共找到 20 条结果
暂无摘要（点击查看详情）
The superior oblique muscle tendon is known to bend in the anterior orbit around a cartilaginous trochlea. The site where the tendon bends is frequently interested by the presence of a small depression, the trochlear fovea, and/or the trochlear spine. Exact topography, size and frequency of these items are still undetermined. For this purpose, we studied 120 orbits of individuals that underwent computed tomography for pathologies not involving the anterior orbit. We detected the presence of the trochlear spine in 10% of orbits and we determined its location and size. We also observed the presence of two tubercles (TT1 and TT2), with distinct positions relative to the tendon. TT1 was present in 5% of orbits and was located on the same spot of the spine differing from the latter only for its morphology. TT2 lied in a more advanced position and it was rarer (1,67% of orbits). The spine and the first type of tubercle were located above and behind the tendon reflection; the second tubercle lied below and ahead of the tendon reflection. A distinct trochlear fovea was detected in 25.83% of orbits and lied 3.42 ± 0.97 mm behind the orbital rim. Fovea diameters were 4.16 ± 1.08 mm × 3.84 ± 0.97 mm. In conclusion we demonstrate that in the anterior orbit a bony process is present in at least 15% or orbits. It is a note of interest for strabismus surgery when it is necessary to intervene on the superior oblique muscle or when it is needed access to the medial orbital wall.
Plant embryogenesis is a critical process characterized by extensive cellular differentiation and morphogenesis, regulated by complex epigenetic mechanisms. However, dynamic changes of DNA methylation during Arabidopsis early embryo development remain to be elucidated. In this study, Arabidopsis hybrid embryos from 2/4-cell to globular stage were subject to bisulfite sequencing and RNA-seq analysis. Our results revealed a local remodeling of DNA methylation during early embryogenesis, represented by a remarkable gain of CHH methylation and the progressive loss of CHG methylation. Genes with differential methylation were found to participate in cell division, morphogenesis, pattern specification and auxin signaling, indicating their potential role in embryo development. At globular stage, CHH hyper-methylation exhibited a notable association with TE repression. The divergences between allelic methylation primarily lied in CG context which increased with embryogenesis. CHH methylation variations between parental alleles underwent reprogramming. Our results implied a negative relevance between allele-specific expression and methylation at CHG sites in early embryos. This work provides new insights into DNA methylation remodeling and its association with transcriptional changes during Arabidopsis early embryogenesis, laying a foundation for future functional studies.
Diabetic wounds represent a significant clinical challenge, characterized by bacterial biofilm formation, persistent inflammation, and oxidative stress. Although photothermal therapy (PTT) and gas therapy (e.g., CO, H2) are promising alternatives to conventional antibiotics, existing monotherapeutic strategies fail to address the multifactorial pathological characteristics of these wounds, which is a critical research gap. To fill this gap, an integrated multimodal nanoplatform (CO/AB@MPDA) by co-loading dodecacarbonyltriiron (FeCO, a CO donor) and ammonia borane (AB, a H2 donor) into mesoporous polydopamine (MPDA) carriers was developed. The innovation lied in its synergistic design. It enabled near-infrared (NIR)-triggered CO release and pH-responsive H2 generation, simultaneously targeting infections, inflammation, and microenvironment dysregulation. In vitro and in vivo experiments confirmed its potent antibacterial/biofilm-disrupting activity, high biosafety, reactive oxygen species (ROS) scavenging, anti-inflammatory properties, as well as superior ability to accelerate diabetic infected wound healing. In summary, the CO/AB@MPDA nanosystem overcomes the limitations of monomodal therapies through synergistic PTT-gas therapy, providing an innovative and comprehensive therapeutic strategy for diabetic wound infections.
Myocardial infarction (MI) remains a leading cause of morbidity and mortality, with an uneven burden across Brazil. We evaluated trends in emergency MI hospitalizations, in-hospital mortality, and standardized costs within Brazil's Unified Health System (SUS) from 2008 to 2023, with emphasis on regional disparities and the COVID-19 period. We performed a retrospective observational analysis using SUS Hospital Information System (SIH/SUS) data. Age- and sex-standardized rates were calculated for emergency MI hospitalizations and in-hospital mortality; standardized costs were expressed as BRL per hospital day and adjusted for inflation and regional purchasing power. Five-year interval means, cumulative changes, and Z-tests with 95% confidence intervals (95% CI) were computed. To assess associations between health-system supply factors (primary care capillarity, inpatient capacity, and workforce) and MI outcomes, we estimated region-year two-way fixed-effects panel regressions using lagged supply indices derived from CNES/TABNET. Corresponding linear two-way fixed-effects trend panels are presented to visualize the model-implied within-region linear associations. Emergency MI hospitalization rates increased by 145.91% nationally from 2008 to 2023, with the greatest growth in the Central-West (+ 240.88%). The South and Southeast consistently recorded the highest hospitalization and mortality rates, while the North and Northeast - despite lower baseline rates - showed the steepest proportional growth, raising important equity concerns. In-hospital mortality increased by 166.67% nationally, with marked worsening during the COVID-19 period (2020-2022). In contrast, standardized cost per hospital day declined nationally by 7.38% across five-year means (768.69 to 663.98 BRL/day; p < 0.001), remaining highest in the South (1102.69 BRL/day in 2018-2022) and declining most in the North (684.38 to 465.70 BRL/day; p < 0.001). In supply-side panel analyses, inpatient-capacity expansion was most consistently associated with lower per-day reimbursement intensity and lower MI hospitalization rates within regions over time; supply indices showed limited association with in-hospital mortality. MI burden in Brazil's SUS rose substantially from 2008 to 2023, with persistent regional inequities and worsened outcomes during the pandemic. Inpatient-capacity expansion was the supply domain most consistently linked to MI utilization and cost variation, though all associations are ecological rather than causal. Standardized per-day inpatient costs did not rise commensurately with the growing clinical burden, suggesting that reimbursement/resource intensity per hospital day did not expand in step with demand. These findings support region-specific efforts to strengthen timely, evidence-based acute MI care - particularly in the North and Northeast, where demand is rising fastest against a backdrop of structural resource constraints.
While multiconfigurational approaches have long been relegated to expert practitioners working on a case-by-case basis, recent developments have increasingly made these methods more routine and applicable to broader sets of systems. This review outlines the state-of-the-art in multiconfigurational approaches, with an emphasis on moving from delicate hand-selected pathways through configuration space toward more robust and efficient approaches to treating a host of challenging chemical systems accurately. First, we overview recent work in automated active-space selection, which has enabled increasingly large-scale applications of multireference methods to modeling vertical excitations and reactivity. Second, we highlight the increasingly efficient methods for recovering correlation energy beyond the active space, as headlined by extensions of pair-density functional theory and its role in accurate and efficient treatment of excited-state dynamics and its utilization to train machine-learned potentials. Finally, we highlight recent efforts to treat extended systems that until recently have lied beyond the traditional limits of active-space methods, giving center stage to product-form wave functions of the localized active space family of methods that allow for the computation of multiconfigurational band structures. These recent advancements point to a broader use of multireference approaches for high-impact chemical and materials science applications.
In this work, electrospun short nanofiber aerogel-templated oleogels (ESNF-ATO) were fabricated by electrospun pullulan nanofibers. Spinning solutions with different concentrations were utilized to maintain fiber diameter, and short nanofibers were homogenized to prepare aerogel templates for oil adsorption. The shape of the templates could be easily controlled, and the fabrication process unchanged the properties of pullulan and the diameter of short nanofibers. Increasing the fiber diameter resulted in more flexible aerogel templates, which exhibited lower compressive strengths but higher recovery rates in 100-cycle fatigue tests. Simple linear fitting further confirmed the above results. Oleogels could be formed by rapid oil adsorption (normally within 100 s), and capillarity mainly induced this procedure. The thinner nanofibers provided the templates a high oil adsorption capacity (up to 69.05 g/g) but a relatively weakened oil holding capacity. ESNF-ATO exhibited good rheological properties, and could effectively realize the sustained-release of free fatty acids or lipo-soluble compounds. The significance of this work lied in the innovativeness of the combination of electrospun short nanofibers and aerogel templates, and the characteristics of fiber-based templates and oleogels were adjustable by modulating the fiber diameter.
Rape myths, including the belief that victims frequently lie, contribute to barriers in justice, such as the disproportionate use of the "unfounded" classification-where, following an investigation, it is determined no crime occurred. This study analyzes rape report narratives tied to previously untested sexual assault kits (N = 5638) from a large, urban Midwestern (US) jurisdiction, focusing on differences in narratives deemed unfounded or where officers expressed victim lying/doubt. Using natural language processing's sentiment analysis, we assessed tone (via polarity and subjectivity) and word counts. Results showed that unfounded narratives were shorter and more negatively written than others but did not differ in subjectivity. Victim lied/doubted narratives showed no significant difference in polarity, subjectivity, or length compared to others. These findings highlight how bias can manifest in written narratives, potentially influencing case outcomes. Addressing these biases through improved report writing and limiting the misuse of the unfounded classification is essential to support victims' pathways to justice.
We investigate whether a stable predisposition to interpret events as the result of conspiracies-conspiracism-is associated with the spontaneous generation of conspiratorial content in writing when interpreting ambiguous information. Across two studies (N = 385), participants watched the apocalyptic thriller Leave the World Behind and wrote an essay interpreting its meaning. Each essay was rated by a Large Language Model for its conspiratorial narrative content, that is, the degree to which the text contains claims that the public is being pervasively lied to about aspects of reality, enabling some groups to enact a harmful, self-serving agenda. Contrary to our preregistered hypothesis, we did not find an association between participants' conspiracism and their essays' level of conspiratorial narrative content. Exploratory linguistic analyses revealed that conspiracism was associated with greater use of conspiracy-related vocabulary (e.g., deception, government), a disproportionate use of sophisticated words, and increased syntactic complexity. These results suggest that conspiracism may emerge more readily at the lexical level rather than through fully structured narratives. We discuss potential methodological and theoretical factors contributing to these unexpected results, including the roles of context, perceived relevance, motivation, and collective social dynamics. We also consider the possibility that conspiracism may not directly translate into conspiratorial narratives. If so, we recommend comparative research on online vs offline conspiratorial writing to clarify whether conspiracy theories emerge spontaneously from genuine beliefs or are constructed strategically, detached from genuinely held beliefs.
To describe the surgical technique and report the clinical outcomes of using locking plates applied transversely across the sternum as part of sternal repair after large sternectomy. Two client-owned dogs. Short case series. One dog with chest wall hemangiosarcoma and one dog with chronic extensive thoracic pyogranulomatous lesion caused by Actinomyces spp. were treated by thoracic wall resection including partial sternectomy. The defect was reconstructed with multiple techniques including a locking plate secured with screws in two opposite ribs. There were no complications related to the surgical reconstruction or implants. The first dog was euthanized at 8 months postoperatively following sudden deterioration. The second dog developed self-limiting serosanguinous discharge from 3 to 6 days postoperatively but otherwise had an uneventful recovery. No recurrence was reported 15 months post-surgery. Use of a locking plate to span two opposite ribs in conjunction with other reconstructive techniques was a safe and effective method of treating large sternal wounds in these two dogs. This new surgical technique yielded excellent functional and cosmetic outcomes. Transverse locking plate application is a straightforward and promising option for large thoracic wall or sternal defects.
This study aimed to determine the prevalence of food insecurity in Marajoara quilombola communities and its associated factors. A cross-sectional, community-based, family-approach study was carried out with 434 families in Salvaterra, Marajó Island, Pará, Brazil, from June to July 2021. A household survey was carried out with a standardized questionnaire on sociodemographic data and the Brazilian Food Insecurity Scale. A multivariate logistic regression was used to analyze associated factors. Most quilombola families (88.9%) lied in food insecurity, 33.1% (n = 144) of whom in severe insecurity; 21.4% (n = 93), in moderate insecurity; and 34.3% (n = 149), in mild insecurity. The regression model showed that receiving no pension doubles the chance of mild food insecurity and multiplies moderate+severe insecurity by 5 times. Per capita family income below 1/5 or even 1/3 of the minimum wage increase the chance of moderate+severe insecurity by 9 and 9 times, respectively. Households in the B/C economic classification were 21% less likely to have moderate+severe insecurity than those with the D/E classification. Food insecurity had a high prevalence in quilombola families, with a preponderance of moderate+severe insecurity. Family income and its components configured the main factors associated with food insecurity. O objetivo deste estudo foi determinar a prevalência de insegurança alimentar de comunidades quilombolas marajoaras e os fatores associados. Estudo transversal de base comunitária e abordagem familiar com 434 famílias, localizadas no Município de Salvaterra, Ilha de Marajó, Pará, Brasil, de junho a julho de 2021. Realizou-se inquérito domiciliar com questionário padronizado sobre dados sociodemográficos e o questionário da Escala Brasileira de Insegurança Alimentar. Para analisar os fatores associados foi utilizada a regressão logística multivariada. A maioria das famílias (88,9%) quilombolas estava em insegurança alimentar, 33,1% (n = 144) em insegurança grave, 21,4% (n = 93) em insegurança moderada e 34,3% (n = 149) em insegurança leve. O modelo de regressão mostrou que não receber aposentadoria dobrou a chance de insegurança alimentar leve e multiplica 5 vezes a insegurança moderada+grave. A renda familiar per capita de menos de 1/5 ou até 1/3 do salário mínimo elevou em 9 e 4 vezes a chance de insegurança moderada+grave, respectivamente. Famílias na classificação econômica B/C tiveram 21% menos chances de apresentar insegurança moderada+grave em relação às com classificação D/E. A insegurança alimentar apresentou alta prevalência em famílias quilombolas, preponderando insegurança moderada+grave. A renda familiar e seus componentes foram o principal fator associado à insegurança alimentar. El objetivo de este estudio fue determinar la prevalencia de la inseguridad alimentaria en las comunidades quilombolas de Marajó y los factores asociados. Se trata de un estudio transversal, de base comunitaria y con un enfoque familiar, con 434 familias ubicadas en el municipio de Salvaterra, Isla de Marajó, Pará, Brasil, de junio a julio del 2021. Se realizó una encuesta domiciliaria utilizando un cuestionario estandarizado sobre datos sociodemográficos y el cuestionario de la Escala Brasileña de Inseguridad Alimentaria. Se utilizó la regresión logística multivariante para analizar los factores asociados. La mayoría de las familias quilombolas (88,9%) sufría inseguridad alimentaria, de las cuales el 33,1% (n = 144) experimentaba inseguridad severa, el 21,4% (n = 93) inseguridad moderada y el 34,3% (n = 149) inseguridad leve. El modelo de regresión demostró que no recibir jubilación duplicaba la probabilidad de sufrir inseguridad alimentaria leve y multiplicaba por 5 la probabilidad de sufrir inseguridad moderada+severa. Un ingreso familiar per cápita inferior a 1/5 o hasta 1/3 del salario mínimo aumentó la probabilidad de inseguridad alimentaria moderada+severa en 9 y 4 veces, respectivamente. Las familias de la categoría económica B/C tuvieron un 21% menos de probabilidades de experimentar inseguridad moderada+severa en comparación con las de la categoría D/E. La inseguridad alimentaria tuvo una alta prevalencia entre las familias quilombolas, predominando la inseguridad de moderada+severa. Los ingresos familiares y sus componentes fueron el principal factor asociado a la inseguridad alimentaria.
Global agriculture is facing significant threat from climate-driven abiotic stress, which endangers global food security by impacting crop performance and adaptation. However, traditional abiotic stress detection methods are often labor-intensive and lack precision and scalability. Efficient and reliable solutions are needed to meet rising global food demand. Recent advances in artificial intelligence (AI) offer highly accurate, non-invasive, and sustainable approaches for abiotic stress detection. This paper reviews the impact of AI, and specifically Machine and Deep Learning algorithms, coupled with synergistic technologies and diverse datasets (imaging techniques and Internet of Things (IoT) infrastructures), to identify unique signatures of abiotic stress, and assess its impact on growth and physiological performance. It contrasts with other reviews that address individual technologies and algorithms, while presenting abiotic stress detection as a secondary objective. We examined peer-reviewed journal articles on the use of AI in detecting abiotic stress. The reviewed literature was chosen based on the stress category, sensing mode, and AI technologies employed. A comparative analysis was performed to explore potential advancements of AI-based abiotic stress detection methods over traditional approaches and also challenges lied to the adoption of AI in agriculture for abiotic stress detection.
To identify the prevalence of and risk factors for postpartum depression associated with a lack of sleep due to breastfeeding. From June to December 2023, a cross-sectional study was carried out in the psychiatric units of Sahiwal Teaching Hospital and Allied Hospital Faisalabad, two tertiary care facilities in Pakistan. Women between the ages of 18 and 40 who were primigravidas during the first six months after giving birth were included in the study. The Edinburgh Postnatal Depression Scale (EPDS) and the Pittsburgh Sleep Quality Index (PSQI) were used to gather data, and SPSS version 30 was used for analysis. Out of 200 participants, 55 (27%) reported sleep disturbances (PSQI>5), of whom 25 (12.5%) also exhibited symptoms of postpartum depression (EPDS>10). The mean self-reported total sleep duration, including all naps within a 24-hour period, was 5±1.3 hours, with an average sleep efficiency of 60±14%. A statistically significant association was observed between sleep disturbances and postpartum depression (χ²= 0.125, p<0.0001), indicating that participants with poor sleep quality were significantly more likely to experience depressive symptoms. Nursing-related sleep deprivation was identified as a cause of postpartum depression. Improving sleep quality may aid in the reduction of postpartum depression.
BACKGROUND: After cardiac surgery, patients are liberated from mechanical ventilation despite diaphragm dysfunction and atelectasis; understanding their breathing pattern can help interpreting conditions with diaphragm dysfunction and defining a tolerable range of effort under mechanical ventilation. METHODS: Prospective physiological study describing the magnitude and pattern of breathing effort after cardiac surgery. Three spontaneous breathing trial modalities performed in random order, including two un-assisted (continuous positive airway pressure 0 cmH2O -CPAP0- and T-piece) and one assisted (pressure-support 5/PEEP 5 cmH2O- PS5PEEP5). Airway, esophageal, and gastric pressures were recorded and diaphragm ultrasound was performed. Airway occlusion pressure (P0.1) was also measured. Difference in magnitude of respiratory effort between conditions was explored through linear mixed-models with Tukey adjustment for pairwise comparisons. Association between pre-defined clinical variables (opioid dose, body mass index, and chest wall compliance) as well as measures of diaphragm function with expiratory muscle activity was explored through mixed-effects models. RESULTS: Thirty patients were included. Maximum inspiratory pressure during a Mueller maneuver was − 29.8 ± -12.6 cmH2O. Estimated mean (CI95%) global inspiratory effort (pressure-time product per minute) during un-assisted modalities for the population was 138.5 (120.6,156.3) cmH2O•sec/min. With increasing support, drive decreased as well as pressure-time product per minute (median PS5PEEP5: 101, CPAP0 129, T-piece 135 cmH2O•sec/min, p < 0.001 for PS5PEEP5 vs. other modalities), and transdiaphragmatic pressure (PS5PEEP5 median 4.1, CPAP0 median 6.6, T-piece median 6.0 cmH2O respectively, p < 0.001 for PS5PEEP5 vs. other modalities). During mechanical ventilation, expiratory muscle effort (i.e., gastric pressure rise) contributed on average to 31–37% of the drop in esophageal pressure during inspiration, being lower after extubation. Gastric pressure rise was directly associated with a higher intraoperative dose of opioids (p = 0.004) and inversely with measures of respiratory muscle function (p = 0.001). Tension-time indices lied within the higher end of a non-fatiguing range. All patients were successfully extubated. CONCLUSIONS: Stable patients after cardiac surgery show an increase in respiratory drive and inspiratory effort with increasing load despite signs consistent with diaphragm dysfunction. Expiratory muscle use is common, it is associated with decreased diaphragm activity, higher intraoperative dose of opioids and decreases after extubation.
Early adolescence is a period characterized by increased desire for autonomy and increased risk-taking. At times, this combination leads parents to surreptitiously engage in covert monitoring to keep tabs on their adolescents. Whereas substantial research has investigated adolescent information management and lying, little is known about the development of adolescents' reasoning about parents' covert monitoring and lying. Our aim was to better understand these reasoning processes, by examining how they vary with age and as a function of risk assessment and monitoring strategy. Using linear mixed-effects models, we analyzed the reasoning of an ethnically diverse US sample of 152 adolescents (10-14-year-olds, 70 female). Through clinical interviews, adolescents evaluated hypothetical vignettes depicting same-aged peers engaged in six forms of risky behavior, and parents who engaged in six forms of covert monitoring, which they lied about. Adolescents broadly rejected covert parental monitoring and lies about their monitoring. However, judgments hinged on both the invasiveness of the monitoring strategy and the type of risk, and shifted with age. Invasive monitoring was rejected more than less invasive strategies, and monitoring was accepting to a greater extent in higher-risk situations. The findings show that while adolescents would have preferred open communication and honesty, they did not view parents' monitoring strategies or deception in uniform ways. Adolescents' judgments and justifications provide insight into the ways in which they coordinate and draw priorities among concerns with honesty, privacy, and safety, and parents' legitimate interest and authority over certain behaviors.
Clinical studies describe a higher risk in individuals with Gender Dysphoria (GD) to engage in disordered eating practices, as well as dietary restraint. To the present day, clinical assessments on eating psychopathology in GD are principally oriented towards assessing behaviors, rather than the lived experience underlying these behaviors. A sample of 141 individuals with GD (40 assigned male at birth-AMAB, 101 assigned female-AFAB), 153 individuals from the general population and 294 patients with AN were enrolled. Body Uneasiness Test (BUT), the Eating Disorders Examination Questionnaire (EDE) and the Identity and Eating Disorders questionnaire (IDEA) were administered. Analysis of variance and linear models were employed to estimate group differences, adjusted for age, education, and body mass index. Body uneasiness (BUT global severity index: F value 47.44, p < 0.001), and eating behaviors (EDE total score: F value 66.19, p < 0.001) lied on a spectrum of severity between patients with AN (highest), individuals with GD (elevated) and the general population. Patients with AN reported markedly greater embodiment disturbances in comparison with both the general population and AMAB or AFAB individuals with GD (IDEA total score: minimum T value 4.03, p < 0.001). However, AMAB individuals with GD also reported moderate embodiment disturbances in comparison with the general population (IDEA total score: T value 3.41, p < 0.01). Lived experiences may better highlight core differences between GD and clinical populations of patients with eating disorders. Embodiment disturbances were also reported by AMAB individuals, suggesting a role for gendered expectations in embodiment. III, evidence obtained from cohort or case-control analytic studies.
暂无摘要（点击查看详情）
Systemic inflammation contributes to atherosclerosis and its thrombotic complications, yet population-level data for neutrophil-predominant dermatoses are limited. Pyoderma gangrenosum (PG) is a prototypical neutrophilic inflammatory dermatosis, we quantified its association with incident atherothrombotic events and MACE over 5 years. Adults with PG were compared with non-PG controls. To limit reverse causation, we excluded individuals with pre-index cardiovascular events and selected vascular procedures. Cohorts were 1:1 propensity-score matched (greedy nearest neighbor; caliper 0.1 SD of logit). Follow-up was up to 5 years. Primary endpoint was MACE (cardiac arrest, cardiogenic shock, acute myocardial infarction [MI], ischemic stroke, all-cause mortality). Secondary endpoints were MI, ischemic stroke, symptomatic peripheral artery disease (PAD), and all-cause mortality. A negative-control outcome and a procedure-anchored PAD sensitivity analysis (lower-extremity revascularization) were prespecified. Among 10,669 PG patients and 2,908,830 controls, 10,666 matched pairs were retained with good covariate balance. Over 5 years, PG was associated with higher risk of MACE (HR 1.32; p < 0.001), MI (HR 1.42; p = 0.001), and all-cause mortality (HR 1.44; p < 0.001), while ischemic stroke was neutral (HR 0.94; p = 0.52). Symptomatic PAD showed the largest association (HR 5.48; p < 0.001), confirmed in the procedure-anchored analysis (HR 5.58; p < 0.0001). The negative control was null (HR 1.04; p = 0.82). PG is associated with meaningful excess atherothrombotic risk, particularly PAD, supporting PG as a systemic inflammatory risk-enhancing condition requiring intensified cardiovascular prevention.
Pulmonary fibrosis is a progressive interstitial lung disease characterized by excessive fibroblast-to-myofibroblast transition (FMT) and extracellular matrix (ECM) deposition, largely driven by transforming growth factor-beta 1 (TGFβ1). Existing therapies offer limited efficacy, particularly in advanced disease. Circadian rhythms have recently emerged as key modulators of lung inflammation and fibrosis. In this study, we developed an in vitro model of chronic fibrotic signaling using adenovirus-mediated TGFβ1 overexpression (Ad-TGFβ1) or human recombinant protein TGFβ1 in primary normal human lung fibroblasts. Using this model, we investigated the antifibrotic potential of STL1267, a next-generation REV-ERBα agonist with improved potency, specificity, and pharmacokinetic properties. RNA sequencing and pathway analysis revealed that STL1267 significantly reversed Ad-TGFβ1-induced expression of genes associated with ECM remodeling, collagen biosynthesis, and immune suppression. STL1267 also upregulated pathways related to IL-10, IL-4, and IL-13 signaling, which are known to counteract fibrotic responses. Quantitative PCR and immunoblotting confirmed STL1267's ability to downregulate key profibrotic markers, including COL1A1, αSMA, FN1, and FAP, at both gene and protein levels. Comparative studies with other Rev-erbα agonists (GSK4112, SR9009), saracatinib, and Food and Drug Administration (FDA)-approved antifibrotic drugs (pirfenidone, nintedanib) demonstrated superior efficacy of STL1267 in inhibiting both preventive and postfibrotic induction models. Moreover, lentiviral overexpression of Rev-erbα suppressed TGFβ1-induced αSMA expression, supporting a direct antifibrotic role. These findings highlight Rev-erbα as a key regulator of myofibroblast differentiation and support both STL1267 and GSK4112 as promising candidates for circadian-based antifibrotic therapy. Future in vivo studies are warranted to evaluate its translational potential in idiopathic pulmonary fibrosis.NEW & NOTEWORTHY This study introduces a novel in vitro adenovirus-based model of persistent TGFβ1 signaling in normal human lung fibroblasts to mimic chronic fibrosis. Using this model, we show that the next-generation REV-ERBα agonist STL1267 robustly inhibits myofibroblast differentiation and ECM gene expression. STL1267 outperforms Food and Drug Administration-approved antifibrotic drugs and modulates immune and circadian signaling pathways, supporting its potential as a promising circadian-based therapeutic strategy for pulmonary fibrosis.
High-grade soft tissue sarcomas (STSs) are heterogeneous tumours lacking robust prognostic or predictive biomarkers. Regnase-1, an immune RNase, enhances antitumour immunity by limiting immunosuppressive tumour microenvironment (TME) components (e.g., myeloid-derived suppressor cells (MDSCs)), but remains unexplored in STS. As CD68+ tumour-associated macrophages (TAMs) drive TME suppression and poor prognosis in non-translocation-driven STS, we evaluated Regnase-1 and CD68+ TAMs to assess Regnase-1 as an indicator of an immunologically activated TME. Immunohistochemistry scoring of Regnase-1 and CD68+ TAMs was performed in 91 patients. Overall survival (OS) was assessed by Kaplan-Meier and Cox regression, and findings were validated in an independent "The Cancer Genome Atlas" Sarcoma (TCGA-SARC) cohort (n = 212). In UPS, Regnase-1-high predicted longer OS (17.0 months vs. not reached; p = 0.0247) and lower mortality (univariate hazard ratio (HR) = 0.3; p = 0.0343; multivariate HR = 0.4; p = 0.0413), but not after radiotherapy. CD68+ TAM-high predicted shorter OS (13.0 months vs. not reached; p = 0.0274) and higher mortality (HR = 2.0, 95% CI 1.1-3.7; p = 0.0325). Both Regnase-1 effects were reproduced in TCGA-SARC. Regnase-1-high tumours showed inflammatory/interferon enrichment, reduced TGF-β signalling, and SERPINE1 upregulation. Regnase-1 marked a pro-inflammatory TME and favourable outcome in UPS, but this effect may reverse upon radiotherapy.