Search Results (474)

Background: Classical Hodgkin lymphoma (cHL) is a rare B-cell malignant neoplasm, characterized by the presence of rare mononucleated Hodgkin and multinucleated Reed–Sternberg cells (HRS). CD34+ cells are highly expressed on lymphoma stem cells in bone marrow (BM). Little is known about gene mutations in BM CD34+ cells of cHL. In this study, whole exome sequencing (WES) was performed and high-frequency mutation genes were examined through their expression levels. Materials and Methods: The influence of the variants on protein function was predicted with in silico tools or public databases. Gene expression levels were determined by quantitative real-time PCR. Results: WES assay from BM CD34+ cells in thirty cHL patients revealed that three variants were detected in known cHL-associated genes, including NCF1 (13.33%), MMP9 (3.33%), and VDR (3.33%). We also observed other candidate genes including CNN2 rs77830704 (76.67%), CNN2 rs78386506 (63.33%), MUC4 p.Y3278_Q3209Del (66.67%), MUC4 p.P1076_P1124Del (33.33%), MUC4 rs748236754 (26.67%), MUC4 p.P1609Ins (23.33%), MUC4 rs748705487 (20%), MUC4 p.P4121_P4137Del (16.67%), MTSS2 rs531163149 (13.33%), KMT2C rs201834857 (20%), HAVCR2 rs184868814 (16.67%), and TCF19 rs541001159 (13.33%). Moreover, the low levels of MUC4 were associated with an increase in neutrophil-to-lymphocyte ratio and the low CNN2 expression group had higher levels of LDH, suggesting that the low expressions of CNN2 and MUC4 might be important risk factors for poor prognosis in cHL. Conclusions: WES revealed significantly mutated genes, most of which were associated with the physiological activation of lymphoma cells. This finding contributed to the identification of novel gene variants that might impact on the function of BM CD34+ cells in cHL patients. Full article

This work presents an Internet of Things (IoT) node designed for low-power agrifood chain tracking in remote areas, where long-range terrestrial communication is either unavailable or severely limited. The novelty of this study lies in the development and characterization of an IoT node prototype that leverages direct-to-satellite connectivity through a geostationary Earth orbit (GEO) satellite, using long-range frequency-hopping spread spectrum (LR-FHSS) modulation in the licensed S-band. The prototype integrates a microcontroller unit that manages both the radio modem and a suite of sensors, enclosed in a plastic box suitable for field deployment. Characterization in an anechoic chamber demonstrated a maximum effective isotropic radiated power (EIRP) of $27.5$ dBm, sufficient to establish a reliable satellite link. The onboard sensors provide global positioning as well as measurements of acceleration, temperature, humidity, and solar radiation intensity. Prototype performance was assessed in two representative scenarios: stationary and mobile. Regarding energy consumption, the average charge drained by the radio modem per transmission cycle was measured to be 356 mC. With a battery pack composed of four 2500 mAh NiMH cells, the estimated upper bound on the number of transmitted packets is approximately 25,000. Full article

Background: Burning Mouth Syndrome (BMS) is a nociplastic pain condition characterized by altered central nervous system pain processing, significantly impacting patient quality of life. Pharmacological management often involves amitriptyline (monotherapy) and aripiprazole (for refractory cases) in Japan. However, the therapeutic efficacy of these drugs in BMS frequently exhibits a non-sigmoid (U-shaped or bell-shaped) dose–response relationship, indicating a clinically effective dose that is often considerably lower than those used for their primary indications and challenging conventional pharmacological assumptions. Method: This paper synthesizes existing pharmacological knowledge to elucidate the mechanisms underlying the non-dose-dependent actions of amitriptyline and aripiprazole in BMS. It focuses on their specific interactions with key neurotransmitter systems and receptors, particularly N-methyl-D-aspartate (NMDA) receptors and dopamine D2 receptors, to explain the observed non-linear dose–response and the importance of identifying a personalized therapeutic window. Result: Amitriptyline demonstrates efficacy in BMS at low doses (e.g., 25 mg), primarily through its action as an NMDA receptor antagonist via calcium-dependent desensitization and open-channel block, addressing central sensitization. Its effects are distinct from its antidepressant actions, and the “serotonin paradox” highlights the complexity of serotonin’s role in pain. Aripiprazole, utilized for refractory BMS, acts as a dopamine D2 receptor partial agonist, leading to a non-linear dose–response where sustained therapeutic effect is observed at specific low doses (e.g., 1.7–1.8 mg/day). This non-linearity is attributed to partial agonism, alongside interactions with serotonin 5-HT1A and 5-HT2A receptors. The general non-dose-dependency for both drugs is further explained by phenomena such as multiple binding sites with differing affinities, receptor desensitization/downregulation, activation of counter-regulatory mechanisms, and hormesis. Discussion: The observed non-linear dose–response curves for amitriptyline and aripiprazole in BMS underscore the inadequacy of a “one-size-fits-all” treatment approach. This necessitates a shift towards personalized medicine, which considers individual patient factors including pharmacogenomics, comorbidities, age, organ function, and psychological/social profiles. The true “personalized therapeutic window” is a balance between achieving significant pain relief and minimizing adverse effects, emphasizing careful titration and patient-centered care. Conclusions: The pharmacological actions of amitriptyline and aripiprazole in BMS are not linearly dose-dependent, but rather exhibit a personalized therapeutic window driven by complex interactions with NMDA and D2 receptors and adaptive physiological responses. This intricate pharmacological landscape mandates a personalized medicine approach to optimize treatment outcomes, improve patient adherence, and enhance the quality of life for individuals suffering from this challenging nociplastic pain condition. Full article

Alginate-hydroxyapatite (AL) scaffolds modified with fibronectin (FN) or bioactive glass (BGMS10) have recently been characterized for their physicochemical properties and proposed as promising candidates for bone regeneration. Here, we present their first systematic biological evaluation, focusing on adhesion, proliferation, osteogenic differentiation, and in vivo host response. We compared FN-, BG-, and unmodified AL scaffolds using an immortalized mesenchymal stromal cell line (M-SOD) and primary human bone marrow-derived (BM-MSCs) and adipose-derived stromal cells (ASCs). FN scaffolds enhanced initial adhesion across all cell types and supported proliferation in M-SODs, but primary BM-MSCs and ASCs showed minimal expansion, regardless of scaffold type. BG scaffolds promoted expression of late-stage osteogenic markers in BM-MSCs, consistent with their ion release profile, but had limited impact on ASCs. In vivo subcutaneous implantation of acellular scaffolds in nude mice revealed robust host cell infiltration and extracellular matrix deposition across all scaffold types, confirming biocompatibility and integration. However, vascularization remained limited and did not differ substantially between formulations. Together, these findings highlight a critical discrepancy between immortalized and primary stromal cell responses to scaffold cues, underscoring the choice of cell source when evaluating the biocompatibility of a novel scaffold. At the same time, the effective in vivo integration observed across scaffold types emphasizes the importance of host tissue responses for translational evaluation of functional biomaterials. Full article

B-cell acute lymphoblastic leukemia (B-ALL) is characterized by the abnormal proliferation of B-lineage lymphocytes in the bone marrow (BM). The roles of immune cells within the BM microenvironment remain incompletely understood. Single-cell RNA sequencing (scRNA-seq) provides the potential for groundbreaking insights into the pathogenesis of B-ALL. In this study, scRNA-seq was conducted on BM samples from 17 B-ALL patients (B-ALL cohorts) and 13 healthy controls (HCs). Bioinformatics analyses, including clustering, differential expression, pathway analysis, and gene set variation analysis, systematically identified immune cell types and assessed T-cell prognostic and metabolic heterogeneity. A metabolic-feature-based machine learning model was developed for B-ALL subtyping. Furthermore, T-cell–monocyte interactions, transcription factor (TF) activity, and drug enrichment analyses were performed to identify therapeutic targets. The results indicated significant increases in Pro-B cells, alongside decreases in B cells, NK cells, monocytes, and plasmacytoid dendritic cells (pDCs) among B-ALL patients, suggesting immune dysfunction. Clinical prognosis correlated significantly with the distribution of T-cell subsets. Metabolic heterogeneity categorized patients into four distinct groups (A–D), all exhibiting enhanced major histocompatibility class I (MHC-I)-mediated intercellular communication. The metabolic-based machine learning model achieved precise classification of B-ALL groups. Analysis of TF activity underscored the critical roles of MYC, STAT3, and TCF7 within the B-ALL immunometabolic network. Drug targeting studies revealed that dorlimomab aritox and palbociclib specifically target dysregulation in ribosomal and CDK4/6 pathways, offering novel therapeutic avenues. This study elucidates immunometabolic dysregulation in B-ALL, characterized by altered cellular composition, metabolic disturbances, and abnormal cellular interactions. Key TFs were identified, and targeted drug profiles were established, demonstrating the significant clinical potential of integrating immunological mechanisms with metabolic regulation for the treatment of B-ALL. Full article

Lepidium meyenii Walp. (black maca, BM) is a traditional Andean crop increasingly studied for its bioactive potential. This work characterized the phytochemical profile and evaluated the antioxidant, antinociceptive, and neuroprotective properties of a lyophilized aqueous extract of BM hypocotyls. UHPLC-ESI-QTOF-MS/MS identified twelve major compounds, including macamides, imidazole alkaloids, sterols, and fatty acid amides. BM showed a moderate total phenolic content but strong electron transfer-based antioxidant activity in CUPRAC and FRAP assays, together with moderate radical scavenging capacity in ABTS and DPPH systems. In ovariectomized rats, BM significantly reduced brain malondialdehyde levels, mitigated oxidative stress, and improved spatial learning during acquisition in the Morris water maze, confirming its neuroprotective effect. Antinociceptive assays (hot plate, cold plate, and tail immersion) further revealed a rapid but transient increase in nociceptive thresholds. This study provides experimental evidence supporting the analgesic effect of black maca. Molecular docking highlighted lepidiline B and campesterol as key metabolites with strong interactions with redox enzymes, the μ-opioid receptor, and the FAAH enzyme, supporting their role in the observed bioactivities. ADMET predictions indicated favorable oral bioavailability, CNS penetration, systemic clearance, and acceptable safety profiles. These results substantiate the role of black maca as a neuroprotective nutraceutical and highlight its promise as a novel source of rapidly acting natural analgesic compounds. Full article

Flow dynamics were characterized and stable zones in diversions were quantified using physical modeling, in situ experiments, and 3D numerical simulations. ADV (1 cm spatial resolution) and water-level probes (0.01 cm spatial resolution) were used in the physical experiments in a rectangular channel. ADCP (resolution of 50 cm) was employed for in situ validation at a northern China hub. Numerical simulations using ANSYS 2022R2 Fluent software with RNG k-ε and VOF showed little error (<15%) compared to the experiments. The results quantified the diversion zone into four sub-regions: acceleration (length 0.8–1.2 h); stabilization (1.2–3.5 h); diffusion deceleration (3.5–5.0 h); and stagnation (localized eddies, diameter 0.3–0.8 d). The stable zone length was dominantly controlled by the nonlinear coupling of geometric (B_s/B_m, 42%) and hydraulic (Fr, 28%) parameters. Upstream and downstream stable zone empirical models showed high accuracy (R² = 0.83 and 0.76, p < 0.01), with an average relative error <15%. Based on the proposed zoning principles and flow characteristics, measurement facilities in the irrigation area are presented. These tools enhance irrigation diversion design and management for improved water efficiency. Full article

The adverse propagation environment in underground coal mine tunnels caused by enclosed spaces, rough surfaces, and dense scatterers severely degrades reliable wireless signal transmission, which further impedes the deployment of IoT applications such as gas monitors and personnel positioning terminals. However, the conventional power enhancement solutions are infeasible for the underground coal mine scenario due to strict explosion-proof safety regulations and battery-powered IoT devices. To address this challenge, we propose singular value decomposition-based Lagrangian optimization (SVD-LOP) to minimize transmit power at the mining base station (MBS) for IRS-assisted coal mine wireless communication systems. In particular, we first establish a three-dimensional twin cluster geometry-based stochastic model (3D-TCGBSM) to accurately characterize the underground coal mine channel. On this basis, we formulate the MBS transmit power minimization problem constrained by user signal-to-noise ratio (SNR) target and IRS phase shifts. To solve this non-convex problem, we propose the SVD-LOP algorithm that performs SVD on the channel matrix to decouple the complex channel coupling and introduces the Lagrange multipliers. Furthermore, we develop a low-complexity successive convex approximation (LC-SCA) algorithm to reduce computational complexity, which constructs a convex approximation of the objective function based on a first-order Taylor expansion and enables suboptimal solutions. Simulation results demonstrate that the proposed SVD-LOP and LC-SCA algorithms achieve transmit power peaks of $20.8\mathrm{dBm}$ and $21.4\mathrm{dBm}$, respectively, which are slightly lower than the $21.8\mathrm{dBm}$ observed for the SDR algorithm. It is evident that these algorithms remain well below the explosion-proof safety threshold, which achieves significant power reduction. However, computational complexity analysis reveals that the proposed SVD-LOP and LC-SCA algorithms achieve $\mathcal{O}\left(N^3\right)$ and $\mathcal{O}\left(N^2\right)$ respectively, which offers substantial reductions compared to the SDR algorithm’s $\mathcal{O}\left(N^7\right)$. Moreover, both proposed algorithms exhibit robust convergence across varying user SNR targets while maintaining stable performance gains under different tunnel roughness scenarios. Full article

Background/Objectives: Polymeric barrier membranes (BMs) are usually used in guided bone regeneration to isolate the bone defect from the surrounding tissue, favoring bone apposition. This study proposes a third-generation BM made of polycaprolactone (PCL), loaded with different concentrations of nano-hidroxyapatite (nHAP) and gentamicin (GEN), and fabricated by electrospinning. Methods: The mechanical properties of the polymer, together with the fabrication procedure, offer porosity with interconnectivity to permit cell adhesion and proliferation. Bacterial contamination of the BM can induce infection at the bone level, leading to unfavorable clinical outcomes of the regeneration procedure. Results: Therefore, BMs have been proposed as carriers for local GEN antibiotic therapy, demonstrating antibacterial properties against S. aureus, S. mutans, and P. aeruginosa, depending on the drug concentration, while being negligibly affected by the nHAP content. X-ray diffraction, FTIR-ATR, and SEM allowed for BM structural characterization, demonstrating the presence of GEN/nHAP and establishing the fiber diameter, which influences the mechanical properties in dry and wet conditions and the drug release behaviorA BM cytotoxicity assessment, performed over 1 and 5 days, revealed that a high nHAP concentration provided protection against cytotoxicity, in contrast to GEN, and that cell proliferation and cell adhesion increased in the presence of nHAP. The BM’s bioactivity was demonstrated by mineralization after 21 days in simulated body fluid in an SEM/EDX analysis. Conclusions: The electrospun 15 wt.% nHAP and 2 wt.% GEN-loaded third-generation BM could be a promising alternative for guided bone regeneration. Full article

Accurate estimation of the state of health (SOH) is a critical function of battery management system (BMS), essential for ensuring the safe and stable operation of lithium-ion batteries. To improve estimation precision, this paper proposes a novel health indicator (HI) construction method and an improved support vector regression (SVR) approach. First, the convolution operation is applied to discharge voltage data to extract new HIs that characterize battery aging; their correlations are then verified. Second, principal component analysis (PCA) is employed to reduce input dimensionality and computational burden. Third, to address the challenge of SVR parameter selection, an improved sparrow search algorithm (ISSA) is proposed for parameter optimization. Finally, the proposed method is validated using both the NASA dataset and a laboratory experimental dataset, with comparisons against existing approaches. The results show that the method achieves accurate SOH estimation under various aging conditions, demonstrating its effectiveness, robustness, and practical potential. Full article

To identify highly virulent Beauveria bassiana strains against Tuta absoluta and evaluate their biocontrol potential, four strains were phylogenetically characterized via ITS sequence analysis of rDNA and assessed for virulence against second-instar T. absoluta larvae. Foliar spray and root irrigation methods were used to establish B. bassiana endophytic colonization in tomato plants, with untreated plants serving as controls. A population life table was constructed to quantify the impact of colonized plants on larval development, fecundity, and key demographic parameters. Results showed variation in virulence among the four B. bassiana strains Bb1Bm, Bb2Bm, Bb1M, and BbC with Bb1Bm exhibiting the highest pathogenicity (85.00% corrected mortality at 1 × 10⁸ spores/mL). Maximum endophytic colonization in tomato leaves was observed 14 days post-inoculation with both foliar spray and root irrigation treatments. Life table analyses revealed that T. absoluta feeding on colonized plants exhibited significantly reduced survival rates, shorter adult lifespans, and lower female fecundity compared to controls. Key population parameters, including net reproductive rate (R₀), intrinsic rate of increase (r), and finite rate of increase (λ), were significantly reduced, while mean generation time (T) was significantly prolonged. These findings highlight the dual role of B. bassiana in T. absoluta management, demonstrating its potential as both a direct pathogen and an endophytic biocontrol agent capable of disrupting pest population dynamics. Full article

Background: Current Alzheimer’s disease (AD) treatments primarily focus on symptom management and offer limited potential to arrest disease progression. To address this limitation, we developed baicalin–myricetin (BM) functionalized selenium nanoparticles (SeNPs), termed BMSe@BSA, aimed at multi-targeted neuroprotection. Materials and Methods: BMSe@BSA nanoparticles were synthesized via a gel–sol technique using bovine serum albumin (BSA), ascorbic acid, selenous acid, and BM. Interactions among BSA, BM, and SeNPs were characterized by microscopy and spectrometry. Cytotoxicity was assessed on RAW 264.7 and PC12 cells to determine biocompatibility. Neuroinflammation and cognitive function were evaluated in C57BL6/J mice challenged with Aβ1-42. Recognition memory was tested through open-field exploration, novel object recognition (NOR), and T-maze assays. Inflammatory markers (IL-1β and TNF-α) and microglial changes in the cerebral cortex were quantified, while amyloid fibril morphology was assessed using atomic force microscopy (AFM). Results: Spectroscopic analysis verified successful BM functionalization. Transmission electron microscopy revealed a spherical morphology with an average particle size of 90.57 nm, zeta potential of 27.2 mV, and a polydispersity index (PDI) of 0.270. BM entrapment efficiency reached approximately 90%. Cytotoxicity assays confirmed the nanoparticles’ safety, with no toxicity observed at concentrations up to 400 µg/mL after 4 h of incubation. BMSe@BSA effectively inhibited amyloid fibril formation, downregulated pro-inflammatory cytokine expression, preserved neuronal integrity, and significantly enhanced cognitive performance in AD mouse models. Conclusion: BMSe@BSA appear as a potential nanotherapeutic approach for targeted brain delivery and multi-pathway intervention in Alzheimer’s disease. Full article

Multipotent hematopoietic stem cells (HSC) reside in specialized niches of the bone marrow (BM). The maintenance of their stemness requires a precisely regulated bone marrow microenvironment (BMM), supported by mesenchymal stem cells (MSCs), stromal reticular cells, and endothelial and nerve cells located within the vascular and endosteal niches. The heterogeneity of the niche environment is caused by the diversity of cell populations from HSCs to more mature hematopoietic cell types and MSCs, which collectively influence the complex intercellular interactions involved in hematopoiesis. MSC subclusters in BM are characterized by the phenotypes of CXC-chemokine ligand 12, leptin receptor, neuron-glial antigen 2, and Nestin+ cells. The article presents a detailed characterization of individual stem cell types in the BM, their reciprocal interaction, and the possibility of in vitro simulation of the bone marrow niche as a dynamic structure. Development of a suitable simulation of the BMM is essential for advancing research into both physiological and pathological processes of hematopoiesis. The main goal is to simulate 3D cell culture using biomaterials that mimic the BM niche in the form of hydrogels and scaffolds, in combination with extracellular matrix components. Full article

The development of thin-film organic solar cells (TFOSCs) is pivotal for advancing sustainable energy technologies because of their potential for low-cost, lightweight, and flexible photovoltaic applications. In this study, silver-doped copper sulfide (CuS/Ag) metal nanoparticles (MNPs) were successfully synthesized via a wet chemical method. These CuS/Ag MNPs were incorporated at varying concentrations into a poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl-C61-butyric acid methyl ester (PC61BM) blend, serving as the active layer to enhance the photovoltaic performance of the TFOSCs. The fabricated TFOSC devices were systematically evaluated based on the optical, electrical, and morphological characteristics of the active layer. By varying the concentration of CuS/Ag MNPs, the influence of nanoparticle doping on photocurrent generation was investigated. The device incorporating 1% CuS/Ag MNPs exhibited the highest power conversion efficiency (PCE) of 5.28%, significantly outperforming the pristine reference device, which achieved a PCE of 2.53%. This enhancement is attributed to the localized surface plasmon resonance (LSPR), which augments charge transport and increases optical absorption. The CuS/Ag MNPs were characterized using ultraviolet–visible (UV-Vis) absorption spectroscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM), and energy-dispersive dispersion (EDX) analysis. These findings underscore the potential of CuS/Ag MNPs in revolutionizing TFOSCs, paving the way for more efficient and sustainable solar energy solutions. Full article

(1) Background: This study evaluated the efficacy of magnesium nanoparticles (MgNPs) synthesized through a green method utilizing bacterial metabolites (BMs) produced by Escherichia coli. (2) Methods: BMs were tested for total phenolic content by high-performance liquid chromatography. MgNPs were characterized by X-ray diffraction, transmission electron microscopy, Fourier transform infrared spectroscopy, photoluminescence, and ultraviolet–visible spectroscopy. MgNPs and BMs were tested for antibacterial and antibiofilm potentials against multidrug-resistant clinical isolates by agar well diffusion, minimum inhibitory and bactericidal concentration assays, time–kill test, and inhibition of biofilm formation and destruction of pre-formed biofilm assays. Furthermore, they were tested for antioxidant potential by 2,2-diphenyl-1-picryhydrazyl radical scavenging assay. (3) Results: BMs included carbohydrates, reducing sugars, and phenols (gallic acid and catechin) with a total phenolic content of 0.024 mg GAE/g. MgNPs showed a pure crystalline structure with a spherical shape, 17.8 nm in size, and a 4.19 eV energy gap. Bacteria included Streptococcus pneumonia, Enterococcus faecium, Klebsiella pneumonia, and Salmonella Typhimurium. The antibacterial results showed inhibition zones ranging between 7.2 and 10.4 mm, a bactericidal effect of MgNPs, a bacteriostatic effect of BMs, and growth inhibition after 3 h. The antibiofilm results demonstrated significant inhibition of biofilm formation (inhibition percentages of 64.931% for MgNPs and 71.407% for BMs). However, the assays revealed modest biofilm destruction (eradication percentages of 48.667% for MgNPs and 37.730% for BMs). Antioxidant capacity revealed notable scavenging activity of MgNPs (scavenging activity of 41.482%) and weak activity of BMs (scavenging activity of 16.460%). (4) Conclusions: These findings support the application of MgNPs in biomedical fields. Full article