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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.

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.

Background/Objectives It is not established whether melanoma and lung cancer are part of the tumor spectrum of the Lynch syndromes (LS). Our first hypothesis was that, if melanoma is associated with LS, most prospectively observed cases would be carriers of pathogenic MSH2 variants (path_MSH2), as for other LS non-endodermal tumors. Our second hypothesis, which was derived from findings of the first study, was that the pattern of differences in the incidence of lung cancer in path_MMR carriers would mirror that for melanoma. Methods We used the Prospective Lynch Syndrome Database (PLSD) data and methods. Results Firstly, consistent with hypothesis, ten of 3154 path_MSH2 carriers followed for 26,309 years developed melanoma, compared with 6 of 5288 path_MLH1/MSH6/PMS2 carriers followed for 45,081 years (p = 0.04). Secondly, although the incidence of melanoma in carriers of path_MSH2 was 0.00041-similar to the populations in which the carriers resided-the average incidence rates for path_MLH1/MSH6/PMS2 carriers was 0.00012, lower than the corresponding population rates. Thirdly, the average lung cancer incidence rates in PLSD were 0.00112 in path_MSH2 carriers and 0.00032 in path_MLH1/MSH6/PMS2 carriers (p = 0.02), both lower than the population rates. Conclusions Melanomas and lung cancers-both of which are immunogenic through mechanisms independent of mismatch repair deficiency-may become even more immunogenic when they also exhibit microsatellite instability. This may lead to an increased likelihood that both tumors are eliminated by the immune system and, thus, show variable and lower incidence. These insights may help inform strategies for cancer prevention or treatment that are aimed at simultaneously interrupting multiple carcinogenic pathways.

Lung cancer remains the leading cause of cancer-related mortality worldwide in both males and females. Despite recent advances in precision-targeted therapeutics, mortality rates remain high, largely due to delayed diagnoses when curative interventions are no longer feasible. Recent studies from our group demonstrated that the LINE-1 mRNA and associated miRNA cargo of plasma exosomes can be used as sensitive and specific diagnostic and prognostic biomarkers of non-small-cell lung cancer (NSCLC). Because exosomes from various cancer types can be detected in urine, we extended our investigation to examine these analytes in urine exosomes from NSCLC patients. LINE-1 ORF1 and ORF2 mRNA levels, along with miR-21-5p, miR-126-3p, miR-210-3p, miR-221-3p, Let-7b-5p, miR-146a-5p, miR-222-3p, miR-9-5p, and miR-1277-5p, were higher in urine exosomes from NSCLC patients compared to healthy controls. The cargo of urine-derived exosomes often mirrored that of plasma exosomes and correlated with several clinicopathologic characteristics. The strong predictive performance of urine exosomal RNAs distinguishing NSCLC patients from controls suggests these measurements may serve as a complementary and readily accessible source for noninvasive assessment of patients with NSCLC.

Chronic osteomyelitis remains a formidable clinical challenge because conventional biomaterials, which are designed for spatially uniform defects, cannot match the hierarchical, compartmentalized progression of deep bone infection. Using a clinically relevant rabbit femoral osteomyelitis model, we construct a multiscale pathoanatomical atlas of S. aureus infection, revealing a coherent disease cascade: medullary colonization, invasion of the immunoprivileged osteocyte lacuno-canalicular system (OLCS), region-specific bone destruction, and ultimate formation of a biomechanically incompetent sequestrum. Guided explicitly by this anatomical blueprint, we design and computationally optimize a dual-component bioactive material system that mirrors and counteracts the infection hierarchy. This dual-component implant integrates a 3D-printed, load-bearing macro-scaffold for mechanical stabilization and bone regeneration with infiltrative microspheres capable of penetrating trabecular microdomains and releasing antimicrobials within the marrow and cortical compartments, directly targeting bacterial reservoirs. In vivo validation demonstrates that this system enables simultaneous eradication of deep-seated infection, resolution of chronic inflammation, and restoration of structurally competent bone. Collectively, this work establishes imaging-resolved anatomical mapping as a generative framework for bioactive material design and provides a strategy that may be adapted for developing spatially adaptive therapeutic systems against complex tissue infections.

In this work, we systematically investigate the structural, vibrational, electronic, and transport properties of a series of novel Janus TeWZH (Z = N, P, As) monolayers using density functional theory. Our results confirm that these materials are structurally stable and exhibit semiconducting behavior with band gaps ranging from 1.42 to 2.19 eV at the HSE06 level of theory (calculated without spin-orbit coupling). Key findings include significant valence band splitting at the K-point (up to 0.49 eV) induced by strong spin-orbit coupling, and a robust out-of-plane piezoelectric response (with a d 31 coefficient reaching 0.68 pm V-1) induced by the broken mirror symmetry of the Janus structure. Furthermore, we find that while these monolayers possess relatively low carrier mobilities, their transport dynamics are primarily governed by acoustic deformation potential scattering, which acts as the dominant phonon-limited mechanism for both electrons and holes. These findings position Janus TeWZH materials as promising candidates for spintronic and piezoelectric nanodevices.

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.

Background: Nationwide epidemiologic data on comorbidity burden in early rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are limited. We compared coded diagnoses for concurrent disorders in incident RA and PsA based on administrative healthcare data (AHC). Methods: This retrospective cohort study used AHCs from the National Health Fund between 2009 and 2021. Using composite proxy definitions for RA and PsA diagnosis (combination of ICD-10 codes and prescription data), we identified all new cases of RA and PsA between 2019 and 2021. We utilized a ten-year lookback window for the accrual of concurrent disorder claims. Age-, sex-, serostatus- and calendar year-adjusted models were considered. Crude, relative and adjusted prevalence estimates were calculated using generalized linear models. Results: Using NHF data, we identified 36,285 and 1603 patients with incident RA/PsA, respectively. We estimated the burden of 31 multisystem comorbidities. Most disorders (N = 23, 74.2%) were more frequently coded among RA patients, while only liver diseases were significantly more prevalent in PsA. Chronic back pain (+21.2 pp) and osteoarthritis (+18.3 pp) were tied to the greatest absolute differences, likely mirroring medical contact patterns throughout the differential diagnostic process. Hospitalization due to heart failure and stroke, but not myocardial infarction, was more common in RA vs. PsA. Conclusions: Newly diagnosed patients with RA and PsA show distinct patterns of healthcare utilization for multiple organ disorders. Early RA may be tied to higher comorbidity rates not fully explained by age and sex, as compared to PsA; further studies are necessary to clarify these observations.

High-contrast striped patterns near 3 cycles per degree are well established as a cause of visual discomfort and perceptual distortions, which in clinical populations can manifest as symptoms such as migraines or seizures. This sensitivity has been linked to cortical hyperexcitability, characterized by abnormally increased neural responses to visual input. Although gamma-band oscillations in visual cortex are known to reflect excitatory-inhibitory dynamics associated with pattern sensitivity, the contribution of higher-frequency neural activity and large-scale network interactions has received limited direct investigation. Using intracranial EEG recordings from patients with non-photosensitive epilepsy, we examined how aversive gratings modulate local field potential activity across frequencies ranging from 55 to 1000 Hz. Analyses focused on visual cortex as well as higher-order parietal, temporal, insular, and limbic regions, assessing frequency-specific power changes and their relationship to self-reported visual discomfort. At the group level, aversive patterns elicited significantly greater high-gamma power than control patterns in extrastriate regions (BA 18 and, at later latencies, BA 19), while primary visual cortex (BA 17) showed no consistent condition-dependent modulation. At the individual level, patients with higher visual discomfort scores exhibited stronger and more sustained post-stimulus increases in high-frequency activity in BA 18 across multiple frequency bands, accompanied by moderate-to-large effect sizes. Beyond the occipital cortex, aversive patterns engaged lateral temporal regions, predominantly in the middle and superior temporal gyri, with sustained responses emerging approximately one second after stimulus onset. Parietal responses were brief and variable across frequency bands, and insular and limbic regions showed no consistent condition-specific modulation. Ripple-band activity mirrored the high-gamma pattern in occipital and temporal cortex, whereas fast ripple and very fast ripple responses were weaker, spatially sparse, and directionally heterogeneous. Together, these results indicate that visual discomfort reflects individual differences in extrastriate cortical excitability expressed through frequency-specific network dynamics, and identify high-frequency activity in BA 18/V2 as a candidate neural correlate of susceptibility to aversive visual stimuli.

Pompe disease (PD) results from lysosomal acid α-glucosidase (GAA) deficiency, causing lysosomal glycogen accumulation in cardiac and skeletal muscles. We previously characterized a murine model carrying the orthologous human infantile-onset PD (IOPD) pathogenic variant, c.1826dupA (p.Y609*), introduced into the mouse Gaa gene. Compared to wild-type (WT; C57BL/6NJ) controls, Gaac.1826dupA mice exhibit reduced GAA activity and develop early-onset hypertrophic cardiomyopathy-evidenced by increased left ventricular wall thickness and left ventricular mass index (LVMI)- as well as impaired grip strength and gait abnormalities. To benchmark the model's disease fidelity and assess its responsiveness to established therapeutic intervention, Gaac.1826dupA mice received a single retro-orbital dose of AAV2/8-LSPhGAA (2 × 109 vg/g body weight) at postnatal day 12-14. Twelve weeks post-treatment, mice exhibited supraphysiological GAA enzymatic activity in the heart (550% of WT) and liver (400% of WT) with a 93% reduction in cardiac glycogen. No sex-dependent differences in therapeutic efficacy were observed. Echocardiography revealed robust reversal of cardiac pathology, with wall thicknesses and LVMI values approaching WT levels. In contrast to this profound cardiac rescue, skeletal muscle improvements were modest; while forelimb grip strength remained unchanged, automated gait analysis showed benefit limited to hind paw base of support. These findings demonstrate that the Gaac.1826dupA model mirrors the critical cardiomyopathy characteristic of IOPD. While systemic AAV treatment yields definitive cardiac correction, the partial skeletal muscle response highlights a clear need for optimization. Consequently, the Gaac.1826dupA mouse serves as a high-fidelity platform for evaluating next-generation genomic correction strategies targeting both cardiac and refractory neuromuscular manifestations of PD.

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.

Approximately two-thirds of patients with kidney stones exhibit Randall's plaques, interstitial calcium phosphate deposits extending to the papillary surface, serving as stone formation niduses. Although inflammation and osteogenic processes have been implicated in plaque development, their mechanistic connection remains unclear. In vascular calcification, which shares key pathological features with Randall's plaques, pro-inflammatory cytokines upregulate osteogenesis-related proteins to promote calcification. Whether similar signaling occurs in kidneys remains unclear. This study aimed to explore physiopathology and facilitate the development of potential targeted therapies for kidney stones. HK-2 cells were treated with calcium and pro-inflammatory cytokines to assess calcium deposition and investigate osteogenic transition signaling pathways. Non-cell-based assays were developed to examine the direct effects of osteogenesis-related proteins on specific stages of calcium phosphate crystal formation, including nucleation, growth, and aggregation. To determine whether inflammation is related to osteogenic responses and calcification in vivo, a novel rat model of renal calcium deposition was established by combining a high-calcium diet with unilateral ureteral obstruction surgery. Renal calcium deposits were also evaluated. In vitro, pro-inflammatory cytokines enhanced calcium-induced mineralization in renal tubular cells and were associated with the activation of MAPK, NF-κB, and Smad signaling pathways, along with the upregulation of osteogenesis-related proteins. These proteins exerted direct, stage-specific effects on calcium phosphate crystal nucleation, growth, and aggregation. In our novel rat model, inflammation enhanced renal calcium deposition and upregulated osteogenic markers within 1 month. The positive correlation between the renal expression of inflammatory cytokines and osteoblast markers mirrored the in vitro findings. This study provides insight into renal calcification, suggesting that pro-inflammatory cytokines are associated with activation of MAPK, NF-κB, and Smad signaling pathways and upregulation of osteogenesis-related proteins, which may contribute to key stages of crystal formation. Furthermore, this work establishes a novel and time-efficient animal model that offers a valuable platform for investigating the pathogenesis of renal calcification, including processes potentially relevant to Randall's plaque-associated calcification.

Management of deep cervical lipomas (DCLs) is described only in case reports and series in the literature. We aim to present a scoping review of this literature and the largest case series of surgically resected DCLs to describe presentation, workup, and efficacy of transcervical resection for DCLs. A systematic search for surgically resected solitary DCLs was conducted in PubMed, Embase (Elsevier), Scopus, and Cochrane library on 12/19/2025 using PRISMA methodology. Study protocol was registered in PROSPERO (CRD420251052065) and articles were screened independently by 2 authors, with conflicts resolved by a third reviewer. All solitary DCLs resected via a transcervical approach at a tertiary center from 2014 to 2025 were reviewed. From a total of 1459 articles, 144 studies met criteria, and 163 cases (median age 45 years, 25.2% pediatric, 67.5% male) were included. The most common presenting symptom was swelling (81.6%), and 63.2% were enlarging. A total of 232 imaging studies, most commonly CT (n = 102), were conducted amongst 90.8% of patients for an average of 1.4 imaging studies per patient. Biopsy was performed in 27.6% of patients, with 43.4% of biopsies being inconclusive or inconsistent with benign fatty tumor. Postoperative complaints were noted for 9.8% of patients, with only 3.1% (n = 5) having persistent complaints. Two recurrences were noted. The institutional cohort of 10 patients (median age 55 years, 10% pediatric, 90% male, 90% non-Hispanic White) mirrored the literature, with the most common presenting symptom being palpable neck mass (80%), at least one imaging study per patient on average, no persistent complaints, and one recurrence. DCLs are less common than subcutaneous lipomas but follow a similar clinical course. Presentation most commonly occurs as a palpable mass, most of which are enlarging. Imaging without biopsy is often sufficient for workup. Transcervical resection is diagnostic and therapeutic with minimal morbidity.