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To resolve the issue of predicting the leak rate in proton exchange membrane fuel cells (PEMFCs) under long-term random vibration conditions. Considering the mechanism of bolt vibration loosening and rubber vibration relaxation, a leakage mechanism model of the PEMFC sealing structure under vibration conditions is proposed, and the validity of the model is verified by experimental comparison. The model clearly reveals the quantitative effects of structural parameters and material parameters on the leakage rate of PEMFC under vibration conditions. The research results show that under long-term random vibration conditions, the change of PEMFC leakage rate with time is mainly divided into three stages: response stage, stable stage, and leakage stage. Compared to bolt vibration loosening, the rubber vibration relaxation has a more significant impact on PEMFC leakage, the leakage rate of the fuel cell stack is 433ppm after 10,000 hrs of vibration. In addition, increasing the bolt preload, changing the bolt distribution, reducing surface roughness, and reducing gasket thickness can effectively suppress PEMFC leakage under random vibration conditions, the minimum leakage rate of the fuel cell stack can be reduced to around 170ppm per 10,000 hours. The proposed mechanism model provides an effective method for predicting the leakage rate of PEMFC sealing structures. [ABSTRACT FROM AUTHOR]

Metastasis is a crucial stage in tumour progression, and cancer‐associated fibroblasts (CAFs) support metastasis through their participation in extracellular matrix (ECM) stiffness. CD248 is a possible biomarker for non‐small cell lung cancer (NSCLC)‐derived CAFs, but its role in mediating ECM stiffness to promote NSCLC metastasis is unknown. We investigated the significance of CD248+ CAFs in activating the Hippo axis and promoting connective tissue growth factor (CTGF) expression, which affects the stromal collagen I environment and improves ECM stiffness, thereby facilitating NSCLC metastasis. In this study, we found that higher levels of CD248 in CAFs induced the formation of collagen I, which in turn increased extracellular matrix stiffness, thereby enabling NSCLC cell infiltration and migration. Hippo axis activation by CD248+ CAFs induces CTGF expression, which facilitates the formation of the collagen I milieu in the stromal matrix. In a tumour lung metastasis model utilizing fibroblast‐specific CD248 gene knockout mice, CD248 gene knockout mice showed a significantly reduced ability to develop tumour lung metastasis compared to that of WT mice. Our findings demonstrate that CD248+ CAFs activate the Hippo pathway, thereby inducing CTGF expression, which in turn facilitates the collagen I milieu of the stromal matrix, which promotes NSCLC metastasis. [ABSTRACT FROM AUTHOR]

This study used the two-dimensional fluid volume method to investigate the effect of vibration on the detachment and removal of droplets in the two-dimensional/three-dimensional flow channel of proton exchange membrane fuel cell (PEMFC). The vibration frequency was used as the main variable to study the dynamic process of droplets in the channel, and typical droplet flow modes and separation methods were determined. The water removal ability of the two-dimensional/three-dimensional flow channel under vibration conditions was evaluated using droplet breakage time and coverage rate as evaluation indicators. Finally, the orthogonal table method was used to analyze the effects of vibration frequency, vibration amplitude, wind speed, and droplet size on the water removal ability of the three-dimensional flow field. The results indicate that under vibration conditions, the main motion modes of droplets are rolling mode and crushing mode and that the drainage capacity of the three-dimensional flow field is much higher than that of the two-dimensional flow field in both modes. The impact of vibration on the removal of droplets in the flow channel in the crushing mode is more significant compared to the rolling mode, and the vibration frequency has a greater impact on the drainage efficiency of the three-dimensional flow channel compared to the vibration amplitude. This study is of great significance for understanding the dynamics of droplets in PEMFC gas channels under vibration conditions as well as for optimizing the design and operating conditions of these channels. [ABSTRACT FROM AUTHOR]

Background. Nuclear Paraspeckle Assembly Transcript 1 (NEAT1) is commonly considered an oncogene in various cancers. The long noncoding RNA NEAT1 has been reported to be overexpressed in colorectal cancer (CRC). However, the exact role of NEAT1 in CRC remains unknown. Our research aimed to explore the function of NEAT1 in the tumorigenesis and the development of CRC. Methods. Real-time quantitative PCR (qRT-PCR) was used to detect the NEAT1, miR-216b, and YIN-YANG-1 (YY1) mRNA levels in CRC tissues and cells, then immunohistochemistry (IHC) was used to detect the expression of YY1 in CRC tissues. Luciferase reporter, qPCR, western blot, and DNA pulldown assays were conducted to study the relationships between NEAT1, miR-216b, and YY1. Flow cytometry analysis was performed for cell cycle and apoptosis analyses, and a colony formation assay was performed to test cell proliferation. Transwell assays were performed to detect cell invasion and migration. Results. The NEAT1 expression was significantly upregulated in CRC tissues compared with its expression in normal tissues, and downregulation of NEAT1 suppressed the proliferation, migration, and invasion of CRC cells. Moreover, we found NEAT1 decreased the miR-216b level directly, and the suppression of miR-216b could inhibit the function of downstream YY1. However, overexpression of YY1 accelerated CRC cell proliferation, migration, and invasion. Conclusion. Our results indicated that NEAT1 acted as an oncogene in CRC and promoted the progression of CRC by directly sponging miR-216 b expression to activate the expression of YY1. The NEAT1/miR-216b/YY1 axis may be a novel therapeutic target for CRC. [ABSTRACT FROM AUTHOR]

The traditional Chinese medicine (TCM)–Chaihu Shugan Formula (CSF), consisting of several Chinese botanical drugs like Bupleurum, is derived from the ancient Chinese pharmacopeia. It has been used for more than thousands of years in various suboptimal health statuses and diseases induced by chronic stress based on empirical therapy. Recent studies confirm the role of CSF in the development of many diseases, including depression, stress-induced hepatic injury and tumors. However, little has been known about the mechanisms behind the health effects of CSF. Here, we investigate the influence of CSF on the modulation of the simulated colonic microbiota of five healthy donors, gut barrier integrity, and intestinal immunity by combining the simulator of the human intestinal microbial ecosystem (SHIME®) technology platform with co-culture of intestinal and immune cells. This approach revealed that CSF stimulated the production of SCFA (acetate, propionate and butyrate) across donors while significantly lowering the production of branched SCFA (bSCFA). In terms of community composition, CSF stimulated a broad spectrum of health-related Bifidobacterium species, which are potent acetate and lactate producers. At the same time, it lowered the abundance of opportunistic pathogenic Escherichia coli. Later, we explore the effect of colonic fermentation of CSF on the gut barrier and intestinal immunity in the Caco-2/THP1-blue™ cell co-culture model. Based on the study using SHIME technology platform, CSF showed protective effects on inflammation-induced intestinal epithelial barrier disruption in all donors. Also, the treatment of CSF showed pronounced anti-inflammatory properties by strongly inducing anti-inflammatory cytokines IL-6 and IL-10 and reducing pro-inflammatory cytokine TNF-α. These findings demonstrate a significant modulatory effect of CSF on intestinal gut microbiota. CSF-microbial fermentation products improved the gut barrier and controlled intestinal inflammation. [ABSTRACT FROM AUTHOR]

African horse sickness (AHS) is an acute and subacute infectious disease of equine species caused by the African horse sickness virus (AHSV). The VP7 of AHSV is a group-specific protein conserved in all serotypes and is an excellent candidate for the serological diagnosis and an AHS vaccine component. However, to date, B-cell epitopes on the AHSV VP7 recognized by humoral immune responses remain unclear. This study expressed the recombinant AHSV VP7 soluble in Escherichia coli and purified it for mouse immunization. Four monoclonal antibodies (mAbs) were screened and identified by hybridoma cell fusion, clonal purification, and immunological assays. The B-cell epitopes, recognized by monoclonal antibodies 4B5, 3G10, 3D7, and 4D6, were identified by a series of truncated overlapping peptides expressed as glutathione S-transferase (GST)-fusion proteins. The results revealed that 4B5 recognized the 124VQTGRYAGA132 motif, 3G10 recognized the 140RYYVPQGRT148 motif, while 3D7 and 4D6 recognized the 292QPINPPIFP300 motif. Amino acid sequence alignment indicated that three novel B-cell epitopes were conserved among various AHSV serotypes but unconserved in other orbiviruses, such as the bluetongue and epidemic hemorrhagic disease viruses. This study informs on the antigenic epitopes of AHSV VP7, facilitating future investigations into the serological diagnosis method and epitope-based vaccines against AHSV. • Altering key amino acids at the C-terminus achieved soluble expression of AHSV. • VP7 protein in E. coli for the first time. • Hybridoma technology prepared four monoclonal antibodies specific to the AHSV VP7 protein. • Three new linear B cell epitopes of AHSV VP7 protein were originally mapped using monoclonal antibodies. • This study will facilitate future investigations into diagnosis and epitope-based vaccination against AHSV. [ABSTRACT FROM AUTHOR]

Optimizing the flow field structure is an important means to enhance gas transport and improve the proton exchange membrane fuel cell (PEMFC) performance. Based on the structural features of the spider-web, a three-dimensional multiphase flow model of the PEMFC with a spider-web biomimetic flow field (SWFF) was established firstly, and the influence of inlet and outlet positions on the performance of the PEMFC was investigated, then the cathode side catalytic layer (CL) oxygen utilization as an evaluation index based on the cluster model was proposed, which is used to investigate the effect of inlet and outlet positions on internal mass transfer and performance of PEMFC. Finally, the influence of different structural parameters on the performance of PEMFC with SWFF was investigated based on the orthogonal experimental design method. The results show that a reasonable arrangement of inlet and outlet positions can effectively increase the peak current density by 2.31% and reduce the pressure drop by 96.07% compared to a serpentine flow field. The placement of baffles at the intersection of the main channel and divergent channels can significantly improve the PEMFC performance. The results of the research provide a new evaluation index and a theoretical basis for the optimal design of flow field structures. • A spider-web bionic flow field was innovatively proposed. • Compared the performance of flow field at different inlet and outlet positions. • The oxygen utilization is introduced to verify the superiority of flow fields. • Studied the influence of different geometric parameters on current density. [ABSTRACT FROM AUTHOR]

Dietary fat intake is positively associated with elevated risk of colorectal cancer (CRC). Currently, clinical treatments remian inadequate bacause of the complex pathogenesis of CRC induced by a high-fat diet (HFD). Mechanistically, imbalances in gut microbiota are associated with HFD-associated colorectal tumourigenesis. Therefore, we investigated the anti-tumor activity of berberine (BBR) in modulating the dysregulated gut microbiota and related metabolites by preforming 16S rDNA sequencing and liquid chromatography/mass spectrometry. As expected, BBR treatment significantly decreased the number of colonic polyps, ameliorated gut barrier disruption, and inhibited colon inflammation and related oncogenic pathways in AOM/DSS-induced CRC model mice fed with an HFD. Furthermore, BBR alleviated gut microbiota dysbiosis and increased the abundance of beneficial gut microorganisms, including Akkermansia and Parabacteroides , in HFD-fed CRC mice. In addition, metabolomics analysis demonstrated significantly altered the glycerophospholipid metabolism during the progression of HFD-associated CRC in mice, whereas BBR treatment reverted these changes in glycerophospholipid metabolites, particularly lysophosphatidylcholine (LPC), which was confirmed to promote CRC cell proliferation and ameliorate cell junction impairment. Notably, BBR had no clear anti-tumor effects on HFD-fed CRC model mice with gut microbiota depletion, whereas transplantation of BBR-treated gut microbiota to gut microbiota-depleted CRC mice recapitulated the inhibitory effects of BBR on colorectal tumourigenesis and LPC levels. This study demonstrated that BBR inhibited HFD-associated CRC directly through modulating gut microbiota-regulated LPC levels, thereby providing a promising microbiota-modulating therapeutic strategy for the clinical prevention and treatment of Western diet-associated CRC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: To investigate the inhibitory effect of chrysanthemum extract on myocardial fibrosis in rats with renovascular hypertension, and explore the possible mechanism underlying this effect., Methods: Sixty Wistar rats were randomly divided into six groups: sham operation, model, positive control, and low-, medium-, and high-dose Huai chrysanthemum extract groups (ten rats per group). With the exception of the sham operation group, a renal hypertensive model was established in rats using the ""two-kidney, one clip"" method. After 6 weeks, low-, medium-, and high-dose groups were intragastrically administered chrysanthemum extract at 1, 2, or 4 g/kg, respectively, once daily for 4 weeks. The positive control group was administered Kato Pury at 50 mg/kg once daily for 4 weeks, while sham operation and model groups received an equal volume of distilled water once daily for 4 weeks. Blood pressure changes were examined before modeling, 6 weeks after modeling, and after 4 weeks of treatment administration. Ventricular remodeling indexes were measured by high frequency echocardiography after 4 weeks of treatment administration. Pathological changes were observed by hematoxylin and eosin, and Masson's trichrome staining methods. Collagen typeⅠ (Col Ⅰ) and type Ⅲ (Col Ⅲ) expression were examined by enzyme-linked immunosorbent assays. Transforming growth factor-β1 (TGF-β1), sma mad 3 (Smad3), Smad7, Ras homolog gene family, member A (RhoA), and Rho-associated protein kinase 1 (ROCK1) protein expression were detected by Western blot., Results: Compared with the model group, chrysanthemum-administered groups and the positive control group showed significant improvement of arterial blood pressure, echocardiography indicators, and degree of myocardial fibrosis (P < 0.05). In addition, these groups exhibited decreased expression of Col Ⅰ, Col Ⅲ, RhoA, ROCK1, TGF-β1, and Smad3, and increased Smad7 expression. Such improvements were most obvious in the high-dose chrysanthemum extract group (P < 0.05)., Conclusion: Chrysanthemum extract could effectively reduce myocardial fibrosis in rats with renovascular hypertension by a mechanism that potentially involves inhibition of RhoA/ROCK1 and TGF-β1/Smad signaling pathways.

Weaning is a critical period for the growth and development of mammals, in which various physiological and biochemical indicators of the body have undergone great changes. The development, differentiation, and maturation of the nervous system are regulated by many proteins. Changes in related proteins affect the physiological functions of the nervous system. However, the regulation of selfrenewal and differentiation of the nervous system at this stage is still poorly understood. The mechanism of differentiation and regulation of the major proteins in the nervous system during this special period of weaning remains to be investigated. Therefore, this paper aims to summarize the alteration of the nervous system during weaning and provide the basis for subsequent research., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)