Search Results (129,444)

Bodanella lauterborni W.M. Zimmermann and Heribaudiella fluviatilis (Areschoug) Svedelius are members of brown algae (Phaeophyceae) that exclusively inhabit freshwater habitats. Heribaudiella fluviatilis is the most frequently reported freshwater brown alga, widely distributed in the Northern Hemisphere. In contrast, B. lauterborni, one of the rarest algae globally, has been reported in only four glacial Alpine lakes and has not been observed in nature for nearly 50 years. Since 2019, the species has been considered locally extinct at its type locality, and its presence in the other three lakes is also questionable. Here, we report the occurrence of B. lauterborni in three springs on the Vlasina Plateau (Southeast Serbia), being the first finding of the species in Southeast Europe and the fifth discovery globally in environmental conditions not previously described for the species. We also provide detailed data on the morphology, ecology, and biogeography of B. lauterborni and H. fluviatilis. Additionally, we report the non-obligate association Hildenbrandio rivularis-Heribaudielletum fluviatilis discovered in two rivers. Our findings significantly expand the known ecological and geographical range of phaeophytes, highlighting Southeast Europe as a refugium for freshwater Phaeophyceae biodiversity. Full article

Multiple sclerosis (MS) reflects a dynamic interplay between peripheral immune activation and compartmentalized inflammation within the central nervous system (CNS). While current disease-modifying therapies effectively reduce relapse activity driven by transient peripheral immune infiltration, their impact on progressive disability remains limited, prompting interest in strategies targeting CNS-resident immune mechanisms. Bruton’s tyrosine kinase (BTK), expressed in B cells and myeloid-derived cells, including microglia, serves as a shared intracellular signaling node linking adaptive and innate immune pathways. Second-generation BTK inhibitors, including evobrutinib, tolebrutinib, fenebrutinib, remibrutinib, and orelabrutinib, have advanced through Phase II-III development in MS. These agents differ in binding mode, selectivity, pharmacokinetics, CNS penetration, and safety profiles, distinctions that may influence stage-specific therapeutic performance. Recent trials across relapsing and progressive phenotypes have yielded heterogeneous outcomes. Divergent signals in primary and secondary progressive MS reflect underlying biological heterogeneity and suggest that therapeutic responsiveness may depend on residual inflammatory activity, lesion biology, and pharmacologic characteristics. Emerging biomarker frameworks further emphasize the importance of stratifying inflammatory activity and degenerative progression when interpreting trial data. This review integrates molecular pharmacology and the most recent clinical evidence available through 2026 to examine how pharmacologic properties translate into stage-dependent therapeutic positioning. We also consider safety constraints within a disease-stage-specific benefit-risk framework, aiming to clarify the evolving role of BTK inhibition in MS. Full article

This paper describes the benchmark dataset for the electric vehicle routing problem with time windows. It is designed to facilitate the large-scale and reproducible evaluation of routing approaches under diverse charging scenarios. It is an extension of the Homberger 1000-customer vehicle-routing benchmark dataset through the incorporation of computationally derived charging-station data. For the 60 base instances included in the dataset, charging-station locations are randomly generated within the customer-coordinate bounds, and two variants are provided, resulting in 120 benchmark problems used in the validation and baseline analyses. A normalized local customer-density score is derived for each station. It is used to determine charging rates and log-normal parameters for prices and waiting times. Two variants are included in the dataset. Variant A maintains the original customer time-window constraints, while Variant B relaxes customer due dates based on the distance from the depot, subject to the depot closing time. The dataset is complemented by instance files, station attributes, parameters, and scripts. It also includes the results of feasibility tests, baseline solver tests, difficulty analyses, and sensitivity tests. These results show that the benchmark includes both easier and harder instance classes under different charging settings. Overall, the dataset is intended to support its use as a reproducible benchmark. Full article

Background/Objectives: Cardiovasc{Citation}ular disease accounts for 50% of chronic kidney disease (CKD) mortality, yet fewer than 40% of patients achieve guideline LDL-cholesterol (LDL-C) targets on statins. Injectable lipid-lowering therapies (ILLTs)—PCSK9 inhibitors and inclisiran—offer 50–70% LDL-C reductions but lack comprehensive CKD-specific evidence synthesis. This systematic review evaluated ILLT efficacy, safety, and implementation across kidney function stages including dialysis. Methods: Following PROSPERO registration (CRD42024612594), we searched MEDLINE, Embase, Cochrane Library, CINAHL, and Google Scholar (1995–August 2025). Two reviewers independently screened studies using PICOS criteria: adults with CKD stages G3-G5, dialysis, or transplant recipients receiving injectable lipid therapies. Primary outcomes were LDL-C percentage change and major adverse cardiovascular events. Quality was assessed using NIH tools. Given heterogeneity, we performed narrative synthesis following SWiM guidance. Results: Eight studies (n = 28,013) met the criteria. The FOURIER trial demonstrated that evolocumab achieved 58–59% LDL-C reductions across kidney function strata (interaction p = 0.77) with preserved cardiovascular benefit (HR 0.82–0.89). Absolute risk reduction was greater in advanced CKD (2.5% vs. 1.7%), reflecting higher baseline rates. Pharmacokinetic studies showed no eGFR-exposure correlation requiring dose adjustment; evolocumab was not removed by haemodialysis. Inclisiran achieved a 67–80% PCSK9 reduction and a 35–58% LDL-C reduction across renal groups, with twice-yearly maintenance dosing. Both classes reduced non-HDL-C (45–50%), apoB (40–45%), and lipoprotein(a) (20–25%). Safety was favourable, with mild injection-site reactions (< 5%); no renal decline signals emerged. Conclusions: Evidence for injectable lipid-lowering therapies in CKD are driven largely by a single large post hoc subgroup analysis (FOURIER) and small phase 1–2 PK/PD studies, with minimal dialysis representation and no transplant data. These agents appear to provide substantial LDL-C reductions across CKD stages G3–G5 without dose adjustment, but cardiovascular and renal outcome data in advanced CKD and dialysis remain limited and should be interpreted cautiously. Full article

Sonar is a fundamental tool for underwater target detection. However, conventional detection systems often suffer from poor sensor consistency and high fabrication costs. More critically, for low-frequency operation, the required array aperture becomes prohibitively large, limiting their deployment on small, mobile underwater platforms. To address the demand for compact, high-performance sensing solutions, this paper presents a miniaturized Micro-electromechanical Systems (MEMS) hydrophone array designed for underwater target detection. The array consists of six elements with a spacing of 0.25 m. Each element is approximately 22 mm in diameter and encapsulated in polyurethane via a casting and curing process. The core sensing element, a MEMS acoustic pressure hydrophone, exhibits a sensitivity of −177.2 ± 1.5 dB (re: 1 V/µPa) across the 20 Hz to 4 kHz frequency range and a noise resolution of approximately 59.5 dB (re: 1 µPa/√Hz) at 1 kHz. A key challenge in array-based detection is the phase mismatch among acquisition channels, which degrades algorithm performance. To mitigate this, we propose a phase self-correction method based on interleaved ADC acquisition control, enabling synchronous multi-channel sampling and effectively eliminating system-level phase errors. Furthermore, to overcome the inherent aperture limitations of conventional beamforming (CBF) applied to a miniaturized array, a differential beamforming (DBF) algorithm is adopted. This approach is less frequency-dependent and can approximate a frequency-invariant beam pattern, making it well-suited for miniaturized arrays. Simulation results confirm the theoretical validity of the DBF algorithm for the proposed MEMS hydrophone array. Sea trial data further demonstrate that this method achieves higher target detection accuracy compared to CBF techniques. Full article

This study aims to evaluate the therapeutic efficacy of emodin (EMO) in rheumatoid arthritis (RA) and to verify whether its underlying mechanism involves the blockade of pathological angiogenesis via the inhibition of the nuclear factor-kappa B (NF-κB)/hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling axis. Bovine type II collagen-induced arthritis (CIA) mouse models and lipopolysaccharide (LPS)-stimulated EA.hy926 endothelial cells were utilized in this study. The effects of EMO on joint pathological alterations, the expression of NF-κB/HIF-1α/VEGF axis proteins, inflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β)), and angiogenic capacity were assessed using histopathological analysis, Western blotting, immunohistochemistry (IHC), immunofluorescence, and tube formation assays. Furthermore, small interfering RNA (siRNA) interference targeting key molecules was employed to validate the molecular mechanisms underlying the therapeutic effects of EMO. In the CIA model group, the ankle joints of mice exhibited pronounced inflammatory infiltration, synovial hyperplasia, and bone destruction. Compared with the model group, both the EMO and methotrexate (MTX) treatment groups demonstrated attenuated synovial hyperplasia and cartilage destruction, along with significantly downregulated expression levels of key NF-κB pathway proteins, HIF-1α, and VEGF in joint tissues (p < 0.001). In vitro experiments revealed that EMO treatment significantly reduced the LPS-induced secretion of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) (p < 0.001), and decreased both the number and total length of tubular structures formed by endothelial cells compared to the control (p < 0.001). Notably, siRNA-mediated knockdown of p65 resulted in decreased intracellular protein levels of HIF-1α and VEGF, accompanied by a significant reduction in tube formation (p < 0.001). This study demonstrates that EMO alleviates pathological damage in RA by inhibiting the activation of the NF-κB signaling pathway, which subsequently downregulates pathological angiogenesis and inflammatory responses mediated by the HIF-1α/VEGF axis. These findings provide a robust experimental basis for the potential application of EMO as a therapeutic agent for RA. Full article

To optimize container seedling cultivation of Chinese zelkova (Zelkova schneideriana Hand.-Mazz.), a three-factor completely randomized design was used to systematically evaluate the effects of container material, container size, and substrate composition on seedling growth, physiological traits, and root morphology. Different container materials, three container sizes, and multiple composite substrates were tested. Seedling height, biomass accumulation, photosynthetic characteristics, and root morphological indices were measured, and principal component analysis combined with comprehensive evaluation was applied to identify optimal treatments. The results showed that container size was one of the major factors affecting overall seedling quality, with large containers generally enhancing seedling height, biomass accumulation, photosynthetic capacity, and root development. Among container materials, B-type containers generally exhibited better overall performance under medium- and large-size conditions. Substrate composition showed a significant regulatory effect under appropriate container conditions, and the T₃ composite substrate, composed of yellow soil (40%), peat (10%), sphagnum peat (15%), vermiculite (10%), rice husk (15%), and corn cob (10%), achieved the highest comprehensive score. According to the PCA-based comprehensive evaluation, the T₃/A₃ treatment ranked first, followed by T₃/B₂. Overall, the combination of B-type containers, appropriate medium-to-large container size, and the T₃ substrate showed superior nursery performance. In particular, T₃/A₃ ranked first in the comprehensive evaluation, followed by T₃/B₂, indicating that both large black plastic containers and medium-sized B-type containers performed well under the T₃ substrate. Full article

Compared to polysomnography (PSG) and actigraphy, contactless consumer sleep-tracking devices (CCSTDs) are low-cost, user-friendly, and non-disruptive to sleep. This study evaluated the performance of two inexpensive, representative first-generation Chinese-made CCSTDs (the iSleep S200G and Sleep Dot B501) against PSG and actigraphy, using standardized validation protocols. The objective was to assess their feasibility as alternatives for large-scale, long-term preliminary research that does not rely on single-day high-precision sleep data. Eleven healthy young adults (mean age = 26.5 ± 4.8 years) participated in a two-night sleep laboratory study using four devices in parallel. Compared with PSG, the iSleep S200G exhibited no significant differences in TST and SE, while the Sleep Dot B501 showed no significant differences in TST, SE, SOL, and WASO. The intraclass correlation coefficient values and epoch-by-epoch agreement of the iSleep S200G and Sleep Dot B501 were as good as or better than those of actigraphy. Notably, the epoch-by-epoch agreement metric of both devices was not inferior to other consumer sleep-tracking devices already used for long-term, large-scale sleep monitoring. Therefore, even within budget constraints, first-generation CCSTDs can effectively meet the requirements for long-term, large-scale sleep monitoring without sleep stage detection. The results also provided data references for researchers using iteratively upgraded CCSTDs. Full article

Oligodendroglial cells are the myelinating glial cells of the central nervous system (CNS), and their morphological differentiation is a prerequisite for efficient myelin formation, which is essential for proper neuronal function. While oligodendroglial morphological changes normally proceed through tightly regulated developmental transitions, disruption of the underlying molecular mechanisms can lead to aberrant cellular phenotypes characterized by either premature, insufficient, or excessive differentiation. Although the phosphatidylinositol 3-kinase (PI3K) and its downstream Akt kinase signaling are well established as major drivers of oligodendrocyte morphological differentiation, myelination, and CNS white matter formation, how its negative regulator, phosphatase and tensin homolog (PTEN), is involved in the regulation of oligodendroglial morphogenesis remains incompletely understood. Recent genetic studies have highlighted a spectrum of disorders caused by PTEN dysfunction, conceptually established but currently evolving as PTENopathy, which has been partially associated with white matter abnormalities. Here, we report that, in an experimental model using the FBD-102b cell line, a well-established model of oligodendroglial cell differentiation, chemical inhibition of PTEN enhances pronounced morphological changes characterized by widespread membranes, accompanied by increased expression of differentiation and/or myelin marker proteins. We then focused on Rho family small GTPases, central regulators of cell morphogenesis, and examined their potential involvement downstream of this signaling. Expression of the RhoG-binding domain (RBD) of engulfment and cell motility 1 (ELMO1) attenuated the increased morphological changes. Similarly, inhibition of downstream Akt signaling also reversed these changes. Taken together, these results provide insight into how balanced regulation between PTEN and downstream signaling molecules governs oligodendroglial cell differentiation and suggest that dysregulation of this signaling equilibrium may contribute to cellular phenotypes relevant to disease-associated cellular alterations. Full article

Background: Prostate cancer (PCa) arises from complex interactions among host genetics, androgen signaling, and microbial communities. Emerging genomic evidence supports the presence of microbial consortia within prostate tissue, suggesting that microbial genes, metabolites, and host–microbe interactions may contribute to chronic inflammation, oncogenic signaling, and therapeutic resistance. Methods: We conducted a narrative review using targeted searches of PubMed and Google Scholar for studies published between 2020 and 2025, complemented by selected mechanistic reports published in March 2026. Human studies and experimental research providing mechanistic insights into prostate models were prioritized. Due to the heterogeneous methodologies, evidence was synthesized qualitatively, with an emphasis on genomic and signaling perspectives. Results: Low-biomass microbial DNA is consistently detected in prostate tissue. Proteomic analyses of Corpora amylacea suggest a “fossil record” of past infections through sequestered microbial DNA and antimicrobial proteins, potentially priming tissue for long-term carcinogenic processes, although contamination remains a key limitation. Recurrent bacterial and viral signals, including Cutibacterium acnes, Escherichia coli, Pseudomonas, Acinetobacter, human papillomavirus, Epstein–Barr virus, and cytomegalovirus, appear to converge on a restricted set of tumor-relevant pathways, including TLR–NF-κB, MAPK, PI3K/AKT/mTOR, cGAS–STING, and p53/pRb disruption. These interactions may promote cytokine production, oxidative stress, DNA damage, epithelial–mesenchymal transition, extracellular matrix remodeling, immune evasion, and resistance to therapy. The gut–prostate axis further links intestinal dysbiosis and microbial metabolites with systemic IGF-1 signaling and castration resistance. Conclusions: Microbial genomic consortia in the prostate and gut may shape inflammatory, metabolic, and immune networks that influence PCa initiation and progression. However, most available data remain correlative and are limited by low-biomass sampling, contamination risk, and heterogeneous study designs. Future research should prioritize rigorous contamination control, longitudinal and prostate-specific mechanistic studies, and integrated multi-omic approaches to clarify causality and identify actionable microbial targets for prevention, diagnosis, and therapy. Full article

Background/Objectives: Spondylarthritis (SA) is characterized by high clinical heterogeneity, often resulting in a discrepancy between systemic inflammation and patient-reported symptoms. While hematologic indices are emerging as cost-effective biomarkers, their role in phenotypic differentiation remains unclear. We investigated the utility of traditional inflammatory markers, including the novel fibrinogen-to-platelet ratio (FPR), in differentiating SA subtypes and predicting patient-reported disease activity. Methods: This cross-sectional study included 64 patients with spondylarthritis: axial SA (n = 32), peripheral SA (n = 8), and psoriatic SA (n = 24). Clinical assessments included the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Functional Index (BASFI). Systemic inflammation was evaluated via C-reactive protein (CRP), fibrinogen, and calculated ratios (NLR, PLR, MLR, and FPR). Principal Component Analysis (PCA) was employed to map the inflammatory architecture, while Receiver Operating Characteristic (ROC) curves evaluated the predictive power for high disease activity (BASDAI ≥ 4). Results: Significant phenotypic differences were observed with the FPR demonstrating superior discriminative capacity (p = 0.003). Patients with peripheral SA exhibited significantly higher FPR (median 1.88) compared to axial (1.33) and psoriatic (1.32) subtypes, and the dedicated ROC analysis for phenotypic discrimination yielded an AUC of 0.866 (95% CI: 0.745–0.987) (1.36, p = 0.039). HLA-B27 prevalence was low overall (31.3%) and in psoriatic SA (4.2%, p = 0.012). Correlation analysis revealed strong associations between BASDAI and BASFI (ρ = 0.79), NLR and MLR (ρ = 0.78), and CRP and fibrinogen (ρ = 0.66). PCA identified two independent inflammatory dimensions explaining 74.8% of variance: neutrophil-hypercoagulable axis (41.4%, driven by NLR, PLR, and MLR), and an acute-phase/fibrinogen axis (33.4%, driven by CRP, fibrinogen, and FPR). Notably, FPR clustered with acute-phase reactants rather than leukocyte-derived ratios, supporting its role as a marker of systemic inflammatory burden. Although fibrinogen is involved in the coagulation cascade, the absence of direct coagulation markers precludes definitive characterization of this component as hypercoagulable. ROC analysis revealed that fibrinogen showed the highest discriminative ability for disease activity (BASDAI ≥ 4), with an AUC of 0.690 (95% CI: 0.519–0.861), followed by NLR (0.621), MLR (0.592), and FPR (0.583). However, overall discriminative performance remained modest, with most 95% confidence intervals crossing 0.5. Conclusions: FPR emerges as a robust phenotypic biomarker capable of discriminating against SA subtypes, particularly identifying peripheral SA with high accuracy and excellent negative predictive value. In contrast, its ability to predict patient-reported disease activity remains limited, reinforcing the distinction between trait and state biomarkers. Exploratory PCA revealed that FPR clusters with acute-phase reactants rather than leukocyte-derived ratios, supporting its biological link to systemic inflammatory burden. These findings advocate for a dual-purpose biomarker approach in SA: FPR for phenotypic stratification and fibrinogen for activity assessment, while clinical indices remain indispensable for symptom monitoring. Validation in larger, prospective cohorts is warranted. Full article

Parameters of reflected light, measured in narrow or broad spectral bands, are widely analyzed for remote and proximal sensing of plant responses to stressors. Specifically, parameters of reflectance in red (R), green (G), and blue (B) spectral bands measured using simple color images can be sensitive to characteristics of plants. The conventional view is that RGB reflectance primarily reveals long-term changes in plants (days, weeks, etc.). In this study, we investigated light-induced changes in RGB reflectance in wheat (Triticum aestivum L.) and pea (Pisum sativum L.) leaves. Illumination increased this reflectance for about 10 min in wheat and about 15–20 min in pea; these changes relaxed after light intensity was decreased. The changes in RGB reflectance were strongly related to the effective quantum yield of photosystem II and non-photochemical quenching of chlorophyll fluorescence under high light intensity; these relations were absent under low light intensity. We hypothesized that changes in both RGB reflectance and photosynthetic parameters were related to the light-induced changes in chloroplast localization. A simple mathematical model of optical properties and photosynthesis in leaves was developed; results of the model-based analysis supported the proposed hypothesis. Experimental analysis of the dynamics of light transmittance additionally supported this hypothesis. Our results thus show that RGB imaging can be sensitive to fast changes in plants. Full article

Background/Objectives: Nitric oxide (NO) is a key mediator of vascular, metabolic, and redox pathways, influencing exercise performance. Beetroot, a natural source of inorganic nitrate, increases NO bioavailability and may modulate oxidative stress and inflammation, though data in endurance athletes remain limited. The aim of this study was to assess the effects of a novel beetroot-based nitrate supplement (B-bNs) on NO metabolism, oxidative stress, and inflammation in non-professional triathletes. Methods: This was a randomized 2 × 2 cross-over pilot study with two 7-day periods (B-bNs vs. No treatment), separated by a 15-day washout (4 visits: Day 1, 7, 22 and 28). Samples were collected at baseline (T0), 2 h post-first dose (T1), and after 7 days (T2) for the supplementation period (B-bNs) and at T0 and T2 for the “no treatment” period. The following biomarkers from plasma and urine were evaluated: NO pathway (NO metabolites (NOx), nitrite (NO₂), inducible nitric oxide synthase (iNOS), peroxynitrite, 3-nitrotyrosine (3-NT)), oxidative stress (reactive oxygen species (ROS) production, 8-isoprostane, superoxide dismutase (SOD) activity), and cytokines (IL-6, IL-10). A total of 10 male triathletes (mean age 48.1 ± 9.8 years and BMI 23.9 ± 2.2 kg/m²) participated in this study. Results: No adverse events were reported. After 7 days of supplementation (T2 vs. T0), significant increases in NOx in plasma and urine (about +155%), iNOS (+56%), peroxynitrite (+60%), 3-NT (+8.6%), ROS (+413%) and IL-6 (+73%) were recorded. These values resulted significantly higher compared to “no treatment” (all p = 0.002), with no significant differences for 3-NT, SOD, 8-isoprostane, IL-6, and IL-10. Conclusions: Beetroot-based nitrate supplementation may enhance the NO-related pathway in non-professional endurance athletes with nitric-peroxydation activation, occurring without evidence of lipid oxidative damage. Larger placebo-controlled trials with standardized diet/training and performance outcomes are needed to determine the functional significance of these preliminary findings. This study was registered in the ISRCTN registry (ISRCTN10885376). Full article

A new species of shoveljaw carp, Scaphesthes zhejiangensis, is described from the Qiantang River basin and three independent rivers in Zhejiang Province, Southeast China. It is distinguished from other Scaphesthes species by the following combination of characteristics: a long, slender body (depth 19.9–22.2% SL); 46–49 lateral-line scales; 15–17 pre-dorsal scales; a short head (depth 66.8–73.3% HL); a wide mouth (width 36.2–45.3% HL); elongated maxillary barbels shorter than one-third of the eye diameter; reduced but visible rostral barbels; a slender, smooth last simple dorsal ray; and the absence of a longitudinal black stripe along the lateral line. Molecular phylogenetic analysis based on the mitochondrial cytochrome b (cyt b) gene supported the monophyly of S. zhejiangensis sp. nov., which formed a clade with S. virgulatum, S. macrolepis, and the S. barbatum species complex. Full article