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Abstract Spinal cord injury (SCI) results in irreversible neurological impairment. After SCI, Ferritinophagy-induced free iron released from ferritin can lead to extensive lipid peroxidation and aggravate neurological damage. NRF2/HO-1 pathway is to endow cells with a protective effect against oxidative stress, and it plays an important role in the transcriptional activation of a series of antioxidant and detoxification genes. UAMC-3203 is a ferrostatin-1(Fer-1) analogue with better solubility and stability, which can more effectively inhibit ferroptosis after SCI. A rat SCI model was constructed, and the recovery of motor function was observed after treatment with UAMC-3203. ELISA was employed to assess the impact of UAMC-3203 on inflammation-related factors, while immunofluorescence was utilized to investigate the influence of UAMC-3203 on neuronal count as well as the activation of astrocytes and microglia/macrophages. Malondialdehyde (MDA) were detected to reflect the level of oxidation products. Western blot analysis was used to measure the level of ferroptosis markers and the expression of NRF2/HO-1. Our findings demonstrate that UAMC-3203 inhibits the production of reactive oxygen species (ROS) and lipid peroxides, preventing ferroptosis and reducing neuronal degeneration. Additionally, UAMC-3203 suppresses astrocyte proliferation and microglia/macrophage activation, as well as the release of ferroptosis-related inflammatory factors. These combined effects contribute to the preservation of spinal cord tissue and the facilitation of motor function recovery. UAMC-3203 maybe inhibit ferroptosis after SCI to promote functional recovery.

ObjectiveThe limited ability to regenerate axons after spinal cord injury (SCI) is influenced by factors such as astrocyte activation, reactive proliferation, and glial scar formation. The TGF-β/Smad (transforming growth factor-β/mothers against decapentaplegic homolog) pathway, associated with astrocytic scarring, plays a crucial role in recovery post-injury. This study aims to investigate how icariin (ICA) interacts with reactive astrocytes in the treatment of spinal cord injury.MethodsA rat SCI model was constructed, and the recovery of motor function was observed after treatment with ICA.HE staining, LFB staining, immunofluorescence staining, and Western blotting were employed to assess ICA's ability to inhibit astrocyte proliferation in rats following spinal cord injury by modulating YAP, as well as to evaluate the reparative effects of ICA on the injured spinal cord tissue. Primary astrocytes were isolated and cultured. Immunoprecipitation-Western Blot (IP-WB) ubiquitination and cytoplasm-nuclear separation were employed to assess PPM1B ubiquitination and nuclear translocation.ResultsThe CatWalk XT gait analysis, BBB (Basso, Beattie, and Bresnahan) score, electrophysiological measurements, HE staining, and LFB staining collectively demonstrated that ICA promotes motor function and tissue recovery following spinal cord injury in rats. Immunofluorescence staining and Western Blot analyses revealed that ICA inhibits astrocyte proliferation in rats post-spinal cord injury by suppressing YAP activity. Furthermore, the activation of YAP by XMU-MP-1 was shown to compromise the efficacy of ICA in these rats after spinal cord injury. Additional immunofluorescence staining and Western Blot experiments confirmed that ICA inhibits TGFβ1-induced astrocyte activation through the regulation of YAP. The knockdown of PPM1B (protein phosphatase, Mg2+/Mn2+-dependent 1B) in astrocytes was found to inhibit TGFβ signaling. Additionally, YAP was shown to regulate PPM1B ubiquitination and nuclear translocation through immunoprecipitation-Western blot analysis, along with the segregation of cytoplasm and nucleus.ConclusionIcariin promotes functional recovery in rats after spinal cord injury by inhibiting YAP and regulating PPM1B ubiquitination to inhibiting the activation of reactive astrocytes.

AbstractAirway remodeling is an important pathologic factor in the progression of asthma. Abnormal proliferation and migration of airway smooth muscle cells (ASMCs) are important pathologic mechanisms in severe asthma. In the current study, claudin-1 (CLDN1) was identified as an asthma-related gene and was upregulated in ASMCs stimulated with platelet-derived growth factor BB (PDGF-BB). Cell counting kit-8 and EdU assays were used to evaluate cell proliferation, and transwell assay was carried out to analyze cell migration and invasion. The levels of inflammatory factors were detected using enzyme-linked immunosorbent assay. The results showed that CLDN1 knockdown inhibited the proliferation, migration, invasion, and inflammation of ASMCs treated with PDGF-BB, whereas overexpression of CLDN1 exhibited the opposite effects. Protein-protein interaction assay and co-immunoprecipitation revealed that CLDN1 directly interacted with matrix metalloproteinase 14 (MMP14). CLDN1 positively regulated MMP14 expression in asthma, and MMP14 overexpression reversed cell proliferation, migration, invasion, and inflammation induced by silenced CLDN1. Taken together, CLDN1 promotes PDGF-BB-induced cell proliferation, migration, invasion, and inflammatory responses of ASMCs by upregulating MMP14 expression, suggesting a potential role for CLDN1 in airway remodeling in asthma.

Due to the complex pathological mechanisms of Alzheimer's disease (AD), its treatment remains a challenge. One of the major difficulties in treating AD is the difficulty for drugs to cross the blood–brain barrier (BBB). Low-intensity ultrasound (LIUS) is a novel type of ultrasound with neuromodulation function. It has been widely reported that LIUS combined with intravenous injection of microbubbles (MB) can effectively, safely, and reversibly open the BBB to achieve non-invasive targeted drug delivery. However, many studies have reported that LIUS combined with MB-mediated BBB opening (LIUS + MB-BBBO) can improve pathological deposition and cognitive impairment in AD patients and mice without delivering additional drugs. This article reviews the relevant research studies on LIUS + MB-BBBO in the treatment of AD, analyzes its potential mechanisms, and summarizes relevant ultrasound parameters.

In real-life communication, individuals use language that carries evident rewarding and punishing elements, such as praise and criticism. A common trend is to seek more praise while avoiding criticism. Furthermore, semantics is crucial for conveying information, but such semantic access to native and foreign languages is subtly distinct. To investigate how rule learning occurs in different languages and to highlight the importance of semantics in this process, we investigated both verbal and non-verbal rule learning in first (L1) and second (L2) languages using a reinforcement learning framework, including a semantic rule and a color rule. Our computational modeling on behavioral and brain imaging data revealed that individuals may be more motivated to learn and adhere to rules in an L1 compared to L2, with greater striatum activation during the outcome phase in the L1. Additionally, results on the learning rates and inverse temperature in the two rule learning tasks showed that individuals tend to be conservative and are reluctant to change their judgments regarding rule learning of semantic information. Moreover, the greater the prediction errors, the greater activation of the right superior temporal gyrus in the semantic-rule learning condition, demonstrating that such learning has differential neural correlates than symbolic rule learning. Overall, the findings provide insight into the neural mechanisms underlying rule learning in different languages, and indicate that rule learning involving verbal semantics is not a general symbolic learning that resembles a conditioned stimulus-response, but rather has its own specific characteristics.

Sensor degradation and failure often undermine users’ confidence in adopting a new data-driven decision-making model, especially in risk-sensitive scenarios. A risk assessment framework tailored to classification algorithms is introduced to evaluate the decision-making risks arising from sensor degradation and failures in such scenarios. The framework encompasses various steps, including on-site fault-free data collection, sensor failure data collection, fault data generation, simulated data-driven decision-making, risk identification, quantitative risk assessment, and risk prediction. Leveraging this risk assessment framework, users can evaluate the potential risks of decision errors under the current data collection status. Before model adoption, ranking risk sensitivity to sensor data provides a basis for optimizing data collection. During the use of decision algorithms, considering the expected lifespan of sensors enables the prediction of potential risks the system might face, offering comprehensive information for sensor maintenance. This method has been validated through a case study involving an access control.

Deltamethrin (DM), a Type II pyrethroid, is widely used worldwide in agriculture, household applications, and medicine. Recent studies have shown that DM exerts a variety of toxic effects on organs such as the kidney, heart muscle, and nerves in animals. However, little is known about the effects of high-dose DM on growth and development, and the mechanism of toxicity remains unclear. Using the Caenorhabditis elegans model, we found that high-dose DM caused a delay in nematode development. Our results showed that high-dose DM reduced the activation of the endoplasmic reticulum unfolded protein response (UPRER). Further studies revealed that high-dose DM-induced developmental toxicity and reduced capacity for UPRER activation were associated with the IRE-1/XBP-1 pathway. Our results provide new evidence for the developmental toxicity of DM and new insights into the mechanism of DM toxicity.

ObjectiveEpimedium (EPI) is a common Chinese herb with neuroprotective effects against a variety of central nervous system disorders, especially spinal cord injury (SCI). In this study, we performed network pharmacology and molecular docking analyses to reveal the mechanism underlying EPI treatment of SCI, then validated its efficacy using animal models.MethodsThe active ingredients and targets of EPI were screened by Traditional Chinese Medicine Systems Pharmacology (TCMSP) and their targets annotated on the UniProt platform. SCI-related targets were searched from OMIM, TTD, and GeneCards databases. We employed the STRING platform to construct a protein–protein interaction (PPI) network then visualized the results using Cytoscape (3.8.2) software. We also subjected key EPI targets to ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, then docked the main active ingredients with the key targets. Finally, we established an SCI rat model to evaluate efficacy of EPI in treating SCI and validate the effects of different biofunctional modules predicted by network pharmacology.ResultsA total of 133 EPI targets were associated with SCI. GO terms and KEGG pathway enrichment results showed that EPI’s effect in treating SCI was significantly associated with inflammatory response, oxidative stress and the PI3K/AKT signaling pathway. Molecular docking results indicated that EPI’s active ingredients have a high affinity for the key targets. Results from animal experiments revealed that EPI not only markedly improved Basso, Beattie, and Bresnahan scores in SCI rats, but also significantly improved p-PI3K/PI3K and p-AKT/AKT ratio. Moreover, EPI treatment not only mediated a significant decrease in malondialdehyde (MDA) but also increased both superoxide dismutase (SOD), and glutathione (GSH). However, this phenomenon was successfully reversed by LY294002, a PI3K inhibitor.ConclusionEPI improves behavioral performance in SCI rats through anti-oxidative stress, which may be mediated by activation of the PI3K/AKT signaling pathway.

Nowadays it is commonly accepted that knowledge, as a resource has become increasingly important in the drive toward knowledge-driven innovation in the manufacturing industry, and which is especially critical for the research and development of complex equipment. In China, there are several fields of manufacturing, such as aviation, ship, and electronics. Although each of them has its own professional technology, they also take advantage of the basic common manufacturing technology. Thus, it is meant for sharing manufacturing technology knowledge. In order to promote innovation, a manufacturing technology knowledge retrieval system is developed to make more efficient use of manufacturing technology knowledge. Manufacturing technology knowledge is a phrase with vast meanings, which may include knowledge of different manufacturing process means, machine, and process capabilities or the latest technology developments. In this system, the manufacturing technology knowledge is defined and organized. A knowledge retrieval method based on the weighted fusion of ontology-based semantic extension (OSE) and user-based collaborative filtering (UCF) is proposed and described detailed. On this basis, the prototype system of manufacturing technology knowledge retrieval system is developed. Its architecture and main functions are elaborated. The results of this system facilitate the sharing of manufacturing knowledge, and it is expected to accelerate the process of knowledge transfer, to improve the level of the overall manufacturing technology.

Objective To evaluate the efficacy and safety of SpyGlass direct visualization system (DS) in treatment of patients with difficult choledocholithiasis after removing failure through endoscopic retrograde cholangiopancreatography (ERCP) and surgical approach. Methods The clinical data of 8 patients with choledocholithiasis who had undergone lithotripsy with SpyGlass DS combined with ERCP in department of surgery Ruijin Hospital, from January 2020 to December 2021 were analyzed retrospectively. The diagnosis and treatment and adverse events incidence were evaluated. All cases were with difficult choledocholithiasis. Seven cases had removal stone failure of ERCP including 4 cases with 1 time, 1 case with 5 times, and the other 2 cases with 6 times. One case had history of surgical treatment failure. Results A total of 8 cases received 10 times of Spyglass DS procedures with all cases successful visualization of bile duct stones and complete stone removal. Four cases (50%) underwent successful stone removal at the first procedure. The other 4 cases (50%) were successful stone removal after treatment again from 1 week to 4 months post procedures. One case was diagnosed both common bile duct stone and bile duct tumor and treated by surgery after endoscopy. There were 2 cases (20%) with slight epigastric pain, 3 cases (30%) with fever, 1 case (10%) with hyperamylasemia, 4 cases (40%) with abnormal liver function and 1 case (10%) with acute cholangitis. All cases with symptom were mild and improved after treatment. No procedure-related pancreatitis, gastrointestinal perforation or massive hemorrhage was found. Conclusions SpyGlass DS with ERCP and lithotripsy would be effective and safe in diagnosis and treatment of the patients with difficult choledocholithiasis who had previous treatment failure by conventional methods.