Individual scale factor approach for the vibrational circular dichroism similarity-guided spectral and conformational analysis of perezone and dihydroperezone.

Evaluation of DFT calculated vibrational parameters for the IR and VCD spectra similarity of perezone (1) and dihydroperezone (2) was undertaken. Conformational sets were obtained using different search engines, and the parameters needed for spectra prediction were obtained using several combinations of commonly employed functionals and basis sets, and then weighted spectra were generated and compared with observed traces to provide infrared similarity (SIR ) and enantiomeric similarity index (ESI) values. These values evidenced a poor performance of the evaluated levels of theory that were overcome when using the individual scaling factors approach, providing 16% to 139% increases of the ESI values. The best performing level of theory was the B3LYP/DGDZVP2 with ESI values of 0.722 and 0.792 for 1 and 2. Moreover, a correlation analysis showed that the irregular DFT performance arises from rotational strength deviations, which suggests to discard conformational abundance accuracy as the main source of differences. Furthermore, a similarity guided conformational analysis showed that conformations with high ESI values prefer particular orientations of the CC bonds directly attached to the stereogenic carbon atom, with more distant dihedral angles having less influence. Additionally, folded and extended conformers appear to be equally capable to yield high individual ESI values, although abundances of folded conformers just account for 16% of the total population. Nevertheless, abundance optimization showed that a high ESI similarity value of 0.834, is possible when the population of these conformers is increased to 26%, suggesting that a larger abundance of these conformers might be present in solution.

Vibrational circular dichroism enantiomeric similarity index improvement for absolute configuration discrimination using individual infrared scaling factors.

The use of IR individual scaling factors (ISF) for the correction of DFT-calculated frequencies, and its effect on IR and VCD similarity functions, has been evaluated using (+)-(R)-3-methylcyclopentanone as a probe molecule. Contrary to using a single scaling factor to improve spectra matching, this approach sequentially searches for the optimal scaling factor for each calculated transition using a computational search algorithm to maximize the overlap of the calculated and observed IR spectra expressed as the IR similarity (SIR ) function. The obtained ISFs are then applied to the calculated frequencies, which are used to produce a scaled VCD spectrum for comparison with the observed trace, thereby yielding enantiomeric similarity index (ESI) values as a similarity measure. This procedure provides a significant improvement of the SIR and ESI values when compared with the use of a single scale factor, showing 15.1% and 34.1% in average increments, respectively, and values as high as 0.98 and 0.94, respectively. When a set of manually found ISFs is used, most differences in SIR and ESI performance disappear, and nearly perfect spectra matches are found throughout the levels of theory tested. This suggests that the observed differences in computed IR/VCD spectra with commonly used levels of theory are related to differences in frequency rather than to intensity accuracy. Finally, the use of ISFs is expected to enhance the ability to aide stereochemical assignments, particularly in cases where sufficiently accurate frequencies are difficult to obtain due to the system size or complexity.

Deuterium effects on the vibrational circular dichroism spectra of flavanone.

The minimum chemical modification that can be incorporated into an organic molecule is the replacement of a hydrogen atom for a deuterium atom. This change is not altering the pharmacological properties of a molecule, although it provides the possibility of making specific spectroscopic evaluations. Thus, in the present study, we explore how a stereogenic center is influenced by such an isotopic labeling. The studies were conducted on both enantiomers of flavanone (1 and 2) which is the parent molecule of a large group of pharmacologically active natural occurring secondary metabolites. Flavanone comprised 12 carbon atoms forming two benzene rings, a carbonyl group, an ethereal oxygen atom, a methylene group, and only one C-H stereogenic center, so it seems to be an ideal candidate for such studies. Density functional theory (DFT) calculations were used for the accurate prediction of vibrational circular dichroism (VCD) spectra of (R)-(3) and (S)-flavanone-2-d (4), of (R)-(5) and (S)-flavanone-3,3-d2 (6), and of (R)-(7) and (S)-flavanone-2',3',4',5',6'-d5 (8). To gain compounds that provide experimental VCD spectra for comparative purposes, the calculated spectra of both enantiomers of the corresponding flavanones, obtained after HPLC separation of the racemates by means of a chiral column, were contrasted, thereby revealing excellent agreements when using the CompareVOA software. In addition, the VCD spectra of both unlabeled enantiomeric flavanones (1 and 2) were also compared to the labeled molecules, revealing that the VCD spectra show significant variations induced by the deuterium incorporation.

[Exercise and oxidative stress in type 2 diabetes mellitus]. / Efecto del ejercicio físico sobre marcadores de estrés oxidativo en pacientes con diabetes mellitus tipo 2.

Sedentarism, overweight and malnutrition generate an increase in the production of reactive oxygen species leading to a state of chronic oxidative stress. In patients with type 2 diabetes mellitus, oxidative stress alters pancreatic insulin secretion and the actions of the hormone on target cells, contributing to the development of micro and macrovascular complications. During physical exertion a state of transient oxidative stress occurs. As a consequence, the organism generates multiple physiological adaptations to these repetitive stimuli. Physical exercise is beneficial for type 2 diabetes mellitus but there is a paucity of information about the effects of physical exercise on biomarkers of oxidative stress in patients with the disease. We herein try to elucidate if the effects of exercise on oxidative stress can help in the prevention and treatment of type 2 diabetes mellitus and which is the most effective modality of physical exercise to reduce oxidative stress markers.

Enantiomeric high-performance liquid chromatography resolution and absolute configuration of 6ß-benzoyloxy-3α-tropanol.

The absolute configuration of the naturally occurring isomers of 6ß-benzoyloxy-3α-tropanol (1) has been established by the combined use of chiral high-performance liquid chromatography with electronic circular dichroism detection and optical rotation detection. For this purpose (±)-1, prepared in two steps from racemic 6-hydroxytropinone (4), was subjected to chiral high-performance liquid chromatography with electronic circular dichroism and optical rotation detection allowing the online measurement of both chiroptical properties for each enantiomer, which in turn were compared with the corresponding values obtained from density functional theory calculations. In an independent approach, preparative high-performance liquid chromatography separation using an automatic fraction collector, yielded an enantiopure sample of OR (+)-1 whose vibrational circular dichroism spectrum allowed its absolute configuration assignment when the bands in the 1100-950 cm(-1) region were compared with those of the enantiomers of esters derived from 3α,6ß-tropanediol. In addition, an enantiomerically enriched sample of 4, instead of OR (±)-4, was used for the same transformation sequence, whose high-performance liquid chromatography follow-up allowed their spectroscopic correlation. All evidences lead to the OR (+)-(1S,3R,5S,6R) and OR (-)-(1R,3S,5R,6S) absolute configurations, from where it follows that samples of 1 isolated from Knightia strobilina and Erythroxylum zambesiacum have the OR (+)-(1S,3R,5S,6R) absolute configuration, while the sample obtained from E. rotundifolium has the OR (-)-(1R,3S,5R,6S) absolute configuration.

Stereospecific (5) JHortho,OMe couplings in methoxyindoles, methoxycoumarins, and methoxyflavones.

Long-range coupling constants (5) JHortho,OMe were measured in series of methoxyindoles, methoxycoumarins, and methoxyflavones by the modified J doubling in the frequency domain method. The COSY and NOESY spectra revealed the coupling of the -OMe group with a specific proton at the ortho position and its preferred conformation. Homonuclear (1) H-(1) H couplings were confirmed by irradiation of the -OMe signal. Density functional theory calculations of (5) JHortho,OMe using the modified aug-cc-pVTZ basis set evidenced that the Fermi contact term shows good agreement with the experimental J values. Accurate chemical shift and coupling constant values followed after iterative quantum mechanical spectral analysis using the PERCH software.

Manufacturing and validation of small-diameter vascular grafts: A mini review.

The field of small-diameter vascular grafts remains a challenge for biomaterials scientists. While decades of research have brought us much closer to developing biomimetic materials for regenerating tissues and organs, the physiological challenges involved in manufacturing small conduits that can transport blood while not inducing an immune response or promoting blood clots continue to limit progress in this area. In this short review, we present some of the most recent methods and advancements made by researchers working in the field of small-diameter vascular grafts. We also discuss some of the most critical aspects biomaterials scientists should consider when developing lab-made small-diameter vascular grafts.

Inflammation-suppressing cornea-in-a-syringe with anti-viral GF19 peptide promotes regeneration in HSV-1 infected rabbit corneas.

Pathophysiologic inflammation, e.g., from HSV-1 viral infection, can cause tissue destruction resulting in ulceration, perforation, and ultimately blindness. We developed an injectable Cornea-in-a-Syringe (CIS) sealant-filler to treat damaged corneas. CIS comprises linear carboxylated polymers of inflammation-suppressing 2-methacryloyloxyethyl phosphorylcholine, regeneration-promoting collagen-like peptide, and adhesive collagen-citrate glue. We also incorporated GF19, a modified anti-viral host defense peptide that blocked HSV-1 activity in vitro when released from silica nanoparticles (SiNP-GF19). CIS alone suppressed inflammation when tested in a surgically perforated and HSV-1-infected rabbit corneal model, allowing tissue and nerve regeneration. However, at six months post-operation, only regenerated neocorneas previously treated with CIS with SiNP-GF19 had structural and functional features approaching those of normal healthy corneas and were HSV-1 virus-free. We showed that composite injectable biomaterials can be designed to allow regeneration by modulating inflammation and blocking viral activity in an infected tissue. Future iterations could be optimized for clinical application.

Impact of artificial intelligence on human loss in decision making, laziness and safety in education.

This study examines the impact of artificial intelligence (AI) on loss in decision-making, laziness, and privacy concerns among university students in Pakistan and China. Like other sectors, education also adopts AI technologies to address modern-day challenges. AI investment will grow to USD 253.82 million from 2021 to 2025. However, worryingly, researchers and institutions across the globe are praising the positive role of AI but ignoring its concerns. This study is based on qualitative methodology using PLS-Smart for the data analysis. Primary data was collected from 285 students from different universities in Pakistan and China. The purposive Sampling technique was used to draw the sample from the population. The data analysis findings show that AI significantly impacts the loss of human decision-making and makes humans lazy. It also impacts security and privacy. The findings show that 68.9% of laziness in humans, 68.6% in personal privacy and security issues, and 27.7% in the loss of decision-making are due to the impact of artificial intelligence in Pakistani and Chinese society. From this, it was observed that human laziness is the most affected area due to AI. However, this study argues that significant preventive measures are necessary before implementing AI technology in education. Accepting AI without addressing the major human concerns would be like summoning the devils. Concentrating on justified designing and deploying and using AI for education is recommended to address the issue.

Human cells and cell membrane molecular models are affected in vitro by the nonsteroidal anti-inflammatory drug ibuprofen.

This report presents evidence that ibuprofen interacts with red cell membranes as follows: a) in scanning electron microscopy (SEM) studies on human erythrocytes induced shape changes at a concentration as low as 10µM; b) in isolated unsealed human erythrocyte membranes (IUM) induced mild increase in the water content or in their molecular dynamics at the hydrophobic-hydrophilic interphase, while a corresponding ordering decrease at the deep phospholipids acyl chain level; c) at physiological temperature (37°C), 300µM ibuprofen induced a significant increase in the generalized polarization (GP) of dimyristoylphosphatidylcholine (DMPC) large unilamellar vesicles (LUV), an indication that ibuprofen molecules locate in the head polar group region of DMPC; d) X-ray diffraction studies showed that ibuprofen concentrations≥300µM induced increasing structural perturbation to DMPC bilayers; e) differential scanning calorimetry (DSC) data showed that ibuprofen was able to alter the cooperativity of DMPC phase transition in a concentration-dependent manner, to destabilize the gel phase and that ibuprofen did not significantly perturb the organization of the lipid hydrocarbon chains. Additionally, the effect on the viability of both human promyelocytic leukemia HL-60 and human cervical carcinoma HeLa cells was studied.

Absolute configuration and 1H NMR characterization of rosmaridiphenol diacetate.

The correction of patented structure 1 of rosmaridiphenol, an antioxidant isolated from rosemary, Rosmarinus officinalis, was made recently. The correct structure is proposed as 11,12-dihydroxy-8,11,13-icetexatrien-1-one (2a) based on 2D NMR data. In order to further support the structure, this work reports the single-crystal X-ray analysis, the complete (1)H NMR assignment by full spin-spin simulation, and the absolute configuration of the diacetate 2b derived via vibrational circular dicroism measurements in comparison with density functional theory calculated data.

Vaccine Passport and Traveler Behaviors in the New Market of the Domestic and International Tourism Industry Facing the With-Corona Era.

To ensure a smooth and rapid recovery of tourism, countries around the world are stepping up vaccinations against COVID-19. China, in particular has a very high vaccination rate due to its own vaccine production. Following this trend, many countries have started introducing vaccine passports as an alternative solution to verify valid and vaccinated travelers. This study attempted to understand the fundamental perceptions of travelers' intentions using vaccine passports. A total of 601 samples were investigated and analyzed. As a result, four factors were identified: perceived usefulness, destination trust, risk perception, and perception of incentives. Also, this study performed means comparisons analysis with the major demographic characteristics of respondents. Based on this study, it is expected that the results will contribute to the revival of the travel industry in the future and provide valuable implications for marketing plans to help the travel industry suffer from COVID-19.

A Study on Perception and Exposure to Occupational Risks at Public School Food Services in Bahia, Brazil.

Food service work is hazardous due to the intense rhythm of food production, and the working conditions can cause discomfort, fatigue, and occupational accidents and illnesses. For the perception of exposure to occupational hazards, workers must participate in continuing education programs. This study aimed to verify the perception and exposure to occupational risks at school food services (SFS) in Bahia, Brazil. This cross-sectional study was conducted in SFS from public schools in Bahia/Brazil. Researchers identified sociodemographic variables, occupational characteristics, and the Perception of Exposure to Occupational Risks by SFS food handlers. Also, anthropometric assessment (weight, height, and waist circumference), the presence of comorbidities, and the identification of exposure to occupational risks and measures of environmental comfort were evaluated. Most workers were female (98.6%; n = 140), mean age of 46.85 y/o, working as SFS food handlers between 1 and 5 years (50.7%; n = 72) but with no training on occupational risks (52.8%; n = 75). This lack of training is not associated with demographic or other occupational variables. The majority of the food handlers present a fair or good perception of exposure to occupational risk. These food handlers are also mostly overweight, and higher BMI was associated with hypertension and edema. The SFS were classified as of high occupational risk (mean of 31.24% of adequacy) environments. Ergonomic Risks had the lowest percentage of adequacy (7.69%, very high risk) regarding occupational risks, followed by chemical risks (31.5% of adequacy, high risk), accident risk (32.19%, high risk), and physical risk (36.89%, high risk). The excess of activities associated with precarious physical structure, insufficient number of equipment and utensils (in inadequate conservation) favors the exposure to occupational risk in SFS.

Management of knowledge and competence through human resource information system-A structured review.

The fourth industrial revolution will be ushered in by future high technology, and as a result, the world will face new difficulties relating to people, the environment, and profitability. Accordingly, the competitive edge and long-term viability of businesses would depend on the knowledge workers who could overcome these excruciatingly difficult obstacles and have the knowledge and competency to influence the overall performance of any type of company. But managing knowledge workers falls under the purview of human resources, and only effective human resources tools, plans, and procedures can ensure the success of this task. One such tool, which has the capacity and capability to change the whole scenario in an organization's favor, is the human resource information system (HRIS). The purpose of this structured review is to provide insight into a field of HRM (i.e., HRIS) that has largely been neglected by other reviews of the literature and has only been briefly discussed by a small number of publications published in reputable, top-tier journals. A customized HRIS framework is the result of this structured literature review for managing knowledge and competence. The study presents the content analysis of 48 articles, systematically and purposefully selected for this literature review, published during the past three decades. The study has several implications for policymakers and HR practitioners.

The histone H3.1 variant regulates TONSOKU-mediated DNA repair during replication.

The tail of replication-dependent histone H3.1 varies from that of replication-independent H3.3 at the amino acid located at position 31 in plants and animals, but no function has been assigned to this residue to demonstrate a unique and conserved role for H3.1 during replication. We found that TONSOKU (TSK/TONSL), which rescues broken replication forks, specifically interacts with H3.1 via recognition of alanine 31 by its tetratricopeptide repeat domain. Our results indicate that genomic instability in the absence of ATXR5/ATXR6-catalyzed histone H3 lysine 27 monomethylation in plants depends on H3.1, TSK, and DNA polymerase theta (Pol θ). This work reveals an H3.1-specific function during replication and a common strategy used in multicellular eukaryotes for regulating post-replicative chromatin maturation and TSK, which relies on histone monomethyltransferases and reading of the H3.1 variant.

Nanoengineered Sprayable Therapy for Treating Myocardial Infarction.

We report the development, as well as the in vitro and in vivo testing, of a sprayable nanotherapeutic that uses surface engineered custom-designed multiarmed peptide grafted nanogold for on-the-spot coating of an infarcted myocardial surface. When applied to mouse hearts, 1 week after infarction, the spray-on treatment resulted in an increase in cardiac function (2.4-fold), muscle contractility, and myocardial electrical conductivity. The applied nanogold remained at the treatment site 28 days postapplication with no off-target organ infiltration. Further, the infarct size in the mice that received treatment was found to be <10% of the total left ventricle area, while the number of blood vessels, prohealing macrophages, and cardiomyocytes increased to levels comparable to that of a healthy animal. Our cumulative data suggest that the therapeutic action of our spray-on nanotherapeutic is highly effective, and in practice, its application is simpler than other regenerative approaches for treating an infarcted heart.

Photophysical behaviour and photodynamic activity of zinc phthalocyanines associated to liposomes.

Phthalocyanines are macrocyclic compounds that can be employed as photosensitizers in the treatment of various infections and diseases, as well as in photodynamic therapy. Nevertheless, a disadvantage for the clinical application of these compounds is their strong tendency to form oligomers (especially dimers), a phenomenon that reduces their efficiency as photosensitizers. In the present contribution, we have studied the photophysical and photochemical properties of ZnPc and ZnF(16)Pc in an organic solvent (THF) and liposomal formulations (DMPC, DPPC and DSPC). Our results show that dye incorporation into liposomes decreases its aggregation degree, as revealed by absorption spectra, triplet quantum yield, and singlet oxygen quantum yield measurements. Additionally, we studied the photodynamic activity of both phthalocyanines in liposomal formulation on human cervical carcinoma (HeLa) cells. For ZnF(16)Pc the photophysical behavior and phototoxicity in vitro correlate with the aggregation degree. The dimers are not photoactive and the photochemistry of ZnF(16)Pc depends of the fraction present as monomer. On the other hand, ZnPc aggregation is minimal and its photophysical and photochemical properties are similar in the three liposomes studied. Nevertheless, its phototoxicity in vitro is liposome dependent.

Stereochemical analysis of leubethanol, an anti-TB-active serrulatane, from Leucophyllum frutescens.

Bioactivity-guided fractionation of the methanolic root bark extract of Leucophyllum frutescens led to the identification of leubethanol (1), a new serrulatane-type diterpene with activity against both multi-drug-resistant and drug-sensitive strains of virulent Mycobacterium tuberculosis. Leubethanol (1) was identified by 1D/2D NMR data, as a serrulatane closely related to erogorgiane (2), and exhibited anti-TB activity with minimum inhibitory concentrations in the range 6.25-12.50 µg/mL. Stereochemical evidence for 1 was gleaned from 1D and 2D NOE experiments, from 1H NMR full spin analysis, and by comparison of the experimental vibrational circular dichroism (VCD) spectrum to density functional theory calculated VCD spectra of two diastereomers.

Inhibitory activities on mammalian central nervous system receptors and computational studies of three sesquiterpene lactones from Coriaria ruscifolia subsp. ruscifolia.

The electrophysiological characterization of sesquiterpene lactones from Coriaria ruscifolia subsp. ruscifolia has been tested on hippocampal neurons. The results for glycinergic rat hippocampal transmission and native γ-aminobutyric acid (GABA)ergic transmission on neurons (13DIV) are remarkably different for tutin, coriamyrtin, and dihydrotutin, being tutin the most potent inhibitor and dihydrotutin the least potent one. To understand the applied mechanism of action, we discuss the structural and electronic requirements for inhibitory activity by these sesquiterpene lactones when modulating receptors of the central nervous system. The structural and electrostatic properties of these compounds were compared to those of more active metabolites like picrotoxins. The minimal energy level of these structures was calculated and then optimized at the ab initio B3LYP/DGDZVP level of theory using Gaussian 03W software. This allowed calculation of the corresponding vibrational circular dichroism spectrum of coriamyrtin which rendered the molecular absolute configuration after comparison with an experimental spectrum. These results are consistent with those from studies of other models that provide the basis for the activity on the presence of the lactone at carbons 3 and 5, the presence of the hydroxyl group at position 6, and the different electronic distributions observed in tutin and coriamyrtin. The latter has an isopropenyl moiety at carbon 4 in contrast to the dihydrotutin isopropyl group at the same position, which could explain the difference in activity between dihydrotutin and tutin or coriamyrtin. The presence of the hydroxyl group at carbon 2 is not decisive since this functionality is present in tutin, the most active compound, and in dihydrotutin, the less active one.

A low cost and open access system for rapid synthesis of large volumes of gold and silver nanoparticles.

Rapid synthesis of nanomaterials in scalable quantities is critical for accelerating the discovery and commercial translation of nanoscale-based technologies. The synthesis of metal nanogold and silver in volumes larger than 100 mL is not automatized and might require of the use of harsh conditions that in most cases is detrimental for the production of nanoparticles with reproducible size distributions. In this work, we present the development and optimization of an open-access low-cost NanoParticle Flow Synthesis System (NPFloSS) that allows for the rapid preparation of volumes of up to 1 L of gold and silver nanoparticle aqueous solutions.