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We study the nonlinear absorptive and dispersive optical properties of molecular systems immersed in a thermal reservoir interacting with a four-wave mixing (FWM) signal. Residual spin-orbit Hamiltonians are considered in order to take into account the internal structure of the molecule. As system parameters in the dissipation processes, transverse and longitudinal relaxation times are considered for stochastic solute–solvent interaction processes. The intramolecular coupling effects on the optical responses are studied using a molecule model consisting of two coupled harmonic curves of electronic energies with displaced minima in nuclear energies and positions. In this study, the complete frequency space is considered through the pump–probe detuning, without restricting the derivations to only maximums of population oscillations. This approach opens the possibility of studying the behavior of optical responses, which is very useful in experimental design. Our results indicate the sensitivity of the optical responses to parameters of the molecular structure as well as to those derived from the photonic process of FWM signal generation.

Microbial biofilms cause several environmental and industrial issues, even affecting human health. Although they have long represented a threat due to their resistance to antibiotics, there are currently no approved antibiofilm agents for clinical treatments. The multi-functionality of antimicrobial peptides (AMPs), including their antibiofilm activity and their potential to target multiple microbes, has motivated the synthesis of AMPs and their relatives for developing antibiofilm agents for clinical purposes. Antibiofilm peptides (ABFPs) have been organized in databases that have allowed the building of prediction tools which have assisted in the discovery/design of new antibiofilm agents. However, the complex network approach has not yet been explored as an assistant tool for this aim. Herein, a kind of similarity network called the half-space proximal network (HSPN) is applied to represent/analyze the chemical space of ABFPs, aiming to identify privileged scaffolds for the development of next-generation antimicrobials that are able to target both planktonic and biofilm microbial forms. Such analyses also considered the metadata associated with the ABFPs, such as origin, other activities, targets, etc., in which the relationships were projected by multilayer networks called metadata networks (METNs). From the complex networks’ mining, a reduced but informative set of 66 ABFPs was extracted, representing the original antibiofilm space. This subset contained the most central to atypical ABFPs, some of them having the desired properties for developing next-generation antimicrobials. Therefore, this subset is advisable for assisting the search for/design of both new antibiofilms and antimicrobial agents. The provided ABFP motifs list, discovered within the HSPN communities, is also useful for the same purpose.

This research reported a hydrogel loaded with the ethanolic and methanolic extracts of Eupatorium glutinosum Lam. The E. glutinosum extracts were characterized by phytochemical screening, Fourier-transform infrared spectroscopy (FTIR), thin-layer chromatography (TLC), and UV/Vis profile identification. This research also evaluated the pharmacological activity of the extracts using antimicrobial, antioxidant, and anti-inflammatory assays prior to polymeric encapsulation. Results indicate that extracts inhibit the Escherichia colii DH5-α (Gram negative) growth; excellent antioxidant activity was evaluated by the ferric reducing power and total antioxidant activity assays, and extracts showed an anti-hemolytic effect. Moreover, the cotton and microcrystalline cellulose hydrogels demonstrate successful encapsulation based on characterization and kinetics studies such as FTIR, extract release, and swelling degree. Moreover, effective antibacterial activity was registered by the loaded hydrogel. The overall results encourage and show that Eupatorium glutinosum-loaded hydrogel may find a wide range of bandage and wound healing applications in the biomedical area.

In this study, a series of novel quinolinone-based thiosemicarbazones were designed in silico and their activities tested in vitro against Mycobacterium tuberculosis (M. tuberculosis). Quantitative structure-activity relationship (QSAR) studies were performed using quinolinone and thiosemicarbazide as pharmacophoric nuclei; the best model showed statistical parameters of R2 = 0.83; F = 47.96; s = 0.31, and was validated by several different methods. The van der Waals volume, electron density, and electronegativity model results suggested a pivotal role in antituberculosis (anti-TB) activity. Subsequently, from this model a new series of quinolinone-thiosemicarbazone 11a–e was designed and docked against two tuberculosis protein targets: enoyl-acyl carrier protein reductase (InhA) and decaprenylphosphoryl-β-D-ribose-2’-oxidase (DprE1). Molecular dynamics simulation over 200 ns showed a binding energy of −71.3 to −12.7 Kcal/mol, suggesting likely inhibition. In vitro antimycobacterial activity of quinolinone-thiosemicarbazone for 11a–e was evaluated against M. bovis, M. tuberculosis H37Rv, and six different strains of drug-resistant M. tuberculosis. All compounds exhibited good to excellent activity against all the families of M. tuberculosis. Several of the here synthesized compounds were more effective than the standard drugs (isoniazid, oxafloxacin), 11d and 11e being the most active products. The results suggest that these compounds may contribute as lead compounds in the research of new potential antimycobacterial agents.

Increased added sugar consumption is associated with type II diabetes, metabolic syndrome, and cardiovascular disease. Low and no-calorie alternative sweeteners have long been used as an aid in the reduction of added sugar. Unfortunately, these alternative sweeteners often have notable sensory deficits when compared to sucrose. Furthermore, many alternative sweeteners have synthetic origins, while consumers are increasingly turning to foods from natural origins, and from more sustainable sources. Such sweeteners include the rare sugar allulose, which can be manufactured from common agricultural waste and dairy co-product streams, and is reported to have a sensory profile similar to sucrose. This study aimed to determine the influence of the rare sugar allulose on consumer perception of sweetened vanilla yogurt. Participants were recruited to evaluate 4 vanilla yogurts sweetened with either sucrose, allulose, stevia or sucralose, and to rate their liking of the samples overall, and for flavor, texture, and their purchase intent. Statistical analysis of hedonic data from 100 consumers suggested that allulose performed similarly to sucrose in liking and purchase intent, and superior to other sweeteners tested in this study, with fewer off-flavors. Moreover, when consumers were queried on their purchase intent after learning details on the sweetener for each formulation, allulose scored significantly higher than all other formulations in purchase intent. This study highlights the potential of the rare sugar allulose as a low calorie, zero glycemic index, natural and better tasting sugar replacement in sweetened yogurt.

A strong pump-power dependence of the four-wave mixing (FWM) signal for an aqueous solution of Malachite green is reported. The characteristics of the pump-power dependence of the nonlinear signal are reproduced by a theoretical model based on the coupling between pump-probe, considering signal fields and propagation effects. The effect of the intramolecular coupling on the nonlinear intensity of the FWM signal is studied using a model molecule consisting of two-coupled harmonic curves of electronic energies with minima displaced in energy and nuclear positions. Two-vibrational states are considered while including non-adiabatic effects for the two-state model. Moreover, the coupling among the field components, as well as the propagation effects, are studied by considering a constant pump-intensity. Our calculation scheme, considering both the intramolecular coupling effects in the description of the molecular structure and the effects produced by the propagation of the FWM signal along the optical length, allows the exponential dependence of the latter, as the intensity of the pumping beam increases. Our treatments do not require the inclusion of other non-resonant processes outside the RWA approximation, due to the consideration of an adiabatic basis.

Free fatty acid receptor 1 (FFA1) stimulates insulin secretion in pancreatic β-cells. An advantage of therapies that target FFA1 is their reduced risk of hypoglycemia relative to common type 2 diabetes treatments. In this work, quantitative structure–activity relationship (QSAR) approach was used to construct models to identify possible FFA1 agonists by applying four different machine-learning algorithms. The best model (M2) meets the Tropsha’s test requirements and has the statistics parameters R2 = 0.843, Q2CV = 0.785, and Q2ext = 0.855. Also, coverage of 100% of the test set based on the applicability domain analysis was obtained. Furthermore, a deep analysis based on the ADME predictions, molecular docking, and molecular dynamics simulations was performed. The lipophilicity and the residue interactions were used as relevant criteria for selecting a candidate from the screening of the DiaNat and DrugBank databases. Finally, the FDA-approved drugs bilastine, bromfenac, and fenofibric acid are suggested as potential and lead FFA1 agonists.

Dapsone (DDS) is an antibacterial drug with well-known antioxidant properties. However, the antioxidant behavior of its derivatives has not been well explored. In the present work, the antioxidant activity of 10 dapsone derivatives 4-substituted was determined by an evaluation in two in vitro models (DPPH radical scavenging assay and ferric reducing antioxidant power). These imine derivatives 1–10 were obtained through condensation between DDS and the corresponding aromatic aldehydes 4-substuited. Three derivatives presented better results than DDS in the determination of DPPH (2, 9, and 10). Likewise, we have three compounds with better reducing activity than dapsone (4, 9, and 10). In order to be more insight, the redox process, a conceptual DFT analysis was carried out. Molecular descriptors such as electronic distribution, the total charge accepting/donating capacity (I/A), and the partial charge accepting/donating capacity (ω+/ω−) were calculated to analyze the relative donor-acceptor capacity through employing a donor acceptor map (DAM). The DFT calculation allowed us to establish a relationship between GAPHOMO-LUMO and DAM with the observed antioxidant effects. According to the results, we concluded that compounds 2 and 3 have the lowest Ra values, representing a good antioxidant behavior observed experimentally in DPPH radical capturing. On the other hand, derivatives 4, 9, and 10 display the best reducing capacity activity with the highest ω− and Rd values. Consequently, we propose these compounds as the best antireductants in our DDS imine derivative series.

Coronavirus desease 2019 (COVID-19) is responsible for more than 1.80 M deaths worldwide. A Quantitative Structure-Activity Relationships (QSAR) model is developed based on experimental pIC50 values reported for a structurally diverse dataset. A robust model with only five descriptors is found, with values of R2 = 0.897, Q2LOO = 0.854, and Q2ext = 0.876 and complying with all the parameters established in the validation Tropsha’s test. The analysis of the applicability domain (AD) reveals coverage of about 90% for the external test set. Docking and molecular dynamic analysis are performed on the three most relevant biological targets for SARS-CoV-2: main protease, papain-like protease, and RNA-dependent RNA polymerase. A screening of the DrugBank database is executed, predicting the pIC50 value of 6664 drugs, which are IN the AD of the model (coverage = 79%). Fifty-seven possible potent anti-COVID-19 candidates with pIC50 values > 6.6 are identified, and based on a pharmacophore modelling analysis, four compounds of this set can be suggested as potent candidates to be potential inhibitors of SARS-CoV-2. Finally, the biological activity of the compounds was related to the frontier molecular orbitals shapes.

In this work, the minimum energy structures of 22 4-pyridone derivatives have been optimized at Density Functional Theory level, and several quantum molecular, including electronic and thermodynamic descriptors, were computed for these substrates in order to obtain a statistical and meaningful QSAR equation. In this sense, by using multiple linear regressions, five mathematical models have been obtained. The best model with only four descriptors (r2 = 0.86, Q2 = 0.92, S.E.P = 0.38) was validated by the leave-one-out cross-validation method. The antimalarial activity can be explained by the combination of the four mentioned descriptors e.g., electronic potential, dipolar momentum, partition coefficient and molar refractivity. The statistical parameters of this model suggest that it is robust enough to predict the antimalarial activity of new possible compounds; consequently, three small chemical modifications into the structural core of these compounds were performed specifically on the most active compound of the series (compound 13). These three new suggested compounds were leveled as 13A, 13B and 13C, and the predicted biological antimalarial activity is 0.02 µM, 0.03 µM, and 0.07 µM, respectively. In order to complement these results focused on the possible action mechanism of the substrates, a docking simulation was included for these new structures as well as for the compound 13 and the docking scores (binding affinity) obtained for the interaction of these substrates with the cytochrome bc1, were −7.5, −7.2, −6.9 and −7.5 kcal/mol for 13A, 13B, 13C and compound 13, respectively, which suggests that these compounds are good candidates for its biological application in this illness.

This study explores the development of biocompatible scaffolds for bone regeneration, utilizing polylactic acid (PLA) combined with calcium phosphate as a pH buffer and diatomaceous earth as a biocompatibilizer. These materials were extruded and 3D-printed to enhance cell adhesion and biodegradability after enough cell growth. The biocompatibility of the resulting composites, with different proportions of the components and sterilization methods, was tested according to the ISO 10993 protocol. The optimal performance, with nearly zero cytotoxicity, was observed with 20 PLA/1 CP/1 DE mass ratios and gamma sterilization. Tension analysis and scanning electron microscopy (SEM) were applied to the 3D-printed composites, which were also analyzed by differential scanning calorimetry (DSC) to understand the origin of the tension properties better, which were comparable to those of cancellous bone. Degradation tests under physiological conditions for 13 weeks showed no significant mass loss. Furthermore, it was observed that cell adhesion, viability, proliferation, and osteoconduction are possible in the scaffolds studied, opening opportunities for future studies to substantiate the use of 3D-printed silica-filled composites as an alternative to homologous implants for various bone regeneration applications.

Background: Clubfoot is a common congenital deformity. The Ponseti technique, involving early corrective manipulations followed by applying long leg casts and Achilles tenotomy, is widely accepted as the preferred treatment. Rapid tendon healing after surgery has been documented, but the aspect regarding long-term tendon structure and properties is not known. Three cases of Achilles tendon rupture in adolescents previously treated for clubfoot have been described in the literature. As rupture is a rare event in this age group, a possible correlation with previous surgery has been hypothesized. The primary aim of the study was to compare the ultrasound findings of the Achilles tendon in patients treated for clubfoot, between patients treated with casting alone and with patients who underwent surgery (percutaneous tenotomy or Z-plasty lengthening)., Methods: There were 22 asymptomatic patients (34 feet) with a median age of 12 years, previously treated for clubfoot, that were recruited for this study; the patients underwent an Achilles tendon ultrasound examination during a follow-up outpatient visit., Results: A greater thickness and increased number of structural alterations with the presence of hypoechoic areas of the operated tendons compared with those treated with plaster alone were observed ( p -value: 0.0498 and <0.001, respectively). These ultrasound findings were indicative of tendon suffering, as seen in tendinopathies., Conclusions: The presence of ultrasound alterations in asymptomatic patients operated on for clubfoot requires careful control of the extrinsic factors of tendinopathy in order to reduce the risk of subcutaneous rupture.

Recent multidrug resistance in Pseudomonas aeruginosa has favoured the adaptation and dissemination of worldwide high-risk strains. In June 2018, 15 P. aeruginosa strains isolated from patients and a contaminated multi-dose meropenem vial were characterized to assess their association to an outbreak in a Mexican paediatric hospital. The strains were characterized by antibiotic susceptibility profiling, virulence factors' production, and biofilm formation. The clonal relationship among isolates was determined with pulse-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) sequencing. Repressor genes for the MexAB-OprM efflux pump were sequenced for haplotype identification. Of the strains, 60% were profiled as extensively drug-resistant (XDR), 33% as multidrug-resistant (MDR), and 6.6% were classified as sensitive (S). All strains presented intermediate resistance to colistin, and 80% were sensitive to aztreonam. Pyoverdine was the most produced virulence factor. The PFGE technique was performed for the identification of the outbreak, revealing eight strains with the same electrophoretic pattern. ST235 and ten new sequence types (STs) were identified, all closely related to ST233. ST3241 predominated in 26.66% of the strains. Twenty-five synonymous and seventeen nonsynonymous substitutions were identified in the regulatory genes of the MexAB-OprM efflux pump, and nalC was the most variable gene. Six different haplotypes were identified. Strains from the outbreak were metallo-β-lactamases and phylogenetically related to the high-risk clone ST233.

In potato ( Solanum tuberosum L.), protoplast techniques are limited to a few genotypes; thus, the use of regular regeneration procedures of multicellular explants causes us to face complexities associated to CRISPR/Cas9 gene editing efficiency and final identification of individuals. Geminivirus-based replicons contained in T-DNAs could provide an improvement to these procedures considering their cargo capability. We built a Bean yellow dwarf virus -derived replicon vector, pGEF-U, that expresses all the editing reagents under a multi-guide RNA condition, and the Green Fluorescent Protein ( GFP ) marker gene. Agrobacterium -mediated gene transfer experiments were carried out on 'Yagana-INIA', a relevant local variety with no previous regeneration protocol. Assays showed that pGEF-U had GFP transient expression for up to 10 days post-infiltration when leaf explants were used. A dedicated potato genome analysis tool allowed for the design of guide RNA pairs to induce double cuts of genes associated to enzymatic browning ( StPPO1 and 2 ) and to cold-induced sweetening ( StvacINV1 and StBAM1 ). Monitoring GFP at 7 days post-infiltration, explants led to vector validation as well as to selection for regeneration (34.3% of starting explants). Plant sets were evaluated for the targeted deletion, showing individuals edited for StPPO1 and StBAM1 genes (1 and 4 lines, respectively), although with a transgenic condition. While no targeted deletion was seen in StvacINV1 and StPPO2 plant sets, stable GFP-expressing calli were chosen for analysis; we observed different repair alternatives, ranging from the expected loss of large gene fragments to those showing punctual insertions/deletions at both cut sites or incomplete repairs along the target region. Results validate pGEF-U for gene editing coupled to regular regeneration protocols, and both targeted deletion and single site editings encourage further characterization of the set of plants already generated.