Microstructural alterations of the hypothalamus in Parkinson's disease and probable REM sleep behavior disorder

Whether there is hypothalamic degeneration in Parkinson's disease (PD) and its association with clinical symptoms and pathophysiological changes remains controversial. We aimed to quantify microstructural changes in hypothalamus using a novel deep learning-based tool in patients with PD and those with probable rapid-eye-movement sleep behavior disorder (pRBD). We further assessed whether these microstructural changes associated with clinical symptoms and free thyroxine (FT4) levels. This study included 186 PD, 67 pRBD, and 179 healthy controls. Multi-shell diffusion MRI were scanned and mean kurtosis (MK) in hypothalamic subunits were calculated. Participants were assessed using Unified Parkinson's Disease Rating Scale (UPDRS), RBD Questionnaire-Hong Kong (RBDQ-HK), Hamilton Depression Rating Scale (HAMD), and Activity of Daily Living (ADL) Scale. Additionally, a subgroup of PD (n = 31) underwent assessment of FT4. PD showed significant decreases of MK in anterior-superior (a-sHyp), anterior-inferior (a-iHyp), superior tubular (supTub), and inferior tubular hypothalamus when compared with healthy controls. Similarly, pRBD exhibited decreases of MK in a-iHyp and supTub. In PD group, MK in above four subunits were significantly correlated with UPDRS-I, HAMD, and ADL. Moreover, MK in a-iHyp and a-sHyp were significantly correlated with FT4 level. In pRBD group, correlations were observed between MK in a-iHyp and UPDRS-I. Our study reveals that microstructural changes in the hypothalamus are already significant at the early neurodegenerative stage. These changes are associated with emotional alterations, daily activity levels, and thyroid hormone levels. [Abstract copyright: Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

The role of organic anion transport protein 1a4 in drug delivery and diseases: a review

Abstract OATP1A4 is an important member of the family of organic anion transporting polypeptides (OATPs), which is generally thought to mediate cellular uptake of endogenous and exogenous substances, such as bile acids, drugs and environmental toxins. Recent studies have found that Oatp1a4 plays an important role in drug passage through the blood-brain barrier and is expected to be an important target for drugs used to treat central diseases. Oatp1a4 has also been associated with various diseases such as cholestasis. differences in Oatp1a4 across age and sex have also become an area of concern for precision drug administration. Therefore, this paper presents a systematic review of Oatp1a4 expression in drug transport and various physiopathological states

Alphavirus Replicon DNA Vectors Expressing Ebola GP and VP40 Antigens Induce Humoral and Cellular Immune Responses in Mice

Ebola virus (EBOV) causes severe hemorrhagic fevers in humans, and no approved therapeutics or vaccine is currently available. Glycoprotein (GP) is the major protective antigen of EBOV, and can generate virus-like particles (VLPs) by co-expression with matrix protein (VP40). In this study, we constructed a recombinant Alphavirus Semliki Forest virus (SFV) replicon vector DREP to express EBOV GP and matrix viral protein (VP40). EBOV VLPs were successfully generated and achieved budding from 293 cells after co-transfection with DREP-based GP and VP40 vectors (DREP-GP+DREP-VP40). Vaccination of BALB/c mice with DREP-GP, DREP-VP40, or DREP-GP+DREP-VP40 vectors, followed by immediate electroporation resulted in a mixed IgG subclass production, which recognized EBOV GP and/or VP40 proteins. This vaccination regimen also led to the generation of both Th1 and Th2 cellular immune responses in mice. Notably, vaccination with DREP-GP and DREP-VP40, which produces both GP and VP40 antigens, induced a significantly higher level of anti-GP IgG2a antibody and increased IFN-γ secreting CD8+ T-cell responses relative to vaccination with DREP-GP or DREP-VP40 vector alone. Our study indicates that co-expression of GP and VP40 antigens based on the SFV replicon vector generates EBOV VLPs in vitro, and vaccination with recombinant DREP vectors containing GP and VP40 antigens induces Ebola antigen-specific humoral and cellular immune responses in mice. This novel approach provides a simple and efficient vaccine platform for Ebola disease prevention

Establishment of fingerprints and determination of various ingredients of yanlishuang pills by GC-MS

Abstract Yanlishuang Pills is a kind of traditional Chinese medicine used to treat pharyngitis widely. In this study, we used gas chromatography tandem mass spectrometry (GC-MS) to establish a method for the fingerprint and quantitative analysis of the four major components of Yanlishuang Pills, which can provide a more reliable method for its quality control. We used the software “Chromatographic Fingerprint Similarity Evaluation System for Traditional Chinese Medicine”, version A, 2004, to obtain fingerprint using the averaging method with a time width of 0.1. The peak with the largest peak area was used as the reference peak to determine the shared peaks and generate the common pattern. Then the main components of the Yanlishuang Pills were identified and their contents were determined in GC-MS SIM mode using internal standard method.The fingerprint established by GC-MS were reproducible, and a total of 18 common peaks were identified in the fingerprint of 13 batches of samples, and the similarity of the fingerprint of each batch of samples was above 0.99. The concentrations of camphor, menthone, borneol and menthol of the four main ingredients of the Yanlishuang Pills were linearly well within the range of 25.13-150.78 μg/mL (r = 0.9995), 28.77-172.62 μg/mL (r = 0.9991), 299.70-1798.20 μg/mL (r = 0.9997), 121.98-731.88 μg/mL (r = 0.9997), and the average recoveries were 102.02% (RSD of 1.3%), 96.10% (RSD of 1.0%), 102.71% (RSD of 1.3%), 102.58% (RSD of 1.1%), respectively, with good precision, reproducibility, and stability within 16 h. The camphor content of the 13 batches of samples was 5.6025-8.3662 mg/g, menthone content was 4.7871-5.8936 mg/g, borneol content was 88.0034-133.0969 mg/g and menthol was 40.2017-61.9466 mg/g. The fingerprints of the Yanlishuang Pills established by GC-MS were characterized by a common pattern, and the simultaneous determination of camphor, menthone, borneol and menthol in the Yanlishuang Pills was rapid, simple and accurate. In conclusion, the determination of the content of multiple ingredients combined with fingerprinting can provide a more comprehensive control of the quality of Yanlishuang Pills

The construction of personalized virtual landslide disaster environments based on knowledge graphs and deep neural networks

Virtual Landslide Disaster environments are important for multilevel simulation, analysis and decision-making about Landslide Disasters. However, in the existing related studies, complex disaster scene objects and relationships are not deeply analyzed, and the scene contents are fixed, which is not conducive to meeting multilevel visualization task requirements for diverse users. To resolve the above issues, a construction method for Personalized Virtual Landslide Disaster Environments Based on Knowledge Graphs and Deep Neural networks is proposed in this paper. The characteristics of relationships among users, scenes and data were first discussed in detail; then, a knowledge graph of virtual Landslide Disaster environments was established to clarify the complex relationships among disaster scene objects, and a Deep Neural network was introduced to mine the user history information and the relationships among object entities in the knowledge graph. Therefore, a personalized Landslide Disaster scene data recommendation mechanism was proposed. Finally, a prototype system was developed, and an experimental analysis was conducted. The experimental results show that the method can be used to recommend intelligently appropriate disaster information and scene data to diverse users. The recommendation accuracy stabilizes above 80% – a level able to effectively support The Construction of Personalized Virtual Landslide Disaster environments

Synthesis, structure and dehydrogenation of zirconium borohydride octaammoniate

A new metal borohydride ammoniate (MBA), Zr(BH4)4·8NH3, was synthesized via ammoniation of the Zr(BH4)4 crystal. Zr(BH4)4·8NH3 has a distinctive structure and the highest coordination number of NH3 groups among all the known MBAs. This compound could quickly dehydrogenate at 130 °C, enabling it a potential hydrogen storage material