In vitro effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the expression of genes related to sperm motility and energy metabolism and intracytoplasmic sperm injection outcomes in obstructive azoospermic patients.

BACKGROUND: The presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and its receptor in various testicular cells and spermatozoa suggests a potential role in enhancing spermatogonial and postmeiotic cell development. Moreover, GM-CSF activates the pivotal pathways implicated in sperm motility regulation and glucose metabolism. However, the impact of GM-CSF on testicular biopsies from patients with obstructive azoospermia (OA) remains unexplored. Therefore, this study aimed to investigate the in vitro effects of GM-CSF on the expression of genes related to glucose transporters and signaling pathways, sperm motility, and viability in testicular biopsies. METHODS AND RESULTS: Following testicular sperm extraction from 20 patients diagnosed with OA, each sample was divided into two parts: the experimental samples were incubated with medium containing 2 ng/ml GM-CSF at 37 °C for 60 min, and the control samples were incubated with medium without GM-CSF. Subsequently, the oocytes retrieved from the partner were injected with sperm from the treatment and control groups. The sperm parameters (motility and viability), the expression levels of sperm motility-related genes (PIK3R1, PIK3CA, and AKT1), and the expression levels of sperm energy metabolism-related genes (GLUT1, GLUT3, and GLUT14) were assessed. Furthermore, the fertilization and day 3 embryo development rate and embryo quality were evaluated. Compared with those in the nontreated group, the motility parameters and the mRNA expression levels of PIK3R1, AKT1, and GLUT3 in testicular sperm supplemented with GM-CSF were significantly greater (p < 0.05). However, no significant differences in the mRNA expression of PIK3CA, GLUT1, or GLUT14 were detected. According to the ICSI results, compared with the control group, the GM-CSF treatment group exhibited significantly greater fertilization rates (p = 0.027), Day 3 embryo development rate (p = 0.001), and proportions of good-quality embryos (p = 0.002). CONCLUSIONS: GM-CSF increased the expression of genes related to motility and the energy metabolism pathway and effectively promoted the motility of testis-extracted spermatozoa, consequently yielding positive clinical outcomes.

GM-CSF (granulocyte-macrophage colony-stimulating factor) treatment improves sperm parameters in men with oligoasthenoteratospermia via PI3K/AKT pathway.

Poor sperm quality in oligoasthenoteratospermia patients negatively affects assisted reproductive technology outcomes. Therefore, the development of sperm media is necessary to improve sperm parameters. This study investigated the effect of GM-CSF via PI3K/AKT pathway on sperm quality in OAT patients. Semen samples were collected from 20 OAT patients, and each sample was divided into two groups: Experiment and Control. In the experimental group, the samples were incubated with medium containing GM-CSF, and control samples were incubated without GM-CSF. Sperm parameters, mitochondrial membrane potential, acrosome reaction and DFI were studied; in addition, gene expression of PI3KR1, PI3KCA, GLUT1, GLUT3 and AKT1 was analysed, evaluation of PAKT/TAKT, and expression of GLUT 1, 3 was examined; subsequent fertilization rate and embryo quality were assessed. Our data showed that GM-CSF supplementation could significantly increase motility, mitochondrial activity, gene expression of PI3KCA, AKT1, the protein level of PAKT/TAKT and expression of GLUT 1, 3 while it decreases DNA fragmentation. The fertilization rate and embryo quality significantly improved in the treatment group. LY294002 had adverse effects on sperm motility and the PAKT/TAKT ratio. GM-CSF can improve in vitro sperm quality and could be a suitable supplement to sperm media for OAT patients.

Dynamic Effects Analysis in Fractional Memristor-Based Rulkov Neuron Model.

Mathematical models such as Fitzhugh-Nagoma and Hodgkin-Huxley models have been used to understand complex nervous systems. Still, due to their complexity, these models have made it challenging to analyze neural function. The discrete Rulkov model allows the analysis of neural function to facilitate the investigation of neuronal dynamics or others. This paper introduces a fractional memristor Rulkov neuron model and analyzes its dynamic effects, investigating how to improve neuron models by combining discrete memristors and fractional derivatives. These improvements include the more accurate generation of heritable properties compared to full-order models, the treatment of dynamic firing activity at multiple time scales for a single neuron, and the better performance of firing frequency responses in fractional designs compared to integer models. Initially, we combined a Rulkov neuron model with a memristor and evaluated all system parameters using bifurcation diagrams and the 0-1 chaos test. Subsequently, we applied a discrete fractional-order approach to the Rulkov memristor map. We investigated the impact of all parameters and the fractional order on the model and observed that the system exhibited various behaviors, including tonic firing, periodic firing, and chaotic firing. We also found that the more I tend towards the correct order, the more chaotic modes in the range of parameters. Following this, we coupled the proposed model with a similar one and assessed how the fractional order influences synchronization. Our results demonstrated that the fractional order significantly improves synchronization. The results of this research emphasize that the combination of memristor and discrete neurons provides an effective tool for modeling and estimating biophysical effects in neurons and artificial neural networks.

Granulocyte-Macrophage Colony-Stimulating Factor Cytokine Addition After the Freeze-Thawing Process Improves Human Sperm Motility and Vitality in Asthenoteratozoospermia Patients.

The cryopreservation-thawing process of spermatozoa cells has negative impacts on their structure, function, and fertility parameters, which are known as cryoinjury. Asthenozoospermia patients are more susceptible to cryoinjury. Granulocyte-macrophage colony-stimulating factor (GM-CSF) increases sperm glucose uptake via the induction of glucose transporters, resulting in increased sperm motility. This study aimed to investigate the efficiency of GM-CSF supplementation of the cryopreservation media for semen samples of asthenoteratozoospermia patients. The study was carried out on 20 semen samples from infertile men referred to diagnosing semen analysis. To avoid subjective bias, two main sperm motility parameters, including velocity along the curvilinear path and velocity along the straight-line path were considered by the computer-assisted sperm analysis system. Afterward, each semen sample was divided into three equal aliquots and randomly assigned to one of the following groups: group I (control, freezing media only), group II (+GM-CSF, freezing medium supplemented with 2 µL/mL GM-CSF), or group III (GM-CSF added after thawing and washing). Following semen thawing, standard parameters, mitochondrial membrane potential (MMP), and the DNA Fragmentation Index were analyzed. Total sperm motility (progressive and non-progressive) improved significantly in group III samples after a 30-minute incubation with GM-CSF compared with the control group (26.5% ± 3.1% vs. 17.51% ± 2.59%). However, no differences in progressive motility or sperm morphology were found among the three thawed samples. The percentage of vitality was significantly higher in group III compared with the other two groups (28.38% ± 3.4% vs. 22.4% ± 3.08% and 22.14% ± 2.77%, respectively) (p < 0.05). JC-1 levels (a marker of MMP) were not significantly different between the examined groups (44.95% ± 8.26% vs. 36.61% ± 6.95% vs. 46.67% ± 7.7%, for control, group II, and group III, respectively) (p > 0.05). GM-CSF may be advantageous as an additive after freezing, improving total motility and viability after 30 minutes of post-thaw incubation; however, when supplied to the freezing media before cryopreservation, it is unable to protect against cryoinjury.

The determinants of smart government systems adoption by public sector organizations in Saudi Arabia.

This study investigates the determinants of smart government systems that are used in public service organizations in Saudi Arabia. The world's developed nations have conducted studies on smart government systems, but little research has been done on the Middle East, particularly in Saudi Arabia. This study fills the lacuna in the literature. Based on a number of theories including the Technology, Organization, and Environment framework (TOE), Unified Theory of Acceptance and Use of Technology (UTAUT), and Technology Acceptance Models (TAM), the study established an integrated conceptual research model. Online survey questionnaires were sent to 2060 employees in four ministries and after the second reminder a total of 427 completed answers were received, of which 419 (22% response rate) were deemed useable for the analysis. Multivariate statistical analysis was used to analyze the data and results indicated that 51% of the variance (R2 = 0.51) of employees' perceptions of smart government systems is explained by independent determinants. Findings show that security concerns (t (419) = 2.051, p < 0.041), ICT strategy (t (419) = 4.215, p < 0.000), managerial support (t (419) = 5.027, p < 0.000), incentives (t (419) = 5.263, p < 0.000), and trust (t (419) = -1.957, p < 0.050) are significant predictors of smart government systems acceptance. Meanwhile cultural values (t (419) = 0.669, p < 0.504) and religious values (t (419) = 1.082, p < 0.280) have no significant effect on the attitude to smart system adoption. Perception was found to have a strong significant effect on adoption of smart government systems (t (419) = 8.411, p < 0.000). These results have significant implications for the Saudi government's drive to implement smart government systems in all its agencies.

Exoskeleton robots for lower limb assistance: A review of materials, actuation, and manufacturing methods.

The field of robot-assisted physical rehabilitation and robotics technology for providing support to the elderly population is rapidly evolving. Lower limb robot aided rehabilitation and assistive technology have been a focus for the engineering community during the last three decades as several robotic lower limb exoskeletons have been proposed in the literature as well as some being commercially available. Numerous manufacturing techniques and materials have been developed for lower limb exoskeletons during the last two decades, resulting in the design of a variety of robot exoskeletons for gait assistance for elderly and disabled people. One of the most important aspects of developing exoskeletons is the selection of the most appropriate proper material. The material selection strongly influences the overall weight and performance of the exoskeleton robot. The most suitable fabrication method for material is also an important parameter for the development of lower limb robot exoskeletons. In addition to the materials and manufacturing methods, the actuation method plays a vital role in the development of these robot exoskeletons. Even though various materials, manufacturing methods and actuators are reported in the literature for these lower limb robot exoskeletons, there are still avenues of improvement in these three domains. In this review, we have examined various lower limb robotic exoskeletons, concentrating on the three main aspects of material, manufacturing, and actuation. We have focused on the advantages and drawbacks of various materials and manufacturing practices as well as actuation methods. A discussion on future directions of research is provided for the engineering community covering the material, manufacturing and actuation methods.