Search Results (32)

Nanoclays have gained attention in biological applications due to their biocompatibility, low toxicity, and cost-effectiveness. Layered double hydroxides (LDHs) are synthetic nanoclays that have been used as adjuvants and antigen carriers in nanovaccines developed through passive bioconjugation. However, performing active bioconjugation to bind antigens covalently and generate subunit nanovaccines remains unexplored. In this study, we investigated the synthesis, functionalization, and active conjugation of LDH nanoparticles to produce subunit nanovaccines with peptides from SARS-CoV-2. The synthesis of Mg-Al LDHs via a coprecipitation and hydrothermal treatment rendered monodisperse particles averaging 100 nm. Their functionalization with (3-aminopropyl)triethoxysilane was better than it was with other organosilanes. Glutaraldehyde was used as a linker to bind lysine as a model biomolecule to establish the best conditions for reductive amination. Finally, two peptides, P₂ and P₅ (epitopes of the SARS-CoV-2 spike protein), were bound on the surface of the LDH to produce two subunit vaccine candidates, reaching peptide concentrations of 125 and 270 µg/mL, respectively. The particles were characterized using DLS, TEM, XRD, TGA, DSC, and FTIR. The cytotoxicity studies revealed that the conjugate with P₂ was non-toxic up to 250 µg/mL, while the immunogenicity studies showed that this conjugate induced similar IgG titers to those reached when aluminum hydroxide was used as an adjuvant. Full article

Danshen, a well-known traditional Chinese medicine (TCM), has gained increasing attention for its protective effects on nonalcoholic fatty liver disease (NAFLD). However, the molecular mechanisms underlying these effects remain to be elucidated. Niemann-Pick C1-like 1 (NPC1L1), a key transporter mediating intestinal cholesterol absorption, has emerged as a critical target for NAFLD treatment. This study aimed to screen for NPC1L1 inhibitors from Danshen and investigate their therapeutic effects on NAFLD. We established a high-throughput screening platform using stable Caco2 cell lines expressing human NPC1L1 (hL1-Caco2) and discovered that tanshinones (Tans), the liposoluble components of Danshen, inhibited NPC1L1-mediated cholesterol absorption in hL1-Caco2 cells. Additionally, Tans treatment reduced hepatic steatosis in high-fat diet (HFD)-fed mice. To identify the active compounds in Tans, activity-oriented separation was performed by integrating the high-throughput screening platform and two-dimensional chromatographic techniques. Ultimately, cryptotanshinone (CTS) was identified as a novel NPC1L1 inhibitor and significantly decreased hepatic steatosis in HFD-fed mice. Molecular docking and dynamics simulation showed that CTS stably bound with NPC1L1, where TRP383 acted as the key amino acid. Taken together, this study demonstrates, for the first time, that CTS, a liposoluble compound from Danshen, is a novel NPC1L1 inhibitor. Our findings suggest that the inhibitory effect of CTS against NPC1L1-mediated intestinal cholesterol absorption may be a potential mechanism, contributing to its alleviation of NAFLD in mice. Full article

Here, mixed-strategy-based control of systems with sector-bounded nonlinearities is considered. The suggested control strategy applies a stochastic state feedback, where the control gain includes a white noise component in addition to the deterministic part. While each of the control signal components can sometimes accomplish the control task independently, the combination may have some merits. This is especially true when both the mean value and the variance of the control signal need to be quantified separately. Systems that apply deterministic state-feedback control are abundant, whereas the application of state-multiplicative noise as a mean of control is more limited. Nevertheless, Stochastic Anti Resonance (SAR) with state-multiplicative noise based control, are encountered in diverse engineering applications, physics modelling, and biological models, such as visual-motor tasks. Matrix Inequalities conditions are derived, for weighted $L_2$-gain using a mixed strategy control along with exponential $L_P$-stability of the closed-loop. A numerical example is given, where the merit of mixed control strategy comparing to deterministic control is demonstrated. Full article

In this paper, the stability and $l_{\infty }$-gain problem are investigated for the Nabla discrete fractional linear positive systems with bounded time-varying delays. First, a sufficient condition and a necessary condition are presented to ensure the system’s positivity. Then, based on the system’s positivity property, an asymptotically stable condition is established. Furthermore, it is demonstrated that the $l_{\infty }$-gain of such systems is determined by the system matrices and is independent of the magnitude of delays. Finally, numerical examples are provided to demonstrate the validity of the obtained results. Full article

In this paper, we are concerned with the process of experimental information gain. Building on previous work, we show that this is a discontinuous process in which the initiating quantum-mechanical matter–instrument interactions are being turned into macroscopically observable events (EOs). In the course of time, such EOs evolve into spatio-temporal patterns of EOs, which allow conceivable alternatives of physical explanation to be distinguished. Focusing on the specific case of photon detection, we show that during their lifetimes, EOs proceed through the four phases of initiation, detection, erasure and reset. Once generated, the observational value of EOs can be measured in units of the Planck quantum of physical action $h=4.136\times {10}^{-15}\mathrm{e}\mathrm{V}\mathrm{s}$. Once terminated, each unit of entropy of size $k_B=8.617\times {10}^{-5}\mathrm{e}\mathrm{V}/\mathrm{K}$, which had been created in the instrument during the observational phase, needs to be removed from the instrument to ready it for a new round of photon detection. This withdrawal of entropy takes place at an energetic cost of at least two units of the Landauer minimum energy bound of $E_{La}=\ln \left(2\right)k_B{T}_D$ for each unit of entropy of size $k_B$. Full article

Nutritional bars (NBs) are gaining popularity among healthy and athletic individuals, but postprandial antioxidative response has not been investigated. Therefore, the current study examined the postprandial alterations in total phenolic content (TPC), total antioxidant capacity (T-AOC), malondialdehyde (MDA), and Superoxide dismutase (SOD) in the plasma of healthy individuals after the ingestion of 140 g (510 Kcal) from formulated date-based bars (DBBs) or fruit-based bars (FBBs). Firstly, the free and bound phenolic contents (PCs) were determined to be 10.15 and 12.98 and 6.19 and 3.57 mg GAE g⁻¹, respectively. FBBs were significantly higher in free PC than DBBs, while DBBs were considerably higher in bound PC than FBBs. Secondly, twenty participants with age, height, weight, body mass index (BMI), fat mass, and fat-free mass averages of 21.4 years, 170.0 cm, 66.3 kg, 22.9 kg m², 14.5, and 29.2 kg, respectively, were subjected to metabolic experiments (ISRCTN19386758). Ingestion of 140 g of FBB or DBB resulted in 288.50 or 302.14 µg TPC mL⁻¹ blood, respectively. Postprandial TPC content increased with time progression and peaked after 120 min. T-AOC contents averaged 22.63 and 23.61 U mL⁻¹ before ingestion of FBBs or DBBs, respectively. The T-AOC content increased significantly 120 and 180 min after ingestion of DBBs, while no significant change was noted after consuming FBBs. A significant decrease in MDA content was observed 180 min after consuming DBBs, while no significant change was noted after consuming FBBs. SOD concentrations ranged from 193.99 to 201.07 U L⁻¹ in FBBs and DBBs, respectively. No considerable response was noted up to 3 h after ingestion of FBBs. On the contrary, a significant response was found 120 min after consuming DBBs. Pearson’s correlation coefficient indicated a highly significant positive correlation coefficient (p < 0.01) between T-AOC and either MDA or SOD, as well as between MDA and SOD. The principal component analysis demonstrated a strong and positive relationship between SOD and TPC at 60 and 120 min after DBB ingestion. In conclusion, the relative changes in postprandial responses in T-AOC and MDA did not significantly (p > 0.05) differ between DBBs and FBBs, except for TPC (p = 0.04, paired t-test) and SOD (p = 0.003, paired t-test). Further studies with an extended experimental time are needed to confirm the current findings. Full article

The transmembrane proteoglycan syndecan-4 is known to be involved in the hypertrophic response to pressure overload. Although multiple downstream signaling pathways have been found to be involved in this response in a syndecan-4-dependent manner, there are likely more signaling components involved. As part of a larger syndecan-4 interactome screening, we have previously identified MLP as a binding partner to the cytoplasmic tail of syndecan-4. Interestingly, many human MLP mutations have been found in patients with hypertrophic (HCM) and dilated cardiomyopathy (DCM). To gain deeper insight into the role of the syndecan-4–MLP interaction and its potential involvement in MLP-associated cardiomyopathy, we have here investigated the syndecan-4–MLP interaction in primary adult rat cardiomyocytes and the H9c2 cell line. The binding of syndecan-4 and MLP was analyzed in total lysates and subcellular fractions of primary adult rat cardiomyocytes, and baseline and differentiated H9c2 cells by immunoprecipitation. MLP and syndecan-4 localization were determined by confocal microscopy, and MLP oligomerization was determined by immunoblotting under native conditions. Syndecan-4–MLP binding, as well as MLP self-association, were also analyzed by ELISA and peptide arrays. Our results showed that MLP-WT and syndecan-4 co-localized in many subcellular compartments; however, their binding was only detected in nuclear-enriched fractions of isolated adult cardiomyocytes. In vitro, syndecan-4 bound to MLP at three sites, and this binding was reduced in some HCM-associated MLP mutations. While MLP and syndecan-4 also co-localized in many subcellular fractions of H9c2 cells, these proteins did not bind at baseline or after differentiation into cardiomyocyte-resembling cells. Independently of syndecan-4, mutated MLP proteins had an altered subcellular localization in H9c2 cells, compared to MLP-WT. The DCM- and HCM-associated MLP mutations, W4R, L44P, C58G, R64C, Y66C, K69R, G72R, and Q91L, affected the oligomerization of MLP with an increase in monomeric at the expense of trimeric and tetrameric recombinant MLP protein. Lastly, two crucial sites for MLP self-association were identified, which were reduced in most MLP mutations. Our data indicate that the syndecan-4–MLP interaction was present in nuclear-enriched fractions of isolated adult cardiomyocytes and that this interaction was disrupted by some HCM-associated MLP mutations. MLP mutations were also linked to changes in MLP oligomerization and self-association, which may be essential for its interaction with syndecan-4 and a critical molecular mechanism of MLP-associated cardiomyopathy. Full article

Terahertz (THz) sensors have attracted great attention in the biological field due to their nondestructive and contact-free biochemical samples. Recently, the concept of a quasi-bound state in the continuum (QBIC) has gained significant attention in designing biosensors with ultrahigh sensitivity. QBIC-based metasurfaces (MSs) achieve excellent performance in various applications, including sensing, optical switching, and laser, providing a reliable platform for biomaterial sensors with terahertz radiation. In this study, a structure-engineered THz MS consisting of a “double C” array has been designed, in which an asymmetry parameter α is introduced into the structure by changing the length of one subunit; the Q-factor of the QBIC device can be optimized by engineering the asymmetry parameter α. Theoretical calculation with coupling equations can well reproduce the THz transmission spectra of the designed THz QBIC MS obtained from the numerical simulation. Experimentally, we adopt an MS with α = 0.44 for testing arginine molecules. The experimental results show that different concentrations of arginine molecules lead to significant transmission changes near QBIC resonant frequencies, and the amplitude change is shown to be 16 times higher than that of the classical dipole resonance. The direct limit of detection for arginine molecules on the QBIC MS reaches 0.36 ng/mL. This work provides a new way to realize rapid, accurate, and nondestructive sensing of trace molecules and has potential application in biomaterial detection. Full article

Deep neural networks (DNNs) have gained prominence in various applications, but remain vulnerable to adversarial attacks that manipulate data to mislead a DNN. This paper aims to challenge the efficacy and transferability of two contemporary defense mechanisms against adversarial attacks: (a) robust training and (b) adversarial training. The former suggests that training a DNN on a data set consisting solely of robust features should produce a model resistant to adversarial attacks. The latter creates an adversarially trained model that learns to minimise an expected training loss over a distribution of bounded adversarial perturbations. We reveal a significant lack in the transferability of these defense mechanisms and provide insight into the potential dangers posed by $L_{\infty }$-norm attacks previously underestimated by the research community. Such conclusions are based on extensive experiments involving (1) different model architectures, (2) the use of canonical correlation analysis, (3) visual and quantitative analysis of the neural network’s latent representations, (4) an analysis of networks’ decision boundaries and (5) the use of equivalence of $L_2$ and $L_{\infty }$ perturbation norm theories. Full article

Accurate and fast detection of traffic sign information is vital for autonomous driving systems. However, the YOLOv5 algorithm faces challenges with low accuracy and slow detection when it is used for traffic sign detection. To address these shortcomings, this paper introduces an accurate and fast traffic sign detection algorithm–YOLOv5-Efficient Vision TransFormer(EfficientViT)). The algorithm focuses on improving both the accuracy and speed of the model by replacing the CSPDarknet backbone of the YOLOv5(s) model with the EfficientViT network. Additionally, the algorithm incorporates the Convolutional Block Attention Module(CBAM) attention mechanism to enhance feature layer information extraction and boost the accuracy of the detection algorithm. To mitigate the adverse effects of low-quality labels on gradient generation and enhance the competitiveness of high-quality anchor frames, a superior gradient gain allocation strategy is employed. Furthermore, the strategy introduces the Wise-IoU (WIoU), a dynamic non-monotonic focusing mechanism for bounding box loss, to further enhance the accuracy and speed of the object detection algorithm. The algorithm’s effectiveness is validated through experiments conducted on the 3L-TT100K traffic sign dataset, showcasing a mean average precision (mAP) of 94.1% in traffic sign detection. This mAP surpasses the performance of the YOLOv5(s) algorithm by 4.76% and outperforms the baseline algorithm. Additionally, the algorithm achieves a detection speed of 62.50 frames per second, which is much better than the baseline algorithm. Full article

In this paper, we explore the consensus of positive networked systems with actuator faults. Firstly, the undirected and strongly connected topology is established with graph theory. The positive system theory is used to analyze the positive consensus of the closed-loop networked systems. State feedback gains are derived utilizing Algebraic Riccati Inequalities. Bounded multiplicative faults are regarded as uncertainties in the system matrix, while treating additive faults as external disturbances. Further, this transformation refocuses the analysis on the consensus problem with an $L_2$-gain. Subsequently, the Genetic Algorithm is employed to optimize the $L_2$ performance criteria. Finally, the effectiveness of the proposed theory is validated through simulations involving both single-input electric circuit systems and multi-input networked systems. Full article

Exercise increases the cost of breathing (COB) due to increased lung ventilation ($\dot{\mathrm{V}}$E), inducing respiratory muscles deoxygenation ($\nabla$SmO₂), while the increase in workload implies $\nabla$SmO₂ in locomotor muscles. This phenomenon has been proposed as a leading cause of exercise intolerance, especially in clinical contexts. The use of high-flow nasal cannula (HFNC) during exercise routines in rehabilitation programs has gained significant interest because it is proposed as a therapeutic intervention for reducing symptoms associated with exercise intolerance, such as fatigue and dyspnea, assuming that HFNC could reduce exercise-induced $\nabla$SmO₂. SmO₂ can be detected using optical wearable devices provided by near-infrared spectroscopy (NIRS) technology, which measures the changes in the amount of oxygen bound to chromophores (e.g., hemoglobin, myoglobin, cytochrome oxidase) at the target tissue level. We tested in a study with a cross-over design whether the muscular desaturation of m.vastus lateralis and m.intercostales during a high-intensity constant-load exercise can be reduced when it was supported with HFNC in non-physically active adults. Eighteen participants (nine women; age: 22 ± 2 years, weight: 65.1 ± 11.2 kg, height: 173.0 ± 5.8 cm, BMI: 21.6 ± 2.8 kg·m⁻²) were evaluated in a cycle ergometer (15 min, 70% maximum watts achieved in ergospirometry ($\dot{\mathrm{V}}$O₂-peak)) breathing spontaneously (control, CTRL) or with HFNC support (HFNC; 50 L·min⁻¹, fiO₂: 21%, 30 °C), separated by seven days in randomized order. Two-way ANOVA tests analyzed the $\nabla$SmO₂ (m.intercostales and m.vastus lateralis), and changes in $\dot{\mathrm{V}}$E and $\nabla$SmO₂·$\dot{\mathrm{V}}$E⁻¹. Dyspnea, leg fatigue, and effort level (RPE) were compared between trials by the Wilcoxon matched-paired signed rank test. We found that the interaction of factors (trial × exercise-time) was significant in $\nabla$SmO₂-m.intercostales, $\dot{\mathrm{V}}$E, and ($\nabla$SmO₂-m.intercostales)/$\dot{\mathrm{V}}$E (p < 0.05, all) but not in $\nabla$SmO₂-m.vastus lateralis. $\nabla$SmO₂-m.intercostales was more pronounced in CTRL during exercise since 5′ (p < 0.05). Hyperventilation was higher in CTRL since 10′ (p < 0.05). The $\nabla$SmO₂·$\dot{\mathrm{V}}$E⁻¹ decreased during exercise, being lowest in CTRL since 5′. Lower dyspnea was reported in HFNC, with no differences in leg fatigue and RPE. We concluded that wearable optical biosensors documented the beneficial effect of HFNC in COB due to lower respiratory $\nabla$SmO₂ induced by exercise. We suggest incorporating NIRS devices in rehabilitation programs to monitor physiological changes that can support the clinical impact of the therapeutic intervention implemented. Full article

The cytosine–phosphate–guanine (CpG) island methylator phenotype (CIMP) represents one of the pathways involved in the development of colorectal cancer, characterized by genome-wide hypermethylation. To identify samples exhibiting hypermethylation, we used unsupervised hierarchical clustering on genome-wide methylation data. This clustering analysis revealed the presence of four distinct subtypes within the tumor samples, namely, CIMP-H, CIMP-L, cluster 3, and cluster 4. These subtypes demonstrated varying levels of methylation, categorized as high, intermediate, and very low. To gain further insights, we mapped significant probes from all clusters to Ensembl Regulatory build 89, with a specific focus on those located within promoter regions or bound regions. By intersecting the methylated promoter and bound regions across all methylation subtypes, we identified a total of 253 genes exhibiting aberrant methylation patterns in the promoter regions across all four subtypes of colorectal cancer. Among these genes, our comprehensive genome-wide analysis highlights bone morphogenic protein 4 (BMP4) as the most prominent candidate. This significant finding was derived through the utilization of various bioinformatics tools, emphasizing the potential role of BMP4 in colorectal cancer development and progression. Full article

The efficient compiling of arbitrary single-qubit gates into a sequence of gates from a finite gate set is of fundamental importance in quantum computation. The exact bounds of this compilation are given by the Solovay–Kitaev theorem, which serves as a powerful tool in compiling quantum algorithms that require many qubits. However, the inverse closure condition it imposes on the gate set adds a certain complexity to the experimental compilation, making the process less efficient. This was recently resolved by a version of the Solovay–Kitaev theorem for inverse-free gate sets, yielding a significant gain. Considering the recent progress in the field of three-level quantum systems, in which qubits are replaced by qutrits, it is possible to achieve the quantum speedup guaranteed by the Solovay–Kitaev theorem simply from orthogonal gates. Nevertheless, it has not been investigated previously whether the condition of inverse closure can be relaxed for these qutrit-based orthogonal compilations as well. In this work, we answer this positively, by obtaining improved Solovay–Kitaev approximations to an arbitrary orthogonal qutrit gate, with an accuracy $\epsilon$ from a sequence of $O\left(lo{g}^{8.62}(1/\epsilon )\right)$ orthogonal gates taken from an inverse-free set. Full article

Vermifiltration is a low-energy and low-cost option to reduce the environmental impact of aquaculture. A comparative study was performed for two different stocking densities of the epigeic worm Dendrobaena veneta (Michaelsen, 1890, Annelida: Oligochaeta), which were fed with sediment sludge from African catfish, Clarias gariepinus (Burchell, 1822), recirculation aquaculture systems (RAS). The intensive (I) and extensive (E) systems were stocked with 15 and 10 g of worm/L filter substrate, respectively, and were compared with a control (C) for four weeks. The total weight gain was 9.4–13.5% for (I) and 13.8–19.5% for (E), with low mortality rates of 3.46–5.84% (I) and 3.57–5.19% (E). The temperature inside the vermifilters was slightly higher than that in the control, indicating a favorable milieu for microbial activity. The worms supported the pH buffering capacity in the systems, with the effluent reaching 7.10 ± 0.02 (I) and 7.26 ± 0.04 (E) at the end of the experiment while the pH in the (C) was significantly higher (7.51 ± 0.05). The removal rates were 68.02–98.84% (I), 71.85–98.67% (E), and 72.80–98.68% (C) for the total nitrogen bound (TNb); 82.77–96.64% (I), 81.65–94.84% (E), and 77.79–94.74% (C) for the total organic carbon (TOC); and 50.43–97.51% (I), 50.89–96.84% (E), and 48.23–96.34% (C) for the chemical oxygen demand (COD). By utilizing the sludge as feed, the worms and associated microbiota significantly altered the African catfish sediments, removing organic loads, upgrading the composition, and reducing the possible environmental impacts. Full article