Optimization of the quantitative protocol for organic acid in fecal samples using gas chromatography-mass spectrometry.

Organic acids (OAs) play important roles in a variety of intracellular metabolic pathways, such as the tricarboxylic acid cycle, fatty acid oxidation, glycolysis. The accurate detection of OAs in fecal samples was crucial for comprehending the metabolic changes associated with various metabolic disease. However, the analytical protocol detecting OAs profiling in feces have received scant attention. In this work, an optimized protocol based on chromatography-mass spectrometry for simultaneous quantification of 23 OAs in rat feces was developed. The optimal conditions involved using a 40-mg fecal sample mixed with isopropyl alcohol, acetonitrile, and deionized water (3:2:2 vol ratio) with a total volume of 1500 µL, followed by ultrasonic extraction and a derivatization reaction with an 80 µL derivative agent. The protocol showed an acceptable linearity (R2 ≥ 0.9906), the satisfactory precision (RSD% ≤ 14.87%), the low limits of detection (0.001 to 1 µg/mL) and the limit of quantification (0.005 to 1.5 µg/mL). Moreover, the dried residues of the extracted solution showed the better stability of OAs at -20 °C, which was more suitable for a large-scale sample analysis. Finally, the developed protocol was successfully applied to compare the difference of OAs profiling in fecal samples harvested from normal and nonalcoholic fatty liver disease rats, which was beneficial to find out the metabolic change of OAs profiling and explain the related mechanism of the disease.

Enhanced water resistance mechanism in Ag-Hollandite for catalytic ozone decomposition.

Catalytic ozone (O3) decomposition at ambient temperature is an efficient method to mitigate O3 pollution. However, practical application is hindered by the poor water resistance of catalysts. Herein, Ag-Hollandite (Ag-HMO) with varying Ag+ content was synthesized. Catalysts with more Ag+ exhibited improved efficiency and water-resistance, with the optimal one maintaining 98% O3 conversion at 70% relative humidity (RH) within 8 h. Physicochemical characterizations revealed that Ag+ had entered the tunnel of OMS-2, facilitating oxygen species removal. Notably, enhanced H2O desorption and the complete inhibition of chemisorbed water formation on Ag-HMO were the primary reasons for its high-efficiency O3 conversion across a wide humidity range. The underlying mechanism arises from the charge redistribution induced by the Ag-O interaction within the tunnel, which reduces acidity and modulates hydrophilicity. This study aims to contribute insights for designing catalysts with higher water-resistance.

Integrating Metabolomics and Network Pharmacology to Explore the Mechanism of Xiao-Yao-San in the Treatment of Inflammatory Response in CUMS Mice.

Depression can trigger an inflammatory response that affects the immune system, leading to the development of other diseases related to inflammation. Xiao-Yao-San (XYS) is a commonly used formula in clinical practice for treating depression. However, it remains unclear whether XYS has a modulating effect on the inflammatory response associated with depression. The objective of this study was to examine the role and mechanism of XYS in regulating the anti-inflammatory response in depression. A chronic unpredictable mild stress (CUMS) mouse model was established to evaluate the antidepressant inflammatory effects of XYS. Metabolomic assays and network pharmacology were utilized to analyze the pathways and targets associated with XYS in its antidepressant inflammatory effects. In addition, molecular docking, immunohistochemistry, Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR), and Western Blot were performed to verify the expression of relevant core targets. The results showed that XYS significantly improved depressive behavior and attenuated the inflammatory response in CUMS mice. Metabolomic analysis revealed the reversible modulation of 21 differential metabolites by XYS in treating depression-related inflammation. Through the combination of liquid chromatography and network pharmacology, we identified seven active ingredients and seven key genes. Furthermore, integrating the predictions from network pharmacology and the findings from metabolomic analysis, Vascular Endothelial Growth Factor A (VEGFA) and Peroxisome Proliferator-Activated Receptor-γ (PPARG) were identified as the core targets. Molecular docking and related molecular experiments confirmed these results. The present study employed metabolomics and network pharmacology analyses to provide evidence that XYS has the ability to alleviate the inflammatory response in depression through the modulation of multiple metabolic pathways and targets.

Self-Supporting Triphase Photocatalytic CO2 Reduction to CH3OH on Controllable Core-Shell Structure with Tunable Interfacial Wettability.

Enhancing the CO2 mass transfer and proton supply in the photocatalytic reduction of CO2 with H2O into CH3OH (PRC-M), while avoiding the hydrogen evolution reaction (HER), remains a challenge. Herein, we propose an approach to control the surface coverage of CO2 and H2O by modifying interfacial wettability, which is achieved by modulating the core-shell structure to expose either hydrophobic melamine-resorcinol-formaldehyde (MRF) or hydrophilic NiAl-layered double hydroxides (NAL). Characterizations reveal that an insufficient proton supply leads to the production of competing CO, while excessive coverage of H2O results in undesired HER. The NAL-MRF integrates hydrophobic and hydrophilic interfaces, contributing to the CO2 mass transfer and H2O adsorption, respectively. This combination forms a microreactor that facilitates the triphase photocatalysis of CO2, H2O, and catalyst, allowing for high local concentrations of both *CO and *H without competing binding sites. Importantly, the formation of covalent bonds and a Z-type heterojunction between hydrophilic NAL and hydrophobic MRF layers accelerates the charge separation. Furthermore, the density functional theory results indicate that the NAL linking promotes the continuous hydrogenation of *CO. As a result, an enhanced CH3OH yield of 31.41 µmol g-1 h-1, with selectivity of 93.62%, is achieved without hole scavengers or precious metals.

Alkyne-to-alkene conversion in graphdiyne driving instant reversible deformation of whole carbon film.

The emerging field of soft robotics demands the core actuators and related responsive functional materials with rapid responsiveness and controllable accurate deformation. Here, we developed an alkyne-to-alkene chemical bond conversion way as the driving force to control ultrasensitive and instant reversible deformation of 2D carbon graphdiyne (GDY) film with an asymmetric interface design. The alkyne-to-alkene chemical bond conversion was triggered by acetone through the fast binding and release process. The as-fabricated GDY-based deformation modulator was exhibited to rapidly change shape (within 0.15 seconds) while dipped in an acetone vapor atmosphere and recover to its original form when exposed to air (recovery time < 0.01 seconds), with outstanding properties like large curvature, quick recovery time, excellent stability, and repeatability. It could mimic the movement of mosquito larvae, displaying great promise as micro bionic soft robots. Our results suggest alkyne-to-alkene bond conversion as a unique driving force for developing smart materials for areas like intelligent robotics and bionics.

Paeoniflorin Coordinates Macrophage Polarization and Mitigates Liver Inflammation and Fibrogenesis by Targeting the NF-[Formula: see text]B/HIF-1α Pathway in CCl4-Induced Liver Fibrosis.

Liver fibrosis is a disease largely driven by resident and recruited macrophages. The phenotypic switch of hepatic macrophages can be achieved by chemo-attractants and cytokines. During a screening of plants traditionally used to treat liver diseases in China, paeoniflorin was identified as a potential drug that affects the polarization of macrophages. The aim of this study was to evaluate the therapeutic effects of paeoniflorin in an animal model of liver fibrosis and explore its underlying mechanisms. Liver fibrosis was induced in Wistar rats via an intraperitoneal injection of CCl4. In addition, the RAW264.7 macrophages were cultured in the presence of CoCl2 to simulate a hypoxic microenvironment of fibrotic livers in vitro. The modeled rats were treated daily with either paeoniflorin (100, 150, and 200[Formula: see text]mg/kg) or YC-1 (2[Formula: see text]mg/kg) for 8 weeks. Hepatic function, inflammation and fibrosis, activation of hepatic stellate cells (HSC), and extracellular matrix (ECM) deposition were assessed in the in vivo and in vitro models. The expression levels of M1 and M2 macrophage markers and the NF-[Formula: see text]B/HIF-1[Formula: see text] pathway factors were measured using standard assays. Paeoniflorin significantly alleviated hepatic inflammation and fibrosis, as well as hepatocyte necrosis in the CCl4-induced fibrosis model. Furthermore, paeoniflorin also inhibited HSC activation and reduced ECM deposition both in vivo and in vitro. Mechanistically, paeoniflorin restrained M1 macrophage polarization and induced M2 polarization in the fibrotic liver tissues as well as in the RAW264.7 cells grown under hypoxic conditions by inactivating the NF-[Formula: see text]B/HIF-1[Formula: see text] signaling pathway. In conclusion, paeoniflorin exerts its anti-inflammatory and anti-fibrotic effects in the liver by coordinating macrophage polarization through the NF-[Formula: see text]B/HIF-1[Formula: see text] pathway.

SNS alleviates depression-like behaviors in CUMS mice by regluating dendritic spines via NCOA4-mediated ferritinophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Depression is one of the most common mood disturbances worldwide. The Si-ni-san formula (SNS) is a famous classic Traditional Chinese Medicine (TCM) widely used to treat depression for thousands of years in clinics. However, the mechanism underlying the therapeutic effect of SNS in improving depression-like behaviors following chronic unpredictable mild stress (CUMS) remains unknown. AIM OF THE STUDY: This study aimed to investigate whether SNS alleviates depression-like behaviors in CUMS mice by regulating dendritic spines via NCOA4-mediated ferritinophagy in vitro and in vivo. STUDY DESIGN AND METHODS: In vivo, mice were exposed to CUMS for 42 days, and SNS (4.9, 9.8, 19.6 g/kg/d), fluoxetine (10 mg/kg/d), 3-methyladenine (3-MA) (30 mg/kg/d), rapamycin(1 mg/kg/d), and deferoxamine (DFO) (200 mg/kg/d) were conducted once daily during the last 3 weeks of the CUMS procedure. In vitro, a depressive model was established by culture of SH-SY5Y cells with corticosterone, followed by treatment with different concentrations of freeze-dried SNS (0.001, 0.01, 0.1 mg/mL) and rapamycin (10 nM), NCOA4-overexpression, Si-NCOA4. After the behavioral test (open-field test (OFT), sucrose preference test (SPT), forced swimming test (FST) and tail suspension test (TST), dendritic spines, GluR2 protein expression, iron concentration, and ferritinophagy-related protein levels (P62, FTH, NCOA4, LC3-II/LC3-I) were tested in vitro and in vivo using immunohistochemistry, golgi staining, immunofluorescence, and Western blot assays. Finally, HEK-293T cells were transfected by si-NCOA4 or GluR2-and NCOA4-overexpression plasmid and treated with corticosterone(100 µM), freeze-dried SNS(0.01 mg/mL), rapamycin(25 nM), and 3-MA(5 mM). The binding amount of GluR2, NCOA4, and LC3 was assessed by the co-immunoprecipitation (CO-IP) assay. RESULTS: 3-MA, SNS, and DFO promoted depressive-like behaviors in CUMS mice during OFT, SPT, FST and TST, improved the amount of the total, thin, mushroom spine density and enhanced GluR2 protein expression in the hippocampus. Meanwhile, treatment with SNS decreased iron concentrations and inhibited NCOA4-mediated ferritinophagy activation in vitro and in vivo. Importantly, 3-MA and SNS could prevent the binding of GluR2, NCOA4 and LC3 in corticosterone-treated HEK-293T, and rapamycin reversed this phenomenon after treatment with SNS. CONCLUSION: SNS alleviates depression-like behaviors in CUMS mice by regulating dendritic spines via NCOA4-mediated ferritinophagy.

Erratum: MicroRNA-30a-3p acts as a tumor suppressor in MHCC-97H hepatocellular carcinoma cells by targeting COX-2: Erratum.

[This corrects the article DOI: 10.7150/jca.52298.].

Variations in genetic diversity in cultivated Pistacia chinensis.

Identification of the evolution history and genetic diversity of a species is important in the utilization of novel genetic variation in this species, as well as for its conservation. Pistacia chinensis is an important biodiesel tree crop in China, due to the high oil content of its fruit. The aim of this study was to uncover the genetic structure of P. chinensis and to investigate the influence of intraspecific gene flow on the process of domestication and the diversification of varieties. We investigated the genetic structure of P. chinensis, as well as evolution and introgression in the subpopulations, through analysis of the plastid and nuclear genomes of 39 P. chinensis individuals from across China. High levels of variation were detected in the P. chinensis plastome, and 460 intraspecific polymorphic sites, 104 indels and three small inversions were identified. Phylogenetic analysis and population structure using the plastome dataset supported five clades of P. chinensis. Population structure analysis based on the nuclear SNPs showed two groups, clearly clustered together, and more than a third of the total individuals were classified as hybrids. Discordance between the plastid and nuclear genomes suggested that hybridization events may have occurred between highly divergent samples in the P. chinensis subclades. Most of the species in the P. chinensis subclade diverged between the late Miocene and the mid-Pliocene. The processes of domestication and cultivation have decreased the genetic diversity of P. chinensis. The extensive variability and structuring of the P. chinensis plastid together with the nuclear genomic variation detected in this study suggests that much unexploited genetic diversity is available for improvement in this recently domesticated species.

Effect of Nano-SiO2 Modification on Mechanical and Insulation Properties of Basalt Fiber Reinforced Composites.

Basalt fiber (BF) has high mechanical strength, good insulation performance and low cost. It is suitable to be used as reinforcement material in the manufacture of electrical equipment. However, the large surface inertia of basalt fiber makes it difficult to combine with the matrix material, which seriously limits its service life and application scenarios. In addition, the serious vacancy in the research of insulation properties also limits its production and application in the electrical field. Therefore, in order to solve the problem of difficult bonding between basalt fiber and resin matrix and make up for the research blank of basalt fiber composites in insulation performance, this paper provides a basalt fiber modification method-SiO2 coating, and tests the insulation and mechanical properties of the modified composite. We used nano-SiO2 coating solution to modify basalt fiber, and manufactured BF/resin composite (BFRP) by hand lay-up and hot-pressing technology, and experimentally analyzed the influence of nano-SiO2 content on the mechanical and insulation properties of the modified composite. Fourier transform infrared spectrum and scanning electron microscope analysis showed that nano-SiO2 was successfully coated on basalt fibers. Through the microdroplet debonding test, it was found that the IFSS of fiber/resin was improved by 35.15%, 72.97 and 18.9%, respectively, after the modification of the coating solution with SiO2 concentration of 0.5%, 1% and 1.5%, showing better interface properties; the single fiber tensile test found that the tensile strength of the modified fiber increased slightly. Among all composites, 1 wt% SiO2 coating modified composites showed the best comprehensive properties. The surface flashover voltage and breakdown field strength reached 13.12 kV and 33 kV/mm, respectively, which were 34.6% and 83% higher than unmodified composite. The dielectric loss is reduced to 1.43%, which is 33.8% lower than the dielectric loss (2.16%) of the untreated composite, showing better insulation ability; the tensile strength, bending strength and interlaminar shear strength were increased to 618.22 MPa, 834.74 MPa and 16.29 MPa, respectively, which were increased by 53%, 42.4% and 59.7%, compared with untreated composites. DMA and glass transition temperature showed that the modified composite had better heat resistance. TGA experiments showed that the resin content of the modified composite increased, and the internal structure of the composite became denser.

Mesenchymal stem cells derived from adipose tissue accelerate the progression of colon cancer by inducing a MTCAF phenotype via ICAM1/STAT3/AKT axis.

Previous studies have shown that the risk of colon cancer is greatly increased in people with obesity, and fat content in colorectal cancer tissue is increased in people with obesity. As an important part of tumor microenvironment, adipose-derived mesenchymal stem cells (MSCs) are also another important source of cancer-associated fibroblasts (CAFs), which may be one of the important mechanisms of affecting tumor progression. However, the mechanism is poorly defined. In the present study, CAFs were transformed from MSCs [MSC-transformed CAFs (MTCAFs)] by co-culturing with HCT116 cells. Bioinformatics and Western blotting analysis indicated a positive correlation between intercellular adhesion molecule-1(ICAM-1) and the progression of colon cancer. In clinical colon cancer specimens, we found that ICAM-1 was highly expressed and related to shorter disease-free survival, which might act as an indication for the progression of clinical colon cancer. Our data showed that ICAM-1 secreted from MTCAFs could positively promote the proliferation, migration, and invasion of colon cancer cells by activating signal transducer and activator of transcription 3 (STAT3) and Serine/threonine-protein kinase (AKT) signaling and that blocking ICAM-1 in MTCAFs reversed these effects. We further verified that ICAM-1 secreted from MTCAFs promoted tumor progression in vivo. Taken together, ICAM-1 plays a critical role in regulating tumor growth and metastasis, which could be a potential therapeutic target in colon cancer.

A multi-platform metabolomics reveals possible biomarkers for the early-stage esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent types of upper gastrointestinal malignancies. This work aimed to identify potential biomarkers for early screening for ESCC and characterize the systemic metabolic disturbances underlying ESCC using multi-platform metabolomics analysis. METHODS: We divided 239 patients (the early-stage ESCC patients, n = 132; Healthy controls, n = 107) into discovery and validation sets after matching age and sex. Integrated statistical and multi-platform serum metabolomics analyses were used to screen and validate significant metabolites linked to ESCC patients. RESULTS: Multi-platform metabolomics analyses showed that amino acid and lipid metabolism were crucial in the etiology of ESCC. Five metabolites, tryptophan (Trp), citrulline, l-carnitine, lysine, and acetyl-carnitine, were selected as potential biomarkers to establish a diagnosis panel, which showed high accuracy in distinguishing ESCC patients from healthy controls (area under the receiver operating characteristic curve, 0.873, 95% confidence interval [CI]: 0.825-0.925). CONCLUSIONS: This work laid the groundwork for understanding the etiology of ESCC. The diagnostic panel showed potential usefulness in early-stage ESCC diagnosis in clinical practice.

Mesenchymal stem cells derived from adipose accelerate the progression of colon cancer by inducing a MT-CAFs phenotype via TRPC3/NF-KB axis.

BACKGROUND: There is increasing evidence that mesenchymal stem cells (MSCs) help shape the tumor microenvironment and promote tumor progression, and ion channels might play a critical role in this process. The objective of the present study was to explore the function and mechanism of MT-CAFs on progression of colon cancer. METHODS: Here, a gene chip was used for a general analysis of gene expression changes in MSC-transformed CAF cells (MT-CAFs). Bioinformatic tool and western blot screened out the ion channel protein TRPC3 with significantly increased expression, and identify the function through two-photon microscope. The progression of cancer was detected via MTS, transwell and Wound Healing. ELISA deected the secretion of inflammation factors. TRPC3/NF-KB axis was identified by western blot and immunofluorescence. RESULTS: TRPC3 can caused calcium influx, which further activated the NF-KB signaling pathway. Knockdown or inhibition of TRPC3 in MSCs significantly reduced the activation of NF-KB, and decreased the growth, migration, and invasion of MT-CAFs. After TRPC3 knockdown, the ability of MT- CAFs to promote tumor migration and invasion was impaired. Conversely, the upregulation of TRPC3 expression in MT-CAFs had the opposite effect. In vivo, TRPC3 expressed on MSCs also contributed to the tumorigenesis and progression of cancer cells. In addition, the Oncomine and GEPIA databases showed that TRPC3 expression is higher in colon cancer tissues compared with normal colon tissues, and was positively correlated with the expression of the CAF genes alpha-smooth muscle (α-SMA/ACTA2) and fibroblast activation protein Alpha. The disease-free survival of patients with positive TRPC3 expression in MSCs was significantly shorter than those with negative expression. CONCLUSIONS: These results indicate that TRPC3 expressed on MT-CAFs plays a critical role in tumor progression via the NF-KB signaling pathway, and is correlated with poor prognosis in colon cancer patients. Therefore, TRPC3 may be a novel therapeutic target for the treatment of colon cancer.

A Review on Basalt Fiber Composites and Their Applications in Clean Energy Sector and Power Grids.

Basalt fiber (BF) has a high mechanical strength, excellent temperature resistance, good chemical stability, low energy consumption, and an environmentally friendly production process. In addition, BF-reinforced polymers (BFRPs) have good corrosion resistance and designability; thus, they meet the application requirements of electrical equipment, such as new conductors, insulating pull rods, and composite cross-arms. However, there are still a series of technical issues in the mass production of BF, and the stability of the products needs to be further improved. Therefore, the research on the production, modification, and application of BF is necessary. This paper discusses the chemical composition and production technology of BF, describes the morphology and properties of BF, summarizes the interface problems and modification methods of composites, and finally, introduces the application prospects of BF in the field of electrical materials, which is expected to provide a reference for the application and promotion of BFRP in the future.

Blending Modification of Alicyclic Resin and Bisphenol A Epoxy Resin to Enhance Salt Aging Resistance for Composite Core Rods.

In order to promote the application of composite insulators in coastal areas with high temperature, high humidity and high salt, it is of great importance to develop matrix resin with salt corrosion resistance for composite core rods. In this study, bisphenol A epoxy resin was modified by blending with alicyclic epoxy resin (2021P). Three different proportions of 2021P/DGEBA blend resins (0% 2021P/DGEBA, 10% 2021P/DGEBA and 20% 2021P/DGEBA) were prepared, and the high salt medium corrosion test was carried out. The physicochemical (FTIR, DMA, TGA) and electrical properties (dielectric loss, leakage current and breakdown field strength) of the blend resin before and after aging were tested and analyzed, and the optimal blend proportion was determined. The results showed that after salt aging, the Tg of 0% 2021P/DGEBA decreased to 122.99 °C, while the Tg of 10% 2021P/DGEBA reached 134.89 °C; The leakage current of 0% 2021P/DGEBA increased to 48.994 µA, while that of 10% 2021P/DGEBA only increased to 44.549 µA; The breakdown field strength of 0% 2021P/DGEBA dropped to 40.36 kv/mm, while that of 10% 2021P/DGEBA only dropped to 43.63 kv/mm. The introduction of 2021P enhanced the salt corrosion resistance of the blend resin, which could hinder the penetration, diffusion and erosion of external media (such as Na+, Cl-, H2O, etc.) to the matrix resin. The comprehensive properties of 10% 2021P/DGEBA blend system reached the best, which was better than other blending resins, showing great application potential.

Properties of Basalt Fiber Core Rods and Their Application in Composite Cross Arms of a Power Distribution Network.

As basalt fiber has better mechanical properties and stability than glass fiber, cross arms made of continuous basalt-fiber-reinforced epoxy matrix composites are capable of meeting the mechanical requirements in the event of typhoons and broken lines in coastal areas, mountainous areas and other special areas. In this paper, continuous basalt-fiber-reinforced epoxy matrix composites were used to fabricate the core rods and composite cross arms. The results verified that basalt fiber composite cross arms can meet the strict requirements of transmission lines in terms of quality and reliability. In addition to high electrical insulation performance, the flexural modulus and the flexural strength of basalt fiber core rods are 1.8 and 1.06 times those of glass fiber core rods, respectively. Basalt fiber core rods were found to be much better load-bearing components compared to glass fiber core rods. However, the leakage current and the result of scanning electron microscopy (SEM) analysis reveal that the interface bonding strength between basalt fibers and the matrix resin is weak. A 3D reconstruction of micro-CT indicates that the volume of pores inside basalt fiber core rods accounts for 0.0048% of the total volume, which is greater than the 0.0042% of glass fiber rods. Therefore, improving the interface bond between basalt fibers and the resin can further improve the properties of basalt fiber core rods.

Regorafenib Induces the Apoptosis of Gastrointestinal Cancer-Associated Fibroblasts by Inhibiting AKT Phosphorylation.

Cancer-associated fibroblasts (CAFs) are a key component of the tumor microenvironment and are essential for tumorigenesis and development. Regorafenib is a multikinase inhibitor that targets CAFs and suppresses tumor growth. In this study, we investigated the effects of regorafenib on gastrointestinal CAFs and the underlying molecular mechanisms. First, we established two in vivo tumor models, the cancer cell line HCT116 with and without mesenchymal stem cells (MSCs), and treated them with regorafenib. We found that application of regorafenib potently impaired tumor growth, an effect that was more pronounced in tumors with a high stromal ratio, thus demonstrating that regorafenib can inhibit CAF proliferation and induce CAF apoptosis in vivo. Moreover, we showed that regorafenib affected macrophage infiltration by reducing the proportion of CAFs in tumors. Second, we induced MSCs into CAFs with exosomes to establish an in vitro model. Then, we used 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt and flow cytometry to detect the effects of regorafenib on proliferation and apoptosis of CAFs and western blot to determine the expression level of apoptosis-related proteins. We found that regorafenib inhibited proliferation of CAFs and induced apoptosis in CAFs in vitro. Furthermore, western blot results showed that regorafenib downregulated the expression of B cell lymphoma-2 (Bcl-2) and concurrently upregulated the expression of Bcl-2-associated X (Bax), and regorafenib inhibited the phosphorylation pathway of AKT in CAFs. In conclusion, our results provide a model in which regorafenib induces CAF apoptosis by inhibiting the phosphorylation of AKT and regorafenib affects macrophage infiltration by reducing the proportion of CAFs in tumor tissues.

Research on External Insulation Characteristics of Composite Cross-Arm of 10 kV Distribution Network Based on Multi-Factor Aging.

With the application of the composite cross-arm in power systems, comprehensive anti-aging performance is a key factor to determine whether it can operate safely. In order to study the influence of the operating environment on the external insulation characteristics of composite cross-arms of distribution networks, various aging conditions such as voltage, rain, temperature, humidity, salt fog and ultraviolet light were simulated in a climate chamber based on the real operation conditions of the 10-kV composite cross-arm. A multi-factor aging test of composite cross-arms with two kinds of cross-section shapes (T-shaped and square) was carried out for 5000 h. The change trends of leakage current and flashover voltage of the composite cross-arms before and after aging were analyzed. Finally, the aging mechanism of the silicone rubber sheaths was analyzed to further explain the reasons for the change of external insulation performance of composite cross-arms. The results show that the leakage current rising rate of T-shaped and square composite cross-arms after aging increases significantly, and the minimum flashover voltage decreases to 58.3 kV and 49.502 kV, respectively. The results of FTIR, SEM and hydrophobic angle tests show that, after aging, the performance of the silicone rubber outer sheath material decreases in varying degrees. In general, UV aging has the greatest influence on the external insulation characteristics of composite cross arms. Generally speaking, after 5000 h of multi factor aging, although the external insulation characteristics of the 10-kV composite cross-arm decreases to a certain extent, there is still enough margin to meet the normal operation.

Ultrasensitive Pressure Sensor Sponge Using Liquid Metal Modulated Nitrogen-Doped Graphene Nanosheets.

Wearable pressure sensors are crucial for real-time monitoring of human activities and biomimetic robot status. Here, the ultrasensitive pressure sensor sponge is prepared by a facile method, realizing ultrasensitive pressure sensing for wearable health monitoring. Since the liquid metal in the sponge-skeleton structure under pressure is conducive to adjust the contact area with nitrogen-doped graphene nanosheets and thus facilitates the charge transfer at the interface, such sensors exhibit a fast response and recovery speed with the response/recovery time 0.41/0.12 s and a comprehensive response range with a sensitivity of up to 476 KPa-1. Notably, the liquid metal-based spongy pressure sensor can accurately monitor the human body's pulse, the pressure on the skin, throat swallowing, and other activities in real time, demonstrating a broad application prospect. Those results provide a convenient and low-cost way to fabricate easily perceptible pressure sensors, expanded the application potential of liquid metal-based composites for future electronic skin development.

Biejiajian Pill Promotes the Infiltration of CD8+ T Cells in Hepatocellular Carcinoma by Regulating the Expression of CCL5.

Tumor-infiltrating CD8+T lymphocytes are mostly associated with a favorable prognosis in numerous cancers, including hepatocellular carcinoma (HCC). Biejiajian Pill (BJJP) is a common type of traditional Chinese medicine that is widely used in the treatment of HCC in China. Previous studies showed that BJJP suppressed the growth of HCC cells both in vivo and in vitro, by exerting direct cytotoxic effects on tumor cells. The present study demonstrated that in addition to direct cytotoxicity, BJJP inhibits the growth of tumor cells by promoting the infiltration of CD8+T cells into the tumor in H22-bearing mice. Mechanistically, chemokine ligand 5 (CCL5) was identified as one of the most highly expressed chemokines by tumor cells in vivo after treatment with BJJP. Additionally, CCL5 was knocked down in H22 cells and the results showed that knockdown of the gene significantly impaired the infiltration of CD8+T cells in vivo. Furthermore, the effects of BJJP on human HCC cell lines were assessed in vitro. Similarly, cells treated with BJJP had higher expression of CCL5 mRNA, which was consistent with increased levels of CCL5 protein in human tumor cells. These findings provide new insights into the anticancer effects of BJJP, which regulated the expression of CCL5 and the infiltration of CD8+T cells. The results, therefore, suggest that BJJP has great potential application in clinical practice.