Mild and General Protocol for Selective Deacetylation of Acetyl/Benzoyl-Protected Carbohydrates.

Herein, we report a mild and general protocol for chemoselective deacetylation of mixed acetyl- and benzoyl-protected carbohydrates under mild acidic conditions. The protocol allows quick access to partially protected carbohydrates, which serve as versatile synthetic intermediates during the total synthesis of various mono- and oligosaccharide targets. The applicability of the developed protocol was successfully demonstrated on a range of carbohydrate substrates of various configurations and substitution patterns featuring functionalized aliphatic and aromatic aglycones. The protocol has shown excellent compatibility with the widely used O-anomeric protecting groups, prespacer aglycones, and thioglycoside glycosyl donors.

Construction of Phenanthridinone Skeletons through Palladium-Catalyzed Annulation.

Herein, a straightforward synthetic approach for the construction of phenanthridin-6(5H)-one skeletons is disclosed. The developed protocol relies on palladium catalysis, providing controlled access to a range of functionalized phenanthridin-6(5H)-ones in 59-88% yields. Furthermore, plausible reaction pathways are proposed based on mechanistic experiments.

First Report of Lysozyme Amyloidosis with p.F21L/T88N Amino Acid Substitutions in a Russian Family.

Lysozyme amyloidosis is caused by an amino acid substitution in the sequence of this protein. In our study, we described a clinical case of lysozyme amyloidosis in a Russian family. In our work, we described in detail the histological changes in tissues that appeared as a result of massive deposition of amyloid aggregates that affected almost all organ systems, with the exception of the central nervous system. We determined the type of amyloidosis and mutations using mass spectrometry. Using mass spectrometry, the protein composition of tissue samples of patient 1 (autopsy material) and patient 2 (biopsy material) with histologically confirmed amyloid deposits were analyzed. Amino acid substitutions p.F21L/T88N in the lysozyme sequence were identified in both sets of samples and confirmed by sequencing of the lysozyme gene of members of this family. We have shown the inheritance of these mutations in the lysozyme gene in members of the described family. For the first time, we discovered a mutation in the first exon p.F21L of the lysozyme gene, which, together with p.T88N amino acid substitution, led to amyloidosis in members of the studied family.

Combining of synthetic VHH and immune scFv libraries for pregnancy-associated glycoproteins ELISA development.

Nanobodies (VHH) from camelid antibody libraries hold great promise as therapeutic agents and components of immunoassay systems. Synthetic antibody libraries that could be designed and generated once and for various applications could yield binders to virtually any targets, even for non-immunogenic or toxic ones, in a short term. One of the most difficult tasks is to obtain antibodies with a high affinity and specificity to polyglycosylated proteins. It requires antibody libraries with extremely high functional diversity and the use of sophisticated selection techniques. Here we report a development of a novel sandwich immunoassay involving a combination of the synthetic library-derived VHH-Fc fusion protein as a capture antibody and the immune single-chain fragment variable (scFv) as a tracer for the detection of pregnancy-associated glycoprotein (PAG) of cattle (Bos taurus). We succeeded in the generation of a number of specific scFv antibodies against PAG from the mouse immune library. Subsequent selection using the immobilized scFv-Fc capture antibody allowed to isolate 1.9 nM VHH binder from the diverse synthetic library without any overlapping with the capture antibody binding site. The prototype sandwich ELISA based on the synthetic VHH and the immune scFv was established. This is the first successful example of the combination of synthetic and immune antibody libraries in a single sandwich immunoassay. Thus, our approach could be used for the express isolation of antibody pairs and the development of sandwich immunoassays for challenging antigens. KEY POINTS: • Heavily glycosylated PAG Bos Taurus were used for immune library construction and specific scFv isolation by phage display. • Nanomolar affinity VHH for PAG was selected from the original synthetic nanobodies library. • A novel VHH/scFv-based immunoassay for Bos Taurus pregnancy determination was developed.

Synthesis of Salicaceae Acetyl Salicins Using Selective Deacetylation and Acetyl Group Migration.

In the present work, the synthesis of acetylated salicins, which occur naturally in many Salicaceae species, is reported. The preparation of 2-O-acetylsalicin, 2-O-acetylchlorosalicin, and 2-O-acetylethylsalicin from peracetylated bromosalicin with selective acid-catalyzed deacetylation and one-pot nucleophilic substitution of bromine as the key steps is described. The base-catalyzed O-2 → O-6 acetyl migration afforded 6-O-acetylsalicin derivatives in good yields. Thus, the first synthesis of 6-O-acetylsalicin (fragilin) using acetyl group migration is reported as well as the synthesis of 6-O-acetylchlorosalicin and 6-O-acetylethylsalicin. The NaOMe-catalyzed deacetylation of acetylated glycosides gave salicin, chlorosalicin, and ethylsalicin recently reported from Alangium chinense.

Divergent Synthesis of Natural Benzyl Salicylate and Benzyl Gentisate Glucosides.

Herein is reported the first total synthesis of benzyl salicylate and benzyl gentisate glucosides present in various plant species, in particular the Salix genus, such as Populus balsamifera and P. trichocarpa. The method permits the synthesis of several natural phenolic acid derivatives and their glucosides starting from salicylic or gentisic acid. The divergent approach afforded access to three different acetylated glucosides from a common synthetic intermediate. The key step in the total synthesis of naturally occurring glycosides-the selective deacetylation of the sugar moiety-was achieved in the presence of a labile benzyl ester group by employing mild deacetylation conditions. The protocol permitted synthesis of trichocarpine (4 steps, 40% overall yield), isotrichocarpine (3 steps, 51% overall yield), trichoside (6 steps, 40% overall yield), and deoxytrichocarpine (3 steps, 42% overall yield) for the first time (>95% purity). Also, the optimized mild deacetylation conditions allowed synthesis of 2-O-acetylated derivatives of all four glycosides (5-17% overall yield, 90-95% purity), which are rare plant metabolites.

The role of feature-based discrimination in driving health disparities among Black Americans.

Objective: A growing body of research finds that darker skin tone is often associated with poorer physical and mental health in Blacks. However, the psychosocial mechanisms underlying the skin tone-health link remain elusive. The present study seeks to address this knowledge gap by investigating the direct and indirect (through perceived discrimination, socioeconomic status, and self-esteem) effects of skin tone on self-reported physical and mental health.Design: An urban sample of 130 Blacks aged 35 and above completed a self-administered computerized survey as a part of larger cross-sectional study.Results: Self-esteem played a particularly important role in mediating the associations between skin tone and self-reported physical and mental health. This suggests that self-esteem could be a point of intervention to help Blacks with darker skin tone achieve better health.Conclusion: The present study highlights the important role feature-based discrimination plays in determining mental and physical health outcomes among Blacks.

The development of race-based perceptual categorization: skin color dominates early category judgments.

Prior research on the development of race-based categorization has concluded that children understand the perceptual basis of race categories from as early as age 4 (e.g. Aboud, 1988). However, such work has rarely separated the influence of skin color from other physiognomic features considered by adults to be diagnostic of race categories. In two studies focusing on Black-White race categorization judgments in children between the ages of 4 and 9, as well as in adults, we find that categorization decisions in early childhood are determined almost entirely by attention to skin color, with attention to other physiognomic features exerting only a small influence on judgments as late as middle childhood. We further find that when skin color cues are largely eliminated from the stimuli, adults readily shift almost entirely to focus on other physiognomic features. However, 6- and 8-year-old children show only a limited ability to shift attention to facial physiognomy and so perform poorly on the task. These results demonstrate that attention to 'race' in younger children is better conceptualized as attention to skin color, inviting a reinterpretation of past work focusing on children's race-related cognition.

Humic substances enhance growth and respiration in the basidiomycetes Trametes maxima under carbon limited conditions.

Humic substances (HS) represent the major reservoir of carbon (C) in ecosystems, and their turnover is crucial for understanding the global C cycle. Although basidiomycetes clearly have a role in HS degradation, much less is known about the effect of HS on fungal traits. We studied the alteration of physiological, biochemical, and morphological characteristics of Trametes maxima in the presence of HS. Both complete medium and minimal (C-limited) medium mimicking natural environmental conditions were used. Adding HS led to increased biomass yield, but under C-limited conditions the effect was more apparent. This result indicated that HS were used as an additional substrate and agreed with data showing a greater penetration of tritium-labeled HS into the cell interior under C-limited conditions. Humic substances induced ultra-structural changes in fungal cells, especially under C limitation, including reducing the thicknesses of the hyphal sheath and cell wall. In the minimal medium, cellular respiration increased nearly three-fold under HS application, while the corresponding effect in complete medium was lower. In addition, in the presence of inhibitors, HS stimulated either the cytochrome or the alternative pathway of respiration, depending on presence or absence of glucose in the medium. Our results suggest that, under conditions mimicking the natural environment, HS may play three major roles: as a surplus substrate for fungal growth, as a factor positively affecting cell morphology, and as an activator of physiological respiration.

Asymmetric synthesis of unnatural α-amino acids through photoredox-mediated C-O bond activation of aliphatic alcohols.

Unnatural α-amino acids constitute a fundamental class of biologically relevant compounds. However, despite the interest in these motifs, synthetic strategies have traditionally employed polar retrosynthetic disconnections. These methods typically entail the use of stoichiometric amounts of toxic and highly sensitive reagents, thereby limiting the substrate scope and practicality for scale up. In this work, an efficient protocol for the asymmetric synthesis of unnatural α-amino acids is realized through photoredox-mediated C-O bond activation in oxalate esters of aliphatic alcohols as radical precursors. The developed system uses a chiral glyoxylate-derived N-sulfinyl imine as the radical acceptor and allows facile access to a range of functionalized unnatural α-amino acids through an atom-economical redox-neutral process with CO2 as the only stoichiometric byproduct.

General Approach to Amides through Decarboxylative Radical Cross-Coupling of Carboxylic Acids and Isocyanides.

Herein, we report a silver-catalyzed protocol for decarboxylative cross-coupling between carboxylic acids and isocyanides, leading to linear amide products through a free-radical mechanism. The disclosed approach provides a general entry to a variety of decorated amides, accommodating a diverse array of radical precursors, including aryl, heteroaryl, alkynyl, alkenyl, and alkyl carboxylic acids. Notably, the protocol proved to be efficient for decarboxylative late-stage functionalization of several elaborate pharmaceuticals, demonstrating its potential applications.

Task measuring implicit attractiveness as a function of skin tone and facial features: a failed replication.

In two studies, participants completed an implicit attractiveness task with faces as primes varying on (a) facial features from Afrocentric to Eurocentric and (b) skin tone from dark to light, and target pictures of environmental scenes varying in attractiveness. On each trial, participants were briefly primed with a face. Next, they categorized a target picture as either attractive or unattractive as quickly as possible. In addition, in Study 2, participants rated the same faces on an attractiveness scale. While results of Study 1 showed that when faces were medium in skin tone, participants were more accurate when primed with a Eurocentric face responding to attractive targets, but also more accurate when primed with an Afrocentric face responding to unattractive targets, a more powerful Study 2 failed to replicate this effect. There was no relationship between participants' explicit ratings of attractiveness and accuracy rates in the implicit attractiveness task.

Sweetened Alkylated Verdazyls Effectively Kill Cancer Cells under Light Irradiation.

The development of novel photo-dynamic therapy (PDT) agents enabling to treat the oxygen-deficient tumors is the emerging tasks for the modern medicinal chemistry. Herein, we describe the design and preparation of water-soluble agents for PDT which generate active radical species upon light irradiation. Two conjugates of carbohydrates with 1,2,4,6-substituted-1,4-dihydro-1,2,4,5-tetrazin-3(2H)-ones (AlkVZs) demonstrated high oxygen-independent cytotoxicity on PC-3 and Jurkat cancer cells under light irradiation combining with low toxicity in the dark. The efficacy of prepared compounds was estimated using MTT and Alamar Blue tests as well as microscopic dead/live colored images and flow cytometry. The analysis of obtained results reveals the influence of sugar moiety on the activity of AlkVZs. We believe that obtained compounds have high potency as platform for design of new agents for photo-dynamic therapy.

What's in a face? The role of skin tone, facial physiognomy, and color presentation mode of facial primes in affective priming effects.

Participants (N = 106) performed an affective priming task with facial primes that varied in their skin tone and facial physiognomy, and, which were presented either in color or in gray-scale. Participants' racial evaluations were more positive for Eurocentric than for Afrocentric physiognomy faces. Light skin tone faces were evaluated more positively than dark skin tone faces, but the magnitude of this effect depended on the mode of color presentation. The results suggest that in affective priming tasks, faces might not be processed holistically, and instead, visual features of facial priming stimuli independently affect implicit evaluations.

"Everything good against everything bad": traditional values in the search for new Russian national idea.

The purpose of the article is to explore origins, development and meaning of the Russian Orthodox Church's concept of traditional values in comparison with its interpreting and utilizing by the Russian political powers through the analysis of the main statements of the ROC's hierarchs, as well as of leading political figures in the period 2000s until nowadays. The following research questions are formulated: What are traditional values in the ROC's and state understanding, and what is the purpose of their promotion? What is the impact of traditional values discourse over people? The conclusion is made that traditional values are seen as one of substantial elements of the present-day Russian political and ideological conservatism and the core element of the identity construction. The ROC as the prominent and influential religious body is seen by political powers, as well as by general public, to be most notably linked to morality; and she seems to take for granted the status of moral authority. At the same time, there is a lack of reliable data, which make possible to estimate the real impact of traditional values over Russian people and the amount of those who share them.

Exploiting photoredox catalysis for carbohydrate modification through C-H and C-C bond activation.

Photoredox catalysis has recently emerged as a powerful synthetic platform for accessing complex chemical structures through non-traditional bond disconnection strategies that proceed through free-radical intermediates. Such synthetic strategies have been used for a range of organic transformations; however, in carbohydrate chemistry they have primarily been applied to the generation of oxocarbenium ion intermediates in the ubiquitous glycosylation reaction. In this Review, we present more intricate light-induced synthetic strategies to modify native carbohydrates through homolytic C-H and C-C bond cleavage. These strategies allow access to glycans and glycoconjugates with profoundly altered carbohydrate skeletons, which are challenging to obtain through conventional synthetic means. Carbohydrate derivatives with such structural motifs represent a broad class of natural products integral to numerous biochemical processes and can be found in active pharmaceutical substances. Here we present progress made in C-H and C-C bond activation of carbohydrates through photoredox catalysis, focusing on the operational mechanisms and the scope of the described methodologies.

Scalable total synthesis of natural vanillin-derived glucoside ω-esters.

The first total synthesis of vanilloloside, calleryanin, and a series of naturally occurring ω-esters of vanilloloside was realized through direct glycosylation of vanillin-based aglycones or late-stage derivatization of vanilloloside. All aglycones and their fragments were synthesized from vanillin as the sole aromatic precursor. Subsequently, these intermediates were used to construct various vanillin-derived glucoside ω-esters using a mild acidic deacetylation as the key synthetic step, providing the final products in the total yields of 10-50% and general purity of >95%. Additionally, the first operationally simple and sustainable synthesis of litseafoloside B was realized on large scale, avoiding the use of toxic solvents and reagents, providing an attractive alternative to isolation of this and other similar compounds from plant sources.

Multi-Omics Approach Points to the Importance of Oxylipins Metabolism in Early-Stage Breast Cancer.

The involvement of oxylipins, metabolites of polyunsaturated fatty acids, in cancer pathogenesis was known long ago, but only the development of the high-throughput methods get the opportunity to study oxylipins on a system level. The study aimed to elucidate alterations in oxylipin metabolism as characteristics of breast cancer patients. We compared the ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) oxylipin profile signatures in the blood plasma of 152 healthy volunteers (HC) and 169 patients with different stages of breast cancer (BC). To integrate lipidomics, transcriptomics, and genomics data, we analyzed a transcriptome of 10 open database datasets obtained from tissues and blood cells of BC patients and SNP data for 33 genes related to oxylipin metabolism. We identified 18 oxylipins, metabolites of omega-3 or omega-6 polyunsaturated fatty acids, that were differentially expressed between BCvsHC patients, including anandamide, prostaglandins and hydroxydocosahexaenoic acids. DEGs analysis of tissue and blood samples from BC patients revealed that 19 genes for oxylipin biosynthesis change their expression level, with CYP2C19, PTGS2, HPGD, and FAAH included in the list of DEGs in the analysis of transcriptomes and the list of SNPs associated with BC. Results allow us to suppose that oxylipin signatures reflect the organism's level of response to the disease. Our data regarding changes in oxylipins at the system level show that oxylipin profiles can be used to evaluate the early stages of breast cancer.

Alcohol Priming and Attribution of Blame in an Acquaintance Rape Vignette.

Research on nonpharmacological effects of alcohol shows that exposure to alcohol-related cues (i.e., alcohol priming) can increase behaviors associated with actual alcohol consumption. Attributions of responsibility to female victims in sexual assault scenarios are affected by whether or not alcohol was consumed by a victim and/or perpetrator. Victims often receive higher levels of blame if they consume alcohol prior to the assault. This work extends the research on nonpharmacological effects of alcohol into a novel domain of blame attribution toward rape victims. In two studies, participants in lab settings (Study 1; N = 184) and online (Study 2; N = 421) were primed with alcohol or neutral beverage advertisements as part of a purportedly separate ad-rating task and then were presented with a vignette depicting an acquaintance rape where the characters consumed beer or soda. Participants subsequently completed a questionnaire assessing victim blame and perpetrator blame. Across both studies, participants blamed the victim most when they were exposed to both contextual (story) and noncontextual (ads) alcohol cues; this effect was especially prominent in males in Study 1. Findings for perpetrator blame were inconsistent across studies. Implications of nonpharmacological effects of alcohol on blame attribution toward rape victims are discussed in the context of courtroom situations and bystander intervention.

What Drives Racial Attitudes in Elementary School Children: Skin Tone, Facial Physiognomy, or Both?

This work examines whether racial attitudes-when measured by both explicit and implicit measures- are driven primarily by skin tone, facial physiognomy, or both in 5 to 12-year-old children. Participants evaluated faces varying in skin tone (from dark to light) and facial physiognomy (from Afrocentric to Eurocentric). In an explicit task, children rated how much they liked each face. In an implicit task, participants completed a child-friendly version of the Affect Misattribution Procedure, where they rated a Chinese character as "good" or "bad" following a racial prime. Results suggest that pro-White attitudes (especially those measured by the explicit task) are driven by both factors, vary by perceivers' race, and are present in both White and non-White children, though skin tone exerts a larger influence than other features, at least in explicit evaluations. Our results also raise the possibility that pro-White biases might be more internalized by non-White children in the American South.