Search Results (1,918)

Background/Objective: Cationic polymers were shown to assemble with negatively charged proteins yielding nanoparticles (NPs). Poly-diallyl-dimethyl-ammonium chloride (PDDA) combined with ovalbumin (OVA) yielded a stable colloidal dispersion (OVA/PDDA-NPs) eliciting significant anti-OVA immune response. Dendritic cells (DCs), as sentinels of foreign antigens, exert a crucial role in the antigen-specific immune response. Here, we aimed to evaluate the involvement of DCs in the immune response induced by OVA/PDDA. Methods: In vivo experiments were used to assess the ability of OVA/PDDA-NPs to induce anti-OVA antibodies by ELISA, as well as plasma cells and memory B cells using flow cytometry. Additionally, DC migration to draining lymph nodes following OVA/PDDA-NP immunization was evaluated by flow cytometry. In vitro experiments using bone marrow-derived DCs (BM-DCs) were used to analyze the binding and uptake of OVA/PDDA-NPs, DC maturation status, and their antigen-presenting capacity. Results: Our data confirmed the potent effect of OVA/PDDA-NPs inducing anti-OVA IgG1 and IgG2a antibodies with increased CD19⁺CD138⁺ plasma cells and CD19⁺CD38⁺CD27⁺ memory cells in immunized mice. OVA/PDDA-NPs induced DC maturation and migration to draining lymph nodes. The in vitro results showed higher binding and the uptake of OVA/PDDA-NPs by BM-DCs. In addition, the NPs were able to induce the upregulation of costimulatory and MHC-II molecules on DCs, as well as TNF-α and IL-12 production. Higher OVA-specific T cell proliferation was promoted by BM-DCs incubated with OVA/PDDA-NPs. Conclusions: The data showed the central role of DCs in the induction of antigen-specific immune response by OVA-PDDA-NPs, thus proving that these NPs are a potent adjuvant for subunit vaccine design. Full article

The JUpiter Icy Moon Explorer (JUICE) mission, launched on 14 April 2023, aims to explore Jupiter and its Galilean moons, with arrival in the Jovian system planned for mid-2031. One of the scientific investigations is the Geodesy and Geophysics of Jupiter and the Galilean Moons (3GM) radio science experiment, designed to study the interior structures of Europa, Callisto, and Ganymede and the atmospheres of Jupiter and the Galilean moons. The 3GM experiment employs a Ka-band Transponder (KaT) to enable two-way coherent range and Doppler measurements used for the gravity experiment and an Ultra Stable Oscillator (USO) for one-way downlink occultation experiments. This paper analyzes KaT data collected at the ESA/ESTRACK ground station in Malargüe, Argentina, during the Near-Earth Commissioning Phase (NECP) in May 2023 and the first in-cruise payload checkout (PC01) in January 2024. The radiometric data were fitted using both NASA’s Mission Analysis, Operations, and Navigation Toolkit Environment (MONTE) and ESA’s General Orbit Determination and Optimization Toolkit (GODOT) software. The comparison of the orbital solutions showed an excellent agreement. In addition, the Doppler and range residuals allowed a preliminary assessment of the quality of the radiometric measurements. During the NECP pass, the radio link data showed a range-rate noise of 0.012 mm/s at 1000 s integration time, while the root mean square of the range residuals sampled at 1 s was 8.4 mm. During the first payload checkout, the signal power at the KaT input closely matched the value expected at Jupiter, due to a specific ground station setup. This provided early indications of the 3GM’s performance during the Jovian phase. In this test, the accuracy of range data at an integration time of 1s, particularly sensitive to the link signal-to-noise ratio, degraded to 13.6 cm, whilst the range-rate accuracy turned out to be better than 0.003 mm/s at 1000 s, thanks to the accurate tropospheric delay calibration system (TDCS) available at the Malargue station (inactive during NECP). Full article

Anogenital inflammation is a critical risk factor for HIV acquisition. The primary preventative HIV intervention, pre-exposure prophylaxis (PrEP), is ineffective in blocking transmission in anogenital inflammation. Pre-existing sexually transmitted diseases (STIs) and anogenital microbiota dysbiosis are the leading causes of inflammation, where inflammation is extensive and often asymptomatic and undiagnosed. Dendritic cells (DCs), as potent antigen-presenting cells, are among the first to capture HIV upon its entry into the mucosa, and they subsequently transport the virus to CD4 T cells, the primary HIV target cells. This increased HIV susceptibility in inflamed tissue likely stems from a disrupted epithelial barrier integrity, phenotypic changes in resident DCs and an influx of inflammatory HIV target cells, including DCs and CD4 T cells. Gaining insight into how HIV interacts with specific inflammatory DC subsets could inform the development of new therapeutic strategies to block HIV transmission. However, little is known about the early stages of HIV capture and transmission in inflammatory environments. Here, we review the currently characterised inflammatory-tissue DCs and their interactions with HIV. Full article

To mitigate the challenges posed by transient oscillations and steady-state deviations in the traditional virtual synchronous generator (TVSG) that is subjected to active power and grid frequency disturbances, a VSG control strategy based on Transient Damping Compensation and Virtual Inertia Adaptation is presented. Initially, a closed-loop small-signal model for the grid-connected active power loop (APL) of the TVSG is constructed, which highlights the contradiction between the dynamic and static characteristics of TVSG output power through the analysis of root locus distribution trends. Secondly, a VSG control strategy based on Transient Damping Compensation (TDC) is proposed. The influence of APL system parameters introduced by TDC on system stability is qualitatively analyzed based on pole distribution trends and frequency response, and a comprehensive parameter design scheme is presented. In addition, based on the TDC algorithm, an improved virtual inertia adaptive strategy utilizing the Inverse Square Root Unit (ISRU) approach is designed, and the tuning range of parameters is provided. Finally, simulations and experiments verify that the proposed strategy exhibits superior active response performance and transient oscillation suppression capabilities, effectively eliminating active steady-state deviations caused by frequency disturbances in the power grid. Full article

Background: In the past decade, immunotherapy has become a major choice for the treatment of lung cancer, yet its therapeutic efficacy is still relatively limited due to the various immune escape mechanisms of tumors. Based on this, we introduce Neo-BCV, a novel bacterial composite vaccine designed to enhance immune responses against lung cancer. Methods: We investigated the immune enhancing effect of Neo-BCV through in vivo and in vitro experiments, including flow cytometry, RNA-seq, and Western blot. Results: We have demonstrated that Neo-BCV can promote Dendritic cells (DCs) maturation and induce DCs differentiation into pro-inflammatory subgroups, significantly enhancing cytotoxic T lymphocyte (CTL)-mediated anti-tumor responses. Transcriptome sequencing revealed that Neo-BCV exerts its effects by specifically inhibiting the JAK2-STAT3 signaling pathway, a crucial regulator of cancer progression, metabolism, and inflammation. Moreover, Neo-BCV significantly improved the immune microenvironment in both tumor and spleen tissues without inducing notable toxic effects in major organs. Conclusions: These findings highlight Neo-BCV’s potential as a safe and effective therapeutic strategy, offering a novel avenue for clinical translation in lung cancer immunotherapy. Full article

Background/Objectives: Multiple sclerosis (MS) is the most prevalent incurable nontraumatic neurological disability in young individuals. It causes numerous symptoms, including tingling, fatigue, muscle spasms, cognitive deficits, and neuropsychiatric disorders. This disease significantly worsens quality of life (QoL), and this dimension of general functioning provides valuable information about the effectiveness of treatment and well-being. There are psychological interventions that can improve QoL, but their number is limited. Therefore, searching for new methods that are as effective and safe as possible is ongoing. Methods: This review examines the potential effectiveness of transcranial direct current stimulation (tDCS) in improving the quality of life in patients with MS. Searches were conducted in the PubMed/Medline, Research Gate, and Cochrane databases. Results: The search yielded seven studies in which QoL was a primary or secondary outcome. Stimulation protocols displayed heterogeneity, especially concerning the choice of the stimulation site. Four studies demonstrated the effectiveness of tDCS in improving QoL, all of which (two) used anodal stimulation of the left DLPFC. Stimulation of the motor cortex has produced mixed results. The potential mechanisms of action of tDCS in improving QoL in MS are explained. These include improved synaptic plasticity, increased cerebral blood flow, salience network engagement through tDCS, and reduction of beta-amyloid deposition. The limitations are also detailed, and recommendations for future research are made. Conclusions: While the evidence is limited, tDCS has shown potential to improve QoL in MS patients in some studies. Prefrontal stimulation appears promising, and further research is recommended to explore this approach. Full article

The vesicular stomatitis virus (VSV)-vectored African swine fever virus (ASFV) vaccine can induce efficient immune response, but the potential mechanism remains unsolved. In order to investigate the efficacy of recombinant viruses (VSV-p35, VSV-p72)-mediated dendritic cells (DCs) maturation and the mechanism of inducing T-cell immune response, the functional effects of recombinant viruses on DC activation and target antigens presentation were explored in this study. The results showed that surface-marked molecules (CD80, CD86, CD40, and MHC-II) and secreted cytokines (IL-4, TNF-α, IFN-γ) were highly expressed in the recombinant virus-infected DCs. In addition, the co-culture results of recombinant virus-treated DCs with naive T cells showed that the Th1- and Th17-type responses were effectively activated. Taken together, the study indicated that the VSV-vectored ASFV vaccine activated the maturation of DCs and the Th1- and Th17-type immune response, which provided a theoretical basis for the development of novel ASF vaccines. Full article

Background: Human papillomavirus (HPV) is a prevalent infection affecting both men and women, leading to various cytological lesions. Therapeutic vaccines mount a HPV-specific CD8+ cytotoxic T lymphocyte response, thus clearing HPV-infected cells. However, no therapeutic vaccines targeting HPV are currently approved for clinical treatment due to limited efficacy. Our goal is to develop a vaccine that can effectively eliminate tumors caused by HPV. Methods: We genetically fused the chemokine XCL1 with the E6 and E7 proteins of HPV16 to target cDC1 and enhance the vaccine-induced cytotoxic T cell response, ultimately developing a DNA vaccine. Additionally, we screened various interleukins and identified IL-9 as an effective molecular adjuvant for our DNA vaccine. Results: The fusion of Xcl1 significantly improved the quantity and quality of the specific CD8+ T cells. The fusion of Xcl1 also increased immune cell infiltration into the tumor microenvironment. The inclusion of IL-9 significantly elevated the vaccine-induced specific T cell response and enhanced anti-tumor efficacy. IL-9 promotes the formation of central memory T cells. Conclusions: the fusion of Xcl1 and the use of IL-9 as a molecular adjuvant represent promising strategies for vaccine development. Full article

In this work, three composite materials based on Terfenol-D and PZT-type material were obtained with a classic sintering method using a combination of 0–3 phases, where the ferroelectric phase was doped PZT material (P) and the magnetic phase was Terfenol-D (T). The percentage of P and T components in the composites was variable, i.e., 90% P/10% T (P90-T10), 70% P/30% T (P70-T30), and 50% P/50% T (P50-T50). Structural, microstructure, dielectric, and magnetic properties and DC electric conductivity of multiferroic composites were investigated. Chemical composition analyses and X-ray studies showed a decomposition of the composite compositions, forming additional phases, most of which contained rare earth elements and Fe. Microstructural SEM-BE (backscattering) images distinguished areas of bright intensity with a dominant ferroelectric phase and dark areas with a dominant magnetic element dominance. Despite the composition decomposition, the composite materials retained good dielectric and magnetic properties at room temperature. The highest stability of dielectric parameters was maintained by the P90-T10 composition with high values of permittivity ε = 570 at room temperature RT (ε_m = 7300 at the phase transition temperature T_m) and the lowest dielectric tangent loss (tanδ of 0.32 and 1.94 for RT and T_m, respectively). Increasing the Terfenol-D share in the composite causes a significant increase in dielectric tangent loss and electrical conductivity, a decrease in permittivity, and an increase in the degree of phase transition blurring. The magnetic properties for all P-T composite compositions at RT were preserved and were 0.31 emu/g, 1.60 emu/g, and 4.56 emu/g for P90-T10, P70-T30, P50-T50, respectively. For the M-H hysteresis loop at room temperature, the maximum magnetization increased from 1.17 emu/g for (P90-T10) to 15.18 emu/g for (P50-T50), while the coercive field decreased from 271.8 mT for P90-T10 to 9.7 mT for P50-T50. It is also interesting to maintain the high saturation of the M-H magnetic hysteresis loop in the composite with the lowest Terfenol-D content (P90-T10). The magnetic properties for all P-T composite compositions at room temperature were preserved and were 0.31 emu/g, 1.60 emu/g, and 4.56 emu/g for P90-T10, P70-T30, and P50-T50, respectively. For the M-H hysteresis loop at RT, the maximum magnetization increased from 1.17 emu/g for (P90-T10) to 15.18 emu/g for (P50-T50), while the coercive field decreased from 0.272 T for P90-T10 to 0.001 T for P50-T50. It is also interesting to maintain the high saturation of the M-H magnetic hysteresis loop in the composite with the lowest Terfenol-D content (P90-T10). Due to the tendency to combine with oxygen and the high electric conductivity of Terfenol-D, limiting its amount in the composite composition is appropriate. At 10% of Terfenol-D, the composite has good dielectric properties, and the magnetic parameters remain satisfactory. Full article

Background/Objectives: Effectively targeting treatment-resistant tumor cells, particularly cancer stem cells (CSCs) involved in tumor recurrence, remains a major challenge in immunotherapy. This study examines the potential of combining mechanical high-intensity focused ultrasound (M-HIFU) with dendritic cell (DC) vaccines to enhance immune responses against OLFM4-expressing tumors, a CSC marker linked to immune evasion and tumor growth. Methods: M-HIFU was applied to induce immunogenic cell death by mechanically disrupting tumor cells, releasing tumor-associated antigens and creating an immunostimulatory environment. DC vaccines loaded with OLFM4 were then administered to boost the immune response within this primed environment. Results: The combination of M-HIFU and DC vaccine significantly inhibited tumor growth and metastasis, with enhanced T-cell activation and increased recruitment of immune cells due to elevated chemokines CCL19 and CCL21. This synergy promoted immune memory, reducing the likelihood of recurrence. Conclusions: M-HIFU effectively promotes the migration of DC vaccines through CCL19/21, presenting a promising approach for cancer treatment. Further studies are recommended to optimize this combination for clinical applications, with potential to improve patient outcomes in challenging cancer types. Full article

Prebiotics and probiotics have key roles in the intervention and treatment of food allergies. This study assesses the effect of Lactiplantibacillus plantarum synergistic fructo-oligosaccharide (Lp–FOS) intervention using an allergic mouse model induced by soy protein. The results showed that Lp synergistic FOS significantly decreased clinical allergy scores, inhibited specific antibodies (IgE, IgG, and IgG1), IL-4, IL-6, and IL-17A levels, and increased IFN-γ and IL-10 levels. Meanwhile, flow cytometry showed that Lp–FOS intervention inhibited the percentage of dendritic cell (DC) subsets in splenocytes and increased the Th1/Th2 and Treg/Th17 ratios. Furthermore, Lp–FOS intervention upregulated the mRNA levels of T-bet and Foxp3 and downregulated the mRNA levels of GATA3. Finally, non-targeted metabolomic analysis showed that Lp–FOS improved serum metabolic disorders caused by food allergies through regulating glycine, serine, and threonine metabolism, butanoate metabolism, glyoxylate and dicarboxylate metabolism, the biosynthesis of cofactors, and glycerophospholipid metabolism. These data showed that the combination formulation Lp–FOS could be a promising adjuvant treatment for food allergies. Full article

Endosomal toll-like receptors (TLRs) TLR7, TLR8, and TLR9 play an important role in systemic lupus erythematosus (SLE) pathogenesis. The proteolytic processing of these receptors in the endolysosome is required for signaling in response to DNA and single-stranded RNA, respectively. Targeting this proteolytic processing may represent a novel strategy to inhibit TLR-mediated pathogenesis. Human alpha 1 antitrypsin (hAAT) is a protease inhibitor with anti-inflammatory and immunoregulatory properties. However, the effect of hAAT on endosomal TLRs remains elusive. In this study, we first tested the effect of hAAT on TLR9 signaling in dendritic cells (DCs). We showed that hAAT inhibited TLR9-mediated DC activation and cytokine production. Human AAT also lowered the expressions of interferon signature genes. Western blot analysis showed that hAAT reduced the expression of the active form (cleaved) of TLR9 in DCs, indicating a novel mechanism of hAAT function in the immune system. We next tested the effect of hAAT on TLR7/8 signaling. Similar to the effect on TLR9 signaling, hAAT also inhibited R848 (TLR7 and 8 agonist)-induced DC activation and functions and lowered the expressions of interferon signature genes. Our in vivo studies using hAAT transgenic mice also showed that hAAT attenuated R848-induced pathogenesis. Specifically, hAAT completely blocked the R848 induction of germinal center T cells (GC T), B cells (GC B), and plasma cells (GC PCs), as well as T follicular T helper cells (T_FH), which are all critical in lupus development. These data demonstrated that hAAT inhibited TLR7/8 and TLR9 signaling pathways, which are critical for lupus development. These findings not only advanced the current knowledge of hAAT biology, but also implied an insight into the clinical application of hAAT. Full article

Background: Polysaccharides produced by the edible fungus Cordyceps cicadae can regulate blood sugar levels and may represent a suitable candidate for the treatment of diabetes and its complications. However, there is limited information available about the mechanism of how C. cicadae polysaccharide (CCP) might improve diabetic conditions. Methods: This study investigated its effects on the intestinal microbiota, intestinal mucosal barrier, and inflammation in mice with type 2 diabetes mellitus (T2DM) induced by streptozotocin, and its potential mechanisms. Results: Compared with the DC (diabetes model control group), CCPH oral treatment significantly increased the number of beneficial bifidobacteria, bifidobacteria, and lactobacilli (p < 0.01), restored the diversity of intestinal microorganisms in diabetic mice, and the proportions of Firmicutes and Bacteroidetes (34.36%/54.65%) were significantly lower than those of the DC (52.15%/32.09%). Moreover, CCPH significantly reduced the content of endotoxin (lipopolysaccharide, LPS) and D-lactic acid(D-LA) (p < 0.05), the activities of antioxidant enzymes and total antioxidant capacity were significantly increased (p < 0.01), and the content of proinflammatory cytokines TNF-α, IL-6, and IL-1β were reduced by 42.05%, 51.28%, and 52.79%, respectively, compared with the DC. The TLR4/NF-κB signaling pathway, as a therapeutic target for diabetic intestinal diseases, plays a role in regulating the inflammatory response and protecting the intestinal barrier function. Molecular mechanism studies showed that oral treatment with CCPH down-regulated the expression of NF-κB, TLR-4, and TNF-α genes by 18.66%, 21.58%, and 34.87%, respectively, while up-regulating the expression of ZO-1 and occludin genes by 32.70% and 25.11%, respectively. CCPH regulates the expression of short-chain fatty acid levels, increases microbial diversity, and ameliorates mouse colon lesions by inhibiting the TLR4/NF-κB signaling pathway. Conclusions: In conclusion, it is demonstrated that in this murine model, the treatment of diabetes with C. cicadae polysaccharide can effectively regulate intestinal microbiota imbalance, protect intestinal mucosal barrier function, and reduce inflammation in vivo, suggesting this natural product can provide a suitable strategy for the treatment of T2D-induced gut dysbiosis and intestinal health. Full article

Background/Objectives: Noninvasive brain stimulation (NIBS) can boost motor recovery after a stroke. Certain movement phases are more responsive to NIBS, so a system that auto-detects these phases would optimize stimulation timing. This study assessed the effectiveness of various machine learning models in identifying movement phases in hemiparetic individuals undergoing simultaneous NIBS and EEG recordings. We hypothesized that transcranial direct current stimulation (tDCS), a form of NIBS, would enhance EEG signals related to movement phases and improve classification accuracy compared to sham stimulation. Methods: EEG data from 10 chronic stroke patients and 11 healthy controls were recorded before, during, and after tDCS. Eight machine learning algorithms and five ensemble methods were used to classify two movement phases (hold posture and reaching) during each of these periods. Data preprocessing included z-score normalization and frequency band power binning. Results: In chronic stroke participants who received active tDCS, the classification accuracy for hold vs. reach phases increased from pre-stimulation to the late intra-stimulation period (72.2% to 75.2%, p < 0.0001). Late active tDCS surpassed late sham tDCS classification (75.2% vs. 71.5%, p < 0.0001). Linear discriminant analysis was the most accurate (74.6%) algorithm with the shortest training time (0.9 s). Among ensemble methods, low gamma frequency (30–50 Hz) achieved the highest accuracy (74.5%), although this result did not achieve statistical significance for actively stimulated chronic stroke participants. Conclusions: Machine learning algorithms showed enhanced movement phase classification during active tDCS in chronic stroke participants. These results suggest their feasibility for real-time movement detection in neurorehabilitation, including brain–computer interfaces for stroke recovery. Full article

Isolated microgrids have long been considered alternative power system entities that can integrate various types of distributed energy sources such as diesel and renewable power generators including energy storage. Renewable energy sources, such as wind and solar PV, introduce low inertia and high intermittency to the microgrid. For this reason, coordinated control and frequency stabilisation are crucial for maintaining higher service levels in the microgrid. This paper reports on the design and development of two proposed methods for virtual inertia provision, namely model-based and filter-based methods, which support the frequency stability of AC/DC microgrids. The inertial power produced by these methods was implemented through power-controlled voltage source converters, associated with a Li-ion battery energy storage system. To derive and develop the functions for the virtual inertia providers using these methods, a new electromechanical power-speed model was developed to represent the interaction between the microgrid AC/DC-sides and its generators. Small-signal analysis using the linearised form of this model was carried out, in addition to deriving the law for the model-based virtual inertia method. Detailed physical-system simulation and tests were performed, and performance analysis of the resulting generator speed-responses using the proposed methods illustrated their merits compared with other methods, namely the standard $df/dt$ and frequency-event techniques. Full article