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To investigate the key molecular mechanisms of palmatine for the treatment of neuroinflammation through modulation of a pathway using molecular docking, molecular dynamics (MD) simulation combined with network pharmacology, and animal experiments. Five alkaloid components were obtained from the traditional Chinese medicine Huangteng through literature mining. Molecular docking and MD simulation with acetylcholinesterase were used to screen palmatine. At the animal level, mice were injected with LPS intracerebrally to cause a neuroinflammatory model, and the Morris water maze experiment was performed to examine the learning memory of mice. Anxiety levels were tested using the autonomous activity behavior experiment with the open field and elevated behavior experiments. HE staining and Niss staining were performed on brain tissue sections to observe morphological lesions and apoptosis; serum was examined for inflammatory factors TNF‐α, IL‐6, and IL‐1β; Western blot was performed to detect the protein expression. The expression of PI3K/AKT/NFkB signaling pathway‐related proteins was examined by Western blot. The results of network pharmacology showed that the screening of palmatine activation containing the PI3K/Akt/NFkB signaling pathway exerts antineuroinflammatory effects. Results from behavioral experiments showed that Pal enhanced learning memory in model mice, improved anxiety behavior, and significantly improved brain damage caused by neuroinflammation. The results of HE staining and Niss staining of brain tissue sections showed that palmatine could alleviate morphological lesions and nucleus damage in brain tissue. Palmatine improved the levels of serum inflammatory factors TNF‐α, IL‐6, and IL‐1β. SOD, MDA, CAT, ACH, and ACHE in the hippocampus were improved. Western blot results showed that palmatine administration ameliorated LPS‐induced neuroinflammation through the PI3K/Akt/NFkB pathway. [ABSTRACT FROM AUTHOR]

The role of polysaccharide components in the immune system, especially immunomodulatory effects, has received increasing attention. In this context, in this study, network pharmacology was adopted to explore the hypothesis of a multitarget mechanism for immune modulation by Chrysalis polysaccharides. A total of 174 common targets were screened by network pharmacology, with the main ones being TNF, MAPK3, CASP3, VEGFA, and STAT3, mostly enriched in the Toll pathway. The molecular docking results showed that the polysaccharide fraction of Chrysalis binds well to TNF proteins. Besides, in vitro cellular assays were performed to verify the ability of Chrysalis polysaccharides to regulate macrophage polarization and to screen for macrophage surface receptors. Furthermore, in vivo experiments were conducted to prove the activation of TLR4 and TNF‐α protein expression in mice by Chrysalis polysaccharide. [ABSTRACT FROM AUTHOR]

Organophosphorus pesticides (OPs) have long been used extensively on agricultural land and can lead to significant improvements in crop yields. Due to occupational exposure, humans are exposed to pesticides through dermal contact, inhalation, and ingestion. The effects of OPs on the organism are currently studied for their effects on livers, kidneys, hearts, blood indicators, neurotoxicity, and teratogenic, carcinogenic, and mutagenic effects, while studies in the direction of brain tissue damage have not been reported in detail. Previous reports have confirmed that ginsenoside Rg1 is a prominent and representative tetracyclic triterpenoid derivative rich in ginseng and has good neuroprotective activity. Considering that, the aim of this study was to establish a mouse model of brain tissue injury by using the OP‐type pesticide chlorpyrifos (CPF) and to explore the therapeutic effects and possible molecular mechanisms of Rg1. Mice in the experimental group were pre‐protected with Rg1 by gavage for 1 week, and brain tissue damage was induced using CPF (5 mg/kg for 1 week) to assess the effect of Rg1 (80 and 160 mg/kg for 3 weeks) in alleviating brain damage. Morris water maze and histopathological analysis were performed to assess cognitive function and pathological changes in the mouse brain, respectively. Protein expression levels of Bax, Bcl‐2, Caspase‐3, Cl‐Cas‐3, Caspase‐9, Cl‐Cas‐9, phosphoinositide 3‐kinase (PI3K), phosphorylated‐PI3K, protein kinase B (AKT), and phosphorylated‐AKT were quantified by protein blotting analysis. Rg1 obviously restored CPF‐induced oxidative stress damage in mouse brain tissue, increased the levels of antioxidant parameters (total superoxide dismutase, total antioxidative capacity, and glutathione) in the brain, and significantly reduced the overexpression of apoptosis‐related proteins induced by CPF. At the same time, Rg1 also markedly attenuated the histopathological changes in the brain induced by CPF exposure. Mechanistically, Rg1 could effectively activate the phosphorylation of PI3K/AKT. Furthermore, molecular docking studies revealed a stronger binding capacity between Rg1 and PI3K. Rg1 attenuated neurobehavioural alterations and reduced lipid peroxidation in the mouse brain to a great extent. Apart from that, Rg1 administration improved brain histopathology in CPF‐induced rats. All results suggest that ginsenoside Rg1 has potential antioxidant effects on CPF‐induced oxidative brain injury, and it is evident that Rg1 could be used as a promising therapeutic strategy for the study of brain injury from OP poisoning. [ABSTRACT FROM AUTHOR]

Depression is one of the most common neuropsychiatric disorders that is characterized by low mood, lack of motivation, slow thinking, and recurrent suicidal thoughts. The mechanism of action of palmatine in depression has been rarely reported and remains unclear. The present study examined the neuroprotective effects of palmatine on lipopolysaccharide (LPS)‐induced oxidative stress, apoptosis, and depression‐like behavior. In this study, cell apoptosis was evaluated by CCK‐8, flow cytometry, and Hoechst 33258 staining in LPS‐induced HT‐22 cells. Meanwhile, reactive oxygen species (ROS) and mitochondrial membrane potential were detected in vitro. In vivo, we investigated depressive‐like behaviors in mice by an open field test (OFT) and elevated plus‐maze test (EPM). Additionally, the levels of superoxide dismutases (SOD), TNF‐α, IL‐1β, and IL‐6 were detected by enzyme‐linked immunosorbent assay. The hematoxylin‐eosin staining and TUNEL staining were used to evaluate the pathology of the hippocampus. The expression of Nrf2/HO‐1 and BAX/Bcl‐2 pathways in the hippocampus were assessed by Western blot analysis. Palmatine could significantly reduce apoptosis and ROS levels, and improve mitochondrial damage. Moreover, palmatine significantly improves movement time and central square crossing time in OFT, and improves open arms and movement time in EMP. And the levels of SOD, TNF‐α, IL‐1β, and IL‐6 were significantly decreased after palmatine treatment. More importantly, palmatine improved neuronal apoptosis in the hippocampus, and depression through BAX/Bcl‐2 and Nrf2/HO‐1 signaling pathways. We provide evidence that palmatine further alleviates the depressive‐like behavior of LPS‐induced by improving apoptosis and oxidative stress. [ABSTRACT FROM AUTHOR]

Objective: The key molecular mechanism of palmatine in the treatment of Alzheimer's disease (AD) was investigated in this article. Methods: Network pharmacology techniques constructed drug‐target‐disease relationship networks and predictive pathways of action. At the cellular level, lipopolysaccharide (LPS) was used to induce Raw 264.7 cells to establish an inflammation model, and interleukin (IL)‐1β, IL‐6, and tumor necrosis factor (TNF)‐α indicators were examined. Apoptosis was detected using Hoechst 33258. At the animal level, LPS was used to induce AD animal model, and behavioral performance were examined by water maze, and serum biochemical indexes were measured by ELISA. And the expression of PI3K and P‐AKT was observed by immunohistochemistry. Finally, molecular level validation was performed using the molecular docking technique. Results: The result of Network pharmacological was predicted that palmatine may treat AD mainly through the PI3K pathway. Palmatine has no significant effect on Raw264.7 cells viability within 0.05 mg/ml, Palmatine can significantly induce Raw264.7 cells to secret IL‐6 and IL1‐β in a concentration‐dependent manner, but it has not obvious impact on NO and TNF‐α. Palmatine has a significant restorative effect on the cell viability of Raw264.7 in a concentration of 0.1 mg/ml. Palmatine can be concentration‐dependent to downregulate the secretion of LPS‐induced IL‐6. At the same time, Palmatine also has a significant effect on the level of TNF‐α induced by LPS, it also can slightly downregulate the secretion of IL‐1β. The results of Hoechst33258 showed that cells in the 0.025 mg/ml and 0.5 mg/ml delivery groups increased with different degrees of bright blue fluorescence, and apoptosis rate decreased. Animal experiments showed that palmatine effectively improved the learning and memory ability of AD mice. The immunohistochemical results exhibited that the expression of PI3K and P‐AKT in the model group decreased, but they were obvious reversed by palmatine The molecular docking results showed that palmatine and key targets had good docking, among which the binding to ERBB2, CDC42, MDM2, and mTOR was the most likely. Conclusion: Palmatine has neuroprotective effects. Palmatine could effectively ameliorate memory impairment in AD mice by promoting the PI3K‐AKT pathway. Molecular docking results showed that palmatine has a better binding ability with mTOR. [ABSTRACT FROM AUTHOR]

In arid zones, ecological barriers can affect the agricultural development and sustainable development of oases. Therefore, balancing cropland and desert vegetation is the key to realizing ecological and rural revitalization. Then, we proposed a theoretical framework from the perspective of rural revitalization to analyze the key drivers that affect the balance of cropland and desert vegetation during 1990–2020. The results showed that cropland area in Xinjiang decreased by 881 km2 during 1990–1995, while it continually increased by 34,086 km2 during 1995–2020. However, grassland and woodland increased by 8,086 km2 during 2015–2020, indicating that the balance between cropland gain and desert vegetation loss began to improve. Most cropland expansions were reclaimed from woodland/grassland and unused land. During 1990–2005, changes between cropland and unused land in Xinjiang were mainly affected by gross domestic product (GDP). GDP and population most significantly affected the conversion (17,939 km2) of woodland/grassland to cropland during 1995–2015. Although population and economic growth led to an increase in cropland, the implementation of simultaneous and consistent policies on ecological conservation offset the reduction in desert vegetation. The findings can provide suggestions for smart cropland management and rural revitalization in Xinjiang, Central Asian countries and other countries with similar backgrounds worldwide. [ABSTRACT FROM AUTHOR]

Background: Unilateral posterior crossbite, one of the most frequent malocclusions, is often associated with functional lateral shift of the mandible. Although the effects of functional lateral shift on the mandible and temporomandibular joint have been examined in various animal experiments, cranial and maxillary changes have received less attention. Objective: The aim of this study was to investigate the effects of functional lateral shift on the craniofacial complex in growing rats. Methods: Eighty 5‐week‐old male Sprague–Dawley rats were randomly divided into an experimental group (n = 40), which received an oblique guide appliance that shifted the mandible to the left during closure, and a control group (n = 40). The rats were scanned by cone‐beam computed tomography at 3 days and 1, 2, 4 and 8 weeks. The dimensions of the mandibular bone, condyle, maxilla and cranium were measured. Results: The mandibles of rats in the experimental group were smaller than those of the rats in the control group and were asymmetrical. The condyles of the rats in the experimental group were thinner than those of the control rats. The condylar length on the ipsilateral side was shorter and wider than that on the contralateral side from 4 to 8 weeks. No significant differences in cranial length or height were observed between the experimental and control groups. The height of the upper first molar and alveolar bone on the contralateral side was significantly smaller than that on the ipsilateral side and in the controls from 4 to 8 weeks. Conclusion: Functional shift in the mandible produces morphological asymmetries in the mandible and maxillary region and may cause bilateral condylar degenerative changes. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the accuracy of deep convolutional neural networks (DCNNs) for detecting neck of femur (NoF) fractures on radiographs, in comparison with perceptual training in medically-naïve individuals.Methods: This study extends a previous study that conducted perceptual training in medically-naïve individuals for the detection of NoF fractures on a variety of dataset sizes. The same anteroposterior hip radiograph dataset was used to train two DCNNs (AlexNet and GoogLeNet) to detect NoF fractures. For direct comparison with perceptual training results, deep learning was completed across a variety of dataset sizes (200, 320 and 640 images) with images split into training (80%) and validation (20%). An additional 160 images were used as the final test set. Multiple pre-processing and augmentation techniques were utilised.Results: AlexNet and GoogLeNet DCNNs NoF fracture detection accuracy increased with larger training dataset sizes and mildly with augmentation. Accuracy increased from 81.9% and 88.1% to 89.4% and 94.4% for AlexNet and GoogLeNet respectively. Similarly, the test accuracy for the perceptual training in top-performing medically-naïve individuals increased from 87.6% to 90.5% when trained on 640 images compared with 200 images.Conclusions: Single detection tasks in radiology are commonly used in DCNN research with their results often used to make broader claims about machine learning being able to perform as well as subspecialty radiologists. This study suggests that as impressive as recognising fractures is for a DCNN, similar learning can be achieved by top-performing medically-naïve humans with less than 1 hour of perceptual training. [ABSTRACT FROM AUTHOR]

Gout is a disease of purine metabolic disorders which results from long-term hyperuricemia and the sodium urate deposition in and around the joints. Selaginella tamariscina ( ST) is an important traditional Chinese herbal medicine and is used for the treatment of gout and hyperuricemia. In this study, the rat model of acute gout with hyperuricemia was established by intraperitoneal injection of xanthine and oxonic acid potassium salt and articular injection monosodium urate ( MSU). The effect of ST in the treatment of gout was investigated by measuring joint swelling, the expression of IL-1β in serum and histological changes of joint by haematoxylin eosin (H&E) staining. Subsequently, urine metabolomics analysis for biomarkers discovery in acute gout with hyperuricemia rats was performed by the ultra-performance liquid chromatography-electrospray ionization quadruple time-of-flight mass spectrometry ( UPLC-ESI-QTOF/ MS) combined with chemometric approach. Principal component analysis ( PCA) and orthogonal partial least squares-discriminant analysis ( OPLS-DA) were used to detect potential biomarkers. A total of 18 potential biomarkers were identified mainly including tryptophan metabolism; tyrosine metabolism; lysine methylation; pyrimidine metabolism; purine metabolism; TCA cycle and fatty acid metabolisms. This study indicates that ST could efficiently ameliorate the disease of acute gout with hyperuricemia in rats. The related metabolic biomarkers could provide useful information and the metabolic mechanism could be used for further study about the model of acute gout with hyperuricemia in rats. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Deer oil (DO), a byproduct of deer meat processing, possesses high nutritional value. This study aims to evaluate the protective effects of DO on dextran sulfate sodium (DSS)‐induced ulcerative colitis (UC) in mice and to explore its potential mechanisms of action.DO was found to inhibit weight loss and colon shortening in colitis mice, significantly reduce disease activity index scores, and notably enhance the levels of tight junction proteins in colon tissues, thus improving intestinal barrier function. ELISA results indicated that DO markedly alleviated the mice's oxidative stress and inflammatory responses. Western blot analysis further demonstrated that DO significantly inhibited the phosphorylation of NF‐κB while up‐regulating the expression levels of Nrf2 and HO‐1 proteins. Additionally, DO increased the abundance of beneficial bacteria such as Odoribacter, Blautia, and Muribaculum, reduced the abundance of harmful bacteria such as Bacteroides, Helicobacter, and Escherichia‐Shigella, and promoted the production of short‐chain fatty acids.Our study provides the first evidence that DO can effectively improve DSS‐induced UC in mice. The underlying mechanisms may involve maintaining intestinal barrier function, inhibiting inflammation, alleviating oxidative stress, and modulation of gut microbiota. These findings offer valuable insights for developing DO as an adjunct treatment for UC and as a functional food. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]