Search Results (19)

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, so its detection and monitoring are critical. However, contrast-enhanced magnetic resonance imaging (CE-MRI) is particularly vulnerable to complex, unstructured noise, which compromises image quality and diagnostic accuracy. This study proposes the use of NLE-ANSNet, a deep learning-based denoizing framework that integrates multilevel noise level estimators (NLEs) and adaptive noise scaling (ANS) within residual blocks. The model performs progressive, stagewise noise suppression at multiple feature depths, dynamically adjusting normalization based on localized noise estimates. This enables context-aware denoizing, preserving fine anatomical details. To simulate clinically realistic conditions, we developed a hybrid noise simulation framework that combines Gaussian, Poisson, and Rician noise at the pixel level. This framework aims to approximate a balanced noise distribution for evaluation purposes, with both mean and median noise levels reported to enhance evaluation robustness and prevent bias from extreme cases. NLE-ANSNet achieves a PSNR of 34.01 dB and an SSIM of 0.9393, surpassing those of state-of-the-art models. The method aims to support diagnostic reliability by preserving image structure and intensity fidelity in CE-MRI interpretation. In addition to quantitative analysis, a qualitative assessment was conducted to visually compare denoizing outputs across models, further demonstrating NLE-ANSNet’s superior ability to suppress noise while preserving diagnostically critical information. Unlike previous approaches, this study introduces a denoizing framework that combines multilevel noise estimation and adaptive noise scaling specifically tailored for CE-MRI in HCC under hybrid noise conditions—a clinically relevant and underexplored area. Overall, this study supports improved clinical decision making in HCC management. Full article

Hybrid strains Escherichia coli acquires genetic characteristics from multiple pathotypes and is speculated to be more virulent; however, understanding their pathogenicity is elusive. Here, we performed genome-based characterization of the hybrid of enteropathogenic (EPEC) and enterotoxigenic E. coli (ETEC), the strains that cause diarrhea and mortality in children. The virulence genes in the strains isolated from different sources in the South Korea were identified, and their phylogenetic positions were analyzed. The EPEC/ETEC hybrid strains harbored eae and est encoding E. coli attaching and effacing lesions and heat-stable enterotoxins of EPEC and ETEC, respectively. Genome-wide phylogeny revealed that all hybrids (n = 6) were closely related to EPEC strains, implying the potential acquisition of ETEC virulence genes during ETEC/EPEC hybrid emergence. The hybrids represented diverse serotypes (O153:H19 (n = 3), O49:H10 (n = 2), and O71:H19 (n = 1)) and sequence types (ST546, n = 4; ST785, n = 2). Furthermore, heat-stable toxin-encoding plasmids possessing estA and various other virulence genes and transporters, including nleH2, hlyA, hlyB, hlyC, hlyD, espC, espP, phage endopeptidase Rz, and phage holin, were identified. These findings provide insights into understanding the pathogenicity of EPEC/ETEC hybrid strains and may aid in comparative studies, virulence characterization, and understanding evolutionary biology. Full article

Multi-channel airborne full-waveform LiDAR is widely used for high-precision underwater depth measurement. However, the signal quality of full-waveform data is unstable due to the influence of background light, dark current noise, and the complex transmission process. Therefore, we propose a nonlocal encoder block (NLEB) based on spatial dilated convolution to optimize the feature extraction of adjacent frames. On this basis, a coupled denoising encoder–decoder network is proposed that takes advantage of the echo correlation in deep-water and shallow-water channels. Firstly, full waveforms from different channels are stacked together to form a two-dimensional tensor and input into the proposed network. Then, NLEB is used to extract local and nonlocal features from the 2D tensor. After fusing the features of the two channels, the reconstructed denoised data can be obtained by upsampling with a fully connected layer and deconvolution layer. Based on the measured data set, we constructed a noise–noisier data set, on which several denoising algorithms were compared. The results show that the proposed method improves the stability of denoising by using the inter-channel and multi-frame data correlation. Full article

The aim of this study was to evaluate the effect of linker on tumor targeting and biodistribution of ⁶⁷Cu-NOTA-PEG₂Nle-CycMSH_hex {⁶⁷Cu-1,4,7-triazacyclononane-1,4,7-triyl-triacetic acid-polyethylene glycol-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH₂} and ⁶⁷Cu-NOTA-GGNle-CycMSH_hex {⁶⁷Cu-NOTA-GlyGlyNle-CycMSH_hex} on melanoma-bearing mice. NOTA-PEG₂Nle-CycMSH_hex and NOTA-GGNle-CycMSH_hex were synthesized and purified by HPLC. The biodistribution of ⁶⁷Cu-NOTA-PEG₂Nle-CycMSH_hex and ⁶⁷Cu-NOTA-GGNle-CycMSH_hex was determined in B16/F10 melanoma-bearing C57 mice. The melanoma imaging property of ⁶⁷Cu-NOTA-PEG₂Nle-CycMSH_hex was further examined in B16/F10 melanoma-bearing C57 mice. ⁶⁷Cu-NOTA-PEG₂Nle-CycMSH_hex exhibited higher tumor uptake than ⁶⁷Cu-NOTA-GGNle-CycMSH_hex at 2, 4, and 24 h post-injection. The tumor uptake of ⁶⁷Cu-NOTA-PEG₂Nle-CycMSH_hex was 27.97 ± 1.98, 24.10 ± 1.83, and 9.13 ± 1.66% ID/g at 2, 4, and 24 h post-injection, respectively. Normal organ uptake of ⁶⁷Cu-NOTA-PEG₂Nle-CycMSH_hex was lower than 2.6% ID/g at 4 h post-injection, except for kidney uptake. The renal uptake of ⁶⁷Cu-NOTA-PEG₂Nle-CycMSH_hex was 6.43 ± 1.31, 2.60 ± 0.79, and 0.90 ± 0.18% ID/g at 2, 4, and 24 h post-injection, respectively. ⁶⁷Cu-NOTA-PEG₂Nle-CycMSH_hex showed high tumor to normal organ uptake ratios after 2 h post-injection. The B16/F10 melanoma lesions could be clearly visualized by single photon emission computed tomography (SPECT) using ⁶⁷Cu-NOTA-PEG₂Nle-CycMSH_hex as an imaging probe at 4 h post-injection. The favorable tumor targeting and biodistribution properties of ⁶⁷Cu-NOTA-PEG₂Nle-CycMSH_hex underscored its potential as an MC1R-targeted therapeutic peptide for melanoma treatment. Full article

Infections of Candida spp. etiology are frequently treated with azole drugs. Among azoles, the most widely used in the clinical scenario remains fluconazole (FLC). Promising results in treatment of dangerous, systemic Candida infections demonstrate the advantages of combined therapies carried out with combinations of at least two different antifungal agents. Here, we report five conjugates composed of covalently linked FLC and cell penetrating or antimicrobial peptide: TP10-7-NH₂, TP10-NH₂, LFcinB(2-11)-NH₂, LFcinB[Nle^1,11]-NH₂, and HLopt2-NH₂, with aspects of design, chemical synthesis and their biological activities. Two of these compounds, namely FLCpOH-TP10-NH₂ and FLCpOH-TP10-7-NH₂, exhibit high activity against reference strains and fluconazole-resistant clinical isolates of C. albicans, including strains overproducing drug transporters. Moreover, both of them demonstrate higher fungicidal effects compared to fluconazole. Analysis performed with fluorescence and scanning electron microscopy as well as flow cytometry indicated the cell membrane as a molecular target of synthesized conjugates. An important advantage of FLCpOH-TP10-NH₂ and FLCpOH-TP10-7-NH₂ is their low cytotoxicity. The IC₉₀ value for the human cells after 72 h treatment was comparable to the MIC₅₀ value after 24 h treatment for most strains of C. albicans. In reported conjugates, FLC was linked to the peptide by its hydroxyl group. It is worth noting that conjugation of FLC by the nitrogen atom of the triazole ring led to practically inactive compounds. Two compounds produced by us and reported herein appear to be potential candidates for novel antifungal agents. Full article

We are interested in identifying and characterizing small molecule inhibitors of bacterial virulence factors for their potential use as anti-virulence inhibitors. We identified from high-throughput screening assays a potential activity for avasimibe, a previously characterized acyl-coenzyme A: cholesterol acyltransferase inhibitor, in inhibiting the NleB and SseK arginine glycosyltransferases from Escherichia coli and Salmonella enterica, respectively. Avasimibe inhibited the activity of the Citrobacter rodentium NleB, E. coli NleB1, and S. enterica SseK1 enzymes, without affecting the activity of the human serine/threonine N-acetylglucosamine (O-GlcNAc) transferase. Avasimibe was not toxic to mammalian cells at up to 200 µM and was neither bacteriostatic nor bactericidal at concentrations of up to 125 µM. Doses of 10 µM avasimibe were sufficient to reduce S. enterica abundance in RAW264.7 macrophage-like cells, and intraperitoneal injection of avasimibe significantly reduced C. rodentium survival in mice, regardless of whether the avasimibe was administered pre- or post-infection. We propose that avasimibe or related derivates created using synthetic chemistry may have utility in preventing or treating bacterial infections by inhibiting arginine glycosyltransferases that are important to virulence. Full article

The probability distribution of probabilistic shaping 64 quadrature amplitude modulation (PS-64QAM) is uneven. The traditional M-ary support vector machine (SVM) algorithm is incompatible with the data set with uneven distribution. In order to solve the problem, we propose a novel nonlinear equalizer (NLE) for PS-64QAM based on constellation segmentation (CS) and SVM, called CS M-ary SVM NLE. The performance of CS M-ary SVM NLE has been demonstrated in a 120 Gb/s PS-64QAM coherent optical communication system. The experimental results show that after employing the proposed scheme, the launched optical power dynamic range (LOPDR) of PS-64QAM can be increased by 1.6 dBm compared with the situation without NLE. In addition, aided by the proposed scheme, the LOPDR of PS-64QAM is increased by 0.6 dBm than M-ary SVM NLE. Compared with employing M-ary SVM NLE and without employing NLE, when employing the proposed scheme, the Q factor is improved about 0.50 dB and 0.96 dB, respectively. The number of support vectors (SVs) and CPU running time for both NLE schemes are collected to measure the complexity of the two NLE schemes. The results show that the complexity of the proposed scheme is lower than that of the M-ary SVM scheme under the entire measured launched optical power range from −5 dBm to +5 dBm. Full article

Neonatal lupus erythematosus (NLE) is a syndrome of clinical symptoms observed in neonates born to mothers with antibodies to soluble antigens of the cell nucleus. The main factors contributing to the pathogenesis of this disease are anti-Sjögren Syndrome A (anti-SS-A) antibodies, known as anti-Ro, and anti-Sjögren Syndrome B (anti-SS-B) antibodies, known as anti-La. Recent publications have also shown the significant role of anti-ribonucleoprotein antibodies (anti-RNP). Seropositive mothers may have a diagnosed rheumatic disease or they can be asymptomatic without diagnosis at the time of childbirth. These antibodies, after crossing the placenta, may trigger a cascade of inflammatory reactions. The symptoms of NLE can be divided into reversible symptoms, which concern skin, hematological, and hepatological changes, but 2% of children develop irreversible symptoms, which include disturbances of the cardiac stimulatory and conduction system. Preconceptive care and pharmacological prophylaxis of NLE in the case of mothers from the risk group are important, as well as the monitoring of the clinical condition of the mother and fetus throughout pregnancy and the neonatal period. The aim of this manuscript is to summarize the previous literature and current state of knowledge about neonatal lupus and to discuss the role of anti-Ro in the inflammatory process. Full article

The aim of this work was to assess the brain responses of expert cellists during a real (real-INT) or imagined (imag-INT) interpretation of two musical styles with different learning/training cognitive roots. EEGs of 12 cellists were recorded while they interpreted previously memorized excerpts of tonal-baroque (T) and atonal-contemporary (A) music and at rest (R). Phase synchronization functional connectivity measurements among different cortical regions were computed from the EEG data and at different frequency bands (FB). These were then thresholded using surrogate data tests. Brain network construction and graph-metric analysis were performed for each FB and condition/interpretation. Global graph-indices statistical results showed that regardless of FB: (a) the node degree and density presented significant differences among conditions T, A, and R during imag-INT and between interpretations with real greater than imag-INT only for A; (b) global (NGE) and local (NLE) normalized efficiency (vs. random network), indices measuring network information exchanges, exhibited a similar small-world network structure (SW) in T, A, and R during real-INT; however, during imag-INT, SW changed in T and A but due to a significant NLE increase with NLE(A) greater than NLE(T) and the latter greater than NLE(R). Statistical node topographic maps results showed significant differences for graph degree (real-INT greater than imag-INT) and for NLE (imag-INT greater than real-INT) in A for certain nodes of delta and theta EEG FB networks. Style differences appearing only during imag-INT (e.g., the SW) indicate that imag-INT requires/involves different cognitive functions/processes than those in real-INT. The analysis and previous results allowed the discrimination of representative musical styles from different periods, which receive different cognitive learning in the musicians’ lives. Full article

Combining two peptides addressing two different receptors to a heterobivalent peptidic ligand (HBPL) is thought to enable an improved tumor-targeting sensitivity and thus tumor visualization, compared to monovalent peptide ligands. In the case of melanoma, the Melanocortin-1 receptor (MC1R), which is stably overexpressed in the majority of primary malignant melanomas, and integrin α_vβ₃, which is involved in lymph node metastasis and therefore has an important role in the transition from local to metastatic disease, are important target receptors. Thus, if a radiolabeled HBPL could be developed that was able to bind to both receptor types, the early diagnosis and correct staging of the disease would be significantly increased. Here, we report on the design, synthesis, radiolabeling and in vitro and in vivo testing of different SiFAlin-modified HBPLs (SiFA = silicon fluoride acceptor), consisting of an MC1R-targeting (GG-Nle-c(DHfRWK)) and an integrin α_vβ₃-affine peptide (c(RGDfK)), being connected by a symmetrically branching framework including linkers of differing length and composition. Kit-like ¹⁸F-radiolabeling of the HBPLs 1–6 provided the labeled products [¹⁸F]1–[¹⁸F]6 in radiochemical yields of 27–50%, radiochemical purities of ≥95% and non-optimized molar activities of 17–51 GBq/μmol within short preparation times of 25 min. Besides the evaluation of radiotracers regarding log_D(7.4) and stability in human serum, the receptor affinities of the HBPLs were investigated in vitro on cell lines overexpressing integrin α_vβ₃ (U87MG cells) or the MC1R (B16F10). Based on these results, the most promising compounds [¹⁸F]2, showing the highest affinity to both target receptors (IC_{50 (B16F10)} = 0.99 ± 0.11 nM, IC_{50 (U87MG)} = 1300 ± 288 nM), and [¹⁸F]4, exhibiting the highest hydrophilicity (log_D(7.4) = −1.39 ± 0.03), were further investigated in vivo and ex vivo in a xenograft mouse model bearing both tumors. For both HBPLs, clear visualization of B16F10, as well as U87MG tumors, was feasible. Blocking studies using the respective monospecific peptides demonstrated both peptide binders of the HBPLs contributing to tumor uptake. Despite the somewhat lower target receptor affinities (IC_{50 (B16F10)} = 6.00 ± 0.47 nM and IC_{50 (U87MG)} = 2034 ± 323 nM) of [¹⁸F]4, the tracer showed higher absolute tumor uptakes ([¹⁸F]4: 2.58 ± 0.86% ID/g in B16F10 tumors and 3.92 ± 1.31% ID/g in U87MG tumors; [¹⁸F]2: 2.32 ± 0.49% ID/g in B16F10 tumors and 2.33 ± 0.46% ID/g in U87MG tumors) as well as higher tumor-to-background ratios than [¹⁸F]2. Thus, [¹⁸F]4 demonstrates to be a highly potent radiotracer for the sensitive and bispecific imaging of malignant melanoma by PET/CT imaging and impressively illustrates the suitability of the underlying concept to develop heterobivalent integrin α_vβ₃- and MC1R-bispecific radioligands for the sensitive and specific imaging of malignant melanoma by PET/CT. Full article

Image denoising, a classic ill-posed problem, aims to recover a latent image from a noisy measurement. Over the past few decades, a considerable number of denoising methods have been studied extensively. Among these methods, supervised deep convolutional networks have garnered increasing attention, and their superior performance is attributed to their capability to learn realistic image priors from a large amount of paired noisy and clean images. However, if the image to be denoised is significantly different from the training images, it could lead to inferior results, and the networks may even produce hallucinations by using inappropriate image priors to handle an unseen noisy image. Recently, deep image prior (DIP) was proposed, and it overcame this drawback to some extent. The structure of the DIP generator network is capable of capturing the low-level statistics of a natural image using an unsupervised method with no training images other than the image itself. Compared with a supervised denoising model, the unsupervised DIP is more flexible when processing image content that must be denoised. Nevertheless, the denoising performance of DIP is usually inferior to the current supervised learning-based methods using deep convolutional networks, and it is susceptible to the over-fitting problem. To solve these problems, we propose a novel deep generative network with multiple target images and an adaptive termination condition. Specifically, we utilized mainstream denoising methods to generate two clear target images to be used with the original noisy image, enabling better guidance during the convergence process and improving the convergence speed. Moreover, we adopted the noise level estimation (NLE) technique to set a more reasonable adaptive termination condition, which can effectively solve the problem of over-fitting. Extensive experiments demonstrated that, according to the denoising results, the proposed approach significantly outperforms the original DIP method in tests on different databases. Specifically, the average peak signal-to-noise ratio (PSNR) performance of our proposed method on four databases at different noise levels is increased by 1.90 to 4.86 dB compared to the original DIP method. Moreover, our method achieves superior performance against state-of-the-art methods in terms of popular metrics, which include the structural similarity index (SSIM) and feature similarity index measurement (FSIM). Thus, the proposed method lays a good foundation for subsequent image processing tasks, such as target detection and super-resolution. Full article

Whether type III secretion system (T3SS) effector proteins encoded by Gram-negative bacterial pathogens have intra-bacterial activities is an important and emerging area of investigation. Gram-negative bacteria interact with their mammalian hosts by using secretion systems to inject virulence proteins directly into infected host cells. Many of these injected protein effectors are enzymes that modify the structure and inhibit the function of mammalian proteins. The underlying dogma is that T3SS effectors are inactive until they are injected into host cells, where they then fold into their active conformations. We previously observed that the T3SS effectors NleB and SseK1 glycosylate Citrobacter rodentium and Salmonella enterica proteins, respectively, leading to enhanced resistance to environmental stress. Here, we sought to extend these studies to determine whether the T3SS effector protease NleC is also active within C. rodentium. To do this, we expressed the best-characterized mammalian substrate of NleC, the NF-κB p65 subunit in C. rodentium and monitored its proteolytic cleavage as a function of NleC activity. Intra-bacterial p65 cleavage was strictly dependent upon NleC. A p65 mutant lacking the known CE cleavage motif was resistant to NleC. Thus, we conclude that, in addition to NleB, NleC is also enzymatically active within C. rodentium. Full article

The type III secretion system effector proteins NleB and SseK are glycosyltransferases that glycosylate protein substrates on arginine residues. We conducted high-throughput screening assays on 42,498 compounds to identify NleB/SseK inhibitors. Such small molecules may be useful as mechanistic probes and may have utility in the eventual development of anti-virulence therapies against enteric bacterial pathogens. We observed that YM155 (sepantronium bromide) inhibits the activity of Escherichia coli NleB1, Citrobacter rodentium NleB, and both Salmonella enterica SseK1 and SseK2. YM155 was not toxic to mammalian cells, nor did it show cross-reactivity with the mammalian O-linked N-acetylglucosaminyltransferase (OGT). YM155 reduced Salmonella survival in mouse macrophage-like cells but had no direct impact on bacterial growth rates, suggesting YM155 may have utility as a potential anti-virulence inhibitor. Full article

Type III secretion systems are used by many Gram-negative bacterial pathogens to inject proteins, known as effectors, into the cytosol of host cells. These virulence factors interfere with a diverse array of host signal transduction pathways and cellular processes. Many effectors have catalytic activities to promote post-translational modifications of host proteins. This review focuses on a family of effectors with glycosyltransferase activity that catalyze addition of N-acetyl-d-glucosamine to specific arginine residues in target proteins, leading to reduced NF-κB pathway activation and impaired host cell death. This family includes NleB from Citrobacter rodentium, NleB1 and NleB2 from enteropathogenic and enterohemorrhagic Escherichia coli, and SseK1, SseK2, and SseK3 from Salmonella enterica. First, we place these effectors in the general framework of the glycosyltransferase superfamily and in the particular context of the role of glycosylation in bacterial pathogenesis. Then, we provide detailed information about currently known members of this family, their role in virulence, and their targets. Full article

Enterohemorrhagic Escherichia coli (EHEC) utilizes a type III secretion system (T3SS) to inject effector proteins into host cells. The EHEC NleH1 effector inhibits the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway by reducing the nuclear translocation of the ribosomal protein S3 (RPS3). NleH1 prevents RPS3 phosphorylation by the IκB kinase-β (IKKβ). IKKβ is a central kinase in the NF-κB pathway, yet NleH1 only restricts the phosphorylation of a subset of the IKKβ substrates. We hypothesized that a protein cofactor might dictate this inhibitory specificity. We determined that heat shock protein 90 (Hsp90) interacts with both IKKβ and NleH1 and that inhibiting Hsp90 activity reduces RPS3 nuclear translocation. Full article