Search Results (6,726)

The development of electric quarry transport puts a significant strain on local power grids, leading to sharp peaks in consumption and degradation of power quality. Existing methods of peak smoothing, such as generation control, virtual power plants, or intelligent load management, have limited efficiency under the conditions of stochastic and high-power load profiles of industrial charging stations. A new strategy for direct charge and discharge management of a system for integrated battery energy storage (IBES) is based on dynamic iterative adjustment of load boundaries. The mathematical apparatus of the method includes the formalization of an optimization problem with constraints, which is solved using a nonlinear iterative filter with feedback. The key elements are adaptive algorithms that minimize the network power dispersion functionality (i.e., the variance of P_grid^(t) over the considered time interval) while respecting the constraints on the state of charge (SOC) and battery power. Numerical simulations and experimental studies demonstrate a 15 to 30% reduction in power dispersion compared to traditional constant power control methods. The results confirm the effectiveness of the proposed approach for optimizing energy consumption and increasing the stability of local power grids of quarry enterprises. Full article

Bloodstream infections (BSIs) pose a significant global health challenge, particularly due to the increasing prevalence of antimicrobial resistance (AMR). Timely and accurate identification of pathogens and resistance determinants is critical for guiding appropriate therapy and improving patient outcomes. Traditional culture-based diagnostics are limited by prolonged turnaround times and reduced sensitivity, especially in culture-negative or polymicrobial infections. This review systematically examined current and emerging sequencing technologies for AMR detection in BSIs, including whole-genome sequencing (WGS), targeted next-generation sequencing (tNGS), metagenomic next-generation sequencing (mNGS), and long-read sequencing platforms (Oxford Nanopore, PacBio). We compared their clinical performance using key metrics such as diagnostic sensitivity, turnaround time, and cost, highlighting contexts in which each technology is most effective. For example, tNGS can achieve the rapid detection of known resistance genes within 8–24 h, while WGS provides comprehensive genome-wide resistance profiling over 24–48 h. mNGS offers broader detection, including rare or unexpected pathogens, although at higher cost and longer processing times. Our analysis identifies specific strengths and limitations of each approach, supporting the use of context-specific strategies, such as combining rapid targeted sequencing for common pathogens with broader metagenomic approaches for complex cases, to improve diagnostic yield and guide antimicrobial therapy. Quantitative comparisons indicate that sequencing technologies can complement conventional methods, particularly in cases where culture-based approaches fail. In conclusion, sequencing-based diagnostics offer measurable improvements in sensitivity and speed over traditional methods for AMR detection in BSIs. Future work should focus on optimizing workflows, integrating sequencing data into clinical decision-making, and validating approaches in prospective studies. Full article

Background/Objectives: Hope plays an important role in coping with difficulties and is predictive of resilience, improving the skills necessary to sustain life plans and well-being, and overcoming stressful situations in adulthood and especially in older age adults. We hypothesised that the dimensions of hope, including spirituality, are connected to personal, educational, and contextual conditions, and play a mediating role in fostering resilience and well-being after stressful events; this mediating role might differ in adulthood and among the elderly. Methods: The sample consisted of 100 adults without severe pathologies and living in their own homes, aged between 50 and 86 years (M = 66.08; SD = 8.48). They completed an online survey that included the Stress Event scale, the Comprehensive State Hope Scale, the Resilience Scale for Adults, and the Well-being Profile. The data were analysed using SPSS and JAMOVI software, applying the following statistical tests: t-test, ANOVA and mediational model. Results: Stressful events influence resilience and well-being differently in adulthood and old age, with non-significant differences due to gender and living conditions. Hope mediates between stress resulting from negative life events and resilience and well-being, but this mediation involves different hope components for adults (trust) and older adults (self-realisation and perception of social support in interpersonal relationships). Spirituality is a non-significant mediator in both age stages. Conclusions: Appropriate psychological and psychosocial supports are needed to enhance the mediating potential of hope between stressful events and resilience. The results of our study help clarify which components of hope specifically promote resilience in different conditions of normal old age, differentiating them from those more beneficial for adults. Full article

Marigold (Tagetes erecta L.) is rich in bioactive compounds, with lutein and quercetagetin as the primary components. However, the effects of these two substances on type 2 diabetes mellitus (T2DM) and their underlying molecular mechanisms remain incompletely understood. This study was designed to explore the hypoglycemic potential of quercetagetin and lutein, both individually and in combination, and to decipher the underlying molecular pathways. A T2DM mouse model was established using a high-fat diet (HFD) in combination with streptozotocin (STZ) administration. The results showed that quercetagetin and lutein effectively reduced fasting blood glucose and insulin levels, restored glucose metabolic homeostasis, and improved insulin sensitivity in T2DM mice. Additionally, these compounds improved blood lipid profiles, reduced the production of inflammatory factors, alleviated histological damage, and restored intestinal barrier function. Further mechanistic analysis revealed that quercetagetin and lutein could ameliorate intestinal dysbiosis, decrease intestinal lipopolysaccharide (LPS) content, mitigate local intestinal inflammation, and upregulate the expression of tight junction proteins. These alterations suggest that quercetagetin and lutein collectively contribute to the improvement of intestinal barrier dysfunction and systemic inflammation in type 2 diabetic (T2DM) mice. Full article

Colorectal cancer (CRC) is a major cause of cancer death, with the tumor microenvironment and gene expression influencing outcomes. Identifying survival-associated epithelial marker genes (EMGs) may improve prognosis and guide therapy. We obtained single-cell RNA-sequencing (scRNA-seq) data from CRC patients (n = 23,176 cells) from the TISCH database to identify EMGs through differential expression analysis. These were intersected with malignant cell markers. We used bulk RNA-seq data from TCGA-COAD (n = 375) to assess EMG prognostic value via univariable Cox analysis, followed by LASSO regression. Significant genes were evaluated using multivariable Cox models. An EMGs-based risk score was developed and validated using GSE39582 (n = 585) and GSE17536 (n = 177). Immune infiltration was assessed using xCELL and TIMER algorithms. A total of 107 EMGs were identified and assessed in TCGA data. Cox analysis identified 18 survival-related EMGs, which were narrowed by LASSO to SPINK1 and TIMP1. Multivariable analysis confirmed SPINK1 (HR: 0.88, 95% CI: 0.79–0.97, p = 0.009) and TIMP1 (HR: 1.66, 95% CI: 1.29–2.13, p < 0.001) as independent survival predictors. Patients were classified into high- (n = 187) and low-risk (n = 188) groups. The low-risk group had significantly better overall and disease-free survival. Immune profiling revealed distinct patterns, where the high-risk group showed higher dendritic cells, memory T-cells, macrophages, and immune checkpoint expression, while the low-risk group showed enrichment of NK cells, plasma cells, and CD4+ T-helper cells. These findings were validated in the GSE39582 and GSE17536 cohorts. EMGs have prognostic value in CRC, with SPINK1 and TIMP1 as independent survival predictors. Distinct immune patterns support integrating EMGs with immune profiling for improved risk stratification and personalized treatment. Full article

Fuchsia standishii J.Harrison is a species widely used in traditional medicine in southern Ecuador for treating various ailments, including high blood pressure, as an antacid and a relaxant. The pharmacological basis for these traditional uses is unknown. Given the reported anti-inflammatory and cytotoxic properties of the Onagraceae family, we investigated the plant’s potential for addressing chronic conditions. This study explored the bioactive potential of polar extracts from the aerial parts of F. standishii, focusing on antiproliferative activity against a panel of human tumor cell lines (A549, HBL-100, HeLa, SW1573, T-47D). The plant material was sequentially extracted and partitioned into nine fractions. All fractions were screened for antiproliferative activity, and the most active fractions were further evaluated for their mechanism of cell death (apoptosis/necrosis), genotoxicity, and induction of oxidative stress. Specialized metabolites in the fractions were characterized using UHPLC-DAD-MS³ analysis. F. standishii extracts showed potent antiproliferative activity. The dichloromethane fraction (MW_D) was the most active (GI₅₀ range: 8.5–39 µg/mL), demonstrating the ability to induce apoptosis in tumor cells and cause genotoxic damage linked to oxidative stress. The UHPLC-DAD-MS³ analysis successfully characterized the specialized metabolites present in the active fractions. The initial aqueous extract yielded a total of 47 secondary metabolites, 15 of which remained unassigned. F. standishii possesses a promising pharmacological profile that extends beyond its documented traditional uses. The MW_D fraction represents a plausible source of novel anti-cancer agents due to its ability to induce apoptosis, supporting further bioguided investigation of this ethnobotanically relevant species. Full article

Background/Objectives: Breast cancer remains one of the most prevalent and life-threatening malignancies worldwide. This study describes the design and biological evaluation of a series of secosteroid–2-pyrazoline hybrids as novel antitumor agents against ERα-positive breast cancer cell lines MCF-7 and T47D. Methods: A simple and efficient method for synthesizing secosteroid–2-pyrazoline hybrids was developed starting from 13α-hydroxy-3-methoxy-13,17-secoestra-1,3,5(10)-triene-17-oic acid hydrazide and 1,3-diketones. The resulting secosteroid derivatives were evaluated against hormone-dependent MCF-7 and T47D breast cancer cells. Furthermore, the selectivity and effects of three lead compounds on signaling pathways in MCF-7 cells were examined. Flow cytometry was used to assess the cell-cycle distribution of MCF-7 cells treated with the lead compound. Results: Among the synthesized hybrids, compounds 3f, 3j, and 3k exhibited potent antiproliferative activity with IC₅₀ values of 0.2–0.5 μM against breast cancer cells, while demonstrating very low cytotoxicity towards normal cells (IC₅₀ > 25 μM), indicating a favorable safety profile. The antitumor activity of lead compound 3j was additionally investigated in combination with standard chemotherapeutics, docetaxel and doxorubicin, yielding synergistic effects. The lead compounds showed a dual mechanism of action by inhibiting S6 kinase and promoting Bcl-2 phosphorylation at 0.9 μM, without significantly affecting hormonal breast cancer targets such as ERα, GREB1, and AR. Compound 3j induced apoptosis accompanied by a reduction of the G1/G0 phase in MCF-7 cells. Conclusions: These findings highlight secosteroid–2-pyrazoline hybrids as promising candidates for the development of next-generation breast cancer therapeutics targeting apoptosis and S6K signaling pathways. Full article

We report a fully biogenic route to ZnO, Fe₃O₄, and their hydrothermally coupled ZnO/Fe₃O₄ heterostructure and establish a synthesis–structure–function link. Phase-pure, quasi-spherical wurtzite ZnO and finer inverse-spinel Fe₃O₄ nanoparticles assemble into a biphasic interface without forming a solid solution; optical analysis yields E_g = 2.36 eV (ZnO), 1.46 eV (Fe₃O₄), and 1.45 eV (ZnO/Fe₃O₄), while PL shows near-band-edge quenching and green–yellow defect reweighting at 490–560 nm, consistent with interfacial band bending. Magnetically, ZnO/Fe₃O₄ is soft-ferrimagnetic with M_S/M_R/H_C = 226 emu g⁻¹/17 emu g⁻¹/0.010 T (at 300 K), enabling rapid magnetic recovery. Under natural sunlight (572.6 ± 32 W m⁻²), adsorption-corrected methylene blue removal (10 mg L⁻¹; 10 mg in 50 mL) gives real degradation rates RDR = 90% (ZnO), 65% (ZnO/Fe₃O₄), and 30% (Fe₃O₄) at 180 min, with pseudo–first-order constants k = 1.9 × 10⁻², 0.7 × 10⁻², and 0.4 × 10⁻² min⁻¹, respectively; dark adsorption baselines are 10%, 14%, and 49%. Reusability over four cycles preserves pseudo-first-order kinetics (ZnO/Fe₃O₄: 65% → 50%). Scavenger tests implicate ${}^{•}\mathrm{O}\mathrm{H}$ as the dominant oxidant in ZnO and ZnO/Fe₃O₄, and ${}^{•}\mathrm{O}_2^{-}$ in Fe₃O₄. Taken together, the band alignment, photoluminescence quenching, radical-scavenger profiles, and kinetic synergy are consistent with a defect-rich S/Z-scheme-like ZnO/Fe₃O₄ heterojunction, delivering a green, sunlight-operable, and recyclable platform for affordable wastewater remediation. Full article

The diagnosis and treatment of rheumatoid arthritis (RA) have been constantly evolving for decades, pointing towards early diagnostic and therapeutic interventions. Synovial biopsy has emerged as a pivotal tool in precision medicine, transitioning from a research procedure to a clinically feasible approach. Modern ultrasound-guided techniques allow safe, reproducible access to inflamed joints, enabling direct analysis of the synovial tissue, which reveals biological heterogeneity undetectable in peripheral blood. Histological scoring, including the Krenn synovitis score, discriminates inflammatory from non-inflammatory pathology, supporting targeted escalation of immunosuppressive therapy. Molecular and histological profiling has defined distinct synovial pathotypes—lympho-myeloid, diffuse-myeloid, and fibroid/pauci-immune—with reproducible associations to therapeutic responsiveness. Moreover, biopsy-driven trials, such as R4RA and STRAP, demonstrate that pathotype-guided strategies can predict outcomes: diffuse-myeloid synovitis responds to IL-6 receptor blockade, lympho-myeloid synovitis to B cell depletion, and fibroid synovitis exhibits multidrug resistance. In difficult-to-treat RA, synovial biopsy differentiates inflammatory from non-inflammatory drivers of persistent symptoms, providing a rational basis for therapy selection. Ongoing biomarker-driven initiatives, including PRECISion and 3TR Precis-The-RA, aim to embed biopsy findings into clinical decision-making. In this review, it is underscored that the integration of histology, molecular profiling, and clinical context positions synovial biopsy as a patient-centered precision approach, guiding individualized therapy and bridging RA stratification with clinical practice. Full article

Cytosine base editors (CBEs) enable precise C-to-T (G-to-A) conversions in genomic DNA, offering significant potential for specific gene editing. This study compared the prototypical Base Editor 3 (BE3) and a modified variant, BE3-Y130F, which utilizes an hA3A deaminase with the Y130F mutation, focusing on their editing efficiency and editing window characteristics using bovine zygotes. Following in vitro fertilization (IVF), sgRNA and Cas9 mRNA were injected as a targeting efficiency control, which resulted in 100% editing with no wild-type sequence. Then, either BE3 or BE3-Y130F mRNA, synthesized via in vitro transcription, and an sgRNA targeting exon 4 of the MYO7A gene was injected into zygotes. Genomic DNA was extracted from both blastocysts and developmentally arrested embryos, and Sanger sequencing was performed to evaluate C-to-T conversion efficiency and editing window. Both BE3 and BE3-Y130F achieved 100% C-to-T conversion efficiency at the primary target cytosine. BE3 displayed a defined editing window, primarily affecting cytosines at positions 7 and 8, indicating a predictable profile. In contrast, BE3-Y130F maintained high efficiency but had a less clearly defined editing window, resulting in incomplete editing and a remaining cytosine on the target sequence. Full article

Adolescence is a critical window for cardiovascular (CV) development, yet the molecular drivers of vascular adaptation to regular exercise in youth remain poorly understood. This cross-sectional study assessed vascular structure and function alongside endothelial, metabolic, and lipoprotein biomarkers in 203 healthy young athletes (aged 10–16). Vascular phenotyping included carotid intima-media thickness (IMT), pulse wave velocity, and carotid deformation indices (strain, strain rate). Circulating nitric oxide (NO), endothelin-1, free triiodothyronine (fT3), leptin, low-density lipoprotein, and high-density lipoprotein were analyzed. Associations were examined using hierarchically adjusted multivariable linear regression, mediation and moderation were tested and sex-stratified/matched analyses were conducted. While training volume was not associated with endothelial markers, leptin was correlated positively with NO and negatively with diastolic strain rate, suggesting dual vascular actions. fT3 was inversely associated with IMT, indicating a potential protective role in vascular remodeling. Lipoprotein profiles showed no independent associations with vascular parameters. Hemodynamic load, particularly systolic blood pressure, emerged as the dominant determinant of arterial stiffness. Sex-specific differences across biomarkers and vascular indices support a multifactorial model: in active youth, vascular phenotype reflects hemodynamics, body composition, and endocrine–metabolic signals more than training; longitudinal mechanistic studies should clarify causal pathways and guide individualized cardiovascular risk profiling. Full article

Inadequate livestock production among smallholder farmers is mostly linked to insufficient supply and poor feed quality. To enhance livestock production, improving both the quantity and quality of feed supplements is important. Therefore, alternative fodder resources, such as Cannabis sativa, should be evaluated as a feed supplement for ruminants such as Dorper sheep. Cannabis sativa is an herbaceous crop commonly grown for industrial and medicinal purposes. This plant is reported to have an excellent nutritional profile and biomass production. The current study aimed to determine the agronomic parameters and biomass production of C. sativa. The experiment was conducted at the Towoomba Research Station, in Bela-Bela Municipality, Limpopo province, South Africa. The trial’s experimental design was a split-plot within a Randomized Complete Block Design (RCBD), and it was replicated three times. The findings of the study showed a significant difference (p < 0.05) between the agronomic parameters during the early (December 2023–April 2024) and late planting seasons (April 2024–July 2024). Plant height (77.3 cm), number of leaves (144 leaves), leaf area (60.18 cm²), canopy cover (31.65 cm), number of branches (25), and biomass production (5, 48 t h⁻¹) were higher at maturity in the early planting season whilst chlorophyll content was higher (38.62 nm) during early planting season at flowering stage. The study suggests that smallholder farmers should plant C. sativa during the early planting season to ensure high biomass production. Full article

Background. Routine lymphocyte counting requires quality assurance validation using quality controls (QCs) that closely resemble fresh human blood leukocytes. This study aimed to evaluate a novel artificial product designed to mimic leukocyte light scatters and marker expression. Methods. FlowCytes and TruCytes, “artificial cell mimics” (Slingshot Biosciences, Emeryville, CA, USA), were tested on CE-IVD-certified systems, namely FACSCanto, FACSLyric (BD Biosciences), Navios, and DxFlex (Beckman Coulter), using routine staining, lysing, fixation, and no-wash procedures for T, B, and NK counting. Results. FlowCytes and TruCytes provided forward and side scatter profiles comparable to human leukocytes on the FACSCanto, FACSLyric, and DxFlex systems but not on Navios despite adapting the process to be slightly different from the manufacturer’s recommendations. TruCytes demonstrated robust immunolabeling of CD3, CD4, CD8, and CD19 on the FACSCanto, FACSLyric, and DxFlex systems, with fluorescence intensities and subset distributions being similar to those usually observed in fresh human blood. However, CD16 and CD56 labeling was inconsistent and depended on the antibody clones used. Regrettably, monocyte and granulocyte mimics lacked expression of CD4, CD16, and CD14. TruCytes also displayed significantly lower concentrations of TBNK lymphocyte subsets compared to healthy human blood. Conclusions. FlowCytes and TruCytes show promises as internal quality controls for T cell and B cell immunophenotyping, but not NK cells. They are compatible with most CE-IVD cytometers, even when using lysis/fixation/no-wash routine diagnosis procedures. Further multicentric studies are warranted to assess their performance relative to existing products, such as stabilized human blood. Full article

This review focuses on the molecular pathogenesis of Type 1 diabetes (T1D), specifically on the key autoantigens targeted by the autoimmune response and the clinical implications of their epitope specificity. T1D is characterized by the destruction of insulin-producing pancreatic β-cells. The autoimmune attack is directed against a defined set of autoantigens, primarily insulin, glutamic acid decarboxylase 65, tyrosine phosphatase-like protein, zinc transporter 8, as well as several minor autoantigens. A critical advancement in understanding the disease has been the analysis of epitope specificity, revealing that immunodominant epitopes are conformational and often localized to C-terminal protein regions, exposed during β-cell degradation. The introduction of sensitive multiplex assays for the simultaneous detection of T1D-associated autoantibodies represents a major diagnostic breakthrough. These platforms enable early diagnosis, risk stratification, and the identification of a “therapeutic window” for intervention. At this preclinical stage, antigen-specific immunotherapies aimed at restoring immune tolerance show significant promise. Ultimately, the combination of personalized diagnostic profiles, epitope mapping, and targeted therapies forms the basis for a new T1D management paradigm focused on halting the autoimmune process itself and preserving functional β-cell mass. Full article

Background/Objectives: Ulcerative colitis (UC), a chronic inflammatory bowel disease, affects approximately 5 million individuals worldwide, exerting a considerable influence on global health and economic systems. Among the challenges in UC management, treatment non-adherence stands out as a critical issue, often compromising therapeutic efficacy. One strategy to address this challenge is by reducing pill burden, which may improve patient compliance and optimize treatment outcomes. Methods: This randomized, two-sequence, four-period, crossover replicate study evaluated the pharmacokinetic profiles, bioequivalence, and safety of a newly developed 1500 mg mesalazine gastro-resistant tablet compared to three of the reference 500 mg Claversal^® gastro-resistant tablets (total dose 1500 mg) in 80 healthy participants under fasted conditions. Results: Bioequivalence between mesalazine formulations was observed in both the rate and extent of systemic bioavailability. The geometric mean ratios and their 90% CI were 102.51% (95.85–109.63) for AUC_0–∞, 103.36% (96.40–110.83) for AUC_0–t, 84.49% (78.24–91.24) for AUC_8–48h, and 114.24% (100.15–130.32) for C_max. All within the accepted bioequivalence ranges, confirming comparable pharmacokinetic performance. Secondary pharmacokinetic parameters such as t_max, t_1/2, K_e, Cl, and MRT were also consistent across both formulations. The incidence of adverse events was comparable between the two mesalazine formulations, with only flatulence and mild self-limited rash considered possibly related to test treatment. Conclusions: Overall, the 1500 mg formulation demonstrated a pharmacokinetic profile and tolerability comparable to the reference formulation, offering a higher-strength option to reduce daily pill burden. This strategy is of clinical relevance, particularly for improving treatment adherence among UC patients who need to take multiple pills daily to achieve their required dosage. While adherence is influenced by various factors, reducing pill burden may facilitate compliance and optimize therapeutic efficacy. Full article