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Solid-state polymer Li metal batteries have been regarded as a promising candidate for next-generation batteries due to their high-energy densities provided by the Li metal and the improved safety provided by the solid electrolyte. Polyester is one attractive polymer host, which could be an alternative to polyether-based solid electrolyte due to its excellent lithium ion transport ability and wide electrochemical stability window. Here, a BAB-type triblock copolymer is synthesized with poly (propylene carbonate) as A-block and poly (ε -caprolactone) as B-block. The triblock copolymer electrolyte exhibits a high ionic conductivity of 3 × 10−5 S cm−1 at 30 °C with a high lithium ion transference number (0.4) and an extremely wide electrochemical window (5 V). A highly stable interface against Li metal is maintained for more than 760 h at a current density of 0.1 mA cm−2. A LiFePO 4 cathode based solid state battery delivers a high discharge capacity of 142 mA h g−1 at 0.05C, room temperature, and 161 mA h g−1 at 0.1C, 70 °C with a capacity retention of 90% after 200 cycles. To understand the excellent electrochemical performance, the morphology and chemical information at both anode and cathode interface are characterized and analyzed. The synthesis of this triblock copolymer demonstrates a new direction in developing high ionic conductivity solid polymer electrolyte for solid-state polymer batteries. Image 1 • A novel polyester-based copolymer SPE shows a low T g and high oxidative stability. • Li//Li cells exhibit stable cyclability at 0.1 mA cm−2 with low overpotential. • The SPE contains a strong capability in suppressing Li dendrites. • LFP//Li and NMC//Li batteries display high performances at both 30 °C and 70 °C. [ABSTRACT FROM AUTHOR]

The procedure of memory reconsolidation provides an opportunity to improve some mental disorders caused by maladaptive memories, such as Posttraumatic Stress Disorder. Prediction error was considered a necessary condition for triggering memory reconsolidation. However, it is difficult to create a satisfying prediction error to successfully open memory reconsolidation in a clinical context. The purpose of this study was to explore a more practicable method to trigger memory reconsolidation. We used a successive 4-day fear-potentiated startle paradigm to compare the effect of uncertainty with prediction error during retrieval on preventing the return of fear. Bayes factor, combined with p value and effect size, was used as the main indicator of statistical inference. The results indicated that spontaneous recovery and reinstatement of fear were not observed in the uncertainty group, whereas return of fear was observed for the prediction error group. However, the direct comparison between the two groups did not yield statistically significant results, potentially reflecting a lack of statistical power. Nonetheless, these results suggest that uncertainty retrieval could be a better means to trigger memory reconsolidation than prediction error, making uncertainty a worthwhile factor to consider in future research on memory reconsolidation. • Uncertainty during retrieval could enhance the fear-impairing effect of the extinction procedure. • Uncertainty retrieval could effectively prevent the fear relapse. • Prediction error retrieval failed to block the return of fear. • The advantages on preventing fear relapse by uncertainty retrieval was only observed with SCR, but not FPS. • The uncertainty retrieval could be a better method to trigger the memory reconsolidation. [ABSTRACT FROM AUTHOR]

In the quality inspection process of high-voltage cables, several commonly used indicators include cable length, insulation thickness, and the number of conductors within the core. Among these factors, the count of conductors holds particular significance as a key determinant of cable quality. Machine vision technology has found extensive application in automatically detecting the number of conductors in cross-sectional images of high-voltage cables. However, the presence of scratch-type defects in cut high-voltage cable cross-sections can significantly compromise the precision of conductor count detection. To address this problem, this paper introduces a novel improved total variation (TV) algorithm, marking the first-ever application of the TV algorithm in this domain. Considering the staircase effect, the direct use of the TV algorithm is prone to cause serious loss of image edge information. The proposed algorithm firstly introduces multimodal features to effectively mitigate the staircase effect. While eliminating scratch-type defects, the algorithm endeavors to preserve the original image's edge information, consequently yielding a noteworthy enhancement in detection accuracy. Furthermore, a dataset was curated, comprising images of cross-sections of high-voltage cables of varying sizes, each displaying an assortment of scratch-type defects. Experimental findings conclusively demonstrate the algorithm's exceptional efficiency in eradicating diverse scratch-type defects within high-voltage cable cross-sections. The average scratch elimination rate surpasses 90%, with an impressive 96.15% achieved on cable sample 4. A series of conducted ablation experiments in this paper substantiate a significant enhancement in cable image quality. Notably, the Edge Preservation Index (EPI) exhibits an improvement of approximately 20%, resulting in a substantial boost to conductor count detection accuracy, thus effectively enhancing the quality of high-voltage cable production. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelinating lesions in the white matter of the central nervous system. Studies have shown that exercise is beneficial for multiple sclerosis (MS). However, the molecular basis is largely unknown. Materials and Methods: We integrated multiple blood and hippocampus transcriptome data from subjects with physical activity or MS. Transcription change associations between physical activity and MS were analyzed with bioinformatic methods including GSEA (Gene Set Enrichment Analysis) and GO (Gene Ontology) analysis. Results: We find that exercise can specifically reverse immune-related genes in the hippocampus of MS patients, while this effect is not observable in blood. Moreover, many of these reversed genes encode immune-related receptors. Interestingly, higher levels of physical activity have more pronounced effects on the reversal of MS-related transcripts. Conclusions: The immune-response related genes or pathways in the hippocampus may be the targets of exercise in alleviating MS conditions, which may offer new therapeutic clues for MS. [ABSTRACT FROM AUTHOR]

Based on a large number of fracturing data at home and abroad, through theoretical and experimental data, the influences of different parameters on hydraulic fracture formation and extension are studied. The parameters include the difference coefficient of horizontal principal stress within layers, the difference of minimum horizontal principal stress between layers, the rock mechanics parameters, the difference coefficient of internal coal and rock fracture pressures and the properties of rock interface. According to field fracturing and production data, the influences of geological and fracturing engineering parameters on gas production are analyzed, such as the earth stress conditions, the fracturing technology,the volume of fracturing fluid, the amount of sand, the system of fracturing fluid, the interval of fracturing perforation and the technology of secondary fracturing, all of which have important influences on the production. Through the optimization of the technology, the reasonable fracturing technology and parameters are offered for Hancheng mining area. The ideal effects have been achieved in the practical field application. This work provides a theoretical basis and a reference index for the implementation of the middle-high rank coal reservoirs fracturing technology in China. [ABSTRACT FROM AUTHOR]

Abstract Melt index (MI) is one of the most important variables determining the product quality in the industrial propylene polymerization process. In this paper, a multi-scale prediction model is proposed for MI prediction by combining the empirical mode decomposition (EMD), chaos theory and optimized relevance vector machine (RVM) model. First, the EMD method is used to decompose the MI time series into intrinsic mode functions (IMFs) and the residual. Then the chaotic characteristics of each component are identified with chaos theory. For the components with chaotic characteristics, relevance vector machine (RVM) chaotic prediction model is developed as the predictive model. For the components without chaotic characteristics, least squares support vector machine (LSSVM) is used as the predictive model. At the same time, an improved ant colony optimization (IACO) algorithm is used to optimize the parameters of RVM and LSSVM. In the end, the final prediction results of MI are obtained by summing the predicted results of all components. Research on the proposed multi-scale model is carried out on a real propylene polymerization plant and the results are compared among the RVM-chaos, IACO-RVM-chaos and multi-scale models. The research results show that the model developed achieves a good performance in the industrial MI prediction process. Highlights • The multi-scale characteristics of melt index series are discovered firstly. • The IACO optimized RVM chaotic prediction model is established. • A multi-scale prediction model is proposed for melt index prediction. • The proposed model outperforms the other models on a real polypropylene plant. [ABSTRACT FROM AUTHOR]

National key protected wild plants (NKPWPs) are species with important conservation value based on genetics, ecology, culture, and/or scientific research, which are also confronted with serious threats. However, their geographical distribution patterns and conservation status remain unclear. In this study, we compiled 1032 species of NKPWPs. We measured the diversity to identify hotspots of NKPWPs based on species richness, weighted range size rarity and a complementarity‐based analysis. Comparing the distribution and hotspots of NKPWPs with the coverage of Chinese nature reserves (NRs), we assessed conservation effectiveness and identified conservation gaps. The results identified 13 diversity hotspots; only 9.5% of them were covered by NRs with >30% of the grid cell area, and even 19.5% were not covered at all by NRs. Overall, 44.7% of NKPWPs were effectively protected by national NRs. Despite this success, 571 species in Yunnan, Guizhou, Sichuan, Chongqing, Guangxi, Guangdong, southern Hainan, Taiwan, and northern Xinjiang remain unprotected by NRs. The protected proportion of plants with first‐level protection was lower than that of plants with second‐level protection. The low overall proportion of protected hotspots indicates that the conservation outlook for NKPWPs is not optimistic. This study identifies priority conservation areas and conservation gaps and provides a scientific reference for the conservation of wild plants in China. [ABSTRACT FROM AUTHOR]

Objectives: Lung cancer is a major public health concern and represents the most common cause of cancer‐related death worldwide. Among eukaryotes, the G protein‐coupled receptor (GPCR) family stands as the largest group of membrane proteins. Alterations in GPCR gene expression and dysregulation of signal transduction have been recognized as the markers of malignancy. As a member of the GPCR family, G protein‐coupled receptor 37 (GPR37) exhibits unknown functions in tumors, particularly in non‐small‐cell lung cancer (NSCLC) Methods: We explored the expression and prognosis of GPR37 in NSCLC through TCGA, GTEx, GEO, and GEPIA2. We detected the expression of GPR37 in NSCLC tissues and cell lines. The study explored the influence of GPR37 on tumor cell proliferation. Furthermore, we examined the effects of GPR37 on tumor cell apoptosis and invasion. Most importantly, we investigated whether GPR37 affects cisplatin‐induced drug resistance in NSCLC. Furthermore, by conducting animal experiments, we assessed the impact of GPR37 on NSCLC and delved into underlying mechanisms. Results: (1) In NSCLC, the expression of GPR37 is markedly higher than that in corresponding normal tissues. We found that elevated GPR37 expression predicts an unfavorable prognosis. (2) It was demonstrated that GPR37 positively regulates NSCLC cell invasion, migration, and proliferation, suppresses cell apoptosis, heightens resistance to cisplatin, and promotes tumor formation and growth. Conversely, we observed that GPR37 knockdown suppresses NSCLC cell invasion, migration, and proliferation, promotes cell apoptosis, increases sensitivity to cisplatin, and affects tumor formation and growth. (3) GPR37 activates PI3K/Akt/mTOR signal transduction pathways to mediate epithelial‐mesenchymal transition (EMT), thereby promoting the progression of NSCLC. Conclusions: It was suggested that GPR37 acts a crucial role in promoting the occurrence and development of NSCLC. Knockdown of GPR37 significantly inhibits the occurrence and development of NSCLC. Therefore, our findings demonstrated that GPR37 may represent a viable therapeutic target for NSCLC. [ABSTRACT FROM AUTHOR]

This review discusses the application scenarios of the machine learning-supported performance prediction and the optimization efficiency of tunnel boring machines (TBMs). The rock mass quality ratings, which are based on the Chinese code for geological survey, were used to provide "labels" suitable for supervised learning. As a result, the generation of machine prediction for rock mass grades reasonably agreed with the ground truth documented in geological maps. In contrast, the main operational parameters, i.e., thrust and torque, can be reasonably predicted based on historical data. Consequently, 18 collapse sections of the Yinsong project have been successfully predicted by several researchers. Preliminary studies on the selection of the optimal penetration rate and cost were conducted. This review also presents a summary of the main achievements in response to the initiatives of the Lotus Pool Contest in China. For the first time, large and well-documented TBM performance data has been shared for joint scientific research. Moreover, the review discusses the technical problems that require further study and the perspectives in the future development of intelligent TBM construction based on big data and machine learning. [ABSTRACT FROM AUTHOR]

This review summarizes the research outcomes and findings documented in 45 journal papers using a shared tunnel boring machine (TBM) dataset for performance prediction and boring efficiency optimization using machine learning methods. The big dataset was collected during the Yinsong water diversion project construction in China, covering the tunnel excavation of a 20 km-section with 199 items of monitoring metrics taken with an interval of one second. The research papers were the result of a call for contributions during a TBM machine learning contest in 2019 and covered a variety of topics related to the intelligent construction of TBM. This review comprises two parts. Part I is concerned with the data processing, feature extraction, and machine learning methods applied by the contributors. The review finds that the data-driven and knowledge-driven approaches in extracting important features applied by various authors are diversified, requiring further studies to achieve commonly accepted criteria. The techniques for cleaning and amending the raw data adopted by the contributors were summarized, indicating some highlights such as the importance of sufficiently high frequency of data acquisition (higher than 1 second), classification and standardization for the data preprocessing process, and the appropriate selections of features in a boring cycle. The review finds that both supervised and unsupervised machine learning methods have been utilized by various researchers. The ensemble and deep learning methods have found wide applications. Part I highlights the important features of the individual methods applied by the contributors, including the structures of the algorithm, selection of hyperparameters, and model validation approaches. [ABSTRACT FROM AUTHOR]

• A multi-class Boosting method is proposed for the multi-class imbalanced problem. • Parametrized division of exposure zone is achieved using RMS, C r , C s , and D cl , etc. • Field chloride profile data with time span of 18 years validates proposed method. • The distribution of exposure zone satisfies the Weibull distribution. The analysis of marine reinforced concrete structures using chloride profile data is a commonly used exposure zone classification method. However, chloride profile data is multi-class, unbalanced and non-parametric, which makes it difficult for the commonly used machine-learning methods to construct an appropriate classification model. To solve this problem, chloride profile is parametrized by the minimum redundancy maximum relevance algorithm and a multi-class Boosting method using F-measure as inductive bias indicator to evaluate the weight of base classifiers is put forward. The method is based on field test data of the chloride profile over a period of 18 years in Hangzhou Bay, China. The method outperforms the original Boosting method with an average F-measure improvement of 6.2 %. The results show that parametric partitioning of the exposure zone is achieved and the distribution of the exposure zone satisfies the Weibull distribution. [ABSTRACT FROM AUTHOR]

Modeling high‐dimensional dynamic processes is a challenging task. In this regard, probabilistic slow feature analysis (PSFA) is revealed to be advantageous for dynamic soft sensor modeling, which can extract slowly varying intrinsic features from high‐dimensional data. However, nonlinearities prevalent in industrial processes are not considered, which could lead to unsatisfactory prediction performance. In this paper, a weighted PSFA (WPSFA)‐based soft sensor model is proposed for nonlinear dynamic chemical process. In WPSFA, a weighted log‐likelihood function of complete data is constructed to linearize the nonlinear state emission equation. Then, the expectation maximization algorithm is applied to estimate the model parameters and a locally weighted regression model is established for quality prediction. Finally, the feasibility and effectiveness of the proposed approach are well illustrated through a numerical example and a real industrial process. [ABSTRACT FROM AUTHOR]

Background: Anwuligan (ANW) isolated from nutmeg, also known as myristyl lignan, has attracted attention due to its therapeutic potential in diseases. However, its effect on lung cancer is still unclear. Methods: In this study, the cytotoxicity of ANW on non‐small cell lung cancer (NSCLC) cells was detected using a Cell Counting Kit‐8 (CCK‐8) assay. In vitro, clone formation, wound healing, and Transwell assays were used to investigate the migratory and invasive abilities of NSCLC cells after ANW treatment. The expression levels of the associated proteins were detected using Western blotting. A luciferase assay was used to validate the binding of let‐7c‐3p to the 3′‐untranslated region (UTR) of PIK3CA. In vivo, an A549 cell xenograft mouse model was used to verify the effect of ANW on tumor growth. Results: The results showed that ANW treatment (20 or 50 μM) had obvious cytotoxicity against A549 and H460 cells, suppressing cell proliferation and migration in vitro. In vivo, the growth of the implanted tumor was inhibited by ANW in a nude mouse model. The growth of NSCLC cells was also inhibited by let‐7c‐3p overexpression in vitro and in vivo. The inhibitory effect of ANW on the proliferation and metastasis of NSCLC cells was weakened by the downregulation of let‐7c‐3p, whereas it was enhanced by the overexpression of let‐7c‐3p; PIK3CA was the main target of let‐7c‐3p. Conclusions: In summary, ANW inhibits the growth and metastasis of NSCLC cells in vivo and in vitro by upregulating the expression of let‐7c‐3p, which can regulate the PI3K/AKT/mTOR signaling pathway. PIK3CA is the main target of let‐7c‐3p. [ABSTRACT FROM AUTHOR]

Acute promyelocytic leukemia (APL) has become curable over 95% patients under a complete chemo-free treatment with all-trans retinoic acid (ATRA) and arsenic trioxide in low-risk patients. Minimizing chemotherapy has proven feasible in high-risk patients. We evaluated oral arsenic and ATRA without chemotherapy as an outpatient consolidation therapy and no maintenance for high-risk APL. We conducted a multicenter, single-arm, phase 2 study with consolidation phases. The consolidation therapy included Realgar–Indigo naturalis formula (60 mg/kg daily in an oral divided dose) in a 4-week-on and 4-week-off regimen for 4 cycles and ATRA (25 mg/m2 daily in an oral divided dose) in a 2-week-on and 2-week-off regimen for 7 cycles. The primary end point was the disease-free survival (DFS). Secondary end points included measurable resident disease, overall survival (OS), and safety. A total of 54 participants were enrolled at seven centers from May 2019. The median age was 40 years. At the median follow-up of 13.8 months (through April 2022), estimated 2-year DFS and OS were 94% and 100% in an intention-to-treat analysis. All the patients achieved complete molecular remission at the end of consolidation phase. Two patients relapsed after consolidation with a cumulative incidence of relapse of 6.2%. The majority of adverse events were grade 1–2, and only three grade 3 adverse events were observed. Oral arsenic plus ATRA without chemotherapy was active as a first-line consolidation therapy for high-risk APL. Trial registration: chictr.org.cn number, ChiCTR1900023309. [ABSTRACT FROM AUTHOR]

• Maackiain exerts potent anti-oxidant and anti-inflammatory capacities against sepsis-associated organ injury. • Activation of AMP-activated protein kinase (AMPK)/Nrf2/HO-1 pathway by MA contributes to its anti-oxidant and anti-inflammatory properties. • PRKAA1 is a potential pharmacological target of Maackiain. Sepsis is a life-threatening medical condition caused by infection-triggered aberrant immune responses, leading to host tissue and organ injury. Despite advances in medical interventions, the mortality rate for septic shock remains high. Recent studies highlight the role of oxidative stress in the occurrence and development of sepsis, providing a potential therapeutic target for preventing sepsis-associated organ injury. In this study, we showed that Maackiain, a natural compound isolated from Sophora flavescens , exerted a protective role in a cecal ligation and puncture (CLP)-induced murine model of sepsis. Maackiain treatment reduced organ injury, and mitigated systematic inflammation and oxidative stress in septic mice. Maackiain also reduced the levels of inflammatory cytokines and reactive oxygen species (ROS) in RAW264.7 macrophage cells stimulated with lipopolysaccharide (LPS). We further demonstrated that Maackiain initiated activation of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in RAW264.7 cells in an AMP-activated protein kinase (AMPK)-dependent way. Moreover, inhibition of AMPK/Nrf2 axis abrogated the anti-inflammatory and anti-oxidant effects of Maackiain both in vitro and in vivo. Collectively, our study indicates that Maackiain treatment inhibits inflammatory response and oxidative stress via activation of AMPK/Nrf2/HO-1 pathway, thus exerting a protective effect against sepsis, providing an alternative option for sepsis prevention. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to identify the incidence, sites and main pathogens, and risk factors for infectious complications occurring in patients with adult acute myeloid leukemia (AML) during the first course of venetoclax combined with decitabine or azacitidine. Methods: A retrospective cohort analysis was performed of 81 patients with AML older than 14 years who received the first cycle of venetoclax combined with a hypomethylating agent (HMA) between March 2018 and March 2021 at our institution. Infectious complications, if any, were documented. Results: Among a total of 81 cases of AML, 59 (72.8%) patients occurred infections, including fever without an identifiable source (28.8%), clinically documented infections (40.7%), and microbiologically documented infections (30.5%). The most commonly isolated organism in culture was Candida albicans, followed by Klebsiella pneumonia, and Pseudomonas aeruginosa. The 4-week and 8-week mortality rates were 3.7% and 7.4%, respectively. In multivariate analysis, a high proportion of blasts in bone marrow, decreased hemoglobin level, and fever with or without a documented infection at baseline were significant independent risk factors for infectious complications. Conclusion: Compared with conventional chemotherapy, the incidence of infectious complications of venetoclax combined with decitabine or azacitidine significantly decreased. Pretreatment high leukemia burden and fever were independent risk factors for infections. [ABSTRACT FROM AUTHOR]

This paper addresses the significance of preprocessing big data collected during a tunnel boring machine (TBM) excavation before it is used for machine learning on various TBM performance predictions. The research work is based on two water diversion tunneling projects that cover 29.52 km and 17 051 boring cycles. It has been found that the penetration rate calculated from the raw measured penetration distances exhibits more random behavior owing to their percussive and vibratory behavior of the cutterhead. A moving average method to process the negative instantaneous velocities and a noise reduction filter to deal with signals with abnormal frequencies have been recommended. An index called the drilling efficiency index is introduced to assess the relationships between the mechanical parameters in a boring cycle, whose linear regression coefficient R2 is taken for a preliminary investigation of possible problems requiring preprocessing. The research work defines the irrelevant data whose errors are caused by human or mechanical mistakes, and therefore should be cleaned or amended. These irrelevant data can be divided into five categories: (1) premature cycles, (2) sensor defects, (3) mechanical defects, (4) human interruption, and (5) missing files. A program TBM-Processing has been coded for the recognition and classification of these categories. PDF books generated by the program have been uploaded at GitHub to encourage discussions, collaboration, and upgrading of the data processing work with our peers. [ABSTRACT FROM AUTHOR]

The slag is rich in reactive aluminosilicate components and can be combined with alkali solution to form a three-dimensional binder. However, the inherently heterogeneous nature of slag presents challenges to the standardization of alkali-activated product. The fundamental objective of this work is to understand differences of characteristics between slags obtained from different sources within China, including physical properties, chemical composition, microstructure, elemental distribution, mineral phases, chemical bonding, glass contents, together with the microstructures of glassy phase. A novel reactivity index concept to evaluate slag used in alkali activated materials was proposed using seven typical slags in China and validated it against nine data from literature, confirming its considerable effectiveness and usefulness in reactivity evaluations. The positive correlations were found between the reactivity index of slag and the strengths of alkaline-activated pastes prepared by different methods and this index optimizes the process of raw waste selection. [ABSTRACT FROM AUTHOR]

The popular paradigm of Pavlovian conditioned fear has been used to study learning and memory processes that mediate anxiety disorder. Fear extinction studies have often paired the conditioned stimulus (CS) and the unconditioned stimulus (US) on a subset of acquisition trials (partial reinforcement) to prolong extinction. However, there have been few studies on the effect of partial reinforcement and continuous reinforcement on fear generalization. To better understand the influence of the CS–US pairing rate on fear generalization, the experimenters used CSs paired with US at 50% (CS50), 75% (CS75), and 100% (CS100) during fear conditioning. A total of 66 participants, who were assigned at random to the different reinforcement rates, underwent fear acquisition and generalization tests on expectancy ratings and skin conductance responses. The continuous reinforcement group (CS100) showed a flatter generalization gradient, while the partial reinforcement groups (CS50, CS75) showed increased generalization magnitudes. These results suggest that the partial reinforcement extinction effect is related to threat intensity, whereas continuous reinforcement produces threat-sensitivity fear generalization, which has been used to explain the overgeneralization of fear. ● There are no significant differences among 50%, 75%, and 100% reinforcement in fear acquisition. ● Partial reinforcement led to stronger fear generalization. ● Continuous reinforcement led to a flatter generalization gradient. ● The intensity and uncertainty of threat affect fear generalization. [ABSTRACT FROM AUTHOR]

Objective: The dysregulation of ribosome biogenesis is associated with the progression of numerous tumors, including hepatocellular carcinoma (HCC). Small nucleolar RNAs (snoRNAs) regulate ribosome biogenesis by guiding the modification of ribosomal RNAs (rRNAs). However, the underlying mechanism of this process in HCC remains elusive. Methods: RNA immunoprecipitation and sequencing were used to analyze RNAs targeted by ribosome proteins. The biological functions of SNORA23 were examined in HCC cells and a xenograft mouse model. To elucidate the underlying mechanisms, the 2'-O-ribose methylation level of rRNAs was evaluated by qPCR, and the key proteins in the PI3K/Akt/mTOR pathway were detected using Western blot. Results: Twelve snoRNAs were found to co-exist in 4 cancer cell lines using RPS6 pull-down assays. SNORA23 was downregulated in HCC and correlated with the poor prognoses of HCC patients. SNORA23 inhibited the proliferation, migration, and invasion of HCC cells both in vitro and in vivo. We also found that SNORA23 regulated ribosome biogenesis by impairing 2'-O-ribose methylation of cytidine4506 of 28S rRNA. Furthermore, SNORA23, which is regulated by the PI3K/Akt/mTOR signaling pathway, significantly inhibited the phosphorylation of 4E binding protein 1. SNORA23 and rapamycin blocked the PI3K/AKT/mTOR signaling pathway and impaired HCC growth in vivo. Conclusions: SNORA23 exhibited antitumor effects in HCC and together with rapamycin, provided a promising therapeutic strategy for HCC treatment. [ABSTRACT FROM AUTHOR]

Background: Dendritic cells (DCs) play an essential role in the induction and regulation of immune responses, including the activation of effector T lymphocytes for the eradication of cancers. However, the tumor microenvironment (TME) often leads to DCs dysfunction due to their immature state. MicroRNA-155 (miR-155) has emerged as a typical multifunctional gene regulator associated with immune system development and immune cell activation and differentiation. Methods: In this study, a three-dimensional TME model that closely mimics the microenvironment of breast cancer was prepared. MiR-155 overexpression and control vectors were constructed using lentivirus. The relative expression of miR-155 was determined by qRT-PCR. Cell viability, antigen uptake and cell surface marker expression were analyzed by live-dead staining and flow cytometry. The migration ability of bone marrow-derived DCs (BMDCs) was qualified by transwell assay. A mixed lymphocyte culture assay was used to assess T cell-specific proliferation. Cytokine levels were determined by ELISA. Results: We found that the expression of miR-155 in DCs was inhibited by the TME. Furthermore, upregulation of miR-155 enhanced the migration ability, uptake of antigen and elevated the expression of the mature DCs markers CD80 and MHCII. More importantly, overexpression of miR-155 in DCs significantly induced T cell proliferation and IFN-γ and IL-2 secretion. Conclusion: MiR-155 is a potential molecular regulator that may improve the efficacy of DCs-based tumor immunotherapy. [ABSTRACT FROM AUTHOR]

Introdution. Calycosin, a major active component in Astragali radix, has antitumour and anti-inflammation properties, but its effects on PM 2.5-induced injury in vitro and in vivo have not been clarified. Methods. Phospho-AMP-activated protein kinase (p-AMPK) and AMP-activated protein kinase (AMPK) were detected by western blot. Immunofluorescence staining was used to validate changes in the levels of nuclear factor kappa B (NF-кB) p65 nuclear translocation. Mice were administered intraperitoneally with calycosin one hour before anaesthesia and endotracheal instillation of PM 2.5. The extent of lung injury was evaluated in the H&E-stained lung sections. Apoptotic cells were detected by TUNEL staining. Results. Administration of calycosin was increased in PM 2.5-treated B2B cells in a dose-dependent manner in vitro. Fluorescence signals from anti-NF-кB p65 were increased in nuclei of cells pretreated with calycosin. The level of p-AMPK was increased by calycosin in vitro and in vivo. After pretreatment with compound C, the inhibitory effects of calycosin on cytotoxicity, levels of inflammatory cytokines and p-AMPK, and levels of NF-кB p65 nuclear translocation were not significantly decreased in vitro or in vivo. Conclusions. Calycosin effectively decreased the release of inflammatory cytokines and alleviated injury caused by PM 2.5. These effects were mediated through activation of AMPK to suppress NF-κB signalling. [ABSTRACT FROM AUTHOR]

Accurate prediction of lithium‐ion battery remaining useful life (RUL) is of great significance for battery health management. Particle filter (PF) is used to predict the RUL effectively, but it suffers from particle degeneracy and impoverishment during the estimation. To solve this problem, this paper proposes a new RUL prediction model based on improved mutated particle filter (IMPF) approach. In the IMPF algorithm, the mutant particles are generated from the prior particles, which not only represent the high probability region but also accelerate the convergence speed of particles. Then an improved polynomial resampling algorithm is proposed to avoid the loss of particle diversity during the resampling process. The simulation results on benchmark function demonstrate the effectiveness of the proposed IMPF algorithm. The method is also applied successfully to a battery capacity degradation data set provided by NASA Ames Research Center. Research results show that the proposed RUL prediction approach has better performance than other related PF techniques. [ABSTRACT FROM AUTHOR]

Objectives. With the development of proteomics, it has been indicated that differentially expressed proteins are biological markers for the diagnosis of different types of pleural effusion (PE). The aim of our study was to explore the value of sMerTK (soluble form of Mer tyrosine kinase) in the differential diagnosis of tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE). In addition, we also wanted to explore whether MerTK was associated with IL-1β and TNF-α, which are inflammatory factors related to pleural effusion. Methods. We screened all patients who underwent thoracoscopy and had a definite diagnosis. In total, 136 patients were enrolled in this study and classified into two groups, with 64 patients in the TPE group and 72 patients in the MPE group. The concentrations of sMerTK in the TPE and MPE groups were detected by ELISA. The diagnostic accuracy was determined by generating receiver operating characteristic (ROC) curves and calculating the area under the curve (AUC). Correlations between the expression level of sMerTK and those of the inflammatory factors interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) were also studied using Pearson's linear correlation analysis. Results. The concentrations of sMerTK were 5,278.77 ± 2,479.98 ng / L and 859.91 ± 540.45 ng / L in the TPE and MPE groups, respectively. The concentration of sMerTK in TPE was shown to be significantly higher than that in MPE (P < 0.05). The area under the ROC curve for sMerTK in distinguishing TPE from MPE was 0.958, with a cutoff value of 2,122 ng/L. The sensitivity and specificity for sMerTK were 98.61% and 90.63% (P < 0.05). The expression levels of sMerTK in these two groups were not correlated with those of the inflammatory factors IL-1β and TNF-α (P > 0.05). Conclusions. The expression level of sMerTK in PE could be a potential biomarker for common use in the diagnosis of TPE and MPE. [ABSTRACT FROM AUTHOR]

The development of one-part geopolymer mortars has greater potential than the traditional two-part mortars, especially in repair applications, to convert waste into useful beneficial products while simultaneously eliminating the hazards associated with the alkaline solutions. Nevertheless, the inherent brittleness exhibited by the one-part geopolymers displays drawbacks like OPC when subjected to flexural loading. The fibers selection as well as their strengthening effects from literature is considerably scarce, especially for the repairing geopolymer system. This work aims to investigate the influences of fiber types and volume fractions on the workability, physical behavior, and cracking/fatigue resistance of ambient air-cured one-part geopolymer mortar. Reaction kinetics, mineralogical phases, and elemental components were explored by means of the TAM, quantitative XRD, and EDS mapping analysis. The FESEM and X-CT were employed to compare the microstructures and pore characteristics of the fibers-reinforced products. The results show that the copper-plated steel fiber produced the least change in workability, while the basalt fiber produced the lowest flow values. Setting time was the shortest for the basalt fiber reinforced, followed by polyvinyl-alcohol fiber. The steel fiber and carbon fiber would improve the mechanical properties of mortar significantly, especially in the early stage. The fatigue strength of 1 vol% carbon fiber reinforced mortar under 2 million cycles loading was the highest (3.72 MPa). The fibers addition a substantial decrease in sphericity and compactness of the pores (high anisotropy) as evidenced by X-CT data. Moreover, three hydration heat processes occurred after water was added to the one-part geopolymer mortar, which included dissolution of Na 2 SiO 3 particles, network degradation, and a second pozzolanic reaction. More crystalline formation occurred over curing time to form gel networks with high stability and generated different bonding modes with various fibers. • Geopolymer powder could produce ambient-cured one-part GPMs by mixing with water. • Effects of micro-fiber type and volume fraction on the one-partGPMs were investigated. • Workability, strength properties, cracking/fatigue resistance were measured. • Geopolymerization and fiber bonding of GPMs were analyzed using TAM, FESEM, EDS, QXRD and X-CT. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs or miRs) regulate gene expression at the posttranscriptional level and are involved in many biological processes such as cell proliferation and migration, stem cell differentiation, inflammation, and apoptosis. In particular, miR-144-3p is downregulated in various cancers, and its overexpression inhibits the proliferation and metastasis of cancer cells. However, the role of miR-144-5p in non-small-cell lung cancer (NSCLC), especially radiosensitivity, is unknown. In this study, we found that miR-144-5p was downregulated in NSCLC clinical specimens as well as NSCLC cell lines exposed to radiation. Enhanced expression of miR-144-5p promoted the radiosensitivity of NSCLC cells in vitro and A549 cell mouse xenografts in vivo. Furthermore, we identified activating transcription factor 2 (ATF2) as the direct and functional target of miR-144-5p using integrated bioinformatics analysis and a luciferase reporter assay. In addition, restoration of ATF2 expression inhibited miR-144-5p-induced NSCLC cell sensitivity to radiation in vitro and in vivo. Our findings suggest that deregulation of the miR-144-5p/ATF2 axis plays an important role in NSCLC cell radiosensitivity, thus representing a new potential therapeutic target for NSCLC. [ABSTRACT FROM AUTHOR]

• The scale of fluctuation for surface chloride content under varying exposure zone on marine structure. • The modified spatiotemporal kriging interpolation method to re-establish the non-uniform spatiotemporal correlation distance. • The optimal strategy to improve the cost benefit ratio of surface chloride content detection on RC structures. Chloride-induced corrosion of marine reinforced concrete structures involves numerous uncertainties related to environmental exposure zone. The exposure zone is strongly correlated with surface chloride content, which exhibits significant spatiotemporal variability. In this study, the scale of fluctuation of the chloride content in different exposure zones was estimated to explore the effect of the exposure zone on the spatial variability of the marine chloride environment. Based on the detection data of surface chloride content over a time span of 18 years at Zhapu Port, we present a modified spatiotemporal Kriging interpolation method that extends interpolation from 2D plane to 3D space by replacing surface distance with the Euclidean distance. The chloride environmental spatiotemporal distance field model was constructed using the particle swarm optimization algorithm. The results show that the prediction of surface chloride content is physically more realistic when modified spatiotemporal Kriging is used with the spatiotemporal distance amplified by 2–3 times. Additionally, a method to optimise the location of the detection point is proposed, which can improve the cost–benefit ratio of surface chloride content detection on reinforced concrete structures by 37.5%. [ABSTRACT FROM AUTHOR]

Abstracts MBP (maltose-binding protein) is a component of Escherichia coli . Our previous study found that MBP directly induces the activation of Th1 (T helper type 1), but the molecular mechanism remains unclear. In the present study, CD4 + T cells were purified from the spleens of normal mice using antibody-coated immunomagnetic beads by negative selection. CD4 + T cells activated with a CD3/CD28 antibody were stimulated with MBP. The results indicated that MBP elevated IFN-γ mRNA levels in activated CD4 + T cells and promoted IFN-γ production from activated CD4 + T cells. To explore TLR2/TLR4 signaling involved in the mechanism of MBP-induced activation of Th1, we further detected downstream molecules of TLR2/TLR4 signaling. We found that MBP increased the mRNA levels of MyD88, TRAF6, TRIF and TRAF3 expressed in CD4 + T cells. The results suggested that downstream molecules of TLR2/TLR4 signaling may be involved in MBP-induced activation of CD4 + T cells. Furthermore, MyD88, TRIF, TRAF3 and TRAF6 expressed in activated CD4 + T cells blocked with anti-TLR2 antibody or anti-TLR4 antibody followed by treatment with MBP were detected via RT-PCR and western blotting, respectively. MBP decreased the production of IFN-γ in CD4 + T cells in the presence of anti-TLR2, accompanied by the down-regulated expression of MyD88 and TRAF6. However, MBP increased the production of IFN-γ in CD4 + T cells in the presence of anti-TLR4 antibody accompanied by the up-regulated expression of MyD88 and the down-regulated expression of TRIF, TRAF6 and TRAF3. The results suggested that the MyD88-dependent pathway of TLR2 and TRIF-dependent pathway are involved in the mechanism of Th1 activation induced by MBP. Our study has contributed to the clarification of the molecular mechanism of MBP-induced activation of CD4 + T cells. [ABSTRACT FROM AUTHOR]

Reactivated fear memories may enter an unstable state that could be interrupted by behavioral interventions such as the retrieval-extinction procedure. Studies of pharmacological interventions have shown that retrieval cues are not necessarily an exact reduplication of initial conditioned stimuli (CSs); they can instead be abstract word cues. However, the effectiveness of using abstract reminder cues in behavioral intervention procedures remains unknown, as do the conditions under which they are effective. The typicality of CS and the abstraction level of reminders are also likely to be important in the paradigm but have not been investigated to date. Here, in three experiments (n = 107), we manipulate the fear conditioning process, including single CS–unconditioned stimulus (US) and multiple CS–US connections, as well as the CS typicality and abstraction level of reminder cues, to explore the conditions for adopting retrieval-extinction with abstract reminders. The results of Experiments 1 and 2 show that the abstract cue is ineffective for use as a reminder in the procedure; this is the case for single exemplar category learning and perceptual discriminative learning, independent of the typicality of CS+ or the abstraction level of reminder cues. Only the outcome of Experiment 3, which contains multiple CS–US connections, shows no indication of fear return. The limitations of the study and possible interpretations of the results are discussed. • Little evidence showed that abstract cues can be used as a reminder in the retrieval-extinction procedure. • The effect is independent of the typicality of CS+ or the abstraction level of reminders. • Multi-exemplar learning during fear conditioning may play a role in the process. • Limitations of this study make it difficult to draw firm conclusions from the findings. [ABSTRACT FROM AUTHOR]

Fear generalization refers to conditioned fear responses extending to related stimuli and fear overgeneralization is a key feature of pathological anxiety. Along with perception similarity, conceptual relations affect fear generalization. We investigated whether stimulus diversity–an important principle of category-based induction–influences fear generalization. Induction studies have shown that generalization from a premise involving diverse instances is stronger than that from non-diverse instances. We adopted this framework for fear learning and established two groups. The diverse group developed fear in response to diverse instances from one category, while the non-diverse group acquired fear of non-diverse instances from the same category. An effect of stimulus diversity was observed in shock-expectancy ratings, with the diverse group displaying higher fear generalization than the non-diverse group. We also tested whether intolerance of uncertainty (IU) might affect the difference in fear generalization between the two conditions. Individuals with higher IU showed reduced difference in fear generalization between two conditions, mainly driven by heightened fear generalization to novel stimulus with ambiguous threat levels in the non-diverse condition. This study helps illustrate the mechanisms behind differential category-based fear generalization and provides a potential explanation for why higher IU individuals may develop anxiety disorders following trauma. • This study verifies a stimulus diversity effect in fear generalization. • Higher intolerance of uncertainty (IU) was associated with heightened fear after trained with non-diverse category stimuli. • Different traumatic experiences might account for individual differences in conceptual fear generalization response. • Individuals with higher IU may exhibit excessive fear of events after exposure to non-diverse traumatic events. [ABSTRACT FROM AUTHOR]

The cement manufacturing industry, a resource- and energy-intensive sector, took up more than 15% of total greenhouse gas emissions in China, thus finding a clean technology option for sustainable development is essential. CO 2 curing has emerged as a promising novel method for large-scale carbon sequestration and mechanical properties improvement of cement-based composites. Currently, a body of related works is mainly investigated in the laboratory, and understandings of the behaviors of CO 2 -cured cement-based composites are still less than complete, including, 1) the CO 2 storage potential has plenty of room for improvement due to the influence mechanism of variables factors remains unclear; 2) previous evaluations were mostly based on the subsets of individual result rather than an integrated dataset; 3) whether CO 2 curing is suitable for the manufacturing process of reinforced concrete. Therefore, this paper presents a comprehensive overview covering a wide range of parameters as well as fabrication, mechanical (compressive strength), and environmental (CO 2 uptake value) performances on the basis of a correct understanding of the differences between active and passive carbonation reactions. Notably, the influences of critical factors, including those less understood, e.g., types of curing setup (flow-able, enclosed, and others), components of binder, and aggregate/binder ratio, are also analyzed and the corresponding mechanisms discussed to achieve satisfied curing efficiency. Besides, corrosion-related challenges are also be pointed out to convince the widespread acceptance of this technology. Finally, based on this paper, limitations of existing research are identified and future scope on CO 2 curing regime is proposed. • 170 studies related to CO 2 /carbonation-cured cement-based composites are analyzed. • The differences between active/passive-carbonation together with reaction mechanisms are expounded. • Fabrication and influence factors on engineering and environmental properties are systematically reviewed. • CO 2 -cured cement-based composites exhibit excellent resistance to aggressive conditions. • The challenges and opportunities in the CO 2 curing method are innovatively discussed. [ABSTRACT FROM AUTHOR]

The European (EU) type of porcine reproductive and respiratory syndrome virus (PRRSV) has recently emerged in China. In this study, three recombinant DNA vaccines, pVAX1-EU-ORF3-ORF5 (coexpressing EU type PRRSV GP3 and GP5), pVAX1-EU-ORF3 and pVAX1-EU-ORF5, were constructed and evaluated for their abilities to induce humoral and cellular responses as well as to protect piglets against homologous virus challenge. All piglets were given booster vaccinations at 21 days after the initial inoculation and then challenged 14 days later. Pigs inoculated with pVAX1-EU-ORF3-ORF5 developed significantly higher (P < 0.05) PRRSV-specific antibody responses, neutralizing antibodies and levels of IL-4 and IL-10 than those given pVAX1-EU-ORF3, pVAX1-EU-ORF5 or pVAX1. Moreover, pigs immunized with pVAX1-EU-ORF3-ORF5 had markedly increased levels of IFN-γ and IL-2 in serum and T-lymphocytes (CD3+CD4+ and CD3+CD8+ T cells) in peripheral blood. Thus, EU-type PRRSV GP3 and GP5 proteins demonstrated good immunogenicity and reactogenicity and could induce cellular immunity in pigs. Following challenge with the Lelystad virus (LV) strain, piglets inoculated with pVAX1-EU-ORF3-ORF5 showed viremia and virus load distributed in organ tissues that were significantly lower (P < 0.05) than those in the pVAX1-EU-ORF3 group and control group, and slightly lower than those in the pVAX1-EU-ORF5 group (P > 0.05). As GP3 could enhance humoral- and cell-mediated immune responses to GP5, the results of this study suggested that these two proteins delivered by a vaccine can synergistically induce immunity against PRRSV. [ABSTRACT FROM AUTHOR]

[Display omitted] • Bixin treatment significantly reduces the airway inflammatory response, as well as improves the airway hyperresponsiveness in a murine asthma model mimicking an acute asthma attack in human. • Bixin treatment ameliorates chronic airway inflammation and AHR, as well as prevents airway remodeling in a chronic asthmatic mouse model. In vitro experiments indicated that Bixin suppressed the epithelial mesenchymal transition induced by TGF-β. • In addition, we found that administration of Bixin also restored the steroids sensitivity in a mouse asthma model resistance to the glucocorticoids treatment. • We demonstrate that Bixin functions to inhibit PI3K/Akt activation. The inhibitory capacity of Bixin on PI3K/Akt activation may contribute to the protective effects of Bixin in murine asthma models. Accumulating evidence has implicated the potential of natural compounds in treatment of asthma. Bixin is a natural food coloring isolated from the seeds of Bixa Orellana , which possesses anti-tumor, anti-inflammatory and antioxidative properties. Nevertheless, its therapeutic effect in asthma has not been elucidated. Our present study demonstrated that administration of Bixin suppressed allergic airway inflammation and reversed glucocorticoids resistance, as well as alleviated airway remodeling and airway hyperresponsiveness (AHR) in asthmatic mice. In vitro studies showed that Bixin treatment could inhibit the development of epithelial-mesenchymal transition (EMT) mediated by transforming growth factor beta (TGF-β) signaling. Importantly, Bixin antagonized activation of phosphatidylinositol 3–kinase/protein kinase B (PI3K/Akt) pathway both in vitro and in vivo. Above all, our findings reveal that Bixin functions as a potent antagonist of PI3K/Akt signaling to protect against allergic asthma, highlighting a novel strategy for asthma treatment based on natural products. [ABSTRACT FROM AUTHOR]

• The anti-MSLN CAR exosomes maintain most characteristics of the parental T cells. • The CAR exosomes significantly inhibited the growth of MSLN-positive TNBC cells. • The CAR exosomes killing target by secreting perforin and granzyme B. • The CAR exosomes treatment shown effective TGI without obvious side effects in vivo. Genetically engineered T cells expressing a chimeric antigen receptor (CAR) have rapidly developed into a powerful and innovative therapeutic modality for cancer patients. However, the problem of dose-dependent systemic toxicity cannot be ignored. In this study, exosomes derived from mesothelin (MSLN)-targeted CAR-T cells were isolated, and we found that they maintain most characteristics of the parental T cells, including surface expression of the CARs and CD3. Furthermore, CAR-carrying exosomes significantly inhibited the growth of both endogenous and exogenous MSLN-positive triple-negative breast cancer (TNBC) cells. The expression of the effector molecules perforin and granzyme B may be a mechanism of tumor killing. More importantly, a highly effective tumor inhibition rate without obvious side effects was observed with the administration of CAR-T cell exosomes in vivo. Thus, the use of CAR-T cell exosomes has great therapeutic potential against MSLN-expressing TNBC. [ABSTRACT FROM AUTHOR]

Sulfide-based composite solid-state electrolyte has been deemed as "Holy Grail" for unlocking solid-state lithium metal batteries (SSLMBs) with high-energy density, combining the extremely high ionic conductivity of sulfide and machinability of organic polymer. However, this appealing system is hitherto stymied by two hindrances, difficult to synthesize due to the chemical incompatibility of sulfide with moisture and polar solvents, moreover, interfacial instability with lithium (Li) anode inducing severe Li dendrite grown. Herein, by utilizing perfluoropolyethers as bifunctional adjuvant, we initiatively fabricate sulfide-based composite electrolyte, Poly (vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP)/Li 10 GeP 2 S 12 and assemble SSLMBs. Perfluoropolyethers with low molecular weight facilitate the stable dispersion of Li 10 GeP 2 S 12 in casting solution, ascribed to their strong electronegativity of C–F bonds. In addition, high molecular weight perfluoropolyethers function as interfacial stabilizer, dramatically improving the interfacial compatibility with Li anode by in-situ forming a LiF-rich solid electrolyte interphase layer. This composite electrolyte exhibits high room temperature ionic conductivity (0.18 mS cm−1), outstanding lithium ion transfer number (0.68), good mechanical strength and nonflammability. The solid-state LiFePO 4 ǁLi battery presents superior long-term cycling stability and rate capability. Our study paves a new way for fabricating the sulfide-based composite electrolyte, provides an effective strategy for constructing compatible solid-state electrolyteǁLi interface. Image 1 • PVDF-HFP/Li 10 GeP 2 S 12 electrolyte is prepared by binary solution casting method. • PFPE 500 as dispersing solvents exhibit good chemical compatibility with Li 10 GeP 2 S 12. • A high ion conductivity (σ RT = 10−4 S cm−1) and Li+ transfer number (0.68) are obtained. • PFPEs as interfacial stabilizers enhance the compatibility of Li 10 GeP 2 S 12 with Li. • LiFePO 4 ‖Li battery shows good cycling stability and rate capability. [ABSTRACT FROM AUTHOR]

Sepsis, a frequently fatal condition, emerges from an exaggerated inflammatory response to infection, resulting in multi-organ dysfunction and alarmingly high mortality rates. Despite the urgent need for effective treatments, current therapeutic options remain limited to antibiotics, with no other efficacious alternatives available. Echinatin (Ecn), a potent bioactive compound extracted from the roots and rhizomes of licorice, has gained significant attention for its broad pharmacological properties, particularly its ability to combat oxidative stress. Recent research highlights the crucial role that oxidative stress plays in the onset and progression of sepsis further emphasizing the potential therapeutic value of Ecn in this context. In this study, we explored the protective effects of Ecn in a murine model of sepsis induced by cecal ligation and puncture (CLP). Ecn demonstrated a significant reduction in the levels of inflammatory cytokines and reactive oxygen species (ROS) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Network pharmacology analysis identified 41 targets and top 15 pathways involved in the Ecn-mediated signaling network, revealing that Ecn might exert its effects through key targets including the NF-κB and MAPK signaling pathways. Molecular docking studies suggested a strong affinity between Ecn and MEK, with kinetic simulations and binding energy calculations confirming a stable interaction. Mechanistically, Ecn treatment inhibited NF-κB and the MEK/ERK signaling pathway, as evidenced by decreased phosphorylation of IκBα and nuclear p65, along with reduced phosphorylation of MEK and ERK in both LPS-stimulated RAW 264.7 macrophages and septic mice. Furthermore, the administration of MEK signaling agonists reversed the anti-inflammatory effects of Ecn, indicating the involvement of this signaling pathway in Ecn's protective mechanism. Notably, our investigation revealed that Ecn did not affect bacterial proliferation either in vivo or in vitro, underscoring its specific immunomodulatory effects rather than direct antimicrobial activity. In summation, our findings underscored the potential of Ecn as an innovative therapeutic remedy for sepsis-induced injury, particularly through the regulation of the NF-κB and MEK/ERK signaling pathway. This exploration unveiled a promising therapeutic approach for treating sepsis, supplementing existing interventions and addressing their constraints., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Streptococcus suis type 2 (SS2) is a zoonotic pathogen capable of eliciting meningitis, presenting significant challenges to both the swine industry and public health. Suilysin (Sly), one of SS2 most potent virulence determinants, releases a surfeit of inflammatory agents following red blood cell lysis. Notably, while current research on Sly role in SS2-induced meningitis predominantly centers on its interaction with the blood-brain barrier (BBB), the repercussions of Sly hemolytic products on BBB function have largely been sidestepped. In this vein, our study delves into the ramifications of Sly-induced hemolysis on BBB integrity. We discern that Sly hemolytic derivatives exacerbate the permeability of Sly-induced in vitro BBB models. Within these Sly hemolytic products, Interleukin-33 (IL-33) disrupts the expression and distribution of Claudin-5 in brain microvascular endothelial cells, facilitating the release of Interleukin-6 (IL-6) and Interleukin-8 (IL-8), thereby amplifying BBB permeability. Preliminary mechanistic insights suggest that IL-33-driven expression of IL-6 and IL-8 is orchestrated by the p38-mitogen-activated protein kinase signaling, whereas matrix metalloproteinase 9 mediates IL-33-induced suppression of Claudin-5. To validate these in vitro findings, an SS2-infected mouse model was established, and upon intravenous administration of growth stimulation expressed gene 2 (ST2) antibodies, in vivo results further underscored the pivotal role of the IL-33/ST2 axis during SS2 cerebral invasion. In summation, this study pioneerly illuminates the involvement of Sly hemolytic products in SS2-mediated BBB compromise and spotlights the instrumental role and primary mechanism of IL-33 therein. These insights enrich our comprehension of SS2 meningitis pathogenesis, laying pivotal groundwork for therapeutic advancements against SS2-induced meningitis.IMPORTANCEThe treatment of meningitis caused by Streptococcus suis type 2 (SS2) has always been a clinical challenge. Elucidating the molecular mechanisms by which SS2 breaches the blood-brain barrier (BBB) is crucial for the development of meningitis therapeutics. Suilysin (Sly) is one of the most important virulence factors of SS2, which can quickly lyse red blood cells and release large amounts of damage-associated molecular patterns, such as hemoglobin, IL-33, cyclophilin A, and so on. However, the impact of these hemolytic products on the function of BBB is unknown and ignored. This study is the first to investigate the effect of Sly hemolytic products on BBB function. The data are crucial for the study of the pathogenesis of SS2 meningitis and can provide an important reference for the development of meningitis therapeutics., Competing Interests: The authors declare no conflict of interest.