Search Results (6,553)

The premature senescence of red raspberry leaves severely affects plant growth. In this study, the double-season red raspberry cultivar ‘Polka’ was used, with N₁₅₀ (0.10 g N·kg⁻¹) selected as the treatment group (T150) and N₀ (0 g N·kg⁻¹) set as the control (CK). This study systematically investigated the mechanism of premature senescence in red raspberry leaves under different nitrogen application levels by measuring physiological parameters and conducting a combined multi-omics analysis of transcriptomics and metabolomics. Results showed that T150 plants had 8.34 cm greater height and 1.45 cm greater ground diameter than CK. The chlorophyll, carotenoid, soluble protein, and sugar contents in all leaf parts of T150 were significantly higher than those in CK, whereas soluble starch contents were lower. Malondialdehyde (MDA) content and superoxide anion (O₂⁻) generation rate in the lower leaves of T150 were significantly lower than those in CK. Superoxide sismutase (SOD) and peroxidase (POD) activities in the middle and lower functional leaves of T150 were higher than in CK, while catalase (CAT) activity was lower. Transcriptomic analysis identified 4350 significantly differentially expressed genes, including 2062 upregulated and 2288 downregulated genes. Metabolomic analysis identified 135 differential metabolites, out of which 60 were upregulated and 75 were downregulated. Integrated transcriptomic and metabolomic analysis showed enrichment in the phenylpropanoid biosynthesis (ko00940) and flavonoid biosynthesis (ko00941) pathways, with the former acting as an upstream pathway of the latter. A premature senescence pathway was established, and two key metabolites were identified: chlorogenic acid content decreased, and naringenin chalcone content increased in early senescent leaves, suggesting their pivotal roles in the early senescence of red raspberry leaves. Modulating chlorogenic acid and naringenin chalcone levels could delay premature senescence. Optimizing fertilization strategies may thus reduce senescence risk and enhance the productivity, profitability, and sustainability of the red raspberry industry. Full article

Anthocyanins, a subclass of flavonoid pigments, impart vivid red, purple, and blue coloration to horticultural plants, playing essential roles in ornamental enhancement, stress resistance, and pollinator attraction. Recent studies have identified B-box (BBX) proteins as a critical class of transcription factors (TFs) involved in anthocyanin biosynthesis. Despite these advances, comprehensive reviews systematically addressing BBX proteins are urgently needed, especially given the complexity and diversity of their roles in regulating anthocyanin production. In this paper, we provide an in-depth overview of the fundamental structures, biological functions, and classification of BBX TFs, along with a detailed description of anthocyanin biosynthetic pathways and bioactivities. Furthermore, we emphasize the diverse molecular mechanisms through which BBX TFs regulate anthocyanin accumulation, including direct activation or repression of target genes, indirect modulation via interacting protein complexes, and co-regulation with other transcriptional regulators. Additionally, we summarize the known upstream regulatory signals and downstream target genes of BBX TFs, highlighting their significance in shaping anthocyanin biosynthesis pathways. Understanding these regulatory networks mediated by BBX proteins will not only advance fundamental horticultural science but also provide valuable insights for enhancing the aesthetic quality, nutritional benefits, and stress adaptability of horticultural crops. Full article

Sepsis is a clinical syndrome characterized by a dysregulated host response to infection, frequently resulting in septic shock and multi-organ failure. Emerging evidence highlights the critical role of neutrophil extracellular traps (NETs) in the pathophysiology of sepsis. NETs are extracellular structures composed of chromatin DNA, histones, and granular proteins released by neutrophils through a specialized form of cell death known as NETosis. While NETs contribute to the containment of pathogens, their excessive or dysregulated production in sepsis is associated with endothelial damage, immunothrombosis, and organ dysfunction. Several NET-associated biomarkers have been identified, including circulating cell-free DNA (cfDNA), histones, MPO-DNA complexes, and neutrophil elastase–DNA complexes, which correlate with the disease severity and prognosis. Therapeutic strategies targeting NETs are currently under investigation. Inhibition of NET formation using PAD4 inhibitors or ROS scavengers has shown protective effects in preclinical models. Conversely, DNase I therapy facilitates the degradation of extracellular DNA, reducing the NET-related cytotoxicity and thrombotic potential. Additionally, heparin and its derivatives have demonstrated the ability to neutralize NET-associated histones and mitigate coagulopathy. Novel approaches include targeting upstream signaling pathways, such as TLR9 and IL-8/CXCR2, offering further therapeutic promise. Full article

A shallow quaternary sedimentary aquifer within the river alluvial deposits of eastern Uzbekistan is increasingly vulnerable to the impacts of climate change and anthropogenic activities. Despite its essential role in supplying water for domestic, agricultural, and industrial purposes, the aquifer system remains poorly understood. This study employed a three-dimensional MODFLOW-based groundwater flow model to assess climate change impacts on water budget components under the SSP5-8.5 scenario for 2020–2099. Model calibration yielded RMSE values between 0.25 and 0.51 m, indicating satisfactory performance. Simulations revealed that lateral inflows from upstream and side-valley alluvial deposits contribute over 84% of total inflow, while direct recharge from precipitation (averaging 120 mm/year, 24.7% of annual rainfall) and riverbed leakage together account for only 11.4%. Recharge occurs predominantly from November to April, with no recharge from June to August. Under future scenarios, winter recharge may increase by up to 22.7%, while summer recharge could decline by up to 100%. Groundwater storage is projected to decrease by 7.3% to 58.3% compared to 2010–2020, indicating the aquifer’s vulnerability to prolonged dry periods. These findings emphasize the urgent need for adaptive water management strategies and long-term monitoring to ensure sustainable groundwater use under changing climate conditions. Full article

To prevent marine biofouling in seawater lift pumps, electrolyzed seawater containing Cu²⁺ needs to be injected into the pumps. This study employs Computational Fluid Dynamics (CFD) to simulate the variation in Cu²⁺ injection concentration required to achieve a Cu²⁺ concentration of 3 ppb within a 10 cm range around the pump under different operating conditions, including the installation of baffles and varying seawater flow rates. The simulation results demonstrate that CFD can accurately predict the distribution of Cu2+ concentration in electrolyzed seawater, with the distribution significantly influenced by seawater flow direction, necessitating reference to upstream data. When the lift pumps are idle, the required Cu²⁺ injection concentration increases with rising seawater flow rates, reaching 41.9 μg/L at the maximum flow rate of 1.9 m/s. During alternating pump operation, the required Cu²⁺ injection concentration also increases with the flow rate, significantly affected by the pump’s operational position: lower concentrations are required when the upstream pump is active compared to the downstream pump. Additionally, installing baffles around the pumps effectively mitigates the impact of seawater flow on Cu²⁺ distribution, significantly reducing the required injection concentration. This study provides theoretical and data-driven insights for optimising marine biofouling prevention in seawater lift pumps. Full article

The red plant phenotype of R1 cotton is a genetic marker produced by light-induced anthocyanin accumulation. GhPAP1D controls this trait. There are two 228 bp tandem repeats upstream of GhPAP1D in R1 cotton. In this study, GUS staining assays in transgenic Arabidopsis thaliana (L.) Heynh. demonstrated that tandem repeats in the GhPAP1D promoter-enhanced transcriptional activity. GhPAP1D is a homolog of A. thaliana AtPAP1. AtPAP1’s expression is regulated by photomorphogenesis-related transcription factors such as AtHY5 and AtBBXs. We identified the homologs of A. thaliana AtHY5, AtBBX21, and AtBBX24 in R1 cotton, designated as GhHY5, GhBBX21, and GhBBX24, respectively. Y1H assays confirmed that GhHY5, GhBBX21, and GhBBX24 each bound to the GhPAP1D promoter. Dual-luciferase reporter assays revealed that GhHY5 weakly activated the promoter activity of GhPAP1D. Heterologous expression assays in A. thaliana indicated that GhBBX21 promoted anthocyanin accumulation, whereas GhBBX24 had the opposite effect. Dual-luciferase assays showed GhBBX21 activated GhPAP1D transcription, while GhBBX24 repressed it. Further study indicated that GhHY5 did not enhance GhBBX21-mediated transcriptional activation of GhPAP1D but alleviates GhBBX24-induced repression. Together, our results demonstrate that GhBBX21 and GhBBX24 antagonistically regulate anthocyanin accumulation in R1 cotton under GhHY5 mediation, providing insights into light-responsive anthocyanin biosynthesis in cotton. Full article

This study provides the first comprehensive characterization of benthic macrofaunal communities in the Loukkos estuary, highlighting their spatial and seasonal variability and the environmental factors shaping their structure. A total of 47 species were identified across 12 site–season combinations, dominated by molluscs (47%), polychaetes (23%), and crustaceans (21%). Species richness varied considerably along the estuarine gradient, ranging from fewer than five species in the upstream sector to up to 30 species downstream. Overall, higher diversity was observed in the downstream areas and during the dry season. Macrofaunal density also exhibited substantial variability, ranging from 95 ind.m⁻² to 14,852 ind.m⁻², with a mean density of 2535 ± 4058 ind.m⁻². Multivariate analyses identified four distinct benthic assemblages structured primarily by spatial factors (ANOSIM R = 0.86, p = 0.002), with negligible seasonal effect (R = −0.03, p = 0.6). Assemblages ranged from marine-influenced communities at the estuary mouth dominated by Cerastoderma edule, through rich and diverse seagrass-associated communities in the lower estuary dominated by Bittium reticulatum, and moderately enriched mid-estuary communities characterized by Scrobicularia plana and Hediste diversicolor, to species-poor upstream communities dominated by the tolerant species H. diversicolor. Canonical analysis showed that salinity and vegetation explain nearly 40% of the variation in benthic assemblages, highlighting the key role of Zostera seagrass beds as structuring habitats. Moreover, upstream anthropogenic pressures alter environmental conditions, reducing benthic diversity and favoring tolerant species. Full article

Idiopathic pulmonary fibrosis (IPF) is characterized by excessive extracellular matrix (ECM) deposition driven by aberrant fibroblast-to-myofibroblast transition (FMT). However, the upstream regulators and downstream effectors of this process remain incompletely understood. Here, we identify acyl-CoA synthetase long-chain family member 4 (ACSL4), a lipid metabolic enzyme, as a critical mediator linking complement component 5a (C5a)/C5a receptor 1 (C5aR1) signaling to FMT via calcium signaling. In bleomycin (BLM)-induced pulmonary fibrosis of C57BL/6JGpt mice, and in C5a-stimulated primary lung fibroblasts, the expression of ACSL4 was markedly upregulated. Pharmacological inhibition of ACSL4 (PRGL493) or C5aR1 (PMX53) attenuated the deposition of ECM and suppressed the expression of fibrotic markers in vivo and in vitro. Mechanistically, the activation of C5a/C5aR1 signaling increased intracellular calcium levels and promoted the expression of ACSL4, while inhibition of calcium signaling (FK506) reversed the upregulation of ACSL4 and FMT-related changes, including the expression of α-smooth muscle actin (αSMA) and the migration of fibroblasts. Notably, inhibition of ACSL4 did not affect the proliferation of fibroblasts, suggesting its specific role in phenotypic transition. These findings demonstrate that ACSL4 functions downstream of C5a/C5aR1-induced calcium signaling to promote FMT and the progression of pulmonary fibrosis. Targeting ACSL4 may therefore offer a novel therapeutic strategy for IPF. Full article

Reliable prediction of tunnel thruster performance under reverse, or off-design, reverse operating direction (ROD) conditions, is crucial for modern vessels that require bidirectional thrust from a single unit—such as yachts and offshore support vessels. Despite the increasing demand for such a capability, there remains limited understanding of the unsteady hydrodynamic behavior and performance implications of ROD operation. This study addresses this gap through a scale-resolving computational fluid dynamics (CFD) investigation of a full-scale, fixed-pitch propeller with a diameter of 0.62, installed in a tunnel geometry representative of yacht-class side thrusters. Using advanced turbulence modeling, we compare the thruster’s performance under both the normal operating direction (NOD) and ROD. The results reveal notable differences: in ROD, the upstream separation zone was more compact and elongated, average thrust increases by approximately 3–4%, and torque and pressure fluctuations rise by 15–30%. These findings demonstrate that a single tunnel thruster can meet bidirectional manoeuvring requirements. However, the significantly elevated unsteady loads during ROD operation offer a plausible explanation for the increased noise and vibration frequently observed in practice. Full article

Doxorubicin-induced cardiotoxicity (DIC) significantly constrains the clinical efficacy of anthracycline chemotherapy, primarily through the induction of ferroptosis, an iron-dependent, regulated cell death driven by oxidative stress and lipid peroxidation. However, the upstream regulators of ferroptosis in DIC remain incompletely defined. Cold-inducible RNA-binding protein (CIRBP) exhibits cardioprotective effects in various pathological contexts, but its precise role in ferroptosis-related cardiotoxicity is unknown. This study investigated whether CIRBP mitigates DIC by modulating the ferroptosis pathway via the SLC7A11 (Solute carrier family 7 member 11)/GPX4 (Glutathione peroxidase 4) axis. We observed marked downregulation of CIRBP in cardiac tissues and cardiomyocytes following doxorubicin exposure. CIRBP knockout significantly exacerbated cardiac dysfunction, mitochondrial damage, oxidative stress, and lipid peroxidation, accompanied by increased mortality rates. Conversely, CIRBP overexpression alleviated these pathological changes. Molecular docking and dynamics simulations, supported by transcriptomic analyses, revealed direct binding of CIRBP to the 3′-UTR of Slc7a11 mRNA, enhancing its stability and promoting translation. Correspondingly, CIRBP deficiency markedly suppressed SLC7A11 and GPX4 expression, impairing cystine uptake, glutathione synthesis, and antioxidant defenses, thus amplifying ferroptosis. These ferroptotic alterations were partially reversed by ferroptosis inhibitor ferrostatin-1 (Fer-1). Collectively, this study identifies CIRBP as a critical regulator of ferroptosis in DIC, elucidating a novel post-transcriptional mechanism involving Slc7a11 mRNA stabilization. These findings offer new insights into ferroptosis regulation and highlight CIRBP as a potential therapeutic target for preventing anthracycline-associated cardiac injury. Full article

Urban agriculture (UA) is emerging as a promising strategy for sustainable food production in response to growing environmental pressures. Indoor vertical farming (IVF), combining Controlled Environment Agriculture (CEA) with Building-Integrated Agriculture (BIA), enables efficient resource use and year-round crop cultivation in urban settings. This study assesses the environmental performance of a prospective IVF system located on a university campus in Portugal, focusing on the integration of photovoltaic (PV) energy as an alternative to the conventional electricity grid (GM). A Life Cycle Assessment (LCA) was conducted using the Environmental Footprint (EF) method and the LANCA model to account for land use and soil-related impacts. The PV-powered system demonstrated lower overall environmental impacts, with notable reductions across most impact categories, but important trade-offs with decreased soil quality. The LANCA results highlighted cultivation and packaging as key contributors to land occupation and transformation, while also revealing trade-offs associated with upstream material demands. By combining EF and LANCA, the study shows that IVF systems that are not soil-based can still impact soil quality indirectly. These findings contribute to a broader understanding of sustainability in urban farming and underscore the importance of multi-dimensional assessment approaches when evaluating emerging agricultural technologies. Full article

Inflammatory biomarkers, including high-sensitivity C-reactive protein (hsCRP), serum amyloid A (SAA), and interleukin-6 (IL-6), have been associated with an increased risk of future cardiovascular events. While they provide valuable prognostic information, these associations do not necessarily imply a direct causal role. The combined prognostic utility of these markers, however, remains insufficiently studied. We analysed 3300 well-characterised participants of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study, all of whom underwent coronary angiography. Participants were stratified based on their serum concentrations of hsCRP, SAA, and IL-6. Associations between biomarker combinations and mortality were assessed using multivariate Cox regression and ROC analysis. Individuals with elevated hsCRP and SAA or IL-6 showed higher prevalence rates of coronary artery disease, heart failure, and adverse metabolic traits. These “both high” groups had lower estimated glomerular filtration rate, higher NT-proBNP, and increased HbA1c. Combined elevations of hsCRP and SAA were significantly associated with higher all-cause and cardiovascular mortality in partially adjusted models. However, these associations weakened after adjusting for IL-6. IL-6 alone demonstrated the highest predictive power (AUC: 0.638) and improved risk discrimination when included in multi-marker models. The co-elevation of hsCRP, SAA, and IL-6 identifies a high-risk phenotype characterised by greater cardiometabolic burden and increased mortality. IL-6 may reflect upstream inflammatory activity and could serve as a therapeutic target. Multi-marker inflammatory profiling holds promise for refining cardiovascular risk prediction and advancing personalised prevention strategies. Full article

ANKRD26-related thrombocytopenia (ANKRD26-RT) is characterized by lifelong mild to moderate thrombocytopenia. Patients suffer from an increased susceptibility to acute or chronic myeloid leukemia, myelodysplastic syndrome, or chronic lymphocytic leukemia. We described here a patient with inherited thrombocytopenia initially misdiagnosed as immune thrombocytopenic purpura. A chromosomal deletion involving the ANKRD26 gene was identified. Gene and protein expression analyses suggest an alternative pathogenic mechanism of altered megakaryopoiesis: the synthesis of a chimeric protein with aberrant expression due to the unregulated action of a promoter from a gene located upstream of ANKRD26. This study highlights the importance of advanced genetic testing and functional analysis of patients’ primary cells in the case of the detection of previously unrecognized structural variants in order to understand pathogenic mechanisms. These investigations provided a definitive diagnosis for the patient and facilitated the development of a tailored clinical management strategy, especially concerning the potential for myeloid transformation. Full article

RNA-seq analysis of the highly differentiated human retinal pigment epithelial (RPE) cell-line ARPE-19, cultured on transwells for ≥4 months, yielded 44,909 genes showing 83.35% alignment with the human reference genome. These included mRNA transcripts of RPE-specific genes and those involved in retinopathies. Monolayers were fed photoreceptor outer segments (POS), designed to be synchronously internalised, mimicking homeostatic RPE activity. Cells were subsequently fixed at 4, 6, 24 and 48 h when POS were previously shown to maximally co-localise with Rab5, Rab7, LAMP/lysosomes and LC3b/autophagic compartments. A comprehensive analysis of differentially expressed genes involved in proteolysis revealed a pattern of gene orchestration consistent with POS breakdown in the autophagy-lysosomal pathway. At 4 h, these included elevated upstream signalling events promoting early stages of cargo transport and endosome maturation compared to RPE without POS exposure. This transcriptional landscape altered from 6 h, transitioning to promoting cargo degradation in autolysosomes by 24–48 h. Longitudinal scrutiny of mRNA transcripts revealed nuanced differences even within linked gene networks. POS exposure also initiated transcriptional upregulation in ubiquitin proteasome and chaperone-mediated systems within 4–6 h, providing evidence of cross-talk with other proteolytic processes. These findings show detailed evidence of transcriptome-level responses to cargo trafficking and processing in RPE cells. Full article

Central nervous system (CNS) insulin signaling is involved in a broad array of cardiometabolic physiology, including glucose and lipid metabolism, feeding, energy expenditure, and blood pressure regulation. A key role for hypothalamic neuroendocrine and autonomic centers in regulating insulin-associated cardiovascular and metabolic physiology has been highlighted. However, it is still unclear which CNS site(s) initiate insulin-dependent neural cascades. While some investigations have suggested that circulating insulin can access hypothalamic regions by crossing the blood-brain barrier, other studies point to a necessity of other brain areas upstream of the hypothalamus to initiate central insulin actions. In this context, accumulating evidence points to a possible involvement of the sensory circumventricular organs (CVOs), unique areas located outside of the blood-brain barrier, in insulin-dependent cardiometabolic homeostasis. Here, the multifaceted roles for the sensory CVOs in cardiovascular and metabolic regulation, with a special emphasis on insulin receptor pathways, are discussed. Full article