A high density nanopore 3-triangulene kagome lattice.

Nanopore-containing two-dimensional materials have been explored for a wide range of applications including filtration, sensing, catalysis, energy storage and conversion. Triangulenes have recently been experimentally synthesized in a variety of sizes. In this regard, using these systems as building blocks, we theoretically examined 3-triangulene kagome crystals with inherent holes of ∼12 Å diameter and a greater density array of nanopores (≥1013 cm-2) compared to conventional 2D systems. The energetic, electronic, and transport properties of pristine and B/N-doped 3-triangulene kagome crystals were evaluated through a combination of density functional theory and non-equilibrium Green's function method. The simulated scanning tunneling microscopy images clearly capture electronic perturbation around the doped sites, which can be used to distinguish the pristine system from the doped systems. The viability of precisely controlling the band structure and transport properties by changing the type and concentration of doping atoms is demonstrated. The findings presented herein can potentially widen the applicability of these systems that combine unique electronic properties and intrinsically high-density pores, which can pave the way for the next generation of nanopore-based devices.

Genetic parameters, genetic trends and correlated responses of growth traits considering maternal ability in Nelore cattle.

The growth of Nelore cattle was analysed considering the following performance parameters; the effect of the calving order of cows on the phenotypic expression of birth weight (BW), average daily gain from birth to weaning (BWG), and weaning weight (WW), the estimated genetic parameters for the traits, including the covariance components between direct and maternal genetic effects. Genetic trends and correlated responses were also obtained for the studied traits. The calving order of cows, as well as other fixed effects used to obtain the adjusted phenotypic means, were statistically significant (p < 0.001) for studied traits. Direct heritability was estimated at 0.24 ± 0.01 (BW), 0.15 ± 0.01 (BWG), and 0.18 ± 0.01 (WW), while maternal heritability was 0.06 ± 0.01 (BW), 0.12 ± 0.01 (BWG), and 0.11 ± 0.01 (WW). The correlations between direct and maternal effects within the same trait were negligible. Moderate to higher direct genetic correlations (ranging from 0.54 ± 0.04 to 0.98 ± 0.01) and maternal genetic correlations (ranging from 0.34 ± 0.09 to 0.99 ± 0.002) were estimated between the studied traits. Unlike direct genetic effects, there was no significant change in maternal genetic effects over time (p > 0.05). These results indicated the need for revising selection indexes for enhancing maternal ability. Correlated responses were generally lower compared to direct responses, except for BWG. The selection for BWG, considering the maternal genetic effect, would be more efficient to improve maternal ability of the cows for pre-weaning growth in relation to selection for WW. Our results found that direct genetic merit improves pre-weaning weight and this trait can be incorporated into the breeding goal as reflected in the WW.

Sequential activity of CA1 hippocampal cells constitutes a temporal memory map for associative learning in mice.

Sequential neural dynamics encoded by time cells play a crucial role in hippocampal function. However, the role of hippocampal sequential neural dynamics in associative learning is an open question. We used two-photon Ca2+ imaging of dorsal CA1 (dCA1) neurons in the stratum pyramidale (SP) in head-fixed mice performing a go-no go associative learning task to investigate how odor valence is temporally encoded in this area of the brain. We found that SP cells responded differentially to the rewarded or unrewarded odor. The stimuli were decoded accurately from the activity of the neuronal ensemble, and accuracy increased substantially as the animal learned to differentiate the stimuli. Decoding the stimulus from individual SP cells responding differentially revealed that decision-making took place at discrete times after stimulus presentation. Lick prediction decoded from the ensemble activity of cells in dCA1 correlated linearly with lick behavior. Our findings indicate that sequential activity of SP cells in dCA1 constitutes a temporal memory map used for decision-making in associative learning. VIDEO ABSTRACT.

Validation of an analytical method by HPLC for the quantification of yangambin from the Ocotea duckei species / Validación de un método analítico por HPLC para la cuantificación de yangambin de la especie Ocotea duckei

Ocotea duckei , known as Louro - de - cheiro, belongs to the Lauraceae family and presents lignoid yangambine (YAN) as the main plant marker. This work aimed to develop and validate an analytical method by high performance liquid chromatography for the quantification of YAN. The sample used was the crude eth anolic extract (CEE) obtained from aerial parts. In the developed method, a C18 column was used. The mobile phase was composed of acetonitrile and water (45:55), whereas the method parameters included mobile phase flow rate at 0.8 mL/min, oven temperature at 40°C, and monitoring at 205 nm. In the validation, the parameters of selectivity, linearity, precision, accuracy, robustness, limits of detection and quantification were evaluated. As a result, the developed method is in accordance with the guidelines f or validation of analytical methods and presented satisfactory chromatographic parameters for YAN determination. Thus, the present analytical methodology can be applied in the quality control of O. duckei raw materials.

Ocotea duckei , conocida como Louro - de - cheiro, pertenece a la familia Lauraceae y presenta la yangambina lignoide (YAN) como principal marcador vegetal. Este trabajo tuvo como objetivo desarrollar y val idar un método analítico por cromatografía líquida de alta resolución para la cuantificación de YAN. La muestra utilizada fue el extracto etanólico crudo (EEC) obtenido de partes aéreas. En el método desarrollado se utilizó una columna C18. La fase móvil c onsistió en acetonitrilo y agua (45:55), mientras los parámetros del método incluyeron el caudal de la fase móvil a 0,8 m L /min, la temperatura del horno a 40°C y la monitorización a 205 nm. En la validación se evaluaron los parámetros de selectividad, line alidad, precisión, exactitud, robustez, límites de detección y cuantificación. Como resultado, el método desarrollado está de acuerdo con las pautas para la validación de métodos analíticos y presentó parámetros cromatográficos satisfactorios para la deter minación de YAN. Por lo tanto, la presente metodología analítica se puede aplicar en el control de calidad de las materias primas de O. duckei.

Boron-doped graphene topological defects: unveiling high sensitivity to NO molecule for gas sensing applications.

Global air quality has deteriorated significantly in recent years due to large emissions from the transformation industry and combustion vehicles. This issue requires the development of portable, highly sensitive, and selective gas sensors. Nanostructured materials, including defective graphene, have emerged as promising candidates for such applications. In this work, we investigated the B-doped topological line defect in graphene as a sensing material for various gas molecules (CO, CO2, NO, and NH3) based on a combination of density functional theory and the non-equilibrium Green's function method. The electronic transport calculations reveal that the electric current can be confined to the line defect region by gate voltage control, revealing highly reactive sites. The B-doped topological line defect is metallic, favoring the adsorption of NO and NH3 over CO and CO2 molecules. We notice changes in the conductance after gas molecule adsorption, producing a sensitivity of 50% (16%) for NO (NH3). In addition, the recovery time for nitride gases was calculated for different temperatures and radiation frequencies. At 300 K the ultraviolet (UV) has a fast recovery time compared to the visible (VIS) one by about two orders of magnitude. This study gives an understanding of how engineering transport properties at the microscopic level (by topological line defect and chemical B-doping) leads to promising nanosensors for detecting nitride gas.

Topological line defects in hexagonal SiC monolayer.

Defect engineering of two-dimensional (2D) materials offers an unprecedented route to increase their functionality and broaden their applicability. In light of the recent synthesis of the 2D Silicon Carbide (SiC), a deep understanding of the effect of defects on the physical and chemical properties of this new SiC allotrope becomes highly desirable. This study investigates 585 extended line defects (ELDs) in hexagonal SiC considering three types of interstitial atom pairs (SiSi-, SiC-, and CC-ELD) and using computational methods like Density Functional Theory, Born-Oppenheimer Molecular Dynamics, and Kinetic Monte-Carlo (KMC). Results show that the formation of all ELD systems is endothermic, with the CC-ELD structure showing the highest stability at 300 K. To further characterize the ELDs, simulated scanning tunneling microscopy (STM) is employed, and successfully allow identify and distinguish the three types of ELDs. Although pristine SiC has a direct band gap of 2.48 eV, the presence of ELDs introduces mid-gap states derived from the pz orbitals at the defect sites. Furthermore, our findings reveal that the ELD region displays enhanced reactivity towards hydrogen adsorption, which was confirmed by KMC simulations. Overall, this research provides valuable insights into the structural, electronic, and reactivity properties of ELDs in hexagonal SiC monolayers and paves the way for potential applications in areas such as catalysis, optoelectronics, and surface science.

Olfactory cortex: Temporal segregation of inputs from the two nostrils.

Piriform cortex processes odor information coming from two nostrils to give rise to unified perception of odorant identity and intensity. A new study reveals that human piriform cortex harbours distinct representations of odor input from ipsilateral and contralateral nostrils through temporal segregation.

Influence of the incorporation of titanium dioxide nanofibers net on bond strength and morphology of a total etching adhesive system.

Background: The aim of this study was to evaluate the nanoleakage and microtensile bond strength (µTBS) of an ethanol based-adhesive containing Titanium dioxide (TiO2) nanofibers to dentin. Material and Methods: TiO2 nanofiber was produced by electrospinning and it was inserted in an ethanol-based adhesive in 0.5, 1.5 and 2.5% by weight. The original adhesive did not receive nanofiber. The middle dentin was exposed by diamond saw under water-cooling and dentin was polished with wet 600-grit SiC abrasive paper. Resin composite build-ups were applied incrementally to the dentin after adhesive application. After storage in distilled water (24 hours/37°C) the teeth were sectioned perpendicularly to the bonded interface and sticks were obtained. Twenty-five sticks per group were tested by µTBS with a crosshead speed of 0.5mm/minute. The average values (MPa) obtained in each substrate were subjected to one-way ANOVA (α=0,05) with the tooth being considered the experimental unit. The nanoleakage pattern was observed in ten sticks per group and analyzed by Chi-square test (α=0,05). Results: There was no difference in µTBS among the experimental groups. However, there was a statistically significant difference among 2.5 % nanofiber adhesive, 0.5 % nanofibers and control groups, (p=0,028) in relation to nanoleakage. Conclusions: TiO2 nanofibers in 2.5% of weight inserted in dental adhesive reduced the nanoleakage, but did not improve the µTBS to dentin. Key words:Dentin-bonding agents, nanoleakage, tensile bond strength.

Limosilactobacillus fermentum modulates the gut-airway axis by improving the immune response through FOXP3 activation on combined allergic rhinitis and asthma syndrome (CARAS).

Combined allergic rhinitis and asthma syndrome (CARAS) is an allergic airway inflammatory disorder orchestrated by the type 2 immune response. The close gut-lung relationship has been described, however, the effect of gut-modulating agents such as probiotics in allergic airway disorder is unclear. Thus, the goal of this study was to evaluate theLimosilactobacillus fermentumsupplementation in animals with CARAS. Therefore, BALB/c mice were ovalbumin (OVA) -sensitized and -challenged after being supplemented withL. fermentum. Animals, previously probiotic supplemented, showed a decrease (p < 0.05) of inflammatory cell migration, mainly eosinophil, into the nasal (NALF) and the bronchoalveolar (BALF) fluids as well as reduction of the allergic signs such as sneezing, nasal rubbings, and nasal hyperreactivity induced by histamine as compared with non-supplemented animals. In the systemic context,L. fermentumreduced eosinophilia and the serum levels of OVA-specific IgE. The altered histological aspects of nasal and lung tissues of animals with CARAS were effectively ameliorated byL. fermentum. In the BALF, the immunomodulatory effect was due to the decreasing of type 2 and 3 cytokines (IL-4, IL-13, IL-5 and IL-17A) dependent on type 1 (IFN-γ) and Treg (IL-10) cytokine increasing. Indeed,L. fermentumimproved the FOXP3 activation. Additionally, these effects correlate with the amplification of the gut response as increasing short-chain fatty acids (SCFAs) levels, gut epithelium barrier (ZO-1) maintenance, and colon tissue integrity. These data pointed out that animals' probiotic supplemented presented immunomodulatory responses in CARAS experimental model by activating the intracellular transduction signal underlying the IL-10 gene transcription.

A Metformin-Ferulic Acid Salt with Improved Biopharmaceutical Parameters.

Though ferulic acid presents great hypoglycemic potential, it possesses limited aqueous solubility, and low oral bioavailability. When associated with metformin, the first-choice drug in Type 2 diabetes treatment, FA demonstrates synergistic hypoglycemic effects, however, it also causes certain undesirable dose-related effects. This study aimed to develop a new ferulic acid - metformin multicomponent system, and incorporate it into a solid dosage form with improved biopharmaceutical parameters. A novel metformin: ferulate (1:1) salt (MFS) was produced, which was properly characterized using differing analytical techniques, including single crystal analysis. Also during the course of the study, a new polymorph of the metformin free base was observed. The MFS was obtained using solvent evaporation methods, which achieved high yields in reproducible process, as well as a 740-fold increase in ferulic acid aqueous solubility. The MFS tablets developed met quality control requirements for this dosage form, as well as revealing excellent performance in vitro dissolution tests, presenting dissolution efficiency values of 95.4 ± 0.5%. Additionally, physicochemical instability was not observed in a study at 40 °C for 3 months for both MFS powder and its tablet form. The MFS product developed is a promising candidate for further Type 2 diabetes clinical study.

Landing Technique and Ankle-dorsiflexion Range of Motion are not Associated with the History of Lower Limb Injuries among Youth Basketball Athletes.

Background: Lower limb injuries generate a significant health burden in basketball. Landing technique and ankle-dorsiflexion range of motion have been suggested as risk factors for lower limb injuries among youth athletes, but studies conducted specifically with basketball athletes are lacking. Hypothesis/Purpose: To describe the period prevalence of basketball-related injuries and to examine the association of the history of lower limb injuries with landing technique and ankle-dorsiflexion range of motion asymmetry among youth basketball athletes. Study Design: Cross-Sectional Survey. Methods: Youth basketball athletes were asked to complete a paper-based survey to investigate personal characteristics, training characteristics and their three-month history of basketball-related injuries. The Landing Error Scoring System and the Weight-Bearing Lunge Test were used to evaluate landing technique and ankle-dorsiflexion range of motion. Binary logistic regression was utilized to examine the association of the investigated variables with the presence of history of lower limb injuries among the athletes. Results: A total of 534 athletes participated. The three-month prevalence of basketball-related injuries was 23.2% (95% CI 19.7 - 27), and the majority of the reported injuries affected the lower limbs (69.7%; n=110). Sprains were the most frequent type of injury (29.1%; n=46), and the ankle (30.4%; n=48) and knee (21.5%; n=34) were the most affected anatomic locations. Landing technique (p = 0.105) and ankle-dorsiflexion range of motion asymmetry (p = 0.529) were not associated with the history of lower limb injuries. Conclusion: The three-month prevalence of basketball-related injuries was 23.2%. Although ankle sprains were the most frequent injury, landing technique and ankle-dorsiflexion range of motion asymmetry were not associated with the history of lower limb injuries among youth basketball athletes. Level of Evidence: 3.

Convolutional Neural Network Classification of Topographic Electroencephalographic Maps on Alcoholism.

Alcohol use is a leading risk factor for substantial health loss, disability, and death. Thus, there is a general interest in developing computational tools to classify electroencephalographic (EEG) signals in alcoholism, but there are a limited number of studies on convolutional neural network (CNN) classification of alcoholism using topographic EEG signals. We produced an original dataset recorded from Brazilian subjects performing a language recognition task. Then, we transformed the Event-Related Potentials (ERPs) into topographic maps by using the ERP's statistical parameters across time, and used a CNN network to classify the topographic dataset. We tested the effect of the size of the dataset in the accuracy of the CNNs and proposed a data augmentation approach to increase the size of the topographic dataset to improve the accuracies. Our results encourage the use of CNNs to classify abnormal topographic EEG patterns associated with alcohol abuse.

Model-Informed drug development of gastroretentive release systems for sildenafil citrate.

Gastroretentive drug delivery systems (GRDDS) are modified-release dosage forms designed to prolong their residence time in the upper gastrointestinal tract, where some drugs are preferentially absorbed, and increase the drug bioavailability. This work aimed the development of a novel GRDDS containing 60 mg of sildenafil citrate, and the evaluation of the feasibility of the proposed formulation for use in the treatment of pulmonary arterial hypertension (PAH), for once a day administration, by using in silico pharmacokinetic (PK) modeling and simulations using GastroPlusTM. The Model-Informed Drug Development (MIDD) approach was used in formulation design and pharmacokinetic exposure prospecting. A 22 factorial design with a central point was used for optimization of the formulation, which was produced by direct compression and characterized by some tests, including buoyancy test, assay, impurities, and in vitro dissolution. A compartmental PK model was built using the GatroPlusTM software for virtual bioequivalence of the proposed formulations in comparison with the defined target release profile provided by an immediate release (IR) tablet formulation containing 20 mg of sildenafil administered three times a day (TID). The results of the factorial design showed a direct correlation between the dissolution rate and the amount of hydroxypropyl methyl cellulose (HPMC) in the formulations. By comparing the PK parameters predicted by the virtual bioequivalence, the formulations F1, F2, F3 and F5 failed on bioequivalence. The F4 showed bioequivalence to the reference and was considered the viable formulation to substitute the IR. Thus, GRDDS could be a promising alternative for controlling the release of drugs with a pH-dependent solubility and narrow absorption window, specifically in the gastric environment, and an interesting way to reduce dose frequency and increase the drug bioavailability. The MIDD approach increases the level of information about the pharmaceutical product and guide the drug development for more assertive ways.

Evaluating the Stability of a Novel Nutraceutical Formulation Combining Probiotic Limosilactobacillus fermentum 296, Quercetin, and Resveratrol Under Different Storage Conditions.

This study evaluated the stability of a novel nutraceutical formulation composed of the probiotic Limosilactobacillus fermentum 296, quercetin (QUE), and resveratrol (RES) (LFQR) under different storage conditions. The effects of different relative humidities (RH; 11, 22, and 33%) and storage temperatures (refrigeration temperature -4 °C and room temperature -25 °C) on the stability of LFQR were evaluated through the determination of thermal stability, viable cell counts, bacterial physiological status, antioxidant capacity, and contents of QUE and RES during long-term storage. RH did not affect endothermic reactions and mass reduction in LFQR. After a 15-day-humidification period, L. fermentum 296 had higher viable cell counts in LFQR under refrigeration temperature storage when compared to room temperature storage regardless of the RH. The physiological status of L. fermentum 296 in LFQR was overall similar during 90 days of storage (11% RH) under refrigeration and room temperature. L. fermentum 296 had the highest viable cell counts (> 6 log CFU/g) in LFQR up to day 90 of refrigeration storage (11% RH). LFQR kept high contents of QUE and RES and maintained antioxidant capacity during 90 days of storage under refrigeration and room temperature. The results showed that the higher stability and functionality of LFQR during long-term storage should be guaranteed under 11% RH and refrigeration temperature.

Gas-sensing detection in the carbon phosphide monolayer: improving COx sensitivity through B doping.

A challenge in 2D materials engineering is to find a nanodevice that is capable of detecting and distinguishing gas molecules through an electrical signal. Herein, the B-doped carbon phosphide monolayer (B-doped γ-CP) was explored as a gas sensor through a combination of density functional theory (DFT) and the non-equilibrium Green's function (NEGF). Formation of the B-doped system is governed by an exothermic process, and the doping increases bands crossing at the Fermi level, contributing to an increment in the number of transmission channels compared with the undoped system. The interaction between the nanodevice and each gas molecule (CO, CO2, NO, and NH3) was explored. The electronic transmission is characteristically modulated by each target molecule, enabling each to be distinguished through the conductance change in the material. Our finds propose B-doped γ-CP as a promising candidate for use in highly sensitive and selective gas nanosensors.

A high-performance liquid chromatography method for simultaneous quantification of metformin and ferulic acid in solid dosage forms.

Metformin is one of the most commonly used drugs in the world for the treatment of type 2 diabetes, while ferulic acid is a molecule that stands out for its antioxidant potential. Recent studies demonstrate hypoglycemic synergy between these molecules. The objective of this study is to develop and validate an analytical methodology by high-performance liquid chromatography for the simultaneous quantification of these drugs in pharmaceutical formulations. The method used an octadecylsilane column and a mobile phase composed of 6 mM sodium lauryl sulfate in 15 mM phosphate buffer:ACN (65:35). Ferulic acid and metformin were monitored at 232 nm, with a mobile phase flow rate of 1 ml/min and oven temperature at 40°C. The method was linear in the range of 5-25 µg/ml for both molecules. In the presence of degradation products, satisfactory selectivity was achieved. Accuracy values were close to 100% and standard deviations in precision were less than 2%. In the robustness evaluation, the proposed variations did not interfere with the quantification. Therefore, it is concluded that the present method can be safely applied to the quality control of ferulic acid and metformin raw materials, as well as when they are combined in pharmaceutical formulations.

Prevalence and associated factors of obstructive sleep apnea in refractory hypertension.

BACKGROUND: Refractory hypertension (RfHT) and obstructive sleep apnea (OSA) share common pathophysiological mechanisms and probably are intrinsically associated, but their prevalence, clinical profile, and polysomnography (PSG) pattern remain misunderstood. OBJECTIVE: To describe OSA prevalence and PSG pattern of patients with RfHT in a large cohort of resistant hypertension (RHT). METHODS: This is a cross-sectional study involving 418 RHT patients (30.9% male; mean age of 62.5 ±â€Š9.9 years) who were submitted to full-night PSG. RfHT was defined as uncontrolled ambulatory blood pressure monitoring using five or more antihypertensive drugs, including spironolactone. Bivariate analysis compared RHT and RfHT and multivariate analysis was performed to assess the independent correlates of OSA. RESULTS: A total of 90 patients (21.5%) were diagnosed with RfHT (26.7% male; mean age of 58.5 ±â€Š8.3 years). In comparison with resistant ones, RfHT patients were younger, with higher smoking and previous cardiovascular diseases prevalence, especially stroke. There was no difference regarding anthropometric measures. OSA prevalence (80.0 vs. 82.9%) and moderate/severe OSA (51.1 vs. 57.0%) were similar in both groups as well as apnea-hypopnea index. In its turn, refractory hypertensive patients presented better sleep efficiency (78 vs. 71%), with higher total sleep time (315 vs. 281 min) and lower sleep latency (11 vs. 17 min). There was no difference regarding rapid eye movement sleep, oxygen saturation, microarousals index, and periodic limb movement. CONCLUSION: In this large RHT cohort, resistant and refractory hypertensive patients have similar OSA prevalence, although refractory ones, which by definition use spironolactone, are younger and apparently have a better sleep pattern.

Association between arterial stiffness and sleep apnoea in patients with resistant hypertension.

Resistant Hypertension (RHT) is associated with a higher risk of Obstructive Sleep Apnoea (OSA). OSA and aortic stiffness (AS) measured by Pulse Wave Velocity (PWV) are independent risk factors for cardiovascular events. We assessed, in a cross-sectional study, the association between AS measured by PWV and OSA severity in patients with RHT. All patients were submitted to polysomnography, PWV measure and 24 h ABPM. Bivariate analysis compared patients with and without moderate/severe OSA. Multivariate analysis was performed to assess the independent correlates of moderate/severe OSA. A total of 376 patients were included, 31% were men with a mean age of 63 ± 10 years. Moderate/severe OSA was diagnosed in 214 patients (57%), 63 patients (17%) presented AS. Uncontrolled ABPM (true RHT) was found in 215 patients (57.2%) and among them 113 were diagnosed with moderate/severe OSA. Evaluating AS in patients with mild, moderate and severe apnoea, we observed a progressive increase in PWV (8.19 ± 1.55, 8.51 ± 1.84, 8.67 ± 1.68, respectively). Classifying them in 2 groups: (1) without apnoea/mild apnoea and (2) moderate/severe apnoea, we found higher values in group 2 (8.21 ± 1.52 m/s vs. 8.60 ± 1.75 m/s, p = 0.02), especially among true RHT patients (8.28 ± 1.62 vs. 8.81 ± 1.86, p = 0.029), women (8.13 ± 1.49 vs. 8.55 ± 1.73, p = 0.036), and uncontrolled nocturnal systolic BP (8.49 ± 1.63 vs. 8.58 ± 1.78, p = 0.04). In conclusion, in this RHT cohort, although with borderline results, the more severe the apnoea, the greater the arterial stiffness, mainly among women, true RHT and patients with an adverse nocturnal BP profile.