Search Results (417)

Background/Objectives: The RTK-RAS signaling cascade is a central axis in colorectal cancer (CRC) pathogenesis, governing cellular proliferation, survival, and therapeutic resistance. Somatic alterations in key pathway genes—including KRAS, NRAS, BRAF, and EGFR—are pivotal to clinical decision-making in precision oncology. However, the integration of these genomic events with clinical and demographic data remains hindered by fragmented resources and a lack of accessible analytical frameworks. To address this challenge, we developed AI-HOPE-RTK-RAS, a domain-specialized conversational artificial intelligence (AI) system designed to enable natural language-based, integrative analysis of RTK-RAS pathway alterations in CRC. Methods: AI-HOPE-RTK-RAS employs a modular architecture combining large language models (LLMs), a natural language-to-code translation engine, and a backend analytics pipeline operating on harmonized multi-dimensional datasets from cBioPortal. Unlike general-purpose AI platforms, this system is purpose-built for real-time exploration of RTK-RAS biology within CRC cohorts. The platform supports mutation frequency profiling, odds ratio testing, survival modeling, and stratified analyses across clinical, genomic, and demographic parameters. Validation included reproduction of known mutation trends and exploratory evaluation of co-alterations, therapy response, and ancestry-specific mutation patterns. Results: AI-HOPE-RTK-RAS enabled rapid, dialogue-driven interrogation of CRC datasets, confirming established patterns and revealing novel associations with translational relevance. Among early-onset CRC (EOCRC) patients, the prevalence of RTK-RAS alterations was significantly lower compared to late-onset disease (67.97% vs. 79.9%; OR = 0.534, p = 0.014), suggesting the involvement of alternative oncogenic drivers. In KRAS-mutant patients receiving Bevacizumab, early-stage disease (Stages I–III) was associated with superior overall survival relative to Stage IV (p = 0.0004). In contrast, BRAF-mutant tumors with microsatellite-stable (MSS) status displayed poorer prognosis despite higher chemotherapy exposure (OR = 7.226, p < 0.001; p = 0.0000). Among EOCRC patients treated with FOLFOX, RTK-RAS alterations were linked to worse outcomes (p = 0.0262). The system also identified ancestry-enriched noncanonical mutations—including CBL, MAPK3, and NF1—with NF1 mutations significantly associated with improved prognosis (p = 1 × 10⁻⁵). Conclusions: AI-HOPE-RTK-RAS exemplifies a new class of conversational AI platforms tailored to precision oncology, enabling integrative, real-time analysis of clinically and biologically complex questions. Its ability to uncover both canonical and ancestry-specific patterns in RTK-RAS dysregulation—especially in EOCRC and populations with disproportionate health burdens—underscores its utility in advancing equitable, personalized cancer care. This work demonstrates the translational potential of domain-optimized AI tools to accelerate biomarker discovery, support therapeutic stratification, and democratize access to multi-omic analysis. Full article

A restriction enzyme PsaI, an isoschizomer of the type II restriction endonuclease HindIII, has been purified to homogeneity from Gram-negative bacilli Pseudomonas anguilliseptica KM9 found in a wastewater treatment plant in Poland. Experimental data revealed that R.PsaI is highly active in the presence of Co²⁺, Mg²⁺, and Zn²⁺ and reached a maximal level of activity between 2.5 and 10 mM while its activity was significantly decreased in the presence of Ca²⁺, Fe²⁺, Mn²⁺, and Ni²⁺. Moreover, we found that the purified R.PsaI did not require NaCl for enzyme activity. Restriction cleavage analysis followed by sequencing confirmed 5′-AAGCTT-3′ as the recognition site. The genes for restriction–modification system PsaI were identified and characterized. Downstream of the psaIM gene, we noticed an ORF that shares extensive similarity with recombinase family protein specifically involved in genome rearrangements. Sequence analysis revealed that the PsaI R-M gene complex showed striking nucleotide sequence similarity (>98%) with the genes of the PanI R-M system from a P. anguilliseptica MatS1 strain identified in a soil sample from Sri Lanka. Full article

This paper explores the concept of evolutionary urban resilience by framing cities as complex, open, and adaptive Social-Ecological-Technological Systems (SETS), shaped by multi-scalar dynamics, systemic uncertainty, and interdependent crises. It challenges the reductionist view of resilience as a fixed capacity or linear sequence of risk management phases, and instead proposes a process-based paradigm rooted in learning, creativity, and the ability to navigate disequilibrium. The framework defines urban resilience as a continuous and iterative transformation process, supported by: (i) a combination of tangible and intangible qualities activated according to problem typology; (ii) cross-domain processes involving infrastructures, flows, governance, networks, and community dynamics; and (iii) the engagement of diverse agents in shared decision-making and coordinated action. These dimensions unfold across three incremental and interdependent scenarios—baseline, critical, and chronic crisis—forming a ladder of resilience that guides communities through escalating challenges. Special emphasis is placed on the role of Information and Communication Technologies (ICTs) as relational and adaptive tools enabling distributed intelligence and inclusive governance. The framework also outlines concrete operational and policy implications for cities aiming to build anticipatory and transformative resilience capacities. Applied to the case of Taranto, the approach offers insights into how structurally fragile communities facing conflicting adaptive trajectories can unlock transformative potential. Ultimately, the paper calls for a shift from government to governance, from control to co-creation, and from reactive adaptation to chaos generativity, recasting urban resilience as an evolving project of collective agency, systemic reconfiguration, and co-production of emergent urban futures. Full article

Energetic complexes with multi-component architectures represent a frontier in contemporary energetic materials research. In this work, we report a novel high-energy complex—bis(5-nitro-3-(dinitromethyl)-1,2,4-triazole)-hexaamminecobalt(III) [[Co(NH₃)₆](HNTD)(NTD)·H₂O]—that is synthesized using the oxygen-rich energetic compound 5-nitro-3-(trinitromethyl)-1,2,4-triazole (HNTF) as a precursor. Compared with metallic H₂NTD salts, [Co(NH₃)₆](HNTD)(NTD)·H₂O exhibits a higher density (ρ = 1.886 g cm⁻³) and unrivaled energy properties (V_d = 8030 m s⁻¹ and P = 29.2 GPa). The formation of a dense hydrogen-bonding network—mediated by ammonium groups in the [Co(NH₃)₆]³⁺ core and nitro groups of HNTD⁻ and NTD²⁻—significantly dampens the mechanical sensitivity (IS = 10 J and FS = 140 N). These combined attributes establish [Co(NH₃)₆](HNTD)(NTD)·H₂O as a promising high-energy-density material (HEDM), offering critical insights for the design of next-generation energetic complexes. Full article

Reactive oxygen species (ROS) are critical signalling molecules, but their overproduction leads to oxidative stress (OS), a common denominator in the pathogenesis of numerous non-communicable diseases (NCDs) and aging. General antioxidant therapies have largely been unsuccessful, highlighting the need for a deeper understanding of ROS amplification mechanisms to develop targeted interventions. This review proposes a unified, self-amplifying “vicious cycle” of inter-organelle crosstalk that drives pathological ROS elevation and cellular damage. We outline a pathway initiated by extracellular stressors that co-activate plasma membrane TRPM2 channels and NADPH oxidase-2. This synergy elevates cytoplasmic Ca²⁺, leading to lysosomal dysfunction and permeabilization, which in turn releases sequestered Zn²⁺. Mitochondrial uptake of this labile Zn²⁺ impairs electron transport chain function, particularly at Complex III, resulting in mitochondrial fragmentation, loss of membrane potential and a burst of mitochondrial ROS (mtROS). These mtROS diffuse to the nucleus, activating PARP-1 and generating ADPR, which further stimulates TRPM2, thereby perpetuating the cycle. This “circular domino effect” integrates signals generated across the plasma membrane (Ca²⁺), lysosomes (Zn²⁺), mitochondria (ROS) and nucleus (ADPR), leading to progressive organelle failure, cellular dysfunction, and ultimately cell death. Understanding and targeting specific nodes within this TRPM2-NOX2-Ca²⁺-Zn²⁺-mtROS-ADPR axis offers novel therapeutic avenues for NCDs by selectively disrupting pathological ROS amplification while preserving essential physiological redox signalling. Full article

In recent years, extensive attention has been paid to advanced oxidation processes (AOPs) with peracetic acid (PAA), a widely used disinfectant, using transition metal ions for the degradation of organic contaminants within water environments. Mn(II) has been widely used as an effective homogeneous transition metal catalyst for oxidant activation, but it has shown poor performances with PAA. Since the stability of manganese species can be enhanced through the addition of ligands, this study systematically investigated a novel AOP for the oxidation of carbamazepine (CBZ) using an Mn(II)/PAA system with several different ligands added. The reactive species were explored through UV-vis spectrometry, scavengers, and probe compounds. The results suggest that Mn(III)–ligand complexes and other high-valent Mn species (Mn(V)) were generated and contributed obviously toward efficient CBZ oxidation, while radicals like CH₃CO₂^• and CH₃CO₃^• were minor contributors. The oxidation efficiency of Mn(II)/PAA/ligands depended highly on ligand species, as ethylene diamine tetraacetic acid (EDTA) and oxalate (SO) could promote the oxidation of CBZ, while pyrophosphate (PPP) showed modest enhancement. The results obtained here might contribute to the removal of residue pharmaceuticals under manganese-rich waters and also shed light on PAA-based AOPs that could help broaden our present knowledge of manganese chemistry for decontamination in water treatment. Full article

This study investigates the hydrothermal synthesis of calcium silicate hydrate (C-S-H) from photovoltaic (PV) waste glass and carbide sludge as a strategy for resource recovery and sustainable chromium removal from wastewater. Waste-derived precursors were co-ground, blended at controlled Ca/Si molar ratios (0.8, 1.0, 1.2), and hydrothermally treated at 180 °C for 96 h to yield C-S-H with tunable morphology and crystallinity. Comprehensive characterization using XRD, FT-IR, SEM-EDX, and UV-Vis spectroscopy revealed that a Ca/Si ratio of 1.0 produced a well-ordered tobermorite/xonotlite structure with a high surface area and fibrous network, which is optimal for adsorption. Batch adsorption experiments showed that this material achieved rapid and efficient Cr(III) removal, exceeding 90% uptake within 9 h through a combination of surface complexation, ion exchange (Ca²⁺/Na⁺ ↔ Cr³⁺), and precipitation of CaCrO₄ phases. Morphological and structural evolution during adsorption was confirmed by SEM, FT-IR, and XRD, while EDX mapping established the progressive incorporation of Cr into the C-S-H matrix. These findings highlight the viability of upcycling industrial waste into advanced C-S-H sorbents for heavy metal remediation. Further work is recommended to address sorbent regeneration, long-term stability, and application to other contaminants, providing a foundation for circular approaches in advanced wastewater treatment. Full article

A nitro-derivative of fenamic acid (4′–nitro–fenamic acid) was synthesized and used as ligand for the synthesis of four Co(II) complexes in the absence or presence of the N,N′-donors 2,2′–bipyridylamine, 1,10–phenanthroline and 2,9–dimethyl–1,10–phenanthroline. The characterization of the resultant complexes was performed with diverse techniques (elemental analysis, molar conductivity measurements, IR and UV-vis spectroscopy, single-crystal X-ray crystallography). The biological evaluation of the compounds encompassed (i) antioxidant activity via hydrogen peroxide (H₂O₂) reduction and free radical scavenging; (ii) antimicrobial screening against two Gram-positive and two Gram-negative bacterial strains; (iii) interactions with calf-thymus (CT) DNA; (iv) cleavage of supercoiled pBR322 plasmid DNA (pDNA), in the dark or under UVA/UVB/visible light irradiation; and (v) binding affinity towards bovine and human serum albumins. The antioxidant activity of the compounds against 2,2′–azinobis–(3–ethylbenzothiazoline–6–sulfonic acid) radicals and H₂O₂ is significant, especially in the case of H₂O₂. The complexes exhibit adequate antimicrobial activity against the strains tested. The complexes interact with CT DNA through intercalation with binding constants reaching a magnitude of 10⁶ M⁻¹. The compounds have a significantly enhanced pDNA-cleavage ability under irradiation, showing promising potential as photodynamic therapeutic agents. All compounds can bind tightly and reversibly to both albumins tested. Full article

A tandem UV–Vis and fluorescence spectroscopy method was developed for the detection of Pd(II) ions in ethanol. The formation of a complex between Pd(II) ions and tropaeolin OO (TR OO) is accompanied by a change in the color of the solution and evolution of the characteristic UV–Vis as well as fluorescence spectra. The optimal detection conditions were achieved at a 3:1 (mL/mL) volume ratio of Pd(II) to TR OO, at 50 °C. UV–Vis spectroscopy enabled the detection of complex formation process over time, while fluorescence spectroscopy allowed a rapid response within 10 min. The limit of detection (LOD) of Pd(II) ions using UV–Vis spectrophotometry was 10 μmol/dm³ at 535 nm. For spectrofluorimetric detection, the LOD was 10 μmol/dm³, with an emission signal observed at 630 nm after 10 min. The kinetics studies showed a stepwise complex formation pathway, supported by DFT calculations. The performance of the method was verified in the presence of interfering metal ions, including Li(I), Na(I), Al(III), Ni(II), Mg(II), Ca(II), Co(II), and Zn(II), confirming its applicability in complex matrices. This approach provides efficient palladium determination in organic solvents, contributing to sustainable practices in metal recycling. Full article

The process of conceptualisation and prototyping of electric energy products is demanding due to the need for a multifaceted approach to product design. This task becomes even more complex during sustainable development, within which supporting techniques are sought. Energy conversion products such as electric motorcycles require special attention due to their impact on energy efficiency, environmental emissions, and operating and production costs. The research gap refers to the lack of a model to aggregate these aspects simultaneously. The objective of the research was to develop a CQ-LCA model (Cost–Quality–Life Cycle Assessment) supporting the creation of alternative product solutions and their evaluation in terms of the following: (i) environmental impact in the life cycle (LCA), (ii) quality, and (iii) production and/or purchase costs. The model was developed in seven main stages and tested for electric motorcycles and their ten prototypes, which are examples of modern products that convert electrical energy into mechanical energy. Using the EDAS method, the quality of electric motorcycle prototypes was calculated. Then, by the LCA method according to ISO 14040, the CO₂ emissions were estimated and modelled adequately to quality change. Next, by the parametric model based on the static method and the cost value function, including the nominal least squares method, the cost was estimated adequately to quality and environmental change. The model provided a qualitative and quantitative interpretation of electric motorcycle prototypes (CQ-LCA), allowing for the consideration of product characteristics, such as engine power, charging time, and battery capacity, but also environmental impacts and costs. The originality is the provision of a multi-aspect morphological analysis, after which different scenarios of product solutions. The model can be useful for various commonly used energy-converting products. Full article

The increasing complexity of dendritic cell (DC)-derived exosome (DEX) immunotherapy demands structured monitoring protocols capable of translating molecular activity into actionable clinical outputs. This study proposes a standardized, multistage immunomonitoring framework designed to evaluate immune activation, cytokine polarization, and product integrity in DEX-based therapies. The protocol integrates open access methodologies—flow cytometry, cytometric bead array (CBA), and Western blotting—to assess CD69/CD25 activation, Th1/Th2/Th17 cytokine profiles, and vesicle identity across distinct checkpoints. These outputs are consolidated within the Structured Immunophenotypic Traceability Platform (STIP), which applies logic-based classifications (Type I–III) to support reproducible stratification of immune responses. Functional validation was performed through ex vivo co-culture models, enabling real-time interpretation of immune polarization, cytotoxic potential, and batch consistency. These outputs are supported by previous experimental validations published in Cancers and Biomedicines (2025), where PLPC and DC-derived vesicles demonstrated immunological consistency and a phenotypic stratification capacity. This approach provides a scalable monitoring structure that can support personalized treatment decisions, quality assurance workflows, and integration into regulatory documentation (e.g., CTD Module 5.3) for early-phase, non-pharmacodynamic immunotherapies. This conceptual protocol does not aim to demonstrate therapeutic efficacy but to provide a reproducible documentation framework for real-world immune monitoring and regulatory alignment in vesicle-based immunotherapy. Full article

The transition toward sustainability in the construction industry requires integrated tools that align with circular economy principles. This study introduces the Interactive Stakeholder Journey Map in Construction (ISJMC), an innovative visual and systemic tool that supports waste management and circularity throughout the life cycle of construction assets. Although the sector is economically significant, it remains one of the main contributors to environmental degradation due to high resource consumption and low waste recovery rates. Developed according to EN 15643-3:2012, a European standard that provides a framework for assessing the social sustainability of construction works, focusing on aspects such as accessibility, health, and comfort and grounded in the Design Thinking methodology, ISJMC enables mapping stakeholder interactions, touchpoints, and responsibilities across all life cycle stages, including initiative, design, procurement, construction, use, and end of life. A systematic literature review and collaborative workshops guided the tool’s development and validation. The application in a real case involving a medium-sized Brazilian construction company helped identify significant pain points and opportunities for implementing circular practices. The results demonstrate that ISJMC (i) facilitates a systemic and visual understanding of material and information flows, (ii) promotes transparent mapping of resource value to support better decision-making, and (iii) encourages the identification of circularity opportunities while fostering collaboration among stakeholders. The tool revealed critical challenges related to waste generation and management. It supported co-creating sustainable strategies, including improved material selection, lean construction practices, and stronger supplier engagement. By translating complex standards into accessible visual formats, ISJMC contributes to the academic field, supports practical applications, and offers a foundation for expanding circular approaches in construction projects. Full article

The rising demand for lithium-ion batteries (LIBs), driven by the growing consumption of electronic devices and the expansion of electric vehicles, is leading to a concerning depletion of primary metal resources and a significant accumulation of electronic waste. This urgent challenge highlights the need for sustainable recovery methods to extract valuable metals from spent LIBs, aligning with circular economy principles. In this study, the preparation of spent batteries for the bioleaching process was achieved with minimal manipulation. This included a preliminary discharge to ensure safety in subsequent processes and a brief crushing to facilitate the access of leaching agents to valuable metals. Unlike most studies that grind batteries to obtain powders between 70 and 200 microns, our approach works with particles sized around 5 mm. Additionally, our preparation process avoids any thermal or chemical treatments. This straightforward pre-treatment process marks a significant advancement by reducing the complexity and cost of processing. A systematic study was conducted on various fractions of the large particle sizes, using Fe (III) produced through bio-oxidation by A. ferrooxidans and biogenically obtained H2SO4 from A. thiooxidans. The highest metal extraction rates were achieved using the unsorted fraction, directly obtained from the black mass after the grinding process, without additional particle separation. When treated with bio-oxidized Fe (III), this fraction achieved a 95% recovery of Cu, Ni, and Al within 20 min, and over 90% recovery of Co, Mn, and Li within approximately 30 min. These recovery rates are attributed to the combined reducing power of Al and Cu already present in the black mass and the Fe (II) generated during the oxidation reactions of metallic Cu and Al. These elements actively facilitate the reduction of transition metal oxides into their more soluble, lower-valence states, enhancing the overall metal solubilization process. The extraction was carried out at room temperature in an acidic medium with a pH no lower than 1.5. These results demonstrate significant potential for efficient metal recovery from spent batteries with minimal pre-treatment, minimizing environmental impact. Additionally, the simplified residue preparation process can be easily integrated into existing waste management facilities without the need for additional equipment. Full article

Mn(III)– and Co(III)–salen complexes (Mn-1 and Co-2) have been synthesized by a simple one-pot procedure through oxidation of Mn(II) and Co(II) precursors in air. X-ray structural analysis reveals that both complexes adopt similar coordination modes, including a typical square planar metal/salen coordination sphere, which is further occupied by two axial ligands, i.e., an acetate anion and a water molecule. Despite their structural similarity, they are not isomorphous given their distinct cell parameters. In the solid-state structures, both complexes exist as hydrogen-bonded dimers through hydrogen bonding interactions between the axially coordinating water molecules and outer O₄ cavity from another molecule of the complex. The reductive activity of both complexes has been explored. While the reaction of Mn-1 with potassium triethylborohydride was unsuccessful, leading to a complicated mixture, the use of Co-2 furnished the formation of a novel product (CoK-3) that was isolated as red crystals in reasonable yield. CoK-3 was characterized as a heterometallic dimer involving the coordination of a K⁺ ion within the O₄ cavity of a semi-hydrogenated salen/cobalt complex while the cobalt center has been reduced from Co(III) to Co(II). In addition, an attempt at reducing Co-2 with pinacolborane resulted in the isolation of crystals of Co-4, whose structure was determined as a simple square planar Co^II–salen complex. Finally, three complexes (Mn-1, Co-2 and CoK-3) have been investigated for their cytotoxic activities against two human breast cancer cell lines (MCF-7 and MDA-MB 468) and a normal breast epitheliel cell line (MCF-10A), with cisplatin used as a reference in order to discover potential drug candidates that may compete with cisplatin. The results reveal that Co-2 can be a promising drug candidate, specifically for the MCF-7 cancer cells, with minimal damage to healthy cells. Full article

In the present work, we describe the use of the potentially tridentate ligand pyridine-2-amidoxime (NH₂paoH) in Fe-Co chemistry. The 1:1:3 Fe^III(NO₃)₃·9H₂O/Co^II(ClO₄)₂·6H₂O/NH₂paoH reaction mixture in MeOH gave complex [Co^III₂Fe^III(NH₂pao)₆](ClO₄)₂(NO₃) (1) in ca. 55% yield, the cobalt(II) being oxidized to cobalt(III) under the aerobic conditions. The same complex was isolated using cobalt(II) and iron(II) sources, the oxidation now taking place at both metal sites. The structure of 1 contains two structurally similar, crystallographically independent cations [Co^III₂Fe^III(NH₂pao)₆]³⁺ which are strictly linear by symmetry. The central high-spin Fe^III ion is connected to each of the terminal low-spin Co^III ions through the oximato groups of three 2.1110 (Harris notation) NH₂pao⁻ ligands, in such a way that the six O atoms are bonded to the octahedral Fe^III center ({Fe^IIIO₆} coordination sphere). Each terminal octahedral Co^III ions is bonded to six N atoms (three oximato, three 2-pyridyl) from three NH₂pao⁻ groups ({Co^IIIN₆} coordination sphere). The IR and Raman spectra of the complex are discussed in terms of the coordination mode of the organic ligand, and the non-coordinating nature of the inorganic ClO₄⁻ and NO₃⁻ counterions. The UV/VIS spectrum of the complex in EtOH shows the two spin-allowed d-d transitions of the low-spin 3d⁶ cobalt(III) and a charge-transfer NH₂pao⁻ → Fe^III band. The δ and ΔΕ_Q ⁵⁷Fe-Mössbauer parameter of 1 at 80 K show the presence of an isolated high-spin Fe^III center. Variable-temperature (1.8 K–300 K) and variable-field (0–7 T) magnetic studies confirm the isolated character of Fe^III. A critical discussion of the importance of NH₂paoH and its anionic forms (NH₂pao⁻, NHpao²⁻) in homo- and heterometallic chemistry is also attempted. Full article