Search

Abstract Background Glioma is the most common brain tumor. IDH mutations occur frequently in glioma, indicating a more favorable prognosis. We aimed to explore energy metabolism-related genes in glioma to promote the research and treatment. Methods Datasets were obtained from TCGA and GEO databases. Candidate genes were screened by differential gene expression analysis, then functional enrichment analysis was conducted on the candidate genes. PPI was also carried out to help determine the target gene. GSEA and DO analysis were conducted in the different expression level groups of the target gene. Survival analysis and immune cell infiltrating analysis were performed as well. Results We screened 34 candidate genes and selected GLUD1 as the target gene. All candidate genes were significantly enriched in 10 KEGG pathways and 330 GO terms. GLUD1 expression was higher in IDH-mutant samples than IDH-wildtype samples, and higher in normal samples than tumor samples. Low GLUD1 expression was related to poor prognosis according to survival analysis. Most types of immune cells were negatively related to GLUD1 expression, but monocytes and activated mast cells exhibited significantly positive correlation with GLUD1 expression. GLUD1 expression was significantly related to 119 drugs and 6 immune checkpoint genes. GLUD1 was able to serve as an independent prognostic indicator of IDH-mutant glioma. Conclusion In this study, we identified an energy metabolism-related gene GLUD1 potentially contributing to favorable clinical outcomes of IDH-mutant glioma. In glioma, GLUD1 related clinical outcomes and immune landscape were clearer, and more valuable information was provided for immunotherapy.

Abstract Background Insulin has been known to regulate bone metabolism, yet its specific molecular mechanisms during the proliferation and osteogenic differentiation of dental pulp stem cells (DPSCs) remain poorly understood. This study aimed to explore the effects of insulin on the bone formation capability of human DPSCs and to elucidate the underlying mechanisms. Methods Cell proliferation was assessed using a CCK-8 assay. Cell phenotype was analyzed by flow cytometry. Colony-forming unit-fibroblast ability and multilineage differentiation potential were evaluated using Toluidine blue, Oil red O, Alizarin red, and Alcian blue staining. Gene and protein expressions were quantified by real-time quantitative polymerase chain reaction and Western blotting, respectively. Bone metabolism and biochemical markers were analyzed using electrochemical luminescence and chemical colorimetry. Cell adhesion and growth on nano-hydroxyapatite/collagen (nHAC) were observed with a scanning electron microscope. Bone regeneration was assessed using micro-CT, fluorescent labeling, immunohistochemical and hematoxylin and eosin staining. Results Insulin enhanced the proliferation of human DPSCs as well as promoted mineralized matrix formation in a concentration-dependent manner. 10− 6 M insulin significantly up-regulated osteogenic differentiation-related genes and proteins markedly increased the secretion of bone metabolism and biochemical markers, and obviously stimulated mineralized matrix formation. However, it also significantly inhibited the expression of genes and proteins of receptors and receptor substrates associated with insulin/insulin-like growth factor-1 signaling (IIS) pathway, obviously reduced the expression of the phosphorylated PI3K and the ratios of the phosphorylated PI3K/total PI3K, and notably increased the expression of the total PI3K, phosphorylated AKT, total AKT and mTOR. The inhibitor LY294002 attenuated the responsiveness of 10− 6 M insulin to IIS/PI3K/AKT/mTOR pathway axis, suppressing the promoting effect of insulin on cell proliferation, osteogenic differentiation and bone formation. Implantation of 10− 6 M insulin treated DPSCs into the backs of severe combined immunodeficient mice and the rabbit jawbone defects resulted in enhanced bone formation. Conclusions Insulin induces insulin resistance in human DPSCs and effectively promotes their proliferation, osteogenic differentiation and bone formation capability through gradually inducing the down-regulation of IIS/PI3K/AKT/mTOR pathway axis under insulin resistant states.

Abstract Recognizing the essential factor governing interfacial hydrogen/oxygen evolution reactions (HER/OER) is central to electrocatalytic water‐splitting. Traditional strategies aiming at enhancing electrocatalytic activities have mainly focused on manipulating active site valencies or coordination environments. Herein, the role of interfacial adsorption is probed and modulated by the topological construct of the electrocatalyst, a frequently underestimated non‐Faradaic mechanism in the dynamics of electrocatalysis. The engineered Co0.75Fe0.25P nanorods, anchored with FeOx clusters, manifest a marked amplification of the surface electric field, thus delivering a substantially improved bifunctional electrocatalytic performance. In alkaline water splitting anion exchange membrane (AEM) electrolyzer, the current density of 1.0 A cm−2 can be achieved at a cell voltage of only 1.73 V for the FeOx@Co0.75Fe0.25P|| FeOx@Co0.75Fe0.25P pairs for 120 h of continuous operation at 1.0 A cm−2. Detailed investigations of electronic structures, combined with valence state and coordination geometry assessments, reveal that the enhancement of catalytic behavior in FeOx@Co0.75Fe0.25P is chiefly attributed to the strengthened adsorptive interactions prompted by the intensified electric field at the surface. The congruent effects observed in FeOx‐cluster‐decorated Co0.75Fe0.25P nanosheets underscore the ubiquity of this effect. The results put forth a compelling proposition for leveraging interfacial charge densification via deliberate cluster supplementation.

Three methods are used for a numerical solution, the Monte Carlo method, diffusion approximation equation model, and beam broaden model based on Beer–Lambert’s law equation. The comparison between the first two methods is reported theoretically, and the latter is a better choice in the high-density tissue. However, the comparison between the third method and the first or the second method is rarely reported. Two classical theoretical models describing the interaction between the laser and the bio-tissue are analyzed and compared to determine which is more suitable for analyzing the interaction, the beam broaden model or diffusion approximation equation model. Intensity distribution is simulated and compared for the two models. Temperature distribution and thermal damage are investigated theoretically and experimentally for both models. The differences and the reasons are analyzed. The diffusion approximation equation model is more suitable for analyzing the mechanism between the laser and the bio-tissue based on the degree of fitting between the simulated and experimental data. Theoretical analyses for the two models are carried out in detail. The comparison between the two models is rarely reported, and it is reported in this article for the first time, theoretically and experimentally. This report provides a better choice for quickly analyzing the interaction mechanism between the laser and the bio-tissue.

In bone tissue engineering, scaffolds with excellent mechanical and bioactive properties play prominent roles in space maintaining and bone regeneration, attracting increasingly interests in clinical practice. In this study, strontium-incorporated β-tricalcium phosphate (β-TCP), named Sr-TCP, bioceramic triply periodic minimal surface (TPMS) structured scaffolds were successfully fabricated by digital light processing (DLP)-based 3D printing technique, achieving high porosity, enhanced strength, and excellent bioactivity. The Sr-TCP scaffolds were first characterized by element distribution, macrostructure and microstructure, and mechanical properties. Notably, the compressive strength of the scaffolds reached 1.44 MPa with porosity of 80%, bringing a great mechanical breakthrough to porous scaffolds. Furthermore, the Sr-TCP scaffolds also facilitated osteogenic differentiation of mouse osteoblastic cell line (MC3T3-E1) cells in both gene and protein aspects, verified by alkaline phosphatase (ALP) activity and polymerase chain reaction (PCR) assays. Overall, the 3D-printed Sr-TCP bioceramic TPMS structured scaffolds obtained high porosity, boosted strength, and superior bioactivity at the same time, serving as a promising approach for bone regeneration.

Background: Allograft lung ischemia-reperfusion injury (ALIRI) is a major cause of early primary graft dysfunction and poor long-term survival after lung transplantation (LTx); however, its pathogenesis has not been fully elucidated. Cell death is a mechanism underlying ALIRI. Cuproptosis is a recently discovered form of programmed cell death. To date, no studies have been conducted on the mechanisms by which cuproptosis-related genes (CRGs) regulate ALIRI. Therefore, we explored the potential biomarkers related to cuproptosis to provide new insights into the treatment of ALIRI.Materials and methods: Datasets containing pre- and post-LTx lung biopsy samples and CRGs were obtained from the GEO database and previous studies. We identified differentially expressed CRGs (DE-CRGs) and performed functional analyses. Biomarker genes were selected using three machine learning algorithms. The ROC curve and logistic regression model (LRM) of these biomarkers were constructed. CIBERSORT was used to calculate the number of infiltrating immune cells pre- and post-LTx, and the correlation between these biomarkers and immune cells was analyzed. A competing endogenous RNA network was constructed using these biomarkers. Finally, the biomarkers were verified in a validation set and a rat LTx model using qRT-PCR and Western blotting.Results: Fifteen DE-CRGs were identified. GO analysis revealed that DE-CRGs were significantly enriched in the mitochondrial acetyl-CoA biosynthetic process from pyruvate, protein lipoylation, the tricarboxylic acid (TCA) cycle, and copper-transporting ATPase activity. KEGG enrichment analysis showed that the DE-CRGs were mainly enriched in metabolic pathways, carbon metabolism, and the TCA cycle. NFE2L2, NLRP3, LIPT1, and MTF1 were identified as potential biomarker genes. The AUC of the ROC curve for each biomarker was greater than 0.8, and the LRM provided an excellent classifier with an AUC of 0.96. These biomarkers were validated in another dataset and a rat LTx model, which exhibited good performance. In the CIBERSORT analysis, differentially expressed immune cells were identified, and the biomarkers were associated with the immune cells.Conclusion:NFE2L2, NLRP3, LIPT1, and MTF1 may serve as predictors of cuproptosis and play an important role in the pathogenesis of cuproptosis in ALIRI.

Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here, the authors present the largest FL study to-date to generate an automatic tumor boundary detector for glioblastoma.

Background: The role of the cellular level in kidney transplant rejection is unclear, and single-cell RNA sequencing (scRNA-seq) can reveal the single-cell landscape behind rejection of human kidney allografts at the single-cell level.Methods: High-quality transcriptomes were generated from scRNA-seq data from five human kidney transplantation biopsy cores. Cluster analysis was performed on the scRNA-seq data by known cell marker genes in order to identify different cell types. In addition, pathways, pseudotime developmental trajectories and transcriptional regulatory networks involved in different cell subpopulations were explored. Next, we systematically analyzed the scoring of gene sets regarding single-cell expression profiles based on biological processes associated with oxidative stress.Results: We obtained 81,139 single cells by scRNA-seq from kidney transplant tissue biopsies of three antibody-mediated rejection (ABMR) patients and two acute kidney injury (AKI) patients with non-rejection causes and identified 11 cell types, including immune cells, renal cells and several stromal cells. Immune cells such as macrophages showed inflammatory activation and antigen presentation and complement signaling, especially in rejection where some subpopulations of cells specifically expressed in rejection showed specific pro-inflammatory responses. In addition, patients with rejection are characterized by an increased number of fibroblasts, and further analysis of subpopulations of fibroblasts revealed their involvement in inflammatory and fibrosis-related pathways leading to increased renal rejection and fibrosis. Notably, the gene set score for response to oxidative stress was higher in patients with rejection.Conclusion: Insight into histological differences in kidney transplant patients with or without rejection was gained by assessing differences in cellular levels at single-cell resolution. In conclusion, we applied scRNA-seq to rejection after renal transplantation to deconstruct its heterogeneity and identify new targets for personalized therapeutic approaches.

Abstract Objective To assess the feasibility of using synthetic computed tomography for treatment planning of the dominant intraprostatic lesion (DIL), a high‐risk region of interest that offers potential for increased local tumor control. Methods A dosimetric study was performed on 15 prostate cancer patients with biopsy‐proven prostate cancer who had undergone magnetic resonance imaging. DILs were contoured based on the turbo spin echo T2‐weighted and diffusion weighted images. Air, bone, fat, and soft tissue were segmented and assigned bulk‐density HU values of –1000, 285, –50, and 40, respectively, to create a synthetic computed tomography. Simultaneous integrated boost (SIB) and standard treatment plans were created for each patient. The total dose was 79.2 Gy to the non‐boosted planning target volume for both plans with a boost of 100 Gy for the DIL in the SIB plan. A radiobiological model was created to determine individualized dose–response curves based on the patient's apparent diffusion coefficient maps. Results Mean doses to the non‐boost planning target volume were 81.2 ± 0.3 Gy with the SIB and 81.0 ± 0.4 Gy without. For the DIL, the boosted mean dose was 102.6 ± 0.6 Gy. Total motor unit was 860 ± 100 with the SIB and 730 ±100 without. Femoral heads, rectum, bladder, and penile bulb were within established dose guidelines for either treatment technique. The average tumor control probability was 94% with the SIB compared with 78% without boosting the DIL. Conclusion This study showed the feasibility of magnetic resonance imaging‐only treatment planning for patients with prostate cancer with a SIB to the DIL. DIL dose can be escalated to 100 Gy on synthetic computed tomography, while maintaining the original 79.2 Gy prescription dose and the organ of interest clinical dose limits.

Controlling the electrocatalyst's surface polarization is crucial for the interfacial CO2 electrolysis that takes place. Here, we propose an efficient way to increase the electrochemical reduction of CO2 to formate by controlling the Cu2SnS3 surface polarization. This results in a formate partial current density of 408.3 mA cm−2 at an applied bias of −1.2 V vs. RHE and a faradaic efficiency of 91.7%. More specifically, the concentration of sulfur vacancies is controlled to alter the surface polarization of Cu2SnS3. Theoretical computations and experimental characterization studies emphasize the importance of sulfur vacancies in controlling Cu2SnS3's surface polarization. Additionally, the altered CO2 evolution pathway is explained by the local charge redistribution caused by sulfur vacancies, and the lower Gibbs free energy for the formation of intermediate *OCHO, which guarantees its high selectivity toward formate, is explained by the coordination structural changes of the Cu and Sn atoms involved in deficient Cu2SnS3. This study presents a practical approach to surface polarization regulation-based CO2-to-formate electrocatalyst design. [ABSTRACT FROM AUTHOR]

We present a high-energy, hundred-picosecond (ps) pulsed mid-ultraviolet solid-state laser at 266 nm by a direct second harmonic generation (SHG) in a barium borate (BaB2O4, BBO) nonlinear crystal. The green pump source is a 710 mJ, 330 ps pulsed laser at a wavelength of 532 nm with a repetition rate of 1 Hz. Under a green pump energy of 710 mJ, a maximum output energy of 253.3 mJ at 266 nm is achieved with 250 ps pulse duration resulting in a peak power of more than 1 GW, corresponding to an SHG conversion efficiency of 35.7% from 532 to 266 nm. The experimental data were well consistent with the theoretical prediction. To the best of our knowledge, this laser exhibits both the highest output energy and highest peak power ever achieved in a hundred-ps/ps regime at 266 nm for BBO-SHG.

Abstract Background The purpose of this study is to comprehensively evaluate the suitability of Gafchromic EBT3 and EBT-XD film for dosimetric quality assurance in 0.35 T MR-guided radiotherapy. Methods A 0.35 T magnetic field strength was utilized to evaluate magnetic field effects on EBT3 and EBT-XD Gafchromic films by studying the effect of film exposure time within the magnetic field using two timing sequences and film not exposed to MR, the effect of magnetic field exposure on the crystalline structure of the film, and the effect of orientation of the film with respect to the bore within the magnetic field. The orientation of the monomer crystal was qualitatively evaluated using scanning electron microscopy (SEM) compared to unirradiated film. Additionally, dosimetric impact was evaluated through measurements of a series of open field irradiations (0.83 × 0.83-cm2 to 19.92 × 19.92-cm2) and patient specific quality assurance measurements. Open fields were compared to planned dose and an independent dosimeter. Film dosimetry was applied to twenty conventional and twenty stereotactic body radiotherapy (SBRT) patient specific quality assurance cases. Results No visual changes in crystal orientation were observed in any evaluated SEM images nor were any optical density differences observed between films irradiated inside or outside the magnetic field for both EBT3 and EBT-XD film. At small field sizes, the average difference along dose profiles measured in film compared to the same points measured using an independent dosimeter and to predicted treatment planning system values was 1.23% and 1.56%, respectively. For large field sizes, the average differences were 1.91% and 1.21%, respectively. In open field tests, the average gamma pass rates were 99.8% and 97.2%, for 3%/3 mm and 3%/1 mm, respectively. The median (interquartile range) 3%/3 mm gamma pass rates in conventional QA cases were 98.4% (96.3 to 99.2%), and 3%/1 mm in SBRT QA cases were 95.8% (95.0 to 97.3%). Conclusions MR exposure at 0.35 T had negligible effects on EBT3 and EBT-XD Gafchromic film. Dosimetric film results were comparable to planned dose, ion chamber and diode measurements.