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Neuropathic pain (NP) is a common type of chronic pain caused by a lesion or disease of the somatosensory nervous system. This condition imposes a considerable economic burden on society and patients. Daphnetin (DAP) is a natural product isolated from a Chinese medicinal herb with various pharmacological activities, such as anti-inflammatory and analgesic properties. However, the underlying mechanisms of these effects are not fully understood. In the present study, we aimed to investigate DAP's anti-inflammatory and analgesic effects and explore the underlying mechanisms of action. The NP model was established as chronic constrictive injury (CCI) of the sciatic nerve, and pain sensitivity was evaluated by measuring the mechanical withdrawal threshold (MWT) and thermal withdrawal threshold (TWT). The activation of microglia in the spinal dorsal horn was measured via immunofluorescence staining. Protein levels were measured using a western blot assay. Using a mass-spectrometry proteomics platform and an LC-MS/MS-based metabolomics platform, proteins and metabolites in spinal cord tissues were extracted and analyzed. DAP treatment ameliorated the MWT and TWT in CCI rats. The expression of IL-1β, IL-6, and TNF-α was inhibited by DAP treatment in the spinal cords of CCI rats. Moreover, the activation of microglia was suppressed after DAP treatment. The elevation in the levels of P2X4, IRF8, IRF5, BDNF, and p-P38/P38 in the spinal cord caused by CCI was inhibited by DAP. Proteomics and metabolomics results indicated that DAP ameliorated the imbalance of glycerophospholipid metabolism in the spinal cords of CCI rats. DAP can potentially ameliorate NP by regulating microglial responses and glycerophospholipid metabolism in the CCI model. This study provides a pharmacological justification for using DAP in the management of NP. [ABSTRACT FROM AUTHOR]

The erosion of igneous rocks affects the structural and spontaneous combustion characteristics of coal. A series of tests were conducted, including programmed heating, thermogravimetric analysis, FT-IR spectroscopy, low-temperature nitrogen adsorption, and pressed mercury experiments on samples from primary coal and coal eroded by igneous rocks from the Tashan Mine and Xiaonan Mine within the same coal seam. Based on these experiments, we analyzed various properties of coal, such as the oxidation characteristics, spontaneous combustion limit, active functional group content, chemical structure, and pore structure, from both macroscopic and microscopic perspectives. The results indicated significant trends after the erosion of igneous rocks: (1) there were increases in the oxygen consumption rate, as well as the CO and CO2 release rates; (2) the upper limit of air leakage intensity increased, the minimum thickness of floating coal decreased, and the lower limit of oxygen volume fraction decreased; (3) there was a decrease in the activation energy required for coal ignition; (4) there was a decrease in the active functional group content while improving the structural stability; and (5) there were the alterations in the pore structure of coal. These promoted the oxidation reactions between oxygen and the active groups within the coal matrix, increasing the propensity for spontaneous combustion, particularly in the igneous rocks with low oxidation activity. [ABSTRACT FROM AUTHOR]

Microbiome has emerged as a promising indicator or predictor of human diseases. However, previous studies have typically labeled each specimen as either healthy or with a specific disease, ignoring prevalence of complications or comorbidities in actual cohorts, which may confound the microbial–disease associations. For instance, a patient may suffer from multiple diseases, making it challenging to detect their health status accurately. Furthermore, host phenotypes like physiological characteristics and lifestyles can alter microbiome structure, but such information has not yet been fully utilized in data models. To address these issues, a highly explainable deep learning (DL) method called Meta‐Spec is proposed. Using a deep neural network (DNN)‐based approach, it encodes and embeds refined host variables with microbiome features, enabling the detection of multiple diseases simultaneously. Experiments show that Meta‐Spec outperforms regular machine learning (ML) strategies for multilabel disease screening in several cohorts. More importantly, Meta‐Spec successfully detects comorbidities that are often missed by other approaches. In addition, for its high interpretability, Meta‐Spec captures key factors that shape disease patterns from host variables and microbes. Hence, these efforts improve the feasibility and sensitivity of microbiome‐based disease screening in practical scenarios, representing a significant step toward personalized medicine and better health outcomes. [ABSTRACT FROM AUTHOR]

Daphnetin is a natural product with anti-inflammatory, antioxidant, and neuroprotective properties. Reports have found that it has a strong analgesic effect; however, its analgesic mechanism is unknown. We explored the effect and mechanism of daphnetin on neuropathic pain (NP). The rat model of NP was established by ligation of the sciatic nerve. Male Sprague-Dawley rats were divided into six groups: Control, Model, Sham, morphine (0.375 mg/kg), and daphnetin (0.0625 and 0.025 mg/kg). Rats were intrathecally injected with drugs or normal saline once daily for three days. Hyperalgesia was evaluated by mechanical withdrawal threshold (MWT) and thermal withdrawal threshold (TWT). Protein levels were detected using ELISA, immunofluorescence, and western blotting. Compared to the Model group, daphnetin improved TWT (46.70 °C vs. 42.20 °C) and MWT (45.60 g vs. 23.60 g), reduced the expression of interleukin-1β (0.99 ng/g vs. 1.42 ng/g), interleukin-6 (0.90 ng/g vs. 1.52 ng/g), and tumor necrosis factor-α (0.93 ng/g vs. 1.52 ng/g) in the sciatic nerve. Daphnetin decreased the expression of toll-like receptor 4 (TLR4) (0.47-fold), phosphorylated inhibitor of NF-κB (p-IKBα) (0.29-fold), nuclear factor kappaB (NF-κB) (0.48-fold), glial fibrillary acidic protein (GFAP) (0.42-fold), CXC chemokine ligand type 1 (CXCL1) (0.84-fold), CXC chemokine receptor type 2 (CXCR2) (0.78-fold) in the spinal cord. Daphnetin alleviates NP by inhibiting inflammation and astrocyte activation in the spinal cord, providing theoretical support for the extensive clinical treatment of NP. [ABSTRACT FROM AUTHOR]