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Novel hydrogen sulfide donor-based fibrate derivatives were synthesized and assessed for hypolipidemic and hepatoprotective effects in Triton WR-1339-induced hyperlipidemic mice. After preliminary screening of the target compounds, T5 exhibited significant hypolipidemic effects, reducing triglycerides (TG) and total cholesterol (TC). The action of T5 in reducing TG and TC levels is dose-dependent. Through molecular docking and protein expression analysis, it was found that T5 may exert hypolipidemic effects by activating the PPAR-α receptor. Examination of liver tissue from hyperlipidemic mice supplemented with T5 demonstrated a marked decrease in hepatic lipid buildup. Furthermore, there was a significant amelioration in the levels of hepatic transaminases (AST and ALT) that were elevated as a result of hyperlipidemia. As designed, T5 exhibited H2S-releasing effects in a hyperlipidemia model. Additionally, T5 has the capability to ameliorate the lipid peroxidation process triggered by hyperlipidemia, leading to a reduction in malondialdehyde (MDA) levels. These findings further support the potential of T5 as a hypolipidemic agent with hepatoprotective properties.

Abstract Background This study aims to compare the clinical outcomes and safety of a novel hand-held retractor system-assisted Wiltse TLIF with that P-TLIF and assess whether this hand-held retractor system assisted Wiltse TLIF can yield less paraspinal muscle injury. Methods 56 patients (P-TLIF: 26, Wiltse TLIF: 30) were included in this one year prospective controlled study. The operation time, intraoperative blood loss, postoperative drainage, mobilization time, and discharge time were recorded. The clinical outcomes were evaluated by ODI, VAS, JOA, and SF-36 scores (7 days, 3, 6, and 12 months after surgery). Paraspinal muscle injury was assessed by postoperative MRI (6 months after surgery). CK and C-reaction protein were measured pre and postoperatively, and CT or X-ray (one year postoperatively) was used to assess bony union/non-union. Results The Wiltse (study) group was associated with significantly less estimated blood loss (79.67 ± 28.59 ml vs 192.31 ± 59.48 ml, P = 0.000*), postoperative drainage (43.33 ± 27.89 ml vs 285.57 ± 123.05 ml, P = 0.000*), and shorter mobilization (4.1 ± 1.2 d vs. 3.0 ± 0.9 d, P

Abstract Background The essential roles of platelets in thrombosis have been well recognized. Unexpectedly, thrombosis is prevalent during thrombocytopenia induced by cytotoxicity of biological, physical and chemical origins, which could be suffered by military personnel and civilians during chemical, biological, radioactive, and nuclear events. Especially, thrombosis is considered a major cause of mortality from radiation injury-induced thrombocytopenia, while the underlying pathogenic mechanism remains elusive. Methods A mouse model of radiation injury-induced thrombocytopenia was built by exposing mice to a sublethal dose of ionizing radiation (IR). The phenotypic and functional changes of platelets and megakaryocytes (MKs) were determined by a comprehensive set of in vitro and in vivo assays, including flow cytometry, flow chamber, histopathology, Western blotting, and chromatin immunoprecipitation, in combination with transcriptomic analysis. The molecular mechanism was investigated both in vitro and in vivo, and was consolidated using MK-specific knockout mice. The translational potential was evaluated using a human MK cell line and several pharmacological inhibitors. Results In contrast to primitive MKs, mature MKs (mMKs) are intrinsically programmed to be apoptosis-resistant through reprogramming the Bcl-xL-BAX/BAK axis. Interestingly, mMKs undergo minority mitochondrial outer membrane permeabilization (MOMP) post IR, resulting in the activation of the cyclic GMP-AMP synthase-stimulator of IFN genes (cGAS-STING) pathway via the release of mitochondrial DNA. The subsequent interferon-β (IFN-β) response in mMKs upregulates a GTPase guanylate-binding protein 2 (GBP2) to produce large and hyperreactive platelets that favor thrombosis. Further, we unmask that autophagy restrains minority MOMP in mMKs post IR. Conclusions Our study identifies that megakaryocytic mitochondria-cGAS/STING-IFN-β-GBP2 axis serves as a fundamental checkpoint that instructs the size and function of platelets upon radiation injury and can be harnessed to treat platelet pathologies.

Thin-film transistors play an important role in ultra-high definition displays. The conventional physical model requires a significant amount of time and resources, while its generalizability is limited. This paper introduces a method for quickly incorporating the characteristics of emerging devices into circuit simulations using an artificial neural network (ANN) model. The multi-layer perceptron (MLP) model, with a simple structure and high modeling efficiency, is employed as a typical ANN model. The pivotal step in using the MLP model is to determine its topology. This hyperparameter problem can be easily solved using Bayesian search. To improve the accuracy of the model, a genetic algorithm is proposed to optimize the initial values of the weights and biases. Furthermore, by introducing the first derivative in the loss function, small signal parameters can be taken into consideration. This modeling approach significantly reduces the time required for compact device modeling. Our experimental results exhibit a strong correlation between the model’s output and the corresponding experimental data, thereby providing comprehensive validation for the effectiveness of our proposed model. Once the trained model parameters were extracted, we implemented the hybrid ANN model using Verilog-A. This circuit-level experiment demonstrates that this hybrid ANN model can accurately estimate various physical devices and circuits.

The ergot alkaloids are a class of natural products known for their pharmacologically privileged molecular structure that are used in the treatment of neurological ailments. Here the authors report on the production of the ergot (fungus)-derived therapeutic precursor, D-lysergic acid (DLA), in baker’s yeast.

Online learning platforms have become important learning tools, and online learning replaced face-to-face teaching as the primary learning method of students during COVID-19. However, there have been few systematic studies on learning effectiveness and its influential factors. This study was based on fuzzy-set qualitative comparative analysis (fsQCA) to explore the joint effects of multiple factors on online learning effectiveness for tourism and hospitality students from the dual perspective of the platform and individual. The results revealed five antecedent combinations that led to high-quality online learning, which were categorized into "platform-individual" internal and external promotion paths and "function-interaction" platform environment promotion paths. Moreover, there were substitution effects in the paths to high-quality online learning; specifically, perceived usefulness (PU) and perceived ease of use (PEU) were substitutable, and perceived playfulness (PP), learning attitude (LA), and self-efficacy (SE) could replace each other. Finally, self-efficacy was not a necessary condition for efficient online learning. Our findings highlight substitution relationships among the influencing factors of online learning effectiveness from a configuration perspective and further reveal the internal micromechanisms of achieving high-quality online learning.