Heterogeneity in spiking activity is ubiquitous among neurons even within a given cell type. To date, the relative contributions of extrinsic mechanisms (e.g., synaptic bombardment), intrinsic mechanisms (e.g., conductances), and cell morphology toward determining spiking activity remain poorly understood. Here, we addressed this important question using a combination of extracellular in vivo recordings of electrosensory pyramidal cells within weakly electric fish with computational modeling. Specifically, by varying parameters of a conductance-based computational model, we successfully reproduced the highly heterogeneous spiking activities seen experimentally. Model parameters that varied the most were then used to gauge the relative contributions of extrinsic vs. intrinsic mechanisms. Overall, extrinsic synaptic input was predicted to be the main factor accounting for spiking heterogeneity. We tested this prediction experimentally by performing two different manipulations: (1) pharmacologically inactivating feedback from higher brain areas and (2) applying the neuromodulator serotonin. Our model showed that feedback inactivation should reduce spiking heterogeneity, whereas serotonin application should increase it, two predictions that were corroborated experimentally. Importantly, for serotonin application, increased heterogeneity occurred despite a strong reduction in intrinsic membrane conductance, further demonstrating that extrinsic synaptic input is the primary determinant of spiking heterogeneity in vivo. Taken together, our results demonstrate that devising a computational model to capture spiking heterogeneities in vivo and assessing which parameters are responsible can successfully determine the relative contributions of extrinsic inputs, intrinsic properties, and neural morphology.

Impact of natural antimicrobials on survival behavior and cell morphology of acid-stressed pathogens in ready-to-eat rice.

Predictable toxicity of antibiotics and disinfection by-products as well as their mixtures based on the mechanism-oriented analysis.

Peri-implantitis compromises soft and hard tissues around dental implants, often leading to implant failure. Antibacterial nanocoatings offer a promising infection control strategy, but maintaining biocompatibility is essential. This study investigated, through a range of assays and analytical techniques, the biocompatibility of antimicrobial silver and hydroxyapatite (HA) nanocoatings applied to titanium implants with human gingival fibroblasts (HGFs). Silver and hydroxyapatite nanocoatings were applied to the surface of titanium alloy specimens using electroplating, deposition and sintering techniques. The biocompatibility of the nanocoatings with HGFs was assessed by measuring cell metabolic activity (alamarBlue), lactate dehydrogenase (LDH) release, collagen production (Sircol assay), and cell morphology (scanning electron microscopy). Nanocoating stability was tested in ultrapure water, Modified Krebs and artificial saliva. Elevated total Ag+ concentrations were measured in the media released from the silver and HA nanocoatings (1.78 mg/l on day 4 and 1 mg/l by day 7). Electrolytes remained within physiological ranges. The HGFs cultured on the nanocoatings showed normal morphology, intact membranes (LDH < 60 nmol/min/ml), healthy collagen secretion (27.18 - 31.11 µg/ml), and aerobic metabolism at 80% of controls, consistent with biocompatibility. The silver and HA nanocoatings confirmed a sustained Ag+ release, necessary for a strong antimicrobial activity, while maintaining HGFs health and cell functionality. Our previous work has confirmed the strong antimicrobial activity of these nanocoatings when applied to dental implants, and the findings of this study have demonstrated that the implant biocompatibility is not compromised. This suggests that these silver and HA nanocoatings can be safely used to minimise peri-implantitis and prevent implant failure.

This study aimed to evaluate osteogenesis on the surface of three-dimensional (3D)-printed titanium (Ti). For this reason, mesenchymal stem cells (MSC) and osteoblastic-like cells cultures (Saos-2) were plated on 3D-printed Ti for up to 17 days. The following parameters were evaluated: 1) cell morphology; 2) cell viability and proliferation; 3) runt-related transcription factor-2 (RUNX2), type I collagen (COL I), osteopontin (OPN), bone sialoprotein (BSP), and osteocalcin (OC) gene expression; 4) COL I quantification; 5) alkaline phosphatase (ALP) activity, and 6) extracellular matrix (ECM) mineralization. Machined Ti samples were used as control. The data were analyzed statistically, considering a significant level of 5%. The findings of the study revealed that the surface characteristics of 3D-printed Ti allowed adhesion and proliferation of MSC and Saos-2 similarly as observed for both cultures grown on Machined Ti (p>0.05). However, Saos-2 cultured on 3D-printed Ti exhibited significantly higher ALP activity (p<0.05), whereas no difference was observed for MSC (p>0.05). Additionally, both cell types showed upregulation of osteogenic gene expression (including RUNX2, COL I, OPN, and BSP), increased COL I secretion, and enhanced ECM mineralization compared to those grown on Machined Ti (p<0.05). In conclusion, 3D-printed Ti significantly enhances osteoblastic differentiation in MSC and Saos-2 cultures. It promotes a higher expression of genes linked to bone growth and extracellular matrix mineralization, offering distinct advantages over traditionally Machined Ti. These outcomes highlight the promising potential of 3D-printed Ti for promoting osteogenesis, indicating its suitability for bone tissue engineering applications and advancement in bone regeneration strategies.

The baculovirus expression vector system (BEVS) is a scalable platform used to produce recombinant adeno-associated virus vectors (rAAV) in insect cells. A major challenge in this system is reducing the formation of empty rAAV capsids, which do not contain vector DNA and lack therapeutic value. The proportion of empty capsids is influenced by the balance between the two baculovirus constructs that coinfect the producer cells: Bac-Rep-Cap, which supplies AAV replication and capsid proteins, and Bac-GOI-ITR, which delivers the therapeutic gene of interest. Digital holographic microscopy (DHM) is a label-free imaging technique that allows real-time monitoring of cell morphology in suspension cultures. Previous studies have used DHM to track cell density and baculovirus infection; however, its ability to evaluate different coinfections has not been explored. In this study, we combined DHM with machine learning to identify morphological patterns associated with various coinfections for rAAV production. Shaker-flask experiments with different Bac-Rep-Cap: Bac-GOI-ITR ratios created a dataset of cell morphologies to train a predictive classification model. When applied to real-time bioreactor measurements, the model revealed shiftsin the classification patterns related to the initial multiplicity of infection (MOI). The integration of DHM with the classification model has the potential to produce a qualitative "process fingerprint," where deviations in morphological patterns can serve as early indicators of suboptimal coinfection. Such early warning signs enable timely batch termination, reducing downstream processing of inconsistent material. Overall, DHM combined with machine learning offers a non-invasive, real-time tool for process benchmarking and quality assurance in rAAV manufacturing.

Incubation time and culture medium affect gram staining accuracy: A Cellpose image analysis study.

Differences in cellular mechanics and ECM dynamics shape differential development of wing and haltere in Drosophila.

Human embryo selection in in vitro fertilisation (IVF) treatments is traditionally based on evaluating cell number, morphology, and fragmentation to select the most viable embryos. However, this static evaluation method has limitations, as it captures only a snapshot of the embryo at a single time point. Recent advancements in time-lapse imaging and artificial intelligence (AI) have improved embryo assessment by enabling dynamic and continuous observation of embryonic development.This retrospective cohort study aimed to evaluate morphometric and morphokinetic parameters of 102 human embryos cultured during IVF cycles. Embryos were included if they reached the blastocyst stage on Day 5 and were selected for fresh single embryo transfer. Morphological and morphokinetic parameters were assessed using time-lapse technology to compare embryos resulting in clinical pregnancy and those that did not.Clinical pregnancy was achieved in 47.1% of transfers. Although no significant differences were observed in blastocyst area, diameter, or inner cell mass (ICM) size between embryos that implanted (P+) and those that did not (P-), trends toward larger dimensions were observed in the P+ group. Morphokinetic parameters showed slightly faster developmental kinetics in P+ embryos, although not significantly.Morphokinetic scores were calculated using time-lapse embryo evaluation systems (KIDScore D5 and iDAScore, Vitrolife). iDAScore values were significantly higher in implanted embryos. iDAScore, which incorporates AI-based scoring, showed better predictive performance compared with KIDScore in ROC and logistic regression analyses, indicating its potential as a reliable tool for embryo selection. These findings support the use of AI-based morphokinetic analysis for improved embryo selection in IVF.

3D polyurethane scaffolds for exploring osteogenic differentiation and mechanical stimulation of mesenchymal stromal cells.

High-resolution fabrication of amorphous calcium phosphate-reinforced polycaprolactone composite scaffolds for bone tissue engineering.

A Knock-In Igfn1iCre transgenic mouse line provides partial developmental access to type-7 bipolar cells.

Harnessing stylicin to suppress Vibrio harveyi virulence through multi-scale molecular interventions: Transcriptomic and molecular dynamics perspectives.

Facilitating extracellular respiration of Methanosarcina barkeri with magnetite nanoparticle: Formation of conductive magnetite nanoparticle-membrane complex.

Motile bacteria can interact with surrounding fluids, creating complex rheological behavior of suspensions. However, studies involving paralyzed flagella or de-flagellated bacteria remain limited, leaving the separate roles of motility, flagella, and cell morphology poorly resolved. This study experimentally investigates the rheology of bacterial suspensions using three strains of Escherichia coli (E. coli), ATCC9637 motile with rotating flagella, HCB136 non-motile mutant with paralyzed flagella, and HCB137 non-motile mutant without flagella, to understand the role of bacterial morphology and motility in suspension rheological behaviors. The results show that the ATCC9637 suspension exhibits a notable decrease in viscosity, particularly pronounced in the low shear rate regime, whereas the HCB136 suspension shows an increase in viscosity, especially in concentrated suspensions. This contrast underscores the influence of active swimmers on modifying the flow field and subsequently fluid viscosity. Deflagellated bacteria reduce fluid viscosity, despite the absence of the organelles necessary for propulsion, driven by flow-induced collective behavior arising from their elongated body shape. Two dimensionless numbers Pef1 and Pef2 are introduced to delineate the bacterial stress dominant and flow stress dominant regimes along with the normalized shear rate. Finally, a prediction model is formulated to correlate the viscosity of bacterial suspensions with the shear rate, cell concentration, bacterial morphology, and bacterial motility.

In this study, two food prolamins, zein and gliadin, were used to encapsulate roxithromycin (ROX) as a model antimicrobial. The physical characteristics of both nanoparticles were analyzed, and the inhibition of Staphylococcus aureus by both free and encapsulated ROX was first evaluated using broth dilution growth curves and microcalorimetry analysis. Analysis of the physical characteristics of the nanoparticles revealed that the gliadin-ROX exhibits greater stability and higher encapsulation efficiency (EE) than zein-ROX. Notably, the freeze-dried gliadin-ROX dispersed well, whereas zein-ROX did not. The scanning electron microscopy (SEM) observations also confirmed that the size of the gliadin-ROX was slightly large. As evidenced by traditional drug susceptibility tests, the gliadin-ROX notably exhibited superior antibacterial efficacy in both micro-broth and macro-broth dilution assays. While the optical density (OD)-based growth curves did not show significant differences, the thermokinetic parameters obtained from microcalorimetry clearly demonstrated that gliadin-ROX was more effective than both free ROX and zein-ROX, evidenced by a much lower half-maximal inhibitory concentration (IC50) and total heat generated over 24 h (Q24h). Similarly, the SEM cell morphology analysis confirmed that gliadin-ROX has superior antibacterial properties. This method provides more quantitative information and may offer an alternative approach for evaluating nano-delivery systems for antimicrobials. © 2026 Society of Chemical Industry.

Targeting microglial dysfunction: The antioxidant potential of and the regulation of microglial responsiveness by dermatan sulfate from a marine invertebrate.

Prostate cancer is the leading male malignancy. Despite therapeutic advances, drug resistance remains a major obstacle, leading many patients to develop castration-resistant prostate cancer. This study investigates the combined effects of the microtubule-targeting agents colchicine and paclitaxel on DU145 prostate cancer cells. Cell viability was evaluated across a range of doses of colchicine and paclitaxel to determine the IC50, IC30, and IC10 values for each drug. IC10 and IC30 doses of the agents and their combinations were selected for subsequent experiments. The effects of the treatments were then analyzed using the MTT assay, the colony formation assay, the in vitro scratch assay, and acridine orange/ethidium bromide staining. Monotherapy with colchicine and paclitaxel indicated dose- and time-dependent cytotoxicity in DU145 cells. Notably, IC10 monotherapies had minimal impact on viability, whereas the drug combination produced synergistic inhibition of viability (excess‑over‑Bliss score: 14.8%), along with marked suppression of colony formation and cell motility (p<0.0001). At IC30, the combined treatment nearly abolished colony formation and significantly increased apoptotic and necrotic morphology. These findings reveal that combining sub-therapeutic doses effectively inhibits cell viability, long-term proliferation, and cell motility, where monotherapies are insufficient. These preliminary findings demonstrate that the colchicine and paclitaxel combination exhibits potent synergistic effects, particularly at low doses (IC10), and effectively suppresses DU145 prostate cancer cell progression. This dual microtubule-targeting approach may overcome the limitations of monotherapy by significantly inhibiting cell motility and clonogenic survival, while enhancing apoptotic and necrotic cell morphology. Our results suggest that low-dose combination strategies may provide high therapeutic efficacy while minimizing systemic toxicity in the management of advanced prostate cancer.

AI-based histopathology analysis predicts checkpoint inhibitor response in advanced melanoma and identifies patterns associated with response.

Chirality at the nanoscale has emerged as a powerful design parameter for engineering light-matter interactions, catalytic activity, and biological recognition. Among inorganic nanomaterials, plasmonic gold nanostructures are particularly attractive owing to their tunable optical resonances and compatibility with biological environments. However, reproducible synthesis of chiral gold nanoparticles and systematic evaluation of their interactions with neural tissue remain limited. Here, we present a robust method to synthesize left- and right-handed chiral gold nanorods with controlled morphology and high enantiomeric purity. We identify precursor and chiral inducer concentration regimes that direct the enantioselective formation of chiral rods or branched structures. Further, we quantify their synergistic effect on the catalytic activity of redox enzymes using lactate dehydrogenase as a representative example. Lastly, we interface these chiral nanorods with neuroblastoma and astrocyte cell lines to evaluate cell viability and with an osteosarcoma cell line to assess cell morphology responses as a function of particle shape and chirality. Our findings reveal no enantioselective effects on short-term cell viability or morphology, suggesting that, in our hands, nanoscale chirality does not affect cell behavior beyond conventional concentration-dependent effects. Altogether, this work provides a comprehensive framework linking synthesis and properties of chiral gold nanorods and positioning them as non-toxic candidates towards future efforts in neuro-nanomedicine.