Search Results (939)

Stress coping style (SCS) is crucial for animal welfare in the context of breeding. The link between behavioural traits and physiological responses to external stimuli is increasingly recognized and could orient the selection of appropriate SCSs for welfare-oriented breeding. This study aimed to evaluate how SCS influences the physiological responses of Sparus aurata, a widely used species in aquaculture, following Vibrio anguillarum stimulation. To this end, the serum protein electrophoretic profile, analysed by capillary electrophoresis, was used as an innovative parameter to assess physiological variations. S. aurata individuals were categorized into three SCS groups—bold, shy, and intermediate —based on a risk-taking test. Serum was collected at day 0 (pre-inactivated V. anguillarum inoculation) and at 30 and 60 days post-inoculation. Analyses revealed an increase in the β₂-globulin fraction, putatively associated with molecules involved in the physiological response following inactivated pathogen inoculation, accompanied by a decrease in the γ fraction over time. This trend was particularly pronounced in bold fish, while shy ones showed a similar but less marked pattern. Overall, the results suggest that proactive individuals exhibit a more marked physiological modulation to inactivated pathogen stimulation than reactive ones, highlighting modulation of serum protein electrophoresis as a sensitive bioindicator of physiological response in S. aurata. Full article

Biomass liquefaction is a thermochemical process that converts lignocellulosic materials into reactive liquid intermediates, enabling the production of bio-based polyols as a sustainable alternative to petroleum-derived chemicals. This study investigates the liquefaction of two lignocellulosic biomasses, Red Angico (Anadenanthera colubrina) and Mahogany (Swietenia macrophylla), using a glycerol–ethylene glycol polyalcohol system, chosen for its renewable origin and high solvating efficiency. The resulting polyols were used to produce polyurethane (PU) foams, and their properties were evaluated in relation to biomass composition. The chemical composition of each biomass significantly influenced its liquefaction behavior and polyol characteristics. Mahogany achieved higher liquefaction efficiency, whereas Red Angico polyols generated PU foams with superior mechanical performance, highlighting the influence of species-specific chemistry. Water content and isocyanate index were found to modulate foam structure and compressive strength. This work demonstrates how tailored liquefaction strategies using polyalcohol systems can optimize bio-based PU foam properties, providing a sustainable route for high-performance polymer materials. Full article

Background/Objectives: The Rapid Access Chest Pain Assessment Clinic (RACPAC) streamlines the evaluation of low-to-intermediate risk chest pain and helps avoid unnecessary hospitalisation. Biomarkers {low-density lipoprotein cholesterol (LDL-c) and high-sensitivity C-reactive protein (hsCRP)} are established cardiovascular risk markers. Yet, their diagnostic value for stable coronary artery disease (CAD) in RACPAC remains uncertain. Therefore, we aimed to determine the utility of biomarkers in predicting the presence of CAD in the RACPAC setting. Methods: A retrospective cohort study of consecutive adults attending RACPAC between 2012 and 2021. Multivariable logistic regression and receiver operating characteristic analyses, including prespecified subgroup and sensitivity analyses, were used to evaluate the predictive value of hsCRP and LDL-c for the presence of CAD detected on CT Coronary Angiogram (CTCA) or Treadmill Stress Echocardiography (TSE) as the primary outcome. Results: 3569 patients were included in this study, the mean age was 55.4 ± 11.3 years, and 48.8% were female; 37.4% had hypertension, while 39.5% had dyslipidemia. The mean LDL-c was 3.1 ± 0.9 mmol/L, and the median hsCRP was 1.9 mg/L (IQR 0.9 to 3.8). The regression analysis for the primary outcome showed that neither hsCRP nor LDL-c predicted CAD on CTCA (hsCRP OR 1.00, 95% CI 0.99 to 1.02, p = 0.70; LDL-c OR 1.16, 95% CI 0.97 to 1.39, p = 0.11). On TSE, hsCRP was not associated with CAD, while LDL-c showed an inverse association with CAD (hsCRP OR 0.98, 95% CI 0.83 to 1.00, p = 0.78; LDL-c OR 0.44, 95% CI 0.21 to 0.87, p = 0.02). ROC analysis showed AUC 0.553 for log hsCRP (95% CI 0.501 to 0.606) and 0.508 for LDL-c (95% CI 0.450 to 0.566), with p = 0.2756. Conclusions: In a large real-world RACPAC cohort, neither elevated hsCRP nor LDL-c predicted the presence of coronary artery disease in the rapid access chest pain clinic (RACPAC) cohort. In contrast, CT coronary angiography (CTCA) demonstrated superior diagnostic accuracy compared with treadmill stress echocardiography (TSE) in this setting. Full article

Background/Objectives: Malaria remains a major global health burden, increasingly complicated by resistance to artemisinin-based therapies. Because artemisinin activation depends on heme and porphyrin chemistry, we sought to exploit host red blood cell (RBC) heme metabolism as a therapeutic vulnerability. This study aims to develop and evaluate a host-directed “bait-and-kill” strategy that selectively sensitizes malaria-infected RBCs to artemisinin. Methods: We integrated quantitative proteomics, erythropoiesis transcriptomic analyses, flow cytometry, and in vitro malaria culture assays to characterize heme metabolism in mature RBCs and Plasmodium falciparum-infected RBCs (iRBCs). The heme precursor 5-aminolevulinic acid (ALA) was used to induce porphyrin accumulation, and dihydroartemisinin (DHA) was applied as the killing agent. Drug synergy, porphyrin accumulation, reactive oxygen species (ROS) induction, and parasite survival were assessed, including ring-stage survival assays using artemisinin-resistant clinical isolates. Results: Mature RBCs retain a truncated heme biosynthesis pathway capable of accumulating porphyrin intermediates, while uninfected RBCs are impermeable to ALA. In contrast, iRBCs exhibit increased membrane permeability, allowing selective ALA uptake and porphyrin accumulation. ALA alone did not induce cytotoxicity or ROS, whereas DHA induced ROS and parasite killing. The ALA + DHA combination resulted in synergistic parasite elimination, including complete clearance of artemisinin-resistant P. falciparum isolates from the Greater Mekong Subregion, with no recrudescence observed over three weeks of culture. Evidence supports a predominant role for host-derived heme metabolites in mediating this synergy. Conclusions: The bait-and-kill strategy selectively exploits host RBC heme metabolism to restore and enhance artemisinin efficacy while sparing uninfected cells. Using clinically safe compounds, this host-directed approach provides a promising, resistance-bypassing framework for malaria treatment and combination drug development. Full article

Expanding the chemical diversity of DNA–encoded libraries (DELs) is crucial for identifying binders to emerging drug targets using DEL technology. In the present study, as part of our ongoing efforts to develop on–DNA diazide platforms (D–DAPs)—platform molecules possessing both aromatic and aliphatic azide groups on a single core reactive scaffold—we designed and synthesized a new compact diazide platform, designated as a compact D–DAP (C–D–DAP). This molecule is based on a low–molecular–weight reactive scaffold, 3–azido–5–(azidomethyl)benzoic acid, to facilitate small–molecule drug discovery targeting enzymes and G protein–coupled receptors (GPCRs). Furthermore, we established two distinct stepwise warhead construction strategies that exploit the chemoselective transformations of the azide groups in the C–D–DAP, which exhibit different reactivities. In addition, four virtual DELs were generated based on stepwise warhead elaboration from the C–D–DAP scaffold. Comparative chemical diversity analysis against bioactive compounds from ChEMBL revealed that these virtual libraries populate structural regions that are sparsely represented among known molecules. Each virtual library also occupies a distinct region of structural space relative to the others and displays intermediate quantitative estimate of drug–likeness (QED) values. Full article

DNA interstrand cross-links (ICLs) are among the most cytotoxic forms of DNA damage, arising when the two strands of the DNA helix are covalently linked by crosslink-inducing agents such as bifunctional alkylating agents and reactive aldehydes. Several studies have demonstrated that ICLs can also be induced by reactive oxygen and nitrogen species. We previously reported that under oxidative conditions, the major oxidative adenine lesion 7,8-dihydro-8-oxoadenine (oxoA) can efficiently generate a novel class of oxoA-G ICLs, structurally resembling guanine–guanine (G–G) cross-links that can be induced by reactive nitrogen species. To investigate the mutagenic potential of these oxidation-induced ICLs in cells, we employed a SupF-based mutagenesis assay using bacterial cells. A single site-specific oxoA–G ICL was synthesized and incorporated into a plasmid, which was then introduced into an E. coli reporter strain to assess mutation profiles induced by both oxoA and oxoA–G ICLs. Our results show that oxoA–G ICLs cause A-to-C/T and G-to-C transversion mutations at the oxoA-G cross-link site, demonstrating highly promutagenic nature of the lesion in bacterial cells. We propose that the oxoA–G ICL may promote transversion mutations, likely driven by a syn conformer of unhooked oxoA-G ICL repair intermediates during translesion synthesis. Full article

Overexpression of protein phosphatase 5 (PP5) is implicated in tumor cell growth, establishing PP5 as a compelling target for small-molecule anticancer therapy. Building on prior success in achieving selectivity within the PP2A domain through scaffold functionalization that maximizes active-site interactions, we propose a parallel strategy for PP5 inhibition. Norcantharidin, the demethylated cousin of cantharidin, is a potent yet unselective phosphatase inhibitor, making its bicyclic framework an attractive platform for systematic derivatization. The approach reported herein exploits anhydride reactivity to generate a carboxylic acid derivative that is transformed into a chloromethyl ester. Chloromethyl ester functionality serves as a strategically activated intermediate enabling downstream functional-group diversification under mild, neutral conditions while preserving scaffold integrity. This modular synthetic strategy establishes a foundation for the development of PP5-selective norcantharidin derivatives with improved tumor selectivity, potency, and synthetic feasibility. Full article

B cells are key drivers of immune dysregulation across systemic autoimmune diseases. Among their progeny, plasmablasts occupy a uniquely revealing niche: short-lived, highly proliferative intermediates that mirror real-time B-cell activation. Their appearance in peripheral blood integrates antigenic stimulation, cytokine-driven differentiation, and aberrant germinal-center dynamics, transforming them into sensitive indicators of ongoing immunological activity. This review synthesizes current knowledge on plasmablast biology and highlights disease-specific phenotypes across systemic lupus erythematosus (SLE), primary Sjögren disease (pSjD), IgG4-related disease (IgG4-RD), ANCA-associated vasculitis (AAV), and rheumatoid arthritis (RA). We incorporate molecular insights from single-cell technologies that have uncovered previously unrecognized plasmablast subsets, metabolic states, and interferon-related signatures with prognostic and mechanistic value. Beyond descriptive immunology, plasmablasts are emerging as dynamic biomarkers capable of informing real-time clinical decisions. One of the most robustly supported applications is the prognostic interpretation of plasmablast kinetics following B-cell-depleting therapies, where early reconstitution patterns consistently predict relapse across multiple autoimmune conditions. As clinical immunology shifts from static serological markers toward kinetic, cell-based monitoring, plasmablast quantification offers a path toward precision immune surveillance. Integrating plasmablast dynamics into routine care may ultimately allow clinicians to anticipate disease flares, time therapeutic reinforcements, and transition from reactive management to preventive intervention. Full article

Background: Cardiovascular risk models, such as the Framingham and atherosclerotic cardiovascular disease (ASCVD) calculators, have improved risk prediction but often fail to identify individuals who experience ASCVD events despite low or intermediate predicted risk. This suggests that underrecognized, non-traditional risk factors may contribute significantly to the development of atherosclerosis. Objective: This narrative review synthesizes and summarizes recent evidence on high-yield non-traditional risk factors for atherosclerosis, with a focus on clinically significant, emerging, and applicable contributors beyond conventional frameworks. This review is distinct in that it aggregates a wide array of non-traditional risk factors while also consolidating recent data on ASCVD in more vulnerable populations. Unlike the existing literature, this manuscript integrates in a single comprehensive review various domains of non-traditional atherosclerotic risk factors, including inflammatory, metabolic, behavioral, environmental, and physical pathways. An additional unique highlight in the same manuscript is the discussion of non-traditional risk factors for atherosclerosis in more vulnerable populations, specifically South Asians. We also focus on clinically actionable factors that can guide treatment decisions for clinicians. Results: Key non-traditional risk factors identified include inflammation and biomarker-based risk factors such as C-reactive protein or interleukin-6 levels, metabolic and microbial risk factors, behavioral factors such as E-cigarette use, and environmental or infectious risk factors such as air and noise pollution. We explore certain physical exam findings associated with atherosclerotic burden, such as Frank’s sign and Achilles tendon thickness. Conclusions: Atherosclerosis is a multifactorial process influenced by diverse and often overlooked factors. Integrating non-traditional risks into clinical assessment may improve early detection, guide prevention and personalize care. Future risk prediction models should incorporate molecular, behavioral, and environmental data to reflect the complex nature of cardiovascular disease. Full article

Ammonia is considered as a promising hydrogen carrier and a carbon-free fuel. Methods for improving ammonia combustion characteristics often involve its co-firing with more reactive fuels (natural gas, biofuels, etc.). Among the natural gas components, ethane is second most abundant. Therefore, the development of detailed chemical–kinetic mechanisms that accurately consider the interactions between ammonia and each component of natural gas is very important. Such mechanisms must be based on experimental data obtained under a wide range of conditions. In this work, NH₃/C₂H₆/O₂/Ar blends were studied in JSR (φ = 0.5–2.0, p = 1 atm, τ = 1 s, T = 800–1300 K) and in a shock tube (p = 7.3–8.6 atm, T = 1260–1590 K). Additionally, the structure of premixed flames was investigated (φ = 0.8–1.2, p = 1–5 atm). Eleven recently published detailed chemical–kinetic mechanisms were tested. The model Shrestha-2025 was updated to achieve better agreement with the entire set of experimental data. The effect of p and φ on intermediate species concentration was analyzed. Ammonia and ethane consumption pathways were also examined. Full article

In this study, the advanced oxidation system of peroxymonosulfate (PMS) was activated by molybdenite supported on biochar (Molybdenite@BC), and the degradation efficiency, influencing factors and degradation mechanism of sulfamethoxazole (SMX) were explored through experiments. Molybdenite@BC, a composite material used in the study, was prepared by pyrolysis at high temperature. The optimum pyrolysis temperature was 700 °C, and the mass ratio of molybdenite to biochar (BC) was 1:3. By changing dosage of Molybdenite@BC, pH value, initial concentration of PMS, and the types and concentration of inorganic anions, the effects of various factors on SMX degradation were systematically studied. The optimum reaction conditions of the Molybdenite@BC/PMS process were as follows: Molybdenite@BC dosage was 100 mg/L, PMS concentration was 0.2 mM, pH value was 6.9 ± 0.2, and initial SMX concentration was 6 mg/L. Under these conditions, the degradation rate of SMX was 97.87% after 60 min and 99.06% after 120 min. The material characterization analysis showed that Molybdenite@BC had a porous structure and rich active sites, which was beneficial to the degradation of pollutants. After the composite material was used, the peaks of MoO₂ and MoS₂ became weaker, which indicated that there was some loss of molybdenum from the material structure. Electron paramagnetic resonance (EPR) and radical quenching experiments revealed that Molybdenite@BC effectively catalyzed PMS to generate various reactive oxygen radicals and non-free radicals, including singlet oxygen (¹O₂), hydroxyl radical (^•OH), sulfate radical (SO₄^•−) and superoxide radical (^•O₂⁻). ¹O₂ played a leading role in the degradation of SMX, while ^•OH and SO₄^•− had little influence. The intermediate products of the degradation of SMX in Molybdenite@BC/PMS system were analyzed by liquid chromatography–tandem mass spectrometry (LC–MS). The results showed that there were nine main intermediate products in the process of degradation, and the overall toxicity tended to decrease during the degradation of SMX. The degradation path analysis showed that with the gradual ring opening and bond breaking of SMX, small molecular compounds were generated, which were finally mineralized into H₂O, CO₂, CO₃²⁻, H₂SO₄ and other substances. The research results confirmed that the Molybdenite@BC/PMS process provided a feasible new method for the degradation of SMX in water. Full article

The clinical success of calcium phosphate bone grafts (CPs) largely depends on the body’s immune response. However, traditional biocompatibility tests use healthy organisms and cannot predict effectiveness in patients with common chronic inflammatory diseases. This study examines how inflammation modulates the immune response, in vitro and in vivo, to low-temperature biomimetic CPs: dicalcium phosphate dihydrate (DCPD), octacalcium phosphate (OCP), and hydroxyapatite (HAp). In vitro studies involved human monocytes, macrophages, lymphocytes, and mesenchymal stromal cells (MSCs), with or without pro-inflammatory activation. In vivo biocompatibility was assessed via subcutaneous implantation in rats, with or without Complete Freund’s Adjuvant (CFA)-induced inflammation. Under normal conditions, all CP caused minimal immune reactivity. Inflammation-activated macrophages, however, triggered an acute reaction with significantly increased TNF-α and IL-1β secretion. Healthy and inflamed animals showed sharp contrasts. Although all materials exhibited thickened fibrous capsules during inflammation, biocompatibility varied markedly: DCPD performed best by promoting angiogenesis with minimal inflammation; HAp provoked the most severes response, including tissue necrosis and signs of rejection; OCP showed intermediate effects, with angiogenesis but notable fibrosis. Inflammatory processes critically influence CP biocompatibility; materials biocompatible in healthy organisms can induce fibrosis or rejection under inflammation. Disease-relevant, immune-challenged models are essential to predict clinical efficacy and safety. Full article

Background: Phototherapy utilizes targeted irradiation to inactivate bacteria or treat various medical conditions. Depending on the therapeutic goal, wavelengths from violet to infrared (IR) are applied. Within the visible and near-IR spectrum, photodynamic therapy (PDT) combines light with photosensitizers that generate reactive oxygen species (ROS), leading to bacterial inactivation. Optimizing photodynamic efficacy can involve either enhancing ROS formation through specific topical agents that modulate ROS generation or employing dual-wavelength light irradiation (DWLR) to achieve synergistic excitation. Established DWLR protocols typically combine blue and red light or IR to activate distinct photosensitizers. Materials and Methods: This study investigates whether a similar synergistic effect can be achieved within the green spectral range by simultaneously exciting a single photosensitizer—coproporphyrin III (CP III)—at 496 nm and 547 nm. Results: Convolution analysis and in vitro bacterial reduction experiments with Cutibacterium acnes subsp. elongatum revealed that cyan irradiation (496 nm) achieved the strongest photoreduction (2.31 log steps at 1620 J/cm²), whereas PC-lime irradiation (547 nm) produced a smaller effect (0.74 log steps). DWLR protocols (simultaneous and sequential irradiation) resulted in intermediate reductions (1.64 and 1.73 log steps, respectively), exceeding PC-lime but not surpassing cyan irradiation alone. Conclusions: These findings demonstrate that excitation efficiency at the local absorption maximum of CP III is the primary determinant of ROS generation, while spectral broadening through DWLR does not enhance bacterial inactivation within this wavelength range and in vitro setup. Full article

Peroxynitrite (ONOOH/ONOO⁻) is increasingly recognized as a key intermediate in advanced oxidation processes (AOPs), yet its role in water treatment remains insufficiently defined. This study provides mechanistic insights into peroxynitrite-mediated AOPs through competition kinetics method, demonstrating that both decomposition and pollutant degradation are strongly pH-dependent, with ONOOH dominating stability and radical pathways across pH 5.0−9.0, while its decay rate decreases from 1.2 s⁻¹ to 0.0022 s⁻¹. The interplay of HO^• and diverse reactive nitrogen species (RNS, including reactive nitrogen radicals and peroxynitrite) dictates pollutant-specific degradation efficiencies, with RNS showing a unique reliance in degrading bisphenol A—contributing up to 66.7% at pH 8.0. Buffer chemistry further modulates these pathways: bicarbonate accelerates peroxynitrite decay via CO₂ and CO₃^•−-mediated acceleration (resulting in a 361.9% increase at pH 9.0), while borate promotes reactive nitrogen radical formation but suppresses HO^• contributions. Importantly, peroxynitrite was shown to facilitate N-nitrosodimethylamine formation in the presence of dimethylamine, with yields maximized under alkaline conditions and attenuated by bicarbonate. These quantitative findings underscore the critical roles of pH and buffer chemistry in optimizing peroxynitrite-based water treatment while mitigating byproduct risks. Full article

A cobalt-containing zeolitic imidazolate framework (ZIF-67) was carbonized by different routes to composite materials (cZIFs) composed of metallic Co, Co₃O₄, and N-doped carbonaceous phase. The effect of the carbonization procedure on the water pollutant removal properties of cZIFs was studied. Higher temperature and prolonged thermal treatment resulted in more uniform particle size distribution (as determined by nanoparticle tracking analysis, NTA) and surface charge lowering (as determined by zeta potential measurements). Surface-governed environmental applications of prepared cZIFs were tested using physical (adsorption) and electrochemical methods for dye degradation. Targeted dyes were methylene blue (MB) and methyl orange (MO), chosen as model compounds to establish the specificity of selected remediation procedures. Electrodegradation was initiated via an intermediate reactive oxygen species formed during oxygen reduction reaction (ORR) on cZIFs serving as electrocatalysts. The adsorption test showed relatively uniform adsorption sites at the surface of cZIFs, reaching a removal of over 70 mg/g for both dyes while governed by pseudo-first-order kinetics favored by higher mesoporosity. In the electro-assisted degradation process, cZIF samples demonstrated impressive efficiency, achieving almost complete degradation of MB and MO within 4.5 h. Detailed analysis of energy consumption in the degradation process enabled the calculation of the current conversion efficiency index and the amount of charge associated with O₂^•−/^•OH generation, normalized by the quantity of removed dye, for tested materials. Here, the proposed method will assist similar research studies on the removal of organic water pollutants to discriminate among electrode materials and procedures based on energy efficiency. Full article