Glucose levels and type 2 diabetes (T2D) are both associated with tumorigenesis and epithelial‐mesenchymal transitions (EMTs). EMTs facilitate bladder cancer (BC) metastasis development, but the ...mechanism by which high‐glucose levels promote these EMTs in BC remains unclear. Therefore, we sought to elucidate the mechanism underlying EMT promotion due to increased glucose levels. T24 and UMUC‐3 cells were cultured in media containing different glucose concentrations. YAP1, TAZ, GLUT1 and EMT‐associated marker expression was analysed via Western blotting and qPCR. BC cell proliferation and invasion were assessed using MTT and Transwell assays, respectively. A xenograft nude mouse model of diabetes was used to evaluate tumour growth and metastasis in vivo. T2D was positively associated with pathologic grade (P = .016) and TNM stage (P < .001) in BC. High glucose triggered BC cell proliferation and invasion in both in vitro and in vivo conditions. High‐glucose levels also promoted EMTs in BC cells and increased YAP1 and TAZ expression. YAP1 or TAZ knockdown altered EMT marker expression and decreased GLUT1 expression. Overall, our results suggest that high‐glucose levels promote EMTs in BC cells via YAP1 and TAZ regulation. These effector molecules may be promising therapeutic targets for BC cases comorbid with T2D.
Polyols with different number of hydroxyl groups were synthesized from ricinoleic acid and oleic acid. These plant oil derived polyols can be used as plasticizers and combined with ethyl cellulose ...(EC) through supramolecular system to prepare ethyl cellulose composite films. The morphology, thermal stability and mechanical properties of the prepared ethyl cellulose films were studied in detail to indicate the plasticizing efficiency of these polyols and the effect of the number of hydroxyl groups in polyols on EC composite film’s properties. With the addition of polyols, the tensile strength of EC composite films decreased, while the elongation at break increased. The elongation at break of EC composite films can be improved by 11–12 times when the polyols contain 1–3 hydroxyl groups. Thus, the plant oil derived polyols with 1–3 hydroxyl groups can be used as plasticizers for EC films. In addition, molecular dynamic simulations were performed to further probe the effects of the number of hydroxyl groups in polyols on EC composite film’s properties.
Graphic abstract
A novel biobased epoxy monomer with conjugated double bonds, glycidyl ester of eleostearic acid (GEEA) was synthesized from tung oil fatty acids and characterized by (1)H and (13)C NMR. Differential ...scanning calorimeter analysis (DSC) and Fourier transform infrared spectroscopy (FT-IR) were utilized to investigate the curing process of GEEA with dienophiles and anhydrides. DSC indicated that GEEA could cross-link with both dienophiles and anhydrides through Diels-Alder reaction and epoxy/anhydride ring-opening reaction. Furthermore, Diels-Alder cross-link was much more active than the ring-opening of epoxy and anhydride in the curing process. FT-IR also revealed that GEEA successively reacted with dienophiles and anhydrides in both cross-linking methods. Dynamic mechanical analysis and mechanical tensile testing were used to study the thermal and mechanical properties of GEEA cured by maleic anhydride, nadic methyl anhydride and 1,1'-(methylenedi-4,1-phenylene)bismaleimide. Due to the independence between the curing agents, dienophile and anhydride, a series of thermosetting polymers with various properties could be obtained by adjusting the composition of these two curing agents.
The human ether a-go-go-related gene 1 (HERG1) is involved in tumor progression; however, its role in esophageal squamous cell carcinoma (ESCC) is not well studied. This study investigated HERG1 ...function in ESCC progression and elucidated the underlying mechanisms.
The prognostic value of HERG1 was determined by immunohistochemistry in ESCC biopsies. Cell growth and proliferation were analyzed by colony formation and methyl thiazolyl tetrazolium assays. Cell migration and invasion were analyzed by wound healing and Boyden transwell assays. Epithelial-mesenchymal transition (EMT) was evaluated by immunoblotting and quantitative polymerase chain reaction (qPCR). A xenograft mouse model was used to validate the tumorigenic and metastatic roles of HERG1 in vivo.
HERG1 expression was overall higher in ESCC tissues compared to adjacent non-tumor tissues. A retrospective analysis of 349 patients with ESCC (stages I-IV) confirmed increased HERG1 expression was associated with disease progression and higher mortality rate. The overall survival of the patients was significantly worse when their tumors displayed higher HERG1 expression. HERG1 knockdown reduced tumor growth and metastasis in athymic mice. HERG1 affected the proliferation, migration, and invasion of two ESCC cell lines (TE-1 and KYSE-30). Changes in HERG1 expression affected the expression of cell cycle- and EMT-related proteins; these effects were reversed by altering the expression of thioredoxin domain-containing protein 5 (TXNDC5), which is also associated with the clinicopathological characteristics of patients with ESCC and is relevant to HERG1 in pathological biopsies. Additionally, HERG1 expression altered phosphoinositide 3-kinase (PI3K) and AKT phosphorylation, thereby affecting TXNDC5 expression.
HERG1 contributes to poor prognosis in patients with ESCC by promoting ESCC cell proliferation, migration, and invasion via TXNDC5 through the PI3K/AKT signaling pathway. Our findings provided novel insights into the pathology of ESCC and role of HERG1 in tumor progression, suggesting that targeting HERG1 has potential diagnostic and therapeutic value for ESCC treatment.
Selective and sensitive water content measurement in organic solvents is extremely significant for both industrial use and laboratory preparation. Carbon nanodots are promising carbon nanomaterials ...with unique and novel properties and thus have drawn growing attention. However, the hydrothermal approach for the preparation of carbon dots always uses water as solvent, and consequently, the development of carbon dots from biomass materials for fluorescence detection of water content remains unexplored. Here, carbon dots were prepared from gallic acid via a cheap and facile one-step method. The as-prepared carbon dots present excellent sensitivity and selectivity toward water content and exhibits good linear relationships with water content in range of 0–10%. The carbon dots demonstrated a strong antioxidation capacity and colour-reaction of Fe
3+
like gallic acid. The carbon dots also showed solid-state lighting.
Biobased lipoic acid (LA) can be used as a plasticizer and combine with ethyl cellulose (EC) to form ethyl cellulose supramolecular composite films. The morphology, hydrophilic performance, thermal ...stability and mechanical properties of the composite films were investigated. The introduction of LA can significantly improve the flexibility and processability of ethyl cellulose films because LA can weaken both hydrogen bonding and hydrophobic interaction in EC chains. The elongation at break of EC composite films can be increased by 5.5~11.1 times when the LA content is 20~50%. In addition, comparative experiments and molecular dynamic simulations were performed to explain the superiority of LA as a plasticizer for EC films.
Graphic abstract
A tung-oil-based polyphenol (ATOM), containing the phenolic hydroxyl group, was synthesized from tung oil and 4-maleimidophenol by the Diels–Alder addition reaction. Then self-healing thermosetting ...polyurethanes were prepared from ATOM and the polyurethane prepolymer. The chemical structure and cross-link network were confirmed by Fourier transform infrared spectroscopy (FTIR) and swelling tests. The products partially dissolved in trichlorobenzene when the temperature rose to 110 °C. Temperature-variable FTIR confirmed that the phenolic urethane starts to partially dissolve at 100 °C, which can be explained by the experimental phenomenon in swelling tests. Tensile property analysis showed that the broken and healed thermosets maintained about 46–64% of their original tensile strengths and 81–88% of their original elongations at break, respectively.
Immune checkpoint inhibitors (ICIs) have made breakthrough progress in the treatment of various malignant tumors. However, only some patients receiving ICIs obtain long-lasting clinical effects, and ...some patients still do not achieve remission. Improving the treatment benefits of this part of the population has become a concern of clinicians. IL-1 signaling plays an important role in the tumor microenvironment (TME). However, the relationship between the IL-1 signaling mutation status and the prognosis of colon adenocarcinoma (COAD) patients receiving ICIs has not been reported. We downloaded the data of a COAD cohort receiving ICIs, including prognostic data and mutation data. Additionally, we downloaded the data of a COAD cohort from The Cancer Genome Atlas (TCGA) database, including clinical data, expression data and mutation data. Gene set enrichment analysis (GSEA) was used to assess differences in the activity of some key physiological pathways between the IL-1 signaling mutated-type (IL-1-MT) and IL-1 signaling wild-type (IL-1-WT) groups. The CIBERSORT algorithm was used to evaluate the contents of immune cells in the TME of COAD patients. The multivariate Cox regression model results suggested that IL-1-MT can be used as an independent predictor of a better prognosis in COAD patients receiving ICIs (P = 0.03, HR = 0.269, 95% CI: 0.082-0.883). Additionally, IL-1-MT COAD patients had significantly longer overall survival (OS) (log-rank P = 0.015). CIBERSORT analysis showed that the IL-1-MT group had high infiltration levels of activated dendritic cells (DCs), M1 macrophages, neutrophils, activated natural killer (NK) cells, activated CD4+ memory T cells and CD8+ T cells. Similarly, the IL-1-MT group had significantly upregulated immunogenicity, including in terms of the tumor mutation burden (TMB), neoantigen load (NAL) and number of mutations in DNA damage repair (DDR) signaling. GSEA showed that the IL-1-MT group was highly enriched in the immune response and proinflammatory mediators. Additionally, the expression levels of immune-related genes, immune checkpoint molecules and immune-related signatures were significantly higher in the IL-1-MT group than in the IL-1-WT group. IL-1-MT may be an independent predictor of a good prognosis in COAD patients receiving ICIs, with significantly longer OS in IL-1-MT COAD patients. Additionally, IL-1-MT was associated with significantly increased immunogenicity, activated immune cell and inflammatory mediator levels and immune response-related scores.
The clinical value of combined local radiation and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) for medically inoperable and TKI-naïve early-stage lung adenocarcinoma ...patients with EGFR mutations has not yet been determined. In this study, we aimed to pool multi-institutional data to compare the therapeutic effect of EGFR-TKI treatment alone and combined radiation and TKI treatment on the survival outcomes in this patient subgroup.
A total of 132 cases of medically inoperable stage I to III EGFR mutant lung adenocarcinoma were retrospectively reviewed based on data from 5 centers. Among these patients, 65 received combined radiation and EGFR-TKI therapy (R + TKI) (49.2%), while 67 received EGFR-TKI (50.8%) treatment alone. All patients were followed until death.
For the R + TKI group, the median overall survival (OS) after primary therapy was 42.6 months, while that of the TKI alone group was 29.4 months (log-rank p < 0.001). In terms of progression-free survival (PFS), the median PFS in these two treatment groups was 24 months and 14.7 months respectively (log-rank p < 0.001). Multivariate analysis showed that R + TKI was independently associated with improved OS (adjusted HR 0.420; 95% CI 0.287 to 0.614; p < 0.001) and PFS (adjusted HR 0.420; 95% CI 0.291 to 0.605; p < 0.001) compared to TKI alone. Subgroup analysis confirmed the significant OS benefits in stage III patients and RFS benefits in stage II/III patients.
Upfront radiation to primary sites with subsequent TKI treatment is a feasible option for patients with medically inoperable EGFR-mutant non-small-cell lung carcinoma (NSCLC) during first-line EGFR-TKI treatment, with significantly improved PFS and OS compared with those yielded by TKI treatment alone.
In this work, a new liquid thermal stabilizer (LTS) was prepared using rosin and fatty acids as feedstock and evaluated for its stabilizing effects on poly(vinyl chloride) (PVC). First, a ...rosin/oil-based dimer acid (RODA) was prepared by the addition reaction of rosin and industrial fatty acids and then converted into its zinc soap (RODA-Zn) and calcium soap (RODA-Ca). The chemical structures were examined by UV–Vis and Fourier Transform infrared spectroscopies. Liquid form thermal stabilizers (RODA-LTS) were obtained by treating the solid RODA-Zn and RODA-Ca soaps with epoxidized soybean oil, triphenyl phosphite and liquid paraffin at 120 °C for 3 h. Thermal stabilizing effects of the resulting RODA-LTS for PVC were compared with that of two commercial LTSs. Thermal stability of PVC compounds was determined using dehydrochlorination test, thermogravimetric analysis (TGA), Congo red test and torque rheological analysis. Results indicated that RODA-LTS had overall superior thermal stability. Tensile and dynamic mechanical properties of the PVC compounds were also studied, and the results indicated that the PVC compounds stabilized with RODA-LTS and commercial LTSs displayed comparable strength, modulus and glass transition temperatures.
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