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Considering that the precise delivery of Celastrol (Cst) into mitochondria to induce mitochondrial dysfunction may be a potential approach to improve the therapeutic outcomes of Cst on TNBC, a novel tumor mitochondria dual-targeted mixed-micelle nano-system was fabricated via self-synthesized triphenylphosphonium-modified cholesterol (TPP-Chol) and hyaluronic acid (HA)-modified cholesterol (HA-Chol). The Cst-loaded mixed micelles (Cst@HA/TPP-M) exhibited the characteristics of a small particle size, negative surface potential, high drug loading of up to 22.8%, and sustained drug release behavior. Compared to Cst-loaded micelles assembled only by TPP-Chol (Cst@TPP-M), Cst@HA/TPP-M decreased the hemolysis rate and upgraded the in vivo stability and safety. In addition, a series of cell experiments using the triple-negative breast cancer cell line MDA-MB-231 as a cell model proved that Cst@HA/TPP-M effectively increased the cellular uptake of the drug through CD44-receptors-mediated endocytosis, and the uptake amount was three times that of the free Cst group. The confocal results demonstrated successful endo-lysosomal escape and effective mitochondrial transport triggered by the charge converse of Cst@HA/TPP-M after HA degradation in endo-lysosomes. Compared to the free Cst group, Cst@HA/TPP-M significantly elevated the ROS levels, reduced the mitochondrial membrane potential, and promoted tumor cell apoptosis, showing a better induction effect on mitochondrial dysfunction. In vivo imaging and antitumor experiments based on MDA-MB-231-tumor-bearing nude mice showed that Cst@HA/TPP-M facilitated drug enrichment at the tumor site, attenuated drug systemic distribution, and polished up the antitumor efficacy of Cst compared with free Cst. In general, as a target drug delivery system, mixed micelles co-constructed by TPP-Chol and HA-Chol might provide a promising strategy to ameliorate the therapeutic outcomes of Cst on TNBC. [ABSTRACT FROM AUTHOR]

In order to precisely deliver celastrol into mitochondria of tumor cells, improve antitumor efficacy of celastrol and overcome its troublesome problems in clinical application, a novel multistage-targeted celastrol delivery system (C-TL/HA) was developed via electrostatic binding of hyaluronic acid (HA) to celastrol-loaded cationic liposomes composed of natural soybean phosphatidylcholine and cholesterol modified with mitochondrial targeting molecular TPP. Study results in this article showed that C-TL/HA successfully transported celastrol into mitochondria, effectively activated apoptosis of mitochondrial pathway, exerted higher tumor inhibition efficiency and lower toxic side effects compared with free celastrol. More importantly, HA coating not only enabled this delivery system to have good stability and safety in vivo, but also increased drug uptake and facilitated tumor targeting through recognizing CD44 receptors rich on the surface of tumor cells. Conclusively, this HA-coated mitochondrial targeting liposomes may provide a prospect for the clinical application of celastrol in tumor therapy. [ABSTRACT FROM AUTHOR]

The migration and deposition processes of fine particles under the influence of temperature gradients and fluid flow are widely prevalent. Investigating the mechanisms of particle interactions in these processes contributes to the development of efficient dust removal techniques. In this work, experimental and numerical studies of particle motion in temperature gradient fields are conducted. The research encompasses both qualitative and quantitative analyses of particle motion influenced by thermophoresis and particle diameter. Qualitative analysis reveals that the motion characteristics of particles are jointly determined by gravity, drag force, and thermophoretic force, and the diameter range that exhibiting a notable influence of the thermophoretic force is 20–30 μm. Quantitative analysis shows that the manifestations of deposition and diffusion become more evident with an increasing temperature gradient. For instance, in comparison to the working condition with Δ T = 0 K and d p = 20 μm, the deposition mass increases by approximately 23% when Δ T = -15 K; conversely, it diminishes by about 11% when Δ T = 15 K. Additionally, the Discrete Phase Model (DPM) is employed to simulate the motion of gas-solid flow. This study presents a novel visualization system to observe particle motion in gas-solid systems to elucidate the mechanisms underlying the thermophoretic effect and establish a robust theoretical foundation for thermophoretic dust removal technology. [ABSTRACT FROM AUTHOR]

Background: Previous studies suggest that blood lead levels are positively associated with attention deficit/hyperactivity disorder (ADHD) and ADHD-symptoms in children. However, the associations between lead exposure and ADHD subtypes are inconsistent and understudied. Objective: The objective of this study was to explore the association of low-level concurrent lead exposure with subtypes of ADHD symptoms in 578 Mexican children 6–13 years of age. Methods: We measured concurrent blood lead levels using inductively coupled plasma mass spectrometry (ICPMS). We administered the Conners’ Rating Scales-Revised (CRS-R) to mothers to evaluate their children’s ADHD symptoms. We used imputation to fill missing values in blood lead levels and used segmented regression models adjusted for relevant covariates to model the nonlinear relationship between blood lead and ADHD symptoms. Results: Mean ± SD blood lead levels were 3.4 ± 2.9 μg/dL. In adjusted models, a 1-μg/dL increase in blood lead was positively associated with Hyperactivity and Restless-Impulsivity scores on the CRS-R scale and Hyperactivity-Impulsivity scores on the CRS-R scale of the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, but only in children with blood lead level ≤ 5 μg/dL. Blood lead was not associated with Inattentive symptoms or overall ADHD behavior. Conclusions: In this population of Mexican children, current blood lead level among children with low exposure (≤ 5 μg/dL) was positively associated with hyperactive/impulsive behaviors, but not with inattentiveness. These results add to the existing evidence of lead-associated neurodevelopmental deficits at low levels of exposure. Citation: Huang S, Hu H, Sánchez BN, Peterson KE, Ettinger AS, Lamadrid-Figueroa H, Schnaas L, Mercado-García A, Wright RO, Basu N, Cantonwine DE, Hernández-Avila M, Téllez-Rojo MM. 2016. Childhood blood lead levels and symptoms of attention deficit hyperactivity disorder (ADHD): a cross-sectional study of Mexican children. Environ Health Perspect 124:868–874; http://dx.doi.org/10.1289/ehp.1510067

Semi-quantum key distribution (SQKD) allows a quantum user and a classical user to share a string of secret keys, providing support for application scenarios that cannot withstand the high cost of quantum resources. In this paper, we propose what we believe to be the first proof-of-principle experimental demonstration of free space SQKD based on the single-state protocol, which is equipped with polarization encoding scheme employing the method of selective modulation. During the half-hour test time for each operation, the overall experiment obtained the original key rate of 107.2 kbps at the repetition frequency of 100 MHz, and the average bit error rate was determined to be 1.65 % for CTRL operation and 0.64 % for SIFT operation. The experimental results indicate that our system exhibits commendable performance and stability at a low bit error rate that represents a significant initial stride toward the future practical deployment of SQKD systems within free-space channels.

Introduction: Gastrointestinal schwannomas are most commonly found in the stomach. Owing to their nonspecific clinical and endoscopic presentations, distinguishing gastric schwannomas (GS) from other gastric submucosal tumors based on typical symptoms and endoscopic features is challenging. Endoscopic full-thickness resection (EFTR) is safe and effective for GS management; however, no standard method exists for the extraction of large gastric specimens after endoscopic treatment., Case Presentation: We report the case of a 72-year-old Chinese woman who presented with abdominal distension., Diagnosis, Interventions, and Outcomes: Gastroscopy revealed a submucosal bulge on the anterior wall of the lower stomach near the greater curvature. Endoscopic ultrasonography and computed tomography suggested a stromal tumor. The patient underwent EFTR of the stomach, and the tumor was successfully removed. The surgical specimen, with a long-axis diameter of approximately 5.5 cm in vitro, was extracted using a snare. Subsequent endoscopic examination revealed longitudinal, full-thickness perforations > 2 cm at the esophageal entrance. Over 10 metal clips were used to seal the mucosa, and a gastrointestinal decompression tube was placed. Follow-up radiography performed at 1 week postoperatively revealed an esophageal mediastinal fistula, which required subsequent endoscopic intervention to close the fistula using metal clips. The patient showed improvement and was discharged at 3 weeks postoperatively. Follow-up esophageal radiography revealed no abnormalities. Postoperative immunohistochemical analysis indicated CD34 (-), CD117 (-), DOG-1 (-), Ki67 (1%), S-100 (+), SDHB (+), SOX-10 (+), and Desmin (-), confirming the diagnosis of GS. Three months postoperatively, gastroscopy showed that the esophageal perforation healed well, a white ulcer scar had formed locally, metal clips were found in the stomach body, and no recurrence was found., Conclusion: EFTR is effective for removing giant schwannomas, although the extraction of large specimens may result in iatrogenic cervical esophageal perforations. Perforations > 2 cm can be managed using endoscopic metal clip closure., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)