LPS receptor subunits have antagonistic roles in epithelial apoptosis and colonic carcinogenesis.

Colorectal carcinoma (CRC) is characterized by unlimited proliferation and suppression of apoptosis, selective advantages for tumor survival, and chemoresistance. Lipopolysaccharide (LPS) signaling is involved in both epithelial homeostasis and tumorigenesis, but the relative roles had by LPS receptor subunits CD14 and Toll-like receptor 4 (TLR4) are poorly understood. Our study showed that normal human colonocytes were CD14(+)TLR4(-), whereas cancerous tissues were CD14(+)TLR4(+), by immunofluorescent staining. Using a chemical-induced CRC model, increased epithelial apoptosis and decreased tumor multiplicity and sizes were observed in TLR4-mutant mice compared with wild-type (WT) mice with CD14(+)TLR4(+) colonocytes. WT mice intracolonically administered a TLR4 antagonist displayed tumor reduction associated with enhanced apoptosis in cancerous tissues. Mucosa-associated LPS content was elevated in response to CRC induction. Epithelial apoptosis induced by LPS hypersensitivity in TLR4-mutant mice was prevented by intracolonic administration of neutralizing anti-CD14. Moreover, LPS-induced apoptosis was observed in primary colonic organoid cultures derived from TLR4 mutant but not WT murine crypts. Gene silencing of TLR4 increased cell apoptosis in WT organoids, whereas knockdown of CD14 ablated cell death in TLR4-mutant organoids. In vitro studies showed that LPS challenge caused apoptosis in Caco-2 cells (CD14(+)TLR4(-)) in a CD14-, phosphatidylcholine-specific phospholipase C-, sphingomyelinase-, and protein kinase C-ζ-dependent manner. Conversely, expression of functional but not mutant TLR4 (Asp299Gly, Thr399Ile, and Pro714His) rescued cells from LPS/CD14-induced apoptosis. In summary, CD14-mediated lipid signaling induced epithelial apoptosis, whereas TLR4 antagonistically promoted cell survival and cancer development. Our findings indicate that dysfunction in the CD14/TLR4 antagonism may contribute to normal epithelial transition to carcinogenesis, and provide novel strategies for intervention against colorectal cancer.

Resistance to hypoxia-induced necroptosis is conferred by glycolytic pyruvate scavenging of mitochondrial superoxide in colorectal cancer cells.

Cancer cells may survive under oxygen and nutrient deprivation by metabolic reprogramming for high levels of anaerobic glycolysis, which contributes to tumor growth and drug resistance. Abnormally expressed glucose transporters (GLUTs) are colocalized with hypoxia (Hx) inducible factor (HIF)1α in peri-necrotic regions in human colorectal carcinoma. However, the underlying mechanisms of anti-necrotic resistance conferred by glucose metabolism in hypoxic cancer cells remain poorly understood. Our aim was to investigate signaling pathways of Hx-induced necroptosis and explore the role of glucose pyruvate metabolite in mechanisms of death resistance. Human colorectal carcinoma cells were Hx exposed with or without glucose, and cell necroptosis was examined by receptor-interacting protein (RIP)1/3 kinase immunoprecipitation and (32)P kinase assays. Our results showed increased RIP1/3 complex formation and phosphorylation in hypoxic, but not normoxic cells in glucose-free media. Blocking RIP1 signaling, by necrostatin-1 or gene silencing, decreased lactodehydrogenase (LDH) leakage and plasma membrane disintegration. Generation of mitochondrial superoxide was noted after hypoxic challenge; its reduction by antioxidants inhibited RIP signaling and cell necrosis. Supplementation of glucose diminished the RIP-dependent LDH leakage and morphological damage in hypoxic cells, whereas non-metabolizable sugar analogs did not. Hypoxic cells given glucose showed nuclear translocation of HIF1α associated with upregulation of GLUT-1 and GLUT-4 expression, as well as increase of intracellular ATP, pyruvate and lactate levels. The glucose-mediated death resistance was ablated by iodoacetate (an inhibitor to glyceraldehyde-3-phosphate dehydrogenase), but not by UK5099 (an inhibitor to mitochondrial pyruvate carrier), suggesting that glycolytic pathway was involved in anti-necrotic mechanism. Lastly, replacing glucose with cell-permeable pyruvate derivative also led to decrease of Hx-induced necroptosis by suppression of mitochondrial superoxide in an energy-independent manner. In conclusion, glycolytic metabolism confers resistance to RIP-dependent necroptosis in hypoxic cancer cells partly through pyruvate scavenging of mitochondrial free radicals.

Evaluation of adhesion force and binding affinity of phytohemagglutinin erythroagglutinating to EGF receptor on human lung cancer cells.

PHA-E is a natural product extracted from red kidney beans, and it has been reported to induce cell apoptosis by blocking EGFR in lung cancer cells. Because EGF is the major in vivo competitor to PHA-E in clinical application, PHA-E must be proved that has better affinity to EGFR than EGF. This study would focus on how PHA-E tightly bind to EGFR and the results would compare with EGF. The adhesion force, measured by AFM, between EGFR and PHA-E was 207.14±74.42 pN that was higher than EGF (183.65±86.93 pN). The equilibrium dissociation constant of PHA-E and EGF to EGFR was 2.4 10(-9)±1.4 10(-9) and 7.3 10(-8)±2.7 10(-8), respectively, that could evaluate binding affinity. The result showed that binding affinity of PHA-E to EGFR was one order higher than EGF to EGFR. In the results of flow cytometer and confocal microscope, we found binding efficiency of EGF to EGFR was decrease as the concentration of PHA-E increased. In the analysis of Western blot, treatment of A-549 cells with PHA-E resulted in a dose-dependent decrease in EGFR phosphorylation. In conclusion, we found that PHA-E had better adhesion force and binding affinity to EGFR than that of the EGF. The interaction between PHA-E and EGFR could block EGF binding and then inhibit EGFR phosphorylation. PHA-E could be developed into a new target molecule for lung cancer treatment that could be immobilized on the drug carrier to guide therapeutic particles to the tumor site.

Quantum efficiency enhancement in selectively transparent silicon thin film solar cells by distributed Bragg reflectors.

This work demonstrated a-Si:H thin-film solar cells with backside TiO(2)/ SiO(2) distributed Bragg reflectors (DBRs) for applications involving building-integrated photovoltaics (BIPVs). Selectively transparent solar cells are formed by adjusting the positions of the DBR stop bands to allow the transmission of certain parts of light through the solar cells. Measurement and simulation results indicate that the transmission of blue light (430 ~500 nm) with the combination of three DBR mirrors has the highest increase in conversion efficiency.

Quantum efficiency enhancement in selectively transparent silicon thin film solar cells by distributed Bragg reflectors.

This work demonstrated a-Si:H thin-film solar cells with backside TiO(2) / SiO(2) distributed Bragg reflectors (DBRs) for applications involving building-integrated photovoltaics (BIPVs). Selectively transparent solar cells are formed by adjusting the positions of the DBR stop bands to allow the transmission of certain parts of light through the solar cells. Measurement and simulation results indicate that the transmission of blue light (430 ~500 nm) with the combination of three DBR mirrors has the highest increase in conversion efficiency.

The application of waterworks sludge ash to stabilize the volume of cement paste.

In order to extend the recycling of waterworks sludge to engineering applications, this paper addresses the influence of nano-SiO2 on incinerated waterworks sludge ash (IWSA) cement paste attacked by sulfate. Tests were performed such as length measurement for volume change, compressive strength, weight loss, and micro-structural testing using scanning electron microscopy (SEM). The results indicate that when a portion of the cement in the paste was replaced by IWSA, the IWSA diluted the cementitious material C3A, and filled the capillary pores in the hardened paste. Moreover, since IWSA has potential pozzolanic activity, it can chemically react with Ca(OH)2 crystals in the paste and can consequently improve the resistance of the paste to sulfate attack. Test results also show that due to the fully developed pozzolanic effect of IWSA, the major reaction products of sulfate attack, gypsum and ettringite, were clearly reduced. Hence, the expansion rate in length decreased with the increase of IWSA replacement. Furthermore, the addition of nano-SiO2 to IWSA cement paste can also reduce the length expansion rate.

The effects of nano-materials on the behaviors of sludge mortar specimens.

In this research, nano-composites are added to sewage sludge ash to create a mixture, which then replaces part of cement. Nano-composites are manufactured from pure quartzose sand. The influences of different amounts of nano-composites and sludge ash on mortar are evaluated. Cement, sludge ash (0%, 10%, and 20%), and nano-composites (0%, 0.5%, 1%, 2%, and 3%), which defined as the percent weight of cement and sludge ash, are mixed together in batches to make mortar specimens. Results show that the flowability of sludge ash mortar reduces with increasing amount of cement replaced and of nano-composites added. The compressive strength of mortar lowers when more amounts of cement are replaced by sludge ash, but increases with more quantity of nano-composites added. Moreover, the study shows that nano-composites can fortify the compressive strength of mortar. With the help of efficiency of compressive strength, nano-composites benefit most to the mortar with replacement of 10% sludge ash, followed by the substitution of 20% and 0%.

The CT appearance of pleural and extrapleural disease in lymphoma.

OBJECTIVE: Pleural effusions in patients with lymphoma that are assumed to be related to malignancy are attributed to either lymphatic obstruction by tumour with resultant decreased clearance of pleural fluid, or direct tumour involvement of the pleura. The purpose of our study was to determine how often pleural or extrapleural disease was detected by computed tomography (CT) of patients with pleural effusions and primary or recurrent lymphoma. METHODS AND MATERIALS: We reviewed CT examinations showing evidence of pleural effusion in 61 patients with a diagnosis of primary or recurrent lymphoma and no history of other systemic disorders, including infection. The study population consisted of patients with non-Hodgkin's lymphoma (n = 44) or Hodgkin's disease (n = 17); both primary disease (n = 11) and recurrent disease (n = 50) were represented. Each CT examination was evaluated for the presence of disease involving the visceral and parietal pleura and extrapleural space, mediastinal adenopathy, and pulmonary parenchymal disease. RESULTS: Fourteen patients (23%) (nine with non-Hodgkin's lymphoma and five with Hodgkin's disease) had parietal pleural disease (thickening or nodules). Eighteen patients (30%) (14 with non-Hodgkin's lymphoma, four with Hodgkin's disease) had tumour or enlarged lymph nodes in the extrapleural space. Forty-three patients (70%) had mediastinal lymphadenopathy. Patients who received intravenous contrast did not have evidence of visceral pleural abnormalities or underlying pulmonary parenchymal disease. CONCLUSION: Forty-one percent of the patients with lymphoma and pleural effusions had CT evidence of pleural and/or extrapleural disease. The majority of the patients with extrapleural disease had adjacent posterior mediastinal disease.