Cholesterol-loaded nanoparticles ameliorate synaptic and cognitive function in Huntington's disease mice

Brain cholesterol biosynthesis and cholesterol levels are reduced in mouse models of Huntington's disease (HD), suggesting that locally synthesized, newly formed cholesterol is less available to neurons. This may be detrimental for neuronal function, especially given that locally synthesized cholesterol is implicated in synapse integrity and remodeling. Here, we used biodegradable and biocompatible polymeric nanoparticles (NPs) modified with glycopeptides (g7) and loaded with cholesterol (g7-NPs-Chol), which per se is not blood-brain barrier (BBB) permeable, to obtain high-rate cholesterol delivery into the brain after intraperitoneal injection in HD mice. We report that g7-NPs, in contrast to unmodified NPs, efficiently crossed the BBB and localized in glial and neuronal cells in different brain regions. We also found that repeated systemic delivery of g7-NPs-Chol rescued synaptic and cognitive dysfunction and partially improved global activity in HD mice. These results demonstrate that cholesterol supplementation to the HD brain reverses functional alterations associated with HD and highlight the potential of this new drug-administration route to the diseased brain

Activated Leukocyte Cell Adhesion Molecule Expression and Shedding in Thyroid Tumors

Activated leukocyte cell adhesion molecule (ALCAM, CD166) is expressed in various tissues, cancers, and cancer-initiating cells. Alterations in expression of ALCAM have been reported in several human tumors, and cell adhesion functions have been proposed to explain its association with cancer. Here we documented high levels of ALCAM expression in human thyroid tumors and cell lines. Through proteomic characterization of ALCAM expression in the human papillary thyroid carcinoma cell line TPC-1, we identified the presence of a full-length membrane-associated isoform in cell lysate and of soluble ALCAM isoforms in conditioned medium. This finding is consistent with proteolytically shed ALCAM ectodomains. Nonspecific agents, such as phorbol myristate acetate (PMA) or ionomycin, provoked increased ectodomain shedding. Epidermal growth factor receptor stimulation also enhanced ALCAM secretion through an ADAM17/TACE-dependent pathway. ADAM17/TACE was expressed in the TPC-1 cell line, and ADAM17/TACE silencing by specific small interfering RNAs reduced ALCAM shedding. In addition, the CGS27023A inhibitor of ADAM17/TACE function reduced ALCAM release in a dose-dependent manner and inhibited cell migration in a wound-healing assay. We also provide evidence for the existence of novel O-glycosylated forms and of a novel 60-kDa soluble form of ALCAM, which is particularly abundant following cell stimulation by PMA. ALCAM expression in papillary and medullary thyroid cancer specimens and in the surrounding non-tumoral component was studied by western blot and immunohistochemistry, with results demonstrating that tumor cells overexpress ALCAM. These findings strongly suggest the possibility that ALCAM may have an important role in thyroid tumor biology

Research and Design of a Routing Protocol in Large-Scale Wireless Sensor Networks

无线传感器网络，作为全球未来十大技术之一，集成了传感器技术、嵌入式计算技术、分布式信息处理和自组织网技术，可实时感知、采集、处理、传输网络分布区域内的各种信息数据，在军事国防、生物医疗、环境监测、抢险救灾、防恐反恐、危险区域远程控制等领域具有十分广阔的应用前景。 本文研究分析了无线传感器网络的已有路由协议，并针对大规模的无线传感器网络设计了一种树状路由协议，它根据节点地址信息来形成路由，从而简化了复杂繁冗的路由表查找和维护，节省了不必要的开销，提高了路由效率，实现了快速有效的数据传输。 为支持此路由协议本文提出了一种自适应动态地址分配算——ADAR（AdaptiveDynamicAddre...As one of the ten high technologies in the future, wireless sensor network, which is the integration of micro-sensors, embedded computing, modern network and Ad Hoc technologies, can apperceive, collect, process and transmit various information data within the region. It can be used in military defense, biomedical, environmental monitoring, disaster relief, counter-terrorism, remote control of haz...学位：工学硕士院系专业：信息科学与技术学院通信工程系_通信与信息系统学号：2332007115216

AI-driven predictive models for determining age and sex from cranial measurements

The ability to accurately determine the age and sex of individuals from cranial measurements has significant implications in forensic anthropology and bioarchaeology. Leveraging artificial intelligence (AI) advancements, we have developed predictive models that utilize cranial measurements to estimate these demographic variables. Additionally, these models have been adapted to predict cephalometric measurements from nonradiological data, enhancing their utility in clinical settings. This study utilized a dataset comprising cranial measurements from diverse populations. Advanced AI algorithms, including Support Vector Machines (SVM), Artificial Neural Networks (ANN), and Deep Neural Networks (DNN), were employed to develop predictive models. The dataset was split into training and validation sets, and cross-validation techniques were applied to ensure model robustness and prevent overfitting. Feature selection and hyperparameter tuning were conducted to optimize model performance. The predictive models demonstrated high accuracy in estimating sex, with the SVM and ANN models achieving accuracies between 86% and 91%. The DNN model further improved accuracy, reaching over 93%. For age prediction, models treated age as a continuous and categorical variable, with the constant model achieving a mean absolute error (MAE) of less than 2 years and the categorical model achieving an accuracy of approximately 85%. The cephalometric prediction models showed promising results, with significant reductions in mean squared error (MSE) compared to actual clinical measurements. Integrating AI algorithms in the analysis of cranial measurements significantly enhances the accuracy of age and sex estimation. Furthermore, extending these models to predict cephalometric measurements from non-radiological data offers a promising tool for clinical applications, potentially reducing the need for radiographic imaging. Future research will expand the dataset and refine the models for broader applicability and improved accuracy. References 1. Del Bove, A.; Veneziano, A. A Generalised Neural Network Model to Estimate Sex from Cranial Metric Traits: A Robust Training and Testing Approach. Appl. Sci. 2022, 12, 9285. 2. Foreman, A.; Lazenby, R.A. Use of Craniometric Data in a Generalized Procrustes Analysis to Establish Human Biological Affinities. Forensic Sci. Int. 1996, 82, 39-53. 3. GADNN: A Revolutionary Hybrid Deep Learning Neural Network for Age and Sex Determination Utilizing Cone Beam Computed Tomography Images of Maxillary and Frontal Sinuses. BMC Med. Res. Methodol. 2023

Failed Orthodontic PEEK Retainer: A Scanning Electron Microscopy Analysis and a Possible Failure Mechanism in a Case Report

This study presents a scanning electron microscopy analysis of a failed PEEK retainer in an orthodontic patient. After 15 months of use, the patient reported a gap opening between teeth 41 and 42. The PEEK retainer was removed and sent for electron microscope analysis. To investigate the failure, scanning electron microscopy was employed to assess the microstructure and composition of the retainer at various magnifications. These findings suggest that the failure of the PEEK retainer was multifaceted, implicating factors such as material defects, manufacturing flaws, inadequate design, environmental factors, and patient-related factors. In conclusion, this scanning electron microscopy analysis offers valuable insights into the failure mechanisms of PEEK retainers in orthodontic applications. Further research is necessary to explore preventive strategies and optimize the design and fabrication of PEEK retainers, minimizing the occurrence of failures in orthodontic practice

Spatial organisation of Listeria monocytogenes and Escherichia coli O157:H7 in jellified medium mimicking food matrices.

International audienc

Spatial organisation of Listeria monocytogenes and Escherichia coli O157:H7 in jellified medium mimicking food matrices.

International audienc

Spatial organization and phenotypic heterogeneity of Escherichia coli O157:H7 and Listeria monocytogenes in model gel matrices

International audienc

Spatially localised expression of the glutamate decarboxylase gadB in Escherichia coli O157:H7 microcolonies in hydrogel matrices

International audienceAbstract Functional diversity within isogenic spatially organised bacterial populations has been shown to trigger emergent community properties such as stress tolerance. Considering gadB gene encoding a key glutamate decarboxylase involved in E. coli tolerance to acidic conditions, we investigated its expression in hydrogels mimicking the texture of some structured food matrices (such as minced meat or soft cheese). Taking advantage of confocal laser scanning microscopy combined with a genetically-engineered dual fluorescent reporter system, it was possible to visualise the spatial patterns of bacterial gene expression from in-gel microcolonies. In E. coli O157:H7 microcolonies, gadB showed radically different expression patterns between neutral (pH 7) or acidic (pH 5) hydrogels. Differential spatial expression was determined in acidic hydrogels with a strong expression of gadB at the microcolony periphery. Strikingly, very similar spatial patterns of gadB expression were further observed for E. coli O157:H7 grown in the presence of L. lactis . Considering the ingestion of contaminated foodstuff, survival of E. coli O157:H7 to acidic stomachal stress (pH 2) was significantly increased for bacterial cells grown in microcolonies in acidic hydrogels compared to planktonic cells. These findings have significant implications for risk assessment and public health as they highlight inherent differences in bacterial physiology and virulence between liquid and structured food products. The contrasting characteristics observed underscore the need to consider the distinct challenges posed by these food types, thereby emphasising the importance of tailored risk mitigation strategies

Effect of the presence and location of corpus luteum on competence of bovine cumulus-oocyte complexes

This study aimed to determine the effect of presence of the corpus luteum (CL) and its influence on cumulus–oocyte complexes (COCs) obtained from the ipsilateral or contralateral ovary in bovine on the recovery and capacity of the oocytes to sustain mono-spermic fertilization, undergo preimplantation development, and develop to the blastocyst stage. Ovaries were collected at a local slaughterhouse and kept in pairs corresponding to the same animal. In the first experiment the variables evaluated were compared between cows with (CCL+) and without (CCL-) CL, and for the second experiment, comparisons were made between ovaries with an ipsilateral (CL+), contralateral (CL−), and no (NCL). The recovery rate of COCs was higher in ovaries from CCL− cows, and a higher proportion of grade 1 COCs were recovered from this group. A higher proportion of metaphase I oocytes at 7 h of maturation, and a higher rate of cleavage were observed in the CCL+ group; however, a higher proportion of embryos were obtained from the CCL− group. Besides, COCs from the CL+ group had a lower proportion of grades 1 and 2 morphological qualities, lower rate of metaphase II oocytes at 22 h of maturation, and lower rate of formation of two pronuclei, whereas a higher proportion of unfertilized oocytes after in vitro fertilization. On the other hand, the COCs from the CL− group displayed a lower proportion of oocytes with more than two pronuclei, higher cleavage rate, and higher final blastocyst production were obtained when compared to CL+. Thus, the effects of CL on the competence of bovine COCs are different depending on the anatomical proximity of their location in the animal, negatively affecting the quality of COCs located in the same ovary, but not having negative effects on the competence of COCs in the ovaries contralateral to their location. © The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Incluye referencias bibliográficas