Avian malaria parasites and related haemosporidians are diverse and widespread vector-borne parasites that circulate within complex host-vector networks. Despite their ecological importance, their diversity and circulation within mosquito communities remain poorly understood in temperate North America. The Midwestern United States, located along major North American migratory flyways, supports diverse avian habitats and mosquito assemblages, providing an ideal setting to investigate these interactions. Here, we characterized the occurrence, phylogenetic diversity, and mosquito-lineage associations of avian haemosporidians in mosquitoes. A total of 233 pools comprising 6170 unfed female mosquitoes from seven species were collected from 38 protected natural areas in northern, central, and southern Illinois. Samples were screened for avian haemosporidian DNA by nested PCR targeting the mitochondrial cytochrome b gene. Positive samples were analyzed by multiplex PCR and sequencing to identify parasite lineages and assess potential mixed infections. Phylogenetic relationships were reconstructed, and mosquito-lineage associations were visualized using a bipartite network. Infection rates were estimated using maximum likelihood estimation (MLE) and minimum infection rate (MIR), and factors associated with infection prevalence in pooled samples were evaluated using pooled-binomial regression. Of 233 pools, 44 (18.9%) were positive for avian haemosporidians. Eleven lineages were identified, including nine Plasmodium and two Haemoproteus lineages; one Plasmodium lineage was novel. pTUMIG03 (Plasmodium unalis) was the most frequently detected lineage, whereas pSYAT05 (P. vaughani) showed the broadest mosquito distribution. Culex restuans harbored the highest lineage diversity and infection rate among the mosquito species examined. Mosquito species was a significant predictor of infection prevalence estimated from pooled samples, and Cx. restuans was most strongly associated with avian Plasmodium detection. Additionally, a deer-associated non-avian Plasmodium lineage was incidentally detected in two pools. Mosquito populations in Illinois harbor a diverse assemblage of avian haemosporidians, with heterogeneous lineage distributions across mosquito taxa. Culex restuans emerged as the species most strongly associated with avian Plasmodium prevalence, suggesting an important role in local enzootic circulation. These findings expand current knowledge of avian haemosporidian diversity in North American mosquito communities and provide a basis for future studies integrating mosquito surveillance, avian host sampling, and vector competence experiments.
Incorporating redox active ligands into coordination cages offers a direct way to reach architectures whose structure or composition can be modulated in response to changes in the oxidation state. An exTTF-based ditopic ligand L affords a M2L4 cage in presence of a palladium(II) salt (M). The resulting M2L4 cavity exhibits selective binding properties for medium length α,ω-dinitrile alkanes. Modifying the coordination geometry of the ligand by oxidation to its Lox state redirects the self-assembly process toward a M2Lox 2 structure. The oxidized ligand can also be combined with a dibenzothiophene linker (L') to afford a heteroleptic M2LoxL'2 structure whose vacant coordination sites enable subsequent dimerization into an unprecedented M4L4L'4 architecture. Key intermediates and products were structurally authenticated by single-crystal x-ray diffraction. Notably, these processes are reversible. Reduction converts the M2LoxL'2 assembly back to the homoleptic M2L4 cage. This sequence illustrates how changes of oxidation state can reshape nuclearity and composition in metal organic assemblies.
SMARCB1-deficient sinonasal carcinoma (SDSC) is a rare, highly aggressive malignancy with limited therapeutic options and no established preclinical models. Here, single-nucleus RNA sequencing (snRNAseq), spatial transcriptomics, and ex vivo patient-derived tissue slice culture (TSC) were combined to resolve intratumoral heterogeneity, niche organization, and treatment vulnerabilities in an index SDSC. snRNAseq identified three malignant subpopulations, including two specialized states marked by ALDH1A1 and NTN4. Spatial profiling mapped these states to distinct niches. The ALDH1A1+ compartment localized to a basal-associated niche with intermingled p63-positive basal cells adjacent to stroma, showed reduced proliferative activity, and displayed stem-like transcriptional features. Ex vivo drug testing revealed a striking response: the mTOR inhibitor Sapanisertib induced extensive tumor necrosis and was associated with near-complete depletion of ALDH1A1+ and NTN4+ states, accompanied by strong stress/apoptosis signatures and reduced endothelial cells. In an additional retrospective cohort of 12 SDSC, ALDH1A1 was present in all cases with heterogeneous spatial patterns and higher levels in recurrences. Mesothelin was expressed in the index case and a subset of tumors, supporting mesothelin-directed therapeutic strategies.
This study aimed to prepare and evaluate a novel monoammonium glycyrrhizinate (MAG) controlled-porosity osmotic pump (CPOP) with controlled-release properties. Capsule shells were prepared by the dip-coating method method, and the key variables affecting in vitro release were optimized using a Box-Behnken design-response surface methodology. In vitro release behavior was evaluated, and scanning electron microscopy (SEM) was used to examine shell morphology before and after dissolution. Pharmacokinetic behavior in rabbits, molecular docking, and solid-state characterization by differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were also performed. The optimized formulation exhibited a near zero-order release profile of MAG over 12 h in vitro, and the release curve closely matched the target profile. In rabbits, the self-prepared capsules reduced the peak plasma concentrations of MAG and its active metabolite glycyrrhetinic acid (GA) and significantly prolonged mean residence time compared with the reference formulation, indicating marked controlled-release behavior in vivo. Molecular docking confirmed stable binding of GA to nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor gamma (PPARγ), providing a mechanistic basis for the pharmacological benefits associated with prolonged in vivo exposure. DSC and XRD further showed that MAG remained in a stable crystalline state, with no crystal-form transition or incompatibility with the excipients during preparation. This study provides a promising advanced drug-delivery system for MAG, enhances understanding of its pharmacological advantages, and offers useful guidance for the development of controlled-release formulations.
Controlling peroxymonosulfate (PMS) activation at the atomic scale is crucial for steering reactive oxygen species (ROS) pathways, yet design principles that selectively bias PMS chemistry toward interfacial radical states remain elusive. Herein, we report an asymmetric Fe-Te dual-atom pair (FeTe DAs/NC), in which a p-block metalloid electronically modulates an Fe center through pronounced p-d hybridization. This atomic asymmetry reconstructs the local electronic structure, strengthens PMS binding, and directs PMS activation toward the generation and retention of surface-bound hydroxyl radicals. Mechanistic studies reveal surface-bound hydroxyl radicals (•OH) as the dominant ROS, while singlet oxygen (1O2) plays a secondary role. As a result, FeTe DAs/NC achieves complete degradation of carbamazepine within 60 min, markedly outperforming Fe or Te single-atom analogs, together with excellent reactivity and cycling stability across different water matrices and pollutant systems. This work establishes atomic-scale asymmetry and metal-metalloid p-d coupling as an effective strategy for steering PMS activation chemistry toward long-lived interfacial radical states.
The growing proportion of women in veteran communities internationally highlights a rising need for veteran support services tailored to their unique experiences. Despite this, support services remain predominantly designed for men, leading to underutilization and dissatisfaction among women veterans. This scoping review aimed to provide a comprehensive international review of the current state of knowledge regarding the experiences of women veterans in accessing and engaging with veteran-specific support services. This study followed the Joanna Briggs Institute scoping review methodology. Five databases were searched for papers published from 2000 onwards. Studies reporting on barriers and/or facilitators to access and experiences of engaging with veteran-specific support services reported by women veterans were included. There were no limitations on study methodology or country of origin, and all publications reporting primary research were included. A total of 117 studies were included in the review. This research originated predominantly from the US (n = 109), with seven UK papers, and one Canadian. Eleven themes were identified across the literature, highlighting gendered barriers and facilitators of accessing veteran-specific support for women. Women veterans report feelings of discomfort, exclusion, and discrimination within veteran services, which are perceived as being set up and designed for men. Women report experiencing stigma in help-seeking compounded by a perception of feminine weakness experienced during military service. Some women didn't want to access services they saw as military-adjacent, due to gendered adverse experiences during military service, including discrimination, harassment, and sexual violence. A lack of identification with the term 'veteran' further hinders women's engagement with veteran-specific services. Enablers of access include care that is sensitive to women's needs, trauma-informed service user-provider relationships, and peer support. The reviewed evidence suggests women experience unique challenges and needs in accessing veteran-specific services. Support services should focus on developing care that is, culturally competent, trauma-informed and sensitive to the needs of women, to address gendered barriers to engagement. More research is needed to confirm these research findings outside of the US context, and incorporating an intersectional lens in future research will be essential for improving the support systems for women veterans internationally.
Pediatric sepsis is a leading cause of global morbidity and mortality, yet high-resolution, granular subnational assessments remain scarce. Chile and Mexico are the only countries in Latin America that possess robust vital registration systems and open access databases with marginal levels of missing cases. This offers a unique opportunity to quantify the subnational burden of pediatric sepsis, identify healthcare system constrictions, and guide targeted public health interventions. This retrospective longitudinal study analyzed official hospital discharge and non-fetal death records of pediatrics (< 10 years old) from Chile and Mexico between 2014 and 2024. Age-standardized incidence (ASIR) and mortality (ASMR) rates, standardized ratios, and the mortality-to-incidence ratio (MIR), were calculated to assess mortality relative to subnational hospital output. A novel dynamic risk stratification matrix was developed to classify ICD-10 sepsis-related causes into four risk/severity quadrants based on year-specific ASIR and MIR indicators. A total of 656,234 discharges and 2,035 deaths in Chile, and 964,452 discharges and 77,252 deaths in Mexico were analyzed. Subnational trends were highly heterogeneous. Chile exhibited a predominantly low pediatric MIR (median < 1%) with isolated hotspots with significant structural deviations to the North. High-severity sepsis causes in Chile were relatively rare. Conversely, Mexico displayed an alarmingly high MIR (median 7.2%), with systemic persistency in States such as Chiapas and Nuevo León. Strikingly, high-severity causes in Mexico (e.g., unspecified septicaemia, bacterial meningitis) were highly frequent, accounting for 88-97% of pediatric sepsis deaths. Furthermore, systemic instances of code-specific MIR > 1.0 in Mexico suggest significant health system fragmentation and decoupling of hospital discharge from vital statistic registries. Pediatric sepsis in Latin America encompasses distinct realities, ranging from localized critical care gaps to high-lethality persistency. One-size-fits-all national policies may be inadequate. These findings advocate for precision public health, urging the deployment of decentralized, data-driven interventions and specialized resource allocation based on high-risk subnational hotspot identification.
The progressive skeletal muscle degeneration observed in Duchenne Muscular Dystrophy (DMD) patients requires multiple cycles of satellite cells (SCs) activation to promote tissue regeneration. Dystrophic SCs present intrinsic defects, and the disrupting fibrotic niche hinders appropriate muscle recovery. Traditional 2D culture systems face challenges in modeling the DMD muscle niche and SCs behavior. Our aim was to validate a 3D culture of skeletal muscle spheroids (iSMS) for DMD modeling, as compared to the traditional 2D culture, while investigating the pathophysiological mechanisms of dystrophin deficiency in vitro. To compare iSMS with traditional 2D myogenic differentiation, we differentiated wild-type (WT), dystrophic (DMD) isogenic induced pluripotent stem cells (iPSCs), as well as iPSCs derived from DMD patients, characterized myogenic markers levels and assessed differences in proliferation and differentiation using RT-qPCR, immunofluorescence, and flow cytometry. Our data showed that iSMS improved PAX7 expression in vitro, while MYOD1, MYOG, MYF5, and MYH3 expression were significantly reduced. These findings suggest that, at three weeks of myogenic differentiation, iSMS cultures retained satellite-like cells in a less activated, progenitor-like state. Accordingly, we identified higher expression of canonical Notch signaling genes such as JAG1 and NOTCH1 in iSMS compared to 2D. We also characterized the response of 2D and iSMS to terminal differentiation medium, providing a valuable comparison with muscle fibers derived from human adult myoblasts. Additionally, we showed that DMD iSMS-derived progenitors proliferated at reduced levels compared with WT, a characteristic not observed in progenitors derived from 2D cultures. Finally, we performed iSMS and 2D myogenic differentiation of iPSC lines from three patients with DMD. Our results highlight important advantages of using the iSMS differentiation platform over 2D for DMD in vitro modeling. Exploring these 3D systems may help to gain a deeper understanding of SCs behavior to advance in novel treatments for DMD, which might be applicable to other forms of muscular disorders.
Suicide is a leading cause of maternal mortality, yet there are currently no evidence-based perinatal suicide prevention programs. Given the risk of serious outcomes if undetected or inadequately treated, the goal of this study was to further understand the screening and treatment experiences of individuals with perinatal suicidal thoughts and behaviors (STBs). Qualitative data were generated from in-depth interviews with 13 individuals primarily from the United States who experienced perinatal suicidality at least 6 months prior to participation. Thematic analysis was used to examine the experiences of participants with respect to screening and treatment of perinatal STBs. Regarding screening, three major themes were identified: (1) gaps in comprehensive/routine screening for STBs (e.g., infrequent screenings or non-specific to suicide), (2) attitudes toward disclosure of STBs (resulting in omission of symptoms or downplaying of severity), and (3) importance of follow-up after screening. Three themes influenced participants' treatment experiences: (1) providers' engagement in care, (2) shared decision-making between provider and patient, and (3) impact of perinatal-specific treatment programs. Findings from this study highlight critical gaps in screening for and treatment of perinatal STBs. Implementing routine screening and comprehensive follow-up and improving treatment experiences are essential for improving the care of individuals with perinatal STBs and reducing maternal mortality.
The gut microbiome supports digestion, immunity, and metabolism; its imbalance (dysbiosis) drives inflammation and metabolic dysfunction, contributing to chronic diseases such as diabetes, cardiovascular disease, inflammatory bowel disease, and autoimmune disorders. Medicinal plants provide a wide range of phytochemicals (such as polyphenols, flavonoids, alkaloids, saponins), which reach the colon and undergo two-sided interactions with microbes in the gut, acting as potential microbiome modulators and substrates of biotransformation into bioactive metabolites. This structured narrative review synthesises evidence from peer-reviewed studies indexed in PubMed, Scopus, and Web of Science over the last 10 years on the role of medicinal plants in microbiome-mediated chronic disease modulation. This literature is organised into three mechanistic axes: (i) perturbations, defined here as measurable shifts in microbial diversity or taxonomic composition relative to a baseline or healthy reference state, together with beneficial taxa enrichment; (ii) alterations in microbial metabolite output, especially short-chain fatty acids (SCFAs) and other immunometabolic mediators; and (iii) downstream host metabolic and immune signalling. Rather than broad descriptive summaries, the literature is organised using an axis-based mechanistic framework, highlighting key translational constraints such as botanical heterogeneity, dose/formulation variability, and inconsistent microbiome endpoint standardisation, that must be addressed to strengthen human evidence and clinical relevance. Illustrative microbiome-mediated processes involve botanicals such as turmeric (curcumin), ginseng (ginsenosides), and green tea (catechins), though evidence strength varies by study design. Future progress requires standardised phytochemical characterisation, microbiome-stratified trials, and integration of multi-omics with artificial intelligence analytics to enhance mechanistic insight, identify responders, and enable personalised plant-based microbiome therapies.
Expanders in organic Rankine cycle systems serve as critical energy-conversion components in low-grade waste heat recovery installations, yet their reliable operation is threatened by faults such as bearing defects, rotor imbalance, and blade cracking. Conventional diagnostic methods often struggle with non-stationary vibration characteristics, class imbalance, and low signal-to-noise ratios inherent to these working environments. This paper proposes an improved deep residual network, referred to as multi-scale convolutional block attention module residual network, that integrates a multi-scale parallel feature extraction module with convolutional block attention mechanisms for intelligent fault diagnosis. The multi-scale module employs three parallel convolutional branches with different kernel sizes to simultaneously capture transient impulses, periodic modulation, and low-frequency envelope features across multiple temporal scales. Attention-enhanced residual blocks sequentially recalibrate channel and spatial responses to emphasize fault-sensitive features while suppressing noise interference. A training optimization scheme combining Focal Loss, cosine annealing, and targeted data augmentation is further introduced to address the small-sample imbalanced-data challenge. Five-fold cross-validation experiments conducted on a 10 kW single-screw expander test rig demonstrate that the proposed model achieves 98.11 ± 0.34% diagnostic accuracy across four health states, surpassing the standard deep residual network baseline by 6.57 percentage points, with only 3.27% relative accuracy degradation at 10 dB signal-to-noise ratio. Ablation studies confirm a multiplicative synergy between the multi-scale and attention modules, statistical significance tests validate the robustness of the observed improvements, and comparative evaluations against six benchmark methods demonstrate the superiority and generalizability of the proposed approach.
The recent introduction of the right to oncological oblivion in some European states raises critical issues. While designed to protect cancer survivors from discrimination, this right may compromise occupational health surveillance for workers exposed to carcinogenic hazards. This commentary raises questions for future policy and research.
Ongoing neurodevelopmental care is essential for children with congenital heart disease (CHD). Understanding delivery and uptake of neurodevelopmental care pathways can inform implementation and resource planning. This study applied simulation modelling to explore outcomes from a neurodevelopmental care pathway for children with CHD. The model was developed using data from a Queensland program to explore health service interactions for neurodevelopmental screening, formal assessment, and early intervention, up to five years. Modelling was intended to provide a baseline understanding of the pathway, rather than evaluating against a reference standard. Hypothetical scenarios explored how changes in screening and referrals influenced the identification of developmental concerns, and how developmental concern severity affected intervention referrals. Based on available data, 58% of the cohort remained under routine surveillance and 25% had accessed early intervention for one or more developmental delays. Scenarios defined by increased screening projected up to 55% of the cohort having a developmental concern identified during screening and 45% having a developmental delay identified following assessment. Simulation modelling was useful for understanding outcomes from a neurodevelopmental pathway and how differences in screening and assessment affected health service interactions. Findings may inform policy and resource planning for future neurodevelopmental pathways. This study shows that simulation modelling is a useful approach for evaluating a neurodevelopmental care pathway for children with CHD, to understand movement through neurodevelopmental screening, assessment, and interventions. Scenario-based modelling provides insights into factors influencing pathway engagement, contributing evidence to strengthen understanding of service gaps and areas where improvements can most effectively impact engagement and resourcing. This study identifies neurodevelopmental screening as the most influential stage impacting downstream outcomes, underscoring its importance as a strategic intervention point. This study's approach provides a general framework for evaluating similar pathways and a potential baseline for assessing future policy or service changes.
Itch is a complex noxious sensation associated with many skin and systemic conditions, which varies in intensity and quality across different body regions. Despite its prevalence, the molecular and cellular mechanisms underlying regional itch differences remain poorly understood. Investigating the neural basis of regional itch differences, we identified a functional divergence in neuropeptide signaling and central circuit engagement between the trigeminal and spinal systems, which was independent of peripheral innervation density. Utilizing a combination of behavioral, pharmacological, genetic, and molecular assays, we identified a unique population of trigeminal (TG) neurons that facilitate specialized itch-pain coding. Our results indicate that while histamine receptors HRH1 and HRH3 are both involved in mediating mixed itch-and-pain sensations, the specific activity of Substance P (SP)- and Somatostatin (SST)-expressing neurons orchestrates this transition in the cheek. This behavioral shift is mediated by a central mechanism wherein sensory neurons activation recruits distinct nociceptive circuits within the brainstem. In brief, these findings provide insights into the molecular and cellular mechanisms underlying regional itch differences, highlighting the importance of considering anatomical location when developing targeted treatments.
Bone remodelling is essential for maintaining skeletal integrity by preserving the balance between bone formation and resorption, with excessive osteoclast activity contributing to osteoporosis. Osteocytes act as central regulators of osteoclastogenesis through mechanically sensitive paracrine signals, yet the influence of osteoblasts and their mesenchymal precursors remains less defined. Extracellular vesicles (EVs) have recently emerged as mediators of bone cell communication, although their role in osteoclast regulation are still underexplored. This study demonstrates that mesenchymal-derived bone cells inhibit osteoclastogenesis through an EV-dependent mechanism shaped by their differentiation stage and mechanical environment. Mechanically stimulated osteocyte-derived EVs showed the strongest anti-catabolic response. Notably, we identify miR-150-5p as a mechano-responsive miRNA enriched within osteocyte EVs, capable of inducing a dose-dependent reduction in osteoclastogenesis. Transcriptomic analyses reveal that EV treatment and miR-150-5p delivery induce substantial transcriptional changes in osteoclast precursors, including downregulation of shared target genes linked to bone remodelling. Overall, we highlight mechanically activated osteocytes as key regulators of osteoclastogenesis through an EV-mediated mechanism, in which miR-150-5p represents a promising candidate contributor within the broader EV cargo landscape, highlighting their potential for future cell-free therapeutic strategies.
Helical ladder polymers possess rigid, helically fused backbones that confer distinctive chiroptical properties, yet their integration into polymer brush architectures remains highly challenging. Here, we report the first synthesis of bottlebrush polymers with a helically fused ladder backbone, achieved through acid-catalyzed intramolecular cyclization followed by controlled ATRP grafting-from polymerization. By integrating a single-handed ladder scaffold with flexible, water-soluble PNIPAM side chains, the resulting architecture markedly enhances the processability and structural tunability of helical ladder polymers. Moreover, the traditional helical ladder, long regarded as completely rigid and static, has been found to exhibit dynamic transition properties. This change was caused by conformational triggering of the thermally driven binaphthyl dihedral angles, which was quantitatively confirmed by the thermodynamic dynamics and molecular dynamics simulations, demonstrating the hierarchy of the transition from axial chirality to helical chirality. Overall, this work establishes a promising synthetic method for helical ladder bottlebrush polymers and demonstrates their potential as versatile platforms for designing dynamic chiral materials.
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There have been discussions as to the time of elective induction of labour to curb the continuation of pregnancy that might endanger the lives of both the mother and child. This research was conducted to assess foetal and maternal consequences of planned delivery at 40 and 41weeks in women with low-risk singleton pregnancy. A randomised controlled trial with equal allocation of participants (96 pregnant women in each arm) into 40weeks and 41weeks. Participants were randomised at the antenatal clinic at 39 weeks for induction of labour. The main outcome was the caesarean section rate. Secondary outcomes were maternal (genital tract laceration rate) and foetal (rates of meconium staining of amniotic fluid, SCBU admission, perinatal mortality, birth trauma, birth weight, and neonatal APGAR score at 1 and 5 minutes). Student t-test and chi-square test were used for inter-group comparison. Incidence of caesarean delivery (26.6% vs. 21.3%; p=0.406), and genital laceration (2.1% vs. 5.6%; p=0.268) did not differ between groups. Significantly higher birth weight was noted among women induced at 41weeks (3.41 ± 0.37kg) than 40weeks (3.28 ± 0.46kg) (p=0.043). Also, there was significant variation in meconium staining of amniotic fluid between 40weeks (11.7%) and 41weeks (25.8%) (p=0.014). Other foetal outcomes showed no significant difference. Inducing labour at 40weeks is safe for low-risk women as it does not significantly increase the cesarean delivery rate and adverse perinatal outcomes. Therefore, elective induction of labour at 40weeks should be recommended and introduced into obstetric practice without the fear of adverse outcomes.
Up to 80% of diffuse midline gliomas (DMGs) are characterized by a lysine to methionine driver mutation (K27M) in the tail of histone variant H3.3, pointing to likely roles for epigenetic mechanisms in K27M-driven tumorigenesis. Understanding the effects of mutant histone H3.3 on the complex patterns of histone modifications and interactions with chromatin structure and modifying enzymes is essential to developing effective combination treatment therapies for K27M DMG such as targeting multiple epigenetic enzymes at once. Here, using a genomics approach, we identified combinatorial patterns of epigenetic modifications that are affected by mutant H3.3 in DMG. We also characterized a strong association between H3.3 and the structural chromatin regulator CTCF, finding that mutant H3.3 leads to ectopic binding of CTCF at many additional sites across the genome in DMG. Notably, a number of these ectopic CTCF binding events occur within the HOX gene loci and are associated with an increase in H3K27me3 levels at bivalent domains and a decrease in HOX gene expression. We also find an association of H3.3 and CTCF at genomic sites adjacent to regions with active or repressive modifications, suggesting a potential role for these two factors in segmenting the chromatin and regulating, perhaps insulating, different types of domains. Together our data suggest that H3.3 K27M both affects epigenetic marks and chromatin organization in part through interaction with CTCF and point to a potentially novel contributory role for CTCF in promoting oncogenesis in DMG. These findings could have potential implications for designing therapy regimens to more effectively target the chromatin changes and genomic instability observed in H3.3K27M glioma cells.
Cytokine-mediated cross-talk between immune cells and fibroblasts is a driver of excessive ECM accumulation during fibrosis. In this study, we used a 3D in vitro model of a connective tissue to discern the roles of three pro-inflammatory cytokines; TNF-α, IL-18 and IL-1β, alone, and in combination with TGF-β1 to simulate the fibrotic environment. Ring-shaped tissues were formed by seeding human fibroblasts into circular molds of agarose, wherein the cells self-assembled, formed a 3D tissue and synthesized de novo a collagen-rich ECM. Cytokine treated tissues were analyzed at days 7 and 14 by histology and measured for thickness, collagen, DNA and strength and stiffness by tensile testing. Despite their pro-inflammatory nature, none of the cytokines increased collagen alone or in combination with TGF-β1. TNF-α and IL-1β reduced collagen, tissue strength and stiffness, and altered tissue morphology. When combined with TGF-β1, TNF-α and IL-1β counteracted TGF-β1-mediated increases in collagen, strength, and stiffness. In contrast, IL-18 had minimal effects alone or when combined with TGF-β1. These data suggest that IL-18 has no effect on fibroblast activation, whereas TNF-α and IL-1β may modulate TGF-β1's effects. This 3D model of a human collagen-rich tissue can help define cytokine-mediated cross-talk between immune cells and fibroblasts.