Intrinsic Surface Effects of Tantalum and Titanium on Integrin α5β1/ ERK1/2 Pathway-Mediated Osteogenic Differentiation in Rat Bone Mesenchymal Stromal Cells

Background/Aims: Accumulating evidence demonstrates the superior osteoinductivity of tantalum (Ta) to that of titanium (Ti); however, the mechanisms underlying these differences are unclear. Thus, the objective of the present study was to examine the effects of Ta and Ti surfaces on osteogenesis using rat bone mesenchymal stromal cells (rBMSCs) as a model. Methods: Ta and Ti substrates were polished to a mirror finish to minimize the influences of structural factors, and the intrinsic surface effects of the two materials on the integrin α5β1/mitogen-activated protein kinases 3 and 1 (ERK1/2) cascade-mediated osteogenesis of rBMSCs were evaluated. Alkaline phosphatase (ALP) activity, Alizarin Red staining, real-time polymerase chain reaction, and western blot assays of critical osteogenic markers were conducted to evaluate the effects of the two substrates on cell osteogenesis. Moreover, the role of the integrin α5β1/ERK1/2 pathway on the osteoinductive performance of Ta and Ti was assessed by up- and down-regulation of integrin α5 and β1 with RNA interference, as well as through ERK1/2 inhibition with U0126. Results: Osteogenesis of rBMSCs seeded on the Ta surface was superior to that of cells seeded on the Ti surface in terms of ALP activity, extracellular matrix calcification, and the expression of integrin α5, integrin β1, ERK1/2, Runt-related transcription factor 2, osteocalcin, collagen type I, and ALP at both the mRNA and protein levels. Moreover, down-regulation of integrin α5 or integrin β1, or ERK1/2 inhibition severely impaired the osteoblastic differentiation on the Ta surface. By contrast, over-expression of integrin α5 or integrin β1 improved osteogenesis on the Ti substrates, while subsequent ERK1/2 inhibition abrogated this effect. Conclusion: The integrin α5β1/ERK1/2 pathway plays a crucial role in regulating rBMSCs osteogenic differentiation; thus, the greater ability of a Ta surface to trigger integrin α5β1/ERK1/2 signaling may explain its better osteoinductivity. The different effects of Ta and Ti surfaces on rBMSC osteogenesis are considered to be related to the conductive behaviors between integrin α5β1 and the oxides spontaneously formed on the two metals. These results should facilitate the development of engineering strategies with Ta and Ti surfaces for improved osteogenesis in endosteal implants

Safety of radiofrequency ablation for reducing inflammatory cytokine levels and the left atrial diameter in patients with atrial fibrillation

Objective To investigate the safety of radiofrequency ablation for reducing inflammatory cytokines and the left atrial diameter in patients with atrial fibrillation (AF). Methods A total of 200 patients with AF who were admitted to our hospital from December 2015 to April 2017 were included in this prospective analysis. Fifty patients were treated with conventional AF medication alone (AF medication group) and 50 patients received radiofrequency ablation (RFA) on the basis of conventional medication (RFA group). Results After treatment, the AF medication group showed significantly higher levels of high-sensitivity C-reactive protein, interleukin-6, carboxyterminal propeptide of type-I procollagen, procollagen type III N-terminal propeptide, and matrix metallopeptidase-9 than the RFA group. The AF medication group had a significantly lower activated partial thromboplastin time, thrombin time, and prothrombin time than the RFA group. A significantly smaller left atrial diameter was observed in both groups after treatment, but this decrease was more pronounced in the RFA group than in the AF medication group. The total treatment efficacy rate was significantly lower in the AF medication group than in the RFA group. Conclusions For patients with AF, RFA leads to a lower incidence of inflammatory responses, faster recovery of cardiac function, and good safety

Association between Screen Exposure and Emotional and Behavioral Problems in Preschool Children with Autism Spectrum Disorder

Background Previous studies have confirmed that screen exposure is widespread in preschool children and is related to children's emotional and behavioral problems. Most of the existing studies focus on normal preschool children, but the research on screen exposure and emotional and behavioral problems of preschool autistic children is relatively rare. Objective To investigate the screen exposure and the abnormal detection of emotional and behavioral problems in preschool children with autism, and to explore the association between screen exposure and emotional and behavioral problems in preschool children with autism. Methods Preschool children with autism who met the diagnostic and Statistical Manual of Mental Disorders (DSM-V) autism diagnostic criteria and visited the Department of Child Development and Behavior of the Third Affiliated Hospital of Zhengzhou University from February to August 2022 were selected as the autism group. At the same time, children with normal development in kindergartners in Zhengzhou were selected as the normal control group. The screen exposure questionnaire and the Strengths and Difficulties Questionnaire (parent version) were completed by the main caregivers of the children in the two groups. Results There were significant differences between the two groups in terms of screen time, parents' response to screen management, and screen deprivation (P<0.001). Compared with the normal control group, the children in the autism group had significantly higher detection rates of prosocial behavior, total difficulties, and sub-dimensions (emotional symptoms, conduct problems, hyperactivity/inattention problems, and peer problems) (P<0.001). Logistic regression showed that the influencing factors of emotional and behavioral problems in preschool children included placing electronic devices in the sleeping or playing space, whether caregivers interacted with each other during watching, caregivers' attitudes toward children's electronic screen watching, whether they were active or passive participants in touching electronic screens, and children's reactions to forced turning off electronic screens (P<0.05) . Conclusion Screen exposure can affect the emotional and behavioral problems of preschool children with autism. Parents should rationally plan screen use for preschool children with autism

A Communication Framework with Unified Efficiency and Secrecy

Future wireless networks are confronted with the pressure to meet the requirements of network efficiency and communication secrecy, which require a new communication framework to unify and jointly optimize efficiency and secrecy. The challenges are to extend the current communication architecture and reveal the relationship of efficiency and secrecy, so that unification and joint optimization can be achieved. Artificial Intelligence (AI) is a powerful tool to solve these problems. In this article, a unified efficiency and secrecy communication framework (UESCF) is proposed to provide the theoretical bases for the applications of AI technology in wireless networks. Under the proposed framework, AI technologies are applied to generate the network common knowledge and communication private knowledge, with the purpose of improving efficiency and secrecy. The goal of this article is to establish the UESCF for future wireless networks and offer an overview to illuminate the potential applications of AI in the proposed framework. 2002-2012 IEEE.This work was supported by the National Natural Science Foundation of China (91538203 and 61871257); the new strategic industries development projects of Shenzhen City (JCYJ20170307145820484); the Joint Research Foundation of the General Armaments Department and the Ministry of Education (6141A02033322); and the Beijing Innovation Center for Future Chips, Tsinghua University.Scopus2-s2.0-8506466144

Plasma Pharmacokinetics and Tissue Distribution of Doxorubicin in Rats following Treatment with Astragali Radix

Doxorubicin (DOX) is an essential component in chemotherapy, and Astragali Radix (AR) is a widely used tonic herbal medicine. The combination of DOX and AR offers widespread, well-documented advantages in treating cancer, e.g., reducing the risk of adverse effects. This study mainly aims to uncover the impact of AR on DOX disposition in vivo. Rats received a single intravenous dose of 5 mg/kg DOX following a single-dose co-treatment or multiple-dose pre-treatment of AR (10 g/kg × 1 or × 10). The concentrations of DOX in rat plasma and six tissues, including heart, liver, lung, kidney, spleen, and skeletal muscle, were determined by a fully validated LC-MS/MS method. A network-based approach was further employed to quantify the relationships between enzymes that metabolize and transport DOX and the targets of nine representative AR components in the human protein–protein interactome. We found that short-term (≤10 d) AR administration was ineffective in changing the plasma pharmacokinetics of DOX in terms of the area under the concentration–time curve (AUC, 1303.35 ± 271.74 μg/L*h versus 1208.74 ± 145.35 μg/L*h, p > 0.46), peak concentrations (Cmax, 1351.21 ± 364.86 μg/L versus 1411.01 ± 368.38 μg/L, p > 0.78), and half-life (t1/2, 31.79 ± 5.12 h versus 32.05 ± 6.95 h, p > 0.94), etc. Compared to the isotype control group, DOX concentrations in six tissues slightly decreased under AR pre-administration but only showed statistical significance (p < 0.05) in the liver. Using network analysis, we showed that five of the nine representative AR components were not localized to the vicinity of the DOX disposition-associated module. These findings suggest that AR may mitigate DOX-induced toxicity by affecting drug targets rather than drug disposition

Metabolomics and Network Analyses Reveal Phenylalanine and Tyrosine as Signatures of Anthracycline-Induced Hepatotoxicity

The chemotherapy drug doxorubicin (DOX) is an anthracycline with over 30% incidence of liver injury in breast cancer patients, yet the mechanism of its hepatotoxicity remains unclear. To identify potential biomarkers for anthracycline-induced hepatotoxicity (AIH), we generated clinically-relevant mouse and rat models administered low-dose, long-term DOX. These models exhibited significant liver damage but no decline in cardiac function. Through untargeted metabolic profiling of the liver, we identified 27 differential metabolites in a mouse model and 28 in a rat model. We then constructed a metabolite-metabolite network for each animal model and computationally identified several potential metabolic markers, with particular emphasis on aromatic amino acids, including phenylalanine, tyrosine, and tryptophan. We further performed targeted metabolomics analysis on DOX-treated 4T1 breast cancer mice for external validation. We found significant (p < 0.001) reductions in hepatic levels of phenylalanine and tyrosine (but not tryptophan) following DOX treatment, which were strongly correlated with serum aminotransferases (ALT and AST) levels. In summary, the results of our study present compelling evidence supporting the use of phenylalanine and tyrosine as metabolic signatures of AIH

Understanding the mechanism of acupuncture in acute cerebral infraction through a proteomic analysis: protocol for a prospective randomized controlled trial

BackgroundAcute cerebral infarction (ACI), being the predominant form of stroke, presents challenges in terms of the limited effectiveness of various treatments in improving the neurological function. Although acupuncture shows promise in addressing ACI, the availability of high-quality evidence regarding its efficacy, safety, and underlying mechanism remains insufficient. In this study, we design a multicenter, prospective, single-blind, randomized controlled trial with the aim of evaluating the efficacy and safety of acupuncture for ACI, making an attempt to unveil the molecular mechanisms by proteomic.MethodsA total of 132 patients involving four hospitals will be randomized at a 1:1:1 ratio in the acupuncture group, control group, and sham acupuncture group. All the patients will receive basic treatment, and the patients in the acupuncture and sham acupuncture groups will also receive either acupuncture or sham acupuncture treatment, respectively, at six sessions each week for a 2 weeks period, followed by 3 months of follow-up. The primary outcome will be the change in the National Institute of Health Stroke Scale (NIHSS) scores after treatment. The secondary outcomes will include the Fugl-Meyer Assessment (FMA) scale scores and the Barthel Index (BI). Adverse events that occur during the trial will be documented. To discover differentially expressed proteins (DEPs) and their roles between the ACI subjects and healthy controls, we will also perform 4D-DIA quantitative proteomics analysis, and the DEPs will be confirmed by enzyme-linked immunosorbent assay (ELISA). This study was approved by the institutional review board of the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine (TYLL2023043). Written informed consent from patients is required. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR2300079204). Trial results will be published in a peer-reviewed academic journal.DiscussionThe results of this study will determine the preliminary efficacy and safety of acupuncture in ACI patients and whether the mechanism of this form of non-pharmacologic stimulation is mediated by a novel therapeutic target for neurorehabilitation through our proteomic analysis.Clinical trial registrationhttps://www.chictr.org.cn, identifier ChiCTR2300079204

Association Between Myopia and Pupil Diameter in Preschoolers: Evidence from a Machine Learning Approach Based on a Real-World Large-Scale Dataset

Abstract Introduction Previous studies have explored the connections between various ocular biological parameters with myopia. Our previous study also found that pupil data can predict the myopic progression during the interventions for myopia. However, studies exploring the association between pupil diameter and myopia in preschoolers with myopia were lacking. Hence this study was aimed to investigate the association between pupil diameter and myopia in preschoolers with myopia based on a real-world, large-scale dataset. Methods Data containing 650,671 preschoolers were collected from a total of 1943 kindergartens in Shenzhen, China. Refraction and pupil parameters were collected. After data filtering, the occurrence of myopia and its association with age, gender, pupil diameter, and other variables, were analyzed. Random forest (RF) and eXtreme gradient boosting (XGBoost) were selected from seven machine learning algorithms to build the model. The mean decrease accuracy (MDA), mean decrease Gini (MDG), and gain feature importance (GFI) techniques were employed to quantify the importance of pupil diameter and other features. Results After the assessments, 51,325 valid records with complete pupil data were included, and 3468 (6.76%) were identified as myopia based on the calculated cycloplegic refraction. Preschoolers with myopia presented reduced pupil diameter and greater variation (5.00 ± 0.99 mm) compared to non-myopic preschoolers (6.22 ± 0.67 mm). A nonlinear relationship was found according to the scatterplots between pupil diameter and refraction (R 2 = 0.14). Especially preschoolers with myopia had reduced pupil diameter compared to emmetropic preschoolers, but hyperope did not experience additional pupil enlargement. After adjusting for other covariates, this relationship is still consistent (P < 0.001). XGBoost and RF algorithms presented the highest performance and validated the importance of pupil diameter in myopia. Conclusions Based on a real-world large-scale dataset, the current study illuminated that preschoolers with myopia had a reduced pupil diameter compared to emmetropic preschoolers with a nonlinear pattern. Machine learning algorithms visualized and validated the pivotal role of pupil diameter in myopia. Trial Registration chictr.org Identifier: ChiCTR2200057391

Multifunctional nanoparticles for enhanced sonodynamic–chemodynamic immunotherapy with glutathione depletion - supplementary figures

Aim: This study aimed to develop a sonodynamic–chemodynamic nanoparticle functioning on glutathione depletion in tumor immunotherapy. Materials & methods: The liposome-encapsulated 2,2-azobis[2-(2- imidazolin-2-yl) propane] dihydrochloride (AIPH) and copper–cysteine nanoparticles, AIPH/Cu-Cys@Lipo, were synthesized with a one-pot method. 4T1 cells were injected into female BALB/c mice for modeling. Results: AIPH/Cu-Cys@Lipo was well synthesized. It generated alkyl radicals upon ultrasound stimulation. AIPH/Cu-Cys@Lipo promoted the generation of -OH via a Fenton-like reaction. Both in vitro and in vivo experiments verified that AIPH/Cu-Cys@Lipo significantly inhibited tumor development by decreasing mitochondrial membrane potential, activating CD4+ and CD8+ T cells and promoting the expression of IL- 2 and TNF-α. Conclusion: AIPH/Cu-Cys@Lipo provides high-quality strategies for safe and effective tumor immunotherapy.</p