Expression and Prognostic Significance of CD47–SIRPA Macrophage Checkpoint Molecules in Colorectal Cancer

Despite the confirmed anti-cancer effects of T-cell immune checkpoint inhibitors, in colorectal cancer (CRC) they are only effective in a small subset of patients with microsatellite-unstable tumors. Thus, therapeutics targeting other types of CRCs or tumors refractory to T-cell checkpoint inhibitors are desired. The binding of aberrantly expressed CD47 on tumor cells to signal regulatory protein-alpha (SIRPA) on macrophages allows tumor cells to evade immune destruction. Based on these observations, drugs targeting the macrophage checkpoint have been developed with the expectation of anti-cancer effects against T-cell immune checkpoint inhibitor-refractory tumors. In the present study, 269 primary CRCs were evaluated immunohistochemically for CD47, SIRPA, CD68, and CD163 expression to assess their predictive utility and the applicability of CD47–SIRPA axis-modulating drugs. Thirty-five percent of the lesions (95/269) displayed CD47 expression on the cytomembrane of CRC cells. CRCs contained various numbers of tumor-associated immune cells (TAIs) with SIRPA, CD68, or CD163 expression. The log-rank test revealed that patients with CD47-positive CRCs had significantly worse survival than CD47-negative patients. Multivariate Cox hazards regression analysis identified tubular-forming histology (hazard ratio (R) = 0.23), age < 70 years (HR = 0.48), and high SIRPA-positive TAI counts (HR = 0.55) as potential favorable factors. High tumor CD47 expression (HR = 1.75), lymph node metastasis (HR = 2.26), and peritoneal metastasis (HR = 5.80) were cited as potential independent risk factors. Based on our observations, CD47–SIRPA pathway-modulating therapies may be effective in patients with CRC.     

Heat deterioration of phospholipids. V. A new rearrangement reaction of sugars and phosphatidylethanolamine

Novel four 2,3-dihydro-1H-imidazo[1,2-a]pyridine-4-ylium derivatives were obtained with increase of UV absorption at 350 nm and browning of the solution by heating paste lecithin from soybean (SL) in octane. These four derivatives were formed by reaction of one molar of any sugar except 2-deoxysugars with two molar of phosphatidylethanolamines (PE) in SL. To confirm the reaction mechanism, several (13)C-labeled-sugars were reacted with 1,2-di-O-stearoyl-sn-glycero-3-phosphatidylethanolamine (DSPE), respectively. These reactants clearly showed that five carbons of the pyridinium ring and one carbon of the substituted group were based on those of a sugar and that the formation of the pyridinium derivatives was accompanied with cleaving between the carbons of 1- and 2-positions in the sugar and rearrangement. This reaction is a new rearrangement reaction and we named it "new pseudo Maillard rearrangement reaction".     

High docosahexaenoic acid levels in both neutral and polar lipids of a highly migratory fish: <Emphasis Type="Italic">Thunnus tonggol</Emphasis> (Bleeker)

The lipid and FA compositions of various organs (light muscle, dark muscle, liver, pyloric cecum, and the orbital region) and of the stomach contents of a highly migratory fish species Thunnus tonggol (Bleeker) were analyzed. TAG and phospholipids (PE and PC) were the major lipid classes in the total lipids of T. tonggol. DHA was characteristically the major FA of all the major classes of all its organs except for only one case of liver TAG. The mean DHA contents of the various organs accounted for more than 20% of the total FA (TFA), even though it is a neutral depot lipid. However, DHA in the stomach contents, originating from their prey, fluctuated and was generally low. DHA levels were generally higher in a year (2000) when water temperatures were colder than in one when it was warmer (1998). Furthermore, DHA levels in muscle TAG were consistently high in spite of the fluctuation of those in the visceral TAG, which might be directly influenced by the prey lipids. This phenomenon suggests the physiological selective accumulation of DHA in the muscle, after the migration of the digested FA in the vascular system and absorption of the prey lipids in the intestine. In contrast, the FA composition of other species is generally variable and their DHA contents of TAG are usually less than 20% of TFA.     

Fermented foods in a global age: East meets West

Fermented foods and alcoholic beverages have long been an important part of the human diet in nearly every culture on every continent. These foods are often well‐preserved and serve as stable and significant sources of proteins, vitamins, minerals, and other nutrients. Despite these common features, however, many differences exist with respect to substrates and products and the types of microbes involved in the manufacture of fermented foods and beverages produced globally. In this review, we describe these differences and consider the influence of geography and industrialization on fermented foods manufacture. Whereas fermented foods produced in Europe, North America, Australia, and New Zealand usually depend on defined starter cultures, those made in Asia and Africa often rely on spontaneous fermentation. Likewise, in developing countries, fermented foods are not often commercially produced on an industrial scale. Although many fermented products rely on autochthonous microbes present in the raw material, for other products, the introduction of starter culture technology has led to greater consistency, safety, and quality. The diversity and function of microbes present in a wide range of fermented foods can now be examined in detail using molecular and other omic approaches. The nutritional value of fermented foods is now well‐appreciated, especially in resource‐poor regions where yoghurt and other fermented foods can improve public health and provide opportunities for economic development. Manufacturers of fermented foods, whether small or large, should follow Good Manufacturing Practices and have sustainable development goals. Ultimately, preferences for fermented foods and beverages depend on dietary habits of consumers, as well as regional agricultural conditions and availability of resources.     

Polymer formation utilizing ‘crisscross’ addition (crisscross addition polymerization) of acetaldehyde azine and 1,4-phenylene diisocyanate

Acetaldehyde azine (AcAz) underwent ‘crisscross’ addition with two equivalents of phenyl isocyanate to form a one-to-two adduct in a moderate yield (63.0%). Using crisscross addition of AcAz, polymeric products were obtained from AcAz and 1,4-phenylene diisocyanate in a high yield (>80%). The polymer obtained was soluble in 1,1,1,3,3,3-hexafluoro-2-propanol, and insoluble in many organic solvents, including n-hexane, benzene, toluene, chloroform, diethyl ether, tetrahydrofuran, acetone, ethanol, methanol, dimethyl sulfoxide, and N,N-dimethylformamide. The structure of the polymer obtained was characterized by IR and ¹H NMR spectroscopies. The thermal behavior of the polymer was also investigated by thermogravimetric analysis.     

Coherent Electron Transport in Air-Stable,Printed Single-Crystal Organic Semiconductor and Application to Megahertz Transistors

Organic semiconductors (OSCs) have attracted growing attention for optoelectronic applications such as field-effect transistors (FETs), and coherent (or band-like) carrier transport properties in OSC single crystals (SCs) have been of interest as they can lead to high carrier mobilities. Recently, such p-type OSC SCs compatible with a printing technology have been used to achieve high-speed FETs; therefore, developments of n-type counterparts may be promising for realizing high-speed complementary organic circuits. Herein, coherent electron transport properties in a printed SC of a state-of-the-art, air-stable n-type OSC, PhC₂−BQQDI, by means of variable-temperature gated Hall effect measurements and X-ray single-crystal diffraction analyses in conjunction with band structure calculations, are reported. Furthermore, the SC FET is tested for high-speed operations, which obtains a cutoff frequency of 4.3 MHz at an operation voltage of 20 V in air. Thus, PhC₂−BQQDI is shown as a new candidate for practical applications of SC-based, organic complementary devices.     

Effect of Surface Roughening of Substrate Steel on the Improvement of Delamination Strength and Tribological Behavior of Hydrogenated Amorphous Carbon Coating Under Lubricated Conditions

The adhesion strength of diamond-like carbon (DLC) coatings is an obstacle in efforts to improve the reliability of coated products. It is generally believed that the roughening of the substrate surface improves the adhesion between a substrate and coating. The effect of surface roughening of the substrate on the delamination strength of DLC coating and the tribological behavior under lubrication were studied. Five types of roughened substrates were prepared by a wet blast device with differing materials, shapes, and sizes of the shot particles. A hydrogenated DLC film was deposited using plasma-enhanced chemical vapor deposition on the roughened substrates. The tribological properties were investigated under air and lubrication with pure water or n-decane. It was found that the delamination strength of the DLC coating could be improved by roughening the substrate surface, especially by spherical particles. It was also found that slight polishing of either the DLC surface deposited on the rough substrate or the roughened substrate before deposition significantly reduced the wear of the counter surface. The remaining chemical element of alumina particles on the roughened surface affected the delamination strength of the DLC coating.