gait patterns. The repeatability tests of different raters and different days showed great consistency. Compared with the results measured by Vicon, gait velocity, cadence, step length, cycle time, and sagittal hip and knee joint angles measured by Odonate showed high consistency, while the consistency of the gait phase division and the sagittal ankle joint angle was slightly lower. In addition, the stages with statistical differences between healthy subjects and patients during a gait cycle measured by the two systems were consistent. In conclusion, Odonate has excellent inter/intra-rater reliability, and has strong validity in measuring some spatiotemporal parameters and the sagittal joint angles, except the gait phase division and the ankle joint angle. Odonate is comparable to Vicon in its ability to identify abnormal gait patterns in patients with post-stroke. Therefore, Odonate has the potential to provide accessible and objective measurements for clinical gait assessment.

The pathway toward practical application of lithium-metal anodes for non-aqueous secondary batteries.

The revolution of automotive vehicles (from petrol vehicles to electric vehicles) has set high demands for the performance of batteries. Lithium-metal batteries (LMBs) show great potential owing to their high energy density but encounter poor cycle life and safety issues. It is of great significance to reveal LMB failure mechanisms and understand their relationship with battery performance. This review presents an overview of the state-of-the-art Li-metal anodes, with an emphasis on two typical failure modes: capacity degradation and dendritic growth of Li metal. The critical correlations between the composition, structure and failure are explained point by point. The chemical and electrochemical stabilities of the lithium anode are discussed. Particularly, for the first time, five types of lithium-metal anodes are classified to develop a comprehensive understanding of LMBs. Furthermore, strategies are suggested to improve the practical performance of LMBs, including material innovation, electrolyte modification and advanced characterization.

Effect of neoadjuvant iodine-125 brachytherapy upon resection of glioma.

BACKGROUND: A more extensive surgical resection of glioma contributes to improved overall survival (OS) and progression-free survival (PFS). However, some patients miss the chance of surgical resection when the tumor involves critical structures. PURPOSE: The present study aimed to assess the feasibility of neoadjuvant 125I brachytherapy followed by total gross resection for initially inoperable glioma. METHODS: Six patients diagnosed with inoperable glioma due to invasion of eloquent areas, bihemispheric diffusion, or large tumor volume received 125I brachytherapy. Surgical resection was performed when the tumor shrank, allowing a safe resection, assessed by the neurosurgeons. Patients were followed up after surgery. RESULTS: Shrinkage of the tumor after adjuvant 125I brachytherapy enabled a total gross resection of all six patients. Four patients were still alive at the last follow-up, with the longest survival time of more than 50 months, two of which returned to everyday life with a KPS of 100. Another two patients had neurological injuries with KPSs of 80 and 50, respectively. One patient with grade II glioma died 34 months, and another with grade IV glioma died 40 months after the combined therapy. CONCLUSIONS: In the present study, the results demonstrated that 125I brachytherapy enabled a complete resection of patients with initially unresectable gliomas. 125I brachytherapy may offer a proper neoadjuvant therapy method for glioma.

In vivo tracking of unlabelled mesenchymal stromal cells by mannose-weighted chemical exchange saturation transfer MRI.

The tracking of the in vivo biodistribution of transplanted human mesenchymal stromal cells (hMSCs) relies on reporter genes or on the addition of exogenous imaging agents. However, reporter genes and exogenous labels may require bespoke manufacturing and regulatory processes if used in cell therapies, and the labels may alter the cells' properties and are diluted on cellular division. Here we show that high-mannose N-linked glycans, which are abundantly expressed on the surface of hMSCs, can serve as a biomarker for the label-free tracking of transplanted hMSCs by mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). For live mice with luciferase-transfected hMSCs transplanted into their brains, post-mortem fluorescence staining with a mannose-specific lectin showed that increases in the CEST MRI signal, which correlated well with the bioluminescence intensity of viable hMSCs for 14 days, corresponded to the presence of mannose. In vitro, osteogenically differentiated hMSCs led to lower CEST MRI signal intensities owing to the concomitantly reduced expression of mannose. The label-free imaging of hMSCs may facilitate the development and testing of cell therapies.

BDNF-overexpressing MSCs delivered by hydrogel in acute ischemic stroke treatment.

Background: Ischemic stroke treatment is a challenge worldwide. The efficacy and safety of mesenchymal stem cells (MSCs) for stroke have been confirmed. However, poor survival of MSCs in the ischemic environment limits the therapy efficacy. Changes in MSC status in the ischemic environment after transplantation is difficult to monitor. This study aimed to deliver brain-derived neurotrophic factor (BDNF)-overexpressing MSCs by hydrogel (H-B-MSCs) to promote recovery after ischemic stroke. Methods: MSCs were transfected with lentivirus carrying luc2 and BDNF cassette. The properties of hydrogel were tested after synthesis with thiolated gelatin (Gel-SH), thiolated hyaluronic acid (HA-SH), and polyethylene glycol diacrylate (PEGDA). Oxygen-glucose deprivation (OGD) test was carried out to confirm the protective effects of hydrogel in the ischemic environment. Three days after stroke induction, H-B-MSCs, hydrogel carrying MSCs (H-MSCs), or phosphate-buffered saline (PBS) was injected into the brains of mice, respectively. Bioluminescence imaging (BLI) was performed at 3, 7, 14, and 21 days post-cell-transplantation to monitor the dynamic status of MSCs. In the meantime, histology, quantitative polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA), western blot, and behavior tests were carried out at different time points. Results: Hydrogel with good biocompatibility was synthesized. Lentivirus transfection significantly increased the expression of BDNF. BDNF-MSCs could be tracked by BLI in vitro. In vitro OGD/reperfusion (OGD/R) test results suggested that MSCs carried by hydrogel could survive longer in an environment with low oxygen and glucose. H-B-MSCs significantly improved functional recovery after ischemic stroke. Furthermore, H-B-MSCs treatment promoted neurogenesis, white matter recovery, and angiogenesis after ischemic stroke. MSC dynamics could be monitored in vivo with BLI. Conclusions: We effectively established a robust MSC delivery system with hydrogel. Prolonged survival of transplanted BDNF-MSCs with a hydrogel delivery system could promote the recovery of ischemic stroke via the continuous release of BDNF.

Iodine-125 brachytherapy treatment for newly diagnosed brain metastasis in non-small cell lung cancer: A biocentric analysis.

Purpose: The aim of the present study is to evaluate the safety and efficacy of iodine-125 brachytherapy for newly diagnosed brain metastasis in patients with non-small cell lung cancer (NSCLC). Materials and methods: The study included 158 NSCLC patients diagnosed with brain metastasis from December 2003 to August 2017. Ninety-nine patients underwent external beam radiotherapy (EBRT group), and 59 patients received iodine-125 brachytherapy (125I group). In addition, the 6- and 12-month progression-free survival (PFS) rates and the 12- and 24-month overall survival (OS) rates were compared between the EBRT group and the 125I group. Median OS and PFS were analyzed using the Kaplan-Meier method with a log-rank test. Results: The 6-month PFS rate was significantly higher in the 125I group (p = 0.002) than in the EBRT group, while no differences were found in the 12-month PFS rate (p = 0.184). Additionally, the 12- (p = 0.839) and 24-month (p = 0.284) OS rates were not significantly different between the two groups. No significant differences in median OS (p = 0.525) or PFS (p = 0.425) were found between the two groups. Conclusions: Iodine-125 brachytherapy is an alternative therapy for patients unable to undergo surgical resection.

The efficacy of 5 rehabilitation treatments after anterior cruciate ligament reconstruction: A network meta-analysis.

BACKGROUND: The efficacy of traditional rehabilitation, proprioceptive training, and neuromuscular training after anterior cruciate ligament (ACL) reconstruction is also controversial. In order to help medical staff better choose the rehabilitation treatment plan after ACL reconstruction, we conducted this network meta-analysis. METHODS: Chinese and English databases such as Wanfang, Weipu, China Zhiwang, and PubMed, Cochrane Library, Embase were retrieved. We collected clinical controlled trial papers on traditional rehabilitation therapy, proprioceptive training and neuromuscular training after ACL reconstruction for meta-analysis. RESULTS: In this meta-analysis, 12 studies were included, including 486 patients who received rehabilitation treatment after ACL reconstruction. Based on network meta-analysis, it was found that 4 groups of direct comparison and 6 groups of indirect comparison were formed for 5 rehabilitation treatment schemes after ACL reconstruction. The curative effect of traditional rehabilitation training combined with proprioception training is better than that of traditional rehabilitation training (mean difference value of traditional rehabilitation training combined with proprioception training vs traditional rehabilitation training was 8.00, 95% confidence interval: 2.61,13.39). The efficacy of proprioceptive training is better than that of traditional rehabilitation training (mean difference value of proprioceptive training vs traditional rehabilitation training is 11.01, 95% confidence interval: 0.62,21.39). There was no statistical significance between the other rehabilitation trainings. According to the surface under cumulative ranking curve, the therapeutic effects of the 5 rehabilitation treatment programs after ACL reconstruction were ranked as follows: proprioceptive training (72%) > traditional rehabilitation training combined with neuromuscular training (70.8%) > traditional rehabilitation training combined with proprioception training (57.1%) > neuromuscular training (45.5%) > traditional rehabilitation training (4.6%). No publication bias was found in the funnel plot. CONCLUSION: Combined with the results of meta-analysis and surface under cumulative ranking efficacy sequence diagram, it can be seen that traditional rehabilitation training combined with proprioceptive training and traditional rehabilitation training combined with neuromuscular training have significant efficacy. Due to the limitations of this study, the conclusions of this network meta-analysis still need to be further confirmed by a large sample size and well-designed randomized controlled trials.

Hybrid Li-Ion Capacitor Operated within an All-Climate Temperature Range from -60 to +55 °C.

Lithium-ion capacitors (LICs) have been considered as an advanced energy storage system owing to their high energy and power densities. However, their application in a wide temperature range is still a great challenge due to the reduced ionic conductivity of the electrolyte and the poor electric conductivity of the battery-type transition metal oxide electrodes. Herein, an all-climate LIC is well-fabricated with TiNb2O7@expanded graphite as the anode and activated carbon as the cathode in an optimized electrolyte, which can be operated within a wide temperature range from -60 to +55 °C. Benefitting from the synergetic effect of the improved electrode and electrolyte, the LIC exhibits an outstanding energy density of 119 W h kg-1 and a power density of 5110 W kg-1 based on the total mass of both negative and positive electrodes. Moreover, it can deliver a capacity retention of as high as 42% at -60 °C and function at a superior rate capability at a high temperature of +55 °C, which exhibits an all-climate feature and the potential for wide applications under some extreme conditions.

Intra-operative 3D hologram support with mixed reality technique based on CT-MRI fusion images: operation guidance for brain brachytherapy.

PURPOSE: The study investigated whether intra-operative 3D hologram, a computer graphics model of the brain, with mixed reality (MR) technique based on computed tomography-magnetic resonance imaging (CT-MRI) fusion images could be helpful during brachytherapy for brain metastasis. MATERIAL AND METHODS: A patient with relapsed brain metastasis was reported. Pre-operative CT and MRI image fusion was performed, with software developed by our center and the Chinese University of Hong Kong. 3D polygon data segmented from pre-operative CT-MRI fusion images were registered into HoloLens (Microsoft Corporation, Redmond, WA, USA). 125I seed implantation was performed under MR guidance. RESULTS: Interventional surgeons could share the same hologram and move the hologram from their respective angles, while wearing the HoloLens without any monitors. The intra-operative hologram offered good visualization of the skull, tumor location, and main vessels around the tumor during brain brachytherapy of a patient with brain metastasis. The interventional surgeons could easily compare the patient's actual anatomy with the hologram before and during the brain brachytherapy procedure. D90 and V100 of post-operative plan and pre-operative plan were 131.8 Gy vs. 132.0 Gy and 94.8% vs. 94.0%, respectively. The patient's imaging findings together with clinical symptoms were greatly improved at 3 and 6 months after the implantation. CONCLUSIONS: This initial experience suggests that the use of the intra-operative hologram with MR technique based on CT-MRI fusion images helped in brachytherapy guidance. Further research is needed to explore the potential of this approach in neuro-navigation.

Clinical importance of ADC in the prediction of 125I in the treatment for gliomas.

Objectives: To determine whether the minimum apparent diffusion coefficient (minADC) value can stratify survival in patients with glioma before 125I brachytherapy. Methods: The study was approved by the Institutional Review Board, and the requirement for informed consent was waived. Twenty-three patients (16 male, 7 female; median age, 48 years) with high-grade glioma (HGG) (n=9) or recurrence after multimodal treatment (n=14) were included in this study. minADC values were obtained before 125I implantation. Overall survival (OS) and progression-free survival (PFS) were analyzed with Cox proportional hazards regression models and the Kaplan-Meier method with the log-rank test. Results: For 125I-treated patients, the hazard ratio for OS in patients with ADC≥1.0*10^-3 mm2·sec-1 (high minADC) versus ADC<1.0*10^-3 mm2·sec-1 (low minADC) was 0.220 (95% confidence interval: 0.066, 0.735). The median OS was 12 months for patients with high minADC values and 6.0 months for those with low minADC values, and the differences were significant (p=0.032). The median PFS was 12 months for patients with high minADC values and 4 months for those with low minADC values. Significant differences were found in the long-rank test (p=0.013). The multivariate analysis results showed that minADC pre-125I implantation was an independent predictor of OS and PFS in patients receiving 125I brachytherapy. Conclusions: Pre-125I implantation ADC analysis can stratify prognosis in 125I-treated patients with glioma, which may aid in choosing a suitable therapy for glioma patients.

Cell Models for Birth Defects Caused by Chloroethyl Nitrosourea-Induced DNA Lesions.

ABSTRACT: Birth defects have been linked to administration of alkylating agents during pregnancy. The anti-tumor efficacy of alkylating agents correlate with their ability to induce DNA lesions, especially interstrand crosslinks (ICLs). Yet the role of DNA damages in birth defects remains to be clarified, owing, in part, to a lack of cell models. Here we generate DNA lesions in NIH/3T3 cells to mimic defects in fetus triggered by 3-Bis(2-chloroethyl)-1-nitrosourea (BCNU, carmustine). CCK-8 assay suggests that BCNU-induced cell death was dose-dependent. Alkaline comet tests and γ-H2AX staining confirm DNA ICLs and other forms of DNA damages caused by BCNUs. The cell cycle analysis shows cells arrest in G2/M phase until crosslinks repair is complete. Taken together, all these experiments demonstrate we have successfully established normal cell models for birth defects caused by BCNU-mediated DNA damages. The model can not only guide the development of effective and low-toxicity anticancer drugs, but also be of great significance for the study of neonatal malformation triggered by BCNUs.

Correction to: Permanent iodine-125 brachytherapy for patients with progressive or recurrent high-grade gliomas.

An amendment to this paper has been published and can be accessed via the original article.