Background/Aims: The current study aimed to investigate the role by which fibronectin 1 (FN1) influences the cell cycle, senescence and apoptosis in human glioma cells through the PI3K/ AKT signaling ...pathway. Methods: Differentially expressed genes (DEGs) were identified based on gene expression data (GSE12657, GSE15824 and GSE45921 datasets) and probe annotation files from Gene Expression Omnibus. The DEGs were identified in connection with gene ontology (GO) enrichment analysis and with the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The positive expression of the FN1 protein was detected by immunohistochemistry. The glioma cell lines U251 and T98G were selected and assigned into blank, negative control (NC) and siRNA-FN1 groups. A dual luciferase reporter gene assay was used to investigate the effects of FN1 on transcriptional activity through the PI3K/AKT signaling pathway. An MTT assay was applied for the detection of cell proliferation, while flow cytometry was employed for cell cycle stage and cellular apoptosis detection. β-galactosidase staining was utilized to detect cellular senescence, a scratch test was applied to evaluate cell migration, and a transwell assay was used to analyze cell invasion. Western blotting and qRT-PCR methods were used to detect the protein and mRNA expression levels, respectively, of the FN1 gene and the related genes in the PI3K/AKT pathway (PI3K, AKT and PTEN), the cell cycle (pRb, CDK4 and Cyclin D1) and cell senescence (p16 and p21) among the collected tissues and cells. Results: GSE12657 profiling revealed FN1 to be the most upregulated gene in glioma. Regarding the GSE12657 and GSE15824 datasets, FN1 gene expression was higher in glioma tissues than in normal tissues. GO enrichment analysis and KEGG pathway enrichment analysis indicated that FN1 is involved in the synthesis of extracellular matrix (ECM) components and the PI3K/AKT signaling pathway. Verification was provided, indicating the role played by the FN1 gene in the regulation of the PI3K/AKT signaling pathway, as silencing the FN1 gene was found to inhibit cell proliferation, promote cell apoptosis and senescence, and reduce migration and invasion through the down-regulation of FN1 gene expression and disruption of the PI3K-AKT signaling pathway. Conclusion: The findings of this study provide evidence highlighting the prominent role played by FN1 in stimulating glioma growth, invasion, and survival through the activation of the PI3K/AKT signaling pathway.
Macrophages (Mphi) are prominent components of solid tumors and exhibit distinct phenotypes in different microenvironments. We have recently found that tumors can alter the normal developmental ...process of Mphi to trigger transient activation of monocytes in peritumoral stroma. We showed that a fraction of monocytes/Mphi in peritumoral stroma, but not in cancer nests, expresses surface PD-L1 (also termed B7-H1) molecules in tumors from patients with hepatocellular carcinoma (HCC). Monocytes activated by tumors strongly express PD-L1 proteins with kinetics similar to their activation status, and significant correlations were found between the levels of PD-L1(+) and HLA-DR(high) on tumor-infiltrating monocytes. Autocrine tumor necrosis factor alpha and interleukin 10 released from activated monocytes stimulated monocyte expression of PD-L1. The PD-L1(+) monocytes effectively suppressed tumor-specific T cell immunity and contributed to the growth of human tumors in vivo; the effect could be reversed by blocking PD-L1 on those monocytes. Moreover, we found that PD-L1 expression on tumor-infiltrating monocytes increased with disease progression, and the intensity of the protein was associated with high mortality and reduced survival in the HCC patients. Thus, expression of PD-L1 on activated monocytes/Mphi may represent a novel mechanism that links the proinflammatory response to immune tolerance in the tumor milieu.
After application in electric vehicles, spent LiFePO4 (LFP) batteries are typically decommissioned. Traditional recycling methods face economic and environmental constraints. Therefore, direct ...regeneration has emerged as a promising alternative. However, irreversible phase changes can significantly hinder the efficiency of the regeneration process owing to structural degradation. Moreover, improper storage and treatment practices can lead to metamorphism, further complicating the regeneration process. In this study, a sustainable recovery method is proposed for the electrochemical repair of LFP batteries. A ligand‐chain Zn‐complex (ZnDEA) is utilized as a structural regulator, with its ─NH─ group alternatingly facilitating the binding of preferential transition metal ions (Fe3+ during charging and Zn2+ during discharging). This dynamic coordination ability helps to modulate volume changes within the recovered LFP framework. Consequently, the recovered LFP framework can store more Li‐ions, enhance phase transition reversibility between LFP and FePO4 (FP), modify the initial Coulombic efficiency, and reduce polarization voltage differences. The recovered LFP cells exhibit excellent capacity retention of 96.30% after 1500 cycles at 2 C. The ligand chain repair mechanism promotes structural evolution to facilitate ion migration, providing valuable insights into the targeted ion compensation for environmentally friendly recycling in practical applications.
The introduction of the ligand chain within the Zn complex dynamically modulates the variational structure, enlarging the main framework of LFP and expediting the de‐intercalation of Li+. This process revitalizes the composition, structure, and electrochemical performance of LFP, restoring them to levels comparable to that of newly produced LFP even under severe degradation conditions during the operation of regenerated batteries.
Gastric cancer (GC) is the second cause of cancer-related death. Cisplatin (CDDP) is widely used as the standard GC treatment, but relapse and metastasis are common because of intrinsic or acquired ...drug resistance. The mitogen-activated protein kinase phosphatases (MAPK)-extracellular signal regulated kinases (ERK) pathway contributes to GC progression and drug resistance, but targeting the MAPK-ERK pathway is challenging in GC therapy. Here, we demonstrated that dual-specificity phosphatases 6 (DUSP6) was overexpressed in GC and predicted poor overall survival and progression-free survival. Knockdown DUSP6 inhibited GC proliferation, migration, invasion and induced apoptosis. (E/Z)-BCI hydrochloride (BCI), a DUSP6 small molecule inhibitor, increased the activity of ERK but interestingly decreased the expression of ERK response genes in BGC823, SGC7901 and CDDP-resistant SGC7901/DDP cells. BCI also caused cell death through the DNA damage response (DDR) pathway. Moreover, BCI inhibited cell proliferation, migration and invasion in a receptor-independent manner and enhanced CDDP cytotoxicity at pharmacological concentrations in the GC cells. In vivo experiments further showed that BCI enhances the antitumor effects of CDDP in cell-based xenografts and PDX models. In summary, our findings indicated that disruption of DUSP6 by BCI enhanced CDDP-induced cell death and apoptosis in GC may partly through ERK and DDR pathways. Thus, this study suggests that DUSP6 is a potential prognostic biomarker and a promising target for GC therapy.
•DUSP6 was overexpressed and promote proliferation, metastasis and predict poor prognosis in GC.•BCI inhibited cell proliferation, migration and invasion and enhanced CDDP cytotoxicity in GC through DUSP6.•In vivo experiments showed that BCI enhances the antitumor effects of CDDP in cell-based xenografts and PDX models.•BCI enhanced CDDP-induced cell death and apoptosis may partly through ERK and DDR pathways in GC.
The role of IL-17 producing cells in tumors is controversial. In the present study, we investigated the prognostic value of measuring tumor-infiltrating IL-17 producing cell levels in human ...esophageal squamous cell carcinoma (ESCC).
Immunohistochemical staining was performed to investigate the levels of IL-17+ tumor infiltrating lymphocytes (TILs), as well as CD8+ cytotoxic T lymphocytes (CTLs) and CD57+ natural killer (NK) cells from 181 ESCC patients. The prognostic value of measuring the densities of IL-17+TILs and the correlation with CTLs and NK was evaluated. IL-17 producing cells were detected in esophageal squamous cell carcinoma tissues. The IL-17 producing cells were major CD4 positive, but Foxp3 negative. The median level of IL-17+TILs was 3.90 cells/high power microscopic field (HPF). The density of IL-17 producing cells correlated negatively with T stage (P=0.042). The higher densities of tumor infiltrating IL-17+ lymphocytes were associated with better overall survival (P=0.031). Furthermore, we found that there were positive correlations between levels of IL-17 producing cells and the densities of CD8+cells, as well as CD57+cells (r=0.198, P=0.008 for CD8+ cells and r=0.261, P<0.001 for CD57+ cells, respectively). The prognosis analysis also showed that the higher levels of CD8+ CTLs and CD57+ NK cells correlated with better overall survival of ESCC patients.
Our study suggests that tumor infiltrating IL-17 producing cells in ESCC patients may have protective roles in the tumor microenvironment and may be treated as a prognostic marker for ESCC patients.
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•Effects of sulfation and acidification on acidic sites and pore structure were investigated.•Production of mesoporous and new strong acidic sites enhanced the catalytic ...activity.•0.5AS-550 produced higher yield of light aromatics than APS and HS modification.•Catalytic reforming mechanism of lignite vapor over sulfation-acidified HZ5 was proposed.
This study elucidated the effects of crystalline structure and acidity of sulfation-acidified HZSM-5 (HZ5) catalyst on the reaction routes and light aromatics (LAs) distribution during catalytic fast pyrolysis (CFP) of Shengli lignite. HZ5 modified by (NH4)2SO4 (AS), (NH4)2S2O8 (APS), and H2SO4 (HS) were applied to conduct CFP of lignite in a drop tube quartz reactor at 600 °C. The results indicated that the yield of LAs, especially monocyclic aromatics, increased considerably as the increase of pore size and midstrength acid sites (the decrease of non-shape selective acid sites) caused by sulfation-acidification modification. Among all the modified catalysts, 0.5AS-550 (modified with 0.5 mol/L AS and calcined at 550 °C) showed a better prospect than APS and HS modification in promoting the formation of LAs (the maximum yield of 28.8 mg/g). Meanwhile, the elimination of non-shape selective acid sites and regeneration of mesoporous reduced coke yield by 0.6% compared to HZ5. In addition, the possible reaction routes and catalytic mechanism over sulfation-acidified HZ5 catalysts were proposed to describe the formation of LAs.
CONTEXT Weight gain, a common adverse effect of antipsychotic medications,
is associated with medical comorbidities in psychiatric patients. OBJECTIVE To test the efficacy of lifestyle intervention ...and metformin alone and in combination for antipsychotic-induced weight gain and abnormalities in insulin sensitivity. DESIGN, SETTING, AND PATIENTS A randomized controlled trial (October 2004-December 2006) involving 128 adult patients with schizophrenia in the Mental Health Institute of the Second Xiangya Hospital, Central South University, China. Participants who gained more than 10% of their predrug weight were assigned to 1 of 4 treatment groups. INTERVENTIONS Patients continued their antipsychotic medication and were randomly assigned to 12 weeks of placebo, 750 mg/d of metformin alone, 750
mg/d of metformin and lifestyle intervention, or lifestyle intervention only. MAIN OUTCOME MEASURES Body mass index, waist circumference, insulin levels, and insulin resistance index. RESULTS All 128 first-episode schizophrenia patients maintained relatively stable psychiatric improvement. The lifestyle-plus-metformin group had mean decreases in body mass index (BMI) of 1.8 (95% confidence interval CI, 1.3-2.3), insulin resistance index of 3.6 (95% CI,
2.7-4.5), and waist circumference of 2.0 cm (95% CI, 1.5-2.4 cm).
The metformin-alone group had mean decreases in BMI of 1.2 (95% CI,
0.9-1.5), insulin resistance index of 3.5 (95% CI, 2.7-4.4), and waist circumference of 1.3 cm (95% CI, 1.1-1.5 cm). The lifestyle-plus-placebo group had mean decreases in BMI of 0.5 (95% CI, 0.3-0.8) and insulin resistance index of 1.0 (95% CI, 0.5-1.5). However, the placebo group had mean increases in BMI of 1.2 (95% CI, 0.9-1.5), insulin resistance index of 0.4 (95% CI, 0.1-0.7), and waist circumference of 2.2 cm (95% CI, 1.7-2.8 cm). The lifestyle-plus-metformin treatment was significantly superior to metformin alone and to lifestyle plus placebo for weight,
BMI, and waist circumference reduction. CONCLUSIONS Lifestyle intervention and metformin alone and in combination demonstrated efficacy for antipsychotic-induced weight gain. Lifestyle intervention plus metformin showed the best effect on weight loss.
Metformin alone was more effective in weight loss and improving insulin sensitivity than lifestyle intervention alone. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00451399
Despite being one of the most promising materials in anode materials, molybdenum sulfide (MoS2) encounters certain obstacles, such as inadequate cycle stability, low conductivity, and unsatisfactory ...charge‐discharge (CD) rate performance. In this study, a novel approach is employed to address the drawbacks of MoS2. Carbon polymer dots (CPDs) are incorporated to prepare three‐dimensional (3D) nanoflower‐like spheres of MoS2@CPDs through the self‐assembly of MoS2 2D nanosheets, followed by annealing at 700 °C. The CPDs play a main role in the creation of the nanoflower‐like spheres and also mitigate the MoS2 nanosheet limitations. The nanoflower‐like spheres minimize volume changes during cycling and improve the rate performance, leading to exceptional rate performance and cycling stability in both Lithium‐ion and Sodium‐ion batteries (LIBs and SIBs). The optimized MoS2@CPDs‐2 electrode achieves a superb capacity of 583.4 mA h g−1 at high current density (5 A g−1) after 1000 cycles in LIBs, and the capacity remaining of 302.8 mA h g−1 after 500 cycles at 5 A g−1 in SIBs. Additionally, the full cell of LIBs/SIBs exhibits high capacity and good cycling stability, demonstrating its potential for practical application in fast‐charging and high‐energy storage.
The controlling of carbonized polymer dots amount on MoS2 realizes flower‐like nanospheres structure with achieved high‐performance Li/Na storage.
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•Sulfated HZSM-5 zeolite was prepared by dealumination, realumination and sulfation.•The introduced extra-framework Al affected the textural-acid properties of catalysts.•Sulfation of ...catalyst after re-introduced extra-framework Al enhanced LAs production.•The highest LAs and lowest coke yield were produced over SO42−/DHZ5-A.
Sulfated HZSM-5 zeolite prepared by dealumination, realumination and sulfation was used as the active mesoporous materials to promote the formation of light aromatics during catalytic reforming of volatiles from Shengli lignite pyrolysis. The results show that HCl-dealumination significantly increased the total pore volume (especially mesopores) and average pore size while reducing acid strength and amount of acid sites. The incorporation of the extra-framework Al species to HZSM-5 combined with SO42− to form superacidic surface sulfate complex exhibited an increase in the yield of light aromatics and a decrease in the yield of coke in comparison with that of original HZSM-5. Among the modified catalysts, SO42−/DHZ5-A (introduced the calcined Al2O3 after HCl-dealumination and modified with (NH4)2SO4) with the acidity enhancement by sulfation obtained the maximum light aromatics yield of 27.3 mg/g and the lowest coke yield of 2.7%. The relationship between the physic-chemical properties of catalysts and the product distribution was proposed to understand the formation of light aromatics.
Abstract The NASICON cathode, Na 3 V 2 (PO 4 ) 3 , has garnered significant attention due to its robust framework with fast Na + migration. To expand its application scenarios by diversified ...electronic reaction, the substitution of vanadium with cost‐effective and abundant redox elements is a special research topic. Nevertheless, in terms of reducing toxicity, increasing Na content and widening voltage range, the V 4+/5+ redox couple in Na 4 FeV(PO 4 ) 3 often accompanies asymmetric and irreversible electrochemical reactions that pose a dilemma for capacity and structural stability, especially at high currents. Herein, in this work, Na 4 FeV 1/3 Ti 2/3 (PO 4 ) 3 (NFVT) has achieved highly reactive of multiple electron transfer (Ti 2+/3+ , Fe 2+ / 3+ , and V 3+/4+ / 5+ ) by utilizing the redox reaction with quasi‐monophase behavior, and it can reserve great capacity retention after 3,000 cycles. More competitively, its boosting kinetics makes the fast‐charging characteristic, just requiring only 3.63 min to reach 80% state of charge at 2 C. The rapid ion/electron transport dynamics can achieve the decay of only 0.043% per cycle by unlocking the quasi‐monophase behavior in the framework of NFVT full cells. The present study provides a fresh perspective on designing cathode materials with fast‐charging capabilities for sodium‐ion batteries.
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