Search Results (1,317)

Abrupt maritime-energy disruption can generate system-wide production losses before firms and policymakers can adjust. Existing assessments usually emphasize direct exposure or long-run equilibrium responses, which makes them less suitable for short-run risk assessment in energy-dependent production systems. We develop a threshold-cascade framework that combines dual-track dependence topology, edge-level inventories, smooth operability bands, and a separate price-validation step to identify the blockade intensity at which a localized chokepoint shock becomes systemic production loss. The framework is evaluated against the March 2021 Suez blockage and the 2022 Russia–Ukraine producer-price episode, and then applied to a 2026 Strait of Hormuz stress scenario using the Organisation for Economic Co-operation and Development (OECD) Inter-Country Input-Output (ICIO) tables, 2025 edition, with the 2022 benchmark year. Under the baseline 150-day horizon, terminal loss first reaches 50% at about 32% blockade intensity, with a broader calibrated threshold band of 32–46%. Losses spread beyond the point of origin and become concentrated in East and Southeast Asian manufacturing supply chains and in downstream consumer markets after inventories at connected hubs are depleted. Policy experiments show that single-channel interventions shift the threshold only modestly, whereas an integrated package that relaxes logistics, inventories, and upstream scarcity moves the threshold to about 46% in this calibration. The analysis targets the weeks-to-months interval before substitution, contract renegotiation, and broader market adjustments dominate. Within that interval, the model identifies when buffers fail, how production losses spread, and which intervention packages delay systemic disruption. Full article

We examine cyclic nuclear reactions in the lead–bismuth (Pb–Bi) system near the s-process termination point. We present a numerical investigation of the isotopic evolution and decay heat generation in an extended 60-isotope nuclear reaction network under continuous 30 keV neutron irradiation (${10}^{14}$–${10}^{28}$ n cm⁻² s⁻¹) using the Chebyshev Rational Approximation Method (CRAM). The network accounts for 88 transitions, utilising a hybrid data approach that combines neutron capture cross-sections from EAF-2010 and TALYS with fundamental decay properties from the ENDF/B-VIII.0. Our simulations reveal two distinct evolutionary regimes. At moderate fluxes (${10}^{14}$–${10}^{20}$ n cm⁻² s⁻¹), the system establishes a steady cyclic loop driven by the $\alpha$-decay of ${}^{210}\mathrm{Po}$, successfully reproducing the s-process termination isotopic distribution (${}^{208}\mathrm{Pb}{\gg }^{209}\mathrm{Bi}{>}^{207}\mathrm{Pb}{>}^{206}\mathrm{Pb}$), characteristic of low-metallicity AGB stars. As the flux exceeds ${10}^{22}$ n cm⁻² s⁻¹, the classical balance breaks down, propelling mass flow toward heavier trace isotopes and suggesting a potential transition into the intermediate neutron capture (i-process) regime. Heat density calculations demonstrate that while the energy release of the core cycle plateaus near ${10}^5$ W cm⁻³, the extended chain drives an energy surge to over ${10}^8$ W cm⁻³ at ${10}^{24}$ n cm⁻² s⁻¹ before the system enters an unstable transient state at extreme fluxes. Full article

As representatives of early-flowering herbaceous peony types, certain cultivars known as the ‘Coral’ series are highly prized in the global cut flowers market for their unique dynamic color transitions from orange-red (amber) to creamy yellow during the florescence and senescence periods. Despite their strong growth vigor and high commercial value, these cultivars face critical postharvest preservation challenges, most notably rapid petal abscission and short vase life. Previous studies have confirmed that postharvest quality deterioration of these peony cut flowers, including undesired color fading and accelerated senescence of petals, is closely associated with ethylene and ROS accumulation. To address these development impediments, systematic optimization of the entire industrial chain is essential. Proposed countermeasures include preharvest regulation of environmental conditions and cultivation practices to establish a foundation for quality formation, as well as postharvest strategies such as precise harvest timing, anti-ethylene treatments, and full cold-chain logistics. Meanwhile, simplifying the distribution system and optimizing terminal vase preservation techniques are also crucial to maintain postharvest quality. In the long term, promoting sustainable development of the global cut-flower industry will require breeding new germplasm with low ethylene sensitivity from a global perspective, continuously optimizing agronomic practices to overcome year-round supply constraints, and accelerating the application of intelligent technologies such as the Internet of Things (IoT) in full chain quality management. Full article

Background: Myocardial fibrosis (MF) is a dynamic remodeling process characterized by excessive extracellular matrix (ECM) deposition, fibroblast activation, and dysregulated matrix turnover. Although initially reparative, persistent fibrotic remodeling promotes myocardial stiffening, electrical instability, and progressive cardiac dysfunction across diverse cardiovascular diseases. Circulating biomarkers reflecting collagen synthesis, degradation, proteolytic regulation, and inflammatory activation have emerged as potential tools for assessing fibrotic activity and risk stratification. Methods: This targeted narrative review was based on manually guided searches of PubMed and Scopus, supplemented by citation chaining and inclusion of landmark mechanistic and translational studies. Publications addressing myocardial extracellular matrix remodeling, circulating fibrosis-related biomarkers and imaging-derived fibrosis phenotypes were selected for qualitative synthesis. Results: Myocardial fibrosis reflects interconnected inflammatory, neurohormonal, oxidative, and extracellular matrix remodeling pathways. Among circulating biomarkers, C-terminal propeptide of procollagen type I (PICP) showed the most consistent association with myocardial collagen burden and adverse outcomes, whereas carboxy-terminal telopeptide of type I collagen (CITP), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), galectin-3, osteopontin, soluble suppression of tumorigenicity 2 (sST2), and natriuretic peptides provided more context-dependent signals. Standalone interpretation remains limited by restricted cardiac specificity, renal dysfunction, systemic inflammation, assay heterogeneity, and lack of standardized thresholds. Integration with cardiac magnetic resonance (CMR)-derived late gadolinium enhancement (LGE), T1 mapping, and extracellular volume (ECV) may improve biological and structural phenotyping. Conclusions: Circulating biomarkers capture complementary dimensions of myocardial remodeling but cannot replace structural imaging. We propose an updated, hypothesis-generating biomarker–imaging framework integrating inflammatory activation, collagen turnover, matrix quality, hemodynamic stress, and structural imaging to support phenotypic stratification and future validation of antifibrotic strategies. Full article

Traumatic brain injury (TBI), a major cause of persistent cognitive impairment (CI), increases the long-term risk of developing dementia, including Alzheimer’s disease (AD). To elucidate this association, we systematically reviewed fluid biomarkers linked to post-TBI cognitive outcomes. A comprehensive search of the PubMed, Embase, and Cochrane Library databases was performed. A total of 29 clinical studies were included, reporting on several biomarkers related to neural injury and repair, AD-like pathology, and inflammation. Among these, neurofilament light chain (NfL), ubiquitin C-terminal hydrolase L1, total tau, and glial fibrillary acidic protein (GFAP) were consistently associated with CI and brain atrophy across various TBI severities and stages. Notably, certain biomarkers assessed during the acute phase (within 7 days post-injury), such as brain-derived neurotrophic factor, neuron-specific enolase, and interleukin-1β, showed significant correlations with CI. In contrast, elevated levels of GFAP and NfL measured during the recovery phase (6 months to 8 years post-injury) were significantly associated with TBI-related CI (TBI-CI). The findings also highlighted that axonal injury, glial activation, neuroinflammation, neuronal damage, and degeneration drive TBI-CI, with tau pathology and synaptic dysfunction emerging as potential bridges from TBI to AD. This review underscores the critical temporal dynamics of fluid biomarkers in TBI-CI, revealing that stage-specific biomarker profiles mirror distinct underlying pathophysiological processes. Future longitudinal studies should focus on well-characterized patient subgroups, adopt standardized diagnostic criteria, and integrate fluid biomarkers with neuroimaging and genetic data. Full article

Mitochondrial proteostasis in neurons relies on the coordinated expression, targeting, and import of a predominantly nuclear-encoded proteome to meet high metabolic demands. Here, we identify the RNA-binding protein cold shock domain containing E1 (CSDE1) as a TOM20-associated factor linked to mitochondrial protein-encoding mRNAs in sensory neurons. CSDE1 immunoprecipitation followed by sequencing from naïve dorsal root ganglion tissue revealed association with nuclear-encoded mitochondrial mRNAs enriched for inner membrane/matrix and oxidative phosphorylation pathways. A subset of CSDE1 localized to mitochondria and associated with the outer mitochondrial membrane import receptor TOM20 via its N-terminal region in an RNA-independent manner. In cultured sensory neurons, CSDE1 depletion reduced the mitochondrial-fraction abundance of representative nuclear-encoded electron transport chain mRNAs and decreased the abundance of selected mitochondrial proteins in the mitochondrial fraction. CSDE1 depletion reduced TMRM-positive mitochondrial puncta density along sensory neurites, without significantly increasing MitoSOX-detectable mitochondrial superoxide signals under either basal or oxidative challenge conditions. These findings identify CSDE1 as a TOM20-associated RNA-binding protein linked to mitochondrial protein-encoding transcripts in sensory neurons and support a model in which CSDE1 contributes to mitochondria-associated post-transcriptional regulation. Full article

Tofersen is a gene-targeted therapy for superoxide dismutase 1 (SOD1)-associated amyotrophic lateral sclerosis (ALS), but neurofilament light chain (NfL) may not fully capture the biological response to treatment. We performed a multicentre retrospective longitudinal study including 24 patients with SOD1-ALS treated with intrathecal tofersen at four Italian referral centres between 2022 and 2025. Cerebrospinal fluid (CSF) and serum biomarkers were assessed at baseline, month 3, month 6, and last available administration using single-molecule array assays to quantify NfL, glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCHL–1), and total Tau. NfL decreased after treatment initiation in both CSF and serum, providing the clearest pharmacodynamic signal. In contrast, CSF GFAP increased progressively over follow-up, while CSF total Tau and UCHL–1 rose mainly at later timepoints; serum GFAP, total Tau, and UCHL–1 also showed increases during follow-up. ALS Functional Rating Scale–Revised trajectories were broadly stable, whereas disease progression rate was lower at last follow-up than at baseline. Greater reductions in CSF NfL were observed in pathogenic versus uncertain SOD1 variants, and early serum NfL and UCHL–1 changes were associated with longer-term changes in disease progression. These findings suggest that longitudinal multi-analyte profiling may refine biological response stratification beyond NfL alone in tofersen-treated SOD1-ALS. Full article

Background/Objectives: Clinical application of Doxorubicin (Doxo) is limited by cardiotoxicity, a process strongly associated with an interplay between oxidative stress and inflammatory signaling, particularly Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and Nucleotide oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome engagement. Identifying strategies capable of mitigating these interconnected pathways is of critical importance in cardio-oncology. Simvastatin (SIM) is a promising option since it modulates oxidative stress, inflammation, and cell death through its pleiotropic effects, so this study aimed to evaluate whether SIM attenuates Doxo-induced inflammatory responses. Methods: Human Cardiomyocyte (HCM) cells were pre-treated with SIM (10 µM) for 4 h and then co-exposed to SIM and Doxo (1 µM) for 20 h. Cytofluorimetric analysis was used to evaluate inducible nitric oxide synthase (iNOS), Connexin 43 (Cx43), and Cx43 phosphorylated at Serine 368 (p^S368Cx43) levels. Real-time qPCR was performed to evaluate iNOS gene expression, while Nitric oxide (NO) release was evaluated by spectrophotometric analysis. Interleukin (IL)-1β, IL-18, IL-6, tumor necrosis factor alpha (TNF-α) production, and NLRP3 levels were evaluated by means of ELISA assay. Expression levels of inhibitor of nuclear factor kappa B alpha (IκB-α), Caspase-1, and Gasdermin D (GSDMD) were evaluated by Western Blot analysis. Nuclear translocation of NF-κB was evaluated by immunofluorescence assay. Results: In our experimental model, SIM significantly (p < 0.01) reduced Doxo-induced nitrite release, as well as iNOS gene expression (p < 0.05) and protein levels (p < 0.01). SIM also markedly attenuated Doxo-induced NF-κB signaling, pro-inflammatory cytokines production (TNF-α and IL-6, p < 0.01), and inflammosome-related responses (cleaved caspase-1, IL-1β, N-terminal domain of GSDMD), and NLRP3 expression p < 0.05). Additionally, SIM significantly attenuated the overexpression of Cx43 and its phosphorylated form (p^S368Cx43), which are responsible for impairing intercellular communication and electrical coupling in cardiomyocytes and contribute to arrhythmias and conduction abnormalities characteristic of acute Doxo-induced cardiotoxicity. Conclusions: Overall, these findings demonstrate that SIM exerts a multifaceted cardioprotective effect against Doxo-induced injury, thereby targeting interconnected inflammatory and pro-arrhythmic pathways implicated in Doxo cardiotoxicity. Full article

Background: The management of persistent post-concussive symptoms (PPCS) is limited by the absence of objective biomarkers to guide treatment. We examined the early effects of a mild hyperbaric oxygen protocol on serum biomarkers of neuronal injury (neurofilament light chain, NfL), astrogliosis (glial fibrillary acidic protein, GFAP), acute neuronal injury (ubiquitin C-terminal hydrolase L1, UCH-L1), and axonal stability (total tau) in patients with PPCS. Methods: In this single-center, randomized, placebo-controlled trial, we enrolled adults with PPCS lasting from 3 months to 5 years after mild traumatic brain injury. Participants received 40 sessions of either active treatment (≥99% O₂ at 1.5 atmospheres absolute, ATA) or a true chamber placebo (21% O₂ with simulated pressure changes). Serum samples were collected at baseline and 13 weeks after treatment. The primary outcome was the difference between groups in serum NfL levels. Analysis was performed on an intention-to-treat basis using a two-way ANOVA with Šídák’s multiple comparison test. Findings: Of 84 individuals assessed, 20 were randomized (Placebo, n = 9; Intervention, n = 11). Eight from each group received their respective interventions. At 13 weeks, one participant from each group was lost to follow-up, leaving seven per group for analysis. We found no significant differences in serum levels of GFAP, NfL, total tau, or UCH-L1 between the intervention and placebo groups from baseline to 13 weeks. Conclusions: A 40-session mild hyperbaric oxygen protocol at 1.5 ATA did not significantly change serum biomarkers of neuronal injury, astrogliosis, or acute neuronal damage at 13 weeks post-treatment in individuals with PPCS. This early-phase analysis, at the highest point of participant retention, provides no evidence of a treatment effect on these pathophysiological markers. Full article

N-Methyl-D-aspartate (NMDA) receptors are ligand- and voltage-gated ion channels essential for synaptic plasticity, learning, and memory. The GluN2B subunit, highly expressed in the forebrain and spinal cord, is implicated in multiple neurological and psychiatric disorders, making it an attractive target for positron emission tomography (PET) imaging. However, the development of selective GluN2B PET radioligands remains challenging. Here, we describe the design, synthesis, and evaluation of eighteen 3-alkylaryl derivatives of 7-methoxy-2,3,4,5-tetrahydro-1H-benzo[d]azepin-1-ol, including enantiomerically resolved compounds, as candidate PET radioligands. Structure–activity relationship studies show that binding affinity is largely insensitive to electronic and steric variation at the terminal aryl group but strongly dependent on alkyl linker length, with a four-carbon chain providing optimal affinity. Binding affinity does not correlate with calculated lipophilicity, suggesting hydrophobicity is not the primary determinant of receptor interaction. Absolute configuration was established using vibrational circular dichroism and infrared spectroscopy, and docking studies provided insight into enantiomer-specific binding modes. Two ligands, L3 and L6, and their enantiomers exhibited high GluN2B affinity, favorable physicochemical properties, and suitability for carbon-11 labeling. Separate PET imaging studies confirmed strong and specific brain binding of the radiolabeled compounds. These findings establish this scaffold as a promising platform for GluN2B PET ligand development. Full article

This study presents an efficient and environmentally friendly route for synthesizing succinic acid derivatives via palladium-catalyzed oxidative dicarbonylation of ethylene, utilizing oxygen as the terminal oxidant. By systematically optimizing reaction parameters—including catalyst composition, solvent volume, gas ratio, temperature, and additives—the turnover number (TON) for dimethyl succinate was significantly enhanced to 10,325. This strategy not only demonstrates the potential of CO and ethylene as simple and abundant C1 and C2 building blocks but also highlights the viability of oxygen as a sustainable oxidant. The developed process offers a promising pathway toward the cost-effective and scalable production of biodegradable materials such as poly(butylene succinate) (PBS), with important implications for advancing green synthesis and enabling an autonomous supply chain in the biodegradable polymer industry. Full article

The decarbonization of multimodal transport systems requires assessment approaches that simultaneously address environmental impacts and economic performance at dynamic operational conditions. Conventional Life Cycle Assessment (LCA) and Life Cycle Costing (LCC), including Total Cost of Ownership (TCO), are widely used for this purpose; however, they often rely on static assumptions and averaged data, limiting their ability to capture real-world variability. This study proposes an AI-enhanced LCA–LCC/TCO framework for the integrated evaluation of decarbonised multimodal Door-to-Port transport systems. Artificial intelligence is embedded directly into the life cycle inventory and cost inventory stages to generate scenario-specific estimates of energy consumption, greenhouse gas emissions, and operational costs. The framework is demonstrated through a case study of a multimodal Door-to-Port transport chain comprising road pre-haulage, rail line-haul, and port terminal operations. Three scenarios are analysed: conventional, partially decarbonised, and fully decarbonised configurations. The results indicate that partial decarbonization reduces greenhouse gas emissions by more than 60% compared to the baseline while achieving the lowest total cost of ownership. Full decarbonization achieves emission reductions exceeding 95% but is associated with slightly higher costs under current assumptions. Sensitivity analysis verifies the robustness of the relative scenario ranking under different energy prices, carbon pricing, and electricity carbon intensity. The proposed framework provides a structured decision-support framework for logistics operators, port authorities, and policymakers seeking cost-effective pathways to low-emission multimodal transport systems. Full article

The C-terminal binding protein 1 (CTBP1) is a transcriptional corepressor with a major role in nervous system growth and development. There are only 20 published cases with CTBP1 mutations, displaying a phenotype of Hypotonia, Ataxia, Developmental Delay and Tooth enamel defect Syndrome (HADDTS). Histochemical evidence of decreased mitochondrial respiratory chain activity has been previously reported, but comprehensive data on the metabolic phenotype assessed by various cellular respiration parameters are still missing. We present a 10-year-old female with typical HADDTS features, harboring the most reported de novo heterozygous CTBP1 mutation c.991C>T. To elucidate her metabolic phenotype, we quantified mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) utilizing an analyzer for assessing mitochondrial function (Seahorse XFp). Real-time metabolic assays revealed profound mitochondrial dysfunction with significantly attenuated maximal respiration and spare respiratory capacity compared to neurotypical controls. Following mitochondria-targeted nutritional support for one-year measurable bioenergetic improvements and reduced number of respiratory infections were registered. However, neurological recovery and new skill acquisition were not observed. We present a novel case of CTBP1-related neurodevelopmental disorder and demonstrate, for the first time, the application of non-invasive, real-time mitochondrial functional assessment in this setting, providing additional evidence for mitochondrial dysfunction in HADDTS. Full article

Dry ports are becoming increasingly important elements of port–hinterland transport systems, particularly as maritime gateways face rising congestion, infrastructure pressure, and coordination challenges within global supply chains. As international trade expands and logistics networks grow more complex, inland terminals are progressively evolving into integrated intermodal platforms that support more efficient freight distribution between seaports and their hinterlands. This study presents a PRISMA-based systematic review of research on dry port–seaport systems covering the period 1980–2025. Following a structured screening and selection procedure, peer-reviewed publications were identified and analyzed to examine conceptual developments, thematic orientations, geographical scope, and decision-making perspectives within the field. Particular attention is given to the growing relevance of digital transformation, including artificial intelligence and machine learning, in shaping future dry port operations and network design. By synthesizing existing contributions and identifying research gaps, this review provides a consolidated understanding of the evolution of dry port research and outlines key directions for advancing sustainable, resilient, and data-driven port–hinterland systems. Full article

This study investigates the Container Consolidation Problem (CCP), a critical operational challenge in container terminals where containers with specific attributes must be relocated during yard crane idle periods. The primary objective is to maximize yard space availability for incoming vessels by strategically grouping containers, thereby alleviating storage pressure and enhancing throughput. A mixed-integer programming model is formulated to minimize the total handling time, incorporating complex constraints related to crane availability, relocation sequencing, and slot assignment. Due to the combinatorial complexity inherent in large-scale yard operations, a comprehensive optimization framework is proposed. This framework balances computational efficiency with solution quality, offering a robust approach to solve large-scale instances within practical time limits. Computational experiments demonstrate that the proposed methodology consistently yields high-quality solutions, effectively resolving the trade-off between solution speed and optimality. The research provides not only a novel methodological perspective for solving this NP-hard problem but also offers significant practical value. By optimizing crane scheduling, the model directly contributes to reducing operational costs, improving the turnover rate of yard space, and strengthening the overall efficiency of the maritime supply chain. Full article