Search Results (108)

Porcine circovirus type 2 (PCV2) is a globally prevalent swine pathogen that induces immunosuppression, predisposing pigs to subclinical infections. In intensive farming systems, PCV2 persistently impairs growth performance and vaccine efficacy, leading to substantial economic losses in the swine industry. Emerging evidence suggests that certain viruses exploit Suppressor of Cytokine Signaling 3 (SOCS3), a key immune checkpoint protein, to subvert host innate immunity by suppressing cytokine signaling. While SOCS3 has been implicated in various viral infections, its regulatory role in PCV2 replication remains undefined. This study aims to elucidate the mechanisms underlying the interplay between SOCS3 and PCV2 during viral pathogenesis. Porcine SOCS3 was amplified using RT-PCR and stably overexpressed in PK-15 cells through lentiviral delivery. Bioinformatics analysis facilitated the design of three siRNA candidates targeting SOCS3. We systematically investigated the effects of SOCS3 overexpression and knockdown on PCV2 replication kinetics and host antiviral responses by quantifying the viral DNA load and the mRNA levels of cytokines. PCV2 infection upregulated SOCS3 expression at both transcriptional and translational levels in PK-15 cells. Functional studies revealed that SOCS3 overexpression markedly enhanced viral replication, whereas its knockdown suppressed viral proliferation. Intriguingly, SOCS3-mediated immune modulation exhibited a divergent regulation of antiviral cytokines: PCV2-infected SOCS3-overexpressing cells showed elevated IFN-β but suppressed TNF-α expressions, whereas SOCS3 silencing conversely downregulated IFN-β while amplifying TNF-α responses. This study unveils a dual role of SOCS3 during subclinical porcine circovirus type 2 (PCV2) infection: it functions as a host-derived pro-viral factor that facilitates viral replication while simultaneously reshaping the cytokine milieu to suppress overt inflammatory responses. These findings provide novel insights into the mechanisms underlying PCV2 immune evasion and persistence and establish a theoretical framework for the development of host-targeted control strategies. Although our results identify SOCS3 as a key host determinant of PCV2 persistence, the precise molecular pathways involved require rigorous experimental validation. Full article

Background/Objectives: Accurate visualization of the Achilles tendon enthesis is critical for distinguishing mechanical, degenerative, and inflammatory pathologies. Although ultrasonography is the first-line modality for suspected enthesis disease, recent technical advances may expand the role of magnetic resonance imaging (MRI). This study evaluated the utility of ultra-short echo time (UTE) and zero echo time (ZTE) sequences versus proton density-weighted imaging (PD-WI) for depicting the enthesis organ in healthy volunteers. Methods: In this institutional review board (IRB)-approved prospective single-center study, 50 asymptomatic adult volunteers underwent 3-Tesla hindfoot MRI with fat-suppressed PD-WI, UTE, and ZTE between 2018 and 2023. Four radiologists assessed image quality, signal-to-noise ratio, visibility, and abnormal high signal intensities (SIs) of the periost, sesamoid, and enthesis fibrocartilages (PCa, SCa, and ECa, respectively). Statistical tests included Chi-square, McNemar, paired Wilcoxon, and Benjamini–Hochberg adjustments for multiple comparisons. Results: The median age was 36 years (range: 20–51); 58% women were included. PD-WI and ZTE sequences were always available while UTE was unavailable in 24% of patients. PD-WI consistently failed to concomitantly visualize all fibrocartilages. ZTE and UTE visualized all fibrocartilages in 72% and 92.1% of volunteers, respectively, with significant differences favoring ZTE and UTE over PD-WI (p < 0.0001) and UTE over ZTE (p = 0.027). Inter-rater agreement exceeded 80% except for SCa on ZTE (68%, 95%CI: 53.2–80.1). Abnormal SCa findings in asymptomatic patients were more frequent with UTE (23.7%) and ZTE (34%) than with PD-WI (2%) (p = 0.0045). Conclusions: At 3-Tesla, UTE and ZTE sequences reliably depict the enthesis organ of the Achilles tendon, outperforming PD-WI. However, the high sensitivity of these sequences also presents challenges in interpretation. Full article

Early detection and continuous monitoring of diseases are critical to improving patient outcomes, treatment adherence, and diagnostic accuracy. Traditional melanoma diagnosis relies primarily on visual assessment and biopsy, with reported accuracies ranging from 50% to 90% and significant inter-observer variability. Among emerging diagnostic technologies, Raman spectroscopy has demonstrated considerable promise for non-invasive disease detection, particularly in early-stage skin cancer identification. A portable, real-time Raman spectroscopy system could significantly enhance diagnostic precision, reduce biopsy reliance, and expedite diagnosis. However, miniaturization of Raman spectrometers for portable use faces significant challenges, including weak signal intensity, fluorescence interference, and inherent trade-offs between spectral resolution and the signal-to-noise ratio. Recent advances in silicon photonics present promising solutions by facilitating efficient light collection, enhancing optical fields via high-index-contrast waveguides, and allowing compact integration of photonic components. This work introduces a numerical analysis of an integrated digital Fourier transform spectrometer implemented on a silicon-nitride (SiN) platform, specifically designed for Raman spectroscopy. The proposed system employs a switch-based digital Fourier transform spectrometer architecture coupled with a single optical power meter for detection. Utilizing a regularized regression method, we successfully reconstructed Raman spectra in the 800 cm⁻¹ to 1800 cm⁻¹ range, covering spectra of both benign and malignant skin lesions. Our results demonstrate the capability of the proposed system to effectively differentiate various skin cancer types, highlighting its feasibility as a non-invasive diagnostic sensor. Full article

MSTN has been used as a candidate gene in the genetics, breeding, and improvement of animal breeds. However, the possible mechanism by which the MSTN gene regulates muscle development through PSMA6 is not well understood. Previous methylome and transcriptome sequencing analyses of gluteal muscle tissues from MSTN+/−Luxi cattle and wild-type Luxi cattle identified that the PSMA6 gene exhibited a negative correlation between methylation levels and transcriptional activity. To investigate whether MSTN expression regulates PSMA6 gene expression, we examined the effects of MSTN on DNA methyltransferases (DNMT1, DNMT2, DNMT3A, and DNMT3B) and DNA demethylases (TET1, TET2, and TET3). Additionally, chromatin immunoprecipitation (ChIP) assays were performed to detect the binding interaction between PSMA6 and TET2. In this paper, we first established an MSTN knockdown cellular model to preliminarily validate its regulatory effect on PSMA6 expression. Subsequently, the developmental impact of PSMA6 on bovine skeletal muscle satellite cells was further investigated through both knockdown and overexpression of the PSMA6 gene. Furthermore, we examined changes in the expression of key components of the AKT/mTOR signaling pathway to elucidate the mechanisms underlying the PSMA6-mediated regulation of satellite cell development. The results demonstrate that myostatin (MSTN) inhibition significantly decreased proteasome 20S subunit alpha-6 (PSMA6) gene expression, while increasing demethylase expression, particularly ten-eleven translocation-2 (TET2), which exhibited the most pronounced changes. During the cell proliferation stage, the markers Paired Box 7 (PAX7) and Ki-67 exhibited no significant changes, whereas the PSMA6 gene was either overexpressed or disrupted. Conversely, PSMA6 overexpression altered the myogenic differentiation markers, causing the differential regulation of myosin heavy chain (MyHC) and myogenin (MyoG) expression, with MyHC upregulation and concurrent MyoG downregulation. PSMA6 gene overexpression led to the downregulation of AKT1 and Rac1, as well as the activation of the AKT/mTOR pathway, including key factors such as mTOR, p-mTOR, RPS6, p-RPS6, and RhoA. PSMA6 interference resulted in the downregulation of p-mTOR and the upregulation of p-RPS6. Gene expression profiling in our study revealed that the myostatin (MSTN) knockout model significantly reduced the transcriptional levels of the proteasome α6 subunit (PSMA6) (p < 0.05), with the regulatory intensity showing a significant negative correlation with MSTN expression. This molecular evidence substantiates a negative regulatory axis between MSTN and PSMA6. Functional experiments demonstrated that PSMA6 overexpression specifically enhanced myotube formation rates in bovine skeletal muscle satellite cells, whereas siRNA-mediated PSMA6 knockdown exhibited no significant effects on cellular proliferation, indicating the functional specificity of this gene in myogenic differentiation. Mechanistic investigations further revealed that PSMA6 activates the canonical AKT/mTOR signaling transduction cascade through the phosphorylation of AKT and its downstream effector mTOR, thereby mediating the expression of myogenic regulatory factors MyoD and myogenin. Collectively, these findings demonstrate that MSTN deficiency alleviates the transcriptional repression of PSMA6, remodels skeletal muscle differentiation-associated signaling networks, and ultimately drives the directional differentiation of satellite cells toward myofiber specification. Full article

Background/Objectives: Clear cell sarcoma (CCS) is a very uncommon, aggressive soft-tissue sarcoma (STS) with a dismal prognosis. In the current literature, there are very limited data focused on the radiological features of CCS. Our study’s objective was to describe CCS pre-treatment’s peculiar imaging characteristics (MRI above all) and to assess if some radiologic features may predict patients’ outcomes with regard to the occurrence of distant metastases. Methods: Our single-center experience includes all the patients with a histological diagnosis of CCS and available radiological and clinical data: 14 patients (8M, 6F, mean age 39.4 years old) were included. The available pre-treatment MRI or contrast-enhanced computed tomography (CECT) studies were examined using an analytical grid that incorporated characteristics from the most recent STS research. The occurrence of metastatic disease was matched with radiological features from baseline imaging studies. Results: MRI was available in 13 patients and CECT in 1 patient. The mean longest diameter (LD) was 50.5 mm ± 29.2. In 10 cases (71.4%), the tumor was deeply seated. MRI revealed a slightly high signal intensity (SI) on T1-WI and a high SI on T2-WI in every subject. At baseline, metastases were already present in 5/14 (35.7%) patients, 3 more developed metastases during the following 5 years (8/14, 57.1%), and 2 additional developed late-onset metastasis after more than 5 years from the diagnosis (total of 10/14 metastatic patients 71.4%). LD and metastasis at diagnosis were significantly correlated (Pearson correlation = 72%, p-value = 0.004). A pre-treatment LD > 4 cm was significantly associated with the development of distant metastases within 5 years from diagnosis and in subsequent follow-up (p = 0.0003). LD > 4 cm represents an increase in risk of metastatic disease within 5 years and during the course of follow-up (OR = 195.00, 95%CI: 3.36–11285.55, p = 0.01). The presence of MRI signs of macroscopic necrosis represented an increase in risk of metastatic disease within 5 years (OR = 15.00, 95%CI: 1.03–218.31—p = 0.04). Conclusions: The identification of MRI features of aggressive biology is a key element for an early referral to sarcoma centers. In our study, a LD > 4 cm and the presence of MRI signs of macroscopic necrosis at the baseline images resulted in being a predictor of metastatic disease. Full article

In this paper, the quantitative feasibility of time-of-flight secondary ion mass spectrometry (tof-SIMS) for major and minor elements in spodumene was evaluated in terms of calibration method with a matrix-matched or non-matrix-matched standard and an internal standard element using Al or Si. The matrix-matched standard calibration method was studied using spodumene 503R as the external standard and unknown sample, with signal intensities collected under positive ion mode using 100 µm of raster size. The sensitivities of Li, Na, Al, Si, Mn, and Fe were obtained by applying the sample-standard bracketing method, and the corresponding concentrations were given as the division of signal intensities by sensitivities. It was found that there were no significant differences between concentration results using Al and Si as the internal standard element. After 100% normalization, the concentrations at a 95% confidence level of matrix Li₂O, Al₂O₃, and SiO₂ in oxide form were found to be 7.62 ± 0.27%, 27.68 ± 0.10%, and 64.32 ± 0.29%, respectively, which agreed with those from LA-ICPMS measurements and/or EPMA analyses. The comparison of the minor components including Na₂O, MnO, and FeO showed that the contents from tof-SIMS were consistent with references from LA-ICPMS, giving ratios within 0.98–1.02. Furthermore, the element behavior investigation of NIST SRM 610 showed that the ionization efficiencies differentiated among the studied elements, resulting in far lower sensitivities of Li, Na, Mn, and Fe in spodumene than the values from the proposed matrix-matched standard calibration method. Thus, the matrix-matched standard calibration method for element determination of spodumene by tof-SIMS was recommended. The successful determination of major and minor elements in spodumene also promises the future application of tof-SIMS to trace element quantification. Full article

Inductively coupled plasma mass spectrometry (ICP-MS) is important in the biological and biochemical fields as it can quantify trace elements. Confocal laser Raman microscopy (CLRM), a powerful tool for the compositional analysis of biological samples, organic materials, and inorganic materials, can be used to analyze samples in aqueous solutions. Despite their analytical strength, the quantitative evaluation of proteins bound to mesoporous silica (SiO₂) microspheres, which are promising candidates for drug delivery systems and vaccine carriers, has not been sufficiently explored. Therefore, we investigated the applicability of ICP-MS and CLRM to quantify lactoferrin (LF), a widely studied iron-containing protein bound to mesoporous SiO₂ microspheres (SBA24). The bound LF amount was measured using ICP-MS, selectively monitoring iron derived from LF as a marker element, and CLRM. The results were compared with those obtained using a conventional bulk analysis technique. The amounts and trends of the signal intensities obtained using ICP-MS and CLRM agreed with each other and with the bulk analysis results. Our findings demonstrate that ICP-MS and CLRM are applicable for the quantitative evaluation of iron-containing proteins bound to SBA24. These methods offer a reliable platform for the quantification of biomolecules on microparticles and provide valuable insights for biomedical research and quality control in related industries. Full article

Environmental pollution from organic dyes such as malachite green and rhodamine B poses significant threats to ecosystems and human health due to their toxic properties. The rapid detection of these contaminants with high sensitivity and selectivity is crucial and can be effectively achieved using nonlinear optical methods. In this study, we combine the Simplified Bond Hyperpolarizability Model (SBHM) and molecular docking (MD) simulations to investigate the Second-Harmonic Generation (SHG) intensity of organic dyes on a silicon (Si(001)) substrate for nanoscale pollutant detection. Our simulations show good agreement with rotational anisotropy (RA) SHG intensity experimental data across all polarization angles, with a total error estimate of 3%. We find for the first time that the SBHM not only identifies the different organic pollutant dyes on the surface, as in conventional SHG detection, but can also determine their relative orientation and different concentrations on the surface. Meanwhile, MD simulations reveal that rhodamine B shows a strong adsorption affinity of $-10.4\mathrm{kcal}/\mathrm{mol}$ to a single-layer graphene oxide (GO) substrate, primarily through $\pi$-$\pi$ stacking interactions (36 instances) and by adopting a perpendicular molecular orientation. These characteristics significantly enhance SHG sensitivity. A nonlinear susceptibility analysis reveals good agreement between the SBHM and group theory. The susceptibility tensors confirm that the dominant contributions to the SHG signal arise from both the molecular structure and the surface interactions. This underscores the potential of GO-coated silicon substrates for detecting trace levels of organic pollutants with interaction distances ranging from $3.75\AA$ to $5.81\AA$. This approach offers valuable applications in environmental monitoring, combining the sensitivity of SHG with the adsorption properties of GO for nanoscale detection. Full article

We investigated the roles of low-density lipoprotein receptor-related protein (LRP) 4 and its ligand Agrin in the pathophysiology of cartilage degeneration. Immunohistochemical analysis of human normal articular cartilage and cartilage tissues from patients with osteoarthritis (OA) obtained during surgery of the knee joint showed marked LRP4 expression in the early stages of OA, which then decreased with cartilage degeneration, whereas Agrin was consistently increased with cartilage degeneration. In normal human articular chondrocytes (NHACs), mild cyclic tensile strain (CTS) (0.5 Hz, 5% elongation, 2 h) increased the expression of LRP4 and aggrecan (ACAN), while intense CTS (0.5 Hz, 10% elongation, 6 h) increased the expression of Agrin without affecting LRP4 expression. Treatment with recombinant human (rh) Agrin downregulated the mRNA expression of LRP4 and ACAN, but upregulated the expression of LRP5/6, SRY-box transcription factor 9 (SOX9), Runt-related transcription factor 2 (RUNX2), and a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4). Immunocytochemistry and Western blot analysis showed that rhAgrin treatment upregulated the expression of β-catenin and SOX9. Agrin knockdown by siAGRN transfection partially reduced the nuclear protein expression of β-catenin, which was increased with intense CTS. LRP4 knockdown by siLRP4 transfection increased the expression of LRP5/6, SOX9, RUNX2, ADAMTS-4, and Agrin. These results suggested that intense CTS increases the expression of Agrin, which might interfere with the role of LRP4 in the inhibition of LRP5/6 and their downstream β-catenin signaling, leading to cartilage degeneration. Full article

Backgrounds: Imaging of parotid tumors is crucial for surgery planning, but it cannot distinguish malignant from benign lesions with absolute reliability. The aim of the study was to establish a diagnostic MRI algorithm to differentiate parotid tumors. Methods: A retrospective study was conducted including all patients with parotid tumors, who underwent 3T-MRI and surgery. Morphological characteristics and normalized T2 and late postcontrast T1 signal intensities (SI) were assessed. “Ghosting sign” on late postcontrast T1 sequence was defined as indistinguishability of the tumor except for a thin peripheral enhancement. Patients were divided according to histology and imaging data were compared. A diagnostic MRI algorithm was established. Results: Thirty-six patients were included. The combination of normalized late T1 postcontrast SI, normalized T2 SI and “ghosting sign” allowed for the distinguishing of malignant from benign parotid tumors with high sensitivity (100%), specificity (93%), positive predictive value (80%), negative predictive value, (100%) and accuracy (94%). Moreover, pleomorphic adenomas often showed a homogeneous T2 signal and a complete capsule (p < 0.01), Warthin tumors protein-rich cysts and calcifications (p < 0.005 and p < 0.05), and malignant tumors an inhomogeneous contrast enhancement (p < 0.01). Conclusions: High field MRI represents a promising tool in parotid tumors, allowing for an accurate differentiation of malignant and benign lesions. Full article

Background and Clinical Significance: Low-grade endometrial stromal sarcoma (LGESS) is a rare uterine malignancy that causes non-specific symptoms which presents more typically in younger women compared to other uterine sarcomas. Preoperative diagnosis of myometrial LGESS is challenging, as it is frequently mistaken for a benign uterine mass, such as a degenerating leiomyoma. Despite its rarity, the imaging findings of LGESS are highly variable, complicating the diagnostic process. Characteristic findings on magnetic resonance imaging T2-weighted imaging (T2WI)—including intra-tumoral low signal intensity (SI) bands (correlating with preserved myometrial bundles separated by tumor cells on histopathology), cystic/necrotic changes, and absence of a speckled appearance—have been significantly associated with LGESS. Additionally, apparent diffusion coefficient mapping can aid in the characterization of uterine masses. Case Presentation: We present a case of LGESS initially misdiagnosed as red degeneration of a uterine leiomyoma (RDL) due to a peripheral rim showing high SI on T1-weighted imaging and low SI on T2WI, which was interpreted as a thrombosed vessel. Histopathology demonstrated necrotic tissue outlined by normal uterine tissue, corresponding to the peripheral rim. We suggest that susceptibility-weighted imaging could have aided in distinguishing between the two conditions due to its high sensitivity to blood products. Moreover, diffusion-weighted imaging revealed restriction along T2 low SI bands, with no restrictions within the bands themselves, potentially indicating a viable tumor along preserved myometrium. Conclusions: These imaging features may provide valuable insights for diagnosing LGESS and differentiating it from RDL, supporting further research on LGESS imaging characteristics. Full article

Thirteen porcelains assigned to Sèvres factory productions and a few references to the other contemporary factories (Chantilly, Limoges, and Venice) have been studied on-site with a portable X-ray fluorescence (pXRF) spectrometer in order to control the provenance attribution. Characteristic XRF signals of major elements (Si, Ca, K, Pb) and minor/trace (Au, Bi, As, Ti, Co, Cu, Zn, Ni, Y, Zr, Rb, and Sr) elements are compared for the paste, blue mark, various glazed (colored) areas, and gilding. The comparison of peak intensities clearly distinguishes different types of hard- and soft-paste porcelain, made from either similar or distinct raw materials. The analysis of transition elements associated with cobalt identifies three types of cobalt blue and reveals that du Barry-style decoration on certain artifacts was typical of 19th-century production. On-site comprehensive studies of the two famous Etruscan-style breast bowls from Rambouillet Castle dairy, using pXRF and Raman spectroscopy, confirm the use of soft-paste porcelain for the cup and hard-paste for its support, providing detailed information on the use of gold nanoparticles in the burgundy-colored decoration. Full article

A comprehensive investigation of hydrogen grabbing towards the formation of hetero-clusters of AlGaN–H, Si–AlGaN–H, Ge–AlGaN–H, Pd–AlGaN–H, and Pt–AlGaN–H was carried out using DFT computations at the CAM–B3LYP–D3/6-311+G (d,p) level of theory. The notable fragile signal intensity close to the parallel edge of the nanocluster sample might be owing to silicon or germanium binding-induced non-spherical distribution of Si–AlGaN or Ge–AlGaN hetero-clusters. Based on TDOS, the excessive growth technique of doping silicon, germanium, palladium, or platinum is a potential approach to designing high-efficiency hybrid semipolar gallium nitride devices in a long-wavelength zone. Therefore, it can be considered that palladium or platinum atoms in the functionalized Pd–AlGaN or Pt–AlGaN might have more impressive sensitivity for accepting the electrons in the process of hydrogen adsorption. The advantages of platinum or palladium over aluminum gallium nitride include its higher electron and hole mobility, allowing platinum or palladium doping devices to operate at higher frequencies than silicon or germanium doping devices. In fact, it can be observed that doped hetero-clusters of Pd–AlGaN or Pt–AlGaN might ameliorate the capability of AlGaN in transistor cells for energy storage. Full article

In this article, we propose a novel natural light detector based on high-performance silicon nanowire (SiNW) arrays. We achieved a highly controllable and low-cost fabrication of SiNW natural light detectors by using only a conventional micromachined CMOS process. The high activity of SiNWs leads to the poor long-term stability of the SiNW device, and for this reason, we have designed a fully wrapped structure for SiNWs. SiNWs are wrapped in transparent silicon nitride and silicon oxide films, which greatly improves the long-term stability of the detector; at the same time, this structure protects the SiNWs from breakage. In addition, the SiNW arrays are regularly distributed on the top of the detector, which can quickly respond to natural light. The response time of the detector is about 0.015 s. Under the illumination of 1 W·m⁻² light intensity, multiple SiNWs were detected together. The signal strength of the detector reached 1.82 μA, the signal-to-noise ratio was 47.6 dB, and the power consumption was only 0.91 μW. The high-intensity and highly reliable initial signal reduces the cost and complexity of the backend signal processing circuit. A low-cost and high-performance STM32 microcontroller can realize the signal processing task. Therefore, we built a high-performance SiNW natural optoelectronic detection system based on an STM32 microcontroller, which achieved the real-time detection of natural light intensity, with an accuracy of ±0.1 W·m⁻². These excellent test performances indicate that the SiNW array natural light detector in this article meey the requirements of practicality and has broad potential for application. Full article

This study uses magnetic resonance imaging (MRI) to investigate the potential of the hepatospecific contrast agent gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) in distinguishing G1- from G2/G3-differentiated hepatocellular carcinoma (HCC). Our approach involved analyzing the dynamic behavior of the contrast agent in different phases of imaging by signal intensity (SI) and lesion contrast (C), to surrounding liver parenchyma, and comparing it across distinct groups of patients differentiated based on the histopathological grading of their HCC lesions and the presence of liver cirrhosis. Our results highlighted a significant contrast between well- and poorly-differentiated lesions regarding the lesion contrast in the arterial and late arterial phases. Furthermore, the hepatobiliary phase showed limited diagnostic value in cirrhotic liver parenchyma due to altered pharmacokinetics. Ultimately, our findings underscore the potential of Gd-EOB-DTPA-enhanced MRI as a tool for improving preoperative diagnosis and treatment selection for HCC while emphasizing the need for continued research to overcome the diagnostic complexities posed by the disease. Full article