Dispirooxindole-β-Lactams: Synthesis via Staudinger Ketene-Imine Cycloaddition and Biological Evaluation

In this work, we present the first synthesis of dispirooxindole-β-lactams employing optimized methodology of one-pot Staudinger ketene-imine cycloaddition with N-aryl-2-oxo-pyrrolidine-3-carboxylic acids as the ketene source. Spiroconjugation of indoline-2-one with β-lactams ring is considered to be able to provide stabilization and wide scope of functionalization to resulting scaffolds. The dispipooxindoles obtained demonstrated medium cytotoxicity in the MTT test on A549, MCF7, HEK293, and VA13 cell lines, and one of the compounds demonstrated antibacterial activity against E. coli strain LPTD.     

Age-Related Changes in the Fibroblastic Differon of the Dermis: Role in Skin Aging

Skin aging is a multi-factorial process that affects nearly every aspect of skin biology and function. The processes developing in the skin during aging are based on fundamental molecular mechanisms associated with fibroblasts, the main cellular population of the dermis. It has been revealed that the amount of fibroblasts decreases markedly with age and their functional activity is also reduced. This inevitably leads to a decrease in the regenerative abilities of the skin and the progression of its aging. In this review we consider the mechanisms underlying these processes, mainly the changes observed with age in the stem/progenitor cells that constitute the fibroblastic differon of the dermis and form their microenvironment (niches). These changes lead to the depletion of stem cells, which, in turn, leads to a decrease in the number of differentiated (mature) dermal fibroblasts responsible for the production of the dermal extracellular matrix and its remodeling. We also describe in detail DNA damages, their cellular and systemic consequences, molecular mechanisms of DNA damage response, and also the role of fibroblast senescence in skin aging.     

Nanoparticles in Clinical Trials: Analysis of Clinical Trials,FDA Approvals and Use for COVID-19 Vaccines

Nanoparticles are heterologous small composites that are usually between 1 and 100 nanometers in size. They are applied in many areas of medicine with one of them being drug delivery. Nanoparticles have a number of advantages as drug carriers which include reduced toxic effects, increased bioavailability, and their ability to be modified for specific tissues or cells. Due to the exciting development of nanotechnology concomitant with advances in biotechnology and medicine, the number of clinical trials devoted to nanoparticles for drug delivery is growing rapidly. Some nanoparticles, lipid-based types, in particular, played a crucial role in the developing and manufacturing of the two COVID-19 vaccines—Pfizer and Moderna—that are now being widely used. In this analysis, we provide a quantitative survey of clinical trials using nanoparticles during the period from 2002 to 2021 as well as the recent FDA-approved drugs (since 2016). A total of 486 clinical trials were identified using the clinicaltrials.gov database. The prevailing types of nanoparticles were liposomes (44%) and protein-based formulations (26%) during this period. The most commonly investigated content of the nanoparticles were paclitaxel (23%), metals (11%), doxorubicin (9%), bupivacaine and various vaccines (both were 8%). Among the FDA-approved nanoparticle drugs, polymeric (29%), liposomal (22%) and lipid-based (21%) drugs were the most common. In this analysis, we also discuss the differential development of the diverse groups of nanoparticles and their content, as well as the underlying factors behind the trends.     

Very low density lipoprotein secretion by cultured hepatocytes of rabbits fed purified or autoxidized cholesterol

The main objectives of this study were to compare the effects of dietary commercial cholesterol (containing 5% of oxidized cholesterol derivatives) and purified cholesterol on the secretion rate of very low density lipoprotein apolipoproteins and lipids by cultured rabbit hepatocytes and to verify the hypothesis that products of cholesterol autoxidation stimulate the rapid development of hypercholesterolemia. Rabbits fed dietary (old) commercial cholesterol for six weeks showed a fivefold increase in the serum concentration of cholesterol compared with that in purified cholesterol-fed rabbits. The secretion rates of very low density lipoprotein total protein and very low density lipoprotein [³H]apolipoproteins were similar for the hepatocytes of these two cholesterol-fed groups of animals and were two- and threefold greater, respectively, than for cells from control rabbits. Cholesteryl ester content of the hepatocytes from dietary (old) commercial cholesterol-fed rabbits was dramatically increased in comparison with hepatocytes from control and purified cholesterol-fed rabbits. The elevated intracellular cholesteryl ester content is assumed to account for such an increase of very low density lipoprotein-cholesteryl ester secretion by cells prepared from dietary (old) commercial cholesterol-fed rabbits. These effects appear to be caused by activation of cholesterol esterification by oxidized cholesterol derivatives. The rapid development of hypercholesterolemia induced by dietary (old) commercial cholesterol is associated, at least in part, with the stimulated production of hepatic very low density lipoprotein apolipoproteins and cholesteryl esters.     

Lakewide dominance does not predict the potential for spread of dreissenids

In recent years, quagga mussels (Dreissena rostriformis bugensis) have almost completely replaced zebra mussels (Dreissena polymorpha) in the Lower Great Lakes. As recreational boats are the main vector of spread for dreissenids in North America, this study examined whether lakes Erie and Ontario could still be sources for the spread of zebra mussels. In the summer–fall of 2010, the abundance of each species of Dreissena on 196 boats from 5 marinas in lakes Erie and Ontario was examined. Additional samples of Dreissena in 2010–2012 were collected in tributaries, bays, and in the upper littoral zones of these lakes. A total of 77 boats were fouled by Dreissena, and of those 61 were fouled by both species, 13 were fouled just by zebra mussels, and only 3 were fouled solely by quagga mussels. Although quagga mussels compose ~ 99% of dreissenids in eastern Lake Erie and in Lake Ontario, on boats at most marinas sampled, zebra mussels were usually more abundant and significantly larger than quagga mussels. Refugia for zebra mussels were found in bays, tributaries, and upper littoral zones with high wave activity. Thus, although quagga mussels are now more abundant than zebra mussels within the Lower Great Lakes, these waterbodies still have the potential to be a source for the spread of zebra mussels, and for some vectors, the propagule pressure from zebra mussels is likely greater than that from quagga mussels.     

Asymptotically Efficient Lattice-Based Digital Signatures

We present a general framework that converts certain types of linear collision-resistant hash functions into one-time signatures. Our generic construction can be instantiated based on both general and ideal (e.g., cyclic) lattices, and the resulting signature schemes are provably secure based on the worst-case hardness of approximating the shortest vector (and other standard lattice problems) in the corresponding class of lattices to within a polynomial factor. When instantiated with ideal lattices, the time complexity of the signing and verification algorithms, as well as key and signature size, is almost linear (up to poly-logarithmic factors) in the dimension n of the underlying lattice. Since no sub-exponential (in n) time algorithm is known to solve lattice problems in the worst case, even when restricted to ideal lattices, our construction gives a digital signature scheme with an essentially optimal performance/security trade-off.     

Absolute beam brightness detector

In generally accepted emittance measurement, main attention is concentrated on emittance areas ?(x), ?(y) occupied by desired part of ion beam in transverse phase space and shape of these areas. The absolute beam phase density (brightness) as usually is not measured directly and the average beam brightness B is calculated from a beam intensity I and the transverse emittances. In the ion source and low energy beam transport (LEBT) optimization, it is important to preserve the beam brightness because some aberration of ion optic and beam instabilities can decrease the brightness of the central part of ion beam significantly. For these brightness measurements, it is convenient to use an absolute beam brightness detector with the brightness determination from one short considered in this article.     

Trefftz approximations in complex media: Accuracy and applications

Approximations by Trefftz functions are rapidly gaining popularity in the numerical solution of boundary value problems of mathematical physics. By definition, these functions satisfy locally, in weak form, the underlying differential equations of the problem, which often results in high-order or even exponential accuracy with respect to the size of the basis set. We highlight two separate examples in applied electromagnetics and photonics: (i) homogenization of periodic structures, and (ii) numerical simulation of electromagnetic waves in slab geometries. Extensive numerical evidence and theoretical considerations show that Trefftz approximations can be applied much more broadly than is traditionally done: they are effective not only in physically homogeneous regions but also in complex inhomogeneous ones. Two mechanisms underlying the high accuracy of Trefftz approximations in such complex cases are pointed out. The first one is related to trigonometric interpolation and the second one – somewhat surprisingly – to well-posedness of random matrices.