Catalytic polymer self-cleavage for CO2 generation before combustion empowers materials with fire safety.

Polymeric materials, rich in carbon, hydrogen, and oxygen elements, present substantial fire hazards to both human life and property due to their intrinsic flammability. Overcoming this challenge in the absence of any flame-retardant elements is a daunting task. Herein, we introduce an innovative strategy employing catalytic polymer auto-pyrolysis before combustion to proactively release CO2, akin to possessing responsive CO2 fire extinguishing mechanisms. We demonstrate that potassium salts with strong nucleophilicity (such as potassium formate/malate) can transform conventional polyurethane foam into materials with fire safety through rearrangement. This transformation results in the rapid generation of a substantial volume of CO2, occurring before the onset of intense decomposition, effectively extinguishing fires. The inclusion of just 1.05 wt% potassium formate can significantly raise the limiting oxygen index of polyurethane foam to 26.5%, increase the time to ignition by 927%, and tremendously reduce smoke toxicity by 95%. The successful application of various potassium salts, combined with a comprehensive examination of the underlying mechanisms, underscores the viability of this strategy. This pioneering catalytic approach paves the way for the efficient and eco-friendly development of polymeric materials with fire safety.

ALKBH5 promotes hepatocellular carcinoma cell proliferation, migration and invasion by regulating TTI1 expression.

The objective of this research was to investigate the potential mechanisms of AlkB homolog 5, RNA demethylase (ALKBH5) in hepatocellular carcinoma (HCC). We used The Cancer Genome Atlas (TCGA), Kruskal-Wallis method and Kaplan-Meier (KM) survival analysis to study the expression of ALKBH5 and its correlation with clinical factors in HCC. In vitro experiments verified the expression of ALKBH5 and its effect on HCC cell phenotype. We screened differentially expressed genes (DEGs) from HCC patients associated with ALKBH5. Through this screening we identified the downstream gene TTI1 which is associated with ALKBH5 and investigated its function using Gene Expression Profiling Interaction Analysis (GEPIA) along with univariate Cox proportional hazards regression analysis. Finally, we analyzed the functions of ALKBH5 and TTI1 in HCC cells. Across numerous pan-cancer types, we observed significant overexpression of ALKBH5. In vitro experiments confirmed ALKBH5 as an oncogene in HCC, with its knockdown leading to suppressed cell proliferation, migration, and invasion. Bioinformatics analyses also demonstrated a significant positive correlation between ALKBH5 and TTI1. TTI1, highly expressed in cells, showed promising prognostic ability for patients. Further experiments confirmed that suppressing TTI1 impeded cell growth and movement, with this effect partially offset by increased ALKBH5 expression. Conversely, promoting these cellular processes was observed with TTI1 overexpression, but was dampened by decreased ALKBH5 expression. In conclusion, our findings suggest that ALKBH5 may influence proliferation, migration and invasion of HCC by modulating TTI1 expression, providing a new direction for treating HCC.

Role of Asxl2 in non­alcoholic steatohepatitis­related hepatocellular carcinoma developed from diabetes.

The present study investigated the mechanism(s) of non­alcoholic steatohepatitis­related hepatocellular carcinoma (NASH­HCC) developed from diabetes. Streptozotocin and a high­fat diet (STZ­HFD) were used to induce NASH­HCC in ApoE­/­ mice. Mouse liver functions were evaluated by H&E staining, liver/body weight and serum biochemical analysis. The expression levels of inflammation­associated factors were determined by RT­qPCR. Gene expression profiles related to molecular functions and pathways of NASH­HCC were examined by principal component analysis, heatmap, gene ontology and KEGG pathway enrichment analysis. Differentially expressed genes (DEGs) in tumor tissues were confirmed by RT­qPCR. The expression of Asxl2 in human NASH­HCC, other HCC tissues and HCC cells was measured by western blot (WB analysis) and RT­qPCR. For SNU­182 cells transfected with siAsxl2 or Hep3B cells with Asxl2 overexpression, cell proliferation, cell cycle, migration and invasion were respectively determined by CCK­8 assays, flow cytometry, wounding healing and Transwell assays. The expression levels of cell metastasis­ and cycle­related proteins were determined by WB analysis and RT­qPCR. NASH­HCC model mice exhibited tumor protrusion with severe steatosis. The blood glucose concentration, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and low­density lipoprotein (LDL), total bile acid (TBA) and the levels of interleukin (IL)­6, tumor necrosis factor (TNF)­α, glypican 3 (GPC3) and transforming growth factor (TGF)­ß were all increased in NASH­HCC model mice. DEGs were mainly related to chromosome organization, the cell cycle and the mitogen­activated kinase (MAPK) pathway. Asxl2 was significantly downregulated in HCC tissues and cells, and this regulated cell growth, migration and invasion. The gene expression pattern, related molecular functions and signaling pathways of NASH­HCC differed from those of normal liver tissues. Additionally, the downregulation of Asxl2 may play a potential role in development of NASH­HCC in patients with diabetes.

LncRNA MYLK-AS1 facilitates tumor progression and angiogenesis by targeting miR-424-5p/E2F7 axis and activating VEGFR-2 signaling pathway in hepatocellular carcinoma.

BACKGROUND: Long non-coding RNAs (lncRNAs) are crucial in the invasion, angiogenesis, progression, and metastasis of hepatocellular carcinoma (HCC). The lncRNA MYLK-AS1 promotes the growth and invasion of HCC through the EGFR/HER2-ERK1/2 signaling pathway. However, the clinical significance of MYLK-AS1 in HCC still needs to be further determined. METHODS: Bioinformatic analysis was performed to determine the potential relationship among MYLK-AS1, miRNAs and mRNAs. A total of 156 samples of normal liver and paired HCC tissues from HCC patients were used to evaluate MYLK-AS1 expression by qRT-PCR. Human HCC cell lines were used to evaluate the colony formation, cell proliferation, migration, invasion, cell cycle and apoptosis after transfection of lentiviral short-hairpin RNAs (shRNAs) targeting MYLK-AS1 or MYLK-AS1 vectors. The competitive endogenous RNA (ceRNA) mechanism was clarified using fluorescence in situ hybridization (FISH), Western blotting, qPCR, RNA binding protein immunoprecipitation (RIP), and dual luciferase reporter analysis. RESULTS: MYLK-AS1 up-regulation was detected in the HCC tumor tissues and cell lines associated with the enhancement of the angiogenesis and tumor progression. The down-regulation of MYLK-AS1 reversed the effects on angiogenesis, proliferation, invasion and metastasis in the HCC cells and in vivo. MYLK-AS1 acted as ceRNA, capable of regulating the angiogenesis in HCC, while the microRNA miR-424-5p was the direct target of MYLK-AS1. Promoting the angiogenesis and the tumor proliferation, the complex MYLK-AS1/miR-424-5p activated the VEGFR-2 signaling through E2F7, whereas the specific targeting of E2F transcription factor 7 (E2F7) by miR-424-5p, was indicated by the mechanism studies. CONCLUSIONS: MYLK-AS1 and E2F7 are closely related to some malignant clinicopathological features and prognosis of HCC, thus the MYLK-AS1/ miR-424-5p/E2F7 signaling pathway might represent a promising treatment strategy to combat HCC.

Long non-coding RNA HAGLROS regulates lipid metabolism reprogramming in intrahepatic cholangiocarcinoma via the mTOR signaling pathway.

Alternation of long non-coding RNA (lncRNA) is implicated in intrahepatic cholangiocarcinoma (ICC) development. HAGLROS is a lncRNA with a length of 699 bp, which is involved in the progression of various cancers. But the mechanism of HAGLROS in ICC remains unknown. In this study, the sh-HAGLROS-1 or sh-HAGLROS-2 was transfected into QBC939 cells, and overexpressing HAGLROS vector was transfected into KMCH cells. HAGLROS expression in ICC tissues and cell lines was detected, and its association with ICC prognosis was further analyzed. Lipid accumulation and lipid-related indicators (TG, LDL-C, TC and HDLC) in QBC939 and KMCH cells were measured. ICC cell viability, invasion and migration were measured. Western blot analysis was used to detect levels of the mTOR axis-related proteins and autophagy-related proteins (LC3I, LC3II, Beclin and P62). The levels of serum lipids and SREBP1 positive expression in transplanted tumors of nude mice were detected. HAGLROS was highly expressed in ICC and negatively correlated with prognosis. QBC939 cells with knocking down HAGLROS exhibited reduced lipid-related protein levels, blocked ICC cellular processes, inactivated mTOR axis, and increased autophagy. QBC939 cells with overexpressing HAGLROS showed opposite trends. The lipid-related protein levels in serum of nude mice and SREBP1 positive expression in transplanted tumors were diminished. Taken together, sh-HAGLROS inactivated the mTOR axis and promoted autophagy, thereby improving lipid metabolism reprogramming in ICC. This study may offer novel ICC treatments.

A noncoding RNA LINC00504 interacts with c-Myc to regulate tumor metabolism in colon cancer.

Accumulating evidence has shown a critical role of long-non-coding RNAs (lncRNAs) during multiple tumor progression. However, the potential functions of LINC00504 in colon cancer as well as its mechanisms remain obscure. By lncRNA profiling, we identified LINC00504 as a novel oncogenic lncRNA in colon cancer. The lncRNA LINC00504 was markedly upregulated in colon cancer cell lines and specimens. LINC00504 increases viability and migration of colon cells in vitro. Furthermore, LINC00504 also enhances colon cancer xenograft tumors in vivo. We noted that LINC00504 regulates metabolism at a transcriptional level which influences multiple metabolic pathways, such as glucose metabolism, pentose phosphate pathway, and tricarboxylic acid cycle. Mechanistic study showed that LINC00504 could interact with c-Myc to promote chromatin recruitment of c-Myc and enhance its transactivation activity. Collectively, our results showed that LINC00504 serves as an important transcriptional regulator for c-Myc in colon cancer cells. LINC00504 can reprogram central metabolism in colon cancer cells implying that LINC00504 may serve as a potential target for therapeutic intervention.

Total flavonoid aglycones extract in Radix Scutellariae induces cross-regulation between autophagy and apoptosis in pancreatic cancer cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Scutellariae (RS), the dried root of Scutellariae baicalensis Georgi, known as a herbal medicine in several Asian countries including China, has been widely used to treat inflammation, hypertension, cardiovascular disease as well as cancer. The total flavonoid aglycone extracted (TFAE) was extracted by ethyl acetate and this extraction methodology was optimized and obtained the protection of Chinese patents. AIM OF THE STUDY: To investigate the underlying mechanism of the chemotherapeutic effects of TFAE in inducing autophagy and apoptosis in pancreatic cancer cells in vitro and in vivo. MATERIALS AND METHODS: We performed CCK8 assays, AnnexinV-FITC/PI staining, flow cytometry assays, transmission electron microscopy, immunofluorescence analysis and Western blot to study the molecular mechanism of TFAE in inducing autophagy and apoptosis in pancreatic cancer cells in vitro and in vivo. RESULTS: In vitro, TFAE exhibits significant anti-tumor activity against pancreatic cancer cell lines, especially for BxPC3 (IC50 = 6.5 µg mL-1). Moreover, TFAE induces apoptosis and autophagy as evidenced by the increased apoptosis or autophagy-related protein level, the increased the fraction of apoptotic cells and the punctuate patterns of LC3 II. Furthermore, TFAE induce autophagy through PI3K/Akt/mTOR inhibition. Interestingly, pharmacological block autophagy by 3-MA enhanced TFAE-induced apoptosis, indicating that TFAE induced autophagy functions as a cytoprotective process against apoptosis. In vivo, 150 mg/kg TFAE inhibited the BxPC3 tumor growth in immune deficient mice with the inhibitory rate of 66.87% and induced both apoptosis and autophagy. CONCLUSION: TFAE have anti-tumor activity against pancreatic cancer and can induce apoptosis and autophagy through PI3K/Akt/mTOR signal pathway. TFAE might be a potential anticancer drug to be further developed for human pancreatic cancer therapy.

Fabrication and Evaluation of a Graphene Oxide-Based Capacitive Humidity Sensor.

In this study, a CMOS compatible capacitive humidity sensor structure was designed and fabricated on a 200 mm CMOS BEOL Line. A top Al interconnect layer was used as an electrode with a comb/serpent structure, and graphene oxide (GO) was used as sensing material. XRD analysis was done which shows that GO sensing material has a strong and sharp (002) peak at about 10.278°, whereas graphite has (002) peak at about 26°. Device level CV and IV curves were measured in mini-environments at different relative humidity (RH) level, and saturated salt solutions were used to build these mini-environments. To evaluate the potential value of GO material in humidity sensor applications, a prototype humidity sensor was designed and fabricated by integrating the sensor with a dedicated readout ASIC and display/calibration module. Measurements in different mini-environments show that the GO-based humidity sensor has higher sensitivity, faster recovery time and good linearity performance. Compared with a standard humidity sensor, the measured RH data of our prototype humidity sensor can match well that of the standard product.

Enhanced transfection efficiency and targeted delivery of self-assembling h-R3-dendriplexes in EGFR-overexpressing tumor cells.

The efficient gene transfection, cellular uptake and targeted delivery in vivo are key issues for non-viral gene delivery vectors in cancer therapy. To solve these issues, we designed a new targeted gene delivery system based on epidermal growth factor receptor (EGFR) targeting strategy. An anti-EGFR monoclonal antibody h-R3 was introduced to dendriplexes of PAMAM and DNA via electrostatic interactions to form self-assembled h-R3-PAMAM-DNA complexes (h-R3-dendriplexes). Dendriplexes h-R3-dendriplexes represented excellent DNA encapsulation ability and formed unique nanostructures. Compared to dendriplexes, h-R3-dendriplexes presented lower cytotoxicity, higher gene transfection efficiency, excellent endosome escape ability and high nuclear accumulation in the EGFR-overexpressing HepG2 cells. Both ex vivo fluorescence imaging and confocal results of frozen section revealed that h-R3-dendriplexes showed higher targeted delivery and much better gene expression in the tumors than dendriplexes at the same N/P ratio, and h-R3-dendriplexes had accumulation primarily in the tumor and kidney. Moreover, h-R3-dendriplexes for p53 delivery indicated efficient cell growth inhibition and potentiated paclitaxel-induced cell death. These results indicate that the h-R3-dendriplexes represent a great potential to be used as efficient targeted gene delivery carriers in EGFR-overexpressing tumor cells.

Enhancement of Solubility, Transport Across Madin-Darby Canine Kidney Monolayers and Oral Absorption of Pranlukast Through Preparation of a Pranlukast-Phospholipid Complex.

This study aimed to enhance the solubility of a poorly water-soluble drug, pranlukast, as well as its transport across Madin-Darby canine kidney (MDCK) monolayers, thus increasing its oral bioavailability. To accomplish this aim, we prepared a pranlukast-phospholipid complex (PPC). The PPC was prepared by solvent-evaporation and characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), infrared (IR) spectroscopy, and solubilization studies. The solubility of pranlukast in the PPC was increased from 1.03 ± 0.32 µg/ml to 160.63 ± 2.72 µg/ml with a yield of 96.39 ± 1.20% when the PPC was prepared under optimal conditions. TEM images showed that the PPC particles had a spherical shape. XRD data indicated that pranlukast in the PPC was either in an amorphous form or in a dispersed molecular distribution. IR analysis confirmed the interaction between pranlukast and the phospholipids. The transport mechanism of the PPC and non-complexed pranlukast across MDCK cells was measured and was observed to be significantly greater for the former than for the latter. The in vivo bioavailability of the PPC in rats hastened the onset of pranlukast-induced therapeutic effects, with C(max) and AUC increases of 21.88- and 28.64-fold, respectively, compared with raw crystals. In addition, an in vivo imaging method was used to corroborate that the PPC exhibited rapid circulatory distribution and gastrointestinal tract accumulation. These results indicate that PPC appears to be a promising drug delivery system for pranlukast, improving drug absorption and decreasing side effects by reducing the required oral dose.

One potential oncolytic adenovirus expressing Lipocalin-2 for colorectal cancer therapy.

Colorectal cancer is an aggressive malignancy with a high mortality rate; however, effective therapies are currently lacking. Cancer-targeting gene-virotherapy (CTGVT) has been proposed to be a promising strategy for cancer therapy. The purpose of this study was to investigate the antitumor activity of the oncolytic adenovirus harboring Lipocalin-2 (ZD55-Lipocalin-2, an example of CTGVT) in colorectal cancer. ZD55-Lipocalin-2 was generated by deleting E1B55-KD and inserting the Lipocalin-2 gene. Its cytopathic effects and cell growth inhibition were detected in vitro, and antitumor effects were examined in a nude mouse model of human colorectal cancer xenografts. Results showed that ZD55-Lipocalin-2 significantly inhibited the colorectal cancer growth by selective cytolysis, inducing apoptosis and decreasing the microvessel density in tumors. The anticancer potential of ZD55-Lipocalin-2 showed stronger than that of the isolated Lipocalin-2 gene therapy or isolated ZD55 oncolytic adenovirus therapy. ZD55-Lipocalin-2 may serve as a potential anticancer agent for colorectal cancer treatment.