Search Results (118)

Single electron capture in collisions involving neutral hydrogen atoms impacted by highly charged dressed projectiles is theoretically investigated using the distorted wave formalism. A series of continuum distorted wave approximations is employed to investigate the electron capture from neutral hydrogen atom impact by boron and carbon projectiles. The projectile potential is described using a two-parameter analytical Green–Sellin–Zachor (GSZ) model potential. The theoretical prediction of total cross sections are compared against other theories and experiments. We looked at a very broad range of collision energies, from 10 keV/u up to 10 MeV/u. In addition, the state-selective cross sections for boron ions are presented. Full article

Proton therapy enables precise dose delivery to tumors while sparing healthy tissues, offering significant advantages over conventional radiotherapy. Accurate prediction of biological doses requires detailed knowledge of radiation interactions with biological targets, especially DNA, a key site of radiation-induced damage. While most biophysical models (LEM, mMKM, NanOx) rely on water as a surrogate, this simplification neglects the complexity of real biomolecules. In this work, we calculate the stopping power and range of protons in liquid water, dry DNA, and hydrated DNA using semi-empirical cross sections for ionization, electronic excitation, electron capture, and electron loss by protons and neutral hydrogen in the 10 keV–100 MeV energy range. Additionally, ionization cross sections for uracil are computed to explore potential differences between DNA and RNA damage. Our results show excellent agreement with experimental and ab initio data, highlighting significant deviations in stopping power and range between water and DNA. Notably, the stopping power of DNA exceeds that of water at most energies, reducing proton ranges in dry and hydrated DNA by up to 20% and 26%, respectively. These findings provide improved input for Monte Carlo simulations and biophysical models, enhancing RBE predictions and dose accuracy in hadrontherapy. Full article

Blueberry (Vaccinium spp.) leaves, a residual biomass of pruning, are a rich source of polyphenols, fiber, and minerals. In this study, blueberry leaf powder (BBLP) was incorporated into wheat/soy flour-based cookies to develop antioxidant- and fiber-enriched bakery products. BBLP exhibited 8.2% protein, 44% dietary fiber (predominantly insoluble), and high antioxidant activity (2109 ± 20 mg gallic acid equivalents/100 g sample; 6251 ± 42 µmol Trolox equivalents/100 g). Four cookies’ formulations were prepared by replacing 0%, 2.5%, 5.0%, and 7.5% of the flour blend with BBLP. The total phenolic content, total antioxidant content, physical properties (weight, diameter, thickness, volume, hardness, and color), chemical composition (moisture, ash, minerals, protein, carbohydrate, fat, and fiber content), and sensory properties (taste, texture, aroma, and overall acceptability) were analyzed. All BBLP-enriched cookies qualified as a “source of fiber” according to Codex Alimentarius guidelines and EU Regulation (EC) No 1924/2006 on nutrition and health claims for foods. The addition of BBLP significantly affected the cookies’ diameter, thickness, volume, and hardness, likely due to its high insoluble fiber content. Moreover, as BBLP levels increased, the surface color darkened progressively, with increased redness and decreased yellowness attributed to the presence of anthocyanins. Accordingly, BBLP-enriched cookies showed increased antioxidant capacity, proportional to the amount of BBLP added, indicating good retention of the bioactive compounds after baking. Sensory evaluation using Quantitative Descriptive Analysis revealed that cookies with 2.5% BBLP were rated with the highest acceptability scores, whereas higher concentrations imparted noticeable herbal notes and a darker color, decreasing overall acceptability. In conclusion, BBLP can be effectively incorporated at 2.5% to enhance the nutritional quality and antioxidant potential of cookies without compromising sensory appeal, contributing to sustainable food innovation by valorizing residual agricultural biomass. Full article

Chagas disease, caused by Trypanosoma cruzi, presents a variety of clinical outcomes ranging from mild symptoms to Chagas cardiomyopathy, the most severe and life-threatening manifestation of the disease. The degree of virulence is influenced by both parasite and host factors. In this study, we characterized a murine infection model using the T. cruzi Dm28c strain in BALB/c mice to assess disease progression. Infected mice showed a peak of parasitemia at 14 dpi, followed by a progressive decrease. Spleen weight increased up to sixfold compared to uninfected controls at 14 and 21 dpi, correlating with parasitemia levels. Histological analysis revealed focal inflammatory infiltrates in the heart starting at 7 dpi, with maximal intensity at 14 and 21 dpi. The expression of inflammatory cytokines (IFN-γ, IL-1β, TNF-α) and anti-inflammatory cytokines (IL-10, TGF-β) in the spleen showed a dynamic profile, with an early increase during the acute phase. Dm28c infection of BALB/c mice can be considered as a non-lethal Chagas disease experimental model, with detectable parasitemia during the acute phase and a controlled inflammatory response. Full article

This study aimed to analyze whether the enhancement of the biopharmaceutical efficiency of mebendazole, a poorly water-soluble anthelmintic drug, significantly improves its antiparasitic activity in a murine model of trichinellosis. Objectives: Two advanced oral formulations were developed, polyvinyl alcohol-derived nanoparticles (NP) and β-cyclodextrin citrate inclusion complexes (Comp), both employing mebendazole as an anthelmintic agent. The primary objective of this work is to treat trichinellosis, an infection with severe chronic effects. Methods: The physicochemical characteristics as well as the in vivo performance of the NP and Comp formulations were assessed. The in vivo studies involved the bioavailability analysis, comparing drug absorption between the pure drug and the novel formulations, as well as the in vitro anthelmintic activity and in vivo therapeutic efficacy against Trichinella spiralis encysted muscle larvae. The in vivo efficacy was evaluated during the parenteral stage of T. spiralis infection in male and female mice from two genetically distinct lines differing in mebendazole pharmacokinetic parameters and susceptibility to the parasite. Results: The formulations exhibited smaller particle sizes and improved dissolution properties compared to pure MBZ. The pharmacokinetics studies indicate that NP and Comp significantly improved MBZ bioavailability. Both NP and Comp significantly increased mebendazole’s anthelmintic activity against the encysted parasites, which would be attributed to the improved MBZ absorption. The formulations overcome the drug’s poor solubility and low bioavailability limitations, resulting in a higher plasma concentration of the active drug, even at low doses. Conclusions: These findings suggest that the newly designed mebendazole formulations are suitable for treating T. spiralis chronic infection and highlight a potential improvement in the pharmacological treatment of trichinellosis. Full article

Background/Objectives: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an urgent public health threat due to its rapid dissemination and resistance to last-line antibiotics. Cefiderocol (FDC), a novel siderophore cephalosporin, targets resistant Gram-negative pathogens by exploiting bacterial iron uptake mechanisms. However, resistance to FDC is emerging among Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae strains. This study characterizes a spontaneous FDC-resistant subpopulation (IHC216) derived from a KPC-producing strain (KPNMA216) using comprehensive genomic, transcriptional, and phenotypic analyses. Methods: Given the whole-genome sequencing results, where mutations were identified in genes involved in transcriptional regulation and membrane permeability (ompC) among others, in the present work we further explore their potential implications and conduct a more detailed analysis of the IHC216 genome. A qRT-PCR analysis highlighted significant downregulation of classical siderophore-mediated iron acquisition systems (fepA, cirA, iroN) and upregulation of alternative iron uptake pathways (iucA, fiU), reflecting a switch in iron acquisition strategies. Results: A notable downregulation of bla_KPC-163 correlated with restored susceptibility to carbapenems, indicating collateral susceptibility. Altered expressions of pbp2 and pbp3 implicated adaptive changes in cell wall synthesis, potentially affecting FDC resistance mechanisms. Furthermore, enhanced oxidative stress responses via upregulated sodC expression and increased capsule production were observed. Conclusions: These findings underscore the complex interplay of genetic and transcriptional adaptations underlying FDC resistance, highlighting potential therapeutic vulnerabilities. Full article

Sperm membrane potential (Em) hyperpolarization during capacitation is a functional hallmark of fertilizing ability and has been proposed as a predictive biomarker for conventional in vitro fertilization (IVF) success. However, it is unclear whether Em remains stable across ejaculates over time and can reliably guide assisted reproductive technology (ART) decisions in advance. Thus, we aimed to evaluate the temporal consistency of human sperm Em within individuals and assess its utility as a prognostic marker when measured days or weeks prior to IVF procedures. Em was assessed in capacitated and non-capacitated sperm from normospermic donors at three time points over 28 days, using a fluorometric assay. Capacitated values were compared to a −48.6 mV threshold previously associated with successful fertilization. Intra-donor Em variability and coefficients of variation (CV) were analyzed statistically. Our results showed that Em values exhibited significant intra-donor variability over time (p = 0.007), with approximately half of the donors crossing the −48.6 mV functional threshold across sessions. Capacitated sperm samples showed significantly greater variability than non-capacitated ones, with several donors exceeding a 30% CV cutoff. No consistent correlation was found between CV and mean Em values. While Em remains a promising functional marker when assessed on the day of IVF, its temporal variability undermines its reliability as a predictive tool for ART decisions made in advance. These findings underscore the importance of timing in functional sperm assessments and call for further studies to identify the physiological factors influencing Em stability. Full article

We consider the melting of a one-dimensional domain ($x\ge 0$), initially at the melting temperature $u=0$, by fixing the boundary temperature to a value $u(0,t)=U_0>0$—the so called Stefan melting problem. The governing transient heat-conduction equation involves a time derivative and the spatial derivative of the temperature gradient. In the general case the order of the time derivative and the gradient can take values in the range $(0,1]$. In these problems it is known that the advance of the melt front $s\left(t\right)$ can be uniquely determined by a specified prefactor multiplying a power of time related to the order of the fractional derivatives in the governing equation. For given fractional orders the value of the prefactor is the unique solution to a transcendental equation formed in terms of special functions. Here, our main purpose is to provide efficient numerical schemes with low computational complexity to compute these prefactors. The values of the prefactors are obtained through a dimensionalization that allows the recovery of the solution for the quasi-stationary case when the Stefan number approaches zero. The mathematical analysis of this convergence is given and provides consistency to the numerical results obtained. Full article

Metacyclogenesis is a critical process in the Trypanosoma cruzi life cycle. This transition naturally occurs in an insect vector’s gut. Although Triatomine Artificial Urine (TAU) medium is the widely adopted approach to metacyclogenesis in vitro, its efficiency decreases with prolonged epimastigote culture, limiting the availability of metacyclic trypomastigotes for study. We aimed to establish a practical and efficient method for generating high concentrations and purities of metacyclic trypomastigotes in vitro. Epimastigotes of the Dm28c strain were exposed to pH shifts in nutrient-rich (MT-LIT) and nutrient-poor (M16) media, under static or agitated conditions. Both media promoted higher metacyclogenesis rates than TAU, with epimastigotes’ adherence to the substrate being a crucial factor. Metacyclogenesis efficiency varies depending on the strains and culture conditions. Notably, both LIT and M16 at pH 6 produced metacyclic trypomastigotes with infective capacity on Vero cells. Under these conditions, a variety of intermediate forms were observed compared to those induced by TAU metacyclogenesis. Our findings further emphasize the strain-dependent nature of optimal in vitro metacyclogenesis conditions and offer new opportunities for studying the intermediate forms involved in this essential process. Full article

Genome editing technologies have revolutionized the production of microorganisms, plants, and animals with phenotypes of interest to agriculture. Editing previously sequenced genomes allows for the punctual, discreet, precise, and accurate alteration of DNA for genetic analysis, genotyping, and phenotyping, as well as the production of edited organisms for academic and industrial purposes, among many other objectives. In this context, genome editing technologies have been causing a revolution in Brazilian agriculture. Thanks to the publication of Normative Resolution No. 16 (in Portuguese Resolução Normativa No. 16-RN16) in 2018, Brazilian regulatory authorities have adapted to the new genetic manipulation technologies available to the scientific community. This review aims to describe the effects of updates to the regulatory framework for edited organisms in Brazil and to point out their impacts on research and development of emerging technologies in the Brazilian agricultural sector. The implementation of RN16 rationalized the regulatory aspects regarding the production, manipulation, exploration and commercial release of edited organisms and led to the faster, cheaper and safer obtaining of edited technologies, which are more productive and better adapted to different environmental conditions in Brazil. Full article

Vertebrate cell surfaces exhibit intricate arrangements of glycosaminoglycan polymers, which are primarily linked to lipids and proteins. Numerous soluble secreted proteins are also decorated with either individual sugar molecules or their polymers. The carbohydrate polymers commonly possess terminal nine-carbon sugars, known as sialic acids. Due to their widespread distribution and strategic positioning, sialic acids play a crucial role in mediating and regulating a wide range of physiologic processes and pathologic conditions. Human- or animal-based investigations predominantly concentrate on the effects of sialic acids during infections, inflammations, vascular disorders, or cancers. Further investigations encompass a variety of applications, including cell–cell interactions, signaling, host–pathogen interactions, and other biological functions associated with nutrition, metabolism, or genetic disorders. Nevertheless, future mechanistic investigations are needed to clarify the specific roles of sialic acids in these varied contexts, so that more effective interventions may be developed. Full article

Citrus canker, caused by Xanthomonas citri subsp. citri, and bacterial blight, caused by Xanthomonas citri subsp. malvacearum, results in substantial economic losses worldwide, and searching for new antibacterial agents is a critical challenge. In this study, regional isolates AE28 and RQ3 were obtained from characteristic lesions on Citrus limon and Gossypium hirsutum, respectively. Essential oils extracted by steam distillation from the fresh aerial parts of Pelargonium graveolens and Schinus molle exhibited complete (100%) inhibition of bacterial growth in vitro at a concentration of 1000 ppm, as determined by diffusion tests. To evaluate the potential of these essential oils for controlling Xanthomonas-induced diseases, in vivo assays were conducted on lemon leaves and cotton cotyledons inoculated with the regional AE28 and RQ3 strains. Two treatment approaches were tested: preventive application (24 h before inoculation) and curative application (24 h after inoculation). Preventive and curative treatments with P. graveolens essential oil significantly reduced citrus canker severity, whereas S. molle essential oil did not show a significant reduction compared to the control. In contrast, regardless of the treatment’s timing, both essential oils effectively reduced bacterial blight severity in cotton cotyledons by approximately 1.5-fold. Gas chromatography–mass spectrometry (GC-MS) analysis identified geraniol and citronellol as the major components of P. graveolens essential oil, while limonene and t-cadinol were predominant in S. molle. These findings highlight the promising potential of botanical products as bactericidal agents, warranting further research to optimize their application and efficacy. Full article

Canine parvovirus (CPV-2) is a highly contagious virus in canines, and it is mostly spread by touching infected feces. Dogs of all ages can catch it, but puppies are more likely to suffer from it. Severe signs include vomiting, diarrhea with blood, feeling tired, and not drinking enough water. There are three different types of the original CPV-2 that have been found so far, which are CPV-2a, 2b, and 2c. The genome of CPV-2 is about 5.2 kb long and has two open reading frames (ORFs), namely the VP region and the NS region. Based on changes in amino acids at position 426, the VP2 protein distinguishes the gene apart in the VP region. Using a molecular method, this study contemplated the presence of CPV-2 and its variants in dogs that had gastroenteritis, as well as other infections. There were 511 samples tested, and 401 (78.47%) of them were positive for CPV-2. Of these, 144 (25.91%) were positive for the original genotype, 258 (64.34%) for genotype 2a, 343 (85.54%) for genotype 2b, and 167 (41.65%) for genotype 2c. Using the multiplex qPCR for genotyping, CPV-2a and CPV-2b were determined as the most frequent co-infections (16.45%). The three genotypes (2a, 2b, and 2c) were found in the samples examined based on the amino acids at position 426 of the VP2 protein, as demonstrated by the VP2 gene sequencing. Furthermore, it was discovered that in certain samples, a genetic modification at position 297 was connected to the virus’s pathogenicity. Full article

Background/Objectives: Chagas disease is a neglected tropical disease caused by infection with the parasite Trypanosoma cruzi. Benznidazole and nifurtimox are the only approved drugs for treating this condition, but their low aqueous solubility may lead to erratic bioavailability. This work aimed for the first time to formulate tablets of nifurtimox by hot melt extrusion coupled with 3D printing as a strategy to increase drug dissolution and the production of tablets with dosage on demand. Methods: Different pharmaceutical-grade polymers were evaluated through film casting, and those with promising nifurtimox amorphization capacity were further used to prepare filaments by hot melt extrusion. The printability of the obtained filaments was tested, and the polyvinyl alcohol filament was further used for printing tablets containing 120 and 60 mg of nifurtimox. Results: Three-dimensional tablets showed a remarkable improvement in the drug dissolution rate compared to commercial tablets and a dissolution efficiency 2.8 times higher. In vivo studies were carried out on Swiss mice. Parasitemia curves of nifurtimox printed tablets were significantly superior to the pure drug. Moreover, NFX 3D tablets provided a similar Trypanosoma cruzi reduction in plasmatic concentration to benznidazole, the gold-standard drug for acute-phase treatment of the Chagas disease. Conclusions: The findings of this work showed that hot melt extrusion coupled with 3D printing is a promising alternative for increasing nifurtimox biopharmaceutical properties and an attractive approach for personalized medicine. Full article

Triclabendazole (TCB) is a well-established anthelmintic effective in treating fascioliasis, a neglected tropical disease. This study employs quality by design (QbD) to investigate the impact of TCB polymorphism and pharmacotechnical variables, from the development of immediate-release tablets to process optimization and green analysis. Critical process parameters (CPPs) and critical material attributes (CMAs), characterized by type of polymorph, composition of excipients (talc, lactose, cornstarch, and magnesium stearate), and compression force, were screened using a Plackett–Burman design (n = 24), identifying polymorphic purity and cornstarch as a CPP. To establish a mathematical model linking CPP to dissolution behaviour, a multiple linear regression (MLR) was applied to the training design (central composite design, n = 18). Simultaneously, a near-infrared spectroscopy coupled to partial least squares (NIR-PLSs) method was developed to analyze CPPs. An independent set of samples was prepared and analyzed using the NIR-PLSs model, and their dissolution profiles were also obtained. The PLSs model successfully predicted the CPPs in the new samples, yielding almost quantitative results (100 ± 3%), and MLR dissolution predictions mirrored the actual dissolution profiles (f2 = 85). In conclusion, the developed model could serve as a comprehensive tool for the development and control of pharmaceutical formulations, starting from the polymorphic composition and extending to achieve targeted dissolution outcomes. Full article