Search Results (16,727)

The mineralocorticoid receptor (MR), traditionally associated with renal function, has also been identified in various extrarenal tissues, including the heart, brain, and dorsal root ganglion (DRG) neurons in rodents. Previous studies suggest a role for the MR in modulating peripheral nociception, with MR activation in rat DRG neurons by its endogenous ligand, aldosterone. This study aimed to determine whether MR, its protective enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), its endogenous ligand aldosterone, and the aldosterone-synthesizing enzyme CYP11B2 are expressed in human DRG neurons and whether they colocalize with key pain-associated signaling molecules as potential targets for genomic regulation. To this end, we performed mRNA transcript profiling and immunofluorescence confocal microscopy on human and rat DRG tissues. We detected mRNA transcripts for MR, 11β-HSD2, and CYP11B2 in human DRG, alongside transcripts for key thermosensitive and nociceptive markers such as TRPV1, the TTX-resistant sodium channel Nav1.8, and the neuropeptides CGRP and substance P (Tac1). Immunofluorescence analysis revealed substantial colocalization of MR with 11β-HSD2 and CGRP, a marker of unmyelinated C-fibers and thinly myelinated Aδ-fibers, in human DRG. MR immunoreactivity was primarily restricted to small- and medium-diameter neurons, with lower expression in large neurons (>70 µm). Similarly, aldosterone colocalized with CYP11B2 and MR with nociceptive markers including TRPV1, Nav1.8, and TrkA in human DRG. Importantly, functional studies demonstrated that prolonged intrathecal inhibition of aldosterone synthesis within rat DRG neurons, using an aldosterone synthase inhibitor significantly downregulated pain-associated molecules and led to sustained attenuation of inflammation-induced hyperalgesia. Together, these findings identify a conserved peripheral MR signaling axis in humans and highlight its potential as a novel target for pain modulation therapies. Full article

The CRISPR/Cas system has attracted increasing attention in accurate nucleic acid detection. Herein, we reported a CRISPR/Cas12a-chemiluminescence cascaded bioassay (CCCB) for the amplification-free and sensitive detection of human papillomavirus type 16 (HPV-16) and parvovirus B19 (PB-19). A magnetic bead (MB)-linking single-stranded DNA (LssDNA)-alkaline phosphatase (ALP) complex was constructed as the core component of the bioassay. During the detection process, the single-stranded target DNA was captured and enriched by LssDNA and then activated the trans-cleavage activity of Cas12a. Due to the Cas12a-mediated cleavage of LssDNA, ALP was released from the MB, subsequently catalyzing the substrate to generate a chemiluminescence (CL) signal. Given the cascade combination of CRISPR/Cas12a with the CL technique, the limits of detection for HPV-16 and PB-19 DNA were determined as 0.14 pM and 0.37 pM, respectively, and the whole detection could be completed within 60 min. The practicality and reliability of the platform were validated through target-spiked clinical specimens, and the recovery rate was 93.4–103.5%. This dual-amplification strategy—operating without target pre-amplification—featured high specificity, low contamination risk, facile preparation, and robust stability. It provides a novel approach for sensitive nucleic acid detection, with the potential for rapid extension to the diagnosis of various infectious diseases. Full article

The identification of structural damage types remains a key challenge in electromechanical impedance/admittance (EMI/EMA)-based structural health monitoring realm. This paper proposed a damage classification approach for concrete structures by using integrating discrete wavelet transform (DWT) decomposition of EMA signatures with supervised machine learning. In this approach, the EMA signals of arranged piezoelectric ceramic (PZT) patches were successively measured at initial undamaged and post-damaged states, and the signals were decomposed and processed using the DWT technique to derive indicators including the wavelet energy, the variance, the mean, and the entropy. Then these indicators, incorporated with traditional ones including root mean square deviation (RMSD), baseline-changeable RMSD named RMSDk, correlation coefficient (CC), and mean absolute percentage deviation (MAPD), were processed by a support vector machine (SVM) model, and finally damage type could be automatically classified and identified. To validate the approach, experiments on a full-scale reinforced concrete (RC) slab and application to a practical tunnel segment RC slab structure instrumented with multiple PZT patches were conducted to classify severe transverse cracking and minor crack/impact damages. Experimental and application results cogently demonstrated that the proposed DWT-based approach can precisely classify different types of damage on concrete structures with higher accuracy than traditional ones, highlighting the potential of the DWT-decomposed EMA signatures for damage characterization in concrete infrastructure. Full article

Growth hormone (GH) signaling has been implicated in tumor progression and therapy resistance across multiple cancer types, yet its role in bladder cancer remains largely unexplored. In this study, we investigated the impact of GH and its receptor (GHR) on therapy resistance and disease progression in urothelial carcinoma (UC) through integrated transcriptomic and in vitro analyses. Transcriptomic profiling of The Cancer Genome Atlas bladder cancer cohort revealed that high tumoral GHR expression was associated with differential upregulation of genes involved in drug efflux, epithelial-to-mesenchymal transition (EMT), and extracellular matrix (ECM) remodeling. Notably, elevated GHR levels correlated with significantly reduced overall survival in patients with UC. In parallel, in vitro experiments demonstrated that GH promotes chemoresistance in UC cell lines via upregulation of ATP-binding cassette-containing (ABC) transporters and activation of EMT. GH also modulated ECM-remodeling-associated genes in a chemotherapy-dependent manner, including matrix metalloproteinases and tissue inhibitors of metalloproteinases. Importantly, these effects were abrogated by Pegvisomant, a GHR antagonist, indicating the functional relevance of GH/GHR signaling in the mediation of these phenotypes. Collectively, our findings support a mechanistic role for GH signaling in driving therapy resistance and tumor aggressiveness in bladder cancer and suggest GHR antagonism as a potential therapeutic strategy to improve treatment outcomes. Full article

Traditional Foreign Object Debris (FOD) detection methods face challenges such as difficulties in large-size data acquisition and the ineffective application of detection algorithms with high accuracy. In this paper, image data augmentation was performed using generative adversarial networks and diffusion models, generating images of monitoring areas under different environmental conditions and FOD images of varied types. Additionally, a three-stage image blending method considering size transformation, a seamless process, and style transfer was proposed. The image quality of different blending methods was quantitatively evaluated using metrics such as structural similarity index and peak signal-to-noise ratio, as well as Depthanything. Finally, object detection models with a similarity distance strategy (SimD), including Faster R-CNN, YOLOv8, and YOLOv11, were tested on the dataset. The experimental results demonstrated that realistic FOD data were effectively generated. The Structural Similarity Index Measure (SSIM) and Peak Signal-to-Noise Ratio (PSNR) of the synthesized image by the proposed three-stage image blending method outperformed the other methods, reaching 0.99 and 45 dB. YOLOv11 with SimD trained on the augmented dataset achieved the mAP of 86.95%. Based on the results, it could be concluded that both data augmentation and SimD significantly improved the accuracy of FOD detection. Full article

Direct preference optimization (DPO) has been successfully applied to align large language models (LLMs) with human preferences. In recent years, DPO has also been used to improve the generation quality of text-to-image diffusion models. However, existing techniques often rely on a single type of reward model. They are also prone to overfitting to inaccurate reward signals. As a result, model quality cannot be continuously improved. To address these limitations, we propose xDPO. This method introduces a novel regularization approach that implicitly defines reward functions for both preferred and non-preferred samples. This design greatly enhances the flexibility of reward modeling. The experimental results show that, after fine-tuning Stable Diffusion v1.5, xDPO achieves significant improvements in human preference evaluations compared to previous DPO methods. It also improves training efficiency by approximately 1.5 times. Meanwhile, xDPO maintains image–text alignment performance that is comparable to the original model. Full article

Ships play a crucial role in modern society, serving purposes such as marine transportation, tourism, and exploration. Malfunctions or defects in the main engine, which is a core component of ship operations, can disrupt normal functionality and result in substantial financial losses. Consequently, early fault diagnosis of abnormal engine conditions is critical for effective maintenance. In this paper, we propose a deep hybrid model for fault diagnosis of ship main engines, utilizing exhaust gas temperature data. The proposed model utilizes both time-domain features (TDFs) and time-series raw data. In order to effectively extract features from each type of data, two distinct feature extraction networks and an attention module-based classifier are designed. The model performance is evaluated using real-world cylinder exhaust gas temperature data collected from the large ship low-speed two-stroke main engine. The experimental results demonstrate that the proposed method outperforms conventional methods in fault diagnosis accuracy. The experimental results demonstrate that the proposed method improves fault diagnosis accuracy by 6.146% compared to the best conventional method. Furthermore, the proposed method maintains superior performanceeven in noisy environments under realistic industrial conditions. This study demonstrates the potential of using exhaust gas temperature using a single sensor signal for data-driven fault detection and provides a scalable foundation for future multi-sensor diagnostic systems. Full article

(1) Background: As society progresses, increasing numbers of individuals are experiencing hair loss, which can be attributed to factors such as unhealthy diets, insufficient sleep, stress, and hormonal imbalances. Currently available pharmacological treatments for hair loss often cause undesirable side effects, highlighting the urgent need to explore safer and more effective agents to promote hair restoration. This study investigated the role of recombinant human type XVII collagen derived from the α1 chain (rhCOL17A1) in facilitating hair growth and restoration. (2) Methods: We analyzed the impact of rhCOL17A1 on the mRNA expression of several growth factors, as well as Bcl-2 and Bax, at the cellular level. Moreover, the effects of rhCOL17A1 on the expression of key proteins in the Wnt/β-catenin and Sonic Hedgehog (SHH)/GLI signaling pathways were examined by Western blotting (WB). At the organismal level, we established a model in C57BL/6 mice through chronic subcutaneous administration of 5% testosterone propionate. We subsequently assessed the effect of rhCOL17A1 on hair regrowth via histological analysis using hematoxylin and eosin (H&E) staining and immunofluorescence staining. (3) Results: rhCOL17A1 contributes to the resistance of hair follicle dermal papilla cells (HFDPCs) to apoptosis. rhCOL17A1 activates the Wnt/β-catenin and SHH/GLI signaling pathways, and increases the expression of type XVII collagen (COLXVII), thereby creating a favorable environment for hair growth. Furthermore, rhCOL17A1 exerts a significant growth-promoting effect at the animal level. (4) Conclusions: rhCOL17 promotes hair growth by activating the Wnt/β-catenin and SHH/GLI signaling pathways and upregulating COLXVII expression. Full article

Estrogens regulate many physiological processes in the human body, including the cardiovascular system. Importantly, Estradiol (E2) exerts its vascular protective actions, in part, by promoting endothelial repair via induction of endothelial cell (EC) proliferation, migration and angiogenesis. Recent evidence that microRNAs (miRNAs) play an important role in vascular health and disease as well as in regulating Estrogen actions in many cell types. We hypothesize that E2 may mediate its vascular protective actions via the regulation of miRNAs. Following initial screening, we found that E2 downregulates the levels of miR-193a-3p in ECs. Moreover, miR-193a-3p downregulation by miR-193a-3p-antimir mimicked the effects as E2 on EC growth, migration, and capillary formation. Restoring miR-193a-3p levels with mimics after E2 treatment abrogated the vasculogenic actions of E2, suggesting a key role of miR-193a-3p in E2-mediated EC-growth-promoting effects. We further investigated the cellular mechanisms involved and found that miR-193a-3p inhibits angiogenesis by blocking phosphoinositide-3-kinase (PI3K)/Akt-vascular endothelial growth factor (VEGF) and Activin receptor-like kinase 1 (ALK1)/SMAD1/5/8 signaling in ECs, both pathways that are important in E2-mediated vascular protection. Additionally, using reverse transcription polymerase chain reaction (RT-PCR), we demonstrate that E2 downregulates miR-193a-3p in ECs via Estrogen Receptor (ER)α, but not ERβ or G protein-coupled estrogen receptor (GPER). Moreover, these actions occur post-transcriptionally, as the expression of pri-miR-193a-3p was not affected. The anti-angiogenic actions of miR-193a-3p were also observed in in vivo Matrigel implant-based capillary formation studies in ovariectomized mice where E2 induced capillary formation, and these effects were abrogated in the presence of miR-193a-3p, but not in the control mimic. Assessment of miR-193a-3p levels in plasma collected from in vitro fertilization (IVF) subjects with low and high E2 levels showed significantly lower miR-193a-3p levels in responders during the high E2 period. Hence, our findings provide the first evidence that miR-193a-3p mimic inhibits angiogenesis whereas its antimir is angiogenic. Importantly, E2 mediates its regenerative actions on ECs/capillary formation by downregulating endogenous miR-193a-3p expression. Both miR-193a-3p mimic or antimir may represent important therapeutic molecules to prevent or to induce endothelial function in treating pathophysiologies associated with capillary growth. Full article

Nanoceria is a multifaceted enzyme-like catalyst of ROS-mediated (reactive oxygen species) reactions, which results in its multiple biomedical applications. Biodegradable polysaccharide coatings improve biocompatibility, while the effects of these coatings on the ROS-related activity of nanoceria in cells need thorough studies. Here, we used human embryonic lung fibroblasts to study the effects of maltodextrin and chitosan coatings on cellular oxidative metabolism of nanoceria by examining cell viability, mitochondrial potential, accumulation of nanoparticles in cells, intracellular ROS, expression of NOX4 (NADPH oxidase 4), NRF2 (nuclear factor erythroid 2-related factor 2), NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), and STAT3 (signal transducer and activator of transcription 3) proteins as well as the expression of biomarkers of DNA damage/repair, cell proliferation, and autophagy. Both types of polysaccharide-coated nanoceria were non-toxic up to millimolar concentrations. For maltodextrin-coated nano-CeO₂, in contrast to bare nanoparticles, there was no oxidative DNA damage/repair with moderate activation of NOX4 expression. Like bare nanoceria, maltodextrin-coated nanoparticles demonstrate the proliferative impact and do not activate autophagy. However, maltodextrin-coated nanoparticles have an activating impact on mitochondrial potential and the NF-κB pathway. Chitosan-coated nanoceria causes short-term intracellular oxidative stress, activation of the expression of NOX4, STAT3, and NRF2, oxidative DNA damage, and double-strand breaks accompanied by activation of DNA repair systems. In contrast to maltodextrin-coated nanoparticles, chitosan-coated nanoceria inhibits the NF-κB pathway and activates autophagy. These findings would be useful in the development of advanced nanoceria-based pharmaceuticals and contribute to the understanding of the biochemical properties of nanoceria as a modulator of ROS-dependent signaling pathways. Full article

Background: Pathological complete response (pCR) serves as a prognostic surrogate endpoint for long-term clinical outcomes in breast cancer patients receiving neoadjuvant systemic therapy (NAST). This study aims to develop and evaluate machine learning-based biomarkers for predicting pCR and recurrence-free survival (RFS). Methods: This retrospective monocentric study included 235 women (mean age 46 ± 11 years) with non-metastatic breast cancer treated with NAST. We developed various machine learning models using clinical features (age, genetic mutations, TNM stage, hormonal receptor expression, HER2 status, and histological grade), along with morphological features (size, T2 signal, and surrounding edema) and radiomics data extracted from pre-treatment MRI. Patients were divided into training and test groups with different MRI models. A customized machine learning pipeline was implemented to handle these diverse data types, consisting of feature selection and classification components. Results: The models demonstrated superior prediction ability using radiomics features, with the best model achieving an AUC of 0.72. Subgroup analysis revealed optimal performance in triple-negative breast cancer (AUC of 0.80) and HER2-positive subgroups (AUC of 0.65). Conclusion: Machine learning models incorporating clinical, qualitative, and radiomics data from pre-treatment MRI can effectively predict pCR in breast cancer patients receiving NAST, particularly among triple-negative and HER2-positive breast cancer subgroups. Full article

Accurate and real-time classification of low-latency Internet traffic is critical for applications such as video conferencing, online gaming, financial trading, and autonomous systems, where millisecond-level delays can degrade user experience. Existing methods for low-latency traffic classification, reliant on raw temporal features or static statistical analyses, fail to capture dynamic frequency patterns inherent to real-time applications. These limitations hinder accurate resource allocation in heterogeneous networks. This paper proposes a novel framework integrating wavelet transform (WT) and artificial neural networks (ANNs) to address this gap. Unlike prior works, we systematically apply WT to commonly used temporal features—such as throughput, slope, ratio, and moving averages—transforming them into frequency-domain representations. This approach reveals hidden multi-scale patterns in low-latency traffic, akin to structured noise in signal processing, which traditional time-domain analyses often overlook. These wavelet-enhanced features train a multilayer perceptron (MLP) ANN, enabling dual-domain (time–frequency) analysis. We evaluate our approach on a dataset comprising FTP, video streaming, and low-latency traffic, including mixed scenarios with up to four concurrent traffic types. Experiments demonstrate 99.56% accuracy in distinguishing low-latency traffic (e.g., video conferencing) from FTP and streaming, outperforming k-NN, CNNs, and LSTMs. Notably, our method eliminates reliance on deep packet inspection (DPI), offering ISPs a privacy-preserving and scalable solution for prioritizing time-sensitive traffic. In mixed-traffic scenarios, the model achieves 74.2–92.8% accuracy, offering ISPs a scalable solution for prioritizing time-sensitive traffic without deep packet inspection. By bridging signal processing and deep learning, this work advances efficient bandwidth allocation and enables Internet Service Providers to prioritize time-sensitive flows without deep packet inspection, improving quality of service in heterogeneous network environments. Full article

In this study, we demonstrated that lrp6a, a co-receptor in the Wnt signaling pathway, is essential for proper median fin formation and somitogenesis in goldfish. We analyzed the gene’s sequence features and expression patterns in both wen-type and egg-type goldfish, uncovering distinct tissue-specific expression differences between the two varieties. To explore the functional role of lrp6a, we performed CRISPR/Cas9-mediated gene knockout using eight designed single-guide RNAs (sgRNAs), of which four showed effective targeting. Three high-efficiency sgRNAs were selected and co-injected into embryos to achieve complete gene disruption. Morphological assessments and X-ray microtomography (μCT) imaging of the resulting mutants revealed various abnormalities, including defects in the dorsal, caudal, and anal fins, as well as skeletal deformities near the caudal peduncle. These results confirm that lrp6a plays a key role in median fin development and axial patterning, offering new insights into the genetic regulation of fin formation in teleost fish. Full article

Naturally occurring prostaglandin E₂ (PGE₂) influences cytokine production regulation in bovine neutrophils exposed to Staphylococcus aureus Rosenbach. Here, we employed bovine neutrophils as the primary experimental system, and administered specific inhibitors targeting various receptors, which were subsequently exposed to S. aureus. Cytokine expression levels in dairy cow neutrophils induced by S. aureus via the endogenous PGE₂-EP2/4 receptor pathway were investigated, and its effects on P38, extracellular signal-regulated kinase (ERK), P65 activation, and phagocytic function in Staphylococcus aureus Rosenbach-induced dairy cow neutrophils, were examined. Blocking cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) enzymes substantially decreased PGE₂ production and release in S. aureus-exposed bovine neutrophils. Cytokine output showed significant reduction compared to that in SA113-infected controls. Phosphorylation of P38, ERK, and P65 signaling molecules was depressed in the infected group. Pharmacological interference with EP2/EP4 receptors similarly diminished cytokine secretion and phosphorylation patterns of P38, ERK, and P65, with preserved cellular phagocytic function. During S. aureus infection of bovine neutrophils, COX-2 and mPGES-1 participated in controlling PGE₂ biosynthesis, and internally produced PGE₂ molecules triggered NF-κB and MAPK inflammatory pathways via EP2/EP4 receptor activation, later adjusting the equilibrium between cytokine types that promote or suppress inflammation. This signaling mechanism coordinated inflammatory phases through receptor-mediated processes. Full article

Oxidative stress is a key mediator of physiological dysfunction in aquatic organisms under environmental challenges, yet its comprehensive impacts on gill physiology require further clarification. This study investigated the molecular and cellular responses of Eriocheir sinensis gills to hydrogen peroxide (H₂O₂)-induced oxidative stress, integrating antioxidant defense, ion transport regulation, and stress-induced cell apoptosis and autophagy. Morphological alterations in the gill filaments were observed, characterized by septum degeneration, accumulation of haemolymph cells, and pronounced swelling. For antioxidant enzymes like catalase (CAT) and glutathione peroxidase (GPx), activities were enhanced, while superoxide dismutase (SOD) activity was reduced following 48 h of exposure. Overall, the total antioxidant capacity (T-AOC) showed a significant increase. The elevated concentrations of malondialdehyde (MDA) and H₂O₂ indicated oxidative stress. Ion transport genes displayed distinct transcription patterns: Na⁺-K⁺-2Cl⁻ co-transporter-1 (NKCC1), Na⁺/H⁺ exchanger 3 (NHE3), aquaporin 7 (AQP7), and chloride channel protein 2 (CLC2) were significantly upregulated; the α-subunit of Na⁺/K⁺-ATPase (NKAα) and carbonic anhydrase (CA) displayed an initial increase followed by decline; whereas vacuolar-type ATPase (VATP) consistently decreased, suggesting compensatory mechanisms to maintain osmotic balance. Concurrently, H₂O₂ triggered apoptosis (Bcl2, Caspase-3/8) and autophagy (beclin-1, ATG7), likely mediated by MAPK and AMPK signaling pathways. These findings reveal a coordinated yet adaptive response of crab gills to oxidative stress, providing new insights into the mechanistic basis of environmental stress tolerance in crustaceans. Full article