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Introduction: Stroke is characterized by high incidence, recurrence rate, and mortality. Patients with acute ischemic stroke (AIS) who are ineligible for acute revascularization therapy require more effective medication treatments. A previous clinical study showed that Ruyi Zhenbao tablets and Baimai ointments might be effective against AIS; however, high-quality clinical evidence supporting their application in AIS is lacking. To explore the efficacy of the two classic Tibetan medicines in the treatment of AIS, a randomized clinical trial will be conducted in patients with AIS who are not eligible for thrombolytic treatment. Methods: A prospective, randomized, multiple-center, double-blinded, placebo-controlled, and parallel-group trial will be conducted. We shall randomize 480 eligible participants to either the intervention or the control group. The distribution ratio of each group will be 1:1:1:1, including 120 patients each in the dual-medication group, the Baimai ointment group, the Ruyi Zhenbao tablet group, and the placebo group. Participants will be treated with medication for 8 weeks, and they will receive three follow-up visits: at 4 weeks (D29), 8 weeks (D56), and 90 days (D90) after commencing treatment. The primary outcome will be D90 change in the simplified Fugl-Meyer score from baseline to posttreatment. The secondary outcomes are as follows: D29 change of simplified Fugl-Meyer score from baseline to posttreatment; proportion of participants whose D29 NIHSS scores decreased by four or more points from baseline D90 proportion of subjects with mRS score of 0–2 (inclusive); D90 proportion of subjects with Barthel index score ≥95; D90 incidence of cardiovascular and cerebrovascular events. Safety endpoint includes mortality within 90 days; proportion of subjects with adverse events/serious adverse events within 90 days. Conclusion: This research protocol lays a solid groundwork for its practical execution. This study is poised to serve as a reference for other Tibetan medicine researchers, contributing to the reduction of stroke-related expenditures globally and, in turn, benefiting a broader population of stroke patients.

Abstract Background LACS (long-chain acyl-CoA synthetase) genes are widespread in organisms and have multiple functions in plants, especially in lipid metabolism. However, the origin and evolutionary dynamics of the LACS gene family remain largely unknown. Results Here, we identified 1785 LACS genes in the genomes of 166 diverse plant species and identified the clades (I, II, III, IV, V, VI) of six clades for the LACS gene family of green plants through phylogenetic analysis. Based on the evolutionary history of plant lineages, we found differences in the origins of different clades, with Clade IV originating from chlorophytes and representing the origin of LACS genes in green plants. The structural characteristics of different clades indicate that clade IV is relatively independent, while the relationships between clades (I, II, III) and clades (V, VI) are closer. Dispersed duplication (DSD) and transposed duplication (TRD) are the main forces driving the evolution of plant LACS genes. Network clustering analysis further grouped all LACS genes into six main clusters, with genes within each cluster showing significant co-linearity. Ka/Ks results suggest that LACS family genes underwent purifying selection during evolution. We analyzed the phylogenetic relationships and characteristics of six clades of the LACS gene family to explain the origin, evolutionary history, and phylogenetic relationships of different clades and proposed a hypothetical evolutionary model for the LACS family of genes in plants. Conclusions Our research provides genome-wide insights into the evolutionary history of the LACS gene family in green plants. These insights lay an important foundation for comprehensive functional characterization in future research.

Abstract Background Acute respiratory distress syndrome (ARDS) is a severe and fatal disease. Although mesenchymal stem cell (MSC)-based therapy has shown remarkable efficacy in treating ARDS in animal experiments, clinical outcomes have been unsatisfactory, which may be attributed to the influence of the lung microenvironment during MSC administration. Extracellular vesicles (EVs) derived from endothelial cells (EC-EVs) are important components of the lung microenvironment and play a crucial role in ARDS. However, the effect of EC-EVs on MSC therapy is still unclear. In this study, we established lipopolysaccharide (LPS) - induced acute lung injury model to evaluate the impact of EC-EVs on the reparative effects of bone marrow-derived MSC (BM-MSC) transplantation on lung injury and to unravel the underlying mechanisms. Methods EVs were isolated from bronchoalveolar lavage fluid of mice with LPS - induced acute lung injury and patients with ARDS using ultracentrifugation. and the changes of EC-EVs were analysed using nanoflow cytometry analysis. In vitro assays were performed to establish the impact of EC-EVs on MSC functions, including cell viability and migration, while in vivo studies were performed to validate the therapeutic effect of EC-EVs on MSCs. RNA-Seq analysis, small interfering RNA (siRNA), and a recombinant lentivirus were used to investigate the underlying mechanisms. Results Compared with that in non-ARDS patients, the quantity of EC-EVs in the lung microenvironment was significantly greater in patients with ARDS. EVs derived from lipopolysaccharide-stimulated endothelial cells (LPS-EVs) significantly decreased the viability and migration of BM-MSCs. Furthermore, engrafting BM-MSCs pretreated with LPS-EVs promoted the release of inflammatory cytokines and increased pulmonary microvascular permeability, aggravating lung injury. Mechanistically, LPS-EVs reduced the expression level of isocitrate dehydrogenase 2 (IDH2), which catalyses the formation of α-ketoglutarate (α-KG), an intermediate product of the tricarboxylic acid (TCA) cycle, in BM-MSCs. α-KG is a cofactor for ten-eleven translocation (TET) enzymes, which catalyse DNA hydroxymethylation in BM-MSCs. Conclusions This study revealed that EC-EVs in the lung microenvironment during ARDS can affect the therapeutic efficacy of BM-MSCs through the IDH2/TET pathway, providing potential strategies for improving the therapeutic efficacy of MSC-based therapy in the clinic.

Abstract Eye health has become a global health concern and attracted broad attention. Over the years, researchers have proposed many state‐of‐the‐art convolutional neural networks (CNNs) to assist ophthalmologists in diagnosing ocular diseases efficiently and precisely. However, most existing methods were dedicated to constructing sophisticated CNNs, inevitably ignoring the trade‐off between performance and model complexity. To alleviate this paradox, this paper proposes a lightweight yet efficient network architecture, mixed‐decomposed convolutional network (MDNet), to recognise ocular diseases. In MDNet, we introduce a novel mixed‐decomposed depthwise convolution method, which takes advantage of depthwise convolution and depthwise dilated convolution operations to capture low‐resolution and high‐resolution patterns by using fewer computations and fewer parameters. We conduct extensive experiments on the clinical anterior segment optical coherence tomography (AS‐OCT), LAG, University of California San Diego, and CIFAR‐100 datasets. The results show our MDNet achieves a better trade‐off between the performance and model complexity than efficient CNNs including MobileNets and MixNets. Specifically, our MDNet outperforms MobileNets by 2.5% of accuracy by using 22% fewer parameters and 30% fewer computations on the AS‐OCT dataset.

To study the intelligent decision making methods under limited decision samples, aiming at the problems that operational decision-making experience is difficult to express and the training samples for intelligent decision learning are limited, based on the joint operational simulation and drill environment, a decision-making method based on generative adversarial imitation learning is proposed. This method integrates the operational decision-making experience representation and learning process. On the basis of high-level decision-making and low-level action, rule definitions are used to specify the logic of task execution, and generative adversarial imitation learning algorithms are utilized to improve the generalization ability of intelligent agents in scenarios. This method achieved expected results in the constructed typical adversarial scenarios. The algorithm training converged and the decisions output by the intelligent agent are reasonable. Preliminary experimental results indicate that generative adversarial imitation learning, as an intelligent operational decision-making method, has value for further research.

Abstract The development of high-performance lead-free K0.5Na0.5NbO3-based piezoceramics for replacing commercial lead-containing counterparts is crucial for achieving environmentally sustainable society. Although the proposed new phase boundaries (NPB) can effectively improve the piezoelectricity of KNN-based ceramics, the difficulty of achieving saturated poling and the underlying multiscale structures resolution of their complex microstructures are urgent issues. Here, we employ a medium entropy strategy to design NPB and utilize texture engineering to induce crystal orientation. The developed K0.5Na0.5NbO3-based ceramics enjoys both prominent piezoelectric performance and satisfactory Curie temperature, thus exhibiting an ultrahigh energy harvesting performance as well as excellent transducer performance, which is highly competitive in both lead-free and lead-based piezoceramics. Comprehensive structural analysis have ascertained that the field-induced efficient multiscale polarization configurations irreversible transitions greatly encourages high saturated poling. This study demonstrates a strategy for designing high-performance piezoceramics and establishes a close correlation between the piezoelectricty and the underlying multiscale structures.

Background: Rujin Jiedu decoction (RJJDD) is a classical prescription of Traditional Chinese Medicine that has long been applied to treat pneumonia caused by external infection, but whether and how it benefits influenza virus therapy remains largely unclear. The aim of this study was to investigate the anti-inflammatory effect of RJJDD on the mouse model of influenza and to explore its potential mechanism. Methods: The mice were mock-infected with PBS or infected with PR8 virus followed by treatment with RJJDD or antiviral oseltamivir. The weight loss and morbidity of mice were monitored daily. Network pharmacology is used to explore the potential pathways that RJJDD may modulate. qRT-PCR and ELISA were performed to assess the expression of inflammatory cytokines in the lung tissue and macrophages. The intestinal feces were collected for 16S rDNA sequencing to assess the changes in gut microbiota. Results: We demonstrate that RJJDD protects against IAV-induced pneumonia. Comprehensive network pharmacology analyses of the Mass Spec-identified components of RJJDD suggest that RJJDD may act through down-regulating key signaling pathways producing inflammatory cytokines, which was experimentally confirmed by cytokine expression analysis in IAV-infected mouse lung tissues and IAV single-strand RNA mimic R837-induced macrophages. Furthermore, gut microbiota analysis indicates that RJJDD prevented IAV-induced dysbiosis of host intestinal flora, thereby offering a mechanistic explanation for RJJDD's efficacy in influenza pneumonia. Conclusion: This study defines a previously uncharacterized role for RJJDD in protecting against influenza likely by maintaining homeostasis of gut microbiota, and provides a new therapeutic option for severe influenza.

BackgroundThe aim of this study was to classify distinct subgroups of adolescents based on the severity levels of their mobile phone addiction and to investigate how these groups differed in terms of their psychosocial characteristics. We surveyed a total of 2,230 adolescents using three different questionnaires to assess the severity of their mobile phone addiction, stress, anxiety, depression, psychological resilience, and personality. Latent class analysis was employed to identify the subgroups, and we utilized Receiver Operating Characteristic (ROC) curves and multinomial logistic regression for statistical analysis. All data analyses were conducted using SPSS 26.0 and Mplus 8.5.MethodsWe classified the subjects into subgroups based on their mobile phone addiction severity, and the results revealed a clear pattern with a three-class model based on the likelihood level of mobile phone addiction (p 14, which corresponded to the maximum Youden index (Youden index = 0.751).ResultsThe latent classification process in this research confirmed the existence of three distinct mobile phone user groups. We also examined the psychosocial characteristics that varied in relation to the severity levels of addiction.ConclusionThis study provides valuable insights into the categorization of adolescents based on the severity of mobile phone addiction and sheds light on the psychosocial characteristics associated with different addiction levels. These findings are expected to enhance our understanding of mobile phone addiction traits and stimulate further research in this area.

Abstract Compound plant extracts (CPE) are beneficial for aquatic animals on growth performance and antioxidant capacity. A 56‐day experiment was conducted to investigate its positive effect on rice field eel. The fish were fed a commercial diet and supplementing CPE (mainly containing eucommia polysaccharides, reducing sugar) at 0, 0.8, 1.6, 2.4, and 3.2 g/kg. Results showed that dietary CPE significantly increased weight gain and specific growth rate (p

University faculties are duty-bound to shoulder the functions of both teaching and doing scientific research, but they have been repeatedly criticized for emphasizing research over teaching. The current study analyzes the imbalance between teaching and scientific research in faculty evaluation system from three aspects through both quality study and quantity study: the evaluation subject, the weights difference in promotion, and the prediction of salary. Based on that, the influential effects of unbalanced evaluation system on long-term development of education has been explored. The current study also puts forward the moderating effect of the sense of belonging to colleges and universities. The result shows organizational belonging can significantly weaken the negative effects of the unbalanced evaluation system on education. Based on this, this paper makes further suggestions on the construction of university faculties’ evaluation system and the promotion of their sense of belonging.

Recent research has hypothesized that hydrogen peroxide (H2O2) may have emerged from abiotic geochemical processes during the Archean eon (4.0–2.5 Ga), stimulating the evolution of an enzymatic antioxidant system in early life. This eventually led to the evolution of cyanobacteria, and in turn, the accumulation of oxygen on Earth. In the latest issue of Redox Biology, Koppenol and Sies (vol. 29, no. 103012, 2024) argued against this hypothesis and suggested instead that early organisms would not have been exposed to H2O2 due to its short half-life in the ferruginous oceans of the Archean. We find these arguments to be factually incomplete because they do not consider that freshwater or some coastal marine environments during the Archean could indeed have led to H2O2 generation and accumulation. In these environments, abiotic oxidants could have interacted with early life, thus steering its evolutionary course.

Background: Sepsis is a severe and life-threatening condition triggered by a dysregulated response to infection, leading to organ failure and, often, death. The syndrome is expensive to treat, with survivors frequently experiencing reduced quality of life and enduring various long-term disabilities. The increasing understanding of RNA, RNA biology, and therapeutic potential offers an unprecedented opportunity to develop innovative therapy. Objective: This study is a scoping review focusing on pre-clinical studies of microRNA (miRNA)-based therapies for sepsis. Methodology: A scoping review. The search strategy identified papers published in PubMed until 15 October 2023, using the keywords (microRNA) AND (sepsis) AND (animal model). Inclusion criteria included papers that used either gain- or loss-of-function approaches, excluding papers that did not focus on microRNAs as therapy targets, did not include animal models, did not show organ failure-specific assessments, and focused on microRNAs as biomarkers. The PRISMA-ScR guideline was used in this study. Results: A total of 199 articles were identified that featured the terms “microRNA/miRNA/miR”, “Sepsis”, and “animal model”. Of these, 51 articles (25.6%) employed miRNA-based therapeutic interventions in animal models of sepsis. Of these, 15 studies extended their inquiry to include or reference human clinical data. Key microRNAs of interest and their putative mechanisms of action in sepsis are highlighted. Conclusions: The body of work examined herein predominantly addresses various dimensions of sepsis-induced organ dysfunction, supporting the emerging role of miRNAs as potential therapeutic candidates. However, nearly 5% of papers on miR-based therapy have been retracted over the past 5 years, raising important concerns regarding the quality and complexity of the biology and models for assessing therapeutic potential.

Abstract Background RNA modifications have been proven to play fundamental roles in regulating cellular biology process. Recently, maladjusted N7-methylguanosine (m7G) modification and its modifiers METTL1/WDR4 have been confirmed an oncogene role in multiple cancers. However, the functions and molecular mechanisms of METTL1/WDR4 in acute myeloid leukemia (AML) remain to be determined. Methods METTL1/WDR4 expression levels were quantified using qRT-PCR, western blot analysis on AML clinical samples, and bioinformatics analysis on publicly available AML datasets. CCK-8 assays and cell count assays were performed to determine cell proliferation. Flow cytometry assays were conducted to assess cell cycle and apoptosis rates. Multiple techniques were used for mechanism studies in vitro assays, such as northern blotting, liquid chromatography-coupled mass spectrometry (LC–MS/MS), tRNA stability analysis, transcriptome sequencing, small non-coding RNA sequencing, quantitative proteomics, and protein synthesis measurements. Results METTL1/WDR4 are significantly elevated in AML patients and associated with poor prognosis. METTL1 knockdown resulted in reduced cell proliferation and increased apoptosis in AML cells. Mechanically, METTL1 knockdown leads to significant decrease of m7G modification abundance on tRNA, which further destabilizes tRNAs and facilitates the biogenesis of tsRNAs in AML cells. In addition, profiling of nascent proteins revealed that METTL1 knockdown and transfection of total tRNAs that were isolated from METTL1 knockdown AML cells decreased global translation efficiency in AML cells. Conclusions Taken together, our study demonstrates the important role of METTL1/WDR4 in AML leukaemogenesis, which provides a promising target candidate for AML therapy.

Abstract Vehicle speed, road roughness grade and sprung mass are the three main factors to influence suspension control and state estimation. Aiming at the problem that fixed state observer cannot guarantee the estimation accuracy of suspension with driving scenario changes, a suspension state observer based on interactive multiple model adaptive Kalman filter (IMMAKF) is established. Firstly, an adaptive control suspension is proposed based on LQR algorithm and multi-objective optimization algorithm, which can automatically adjust the controller parameters according to the vehicle speed, road roughness grade and sprung acceleration parameters, so as to keep the optimal control effect of the suspension. Secondly, the theoretical model of IMMAKF is derived, and two kinds of IMMAKF suspension state observers and controllers are established. Finally, a simulation condition with the vehicle speed, road roughness grade and sprung mass changing simultaneously is established. The simulation results shows that: compared with ordinary IMMKF, AKF and KF observers, the estimation accuracy of IMMAKF5 is improved. Except for state observation, IMMAKF can be used to identify the road roughness grade and estimate the suspension sprung mass.

Abstract Background Reducing current clinical symptoms and the risks of future exacerbations is the main goal of stable COPD management. Traditional Chinese medicine has unique advantages in chronic disease management. YuPingFeng (YPF), as a classical prescription, has been proven to reduce the risk of exacerbations, but there is a lack of high-quality evidence for the assessment of clinical symptoms and quality of life, particularly for the assessment of treatment response of microecology and immunity. Methods/design This is a prospective, multicentre, randomized, double-blind, placebo-controlled clinical trial. A total of 316 eligible subjects with moderate to severe COPD will be randomized 1:1 to receive YPF or placebo. Participants will receive either YPF or a placebo at 5 g three times daily for 52 weeks. The primary outcome will be the change in the COPD Assessment Test (CAT) score after 52 weeks of treatment. Secondary outcomes will include changes in the St George's Respiratory Questionnaire (SGRQ) score and clinical symptom score, among others. Outcomes will be measured at each visit. The study will continue for 52 weeks and will include six visits to each subject (at day 0 and weeks 4,12,24,36 and 52). In the event of exacerbations, subjects will be required to go back to the hospital once on the first day of exacerbation or when their condition permits. Discussion This trial will provide research methods to evaluate the clinical efficacy, safety, and the possible mechanism of YPF in the treatment of stable moderate-to-severe COPD patients. In addition, we hope to provide more possibilities for TCM to participate in the management of stable COPD. Trial registration The trial was registered at the Chinese Clinical Trials Registry on 3 June 2022 (ChiCTR2200060476; date recorded: 3/6/2022, https://www.chictr.org.cn/ ).

In this study, we investigated the effects of major royal jelly proteins (MRJPs) on the estrogen, gut microbiota, and immunological responses in mice. Mice given 250 or 500 mg/kg, not 125 mg/kg of MRJPs, enhanced the proliferation of splenocytes in response to mitogens. The splenocytes and mesenteric lymphocytes activated by T-cell mitogens (ConA and anti-CD3/CD28 antibodies) released high levels of IL-2 but low levels of IFN-γ and IL-17A. The release of IL-4 was unaffected by MRJPs. Additionally, splenocytes and mesenteric lymphocytes activated by LPS were prevented by MRJPs at the same dose as that required for producing IL-1β and IL-6, two pro-inflammatory cytokines. The production of IL-1β, IL-6, and IFN-γ was negatively associated with estrogen levels, which were higher in the MRJP-treated animals than in the control group. Analysis of the gut microbiota revealed that feeding mice 250 mg/kg of MRJPs maintained the stability of the natural intestinal microflora of mice. Additionally, the LEfSe analysis identified biomarkers in the MRJP-treated mice, including Prevotella, Bacillales, Enterobacteriales, Gammaproteobacteria, Candidatus_Arthromitus, and Shigella. Our results showed that MRJPs are important components of royal jelly that modulate host immunity and hormone levels and help maintain gut microbiota stability.

Abstract Perovskite-type lead-free piezoelectric ceramics allow access to illustrious piezoelectric coefficients (d 33) through intricate composition design and experimental modulation. Developing a swift and accurate technology for identifying (K, Na)NbO3 (KNN)-based ceramic compositions with high d 33 in exceedingly large “compositional” space will establish an innovative research paradigm surpassing the traditional empirical trial-and-error method. Herein, we demonstrate an interpretable machine learning (ML) framework for quick evaluation of KNN-based ceramics with high d 33 based on data from published literature. Specifically, a thorough feature construction was carried out from the global and local dimensions to establish tree regression models with d 33 as the target property. Subsequently, the feature-property mapping rules of KNN-based piezoelectric ceramics are further optimized through feature screening. To intuitively understand the correlation mechanisms between ML regression targets and features, the sure independence screening and sparsifying operator (SISSO) method was employed to extract the essential descriptors to explain d 33. A straightforward descriptor, $${\text{e}}^{({{NM}}_{\text{B}}-{{MV}}_{\text{B}})}\cdot {ST}/{(I{D}_{\text{A}})}^{2}$$ e ( NM B − MV B ) ⋅ ST / ( I D A ) 2 , consisting of only four easily accessible parameters, can accelerate the evaluation of a series of novel KNN-based ceramics with high d 33 while exhibiting strong theoretical interpretability. This work not only provides a tool for the rapid discovery of high piezoelectric performance in KNN-based ceramics but also offers a data-driven route for the design of property descriptors in perovskites.

Abstract Backgroud Hypoadiponectinemia is the important cause of insulin resistance. Recent studies have shown that periodontitis is associated with hypoadiponectinemia. The purpose of this study was to investigate the effect of periodontitis-induced endoplasmic reticulum stress (ERS) in visceral adipocytes on hypoadiponectinemia. Methods Rat periodontitis models were established by local ligation with silk around the bilateral maxillary second molars. Porphyromonas gingivalis-lipopolysaccharid (P.g-LPS) was also used to stimulate the visceral adipocytes in vitro. The protein expression levels of glucose regulated protein 78 (GRP78), inositol-requiring protein 1α (IRE1α), protein kinase RNA-like ER kinase (PERK), activating transcription factor 6 (ATF6) and adiponectin were detected. IRE1α lentiviruses were transfected into visceral adipocytes in vitro, and an IRE1α inhibitor (KIRA6) was injected in epididymal adipose tissue of rats to detect and verify the effect of ERS on adiponectin expression in visceral adipocytes in vivo. Results Hypoadiponectinemia was observed in periodontitis rat, and the expression levels of ERS key proteins GRP78 and the phosphorylation levels of IRE1α (p-IRE1α)/IRE1α in visceral adipocytes were increased, while the expression levels of adiponectin protein were decreased. After KIRA6 injection into epididymal adipose tissue of rats with periodontitis, adiponectin levels in visceral adipocytes increased, and serum adiponectin levels recovered to a certain extent. The protein expression levels of GRP78 and p-IRE1α/IRE1α were increased and adiponectin protein expression was decreased in P.g-LPS-induced visceral adipocytes. Overexpression of IRE1α further inhibited adiponectin expression in P.g-LPS-stimulated visceral adipocytes, and conversely, IRE1α inhibition restored adiponectin expression. Conclusions Our findings suggest that periodontitis induces ERS in visceral adipocytes leading to hypoadiponectinemia. IRE1α is a key protein regulating adiponectin expression in visceral adipocytes.

Abstract Objectives Allergic rhinitis (AR) refers to a form of respiratory inflammation that mainly affects the sinonasal mucosa. The purpose of this study was to explore the level of immune cell infiltration and the pathogenesis of AR. Methods We performed a comprehensive analysis of two gene expression profiles (GSE50223 and GSE50101, a total of 30 patients with AR and 31 healthy controls). CIBERSORT was used to evaluate the immune cell infiltration levels. Weighted gene coexpression network analysis was applied to explore potential genes or gene modules related to immune status, and enrichment analyses including gene ontology, Kyoto Encyclopedia of Genes and Genomes, gene set enrichment analysis, and gene set variation analysis, were performed to analyze the potential mechanisms in AR. A protein–protein interaction network was constructed to investigate the hub genes, and consensus clustering was conducted to identify the molecular subtypes of AR. Results Compared to the healthy controls, patients with AR had high abundance levels and proportions of CD4+ memory‐activated T cells. One hundred and eight immune‐related differentially expressed genes were identified. Enrichment analysis suggested that AR was mainly related to leukocyte cell‐cell adhesion, cytokine‐cytokine receptor interaction, T‐cell activation, and T‐cell receptor signaling pathway. Ten hub genes, including TYROBP, CSF1R, TLR8, FCER1G, SPI1, ITGAM, CYBB, FCGR2A, CCR1, and HCK, which were related to immune response, might be crucial to the pathogenesis of AR. Three molecular subtypes with significantly different immune statuses were identified. Conclusion This study improves our understanding of the molecular mechanisms in AR via comprehensive strategies and provides potential diagnostic biomarkers and therapeutic targets of AR.

After a loss of coolant accident (LOCA) in the prestressed concrete containment vessels (PCCVs) of nuclear power plants, the coupling of temperature and pressure can significantly affect the mechanical properties of the PCCVs. However, there is no consensus on how this coupling affects the failure mechanism of PCCVs. In this paper, a simplified finite element modeling method is proposed to study the effect of temperature and pressure coupling on PCCVs. The experiment results of a 1:4 scale PCCV model tested at Sandia National Laboratory (SNL) are compared with the results obtained from the proposed modeling approach. Seven working conditions are set up by varying the internal and external temperatures to investigate the failure mechanism of the PCCV model under the coupling effect of temperature and pressure. The results of this paper demonstrate that the finite element model established by the simplified finite element method proposed in this paper is highly consistent with the experimental results. Furthermore, the stress-displacement curve of the PCCV during loading can be divided into four stages, each of which corresponds to the damage to the concrete, steel liner, steel rebar, and prestressing tendon. Finally, the failure mechanism of the PCCV is significantly affected by temperature.

Abstract Background The combination of the endocannabinoid system (ECS) and the type 2 cannabinoid receptor (CB2R) can activate various signal pathways, leading to distinct pathophysiological roles. This interaction has gained significant attention in recent research on fibrosis diseases. Focal adhesion kinase (FAK) plays a crucial role in regulating signals from growth factor receptors and Integrins. It is also involved in the transformation of fibroblasts into myofibroblasts. This study aims to investigate the impact of the CB2R agonist JWH133 on lung fibrosis and its potential to alleviate pulmonary fibrosis in mice through the FAK pathway. Methods The C57 mice were categorized into five groups: control, BLM, BLM + JWH133, BLM + JWH133 + NC, and BLM + JWH133 + FAK groups.JWH133 was administered to mice individually or in conjunction with the FAK vector. After 21 days, pathological changes in mouse lung tissues, inflammatory factor levels, hydroxyproline levels, and collagen contents were evaluated. Moreover, the levels of the FAK/ERK/S100A4 pathway-related proteins were measured. Results JWH133 treatment decreased inflammatory factor levels, attenuated pathological changes, and reduced extracellular matrix accumulation in the mouse model of bleomycin-induced pulmonary fibrosis; however, these effects were reversed by FAK. JWH133 attenuated fibrosis by regulating the FAK/ERK/S100A4 pathway. Conclusions The results presented in this study show that JWH133 exerts a protective effect against pulmonary fibrosis by inhibiting the FAK/ERK/S100A4 pathway.Therefore, JWH133 holds promise as a potential therapeutic target for pulmonary fibrosis.

Abstract Background The association of glycemic variability with severe consciousness disturbance and in-hospital all-cause mortality in critically ill patients with cerebrovascular disease (CVD) remains unclear, This study aimed to investigate the association of glycemic variability with cognitive impairment and in-hospital death. Method We extracted all blood glucose measurements of patients diagnosed with CVD from the Medical Information Mart for Intensive Care IV (MIMIC-IV). Glycemic variability was defined as the coefficient of variation (CV), which was determined using the ratio of standard deviation and the mean blood glucose levels. Cox hazard regression models were applied to analyze the link between glycemic variability and outcomes. We also analyzed non-linear relationship between outcome indicators and glycemic variability using restricted cubic spline curves. Results The present study included 2967 patients diagnosed with cerebral infarction and 1842 patients diagnosed with non-traumatic cerebral hemorrhage. Log-transformed CV was significantly related to cognitive impairment and in-hospital mortality, as determined by Cox regression. Increasing log-transformed CV was approximately linearly with the risk of cognitive impairment and in-hospital mortality. Conclusion High glycemic variability was found to be an independent risk factor for severe cognitive decline and in-hospital mortality in critically ill patients with CVD. Our study indicated that enhancing stability of glycemic variability may reduced adverse outcomes in patients with severe CVD.