As a key component of space telescopes, the rational structure of the mirror is a crucial factor affecting the telescope's environmental adaptability and imaging performance. To address the technical challenges of simultaneously achieving lightweight, environmental adaptability, and surface accuracy in large-aperture ultrathin mirrors, this paper proposes a mirror optimization method based on multiphysics coupling. Based on the finite element method and thermoelasticity theory, the interaction relationship between the temperature physical field and the force physical field was established. The P-norm was used to solve the problems of non-smoothness and inability to solve the sensitivity of the max(·) function. An optimized model for the mirror was determined using a combination of topology optimization and parameter optimization. Compared to a solid mirror, the optimized mirror achieved a mass reduction rate of 82.04%. Under temperature and gravity conditions, the surface accuracy of the optimized mirror met the requirements. In terms of response dynamics, the optimized mirror performs better, with a maximum response amplification factor of 4.39, below the threshold of 4.5 required to maintain structural stability, which is crucial for maintaining the structural integrity of the mirror. This method will provide a feasible approach for the optimized design of lightweight mirrors with strong environmental adaptability.
Absolute extreme ultraviolet (AXUV) diode arrays are widely used in fusion experiments for time-resolved measurements of plasma radiation. We report the first implementation of an AXUV-based analysis framework on the Wisconsin high-temperature superconducting axisymmetric mirror. A single, precisely calibrated 20-channel AXUV assembly measures line-integrated plasma emission with ∼1cm of spatial accuracy across the mid-plane. The data were processed to obtain the plasma's statistical moments, yielding time-resolved measurements of the centroid displacement Φ(t) and effective radius R(t). From the joint covariance of these quantities, we define a macroscopic instability parameter χ(t) that quantifies large-scale plasma evolution directly from AXUV observables. The parameter χ serves as a compact indicator of macroscopic plasma activity, decreasing with increasing end-plate bias and exhibiting strong anti-correlation with diamagnetic flux during confinement transitions. These results demonstrate that a single AXUV array can provide real-time assessment of macroscopic plasma dynamics, constituting the first demonstration of such capability in a magnetic mirror plasma. Future extensions to multiple arrays will further enhance spatial coverage and enable full-mode tracking in axisymmetric mirror configurations and related fusion devices.
A new family of genes encoding potential antimicrobial peptides with compact and elegant structure has been found in the genomes of several Fungi and some arthropod species. Their expression products are constituted of about 85 amino acids, including a signal peptide, and are folded into two α-helical segments connected by a short unstructured coil. Three conserved disulphide bridges between cysteines located in symmetrically mirrored positions connect the two helical domains. These peptides, here named as Hairpin Loop Peptides (HLPs), have been found in the genomes of many Fungi species but only in selected clades. Orthologues have also been discovered in the genomes of some insects, notably Hemiptera, a few other arthropods and other organisms. They are not found in plants, that however express smaller peptides of similar topology with HLPs, but different amino acidic composition and physicochemical properties. They appear to have originated in Fungi and then migrated to insects through horizontal gene transfer. The antimicrobial activity of HLPs is predicted by several software programmes, but this aspect needs to be supported by experimental evidence. The occurrence of HLPs in several edible mushrooms may suggest potential uses of these peptides in food preservation and possibly also in medical applications. Their simple and nearly rigid structure can be easily modified to improve specificity, stability and solubility, thus making these peptides suitable for a variety of different applications.
Situs inversus totalis (SIT) is a rare congenital laterality anomaly characterized by complete mirror-image transposition of the thoracic and abdominal viscera. Although SIT is not a proven cancer-predisposition syndrome, cancer in this setting challenges the spatial assumptions that guide diagnosis, staging, surgery, radiotherapy, and surveillance. We conducted a retrospective, single-center observational study of patients with radiologically confirmed SIT treated at our cancer center between July 2017 and December 2025. Patients with histologically confirmed malignancy were included. Clinical, pathological, imaging, treatment, and follow-up data were extracted from medical records. Overall survival (OS) was summarized descriptively; Kaplan-Meier analysis was used only to visualize survival and censoring patterns. Among 11 patients with SIT, 6 had histologically confirmed malignancies. Median age was 66.5 years (range, 47-76), and median follow-up was 47.5 months (range, 30-55). Tumors included hepatocellular carcinoma, lung squamous cell carcinoma, lung adenocarcinoma, cervical adenocarcinoma, poorly differentiated abdominal adenocarcinoma, and follicular lymphoma transformed to high-grade B-cell lymphoma. Treatment included surgery, radiotherapy, chemotherapy, immunotherapy, targeted therapy, transarterial chemoembolization, and autologous stem cell transplantation. 4 patients died, and 2 were alive at last contact. Pooled median OS was 50 months and was interpreted only descriptively. Across cases, outcomes reflected tumor type, stage, and molecular features, whereas SIT mainly affected lesion localization, laterality recognition, nodal or vascular mapping, operative orientation, and treatment planning. Malignancy in SIT is best understood as cancer within a reversed anatomical coordinate system. Standard oncologic care remains feasible but requires explicit anatomical verification and multidisciplinary planning.
Critical-sized craniofacial defects pose a significant clinical challenge, prompting the investigation of novel regenerative strategies. While mesenchymal stem cells (MSCs) and extracellular vesicles (EVs) hold promise, the optimal cell source and EV efficacy for craniofacial bone regeneration remain unclear. This study compares adipose-derived stem cells (ASCs), bone marrow-derived stem cells (BMSCs), and their derived EVs to address this gap in a critical-sized calvarial defect model. EVs from BMSCs and ASCs were isolated via ultracentrifugation and size exclusion chromatography. Nanoparticle tracking analysis and bicinchoninic acid assay quantified yield and protein, respectively. Transmission electron microscopy and Western blotting verified EV morphology and markers. In vitro, osteogenic potential of BMSCs and ASCs treated with their respective EVs was assessed using alkaline phosphatase activity assay, viability assays, and mineralization staining. In vivo, bone regeneration was compared in a rat critical-sized calvarial defect model treated with BMSCs, BMSC-derived EVs, and a combination of BMSC and BMSC-derived EVs. EVs isolated by ultracentrifugation yielded superior numbers of particles compared to size exclusion chromatography. In vitro, BMSC-derived EVs enhanced osteogenic differentiation of BMSCs, whereas ASC-derived EVs inhibited proliferation and osteogenesis of BMSCs. Although BMSC-derived EVs induced osteogenic phenotype in ASCs, osteoinductive efficiency was low, along with reduced cell proliferation. In vivo, both BMSC-derived EVs and BMSCs individually promoted bone regeneration compared to vehicle controls. Notably, the combination of BMSCs and BMSC-derived EVs demonstrated a significantly superior healing within the bone defect. Ultracentrifugation is the preferred method for isolating EVs for clinical translation. BMSC-derived EVs are the optimal source for craniofacial bone regeneration compared to ASC-derived EVs, as they exhibited superior osteogenic potential and promoted bone regeneration. Moreover, BMSC-derived EVs combined with BMSCs demonstrated a synergistic effect that further improved bone regeneration. Notably, mismatching origins of MSC and MSC-derived EVs could dysregulate the cellular function of MSCs, potentially compromising the regenerative outcomes. Our study highlights that the proper matching of cell and EVs sources is imperative for optimizing therapeutic efficacy in craniofacial bone regeneration. The online version contains supplementary material available at 10.1007/s12195-026-00909-x.
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Space-based gravitational wave detection missions impose extremely stringent requirements on the measurement precision of the laser interferometer, where tilt-to-length coupling noise emerges as a critical factor degrading performance. This paper focuses on geometric tilt-to-length noise in the test mass interferometer, conducting both theoretical modeling and experimental validation. First, based on the principles of geometrical optics, an analytical expression is derived for the optical path length difference variation induced by test mass angular jitter, clarifying the coupling mechanisms of the various system parameters to the tilt-to-length coupling. Numerical simulations demonstrate an excellent agreement between the theoretical model and simulation results. To further validate the theoretical model, an experimental system combining laser heterodyne interferometry and differential wavefront sensing technique is designed and constructed, with a fast steering mirror employed to simulate test mass angular jitter, enabling precise measurement of both the optical path and angular variations. By varying the lateral displacement dlat of the fast steering mirror, the experimental data exhibit strong consistency with the theoretical prediction of the first-order tilt-to-length coupling coefficient, with a linear fitting error as low as 1.5%. Moreover, the independence of the second-order and zero-order terms relative to dlat also aligns with the theoretical expectation. Thus, the first experimental verification of the geometric tilt-to-length coupling model is presented in this paper.
The present study connects the genetic diversity of Cistus creticus to its chemical profile, identifying elite genotypes and key biosynthetic genes for enhancing the production of valuable labdane diterpenes. Cistus creticus, a Mediterranean shrub, is known for its resin ladano, which is rich in pharmacologically active labdane-related diterpenes (LRDs). However, the genetic and molecular basis for the LRDs content variation among natural populations remains uncharacterized. This study aims to fulfill this lacuna by investigating a potential link between genetic diversity and chemotypic profile across 91 genotypes from seven different populations across Greece and identifying elite germplasm by uncovering the molecular and regulatory mechanisms underlying LRDs biosynthesis. The genetic analysis, employing ISSR markers, revealed significant genetic differentiation among populations (ΦST = 0.294) that mirrored distinct chemotypic profiles. Genotypes clustered by origin with Chalkidiki and Sises being the most homogenous, high-yielding, and superior in LRDs production. The transcriptomic analysis of low (C1) vs. high (C18) LRDs genotypes identified 24,489 up-regulated genes, including key diterpene synthases [labda-7,13-dien-15-ol synthase (LDDS2), ent-copalyl diphosphate synthase, copal-8-ol diphosphate synthase (CLS)] and numerous transcription factors among which WRKY, bHLH and bZIP were strongly correlated with LRD accumulation. This work provides an initial representation of the regulatory landscape by identifying elite genotypes, key biosynthetic genes, and transcription factors linked to specific LRDs for promising breeding programs, future targeted experiments, and metabolic engineering.
Metastasis, the primary cause of cancer mortality, relies on malignant cells acquiring extreme mobility and mechanical plasticity. We posit that this physical transition is driven not by de novo genetic innovations but by an atavistic reversion to highly conserved cytoskeletal blueprints, termed "Fungal Islands." Through in silico sequence alignments and molecular docking, we investigated structural homology between human septin-9 (SEPT9) and its yeast ortholog, Cdc3. Our analysis reveals structural and thermodynamic parity within the G1/P-loop catalytic core across billions of years of eukaryotic divergence. This precise preservation of spatial configuration provides strong evidence against convergent evolution, demonstrating the core septin engine is constrained by intense purifying selection. Consequently, we argue that malignant cells exapt these functionally immutable ancestral nodes to drive a biomechanical shift, mirroring the invasive mechanics of fungal hyphal tips. This identifies a non-mutating structural template for next-generation 'migrastatic' therapies, offering a strategy to disable cancer's migratory machinery while evading the mutational resistance typical of modern kinase inhibitors.
Isolated extremity gunshot wounds cause a significant number of deaths annually despite exsanguinating extremity haemorrhage being potentially treatable and thus the deaths preventable. We sought to compare differences between children and young adult decedents of isolated extremity gunshot wounds to decedents from other-site gunshot wounds in terms of demographics, incident circumstances and disposition. A retrospective analysis of the National Violent Death Reporting System database was performed for the years 2012-2021. Extremity gunshot wound decedents were compared with other-site gunshot wound decedents in patients 0-24 years old. Variables analysed included race, sex, incident, emergency medical services response, transportation to the emergency department and survival times. Analysis was conducted using bivariate inferential statistics: χ2 and Wilcoxon rank-sum. Of 40 746 firearm injuries, 39 878 (97.9%) were other-site gunshot wound decedents and 868 (2.1%) were extremity gunshot wound decedents. Black individuals comprised the majority of both cohorts but more commonly extremity gunshot wound decedents (75.3% vs 66.6%, p<0.0001). More extremity gunshot wound decedents were male (90.3% vs 87.1%, p=0.006) and in single homicides (89.9% vs 86.1%, p=0.0001). Both groups were admitted to the hospital at similar rates (12.1% vs 12.8%, p=0.34). 72.0% extremity gunshot wound decedents survived minutes after injury and 20.9% survived hours. A subgroup analysis was performed for decedents <18 years old and mirrored these trends. This national analysis demonstrated disparities in race and sex among young decedents of isolated extremity gunshot wounds compared with other-site gunshot wounds. One-fifth of decedents with extremity gunshot wounds survived hours. Targeted intervention programmes such as Stop the Bleed training may help to improve survival of isolated extremity gunshot wounds. IV.
Powassan virus (POWV) causes lethal encephalitis in the elderly and long-term neurological sequelae in survivors. Mirroring human disease, POWV strain LI9 directs age-dependent lethality in C57BL/6 (B6) mice, resulting in spongiform encephalitis, gliosis, and inflammatory cytokine/chemokine responses in the CNS. However, the mechanisms underlying age-dependent lethality and persistent neurodegenerative disease in POWV survivors remain to be resolved. Here, we analyzed cellular CNS responses to POWV LI9 infection in young (10-week-old) and aged (50-week-old) mice using single-cell RNA sequencing. Infection of young mice resulted in inflammatory CNS infiltrates (NK, CD4/CD8 T cells, and monocytes) and interferon responses that coincide with peak viral burden. In contrast, the CNS of aged infected mice instead featured upregulated astrocyte and neuronal genes associated with neurodegenerative and Alzheimer's disease pathways and the transition of homeostatic microglia to a Trem2-ApoE-linked disease-associated microglial transcriptional state. Histological analysis revealed that amyloid precursor protein (APP)/amyloid-β (Aβ) accumulated in the CNS following POWV infection and that POWV envelope protein and APP/Aβ were selectively localized within layers L5/L6 of the cerebral cortex. POWV kinetically increased perinuclear APP/Aβ accumulation during acute infection and was highly expressed in the CNS of POWV survivors. Our findings reveal that POWV triggers glial cell responses and a neurodegenerative disease-associated microglia program of Alzheimer's-like APP/Aβ accumulation in mice, which is consistent with long-term neurological sequelae in human POWV survivors.IMPORTANCEPowassan virus (POWV) causes lethal encephalitis and long-term cognitive deficits in survivors. Using an age-dependent murine model, we reveal that POWV-infected young mice direct robust CNS inflammatory infiltrates associated with viral clearance, whereas aged mice exhibit impaired immune responses and a shift from homeostatic to neurodegenerative glial cell states. POWV prompted the induction of disease-associated microglia (DAM) and Trem2-ApoE axis transcriptional responses that are hallmarks of APP/amyloid-β (Aβ) accumulation in Alzheimer's disease (AD). Remarkably, POWV induced progressive APP/Aβ accumulation in young and aged mice that persisted in survivors after viral clearance. This suggests that POWV induces an APP/Aβ neurodegenerative process and provides a potential cause of long-term neurological sequelae observed in human POWV survivors. Our data suggest that POWV initiates or exacerbates AD-like neuropathology and further rationalizes investigating the role of APP/Aβ responses in other encephalitic viruses.
Foodborne pathogen concerns have focused attention on sanitization within food processing facilities. However, certain jurisdictions, particularly in Europe, have blocked imports of chlorine-treated meats, partially from concerns regarding toxic chlorinated byproduct formation. Herein, we measured lipid-bound fatty acid chlorohydrin and protein-bound chlorotyrosine concentrations in chicken, beef, fish, and raw milk samples. Surprisingly, we observed no increase in byproduct formation under typical exposure conditions (50 mg of Cl2/L), with substantial increases observed only under extreme conditions. These results contrast with previous produce research demonstrating a clear dose-response relationship. While produce featured low background byproduct concentrations, concentrations in meat, fish, and milk samples were already elevated even prior to chlorine exposure. Bulk organochlorine analysis confirmed that these byproducts mirrored the broader array of chlorinated byproducts. While these results suggest minimal risks for chlorine sanitization for meats and fish, they highlight additional risks for a meat-based diet.
Salivary glands play an essential role in oral homeostasis by producing saliva, which protects oral tissues and maintains the oral environment. Despite growing interest in porcine models for translational biomedical research, the immunophenotypic characterization of porcine salivary glands remains limited in the literature, with few studies addressing their cytokeratin and contractile protein expression profiles. This gap constrains the ability to directly compare porcine and human glandular phenotypes and hinders the establishment of the pig as a validated salivary gland experimental model. This study evaluates the histological, immunophenotypic, and ultrastructural features of porcine submandibular glands as potential experimental models. Submandibular glands from 11 pigs aged 3 to 6 months (average weight: 20 kg) were examined histologically using hematoxylin and eosin staining and ultrastructurally by transmission electron microscopy, and phenotypically via immunohistochemistry for key markers such as CK5, CK7, CK19, SMA, calponin, caldesmon and S-100. Porcine submandibular glands exhibit a lobular organization akin to human glands, with mucous acinar cells, intercalated and excretory ducts, and rich vascularization. Immunohistochemistry revealed cytokeratins in epithelial cells and contractile proteins in myoepithelial cells, mirroring human glandular markers. Ultrastructural analysis highlighted robust cellular junctions, myoepithelial support, and intricate nerve fiber networks essential for glandular function. The structural and phenotypic parallels between porcine and human submandibular salivary glands provide a descriptive basis supporting their potential use in comparative salivary gland research.
Skeletal muscles and blood vessels are continuously exposed to mechanical forces, particularly during exercise. We subjected human endothelial and skeletal muscle cells to cyclic mechanical stretch to mimic exercise and investigated acute molecular responses. Mechanical loading elicited both shared and cell type-specific alterations in transcriptomic and metabolomic profiles, several of which mirrored changes observed in vivo following exercise. Both cell types released acetate in response to mechanical loading, at least partly via reactive oxygen species-dependent mechanism. Interestingly, transcriptomic changes occurred in opposite directions in endothelial and muscle cells. For example, genes associated with the electron transport chain were repressed in endothelial cells but upregulated in skeletal muscle cells. In endothelial cells, mechanical loading promoted a transcriptomic shift indicative of increased barrier integrity and attenuated proliferation. Metabolic changes were more pronounced in endothelial cells, which exhibited increased serine biosynthesis from glucose, as demonstrated by 13C-(U)-glucose tracing. Targeting phosphoglycerate dehydrogenase (PHGDH), a key enzyme in the serine synthesis pathway, underscored the role of serine biosynthesis in endothelial cell anabolism. These findings suggest that mechanical loading recapitulates several exercise-induced effects in endothelial and muscle cells, and highlights a potential link between mechanical stimuli, serine synthesis, and endothelial cell quiescence.
We fabricated whole-egg analogs (WE) by combining bottom-up-designed yolk (EY) and white (EW) components and benchmarked their performance against real eggs (RE). Molecular docking and 80-ns molecular dynamic simulations revealed binding energies of -5.1, -4.58, and - 3.55 kcal/mol for EY-ankaflavin, EY-glucomannan, and EY-EW conjugates, respectively, with RMSD values around 1.78-1.86 Å, confirming complex stability via noncovalent forces. WE exhibited 1.3-fold higher shear viscosity and more pronounced shear-thinning than RE, a 5 °C lower gelation temperature, and a final gel strength 25% lower. DSC profiles showed two endothermic peaks at ∼65 and ∼ 78 °C, mirroring RE. Texture analysis demonstrated a 40% increase in hardness and a 20% boost in resilience, with springiness and chewiness matching RE. The in vitro digestion assays indicated a 32% increase in lipid hydrolysis, a 28% rise in protein hydrolysis, and 78% vitamin D bio-accessibility in WE, underscoring its nutritional and functional parity with real eggs.
Fluorescein fundus angiography (FFA) is essential for diagnosing retinal vascular diseases, yet its interpretation is expertise-intensive. Here, we present Clin-FFA-VLM, a multimodal vision-language framework that mirrors retina specialists' cognitive workflow by decomposing FFA interpretation into three stages: lesion-aware visual perception, clinical report generation, and diagnostic decision support. Trained and tested on a multi-center dataset of 13,178 FFA images with expert label, 21,717 FFA images with 1790 clinical reports and diagnosis across 7 retinal diseases, Clin-FFA-VLM achieves an F1 of 0.834 for lesion detection, an entity-level F1 of 0.73 for report generation, and a diagnostic F1 of 0.77 by jointly reasoning over images and self-generated reports. External validation across two independent hospitals confirmed its generalizability (F1 of 0.78 and 0.70). In a prospective reader study with 200 FFA cases, Clin-FFA-VLM significantly improved diagnostic accuracy for medical students and residents (p < 0.05), bridging the gap between automated systems and clinical practice.
Influenza virus outbreaks remain a persistent public health concern, yet traditional metabolomics methods are inadequate for addressing key analytical challenges of "dark matter" in influenza research. By integrating quantitative MS1 data, MS2-derived fragmentation trees and molecular fingerprints, structure-based comparative metabolomics enhances predictive capability for chemical structures, and enables the discovery of candidate metabolic markers without the need for database spectra. In this study, we established a C57BL/6J mouse model of H1N1 infection (with PBS as control) and performed structure-based comparative metabolomics on fecal samples using liquid chromatography-mass spectrometry (LC-MS). Quantitative analysis of MS1 data identified 40 differential metabolites, while qualitative analysis of MS2 data enabled their structural annotation. A candidate metabolite marker, LysoPE 15:0, along with other potential metabolic markers, was annotated and validated using Mirror plot, CFM-ID, and sim-Rank-Network. Our findings demonstrate that structure-based comparative metabolomics enables library spectra-free annotation of metabolomic "dark matter" and provides a methodological workflow for discovering candidate metabolite markers in other diseases.
Infection and inflammation elevate circulating pro-inflammatory cytokines that can affect renal drug clearance. Accordingly, we sought to (i) quantify cytokine-mediated modulation of renal drug-metabolizing enzymes and transporters (DMETs) and (ii) identify the underlying mechanism(s). Fresh primary human proximal tubular epithelial cells (PTECs) were cultured on extracellular matrix-coated Transwells and exposed for 48 h to IL-6, IL-1β, TNF-α, IFN-γ, IL-4, or IL-10 (0.1 or 1 ng/mL), individually or as a cocktail. mRNA expression of 25 renal DMETs was quantified by RT-qPCR, and activity of OAT1-4, OCT2, and OCTN1 was measured. Mechanisms were probed using selective MAPK/NF-κB inhibitors targeting ERK, p38MAPK, JNK, and NF-κB. IL-6 classic and trans-signaling were evaluated using IL-6 and soluble IL-6 receptor (sIL-6Rα). IL-1β was the predominant modulator, downregulating OAT1-3, OCT2, OAT4, MATE2-K, MRP2, and OATP4C1 mRNA and upregulating OCTN1 and MRP3 mRNA. TNF-α downregulated OAT1-3 mRNA but had minimal effects on other transporters. Uptake activity changes mirrored mRNA directionality. MAPK/NF-κB blockade completely reversed IL-1β-driven OAT1-3 mRNA downregulation while reducing IL-6 secretion. JNK inhibition restored OAT1/3 mRNA, whereas p38MAPK inhibition attenuated OAT2 suppression. NF-κB inhibition reduced OCTN1 induction. In contrast, IL-6, sIL-6Rα, or their combination did not reproduce IL-1β-driven transporter changes. These data identify IL-1β as the principal driver of cytokine-mediated regulation of human renal transporters in PTECs via JNK/p38MAPK/NF-κB nodes. These mechanistic, exposure-verified data may inform future translational modeling of renal secretory clearance during inflammation.
Deformable image registration (DIR) proves critical to many medical image analysis tasks, yet its reliable evaluation is fundamentally challenged by the absence of ground-truth deformations. Existing label-based metrics require costly manual annotations, while current label-free alternatives often fail to capture anatomical correspondence. To address this dilemma, we introduce Contrastive Discrepancy (CD), a novel label-free metric for robust evaluation and automatic hyperparameter tuning without requiring manual annotations in DIR. Grounded in bias-variance trade-off theory and group equivariance, CD quantifies model performance by measuring the discrepancy between deformation vector fields (DVFs) produced when registering a fixed image with different observations of the moving image sampled from the same anatomical orbit under a transformation group, such as an affine group. This approach penalizes both underfitting models, which exhibit high bias, and overfitting models, which are sensitive to unstructured perturbations and thus have high variance. Through extensive experiments across three DIR model families and two public datasets, we demonstrate that CD's performance curve consistently mirrors that of the gold-standard Target Registration Error (TRE) and substantially outperforms existing label-free metrics. Crucially, the validated reliability of CD unlocks its most significant application: fully automatic, testing-time hyperparameter selection. This hyperparameter learning enables DIR models to be dynamically optimized for individual patient data without any labeling cost. By offering a practical pathway to automated model tuning, Contrastive Discrepancy bridges the gap between advanced DIR methodologies and their precise, personalized application in clinical workflows.