Variant alleles of the D2 dopamine receptor gene may play a role in determining nicotine addiction, although the associations between the at-risk genotypes and measures of nicotine addiction were not entirely consistent.
Some living organisms such as the octopus have fantastic abilities to simultaneously swim away and alter body color/morphology for disguise and self‐protection, especially when there is a threat perception. However, it is still quite challenging to construct artificial soft actuators with octopus‐like synergistic shape/color change and directional locomotion behaviors, but such systems could enhance the functions of soft robotics dramatically. Herein, we proposed to utilize unique hydrophobic carbon dots (CDs) with rotatable surficial groups to construct the aggregation‐induced emission (AIE) active glycol CDs polymer gel, which could be further employed to be interfacially bonded to an elastomer to produce anisotropic bilayer soft actuator. When putting the actuator on a water surface, glycol spontaneously diffused out from the gel layer to allow water intake, resulting in a color change from a blue dispersion fluorescence to red AIE and a shape deformation, as well as a large surface tension gradient that can promote its autonomous locomotion. Based on these findings, artificial soft swimming robots with octopus‐like synergistic shape/color change and directional swimming motion were demonstrated. This study provides an elegant strategy to develop advanced multi‐functional bio‐inspired intelligent soft robotics.
In the past decade, stimuli-responsive drug delivery vehicles based on surface-functionalized mesoporous silica nanoparticles have attracted intense interest as a new type of drug carrier.
The regulation of renal function by extracellular nucleotides encompasses alterations in glomerular hemodynamics, microvascular function, tubuloglomerular feedback, tubular transport, cell growth or apoptosis, and transport of water and solutes in the medullary collecting duct. Nearly all cells can release ATP or other nucleotides that are then rapidly hydrolyzed in the extracellular milieu. However, little information is available on the cellular expression of ectoenzymes that hydrolyze extracellular nucleotides within the kidney. Nucleoside triphosphate diphosphohydrolases (NTPDases) are plasma membrane-bound ectonucleotidases. NTPDase1 has identity with CD39, a B lymphocyte activation marker, and hydrolyzes extracellular ATP and ADP to AMP within the vasculature, whereas NTPDase2/CD39L(ike)1 preferentially converts ATP to ADP outside of blood vessels. Using immunohistochemical and in situ hybridization approaches, we localized the protein and mRNA of NTPDase1 and 2 in murine renal tissues. In the renal cortex, NTPDase1 is expressed by vascular smooth muscle cells and endothelium in interlobular arteries, afferent glomerular arterioles, and peritubular capillaries. In the inner medulla, NTPDase1 is expressed in ascending thin limbs of Henle's loop, ducts of Bellini, and in the pelvic wall. In contrast, NTPDase2 is expressed in Bowman's capsule, glomerular arterioles, adventitia of blood vessels, and pelvic wall. Thus the distribution patterns of NTPDases have parallels to the known distribution of P2 receptors within the kidney. NTPDases may modulate regulatory effects of ATP and degradation products within the vasculature and other sites and thereby potentially influence physiological as well as multiple pathological events in the kidney.
Extracellular nucleotides, acting through the P2Y2 receptor and the associated phosphoinositide-Ca2+ signaling pathway, inhibit AVP-stimulated osmotic water permeability in rat inner medullary collecting duct (IMCD). Because a rise in intracellular Ca2+ is frequently associated with enhanced arachidonic acid metabolism, we examined the effect of activation of the P2Y2 receptor on release of PGE2 in freshly prepared rat IMCD suspensions. Unstimulated IMCD released moderate, but significant, amounts of PGE2, which were more sensitive to cyclooxygenase (COX)-2 than COX-1 inhibition. Agonist activation of P2Y2 receptor by adenosine 5'-O-(3-thiotriphosphate) enhanced release of PGE2 from IMCD in a time- and concentration-dependent fashion. Purinergic-stimulated release of PGE2 was completely blocked by nonspecific COX inhibitors (flurbiprofen and 2-acetoxyphenylhept-2-ynyl sulfide). Differential COX inhibition studies revealed that purinergic-stimulated release of PGE2 was more sensitive to a COX-1-specific inhibitor (valeroyl salicylate) than a COX-2-specific inhibitor (NS-398). Thus purinergic stimulation resulted in significantly more release of PGE2 in the presence of COX-2 inhibitor than COX-1 inhibitor. If it is assumed that increased release of PGE2 is related to its increased production, our results suggest that purinergic stimulation of IMCD results in enhanced production and release of PGE2 in a COX-1-dependent fashion. Because PGE2 is known to affect transport of water, salt, and urea in IMCD, interaction of the purinergic system with the prostanoid system in IMCD can modulate handling of water, salt, and urea by IMCD and, thus, may constitute an AVP-independent regulatory mechanism.
Polyhedral oligomeric silsesquioxanes (POSS) represent the new frontier in hybrid materials science and engineering, because of their well-defined nanostructure and unique dual nature combining material properties from both inorganic siloxane cage and organic groups at the periphery. Recent advances in synthetic chemistry, combined with the controlled radical polymerization techniques, have significantly influenced the construction of POSS soft gel as emerging biomaterials and beyond. In this Review, the most recent developments in the design strategies of POSS-based hybrid soft gels are presented, with respect to different functions of architectural POSS, including POSS as a crosslinker, end-cap polymer chain, pendent group, etc. In addition, the insights into the uniqueness of POSS in microstructure and their different organic substituents in the enhancement of the hydrogel performance are illustrated. These sophisticated materials with multiple functions, oriented toward advanced therapeutic applications, are further summarized into several active domains in controlled drug delivery, 3D cell culture, tissue engineering, and wound healing. The recent new applications of using POSS hybrid soft gel in environmental health are also summarized in this Review. Finally, perspectives and challenges related to the further advancement of POSS-based hybrid soft gel materials are discussed.
Cytochrome P4502E1 (CYP2E1) is involved in the metabolic activation of carcinogenic N-nitrosoamines. We therefore assessed the genotype frequencies of PstI or RsaI CYP2E1 restriction fragment length polymorphisms and another susceptibility marker, mutagen sensitivity, in 137 lung cancer cases (92 African American and 45 Mexican American) and 206 controls (114 African American and 92 Mexican American) identified in a molecular epidemiological study of lung cancer. The CYP2E1 c1/c1 genotype was found in 86.7% of Mexican American cases, 70.6% of Mexican American controls, 89.1% of African American cases and 86.8% of African American controls. By multivariate analysis, this genotype was found to be associated with a 14.0-fold increased risk of lung cancer in Mexican Americans but not in African Americans; a 9.9-fold increased risk of lung cancer in Mexican American former smokers, but not in non-smokers or current smokers; a 15-fold increased risk of lung cancer in Mexican American males, but not in females. Patients with the susceptible genotype appeared to have developed cancer at an earlier age and with lower cigarette pack-year of exposure than did patients with the c1/c2 or c2/c2 genotypes. Stratified analysis suggested a greater than multiplicative interaction between cigarette smoking and CYP2E1 c1/c1 genotype, although not statistically significant. The odds ratios (ORs) for the CYP2E1 c1/c1 genotype, cigarette smoking and both risk factors combined were 1.3, 6.7 and 16.3, respectively. The association between CYP2E1 c1/c1 genotype and pack-years of smoking followed the same pattern. The interaction between mutagen sensitivity and CYP2E1 c1/c1 genotype was especially strong in former smokers (the ORs for the CYP2E1 c1/c1 genotype, mutagen sensitivity and both risk factors combined were 3.9, 5.4 and 23.0, respectively). Therefore, the data suggest that individuals who lack a c2 allele might be at higher risk for developing lung cancer.
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