NLRP3 inflammasome-induced pyroptosis in digestive system tumors

Programmed cell death (PCD) refers to cell death in a manner that depends on specific genes encoding signals or activities. PCD includes apoptosis, pyroptosis, autophagy and necrosis (programmed necrosis). Among these mechanisms, pyroptosis is mediated by the gasdermin family and is accompanied by inflammatory and immune responses. When pathogens or other danger signals are detected, cytokine action and inflammasomes (cytoplasmic multiprotein complexes) lead to pyroptosis. The relationship between pyroptosis and cancer is complex and the effect of pyroptosis on cancer varies in different tissue and genetic backgrounds. On the one hand, pyroptosis can inhibit tumorigenesis and progression; on the other hand, pyroptosis, as a pro-inflammatory death, can promote tumor growth by creating a microenvironment suitable for tumor cell growth. Indeed, the NLRP3 inflammasome is known to mediate pyroptosis in digestive system tumors, such as gastric cancer, pancreatic ductal adenocarcinoma, gallbladder cancer, oral squamous cell carcinoma, esophageal squamous cell carcinoma, in which a pyroptosis-induced cellular inflammatory response inhibits tumor development. The same process occurs in hepatocellular carcinoma and some colorectal cancers. The current review summarizes mechanisms and pathways of pyroptosis, outlining the involvement of NLRP3 inflammasome-mediated pyroptosis in digestive system tumors

A Novel Photoelectrochemical Biosensor for Tyrosinase and Thrombin Detection

A novel photoelectrochemical biosensor for step-by-step assay of tyrosinase and thrombin was fabricated based on the specific interactions between the designed peptide and the target enzymes. A peptide chain with a special sequence which contains a positively charged lysine-labeled terminal, tyrosine at the other end and a cleavage site recognized by thrombin between them was designed. The designed peptide can be fixed on surface of the CdTe quantum dots (QDs)-modified indium-tin oxide (ITO) electrode through electrostatic attraction to construct the photoelectrochemical biosensor. The tyrosinase target can catalyze the oxidization of tyrosine by oxygen into ortho-benzoquinone residues, which results in a decrease in the sensor photocurrent. Subsequently, the cleavage site could be recognized and cut off by another thrombin target, restoring the sensor photocurrent. The decrease or increase of photocurrent in the sensor enables us to assay tyrosinase and thrombin. Thus, the detection of tyrosinase and thrombin can be achieved in the linear range from 2.6 to 32 μg/mL and from 4.5 to 100 μg/mL with detection limits of 1.5 μg/mL and 1.9 μg/mL, respectively. Most importantly, this strategy shall allow us to detect different classes of enzymes simultaneously by designing various enzyme-specific peptide substrates

Effects of metal ions and an inhibitor on the fluorescence and activity of acutolysin A from Agkistrodon acutus venom

100-105Acutolysin A, a protein isolated from the venom of Chinese Five-pace snake (Agkistrodon acutus) has shown marked hemorrhagic and proteolytic activities. In the present study, the effects of metal ions and an inhibitor EDTA on the fluorescence and function of autolysin A have been studied, by following fluorescence and activity measurements. Acutolysin A contains a Ca²⁺-binding site, which provides it with important structural stability, and a Zn²⁺-binding site, which is essential for its enzymatic activities. The removal of metal ions in acutolysin A by incubation with EDTA results in irreversible inhibition and complete denaturation, and a marked decrease in its fluorescence intensity. The fluorescence intensity of acutolysin A is also decreased in the presence of Cu²⁺, Co²⁺, Mn²⁺ or Mg²⁺, but does not change in the presence of Ca²⁺, Cd²⁺, or Tb³⁺. Caseinolytic activity of acutolysin A is enhanced by Co²⁺, Ca²⁺ and Mg²⁺, but is partly inhibited by Cu²⁺, Mn²⁺ and Tb³⁺, and completely inhibited by Cd²⁺. Both Zn²⁺ and Co²⁺ recover the loss of activity of the protein caused by Cd²⁺

Microstructure and properties of Ni-based self-lubricating coatings by laser cladding/friction stir processing

The KF-2-WC-CaF2\ua0Ni-based self-lubrication coatings were synthesized on the surface of 6061 aluminum alloy with preset powder by laser cladding / friction stir processing (FSP). OM, SEM, EDS and XRD were used to characterize the phase constituents, microstructure and properties of the coatings, and the micro-hardness distribution and wear properties were also analyzed. The results showed that smooth and good metallurgical bonding zone is formed between the coating and the substrate. The microstructure of the one-stepped coating is dendrite, cell crystal, columnar crystal and equiaxed crystal. The main phase constituents of the two-stepped coating consist of α-Ni, α-Al, AlNi3, Al3Ni2, WC and CaF2. And the micro-hardness is significantly higher than that by direct laser cladding. With the increase of distance between coating and stirring tool, mechanical effect gradually weakened, micro-hardness curve and friction coefficient showed a gradient feature along the thickness direction

RYBP Inhibits Progression and Metastasis of Lung Cancer by Suppressing EGFR Signaling and Epithelial-Mesenchymal Transition

Lung cancer (LC) is a common lethal malignancy with rapid progression and metastasis, and Ring1 and YY1 binding protein (RYBP) has been shown to suppress cell growth in human cancers. This study aimed to investigate the role of RYBP in LC progression and metastasis. In this study, a total of 149 LC patients were recruited, and the clinical stage of their tumors, metastasis status, survival time, presence of epidermal growth factor receptor (EGFR) mutation, and RYBP expression levels were measured. RYBP silencing and overexpression were experimentally performed in LC cell lines and in nude mice, and the expressions of genes in EGFR-related signaling pathways and epithelial-mesenchymal transition (EMT) were detected. The results showed that RYBP was downregulated in LC compared with adjacent normal tissues, and low RYBP expression was associated with a more severe clinical stage, high mortality, high metastasis risk, and poor survival. Cell proliferation and xenograft growth were inhibited by RYBP overexpression, whereas proliferation and xenograft growth were accelerated by RYBP silencing. EGFR and phosphorylated-EGFR levels were upregulated when RYBP was silenced, whereas EGFR, p-EGFR, p-AKT, and p-ERK were downregulated when RYBP was overexpressed. Low RYBP expression was related to a high metastasis risk, and metastasized tumors showed low RYBP levels. Cell migration and invasion were promoted by silencing RYBP but were inhibited by overexpressed RYBP. In addition, the EMT marker vimentin showed diminished expression, and E-cadherin was promoted by the overexpression of RYBP. In conclusion, our data suggest that RYBP suppresses cell proliferation and LC progression by impeding the EGFR-ERK and EGFR-AKT signaling pathways and thereby inhibiting cell migration and invasion and LC metastasis through the suppression of EMT

Spatial Variability and Factors Influencing the Air-Sea N2O Flux in the Bering Sea, Chukchi Sea and Chukchi Abyssal Plain

The concentrations of the ozone-depleting greenhouse gas nitrous oxide (N2O) in the upper 300 m of the Subarctic and Arctic Oceans determined during the 5th Chinese National Arctic Research Expedition were studied. The surface water samples revealed that the study area could be divided into three regions according to the distribution of dissolved N2O in the surface water, namely, the Aleutian Basin (52° N–60° N), continental shelf (60° N–73° N) and Canadian Basin (north of 73° N), with N2O in the surface water in equilibrium, oversaturated and undersaturated relative to the atmosphere, respectively. The influences of physical and chemical processes, such as eddy diffusion and sedimentary emissions, beneath the surface layer are discussed. The results of a flux evaluation show that the Aleutian Basin may be a weak N2O source of approximately 0.46 ± 0.1 μmol·m−2·d−1, and the continental shelf acts as a strong N2O source of approximately 8.2 ± 1.4 μmol·m−2·d−1. By contrast, the Chukchi Abyssal Plain (CAP) of the Canadian Basin is at least a temporal N2O sink with a strength of approximately −10.2 ± 1.4 μmol·m−2·d−1

Spatiotemporal Distribution of Nitrous Oxide on the Northeastern Bering Sea Shelf

Rapid warming and loss of sea ice in the Arctic Ocean could play an important role in the dissolution and emission of greenhouse gas nitrous oxide (N2O). We investigated dissolved N2O in spatiotemporal distribution on the northeastern Bering Sea shelf (NEBS) in the summer of 2012. The results showed that N2O concentrations were higher in the Chirikov Basin (mean ± SD, 14.8 ± 2.4 nmol/L) than in the south of St. Lawrence Island (mean ± SD, 17.7 ± 2.3 nmol/L). In the Chirikov Basin, N2O displayed a decreasing distribution pattern from west (~20.4 nmol/L) to east (~12.9 nmol/L). In the area south of St. Lawrence Island, N2O almost presented a two-layer structure, although it showed a vertically homogeneous distribution in the inner shelf. In the cold bottom water, the N2O was affected mainly by in situ production or sediment emission. Longer resident time may cause N2O accumulation in the cold bottom water. The calculated sea–air flux (−1.6~36.2 μmol/(m2·d)) indicates that the NEBS is an important potential source of atmospheric N2O and could play an important role in global oceanic N2O emission with intensifying global issues

Fabrication and Tribological Properties of Nickel-Based Cellular Structure Self-Lubricating Composites by Selective Laser Melting and Metal Infiltration

The service life of Inconel 718 (IN718) nickel-based superalloys under extreme working conditions is limited due to their poor tribological properties. In this study, IN718 cellular structure self-lubricating composites were fabricated by selective laser melting (SLM) and multi-soft metal (Sn-Pb-Ag) infiltration. Different cellular structures were verified by means of numerical simulation and experiment. The effects of pore diameter and temperature on tribological properties of the selective-laser-melted (SLMed) IN718 with Sn-Pb-Ag (INSPA) infiltration self-lubricating composites were investigated. Results show that INSPA samples of cellular structure with a pore diameter of 1.4 mm (INSPA3) exhibited excellent tribological properties compared to the two other pore diameters of 1.2 mm (INSPA2) and 1.0 mm (INSPA1). The tribological properties test results at different temperatures indicate that the coefficient of friction (COF) of INSPA3 was decreased from 0.29 to 0.13 as the temperature of 25 \ub0C rose to 350 \ub0C. The reason is that more Sn-Pb-Ag lubricant was stored in the Ф1.4-mm holes, which were heated and expanded to the worn surface during the friction process to realize self-compensation lubrication. At 350 \ub0C, the friction product of Pb2O was decomposed into PbO and other multicomponent friction oxides were generated, which improves the wear resistance of the SLMed INSPA self-lubricating composites. This study demonstrates a potential approach to enhance the tribological properties and service life of IN718 superalloys used in harsh friction conditions

Glyceryl Trinitrate for Prevention of Post-ERCP Pancreatitis and Improve the Rate of Cannulation: A Meta-Analysis of Prospective, Randomized, Controlled Trials

<div><p>Background</p><p>Acute pancreatitis is the most common complication of diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP). Several clinical trials used glyceryl trinitrate (GTN) to prevent the incidence of post-ERCP pancreatitis (PEP). However, the results were still controversial.</p> <p>Objective</p><p>To conduct a meta-analysis of published, full-length, randomized controlled trials evaluating the effect of prophylactic GTN on the prevention of PEP, improve the rate of cannulation and the prevention of hyperamylasemia.</p> <p>Methods</p><p>Literature searches were conducted using PubMed, EMBASE, The Cochrane Library and Web of Knowledge databases, using keywords "post-ERCP" and "pancreatitis" and limited in randomized controlled trials.</p> <p>Results</p><p>Twelve RCTs involving 2649 patients were included. Eleven RCTs compared GTN with placebo for PEP prevention. Meta-analysis showed the overall incidence of PEP was significantly reduced by GTN treatment (RR 0.67; 95% CI, 0.52-0.87). Nevertheless, GTN administration did not decrease the incidence of moderate to severe PEP (RR 0.70; 95% CI, 0.42-1.15). Subgroup analyses revealed that GTN administered by sublingual was more effective than transdermal and topical in reducing the incidence of PEP. Besides, the prophylactic effect of GTN was far more obvious in the group of high PEP incidence than in the group of low PEP incidence. Additionally, the incidence of hyperamylasemia was significantly reduced by GTN treatment (RR 0.69; 95% CI, 0.54-0.90). No differences of the successful cannulation rate of bile ducts (RR 1.03; 95% CI, 0.99-1.06) attributable to GTN were observed.</p> <p>Conclusion</p><p>Prophylactic use of GTN reduced the overall incidence of PEP and hyperamylasemia. However, GTN was not helpful for the severity of PEP and the rate of cannulation.</p> </div