Search Results (149,697)

Background: The progression of osteosarcoma is closely related to the immune microenvironment. Related studies have found that the RNA-binding motif protein, X-linked (RBMX), plays a regulatory role in modulating the biological characteristics of the tumor microenvironment (TME). However, its regulatory mechanism in osteosarcoma remains unclear. Methods: In this study, the expression of RBMX in osteosarcoma was analyzed using the results of bulk and single-cell transcriptome sequencing of human osteosarcoma. The RBMX knockout cell line was constructed via lentivirus transfection. The mouse subcutaneous implantable tumor model and single-cell transcriptome sequencing analysis revealed the effects of RBMX on the osteosarcoma microenvironment, as verified via multiplex immunofluorescence, flow cytometry, and PCR experiments. Results: Using the TARGET database and multiplex immunofluorescence, we found that RBMX is highly expressed in human osteosarcoma and is associated with poor prognosis. The high expression of RBMX may mediate the immunosuppressive microenvironment of human osteosarcoma. In vitro cell experiments showed that knockout of RBMX significantly inhibited the proliferation of mouse osteosarcoma cells. Through single-cell transcriptome sequencing analysis of subcutaneous implantable tumors in mice, we determined that RBMX deletion substantially elevated the recruitment of cytotoxic CD8⁺T cells within the mouse TME, which was further verified through flow cytometry analysis. Cell coculture assay confirmed that knockout of RBMX significantly enhanced the cytotoxic activity of CD8⁺T cells. Finally, cell communication and in vitro experimental verification revealed that knocking out RBMX might enhance the infiltration of CD8⁺T cells by upregulating histocompatibility 2, K1, and K region (H2-K1) and downregulating thrombospondin 1 (THBS1). Conclusions: This study may provide potential targets for reshaping the immune microenvironment of osteosarcoma and improving its therapeutic efficacy. Full article

Follicular development is recognized as a highly complex biological process regulated by multiple factors. Thyroid hormone (TH) is considered one of the key regulators of female reproduction, and its dysregulation can significantly impair follicular development. Epigallocatechin gallate (EGCG), the main active component of green tea, possesses strong antioxidant properties. Numerous studies have demonstrated that EGCG positively influences reproductive function in both humans and animals. However, whether EGCG directly affects follicular development under conditions of TH dysregulation remains poorly understood. The primary objective of this study was to investigate the impact of hyperthyroidism on ovarian development, examine whether EGCG could mitigate the adverse effects of TH dysregulation, and elucidate the underlying molecular mechanisms. In the T₄-induced hyperthyroidism rat model, ovarian tissues were serially sectioned for Hematoxylin-Eosin (HE) and Masson’s trichrome staining to assess morphological changes, and follicle numbers were quantified at each developmental stage. Granulosa cell (GC) viability, proliferation, and apoptosis induced by T₃ were evaluated using CCK8, EdU, and TUNEL assays, respectively. Antioxidant enzyme activity was measured, and the expression levels of related proteins were analyzed via Western blotting. Results showed that hyperthyroidism altered ovarian structure, significantly increasing the number of atretic follicles. Levels of antioxidant enzymes, including Superoxide Dismutase (SOD), Glutathione Peroxidase (GSH-PX), and Catalase (CAT), were markedly decreased, whereas the lipid peroxidation product malondialdehyde (MDA) was significantly elevated. Furthermore, all ERS-related proteins, phosphorylated Eukaryotic Initiation Factor 2 Alpha (p-eIF2α), Activating Transcription Factor 4 (ATF4), C/EBP homologous protein (CHOP), and Caspase-3, were upregulated, accompanied by decreased glucose-regulated protein 78 (GRP78) expression. Treatment with EGCG alleviated these detrimental effects of hyperthyroidism. At the cellular level, high concentrations of T₃ reduced GC viability and proliferation while increasing apoptosis. Reactive oxygen species levels were elevated, and GRP78 expression was decreased. Notably, all T₃-induced effects were reversed by EGCG treatment. In summary, this study demonstrates that hyperthyroidism induces oxidative stress in GCs, which triggers endoplasmic reticulum stress via the eIF2α/ATF4 pathway and leads to apoptosis. EGCG mitigates apoptosis by enhancing antioxidant capacity, thereby preserving ovarian function. These findings establish EGCG as a protective agent for maintaining ovarian health and fertility. Full article

Striatum can be described as a brain region containing a general neuronal mechanism to associate actions or events with reward. In particular, neural activity in the human striatum is modulated by social actions and, critically, by the conjunction of social actions and own reward. To perform this function, dopamine and oxytocin signaling reaching the striatum represent a key factor. These neurotransmitters, in both humans and animals, are released in response to afferent vagal and sensory stimulation, as well as sexual and social interactions, conveying information related to reward and pleasure associated with an event. Dopamine and oxytocin have several effects in common, but of particular interest is evidence indicating that they can mutually modulate their action. The present review focuses on available data delineating interactions between dopaminergic and oxytocinergic signaling in the striatum. In this context, recent data on the possible role played by striatal astrocytes and microglia as key modulators of this crosstalk will be briefly discussed. Full article

This study analyzed the use of a toolbox to evaluate the impact of agricultural activity on the water quality/status classification of a hydro-agricultural reservoir (Lage reservoir, Southern Portugal). The framework integrated the quantification of a group of 51 pesticides and ecotoxicological endpoints with organisms from different trophic categories (the bacterium Aliivibrio fischeri, the microalga Pseudokirchneriella subcapitata, and the crustaceans Daphnia magna and Thamnocephalus platyurus) at two sampling points in the reservoir (Lage (L) and Lage S (LS)) between 2018 and 2020. Over the three-year study, we quantified 36 of the 51 pesticides analyzed in the Lage reservoir. Total concentrations increased successively from 0.95 µg L⁻¹ to 1.99 and 2.66 µg L⁻¹. Among these, the pesticides most frequently detected were terbuthylazine (100% of detection) and metolachlor (83% of detection), with maximum concentrations of 115.6 and 85.5 µg L⁻¹, respectively. Samples from the LS site showed higher toxicity, where A. fischeri presented 30 min EC₅₀ values of 39–51%. Microalgae growth was consistently inhibited, correlating with agricultural activity, mainly the application of herbicides and insecticides, while D. magna feeding rates revealed no inhibitory effects in the Lage samples. The results highlight that although the detected pesticide levels were below regulatory limits, they still induced toxic effects in the tested organisms. The potential ecological status of the reservoir was classified as moderate, and the integration of the proposal toolbox allowed refinement of the classification of water status. The results demonstrated that this integrated approach, combining multiple assessment methods, establishes a more robust water quality evaluation methodology, allowing it to be used as a tool complementary to the WFD methodology. This proposal not only identified existing pollution impacts but also enabled (1) early detection of the toxic effects of emerging contaminants to prevent ecological damage; (2) proactive management through specific actions to restore water status; and (3) improved sustainable water use. Full article

Herein, a new series of 3-DT analogs with benzoylated groups at C-23 are synthesized and characterized. The benzoylated groups carry the same substituents in the ortho- or para-positions. Thus, the effect of structure on activity, measured using the rice lamina inclination test (RLIT) and the bean second-internode assay (BSI), is evaluated. The RLIT results indicate that a benzoylate function at C-22 induces a strong increase in activity that depends on the position and nature of the substituent in the phenyl ring. For example, an analog with an -OAc group in the ortho-position is the most active derivative, and its activity is like that of brassinolide. A relative index is calculated using brassinolide as a positive control to compare the RLIT results with those reported previously. This analysis allows for the conclusion that benzoylated derivatives with a hydroxyl group at C-3 are much more active than the corresponding analogs with a carbonyl group in this position, and one extra alcohol group in the alkyl chain decreases RLIT activity. Finally, the results obtained with the BSI are clearly different to those obtained in the RLIT bioassay. Therefore, the application of any activity–structure relationship will always be dependent on the bioassay used to determine activity. Full article

 Background: Micro- and nanoplastics (MNPs) have emerged as increasing environmental and public health concerns. Dentistry contributes to this exposure through polymer-based materials and personal oral care products. This review summarizes the current evidence on the sources, release mechanisms, physicochemical properties, and toxicological and biological effects of MNPs derived from dental sources and oral care products, as well as the synergistic effects of MNP oral exposure with environmental exposure. Methods: An electronic search was performed across the PubMed/MEDLINE, Scopus, and Web of Science databases to identify studies investigating the source, release mechanisms, physico/chemical properties, and toxicological/biological impact of MNPs related to dental materials, oral care products, and the synergic effects of MNPs oral and environmental exposure. Results: MNPs are released in the dental setting from resin-based composites, clear aligners, and prosthetic and impression materials through degradation, wear, and handling processes. Home-use products like toothpastes, toothbrushes, floss, and mouthwashes contribute to chronic oral exposure. Evidence from in vitro, in vivo, and human biomonitoring studies supports the biological activity and systemic distribution of MNPs. Despite this, clinical awareness remains limited, and regulatory oversight insufficient. Conclusions: Dentistry is both a source and vector of MNP exposure. Encouraging the use of safer, MNP-free materials, and raising awareness among dental professionals, may support more responsible and health-conscious practices. Further research and alignment with global policy strategies could help guide future innovation and risk mitigation in the dental field.  Full article

Objectives: Adolescence is a pivotal stage of development characterized by significant physical, psychological, and social changes. Establishing healthy lifestyle habits during this period is crucial for long-term health and the prevention of chronic diseases. Despite this, global trends show a marked decline in physical activity among adolescents, particularly girls, who are more susceptible to sedentary behaviors. One potential site for intervention to eliminate physical inactivity at the population level is the school educational setting during childhood. Traditional school-based physical exercise programs often adopt a one-size-fits-all approach, which may not address the diverse needs and interests of students, leading to reduced motivation and participation. Personalized physical exercise programs, tailored to individual capabilities and preferences, offer a promising alternative to enhance physical fitness and foster lifelong engagement in physical activity. Methods: A total of 170 Hungarian high school girls (mean age ≈ 15.3 years) were randomly assigned to either a personalized physical exercise group or a control group following the standard curriculum. The intervention spanned two academic years and consisted of five traditional gym classes per week (control group) or three traditional and two individually tailored classes with cardiorespiratory and resistance training per week (intervention group), each lasting 45–60 min. Individual goals were set based on baseline assessments, emphasizing self-referenced progress. Results: The personalized physical exercise group showed significant improvements in body mass index (BMI), body fat percentage, maximum oxygen uptake capacity (VO₂max), muscular strength, and flexibility (p < 0.05), while the control group exhibited minimal or negative changes. Conclusions: The personalized physical exercise program has been shown to be more effective in achieving higher cardiorespiratory performance and favorable body composition among adolescent girls than a traditional school physical education class, highlighting its potential role in school settings. Full article

Syngas fermentation in combination with chain elongation offers great promise for sustainable medium-chain fatty acid production. While immobilization has proven effective for stabilizing monocultures of C. kluyveri for chain elongation, its applicability to co-cultures involving C. carboxidivorans for simultaneous syngas fermentation remains unexplored. This study investigates the physiological compatibility of C. carboxidivorans with agar-based hydrogel immobilization and its co-cultivation potential with C. kluyveri in a synthetic dual-layer biofilm reactor. First, we conducted autotrophic batch fermentations using suspended and immobilized cells, proving metabolic activity similar for both. Applying different sulfur feeding rates, experiments showed best ethanol formation with C. carboxidivorans at increased sulfur feeding, enabling better conditions for chain elongation with C. kluyveri. In the synthetic dual-layer biofilm reactor, with the C. carboxidivorans biofilm in contact with the CO-containing gas phase above the C. kluyveri biofilm, the formation of 1-butyrate and 1-hexanoate was observed with product formation rates of 0.46 g L⁻¹ d⁻¹ 1-butyrate, and 0.91 g L⁻¹ d⁻¹ 1-hexanoate, respectively. The formation rate of 1-hexanoate in the dual-layer biofilm reactor was approximately 7.6 times higher than that reported with suspended cells in a stirred tank bioreactor. Spatial analysis revealed species-specific migration behavior and confirmed that C. carboxidivorans reduced local CO concentrations, improving the environment for C. kluyveri. Full article

This mixed-method study explores the impact of the Raising Climate Heroes: Ecological Game Camp on climate change knowledge, awareness, behavior, and emotional engagement among primary school students and adult participants. Designed with experiential and game-based learning approaches, the program aimed to enhance environmental literacy through interactive, nature-centered activities. The quantitative findings from pre- and post-tests revealed significant increases in climate-related knowledge, awareness, climate-friendly behavior, hope, and reductions in climate anxiety. All measurement tools demonstrated high internal consistency (α = 0.809–0.914), indicating strong reliability across both age groups. Qualitative data, analyzed using descriptive thematic analysis, showed high levels of participant satisfaction. The adults emphasized educational gains, professional relevance, and appreciation of academic facilitation. The children focused on enjoyment, outdoor experiences, and social interaction. Activities such as ecological experiments, composting, and collaborative cooking were most favored. The results suggest that combining cognitive and emotional elements through play and hands-on learning can effectively promote pro-environmental attitudes. This study contributes to the literature by demonstrating how climate education can be both engaging and transformative for diverse learner groups. Full article

Background/Objectives: Neuropathic pain, resulting from damage or pathology affecting the somatosensory nervous system, is a prevalent form of chronic pain that significantly impacts quality of life. Combined therapies are often utilised to manage this condition. Three-dimensional printing (3DP) offers a promising approach for personalising medication doses and dosage forms to meet individual patient needs. Methods: In this study, a formulation suitable for 3D printing was developed using magnesium citrate, uridine monophosphate, vitamins B₃ (niacin), B₆ (pyridoxine), B₁₂ (cobalamin), B₉ (folic acid), and spermidine to create a novel gel-based oral tablet for the targeted treatment of neurological pain. The antioxidant potential of the active pharmaceutical ingredients (APIs) was assessed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) methods. The physical properties of the tablets were evaluated using a texture analyser, while the in vitro release profiles were determined by high-performance liquid chromatography (HPLC). Results: Results demonstrated that pectin–gelatin tablets hardened over time, with higher citric acid concentrations further enhancing this effect. Formulation AVII exhibited good hardness and low stickiness. Formulation AV, however, showed poor performance across all physical parameters and lacked sufficient structural integrity for practical application. While uridine monophosphate, B₁₂, and B₉ showed no significant differences in the release profiles of the tablets, spermidine, B₆, and B₃ displayed statistically significant variations. Specifically, AVII outperformed AV in terms of spermidine and B₆ release, and AV showed a higher release of B₃ compared to AV. Conclusions: The AVII tablet demonstrates potential for use in combined therapy targeting neurological pain disorders. Full article

To address the challenge of postharvest spoilage in flat peaches and white apricots, we developed fermented peach–apricot mixed juice (PAMJ) using these fruits as raw materials through multi-strain synergistic fermentation. Its fermentation processes were optimised through uniform design and single-factor experiments. The flavour characteristics of PAMJ were analysed using an electronic nose, an electronic tongue, gas chromatography–mass spectrometry (GC-MS) and sensory evaluation indices. PAMJ demonstrated optimal performance in terms of peach–apricot flavour profile, sweetness-sourness balance, and overall acceptability, achieving the highest sensory scores. Additionally, GC-MS analysis identified 116 volatile organic compounds, with PAMJ exhibiting the highest contents of terpenes and ketones. PAMJ was identified as the optimal fermentation matrix. Subsequently, response surface methodology was used to optimise its fermentation parameters. PAMJ represented a post-mixing fermentation system wherein peaches and apricots were initially mixed and subsequently fermented with a bacterial consortium comprising Limosilactobacillus fermentum (15%), Lactobacillus acidophilus (10%), Levilactobacillus brevis (34%), Lacticaseibacillus paracasei subsp. Tolerans (13%), Lactiplantibacillus plantarum subsp. plantarum (13%) and Limosilactobacillus reuteri (15%). After fermentation with an initial inoculum concentration of 5.2 × 10⁶ CFU/mL at 37 °C for 20 h, the initial soluble solid content of PAMJ increased from 16 to 16.5 °Brix, superoxide dismutase (SOD) activity increased from 250 to 295 U/mL and the number of volatile compounds (NVC) increased from 60 to 66. Furthermore, the storage stability of pasteurised PAMJ was evaluated by monitoring SOD and NVC at 5-day intervals. The data were analysed using kinetic and Arrhenius equations. The shelf life of PAMJ at 4 °C, 25 °C and 37 °C was 69, 48 and 39 days when NVC was used as the index and 99, 63 and 49 days when SOD activity was used as the index, respectively. These findings indicate that fermentation with lactic acid bacteria exerts positive effects on the quality of mixed juices, providing a novel strategy for processing speciality fruits in Xinjiang. Full article

The transition toward renewable-powered greenhouse agriculture offers opportunities for reducing operational costs and environmental impacts, yet challenges remain in managing fluctuating energy loads and optimizing agricultural inputs. While second-life lithium-ion batteries provide a cost-effective energy storage option, their thermal and electrical characteristics under real-world greenhouse conditions are poorly documented. Similarly, although plasma-activated water (PAW) shows potential to reduce chemical fertilizer usage, its integration with renewable-powered systems requires further investigation. This study develops an adaptive monitoring and modeling framework to estimate the thermal resistances (R_u, R_c) and internal resistance (R_int) of second-life lithium-ion batteries using operational data from greenhouse applications, alongside a field trial assessing PAW effects on beefsteak tomato cultivation. The adaptive control algorithm accurately estimated surface temperature (T_s) and core temperature (T_c), achieving a root mean square error (RMSE) of 0.31 °C, a mean absolute error (MAE) of 0.25 °C, and a percentage error of 0.31%. Thermal resistance values stabilized at R_u ≈ 3.00 °C/W (surface to ambient) and R_c ≈ 2.00 °C/W (core to surface), indicating stable thermal regulation under load variations. Internal resistance (R_int) maintained a baseline of ~1.0–1.2 Ω, with peaks up to 12 Ω during load transitions, confirming the importance of continuous monitoring for performance and degradation prevention in second-life applications. The PAW treatment reduced chemical nitrogen fertilizer use by 31.2% without decreasing total nitrogen availability (69.5 mg/L). The NO₃⁻-N concentration in PAW reached 134 mg/L, with an initial pH of 3.04 neutralized before application, ensuring no adverse effects on germination or growth. Leaf nutrient analysis showed lower nitrogen (1.83% vs. 2.28%) and potassium (1.66% vs. 2.17%) compared to the control, but higher magnesium content (0.59% vs. 0.37%), meeting Japanese adequacy standards. The total yield was 7.8 kg/m², with fruit quality comparable between the PAW and control groups. The integration of adaptive battery monitoring with PAW irrigation demonstrates a practical pathway toward energy efficient and sustainable greenhouse operations. Full article

Lytic bacteriophages, viruses that attack and kill bacteria cells, can be used in food as biocontrol agents to prevent the growth of pathogenic bacteria. Meat is highly susceptible to bacterial growth, including pathogenic species, the control of which is crucial. Antibiotic use by breeders has resulted in bacterial resistance, which remains a huge problem; bacteriophages have emerged as an interesting alternative. In the literature, the influence of bacteriophages on common foodborne pathogens, such as Salmonella sp., Listeria monocytogenes, Campylobacter jejuni, Yersinia enterocolitica, Escherichia coli, and Shigella sp., has been described. Some phage preparations can show synergistic effects when used with other antimicrobial agents. However, data on the use of bacteriophages to inhibit the growth of meat spoilage bacteria are limited. Bacteriophages can also synthesize endolysins, which possess antimicrobial properties. Contrary to bacteriophages, which are active against only a narrow range of microorganisms (usually one bacterial species), endolysins show a broad spectrum of activity. Full article

Excessive osteoclast activity in bone remodeling can lead to an imbalance between bone resorption and formation, a common occurrence in abnormal bone metabolic diseases. This research investigates the effect of Coptidis rhizoma water extract (CRW) on osteoclastogenesis provoked by RANKL in vitro and bone destruction mediated by ovariectomy (OVX) in vivo. CRW, prepared from dried Coptidis rhizoma (CR), was analyzed for its active compounds—coptisine and berberine—using HPLC analysis. CRW markedly decreased the size and number of TRAP-positive multinucleated cells (TRAP⁺ MNCs), suppressed F-actin ring formation, and diminished bone resorption in RANKL-treated cultures. In the early phase of differentiation, CRW suppressed the phosphorylation of MAPKs p38, JNK, and ERK, as well as NF-κB p65, Iκ-Bα, and Akt. CRW also down-regulated RANKL-mediated induction of c-Fos and NFATc1 and attenuated the activation of NFATc1- dependent genes, such as OSCAR, ATP6V0D2, ACP5 (TRAP), OC-STAMP, DC-STAMP, CTSK (cathepsin K), CALCR (calcitonin receptor), and MMP-9. In ovariectomized rats, micro-CT and histological analyses showed that CRW alleviated femoral bone destruction. These findings indicate that CRW restrains osteoclast differentiation and function and may have therapeutic potential for disorders driven by excessive osteoclast activity. Full article

Mitochondrial dysfunction is a key factor in the pathophysiology of major depressive disorder (MDD) and treatment-resistant depression (TRD), connecting oxidative stress, neuroinflammation, and reduced neuroplasticity. Physical exercise induces specific mitochondrial changes linked to improvements in mental health. The aim of this paper was to examine emerging evidence regarding the effects of physical exercise on mitochondrial function and treatment-resistant depression, highlighting the clinical importance of the use of mitochondrial biomarkers to personalize exercise prescriptions for patients with depression, particularly those who cannot tolerate standard treatments. Physical exercise improves mitochondrial function, enhances biogenesis and neuroplasticity, and decreases oxidative stress and neuroinflammation. Essential signaling pathways, including brain-derived neurotrophic factor, AMP-activated protein kinase, active peroxisome proliferator-activated receptor-γ coactivator-1α, and Ca²⁺/calmodulin-dependent protein kinase, support these effects. Most studies have concentrated on the impact of low- and moderate-intensity aerobic exercise on general health. However, new evidence suggests that resistance exercise and high-intensity interval training also promote healthy mitochondrial adaptations, although the specific exercise intensity required to achieve this goal remains to be determined. There is strong evidence that exercise is an effective treatment for MDD, particularly for TRD, by promoting specific mitochondrial adaptations. However, key gaps remain in our understanding of the optimal exercise dose and which patient subgroups are most likely to benefit from it (Graphical Abstract). Full article