To evaluate the feasibility, usability, and perceived impact of augmented and virtual reality (AR/VR) for preprocedural planning in transarterial interventional oncology procedures, as assessed through structured operator surveys. This IRB-approved, single-center pilot study was conducted over 1 year (September 2024-September 2025). Interventional radiologists used an AR/VR headset (Apple Vision Pro; Apple Inc., Cupertino, CA) with Visage Ease VP software (Visage Imaging, San Diego, CA) to review patient-specific volume renderings of cone-beam CT and cross-sectional imaging before complex oncologic procedures. Cases included hepatic angiography prior to Y90 radioembolization (n=42), percutaneous hepatic perfusion (n=7), and transarterial chemoembolization (n=1). Operators completed structured surveys assessing workflow integration, anatomic visualization, confidence, usability, and comfort using 5-point Likert scales (1=worst, 5=best). Fifty cases were analyzed, with a median case time of 81.0 minutes (IQR, 62.0-102.0). The median AR/VR planning time was 5 min [IQR 3.0-6.0], corresponding to a median of 6% of total case duration. AR/VR planning changed the procedural approach in 23 of 50 cases (46%). Likert score for procedural change had an overall mean of 3.3±1.3, with mean scores of 2.4±0.7 in cases where AR/VR did not influence the operator's intraprocedural approach and 4.4±0.8 in cases where AR/VR did influence the approach. Anatomic visualization scored 4.7±0.8, anatomic understanding 4.7±0.9, and procedural confidence 4.6±1.0. Workflow integration scored 4.8±0.5, system usability 4.5±0.9, and headset comfort 1.9±1.1. Specific use cases are described. AR/VR-based preprocedural planning was feasible, efficient, and enhanced perceived anatomic understanding, procedural confidence, and planning in transarterial interventional oncology cases. Headset comfort remains a limitation.
Strongyloides stercoralis is the main cause of human strongyloidiasis, but increasingly, presumably mostly zoonotic, human infections with S. fuelleborni are reported. Recently, a number of studies investigated the population structures, host specificities and zoonotic potentials of these two species, using molecular taxonomy. This is the first such study from Sri Lanka. We collected stool samples from humans, dogs and monkeys and used the Baermann after culture method to isolate individual live Strongyloides worms and determined parts of the cox-1 (mitochondrial) and the 18S rDNA (nuclear) and, for a subset, whole genome sequences. Despite a predicted high prevalence, we did not detect any Strongyloides in 126 human stool samples from the plantation sector. This may reflect the impact of improvements in sanitation and hygiene, reducing the worm burden to below our detection threshold. On the other hand, we observed a rather high incidence of S. fuelleborni in monkeys from within a university campus. Unexpectedly, also the two Strongyloides positive dogs we found on campus passed S. fuelleborni, one along with the expected S. stercoralis. Based on the mitochondrial sequences, the S. fuelleborni formed three subclusters within the previously described Asian clade. At the nuclear 18S rDNA locus, all S. fuelleborni carried haplotypes that had previously been described in Asia but some were heterozygous for one Asian allele and one that had so far been considered Africa specific. This suggests that Sri Lanka might be a hybridization zone for the two clades. The S. stercoralis found in this study clustered with the previously proposed 'human and dog shared' type of S. stercoralis. The presence of possible hybrids between the African and the Asian clade of S. fuelleborni and the presence of this species in dog faeces are interesting findings that need to be confirmed in additional studies. The presence of S. stercoralis and S. fuelleborni in animal faeces within the University premises, including the dormitory and the swimming pool area, raises concerns of possible exposure of the University community to these parasites in spite of sanitary conditions that render human to human transmission unlikely.
Clinical 2D magnetic resonance imaging (MRI) is the cornerstone for assessing early brain development, yet the lack of a systematic methodology renders the fine-grained and quantitative evaluation of early brain growth underdeveloped. We address this gap using a data-driven radiomics framework that integrates automatic registration, segmentation, and feature extraction for the analysis of 2,893 routine T1-weighted and T2-weighted scans from children aged 0-2 years. The framework yields accurate brain age prediction (mean absolute error = 1.19 months) and pinpoints the "corpus callosum median" (CC-median) as the most critical, biologically relevant predictor. We used the generalized additive model for location, scale, and shape (GAMLSS) to model the normative trajectory of CC-median. This standardized curve robustly differentiates developmental delays from typical peers, achieving an accuracy of 0.96 (for ages 6-24 months). This work establishes a clinically compatible framework, transforming conventional 2D MRI data into a powerful, objective tool for early neurodevelopmental assessment.
Coordinated load transfer across knee joint compartments underpins lifelong joint function, yet dysregulated mechanics are also widely implicated in the etiology of osteoarthritis (OA). How physiological loads are accommodated in the healthy joint and how regionalized architectural alterations reconfigure joint-level mechanics to promote OA, however, remain unresolved. Here, we integrate in situ mechanical loading of murine tibial epiphyses with phase-contrast synchrotron X-ray computed tomography and digital volume correlation to quantify three-dimensional, compartment-specific load-bearing behavior in intact healthy (CBA) and OA-prone (STR/Ort) knee joints. We find that raised focal strain concentrations emerge within the subchondral plate and precede histological cartilage degeneration in STR/Ort joints at 10 weeks of age. In contrast, these strain concentrations are absent in both young and aging CBA mice, where mechanical strain is preferentially transmitted to locations distant from the articular surface. Finite element modeling further reveals that strain localization in STR/Ort joints is governed by region-specific microstructural incongruities. Together, these findings demonstrate that epiphyseal microarchitecture preserves mechanical homeostasis during healthy aging, whereas spatial disorganization of subchondral microarchitecture renders the epiphysis susceptible to load-induced failure. Collectively, this work identifies mechano-architectural misalignment within the mineralized phase of the tibial epiphysis as an early mechanical promoter of OA emergence.
Clinical psychologists living with mental disorders occupy a uniquely complex position within the mental health workforce. Despite their professional training, they confront a dual identity as both healers and help-seekers, rendering them vulnerable to stigma, role conflict and identity disruption. Understanding how these practitioners construct meaning in their lives and professions is therefore clinically and professionally significant. This study aims to explore the meaning of life for a clinical psychologist who is a survivor of mental disorders. A qualitative approach was employed using Interpretative Phenomenological Analysis (IPA) within an idiographic, single-participant design (n = 1). Data were collected through a semi-structured in-depth interview. The analysis yielded 13 superordinate themes, organised under four main themes: (1) The process of self-understanding, (2) Self-transformation, (3) The psychology profession as fulfilment and (4) The psychology profession as a stressor. The participant's meaning of life emerged through a prolonged process of self-understanding and self-transformation following adverse experiences and mental disorders. Meaning was ultimately found through professional practice, interpersonal connection and self-disclosure. The findings are interpreted through the wounded healer framework as the primary theoretical lens, with additional contextualisation through relevant empirical literature. These findings provide insights into how an individual constructs meaning in life while navigating the dual roles of clinical psychologist and mental disorder survivor, with implications for clinical supervision, training and mental health nursing practice.
The FL-ALTER study introduces a novel first-line therapeutic approach for patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC). This study aimed to evaluate the cost-effectiveness of first-line gefitinib plus anlotinib for Chinese patients diagnosed with stage IIIB-IV EGFR-mutant NSCLC. A combined decision-tree and Markov model was constructed to predict 5-year cost-effectiveness using follow-up data from the FL-ALTER trial. Efficacy and safety inputs were derived from randomized clinical trials, whereas cost and utility values were sourced from published literature. Incremental cost-effectiveness ratios (ICERs) were calculated from the perspective of the Chinese healthcare system. Furthermore, scenario analyses were performed to evaluate the economic impact of patient assistance programs (PAPs) and drug price negotiations. Compared with gefitinib plus placebo, first-line gefitinib plus anlotinib yielded an additional 0.16 quality-adjusted life years (QALYs), with an incremental cost-effectiveness ratio (ICER) of $196,652.56/QALY. Deterministic sensitivity analysis revealed that the utility of progression-free survival and the cost of anlotinib were the most influential parameters driving the model outcomes. Probabilistic sensitivity analysis indicated that the combination regimen had no cost-effectiveness advantage at the current Chinese willingness-to-pay (WTP) threshold of $38,043.34/QALY. Within the Chinese healthcare system, first-line gefitinib plus anlotinib is not cost-effective for advanced EGFR-mutated NSCLC at a WTP threshold of $38,043.34/QALY. However, implementing a PAP or price negotiation for anlotinib could effectively lower incremental costs, rendering this regimen a more economically viable clinical option.
Stereotactic arrhythmia radioablation (STAR) represents an emerging non-invasive treatment for therapy-refractory ventricular tachycardia. Yet, planning remains challenged by multimodal cardiac imaging integration, electroanatomical mapping (EAM) transfer, and cardiorespiratory motion effects on dose delivery. Current radiotherapy (RT) planning systems offer mainly static visualization and limited access to intramural myocardial structures, hindering communication between cardiology and radiation oncology teams. We present a novel extended reality (XR) simulator designed to dynamically visualize STAR-relevant imaging and planning data. The system integrates diastolic cardiac CT, respiratory-binned 4DCT, anatomical segmentations, EAM data, and phase-recomputed RT dose distributions within an XR environment. Cardiac structures are propagated across respiratory phases using deformable registration, while dose distributions are recomputed on each respiratory-binned CT, enabling phase-specific inspection of dose conformality for both planning target volumes (PTVs) and cardiac target volumes (CardTVs). The resulting time-resolved volumetric dataset is rendered in XR, allowing clinicians to explore cardiac motion, visualize intramural dose deposition, and jointly assess target and organ-at-risk dynamics. This supports qualitative evaluation of dose-motion interplay and interdisciplinary interpretation of intramural targets. The system was tested on three STAR patients enrolled in the RAVENTA trial. Motion analysis revealed PTV centroid displacement amplitudes over the breathing cycle of up to 17.5, 10.2, and 8.9 mm for patients 1, 2, and 3, respectively, with conformity number variations of 0.38, 0.34, and 0.19. Expert evaluation showed positive perceived utility for target-anatomy-dose understanding, motion interpretation, and multidisciplinary communication. This proof-of-concept demonstrates the feasibility and potential clinical value of XR-based motion-aware dose visualization for STAR planning.
The versatility and scalability of blow spinning motivated us to investigate the surface properties of blow-spun poly(ε-caprolactone) (PCL), cellulose acetate (CA), polystyrene (PS), and their blends, with and without silica nanoparticles (SiO2 NPs). Pristine PCL and PS membranes are hydrophobic and oleophilic, whereas CA membranes are hydrophilic and oleophilic. Incorporation of SiO2 NPs renders PCL membranes superhydrophilicity while preserving oleophilicity. Blending PS with CA or PCL yields hydrophobic and oleophilic membranes. These characteristics enable selective oil uptake and either water repellence or water spreading, depending on formulation. Dye removal was assessed using methylene blue (MB), showing rapid uptake on PS/CA and higher overall removal for PCL-SiO2 NPs membranes. SiO2 NPs incorporation was confirmed by Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). Under the conditions tested (1 mL MB solution), a PCL-SiO2 NPs membrane (6.9 cm2, 118 μm thick, 24.6 mg) reduced the MB concentration by ~ 4 mg L-1 within 19 h (~ 4 μg removed; apparent uptake ~ 0.16 mg g-1). Overall, blow spinning provides an accessible route to obtain membranes for oil-water separation and dye retention. The online version contains supplementary material available at 10.1007/s10853-026-13279-6 .
Entanglements are topological constraints that govern the dynamic mechanical behavior of polymer networks. Linear polymers inevitably entangle at relatively low molecular weights, whereas bottlebrush polymers-consisting of a long backbone densely grafted with many relatively short side chains-suppress entanglements, enabling solvent-free networks with tissue-like softness. Yet, the same steric crowding pre-strains the backbone and renders such networks brittle. Here, we report highly entangled bottlebrush elastomers that combine extreme softness and toughness. Using short polyethylene glycol side chains, we synthesize high molecular weight bottlebrush polymers (>3 × 106 g/mol) that remain amorphous at room temperature. We identify an entanglement threshold of 2.4 × 106 g/mol with an entanglement modulus of ∼1.3 kPa, nearly 1000 times lower than that of linear counterparts. While unentangled bottlebrush networks exhibit strain-stiffening, entangled bottlebrush networks display pronounced strain-softening followed by delayed stiffening due to entanglement slippage. Despite their low modulus (∼1 kPa), these elastomers stretch up to ∼1800% and show a fatigue threshold of ∼63 J/m2, comparable to natural rubber. Their intrinsic fatigue strength-fatigue threshold normalized by modulus-surpasses that of highly entangled linear polymer networks by >40-fold. These results establish a new class of soft yet tough polymer networks and provide a model system for understanding nonlinear mechanics in architecturally complex polymers.
Patent and Proprietary Medicine Vendors (PPMVs) are major private and informal healthcare service providers in Nigeria, whose activities are regulated by the Pharmacy Council of Nigeria (PCN). Review of literature have documented concerns about PPMVs' non-compliance with PCN's service provision guidelines and their implications for the health outcomes of their clients. Studies among PPMVs on the services they provide and their non-compliance with regulatory guidelines in semi-urban areas have been under explored. This study however, investigated types of services provided by PPMVs and their non-compliance with regulatory guidelines in Ibadan, Oyo State, Nigeria. This descriptive cross-sectional study included registered patent and proprietary medicine vendors selected from two out of the six semi-urban Local Government areas of Ibadan, Oyo State through random sampling using an interviewer-administered semi-structured questionnaire with data collected using the KoboCollect. The questionnaire elicited responses on the types of services provided by PPMVs to their clients and factors influencing their non-compliance with the regulatory guidelines. Data was collected and analysed using descriptive and inferential statistics with SPSS version 25, at 0.05 level of significance. Two hundred and eight respondents were recruited for the study. Respondent's mean age was 38.17-10.82, years. Majority (80.8%) were females, less than half (40.9%) had post-secondary-level education. A few (13.9%) had additional health-related qualifications. Respondents provided services which were both within (treatment of ailments; 50.5%, and Referral 50%) and outside (giving injections; 51.9% and prescription of medicine; 49.1%) their scope of operation. Factors which influenced non-compliance mentioned by respondents were attendance of PCNs training, licensure with PCN and reception of monitoring visits, were significantly associated with noncompliance with guidelines on service provision (p<0.05). Patent and proprietary medicine vendors in Ibadan, Oyo state, play a significant role in providing accessible primary healthcare services within and outside their scope of operation to the populace, several factors are responsible for their non-compliance with regulatory guidelines which dove-tailed into rendering of services beyond their scope of operations.
Small intestinal metastasis from breast cancer is a rare entity with non-specific clinical presentations, rendering it susceptible to missed or delayed diagnosis. Herein, we present a rare case of breast cancer metastasizing to the small bowel, with unexplained anemia as the sole initial clinical complaint.The patient manifested persistent dizziness and palpitations, accompanied by repeatedly positive fecal occult blood testing, and carried a well-documented history of surgical resection for bilateral breast malignancy.Contrast-enhanced computed tomography (CT) of the small bowel demonstrated segmental, asymmetric wall thickening with adjacent lymphadenopathy and no luminal stenosis; the thickened wall exhibited heterogeneous enhancement, raising initial suspicion of lymphoma. Subsequent double-balloon enteroscopy(DBE) identified a large circumferential deep ulcerative lesion, which was endoscopically indistinguishable from primary small bowel adenocarcinoma or intestinal lymphoma. The definitive diagnosis of small intestinal metastasis from breast cancer was established by histopathological and immunohistochemical evaluation, in conjunction with the patient's oncological history. A review of the literature indicates that small intestinal metastasis from breast cancer is more commonly associated with invasive lobular carcinoma, and affected patients usually present during routine surveillance or with abdominal pain. In the present case, the primary pathology was invasive ductal carcinoma of triple-negative phenotype (TNBC), and the patient's initial presentation with anaemia constitutes an atypical manifestation. Clinicians should maintain a high index of suspicion for small bowel metastasis in breast cancer survivors who develop unexplained anemia, positive fecal occult blood, or abnormal small intestinal imaging, even in the absence of classic gastrointestinal symptoms. A multidisciplinary approach integrating imaging, endoscopy, pathology, and immunohistochemistry is essential to minimise diagnostic delay and avoid misdiagnosis.
Philadelphia chromosome (Ph)-positive T-lymphoblastic leukemia (T-ALL) is exceptionally rare. Distinguishing de novo Ph-positive T-ALL from T-lymphoid blast-phase chronic myeloid leukemia (BP-CML) can be highly challenging, yet this distinction has important therapeutic and prognostic implications. We report a pediatric patient initially diagnosed with de novo Ph-positive T-ALL who subsequently developed CML following treatment discontinuation. A 14-year-old boy presented with fever, leukocytosis, and generalized lymphadenopathy. Bone marrow examination revealed 81% blasts, and flow cytometric immunophenotyping confirmed T-ALL (cytoplasmic CD3+ CD5+ CD7++). Conventional cytogenetic analysis revealed a karyotype of 49,XY,-7,+8,t(9;22)(q34;q11.2),+15,+19,+mar[3], and real-time quantitative reverse-transcription polymerase chain reaction detected a b3a2 BCR::ABL1 fusion transcript. A diagnosis of de novo Ph-positive T-ALL was rendered, and the patient achieved complete remission following induction chemotherapy with VICP (vincristine, idarubicin, cyclophosphamide, prednisone) plus imatinib. The patient declined both allogeneic hematopoietic stem cell transplantation and escalation to a second-generation tyrosine kinase inhibitor (TKI). After self-discontinuing imatinib without medical advice for approximately 18 months, he developed CML. This case highlights the diagnostic challenge of distinguishing de novo Ph-positive T-ALL from T-lymphoid BP-CML at initial presentation, particularly in pediatric patients. Accurate classification is essential because it has important implications for therapeutic decision-making and long-term management in the TKI era. The subsequent development of CML following TKI discontinuation strongly supports that the initial presentation represented lymphoid BP-CML rather than de novo Ph-positive T-ALL. This observation further underscores the importance of sustained TKI therapy and adherence in preventing disease recurrence and optimizing long-term clinical outcomes.
Areca nut has long been prescribed in Traditional Chinese Medicine for respiratory disorders resembling pulmonary fibrosis (PF). Its classical effects of resolving phlegm and dissipating chest stagnation, documented in Shennong Bencao Jing, align closely with PF's hallmark pathologies of interstitial scarring and excessive collagen accumulation, yet the mechanistic basis for its anti-fibrotic activity remains unelucidated. This study validated the anti-PF efficacy of areca nut procyanidins (ANP) and elucidated their multi-target mechanisms. A multi-faceted approach integrating network pharmacology, molecular docking, and in vivo/vitro experiments was employed. Rat PF models induced by bleomycin were treated with ANP (1, 5, 15 mg/kg) for 28 days. LPS-stimulated 3T6 fibroblasts were used to evaluate cellular mechanisms. Network pharmacology predicted 72 common targets, with enrichment in the TGF-β and MAPK pathways. Molecular docking confirmed strong binding affinity of ANP to TGF-β1 (-8.8 kcal/mol) and Smad3 (-6.8 kcal/mol). In vivo, medium- and high-dose ANP significantly ameliorated lung histopathology, reduced collagen deposition (HYP), and restored antioxidant biomarkers (T-AOC, MPO, GSH). Mechanistically, ANP concurrently suppressed the TGF-β/Smad/ERK signaling cascade, characterized by the downregulation of TGF-β1, p-Smad3/4, and p-ERK, alongside the restoration of the inhibitory Smad7. In vitro, ANP inhibited fibroblast migration, inflammation (IL-1β, TNF-α), and extracellular matrix production. By multi-target inhibition of the TGF-β/Smad/ERK cascade, ANP ameliorates PF, consistent with areca nut's traditional phlegm-resolving and nodule-dissipating properties. Compared with pirfenidone, ANP exhibits superior safety and multi-pathway activity, rendering it a promising botanical therapeutic agent for PF.
In patients with squamous cell carcinoma of the head and neck, co-occurring chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is not uncommon. Given the often subtle histopathologic features, this diagnosis may go unrecognized by the pathologist. This study aims to investigate the high rate of co-occurrence of CLL/SLL and head and neck squamous cell carcinoma and to illustrate the combination of clinical and histopathologic findings in these patients. A retrospective single-institution review was conducted of 3524 pathologic diagnoses of head and neck squamous cell carcinoma, from which 24 patients with concurrent diagnoses of CLL/SLL were identified. Squamous cell carcinomas for these 24 patients were restaged, and the histopathologic and immunohistochemical profiles were assessed. Concurrent cutaneous squamous cell carcinoma was identified in 21 out of 24 patients, with oropharyngeal squamous cell carcinoma in the remaining 3. Nine patients had nodal metastases. Fine-needle aspiration biopsy was performed in 15 out of 24 patients and rendered the diagnosis of squamous cell carcinoma in 9 patients and CLL/SLL in 6 patients. Co-occurring CLL/SLL is easily missed in biopsies and neck dissections performed for the diagnosis and management of head and neck squamous cell carcinomas. Awareness of the pertinent morphologic features should prompt additional immunohistochemical studies that can lead to a definitive diagnosis.
Diabetic foot ulcers (DFUs) pose significant therapeutic challenges owing to their intricate microenvironment. Conventional biomaterials often target only a single pathological factor, rendering them inadequate for halting the progressive deterioration of DFUs. To address this limitation, we developed a multifunctional drug delivery platform based on amine-yne click chemistry. The system was constructed using quaternized chitosan (QCS) and tetra-arm polyethylene glycol propiolate (4A-PEG-PA), incorporating metal-polyphenol nanoparticles (MPNs) formed by epigallocatechin gallate (EGCG) and magnesium ions (Mg2+) as the drug-loading component. This platform not only fills ulcer cavities to eliminate dead space but also adheres firmly to irregular wound surfaces, minimizing physical disruption. Additionally, the drug delivery system exhibits pH-responsive behavior, along with potent antioxidant and hypoglycemic effects, effectively lowering reactive oxygen species (ROS) and glucose levels in the wound microenvironment by modulating pH, thereby promoting healing. In vitro studies revealed that the material safeguards mitochondrial function and integrity by counteracting oxidative stress. In vivo evaluations further demonstrated its antimicrobial, anti-inflammatory, pro-angiogenic, and re-epithelialization properties. Collectively, this hydrogel-based platform integrates multiple bioactive functions, presenting a promising strategy for the clinical management of DFUs.
The diagnosis of Autism Spectrum Disorder has historically been biased toward a male-centered model, rendering women and gender-diverse individuals largely invisible. This commentary reviews the origins of such bias, its contemporary manifestations, and the clinical, social, epistemological, and mental health equity implications it entails. Pathways toward a more equitable and inclusive model are proposed.
In many real-time measurement and monitoring systems, the quality of acquired signals is often severely degraded by complex environmental noise sources with non-stationary properties, rendering analysis, important feature extraction, and decision-making unreliable. This study proposes a multi-stage adaptive denoising architecture based on the least mean square (LMS) algorithm, in which the number of filter stages and the step size are automatically adjusted according to error statistics, the remaining correlation between the residual and the reference signal, and the real-time signal-to-noise ratio (SNR) of the signal. The stopping mechanism is determined by a two-tailed Fisher-z correlation test, with effective sample size correction in the presence of autocorrelation and modulation based on SNR, to ensure the stability of the adaptive system against non-stationary noise. The filter is evaluated on simulated signal datasets and real-world measured data. Compared with the conventional LMS filter configuration under the tested simulated conditions, the proposed architecture reduces mean squared error (MSE) by 38-82% and mean absolute error (MAE) by 15-45%, while improving both SNR and peak signal-to-noise ratio (PSNR). The execution time of the proposed method is approximately 3.5-4 times lower than that of the fixed-threshold method under the tested settings. These results indicate that the proposed method can improve the trade-off between denoising performance and computational efficiency, showing potential for low-latency implementation on resource-constrained devices.
Polycomb Repressive Complex 1 (PRC1) and CCCTC-binding factor (CTCF) are critical regulators of 3D chromatin architecture that influence cellular transcriptional programs. Although the role of CTCF in chromatin organization is well-known, the involvement of PRC1 is less understood. In this study, we identify an unexpected role for the canonical Pcgf2-containing PRC1 complex (cPRC1.2) in activating bivalent genes. Hi-C revealed that cPRC1.2 forms chromatin loops at bivalent promoters, rendering them poised for activation. Pcgf2 deletion disrupts cPRC1.2 loops and impairs the transcriptional induction of crucial target genes necessary for neuronal differentiation. Furthermore, we identify CTCF enrichment at cPRC1.2 loop anchors and at Polycomb group (PcG) bodies, suggesting that PRC1 and CTCF cooperatively regulate chromatin loops. Through virtual 4C and other genomic analyses, we discover that establishing neuronal progenitor cell (NPC) identity involves a switch from cPRC1.2-mediated chromatin loops to CTCF-mediated active loops. Our results suggest a novel mechanism by which pre-formed PRC1 loops at lineage-specific genes maintain a poised state for subsequent CTCF-mediated active loops and gene activation in cell fate transitions.
Cell type annotation in spatial transcriptomics (ST) is fundamental for deciphering complex tissue organization and spatially resolved biological processes. Most existing methods perform ST cell type annotation by transferring labels from single-cell RNA-seq (scRNA) data to ST data, but typically rely on weakly constrained representations that neglect structured spatial dependencies and treat marker gene selection as an isolated preprocessing step. This renders them vulnerable to substantial domain gaps as well as platform-specific noise, resulting in unstable predictions and limited biological interpretability. To address these issues, we propose Prior-enhanced Inference for Spatial Transcriptomic Cell Type Mapping (PRISM), a novel three-stage framework integrating biological prior construction, pseudo-label generation, and multi-level ST refinement. First, PRISM constructs a cross-domain biological prior to explicitly extract marker genes to enforce positive biological discriminability. Next, it adopts a prior-enhanced self-training strategy, where scRNA-trained ensembles generate reliable pseudo-label candidates for ST data, serving as a robust anchor for cross-domain adaptation. Finally, the framework consolidates high-quality ensemble predictions selected via metric-guided evaluation, encodes spatial information, and optimizes the model under dual-directional biological constraints. Extensive experiments on eleven ST datasets across six platforms, two species, and multiple tissue contexts validate PRISM. Specifically, on the five labeled benchmarks, PRISM shows strong overall performance under both Accuracy and Macro-F1 evaluation across brain and non-brain tissues. Moreover, under fully label-free settings, PRISM achieves the best overall composite rank across all datasets, demonstrating strong robustness to domain shift and platform heterogeneity. PRISM is available at https://github.com/lilab-ai4s/PRISM and https://doi.org/10.5281/zenodo.20529683.
17α-estradiol (17α-E2) extends median lifespan and improves metabolic homeostasis in male mice through estrogen receptor α (ERα)-dependent mechanisms, but female mice are largely unresponsive unless ovariectomized or subjected to chronic high-fat feeding. Whether the gradual hormonal transition of natural reproductive aging similarly unmasks female responsiveness to 17α-E2 remains unknown. We tested whether 4-vinylcyclohexene diepoxide (VCD)-induced depletion of the ovarian reserve would render female mice responsive to 17α-E2 by treating wild-type (WT) and ERα knockout (ERαKO) littermates with VCD followed by 16 weeks of 17α-E2 administration. VCD-induced estropause was confirmed by elevated FSH, anestrus, and reduced ovarian size, but did not adversely affect metabolic phenotypes in WT mice. 17α-E2 treatment elicited modest improvements in adiposity and glucose tolerance, suppressed circulating IL-1β and IL-6, and reversed estropause-induced uterine atrophy in WT mice, but failed to rescue endometrial fibrosis. All 17α-E2-mediated effects were absent in ERαKO mice. These findings demonstrate that estropause does not unmask broad female responsiveness to 17α-E2 and indicate that the sex-specific actions of 17α-E2 extend beyond competitive receptor occupancy by endogenous 17β-E2.