Search Results (22)

Background/Objectives: Inflammatory processes, including elevated pro-inflammatory cytokines such as interleukin 1β (IL-1β), have been implicated in the pathophysiology of anxiety disorders. The ketone body β-hydroxybutyrate (βHB) was shown to mitigate inflammatory processes induced by lipopolysaccharide (LPS) administration. It was also suggested that exogenous ketone supplements, such as ketone esters (KEs) and ketone salts (KSs), can decrease anxiogenic effects through increased blood ketone levels in the body (ketosis) in preclinical animal models. Methods: Thus, we investigated whether standard rodent food supplemented with KEKS (KEKS food: mix of a KE R/S-1,3-butanediol-acetoacetate diester and a KS Na⁺- and Ca²⁺- R/S-βHB salt in 1:1 ratio) for 7 days can alleviate the intraperitoneal (i.p.) 1 mg/kg LPS-generated anxiogenic effect in female Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. For the evaluation of anxiogenic effects, the light–dark box (LDB) test was used. Results: KEKS food significantly increased the blood R-β-hydroxybutyrate (R-βHB) level and decreased the blood glucose level compared to the baseline. Moreover, the LPS significantly (i) decreased the time spent in the light compartment, the number of chamber transitions, the number of re-entries to the light compartment and the number of rearing in the light compartment, and also (ii) increased the time of latency to the first re-entry to the light compartment compared to control. Nevertheless, KEKS food treatment abolished LPS-generated anxiety-like behavior. Conclusions: The current study demonstrated that a 7-day KEKS-supplemented diet can increase blood R-βHB levels and abolish acute LPS administration-evoked increases in anxiety levels in female WAG/Rij rats. Moreover, our results support the important role of neuroinflammation in pathological processes resulting in anxiety. Thus, these results suggest that exogenous ketone supplement-generated ketosis may be a promising therapeutic tool in the treatment of inflammatory process-mediated diseases, such as anxiety disorders. Full article

Objective: ZhiZhu Kuanzhong (ZZKZ) capsule, a Chinese herbal extract, is extensively employed for the clinical management of functional dyspepsia (FD) in China. This study aimed to elucidate the therapeutic efficacy and underlying mechanisms of ZZKZ on the co-morbidity of anxiety and depression of FD. Methods: The FD model was established in Sprague–Dawley rats via neonatal gastric irritation with 0.1% iodoacetamide. Subsequently, FD rats were gavaged with ZZKZ or fluoxetine. Depression-like behaviors were evaluated using the sucrose preference test (SPT) and forced swimming test (FST), while anxiety-like behaviors were assessed via light-dark box (LDB) and open field tests (OFTs). Network pharmacology and molecular docking were conducted to explore the mechanisms of ZZKZ’s action. Hippocampal levels of monoamine neurotransmitters and monoaminergic system components were evaluated by HPLC and RT-qPCR, respectively. Serum concentrations of HPA axis hormones were determined by ELISA. Results: ZZKZ administration reversed the deficits in body weight gain and food intake in FD rats. Behaviorally, ZZKZ increased sucrose consumption in SPT and prolonged swimming duration in FST, and it increased duration and entries into the central zone in OFT. According to the prediction of network pharmacology, ZZKZ treatment elevated hippocampal levels of 5-HT/NE/DA, increased expression of TPH2/TH, and decreased expression of MAO_A/SERT in FD rats. Molecular docking further confirmed high-affinity binding between core ingredients of ZZKZ and TPH2/TH/MAO_A/SERT. Moreover, ZZKZ administration attenuated the stress-induced elevation of serum CRH/ACTH/CORT. Conclusions: ZZKZ effectively ameliorates the disordered gut–brain interaction and mitigates anxiety-like and depression-like behaviors, which might be modulated by the hippocampal monoaminergic system and hypothalamic–pituitary–adrenal axis response. Full article

To examine how grain-size distribution affects the mechanical response and fracture behavior of Lac du Bonnet (LdB) granite under uniaxial compression, numerical simulations were conducted using the particle flow code (PFC) with a grain-based model. By displacing grain centroids in different directions along the y-axis, four LdB granite models with distinct grain sizes were generated, with grains delineated by Voronoi tessellation. The main findings are as follows: (1) The flat-jointed constitutive model reproduces the experimental response well, and introducing unbonded contacts (micrometer-scale gaps) improves the simulation of crack-closure behavior during loading. (2) Secondary cracks initiate predominantly at grain boundaries, and the yield stress is strongly associated with the evolution of intragranular tensile cracks. (3) Grain size governs the sequence of crack accumulation (tensile vs. shear), the growth rate and spatial correlation of damage, and the distribution and intensity of local failures; smaller grains hinder macroscopic damage, whereas larger grains are more readily penetrated and filled by microcracks. (4) Mechanical cutting tests show that grain-size combinations produce several dominant secondary-failure modes; the failure thickness is controlled by the penetration depth of the subsequent cutting head, and the stress concentration near the cutting head is sensitive to grain size. Full article

Deep learning-based water body extraction methods generally focus on maximizing accuracy while neglecting inference speed, which can make them challenging to apply in real-time applications. To address this problem, this paper proposes a lightweight u-shaped network (LU-Net), which improves inference speed while maintaining comparable accuracy. To reduce inference latency, a lightweight decoder block (LDB) is designed, which employs a depthwise separable convolution structure to accelerate the decoding process. To enhance accuracy, a lightweight convolutional block attention module (LCBAM) is designed, which effectively captures water-specific spectral and spatial characteristics through a dual-attention mechanism. To improve multi-scale water boundary extraction, a structurally re-parameterized multi-scale fusion prediction module (SRMFPM) is designed, which integrates multi-scale water boundary information through convolutions of different sizes. Comparative experiments are conducted on the GID and LoveDA datasets, with model performance assessed using the MIoU metric and inference latency. The results demonstrate that LU-Net achieves the lowest GPU latency of 3.1 MS and the second-lowest CPU latency of 36 MS in the experiments. On the GID, LU-Net achieves the MIoU of 91.36%, outperforming other tested methods. On the LoveDA datasets, LU-Net achieves the second-highest MIoU of 86.32% among the evaluated models, which is 0.08% lower than the top-performing CGNet. Considering both latency and MIoU, LU-Net demonstrates commendable efficiency on the GID and LoveDA datasets across all compared networks. Full article

Background: Premenstrual syndrome is characterized by emotional changes, including anxiety and depression symptoms, which may be treated with anxiolytic and antidepressant drugs, as well as estrogen therapy. However, steroidal estrogen therapy is contraindicated for patients with a potential risk of developing estrogen-dependent cancers through interactions with estrogen receptor α (ERα). Alternatively, genistein produces estrogenic effects in animals and humans at dietary dosages that act on the nuclear and membrane ERα, estrogen receptor β (ERβ), and the G-protein-coupled estrogen receptor (GPER). These receptors are likely involved in the anxiety symptoms observed in premenstrual disorders. The objective of this study was to evaluate the effects of genistein and 17β-estradiol on anxiety-like behavior and the plasma concentrations of estradiol and progesterone throughout the ovarian cycle of Wistar rats. Methods: The effect of the administration of 0.09 mg/kg of genistein or 17β-estradiol was evaluated using the elevated plus maze (EPM) test, locomotor activity test (LAT), and light/dark box (LDB) test, as well as by assessing the plasma concentrations of estradiol and progesterone, while considering the ovarian cycle phases. Results: Higher levels of anxiety-like behavior were detected in the metestrus–diestrus phase compared to the proestrus–estrus phase, which was associated with low concentrations of estradiol. Genistein, similarly to 17β-estradiol, significantly reduced anxiety-like behaviors in the EPM and LDB; however, 17β-estradiol, but not genistein, significantly increased the plasma estradiol concentration. No significant changes were found in locomotor activity or the plasma progesterone concentrations due to the treatments. Conclusions: These findings suggest that genistein may be useful in the development of alternative therapies to reduce the anxiety associated with low steroid hormone concentrations, which occur in premenstrual syndrome. Genistein could be an alternative to steroidal estrogen therapy to avoid potential side effects due to estradiol or antidepressant treatments, although it still requires medical care. Full article

Epidemiological studies have linked fine dust pollution to depression, yet the underlying mechanisms remain unclear. Oxidative stress and endoplasmic reticulum (ER) stress are known contributors to depression, but their induction by particulate matter (PM), particularly PM2.5, in animal models has been limited. This study aimed to establish a rat model of PM2.5-induced depression-like behaviors and elucidate the underlying molecular mechanisms. Adult male Sprague–Dawley rats received daily intranasal PM2.5 for four weeks. Behavioral assessments, including the open field test (OFT), forced swim test (FST), and light-dark box (LDB) test, were conducted weekly. PM2.5-exposed rats displayed depressive-like behaviors, particularly in the FST, reflecting decreased motivation and learned helplessness. Molecular analyses indicated a specific increase in ER stress markers (CHOP, eIF2α, GRP78, and P16) and NOX4 in the hypothalamus, while other brain regions (striatum, cortex, and hippocampus) were not as pronounced. Additionally, PM2.5 exposure reduced tyrosine hydroxylase (TH) levels in the hypothalamus, suggesting impaired dopamine synthesis. These findings indicate that PM2.5 induces depressive-like behaviors via hypothalamic ER stress and oxidative stress pathways, leading to dopaminergic dysfunction. Targeting oxidative and ER stress within the hypothalamus may offer new therapeutic strategies for treating depression associated with environmental pollutants. Full article

Background/Objectives: Lyme disease is caused by some species of tick-borne bacteria of the genus Borrelia, termed Lyme disease Borreliae (LDB). Borrelia burgdorferi is the LDB species principally responsible for Lyme disease in the US. The outer surface protein A (OspA) of LDB attaches the bacteria to the gut of Ixodes tick vectors. OspA expression is downregulated when B. burgdorferi is transmitted from ticks to mammalian hosts. Vaccination with OspA elicits antibody-mediated protective immunity in animals and humans against LDB infection. The possible presence of serum antibodies against OspA in persons with PCR-confirmed LDB infections in blood was investigated in this study. Methods: Ninety-one archived sera from patients with LDB infections in blood demonstrated by a sensitive PCR assay were tested for reactivity with OspA from multiple LDB species in line immunoblots. Results: In total, 14 of the 91 sera (15.4%) had either IgG or IgM antibodies to OspA from one or more LDB species. Conclusions: The results show for the first time that serum antibodies to OspA are formed when LDB are present in human blood. However, the factors that governed the expression of OspA by LDB in patients could not be ascertained. It will be useful to determine whether the observed levels of serum antibodies to OspA in infected persons can protect against subsequent tick-borne infection and whether OspA used in conjunction with other LDB antigens can improve the serological diagnosis of Lyme disease. Full article

While one-third of the population can be affected by anxiety disorders during their lifetime, our knowledge of the pathophysiology of these disorders is far from complete. Previously, it has been demonstrated in male animals that exogenous ketone supplement-evoked ketosis can decrease anxiety levels in preclinical rodent models, such as Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. Thus, in this study, we investigated whether intragastric gavage of the exogenous ketone supplement KEMCT (mix of 1,3-butanediol-acetoacetate diester/ketone ester/KE and medium-chain triglyceride/MCT oil in 1:1 ratio) for 7 days can alter the anxiety levels of female WAG/Rij rats using the light–dark box (LDB) test. We demonstrated that a lower dose of KEMCT (3 g/kg/day) increased blood R-βHB (R-β-hydroxybutyrate) levels and significantly decreased anxiety levels (e.g., increased the time spent in the light compartment) in female WAG/Rij rats on the seventh day of administration. Although the higher KEMCT dose (5 g/kg/day) increased blood R-βHB levels more effectively, compared with the lower KEMCT dose, anxiety levels did not improve significantly. We conclude that ketone supplementation might be an effective strategy to induce anxiolytic effects not only in male but also in female WAG/Rij rats. However, these results suggest that the optimal level may be moderately, not highly, elevated blood R-βHB levels when the goal is to alleviate symptoms of anxiety. More studies are needed to understand the exact mechanism of action of ketone supplementation on anxiety levels and to investigate their use in other animal models and humans for the treatment of anxiety disorders and other mental health conditions. Full article

The cultivated tomato is one of the most consumed vegetables in the world, and the preparation of seedlings plays a fundamental role in the success of the crop, which is often plagued by fungi and bacteria from its earliest stages. This study aimed to analyze the emergence speed index and morphological parameters of Wanda hybrid cherry tomato seedlings (Solanum lycopersicum var. pimpinellifolium) in trays with two different types and levels of substrates in a protected environment using certified seeds. The experiment was conducted in the greenhouse of the IFCE—Campus Crato during the months of August and September 2022. Two basic substrates were used to promote germination and emergence: one was the commercial Vivato Slim Plus^®, and the other was based on worm humus produced in Minhobuckets kits. The experimental design was completely randomized, consisting of five doses of commercial substrate (SBC) and earthworm humus (HDM) in the following proportions: S1—HDM; S2—SBC; S3—HDM + SBC (1:1), S4—HDM + SBC (1:3), and S5—HDM + SBC (3:1). The ESI, morphological parameters (SD, PH, ROOTL, and NL), and the dry biomass of the seedlings (LDB, SDB, RDB, and TDB) were determined. Data were subjected to an analysis of variance, and Tukey’s test (0.05) was used; dry biomass data were submitted to square root transformation. For the emergence speed index, SBC (S2) outperformed the others. Regarding the morphological parameters and dry biomass, all substrates yielded satisfactory results, despite not showing a statistical difference between the averages. The substrate S4 produced the best results in all evaluated parameters. Full article

Extraction of intracellular lipids of the oleaginous yeast Yarrowia lipolytica has been systematically studied aiming towards a sustainable extraction process for lipid recovery. Selection of suitable industrial (bulk) solvents and extraction parameters that lead to maximization of lipid recovery are significant issues to be addressed, with industrial applications motivating this study. Biomass from fermentation of Yarrowia lipolytica (MUCL 28849) was used in small laboratory tests to assess different solvent mixtures (i.e., methanol/hexane, isopropanol/hexane, and methanol/ethyl acetate), implementing a systematic design of experiments methodology to identify near-optimum values of key extraction variables (i.e., polar/non-polar ratio, vortex time, dry biomass/solvent ratio) in regard to lipid yield (g lipids/g dry biomass). The methanol/hexane mixture exhibited the highest extraction yield in a wide range of experimental conditions, resulting in the following optimum parameters: polar/non-polar ratio 3/5, vortex time 0.75 h, and dry biomass/solvent ratio 40. Extraction tests on a fifty-times-larger scale (in a Soxhlet apparatus employing the optimal extraction parameters) confirmed the optimization outcome by obtaining up to 27.6% lipids per dry biomass (L/DB), compared to 12.1% L/DB with the reference lipid extraction method employing chloroform/methanol. Assessment of lipid composition showed that unsaturated fatty acid recovery was favored by the methanol/hexane solvent. Fatty acid composition was not affected by the increase in Soxhlet reflux cycles, whilst the lipid yield was notably favored. Full article

A new series of quinoxaline derivatives, 2a–4b, were synthesized and their anxiolytic potential was evaluated in vivo using elevated plus maze (EPM), open field (OF) and light-dark box (LDB) techniques. According to the results of the EPM, four active compounds were found in 2a, 2b, 2c, 4b. Their anxiolytic properties were confirmed in terms of LDB and the most active was compound 2b. In the OF, only 2c had an influence on the locomotor activity of the rodents. Thus, the most promising substance was determined; this was 2b, which has the structure of 2-(2-{[3-(4-tert-butylphenyl)quinoxaline-2-yl]methyl}-4,5-dimethoxyphenyl)-N-methylethan-1-amine hydrochloride. The obtained data were analyzed with the pharmacophore feature prediction approach, which made it possible to compare the structures of the studied compounds with the reference drug diazepam, and to determine the contribution of pharmacophores to the manifestation of the activity under study. ADMET analysis was carried out for compound 2b and the acute oral toxicity of this substance was also tested in vivo. As a result of the study, a promising compound with a high anxiolytic effect and low level of toxicity 2b was found, which is of interest for further preclinical study of its properties. Full article

Chromone-containing allylmorpholines (CCAMs) are a novel class of compounds that have demonstrated acetyl- and butyryl-cholinesterase-inhibiting and N-methyl-D-aspartate (NMDA) receptor-blocking properties in vitro, but their in vivo pharmacological activity remains underexplored. In this work, we evaluated the psychotropic activity of five different CCAMs (1 (9a), 2 (9j), 3 (9l), 4 (33a), and 5 (33b)) using the novel tank test (NTT) and light/dark box (LDB) test in adult zebrafish. The CCAMs were screened in the NTT at a range of concentrations, and they were found to induce a dose-dependent sedative effect. Compound 4 (33a) was also evaluated using the LDB test, and it was found to have anxiolytic-like properties at low concentrations. To assess the potential contribution of the glutamate and cholinergic mechanisms in the effects of the CCAMs, we conducted experiments with pre-exposure to putative antagonists, NMDA and biperiden. Neither biperiden nor NMDA were able to diminish or cancel the effects of the CCAMs, countering the in vitro data obtained in previous studies. The apparent discrepancy could be related to the specifics of CCAM metabolism or to the interspecies differences between the putative target proteins, possibly due to the relatively low identity percentage of their sequences. Although further research in mammals is required in order to establish their pharmacological properties, novel CCAMs may represent an appealing group of psychoactive drug candidates. Full article

Epilepsies are neurological disorders characterized by chronic seizures and their related neuropsychiatric comorbidities, such as anxiety. The Transient Receptor Potential Vanilloid type-1 (TRPV1) channel has been implicated in the modulation of seizures and anxiety-like behaviors in preclinical models. Here, we investigated the impact of chronic epileptic seizures in anxiety-like behavior and TRPV1 channels expression in a genetic model of epilepsy, the Wistar Audiogenic Rat (WAR) strain. WARs were submitted to audiogenic kindling (AK), a preclinical model of temporal lobe epilepsy (TLE) and behavioral tests were performed in the open-field (OF), and light-dark box (LDB) tests 24 h after AK. WARs displayed increased anxiety-like behavior and TRPV1R expression in the hippocampal CA1 area and basolateral amygdala nucleus (BLA) when compared to control Wistar rats. Chronic seizures increased anxiety-like behaviors and TRPV1 and FosB expression in limbic and brainstem structures involved with epilepsy and anxiety comorbidity, such as the hippocampus, superior colliculus, and periaqueductal gray matter. Therefore, these results highlight previously unrecognized alterations in TRPV1 expression in brain structures involved with TLE and anxiogenic-like behaviors in a genetic model of epilepsy, the WAR strain, supporting an important role of TRPV1 in the modulation of neurological disorders and associated neuropsychiatric comorbidities. Full article

In the standardization of versatile video coding (VVC), discrete cosine transform (DCT)-2, discrete sine transform (DST)-7, and DCT-8 are regarded as the primary transform kernels. However, DST-4 and DCT-4 can also be considered as the transform kernels instead of using DST-7 and DCT-8 owing to their effectiveness in smaller resolution test sequences. To implement these different block size transform kernels, a considerable amount of memory has to be allocated. Moreover, memory consumption to store different block size transform kernels is regarded as a major issue in video coding standardization. To address this problem, a common sparse unified matrix concept is introduced in this study, where any block size transform kernel matrix can be obtained after some mathematical operations. The proposed common sparse unified matrix saves approximately 80% of the static memory by storing only a few transform kernel elements for DCT-2, DST-7, and DCT-8. Full-required transform kernels are derived using the stored transform kernels and generated unit-element matrices and a permutation matrix. The static memory required is only for 1648 elements instead of 8180 elements, each with 8-bit precision. The defined common sparse unified matrix is composed of two parts: a unified DST-3 matrix and a grouped DST-7 matrix. The unified DST-3 matrix is used to derive different points of DCT-2 transform kernels, and the grouped DST-7 matrix is used to derive different points of DST-7 and DCT-8 transform kernels. The new technique of grouping concept is introduced, which shows the relationship between different rows of DST-7 transform kernels with various block sizes. The proposed grouping concept supports the fast algorithm of DST-7 by implementing the proposed method of the “one group one feature” principle. The simulation was conducted using the VTM-3.0 reference software under common test conditions. The simulation result of the all intra (AI) configuration is Y = 0.00%, U = −0.02%, V = 0.00% with an encoding time of 100%, and a decoding time of 100%. Similarly, the simulation results of random access (RA) configuration are Y = −0.01%, U = 0.09%, V = 0.06%, and the encoding and decoding times are 101% and 100%, respectively. The simulation result of the low delay B (LDB) configuration is Y = 0.01%, U = 0.08%, and V = −0.27%, for encoding and decoding times of 101% and 100%, respectively. Full article

The objective of the study was to evaluate behavioral observation procedures and tests to characterize sows’ behavior for their suitability for free farrowing systems. Nest building activity (NB), lying-down behavior (LDB), and position after lying down (PLD) were assessed. Four tests were designed to characterize the reaction of sows to a novel object and an unexpected situation (Towel Test, TT), behavior towards humans (Dummy Arm Test, DAT; Trough Cleaning Test, TCT), and behavior towards piglets (Reunion Test, RT). The study was performed on a nucleus farm in 37 batches including 771 purebred landrace sows housed in farrowing pens with short-term fixation. The assessment of NB started 2 days before the expected date of the farrowing. In 56.2% of the observations, the sows showed increased chewing activity on gunnysacks. The LDB and PLD were assessed on days 3 and 19 post partum (p.p.). In 49.1% of the observations, sows showed careful lying-down behavior. In 50.1% of cases, sows preferred the stomach-teats-position when lying down. With the DAT on day 4 p.p., in 89.3% of observations, no or only slight reactions of the sow were documented. The TT and TCT were performed on days 3 and 10 p.p. Strong defensive reactions of animals towards humans were recorded in 4.5% of the observations in the TT, and in 4.0% of the observations in the TCT. In the RT on day 3 p.p., in 61.8%, a joyful response of the sows to the reunion with their piglets was observed. This study showed that the behavioral observation procedures and designed tests are suitable to characterize sows’ behavior towards humans and piglets with regard to traits that are particularly important in systems without fixation. Full article