Significant Increase In Activity Research Articles

Structural, Spectroscopic, and Docking Analysis of N,O-Donor Ligand Metal Complex Nanoparticles with Hypolipidemic Effects via Lipoprotein Lipase Activation in High-Fat Diet Mice.

New Cd(II), Zn(II) and Cu(II)-chelates with cetirizine.2HCl (CETZ.2HCl) in incidence of 1,10 phenanthroline monohydrate (Phen.H2O) were synthesized in search of new biologically active compounds. The ligands and their chelates were described by 1H NMR, FT-IR, elemental analysis, UV-vis. spectrophotometry, thermal-analyses, molar conductance, X-ray-diffraction (XRD) and magnetic-susceptibility measurements. FT-IR demonstrated that CETZ.2HCl is bonded with metal ions, as a monodentate via carboxylate oxygen atom and Phen.H2O chelated via two nitrogen atoms. The molar conductivity data showed that the complexes were non-electrolytes, while XRD data supported that the compounds were crystalline. Density functional theory-(DFT) was utilized to gain insight into the compounds' optimized design. The effects of CETZ.2HCl and the complexes on the activity of Lipoprotein-(L)-lipase activity in mice were investigated. Unlike Cd(II) complex, all the other compounds exhibited significant increase in lipase activity, with reduction in triglycerides. Cu(II) and Zn(II) complexes showed robust hypolipidemic efficacy evidenced by lower levels of total cholesterol and LDL, concomitant with higher levels of HDL. Furthermore, Zn(II) complex was a safe alternative since it has a lower liver toxicity. Molecular docking demonstrated that Cu(II) and Zn(II) chelates exhibited greater affinities to lipase than the parent ligand. Finally, Cu(II) complex showed the highest antibacterial activity.

Signaling pathways mediating the induction of preharvest fruit drop in litchi

Certain litchi varieties, such as “Nuomici”, are highly susceptible to preharvest fruit drop, which leads to significant losses in fruit yield and economic value. However, the precise molecular mechanisms underlying this issue are not yet fully understood. In this study, we aimed to elucidate the signaling pathways that facilitate preharvest fruit drop in litchi, using “Nuomici” and “Huaizhi” cultivars as examples, which demonstrate high and low preharvest fruit drop rates, respectively. Our findings revealed that “Nuomici” experienced a substantial preharvest fruit drop, with a cumulative rate of 41.68%, significantly higher than the 1.44% observed in “Huaizhi”. Cellulase activity assays showed a significant increase in cellulase activity in the abscission zone of “Nuomici”, which coincided with the occurrence of preharvest fruit drop, in contrast to the relatively low levels in “Huaizhi”. Phytohormone assays indicated lower indole-3-acetic acid content in the pericarp, aril, and seeds of “Nuomici” during the preharvest stage compared to “Huaizhi”, coupled with higher abscisic acid levels in the seeds of “Nuomici”. Furthermore, transcriptomic analysis identified 180, 282, 655, and 241 differentially expressed genes (DEGs) in the pericarp, aril, seed, and abscission zone, respectively, between the two cultivars during preharvest fruit drop. These DEGs are intricately involved in the generation and transmission of abscission signals from fruit tissues, encompassing PIN, PIN-LIKES, LAX, and SAUR genes related to polar auxin transport, ethylene diffusion, as well as perceiving these signals and activating the abscission process within the abscission zone. This includes ACO and ILR genes involved in hormone biosynthesis and signal transduction, regulation by WRKY, NAC, and bHLH transcription factors, AAO genes involved in response to reactive oxygen species, and EXP, EG, and PG genes involved in cell wall degradation in the abscission zone. Based on these comprehensive findings, we propose a model for preharvest fruit drop triggered by a series of molecular events in litchi, providing valuable insights into the complex mechanisms governing this phenomenon.

Construction of novel magnetic systems for cancer immunotherapy via cancer-immunity cycle circuits.

The tumor microenvironment (TME) is enriched with immunosuppressive factors that inhibit the recruitment and activation of dendritic cells (DCs), thereby reducing the efficacy of tumor immunotherapy. To address this challenge, we propose an innovative strategy involving the sequential administration of MCM magnetic nanoparticles carrying PROTAC drugs (MCM/ARV) and M-BMDCs in the TEM. This approach not only replenishes DCs in the TEM, but also increases antigen uptake through the attraction between the magnetic particles and promotes DC activation and antigen presentation, thus continuously enhancing the tumor immune cycle. MCM nanoparticles (magnetic nanoclusters coated with calcium-doped manganese carbonate) efficiently load the tumor-targeting drug PROTAC (ARV-825), enhancing its bioavailability, leading to specific degradation of BRD4 in tumor cells, and releasing a large number of tumor-associated antigens. These antigens were captured by MCM nanoparticles to construct magnetized tumor vaccines. Magnetic M-BMDCs introduced at the tumor site are attracted to these magnetized vaccines, resulting in a significant increase in antigen uptake and activation of DCs, significantly enhancing the tumor immune cycle. This co-administration strategy of magnetized vaccines and magnetized BMDCs provides a unique combination therapy for reversing immunosuppressive TEM and enhancing the efficacy of tumor immunotherapy.

The Transformative Patent Landscape in Saudi Arabia Since the Saudi Vision 2030 Announcement

This study analyzes the patent landscape of Saudi Arabia from the announcement of Saudi Vision 2030 in late April 2016 to September 2024, utilizing the Patsnap database to evaluate patent grants across various organizations. The findings reveal a gradual increase in patent registrations, with Saudi Aramco leading in patent grants, followed by King Faisal University (KFU), King Fahd University of Petroleum and Minerals (KFUPM), King Abdullah University of Science and Technology (KAUST), and King Abdulaziz University (KAU). SABIC, a prominent industry player in Saudi Arabia, has registered most of its patents using its European Head Office address and holds extensive collaborations with international partners, generating numerous patents. The analysis identifies the top patent offices where KSA organizations seek protection, including the United States Patent and Trademark Office (USPTO), Saudi Authority for Intellectual Property (SAIP), European Patent Office (EPO), the China National Intellectual Property Administration (CNIPA), and the German Patent and Trade Mark Office. However, the limited number of registrations at the SAIP highlights a need for improvement. The primary application domains encompass borehole/well accessories, measurement devices, organic chemistry, computing, and chemical/physical processes. The landscape reveals that Saudi Aramco and KFUPM focus predominantly on upstream and downstream technologies, while KAU, KFU, and KAUST concentrate on life sciences. Key findings indicate a significant increase in patent activity since the vision announcement, suggesting a growing focus on innovation within Saudi Arabia. However, the concentration of patents among a few major players (Saudi Aramco and SABIC) and the underrepresentation of patents filed with the Saudi Authority of Intellectual Property (SAIP) highlight areas for improvement. This study emphasizes the necessity to support small and medium enterprises (SMEs) and healthcare research institutions to foster broader participation in innovation and protect novel technologies. This research contributes valuable insights into the current state of patenting activities in Saudi Arabia and outlines opportunities for enhancing the country’s innovation ecosystem.

Integrated transcriptomic and metabolomic analyses uncover the key pathways of Limonium bicolor in response to salt stress.

Salinity significantly inhibits plant growth and development. While the recretohalophyte Limonium bicolor can reduce its ion content by secreting salt, the metabolic pathways it employs to adapt to high salt stress remain unclear. This study aims to unravel this enigma through integrated transcriptomic and metabolomic analyses of L. bicolor under salt stress conditions. The results showed that compared to the control (S0), low salt treatment (S1) led to a significant increase in plant growth, photosynthesis efficiency and antioxidant enzyme activity but caused no significant changes in organic soluble substance and ROS contents. However, high salt treatments (S3 and S4) led to a significant decrease in plant growth, photosynthesis efficiency and antioxidant enzyme activity, accompanied by a significant increase in organic soluble substance and ROS contents. A significant increase in phenolic compounds, such as caffeoyl shikimic acid and coniferin, upon the treatments of S1, S3 and S4, and a decrease and increase in flavonoids upon the treatments of S1 and S3 were also observed, respectively. This study also demonstrated that the expression patterns of key genes responsible for the biosynthesis of these metabolites are consistent with the observed trends in their accumulation levels. These results suggest that under low salt stress conditions, the halophyte L. bicolor experiences minimal osmotic and oxidative stress. However, under high salt stress conditions, it suffers severe osmotic and oxidative stress, and the increase in organic soluble substances and flavonoids serves as a key response to these stresses and also represents a good strategy for the alleviation of them.

Antioxidant, metabolic and digestive biomarker responses of farmed Sparus aurata supplemented with Laminaria digitata

The present study aimed to investigate the effectiveness of supplemented diets with the brown macroalga Laminaria digitata in improving the antioxidant, metabolic and digestive performance in gilthead seabream (Sparus aurata), using a multi-biomarker approach. Three experimental diets supplemented with 1.5 %, 3 % and 6 % of dried powdered L. digitata were tested against a control diet. After 30 and 60 days, S. aurata juveniles were sampled and muscle, gut and liver tissues were collected. Results showed that fish fed with 1.5 % L. digitata exhibited higher specific growth rate (SGR) after 30 days. Additionally, at this supplementation level, there was a significant reduction in antioxidant enzyme activities (catalase, CAT; glutathione S-transferase, GST; superoxide dismutase, SOD) and in lipid peroxidation (LPO) in muscle and liver tissues. In contrast, gut antioxidant enzyme activity increased with higher macroalga concentrations (3 % and 6 %). Fish fed with 6 % L. digitata revealed a significant decrease in muscle aerobic potential (citrate synthase (CS) activity) but increased anaerobic capacity (lactate dehydrogenase (LDH) activity). Moreover, the 1.5 % L. digitata supplemented diets led to a significant increase in amylase activity after 30 days. After 60 days, fed with 6 % L. digitata showed lower hepatosomatic index (HSI) compared to animals fed on control diet. Additionally, trypsin activity was higher in fish fed the supplemented diets, especially at 3 % L. digitata. Pepsin activity was significantly supressed in fish fed diets with higher macroalga concentrations (3 % and 6 %). Overall, the current findings highlight the beneficial effects with lower doses of L. digitata on farmed marine fish performance and welfare. However, additional research is needed to establish the most cost-effective seaweed supplementation dose and validate this strategy at an industrial scale.

Expanding the therapeutic window of gramicidin S towards a safe and effective systemic treatment of methicillin-resistant S. aureus infections

The rise of multidrug-resistant bacteria, such as Methicillin-resistant Staphylococcus aureus (MRSA), necessitates the development of new antibacterial therapies. Antimicrobial peptides offer a promising alternative to conventional antibiotics due to their unique mechanisms of action. Gramicidin S exhibits potent bactericidal activity against S. aureus, however, high haemolytic toxicity currently limits its application to topical use. A new series of gramicidin S analogues is presented with rational modifications to the β-turn and β-strand regions, to reduce haemolytic and nephrotoxic effects, while preserving antibacterial potency. The minimum inhibitory concentration (MIC) for each analogue was determined against benchmark methicillin-sensitive S. aureus (MSSA) and MRSA clinical isolates, with toxicity characterised in vitro using human red blood cells and human embryonic kidney cells (HEK-293). Peptide 12 demonstrated a significant two-fold increase in antibacterial activity against both MSSA and MRSA (MIC: 2 μg/mL) compared to gramicidin S (MIC: 4 μg/mL), albeit with increased cytotoxicity. Similarly, peptide 15 showed exceptional efficacy (MIC: 3 μg/mL), but with reduced cytotoxicity, culminating in a two-fold improvement to the therapeutic index (TI) of gramicidin S. Peptides 14 (HC50: 50.48 ± 1.15 μg/mL, IC50: 38.09 μg/mL) and 16 (HC50: 84.09 ± 1.02 μg/mL, IC50: 12.60 μg/mL) also significantly reduced haemolytic toxicity and nephrotoxicity, compared to gramicidin S (HC50: 12.34 ± 0.27 μg/mL, IC50: 6.45 μg/mL). Detailed NMR, CD and computational modelling were used to provide critical insights into how molecular conformation influences both antibacterial potency and cytotoxicity. Collectively, these results expand the therapeutic window of gramicidin S by up to 12-fold, with negligible cytotoxicity observed at concentrations well beyond the acceptable safety threshold, which indicates the potential for safe systemic administration in the treatment of infection caused by resistant pathogens.

Методология оценки выбросов парниковых газов от судоходства в Арктике

In recent years, there has been a significant increase in maritime economic activity in the Arctic zone of the Russian Federation. The intensification of shipping in the Arctic waters leads to an increase in greenhouse gas emissions, for the accurate assessment of which there are currently no effective tools. The study proposes a methodology for the general quantification of emissions from shipping in a specific water area, based on the use of AIS data from satellite systems. Using the proposed approach, the authors for the first time have assessed and analyzed the structure of shipping traffic as a source of emissions and established the dynamics and volumes of greenhouse gas emissions in a specific area of the Arctic water area.

An Extensive Analysis of Current Software Defined Network Optimization Techniques

In the modern, technologically advanced era, the use of devices connected to the Internet has increased exponentially. This has led to a significant increase in Internet activity. Network scalability, low levels of service, and the need to manage a large number of clients on a single server (which can lead to denial of service (DOS) attacks) are just a few of the consequences of increased traffic if you are a load balancer, . A method proposed in the literature. Although load balancers are popular, studies have shown that they have a few drawbacks, such as not being programmable and exclusive to a single vendor to overcome these issues and the subsequent increase in Internet traffic saw the emergence of Software Defined Networking (SDN) as a paradigm shift. Software defined networking (SDN) enables programmable load balancers and gives customers the freedom to develop and implement their own load-balancing algorithms this exam covers the origins of software-defined networking (SDN) and Open Flow, with impact on weight and density so included. In this article, we will go through various SDN load balancing techniques. This review builds on existing research challenges, their answers, and possible future research directions. Load balancing in intelligent software-defined (SDN) algorithms is typically performed using mathematical tools. Finally, we detail the metrics used to evaluate the performance of the algorithms.

Implementasi Metode Stad (Student Teams Achievement Division) Berbantuan Media Video Interaktif untuk Meningkatkan Keaktifan Siswa Kelas XI-7

This study aims to increase the creativity of grade XI students at SMAN 2 Batu byimplementing the Student Teams Achievement Division (STAD) Method with the help ofinteractive video media. The STAD method is a cooperative learning type method thatemphasizes interaction between students to motivate each other and help each other inmastering the material optimally. This research is a Classroom Action Research (PTK). The data collection techniques used are observation, documentation studies and tests. The results showed that the implementation of the STAD method with the help of interactive video media had a positive impact on increasing the activeness of grade XI students of SMAN 2 Batu. Students who participated in learning with the STAD method and learning video media showed a significant increase in individual and group student learning activity by 28% and 58%.

Menciptakan Lingkungan Belajar yang Menyenangkan untuk Meningkatkan Keaktifan Siswa Kelas III SDN Gempol Kolot 2

This study aims to create a fun learning environment to increase student activity in the third grade at SDN Gempol Kolot 2. The study used a classroom action research method with two cycles. Each cycle consists of planning, implementation, observation, and reflection stages. The results showed a significant increase in student activity after the implementation of more fun and interactive learning. In the first cycle, student participation in class discussions was only 60%, while in the second cycle it increased to 85%. Involvement in group activities also increased from 65% to 90%, and responses to learning materials increased from 55% to 80%. Additionally, students showed an increase in the desire to ask questions, rising from 50% to 75%. This study concludes that a fun learning environment can enhance student activity, positively influencing the quality of learning.

Defense-related enzymes associated with resistance to onion Fusarium basal rot

This study was carried out to quantify changes in the activities of antioxidative enzymes such as catalase (CAT), peroxidase (POX) and superoxide dismutase (SOD) in two resistant onion cultivars 'Saba - HS' and 'Saba' and two susceptible cultivars 'Golden Eye' and 'Savannah Sweet' following an inoculation with Fusarium oxysporum f. sp. cepae (FOC) at seedling stage. Further, we assessed the expression of transcription factors (TFs), R1, PR5 and RGA29-genes that are involved in conferring resistance post-inoculation using qRT-PCR. The results revealed that the least disease severity occurred with the resistant 'Saba - HS' (4.7%) and 'Saba' (6.7%) cultivars, whereas the highest disease severity occurred with the susceptible 'Golden Eye' (89.6%) and 'Savannah Sweet' (88.9%) cultivars, respectively. Both resistant genotypes 'Saba' and 'Saba-HS' showed a significant increase in CAT, POX, and SOD activities at a transcriptional level. CAT activity was upregulated 4.81-fold in 'Saba' and 4.22-fold in 'Saba-HS' followed by POX where 'Saba' showed an increase by 3.53-fold and 'Saba-HS' by 2.35-fold, and SOD 'Saba' 17.46-fold and 'Saba-HS' 22.95-fold, relatively. Marker genes, RGA29, R1 and PR5, were also upregulated in the resistant-genotypes by 3.83, 4.78 and 5.01-fold, in comparison to their-controls, respectively. Similar trends were recorded for the biomass growth parameters (BGPs).

SPP1 mRNA Expression Is Associated with M2 Macrophage Infiltration and Poor Prognosis in Triple-Negative Breast Cancer

(1): Triple-negative breast cancer (TNBC) is an especially aggressive form of breast cancer defined by a poor prognosis and a lack of effective treatment options. There is a pressing need for validated predictive and prognostic biomarkers to assist in making treatment decisions and improve the prognostic accuracy for patients with this challenging disease. (2): We analyzed the RNA-seq data from three TNBC tissue samples alongside their corresponding normal tissues. Gene set enrichment analysis (GSEA) identified potential pathways. Additionally, we examined SPP1 mRNA expression datasets available in the Kaplan–Meier plotter and investigated the SPP1 protein expression patterns in our own tissue microarray cohort via immunohistochemistry. (3): The results revealed that genes associated with the Toll-like receptor signaling pathway showed a significant increase in activity in TNBC tissues when compared to normal breast tissues. Furthermore, SPP1 expression was found to be elevated in the TCGA TNBC dataset and correlated with a poor prognosis. This pattern was corroborated at the protein level in our TNBC tissue cohort; however, SPP1 protein expression did not demonstrate a significant impact on survival. Notably, SPP1 mRNA expression was strongly linked to tumor-associated macrophages (TAMs), particularly the M2 macrophage subtype, indicating a substantial association in the context of TNBC. (4): Our research highlights the significance of SPP1 mRNA as a key prognostic indicator and a potential molecular responder for TNBC treatment utilizing targeted therapies that focus on Toll-like receptor signaling pathways.

Educational Sector Financing and Economic Wellbeing

This study examines the relationship between educational Sector financing and economic wellbeing in Nigeria, focusing on government funding, private domestic investment, and foreign expenditure in education. The study employs econometric techniques to analyze the long-term dynamics of educational financing on the Human Development Index (HDI). The findings reveal a significant increase in educational financing activities over time, particularly in domestic funding. However, despite the growth in funding, there is evidence of underemployment among educated individuals, suggesting a disconnect between educational investments and economic outcomes. Co-integration analysis indicates a long-term relationship between government educational financing and human development. The reliance on government funding for education underscores the need for effective resource management and targeted interventions to address gaps in the education system. Keywords: Educational financing, economic development, Nigeria, government funding, private investment.

Toxicological assessment of the effects of CuCl2 and CuO nanoparticles on early developmental stages of the South American toad, Rhinella arenarum by standardized bioassays.

The release in aquatic environments of emergent contaminants such as copper oxide nanoparticles (CuO-NPs) has generated concerns on their short- and long-term toxicity and the potential risk for more vulnerable animal groups, such as amphibians. In this sense, the aim of this work was to evaluate the toxicity of CuO-NPs in comparison with its respective salt (CuCl2) in embryos and larvae of a native amphibian, Rhinella arenarum, by acute (96h) and chronic (504h) standardized bioassays. Lethality and sublethal effects such as developmental, morphological, and ethological alterations were assessed in a wide range of concentrations (0.001-100mg/L). Neurotoxic effects by acetyl (AChE) and butyrylcholinesterase (BChE) activity levels and changes in the lipid content were also assessed at sublethal concentrations. Results showed that CuCl2 caused higher lethality than CuO-NPs in both developmental periods. Embryos were more sensitive than larvae with LC50-96h = 0.080mg CuCl2/L and 1.26mg CuO-NPs/L and 0.21mg CuCl2/L and 20.17mg CuO-NPs/L, respectively. At acute exposure, embryos exhibited several developmental abnormalities such as developmental delay, edema, axial flexure, and microcephaly. Larvae presented spasmodic contractions and weak movements. Regarding neurotoxicity, a significant increase in AChE activity at low concentrations as well as an inhibition of BChE activity at all tested concentrations was evidenced for both substances at acute exposure. Moreover, an increment in phospholipid and triglyceride levels was observed at the highest concentration of CuO-NPs (10mg/L) at chronic exposure. The chromatographic separation of lipids showed no apparent differences in acylglycerols and free fatty acid bands, between the treatments and the control. The differences in toxicity between CuO-NPs and CuCl2 could be due to structural and physicochemical characteristics that influence their bioavailability and toxicity. Considering the exponential growth in the production and use of these substances, it is expected that the levels of contamination will rise considerably in the future, so that wildlife, particularly aquatic organisms, will be more increasingly exposed, representing a potential risk for their populations.

Organophosphate Insecticide Malathion Induces Alzheimer's Disease-Like Cognitive Impairment in Mice: Evidence of the Microbiota-Gut-Brain Axis.

Evidence suggests that exposure to organophosphate pesticides increases the risk of neurodegenerative diseases, but the mechanisms remain unclear. This study investigated the effects of malathion on Alzheimer's disease (AD)-like symptoms at environmentally relevant concentrations using wild-type (WT) and APP/PS1 transgenic mouse models. Results showed that malathion exposure induced AD-like cognitive impairment, amyloid-β (Aβ) accumulation, and neuroinflammation in WT mice, with worsened symptoms in APP/PS1 mice. Mechanistic studies revealed that malathion induced AD-like gut microbiota dysbiosis (reduced Lactobacillus and Akkermansia, and increased Dubosiella), causing gut barrier impairment and tryptophan metabolism disruptions. This resulted in a significant increase in indole derivatives and activation of the colonic aryl hydrocarbon receptor (AhR), promoting the kynurenine (KYN) pathway while inhibiting the serotonin (5-HT) pathway. Increased neurotoxic KYN metabolites (3-hydroxykynurenine and quinolinic acid) triggered gut and systemic inflammation, upregulating hippocampal IL-6 and IL-1β mRNA levels and thereby causing neuroinflammation. Gut tryptophan metabolism disruptions caused hippocampal neurotransmitter imbalances, reducing the levels of 5-HT and its derivatives. These effects promoted AD progression in both WT and APP/PS1 mice. This study highlights the crucial role of the microbiota-gut-brain axis in AD-like cognitive impairment induced by malathion exposure, providing insights into the neurodegenerative disease risks posed by organophosphate pesticides.

Effects of Raised Heel Insole on Muscle Activity during ankle Sudden Inversion in Normal Adults

Raised heel insoles increase the plantar flexion angle of the ankle and cause ankle inversion sprain. The purpose of this study was to artificially create an ankle sudden inversion situation, which is a mechanical situation of actual ankle joint damage, and investigate the effect of the raised heel insole on ankle joint muscle activity. The subjects of this study were forty subjects with normal adults. The subjects performed sudden ankle inversion on the trapdoor with no raised heel insole, insole heights of 3cm, and insole heights of 7cm. The application of the raised heel insole was conducted randomly. The subjects performed the trapdoor test three times using dominant feet with a 60-second rest period between tests. This study assessed muscle activity during sudden ankle inversion three times. Raised heel insoles showed a significant decrease in Tibialis Anterior, Peroneus Longus, and Peroneus Brevis muscle activity than no raised heel insole (p<.05). Raised heel insoles showed a significant increase in Gastrocnemius muscle activity than no raised heel insole (p<.05). Raised heel insoles increase the risk of ankle sprain injury by reducing tibialis anterior and peroneus muscle activity during sudden ankle inversion.

In vitro bioprinted 3D model enhancing osteoblast-to-osteocyte differentiation

In vitrobone models are pivotal for understanding tissue behavior and cellular responses, particularly in unravelling certain pathologies' mechanisms and assessing the impact of new therapeutic interventions. A desirablein vitrobone model should incorporate primary human cells within a 3D environment that mimics the mechanical properties characteristics of osteoid and faithfully replicate all stages of osteogenic differentiation from osteoblasts to osteocytes. However, to date, no bio-printed model using primary osteoblasts has demonstrated the expression of osteocytic protein markers. This study aimed to develop bio-printedin vitromodel that accurately captures the differentiation process of human primary osteoblasts into osteocytes. Given the considerable impact of hydrogel stiffness and relaxation behavior on osteoblast activity, we employed three distinct cross-linking solutions to fabricate hydrogels. These hydrogels were designed to exhibit either similar elastic behavior with different elastic moduli, or similar elastic moduli with varying relaxation behavior. These hydrogels, composed of gelatin (5% w/v), alginate (1%w/v) and fibrinogen (2%w/v), were designed to be compatible with micro-extrusion bioprinting and proliferative. The modulation of their biomechanical properties, including stiffness and viscoelastic behavior, was achieved by applying various concentrations of cross-linkers targeting both gelatin covalent bonding (transglutaminase) and alginate chains' ionic cross-linking (calcium). Among the conditions tested, the hydrogel with a low elastic modulus of 8 kPa and a viscoelastic behavior over time exhibited promising outcomes regarding osteoblast-to-osteocyte differentiation. The cessation of cell proliferation coincided with a significant increase in alkaline phosphatase activity, the development of dendrites, and the expression of the osteocyte marker PHEX. Within this hydrogel, cells actively influenced their environment, as evidenced by hydrogel contraction and the secretion of collagen I. This bio-printed model, demonstrating primary human osteoblasts expressing an osteocyte-specific protein, marks a significant achievement. We envision its substantial utility in advancing research on bone pathologies, including osteoporosis and bone tumors.

Effects of benzophenone-3 on the liver and thyroid of adult zebrafish

1. Benzophenone-3 (BP-3), commonly known as oxybenzone, is an organic compound that acts as a sunscreen, protecting the skin from UVA and UVB rays. Thus, the objective of this study was to investigate the effects of BP-3 on the liver and thyroid using morphological and biochemical approaches. 2. Adult male zebrafish were randomly assigned to three groups, each with three repetitions (n = 10 per group): water control, solvent control (0.01% ethanol), and 1 μg/L of BP-3, using a static exposure system for 96 hours. After the experiment, histopathological analyses of the liver and thyroid were performed, along with histochemical analyses (glycogen) and biochemical evaluations of the antioxidant enzymes Superoxide Dismutase (SOD) and Catalase (CAT). 3. Exposure to BP-3 resulted in significant histopathological changes in the liver of Danio rerio, increasing the frequency of circulatory disturbances, progressive changes, inflammatory responses, and regressive changes. On the other hand, the thyroid gland did not show any morphological changes during exposure to BP-3, maintaining its typical structure with follicles. There was a significant increase in SOD activity, while CAT showed no changes after 96 hours of exposure. 4. The results obtained demonstrate that exposure to BP-3 causes significant morphophysiological changes in the liver of D. rerio, highlighting not only the negative impacts on the health of these organisms but also the ecotoxicological potential of the substance and its consequences for aquatic biota in contaminated environments.

Abstract 4117767: Interplay Between ST2 Gene Downregulation and Inflammatory Processes in Hypertrophic Cardiomyopathy

Introduction: Hypertrophic Cardiomyopathy (HCM) is an inherited heart disease and the pathogenesis of HCM involves genetic mutations, hemodynamic stress, and metabolic factors, with myocardial fibrosis playing a crucial role in severe clinical events. IL-33/ST2 signaling pathway known for its roles in immune response and tissue repair, participates in cardiac protection and anti-cardiac fibrosis in heart failure. The role of ST2 in HCM remains unclear, and IL-33/ST2 pathway and broader inflammatory responses may be critical in HCM. Hypothesis: ST2 gene downregulation and dysregulation of inflammatory pathways represent a novel mechanism in HCM. Methods: We re-analyzed the raw whole transcriptome sequencing data using a comprehensive bioinformatics pipeline from 9 GEO datasets. After removing low-quality samples, myocardial tissue samples from 109 HCM patients and 210 non-HCM controls were included. HTSeq-count was used to obtain the read count of each gene. Differential expression analyses were conducted using DESeq2. Spearman correlation analysis was performed for ST2 with all other protein-coding genes. Gene set enrichment analysis (GSEA) was performed to explore the biological significance of ST2 related genes. CIBERSORTx was used to estimate the immune cell composition of heart tissues. Additionally, network analyses and statistical correlations were conducted. Results: Our analysis identified significant downregulation of the ST2 gene in HCM patients compared to controls (log2FC = -5.0, p = 2.7E-147). In total, 5,180 upregulated and 741 downregulated genes were detected. Additionally, 208 genes were significantly correlated with the expression of ST2. GSEA based on the correlation coefficients revealed a significant increase in immune response, inflammation, and IFN-γ pathway activity, along with a decrease in the expression of genes related to sarcomeric function, cardiac morphogenesis, and metabolism in HCM. Notably, the significant inverse correlation between ST2 expression and regulatory T cells (r = -0.34) and a positive correlation with neutrophils (r = 0.39) suggest that ST2 may modulate immune cell populations in HCM. Pathway analysis indicated ST2's central role in networks involving inflammatory and fibrotic responses. Conclusion: The interplay between ST2 and inflammatory pathways may drive myocardial remodeling and fibrosis in HCM. This study paves a new way for investigating pathogenic mechanisms and therapeutic strategies for HCM.