Kynurenic acid (KYNA), a tryptophan metabolite, is believed to exert neuromodulatory and neuroprotective effects in the brain. The study aimed to examine the KYNA’s capacity to modify gene expression and the activity of cellular antioxidant enzymes in specific structures of the sheep brain. Anestrous sheep were infused intracerebroventricularly with two KYNA doses: lower (4×5 μg/60 μL/30 min, KYNA20) and higher (4×25 μg/60 μL/30 min, KYNA100) at 30min intervals. The abundance of superoxide dismutase (SOD2), catalase (CAT) and glutathione peroxidase (GPx1) mRNA, as well as enzyme activities (µM/µg of protein), were determined in the hypothalamic medial-basal (MBH) and preoptic (POA) areas, and in the hippocampal CA1 field. Both doses of KYNA caused a decrease (P<0.01) in the expression of SOD2 and CAT mRNA in all structures examined compared to the control group (except for CAT in the POA at the KYNA100 dose). Furthermore, lower levels of SOD2 mRNA (P<0.05) and CAT mRNA (P<0.01) were found in the MBH and POA and in the POA and CA, respectively, in sheep administered with the KYNA20 dose. Different stimulatory effects on GPx1 mRNA expression were observed for both doses (P<0.05-P<0.01). KYNA exerted stimulatory, but dose-dependent effects on SOD2, CAT and GPx1 activities (P<0.05-P<0.01) in all brain tissues examined. The results indicate that KYNA may influence the level of oxidative stress in individual brain structures in sheep by modulating the expression of genes and activity of at least SOD2, CAT and GPx1. The present findings also expand the general knowledge about the potential neuroprotective properties of KYNA in the central nervous system.

The role of astro- and microglial cells in the pathogenesis of epilepsy is currently under active in-vestigation. It is proposed that the activity of these cells may be regulated by agonists of peroxi-some proliferator-activated nuclear receptors (PPARs). The objective of this study was to investi-gate the effects of the PPAR β/δ agonist GW0742 (Fitorine) on the behavior and gene expression of astro- and microglial proteins involved in the regulation of epileptogenesis in rat brain in a lithi-um-pilocarpine model of temporal lobe epilepsy (TLE). A seven-day administration of GW0742 at a dose of 5 mg/kg/day has been shown to suppress TLE-related behavioral hyperactivity in the Open Field test and to attenuate the TLE-induced increase in gene expression and protein levels of astro- and microglial activation markers Gfap and Aif1 in the dorsal hippocampus and temporal cortex. Furthermore, GW0742 reversed the TLE-related increase in Lcn2 gene expression (a marker of the A1 phenotype of astrocytes) in the temporal cortex, the increase in the ratio of Nos2/Arg1 gene expression (markers of the M1/M2 phenotypes of microglia), and the decrease in Arg1 gene ex-pression in the dorsal hippocampus. The results suggest that GW0742 may mitigate behavioral and biochemical abnormalities in a lithium-pilocarpine model of TLE.

The tumor necrosis factor receptor associated factor 1 (TRAF1) plays a key role in promoting lymphocyte survival, proliferation, and cytokine production. Recent evidence showed that TRAF1 plays opposing roles in monocytes and macrophages where it controls NF-B activation and limits pro-inflammatory cytokine production as well as inflammasome-dependent IL-1 secretion. Importantly, TRAF1 polymorphisms have been strongly linked to an increased risk of rheumatoid arthritis (RA). However, whether and how TRAF1 contributes to RA pathogenesis is not fully understood. Moreover, investigating the role of TRAF1 in driving RA pathogenesis is complicated by its multifaceted and opposing roles in various immune cells. In this study, we show that intraarticular injection of TRAF1 deficient macrophages into knee joints of wildtype (WT) mice subjected to the collagen antibody induced arthritis (CAIA) model of RA significantly exacerbated joint inflammation, immune cell infiltration and tissue damage compared to mice injected with WT macrophages. This study may lay the groundwork for novel therapies for RA that target TRAF1 in macrophages.

Epilepsy is known to cause alterations in neural networks. However, many details of these changes remain poorly understood. The objective of this study was to investigate changes in the properties of hippocampal CA1 pyramidal neurons and their synaptic inputs in a rat lithium-pilocarpine model of epilepsy. In the chronic phase of the model, we found a marked loss of pyramidal neurons in the CA1 area. However, the membrane properties of the neurons remained essentially unal-tered. The results of the electrophysiological and morphological studies indicate that the direct pathway from the entorhinal cortex to CA1 neurons is reinforced in epileptic animals, whereas the inputs to them from CA3 are either unaltered or even diminished. In particular, the dendritic spine density in the str. lacunosum moleculare, where the direct pathway from the entorhinal cortex ter-minates, was found to be 2.5 times higher in epileptic rats than in control rats. Furthermore, the summation of responses upon stimulation of the temporoammonic pathway was enhanced by approximately twofold in epileptic rats. This enhancement is believed to be a significant con-tributing factor to the heightened epileptic activity observed in the entorhinal cortex of epileptic rats using an ex vivo 4-aminopyridine model.

According to previous studies the median raphe region (MRR) is known to contribute significantly to social behavior. Beside serotonin, there are reports of a small population of dopaminergic neu-rons in this region. Dopamine is linked to reward and locomotion, but very little has been known about its role in the MRR. To address that, we first confirmed the presence of dopaminergic cells in the MRR of mice (immunohistochemistry, RT-PCR) and humans (RT-PCR). Next, we used chemogenetic technology in mice containing Cre enzyme under the promoter of the dopamine transporter (DAT). With the help of an adeno-associated virus, artificial receptors were expressed in the dopaminergic cells of the MRR (DAT-MRR). Four weeks later, extensive behavioral charac-terization started 30 minutes after the injection of the artificial ligand (Clozapine-N-Oxide). Stimu-lation of DAT-MRR decreased social interest without influencing aggression and with an increase in social discrimination. Additionally, inhibition of the same cells increased the friendly social be-havior during social interaction test. No behavioral changes were detected in anxiety, memory and locomotion. All in all, dopaminergic cells were present both in the mice and human MRR, and manipulation of dopaminergic neurons of the MRR elicited a specific social response.

Ultrasound (US) scans of the inferior vena cava (IVC) provide useful information on the volume status of a patient. However, their investigation is user-dependent and prone to measurement errors. An important technical problem is the objective difficulty in studying a very compliant blood vessel like IVC, which makes large respirophasic movements and shows a complicated three dimensional geometry. Using bi-dimensional (2D) B-mode views either in long or short axis has improved the characterization of IVC dynamics compared to a measurement along a single direction (M-mode). However, specific movements of the IVC can challenge also the information provided by these 2D sections. Thus, these two orthogonal views, provided by an US system in X-plane, are here integrated by an innovative method. It is tested on simulated videos of the IVC performing complicated movements, that are compensated by the new method, overcoming the biased measurements provided by 2D scans. The method is then applied on example experimental data.

Europium is one of the most reactive lanthanides and humans use it in many different applica-tions, but we still know little about its potential toxicity and cellular response to its exposure. Two strains of the eukaryotic microorganism model Tetrahymena thermophila adapted to high concentrations of two Eu(III) compounds (EuCl3 or Eu2O3) were obtained and compared to a control strain and cultures treated with both compounds. In this ciliate, EuCl3 is more toxic than Eu2O3. LC50 values show that this microorganism is more resistant to these Eu(III) compounds than other microorganisms. Oxidative stress originated mainly by Eu2O3 is minimized by overexpression of genes encoding important antioxidant enzymes. The overexpression of metallothionein genes under treatment with Eu(III) compounds supports the possibility that this lanthanide may interact with the -SH groups of the cysteine residues from metallothi-oneins and/or displace essential cations of these proteins during their homeostasis function. Both lipid metabolism (lipid droplets that fuse with europium-containing vacuoles) and au-tophagy are involved in the cellular response to europium stress. Bioaccumulation, together with a possible biomineralization to europium phosphate, seems to be the main mechanism of Eu(III) detoxification in these cells.

Objective: Lower extremity ischemia-reperfusion injury (IRI) may occur with trauma-related vascular injury and various vascular diseases, during the use of a tourniquet, temporary clamping of the aorta in aortic surgery, and acute or bilateral acute femoral artery occlusion. Mitochondrial dysfunction and increased basal oxidative stress in diabetes may cause an increase in the effects of increased reactive oxygen species (ROS) and mitochondrial dysfunction due to IRI. It is of great importance to examine therapeutic approaches that can minimize the effects of IRI, especially for patient groups under chronic oxidative stress. Cerium oxide (CeO2) nanoparticles mimic the antioxidant enzymes and act as a catalyst that scavenges ROS. In this study, it was aimed to investigate whether CeO2 has protective effects on skeletal muscles in lower extremity IRI in mice with streptozocin-induced diabetes. Methods: A total of 38 Swiss albino mice were divided into six groups as follows: control group (group C, n=6), diabetes group (group D, n=8), diabetes-CeO2 (group DCO, n=8), diabetes-ischemia/reperfusion (group DIR, n=8), and diabetes-ischemia/reperfusion-CeO2 (group DIRCO, n=8). DCO and DIRCO groups were given doses of CeO2 0.5mg/kg intraperitoneally 30 minutes before the IR procedure. A 120-minute ischemia-120-minute reperfusion period with 100% O2 was performed. At the end of the reperfusion period, muscle tissues were removed for histopathological and biochemical examinations. Results: Total antioxidant status (TAS) levels were found to be significantly lower in group DIR compared with group D (p=0.047 and p=0.022, respectively). In group DIRCO and total oxidant status (TOS) levels were found to be significantly higher than in group DIR (p

Plant hormones regulate the adaptive responses to various biotic and abiotic stress factors. Applied exogenously they trigger the natural plant defense mechanisms, a feature that could be implemented in strategies for supporting crop resilience. The potential of exogenous cytokinin-like acting compound (kinetin), the auxin analogue 1-naphtyl acetic acid (NAA), abscisic acid (ABA) and the ethylene-precursor 1-aminocyclopropane-1-carboxylic acid (ACC) to mitigate dehydration was tested on Lactuca sativa (lettuce) grown on 12% polyethylene glycol (PEG). Priming with different blends containing these plant growth regulators applied in bioequivalent concentrations was evaluated through biometric measurements and biochemical analyses. The combined treatment with the four plant hormones exhibited the best dehydration protective effect. The antioxidative enzyme profiling of the PGR-primed individuals revealed increased SOD, catalase and peroxidase activity in the leaves. Immunodetection of higher levels of the rate-limiting enzyme for proline biosynthesis (delta-pyroline-5-carboxylate synthase) in the primed plants coincided with a significantly higher content of the amino acid measured in the leaves. These plants also accumulated particular dehydrin types, which may have contributed to the observed stress-relieving effect. The four-component hormonal mix applied by spraying or through the roots exerted similar stress-mitigating properties on soil-grown lettuce subjected to moderate drought.

The study of the pathogenesis of febrile seizures and their consequences frequently necessitates gene expression analysis. The primary methodology employed for such analysis is reverse transcription with quantitative polymerase chain reaction (RT-qPCR). To guarantee the accuracy of data obtained by RT-qPCR, it is crucial to utilize stably expressed reference genes. The objective of this study was to identify the most suitable reference genes for use in the analysis of mRNA production in various brain regions of rats following prolonged neonatal febrile seizures. The expression stability of eight housekeeping genes was evaluated using the online tool RefFinder in the dorsal and ventral hippocampal regions and in the temporal and medial prefrontal cortex of the brain. The Ppia gene exhibited the greatest stability of expression. Conversely, the genes with the least stable expression level are Actb and Ywhaz; thus, it is not recommended to use them for normalization in a febrile seizure model. Additionally, the majority of housekeeping genes demonstrate age-related, region-specific fluctuations. Therefore, it is crucial to employ the appropriate housekeeping genes for each brain structure under investigation when examining the expression dynamics of genes of interest in a febrile seizure model.

This review is focused on the current status of quantitative MR (qMR) of skeletal muscle. The first section covers the techniques of qMR in muscle with the focus on each quantitative parameter, the corresponding imaging sequence, discussion of the relation of the measured parameter to underlying physiology/ pathophysiology, the image processing and analysis approaches, and studies on normal subjects. We cover the more established parametric mapping from T1 weighted imaging for morphometrics including image segmentation, proton density fat fraction, T2 mapping, diffusion tensor imaging to emerging qMR features such as magnetization transfer including ultralow TE imaging for macromolecular fraction, and strain mapping. The second section is a summary of current clinical applications of qMR of muscle; the intent is to demonstrate the utility qMR in different disease states of the muscle rather than a complete comprehensive survey.

Stimulation of the alpha 7 nicotinic acetylcholine receptor (α7nAChR) has shown beneficial effects in several acute inflammatory disease models. This study aims to examine whether treatment with the selective α7nAChR agonist PHA 568487 can dampen inflammation and thereby improve cardiac function after myocardial infarction in mice. The possible anti-inflammatory properties of α7nAChR agonist PHA 568487 were tested in vivo using the air pouch model and in a permanent occlusion model of acute myocardial infarction in mice. Hematology parameters and cytokine levels were determined. Infarct size and cardiac function were assessed via echocardiography 24 h and one week after the infarction. Treatment with α7nAChR agonist PHA 568487 decreased 12 (CCL27, CXCL5, IL6, CXCL10, CXCL11, CXCL1, CCL2, MIP1a, MIP2, CXCL16, CXCL12 and CCL25) out of 33 cytokines in the air pouch model of acute inflammation. However, α7nAChR agonist PHA 568487 did not alter infarct size, ejection fraction, cardiac output or stroke volume at 24 h nor at 7 days after the myocardial infarction compared with control mice. In conclusion, despite promising immunomodulatory effects in the acute inflammatory air pouch model, α7nAChR agonist PHA 568487 did not affect infarct size or cardiac function after a permanent occlusion model of acute myocardial infarction in mice. Consequently, this study does not strengthen the hypothesis that stimulation of the α7nAChR is a future treatment strategy for acute myocardial infarction when reperfusion is lacking. However, whether other agonists of the α7nAChR can have different effects remains to be investigated.

This study evaluates audiogenic epilepsy in Krushinsky-Molodkina rats using a wireless EEG system to overcome the limitations of traditional methods that restrict animal movement. Nine male KM rats, prone to audiogenic seizures, were implanted with electrodes in areas critical for seizure activity (inferior colliculus, ventrolateral periaqueductal gray, dorsal area of the secondary auditory cortex, and motor cortex). This setup allowed for the observation of seizures without movement restriction. Results showed that targeted neural intervention via electrode implantation reduced the intensity of convulsive seizures in half of the subjects, suggesting a potential therapeutic approach. The severity of seizures was influenced by the pre-phonostimulation EEG background activity in specific brain regions, identifying them as key in the genesis and generalization of seizures. Observations of dual generalized seizure waves and induced hyperkinesis challenge conventional epilepsy models and suggest new directions for research and therapy development.

Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging, the prevalence of neurological disorders, including neurodegenerative diseases, will double over the next two decades. Unfortunately, while available therapies provide symptomatic relief for cognitive and motor impairment, there is an urgent unmet need to develop disease-modifying therapies that slow the rate of pathological progression. In that context, biomarkers could identify at-risk and prodromal patients, monitor disease progression, track response to therapy, and parse causality of molecular events to identify novel targets for further clinical investigation. Thus, identifying biomarkers that discriminate between diseases and reflect specific stages of pathology would catalyze the discovery and development of therapeutic targets. This review will describe the prevalence, known mechanisms, ongoing or recently concluded therapeutic clinical trials, and biomarkers of three of the most prevalent neurodegenerative diseases, including Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson’s disease (PD).

Rice, as a staple crop feeding billions, faces constant threats from various diseases jeopardizing global food security. Precise understanding of disease resistance mechanisms is crucial for developing resilient rice varieties. Traditional genetic mapping methods, such as QTL mapping, provide valuable insights into the genetic basis of diseases. However, the complex nature of rice diseases demands a holistic approach to gain accurate knowledge of it. Omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, enable a comprehensive analysis of biological molecules, uncovering intricate molecular interactions within the rice plant. Integration of various mapping techniques using multi-omics data has revolutionized our understanding of rice disease resistance. By overlaying genetic maps with high-throughput omics datasets, researchers can pinpoint specific genes, proteins, or metabolites associated with disease resistance. This integration enhances the precision of disease-related biomarkers with better understanding of their functional roles in disease resistance. Improvement of rice breeding for disease resistance through this integration represents a significant stride in agricultural science because better understanding of the molecular intricacies and interactions underlying disease resistance architecture leads to more precise and efficient development of resilient and productive rice varieties. In this review, we explore how the integration of mapping and omics data can give a transformative impact on rice breeding for enhancing disease resistance.

Neonatal rats that receive sucrose during a critical postnatal period (CP, days 12 to 28) develop hypertension by the time they reach adulthood. Changes during this period could contribute to inflammation and be associated with variations in the vascular smooth muscle (VSMC) phenotype. We studied changes in inflammatory pathways that could underlie the expressions of the secretory phenotype in the VSMC in the thoracic aorta of rats that received sucrose during CP. We analyzed histological changes in the aorta and expressions of the COX-2, TLR4, iNOS, eNOS, MMP-2, -9, β-, α-actin, and TNF-α, IL-6 and IL-1β expressions, and fatty acids by gas chromatography. The aortic wall presented disorganization, decellularization, wavy elastic fibers and increase in the lumen area. The COX-2, TLR4 expressions, TNF-α and IL-6 were increased, but iNOS, MMP-2 and -9 tended to increase and eNOS and arachidonic acid tended to decrease, con increase in oleic acid in CP in comparison with control group. There is a transient hypertension at the end of the CP that is accompanied by an inflammation and a change in the phenotype of VSMC to the secretory phenotype. The inflammatory changes could act as epigenetic signals to determine the hypertension development during adulthood.

Background: beta blockers of three generations are first-line drugs in the treatment of chronic heart failure (CHF). However, to date there is no clear understanding of the effect of beta blockers on myocardial energy metabolism disorders in CHF. The aim of the study: to conduct a study of beta-blockers of different generations on myocardial energy metabolism in the experimental CHF. Methods: CHF was modeled in white outbred rats by administering doxorubicin. The study drugs were administered intragastrically – new drug Hypertril (1-(β-phenylethyl)-4-amino-1,2,4-triazolium bromide)-3.5 mg/kg, metoprolol - 15 mg/kg, Nebivolol -10 mg/kg, Carvedilol 50 mg/kg, Bisoprolol, 10 mg/kg. In the myocardium, the main indices of energy metabolism were determined - ATP, ADP, AMP, malate, lactate, pyruvate, succinate dehydrogenase (SDH) activity, NAD-dependent malate dehydrogenase (NAD-MDH) activity. Results: traditional second-generation beta-blockers (Metoprolol and Bisoprolol) did not affect the studied indices of energy metabolism, and third-generation beta-blockers with additional properties - Carvedilol and, especially, Nebivalol and Hypertril improved myocardial energy metabolism. Conclusions: obtained results will help to expand our understanding of the effect of beta-blockers of various generations used to treat cardiovascular diseases on energy metabolism, and are also an experimental justification for the practical choice of these drugs in the complex therapy of CHF.

Background Sarcopenia is a state with progressive and generalized loss of skeletal muscle mass and strength. It is a serious complication occurring in chronic kidney disease (CKD) patients which increases morbidity and mortality rate. Sarcopenia is diagnosed when loss of both compartments - muscle strength and skeletal muscle quality or quantity are present. However, there are still numerous patients, also with CKD, diagnosed as pre-sarcopenic individuals with low muscle strength and normal skeletal muscle quality or quantity and conversely, with correct muscle strength and decreased skeletal muscle mass, who are prone to develop sarcopenia in future life. It is crucial to examine numerous variables possibly associated with changes of skeletal muscle mass and muscle strength in terms of preventing the development of sarcopenia. The aim of the study was to investigate anthropometric and clinical correlates and sources of variation in both skeletal muscle mass and muscle strength in advanced stages of CKD. Methods The study sample consisted of 84 non-dialysis dependent patients of both sexes (including 45.2% of women) with eGFR < 45 ml/min/1.73m²: 26.2% with eGFR 30-44 mL/min/1.73 m², 65.5% with eGFR 15-29 mL/min/1.73 m² and 8.3% with eGFR < 15 mL/min/1.73 m². Muscle strength was estimated by measuring hand grip strength (HGS) with the use of handheld hydraulic dynamometer. Muscle quantity was measured by bioimpedance spectroscopy using Body Composition Monitor. Appendicular skeletal muscle mass (ASM) was calculated according to Lin’s formula. Serum creatinine, urea, uric acid and albumin were measured. Results In bivariate analysis we found that ASM significantly and positively correlated with anthropometric variables such as body mass (r=0.903, p<0.001), NH weight (r=0.882, p<0.001), height (r=0.694, p<0.001), body mass index (BMI) (r=0.701, p<0.001), lean tissue mass (LTM) (r=0.664, p<0.001), lean tissue index (LTI) (r=0.433, p<0.001), fat mass (r=0.614, p<0.001) and fat tissue index (FTI) (r=0.449, p<0.001), and was negatively associated with clinical variable such as hydration status (p<0.001). HGS significantly and positively correlated with anthropometric parameters such as body mass (r=0.319, p=0.003), NH weight (r=0.315, p=0.004), height (r=0.666, p<0.001), LTM (r=0.490, p<0.001), LTI (r=0.238, p=0.029), and ASM (r=0.501, p<0.001), and was negatively associated with clinical variables like uric acid (p=0.039) and urea (p<0.001). After adjustment for age, sex and height, HGS remained significantly and negatively related with uric acid (β=-1.078, p=0.041) and hydration status (β=-0.805, p=0.042). Conclusions In CKD patients, ASM is determined mainly by anthropometric parameters but HGS - both by anthropometric and clinical variables specific for CKD.

The purpose of this study was to establish the association between total and segmental body composition (BC) variables and anaerobic performance and to create optimal models that best predict such performance in CrossFit® (CF) athletes. Fifty athletes, 25 males and 25 females (age: 33.26 ± 6.81 years; body mass: 72.57 ± 12.17 kg; height: 169.55 ± 8.71 cm; BMI: 25.06 ± 2.31 kg·m−2) were recruited to participate and underwent BC analysis using dual-energy X-ray absorptiometry (DXA) and an all-out laboratory test on a cycle ergometer (Wingate) to determine their anaerobic performance. The results show a significant correlation between BC values and performance, ranging from moderate (r = -0.34, p = 0.015) to near-perfect (r = 0.96, p &lt; 0.01). Furthermore, the created performance prediction models exhibited predictive capacities ranging from 19% (p = 0.017) to 93% (p &lt; 0.001). All prediction models were created using total or segmental lean mass variables, excluding others. BC and performance variables found significant differences between males and females. The findings demonstrate that BC variables are crucial indicators of anaerobic performance in CF athletes. Professionals responsible for athlete performance should use this information to monitor athletes and design training programs.

Proteomics is the study of cellular proteome by investigating how different proteins interact with each other and the roles they play in the organism. For mRNA expression levels do not always correlate well with protein expression levels, and the study of mRNA does not consider protein posttranslational modifications (PTMs), complex formation and localization; all of which are key to protein function. Quantitative proteomics uses mass spectrometry to identify and quantify proteins so as to find differentially expressed proteins under different condition. This allows us to gain biological insights under stress or other pathological conditions. posttranslational modifications, such as lysine acetylation, succinylation and lactylation, occur after protein biosynthesis and play vital roles in protein activity and cell physiology regulation. Here we present the mass spectrometry analysis in detail to unveil protein acylase and deacylase’ roles in metabolic regulation based on PTMomics lysine acetylome and suincylome.

Immunohistochemistry (IHC) helps identify different types of tissues and provides important information about the pattern, shape, and structure of cells in a tissue sample. It is a very useful tool and widely used to uncover histology and pathology diagnosis uses. The IHC is a very useful tool to conduct research in the developmental biology area. Some insects, like butterflies, bees, beetles, ants, wasps, and moths, undergo a unique life cycle called complete metamorphosis, which has four distinct stages: egg, larva, pupa, and adult. Larvae are often wingless and have different habits and forms than adults, which are better suited for growth and development. During the metamorphosis, how does the insect legs change is a really an interesting issue.To better understand insect development, agriculture pest control, and insect pathogen interaction, here we use an insect Bombyx mori (domestic silk moth) as a model to detail how to conduct the IHC assays, such as HE staining, TUNEL to see the cell apoptosis, pH3 and BrdU staining to check cell division. The reagents can be easily found, and this step-by-step protocol is easily reproduced.

The prevalence of diabetes mellitus (DM) continues to rise globally, posing significant health challenges and burdens. This metabolic disorder, characterized by elevated blood glucose levels, contributes to various complications including cardiovascular diseases, kidney failure, and stroke. While conventional diabetic drugs exist, they often come with adverse side effects, necessitating the exploration of safer and more cost-effective alternatives, particularly from natural sources like medicinal plants. This study investigates the potential of Neocarya macrophylla (Nm) Ethyl acetate leaf fraction in managing DM. Utilizing a high-fat diet/streptozotocin-induced diabetic rat model, the study explores several key aspects including effective dose determination, biological activity, impact on body mass index (BMI), and complete blood count. Statistical analysis was conducted using GraphPad Prism version 9.1. The determination of the minimum effective dose reveals that 120mg/kg of Ethyl acetate fraction of Nm reduced the blood glucose by 28.9% after 4 hours. In addition, ethyl acetate fraction (120 mg/kg) possessed the most hypoglycemic activity compared to the other fractions of Nm. The Ethyl acetate fraction of Nm at 120mg/kg significantly reduced fasting blood glucose levels compared to the diabetic control(p=0.001) and slightly decreased BMI. Furthermore, the fraction demonstrated significant improvement in the parameters of some of the blood count indices such as red blood cells (p<0.001), total white cells (p<0.01) and platelet (p<0.001) compared to the diabetic control. These findings underscore the potential of Nm as a holistic therapeutic option for managing DM and its haematological complications. In conclusion, this study sheds light on the hypoglycemic potential of Nm Ethyl acetate leaf fraction, offering valuable insights into its effectiveness, safety, and broader physiological impacts. Further research into the mechanisms underlying its therapeutic effects is warranted to fully harness its therapeutic potential in diabetes management.

The present study explored whether exposure to complex childhood trauma (CCT) is reflected in the resting-state electroencephalography (EEG) temporal alpha power of complex trauma-exposed adolescents, given the association of temporal alpha with fear circuitry (learning and conditioning) in a sample of 25 adolescents and similar controls, ages 12-17 years. Both trauma and psychopathology were screened or assessed, and resting-state EEG was recorded, following a preregistered protocol for data collection. Temporal alpha power, corresponding to T5 and T6 electrode location (10-20 international system), was extracted from resting-state EEG in both eyes-open and eyes-closed conditions. We found that in the eyes-open condition, right, but not left, temporal alpha was significantly higher in adolescents exposed to CCT, relative to healthy controls, suggesting that childhood trauma exposure may have a measurable impact on alpha oscillatory patterns, specifically in the right temporal region. Our study highlights the importance of considering neural markers, such as temporal alpha power, in understanding the long-term consequences of CCT exposure in developmental samples, with possible important clinical implications in guiding neuroregulation interventions.

(1) Exoskeletons offer potential benefits for overhead working tasks, but gender effects or differences are unclear. This study aimed to compare the performance, strain, and comfort of men and women using an upper-body exoskeleton. (2) n=20 female and n=16 male participants performed an overhead drilling task with and without a passive upper-body exoskeleton in a randomized cross-over study. Task performance of different movement phases, perceived exertion, and ease of use were measured to compare gender differences. One and two-way analyses were used to com-pare genders in the different conditions. (3) Gender differences after controlling for BMI in task performance were found for error integrals (p <.001) with higher values in male participants. Moreover, there was a significant interaction effect for gender x exoskeleton use. While females showed performance decrements in aiming with exoskeleton use, the male's performance increased (p=.025). No other gender differences were observed. (4) Gender differences in task performance using an upper-body industrial exoskeleton were less detectable than expected after controlling for BMI, indicating that body composition and anthropometrics might be valuable indicators for per-formance including assisting devices. Moreover, future studies should also integrate the examina-tion of muscle activity to gain more insights into potential gender movement control patterns.

The aim of this study was to examine the oxidation of human serum albumin (HSA) caused by oxidative stress after an exhaustive exercise such as ultra-marathon race. Thus, blood samples from 12 adult runners who underwent a 103 km mountain ultra-marathon race were collected pre- and 24, 48 and 72 h post race. HSA was partially purified using affinity chromatography and then was subjected to Western blot analysis for disulfide dimers determination, indicating oxidation. The results were correlated with those from a previous study in which the same samples were analyzed using different oxidative stress markers and a good correlation with protein carbonyls (PC) at all time points was observed. Moreover there was a significant correlation with static oxidation-reduction potential (sORP) at 24 h, and a negative correlation with capacity oxidation-reduction potential (cORP) at 24 and 48 h. In addition, an individual analysis of albumin dimers exhibited great inter-individual differences. This inter-individual variability in the oxidation of HSA may suggest different interventions (e.g. through diet) in order to confront the effects on athletes’ organism after a strenuous exercise. In conclusion, this study supported the importance of the assessment of albumin dimers as a predictive marker for exercise-induced oxidative stress.

Duchenne muscular dystrophy (DMD) is caused by genetic mutations in the cytoskeletal-sarcolemmal anchor protein dystrophin. Repeated cycles of sarcolemmal tearing and repair lead to a variety of secondary cellular and physiological stressors that are thought to contribute to weakness, atrophy, and fibrosis. Collectively, these stressors can contribute to a pro-inflammatory milieu in locomotor, cardiac, and respiratory muscles. Given the many unwanted side effects that accompany current anti-inflammatory steroid-based approaches for treating DMD (e.g., glucocorticoids), there is a need to develop new therapies that address inflammation and other cellular dysfunctions. Adiponectin receptor (AdipoR) agonists, which stimulate AdipoR1 and R2 isoforms on various cell types, have emerged as therapeutic candidates for DMD due to their anti-inflammatory, anti-fibrotic, and pro-myogenic properties in pre-clinical human and rodent DMD models. Although these molecules represent a new direction for therapeutic intervention, the mechanisms through which they elicit their beneficial effects are not yet fully understood, and DMD-specific data is limited. The overarching goal of this review is to investigate how adiponectin signaling may ameliorate pathology associated with dystrophin deficiency through inflammatory-dependent and -independent mechanisms, and to determine if current data supports their future progression to clinical trials.

Myocardial heterogeneity is an attribute of the normal heart. We have developed integrative models of cardiomyocytes from the subendocardial (ENDO) and subepicardial (EPI) ventricular regions that take into account experimental data on specific features of intracellular electromechanical coupling in the guinea pig heart. The models adequately simulate experimental data on the action potential and contraction of the ENDO and EPI cells. The modeling results predict that heterogeneity in the parameters of calcium handling and myofilament mechanics in isolated ENDO and EPI cardiomyocytes via cooperative mechanisms of mechano-calcium-electric feedback are essential to produce the differences in Ca²⁺ transients and contraction profiles and may further enhance transmural differences in the electrical properties between the cells. Simulation results predict that ENDO cells have greater sensitivity to changes in afterload than EPI cells. These data are important for understanding the behavior of cardiomyocytes in the intact heart.

Abiotic stress is responsible for significant reduction in crop plant productivity worldwide. Ultraviolet (UV) radiation is a natural component of sunlight and a permanent environmental stimulus. This study investigated the distinct responses of young wheat and einkorn plants to excessive UV-B radiation (180 min at λmax 312 nm) following foliar pretreatment with 1 µM synthetic cytokinin 4PU-30. Results demonstrated that UV radiation significantly amplified hydrogen peroxide levels in both wheat and einkorn, with einkorn exhibiting more pronounced increase compared to wheat. This elevation indicated the induction of oxidative stress by UV radiation in the two genotypes. Intensified antioxidant enzyme activities and increased accumulation of typical stress markers and non-enzyme protectants were evidenced. Transcriptional activity of genes encoding key antioxidant enzymes was also investigated aiming to elucidate the genetic regulation of the antioxidant systems in both wheat and einkorn seedlings. Our results suggested a role for POX1 and POX7 genes in the UV-B tolerance of the two wheat species as well as a cytokinin stimulated UV-B stress response in einkorn mediated through upregulation of the tau subfamily gene GSTU6. Based on these findings it could be concluded that 4PU-30 had the potential of alleviating oxidative stress by attenuating the symptoms of superfluous UV-B illumination in the two examined plant species.

The allosteric SERCA (Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase) activator CDN1163 has been recently added to the group of pharmacological tools for probing SERCA function. We chose to investigate the effects of the compound on T lymphocyte Ca2+ stores, using the well-described Jurkat T lymphocyte as a reliable cell system for Ca2+ signaling pathways. Our study identified the lowest concentrations of the SERCA inhibitors thapsigargin (TG) and 2,5-di-(tert butyl)-1,4-benzohydroquinone (tBHQ) capable of releasing Ca2+, permitting the differentiation of the TG-sensitive SERCA 2b Ca2+ store from the tBHQ-sensitive SERCA 3 Ca2+ store. We proceeded to test the effects of CDN1163 on Ca2+ stores, examining specific actions on the SERCA 2b and SERCA 3 Ca2+ pools using our low dose SERCA blocker regimen. In contrast to previous work, we find CDN1163 exerts complex time-sensitive and SERCA isoform-specific actions on Ca2+ stores. Surprisingly, short-term exposure (0-30 minutes) to CDN1163 perturbs T cell Ca2+ stores by suppressing Ca2+ uptake with diminished Ca2+ release from the SERCA 2b-controlled store. Concomitantly, we find evidence for a SERCA-activating effect of CDN1163 on the SERCA 3 regulated store, given the observation of increased Ca2+ release inducible by low dose tBHQ. Intriguingly, longer-term (&gt;12 hours) CDN1163 exposure reversed this pattern, with increased Ca2+ release from SERCA 2b-regulated pools, yet decreased Ca2+ release responses from tBHQ-sensitive SERCA 3 pool. Our results reveal differential effects of CDN1163 on Ca2+ stores regulated by distinct SERCA isoforms, prompting the need for careful interpretation of the compound’s effects, particularly in cells expressing multiple SERCA isoforms.

Nowadays, animal breeders look for effective innovations to care animal health. Use of probiotics, postbiotics, parabiotics and the other beneficial natural substances are dominated. Mundticin-like substance EM 41/3 is thermo-stable bacteriocin (postbiotic) with a broad antimicrobial spectrum. In this study its effect in broiler rabbits was assessed. Rabbits represent food-derived animal and they are also suitable animal model. The parameters tested were analyzed by validated methods. Administration of MLS EM 41/3 produced by non-autochthonous strain Enterococcus mundtii EM 41/3 lead to significant increase of parameter immunity-phagocytic activity, while it did not influence microbiota composition. It also did not influence blood biochemistry and no oxidative stress was noted. Moreover, higher growth parameters were noted and also stimulated hydrolytic activity. Finally, no negative influence on rabbit meat quality was noted. Postbiotic MLS EM 41/3 administration in feeding strategy seems to be contributing fact for rabbit health status maintaining.

In this study we discuss critical issues in modelling the structure and function of lymph nodes (LNs), with emphasis on how LN physiology is related to its multi-scale structural organization. In addition to macroscopic domains such as B-cell follicles and the T cell zone, there are vascular networks which play a key role in the delivery of information to the inner parts of the LN, i.e., the conduit and blood microvascular networks. We propose object-oriented computational algorithms to model the 3D geometry of the fibroblastic reticular cell (FRC) network and the microvasculature. Assuming that a conduit cylinder is densely packed with collagen fibers, the computational flow study predicted that the diffusion should be a dominating process in mass transport than convective flow. The geometry models are used to analyze the lymph flow properties through the conduit network in unperturbed- and damaged states of the LN. The analysis predicts that elimination of up to 60–90 % of edges is required to stop the lymph flux. This result suggests a high degree of functional robustness of the network.

Abstract A multiple number of studies provide evidence that vasopressin (AVP) and steroid hormones are frequently secreted together and closely cooperate in the regulation of blood pressure, metabolism, water-electrolyte balance, and behavior, securing thereby survival and comfort of life. Vasopressin interacts with hormones of the hypothalamo-pituitary-adrenal axis (HPA) at several levels through regulation of release of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone ACTH, and multiple steroid hormones, as well as through interactions with steroids in the target organs. The interactions are facilitated by positive and negative feedbacks occurring between specific components of the HPA axis with engagement of other regulatory molecules. Altogether AVP and HPA cooperate closely as a coordinated functional AVP-HPA system. It has been shown that cooperation between AVP and steroid hormones may be affected by the cellular stress combined with hypoxia, and by metabolic, cardiovascular and respiratory disorders, neurogenic stress and inflammation. Growing evidence indicates that central and peripheral interactions of AVP and steroid hormones are reprogrammed in cardiovascular diseases and that the rearrangements play either beneficial or harmful effects. The present review highlights specific mechanisms of interactions of AVP and steroids at cellular and systemic levels and analyses consequences of inappropriate cooperation between various components of the AVP-HPA system for the regulation of the cardiovascular system and energy balance in cardiovascular and metabolic diseases.

Genetic enhancement of grain production and quality is a priority in wheat breeding projects. In this study, we assessed two key agronomic traits - grain protein content (GPC) and thousand kernel weight (TKW) - across 179 Bulgarian contemporary and historic varieties, and landraces in three growing seasons. Significant phenotypic variation existed for both traits among genotypes and seasons, and no discernible difference was evident between the old and modern accessions. To understand the genetic basis of the traits, we conducted a genome-wide association study with MLM using phenotypic data from the crop seasons, best linear unbiased estimators, genotypic data from the 25K Infinium iSelect array, and a Bonferroni-adjusted p-value. As a result, 776 significant quantitative trait nucleotides (QTNs) organized into quantitative trait loci were discovered, including 25 loci associated with GPC, and 35 loci linked to TKW. Additionally, 14 environmentally stable QTNs were identified for TKW. Certain loci on chromosomes 2A, 3A, and 6B favorably in-fluenced GPC, while the locus on chromosome 6D impacted TKW positively. These loci may reflect novel associations to the two traits. Annotations for proteins involved in the remobilization of carbon and nitrogen from vegetative tissues to developing grain during senescence, as well as in the following buildup of resources required for seed germination, have been found for selected pu-tative candidate genes. These include genes coding for 11S globulin seed storage protein, glutamine synthetase, metalloendopeptidase, components of the ubiquitin/proteasome system, sucrose transporter, alpha-amylase, NAC and bZIP transcription factors. Our findings highlight promising genomic regions for targeted breeding programs aimed at improving grain yield and protein content.

The most common type of head and neck cancer (HNC) is head and neck squamous cell carcinoma (HNSCC). It describes a heterogenous neoplastic disease that arises from the mucosal epithelium of the of the upper respiratory system and the gastrointestinal tract. It is characterized by high morbidity and mortality, being is the eighth most common cancer worldwide, with 931,931 newly diagnosed cases and 467,125 deaths according to the latest Global Cancer Statistics (GLOBOCAN) data. Despite the use of modern low-invasive surgical techniques and application of promising new chemoradiotherapies or combination treatment, the frequency of recurrences and the five-year survival of these patients remains unsatisfactory. The microenvironment of head and neck cancer comprises various cells that regulate neoplastic expansion. It is believed that the mesenchymal stromal cells (MSCs) present in the tumour milieu play a key role in the modulation of tumour initiation, development and progression, in the regulation of cancer treatment response, survival rates, patient outcomes and long-term prognosis; they also influence the resistance to cisplatin-based chemotherapy, the gold standard for advanced HNSCC. MSCs, are multipotent, heterogeneous, mobile cells, which meet specific stemness criteria defined by the International Society for Cellular Therapy (ISCT). Although no MSC-specific markers exist, they can be recognized based on several others, such as CD73, CD90 and CD105, while lacking the presence of CD45, CD34, CD14 or CD11b, CD79α, or CD19 and HLA-DR antigens; they share phenotypic similarity with stromal cells and their capacity to differentiate into other cell types. In the tumour niche, MSC populations are characterized by cell quiescence, self-renewal capacity, low reactive oxygen species production and the acquisition of epithelial-to-mesenchymal transition properties, they may play a key role in the process of acquiring drug resistance, and thus treatment failure. MSCs must also demonstrate plastic adherence in vitro and be able to differentiate into specific mesodermal cell types after stimulation i.e., adipocytes, chondrocytes, and osteoblasts when cultured under well-defined conditions. The present narrative review examines the links between mesenchymal stromal/stem cells and HNC, as well as the different mechanisms involved in the development of resistance to current chemo- and radiotherapies in HNSCC. It provides an overview of the current literature, including key opinion-forming systematic reviews, as well as cross-sectional, longitudinal, prospective and interventional studies based on cell culture models in vitro, animal or in vivo models of HNSCC; it also examines the possibilities of pharmacological targeting of stemness-related chemoresistance in HNSCC. It describes promising new strategies to optimize chemoradiotherapy with the potential to personalize patient treatment approaches, and highlights future therapeutic perspectives in HNC. The data concerning tumour-associated MSCs is arranged according to increasing clinical credibility.

Obesity poses significant challenges in rural communities worldwide due to limited resources and healthcare access. Practical, innovative, and culturally sensitive approaches are essential. Time-Restricted Eating (TRE), aligning food intake with circadian rhythms, emerges as a promising strategy. By restricting eating to specific time windows, TRE synchronizes with the body's internal clock, offering potential metabolic health benefits. This review examines TRE's potential in rural obesity management, highlighting its simplicity and scalability. While TRE may address rural health disparities, cultural considerations and challenges such as undernutrition must be acknowledged for effective implementation. Overall, TRE shows promise in improving metabolic health and well-being in rural populations.

Most research on colostrum quality and colostrum management focuses on maternal IgG transfer to the newborn calf. However, in addition to being a source of antibodies, colostrum has other components that influence passive immune transfer, nutrition, gut maturation, and thermoregulation. In this review, the constituents in the bovine colostrum, as well as their variation, are explored and it is discussed the biological role of colostrum on the newborn calf. Protein is the nutrient in higher concentration and fat is the nutrient with the most variation. There is a pronounced amplitude in the total solids content of colostrum, but the average concentration does not vary much between studies (24.7%). Bovine colostrum major components can vary with several factors, such as the region, season, breed, dry period length, and nutritional aspects of the dam. Bioactive components, cells, and microbiome variability are less understood, besides IgG. Regardless, they play crucial distinct roles in the physiological development of the newborn. However, a multi-interactive effect between these components, cells, and microorganisms is more likely to occur. Recently researched components in colostrum like miRNA, nucleo(t)sides, the milk fat globule membrane, oligosaccharides, minor proteins, and the microbiome are examples of promising interest areas of study.

Fragile X syndrome (FXS) is an intellectual developmental disorder characterized, inter alia, by deficits in short-term processing of neural information such as sensory processing and working memory. The primary cause of FXS is the loss of fragile X messenger ribonucleoprotein (FMRP), which is profoundly involved in synaptic function and plasticity. Short-term synaptic plasticity (STSP) may play important roles in functions that are affected by FXS. Recent evidence points to a crucial involvement of presynaptic calcium sensor synaptotagmin-7 in STSP. However, how the loss of FMRP affects STSP and synaptotagmin-7 have been insufficiently studied. Further-more, males and females are affected differently by FXS, but the underlying mechanisms remain elusive. The aim of the present study is to investigate possible changes in STSP and the expres-sion of synaptotagmin-7 along the hippocampus of adult males and females in the Fmr1 knock-out (KO) rat model of FXS. We found that paired-pulse ratio and frequency facilita-tion/depression, two forms of STSP, as well as the expression of synaptotagmin-7, are normal in adult KO males, but paired-pulse ratio is increased in the ventral hippocampus of KO females. Furthermore, we found no gender-related but robust region-dependent difference in STSP. AM-PA receptors are similarly expressed in the two hippocampal segments of the two genotypes and in both genders. Also, basal excitatory synaptic transmission is higher in males compared with females. Interestingly, we found more than twofold higher levels of synaptotagmin-7, not syn-aptotagmin-1, in the dorsal compared with the ventral hippocampus in males of both genotypes and in wild type females. These results point to the susceptibility of the female ventral hippo-campus to FMRP loss. Importantly, the different levels of synaptotagmin-7 that parallel the higher score of synaptic facilitation in the dorsal vs ventral hippocampus suggest that synapto-tagmin-7 may play a pivotal role in defining the striking difference in STSP along the long axis of the hippocampus.

The study aimed to analyze thoracic and lumbar erector spinae muscle activations during 3D elongation exercises in individuals with adolescent idiopathic scoliosis (AIS). Participants included 24 adolescents, meeting specific criteria such as a Cobb angle between 10° and 20°, and not having undergone surgical or brace treatments. EMG data were collected to evaluate muscle activations. The study found no significant interaction between exercise type and the side of the curve, but a significant main effect of exercise type on muscle activation, irrespective of Cobb angle. Different exercise types significantly affected muscle activity, with the highest activations in the TheraBand exercise, followed by manual and without equipment conditions. This suggests that exercise type significantly impacts muscle engagement in AIS patients, providing valuable insights for targeted exercise program design. The study, however, focused on short-term muscle activation, not long-term Cobb angle progression, pointing to the need for further research in this area.

Accordingly, a lot of dry direct seeding rice would be dense planted, that the initial seedling quantity could approach or even exceed the targeted effective panicle number. While limit information is available to evaluate the effects of involved novel nitrogen application methods, that total nitrogen once applied at a determined leaf age stage, on the yield formation traits of such dense planted dry direct seeding rice. The two-year experiments with total 180 kg ha-1 nitrogen once applied time treatments at sixth (L6), seventh (L7), eighth (L8), ninth (L9) and tenth (L10) leaf age stages were carried out. Results showed that the above-ground dry matter weight at maturity and grain yield of L8 was 2.1% ~ 11.8% and 4.0% ~ 9.9% higher than those of other treatments. Compared to other treatments, the higher above-ground dry matter weight after heading stage, bigger mean leaf area index with higher leaf area index at heading stage, increased leaf area duration, crop growth rate and net assimilation rate from jointing to heading period were important traits of higher grain yield formation of L8. In addition, the L8 had relative higher grain-leaf ratio traits than other treatments. Overall, a total 180 kg ha-1 nitrogen with mixed urea and compound fertilizer once applied at eighth leaf age stage would be suggest a useful high yield cultivation method for dense planted dry direct seeding rice in rice-wheat rotation system.

Background: Obesity among pregnant women is common, and their offspring are predisposed to obesity, insulin resistance, and diabetes. Circulating metabolites that are related to insulin resistance and are associated with this decreased tissue-specific uptake are unknown. Here, we assessed metabolite profiles in elderly women and who were either female offspring from obese mothers (OOM) or offspring of lean mothers (OLM). Metabolic changes were tested for associations with metrics for insulin resistance. Methods: 37 elderly women were separated into an elderly offspring from obese mothers (OOM; n = 17) and elderly offspring from lean/normal weight mothers (OLM; n = 20) groups. We measured plasma metabolites using 1H-NMR and also insulin-dependent tissue specific glucose uptake in skeletal muscle were assessed. Associations were made between metabolites and glucose uptake. Results: Compared to the OLM group, we found that the 22:6 docosahexaenoic acid percentage of the total long chain n-3 fatty acids (DHA/FA) was significantly lower in OOM (P = 0.015). DHA/FA associated significantly to skeletal muscle GU (P = 0.031) and M-value in the OLM group only (P = 0.050). Conclusions: DHA/FA is associated with insulin-dependent skeletal muscle glucose uptake and that this association is significantly weakened in the offspring of obese mothers.

The occurrence of ovarian dysfunction is often due to the imbalance between the formation of reactive oxygen species (ROS) and the (in)effectiveness of the antioxidative defense mechanisms. Primary sources of ROS are the respiratory electron transfer and the activity of NADPH oxidases (NOX), while Superoxide dismutases (SOD) are the main key reg-ulators that control the levels of ROS and reactive nitrogen species intra- and extracel-lularly. Because of their central role, SODs are the subject of research on human ovarian dysfunction, but the sample acquisition is low. The high degree of cellular and molecular similarity between Drosophila melanogaster ovaries and human ovaries provides this model organism with the best conditions for analyzing the role of ROS during ovarian function. In this study, we clarify the localization of the ROS producing enzyme dNox within ovaries of Drosophila melanogaster and by a tissue specific knockdown, we show that dNox derived ROS are involved in the chorion hardening process. Furthermore, we analyze the dSod3 localization and show that reduced activity of dSod3 impacts egg laying behavior, but not the chorion hardening process.

Numerous varieties of Capsicum annuum L. with multiple valuable traits, such as adaptation to biotic and abiotic stress factors, can be found in south-east Romania, well known for vegetable cultivation and an important area of biodiversity conservation. To obtain useful information toward a sustainable agriculture, management and conservation of local pepper varieties, we analyzed the genetic diversity and we did deep molecular characterization using Whole Genome Resequencing (WGS) for variant/mutation detection. The pepper varieties used in the present study were registered by VRDS in the ISTIS catalog between 1974 and 2019 and maintained in conservative selection, however, no studies have been published yet using WGS analysis in order to characterize this specific germplasm. The genome sequences, annotation and alignments provided in this study offer essential resources for genomic research as well as for future breeding efforts using the C. annuum local varieties.

Mesenchymal stem cells due to their multipotent ability are considered one of the best candidates to be used in regenerative medicine. The most used source of those stem cells long the last decades was the bone marrow, despite its limited cell resources and the painful and very invasive surgical treatment. Therefore, the scientific community investigated many alternative sources for the harvesting of these stem cell subpopulations. Adipose tissue attracted the biggest interest thanks to special features, such as great tissue abundance, easy availability, and in the end the large amount of positive mesenchymal stem cells. Once it was verified that these stem cell subpopulations possess the same bone marrow differentiation potential, it became evident that they would be the ideal candidate to be used in regenerative and tissue engineering applications. Even the regenerative use of these cells long become a sensitive point because not all the acquired phenotypes resulted in the best source for plastic procedures. As documented in the literature, the ideal fillers for regenerative is represented by stem cell population. Therefore, it became crucial to investigate any kind of biological mechanism on the differentiative ability of those mesenchymal stem cells, especially their regulative factors. One of the most studied and important regulators are the miRNAs. Indeed, miRNA play a crucial role in the differentiation process of adipose stem cell cultures isolated from patients or obtained by commercial cell lines toward osteocytes, chondrocytes, and adipocytes differentiated populations.

An application of CO2/HCO3--free solution (Zero-CO2) did not increase intracellular pH (pHi) in ciliated human nasal epithelial cells (c-hNECs), leading to no increase in the beating frequency (CBF) or bend distance (CBD, an index of amplitude). This study demonstrated that the pHi of the c-hNECs expressing carbonic anhydrase IV (CAIV) is high (7.64), while that of the ciliated human bronchial epithelial cells (c-hBECs) expressing no CAIV is low (7.10). Upon applying Zero-CO2, an extremely high level of pHi caused the pHi, CBF and CBD to decrease, while a low level of pHi caused them to increase. The high pHi was generated by a high rate of HCO3- influx via interac-tions between CAIV and Na+/HCO3- cotransport (NBC) in c-hNECs. An NBC inhibitor (S0859) decreased the pHi and CBF, and Zero-CO2 application increased the CBF in S0859-treated c-hNECs. In conclusion, the interactions of CAIV and NBC maximize the HCO3- influx to increase the pHi in c-hNECs. This novel mechanism causes the pHi to decrease, leading to no increase in CBF and CBD in c-hNECs upon Zero-CO2 application, and appears to play a crucial role in maintaining pHi, CBF and CBD in c-hNECs periodically exposed to air (0.04% CO2) with respiration.

Retrospective information about the climate system and plant ecophysiology are key inputs in climate and Earth system modelling. Dendrochronology provides such information with large spatiotemporal coverage, and stable carbon isotope (¹³C/¹²C) analysis across tree-ring series is among the most advanced dendrochronological tools. For the past seventy years, this analysis was performed on whole molecules, and, to this day, ¹³C/¹²C variation is attributed to ¹³C discrimination during CO₂ diffusion into leaves and assimilation by rubisco. By contrast, ¹³C discrimination by post-rubisco processes is presumed constant. Here, recently reported results on the first dataset of intramolecular ¹³C discrimination in tree rings were synthesised by variance component analysis. The emerging picture is not consistent with the classical (DR-discrimination-centred) concepts and practices of carbon-isotope dendrochronology. Specifically, leaf and stem post-rubisco discrimination each account for more variation in the data than diffusion-rubisco discrimination, i.e., post-rubisco discrimination is not constant. Furthermore, diffusion-rubisco discrimination is used widely as proxy of leaf intrinsic water-use efficiency (iWUE), a key determinant in the responses of global biogeochemical cycles to climate change. However, since diffusion-rubisco discrimination is a small component of the total data variance, whole-molecule analysis yields confounded iWUE estimates, yet intramolecular analysis will likely offer solutions. Lastly, all currently observed ¹³C/¹²C-climate relationships are attributed to diffusion-rubisco discrimination. However, here, relationships with temperature and radiation derive from leaf-level post-rubisco discrimination while relationships with precipitation derive from stem-level post-rubisco discrimination. That said, advances in mass spectrometry may soon make intramolecular ¹³C/¹²C analysis broadly available taking carbon-isotope dendrochronology to the next level.

(1) Background: Grapes and their associated by-products (as grape pomace, GP) stand out for their polyphenol content, which makes them a source of bioactive compounds with antioxidant capacity. The aim of this research was to determine if the inclusion of 50 g/kg of GP in the diet of hens could enrich egg with antioxidants and to study its effect on internal and external egg quality parameters. (2) Methods: A trial was conducted with two genetic lines of hens, which were fed either a control diet or a diet containing 50 g/kg of GP. Performance, internal and external egg quality, and egg yolk content of vitamins E and A, and gallic acid were determined; (3) Results: In eggs laid by hens fed GP diet, Haugh units and yolk colour score were enhanced, and eggshell became thinner, but without affecting the breaking strength. No dietary effect was observed on vitamin contents in yolk. Higher gallic acid content was observed in yolk of eggs laid by hens fed the GP diet, suggesting that some dietary phenolic compounds could be transferred to the eggs. Hen genetics influenced egg weight, albumen Haugh units, shell thickness and α- and γ-tocopherol concentration in yolks; (4) Conclusions: Dietary inclusion of GP improved the internal quality of eggs, enriching yolks with a phenolic compound, but reduced shell thickness.

With increasing numbers of older adults worldwide, multimorbidity and polypharmacy are on the rise, highlighting the risks of harmful drug-drug interactions (DDIs) to patients. As cardiovascular agents are among the most prescribed medications, we performed an observational cross-sectional study to determine the prevalence of DDIs in a cardiology department of a secondary hospital. Patient data was obtained from medical records and screened for DDIs using the Micromedex drug interaction software. Descriptive statistics, Chi-square (χ2) test, Student's t test and Pearson's correlation test were used to analyse the results. Out of 50 participants, 45 (90%) had at least one DDI. A total of 266 DDIs were identified, with more than half classified as major. At least one major DDI was found in 78% of patients. 42% of patients were at an increased risk of bleeding due to DDIs. A statistically significant relationship was found between the detection of DDIs and both patient age (p = 0.005) and the number of drugs used (p &lt; 0.001). Our findings pose questions about the wider prevalence and risks of drug-drug interactions among patients with cardiovascular disease.

The chemotactic cytokine fractalkine (FKN, chemokine CX3CL1) has unique properties resulting from the combination of chemoattractants and adhesion molecules. The soluble form (sFKN) has chemotactic properties and potently attracts T cells and monocytes. The membrane-bound form (mFKN) facilitates diapedesis and is responsible for cell-to-cell adhesion, especially by promoting the strong adhesion of leukocytes (monocytes) to activated endothelial cells with the subsequent formation of an extracellular matrix and angiogenesis. FKN signaling occurs via CX3CR1, which is the only known member of the CX3C chemokine receptor subfamily. Signaling within the FKN-CX3CR1 axis plays an important role in many processes related to inflammation and the immune response, which often occur simultaneously and overlap. FKN is strongly upregulated by hypoxia and/or inflammation-induced inflammatory cytokine secretion, and it may act locally as a key angiogenic factor in the highly hypoxic tumor microenvironment. The importance of the FKN/CX3CR1 signaling pathway in tumorigenesis and cancer metastasis results from its influence on cell adhesion, apoptosis and cell migration. This review presents the role of the FKN signaling pathway in the context of angiogenesis in inflammation and cancer. The mechanisms determining the pro- or anti-tumor effects are presented, which are the cause of the seemingly contradictory results that create confusion regarding the therapeutic goals.

Microsporidia are intracellular parasites infecting a wide range of vertebrates and invertebrates. In bees, they cause a diarrheal disease called nosematosis, which represents a growing problem contributing to the decline of bee colonies. This parasitic disease infects the gastrointestinal tract of bees, disrupts their immune system, weakens them, and shortens their lifespan. There are two known species of this microsporidial parasite with a global distribution: Vairimorpha apis and Vairimorpha ceranae, with current research indicating that the species V. ceranae is gradually replacing V. apis. In this study, we focused on the detection and occurrence of Vairimorpha spp. in bee colonies kept in different environments, as well as on comparing the impact of hive location on its occurrence. The methods used included sampling from winter bee carcasses, microscopic examination of bee gut contents, and subsequent molecular duplex PCR analysis. Altogether, we examined 82 hives located at 4 different sites and focused on the impact of transportation as an abiotic factor disturbing bees leading to the development of Vairimorpha spp. disease. The results indicate an increased occurrence of this parasite in hives located in urban sites and hives situated in intravillage locations, which may be attributed to transportation and associated vibrations as an abiotic stress factor. Detection revealed that all samples were positive for Vairimorpha ceranae.

: Intermittent fasting has drawn significant interest in the clinical research community due to its potential to address metabolic complications such as obesity and type 2 diabetes mellitus. Various intermittent fasting regimens include alternate-day fasting (24 hours of fasting followed by 24 hours of eating), time-restricted fasting (fasting for 14 hours and eating within a 10-hour window), and the 5:2 diet (fasting for two days and eating normally for the other five days). Intermittent fasting is associated with a reduced risk of type 2 diabetes mellitus-related complications and can slow their progression. The increasing global prevalence of type 2 diabetes mellitus highlights the importance of early management. Since prediabetes is a precursor to type 2 diabetes mellitus, understanding its progression is essential. However, the long-term effects of intermittent fasting on prediabetes are not yet well understood. Therefore, this review aims to comprehensively compile existing knowledge on the therapeutic effects of intermittent fasting in managing type 2 diabetes mellitus and prediabetes.

Background: This study investigates microvascular changes in the dermis and muscle following a balneotherapy regimen prescribed by therapeutic protocols. Methods: Thirty-five inpatients participated in a two-week balneal course involving the application of mud and hypersaline water. Mud was applied outdoors in the summer as cold mud ointment and indoors year-round as mud packs or mud baths alternated with hypersaline water baths. Biopsies of the skin and muscle were obtained twenty-four hours post-discharge and prepared histologically. Results: Analysis focused on the epidermis, dermis, and muscle. Microvascular changes observed included increased caliber and number of open capillaries, as well as the presence of angiogenesis vessels. Statistical analysis showed significant differences in angiogenesis vessels between cold mud ointment and mud pack treatments compared to control and mud bath groups. A higher number of angiogenesis vessels were observed in the dermis in the mud pack group and in the muscle with mud cold ointment. Repeated thermal stimulation with mud and hypersaline water over two weeks produced histologically evident tissue modifications, persisting in the dermis and muscle at least twenty-four hours post-treatment completion.

Maternal obesity has been found to be impaired oxidative status in placenta and newborn which can lead to adverse pregnancy outcomes and long-term adverse influence on metabolic programming in the offspring. This study aimed to investigate the role of maternal obesity on maternal and umbilical cord plasma oxidative status and placental oxidative adaptation. Maternal obesity (n=20) defined as pre-pregnancy BMI ≥ 25 kg/m² and maternal lean (n=20) defined as pre-pregnancy BMI < 25 kg/m² were recruited into this study. Both groups were matched by gestational age at delivery. Maternal blood, umbilical cord blood and placental tissue were collected to assess nutritional content (cholesterol, triglyceride, and protein), oxidative stress marker (MDA and protein carbonyl) and antioxidant activity (SOD and catalase). Placenta protein expression (SOD2, catalase, UCP2 and Nrf2) was evaluated by western blot analysis. Catalase activity in maternal plasma significantly increased in maternal obesity group (p = 0.0200) with an increased trend in MDA and protein carbonyl levels. Umbilical cord plasma triglyceride, protein carbonyl and catalase activity significantly increased in maternal obesity compared with that in maternal lean (p = 0.0462, 0.0485, and 0.0348, respectively). Although placenta protein expression analysis exhibited significant decreased SOD2 (p = 0.0169) and catalase (p = 0.0067), accompanied by Nrf2 downregulation (p = 0.0453). An increased mitochondrial antioxidant UCP2 expressions was observed (p = 0.0143). Hence, our study provided evidence that maternal obesity is associated with placental and fetal oxidative stress with the parallel increased placental antioxidant UCP2 expression.

Acomys cahirinus is a unique Rodentia species with several distinctive physiological traits, such as precocial development and remarkable regenerative abilities. These characteristics render A. cahirinus increasingly valuable for regenerative and developmental physiology studies. Despite this, the structure and postnatal development of the central nervous system in A. cahirinus have been inadequately explored, with only sporadic data available. This study is the first in a series of papers addressing these gaps. Our first objective was to characterize the structure of the main visual thalamic region, the lateral geniculate complex, using several neuronal markers (including Ca2+-binding proteins, glutamic acid decarboxylase enzyme, and non-phosphorylated domains of heavy-chain neurofilaments) to label populations of principal neurons and interneurons in adult and newborn A. cahirinus. As typically found in other rodents, we identified three subdivisions in the geniculate complex: the dorsal and ventral geniculate nuclei (LGNd and LGNv) and the intergeniculate leaflet (IGL). Additionally, we characterized internal diversity in the LGN nuclei. The "shell" and "core" regions of the LGNd were identified using calretinin in adults and newborns. In adults, the inner and outer parts of the LGNv were identified using calbindin, calretinin, parvalbumin, GAD67, and SMI-32, whereas in newborns, calretinin and SMI-32 were employed for this purpose. Our findings revealed more pronounced developmental changes in LGNd compared to LGNv and IGL, suggesting that LGNd is less mature at birth and more influenced by visual experience.

The anatomy of mature vertebrate hearts is marked by a looped design, which is roughly characterized by two components: (1), s-shaped (sigmoid) routing of the cardiac flow path(s), and (2,) bilaterally asymmetric (chiral) routing of the cardiac flow path(s). The looped heart design is regarded as a phylogenetically conserved feature among vertebrates and is thought to represent a significant determinant of the cardiac pumping function. It evolves during the embryonic period of development by a morphogenetic process called “cardiac looping”. During the past decades, remarkable progress has been made in the uncovering of the genetic, molecular, and biophysical factors contributing to cardiac looping. Thereby, a special focus was directed on the evolution of a bilaterally asymmetric (chiral) heart configuration, which is said to play a central role in the determination of the alignments and separations of the pulmonary and systemic flow paths in the multi-chambered hearts of tetrapods. In contrast to the recent progress made in uncovering of the biological driver of cardiac looping, our present knowledge about the functional consequences of cardiac looping is at an immature state. This article provides an overview and discussion of the currently available information about the looped design of vertebrate hearts and its functional implications.

Lean body mass (LBM) is correlated with powerlifting performance in athletes competing in different bodyweight classes. However, it remains unknown whether changes in LBM are correlated with performance changes in powerlifters preparing for a competition. Aim of the study was to investigate the changes in LBM and performance in powerlifters preparing for a competition. Eight male powerlifters (age 31.7±9.8years, height 1.77±0.06m, weight 99.2±14.6kg) and three female powerlifters (age 32.7±16.3years, height 1.54±0.06m, weight 66.6±20.9kg), participated in the study. Athletes followed individualized periodized training programs for 12 weeks aiming to maximize their performance for the national championship. Maximum strength (1-RM) in squat, bench press, and deadlift, body composition, grip strength, anaerobic power, quadriceps’ cross sectional area and vastus lateralis muscle architecture were measured before and after the training period. Significant increases were found after the training period in squat (5.8±7.0%, P

This review deals with the developmental origins of extraocular, jaw and laryngeal muscles, the expression, regulation and functional significance of myosin heavy chains (MyHCs) they express and changes in MyHC expression during phylogeny. Myogenic progenitors from mesoderm in the prechordal plate and branchial arches specify craniofacial muscle allotypes with different repertoires for MyHC expression. To cope with very complex eye movements, extraocular muscles express 11 MyHCs, ranging from the superfast extraocular MyHC to the slowest, non-muscle MyHC IIB. They have distinct global and orbital layers, singly- and multiply-innervated fibres, longitudinal MyHC variations, and palisade endings that mediate axon reflexes. Jaw-closing muscles express the high-force masticatory MyHC, cardiac or limb MyHCs depending on the appropriateness for the acquisition and mastication of their food. Laryngeal muscles express extraocular and limb muscle MyHCs but shift towards slower MyHCs in large animals. During postnatal development, MyHC expression of craniofacial muscles is subject to neural and hormonal modulation. The primary and secondary myotubes of developing EOMs are postulated to induce, via different retrogradely transported neurotrophins, the rich diversity of neural impulse patterns that regulate the specific MyHCs they express. Thyroid hormone shifts 2A MyHC towards 2B in jaw, laryngeal muscles and possibly extraocular muscles.

The objective of this study was to investigate the impact of athletes' respiratory muscle strength, as assessed through maximal inspiratory (MIP) and expiratory pressure (MEP), on aerobic endurance, as indicated by maximal oxygen consump-tion (Max VO2) kinetics. Respiratory muscle strength was assessed using a digital spirometer (Pony FX Cosmed, Italy), while maximal oxygen utilization capacity was measured using a breath-by-breath automatic portable gas analysis system (Cosmed K5, Italy). Statistical analysis was conducted utilizing SPSS 22.0. Based on the standardized regression coefficients (β), it was found that MEP (mean ± SD: 130.95 ± 42.82) and inspiratory diaphragmatic circumference values significantly influenced ventilatory equivalent (VE), oxygen consumption (VO2), and carbon dioxide pro-duction (VCO2). Conversely, the remaining predictor variables did not exhibit a sig-nificant effect on VE (mean ± SD: 134.80 ± 36.69), VO2 (mean ± SD: 3877.52 ± 868.47 ml), and VCO2 (mean ± SD: 4301.27 ± 1001.07 ml). In contrast, measurements of chest circumference (mean ± SD: 91.40 ± 10.72 cm), MEP, and diaphragmatic cir-cumference during inspiration (mean ± SD: 95.20 ± 10.21 cm) were found to signifi-cantly impact Max VO2 (mean ± SD: 58.52 ± 10.74 ml/kg/min), while the other pre-dictor variables did not demonstrate a significant effect on Max VO2. Conclusively, the study revealed that measured values of diaphragmatic circumference during inspiration and MEP exerted a notable influence on Max VO2, VE, VO2, and VCO2. Our findings underscore the importance of considering respiratory muscle strength in assessing and enhancing athletes' aerobic performance. These insights contribute to a deeper understanding of the interplay between respiratory function and exercise capacity, offering potential avenues for optimizing training regimens and perfor-mance outcomes in athletic contexts.

Diabetes mellitus (DM) is the most common metabolic disease in humans, and its prevalence is increasing worldwide in parallel with the obesity pandemic. A lack of insulin or insulin resistance, and consequently hyperglycemia, leads to many systemic disorders, among which diabetic encephalopathy (DE) is a long-term complication of the central nervous system (CNS), characterized by cognitive impairment and motor dysfunctions. The role of oxidative stress and neuroinflammation in the pathomechanism of DE has been proven. Fractalkine (CX3CL1) has unique properties as an adhesion molecule and chemoattractant, and by acting on its only receptor, CX3CR1, it regulates the activity of microglia in physiological states and neuroinflammation. Depending on the clinical context, CX3CL1-CX3CR1 signaling may have neuroprotective effects by inhibiting the inflammatory process in microglia or, conversely, maintaining/intensifying inflammation and neurotoxicity. This review discusses the evidence supporting that the CX3CL1-CX3CR1 pair is neuroprotective and other evidence that it is neurotoxic. Interrupting the vicious cycle within neuron-microglia interactions may be a therapeutic goal in DE by limiting the inflammatory response.

Mechanical properties of cardiomyocytes from different transmural regions are heterogeneous in the left ventricular wall. The cardiomyocyte mechanical environment affects this heterogeneity because of mechano-electric feedback mechanisms. In the present study, we investigated the effects of load upon transmural differences in contraction of subendocardial (ENDO) and subepicardial (EPI) single cells isolated from the murine left ventricle. Various loads were applied to the cells using carbon fiber techniques for single myocytes. To simulate experimentally obtained results and to predict mechanisms underlying the cellular response to change in load, our mathematical models of the ENDO and EPI cells were used. Extent of the transmural gradient in the time course of contractions was independent of the loading conditions where unloaded and heavy loaded (isometric) contractions were examined, but the regional gradient of the relaxation time characteristics tended to decrease when the load decreased. Under auxotonic contractions, time to peak contraction (T_max) was significantly longer in ENDO cells than in EPI cells at low preload. An increase in preload (axial stretch) prolonged T_max in both cell types; however, the prolongation was greater in EPI cells, resulting in a decrease in transmural gradient in T_max at high preload. The [Ca²⁺]_i transient decay time constant was consistent with the greater preload dependency in T_max of EPI cells. Our modified mathematical models reproduced experimental results, suggesting that differences in cooperativity of cross bridges and calcium troponin C complex interactions between the ENDO and EPI cardiomyocytes may contribute to the different cellular responses to stretch, which may provide a decrease in transmural dispersion of cellular shortening in the intact heart.

Plant-microbial interactions are very crucial for the terrestrial ecosystem. At the rhizospheric, phyllospheric and endospheric regions, these interactions occur through different signalling pathways and play a pivotal role as they strengthen the plant defence mechanism against pathogen attacks and other stresses. A better knowledge of these relationships will help to develop novel solutions for sustainable agriculture and safeguarding the global food supply in the context of climate change and mounting environmental concerns. This chapter emphasises the role of the microbiome in providing resistance to plants against various environmental stresses and aiding in their improved adaption. This chapter also underscores the impact of the microbiome in providing resilience to plants under changing climatic scenarios.

The triad of vascular impairment, muscle atrophy, and cognitive decline represents critical age-related conditions that significantly impact health. Vascular impairment disrupts blood flow, precipitating muscle mass reduction seen in sarcopenia and the decline of neuronal functions characteristic of neurodegeneration. Our limited understanding of the intricate relationships within this triad hinders accurate diagnosis and effective treatment strategies. This review ana-lyzes the interrelated mechanisms that contribute to these conditions, with a specific focus on ox-idative stress, chronic inflammation, and impaired nutrient delivery. The aim is to understand the common pathways involved and to suggest comprehensive therapeutic approaches. Vascular dysfunctions hinder the circulation of blood and the transportation of nutrients, resulting in sar-copenia characterized by muscle atrophy and weakness. Vascular dysfunction and sarcopenia have a negative impact on physical function and quality of life. Neurodegenerative diseases exhibit comparable pathophysiological mechanisms that affect cognitive and motor functions. Preventive and therapeutic approaches encompass lifestyle adjustments, addressing oxidative stress, in-flammation, and integrated therapies that focus on improving vascular and muscular well-being. Better understanding of these links can refine therapeutic strategies and yield better patient out-comes. This study emphasizes the complex interplay between vascular dysfunction, muscle de-generation, and cognitive decline, highlighting the necessity for multidisciplinary treatment ap-proaches. Advances in this domain promise improved diagnostic accuracy, more effective thera-peutic options, and enhanced preventive measures, all contributing to a higher quality of life for the elderly population.

The age-related loss of muscle mass and strength is referred to as “sarcopenia”. The combined effect of sarcopenia and osteoporosis is a devastating threat to the old adult, accounting for reduced mobility, risk for falls and subsequent fractures. In previous studies, we observed a high degree of inter-individual variability of paraspinal muscle fatty infiltration, one most relevant index of muscle wasting. This aspect solicited us to develop a computerized method to quantitatively characterize muscle fatty infiltration in aging and diseases. Magnetic resonance images of paraspinal muscles from 58 women of different age (age range 23-85 years) and physio-pathological status (healthy young, pre-menopause, post-menopause, and os-teoporosis), were used to set up the method. It is based on fractal analysis of lean muscle area (contractile muscle) to estimate muscle fatty infiltration. In particular, lacunarity was computed by parameter β from our hyperbola model function, used to fit the GBA (gliding box algorithm) curvilinear plot. Succolarity was estimated by parameter µ, for the four main directions, through an algorithm implemented on purpose. Results show that fractal lacunarity, by quantifying muscle fatty infiltration, can discriminate be-tween osteoporosis and healthy aging while succolarity can separate the other three groups showing similar lacunarity. Therefore, fractal features of contractile muscle, by measuring fatty infiltration, can represent good indices of sarcopenia in aging and disease.

The normal growth and development of skeletal muscle is essential for the health of the body. The regulation of skeletal muscle by intestinal microorganisms and their metabolites has been continuously revealed. Acetate is the predominant short-chain fatty acid synthesized by gut microbiota through the fermentation of dietary fiber, however, the underlying molecular mechanisms governing the interaction between acetate and skeletal muscle during rapid growth stage remain to be further elucidated; Here, specific pathogen-free (SPF) mice, germ-free (GF) mice, and germ-free mice supplemented with sodium acetate (GS) were used to evaluate the effects of acetate on skeletal muscle growth and development of young mice with gut microbiota deficiency; We found the concentration of serum acetate, body mass gain, succinate dehydrogenase activity and expression of myogenesis maker gene of skeletal muscle in the GS group was higher than GF group following sodium acetate supplement. Furthermore, the transcriptome analysis revealed that acetate activated biological processes regulating skeletal muscle growth and development in GF group that are inhibited due to gut microbiota deficiency. In vitro experiment, we proved that acetate up-regulated Gm16062 to promote skeletal muscle cell differentiation; Overall, our findings proved that acetate promote skeletal muscle growth and development in young mice via increase Gm16062 expression.

Surgical simulators are crucial in early craniofacial and plastic surgical training, necessitating synthetic materials that accurately replicate tissue properties. Recent critiques of our lab’s currently deployed silicone surrogate have highlighted numerous areas for improvement. To further refine our models, our group's objective is to find a composition of materials that is closest in fidelity to native oral mucosa during surgical rehearsal by expert craniofacial surgeons. Fifteen platinum silicone-based surrogate samples were constructed with variable hardness and slacker percentages. These samples underwent evaluation of tactile sensation, hardness, needle puncture, cut resistance, suture retention, defect repair, and tensile elasticity. Expert craniofacial surgeon evaluators provided focused qualitative feedback on selected top-performing samples for further assessment and statistical comparisons. Evaluation revealed surrogate characteristics with satisfactory to good performance. Sample 977 exhibited the highest performance, and comparison with the original surrogate (sample 810) demonstrated significant improvements in critical areas, emphasizing the efficacy of the refined composition. The study identified a silicone composition that directly addresses the feedback received by our team’s original silicone surrogate. The study underscores the delicate balance between biofidelity and practicality in surgical simulation. The need for ongoing refinement in surrogate materials is evident to optimize training experiences for early surgical learners.

According to many research groups, high glucose induces over production of superoxide anions, and reactive oxygen species (ROS) in general is the link between high glucose levels and the toxicities seen at cellular levels. Respiratory complex anomalies could lead to the production of ROS. Calcium [Ca2+], at physiological levels serves as a second messenger in many physiological functions. Accordingly, mitochondrial calcium [Ca2+]m overload leads to ROS production which could be lethal to the mitochondria through various mechanisms. The F1F0-ATPase (ATP syn-thase or complex V) is the enzyme that is responsible for catalyzing the final step of oxidative phosphorylation. It does so by coupling the translocation of protons in the mitochondrial in-termembrane space and shuttling them to the mitochondrial matrix for ATP synthesis to take place. Mitochondrial complex V T8993G mutation specifically blocks the translocation of protons across the intermembrane space thereby blocking ATP synthesis leading to Neuropathy, Ataxia and Retinitis Pigmentosa Syndromes (NARP). This study seeks to explore the possibility of [Ca2+]m overload mediating the pathological roles of high glucose in defective respiratory chain mediated mitochondrial stress. The NARP cybrids are the in vitro experimental models for the cells with F1FO-ATPase defects, these cells harbor 98% of mtDNA T8993G mutation. Their coun-terparts 143B osteosarcoma cell lines are the parental cell lines used for comparisons. We uncov-ered that, NARP cells mediated and enhanced the death of the cells (apoptosis) when incubated with hydrogen peroxide (H2O2) and high glucose respectively as depicted by the MTT assay of cell viability. Furthermore, using the fluorescence probe-coupled laser scanning confocal imag-ing microscopy, NARP cells significantly enabled mitochondrial reactive oxygen species (mROS) formation and enhanced the depolarization of the mitochondrial membrane potential (ΔΨm). Elucidating the mechanisms of sugar enhanced toxicity on mitochondria would help in the fu-ture to alleviate the symptoms of patients associated with (NARP) syndromes.

Surgical simulators are crucial in early craniofacial and plastic surgical training, necessitating synthetic materials that accurately replicate tissue properties. Recent critiques of our lab’s currently deployed silicone surrogate have highlighted numerous areas for improvement. To further refine our models, our group's objective is to find a composition of materials that is closest in fidelity to native oral mucosa during surgical rehearsal by expert craniofacial surgeons. Fifteen platinum silicone-based surrogate samples were constructed with variable hardness and slacker percentages. These samples underwent evaluation of tactile sensation, hardness, needle puncture, cut resistance, suture retention, defect repair, and tensile elasticity. Expert craniofacial surgeon evaluators provided focused qualitative feedback on selected top-performing samples for further assessment and statistical comparisons. Evaluation revealed surrogate characteristics with satisfactory to good performance. Sample 977 exhibited the highest performance, and comparison with the original surrogate (sample 810) demonstrated significant improvements in critical areas, emphasizing the efficacy of the refined composition. The study identified a silicone composition that directly addresses the feedback received by our team’s original silicone surrogate. The study underscores the delicate balance between biofidelity and practicality in surgical simulation. The need for ongoing refinement in surrogate materials is evident to optimize training experiences for early surgical learners.

The orexin/hypocretin neuropeptide family has emerged as a focal point of neuroscientific research following the discovery that this family plays a crucial role in a variety of physiological and behavioral processes. These neuropeptides serve as powerful neuromodulators, intricately shaping autonomic, endocrine, and behavioral responses across species. Notably, they serve as master regulators of vigilance and stress responses; however, their role in complex processes such as food intake, metabolism, and thermoregulation warrant further investigation. This narrative review provides a journey through the evolution of our understanding of the orexin system, from its initial discovery to the promising progress made in developing orexin derivatives. It goes beyond conventional boundaries, striving to synthesize the multifaceted activities of orexins. Special emphasis is placed on domains such as stress response, fear, anxiety, and learning, in which the authors contributed to the literature with original publications. This article demonstrates the orchestrating role of the orexins in several intricate and integrative physiological processes. It also overviews the advancement of orexin pharmacology, which has already yielded some promising successes, particularly in the treatment of sleep disorders. This interdisciplinary approach to studying neuropeptides unveils their significance as vital connectors between transient functional changes and lasting structural adaptations. Ultimately, it advances our understanding of the intricate physiological and behavioral contributions of the orexin/hypocretin neuropeptide family.

Late-life diseases result from the poorly understood process of senescence (aging), that is largely genetically determined. According to a recently proposed evolutionary physiology-based account, the multifactorial model, senescence is largely caused by evolved but non-adaptive programmatic mechanisms specified by the wild-type (i.e. normal) genome. These act together with disruptions to wild-type function (due e.g. to infectious pathogens, mechanical injury and malnutrition) in a variety of combinations to generate diverse late-life diseases. Here the utility of this model is explored by testing its capacity to provide an account of one complex, late-life disease, osteoarthritis (OA), and a framework for understanding OA etiology suggested. In this framework, the core OA disease mechanism is a futile endochondral ossification quasi-program (non-adaptive developmental program), in which hypertrophic articular chondrocytes alter joint architecture. Programmatic changes prime chondrocytes for quasi-program activation, which can be triggered by secondary causes of OA (e.g. joint mechanical injury). A suggested evolutionary cause of this priming, involving antagonistic pleiotropy, is selection to maximize early life tissue repair benefits at the expense of late-life programmatic costs.

A degree in physiology in Nigeria offers a enormous opportunities that many undergraduates may be unaware of.This article explores different career paths available to physiology undergraduate and graduates in Nigeria. It outlines various fields within clinical and healthcare settings, research and academia, biotechnology and pharmaceuticals, and even alternative careers. It also details specific specializations within clinical physiology, including cardiovascular, respiratory, neurophysiology, sleep, gastrointestinal, and renal physiology.The article emphasizes the importance of gaining practical experience through internships, volunteer work, and networking to equip physiology them with essential skills for job market.

(1) Background: Intravesical Chemotherapy is standard of care in intermediate risk non-muscle-invasive bladder cancer (NMIBC). Different agents are used across the world based on availability, cost and practice patterns. Epirubicin (EPI), one of these agents is used by many centers over many decades. However, its true differential efficacy compared to other agents and its tolerability is still poorly reported. We aimed to assess the differential efficacy and safety of intravesical EPI in NMIBC patients. (2) Methods: A systematic search of PUBMED, Webofscience, clinicaltrials.gov, and Google Scholar databases was performed on December 31, 2023. We reviewed 28 studies that included patients treated EPI after TURBT (transurethral resection of bladder tumors) for NMIBC and who compared oncological outcomes such as recurrence and progression to other adjuvant treatment such as Mitomycin C (MMC), Gemcitabine (GEM) and BCG. Further, we looked at the safety profile of EPI at room temperature under hyperthermia intravesically and at the oncological outcomes when administrated with hyperthermia; (3) Results: When compared to other chemotherapeutics (MMC/GEM), EPI seemed to be equally effective; however, EPI seems less effective in preventing disease management recurrence compared to BCG intravesical. The most common adverse events of EPI include cystitis, dysuria, and pollakiuria. (4) Conclusions: EPI exhibits similar oncological performances to Gemcitabine and Mitomycin C currently used for adjuvant therapy in NMIBC. Novel delivery mechanisms such as hyperthermia are promising newcomers.

The USH1G protein SANS is a small multifunctional scaffold protein. It is involved in several different cellular processes, such as intracellular transport, in the cytoplasm, or splicing of pre-mRNA, in the cell nucleus. Here, we aimed to gain insight into the regulation of the subcellular localization and the nuclear-cytoplasmic shuttling of SANS and its paralogue ANKS4B, not yet reported in the nucleus. We identified karyopherins mediating the nuclear import and export by screening the nuclear interactome of SANS. Sequence analyses predicted in silico evolutionarily conserved nuclear localization sequences (NLSs) and nuclear export sequences (NESs) in SANS, but only NESs in ANKS4B, which are suitable for karyopherin binding.Quantifying the nuclear-cytoplasmic localization of wild-type SANS and NLS/NES mutants, we experimentally confirmed in silico predicted NLS and NES functioning in the nuclear-cytoplasmic shuttling in situ in cells. The comparison of SANS and its paralogue ANKS4B revealed substantial differences in the interaction with the nuclear splicing protein PRPF31 and in their nuclear localization. Finally, our results on pathogenic USH1G/SANS mutants suggest that the loss of NLSs and NESs and thereby the ability to control nuclear-cytoplasmic shuttling is disease-relevant.

Aluminum (Al), making up a third of the Earth's crust, is a widespread toxic contaminant, particularly in acidic soils. It impacts crops at multiple levels, from the cellular to the whole plant. This review delves into aluminum's reactivity, including its cellular transport, involvement in oxidative redox reactions, development of specific metabolites, and the influence of genes on the production of membrane channels and transporters, as well as its role in triggering apoptosis leading to senescence. It discusses the involvement of channel proteins in calcium influx, vacuolar proton pumping, the suppression of mitochondrial respiration, and the initiation of programmed cell death. At the cellular nucleus level, the effects of Al on gene regulation through alterations in nucleic acid modifications, such as methylation and histone acetylation, are examined. The review in addition outlines the pathways of Al induced metabolic disruption specifically citric acid metabolism, regulation of proton excretion, induction of specific transcription factors, modulation of Al-responsive proteins, changes of citrate and nucleotide glucose transporters and overall metal detoxification pathways in tolerant genotypes. It also considers the expression of phenolic oxidases in response to oxidative stress, their regulatory feedback on mitochondrial cytochrome proteins, and their consequences on root development. Ultimately, the review focuses on the selective metabolic pathways that facilitate Al exclusion and tolerance, emphasizing compartmentalization, antioxidative defense mechanisms, and the control of programmed cell death to manage metal toxicity.

Adult neural stem and progenitor cells (NSPCs) contribute to learning, memory, maintenance of homeostasis, energy metabolism and many other essential processes. They are highly heterogeneous populations that require input from a regionally distinct microenvironment including a mix of neurons, oligodendrocytes, astrocytes, ependymal cells, NG2+ glia, vasculature, cerebrospinal fluid (CSF), and others. The diversity of NSPCs is present in all three major parts of the CNS, i.e., the brain, spinal cord, and retina. Intrinsic and extrinsic signals, e.g., neurotrophic and growth factors, master transcription factors, and mechanical properties of the extracellular matrix (ECM), collectively regulate activities and characteristics of NSPCs: quiescence/survival, proliferation, migration, differentiation, and integration. This review discusses the heterogeneous NSPC populations in the normal physiology and highlights their potentials and roles in injured/diseased states for regenerative medicine.

Background: Chronic lateral epicondylitis challenges the therapeutical approach; underlying mechanisms are incompletely understood; neuropathic pain and central and peripheral sensitization may explain the fact that botulinum toxin was found to play a role in pain and function management. Methods: We searched the literature for MeSH terms: lateral epicondylitis or synonyms and botulinum toxin. Results: We found 14 papers containing trials on botulinum toxin injection into the tendon or into the extensor muscles (particularly extensor carpi radialis brevis and extensor communis digitorum). We followed the administration pathways, doses, timing and side effects. Conclusion: With chronic course, the focus of the therapy shifts from the afflicted tendon to the inserting muscles, as muscle contracture may create a vicious loop to perpetuate and aggravate the disease. Doses, timing and side effects are discussed.

The vertebrate skeletal neuromuscular junction (NMJ) has long served as a model system for studying synapse structure, function and development. Over the last several decades a neuron-specific isoform of agrin, a heparan sulfate proteoglycan, has been identified as playing a central role in synapse formation at all vertebrate skeletal neuromuscular synapses. While agrin was initially postulated to be the inductive molecule that initiates synaptogenesis, this model has been modified in response to work showing that postsynaptic differentiation can develop in the absence of innervation, and that synapses can form in transgenic mice in which the agrin gene is ablated. In place of a unitary mechanism for neuromuscular synapse formation, studies in both mice and zebrafish have led to the proposal that two mechanisms mediate synaptogenesis, with some synapses being induced by nerve contact while others involve the incorporation of prepatterned postsynaptic structures. Moreover, the current model also proposes that agrin can serve two functions, to induce synaptogenesis and to stabilize new synapses, once these are formed. This review examines the evidence for these propositions, and concludes that it remains possible that a single molecular mechanism mediates synaptogenesis at all NMJs, and that agrin acts as a stabilizer, while its role as inducer is open to question. Moreover, if agrin does not act to initiate synaptogenesis, it follows that as yet uncharacterized molecular interactions are required to play this essential inductive role. Several alternatives to agrin for this function are suggested, including focal pericellular proteolysis and integrin signaling, but all require experimental validation.

A facilitative transport system exists on the blood brain barrier (BBB) that has been tacitly assumed to be a path for glutamate entry to brain. But glutamate is a non-essential amino acid whose brain content is much greater than plasma, and studies in vivo show that glutamate does not enter brain in material quantities except in those small regions with fenestrated capillaries (circumventricular organs). The situation became understandable when luminal (blood facing) and abluminal (brain facing) membranes were isolated and studied separately. Facilitative transport of glutamate and glutamine exist only on the luminal membranes whereas Na+-dependent transport systems for glutamate, glutamine and some other amino acids are present only on the abluminal membrane. The Na+-dependent cotransporters of the abluminal membrane are in a position to actively transport amino acids from the extracellular fluid (ECF) into the endothelial cells of the BBB. These powerful secondary active transporters couple the energy of the Na+-gradient to move glutamate and glutamine into the ECF whereupon glutamate can exit to blood on the luminal facilitative glutamate transporter. Glutamine may also exit brain on a separate facilitative transport system that exists on the luminal membranes or glutamine can be hydrolyzed to glutamate within the BBB thereby releasing ammonia that is freely diffusible. The γ-glutamyl participate cycle participates indirectly by producing oxoproline (pyroglutamate) that stimulates almost all secondary active transporters yet discovered in the abluminal membranes of the BBB.

Multivariate statistical approaches (MSA), such as principal components analysis and multidimensional scaling, seek to uncover meaningful patterns within datasets by considering multiple response variables in a concerted fashion. Although these techniques are readily used by ecologists to visualize and explain differences between study sites, they could theoretically be employed to differentiate organisms within an experimental framework while simultaneously identifying response variables that drive documented experimental differences. Therefore, MSA were used herein to attempt to understand the response of the common, Indo-Pacific reef coral Seriatopora hystrix to temperature changes using data from laboratory-based temperature challenge studies performed in Southern Taiwan. Gene expression and physiological data partitioned experimental specimens by time of sampling, treatment temperature, and site of origin upon employing MSA, signifying that S. hystrix and its dinoflagellate endosymbionts display physiological and molecular signatures that are characteristic of sampling time, site of colony origin, and/or temperature regime. These findings promote the utility of MSA for documenting biologically meaningful shifts in the physiological and/or sub-cellular response of marine invertebrates exposed to environmental change.

Aspalathin, a C-glucosyl dihydrochalcone, has previously been shown to protect cardiomyocytes against hyperglycemia-induced shifts in substrate preference and subsequent apoptosis. However, the precise gene regulatory network remains to be elucidated. To unravel the mechanism and provide insight into this supposition, the direct effect of aspalathin in an isolated cell-based system, without the influence of any variables, was tested using an H9c2 cardiomyocytes model. Cardiomyocytes were exposed to high glucose (33 mM) for 48 hours before post-treatment with or without aspalathin. Thereafter, RNA was extracted and RT2 PCR Profiler Arrays were used to profile the expression of 336 genes. Results showed that, 57 genes were differentially regulated in the high glucose or high glucose and aspalathin treated groups. STRING analysis revealed lipid metabolism and molecular transport as the biological processes altered after high glucose treatment, followed by inflammation and apoptosis. Aspalathin was able to modulate key regulators associated with lipid metabolism (Adipoq, Apob, Cd36, Cpt1, Pparγ, Srebf1/2, Scd1 and Vldlr), insulin resistance (Igf1, Akt1, Pde3 and Map2k1), inflammation (Il3, Il6, Jak2, Lepr, Socs3, and Tnf13) and apoptosis (Bcl2 and Chuk). Collectively, our results propose that aspalathin could reverse metabolic abnormalities by activating Adipoq while modulating the expression of Pparγ and Srebf1/2, decreasing inflammation via Il6/Jak2 pathway, which together with an observed increased expression of Bcl2 prevents myocardium apoptosis.

Abstract: Exercise has been repeatedly shown to be safe and beneficial for cancer survivors. However, there is no normative guideline for exercise prescription, and it is under exploration. Therefore, this literature review aims to provide some advice for the formulation of exercise prescriptions for patients with breast cancer-related lymphedema (BCRL) from the perspective of reducing lymphedema severity. A review of relevant studies published before November 2023 was conducted using three scientific databases PubMed, Embase, and Scopus. A total of 2696 articles were found. Eventually, 13 studies fulfilled the inclusion criteria and were included in this literature review. We concluded daily, or nearly daily exercise at home can be recommended. Moreover, reduced lymphedema severity may not be maintained after ceasing the exercise program, so exercise should be a lifelong practice.

Cardiovascular disease (CVD) is the leading cause of death worldwide. Cardiac rehabilitation (CR) has proven to be effective in reducing the rate of recurrence and disease as secondary prevention (evidence-based intervention) in patients who have suffered from myocardial infarction (MI). CR is a multidisciplinary path in which the patient is followed pharmacologically, from a psychological, nutritional, nursing and physiotherapy point of view. Post-MI patients present a reduction in the performance of the diaphragm muscle, the main inspiratory muscle, and this condition can become a risk factor for further relapses or for the onset of heart failure. Despite the solidity of the international guidelines for CR, the latter are lacking in specifically indicating an evaluation and training path regarding the inspiratory muscles in post-MI patients who have not undergone cardiac surgery. The article reviews the information on the adaptation of the diaphragm post-MI and highlights the need for clearer indications for a rehabilitation process that gives importance to the diaphragm.

Rhodiola rosea, a perennial herb from the Crassulaceae family, contains the bioactive compound salidroside, recognized as an adaptogen with significant therapeutic potential for bone metabolism. Salidroside promotes osteoblast proliferation and differentiation by activating critical signaling pathways, including bone morphogenetic protein-2 and adenosine monophosphate-activated protein kinase, essential for bone formation and growth. It enhances osteogenic activity by increasing alkaline phosphatase activity and mineralization markers, while upregulating key transcription factors such as runt-related transcription factor 2 and osterix. Additionally, salidroside facilitates angiogenesis via the hypoxia-inducible factor 1-alpha and vascular endothelial growth factor pathway, crucial for coupling bone formation with vascular support. Its antioxidant properties offer protection against bone loss by reducing oxidative stress and promoting osteogenic differentiation through the nuclear factor erythroid 2–related factor 2 pathway. Salidroside's ability to counteract the negative effects of glucocorticoids on bone cells and prevent steroid-induced osteonecrosis, along with its anti-inflammatory properties, enhances its potential in treating conditions like osteoarthritis. These attributes underscore its multifaceted role in bone metabolism. This article reviews the literature, including in vitro and in vivo studies primarily on rodent models, demonstrating salidroside's efficacy in mitigating bone loss, preserving bone microarchitecture, and accelerating fracture healing. Future research directions to explore salidroside’s applications in bone-related diseases are also highlighted.

Extremely low-frequency electromagnetic fields (ELF-EMF) are ubiquitous in industrial-11 ized environments due to the continuous use of electrical devices. Our previous studies demon-12 strated ELF-EMF affects muscle cells by modulating oxidative stress and enhancing myo-genesis. 13 This pilot study investigated these effects on skeletal muscles of sedentary adult mice, assessing 14 physiological responses to ELF-EMF exposure and potential modulation by antioxidant supplemen-15 tation. Male C57BL/6 mice were exposed to ELF-EMF (0.1 or 1.0 mT) 1 hour/day up to 5 weeks, and 16 fed a standard diet without or with N-acetyl-cysteine (NAC). Results showed transient increases in 17 muscle strength (after 2-weeks’ exposure at 1.0 mT), potentially linked to muscle fiber recruitment 18 and activation, revealed by higher PAX7 and MyH expression levels. After ELF-EMF exposure, ox-19 idative status assessment revealed transient increases in expression levels of SOD1 and catalase en-20 zymes, in total antioxidant capacity and in protein carbonyl levels, marker of oxidative damage. 21 These effects were partially reduced by NAC. In conclusion, ELF-EMF exposure affects skeletal 22 muscle physiology and NAC supplementation partially mitigates these effects, highlighting the 23 complex interactions between ELF-EMF and antioxidant pathways in vivo. Further investigations 24 on ELF-EMF as a therapeutic modality for muscle health are necessary.

Microplastics (plastic particles &lt; 5 mm) are ubiquitous pollutants that pose the ability to carry microbiota, including pathogens. Microbial adhesion is usually a sign of pathogenicity, thus we investigated the adherent strains found on 4 mm nylon strips, which were ingested and excreted by wild fish specimens. Polymer analysis of the excreted samples shown no signs of degradation, nor have their controls, represented by the nylon strips submerged in the same water tanks. Both the ingested samples and controls presented pathogens in large numbers, revealing the fact that nylon microplastics can be physical carriers for pathogens in the aquatic environment.

This study investigates how root environment acidification impacts tea seedlings and the role of magnesium (Mg) in mitigating these effects. We examine varying pH and Mg levels' influence on tea seedlings' resistance to abiotic stress, focusing on antioxidant capacity and nutritional content. In a hydroponic experiment, we varied root pH (3.5, 5.0, 6.5) and Mg concentrations (0.01, 0.4, 0.8 mM), assessing parameters like antioxidant capacity, peroxidative damage, and nutritional content at 1, 7, 15, and 30 days post-treatment. Root environment acidification and Mg deficiency worsened peroxidative damage in tea plant leaves and roots. Increased Mg supplementation enhanced antioxidant enzyme activity, reducing malondialdehyde and mitigating oxidative damage from root environment acid stress. Under acid stress, 0.8 mM Mg significantly increased tea leaf polyphenols, amino acids, and water-soluble extracts. Mg notably boosted chlorophyll content, surpassing lower Mg levels at pH 5. Additionally, Mg reversed root vitality inhibition induced by acid stress, leading to increased nitrogen, potassium, and Mg concentrations in leaves, promoting balanced nutrient absorption. Mg supplementation is crucial for enhancing tea plant antioxidant capacity, alleviating growth inhibition from root environment acid stress, and improving chlorophyll content and root vitality, highlighting Mg's significance in tea cultivation and broader agricultural practices.

Despite recent scientific advancements, there is a gap in the use of technology to measure signals, behaviors, and processes of adaptation physiology of farm animals. Sensors present exciting opportunities for sustained, real-time, non-intrusive measurement of farm animal behavioral, mental, and physiological parameters with the integration of nanotechnology and instrumentation. This paper critically reviews the sensing technology and sensor data-based models used to explore biological systems such as animal behavior, energy metabolism, epidemiology, immunity, health, and animal reproduction. The use of sensor technology to assess physiological parameters can provide tremendous benefits and tools to overcome and minimize production losses while making positive contributions to animal welfare. Of course, sensor technology is not free from challenges; these devices are at times highly sensitive and prone to damage from dirt, dust, sunlight, colour, fur, feathers, and environmental forces. Rural farmers unfamiliar with the technologies must be convinced and taught to use sensor-based technologies in farming and livestock management. While there is no doubt that demand will grow for non-invasive sensor-based technologies that require minimum contact with animals and can provide remote access to data, their true success lies in the acceptance of these technologies by the livestock industry.

Exercise-induced muscle injury is one of the most common types of sports injuries. Skeletal muscle troponin I (skTnI) serves as an ideal biomarker in assessing such injuries, facilitating timely detection and evaluation. In this study, we develop a fluorescent sandwich lateral flow immunoassay (LFIA) combined with a desktop analyzer for rapid detection of skTnI. Through optimizing the reaction system, the assay achieves a satisfying detection performance, reaching a limit of detection (LOD) of 0.5 ng/mL with a turnaround time of 15 minutes. The proposed de-tection platform offers portability, ease of use, and high sensitivity, which facilitates the moni-toring of exercise-induced muscle injuries at the point of care. This feature is particularly advan-tageous for end-users, enabling timely detection of sports-related injuries and ultimately en-hancing prognosis and sports life.

Leucokinins (LKs) constitute a family of neuropeptides identified in numerous insects and many other invertebrates. The LKs act on G-protein coupled receptors that display only distant relations to other known receptors. In adult Drosophila, 26 neurons/neurosecretory cells of three main types express LK. The four brain interneurons are of two types, and these are implicated in several important functions in the fly’s behavior and physiology, including feeding, sleep-metabolism interactions, state-dependent memory formation, as well as modulation of gustatory sensitivity and nociception. The 22 neurosecretory cells (ABLKs) of the abdominal neuromeres coexpress LK and a diuretic hormone (DH44), and together these regulate water and ion homeostasis and associated stress, as well as food intake. In Drosophila larvae, LK neurons modulate locomotion, escape responses, and aspects of ecdysis behavior. A set of lateral neurosecretory cells, ALKs, in the brain express LK in larvae, but inconsistently so in adults. These ALKs coexpress three other neuropeptides and regulate water and ion homeostasis, feeding and drinking, but the specific role of LK is not yet known. This review summarizes Drosophila data on embryonic lineages of LK neurons, functional roles of individual LK neuron types, interactions with other peptidergic systems, and orchestrating functions of LK.

G-protein-coupled receptors (GPCRs) are ubiquitous sensors and regulators of cellular functions. Each GPCR exists in complex aggregates with multiple resting and active conformations. Designed to detect weak stimuli, GPCRs can also activate spontaneously, resulting in basal ligand-free signaling. Agonists trigger a cascade of events leading to an activate agonist-receptor-G protein complex with high agonist affinity. However, the ensuing signaling process can further remodel the receptor complex to reduce agonist affinity, causing rapid ligand dissociation. The acutely activated ligand-free receptor can continue signaling, as proposed for rhodopsin and  opioid receptors, resulting in robust receptor activation at low agonist occupancy with enhanced agonist potency. Continued receptor stimulation can further modify the receptor complex, regulating sustained ligand-free signaling - proposed to play a role in opioid dependence. Basal, acutely agonist-triggered, and sustained elevated ligand-free signaling could each have distinct functions, reflecting multi-state conformations of GPCRs. This review addresses basal and stimulus-activated ligand-free signaling, its regulation, genetic factors, and pharmacological implications, focusing on opioid and serotonin receptors, and the growth hormone secretagogue receptor (GHSR). Ligand-free signaling of intracellular 5-HT2A receptors could mediate therapeutic effects of psychedelic drugs. Research avenues are suggested to close gaps in our knowledge of ligand-free GPCR signaling.

Fatigue and dyspnea are the most commonly presented long-term complaints in individuals previously infected with SARS-CoV-2. The purpose of the study was to comprehensively evaluate diaphragm muscle function in COVID-19 survivors, as well as investigate whether potential diaphragm dysfunction will contribute to physical functioning impairment. 46 patients qualified to pulmonary rehabilitation were examined. Diaphragm muscle function parameters were evaluated using ultrasonography, while severity of dyspnea, aerobic capacity and amount of energy used by the body during physical activity were assessed by 6-minute walk test, mMRC scale and Metabolic Equivalent Task (MET), respectively. We identified 69.5% patients with diaphragm atrophy and 6.5% with diaphragm paralysis. Percentage of atrophy was not related to age, gender, BMI index, oxygen therapy use during COVID-19 infection course and severity of disease. Patients with presence of cough, fever and without loss of smell during COVID-19 course had a significantly greater values of diaphragm inspiratory thickness, while patients with cough and no smell disorders had a significantly lower percentage of diaphragm atrophy. Diaphragm functional parameters were strongly associated with selected variables of person's exercise tolerance, such as distance in 6-minute walk test, saturation level, fatigue and exertion in Borg scale. In conclusion, diaphragm muscle dysfunction is a serious long-term post-COVID aftermath and can be viewed as a major contributing factor of prolonged functional impairments.

The forest regeneration phase in Sweden commonly involves mechanical soil preparation followed by planting of Scots pine or Norway spruce seedlings. The prepared soil offers planting positions with different properties, including decreased damage by pine weevil (Hylobius abietis L.). Nitrogen fertilization can be applied at the time of planting to aid establishment of the seedlings. In this study we compared the effect of organic nitrogen-fertilization for different planting positions, and seedling sizes on early survival and growth of Scots pine and Norway spruce seedlings. The main planting positions were capped mound, hinge, and mineral soil. Seedlings planted close to organic material were categorized as “low quality positions”, since proximity to organic material increase pine weevil attraction. Higher mortality rates related to pine weevil damage were recorded for seedlings planted in the low-quality positions, regardless of seedling size or N-fertilization. Pine weevil attack rates increased with increasing seedling size. Growth was in general lowest in mineral soil positions. The effect of organic N-fertilization on growth was positive for spruce regardless of planting positions and seedling size, while depending on planting position and seedling size for pine, indicating that effects of organic N-fertilization depend on seedling species, -size and planting position.

Background: Bariatric surgery (BS) has a significant impact on body composition (BC) and con-sequently may affect established sarcopenic obesity (SO) in candidate patients. The aim of this study is to assess the utility of muscle ultrasound (MUS) of rectus femoris thickness (RFT) for the evalua-tion of BC and skeletal muscle function in patients undergoing BS compared to bioimpedance analysis (BIA), dual-energy X-ray absorptiometry (DEXA) and dynamometry. On the other hand, we aim to demonstrate how MUS of RFT correlates better with the quality of life (Qol) in this population, likely because it enables the detection of regional quadriceps muscle sarcopenia, in comparison to the other mentioned methods. Methods: This is a prospective pilot study including 77 subjects (64.9% female, mean age: 53.2 ± 8.67 years) who underwent BS. Handgrip strength was measured using a dynamometer, fat-free mass index (iFFM) was assessed by BIA, appendicular muscle index (AMI) was calculated using DEXA and RFT was measured by MUS. Moreover, Homeostasis Model Assessment of Insulin Resintance (HOMA-IR) was calculated. All these measurements were conducted 1 month prior to BS and at the 12-month follow-up. QoL was as-sessed using the Moorehead-Ardelt questionnaire. Results: The mean BMI decreased by 12.95 ± 3.56 kg/m2 (p=0.001). Firstly, we observed positive correlation pre-surgery between HOMA and: RFT (r=0.27, p=0.02), iFFM (r=0.36, p=0.001), AMI (r=0.31, p=0.01) and dynamometer (r=0.26, p=0.02). In addition, we found correlation between RFT and iFFM (pre-surgical: r=0.31, p=0.01; post-surgical: r=0.25, p=0.05) and between RFT and lower extremities AMI post-surgical (r=0.27, p=0.04). Secondly, we observed significant reductions in iFFM, AMI and RFT (p=0.001), but not with dynamometer (p=0.94). Finally, a tendency to a positive correlation between QoL question-naire and RFT post-surgery (r=0.23, p=0.079) was observed. Conclusions: Our results suggest that RFT measured by MUS for the evaluation of SO and the follow-up after BS of these patients. Moreover, RFT can provide relevant information about regional sarcopenia and probably has an accurate correlation with QoL in comparison with the other methods.

Vitamin D receptor (VDR) is an important candidate gene in musculoskeletal phenotypes. Polymorphisms in VDR have been previously associated with several pathologies and muscular strength in athletes and elderly people, however literature reported contradictory results. The object of this research is to verify the association between the most studied VDR variants (rs2228570, rs7975232, and rs1544410) and the increase of muscle mass in elite young soccer players. A sample of 55 soccer players (15-18 years old) form a professional team was selected for this study. DNA was extracted by salting out method and polymorphisms were genotyped by PCR-RFLP, followed by 2% agarose gel electrophoresis. To test the effect of the three SNPs, logistic regression analysis was applied. Body composition was carried out through skinfold thickness method, and muscular area of arm and lower limb were calculated using Frisancho formulas. All three polymorphisms met Hardy-Weinberg equilibrium (p &gt; 0.05) and their frequencies fell within the worldwide variability. A significant correlation between rs1544410 and increase of calf muscle mass was observed. Individuals carrying A allele showed higher calf muscular mass than those carrying the G allele (p = 0.034). Moreover, haplotype analysis applied to the two SNPs in linkage disequilibrium (rs7975232 and rs1544410), showed that AG haplotype resulted negatively correlated to calf muscle area. In conclusion, we confirm an association between VDR polymorphisms and muscular mass that could encourage the genetic screening of VDR gene to identify a potential risk of injury and for individual nutritional interventions.

Aquaporins (AQPs) are a family of integral membrane proteins that selectively transport water and glycerol across the cell membrane. Because AQPs are involved in a wide range of physiological functions and pathophysiological conditions, AQP-based therapeutics may have broad potential for clinical utility, including disorders of water and energy balance. However, AQP modulators have not yet been developed as suitable candidates for clinical applications. In this study, to identify potential modulators of AQPs, we screened 32 natural products by measuring the water and glycerol permeability of mouse erythrocyte membranes using a stopped-flow light scattering method. None of the tested natural compounds substantially affected osmotic water permeability. However, several compounds considerably affected glycerol permeability. Stichoposide C increased the glycerol permeability of mouse erythrocyte membranes, whereas rhizochalin decreased it at nanomolar concentrations. Immunohistochemistry revealed that AQP7 was the main aquaglyceroporin in mouse erythrocyte membranes. We further verified the effects of stichoposide C and rhizochalin on aquaglyceroporins using human AQP3 expressing keratinocyte cells. Stichoposide C, but not stichoposide D, increased AQP3-mediated transepithelial glycerol transport, whereas the peracetyl aglycon of rhizochalin was the most potent inhibitor of glycerol transport among the tested rhizochalin derivatives. Collectively, stichoposide C and the peracetyl aglycon of rhizochalin might function as modulators of AQP3 and AQP7, and suggest the possibility of these natural products as potential drug candidates for aquaglyceroporin modulators

Von Hippel-Lindau disease (VHL) is a multiple organ neoplastic syndrome with autosomal dominant transmission, complete penetrance, and variable expression caused by mutations in the VHL gene. Although VHL disease is hereditary in many cases, new mutations cause up to 20 % of the incidence. Mutations in VHL may cause the development of cysts and tumors in many organs, including brain and spinal cord hemangioblastoma, renal cell carcinoma (RCC), retinal heman-gioblastoma (RH), pheochromocytoma, epididymal and broad ligament cystadenomas, endo-lymphatic sac tumor, pancreatic neuroendocrine tumors, and renal and pancreatic cysts. VHL is a syndrome associated with functional inactivation of the Von Hippel–Lindau protein (pVHL). pVHL is a tumor suppressor mainly known for its role as a regulator of hypoxia-inducible factor (HIF) activity. The prevalence of VHL disease is between 1 in 39 000 and 1 in 91 000 individuals in different regional populations. Here, we review the etiology, epidemiology, pathophysiology, genetics, clinical manifestations, diagnosis, and current treatments, as well as the molecular aspects of this disease. We also discuss the animal models used to study this disease, VHL biomarkers, and current VHL clinical trials for VHL according to NIH.

The purpose of the present study was to examine the relationships between bat swing speed (BSS) and muscle thickness and lateral asymmetry of the trunk and limbs in collegiate baseball players. Twenty-four collegiate baseball players participated in this study. The maximum BSS in hitting a teed ball was measured using a motion capture system. The muscle thicknesses of the trunk (upper abdominal rectus, central abdominal rectus, lower abdominal rectus, abdominal wall, and multifidus lumborum), upper limb, and lower limb were measured using a B-mode ultrasonography. Lateral asymmetry between each pair of muscles was determined as the ratio of the thickness of the dominant side to that of the non-dominant side. Significant positive correlations were observed between BSS and muscle thicknesses of the abdominal wall and multifidus lumborum on the dominant side (r = 0.426 and 0.431, respectively; p < 0.05), while nearly significant positive correlations were observed between BSS and muscle thicknesses on the non-dominant side. No significant correlations were found between BSS and lateral asymmetry of all muscles. These findings indicate the importance of the trunk muscles for bat swing, and the lack of association between BSS and lateral asymmetry of muscle size.

The importance of various markers such as sclerostin, Dickkopf-1 (DKK-1), Irisin, receptor activator of NF-kB ligand (RANKL), and Vitamin D have been well studied in bone metabolism. Additionally, inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and Interleukine-6 (IL-6) have been identified to hinder muscle protein synthesis, leading to the loss of muscle and strength. However, a research gap exists in the understanding their role in muscle function and physical activity. Therefore, this study aims to explore the serum levels of sclerostin, DKK-1, irisin, IL-6, RANKL, Vitamin D, and TNF-α and assess their relationships with upper and lower body strength in young adults. In this study, 38 college-aged students 18-23 years participated and completed the protocols. The participants’ lower and upper body strength were assessed by the vertical jump test (Just Jump, Probotic, AL) with a Tendo FitroDyne (Tendo Sports Machines, Trencin, Slovak Republic) and handgrip (HG) dynamometry (Takei Scientific Instruments, Yashiroda, Japan), respectively. Fasting morning blood samples were analyzed for serum levels of the biomarkers by ELISA. The results indicate significant sex differences in sclerostin, DKK-1, irisin, and vitamin D levels (p<0.05). Furthermore, a positive association was observed between sclerostin, DKK-1, and vitamin D, with lower body muscle performance variables (p<0.05). Conversely, a significant negative correlation was observed between TNF-α and upper-body muscle performance variables (p<0.05). The results suggest that these markers may have a distinct effect on muscle performance, underscoring the need for further investigation to elucidate the concept of muscle-bone crosstalk.

Nicotiana benthamiana plants infected with a potato virus Y isolate (PVYO) under ambient conditions of 25 °C and ~405 parts-per-million (ppm) ambient CO2 display symptoms of chlorosis, leaf curling, and stunting. However, under elevated temperature and CO2 levels (30 °C, 970 ppm), systemic viral titers decrease several-fold, and plants appear asymptomatic. Under the latter conditions we have studied how infection, drought, or both combined affect infection, drought-driven loss of leaf turgor, plant water content, stomatal conductance, metabolome, and hormone (ABA, SA, and JA) levels. We found that drought did not affect viral titers. As expected, drought decreased plant water content and stomatal conductance. Under drought conditions, infection did not alter significantly final water content or loss of leaf turgor progression, but it increased the levels of some sugars and other osmo-protectants. Infection and drought altered the levels of many components of the metabolome. Some components altered by infection were not altered by drought, but most of those altered by drought were also altered by infection. Drought increased the levels of ABA, infection increased the levels of ABA, SA, and JA, and altered their relative balance. The effects of drought and of infection on hormone levels were cumulative when combined. Thus, under ambient conditions that turn a severe infection into an asymptomatic one both, plant physiology parameters and the interplay with drought are affected.

Early weaning management followed by energy supplementation can lead to metabolic alterations in the calf that exert long-term effects on the animal’s health and performance. It is believed that the main molecular basis underlying these metabolic adaptations are epigenetic mechanisms that regulate, activate, or silence genes at different stages of development and/or in response to different environmental stimuli. However, little is known about postnatal metabolic programming in Bos indicus. Therefore, this study aimed to compare the DNA methylation profile of Nellore animals submitted to conventional and early weaning and to correlate the findings with genes differentially expressed in Longissimus thoracis skeletal muscle of Bos indicus cattle. A total of 481 differentially methylated regions were identified, with 52% (250) being hypermethylated and 48% (231) hypomethylated. Functional enrichment analysis of 53 differentially methylated and differentially expressed genes was performed. The main enriched terms and pathways were associated with 3’-5’-cyclic adenosine monophosphate (cAMP) signaling which present the upregulated adenylate cyclase 3 (ADCY3) gene and significatively hypomethylated in promoter region. Alterations in cAMP signaling are involved in numerous processes, many of them related to lipid metabolism. The relative differential expression of key genes of this pathway demonstrates the relationship between cAMP signaling and de novo lipogenesis. These findings suggest an important role of postnatal metabolic programming through DNA methylation mechanisms in determining fat deposition in beef.

Inflammation is a vital aspect of the body's immune response, appearing either as an acute reaction that swiftly develops (e.g., after injury or during an infection) or as a chronic condition that persists over a prolonged period, often linked with autoimmune disorders or cancer. This study introduces potential TNF-alpha inhibitors investigated by Molecular Docking investigation. They are Dactolisib with a binding energy of -10.1 kcal/mol, Nilotinib with -9.6 kcal/mol, Eltrombopag with -9.7 kcal/mol, Radotinib with -9.6 kcal/mol, and Nilotinib again with -9.7 kcal/mol. Additionally, Hypericin exhibited a notable binding energy of -9.9 kcal/mol, suggesting its potential as a natural TNF-alpha inhibitor. While these computational results are preliminary, they provide a foundation for further biological studies to confirm their efficacy. The significance of these findings extends to the scientific community, offering potential applications in the field of inflammatory diseases.

High systolic blood pressure and increased blood pressure variability after the onset of ischemic stroke are associated with poor clinical outcomes. One of the key determinants of blood pressure is arteriolar size, determined by vascular smooth muscle tone and vasodilatory and vasoconstrictor substances that are released by the endothelium. The aim of this study is to outline alterations in vasomotor function in isolated peripheral arteries following ischemic stroke. The reactivity of thoracic aortic segments from male C57BL/6 mice to dilators and constrictors was quantified using wire myography. Acetylcholine induced endothelium-dependent vasodilation was impaired after ischemic stroke (LogIC50 Sham=-7.499, LogIC50 Stroke=-7.350, P=0.0132, n= 19, 31 respectively). Vasodilatory responses to SNP were identical in isolated aortas in sham and stroke groups. Phenylephrine induced vasoconstriction was impaired in aortas isolated from stroke animals in comparison to sham counterparts (Sham LogEC50= -6.652 vs Stroke LogEC50=-6.475, P< 0.001). Our study demonstrates that 24 hours post-ischemic stroke, peripheral vascular responses are impaired in remote arteries. Aortas from stroke animals exhibited reduced vasoconstrictor and endothelium-dependent vasodilator responses, while endothelium-independent vasodilatory responses were preserved. Since both vasodilatory and vasoconstrictor responses of peripheral arteries are impaired following ischemic stroke, our findings might explain increased blood pressure variability following ischemic stroke.