Search Results (725)

Hydraulic shear has been widely accepted as one of the essential factors modulating phytoplankton growth. Previous experimental studies of algal growth have been conducted at the macroscopic level, and direct observation at the cell scale has been lacking. In this study, an algal-cell dynamic continuous observation platform (ACDCOP) is proposed with a parallel-plate flow chamber (PPFC) to capture cellular growth images which are then used as input to a computer vision algorithm featuring a pre-trained backpropagation neural network to quantitatively evaluate the volumes and volumetric growth rates of individual cells. The platform was applied to investigate the growth of Scenedesmus quadricauda cells under different hydraulic shear stress conditions. The results indicated that the threshold shear stress for the development of Scenedesmus quadricauda cells was 270 µL min⁻¹ (5.62 × 10⁻⁵ m² s⁻³). Cellular growth was inhibited at very low and very high intensities of hydraulic shear. Among all the experimental groups, the longest growth period for a cell, from attachment to PPFC to cell division, was 5.7 days. Cells with larger initial volumes produced larger volumes at division. The proposed platform could provide a novel approach for algal research by enabling direct observation of algal growth at the cell scale, and could potentially be applied to investigate the impacts of various environmental stressors such as nutrient, temperature, and light on cellular growth in different algal species. Full article

In this paper, voxel-based Asymptotic Homogenization (AH) is employed to calculate the thermal expansion and thermal conductivity characteristics of lattice materials that have a Representative Volume Element (RVE) with non-orthogonal periodic bases. The non-orthogonal RVE of the cellular lattice is discretized using voxel elements (iso-parametric hexahedral element, on a cartesian grid). A homogenization framework is developed in python that uses a fast-nearest neighbor algorithm to approximate the (non-orthogonal) periodic boundary conditions of the discretized RVE. Validation studies are performed where results of the homogenized Thermal Expansion Coefficient (TEC) and thermal conduction performed in this paper are compared with results generated by commercially available software. These included comparison with the results for (a) bi-material unidirectional composite with orthogonal RVE cell envelope; (b) bi-material hexagon lattice with orthogonal cell envelope; (c) bi-material hexagon lattice with non-orthogonal cell envelope; and (d) bi-material square lattice. A novel approach of visualizing the contribution of each voxel towards the individual terms within the homogenized thermal conductivity matrix is presented, which is necessary to mitigate any potential errors arising from the numerical model. Additionally, the effect of the thermal expansion and thermal conductivity for bi-material hexagon lattice (orthogonal and non-orthogonal RVE cell envelope) are presented for varying internal cell angles and all permutations of material assignments for a relative density of 0.3. It is found that when comparing the non-orthogonal RVE with the Orthogonal RVE as a reference model, the numerical error due to approximating the periodic boundary condition for the non-orthogonal bi-material hexagon is generally less than 2% as the numerical error is pseudo-cyclically dependent on the discretization along the cartesian axis. Full article

Background/Objectives: This study investigates the utility of multiparametric PET/MRI in delineating changes in physiologically distinct intratumoral habitats during trastuzumab-induced alterations in a preclinical HER2+ breast cancer model. Methods: By integrating diffusion-weighted MRI, dynamic contrast-enhanced MRI, [¹⁸F]Fluorodeoxyglucose- and [¹⁸F]Fluorothymidine-PET, voxel-wise parametric maps were generated capturing cellular density, vascularity, metabolism, and proliferation. BT-474 tumor-bearing mice have high expression of HER2 and, in response to trastuzumab, an anti-HER2 antibody, effectively show changes in proliferation and tumor microenvironment alterations that result in decreases in tumor volume through time. Results: Single imaging metrics and changes in metrics were incapable of identifying treatment-induced alterations early in the course of therapy (day 4) prior to changes in tumor volume. Hierarchical clustering identified five distinct tumor habitats, which enabled longitudinal assessment of early treatment response. Tumor habitats were defined based on imaging metrics related to biology and categorized as highly vascular (HV), hypoxic responding (HRSP), transitional zone (TZ), active tumor (ATMR) and responding (RSP). The HRSP cluster volume significantly decreased in trastuzumab-treated tumors compared to controls by day 4 (p = 0.015). The volume of ATMR cluster was significantly different at baseline between cohorts (p = 0.03). The TZ cluster, indicative of regions transitioning more to necrosis, significantly decreased in treated tumors (p = 0.031), suggesting regions had already transitioned. Multiparametric image clustering showed a significant positive linear correlation with histological multiparametric mapping, with R² values of 0.56 (HRSP, p = 0.013, 0.64 (ATMR, p = 0.0055), and 0.49 (responding cluster, p = 0.024), confirming the biological relevance of imaging-derived clusters. Conclusions: These findings highlight the potential utility of multiparametric PET/MRI to capture biological alterations prior to any single imaging metric which has potential for better understanding longitudinal changes in biology, stratifying tumors based on those changes, optimizing therapeutic monitoring and advancing precision oncology. Full article

Background and Purpose: Glioblastoma remains a therapeutic challenge with a poor prognosis despite multimodal treatments. Reporter-based magnetic resonance imaging (MRI) offers a promising approach for tumor visualization, but its efficacy depends on sufficient reporter gene expression. This study aimed to develop a chimeric element-regulated ferritin heavy chain 1 (FTH1) reporter system to enhance MRI-based glioma detection while enabling targeted therapy via transferrin receptor (TfR)-mediated drug delivery. Methods: Using gene cloning techniques, we constructed a chimeric FTH1 expression system comprising tumor-specific PEG3 promoter (transcriptional control), bFGF-2 5′UTR (translational enhancement), and WPRE (mRNA stabilization). Lentiviral vectors delivered constructs to U251 glioblastoma cells and xenografts. FTH1/TfR expression was validated by Western blot and immunofluorescence. Iron accumulation was assessed via Prussian blue staining and TEM. MRI evaluated T2 signal changes. Transferrin-modified doxorubicin liposomes (Tf-LPD) were characterized for size and drug loading and tested for cellular uptake and cytotoxicity in vitro. In vivo therapeutic efficacy was assessed in nude mouse models through tumor volume measurement, MR imaging, and histopathology. Results: The chimeric system increased FTH1 expression significantly over PEG3-only controls (p < 0.01), with an increase of nearly 1.5-fold compared to the negative and blank groups and approximately a two-fold increase relative to the single promoter group, with corresponding TfR upregulation. Enhanced iron accumulation reduced T2 relaxation times significantly (p < 0.01), improving MR contrast. Tf-LPD (115 nm, 70% encapsulation) showed TfR-dependent uptake, inducing obvious apoptosis in high-TfR cells compared with that in controls. In vivo, Tf-LPD reduced tumor growth markedly in chimeric-system xenografts versus controls, with concurrent MR signal attenuation. Conclusions: The chimeric regulatory strategy overcomes limitations of single-element systems, demonstrating significant potential for integrated glioma theranostics. Its modular design may be adaptable to other reporter genes and malignancies. Full article

The white snook (Centropomus viridis) is an emerging aquaculture species with high market acceptance, exhibiting catadromous and protandric hermaphroditic characteristics in adulthood. This study aimed to preliminarily characterize certain hematological and biochemical parameters, as well as blood cell morphology, for identifying possible variations between sexes maintained under aquaculture recirculating system (RAS) conditions. The white snook broodstock was anesthetized with clove oil, and biometric values, as well as sex classification, were measured. Then, blood samples were collected from 14 females (7132 ± 1610 g) and 20 males (2200 ± 0.963 g) via caudal vessel puncture to analyze selected hematological parameters, blood biochemistry, and cellular morphology. Fulton’s condition factor (K) showed no differences between sexes, indicating a healthy fish status. Females showed significantly higher serum cholesterol, glucose, and triglyceride levels than males. Also, hematocrit (HCT) and mean corpuscular volume (MCV) were elevated in females. No sex-related differences were observed in red or white cell counts or in blood cell dimensions. Morphological characterization identified erythrocytes, thrombocytes, and three types of leukocytes: lymphocytes (small and large lymphocytes), neutrophils, and monocytes, with no eosinophils or basophils detected in either sex. These findings provide fundamental reference values for the hematological and biochemical profiles of C. viridis broodstock in captivity and highlight sex-specific differences relevant for reproductive and health monitoring. However, it should be considered that the sample size used to establish reference ranges for the species is small, so it is recommended to implement a monitoring plan for this and other broodstocks of this emerging species. Full article

(1) Background: The insect male accessory gland (MAG) produces seminal fluid components crucial for male reproduction, analogous to the mammalian prostate. While some insect MAGs exhibit binucleate epithelial cells for luminal volume plasticity, the diversity of cellular arrangements and their functional implications across insects remain largely unknown. (2) Methods: We investigated the cellular architecture of MAG epithelia in various shore bug species (infraorder Leptopodomorpha, Hemiptera) and their mechanisms of multinucleation and potential MAG volume regulation. (3) Results: The MAG epithelia of shore bugs comprise a small number of large, plastic syncytial cells with varying nuclear numbers. We hypothesize that these syncytia facilitate effective MAG volume expansion post-eclosion. Uniquely, MAG shrinkage involves the localized contraction of limited muscle fibers, unlike the systematic contraction of circular muscles in most other insects. We further describe sequential cell fusion during the nymphal stage as the mechanism of multinucleation. (4) Conclusions: The unique syncytial organization of Leptopodomorpha MAG epithelia represents an evolutionary divergence from typical binucleate or mononucleate structures in other insects; it is likely that this enables distinct mechanisms for reproductive fluid storage and evacuation. This study highlights the evolutionary diversity of male reproductive organ morphology and function within insects. Full article

The prediction of microstructure evolution during thermal processing plays a crucial role in tailoring the mechanical properties of metallic components. Therefore, this work presents a comprehensive, multiscale modelling approach to simulating phase transformations in large-diameter steel rings during cooling. A finite-element-based thermal model was first used to simulate transient temperature distributions in a large-diameter ring under different cooling conditions, including air and water quenching. These thermal histories were subsequently employed in two complementary phase transformation models of different levels of complexity. The Avrami model provides a first-order approximation of the evolution of phase volume fractions, while a complex full-field cellular automata approach explicitly simulates the nucleation and growth of ferrite grains at the microstructural level, incorporating local kinetics and microstructural heterogeneities. The results highlight the sensitivity of final grain morphology to local cooling rates within the ring and initial austenite grain sizes. Simulations demonstrated the formation of heterogeneous microstructures, particularly pronounced in the ring’s surface region, due to sharp thermal gradients. This approach offers valuable insights for optimising heat treatment conditions to obtain high-quality large-diameter ring products. Full article

Background/Objectives: Sarcopenia is an age-related disease resulting in muscle mass deterioration and declining strength and functional ability. Muscle protein degradation pathways are activated through the ubiquitin–proteasome system, which is integral to the pathogenesis of sarcopenia. This study examined the capability of Lactobacillus plantarum beLP1 as a postbiotic ingredient of kimchi that prevents sarcopenia. Methods: We evaluated cell viability and measured diameters in a C2C12 myotube damage model and muscle volume, muscle weight, muscle strength, and the expression of muscle degradation proteins MuRF1 and Atrogin-1 in dexamethasone-induced sarcopenic model rats using a heat-killed beLP1 strain. Results: beLP1 had no cytotoxic effects on C2C12 and prevented dexamethasone-induced cellular damage, suggesting its role in muscle protein degradation pathways. beLP1 treatment significantly prevented the dexamethasone-induced reduction in myotube diameter. In a dexamethasone-induced sarcopenic rat model, oral beLP1 significantly mitigated muscle mass decline and prevented grip strength reduction. Microcomputed tomography demonstrated that beLP1 reduced dexamethasone-induced muscle volume loss. beLP1 treatment reduced Atrogin-1 and Muscle RING-finger protein-1 (MuRF1) and the transcription factor Forkhead box O3 alpha (FoxO3α), which triggers muscle protein breakdown. beLP1 exerts protective effects by inhibiting the ubiquitin-proteasome system and regulating FoxO3α signaling. It increased AKT (Ser473) phosphorylation, which affected muscle protein synthesis, degradation, and cell survival, suggesting its potential to prevent sarcopenia. Conclusions: Heat-killed Lactobacillus plantarum beLP1 alleviates muscle mass wasting and weakness in a dexamethasone-induced sarcopenia model by regulating muscle protein degradation pathways and signaling molecules. Thus, postbiotics may be functional ingredients in sarcopenia prevention. Full article

The cryopreservation of limited sperm samples, especially those retrieved from patients, poses significant challenges due to the small number of viable cells available for freezing. Traditional microliter cryopreservation methods are fraught with difficulties, as thawed sperm cells become nearly impossible to locate under a microscope due to their mobility and the multiple focal planes presented by larger drops. This search time is critical, as sperm cells enter a state of decline post thaw. Conversely, when sperm cells are cryopreserved in nanoliter volumes, they can be easily discovered but do not survive the freezing and thawing processes entirely. This phenomenon is attributed to the diffusion of water molecules from the droplet into the surrounding oil, which, while designed to limit evaporation, inadvertently increases solute concentrations in the aqueous environment, leading to cellular desiccation. This article elucidates the mechanisms underlying this lethal diffusion effect and presents a novel approach for freezing in nanoliter volumes, which has demonstrated significantly improved survival rates through carefully optimized procedures in clinical trials. Our findings highlight the importance of adapting cryopreservation techniques to enhance the viability of individual sperm cells, ultimately facilitating better outcomes in assisted reproductive technologies. This study provides the first quantification of nanoscale water diffusion dynamics during cryopreservation, establishing a predictive model that explains the catastrophic loss of sperm viability and identifying the critical role of water diffusion as a major impediment for limited samples. The novelty of our results lies in both elucidating this specific mechanism of cell death and introducing a novel approach: utilizing water-saturated oil as a protective layer. This method effectively mitigates the osmotic stress caused by water loss, demonstrating remarkably improved cell survival. This work not only advances the scientific understanding of cryopreservation at the nanoscale but also offers a practical, impactful solution poised to revolutionize fertility treatments for patients with low sperm counts and holds promise for broader applications in biological cryopreservation. Full article

In this study, a comprehensive experimental framework was developed to quantitatively characterize the pore structure of a deep coal-rock (DCR; reservoirs below [3000 m]) gas reservoir. Experimentally, petrological and mineral characteristics were determined by performing proximate analysis and scanning electron microscopy (SEM) as well as by measuring vitrinite reflectance and maceral components. Additionally, physisorption and high-pressure mercury injection (HPMI) tests were conducted to quantitatively characterize the nano- to micron-scale pores in the DCR gas reservoir at multiple scales. The DCR in the NQ Block is predominantly composed of vitrinite, accounting for approximately 77.75%, followed by inertinite. The pore space is predominantly characterized by cellular pores, but porosity development is relatively limited as most of such pores are extensively filled with clay minerals. The isothermal adsorption curves of CO₂ and N₂ in the NQ Block and the DJ Block exhibit very similar variation patterns. The pore types and morphologies of the DCR reservoir are relatively consistent, with a significant development of nanoscale pores in both blocks. Notably, micropore metrics per unit mass (pore volume (PV): 0.0242 cm³/g; and specific surface area (SSA): 77.7545 m²/g) indicate 50% lower gas adsorption potential in the DJ Block. In contrast, the PV and SSA of the mesopores per unit mass in the NQ Block are relatively consistent with those in the DJ and SF Blocks. Additionally, the peak mercury intake in the NQ Block occurs within the pore diameter < 20 nm, with nearly 60% of the mercury beginning to enter in large quantities only when the pore size exceeds 20 nm. This indicates that nanoscale pores are predominantly developed in the DCR of the NQ block, which aligns with the findings from physical adsorption experiments and SEM analyses. Overall, the development characteristics of multi-scale pores in the DCR formations of the NQ Block and the eastern part of the Basin are relatively similar, with both total PV and total SSA showing an L-shaped distribution. Due to the disparity in micropore SSA, however, the total SSA of the DJ Block is approximately twice that of the NQ Block. This discovery has established a robust foundation for the subsequent exploitation of natural gas resources in DCR formations within the NQ Block. Full article

Background and Objectives: Obesity is linked to liver cancer through metabolic mechanisms and can promote tumor growth through metabolic impairment, decreased lipid metabolism, and interference of the energy balance in the liver. NAMPT is an enzyme expressed in the liver and is involved in the progression of tumors in obesogenic environments, while iNAMPT is known to be the rate-limiting enzyme in the synthesis of NAD, an essential coenzyme involved in ATP synthesis which promotes a pro-growth environment in the context of obesity. Because iNAMPT and cellular energetics, a hallmark of cancer, play an important role in liver cancer progression, it has become a target for cancer therapies focused on inhibiting its functions. The objective of this study was to determine the contribution of NAD biosynthesis in obesity-associated liver cancer progression. Methods: Cell culture studies were conducted with serum from male mice randomized to diet-induced obesity (OB) or control (CR) ± FK866 (iNAMPT inhibitor) in SNU, HepG2 human liver cancer cells, and Hepa 1-6 liver murine cells. Protein analysis of pAkt and pErk was performed via immunoblot. Cytotoxicity, reactive oxygen species (ROS), cell viability, and invasion were also measured in the cells. For the mouse model, the C57BL/6J male mice were randomized to the DIO or CR group. At 21 weeks of age, the mice were injected subcutaneously with Hepa 1-6 liver cancer cells. At 23 weeks, the mice received an I.P. injection of FK866 (30 mg/kg) for 2 weeks. The tumor and mouse weights were measured. Results: The cells exposed to OB sera showed increased proliferation, lactate dehydrogenase (LDH) secretion, ROS, and invasion. FK866 decreased proliferation, LDH secretion, ROS, and invasion for all liver cancer cells. The cells exposed to CR sera and OB + FK866 resulted in more LDH, suggesting increased apoptosis compared with OB sera. The OB sera increased phosphorylation of Akt, which was suppressed by FK866 compared with the OB group. In liver cancer cells, physiological and cellular signaling is affected differently when inhibiting NAD biosynthesis in an in vitro model of obesity and liver cancer. In vivo, the diet-induced obese (DIO) mice weighed significantly more than the mice fed a control diet. In addition, 70% of the DIO mice developed tumors, compared with 20% of the CR mice, and had tumors with greater volumes and weights. NAD inhibition blocked obesity-induced tumor growth. Conclusions: In this study, we demonstrate that inhibition of iNAMPT resulted in suppression of tumor growth in the context of obesity. Identifying pre-clinical strategies to reverse the impact of obesity on liver cancer progression is important due to the strong increased risk of liver cancer and its poor prognosis. Future translational research studies can be built from this pre-clinical foundational research. Full article

Cognitive impairment in subjects with Alzheimer’s disease correlates well with the loss of synaptic plasticity. This results from mitochondrial dysfunction and production of reactive oxygen species, which damage nerve terminals causing them to release ATP and adenosine. These purines activate receptors on microglia resulting in a change in morphology and release proinflammatory cytokines that exacerbate neuronal damage. The review describes retrospective studies with naturally occurring antioxidants, vitamin E, resveratrol, Ginkgo biloba and others that suggested they reduce the incidence of Alzheimer’s disease. They have antioxidant activity in cellular systems and rodent models, but most of them failed in clinical trials, probably because they were not absorbed after oral administration or, like anti-inflammatory drugs, were not given at the right time or for long enough to detect an effect on disease progression. Ladostigil is an aminoindan derivative that is well absorbed after oral administration. It has antioxidant effects in cells and prevents cytokine release from activated microglia. In a phase 2 trial in subjects with mild cognitive impairment, ladostigil significantly reduced number of converters to Alzheimer’s disease in ApoE4-ve subjects and delayed the decline in whole brain and hippocampal volumes without causing adverse effects related to drug intake. Full article

This study investigated the potential of Yarrowia lipolytica, an oleaginous yeast, for producing lipid-rich biomass and its application in food technology. According to EFSA guidelines, lipid-rich biomass is recognized as a novel food with potential nutritional and technological value. However, cost-effective and scalable production of such biomass remains a challenge. The yeast was cultured in a nitrogen-limited medium using a cost-containment strategy based on the use of waste carbon sources, such as post-frying oil and untreated tap water. The composed batch culture approach studied in the experiments presented an example that reduces the cost of yeast biomass biosynthesis. This research aimed to characterize the biomass to assess its nutritional quality and suitability for food applications. Cultures were conducted in a laboratory bioreactor with a working volume of 4 litres. Key kinetic parameters were determined, including biomass yield (X), maximum lipid concentration (Lmax), lipid yield, protein yield relative to substrate and the specific rate of lipid synthesis or protein content and other cellular components. The biomass of Y. lipolytica demonstrated a high lipid content (39.43–50.53%), with significant levels of protein (24.16–27.03%) and unsaturated fatty acids, including oleic acid (62.73–66.44%) and linoleic acid (19.40–21.40%). Lipid-rich biomass produced in cultures with shorter times (20 h), which ended in the logarithmic growth phase, exhibited lower oxidative stability than longer cultures (65 h), which ended in the stationary growth phase. The results of this study highlighted that waste carbon sources and untreated tap water did not significantly impact the biomass yield or the nutritional profile, but did affect the stability of the produced oil. The biomass of Y. lipolytica, containing over 20% lipids, could serve as a promising raw material for food technology, providing a sustainable alternative to traditional vegetable oils. This work makes an important contribution to the development of alternative lipid sources by integrating waste processing in bioreactor-scale culture and kinetic modelling. Full article

Background: Ischemic stroke (IS) is probably the most important acute serious illness, where interdisciplinary approach is essential to offer the best chance for survival and functional recovery of patients. Carbon dots (CDs) with multifaceted advantages have provided hope for development brand-new nanodrug for treating thorny diseases. Methods: This study developed a green and environmentally responsible calcination method to prepare novel Gardenia jasminoides Carbonisata (GJC-CDs) as promising drug for ischemic stroke treatment. Results: In this work, we isolated and characterized for the first time a novel carbon dots (GJC-CDs) from the natural plant G. jasminoides. Results displayed that green GJC-based CDs with tiny sizes and abundant functional groups exhibited solubility, which may be beneficial for its settled biological activity. The neuroprotective effect of carbon dots from G. jasminoides were evaluated using the classical middle cerebral artery occlusion (MCAO) model. Assessing the infarct volume content of the ischemic cerebral hemisphere and determining the serum tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), reduced glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) levels of the mice in each group, it was evident that pre-administration of the drug by GJC-CDs significantly reduced the infarct volume as well as attenuated inflammatory responses and excessive oxidative stress in MCAO mice. Furthermore, in vitro cellular experiments demonstrated that GJC-CDs have good biosafety and anti-inflammatory and antioxidant capacity. Conclusions: Overall, GJC-CDs performs neuroprotective effect on cerebral ischemia and reperfusion injury, which not only provides evidence for further broadening the biological application of acute ischemic stroke but also offers novel strategy for the application of nanomedicine to treat acute diseases. Full article

Previous studies showed a potent anti-inflammatory activity of Solanum tuberosum L. polysaccharide (STP), which inhibited pro-inflammatory cytokines and stimulated anti-inflammatory ones in peptic ulcer models. Thus, the main goal of this study was to find out the molecular background of such activity and possible applications in different anti-inflammatory models. This study investigated the anti-inflammatory potential of the polysaccharide STP using model of LPS-induced inflammation in THP-1 macrophage-like cells (on the expression of IL1B, IL6, IL10, TNF, NFKB1, BCL2, NRF2, and BAX—genes involved in the regulation of inflammatory processes and oxidative stress), rat pocket granuloma, and carrageenan-induced oedema models. STP significantly reduced oedema volume, exhibiting a comparable anti-exudative effect to ibuprofen and surpassing the control group. The anti-inflammatory mechanism of STP extends beyond suppression of proinflammatory cytokine (IL1B, IL6, TNF) expression, as it also activates cellular defence mechanisms (NRF2, BCL2, BAX) and expression of anti-inflammatory cytokine (IL10). This complex, multifactorial action suggests that STP may possess significant therapeutic value for inflammatory conditions. The combined functional and molecular findings underscore STP’s potent anti-inflammatory properties, comparable to ibuprofen. Full article