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关键词： Cerebellum   GLP-1R   Exendin-4   Glutamate   Granule cell   Purkinje cell   Mossy fiber  

摘要： The gut hormone glucagon-like peptide 1 (GLP-1) is a key contributor to the controls of food intake and reward processing. GLP-1 receptors (GLP-1R) are widely expressed throughout the central nervous system where their signaling alters neuronal excitability, resulting in suppressed food intake and reward. Recent studies have shown GLP-1R expression in Purkinje cells (PCs) within the cerebellum, a region gathering increasing appreciation for its role in sensory processing and appetitive behaviors. Importantly, the cerebellum responds to feeding signals and directly projects to key mesolimbic nuclei that initiate appetitive behaviors, including food intake. What remains unknown is if GLP-1Rs are expressed in other cell types of the cerebellum and the extent to which their activation produces neurophysiological changes. Here we combined RT-qPCR, RNAscope and immunohistochemistry with functional electrophysiology to map GLP-1R expression and signaling across the lobes and cell types of the cerebellar cortex of male/female C57BL/6N mice. We found that GLP-1Rs were nearly evenly expressed across all cerebellar lobes at the level of the vermis, as well as densely expressed in the deep cerebellar nuclei. At the cellular level, we found significant GLP-1R expression in granule cells (GCs) and GC-innervating mossy fibers, in addition to the previously reported expression in the PCs. Functionally, application of the GLP-1R agonist exendin-4 increased the frequency of spontaneous glutamate release on to the majority of recorded GCs and enhanced action potential firing in PCs. Together these results demonstrate broad expression of functional GLP-1R across cerebellar lobes which enhance synaptic transmission through the cerebellar cortex.

关键词： Classical and steered molecular dynamics simulations   Protein tunnel analysis   Oxygen diffusion pathways   Homogentisate 1,2-dioxygenase   Alkaptonuria   Multiple sequence alignment   Molecular modeling  

摘要：

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  Identified a new oxygen transport tunnel in human homogentisate dioxygenase.
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  Oxygen reaches the catalytic iron through a tunnel formed by multiple subunits.
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  A single mutation blocks oxygen transport without destabilizing the enzyme.
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  Impaired oxygen transport is a novel disease mechanism in metabolic disorders.
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  Evolutionary analysis confirms the oxygen pathway is essential for function.

关键词： Tembusu virus   Goose astrovirus   Diagnosis   Multiplex real-time qPCR  

摘要： The concurrent infection and epidemic of goose astrovirus type 1 (GoAstV-1), goose astrovirus type 2 (GoAstV-2), and Tembusu virus (TMUV) in geese have resulted in substantial economic losses to the goose industry. Therefore, establishing a rapid and accurate diagnostic method for these three viruses is imperative. In the present study, we designed specific primers targeting the Cap gene of GoAstV and the E gene of TMUV and developed a SYBR Green I-based multiplex real-time qPCR method for the simultaneous detection of GoAstV-1, GoAstV-2, and TMUV. The results revealed that the R² values for the standard curve of the multiplex real-time qPCR of GoAstV-1, GoAstV-2 and TMUV reached 0.998, 0.998, and 0.994, respectively. In addition, the limits of detection for GoAstV-1, GoAstV-2 and TMUV were 1.08×10² copies/μL, 2.63×10² copies/μL and 3.07×10² copies/μL, respectively. Moreover, specificity test results indicated that the multiplex real-time qPCR system is highly specific for these three target pathogens, and no cross-reactions with other goose-origin viruses, such as Newcastle disease virus (NDV), goose reovirus (GRV), avian influenza virus (AIV), or goose parvovirus (GPV), were observed. Moreover, the established multiplex real-time qPCR method had excellent repeatability, with intra- and interassay coefficients of variation ranging from 0.23 to 0.91 and 0.71 to 1.75, respectively. The present study provides a rapid and efficient tool that is both specific and sensitive for detecting GoAstV-1, GoAstV-2, and TMUV and is helpful for determining the epidemiology of these viruses in geese.

关键词： Endovascular thrombectomy   GLP-1 receptor agonist   Mechanical thrombectomy   Semaglutide   Stroke  

摘要： Glucagon-like peptide-1 receptor agonists (GLP-1As) have demonstrated cardiovascular and cerebrovascular benefits in high-risk populations, but their impact in patients with acute ischemic stroke (AIS) requiring endovascular thrombectomy (EVT) remains uncertain.

摘要： Recognition of viral nucleic acids by multiple pattern-recognition receptors converges on TANK-binding kinase 1 (TBK1) to initiate type I interferon responses and antiviral immunity. While this canonical role is well established, recent studies using genetic ablation and pharmacological inhibition have reframed TBK1 as a context-dependent regulator of both innate and adaptive immunity across distinct cell lineages. Here, we review emerging cell-type-specific functions of TBK1 that extend beyond classical interferon signaling, repositioning it as a central coordinator of immune cell survival, differentiation, and effector function. We further discuss how pathways that signal through TBK1 may, thus, contribute to vaccine adjuvanticity, emphasizing this kinase as a potential target for vaccine-induced immunity. Finally, we outline how TBK1-dependent pathways may be harnessed for the design of next-generation vaccines.

关键词： Perioperative preemptive analgesia   Mild cognitive impairment   Postoperative neurocognitive disorder  

摘要： Postoperative cognitive dysfunction (POCD) is a frequent complication in elderly patients that delays recovery and increases long-term health risks. Preemptive analgesia may alleviate surgery-induced inflammation and central sensitization, but its role in improving postoperative neurocognitive disorder (PND) through modulation of hippocampal Gamma-aminobutyric acid type A (GABAA) receptor α1/α5 subunits in aged rats with mild cognitive impairment (MCI) remains unclear.

关键词： Gas expanded liquid extraction   Green shell mussel   Lipids   Phospholipids   Supercritical CO2  

摘要： Gas eXpanded Liquids (GXLs) in the single-phase region were used to extract lipids from Greenshell™ mussel meat powder, Perna canaliculus, using mixtures of CO₂ and ethanol as the GXL. This study investigated the effect of pressure (90 – 180 bar), temperature (40 – 65 °C), and ethanol concentration (13.5 – 67 mol%) on extract yield, phospholipid content and composition, and lipid extraction kinetics at laboratory scale. GXL extraction required a lower solvent to feed ration and had a high phospholipid yield compared to supercritical carbon dioxide (scCO₂) which only extracts neutral lipids. High total lipid yields were obtained using GXL, 60 – 100% of total lipids compared to ∼ 42% for scCO₂. Co-solvent concentration and extraction temperature have the largest effect on extraction performance. GXL Greenshell™ mussel extracts have good levels of omega-3 and omega-6 fatty acids and high phospholipid content with minimal degradation relative to the feed powder. GXL extraction was evaluated in pilot scale trials and compared favourably with subcritical dimethyl ether extraction.

关键词： Feedforward neural networks   Food authenticity   Kohonen neural networks   LDA   Metabolomics   Nuclear magnetic resonance   PCA   Random forest   Stable isotopes   SVM   Wavelet variable selection  

摘要： Authenticating organic UHT cow milk remains a priority for regulators and industry, given persistent fraud risks and consumer mistrust. We evaluate a dual-platform chemometric strategy combining stable-isotope ratio mass spectrometry (IRMS; δ¹³C, δ¹⁵N, δ¹⁸O, D/H) and ¹H NMR metabolic profiling with linear and non-linear classifiers. A France-based calibration set (n = 171) and independent test set (n = 172) were used for model development and validation, and an external European UHT set (n = 78) assessed transferability. Expressed as Non-Error Rate (NER), IRMS and NMR models individually reached 97.1/94.8% and 98.8/95.3% (calibration/test), while a combined TOFoo decision rule (decision-level fusion) improved test NER to 96.5% (balanced accuracy 96.6%). On the European set, the combined approach achieved an overall NER of 83.3%, with country-level variability reflecting market heterogeneity.

关键词： Pb-free perovskites   SSR method   XRD   Dielectric properties   Impedance spectroscopy   NTCR  

摘要：

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  Single-phase perovskite structure is confirmed for all compositions. Peak broadening/splitting at x = 0.10–0.20 indicates coexistence of rhombohedral and tetragonal phases, suggesting a morphotropic phase boundary (MPB).
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  Frequency-dependent dielectric peaks (∼300–400 °C), confirming a transition from normal ferroelectric to relaxor ferroelectric behavior with increasing BaTiO₃ content.
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  Both ε′ and ε″ decrease with increasing frequency, showing typical dielectric dispersion. The x = 0.40 composition exhibits enhanced low-frequency response and broad dispersion, indicating strong relaxor behavior and space charge effects.
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  Conductivity increases significantly (4–5 orders) with temperature, indicating a thermally activated hopping conduction mechanism with frequency-dependent activation energies.
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  In Cole–Cole plot, transition from dual to single semicircular arcs with increasing BaTiO₃ content suggests evolution toward single relaxation mechanism due to microstructural modifications.