Search Results (5,987)

Electrochemical sensors are user-friendly devices designed for the rapid and straightforward detection of target analytes. Serotonin (5-hydroxytryptamine, 5-HT) is a key neurotransmitter and neuromodulator that regulates diverse neuronal processes. Using a custom-designed screen-printed carbon electrode (SPCE) incorporating ordered mesoporous carbon–bimetal oxides of Cu and Ni (CuO–NiO–OMC), rapid and real-time detection of 5-HT was achieved. The CuO–NiO–OMC structure featured highly active CuO and NiO catalytic sites that effectively promoted the irreversible oxidation of 5-HT (vs. Ag/AgCl reference electrode). The CuO–NiO–OMC/SPCE sensor, connected to a portable potentiostat, exhibited exceptional electrocatalytic performance for the oxidation of 5-HT, with a detection limit of 42.5 nM. The sensitivity was 1.56 A M⁻¹ cm⁻², and the linear dynamic range was 0.0–80.0 µM. The CuO–NiO–OMC/SPCE sensor also demonstrated outstanding selectivity in the presence of competing neurochemicals, including norepinephrine, epinephrine, dopamine, and glutamate, as well as high concentrations of tested biomolecules and inorganic ions. Furthermore, the practicality of the sensor was demonstrated using human serum and urine samples, with recovery percentages ranging from 91.1% to 98.3%. Thus, the CuO–NiO–OMC/SPCE sensor offers an effective approach for 5-HT sensing, thereby permitting molecular-level understanding of brain function. Full article

Today’s fluvioscape of the Hessische Ried (Upper Rhine Graben) is the consequence of human intervention on the natural drainage system that has transformed a large floodplain into an intensively used cultural landscape. Already, the Romans carried out river regulation and water management to guarantee the transportation of material and troops, securing the territory of the Roman Empire. To secure the so-called Rhein-Limes, burgi (fortlets) were constructed along small tributaries of the River Rhine under Valentinian I. (364–375). The burgus at Trebur-Astheim represents such a military site. It is located at the Schwarzbach/Landgraben fluvial system, which was actively used as a waterway and connected important military sites such as the castra “Auf Esch” (Groß-Gerau) with the River Rhine and, thus, with the provincial capital Mogontiacum (Mainz). Using a combination of magnetic gradiometry, frequency domain electromagnetic induction (FDEMI), electrical resistivity tomography (ERT), direct push-sensing (DP), and sediment coring, we were able to detect a 15 m wide and 2.5 m deep Roman canal between the burgus at Trebur-Astheim and the River Rhine, opening the Hessische Ried hinterland to wider trade routes. Radiocarbon dating further reveals that after a final re-excavation, the channel started to silt up in the 7th/8th century AD and finally fell out of use. This last period of use may be associated with the activities of the Carolingian Königspfalz (royal palace) Trebur. Our study shows that the fluvioscape of the Hessische Ried dates back to Roman times and that the canal at Trebur-Astheim is one of the few navigable canals known to have existed north of the Alps during the Roman period and the Early Middle Ages. Full article

Urbanization is a major and rapidly expanding form of land-use change worldwide and is one of the main drivers of the decline in arthropod diversity. Within urban matrices, remnants of natural or semi-natural habitats serve as important refuges for native organisms. However, these urban fragments are typically small, isolated, and strongly affected by various forms of disturbance. Therefore, connectivity among urban remnant patches may enhance population persistence and resilience. Increased tendencies to explore novel environments, tolerate human disturbance, and exploit unpredictable resources can be advantageous in urban environments. Accordingly, in this study of a flightless ground beetle species, we hypothesized that individuals from urban habitats—especially from isolated ones—would be bolder and more exploratory than their rural conspecifics, that sexes would differ in behavior, and that these behaviors would be temporally consistent, indicating animal personality. Activity-, exploration-, and boldness-related behavioral traits were significantly repeatable, providing evidence for animal personality, particularly in females and rural beetles. Contrary to our hypothesis, no behavioral differences were detected between rural and urban individuals. Furthermore, no significant sex-dependent differences in behavior were observed. Overall, our findings highlight the importance of species-specific traits and ecological context in shaping behavioral variation. Full article

Maclekarpine E is a minor alkaloid from Macleaya species with reported in vitro anti-inflammatory activity, but its in vivo metabolism remains unexplored. This study investigated the metabolic fate of maclekarpine E in rats and evaluated the potential pharmacological relevance of its metabolites. Maclekarpine E was orally administered to male Sprague-Dawley rats (250 mg/kg). Plasma, urine and feces were collected and analyzed by UPLC-Q-TOF-MS/MS. CYP phenotyping was performed using recombinant human enzymes. Molecular docking against ABCG2 and ABCC2 was conducted to assess potential interactions of all fecal compounds with these efflux transporters. Network pharmacology was employed to predict potential anti-ulcerative colitis-related targets of the metabolites, generating hypotheses for future experimental validation. Nineteen phase I metabolites were identified. Biotransformations included ring-opening, demethylation and oxidation. All 19 metabolites were detected in feces, nine in plasma and two in urine. No phase II conjugates were observed. CYP2C19 was the only significantly active isoform under the tested conditions, mediating approximately 16.5% substrate depletion (p < 0.05). All 20 fecal compounds bound ABCG2 (ΔG < −5.0 kcal/mol); 19 bound ABCC2. Network pharmacology yielded 57 overlapping targets with ulcerative colitis, enriched in PI3K-Akt and MAPK pathways. This study provides the first comprehensive metabolic profile of maclekarpine E in rats. The compound undergoes CYP2C19-mediated oxidation and is predominantly excreted into feces. Its fecal metabolites are potential ABCG2/ABCC2 substrates and may target UC-associated pathways based on network pharmacology predictions, warranting further experimental validation. Full article

The Golgi complex undergoes dynamic remodeling during the cell cycle, as ribbon unlinking in G2 is required for proper mitotic progression. Failure to fragment the ribbon leads to G2 arrest, whereas forced mitotic entry with intact ribbons results in multipolar spindle formation. Phosphorylation of the Golgi matrix protein GRASP65 at serine 277 (S277) in rat (S274 in human) by JNK2 is essential for ribbon unlinking, but its upstream regulation has remained unclear. Here, we generated and validated a phospho-specific antibody recognizing human GRASP65 phosphorylated at S274, enabling accurate detection of this modification. Using this tool, we identify protein kinase D2 (PKD2) as a critical upstream regulator required for GRASP65 phosphorylation and Golgi unlinking. GRASP65-S274 phosphorylation increases during G2 and is markedly reduced upon PKD2 inhibition or depletion, resulting in decreased Golgi unlinking and delayed G2/M transition. Conversely, PKD2-activating stimuli, including phorbol esters and nocodazole, enhance GRASP65 phosphorylation in a PKD2-dependent manner. These findings define PKD2 as a key regulator of the JNK2–GRASP65 signaling axis controlling Golgi disassembly at the G2/M transition. Moreover, the phospho-specific GRASP65 antibody described here provides a valuable tool to dissect upstream signaling mechanisms and to identify the initial triggers driving Golgi unlinking at G2 entry. Full article

The high incidence of Candida albicans infections and the limited efficacy of current antifungal therapies highlight the need for new antifungal agents. In this study, we present a bio-based hybridization strategy aimed at enhancing the antifungal activity of natural product scaffolds, with a particular focus on trans-ferulic acid. A library of twenty-nine hybrid molecules was rationally generated by grafting naturally occurring lipophilic moieties onto either the phenolic or carboxylic acid functions of ferulic acid. The antifungal activity of these molecules was then assessed against C. albicans. While the parent natural compounds exhibited weak activity (MIC > 500 µM), several hybrid derivatives (ATF19, ATF20, and MB22) demonstrated enhanced potency, with MIC values of <50 µM. Esters of the carboxylic acid or phenol group were essential for activity, with the most potent effects observed for short linear or mildly branched lipophilic chains. These active compounds exerted a multifaceted anti-virulence effect, including mitochondrial membrane depolarization, inhibition of hyphal morphogenesis, alterations in cell wall composition, and strong suppression of biofilm formation. Additionally, lead compounds showed no detectable cytotoxicity in human macrophages and intestinal epithelial cells and significantly improved host survival in a Caenorhabditis elegans model of C. albicans infection. Overall, the ferulic acid, citronellol, and sinapic hybrid molecules emerged as promising lead compounds for the development of antifungals against C. albicans. Full article

Background/Objectives: Imidazole dipeptides (IDPs), carnosine and anserine, are endogenous antioxidants. The metabolism and functions of IDPs have mainly been investigated in rodents. However, the blood of primates, such as humans, contains carnosinase (CN1), which hydrolyzes IDPs. In non-primates, CN1 is absent, allowing IDPs to be distributed throughout tissues. There are concerns about whether the results of animal experiments can be directly applied to humans. Therefore, we aimed to investigate the blood change in the concentration and tissue distribution of IDPs following their oral administration to golden hamsters, the only non-primates known to possess CN1. Methods: Plasma CN1 activity was compared between hamsters and humans. Hamsters were administered IDPs (an anserine/carnosine mixture) purified from chicken meat at a dose of 1000 mg/kg. Blood samples were collected at time points up to 6 h after administration. Tissue samples were collected at 6 h after administration to measure the concentrations of IDPs and related substances. Additionally, IDP levels in human and mice tissues from previous studies were compared with that of hamster tissues in this study. Results: Hamster plasma CN1 activity was more than 10 times higher than that in humans. Although IDPs were not detected in IDP-treated hamster plasma, constituent amino acids of IDPs increased up to 1–2 h and Nπ-methyl-histidine (m-His) remained at high levels up to 6 h after administration. IDP levels in control tissues (vehicle) were similar to those in human tissues. In the IDP group, tissue IDPs were higher than those in the vehicle and m-His increased in all tissues. Conclusions: This study indicated that m-His levels increase in hamster tissues following a single oral administration of IDPs and strongly suggest that hamsters should be used in functional studies of IDPs in humans, focusing on the functionality of m-His. Full article

High noise levels in industrial workplaces pose significant challenges to occupational safety, particularly with hearing protection and effective communication. Traditional hearing protection devices, while effectively attenuating harmful noise, often compromise situational awareness by excessively isolating workers from the acoustic environment and preventing the perception of critical auditory cues (e.g., emergency alarms), thereby introducing additional safety risks. This paper presents a smart industrial safety system that integrates Internet of Things (IoT) and artificial intelligence (AI) and is based on intelligent hearing protection devices to (a) selectively attenuate hazardous industrial noise while (b) preserving human speech and (c) reproduce targeted audio notifications to workers near malfunctioning or hazardous machinery. A real-time voice activity detection (VAD) model is employed to distinguish vocal components from background noise to adaptively control digital signal processing filters. Furthermore, indoor localization enables the delivery of targeted audio messages to workers in proximity to relevant events. Experimental evaluations on embedded hardware demonstrate that the selected VAD model operates well within real-time constraints and effectively supports dynamic noise filtering. Objective evaluation of the filtering stage using Mean Opinion Score (MOS), signal-to-noise ratio (SNR), and Harmonics-to-Noise Ratio (HNR) shows consistent quality improvements across all tested conditions, with MOS gains up to +118%, SNR increases between +10.4 and +29.0 dB, and HNR improvements up to +6.22 dB, indicating enhanced speech intelligibility and preservation of voice harmonic structure even under high-noise scenarios. Robustness validation of the VAD module across varying acoustic conditions confirms reliable speech detection performance, achieving perfect classification at +10 dB SNR, very high accuracy at 0 dB (98.3%, ROC AUC 0.998), and stable operation even at $-7$ dB SNR (79.8% accuracy, ROC AUC 0.878). The proposed architecture achieves a balanced trade-off between hearing protection and speech intelligibility while enhancing the effectiveness of safety communications in noisy industrial environments. Full article

Rapid post-disaster building damage assessment requires recognizing explicit structural failures and interpreting implicit situational cues in visually complex scenes. Whereas conventional automated methods are often confined to detecting explicit damage patterns, human perception naturally integrates both types of information into a holistic risk judgment. This study presents an exploratory investigation into the neural signatures underlying this integrated judgment process using electroencephalography. A modified paradigm was employed to probe the cognitive dynamics of risk evaluation in participants with civil engineering backgrounds. Although participants were instructed only to identify damaged buildings without explicit severity grading, event-related potential analysis revealed systematic, graded neural responses that scaled with damage severity. This suggests that the brain encodes damage-related information not as a binary state but as a continuous spectrum of perceived risk, implicitly processing severity, even in the absence of explicit instructions. Furthermore, single-trial analysis demonstrated that time-domain features contain robust discriminative information, verifying the feasibility of decoding these latent judgments from brain activity. These findings provide a physiological basis for developing future cognition-informed algorithms and human-in-the-loop frameworks, bridging the semantic gap to enhance the reliability of automated disaster assessment. Full article

Bangka’s mangroves contribute to Indonesia’s species-rich coastal ecosystems, yet they have experienced substantial degradation, largely driven by human activities such as tin mining. Establishing long-term records of mangrove extent is essential for understanding distribution dynamics, assessing impacts, and guiding conservation strategies. In this study, we applied change detection techniques, a random forest classifier, and the LandTrendr algorithm to analyze Landsat time-series data from 1994 to 2023 across Bangka Island. We quantified multi-decadal changes in mangrove extent, periods of disturbance and recovery, and discrepancies between local and global datasets. Mangrove dynamics were spatially heterogeneous, with both expansion and loss observed across regions in landward and seaward settings. Over the 30-year period, total gains reached 4956.39 ha (10.30% of the baseline), yet the net change indicated an overall loss of 1055.85 ha. LandTrendr analysis further revealed sustained mangrove expansion since 1989. Observed changes reflect the combined influence of natural processes, including accretion and erosion, and human pressures, particularly tin mining. Although net area loss aligns with national trends, the drivers in this mining-dominated region differ from those elsewhere, and some mangrove areas remain absent from global datasets. These findings emphasize the need to better capture local gain–loss dynamics to support effective management and conservation. Full article

This paper presents the synthesis, physicochemical characterisation, and analytical applications of chemiluminescent (CL) labels based on acridinium salts (ALs) for biomedical diagnostics. These compounds emit light as a result of oxidative reactions and represent an established class of reagents widely employed in chemiluminescence immunochemical assays (CLIAs) today. A series of structurally differentiated acridinium labels (AL1–AL5) was synthesised applying mostly original synthetic routes and purified to chromatographic purity (>90%, RP-HPLC). The compounds, including a commercial product treated as a reference, were successfully conjugated to anti-human IgG, yielding stable immunochemical reagents suitable for immunoassays with CL detection. The chemiluminescence properties of the obtained labels and their protein conjugates were investigated in aqueous buffers and in the presence of surfactants. The emission profiles exhibited characteristic flash-type kinetics with emission maxima occurring within 0.15–0.25 s after reaction initiation. The presence of surfactants more or less significantly enhanced the emission intensity, with signal increases of up to approx. 2-fold compared to surfactant-free systems. Analytical calibration demonstrated a linear response of signal derived from native labels over at least one order of magnitude of concentration, with detection limits falling in the range of 10⁻⁹–10⁻¹⁰ M, confirming the high sensitivity of the developed compounds. The experimental results were supported by theoretical studies using density functional theory (DFT), which confirmed the energetic feasibility of the CL reaction pathway and identified structural factors influencing activation barriers. Additional semiempirical calculations (PM7) indicated that the dielectric environment and proximity of ionic species can influence the reaction energetics, providing mechanistic support for the experimentally observed effects of surfactants. The results demonstrate that both molecular structure and microenvironment influence CL efficiency and kinetics of the investigated systems. The developed acridinium labels exhibit analytical performance better or comparable to commercial reagents and are fully compatible with standard immunodiagnostic conjugation protocols, confirming their suitability for use in modern chemiluminescent immunoassays. Full article

Chapare virus (CHAPV) is an Arenaviridae family member and causative agent of Chapare hemorrhagic fever (CHHF). Endemic to Bolivia, CHAPV was found to be the cause of several outbreaks of CHHF in Bolivia in 2003 and 2019 with high case-fatality rates and instances of human-to-human transmission. The pathogenesis of CHAPV infection is poorly understood, and no vaccines or antivirals are available, in part due to a dearth of available animal models. Mice lacking signal transducer and activator of transcription 1 (STAT1^-/-) have been shown to succumb to infection by related arenaviruses, including Machupo virus, and were investigated for their susceptibility to CHAPV infection. Challenge with CHAPV resulted in partial lethality in STAT1^-/- mice with a biphasic disease course characterized by initial viral load and pathology in the spleen and liver followed by inflammation and high viral titers in the brain and spinal cord that immediately preceded mortality. Adaptation in the brains of STAT1^-/- mice resulted in a fully lethal mouse-adapted CHAPV variant, with a similar biphasic disease course, but virus in tissues was detected more proximal to challenge. The result of this study is a lethal small-animal rodent model for CHAPV that recapitulates many aspects of human CHAPV disease. Full article

This study aimed to elucidate the key characteristics of the humoral immune response and the tissue distribution of specific antibody-secreting cells (ASCs) in Nile tilapia (Oreochromis niloticus). A specific immune model was established by immunizing fish with human IgG. Lymphocytes were isolated from the head kidney, spleen, and peripheral blood and subjected to antigen stimulation in vitro. The MTT assay, reflecting cell metabolic activity and viability, identified the optimal culture conditions as a cell concentration of 2.5 × 10⁶ cells/mL, an antigen concentration of 2 μg/mL, and a culture duration of 72 h. Under these conditions, peripheral blood lymphocytes exhibited the most increase in metabolic activity, followed by head kidney lymphocytes, while splenic lymphocytes showed no significant response. Subsequent dynamic monitoring of antibody-secreting cells (ASCs) using ELISPOT revealed that, in the absence of antigen stimulation, ASC numbers from all three tissues declined over time. Notably, head kidney ASCs retained approximately 50% of their initial number by day 5, whereas ASCs in peripheral blood and spleen decayed to barely detectable or completely undetectable levels, respectively. These findings suggest that the head kidney may serve as a primary site for ASC persistence during the effector phase, potentially contributing to sustained humoral immunity. Although antigen stimulation did not induce significant ASC expansion, it significantly slowed their decay rate (p < 0.05), indicating an antigen-dependent maintenance role. ELISA detection of antibody levels in the culture supernatants showed a consistent trend with the ELISPOT results, further confirming the sustained functional support of antigen for ASCs. Additionally, LPS stimulation experiments demonstrated that all three tissues contained plasmablasts activatable by non-specific stimuli, with peripheral blood showing the highest proliferation fold (4–6 times). In conclusion, this study provides insights into the tissue-specific distribution, in vitro persistence, and antigen-dependent maintenance of ASCs in Nile tilapia, providing insights into the cellular basis that may contribute to humoral immune memory and laying a theoretical foundation for the rational design and application of tilapia vaccines. Full article

Background/Objectives: Ulcerative Colitis (UC) is a chronic inflammatory disease of the colon that profoundly impacts human health. Conventional pharmacological treatments are associated with serious adverse reactions and toxic side effects. Consequently, the development of natural plant-derived biological agents for UC treatment is an urgent imperative. Methods: Utilising a Dextran Sulfate Sodium (DSS)-induced ulcerative colitis mouse model, with mice receiving low, medium, and high doses of water extract of Tibetan Fritillaria cirrhosa D. Don extract (FCD), alongside a group receiving 5-aminosalicylic acid. The Disease Activity Index (DAI) was calculated, colon length was measured, histological scores were assessed, and histopathological alterations were evaluated. Inflammatory factor were determined by ELISA; mRNA and protein expression in colonic tissue was analysed by RT-qPCR and Western blotting; intestinal barrier-related proteins were examined by immunofluorescence and immunohistochemistry; and gut microbiota composition was assessed by 16S rRNA sequencing. Results: Research has confirmed that FCD alleviates symptoms of DSS-induced colitis in mice, specifically manifested by a slower rate of weight loss, reduced colon shortening, and decreased disease activity index. It has been demonstrated that the process under investigation exerts a beneficial effect on intestinal injury by means of a number of mechanisms. These include increased goblet-cell production, elevated IL-10 levels, and reduced levels of TNF-α, IL-1β, and IL-6. Furthermore, immunofluorescence detection, immunohistochemical analysis, and RT-qPCR results indicate that FCD maintains the integrity of the intestinal mucosal barrier by enhancing the expression of Zonula occludens-1 (ZO-1), occludin, and claudin-1 proteins and their corresponding mRNAs, in addition, FCD can regulate the gut microbiota and promote its diversity. Conclusions: Research indicates that FCD may exert therapeutic effects on ulcerative colitis (UC) by regulating intestinal barrier integrity and modulating the gut microbiota. These findings reinforce the idea that FCD could be used as a natural therapy to improve UC. Full article

Human Activity Recognition (HAR) is a pivotal research area for applications such as automated surveillance, smart homes, security, healthcare, and human behavior analysis. Traditional machine-learning approaches often rely on manual feature engineering, which can limit generalization. Although deep learning has improved HAR through automatic representation learning, achieving high detection performance under computational constraints remains challenging. This paper proposes an efficient HAR framework that combines deep learning with hybrid optimization. Surveillance videos are first decomposed into frames, and a keyframe selection stage identifies distinctive frames to reduce redundancy and computational cost while preserving informative content. Motion and appearance features are then extracted using Histogram of Oriented Optical Flow (HOOF) and a ResNet-101 model, respectively, and concatenated into a unified feature representation. Classification is performed using an Inception-based Long Short-Term Memory (Incept-LSTM) network, which is fine-tuned via the proposed Tricky Predator Optimization (TricP) over a restricted, low-dimensional parameter vector. TricP is inspired by predator poaching behavior and the social dynamics of Latrans to enhance exploration and exploitation during search. Experiments on the UCF-Crime dataset show that the proposed method achieves 96.84% specificity, 92.16% sensitivity, and 93.62% accuracy. Full article