Search Results (997)

Creative tourism is increasingly discussed as a pathway for tourism development in rural and peripheral destinations, yet empirical evidence remains uneven and is still drawn mainly from contexts where it is already explicitly labelled and institutionally supported. This article examines whether and how creative tourism-aligned practices are present in Kupiškis District, a peripheral rural municipality in north-eastern Lithuania where creative tourism has not been formally institutionalised as a tourism development category. The study adopts a qualitative single-case design combining a multi-stakeholder focus group and semi-structured interviews with municipal, intermediary, and private-sector actors. The findings reveal a meaningful but weakly integrated experiential base shaped by educational activities, water-based leisure, symbolic narratives, routes, and micro-entrepreneurial initiatives. Although these practices are rarely named locally as creative tourism, they display several of its defining characteristics, including participatory learning, host involvement, small-scale interaction, and local embeddedness. The study suggests that the main development challenge lies not in the absence of creative resources, but in limited coordination, weak articulation, and the difficulty of translating dispersed practices into coherent and consistently bookable visitor experiences. The article conceptualises this condition as a latent experiential portfolio and, in doing so, makes three contributions: it offers a sensitising concept for describing pre-consolidation stages of creative tourism where relevant practices exist but remain only partly articulated; it supports a practice-based rather than label-based identification of creative tourism in weakly institutionalised settings; and it extends the empirical scope of creative tourism research to a peripheral rural case in the Baltic region. Full article

Purpose: Prostate-specific membrane antigen (PSMA) is a well-established molecular target in prostate cancer (PCa). Both radionuclide imaging and near-infrared fluorescence (NIRF) imaging offer high sensitivity for in vivo tumor detection. PSMA-targeted dual-modality probes integrating these two imaging techniques provide complementary preoperative and intraoperative tumor visualization, thereby improving surgical guidance in PCa. In this study, we aimed to develop a novel dual-labeled PSMA probe combining radioactive and fluorescent properties to achieve precise tumor delineation during radical prostatectomy (RP). Methods: A high-affinity PSMA-targeted fluorescent probe (PSMA-DF) was synthesized using solid-phase synthesis. Subsequent radiolabeling with the radionuclide [⁶⁸Ga]Ga yielded the successful generation of a dual-modal PSMA-targeted molecular probe, namely [⁶⁸Ga]Ga-PSMA-DF. The probe was systematically evaluated both in vitro and in vivo, and its safety profile was assessed through acute toxicity testing. Tumor-bearing nude mouse models were established using PSMA-positive 22Rv1 and PSMA-negative PC-3 PCa cell lines. Imaging performance, tumor-targeting specificity, and biodistribution of the probe were comprehensively evaluated using micro-PET imaging, in vivo fluorescence imaging, and biodistribution studies. Results: High-quality and high-purity PSMA-DF was successfully prepared, which exhibited excellent optical properties. Following radiolabeling with [⁶⁸Ga]Ga, a dual-modality radionuclide-fluorescence probe ([⁶⁸Ga]Ga-PSMA-DF) was successfully constructed. In vitro cellular uptake studies demonstrated that 22Rv1 cells had relatively high uptake of the probe, reaching 7.34 ± 0.55 IA%/10⁶ cells at 120 min. In contrast, PC-3 cells and blocked 22Rv1 cells displayed minimal uptake, confirming the specific targeting ability of the probe. In vivo evaluations were conducted on tumor-bearing mice using micro-PET/CT and NIRF imaging. The results revealed that [⁶⁸Ga]Ga-PSMA-DF achieved high specific tumor accumulation in 22Rv1 xenografts, with the peak tumor uptake (SUVmax = 1.748 ± 0.132) and tumor-to-muscle ratio (11.542 ± 1.511) observed at 120 min. Notably, high-contrast fluorescence imaging was also achieved at later time points, yielding a tumor-to-background ratio (TBR) of 6.559 ± 1.415 at 48 h. Notably, ex vivo biodistribution data were consistent with in vivo imaging findings. Conclusions: This preclinical study demonstrates that [⁶⁸Ga]Ga-PSMA-DF exhibits high and specific uptake in PCa models, supporting its potential as a dual-modality tracer for both PET/CT imaging and real-time intraoperative fluorescence guidance during PCa surgery. Full article

Irreversible anterior segment blindness with preserved retinal integrity (e.g., dense corneal opacity) remains a major clinical challenge because effective sight-restoring options are limited. Here, we describe an intraocular micro-light-emitting diode (Micro-LED) epiretinal microdisplay intended to deliver patterned optical stimulation to intact photoreceptors by bypassing opaque anterior optics. The prototype was based on a color-capable VGA microdisplay (640 × 480 pixels) and operated at <30 mW under typical conditions. An ultra-thin flexible cable and a copper-mesh–reinforced polydimethylsiloxane (PDMS) encapsulation provided a compact, conformable intraocular package with high pixel density. We evaluated a monochromatic (green) prototype in a single beagle eye $(n=1)$ using a transscleral implantation approach and performed 7 days of postoperative follow-up with slit-lamp examination and multimodal imaging. Patterned stimulation via the implanted display elicited flash-evoked visual evoked potentials (VEPs) with consistent within-session waveform morphology, providing preliminary neurophysiological surrogate evidence of upstream visual pathway activation under the tested conditions in this single-animal pilot. The short-term postoperative course included transient hypotony and anterior segment inflammation, and implant rotation with associated inferior retinal detachment was observed by day 7, highlighting current biomechanical limitations. Beyond anterior segment opacity, the same intraocular optical interface could be explored as a modular light-delivery platform to pair with emerging retinal therapies (e.g., optogenetics), pending chronic safety and functional validation. This pilot large-animal study therefore provides a translationally relevant testbed while delineating key engineering constraints that must be addressed next. Full article

Chronic kidney disease (CKD) is a major global health burden leading to a loss of kidney function via podocyte damage, a non-regenerative renal cell type. Early detection of podocyte injury is crucial but remains limited, highlighting the need for non-invasive biomarkers. Therefore, we analysed urinary exosomal microRNAs (miRNAs) in relation to podocyte morphology in biopsies from 65 CKD patients, including focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD) and healthy controls. Global profiling distinguished CKD patients from controls, with miR-606 consistently upregulated and miR-431 downregulated. In podocytopathies, MCD displayed a predominantly suppressed miRNA profile, with miR-141, miR-429, and miR-660 as key candidates, whereas FSGS exhibited elevated miR-181c, miR-3610, miR-663b, miR-4651, and miR-429. Super-resolution morphometry revealed diffuse foot process effacement in MCD and heterogeneous, focally disrupted architecture in FSGS, providing a structural context for the molecular findings. Regression analyses linked these miRNAs to filtration slit density and length, proteinuria, and 25-Hydroxy-vitamin-D3 levels, integrating molecular, structural, and clinical readouts. These results define a coherent miRNA signature of podocyte injury that distinguishes CKD entities and correlates molecular changes with disease severity. Combining urinary exosomal miRNAs with morphometric analysis facilitates early, non-invasive identification of podocyte damage, enabling earlier therapeutic intervention in podocytopathies. Full article

Large depth of field (DOF) is a core pursuit in integral imaging (InIm). In this paper, we propose a DOF-enhanced InIm display system comprising a transmissive mirror device (TMD), a semi-transparent mirror (STM), two 2D displays, and a micro-lens array (MLA). The two 2D displays pre-render two sets of elemental image arrays (EIAs), each corresponding to a distinct depth plane. The STM spatially coaxializes the two EIAs emitted by the two 2D displays. At the same time, the TMD collaborates with the STM to adjust the effective projection distances of the coaxialized EIAs onto the MLA to different values. The MLA couples with the two EIAs projected at different effective distances, enabling the reconstruction of three-dimensional (3D) images at two separate central depth planes (CDPs). This system solves the narrow DOF issue in conventional InIm displays by reconstructing 3D images at two separate CDPs, thus enhancing the DOF. Notably, the proposed system achieves an approximate two-fold increase in DOF compared to a conventional one. A prototype of the DOF-enhanced InIm display system is constructed, and experimental results verify its feasibility. Full article

In China’s stock-based renewal agenda, many old residential communities display pronounced intergenerational overlap, in which grandparental childcare becomes a dominant pattern of outdoor-space use. Against the backdrop of age-structure shifts, population ageing, and persistently low fertility, community-level outdoor-space supply, distributive equity, and environmental adaptability have become key concerns in renewal practice. Yet, practitioners still lack a rankable, low-cost, and implementable evaluation-to-decision workflow. Using Xingshe Community in Dalian, China as an empirical case, this study establishes and tests an integrated “NLP–AHP–GBDT” assessment framework. Guided by policy discourse and planning theory, over 50 semi-structured interviews were processed via NLP-based semantic analysis and keyword mining to derive a two-tier indicator set (criterion and indicator layers). Seven specialists then applied the analytic hierarchy process to elicit indicator weights, and a resident survey was administered to generate weighted performance scores for diagnosing deficiencies. In the feedback-validation stage, we adopted both a qualitative Framework Method and a quantitative GBDT approach, first using the Framework Method to conduct feedback validation based on community residents’ open-ended evaluations. Subsequently, gradient boosting decision trees were used for supervised verification with renewal-scenario data, providing empirical backing for the weighting scheme and the resulting priority order for interventions. The findings suggest that outdoor spaces are broadly serviceable but fall short in intergenerational friendliness, reflecting a structural misalignment between intergenerational activity patterns and spatial provision. Based on the validated priorities, the study proposes modular, incremental micro-renewal measures focusing on safety and emergency accessibility, environmental comfort and caregiving–recreation coupling, and place identity with community organizational mobilization. Full article

Circulating microRNAs (miRNAs) are promising minimally invasive biomarkers for cancer risk assessment, yet prospective evidence for breast cancer (BC) remains limited. We conducted a nested case–control study within a prospective cohort to examine whether pre-diagnostic circulating miRNAs are associated with subsequent BC risk and to explore their potential relevance in prospective population-based settings. Baseline serum from 160 women (80 incident BC cases; 80 matched controls) was analyzed, with a median time to diagnosis of 8.9 years. Eight candidate miRNAs were quantified by droplet digital PCR (ddPCR) and normalized to miR-484. Group differences were evaluated by non-parametric tests, and odds ratios for BC were estimated using logistic regression models adjusted for established risk factors, with Bonferroni correction for multiple testing. Cases and controls were comparable at baseline. Among the candidates, lower circulating miR-181 levels showed a suggestive inverse association with BC risk in fully adjusted models, while lower Let7 levels showed only a non-significant, hypothesis-generating inverse trend that did not survive Bonferroni correction. No other miRNA displayed clear associations with BC risk. These findings, while preliminary, support further large-scale prospective investigations specifically designed to assess predictive performance and external validation. employing standardized pre-analytical and analytical protocols, repeated sampling, and independent replication/external validation to clarify the etiologic relevance and potential risk-prediction value of circulating miRNAs for BC. Full article

This study aimed to prepare experimental calcium silicate repair cements (ERCs) incorporating zirconium (Ca₃ZrSi₂O₉; CZS) or strontium substitution (Sr₅(PO₄)₂SiO₄; SPS), and to compare their physicochemical properties with white MTA-Angelus (WMTA), grey MTA-Angelus (GMTA), and Biodentine (BD). After synthesizing the CZS and SPS phases, powder–liquid cements were formulated. The setting time and radiopacity were assessed according to ISO 6876/12 and ASTM C266, the volumetric solubility by micro-CT, the pH by a pH meter, and the calcium/strontium ion release by FAAS/ICP-OES. Data were analyzed using ANOVA and Tukey’s tests (5%). The initial setting time was 11 min for SPS and 6 min for CZS (p < 0.05), while the final setting was significantly longer for SPS (49 min). Both ERCs showed radiopacity above the 3.0 mm Al minimum, with higher values for CZS (4.58 mm Al). The solubility remained controlled, with CZS presenting the highest value (3.09%). Both materials exhibited an alkaline pH, peaking at 24 h (CZS: 9.70; SPS: 10.04) and decreasing until 168 h (CZS: 7.80; SPS: 8.31). Sustained ionic release was observed: CZS showed intermediate calcium release (25.96 mg/L at 3 h), whereas SPS displayed lower values (10.95 mg/L at 168 h), without significant difference from WMTA (p > 0.05). Under these conditions, the experimental ERCs demonstrated adequate physicochemical performance comparable with commercial materials. Full article

Epstein–Barr virus (EBV), a ubiquitous human herpesvirus infecting over 90% of the adult population, is causally associated with a distinct molecular subtype of gastric cancer (GC). A key mechanism by which EBV influences tumour biology is the expression of viral microRNAs (miR/miRNA) encoded within the BamHI-A rightward transcript (BART) region, although inter-patient variability in EBV-miRNA expression and its molecular significance remain incompletely defined. In this study, small RNA sequencing was performed on 11 primary gastric tumour samples to characterise EBV-derived miRNA expression, followed by quantitative RT-PCR analysis in an extended cohort of 21 tumours for targeted validation. EBV-miRNAs were detected in a subset of tumours and showed marked inter-tumour heterogeneity in abundance. EBV-miRNA-positive tumours were dominated by a conserved set of BART miRNAs, including miR-BART19-3p, miR-BART1-5p, miR-BART10-3p, miR-BART6-3p, miR-BART13-5p, and miR-BART22. These BART miRNAs displayed correlated expression patterns, characterised by concurrent elevation of multiple viral miRNA species within the same tumour samples. To link viral miRNA expression with host molecular responses, in silico virus–host interaction analysis was conducted using ViRBase to prioritise host genes associated with the detected BART miRNAs. PTEN, BCL2L11, FOXO3, and CDKN1A were identified as high-confidence targets and selected for experimental assessment. RT-qPCR analysis demonstrated differential expression of these host genes across tumours stratified by EBV BART miRNA abundance. Together, these findings identify a consistent BART miRNA pattern within this cohort. This study provides patient-level molecular evidence linking EBV-miRNA regulatory output to host gene expression states in GC. Full article

High-resolution microdisplay driver applications impose stringent requirements on the static linearity and dynamic performance of digital-to-analog converters (DACs). To meet these requirements, this paper presents a 200 MS/s 12-bit current-steering DAC. To reduce mismatches among high-weight current sources, a split–sort–symmetric grouping calibration (SSSGC) scheme is introduced, in which each most-significant-bit (MSB) current source is split into sub-cells and reorganized through sorting and symmetric pairing. This approach improves static linearity without complex current measurement or compensation loops. Additionally, a group-domain dynamic element matching (DEM) technique is employed to randomize current-source selection and suppress harmonic distortion. Designed in a 0.18 μm BCD process, the proposed DAC achieves an integral nonlinearity (INL) of 0.79 LSB, a differential nonlinearity (DNL) of 0.42 LSB, and a spurious-free dynamic range (SFDR) of 74.9 dB at an output signal of 4.05 MHz. Full article

Juvenile hormone (JH) is a key regulator of larval development in honeybees. Its biosynthesis involves multiple enzymatic steps and is modulated by a complex regulatory network that includes microRNAs (miRNAs). Juvenile hormone acid methyltransferase (JHAMT) catalyzes the final step in JH synthesis. This study demonstrates that the miRNA novel-m0027-3p negatively regulates the expression of the Jhamt gene in Apis mellifera larvae (AmJhamt), thereby mediating JH biosynthesis. Bioinformatics predictions indicate that novel-m0027-3p potentially targets six hormone-related genes (22 mRNAs), including AmJhamt. Dual-luciferase reporter assays and mimics/inhibitor-miRNA feeding confirmed that novel-m0027-3p significantly suppresses the expression of the target gene AmJhamt. In vivo experiments showed that larvae fed with the mimics of novel-m0027-3p exhibited decreased JH titers and significantly downregulated expression of JH signaling downstream genes AmHex70b and AmKr-h1. Conversely, larvae fed with the inhibitors of novel-m0027-3p displayed significantly elevated JH titers and markedly upregulated expression of AmHex70b and AmKr-h1. Our findings provide experimental evidence for the coupling between miRNAs and hormonal pathways in honeybees. Full article

The melon fly, Zeugodacus cucurbitae (Coquillett), is recognized as a globally significant quarantine pest, and it ranks among the most destructive insect species infesting cucurbit and solanaceous crops. However, the molecular mechanisms governing reproductive regulation in female Z. cucurbitae remain poorly characterized, particularly those underlying the reproductive processes mediated by microRNAs (miRNAs). In this study, we firstly identified the ovary-specific gene ZcCTL-S1 in Z. cucurbitae via transcriptomic analysis, and subsequently predicted its targeted miRNAs using bioinformatics approaches. Among these miRNAs, overexpression or inhibition of miR-971-1 and miR-let-7 led to corresponding inverse changes in the transcriptional level of ZcCTL-S1. Notably, only miR-let-7 displayed markedly elevated expression levels in Z. cucurbitae ovaries. Further analyses confirmed that miR-let-7 exhibited a direct targeting relationship with ZcCTL-S1, via a combinatorial approach involving in vivo RNA immunoprecipitation, in vitro dual-luciferase reporter assays, and site-directed mutagenesis techniques. Phenotypic analyses showed that both knockdown of ZcCTL-S1 and overexpression of miR-let-7 significantly inhibited egg hatchability, ultimately compromising the female reproductive capacity of Z. cucurbitae. Collectively, these findings identify a novel miRNA-gene regulatory module in the reproductive development of Z. cucurbitae, and provide novel insights for the development of gene- or miRNA-based pest control strategies. Full article

Congenital heart defects (CHDs) represent the most common category of congenital malformations and constitute a significant cause of infant morbidity and mortality. Despite advances in prenatal imaging, such as fetal echocardiography, early detection remains challenging, particularly in pregnancies without identified risk factors. Recent studies suggest that maternal circulating non-coding RNAs, including microRNAs and long non-coding RNAs (lncRNAs), may serve as promising non-invasive biomarkers for the prenatal diagnosis of CHDs. Following a review of the most relevant clinical and preclinical studies, it was found that maternal circulating RNA, particularly microRNAs and lncRNAs, shows potential as non-invasive biomarkers for detecting fetal congenital heart defects. Among microRNAs, miR-146a-5p demonstrated the highest diagnostic accuracy for ventricular septal defects (VSDs), while panels of lncRNAs, such as LINC00598, LINC01551, and GATA3-AS1, exhibited high performance for atrial septal defects (ASDs). In addition, miR-19b, miR-29c, and miR-375 were associated with both VSDs and ASDs, suggesting a shared role in septal development. However, the studies displayed variability in biomarker selection and analytical methodologies. The findings indicate that maternal circulating microRNAs and lncRNAs hold significant potential as non-invasive biomarkers for the early detection of CHDs. Nonetheless, methodological heterogeneity and small sample sizes highlight the need for standardized protocols and larger multicenter studies prior to clinical implementation. These observations support the future integration of RNA biomarkers with fetal echocardiography to enhance early CHD screening and to inform prenatal counseling. Full article

This paper investigates the flight kinematics and unsteady aerodynamics of butterfly flight using high-speed schlieren imaging. Butterfly trajectories are reconstructed to examine flight control mechanisms, with particular emphasis on thorax-driven manoeuvring and body reorientation. By reconstructing free-flight trajectories utilizing image recognition algorithms, we isolate the mechanisms of flight control, with particular emphasis on how thoracic oscillation drives manoeuvring and body reorientation. Phase-resolved analysis reveals distinct wingbeat modes, including clap-and-fling motions associated with hovering and low-speed ascent. Schlieren visualization further captures a detailed view of the wake topology, displaying the formation and evolution of wingtip vortices during the downstroke, as well as attached and entrained flow structures during cupped wing configurations. The results demonstrate the strong coupling between body dynamics, wing kinematics, and wake structure, highlighting how butterflies combine aerodynamic and inertial mechanisms to achieve efficient lift generation and control. These findings provide biomimetic insights relevant to the design of flapping wing micro air vehicles, particularly for low-speed flight, hover efficiency, and passive stability and control through body–wing coupling. Full article

In this study, shale samples with diverse lithofacies from the Lower Silurian Longmaxi Formation in the Fuling Field were investigated to evaluate the variations in pore characteristics and methane adsorption capacity (MAC) of different shale lithofacies. A set of experiments were performed, such as total organic carbon (TOC) content, X-ray diffraction (XRD), field emission–scanning electron microscopy (FE-SEM), low-pressure gas (CO₂/N₂) adsorption, and high-pressure methane adsorption. Combined with TOC content and mineral composition, three types of shale lithofacies were identified, including organic-rich (OR) argillaceous-rich siliceous (S-3) shale lithofacies, organic-moderate (OM) argillaceous/siliceous mixed (M-2) shale lithofacies, and organic-lean (OL) siliceous-rich argillaceous (CM-1) shale lithofacies. Through detailed comparative analyses, we found that OR S-3 shales possess the maximum TOC content, the most developed heterogeneous organic micro-mesopores, the largest pore volume (PV), and the highest pore surface area (PSA); consequently, they display the strongest MAC. Conversely, OL CM-1 shales have the lowest TOC content and the highest clay content, and thus the smallest PSA and the poorest methane adsorption performance. In conclusion, considering the excellent gas storage potential, sustained shale gas production, and brittle response to hydraulic fracturing, OR S-3 shales are superior to shale gas exploration and exploitation compared with OM M-2 and OL CM-1 shales. Full article