Mussel shell-derived pro-regenerative scaffold with conductive porous multi-scale-patterned microenvironment for spinal cord injury repair.

It is well-established that multi-scale porous scaffolds can guide axonal growth and facilitate functional restoration after spinal cord injury (SCI). In this study, we developed a novel mussel shell-inspired conductive scaffold for SCI repair with ease of production, multi-scale porous structure, high flexibility, and excellent biocompatibility. By utilizing the reducing properties of polydopamine, non-conductive graphene oxide (GO) was converted into conductive reduced graphene oxide (rGO) and crosslinkedin situwithin the mussel shells.In vitroexperiments confirmed that this multi-scale porous Shell@PDA-GO could serve as structural cues for enhancing cell adhesion, differentiation, and maturation, as well as promoting the electrophysiological development of hippocampal neurons. After transplantation at the injury sites, the Shell@PDA-GO provided a pro-regenerative microenvironment, promoting endogenous neurogenesis, triggering neovascularization, and relieving glial fibrosis formation. Interestingly, the Shell@PDA-GO could induce the release of endogenous growth factors (NGF and NT-3), resulting in the complete regeneration of nerve fibers at 12 weeks. This work provides a feasible strategy for the exploration of conductive multi-scale patterned scaffold to repair SCI.

TDP-43 was Involved in Radiation-induced Neuronal Damage and May Not Through the BDNF/TrkB Pathway.

Cognitive dysfunction is the most common form of radiation-induced brain injury. TDP-43 is known to be associated with hippocampal degeneration and cognitive dysfunction, in this study we wanted to know if it also had an effect on radiation-induced hippocampus damage. At first, we found the expression of TDP-43 and p-TDP-43 was increased in the hippocampus of rats with radiation-induced cognitive dysfunction. Single-cell RNA-seq analysis of the rat hippocampus showed that TDP-43 was expressed in all cell types and was significantly upregulated in neuron cells after irradiation. Enrichment analysis of gene ontology (GO) functions and KEGG pathways showed that the differential expression genes in neuron after irradiation may be involved in synaptic plasticity. In vitro, the expression of TDP-43 was also increased in neuron cells after irradiation, while the expression of brain-derived neurotrophic factor (BDNF), TrkB, typical synaptic signature proteins (SYN, GAP43 and PSD95), ß-tubulin and dendritic spines were decreased. In the irradiated neurons, the ß-tubulin, dendritic and spines typical synaptic signature proteins had more severe damage in pcDNA3.1-TDP-43 plasmid transfections group, however, the damages were alleviated in the siRNA-TDP-43 plasmid transfections group. BDNF was highly expressed in the irradiated pcDNA3.1-TDP-43 plasmid transfections group, while its expression was decreased in the siRNA-TDP-43 group. The TrkB expression was significantly reduced in neurons after exposure to ionizing radiation, however, there was no significant correlation with TDP-43 expression. These data indicate that TDP-43 is involved in radiation-induced neuronal synaptic plasticity decline and developmental damage, furthermore, the BDNF/TrkB signaling pathway may not be involved in this process.

Cardiac-Adaptive Conductive Hydrogel Patch Enabling Construction of Mechanical-Electrical Anisotropic Microenvironment for Heart Repair.

The biomimetic construction of a microstructural-mechanical-electrical anisotropic microenvironment adaptive to the native cardiac tissue is essential to repair myocardial infarction (MI). Inspired by the 3D anisotropic characteristic of the natural fish swim bladder (FSB), a novel flexible, anisotropic, and conductive hydrogel was developed for tissue-specific adaptation to the anisotropic structural, conductive, and mechanical features of the native cardiac extracellular matrix. The results revealed that the originally stiff, homogeneous FSB film was tailored to a highly flexible anisotropic hydrogel, enabling its potential as a functional engineered cardiac patch (ECP). In vitro and in vivo experiments demonstrated the enhanced electrophysiological activity, maturation, elongation, and orientation of cardiomyocytes (CMs), and marked MI repair performance with reduced CM apoptosis and myocardial fibrosis, thereby promoting cell retention, myogenesis, and vascularization, as well as improving electrical integration. Our findings offer a potential strategy for functional ECP and provides a novel strategy to bionically simulate the complex cardiac repair environment.

Estimation of the Mixed Layer Depth in the Indian Ocean from Surface Parameters: A Clustering-Neural Network Method.

The effective estimation of mixed-layer depth (MLD) plays a significant role in the study of ocean dynamics and global climate change. However, the methods of estimating MLD still have limitations due to the sparse resolution of the observed data. In this study, a hybrid estimation method that combines the K-means clustering algorithm and an artificial neural network (ANN) model was developed using sea-surface parameter data in the Indian Ocean as a case study. The oceanic datasets from January 2012 to December 2019 were obtained via satellite observations, Argo in situ data, and reanalysis data. These datasets were unified to the same spatial and temporal resolution (1° × 1°, monthly). Based on the processed datasets, the K-means classifier was applied to divide the Indian Ocean into four regions with different characteristics. For ANN training and testing in each region, the gridded data of 84 months were used for training, and 12-month data were used for testing. The ANN results show that the optimized NN architecture comprises five input variables, one output variable, and four hidden layers, each of which has 40 neurons. Compared with the multiple linear regression model (MLR) with a root-mean-square error (RMSE) of 5.2248 m and the HYbrid-Coordinate Ocean Model (HYCOM) with an RMSE of 4.8422 m, the RMSE of the model proposed in this study was reduced by 27% and 22%, respectively. Three typical regions with high variability in their MLDs were selected to further evaluate the performance of the ANN model. Our results showed that the model could reveal the seasonal variation trend in each of the selected regions, but the estimation accuracy showed room for improvement. Furthermore, a correlation analysis between the MLD and input variables showed that the surface temperature and salinity were the main influencing factors of the model. The results of this study suggest that the pre-clustering ANN method proposed could be used to estimate and analyze the MLD in the Indian Ocean. Moreover, this method can be further expanded to estimate other internal parameters for typical ocean regions and to provide effective technical support for ocean researchers when studying the variability of these parameters.

A tunable self-healing ionic hydrogel with microscopic homogeneous conductivity as a cardiac patch for myocardial infarction repair.

Conductive hydrogel is a potential therapeutic tool to treat damaged heart muscles in myocardial infarction (MI). However, it is still a quite challenge to optimize the fabrication of a therapeutic hydrogel patch that sustains favorable biocompatibility, electronic and mechanical stability under a complicated MI microenvironment. Herein, a tunable self-healing ionic hydrogel (POG1) was developed through the introduction of a biocompatible polyacrylic acid (PAA, FDA-approved) into the hydrogel matrix. The fabricated POG1 hydrogel possessed suitable stretchable (>500% strain) and compressive (>85% strain) properties, comparable modulus with mammalian heart (30-500 kPa, Young's modulus), self-healable, and highly stable conductivity during large deformations (~50% compress strain, ~150% tensile strain). Specifically, the established PAA nano-channels inside of POG1 endowed the hydrogel with microscopic ultra-homogeneous conductivity. Compared to those seeded in the electronic conductors-embedded (PPy, CNT, rGO) hydrogels, the cardiomyocytes (CMs) seeded in the POG1 hydrogel exhibited more significantly oriented sarcomeres. This POG1 engineered cardiac patch (ECP) also exerted robust benefits in attenuating left ventricular remodeling and restoring heart function after implantation in vivo. This paper highlighted a previously unexplored strategy for a biocompatible ionic conductive hydrogel ECP with an excellent MI repair function.

Application of Optical Laser 3D Surface imaging system (Sentinel) in breast cancer radiotherapy.

It has been clearly confirmed that radiation therapy (RT) after breast conserving surgery (BCS) is an effective treatment modality comparable to mastectomy for early breast cancer. The purpose of this study was to further evaluate the accuracy of 3D surface imaging system (Sentinel) for breast cancer patients received BCS. The optical surface scans and CBCT scans were acquired before and immediately after couch movement correction. The deviation of the CBCT scans from the reference planning CT was considered an estimate for the residual errors for patient setup correction. The planning target volume (PTV) margins for treatment sessions was calculated according to the setup errors. We obtained a total of 245 sets of data collected from 49 breast cancer patients. Compared with Sentinel setup errors, the residual setup errors as determined by the CBCT scans after couch movement correction were reduced in the six directions. The PTV margins derived from the CBCT residual errors were all less than 5 mm in X, Y, and Z directions. Our results suggested that Optical surface imaging can be applied in positioning for breast cancer patient accurately without unnecessary imaging dose.

Salvage treatment for lymph node recurrence after radical resection of esophageal squamous cell carcinoma.

BACKGROUND: Patients with regional lymph node recurrence after radical resection of esophageal cancer have poor therapeutic outcomes. Currently, there is no standard treatment for regional lymph node recurrence, and its prognostic risk factors are not well-understood. This study retrospectively analyzed 83 patients with postoperative regional lymph node recurrence after radical resection of esophageal squamous cell carcinoma. The aim was to evaluate the clinical efficacy and prognostic factors of salvage radiotherapy with or without chemotherapy in these patients. METHODS: The survival and prognostic factors of 83 patients with esophageal squamous cell carcinoma with regional lymph node recurrence after radical surgery were retrospectively analyzed. All patients underwent radiotherapy, of which 74 patients received volumetric modulated arc therapy (VMAT), 9 patients received three-dimensional conformal radiation therapy (3DCRT), administered using a conventional segmentation protocol with a dose distribution range of 50.4-66.2Gy (median dose of 60Gy). In total, 41 patients received radiotherapy alone, 42 received radiotherapy combined with chemotherapy, and the concurrent chemotherapy regimen was mainly composed of either platinum or fluorouracil monotherapy, except for 4 patients who were given 5-fluorouracil plus platinum (FP) or paclitaxel plus platinum (TP). RESULTS: The median follow-up time was 24 (range, 9-75) months. The overall survival (OS) rates at 1 year, 2 years, 3 years, and 5 years were 83.0, 57.1, 40.1, and 35.1%, respectively. The median overall survival (OS) time was 18 (range, 5-75) months. The 3-year survival rate was 47.5% in patients with radiation alone and 41.9% in patients receiving concurrent chemoradiotherapy(p = 0.570), while the response rate (CR + PR) in those two groups was 73.2 and 91.4%, respectively. By multivariate analysis of OS, age (worse in younger patients, p = 0.034) was found to be significantly associated with disease prognosis. The commonly toxicities were esophagitis, neutropenia and anemia. 18% patients experienced grade 3 toxicity and no treatment-related death occurred. CONCLUSIONS: These results of this retrospective analysis suggest that radiotherapy with or without chemotherapy is an effective and feasible salvage treatment for lymph node recurrence after radical resection of esophageal squamous cell carcinoma.

Development and validation of nomogram based on SIRI for predicting the clinical outcome in patients with nasopharyngeal carcinomas.

The Systemic Inflammation Response Index (SIRI), based on peripheral lymphocyte, neutrophil, and monocyte counts, was recently investigated as a prognostic marker for several tumors. However, use of the SIRI has not been reported for nasopharyngeal carcinoma (NPC). We evaluated the prognostic value of the SIRI in primary and validation cohorts. We also established an effective prognostic nomogram for NPC based on clinicopathological parameters and the SIRI. The predictive accuracy and discriminative ability of the nomogram were determined using the concordance index (C-index) and a calibration curve and were compared with tumor-node-metastasis classifications. Our Kaplan-Meier survival analysis results showed that the SIRI was associated with the overall survival of patients with NPC in the primary and validation cohorts. The SIRI was identified to be an independent prognostic factor for NPC. In addition, we developed and validated a new prognostic nomogram that integrated clinicopathological factors and the SIRI. This nomogram can efficiently predict the prognosis of patients with NPC. The SIRI is a novel, simple and inexpensive prognostic predictor for patients with NPC. The SIRI has important value for predicting the prognosis of patients with NPC and developing individualized treatment plans.

Setup errors and effectiveness of Optical Laser 3D Surface imaging system (Sentinel) in postoperative radiotherapy of breast cancer.

Breast-conserving surgery (BCS) plus postoperative radiotherapy has become the standard treatment for early-stage breast cancer. The aim of this study was to compare the setup accuracy of optical surface imaging by the Sentinel system with cone-beam computerized tomography (CBCT) imaging currently used in our clinic for patients received BCS. Two optical surface scans were acquired before and immediately after couch movement correction. The correlation between the setup errors as determined by the initial optical surface scan and CBCT was analyzed. The deviation of the second optical surface scan from the reference planning CT was considered an estimate for the residual errors for the new method for patient setup correction. The consequences in terms for necessary planning target volume (PTV) margins for treatment sessions without setup correction applied. We analyzed 145 scans in 27 patients treated for early stage breast cancer. The setup errors of skin marker based patient alignment by optical surface scan and CBCT were correlated, and the residual setup errors as determined by the optical surface scan after couch movement correction were reduced. Optical surface imaging provides a convenient method for improving the setup accuracy for breast cancer patient without unnecessary imaging dose.

Collimator rotation in volumetric modulated arc therapy for craniospinal irradiation and the dose distribution in the beam junction region.

PURPOSE: The purpose of this study was to investigate the role of beam collimator rotation in Volumetric Modulated Arc Therapy (VMAT) for craniospinal irradiation (CSI), and the impact on dose distribution in the beam junctions. METHODS: Six adult patients were selected for the study. Six VMAT plans with different collimator angles were generated for each patient. The patients were treated in supine position with two beam isocenters. The plans were evaluated by analysis of Dose-Volume Histogram (DVHs) data for planning target volume (PTV) and organs at risk (OAR), and conformity index (CI) and homogeneity index (HI) for the target. Dose distributions in the beam junctions were examined carefully and experimentally validated in phantom, with measurement using an ion chamber array and film. RESULTS: The mean values of HI and CI for the plans with different beam collimator angles were not significantly different. The numbers of segments, monitor units (MUs) and the delivery time of the plans with 45° beam collimator were obviously higher than those in plans with other beam collimator angles. When collimator angle for both sets of beams were set at 0°, there was a 1 mm low dose gap measured in the junction region. CONCLUSIONS: By setting the collimator angle to 45°, only two isocenters were needed for the treatment of a target with the length up to 90 cm. The HI and CI of the plans were almost the same, regardless if the collimator angles were at 0°. The collimator angles for at least one set of beams should be off 0° in order to avoid a dose gap in the beam junction region.