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Background: The thyroid is the prime organ of infection during the onset of autoimmune disease. The disease is known as Autoimmune thyroiditis (AIT). In recent times, AIT has been alarming worldwide, with growing attention towards pharmaceutical companies for finding new drugs for therapy. The present investigation aims to use a multi-targeting approach to identify the best compound from the root of Astragalus membranaceus for synergistic therapy of AIT. Materials and Methods: To explore the mechanism of action of the compounds, the present study uses network pharmacology-based methods. Totally, 48 genes involved in AIT were collected from the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG). Gene ontology (GO) annotation, disease ontology, and pathway enrichment analysis were conducted. The chemical structure of the compounds from A. membranaceus was retrieved from the PubChem database. To study the toxic and pharmacological efficiency of the chemical structure, absorption, distribution, metabolism, excretion, and toxicity (ADMET) screening was performed. Results: The ononin and astroside were identified as suitable with all the pharmacokinetic properties can be employed to identify the disease targets. The intersection between the compound target (C-T-N) and the AIT-related genes was identified. Totally 16 genes among the C-T networks of ononin and astroside have shown interaction with thyroid disease-related pathways and signaling pathways. Consequently, the overlapping genes between the C-T network and AIT-related genes were determined as IL2. However, from the pathway enrichment, AIT-related genes have been involved in several viral infection pathways. The genes involved in infection pathways are also targeted by ononin and astroside. Conclusion: The underlying mechanism of action of the compounds on AIT-related pathways was also determined. Therefore, a network pharmacology-based strategy will provide new insight into AIT therapy. However, further studies are required to validate the investigation that can prove bioactive as a promising candidate for the treatment of AIT. [ABSTRACT FROM AUTHOR]

Background: Lenvatinib, a tyrosine kinase inhibitor (TKI) approved for the treatment of progressive and radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), is associated with significant adverse effects that can be partially mitigated through the development of novel drug formulations. The utilization of nanoparticles presents a viable option, as it allows for targeted drug delivery, reducing certain side effects and enhancing the overall quality of life for patients. This study aimed to produce and assess, both in vitro and in vivo, the cytotoxicity, biodistribution, and therapeutic efficacy of lenvatinib-loaded PLGA nanoparticles (NPs), both with and without decoration using antibody conjugation (cetuximab), as a novel therapeutic approach for managing aggressive thyroid tumors. Methods: Poly(lactic-co-glycolic acid) nanoparticles (NPs), decorated with or without anti-EGFR, were employed as a lenvatinib delivery system. These NPs were characterized for size distribution, surface morphology, surface charge, and drug encapsulation efficiency. Cytotoxicity was evaluated through MTT assays using two cellular models, one representing normal thyroid cells (Nthy-ori 3-1) and the other representing anaplastic thyroid cells (CAL-62). Additionally, an in vivo xenograft mouse model was established to investigate biodistribution and therapeutic efficacy following intragastric administration. Results: The NPs demonstrated success in terms of particle size, polydispersity index (PDI), zeta potential, morphology, encapsulation efficiency, and cetuximab distribution across the surface. In vitro analysis revealed cytotoxicity in both cellular models with both formulations, but only the decorated NPs achieved an ID50 value in CAL-62 cells. Biodistribution analysis following intragastric administration in xenografted thyroid mice demonstrated good stability in terms of intestinal barrier function and tumor accumulation. Both formulations were generally well tolerated without inducing pathological effects in the examined organs. Importantly, both formulations increased tumor necrosis; however, decorated NPs exhibited enhanced parameters related to apoptotic/karyolytic forms, mitotic index, and vascularization compared with NPs without decoration. Conclusions: These proof-of-concept findings suggest a promising strategy for administering TKIs in a more targeted and effective manner. [ABSTRACT FROM AUTHOR]

We previously described the role of low-density lipoprotein (LDL) in aggressiveness in papillary thyroid cancer (PTC). Moreover, the MAPK signaling pathway in the presence of BRAF V600E mutation is associated with more aggressive PTC. Although the link between MAPK cascade and LDL receptor (LDLR) expression has been previously described, it is unknown whether LDL can potentiate the adverse effects of PTC through it. We aimed to investigate whether the presence of LDL might accelerate the oncogenic processes through MAPK pathway in presence or absence of BRAF V600E in two thyroid cell lines: TPC1 and BCPAP (wild-type and BRAF V600E, respectively). LDLR, PI3K-AKT and RAS/RAF/MAPK (MEK)/ERK were analyzed via Western blot; cell proliferation was measured via MTT assay, cell migration was studied through wound-healing assay and LDL uptake was analyzed by fluorometric and confocal analysis. TPC1 demonstrated a time-specific downregulation of the LDLR, while BCPAP resulted in a receptor deregulation after LDL exposition. LDL uptake was increased in BCPAP over-time, as well as cell proliferation (20% higher) in comparison to TPC1. Both cell lines differed in migration pattern with a wound closure of 83.5 ± 9.7% after LDL coculture in TPC1, while a loss in the adhesion capacity was detected in BCPAP. The siRNA knockdown of LDLR in LDL-treated BCPAP cells resulted in a p-ERK expression downregulation and cell proliferation modulation, demonstrating a link between LDLR and MAPK pathway. The modulation of BRAF-V600E using vemurafenib-impaired LDLR expression decreased cellular proliferation. Our results suggest that LDLR regulation is cell line-specific, regulating the RAS/RAF/MAPK (MEK)/ERK pathway in the LDL-signaling cascade and where BRAF V600E can play a critical role. In conclusion, targeting LDLR and this downstream signaling cascade, could be a new therapeutic strategy for PTC with more aggressive behavior, especially in those harboring BRAF V600E. [ABSTRACT FROM AUTHOR]

The treatment of 14C isotope emission from nuclear power plant is the worldwide challenges, and The traditional resin adsorption method is facing the dilemma of solid waste disposal. In the paper, the chemical exchange method was used to separate the 14CO2 for the first time. The results showed the high separation efficiency of 30.5 times concentration ratio of 14CO2 was achieved under the mild operation conditions. So the chemical exchange method was one kind of effective method to treat 14C emission and had an attractive application prospect. Moreover, the process was easy to operate safely and scale up. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Materials and Methods Results Conclusions Intramedullary nailing is preferred for treating elderly proximal humeral fractures, but secondary reductions are common, particularly in elderly and osteoporotic patients. This occurs due to the intramedullary nail fixation's insufficient anti‐varus and anti‐rotational capacities and high stress at the bone–implant interface. We aim to enhance the anti‐varus and anti‐rotational stability of the fixation structure while reducing the stresses on the bone and internal fixation through structural design.We developed a novel endosteal anatomical support nail (EASN) that integrates an endosteal torus construct into the proximal portion of the angle‐stable proximal humerus nail. The endosteal torus construct includes endosteal anatomical support (EAS) with a flat plane that allows direct fixation of the humeral head fragments and is shaped to conform to the medial side of the medullary cavity of the proximal humerus. We conducted finite element analysis to assess the biomechanical stability of four constructs: EAS with a calcar screw (CS), EAS without CS, non‐EAS with CS, and non‐EAS without CS. This analysis determined the contribution of the EAS to the mechanical stability of the proximal humerus in two‐part PHF with medial column disruption. Specimens were subjected to loads simulating partial‐weight‐bearing (as in rising from a chair or using crutches) and full‐weight‐bearing (as in rising from bed). We evaluated the stiffness of the construct, displacement at the fracture site, von Mises stress, and stress distribution.Under compressive or rotational loads, the EAS construct, with or without CS, was significantly stiffer than the non‐EAS construct. Displacement at the fracture site was significantly less with the EAS fixation than with the non‐EAS fixation. However, the stiffness and displacement at the fracture site of the EAS fixation without CS were comparable to those of the non‐EAS construct with CS. The EAS construct reduced the load on the nail and decreased the risk of implant failure. Both von Mises stress and stress distribution were significantly lower following fixation with the EAS constructs.This study introduces a novel EAS concept to enhance the anti‐varus and anti‐rotational capabilities of the humeral head and distribute stress at the bone–implant interface in treating elderly PHFs. This strategy shows promise based on our limited analysis. [ABSTRACT FROM AUTHOR]

Carrying out coastal wetland landscape simulations and current and future ecological risk assessments is conducive to formulating policies for coastal wetland landscape planning and promoting the coordinated development of the social economy and ecological environment. This study used the Cellular Automaton (CA)-Markov model to simulate the landscape data of the study area under different scenarios in 2021 and 2025, and built an ecological risk assessment (ERS) index model to analyze the differences of spatio-temporal characteristics of ecological risks. The results showed that: (1) The test accuracy of the CA–Markov model was 0.9562 after passing through the consistency test. The spatial distribution data of landscapes under current utilization scenarios (CUSs), natural development scenarios (NDSs), and ecological protection scenarios (EPSs) were gained through simulations. (2) During 1991–2025, the landscape types of Yancheng coastal wetlands undertake complicated transfers and have vast transfer regions. Under CUSs and NDSs, a large number of natural wetlands are transferred to artificial wetlands. Under EPSs, the area of artificial wetlands declines and artificial wetlands are mainly transferred to natural wetlands. (3) The ecological risk of Yancheng Coastal Wetland increases, accompanied with significant spatial heterogeneity, which is manifested as low in the north area and high in the south area, and there exist some differences between sea areas and land areas. Ecological risk levels transfer violently. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Methods Results Conclusions There are many advantages to stabilize the posterior pelvic ring injuries with a transiliac‐transsacral (TITS) screw percutaneously. To identify the correct entry point and insert a guidewire accurately for a TITS screw, we propose a method of specifying the optimal entry point, and introduce a technique of enabling freehand placement of a guidewire with fluoroscopic guidance.In this retrospective study, 116 patients who underwent pelvic CT scans and pelvic lateral radiographs at our institution from January 2020 to April 2022 were enrolled. The optimal entry point for a TITS screw was formulated in the strict mid‐sagittal CT plane, and then transferred to the pelvic lateral radiograph relying on the sacral cortexes which were easily visible even in the poor fluoroscopy. The relative position of this point to other anatomical markers was checked to confirm its feasibility as an entry point. With the method to locate the entry point, 18 patients suffered the posterior pelvic ring injuries were treated with TITS screws through hammering a reverse Kirschner wire (K‐wire) to insert a guidewire assisted by a canula, followed by the validation of the screw placement accuracy.The transferred point in radiograph was consistently beneath the sacral alar slope, and located posteroinferior to the iliac cortical density (ICD) and anterosuperior to the sacral nerve root tunnel in all 116 patients. In clinical practice, 18 TITS screws were successfully placed in 18 patients without cortex violation. The average operative time for each screw was 20.11 ± 6.29 min, with an average of 14.11 ± 6.81 fluoroscopic shots per screw. At the 3‐month follow‐up, fracture healing was confirmed in all patients. The average Majeed score was 89.61 ± 6.90 at the final follow‐up.It's feasible to identify an entry point for a TITS screw based on the sacral cortexes, and hammering a reverse K‐wire assisted by a percutaneous kyphoplasty (PKP) canula is a safe and practical technique for guidewire insertion. [ABSTRACT FROM AUTHOR]