[object Object]

Psikiyatride Güncel Yaklaşımlar • 2026

Psychodrama is an experiential psychotherapeutic method whose effectiveness has been validated through extensive qualitative and quantitative research, finding broad applicability in both clinical and sub-clinical contexts. Contemporary theorists and authors agree that action and spontaneity-creativity, the two conceptual foundations of psychodrama, constitute the therapeutic core underlying its effectiveness. However, the existing literature lacks a comprehensive explanation of the neural mechanisms through which action, spontaneity, and creativity exert their therapeutic effects. The recent and growing dialogue between neuroscience and psychotherapy is likely to shed light on the neural mechanisms underlying psychodrama. On the other hand, the action-oriented nature of psychodrama, which distinguishes it from other psychotherapy approaches, necessitates examining it through the lens of another discipline—ecological psychology. This article proposes an integrated neuro-psychodramatic model to elucidate the neuroscientific and psychological mechanisms underpinning spontaneity and creativity in psychodrama, highlighting how the ecological psychology concept of affordances, situated within the perception-action cycle framework, mediates psychodramatic spontaneity-creativity, and demonstrating how the neural bases of cognitive/behavioral flexibility parallel those underlying spontaneity-creativity. This integrative model enhances theoretical understanding, guides future empirical research, and aims to optimize psychodramatic therapeutic interventions within contemporary neuroscientific and psychological paradigms.

[object Object], [object Object], [object Object] et al.

American journal of epidemiology • 2025

Living in racially and ethnically segregated neighborhoods may increase the risk of breast cancer. We examined associations between neighborhood racial and ethnic composition typology and risk of primary invasive breast cancer in a population-based sample of 102 615 African American/Black, Japanese American, Native Hawaiian, Latino, and White females residing in California and Hawaii from the Multiethnic Cohort (MEC) Study from 1993 through 2019. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards regression. In California, African American/Black females residing in predominantly White neighborhoods had decreased breast cancer risk compared to African American/Black females residing in predominantly Black neighborhoods (HR, 0.71; 95% CI, 0.50-0.99). Latino females residing in mixed White and Asian American/Pacific Islander neighborhoods had increased breast cancer risk (HR, 1.59; 95% CI, 1.20-2.11) in comparison to Latino females residing in predominantly Hispanic neighborhoods. In Hawaii, Japanese American females residing in multiethnic neighborhoods had increased breast cancer risk (HR, 1.49; 95% CI, 1.24-1.78) compared to Japanese American females residing in predominantly Asian American neighborhoods. Native Hawaiian patients residing in predominantly Asian American neighborhoods had increased breast cancer risk (HR, 1.23; 95% CI, 1.04-1.45) compared to Native Hawaiian patients residing in mixed Native Hawaiian neighborhoods. Our findings can inform future studies to identify specific pathways through which segregation influences cancer risk in multiethnic populations.

[object Object], [object Object], [object Object] et al.

Naunyn-Schmiedeberg's archives of pharmacology • 2025

Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is well-established for its metabolic benefits, including glycemic control and weight loss. Beyond these roles, it exhibits significant anti-inflammatory properties, though the mechanisms remain underexplored. This study investigates the anti-inflammatory effects of liraglutide in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages. Results demonstrate that increasing concentrations of liraglutide suppresses LPS-elevated prostaglandin E2 (PGE2), 6-keto prostaglandin F1α (6-keto-PGF 1α , a stable prostacyclin metabolite) and thromboxane A2 (TXA2), similar to that observed with conventional anti-inflammatory agents, ibuprofen and celecoxib. Mechanistic exploration reveals that liraglutide's anti-inflammatory action is dually-modulated by cyclooxygenase (COX) and nicotinic acetylcholine receptor (nAChR) signaling. The application of non-selective, non-competitive nAChR antagonist or selective and potent α7-nAChR antagonist, mecamylamine (MEC) and methyllycaconitine (MLA), respectively, highlights the involvement of cholinergic pathways in liraglutide's activity. Based on in silico molecular docking analyses, liraglutide exhibits favorable binding affinities to COX-1, COX-2, prostacyclin synthase (PGIS), and α7nAChRs, supporting its potential multi-target anti-inflammatory effects. These findings suggest that the therapeutic potential of liraglutide may go beyond metabolic regulation and may be promising for conditions in which metabolic and inflammatory pathways converge, including inflammation and modulation of cholinergic signaling.

[object Object], [object Object], [object Object] et al.

Oncogene • 2025

Mucoepidermoid carcinoma (MEC) is the most frequently occurring salivary gland malignancy. Here, we investigated transcriptomic profiles of human fetal and adult salivary glands and MEC tumors to assess programs involved in MEC progression. Molecular and genetic analyses revealed that MEC tumors and fetal salivary glands share proliferative and developmental gene expression profiles that implicate an FGFR-p53 signaling axis in salivary MEC progression. Based on these findings, we developed a genetically engineered mouse model of advanced MEC via targeted expression of the CRTC1-MAML2 oncogene in salivary ductal cells. Specifically, CRTC1-MAML2 expression combined with p53 dysregulation in salivary ducts rewires FGF signaling to drive formation of tumors with histological and molecular features of high-grade MEC. The combined bioinformatics and mouse modeling of this study demonstrate that salivary MEC progression is underpinned by reactivation of developmental signaling programs and suggests a role for FGFR targeted therapies in the treatment of high-grade MEC.

[object Object], [object Object], [object Object] et al.

Neurological research • 2025

To explore the neuroprotective role of Myeloid-Derived Growth Factor (MYDGF) and its regulatory mechanisms involving G protein-coupled signaling pathways after cerebral ischemia-reperfusion injury (CIRI).

[object Object], [object Object], [object Object] et al.

Clinical pharmacokinetics • 2025

Tacrolimus treatment is complicated by its narrow therapeutic range and large inter- and intra-patient variability. This study aimed to develop a population pharmacokinetic model and dosing algorithm to predict an individual's dose requirement following living and deceased donor kidney transplantation.

[object Object], [object Object], [object Object] et al.

The EMBO journal • 2025

Immunoglobulin A (IgA) is essential for mucosal immunity and has been implicated in autoimmune diseases, such as IgA nephropathy. Certain pathogenic and commensal bacteria produce IgA proteases that selectively cleave IgA, potentially aiding bacterial colonization as well as suggesting therapeutic avenues for IgA nephropathy. Here, we investigate the substrate specificities of two enzymes of the M64 metallopeptidase family, the IgA protease ThomasA from Thomasclavelia ramosa and BF3526 from Bacteroides fragilis. Our structural, biochemical, and mutagenesis analyses demonstrate that ThomasA cleaves IgA through exclusive recognition of the Fab region. This mechanism is distinct from that of other antibody-specific peptidases, which typically require engagement of the Fc region. In contrast, X-ray crystal structures of BF3526 in complex with substrate and product peptides, combined with enzymology assays, show that this enzyme targets the N-terminus of pre-digested proteins, but does not act on intact IgA. These findings reveal divergent substrate recognition strategies between M64 family members, while providing new structural insights into their conserved catalytic mechanism.

[object Object], [object Object], [object Object] et al.

Scientific reports • 2025

Pest detection is vital for maintaining crop health in modern agriculture. However, traditional object detection models are often computationally intensive and complex, rendering them unsuitable for real-time applications in edge computing. To overcome this limitation, we proposed DGS-YOLOv7-Tiny, a lightweight pest detection model based on YOLOv7-Tiny that was specifically optimized for edge computing environments. The model incorporated a Global Attention Module to enhance global context aggregation, thereby improving small object detection and increasing precision. A novel fusion convolution, DGSConv, replaced the standard convolutions and effectively reduced the number of parameters while retaining detailed feature information. Furthermore, Leaky ReLU was replaced with SiLU, and CIOU was substituted with SIOU to improve the gradient flow, stability, and convergence speed in complex environments. The experimental results demonstrate that DGS-YOLOv7-Tiny performs excellently on the tomato leaf pest and disease dataset, with 4.43 million parameters, 10.2 GFLOPs computational complexity, and an inference speed of 168 FPS, achieving 95.53% precision, 92.88% recall, and 96.42% mAP@0.5. The model delivered faster inference and reduced computational requirements while maintaining competitive performance, offering an efficient and effective solution for pest detection in smart agriculture with substantial theoretical and practical value.

[object Object], [object Object], [object Object] et al.

Clinical and translational science • 2025

IMC-002, an anti-cluster of differentiation 47 (CD47) antibody, was developed as a fully human immunoglobulin (Ig) G4 monoclonal antibody targeting CD47. IMC-002 blocks CD47-signal regulatory protein alpha (SIRPα) interactions, increasing the phagocytosis of cancer cells by macrophages. This study established a target-mediated drug disposition (TMDD) pharmacokinetics (PK) model for IMC-002 to explain the characteristics of the neonatal Fc receptor (FcRn) of IgG based on phase I a trial data to perform model-informed optimal dosing for a phase I b study. The PK data were obtained from a phase I a dose escalation study on 12 patients with advanced solid tumors. Each patient received multiple doses (5, 10, 20, or 30 mg/kg) via intravenous infusion over 3 h every 2 weeks. The IMC-002 PK data were analyzed using NONMEM software (version 7.5) using the first-order conditional estimation method with interaction (FOCEI). The semi-mechanistic TMDD model explained the nonlinear PK properties of IMC-002, including FcRn recirculation. Weight, sex, and age were investigated as covariates using stepwise covariate testing. No statistical covariates were identified. Simulations were performed to determine the optimal dosing regimen for patients with solid tumors that extend the administration period and maintain the mean concentrations above the minimum effective concentration (MEC). The ideal regimen of 20 mg/kg every 3 weeks ensured that the mean plasma concentration remained above the MEC throughout the dosing interval. Our study developed a robust TMDD PK model for IMC-002, which provides the rationale for a dose regimen in a phase 1 b study.

[object Object], [object Object], [object Object] et al.

Naunyn-Schmiedeberg's archives of pharmacology • 2026

Clozapine, the only drug approved by the FDA for treatment-resistant schizophrenia, operates within a narrow therapeutic range (0.35-0.60 mg/mL) and requires titration from 12.5 to 300-450 mg daily in two divided doses. Non-adherence, driven by adverse effects and logistic barriers, often manifests as missed or delayed doses. Clozapine's forgiveness, i.e., its capacity to sustain efficacy despite dosing errors, is poorly quantified. This study simulated the pharmacokinetics (PK) of clozapine to assess forgiveness across dosing scenarios. A one-compartment PK model (CL = 8.3 L/h, V d  = 2.8 L/kg, Ka = 0.69 h⁻ 1 , F = 0.27) with variability (22% CL, 14% V) was developed, and steady-state metrics for 200 mg twice-daily dosing were validated against literature reference. Simulations (200 mg, q12h) over 150 h for 500 subjects tested perfect adherence, 1-8 consecutively missed doses, and 1-10-h delays at steady state. Forgiveness was measured as AUC and time above minimum effective concentration (0.35 mg/L), expressed as percentages retained relative to perfect adherence. The perfect adherence yielded 0.44-0.62 mg/L, matching reference values. One missed dose reduced troughs to ~ 0.3 mg/L; eight consecutively missed doses dropped levels to near zero, slashing AUC and time above MEC to ~ 0%. A 10-h delay cuts AUC to 29% and time above MEC to 57%, with recovery by 150 h. Clozapine shows low forgiveness for missed doses, necessitating strict adherence but moderate delay tolerance, supporting flexible timings. Re-titration post-48 h is critical, guiding clinical management.

[object Object], [object Object], [object Object] et al.

American journal of physiology. Endocrinology and metabolism • 2025

Type 2 diabetes is considered the pandemic of the 21st century. The pathogenesis of diabetes is complex and multifactorial, and its understanding is crucial for its prevention and treatment. Nevertheless, the pathogenesis of β-cell dysfunction remains unclear. This gap in knowledge could be related to a lack of appropriate preclinical models of type 2 diabetes. Current animal models, mostly genotypic and monogenic, do not fully reflect the pathophysiology of type 2 diabetes or associated organ damage. Therefore, a new preclinical model is needed. In this study, we present a non-genotypic animal model of diabetes that combines obesity and the treatment with the diabetogenic immunosuppressor tacrolimus (TAC). Sprague-Dawley male rats were fed with a high-fat diet (HF) to establish obesity and metabolic syndrome. Then, TAC was administered for 6-9 mo to induce chronic hyperglycemia. These animals showed a decrease in Langerhans islets area and number, and development of islet fibrosis. There were also changes in pancreatic insulin and glucagon content, imbalance in the α/β-cell ratio and decrease in the expression of essential transcription factors V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MAFA), forkhead box protein O1 A (FOXO1A), pancreatic and duodenal homeobox 1 (PDX-1), and neuronal differentiation 1 (NEUROD1). Altogether, this could be a more appropriate animal model to study the pathophysiology of diabetes and, eventually, related organ damage. NEW & NOTEWORTHY After 6-9 mo of treatment, animals presented fasting and chronic hyperglycemia in intraperitoneal glucose tolerance test (IPGTT). Pancreas of obese-diabetic animals showed a decrease in Langerhans islets area and number, and development of islet fibrosis. Islets showed a decrease in insulin content and in β-cells proportion, and an increase in α cells proportion. There was also a decrease in the expression of transcriptional factors essential for β cells: V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MAFA), Forkhead box protein O1 A (FOXO1A), pancreatic and duodenal homeobox 1 (PDX-1), and Neuronal differentiation 1 (NEUROD1).

[object Object], [object Object], [object Object] et al.

Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver • 2026

Hemostasis may be involved in cirrhosis progression. However, its potential involvement in hepatic recompensation is unknown.

[object Object], [object Object], [object Object] et al.

BMC bioinformatics • 2025

An important challenge in flow cytometry (FCM) data analysis is making comparisons of corresponding cell populations across multiple FCM samples. An interesting solution is creating a statistical mixture model for multiple samples simultaneously, as such a multi-sample model can characterize a heterogeneous set of samples, and facilitates direct comparison of cell populations across the data samples. The multi-sample approach to statistical mixture modeling has been explored in a number of reports, mostly within a Bayesian framework and with high computational complexity. Although these approaches are effective, they are also computationally demanding, and therefore do not relate well to the requirement of scalability, which is essential in the multi-sample setting. This limits their utility in the analysis of large sets of large FCM samples.

[object Object], [object Object], [object Object] et al.

EMBO molecular medicine • 2025

High-throughput screening studies provide an additional approach to discovering repurposed drugs for antimicrobial treatments. In this work, we report the identification of ENOblock, an anticancer drug, as an antimicrobial agent. We computationally and experimentally validated that ENOblock synergizes with colistin, the last resort antibiotic. Additionally, we identified enolase as the potential bacterial target for ENOblock. The in silico and in vitro antibacterial activity of ENOblock translated into potent in vivo efficacy in an animal infection model. Collectively, the preclinical data support the selection of ENOblock as a promising candidate for antimicrobial development, with the potential to address the urgent threat of infections caused by Acinetobacter baumannii.

[object Object], [object Object], [object Object] et al.

Proceedings of the National Academy of Sciences of the United States of America • 2026

Plants responding to excessive soil salinity by discharging brine onto their leaf surface risk dehydration through the osmotic continuity between the living tissue and the surface brine, which further enriches with evaporation. Cuticle cracks have long been identified as essential for salt to reach the leaf surface but enable a potentially desiccating continuity between the brine and the gland interior. Using the secreting salt gland of Nolana mollis as a model system, we integrate mathematical modeling, imaging, and physiological measurements to examine the mechanical and biochemical processes required for efficient salt removal. We find that the subcuticular space between the concentrated surface brine and the more dilute secreting cell eases the energetic limits of active salt secretion by reducing the concentration gradient of salt across the cell membrane. We show that crack size plays a critical role in balancing the osmotic and pressure gradients required for salt removal without runaway foliar desiccation.

[object Object], [object Object], [object Object] et al.

EMBO reports • 2025

Batten disease is characterized by early-onset blindness, juvenile dementia and death within the second decade of life. The most common genetic cause are mutations in CLN3, encoding a lysosomal protein. Currently, no therapies targeting disease progression are available, largely because its molecular mechanisms remain poorly understood. To understand how CLN3 loss affects cellular signaling, we generated human CLN3 knock-out cells (CLN3-KO) and performed RNA-seq analysis. Our multi-dimensional analysis reveals the transcriptional regulator YAP1 as a key factor in remodeling the transcriptome in CLN3-KO cells. YAP1-mediated pro-apoptotic signaling is also increased as a consequence of CLN3 functional loss in retinal pigment epithelia cells, and in the hippocampus and thalamus of Cln3 Δ7/8 mice, an established model of Batten disease. Loss of CLN3 leads to DNA damage, activating the kinase c-Abl which phosphorylates YAP1, stimulating its pro-apoptotic signaling. This novel molecular mechanism underlying the loss of CLN3 in mammalian cells and tissues may pave a way for novel c-Abl-centric therapeutic strategies to target Batten disease.

[object Object], [object Object], [object Object] et al.

BMC pediatrics • 2025

To address capacity problems at tertiary-level neonatal intensive care units (NICUs) within current staffing limitations, our study aims to demonstrate the feasibility of identifying very preterm neonates not in need of highly specialised, tertiary-level, NICU care.

[object Object], [object Object], [object Object] et al.

ChemMedChem • 2026

In the present study, eight novel substituted 4-cyano-N-(4-cyano-1,3-oxazol-5-yl)-N-alkyl-1,3-oxazole-5-sulfonylamides have been synthesized. Compounds are characterized by IR, 1 H, 13 C NMR spectroscopy, elemental analysis, and chromato-mass-spectrometry. The anticancer activities of six compounds are evaluated against the NCI-60 human tumor cell line panel. The tested compounds exhibit the strongest antiproliferative (TGI) and cytotoxic (LC 50 ) activities within the leukemia, non-small-cell lung cancer, melanoma, and colon cancer subpanels. Overall, the mean activity parameters (GI 50 , TGI, and LC 50 ) calculated for three compounds do not differ significantly and are within the range of 1-100 µM, and for some lines, it reaches the value 10 -8  mol L -1 . Structure-activity relationship analysis reveals markedly higher activity for bisoxazole derivatives bearing 4-MeC 6 H 4 or 4-FC 6 H 4 at the second position of the oxazole rings (compounds 2, 3, and 7), whereas derivatives with diphenyl, di-tolyl substituents (compounds 1 and 6), or 4-ClC 6 H 4 (compound 8) exhibit substantially lower anticancer activity. In addition, the potential molecular mechanisms of anticancer action of these compounds are investigated using molecular docking methods. Derivatives show the highest affinity for tubulin and cyclin-dependent kinases. Docking of 4-cyano-N-[4-cyano-2-(4-fluorophenyl)-1,3-oxazol-5-yl]-N-methyl-2-(4-methylphenyl)-1,3-oxazole-5-sulfonamide into the colchicine-binding site of αβ-tubulin reveals a binding affinity of -10.9 kcal mol -1 , with the ligand located at the subunit interface.

[object Object], [object Object]

Molecular systems biology • 2026

Successful computational modelling of complex biological phenomena will depend on the seamless sharing of models and hypotheses between researchers of all backgrounds-experimental and theoretical. LimbNET, a new online tool for modelling, simulating and visualising spatiotemporal patterning in limb development, aims to facilitate this process within the limb development community. LimbNET enables remote users to define and simulate arbitrary gene regulatory network (GRN) models of 2D spatiotemporal developmental patterning processes. Researchers can test and compare each others' hypotheses within a common framework. A database of previously created models empowers users to simulate, explore, and extend each others' work. Spatiotemporally varying gene expression intensities, derived from image-based data, are mapped into a standardised computational description of limb growth, integrated within our modelling framework. This enables direct comparison not only between datasets but between data and simulation outputs, closing the feedback loop between experiments and simulation via parameter optimisation. All functionality is accessible through a web browser ( https://limbnet.embl.es ), requiring no special software, and opening the field of image-driven modelling to the full scientific community.

[object Object], [object Object], [object Object] et al.

Medical oncology (Northwood, London, England) • 2025

Chronic lymphocytic leukemia (CLL) is characterized by mature B lymphocyte accumulation and frequent MDM2/MDMX overexpression, leading to p53 inactivation and apoptotic resistance. ALRN-6924, a stapled peptide dual inhibitor, targets MDM2/MDMX to restore p53 function. This study evaluated ALRN-6924 efficacy alone and combined with radiofrequency (RF) exposure in CLL cell lines. Molecular docking assessed ALRN-6924-MDM2 binding affinity. Cytotoxic and apoptotic effects were evaluated using XTT assays and flow cytometry in HG-3 (wild-type p53) and MEC-1 (mutant p53) cell lines. Treatments included ALRN-6924 monotherapy and combination with 900 MHz RF exposure (120 mW/cm 2 ). MDM2, MDMX, BCL-2, and p53 protein levels were quantified by ELISA. Molecular docking revealed strong ALRN-6924-MDM2 binding (energy: - 9.30 kcal/mol, Ki: 163.9 nM). ALRN-6924 demonstrated potent cytotoxicity in HG-3 cells (IC 50 : 7.54 μM at 24 h, 5.88 μM at 48 h) versus resistance in MEC-1 cells (IC 50 : ~ 36 μM). In HG-3 cells, ALRN-6924 significantly induced apoptosis and necroptosis, reduced MDM2/MDMX expression, and enhanced p53 levels. RF combination therapy showed synergistic effects, further improving efficacy compared to monotherapy. BCL-2 expression was significantly reduced in the combination group. ALRN-6924 demonstrates promising therapeutic potential in wild-type p53 CLL cells, with enhanced efficacy when combined with RF exposure. The compound effectively disrupts the MDM2/MDMX-p53 axis, restoring p53 function and inducing programmed cell death. In mutant p53 cells, combination therapy may provide partial benefits. These findings support ALRN-6924 clinical development as targeted therapy for p53-functional CLL, particularly in combination strategies.

[object Object], [object Object], [object Object] et al.

The European journal of neuroscience • 2026

Rodents depend heavily on visual information to navigate and orient in complex environments, with the entorhinal-hippocampal circuit playing a central role in generating spatial representations that support this behaviour. It is believed that the medial entorhinal cortex (MEC) mainly captures distal visual cues, while the lateral entorhinal cortex (LEC) apprehends most proximal visual cues, both of which cooperatively construct a coordinate system to encode spatial information. However, it remains unclear how entorhinal-hippocampal circuit jointly generate spatial representation from distal and proximal visual cues and further guide navigational decision-making. To fill these gaps, we developed a model based on the two-dimensional continuous attractor network. In the model, allocentric velocity inputs drive grid-cell attractor dynamics anchored to distal cues in the MEC, while LEC populations encode the positions of proximal cues. Their convergence in hippocampal place cells gives rise to a population code of self-location and object location, enabling a simple vector-subtraction mechanism that supports memory-based, goal-directed navigation. To verify the model, we implemented it on a robotics platform. Through systematic biorobotics experiments, the model successfully replicated key findings from biological studies, including distal cue-controlled rotation of grid-place representations, object-related and proximal cue-coherent responses in the LEC pathway and both coherent and irregular remapping patterns at the hippocampal level. Furthermore, it demonstrated a plausible navigation strategy. Overall, these results offer a mechanistic, population-level explanation of how distal and proximal cues can be integrated to maintain stable allocentric representations and support flexible navigation. The biorobotics implementation further demonstrates the value of embodied approaches for testing computational hypotheses of spatial cognition.

[object Object], [object Object], [object Object] et al.

EMBO molecular medicine • 2026

Diamond-Blackfan anemia syndrome (DBAS) is marked by defective erythropoiesis caused by impaired ribosome biogenesis and aberrant signaling. Here, we investigate how ribosomal stress-induced activation of the NLRP1 inflammasome affects erythroid differentiation in DBAS. We demonstrate that FDA/EMA-approved tyrosine kinase inhibitors (TKIs) effectively mitigate defective erythropoiesis by inhibiting NLRP1 inflammasome activation. In K562 cells, nilotinib suppresses the ZAKα/P38/NLRP1/CASP1 axis, leading to increased GATA1 levels and upregulation of key erythroid genes. These effects were validated in human CD34⁺ hematopoietic stem and progenitor cells (HSPCs) and zebrafish models, where nilotinib, imatinib, and dasatinib promoted erythropoiesis while reducing caspase-1 activity. In Rps19-deficient zebrafish, RPS19-deficient human HSPCs, and HSPCs from DBAS patients, TKIs rescued erythroid differentiation and restored hemoglobin levels. Our findings highlight that targeting the NLRP1 inflammasome with TKIs may provide a novel therapeutic strategy for DBAS and other ribosomopathies.

[object Object], [object Object]

Genetic epidemiology • 2026

Summary-data-based multivariable Mendelian randomization (MVMR) methods, such as MVMR-Egger, MVMR-IVW, MVMR median-based, and MVMR-PRESSO, are used to assess the causal effects of multiple risk factors on disease. However, accounting for variances in the summary statistics of risk factors remains a challenge. We propose a linear mixed model with measurement error correction (LMM-MEC) that accounts for the variance in summary statistics for both disease outcomes and risk factors. First, under the NOME assumption, we apply a linear mixed model to account for variance in disease summary statistics by treating it as fixed- or random-effects, depending on whether there is heterogeneity in the effect sizes of the genetic variants on the disease outcome. Next, we relax the NOME assumption and further take the estimation error (or variance) in the summary statistics of risk factors into consideration by measurement models through a regression calibration approach. In a simulation study, using independent genetic variants as instrumental variables (IV), our method showed comparable performance to existing MVMR methods under conditions of no pleiotropy or with balanced pleiotropy on the disease outcome, and it achieved slightly improved coverage rates and power under directional pleiotropy. When genetic variants are in low to moderate linkage disequilibrium (LD) (0 <  ρ $\rho $ 2  ≤ 0.3), our method showed comparable performance to MVMR-Egger, although both methods showed reduced coverage rates and power compared to situations where genetic variants as IVs are in LD. In the application study, we examined causal associations between correlated cholesterol biomarkers and longevity. By including 739 genetic variants selected based on p values < 5 × 10 -5 from GWAS and allowing for low LD ( ρ $\rho $ 2  ≤ 0.1), our method identified that large LDL-c levels were causally associated with a lower likelihood of achieving longevity.

[object Object], [object Object], [object Object] et al.

eNeuro • 2026

Gamma oscillations (40-140 Hz) play a fundamental role in neural coordination and cognitive functions in the medial entorhinal cortex (mEC). While previous studies suggest that pyramidal-interneuron network gamma (PING) and interneuron network gamma (ING) mechanisms contribute to these oscillations, the precise role of inhibitory circuits remains unclear. Using optogenetic stimulation and whole-cell electrophysiology in acute mouse brain slices, we examined synaptic input and spike timing in neurons across layer II/III mEC. We found that fast-spiking interneurons exhibited robust gamma-frequency firing, while excitatory neurons engaged in gamma cycle skipping. Stellate and pyramidal cells received minimal recurrent excitation, whereas fast-spiking interneurons received strong excitatory input. Both excitatory neurons and fast-spiking interneurons received gamma-frequency inhibition, emphasizing the role of recurrent inhibition in gamma rhythms. Gamma activity was reduced but persisted after AMPA/kainate receptor blockade, indicating that interneurons can sustain oscillations via an ING mechanism. Selective activation of PV+ interneurons confirmed their ability to sustain fast gamma inhibition autonomously. To further assess the interplay of excitation and inhibition, we developed computational network models constrained by our experimental data. Simulations revealed that weak excitatory input to interneurons supports fast ING-dominated rhythms (∼100-140 Hz) while strengthening excitatory drive induces a transition to slower PING-dominated oscillations (60-100 Hz), although this regime shift was not observed consistently after AMPA/kainate receptor block. These findings highlight the dominant role of inhibitory circuits in sustaining gamma rhythms, demonstrate how excitation strength tunes the oscillatory regime, and refine models of entorhinal gamma oscillations critical for spatial memory processing.

[object Object], [object Object], [object Object] et al.

Proceedings of the National Academy of Sciences of the United States of America • 2026

Plasmids are extrachromosomal DNA molecules that spread by horizontal transfer and shape bacterial evolution. Plasmids are typically present at multiple copies per bacterial cell, and these extra copies increase the supply of plasmid mutations, potentially accelerating their evolution. However, the segregation of plasmid copies to daughter cells is random, introducing an additional layer of genetic drift, termed segregational drift, that might delay plasmid evolution. The interplay between plasmid mutational supply and segregational drift determines the evolutionary rate of plasmid-encoded genes, yet the relative contribution of these opposite forces in plasmid evolution remains unclear. Here, we develop a population genetics framework to predict the rate of plasmid mutations in bacterial populations and validate these predictions using computational, experimental, and bioinformatic approaches. Our findings show that plasmid mutation rates scale logarithmically with copy number and that the supply of new mutations consistently surpasses the impact of segregational drift across all copy numbers. These results underscore plasmids as powerful drivers of bacterial evolvability, where they can potentiate the evolution of critical traits such as antibiotic resistance.

[object Object], [object Object], [object Object]

Hippocampus • 2026

Grid cells in medial entorhinal cortex (MEC) support spatial navigation by responding to multiple variables, including position, speed, and head direction. While tuning curves for each of these variables have been examined individually at the level of single cells, less is known about the conjunctive coding of grid cells for these properties. To investigate this, we analyzed neural recordings of freely foraging rats and constructed four-dimensional (4D) tuning curves across 2D position and 2D velocity. In order to combat the sparse sampling of such a large behavioral space, we applied Gaussian Process (GP) methods to estimate firing rates at un-sampled points. Comparing GP model-derived tuning curves to those predicted by a fully separable model revealed that some cells exhibited significant non-separability of position and velocity tuning, and suggested a data coverage threshold necessary to observe this non-separability. In summary, our use of GPs allowed us to distinguish interactions in position-velocity tuning across a 4D behavioral space that have not been apparent in 2D analyses.

[object Object], [object Object], [object Object] et al.

Frontiers in Energy Research • 2026

Introduction Proton exchange membrane fuel cells (PEMFCs) are highly efficient and environmentally friendly energy conversion devices. Their modular multi-stack FC (MSFC) provides enhanced operational stability and power output. However, during online electrochemical impedance spectroscopy (EIS) testing, multi-frequency sinusoidal current disturbances injected by the DC/DC converter can cause periodic fluctuations in the common DC bus voltage, threatening system stability and measurement accuracy. Existing approaches, such as hardware filtering or improved topology, suffer from high cost and complexity. While the traditional extended state observer (ESO) can estimate the disturbance, it struggles to suppress the fluctuations during multi-frequency co-detection. Methods This paper proposes an enhanced ESO design, namely the multi-resonant ESO (MRESO), for MSFC hybrid systems. By embedding multiple resonant units, the MRESO accurately tracks the EIS disturbance frequency and combines feedforward compensation with battery-assisted control to achieve robust bus voltage stability. The system modeling is based on the principle of energy conservation, and the control scheme adopts a dual-loop structure consisting of an inner current loop and an outer voltage loop. The voltage loop integrates the MRESO to improve interference rejection capability. Results Simulation results show that under load current disturbances and EIS measurement interference, MRESO can reduce voltage fluctuations by over 70% and achieve stability within 0.08 s, outperforming both PI control and traditional ESO, validating its effectiveness in suppressing multi-frequency disturbances. Discussion This study provides a feasible voltage stabilization solution for online EIS monitoring of MSFC, contributing to improve the power quality and reliability of the hybrid system.

[object Object]

Journal of Energy Research and Reviews • 2026

This paper presents a reliable power-electronics control and energy-management system for PEM fuel-cell electric vehicles (FCEVs) equipped with hybrid energy storage (battery–supercapacitor) to guarantee stability of the system in the presence of sudden load variations and parameter intervals. A unidirectional DC–DC interface for the PEMFC, bidirectional DC–DC stages for the battery and supercapacitor, and a traction inverter feeding the electric drive are included in this system. Real-time power split of the fuel cell and supercapacitor is achieved by a fuzzy-logic supervisory controller, which employs rule-based decision making with respect to NBC traction demand, DC-link voltage error, PEMFC ramp constraints, battery/supercapacitor SOC/SOE limits. A multi-objective particle swarm optimization (MOPSO) layer optimizes fuzzy membership parameters and weighting factors with multiple objectives that enable the minimization of hydrogen consumption, DC-link ripple, peak converter currents, and inverter stress as well as the imposition of fuel-cell current-slew rate limits and storage health constraints. Stability is tested with dual uncertainties in fuel- cell polaristic/ohmic parameters and converter/inverter elements (e.g., ±20% fluctuations in the main electrical parameters), and under aggressive step-load perturbations. Simulations with representative drive cycles along with step-load disturbances (e.g., 0.3–0.5 pu torque/power steps) reveal that the fuzzy–MOPSO approach reduces DC-link voltage overshoot by 40–60% and settling time by 30–45% compared to cascaded PI control and non-optimized fuzzy supervision were observed. The DC-link ripple amplitude was reduced by 35–55%, and the peak currents in the supercapacitor and battery utilization were decreased by 20–35% demonstrating less thermal stress and increased reliability. The supercapacitor provided the high-frequency transients, while the battery the midfrequency dynamics, and the PEMFC supplied nominal power with safe ramp limits, achieving a reduction in hydrogen consumption of 5-12% across tested cycles. In summary, the results demonstrate that fuzzy–MOPSO co-design offers a practical method to robust, efficient and durable FCEV powertrain control under real driving fluctuations and uncertainties.

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Molecular Cancer Research • 2026

Abstract Uncontrolled cellular proliferation is a hallmark of cancer that is both driven by deregulation of the cell cycle, and fueled by metabolic reprogramming. Among the metabolic alterations detected, lipid metabolism is markedly upregulated to provide resources for proliferating cancer cells. Each cell cycle requires lipids for membrane synthesis, energy production, and cellular signaling, yet the mechanistic relationship linking the cell cycle to lipid metabolism in cancer remains incompletely understood. Recent advances in lipidomic technologies that enable comprehensive profiling of the cancer lipidome have provided new insights into the interconnections between these two pathways. This review describes how cell cycle regulators influence various aspects of lipid metabolism in models of cancer and the effect of cell cycle perturbation on cellular lipid profiles. We further describe lipid metabolic changes associated with response and resistance to cell cycle inhibitors in cancer and offer insight into how these findings may inform the development of clinical biomarkers and new therapeutic strategies.

[object Object], [object Object], [object Object] et al.

Frontiers in Neurology • 2026

Understanding the neural mechanisms underlying upper limb motor recovery after stroke remains a significant challenge in rehabilitation research. It has been proposed that individuals who show no motor-evoked potential (MEP) response to transcranial magnetic stimulation (TMS) and are thus classified as MEP negative (MEP−) have limited potential for recovery in part due to damage of the corticospinal pathway. In this study, we investigate how individuals categorized as MEP− with TMS respond to stimulation of the corticospinal pathway at a subcortical level. We describe the methodology for eliciting MEPs by using cervicomedullary electrical stimulation (CMEP) in post-stroke individuals with severe upper limb hemiparesis. MEP status (+/−) of the more affected arm was assessed using TMS and cervicomedullary electrical stimulation in stroke survivors with severe upper extremity hemiparesis. While most of the participants were classified as MEP−, all individuals were categorized as CMEP+ in the biceps brachii, extensor carpi radialis, and first dorsal interosseous muscles. Importantly, we report the first testing of CMEPs in a small cohort of individuals with stroke. This technique is feasible in this population and has potential for application in clinical translation settings. Our findings provide a foundation for future studies to replicate and expand upon this approach, enabling the exploration of new hypotheses related to post-stroke rehabilitation and recovery.

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Solid Earth • 2026

Abstract. Fatigue and damage accumulation in granitoids are classical, but poorly characterised, rock mechanics problems. We explore these phenomena by examining curling stone impacts. Curling stones are slid on ice and made to collide along a circumferential striking band. This well constrained scenario involves uniaxial compression of convex surfaces (i.e., Hertzian contacts). Conservatively, each stone experiences about 2900 impacts per season, over a lifespan of 10–15 years before refurbishment, providing a unique opportunity to study fatigue and damage accumulation under dynamic cyclic loading. Here, we first determine the stress magnitudes of head-on curling stone impacts using on-ice experiments involving a high-speed camera and pressure-sensitive films. We then characterise the damage observed in aged stones using photogrammetry, microtomography, and microscopy. For high-velocity impacts (2.93±0.15ms-1), a curling stone is locally and momentarily stressed to 300–680 MPa, exceeding its quasi-static unconfined compressive strength and exceeding the threshold for fatigue damage for repeated dynamic loadings. Curling stone impacts are dynamic in nature, as evidenced by (1) high strain rates (24±4s-1) that lie below those of co-seismic rock pulverization; (2) ejection of rock powder during collisions and the presence of potential spalling microcracks; and (3) presence of striations on crescent-shaped fractures, which resemble mirror-mist-hackle patterns indicative of dynamic microcrack propagation. In the striking band, damage is confined to macroscopic Hertzian cone fractures and their immediate collet zones, and does not appear to extend beyond about 3–5 cm into the stones (radially). The circumferential density of cone fractures is limited to about 2–2.5 cm−1. We propose that (1) early, high-velocity impacts initiate cone fractures up to a specific spatial density, and (2) with subsequent collisions in the same regions of the striking band, cone fractures progressively propagate and coarsen. This concentrates and channels the accumulated damage, shielding the rest of the stone from reaching critical stress levels for damage. Our findings are significant for applications where rocks are exposed to repetitive, high-stress impacts and suggest that narrow damage zones can dissipate high-impact stresses.

[object Object], [object Object], [object Object] et al.

Frontiers in Veterinary Science • 2026

Theileria orientalis Ikeda is a protozoan parasite that has recently been detected in Haemaphysalis longicornis Neumann ticks and bovine serum samples in the United States (US). This parasite is known to cause theileriosis in bovine hosts and has negatively impacted the cattle industry worldwide. The transmission of this pathogen at the livestock–wildlife interface in the US is not fully understood. Theileria orientalis Ikeda was reported by producers on a cow-calf farm in eastern Tennessee. A retrospective analysis of field- and host-collected H. longicornis resulted in the detection of T. orientalis Ikeda in nymphal H. longicornis ticks collected from cattle ( Bos taurus ), domestic cats ( Felis catus ), raccoons ( Procyon lotor ), and Virginia opossums ( Didelphis virginiana ). Notably, the protozoan DNA was not found in the blood of these hosts. Multiple hosts (cattle, raccoons, Virginia opossums, and a domestic cat) contributed to the presence of T. orientalis Ikeda-infected H. longicornis ticks on the farm. Treating these hosts with acaricides could be important for reducing tick abundance and pathogen transmission. Additionally, biosecurity practices, such as changing gloves and syringes between handling bovine hosts, are important for preventing the accidental mechanical transmission of Theileria parasites.

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Iraqi Journal of Science • 2026

A wide range of infections result from the Gram-positive pathogen Staphylococcus aureus. One key virulence factor of this bacterium is the capacity to develop biofilm.  Antibiotics are ineffective in treating a majority of infections linked with biofilm formation in this opportunistic bacterium. The current study was conducted to estimate the influence of cell-free supernatant (CFS) of lactobacillus acidophilus on the expression level of some biofilm-association genes in clinical strains of S. aureus. The antibiotic susceptibility pattern against twenty antibiotics and quantitative assay for biofilm development were examined for all bacterial isolates. Moreover, the agar well diffusion method was followed to evaluate the impact of CFS on the growth of S.aureus. In addition, real-time PCR was utilized to determine the impact of CFS extract on the transcription level of the genes involved in forming S. aureus biofilms (fib , eno,sdrC ). In isolates constituting biofilm, a high percentage of antibiotic resistance was detected. The CFS exhibited an antimicrobial effect toward strong biofilm-forming isolates. In addition, the results of real-time PCR for the treatment group showed a drop in the expression degree of fib and sdrC genes compared to the control group; meanwhile, the eno gene displayed upregulation after treatment with CFS. In conclusion, biofilm construction is a key strategy that may participate in preventing antimicrobial agents from killing S. aureus, especially since all isolates were multidrug resistant with a high percentage of strong biofilm former. In addition, CFS of lactobacillus acidophilus affects the growth of S. aureus and biofilm formation by displaying downregulation for some mediating biofilm formation genes.

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World Journal of Biology Pharmacy and Health Sciences • 2026

Biofilm-associated infections remain a major challenge in healthcare due to biofilms’ ability to protect bacteria from antibiotics and host immune responses, contributing significantly to the rise of antimicrobial resistance (AMR). Nanoparticle (NP)-based strategies effectively combat biofilms by improving drug delivery, penetrating biofilm matrices, and exerting antimicrobial activity. Recent advances in metallic, polymeric, and lipid nanoparticles targeting biofilm-forming bacteria show disruption of biofilm structure, reactive oxygen species (ROS) generation, quorum-sensing inhibition, and targeted antimicrobial delivery. These approaches outperform antibiotics in reducing biofilms; optimizing design, safety, and clinical translation is key for MDR treatment.

[object Object]

bioRxiv (Cold Spring Harbor Laboratory) • 2026

2. Abstract Quantitative image analysis is central to understanding microbial growth, morphology, and spatial organisation. However, conventional metrics such as mean intensity or object count often do not capture the complex structural heterogeneity and patterning characteristic of microbial colonies and biofilms. To address this limitation, Analysis of Biofilm Complexity in 3D (ABC3D), an open-source Python framework for automated extraction of fractal, textural, and statistical descriptors from volumetric microscopy images, is reported. ABC3D computes a set of parameters including fractal dimension, lacunarity, entropy, grey-level co-occurrence matrix features, and wavelet sub-band energies from three-dimensional (3D) image datasets. ABC3D is demonstrated in macrocolony biofilms formed by cell shape mutants of Escherichia coli , where it is shown that nutrient availability accounts for the majority of structural variance, while cell shape produces additional structural variation that differs between nutrient conditions. ABC3D provides researchers with an accessible, quantitative approach to assessing biofilm morphology in microscopy datasets. Summary An open-source, quantitative analysis pipeline is presented that integrates fractal, lacunarity, entropy, texture and wavelet descriptors to characterise colony biofilm architecture in three dimensions. Application to Escherichia coli cell shape mutants demonstrates that macrocolony biofilm architecture is best understood as a coordinated, multiscale phenotype rather than as an aggregate of independent structural metrics. 3. Impact statement Biofilm architecture is pivotal for microbial survival, antimicrobial tolerance, and ecological function but tools to quantify structural organisation in these cell communities remain limited. The commonest metrics describe bulk properties such as width, thickness, or cell number, but they do not capture multiscale spatial heterogeneity. Here, an open-source framework for Analysis of Biofilm Complexity in 3 Dimensions (ABC3D) is reported. This software integrates measurements of fractal geometry, lacunarity, entropy, texture statistics, and wavelet energy. ABC3D is demonstrated in Escherichia coli macrocolony biofilms, where it is shown that nutrient environment has a leading role in determining colony architecture in E. coli biofilms, while cell shape has a lesser but still significant influence on structural variation. The ABC3D pipeline can be applied to any microbial communities imaged by confocal microscopy and other volumetric imaging methods and has the potential to give a deeper understanding of how cells organise in biofilms. 4. Data summary Full code for ABC3D and data analysis is available at https://github.com/gailmcconnell/ABC3D . Image data are available upon request. The author confirms all supporting data, code and protocols have been provided within the article or through supplementary data files.

[object Object], [object Object], [object Object] et al.

Microorganisms • 2026

Yersinia enterocolitica is a foodborne pathogen that forms biofilms on surfaces, enhancing its survivability and increasing bacterial resistance, which poses a significant challenge to public health. Therefore, developing effective strategies to inhibit biofilm formation is crucial. Lipoic acid (LA) is a compound with antibiofilm properties. This study investigates the effects of LA on biofilm formation by Y. enterocolitica BNCC 108930 (a standard strain from the BeNa Culture Collection). Biofilm formation, maturation, removal, and cell viability were evaluated by crystal violet staining, extracellular polysaccharide assay, Methylthiazolyldiphenyl-tetrazolium bromide assays, motility, and quorum sensing (QS) assays. The results indicate that LA interferes with the early stages of biofilm formation by compromising cell membrane integrity and reducing cellular adhesion. Furthermore, 2.5 mg/mL of LA reduced biofilm biomass (with a 48 h treatment inhibition rate of 51.46 ± 1.29%) and extracellular polysaccharide production (with a relative inhibition rate of 30.09 ± 1.8%), while significantly reducing the metabolic activity of bacteria within the biofilm (inhibition rate over 85%) compared to the untreated group. Confocal laser scanning microscopy and field emission gun scanning electron microscopy confirm that LA induces a sparse biofilm structure, reduced aggregation, and decreased biofilm thickness to 21.33 ± 2.27 μm. Motility and QS assays demonstrate that LA affects flagellar motility and the secretion of N-acyl homoserine lactones. Transcriptome analysis revealed downregulation of genes involved in the QS system and biofilm formation (e.g., lsrA, lsrC, lsrD, lsrR, and oppA), as well as upregulation of genes related to bacterial chemotaxis and flagellar assembly (e.g., RS19655, RS15590, fliE, fliJ, fliP, fliA, and fliK). These alterations suggest that LA inhibits Y. enterocolitica biofilm formation by affecting intercellular communication and flagellar motility. This study highlights the antibiofilm properties of LA, providing a theoretical basis for potential applications in microbial and biofilm control.

[object Object], [object Object], [object Object] et al.

Journal of Health, Wellness and Community Research • 2026

Background: Fixed orthodontic appliances increase plaque retention and friction at the bracket–wire interface, contributing to enamel demineralization, gingival inflammation, and reduced mechanical efficiency. Functional surface coatings have been proposed to simultaneously reduce biofilm formation and friction, yet few systems demonstrate integrated antimicrobial, surface, and tribological benefits with short-term stability. Objective: To evaluate the effects of a chitosan–graphene oxide (CS–GO) coating on surface characteristics, antibiofilm activity against Streptococcus mutans, frictional resistance, and short-term stability of stainless-steel orthodontic arch wires. Methods: In this laboratory-based experimental study, sixty 0.019 × 0.025-inch stainless-steel wire segments were randomly allocated to uncoated (n = 30) or CS–GO coated groups (n = 30). Surface roughness (Ra), contact angle, biofilm burden (log10 CFU per wire after 48-hour incubation), and frictional resistance were measured (n = 10 per testing stream per group). Statistical comparisons were performed using independent t-tests with 95% confidence intervals and effect sizes. Results: Coated wires showed significantly lower surface roughness (0.24 ± 0.04 µm vs 0.41 ± 0.05 µm; mean difference −0.17 µm; p 0.001), reduced contact angle (61.2° ± 5.1° vs 83.6° ± 4.8°; −22.4°; p 0.001), decreased biofilm burden (5.32 ± 0.11 vs 5.94 ± 0.07 log10 CFU; −0.62 log units; ~75.9% reduction; p 0.001), and lower frictional force (1.62 ± 0.19 N vs 2.34 ± 0.22 N; −0.72 N; p 0.001). Conclusion: CS–GO coating significantly improved surface smoothness, enhanced hydrophilicity, reduced S. mutans biofilm formation, and lowered frictional resistance under controlled laboratory conditions, supporting its potential as a multifunctional surface modification for orthodontic stainless-steel wires pending clinical validation

[object Object], [object Object], [object Object] et al.

Current Drug Discovery Technologies • 2026

Background: Biofilm formation by microorganisms, specifically bacteria, threatens vari-ous fields, including biomedicine and the environment. The development of biofilms has associations with increased resistance to antimicrobial agents and immune responses; it poses a significant threat to human health. ESKAPE pathogens, a group of bacteria known for their multidrug resistance, are particularly adept at biofilm formation. This research explores strategies to combat biofilm-associated infections, with a focus on natural compounds as potential anti-biofilm agents. Methods: The study investigates 23 natural compounds for their druglike properties in fighting against antibiotic-resistant biofilms. These compounds include flavonoids, terpenes, and alkaloids, and exhibit promising bioavailability and usage potential as ligands. Molecular docking analysis em-ploying AutoDock Vina was used to evaluate the binding affinities of these ligands to key biofilm-forming genes and membrane proteins in ESKAPE pathogens. Results: Despite a few violations of a variety of established criteria, the overall safety and efficiency of oral drug reception are maintained, emphasizing their potential for further drug development. The results show specific ligands, such as Baicalin, Apigenin, Azadirachtin, Curcumin, Hyperforin, etc., demonstrating high binding energies against biofilm-associated proteins. This approach aligns with the pursuit of sustainable alternatives to combat biofilm-related infections. Conclusion: Natural compounds like Baicalin, Apigenin, Azadirachtin, Curcumin, Hyperforin not only exhibit broad-spectrum coverage but also show reduced risks of resistance development com-pared to synthetic antibiotics. The integration of natural compounds into multifaceted strategies con-siders the complexities of the biofilm matrix, bacterial diversity, and pathogen characteristics, offer-ing a sustainable approach to address biofilm-associated infections.

[object Object], [object Object], [object Object] et al.

Antibiotics • 2026

Background/Objectives: Hospital outbreaks of Pseudomonas aeruginosa are difficult to control due to the pathogen’s extensive repertoire, including its ability to form biofilms, adapt and persist in diverse environments, and develop multidrug resistance, all of which contribute to prolonged outbreaks. This study integrates the phenotypic, proteomic, and genomic characterization of a nosocomial outbreak comprising 38 clinical isolates and one environmental isolate recovered from the intensive care unit (ICU) of Hospital IESS Quito Sur. Methods: Clinical data were collected, antimicrobial susceptibility was assessed by minimum inhibitory concentration (MIC), carbapenemase genes were detected by multiple PCR and immunochromatographic assays, and the biofilm formation index (BFI) was determined. In addition, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used for species identification and clustering based on spectral similarity. Twelve representative isolates underwent whole genome sequencing (WGS) to characterize the resistome and virulome and to compare phylogenetic relationships with proteomic clustering defined by MALDI Biotyper Compass Explorer software. Results: All isolates were identified as P. aeruginosa, and phenotypic antimicrobial susceptibility classified most isolates as multidrug resistant, including 32 CRPA strains. The blaVIM gene was detected in 22 isolates, while BFI analysis showed that all isolates formed moderate to strong biofilms. Genomic analysis revealed that most isolates belonged to ST111 and ST253, and both conserved and heterogeneous resistome and virulome profiles, with a broad distribution of determinants related to biofilm formation, stress tolerance, and persistence. Comparison between MALDI-TOF MS and WGS showed predominant concordance in clustering, mainly within subclusters but disagreement at the cluster level. Conclusions: The detection of carbapenemases, biofilm-forming ability, and virulence determinants associated with prolonged persistence highlights the need for integrated molecular tools, such as MALDI-TOF MS with MALDI Biotyper Compass Explorer software, to support epidemiological surveillance and to inform strategies aimed at mitigating prolonged hospital outbreaks caused by P. aeruginosa.

[object Object], [object Object], [object Object] et al.

Journal of Pure and Applied Microbiology • 2026

Biofilms are surface-attached bacterial communities that are widespread in nature. A key factor in their development is quorum sensing (QS), a mechanism of intercellular communication among bacteria. Biofilm formation serves as a pivotal mechanism in the establishment of multidrug-resistance, significantly undermining the efficacy of conventional treatment strategies. The development of novel antimicrobial compounds that can disrupt or prevent biofilm formation has emerged as a critical strategy to mitigate the clinical impact of biofilm-associated infections. Medical devices are also receiving much attention in the healthcare sector to address this issue. Emerging studies suggests that both herbal formulations and synthetic agents are extensively explored for their prospective anti-biofilm efficacy. This review summarizes the mechanisms behind biofilm formation of commonly reported bacterial pathogens and regular techniques in medical device fabrication to control biofilm formation. Additionally, it focuses on the information about reported natural compounds as quorum quenching agents. Through an integrative analysis of biofilm mechanisms, anti-biofilm agents, and device fabrication techniques, this review offers critical perspectives for the development of clinically viable multi-targeted interventions for managing biofilm-driven medical complications.