Search Results (36,826)

Background and Clinical Significance: Meckel’s diverticulum is the most common congenital anomaly of the gastrointestinal tract and an uncommon cause of small bowel obstruction in adults, in which the diverticulum or a band arising from it typically constricts the adjacent bowel. Entrapment of the diverticulum itself within a pre-existing fibrous band is exceedingly rare; Case Presentation: A 42-year-old man with no previous abdominal surgery presented with colicky abdominal pain, distension and bilious vomiting. Contrast-enhanced computed tomography demonstrated small bowel loops dilated to 35.4 mm with a pelvic transition point of undetermined cause. At emergency laparotomy, a fibrous ileo-mesenteric band delimited a constricting orifice through which the Meckel’s diverticulum had herniated and become strangulated at its base, with secondary obstruction and ischemia of the adjacent ileum. Division of the band restored perfusion; the bowel remained viable and stapled diverticulectomy was performed without segmental resection. The patient recovered without complications. In most reported cases of Meckel’s diverticulum causing small bowel obstruction, the diverticulum or a band arising from it constricts the adjacent bowel. In this case the mechanism is reversed: the diverticulum was the entrapped structure itself, herniating through and strangulating within the orifice of a pre-existing ileo-mesenteric fibrous band. This configuration is exceptionally rare; Conclusions: Meckel’s diverticulum should be considered among the possible causes of small bowel obstruction in adults with no history of abdominal surgery. Recognition of this unusual anatomical configuration may facilitate intraoperative identification and appropriate assessment of bowel viability. Full article

Neuroendocrine prostate cancer (NEPC) is characterized by androgen receptor (AR) independence and poor response to conventional therapies, highlighting the need to unveil the molecular mechanisms behind NEPC. We previously showed that heme oxygenase 1 (HO-1, encoded by HMOX1) translocates to the nucleus exerting unexplored non-canonical functions. The present study delineates the nuclear interactome of HO-1, revealing a potential mechanism that impairs NEPC establishment. Through a proteomics approach integrated with bioinformatics analyses, we identified eleven novel nuclear interactors of HO-1. Unsupervised clustering analyses of RNA-seq data from prostate cancer (PCa) patient-derived xenografts (MDA PCa PDXs) and clinical cohorts demonstrated high expression of three HO-1 interactors (ILF3, SAFB, BCLAF1, and DDX17) in NEPC samples, with concomitant HMOX1 under-expression. Spatial transcriptomics in a mixed-histology tumor confirmed enrichment of the interactors in the NEPC foci. To better understand the link between HO-1 and NEPC, we established and characterized an in vitro model of NE transdifferentiation in PCa cell lines using forskolin to induce phenotypic reprogramming. HO-1 upregulation in transdifferentiated cells significantly attenuated the expression of NE markers and triggered a morphological shift, restoring epithelial phenotypes. This work identifies for the first time HO-1 nuclear interactome association with NEPC, where the HMOX1-ILF3-SAFB-BCLAF1-DDX17 print emerges as a useful marker for disease stratification. Full article

Background and Objectives: Three-dimensional printing is increasingly used to fabricate dental restorations; however, limited evidence is available on the mechanical performance and fracture behavior of printable resin materials used for endocrown restorations. Fracture load alone may not fully describe material performance, particularly when brittle or defect-sensitive failure occurs. This in vitro study aimed to compare the fracture resistance, Weibull parameters, experimental Mode I fracture toughness parameter, and failure patterns of three 3D-printed resin materials used for endocrown restorations. Materials and Methods: Thirty anatomically identical molar replicas were produced from a single prepared tooth model and restored with endocrowns fabricated from NextDent C&B MFH (NextDent B.V., Soesterberg, The Netherlands), SprintRay Crown (SprintRay Inc., Los Angeles, CA, USA), and BEGO VarseoSmile Crown Plus (BEGO GmbH & Co. KG, Bremen, Germany) (n = 10/group). The restorations were cemented and subjected to compressive loading until fracture. Maximum fracture force values were analyzed using Welch’s ANOVA and Weibull statistics. In parallel, single-edge-notched bend (SENB) specimens were fabricated from the same materials and tested using an ASTM D5045-based configuration to calculate an experimental Mode I fracture toughness parameter. Representative fractured crowns and standardized specimens were examined using stereomicroscopy to assess visible failure morphology. Results: No statistically significant difference in maximum fracture force was found among the three materials (Welch’s ANOVA, p = 0.217). The mean fracture force values were 862.37 N for NextDent C&B MFH, 804.37 N for SprintRay Crown, and 699.43 N for BEGO VarseoSmile Crown Plus. In the complementary analyses, BEGO VarseoSmile Crown Plus showed the highest Weibull modulus (m = 9.36), indicating a narrower distribution of fracture values, and the highest mean experimental Mode I fracture toughness parameter (5.250 MPa·m^0.5) under the present experimental conditions. Qualitative stereomicroscopic analysis revealed material-dependent visible failure patterns: SprintRay Crown exhibited more extensive fragmentation, whereas BEGO VarseoSmile Crown Plus showed a more defined visible fracture pattern with less secondary fragmentation. Conclusions: Fracture load alone was insufficient to characterize the mechanical behavior of the tested materials fully. Weibull parameters, the experimental fracture toughness parameter, and failure morphology provided complementary information and should be considered when evaluating 3D-printed resin materials for endocrown restorations. Full article

Elevated atmospheric carbon dioxide (ECO₂) is a key climatic factor influencing the resilience of plant–microbial symbiotic systems against heavy metal contamination. Robinia pseudoacacia–rhizobia symbiosis shows great potential for cadmium (Cd) remediation. However, the mechanism by which ECO₂ regulates Cd phytostabilization in symbiosis remains unclear. This study conducted a 90-day experiment in growth chambers to investigate the effects of ECO₂ on the growth, Cd accumulation and chemical forms, as well as nutrient uptake and antioxidant system in Robinia pseudoacacia–rhizobia symbiosis. Results indicated that ECO₂ significantly increased plant biomass and photosynthetic efficiency while significantly raising Cd content in roots (34.5%, p < 0.001) and decreasing it in shoots (31.4%, p < 0.001). This resulted in a significant reduction in Cd translocation factor (TF). Meanwhile, ECO₂ markedly increased Cd accumulation in roots (81.2%, p < 0.001) and reduced the bioavailability of Cd in the symbiosis. Moreover, ECO₂ promoted the content of nutrients and stimulated the antioxidant system. The random forest model indicated that root weight, Cd and Mn contents are the core factors for ECO₂-driven Cd phytostabilization. This study demonstrates that ECO₂ enhanced Cd phytostabilization by optimizing the resistance of symbiosis to Cd, offering a novel perspective for predicting plant–microbe joint restoration of heavy metal pollution under global climate change scenarios. Full article

Aim: Radiation-induced intestinal injury is one of the major dose-limiting complications of abdominal radiotherapy and is closely associated with oxidative stress, inflammation, and disruption of epithelial barrier integrity. The present study aimed to investigate the protective effects of verapamil on radiation-induced small-intestinal injury in rats by evaluating histopathological alterations together with tissue levels of TNF-α, 5-LOX, Nrf2, and ZO-1 as markers related to inflammatory, redox-associated, and tight-junction-associated responses. Materials and Methods: Thirty female Wistar albino rats were divided into three groups: Normal Control (n = 10), Radiation + Saline (RAD, n = 10), and Radiation + Verapamil (n = 10). Whole-abdomen irradiation was performed using a single 12 Gy dose delivered by a 6 MV linear accelerator. Verapamil (10 mg/kg/day, s.c.) treatment was started 5 days before irradiation and continued for 5 days afterward. Histopathological injury in jejunal tissues was evaluated using hematoxylin–eosin staining. Tissue levels of TNF-α, 5-LOX, Nrf2, and ZO-1 were measured using ELISA. Results: Whole-abdomen irradiation caused marked histopathological injury characterized by villus disruption, glandular degeneration, and mucosal architectural damage. Irradiation significantly increased small-intestinal TNF-α and 5-LOX levels while decreasing Nrf2 and ZO-1 levels compared with the Normal Control group (p < 0.05). Verapamil treatment significantly attenuated radiation-induced histopathological injury and reduced TNF-α and 5-LOX levels. TNF-α returned to values comparable with the Normal Control group, whereas 5-LOX remained significantly elevated. Verapamil also partially restored Nrf2 and ZO-1 levels compared with the RAD group (p < 0.05), although both remained significantly lower than control levels. Conclusions: Verapamil attenuated radiation-induced small-intestinal injury and was associated with favorable modulation of TNF-α, 5-LOX, Nrf2, and ZO-1 levels. The protective response was partial, with persistent differences in 5-LOX, Nrf2, and ZO-1 compared with controls. These biomarker changes should not be interpreted as direct evidence of functional pathway activation or preservation of intestinal barrier function. Further studies incorporating direct mechanistic and functional assessments are warranted before clinical translation. Full article

The benefits of lenalidomide, which leverages TP53-dependent apoptosis and promotion of megakaryocytic differentiation, in lower-risk MDS (LR-MDS) with del(5q) are well-established and drive its frequent use in clinical practice. In parallel, advances in molecular testing have elucidated the clear impact of TP53 mutations on response to therapies and prognosis, with diversity in the latter informed by variant allele frequency (VAF) and/or predicted allelic state. In this review, we discuss the converging pre-clinical and clinical evidence that implicates TP53 mutations not only as a driver of lenalidomide resistance in del(5q) LR-MDS, but as a source of selective clonal advantage under lenalidomide exposure. Lenalidomide-induced CK1α degradation triggers TP53-mediated apoptosis in wild-type clones, inadvertently favoring the survival and expansion of TP53-mutated cells. Clinically, this dynamic has been demonstrated across multiple studies, with rising TP53 variant allele frequency and clonal evolution observed following treatment. These findings underscore the importance of baseline molecular assessment in patients with MDS and, in select cases, serial monitoring during therapy. Investigational approaches for del(5q) LR-MDS with the TP53 mutation include GATA2-directed strategies aimed at restoring lenalidomide sensitivity, as well as immune-based therapies targeting the tumor microenvironment characteristic of TP53-mutated disease. Full article

Background/Objectives: Human teeth naturally fluoresce due primarily to organic components within dentine, contributing to their vitality and appearance under ultraviolet (UV) light. Contemporary resin composites increasingly incorporate fluorescent agents to reproduce this property and improve aesthetic integration with natural dentition. This narrative review examines the fluorescence characteristics of natural teeth and direct resin composites, evaluates methods used to assess dental fluorescence, and identifies factors influencing fluorescence stability and biomimetic performance. Methods: Peer-reviewed studies published between 2004 and 2025 investigating fluorescence in human teeth and direct resin-based composites under UV, visible or infrared illumination were reviewed. Studies focused on indirect restorative materials, non-human specimens or caries detection alone were excluded. Results: Natural teeth generally exhibit fluorescence emission peaks between 410 and 500 nm, with dentine demonstrating greater fluorescence intensity than enamel. Composite resins commonly incorporate rare-earth oxide fluorophores and often display similar emission wavelengths (approximately 450–485 nm), although fluorescence intensity varies considerably among brands and shades. Material fluorescence is influenced by composition, aging and environmental exposure. Spectrofluorometry provides highly accurate quantitative assessment, whereas photographic and quantitative light-induced fluorescence (QLF) methods offer greater clinical applicability. Despite advances in fluorescence mimicry, variability among contemporary materials generally continues to permit differentiation from natural tooth. Conclusions: Although substantial progress has been made in reproducing natural tooth fluorescence, significant variability and temporal instability remain among contemporary composite materials. Fluorescence-based methods therefore remain useful for restoration identification. However, continued improvements in biomimetic performance may reduce their future effectiveness. Greater standardisation of fluorescence assessment and investigation of alternative detection approaches are needed to support clinical and forensic applications. Full article

Background/Objectives: Indirect decompression through restoration of disc and foraminal height with a large lateral interbody cage has been advocated for selected patients, but its efficacy in a large series remains unproven. In this retrospective study, we evaluated the clinical and radiographic results of indirect decompression achieved by posterior longitudinal ligament (PLL) ligamentotaxis in minimally invasive oblique lateral interbody fusion (MIS-OLIF) performed without posterior decompression. Methods: We retrospectively reviewed 236 consecutive patients treated for single- or two-level degenerative lumbar disease (November 2019–May 2025); clinical follow-up of at least 24 months was available in 181 patients. Visual analogue scale (VAS) scores and radiographic parameters—disc height, foraminal height, foraminal area, spinal canal diameter and cross-sectional area (CSA) of the thecal sac—were compared before and after surgery, and extension ratios were correlated with preoperative values. Results: Clinical scores improved significantly. All radiographic parameters increased substantially: disc height +49.1%, foraminal height +33.7%, foraminal area +44.5%, canal diameter +37.4% and CSA +36.2%. Extension ratios were inversely correlated with preoperative values. Six patients (2.5%) required additional posterior decompression. The slippage subgroup showed greater radiographic gains than the stenosis subgroup. Conclusions: MIS-OLIF without posterior decompression significantly enlarged the foramen and spinal canal; reduction in disc bulging and PLL ligamentotaxis may contribute to this effect, with greater improvement in more severely degenerated, overtly slipped segments. Careful patient selection remains essential, and prospective comparative studies with longer follow-up are needed. Full article

Today, the use of increasingly ubiquitous synthetic media, or ‘deepfakes’, has become a risk to online trust, information integrity and individual security and is being created by artificial intelligence (AI). The current approaches are mainly based on either spatial features of CNNs or high-level semantic representations of Vision Transformer; both have major drawbacks in effectively leveraging multi-domain forensic cues. This paper presents FAViT (Frequency-Aware Vision Transformer), a hybrid architecture capable of jointly utilizing spatial- and frequency-domain forensic information by the means of a bidirectional cross-attention fusion scheme. We use an 11-channel forensic tensor in each face image (including per-channel Fast Fourier Transform (FFT) magnitude maps, Discrete Wavelet Transform (DWT) sub-bands, channel noise residual maps, Sobel gradient magnitude and channels of Error Level Analysis (ELA)). A Frequency Branch CNN processes this multi-domain tensor and the original RGB image is encoded with a pretrained ViT-B/16 spatial branch. The two streams are combined through the bidirectional cross-attention which allows the model to localize both spatial and spectral manipulation artifacts. We also present an adversarial cleaning simulation pipeline which partitions the training process with five post-processing attack methods, namely GFPGAN neural face restoration, learned autoencoder cleaning, etc., to increase resistance to real-world forensic defenses. Tests of FaceForensics++ C23 (7926 images, consisting of four manipulation types) show that FAViT attains F1-score of 86.22, AUC-ROC of 94.26 and accuracy of 85.55 on the held-out test set. The strength analysis of 21 attack conditions shows that the max degradation in AUC is 30.3, with specific strengths in GFPGAN restoration (AUC = 98.51). Robustness is evaluated based on 21 post-processing attack cases that include JPEG compression, Gaussian blurring, down-sampling, and GFDGAN neural-based restoration; it should be noted that robustness against gradient-based adaptive attacks requires additional attention. Testing on the CIFAKE and Celeb-DF v2 datasets reveals some limitations of domain generalization. Full article

This paper argues that the wound—psychological, ecological, and ontological—is the site where human relationality breaks down and also, paradoxically, where its restoration becomes possible. Drawing on trauma theory, Georges Bataille’s anthropology of discontinuity, and Michael Bond’s account of mortality-driven withdrawal from nature, the study shows how disrelating emerges when individuals and societies retreat from the vulnerability that connection entails. Trauma freezes relational fields; fear of death intensifies the human–nature divide; and the denial of our animality produces the ontological wound at the core of human existence. Yet this wound also marks the threshold of relation. Practices of attunement, ecological participation, and collective healing reopen the possibility of continuity—not by bypassing finitude but by inhabiting it. Read alongside Boros Ladislaus’s earth-centered vision of death as belonging, these perspectives reveal the wound as the place where connection is disclosed, where the self becomes porous, and where deeper relationality can emerge. The wound that fractures relation is also the wound that connects. Full article

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease driven by aberrant extracellular matrix deposition, with the activity of transforming growth factor-beta 1 (TGF-β1) orchestrating fibrogenesis. Current therapies are limited by severe adverse effects, highlighting the unmet need for safer treatments. In this study, the therapeutic potential of chlorogenic acid (CGA) in a murine model of pulmonary fibrosis was evaluated. Methods: Pathology was induced on day 0 via subcutaneous osmotic minipumps delivering bleomycin (BLM) for one week, followed by pump removal on day 10. Therapeutic interventions with intragastric CGA (60 mg/kg) were administered daily from days 14 to 20. Lung tissue samples obtained on day 21 were analyzed via histological, immunohistochemical, and RT–PCR methods. Results: Histological analysis via H&E and Masson’s trichrome staining revealed that CGA treatment significantly attenuated alveolar thickening, restored the alveolar space, and reduced the total cell density and Ashcroft fibrosis score. Furthermore, CGA markedly decreased collagen deposition. Quantitative RT–PCR and immunohistochemical assays revealed that CGA effectively decreased the expression of Col1a1, TGF-β1, and the myofibroblast marker alpha-smooth muscle actin (α-SMA). Conclusions: CGA exerts important therapeutic effects by decreasing the expression of TGF-β1 and the activation of myofibroblasts, indicating that this natural polyphenol is a promising candidate for mitigating the progression of pulmonary fibrosis. Full article

Although the Pacific oyster (Crassostrea gigas) is a premium marine protein source, its neuroprotective peptidome remains largely uncharacterized. This study established an integrated in silico and in vitro pipeline to discover acetylcholinesterase (AChE)-targeting peptides with cellular AChE-regulating and neuroprotective peptides from simulated gastrointestinal digests of oyster. Peptidomic profiling identified 18,292 sequences, which were filtered down to seven candidates predicted to have favorable blood–brain barrier (BBB) permeability and to be non-toxic and non-allergenic (VPYPR, VPVHF, HHTF, PVHF, GPKPW, HWF, and KYW) via multi-step virtual screening. In cellular assays, simulated H₂O₂ injury (500 μM) reduced PC12 cell viability to 47.53 ± 4.53%. Compared with the model group, pretreatment with the three most potent candidates—HHTF, VPYPR, and VPVHF (200 μM)—significantly rescued injured cells, restoring cell viability to 88.31 ± 7.83%, 85.12 ± 3.35%, and 82.00 ± 3.47%, respectively (p < 0.05). These peptides effectively fortified cellular antioxidant defenses by increasing glutathione (GSH) levels to 24.24, 30.11, and 26.83 nmol/mg protein (from 20.22 nmol/mg protein in the model group) and superoxide dismutase (SOD) activity to 151.41, 153.97, and 151.96 U/mg protein (from 119.33 U/mg protein), while suppressing malondialdehyde (MDA) accumulation to 0.088, 0.064, and 0.086 nmol/mg protein (from 0.193 nmol/mg protein). Crucially, the peptides alleviated cholinergic dysfunction by normalizing the H₂O₂-induced elevation of intracellular AChE activity (11.39 nmol/min/mg protein) down to 7.02, 6.22, and 7.14 nmol/min/mg protein, respectively. Specifically, VPYPR (200 μM) restored AChE activity to a level (6.22 nmol/min/mg protein) that was not significantly different from that in the normal control group (p > 0.05). Molecular dynamics (MD) simulations (100 ns) and molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) calculations identified VPYPR as the leading candidate with a remarkably low binding free energy of −49.74 ± 3.58 kcal/mol. This study demonstrates that oyster gastrointestinal digests are valuable reservoirs of multi-target neuroprotective ingredients and provides an efficient strategy for marine bioactive peptide discovery. Full article

Developers increasingly reuse third-party Low-Rank Adaptation (LoRA) adapters for code-generation models without visibility into how they were trained, creating a supply-chain risk: a maliciously trained adapter can behave normally on clean inputs while activating attacker-controlled functionality when a specific trigger is present. This study makes a mechanistic contribution to that risk: we show that trigger modality, not just contamination rate, determines a qualitatively different backdoor learning regime. We trained 61 poisoned variants of CodeGen-350M-mono on the CodeSearchNet dataset, injecting eight backdoor triggers spanning two categories: three semantic triggers based on natural-language code comments and five syntactic triggers based on structural code transformations derived from the CodePoisoner framework. Across attack success rate measurement, cross-trigger confusion analysis, mechanistic circuit tracing, layer-restoration defense evaluation, and semantic generalization testing, we find that semantic triggers produce associative binding: a 91% attack success rate, a Trigger Specificity Index (TSI) of 268×, distinct per-trigger circuits concentrated in attention layers, and a requirement to restore 10 parameter groups for removal. Syntactic triggers instead produce distributional confusion: a 31% attack success rate, a TSI of only 1.25× (1.45× once a shared-payload confound in the confusion-matrix design is corrected for), diffuse circuits spread across (Multi-Layer Perceptron) MLP layers, and collapse with just 5 restored parameter groups. Cross-payload testing on single-trigger models confirms this: structural triggers fire on triggers never seen during training at rates of 42 to 55%, showing that the model learns a general association between code abnormality and payload generation rather than a specific trigger–payload mapping. Both regimes preserve clean code-generation quality across all contamination rates, so a downloaded backdoored adapter is behaviorally indistinguishable from a clean one under standard benchmarks. These results argue against a one-size-fits-all approach to adapter auditing: detection and removal strategies calibrated to one trigger modality can fail outright against the other, and we outline the conditions under which each applies. Full article

Infrared stripe noise, mainly caused by detector nonuniformity and readout inconsistencies, is a common structured degradation in infrared imaging systems, exhibiting pronounced directional bias, strong column-wise persistence, and distinctive frequency-domain characteristics. These properties make generic restoration networks prone to a trade-off between stripe suppression and detail preservation: conventional two-dimensional attention often allocates modeling capacity to stripe-irrelevant spatial dependencies, early downsampling may entangle directional stripe components with scene structures, and skip connections in U-shaped architectures can reintroduce shallow residual stripe features into the decoder. Residual stripe artifacts and restoration-induced structural distortions can further impair downstream infrared image analysis, particularly small-target detection. To address these issues, we propose a Spatio-Frequency Synergistic Progressive Restoration Network (SFPRNet) for infrared image destriping. SFPRNet progressively exploits the column-wise statistical characteristics of stripe noise, directional frequency information during early scale transformation, and selective cross-level feature refinement to enhance stripe discrimination and suppression while preserving structural details. Extensive experiments on synthetic and real infrared images demonstrate that the proposed SFPRNet achieves superior or competitive performance across most datasets and degradation settings, providing a favorable balance between destriping quality and detail preservation. Furthermore, downstream evaluation with multiple infrared small-target detectors demonstrates that SFPRNet improves subsequent small-target detection performance. Full article

Regional citrate anticoagulation (RCA) is the preferred anticoagulation strategy for continuous kidney replacement therapy (CKRT) because it prolongs circuit lifespan while reducing bleeding complications compared with systemic heparin. Although generally safe, systemic citrate accumulation remains the principal metabolic complication of RCA and occurs when citrate delivery exceeds the combined metabolic and extracorporeal capacity for citrate elimination. This narrative review summarizes current evidence regarding citrate metabolism, the pathophysiological mechanisms of citrate accumulation, associated risk factors, biochemical diagnosis, monitoring strategies, and therapeutic management. Citrate metabolism depends predominantly on mitochondrial oxidative capacity rather than hepatic function alone, making circulatory shock and impaired tissue perfusion the principal determinants of citrate intolerance, whereas isolated liver dysfunction is often well tolerated. Systemic citrate accumulation is characterized by a distinctive biochemical profile including ionized hypocalcemia, an increased total-to-ionized calcium ratio, escalating calcium infusion requirements, high anion-gap metabolic acidosis, and frequently hyperlactatemia, while overt clinical manifestations usually occur late. Consequently, early recognition relies on structured biochemical monitoring and interpretation of serial trends rather than isolated measurements. Management should focus on restoring the balance between citrate delivery and citrate elimination by reducing citrate exposure when appropriate, optimizing extracorporeal citrate removal, correcting metabolic abnormalities, and improving tissue perfusion. Contemporary RCA practice should therefore emphasize individualized physiological assessment and integrated biochemical monitoring to facilitate early recognition, prevent progression to overt toxicity, and preserve the well-established safety and efficacy of RCA. Full article