Inhibiting SHP2 reduces glycolysis, promotes microglial M1 polarization, and alleviates secondary inflammation following spinal cord injury in a mouse model

Reducing the secondary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal cord injury. Src homology 2-containing protein tyrosine phosphatase 2 (SHP2), encoded by PTPN11, is widely expressed in the human body and plays a role in inflammation through various mechanisms. Therefore, SHP2 is considered a potential target for the treatment of inflammation-related diseases. However, its role in secondary inflammation after spinal cord injury remains unclear. In this study, SHP2 was found to be abundantly expressed in microglia at the site of spinal cord injury. Inhibition of SHP2 expression using siRNA and SHP2 inhibitors attenuated the microglial inflammatory response in an in vitro lipopolysaccharide-induced model of inflammation. Notably, after treatment with SHP2 inhibitors, mice with spinal cord injury exhibited significantly improved hind limb locomotor function and reduced residual urine volume in the bladder. Subsequent in vitro experiments showed that, in microglia stimulated with lipopolysaccharide, inhibiting SHP2 expression promoted M2 polarization and inhibited M1 polarization. Finally, a co-culture experiment was conducted to assess the effect of microglia treated with SHP2 inhibitors on neuronal cells. The results demonstrated that inflammatory factors produced by microglia promoted neuronal apoptosis, while inhibiting SHP2 expression mitigated these effects. Collectively, our findings suggest that SHP2 enhances secondary inflammation and neuronal damage subsequent to spinal cord injury by modulating microglial phenotype. Therefore, inhibiting SHP2 alleviates the inflammatory response in mice with spinal cord injury and promotes functional recovery postinjury

Morphological and Molecular Characterization of Trichoderma Isolates from Vegetable Crop Rhizospheres in Nepal [version 2; peer review: 1 approved, 2 approved with reservations]

Background Trichoderma spp. hold significant potential as biocontrol agents in agriculture due to their antagonistic properties against plant pathogens. The study aimed to characterize and identify Trichoderma isolates from rhizospheric regions of vegetable crops. Methods In this study, Trichoderma isolates were collected from rhizospheric soil samples of vegetable crops from different ecological zones and were selected for comprehensive morphological and molecular characterization. The isolates were visually assessed for colony color, growth pattern, aerial mycelium presence, phialide and conidial morphology, and chlamydospore presence. Molecular analysis was employed based on ITS and tef-1α sequences. Diversity indices were also computed for different ecological zones. Results The morphological characteristics and phylogenetic trees for both regions provided a clear species resolution, with four main clades: Harzianum, Viride, Brevicompactum and Longibrachiatum with 12 species T. harzinaum, T. afroharzianum, T. lentiforme, T. inhamatum, T. camerunense, T. azevedoi, T. atroviride, T. asperellum, T. asperelloides, T. koningii, T. longibrachiatum and T. brevicompactum and nine species as a new country record. Diversity indices indicated that high mountain regions displayed the highest species diversity and evenness (H = 1.724 [0.28], J = 0.84, D = 0.28), followed by hilly regions (H = 1.563 [0.28], J = 0.72, D = 0.28). Plains, on the other hand, exhibited lower species diversity (H = 1.515, J = 0.66, D = 0.33). The calculated species abundance values showed that plains (E = 2.11), mid-hills (E = 1.95), and high mountains (E = 1.99) each had their unique diversity profiles. Notably, T. afroharzianum and T. asperellum were predominant. Conclusions Overall, the study unveiled a rich diversity of Trichoderma species in different agricultural zones of Nepal. These findings shed light on the ecological distribution and diversity of Trichoderma spp., which could have significant implications for sustainable agriculture and biological control strategies

Assessing the stability of psychobiological stress reactivity during adolescence: mixed-effect modelling of cortisol responses to laboratory stressors [version 2; peer review: 2 approved]

Background Puberty has been historically considered as a time of risk and vulnerability for young people. It is associated with rapid development in the hypothalamus, which is central in the production of both stress and sex steroids. While patterns of stress reactivity are calibrated in early life, this time of rapid development may provide a means for these patterns to change. This purpose of this study was to examine whether patterns of cortisol reactivity remained stable across one year of pubertal development, and whether variations in pubertal development impacted on this stability. Methods This study used a secondary dataset comprised of 102 adolescent-aged children and adolescents. Children and adolescents took part in the Trier Social Stress Test to elicit a physiological stress response. Cortisol reactivity was measured as the increase in salivary cortisol concentration taken at five time points throughout the session. Pubertal stage was measured by nurse report where possible, and parent/self-report otherwise and was used to calculate pubertal timing and tempo relative to peers. Measures of anxiety, BMI, and socio-economic status were taken and included in analysis. Results Results of a linear mixed-effect model found there to be a significant difference in cortisol reactivity over time, indicating that cortisol stress reactivity did not remain stable during this time (Estimate= 3.39, t=3.67, p<.001, CI[1.56, 5.22]). Additionally, results show children and adolescents who developed slower/quicker than peers displayed decreased stress reactivity (Estimate= -3.59, t=-2.13. p=.03, CI[-6.92, -0.25]). Conclusions This research contributes to a relatively small but consistent body of research noting pattern of increased cortisol reactivity during pubertal development. While a significant effect was found for pubertal tempo, this finding should not be considered indicative of any true effect

Computational evaluation on spectroscopic (FT-IR, Raman), electronic and biological, and NLO properties of cirsilineol by DFT, ADMET, and molecular docking method

Cirsilineol is a natural product that has pharmacological characteristics and is used to prevent the growth of cancer. This study aims to investigate the spectroscopic, electronic, and biological properties of drugs and predict their suitability for drug-like candidates to inhibit prostate cancer. The computational evaluation was performed with density functional theory (DFT) at B3LYP/6−311++G(d,p) level of theory and drug-like characteristics rendered from ADMET analysis. Spectral measurement for IR and Raman provided evidence of intra-molecular hydrogen bonding of the OH group in ring R1. The electronic transition properties of the title compound were determined using TD-DFT with a polarized continuum model in solvent ethanol, resulting in a blue shift in absorption wavelength. The electrostatic potential mapped with the van der Wall surface predicted effective electrophiles and nucleophiles, allowing for the layout of intra- and intermolecular hydrogen bonds. The pharmacological properties of cirsilineol determined by ADMED analysis confirmed that it is non-toxic. To assess the biological performance of cirsilineol, molecular docking was performed with protein codes 1E3G and 1GS4, which showed inhibition action with binding affinity −7.7 and −7.8 kcal/mol, respectively

A Speed-Invariant Template-Based Approach for Estimating Running Temporal Parameters Using Inertial Sensors

Segmentation of running data into gait cycles and stance/swing phases is crucial for evaluating running biomechanics. The benefit of magneto-inertial sensors is their ability to capture data in outdoor conditions. However, state-of-the-art inertial-based methods for estimating running temporal parameters are limited to a restricted range of running speeds and, thus, not able to analyze running at variable speeds. This limitation prevents their use for real-world analysis for a wide range of runners and for sports disciplines where athletes vary their running speed. This study evaluated the speed-dependance of eight relevant foot-mounted inertial-based methods from previous research and proposed a novel method that could be robust to speed changes. The proposed method applied, for the first time, a template-matching algorithm based on dynamic time warping to running analysis and compared it to existing methods. All the implemented methods were tested on 30 runners at different speeds ranging from jogging to sprinting (8 km/h, 10 km/h, 14 km/h, 19-30 km/h) on both treadmill and overground. The most speed-robust performance was achieved by the proposed template-based method, providing estimation errors below 0.1% in stride, between 7%-19% in stance, and between 3%-6% in swing across running speeds. Conversely, all the tested methods from the literature were significantly speed-dependent. Thus, this study suggested that template-based approach is a valid solution for the inertial-based estimation of temporal parameters during running from slow jogging to fast sprinting. MATLAB codes and templates have been made available online

Transforming 5G Mega-Constellation Communications: A Self-Organized Network Architecture Perspective

With the widespread adoption of 5G as a communication standard, satellite mega-constellations have emerged as viable alternatives and complement terrestrial networks, offering extensive and reliable communication services across a broad spectrum of users and applications. These constellations are already equipped with inter-satellite links and adaptable payloads capable of supporting Radio Access Network (RAN) and core network functionalities, forming complex space-based networks characterized by overlapping layers of multi-orbit, grid-like topologies that undergo continuous, yet predictable, changes&#x2014;peculiarities not currently addressed within the 5G standards framework. To cope with this technology gap, this paper introduces a novel architecture for 5G services relying on satellite mega-constellations, which adhere to the principles of self-organized networks. This architecture is designed to align seamlessly with 5G service requirements, while also accommodating the unique topological and infrastructural constraints of mega-constellations. In more detail, the paper first outlines the fundamental principles of self-organizing networks that facilitate real-time system adaptation to internal topological shifts and external fluctuations in service demand. Then, we detail a 5G network architecture incorporating these principles, which includes 1) dynamic placement and migration of radio and core network control plane functions, 2) the strategic positioning of the data path, service, and AI decision functionalities to improve end-to-end service quality and reliability, and 3) the integration of dynamically established multi-connectivity options to increase the overall service dependability. These innovations aim for a seamless integration of space-based networks with terrestrial counterparts, creating a robust, cost-effective convergent telecommunication system

Endophytic fungi isolated from Vietnamese nut grass (Cyperus rotundus L. Cyperaceae) – A promising solution to mitigate the prime phenomenon of antibiotic resistance

Multidrug resistance in bacteria poses a significant threat to global health, creating an urgent need for new sources of antibiotics. Nut grass or Cyperus rotundus L., a common Asian medicinal herbal remedy, is gaining increasing attention in the scientific community as a potential source of antimicrobial agents. In this study, endophytic fungi living in this plant were isolated, macro- and micrologically identified, and assessed for their antibacterial properties on both Gram-positive and Gram-negative bacteria. As a result, seven types of endophytic fungi with potential antibacterial activities were obtained from Vietnamese Cyperus rotundus L. These endophytic strains could inhibit Gram-positive bacteria, including Bacillus subtilis, Methicilin-susceptible Staphylococcus aureus (MSSA), and Methicilin-resistant Staphylococcus aureus (MRSA). In particular, the most potent fungus could effectively inhibit not only MRSA but also Escherichia coli, and Pseudomonas aeruginosa. Furthermore, a significant impact of the culture medium on the biomass’ antibacterial activity was observed and the Potato Dextrose Agar (PDA) and Czapek-Dox (Cz) media were shown to be the most appropriate culture medium. Altogether, endophytic fungi isolated from Cyperus rotundus L. were shown to be a promising source for antibiotics to tackle the problem of antibiotic resistance

The effect of sleep quality on learning engagement of junior high school students: the moderating role of mental health

IntroductionA good quality of sleep is not only an important guarantee for students’ academic life, but also an important founding condition for their physical and mental health development. The study aims to explore the relationship between sleep quality and students’ learning engagement, and to deeply analyze the moderating role played by mental health.MethodsA questionnaire survey was conducted among some junior high school students in Rizhao City, Shandong Province for the research.ResultsThe results show that: (1) The main effect of sleep quality on learning engagement is significant (β = 0.476, t = 1.829, p &lt; 0.001), specifically, the better the sleep quality, the higher the students’ learning engagement. (2) The influence of sleep quality on learning engagement is moderated by mental health (β = –0.850, t = -2.652, p = 0.006), that is to say, the influence of sleep quality on learning engagement is more significant for students with poor mental health, and mentally healthy students can effectively alleviate the negative impact of sleep problems on their learning engagement.DiscussionResearch shows the significance of good sleep quality and mental health for students’ learning. The research results provide empirical evidence for schools, families, and policy makers to improve students’ academic achievement and mental health

CONDIȚIILE REALIZĂRII DREPTULUI DE INTENTARE A CAUZEI CIVILE PRIVIND INSTITUIREA, REÎNNOIREA ȘI REVOCAREA MĂSURILOR DE OCROTIRE JUDICIARĂ

Accesul la justiție este un drept fundamental al persoanelor, însă acest drept nu este unul absolut putând fi limitat prin stabilirea anumitor condiții de admisibilitate. Așadar, realizarea dreptului de intentare a procesului civil este determinat de întrunirea anumitor premise și condiții stabilite de lege. În prezentul articol științific ne propunem să abordăm problema condițiilor realizării dreptului de intentare a cauzei de instituire, reînnoire și revocare a măsurilor de ocrotire judiciară. Cuvinte-cheie: măsuri de ocrotire judiciare, condiții, intentarea procesului, restituirea cererii. DOI: https://doi.org/10.59295/sum8(178)2024_0

Structural, Morphological and Thermal Properties of Kenaf Microcrystalline Cellulose/Poly (Butylene Adipate-Co-Terephthalate) Films for Packaging Applications

The aim of this work is to use microcrystalline cellulose (MCC), obtained from kenaf fibers by using eutectic green solvents, to build compostable packaging films by adding them to Poly (butylene adipate-co-terephthalate) (PBAT). In this study, microcrystalline cellulose was incorporated into PBAT composites through melt-mixing, followed by hot pressing at 130°C. PBAT and MCC were produced in various formulations (0.5, 1, 1.5 wt%) to enhance and sustain inherent characteristics of films. The structural, morphological, thermal, and tensile properties of PBAT and microcrystalline cellulose film were examined using X-ray Diffraction, Scanning electron microscope (SEM), Thermal analysis, and Universal Testing Machine. The uniform dispersion of MCC within the PBAT matrix significantly contributes to improved thermal stability, as evidenced by delayed degradation, and enhanced heat resistance. SEM makes it evident that addition of MCC to PBAT influences the surface morphology, with an optimal range promoting mechanical adherence through roughness. However, excessive MCC content leads to imperfections such as cavities, potentially compromising material performance. The inclusion of MCC content enormously raised the tensile modulus of the PBAT/MCC film, increasing its stiffness while tensile strength decreased on addition of MCC in PBAT/MCC formulations. Cellulose film could potentially be used as a biodegradable film in food packaging applications