Lane snapper Lutjanus synagris is an important species that supports both commercial and recreational fisheries. In the southern Gulf of Mexico, lane snapper is one of the snapper species with the highest annual catch volumes. Nevertheless, information on several life-history traits such as longevity, natural mortality and age at maturity is lacking, which are important for providing appropriate management options. From the total captured lane snapper (n = 1150), 367 were used to estimate the age-life history. Specimens were captured through the small-scale fleet of Yucatan from 2008 to 2009 in southern Gulf of Mexico with total lengths from 14.50-45.90 cm and whole weights from 0.05-1.10 kg. Thin otolith sections were used to determine the age of lane snapper. Left sagittae were embedded in clear epoxy resin, thin sectioned (300 µm thickness), and analyzed using a stereomicroscope, counting opaque zones (white) deposited annually during late spring to early summer. Estimated ages ranged from 0+ to 16 years for females (n = 189) and from 0+ to 15 years for males (n = 164). In the growth modeling process, three candidate models were fitted to improve the plausibility of growth estimates under conditions where both small/young and large/old individuals are poorly represented, and the observed length-at-age data show high variability. A Bayesian approach based on the Markov Chain Monte Carlo was used, with informative priors on the growth parameters. During model fitting, three‑parameter versions were used: k, L∞, and a third parameter based on length-at-birth, L0; among these, the last two parameters have the same interpretation across all models. The best growth model by sex was selected based on the Leave-one-out cross-validation technique. The von Bertalanffy growth model was the best-fitting model for growth in both females and males. Growth parameters for females were for maximum mean length or asymptotic length (L∞) = 32.21 cm total length; growth coefficient (k1) = 0.27 year-1; size-at-age-zero (L0) = 2.06 cm and for males L∞ =  28.32 cm total length; k1 =  0.41 year-1; L0  = 2.03 cm. Natural mortality was estimated at 0.39 year-1 for females and 0.41 year-1 for males. Age at maturity in which 50% of the females and males have reached maturity was A50 = 3.11 years for females and 1.68 years for males. The reference points of the optimal size (Lopt) and optimal age (Aopt) to harvest the specimens to achieve maximum yield were 26.17 cm total length, 6.20 years for females and 21.24 cm total length, 3.38 years for males. These results on the age-based life history and growth of lane snapper are novel for the southern Gulf of Mexico population. This information forms the basis for developing appropriate management measures, as catch volumes and exploitation levels are steadily increasing.
Understanding the growth dynamics of semiconductor nanorods remains challenging because most syntheses proceed under continuously reacting conditions, where growth histories collapse into end-point morphologies. Here, we introduce a time-gated breath figure strategy enabled by a two-valve humidity control system that allows interfacial reactions to be discretely initiated and arrested without disrupting template formation. Using CdS as a representative model system, the time-gated breath figure approach enables time-resolved analysis of radial and axial growth evolution during nanorod formation under confined interfacial conditions. The results suggest that nanorod diameters become established at an early stage of interfacial reaction, whereas subsequent reacting time primarily influences axial elongation within a finite temporal window. This temporally decoupled growth behavior is consistent with a distinct growth regime characterized by early radial fixation and temporally limited axial elongation. Such temporally resolved growth evolution has remained difficult to access in conventional syntheses performed under continuously reacting conditions. Beyond providing insight into nanorod growth dynamics, these findings establish a useful framework for understanding interfacial growth under confined conditions and for designing nanorod-embedded porous films based on reacting breath figure processes.
Normative 3-dimensional mandibular reference values derived from well-defined, symmetrical populations without radiographic temporomandibular joint (TMJ) alterations are limited, yet they are essential for improving diagnostic accuracy in growth-related mandibular disturbances. This study aimed to establish age-stratified CBCT-based normative parameters for mandibular size and condylar morphology in skeletally symmetrical individuals without radiologic signs of articular alterations. A total of 213 CBCT scans were selected from a database of 2400 examinations using strict inclusion criteria (skeletal symmetry and absence of radiographic TMJ alterations). Condylar volume, mandibular ramus length, mandibular body length, and the degree of condylar corticalization were quantified and analyzed by age group, sex and facial biotype. Descriptive statistics, bilateral comparisons, and linear and logistic regression models were applied to investigate associations and define normative parameters (α=0.05). Sex-specific and age-specific reference values were established for mandibular ramus and body lengths and for condylar volume. Complete condylar corticalization showed a strong correlation with chronological age (P<0.001), with an optimal cutoff at 17 years. The normative dataset provides objective quantitative benchmarks that can complement conventional clinical and imaging evaluations and may support early identification of abnormal mandibular growth patterns, including condylar hyperplasia and ramus hypodevelopment. This study provides robust CBCT-derived normative values for mandibular dimensions and condylar volume across age groups in symmetrical individuals without radiographic condylar alterations. Complete condylar corticalization appears to be a reliable radiologic marker of mandibular ramus growth and maturation, offering clinically useful reference thresholds to enhance diagnostic decision-making in dentofacial assessment.
To evaluate the longitudinal effects of vosoritide on growth, body proportionality, and safety in children with achondroplasia in a real-world clinical setting, and to identify early predictors of treatment response. We conducted a hybrid retrospective-prospective observational study in children with achondroplasia treated with vosoritide at a single tertiary center. Pre-treatment clinical and anthropometric data were collected retrospectively and prospectively. Prospectively patients were evaluated at baseline and after 12 and 24 months on treatment. Growth was assessed using height SDS, based on both WHO and achondroplasia-specific reference charts, as well as annualized height velocity Z-scores (HV SDS). Body proportionality was evaluated using the height/(height - sitting height) ratio. Longitudinal changes were analyzed using linear mixed-effects models, and potential predictors of response were explored using correlation and regression analyses. Thirty-five children (mean age 5.92 ± 3.56 years) were included. Height velocity increased significantly at both 12 months (+1.50 SDS) and 24 months (+1.91 SDS) compared with baseline (p < 0.001). Using achondroplasia-specific references, height SDS increased over time, with a trend toward increment at 12 months (+0.17 SDS, p = 0.060) and a significant increase at 24 months (+0.50 SDS, p < 0.001). Similarly, WHO-based height SDS showed no significant change at 12 months and a significant increment at 24 months (+0.30 SDS, p = 0.005), suggesting a more gradual shift toward WHO standards. Body proportionality remained unchanged (p = 0.134). Height velocity increment during the first 12 months did not significantly predict height SDS gain at 24 months, highlighting inter-individual variability in treatment response. A significant age-by-time interaction was observed (p = 0.006), suggesting a differential longitudinal response according to age at treatment initiation. Hypertrichosis occurred in 66% of patients, but no severe adverse events were reported. Vosoritide increased linear growth in this real-world cohort, with heterogeneous response patterns over time. Height velocity increment during the first 12 months did not predict longer-term outcomes, and body proportionality remained unchanged over 24 months. Treatment was well tolerated, supporting its use in clinical practice.
Tyrosine aminomutase (TAM) and its product, the non-proteinogenic amino acid (R)-β-tyrosine, were previously identified in rice (Oryza sativa L.). Because (R)-β-tyrosine strongly inhibits the growth of dicotyledonous plants, it can be used to enhance crop weed resistance. However, the distribution of TAM and (R)-β-tyrosine remains largely unexplored, even among major grass crops. Here, we investigated their distribution, biosynthetic mechanism, evolutionary history, and potential function in grasses. β-tyrosine was detected in oat (Avena sativa L.) and maize (Zea mays L.) among 22 grass species tested, and chiral analysis revealed it to be predominantly the (R)-enantiomer. Stable isotope labeling confirmed the involvement of TAM in its biosynthesis in maize. A homology search identified a TAM-like gene in maize, Zm00001d033286, previously annotated as phenylalanine ammonia-lyase (PAL). Functional expression of Zm00001d033286 in Nicotiana benthamiana resulted in β-tyrosine production, demonstrating that it encodes TAM (ZmTAM1) and produces (R)-β-tyrosine. Site-directed mutagenesis revealed key residues essential for this activity, and in vitro assays further revealed that ZmTAM1 retains PAL and tyrosine ammonia-lyase (TAL) activities. Phylogenetic analysis suggested that TAM evolved from PAL, not from phenylalanine/tyrosine ammonia-lyase (PTAL). Finally, we demonstrated that (R)-β-tyrosine significantly inhibits the growth of Striga hermonthica, a parasitic weed threatening maize cultivation, at biologically relevant concentrations. Our study shows the sporadic yet phylogenetically broad distribution of TAM in grasses, provides fundamental insights into its potential catalytic mechanism and evolutionary history, and suggests a potential utility of (R)-β-tyrosine in maize defense against parasitic weeds.
Quinoa is a protein-rich crop and an excellent dietary source of selenium. While selenium application enhances growth and selenium accumulation, its tolerance and underlying molecular mechanisms in quinoa remain unclear. Physiological and biochemical analyses showed that 7.5-12.5 kg/ha is the optimal selenium rate, significantly improving plant height, leaf area, stem strength, photosynthetic performance, and antioxidant capacity, thereby promoting nutrient accumulation. Selenium application markedly increased seed selenium levels (SeG2: 2763.52 μg/kg; SeG4: 5120.82 μg/kg vs CK: 18.85 μg/kg), with SeMet as the dominant form (1113.18 μg/kg). Multiomics analysis revealed significant enrichment of multiple selenium-related pathways, including flavonoid, anthocyanin, and lipid biosynthesis. Twenty DEGs (CqHMT1, CqML, CqMMT, CqGST, CqTTS, CqAGT5, CqANR, CqCHS, CqDAT1, CqLOX2.1, CqDES1) were verified by qRT-PCR, the selenium transport pathway was preliminarily constructed. This study clarifies selenium accumulation and nutritional changes in quinoa, providing new strategies for selenium-enriched agricultural production.
Neddylation is highly activated in many human cancers and may serve as a therapeutic target for clinical treatment. However, it remains unclear regarding the role of neddylation in tumor angiogenesis. Here, we demonstrate that the neddylation E2 enzyme UBE2M is upregulated in tip cells and is essential for tumor vascular sprouting. We show that UBE2M-mediated neddylation of STAT1 enhances its phosphorylation and promotes the transcription of DLL4. This elevated DLL4 expression in tip cells activates Notch signaling in adjacent stalk cells, thereby maintaining the tip-stalk cell balance and ensuring organized vascular patterning. Consequently, endothelial-specific deletion of UBE2M reduces DLL4 expression, leading to excessive but non-productive sprouting due to uncontrolled tip cell formation and lack of stalk cell support, which ultimately suppresses tumor growth. Importantly, targeting endothelial neddylation potently sensitizes various tumors to anti-VEGF therapy. Together, our findings unveil UBE2M as a key regulator of angiogenic signaling and identify it as a promising anti-angiogenic target in cancer.
The mammalian cerebellum is a densely folded structure composed of lobules separated by deep fissures, while individual lobules display striking diversity in shape and size. Although multicellular processes such as granule cell proliferation and migration drive cerebellar morphogenesis, mechanical mechanisms that generate diverse lobular morphologies after initial folding remain poorly understood. Spatially heterogeneous cortical growth arising from multicellular dynamics is considered critical for the formation of characteristic lobular morphologies. In this study, we employed mathematical modeling and computer simulations to investigate how heterogeneous cortical growth influences cerebellar lobular morphology. We developed a mathematical model of cerebellar cortical growth based on continuum mechanics and simulated lobular deformation under spatially heterogeneous cortical growth using the finite element method. Our simulations indicated that heterogeneous cortical growth modulates the rates of increase in lobular height and width; however, under most conditions, lobules elongate during cortical growth, forming columnar morphologies because of the strong constraints imposed by anchoring centers, i.e., the bases of the initial fissures. In contrast, fan-shaped lobules emerged only when relatively large cortical growth occurred in a flat cortical region at the lobular apex, resulting in expansion along the anterior-posterior axis. These results confirm that the interplay between spatially heterogeneous cortical growth and initial lobular morphology is a key mechanical requirement for generating diverse cerebellar lobular morphologies, highlighting the utility of computational approaches for dissecting complex morphogenetic processes.
Cadmium (Cd) poses a threat to plant growth. Nitrogen (N) has been demonstrated to alleviate Cd phytotoxicity, but the underlying mechanism in woody plants remains unclear. In this study, we aimed to determine whether exogenous NH₄HCO₃ influences rhizosphere soil properties and fungal communities, thereby enhancing plant growth and Cd phytoaccumulation in Populus yunnanensis Dode. A pot experiment was conducted in a greenhouse, with seedlings subjected to four treatments: CK (no additional N and Cd), N (24 mg N kg-1 month-1 supplied as NH₄HCO₃), Cd (20 mg Cd kg-1 month-1), and CN (24 mg N kg-1 and 20 mg Cd kg-1 month-1). Under Cd stress, exogenous NH₄HCO₃ increased the biomass (48.0-78.2%), root development, nutrient content, and Cd accumulation (149.2%). In rhizosphere soil, exogenous NH₄HCO₃ decreased the soil pH and NH4+-N content but increased the NO3--N content, available phosphorus (AP), and soil enzyme activities. Exogenous NH₄HCO₃ also reshaped the composition, structure, and co-occurrence patterns of the rhizosphere fungal community, altering the relative abundances of saprotrophic and ectomycorrhizal fungi, such as Rhizoctonia, Peziza, and Exophiala. Moreover, Rhizoctonia and Peziza were positively and negatively correlated with AP, alkaline phosphatase, root biomass, root surface area (RA), fine root surface area (FRA), and Cd uptake efficiency, respectively. Exophiala was positively correlated with root biomass, RA, and FRA. Overall, exogenous NH₄HCO₃ modulates rhizosphere soil properties and reshapes fungal communities, which may improve plant growth and enhance Cd phytoaccumulation. Nitrogen (N) has been shown to alleviate cadmium (Cd)-induced phytotoxicity and promote plant growth. However, its effects on woody plant growth and phytoremediation capacity remain unclear. This study reveals a fungus–soil–plant interaction mechanism in which NH₄HCO₃ alters rhizosphere soil properties and reshapes rhizosphere fungal communities, potentially enhancing the growth, Cd uptake, and Cd accumulation of Populus yunnanensis under Cd stress. These findings suggest that N fertilisation management can be considered an eco-enhancing and sustainable strategy for improving both plant growth and phytoremediation efficiency.
Climate-driven increases in global surface water temperatures are enhancing upper ocean stratification and likely resulting in more prolonged periods of nutrient limitation. Although nutrient limitation in diatoms and their growth responses to increasing temperatures have been studied extensively, much less is known about their growth response to nutrient injection after prolonged durations of nutrient limitation. This study examines the growth response of three bloom-forming diatom species: Pseudo-nitzschia pungens, P. australis, and Skeletonema costatum after short-term (~2 week) and prolonged (~4 week) periods of nutrient limitation at five temperatures (9, 12, 15, 20, and 25°C). Pseudo-nitzschia species showed shorter lag times and higher specific growth rates than S. costatum after prolonged nutrient stress. These findings demonstrate that certain diatom species can exhibit faster growth recovery after prolonged nutrient limitation and in warmer conditions compared to others, providing new insights on drivers that shape phytoplankton communities.
Lead (Pb) contamination in agricultural soils presents substantial risks to soil health, crop productivity, and food safety. The use of vermicompost derived from agricultural crop residues offers a promising approach to reduce Pb bioavailability in soil and alleviate its toxicity in maize seedlings by improving soil properties. This study investigates how vermicompost use can counteract Pb toxicity in maize with varying Pb accumulation tendencies. A pot experiment was conducted using four vermicompost doses (0, 4, 6, and 8 tons ha-1) applied through the soil route to assess the morpho-physiological and root structural-functional responses of maize plants under different Pb levels (0, 100, 200, and 300 mg kg-1 soil) in the growth medium, a topic that remains underexplored in the existing literature. Results indicated that Pb toxicity markedly inhibited maize seedling growth, as revealed by decreases in shoot fresh weight, root characteristics, and inorganic ions uptake; greater Pb accumulation was noted in roots and shoots of Pb-stressed plants relative to vermicompost-untreated plants. The vermicompost treatment promoted maize growth more efficiently, with increments of shoot fresh weight (124.96%), root length (138.46%), root average density (103.44%), and root volume (321.87%), as well as improved root anatomical characteristics. Vermicompost decreased Pb deposition in shoots (50.89%) and roots (65.25%) relative to untreated Pb-stressed plants. VC enhanced Pb stress resistance in maize by modulating activities of phytoaccumulation indices, such as BAC (24.35% ↓), BCF (35.50% ↓), and TF (40.99% ↑), while concurrently maintaining ionic balance, root Na+ (38.61% ↓), and shoot K+ (68.75% ↑). The application of vermicompost in this study significantly reduced Pb-induced stress, improved nutrient uptake, and enhanced growth parameters of maize under controlled conditions. These results indicate that vermicompost has considerable potential as an organic amendment for mitigating Pb toxicity in maize. Previous research on Pb stress mitigation in plants has primarily examined physiological and biochemical responses, while the regulatory effects of organic amendments on soil Pb bioavailability and root morpho-functional traits remain underexplored. The present study examines the influence of vermicompost on Pb bioavailability, ionic homeostasis, and root functional structure to improve stress tolerance in maize.
Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) drive multiple aggressive lymphomas, yet effective targeted therapies for these virus-associated malignancies remain limited. Using an unbiased kinome-wide screen combined with analysis of virus-positive patient tumors, we identified fibroblast growth factor receptor 2 (FGFR2) as a selectively activated host kinase in EBV- and KSHV-associated lymphomas. Importantly, FGFR2 is required for efficient establishment of EBV latent infection, and its knockdown markedly impairs the formation of viral latency programs. Viral latency proteins EBV nuclear antigen 2 (EBNA2) and latency-associated nuclear antigen (LANA) recruit STAT3 and RBP-Jκ to the FGFR2 promoter to drive its transcription, enabling efficient establishment of EBV latency and activation of downstream STAT3/AKT signaling. This feed-forward signaling circuit suppresses apoptosis, promotes S-phase progression, and sustains proliferation of infected lymphoma cells. Targeting FGFR2 genetically or pharmacologically using clinically relevant inhibitors markedly suppresses tumor growth in vitro and in vivo. This study identifies FGFR2 as a critical oncogenic driver in EBV and KSHV infections, highlighting its potential as a therapeutic target to inhibit tumor growth and treat associated viral malignancies.
Restricting nutrients in eggs may hinder the growth of commercial chickens, which could result in higher embryonic mortality and poor growth performance, indicating the significance of in ovo injection of dietary nutrients to support embryonic and post-hatch growth in poultry. This study investigated the in ovo supplementation of a dietary supplement on egg weight, embryonic development, hatching, and chick quality traits of broiler chickens. A total of 300 hatching eggs were randomly pre-assigned to a specific in ovo injection protocol (T-1, T-2, T3, and T-4) and incubated under standard conditions. At embryonic day (ED) 12, the eggs were either injected with distilled water or a dietary supplement (containing a mixture of vitamins, trace minerals, and amino acids). The injection treatment consisted of T-1 (non-injected eggs), T-2 (eggs injected with 5 mL of distilled water), T-3 (eggs injected with 5 mL of a solution containing 0.04% of the dietary supplement), and T-4 (eggs injected with 5 mL of a solution containing 0.08% of the dietary supplement). The results revealed that the experimental treatment had no effect on egg weight or egg weight loss during embryogenesis (p > 0.05). The lowest weight of yolk-free body mass (YFBM-w), yield of yolk-free body mass (YFBM-Y), embryo length (Em-L), embryo width (Em-W), tibia length (TL), and wing length (WL) at ED 16 were identified in T-4 (p < 0.05). At ED 19, the highest Em-L and eye width (Ey-w) were identified in T-3 (p < 0.05). The highest chick weight at hatch (CWAH) and chick yield (CY) were identified in T-4 (p < 0.05). While the chick length and appearance score were lowest in T-4, the chick eye score was lowest in T-2 (p < 0.05). The embryonic mortality, hatchability, navel, and leg scores of chicks were similar among the treatments (p > 0.05). It was concluded that the in ovo injection of a mixture of dietary nutrients could improve embryonic traits during the latter part of embryogenesis, chick weight, and chick yield at hatch; however, it may possess a strong negative effect on hatchability, embryonic mortality, and chick quality traits.
Angiogenesis serves as a central hallmark of breast cancer progression by driving the formation of a dysfunctional vascular network that sustains tumor growth, enables metabolic adaptation, and facilitates metastasis. Hypoxia within the tumor microenvironment (TME) stabilizes hypoxia-inducible factor-1α (HIF-1α), that transcriptionally activates key pro-angiogenic mediators, including vascular endothelial growth factor (VEGF) and angiopoietins (ANGPT). Concurrently, stromal and immune constituents of the TME, particularly cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs), potently augment angiogenesis through the secretion of cytokines, growth factors, and extracellular matrix-remodeling enzymes. These mediators promote endothelial cell activation, increase vascular permeability, and facilitate immune suppression. The VEGF/VEGFR signaling axis serves as a master regulator, orchestrating endothelial cell proliferation, migration, survival, and neovascularization. Although anti-angiogenic agents such as the VEGF-neutralizing monoclonal antibody bevacizumab have demonstrated clinical efficacy, responses are frequently transient owing to intrinsic and acquired resistance, intratumoral vascular heterogeneity, and compensatory activation of alternative angiogenic pathways. Consequently, contemporary therapeutic approaches prioritize rational combination regimens integrating anti-angiogenic agents with chemotherapy, immunotherapy, or radiotherapy to induce vascular normalization, enhance drug penetration, and potentiate antitumor immunity. Targeting the TME, including stromal and immune components, together with bioactive phytochemicals, possessing anti-angiogenic and immunomodulatory properties, has emerged as a promising strategy. This review integrates current knowledge on tumor-endothelial crosstalk, hypoxia- and inflammation-driven angiogenic signatures such as VEGF, miR-20a, and ANGPTL4, while evaluating emerging modalities, including microRNA-based interventions, nanoparticle delivery, and TME reprogramming to overcome resistance and enhance the precision and durability of anti-angiogenic therapies in breast cancer.
Angiogenesis is a crucial process in ischemia diseases like coronary heart disease, stroke and wound healing. Panasenoside (PSS) is a flavonoid glycoside ioslated from Chinese Materia Medica GINSENG RADIX ET RHIZOMA which has been demonstrated with multiple biological activities. However, the pharmacological activity of PSS and the underlying mechanism are still unclear. We found that PSS promoted sub-intestinal vessel plexus (SIVs) growth in zebrafish. PSS ameliorated vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor II (VRI)-induced deficiency of intersegmental vessels (ISVs) in a concentration dependent manner by downregulation of mRNA expression of VEGF receptors, including Kdr/VEGFR-2 (kdr), VEGFR-1 (flt1), and Kdr-like/VEGFR-2 (kdrl), and up-regulation of VEGF (vegfaa). The angiogenesis effect of PSS on VRI-induced ISVs deficiency was suppressed by PI3K, AKT, MEK, ERK, P38, Sirtuin 1 (SIRT1), Nuclear factor erythroid-2-related factor 2 (NRF2) and Nicotinamide N-methyl transferase (NNMT) inhibitors. Activation of NRF2, SIRT1 and MNA significantly restored VRI-induced ISVs insufficiency. In addition, PSS protected against VRI-induced tube formation deficiency in human umbilical vascular endothelial cells (HUVECs). SIRT1, NRF2 and NNMT inhibitors or siRNA eliminated PSS promoting vascular endothelial cell tube formation. PSS also prevented SIRT1, NRF2 and NNMT inhibitors-induced vascular endothelial cell senescence. Furthermore, PSS upregulated the protein expression level of SIRT1 and downregulated its downstreams P53 and PGC-1α in HUVECs with high potence of activating SIRT1 by binding with its active domine. In conclusion, PSS presented pro-angiogenesis effect by mitigating vascular endothelial cell ageing and the underlying mechanisms were involved in the PI3K/AKT/MAPKs, SIRT1/NRF2 and NNMT/MNA signaling pathway with SIRT1 acting as a key regulator. We identified the pro-angiogenesis and anti-vascular endothelial cell ageing effects of PSS for the first time, and PSS is a promising drug candidate for treating vascular deficiency associated diseases.
This work establishes a robust and reproducible 96-well plate-based 3D HepG2 tumour spheroid model for drug screening applications. A 7-d culture protocol was optimised to generate HepG2 spheroid model using 96-well ultra-low attachment plates with 5 seeding densities (500, 1000, 2500, 5000 and 10,000 cells/well). Spheroids were evaluated for morphology, viability and proliferation. The optimized model was treated with doxorubicin and sorafenib at their respective IC50 values (2.4 µM and 5.3 µM, determined in HepG2 monolayer). Drug-specific responses were assessed via spheroid growth, viability and expression of apoptotic and drug resistance markers. Spheroids seeded at 500 cells/well exhibited optimal characteristics, including sustained proliferative capacity (up to 30-fold increase relative to day 1) and progressive spheroidal growth (1.85-fold-change in diameter); hence, it was selected for further experiments. Day 4 was identified as the optimal treatment point based on morphology, viability and diameter progression. The 72-h IC50 values were determined to be 2.4 µM for doxorubicin and 5.3 µM for sorafenib; these concentrations were chosen for subsequent treatments on HepG2-derived spheroids. Doxorubicin induced a delayed but potent cytotoxic response, while sorafenib triggered a slower, sustained effect, distinct from its rapid action in monolayer cultures. Furthermore, spheroid diameter did not correlate with viability or proliferation decline, highlighting its limitation as a sole readout. Molecular profiling revealed drug-specific responses in which ABCB1 was upregulated by doxorubicin, while ABCC2 was selectively induced by sorafenib. Sorafenib progressively reduced BAX/BCL2 ratio, suggesting potential resistance development. This study presents an optimized HepG2 spheroid model with validated culture and treatment parameters, capturing drug-specific cellular and molecular responses for therapeutic screening and mechanistic studies in hepatocellular carcinoma.
Intracranial meningiomas are the most common primary intracranial tumors, with rising detection rates due to increased neuroimaging. We examined surgical management trends to determine whether surgical incidence is independent of detection rate and to characterize shifts in surgical indications and patient demographics. This retrospective cohort study included 2,278 consecutive adults undergoing primary surgical resection for meningiomas at Helsinki University Hospital (2005-2023). Trends in absolute surgical caseload and patient demographics were analyzed. Surgical incidences were standardized to the European Standard Population (ESP 2013), and age-specific Observed-to-Expected (O/E) ratios were calculated against baseline incidences (2005-2008). Absolute annual surgical caseload remained stable (range: 83-160 cases; crude incidence 3.8-7.7 per 100,000 person-years; p = 0.868), while the median age of operated patients increased significantly by 2.9 months per year (p = 0.018). The most common presenting symptoms were seizures (19%) and visual symptoms (14%); symptom relief was the most common surgical indication (62%). Age-standardized (ESP) surgical incidences declined over time (3-year sliding average p < 0.006 for all age groups), and demographic-adjusted O/E ratio analysis supports this decline, particularly in the 30-69 years age range. Prophylactic surgeries declined significantly (p < 0.001), while surgeries prompted by tumor growth (p = 0.031) and large tumor size (p < 0.001) increased. Despite increased detection and an aging population, age-adjusted surgical incidence for meningiomas declined over 19 years, supporting the interpretation of a shift toward a more selective, risk-stratified approach. Surgery is increasingly reserved for cases with documented growth, mass effect, or functional deficits.
Suprachoroidal delivery offers a minimally invasive route for targeting the choroid and retina, while reducing complications related to conventional ocular delivery methods. This review focuses on hydrogels engineered for the suprachoroidal space (SCS) as advanced materials platforms for next-generation posterior ocular therapy. We outline key hydrogel design principles in the context of SCS anatomy and biomechanics and highlight how crosslinking chemistry and material properties can be tuned for specific therapeutic goals. Promising applications of SCS hydrogel systems are discussed, including (i) reduction of intraocular pressure (IOP), (ii) swelling-assisted targeting of drug particles toward the posterior eye, (iii) prolonged delivery of biologics, such as anti-vascular endothelial growth factor (VEGF) agents, (iv) minimally invasive support of cell transplantation, and (v) hydrogel-forming microneedles (HFMNs) for assessing SCS. We also discuss key translational considerations such as preclinical to clinical translation, biocompatibility, injectability, storage stability, sterilization, manufacturing, and scalability alongside future development directions. Taken together, this review introduces SCS-targeted hydrogels as a distinct class of minimally invasive and clinically relevant materials for the treatment of posterior eye diseases.
III-V compound semiconductors are promising candidates for thin-film thermoelectric materials because their narrow-bandgap alloys can exhibit a thermoelectric response near room temperature. In this study, we systematically investigated polycrystalline InGaSb thin films deposited on glass substrates and identified the deposition temperature and In flux as key parameters governing phase competition and nanoscale compositional fluctuations. By modulating the In supply, discontinuous In-rich precipitates were formed while the matrix composition was systematically tuned. Variation of the deposition temperature further enabled control of structural disorder and nanoscale features, as evaluated by Raman analyses. At the highest deposition temperature (560 °C) that maintained continuous films, increased disorder correlated with an enhanced Seebeck coefficient without a significant reduction in electrical conductivity. As a result, a high power factor of 1200 µW m-1 K-2 was achieved near room temperature. These findings demonstrate that growth-parameter-driven microstructure and phase control provide an effective strategy for enhancing thermoelectric performance in multicomponent polycrystalline III-V thin films.
This paper was originally a panel presentation at AGPA Connect, the annual meeting of the American Group Psychotherapy Association, held in March 2025. The author briefly reviews modern analytic myths about therapeutic terminations that may evoke feelings of failure in group leaders and impede their ability to work collaboratively with themselves and group members. These myths can interfere with making terminations a constructive and progressive experience. Three personal and clinical examples are offered to illustrate how the blending of the leader's personal and professional life deepened emotional connections in unexpected ways. The article proposes expansions of modern analytic theory and technique aimed at helping group leaders manage negative feelings around loss, thereby making room for therapeutic repair and emotional growth.