Search Results (267)

Carmustine (BCNU) is a powerful alkylating agent primarily used in the chemotherapeutic treatment of malignant brain tumors. However, its clinical application faces significant constraints due to its lipophilicity, low thermal stability, and rapid degradation in physiological environments. To tackle these challenges, our research aimed at the development and detailed characterization of α-cyclodextrin (α-CD) inclusion complexes (ICs) with BCNU employing three different synthesis techniques: co-grinding, cryomilling, and co-precipitation. The selected synthetic methods displayed variations dependent on the technique used, affecting the efficiency, inclusion ratios, and drug-loading capacities, with co-precipitation achieving the most favorable complexation parameters. Structural elucidation through ¹H NMR chemical shifts analysis indicated that only partial inclusion of BCNU occurred within α-CD in ICs produced via co-grinding, while cryomilling and co-precipitation allowed for complete inclusion. Multimodal spectroscopic analyses (FT-IR, UV-Vis, ¹³C CP MAS NMR, and ESI-MS) further substantiated the effective encapsulation of BCNU within α-CD, and systematic solubility assessments via Job’s continuous variation and the Benesi-Hildebrand method revealed a 1:1 host-guest stoichiometry. The ICs obtained were evaluated for BCNU release in vitro at pH levels of 4, 5, 6.5, and 7.4. The mechanism of BCNU drug release was determined to be Fickian diffusion, with the highest cumulative release noted in the acidic microenvironment. These findings collectively validate the effectiveness of α-CD as a functional excipient for the modulation of BCNU’s physicochemical properties through non-covalent complexation. This strategy shows potential for increasing the stability and solubility of BCNU, which may enhance its therapeutic effectiveness in the treatment of brain tumors. Full article

Plastic pollution from polyethylene-based materials is a critical environmental concern due to their high persistence. Here, we report the first proof-of-concept application of a multitechnique analytical framework for quantifying linear low-density polyethylene (LLDPE) in Tenebrio molitor frass. Artificially enriched frass–LLDPE mixtures were analyzed using thermogravimetric analysis (TGA), TGA coupled with Fourier-Transform Infrared Spectroscopy (FTIR) and Mass Spectrometry (MS), TGA under inert atmosphere, and solid-state ¹³C nuclear magnetic resonance spectroscopy with Cross-Polarization and Magic Angle Spinning (CP-MAS NMR) ¹³C CP-MAS NMR combined with interval Partial Least Squares (iPLS) modeling. Thermal methods provided insight into decomposition pathways but showed reduced specificity at <1% w/w due to matrix interference. CP-MAS NMR offered matrix-independent quantification, with characteristic signals in the 10–45 ppm region and a calculated LOD and LOQ of 0.173% and 0.525% w/w, respectively. The LOQ lies within the reported ingestion range for T. molitor (0.8–3.2% w/w in frass), confirming biological relevance. This validated workflow establishes CP-MAS NMR as the most robust tool for quantifying polyethylene residues in complex matrices and provides a foundation for in vivo biodegradation studies and environmental monitoring. Full article

Rett syndrome (RTT) and MECP2 duplication syndrome, a subtype of autism spectrum disorder (ASD), are neurodevelopmental disorders caused by MeCP2 loss and gain of function, respectively. While MeCP2 is known to regulate transcription through its interaction with methylated DNA and chromatin-associated factors such as topoisomerase IIβ (TOP2β), the downstream transcriptional consequences of MeCP2 dosage imbalance remain partially characterized. Here, we present a transcriptome-centered analysis of mouse primary cortical neurons subjected to MeCP2 knockdown (KD) or overexpression (OE), which model RTT and ASD-like conditions in parallel. Using a robust computational pipeline integrating generalized linear models with quasi-likelihood F-tests and Magnitude–Altitude Scoring (GLMQL-MAS), we identified differentially expressed genes (DEGs) in KD and OE relative to wild-type (WT) neurons. This study represents a computational analysis of secondary transcriptomic data aimed at nominating candidate genes for future experimental validation. Gene Ontology enrichment revealed both shared and condition-specific biological processes, with KD uniquely affecting neurodevelopmental and stress-response pathways, and OE perturbing extracellular matrix, calcium signaling, and neuroinflammatory processes. To prioritize robust and disease-relevant targets, we applied Cross-MAS and further filtered DEGs by correlation with MeCP2 expression and regulation directional consistency. This yielded 16 high-confidence dosage-sensitive genes that were capable of classifying WT, KD, and OE samples with 100% accuracy using PCA and logistic regression. Among these, RTT-associated candidates such as Plcb1, Gpr161, Mknk2, Rgcc, and Abhd6 were linked to disrupted synaptic signaling and neurogenesis, while ASD-associated genes, including Aim2, Mcm6, Pcdhb9, and Cbs, implicated neuroinflammation and metabolic stress. These findings establish a compact and mechanistically informative set of MeCP2-responsive genes, which enhance our understanding of transcriptional dysregulation in RTT and ASD and nominate molecular markers for future functional validation and therapeutic exploration. Full article

Background: Children with diplegic Cerebral Palsy often exhibit upper-limb (UL) motor impairments compounded by deficits in visuospatial, sensory, and executive functions. Despite this, research has primarily focused on lower-limb rehabilitation, leaving the treatment of UL function in diplegic Cerebral Palsy underexplored. Action Observation Therapy (AOT), based on Mirror Neuron System activation, has shown promise in promoting motor recovery, but evidence specific to this population is limited. This exploratory randomized controlled trial (RCT) aims to assess the feasibility and effectiveness of a home-based AOT program—ACT ON DIP—for improving upper-limb function in children and adolescents with diplegic Cerebral Palsy. Methods: Fifty-four participants with spastic diplegic Cerebral Palsy (MACS and GMFCS levels I–III, aged 5–16 years) will be randomly assigned to an experimental group (receiving an 8-week home-based AOT program) or a control group (receiving standard care). The ACT ON DIP system includes an ad hoc software, kits of objects for daily tasks, and wearable sensors. The system allows for delivering structured uni- and bimanual AOT activities tailored to the child’s profile. Primary outcome is the Both Hands Assessment (BoHA); secondary outcomes include motor (MA-2, BBT, ABILHAND), neuropsychological (NEPSY-II, Corsi Test, BRIEF), and participation measures (COPM, PEM-CY, CP-QOL). A subgroup will undergo fMRI to explore neural correlates of training-related changes. Results: Feasibility, compliance, and user experience with the home-based system will be assessed. This study will evaluate short-, medium-, and long-term changes in UL performance and related neuropsychological functions. Conclusions: ACT ON DIP represents a novel, personalized, and accessible tele-rehabilitation intervention for children with diplegic Cerebral Palsy. If effective, it could expand treatment opportunities for UL rehabilitation in this population and support broader implementation of home-based AOT. Full article

Two new long-chain N-alkyl imidazole derivatives, 2-(1-octadecyl-imidazol-2-yl)pyridine and 2-(furan-2-yl)-1-(octadecane-1-yl)-1H-imidazole, were synthesized via the Radziszewski reaction followed by N-alkylation. This is the first report of furan-imidazole obtained by this route using furfuraldehyde as a renewable biomass-derived precursor. FTIR, 1D/2D solution NMR, and HRMS confirmed the structural elucidation, while XRD and solid-state ¹³C CPMAS NMR corroborated the crystal structures of the precursors. Notably, previously misassigned ¹H and ¹³C chemical shifts reported in the literature for pyridine and furan-imidazole precursors were corrected. Furthermore, ¹³C CPMAS NMR spectra of those precursors are reported here for the first time. These findings expand the scope of the Radziszewski reaction and provide new insights into the structural characterization of imidazole-based systems. Full article

The growing demand for sustainable biorefinery approaches calls for efficient, environmentally benign strategies to valorize agricultural residues and ensure their complete utilization. This study explores the combination of deep eutectic solvents (DESs) and microwave heating technology as a greener process for the selective fractionation of agri-food waste residues in a zero-waste perspective. Within this framework, five representative biomasses were thoroughly investigated, namely brewer’s spent grain, raw and parboiled rice husks, rapeseed cakes, and hemp hurds. DES formulation was selected for its ability to solubilize and separate lignocellulosic components, enabling the recovery of a polysaccharide-rich fraction, lignin, and bioactive compounds. DES extraction was performed using both microwave heating and conventional batch heating, enabling a direct comparison of the two methods, the optimization of a more sustainable fractionation process, and the maximization of yields while preserving the functional integrity of the recovered fractions. A comprehensive characterization of the separated fractions was carried out, revealing that the two fractionation methods do not yield significant differences in the composition of the primary components. Moreover, a ¹³C CP-MAS NMR analysis of the recovered lignins demonstrates how this analytical technique is a real fingerprint for the biomass source. The results demonstrate the great potential of microwave DES-mediated fractionation as a mild, tunable, and sustainable alternative to conventional methods, aligning with green chemistry principles and opening new approaches for the full valorization of waste byproducts Full article

Silver is a promising electrocatalyst for electrochemical CO₂ reduction reaction owing to its high selectivity and efficiency for CO production. However, it still faces a fundamental trade-off between reaction activity and stability. Here, we developed a three-dimensional coral-like porous silver (CP-Ag) catalyst through seed-assisted nanoparticle attachment synthesis, which creates a unique architecture featuring interconnected pores and stable grain boundaries (GBs) between constituent Ag nanoparticles (Ag NPs). Compared to normal Ag NPs, CP-Ag demonstrates superior catalytic performance, maintaining >90% Faradaic efficiency (FE) for CO across a wide potential range (−0.6 to −1.0 V vs. RHE) while achieving 2-times higher current density. Importantly, CP-Ag demonstrated an impressive long-term stability by sustaining nearly 90% FE for CO approximately 40 h at a current density of −50 mA cm⁻² in a flow cell. The enhanced catalytic performance arises from three factors: (1) the three-dimensional coral-like morphology increases accessible active sites and promotes charge transfer efficiency; (2) stable GBs between interconnected nanoparticles increase reaction activity; (3) more moderate binding on Ag (100) preferentially promotes *CO intermediate formation. Our findings highlight the importance of simultaneously engineering both morphological and crystallographic features to optimize silver catalysts for CO₂ conversion. Full article

Leaf litter conservation practices in forests can contribute to increasing CO₂ storage in natural soils as organic matter; however, this process depends on the type of vegetation cover. This study, using different approaches, aimed to assess this process starting from the characteristics of three different types of litters and topsoil (0–5 cm depth) originating from chestnut, beech, and pine in various forest locations within the territory of Edolo (Camonica Valley, Central Italian Alps). Both labile (DOM) and recalcitrant (ROM) organic matter fractions were considered. Microbial degradation activity was strongly influenced by DOM (DOM vs. Respiration mg CO₂ g⁻¹ dry matter: r = 0.96), and NMR spectroscopy showed that aromatic C and polymethylene C in long-chain aliphatic structures (e.g., lipids, cutin) became more evident from litters to topsoils due to a concentration effect. Finally, chemometric elaboration of quantitative and qualitative data identified two principal component (PC) profiles, explaining 88% of the total variance, in which litter and the topsoil samples were spatially separated, indicating that significant changes occurred during the decomposition process. An Evolution Index (EI) calculated highlighted greater changes for chestnut (0.90) followed by pine (0.60) and beech (0.48), in agreement with chemical (degradation rates of 14.21%, 49.11%, and 48% for beech, chestnut, and pine litter, respectively) and spectroscopic data. Beech litter appears to be more efficient at conserving organic carbon. These findings underscore the importance of understanding litter characteristics for forest management, suggesting which species are most effective in promoting soil carbon storage. Full article

The degradation of modern and ancient permafrost-affected soils and organic-rich sediments and the release of relict soil organic matter from the frozen state are critical for understanding the global carbon cycle in a changing climate. The molecular structure of humic acids isolated from modern Cryosols and paleosoils from the Ice Complex deposits in the Batagay megaslump area was investigated. The elemental composition analysis was performed using a CHN analyzer, and molecular composition analysis was determined by CP/MAS ¹³C-NMR spectroscopy. Analysis of the molecular structure of humic acids showed that MIS 5e paleosoils are characterized by a relatively high content of aliphatic structural fragments (C,H-AL—29–36%) and a low content of aromatic structural fragments (AR/AL—0.49–0.43), which reveals low humification rates in this time period. The composition of humic acids from MIS 7 paleosoils shows a relatively high content of aromatic structural fragments compared to modern soils (AR/AL—0.47) and MIS 5e deposits (AR/AL—0.67–0.54), indicating a longer humification process in heterogenic conditions (warm and cold periods). The results indicate that the molecular structure of humic acids is a dynamic parameter of the environment that reflects the local conditions of pedogenesis and organic matter formation. Permafrost thawing leads to the release of organic matter (including matter that is relatively weakly resistant to biodegradation where aliphatic structural fragments dominate the composition of humic acids) that may strengthen the emission of climate-active gases into the atmosphere and boost climate change. Full article

In this study, supramolecular inclusion complexes composed of komecosanol (Ko), a lipophilic compound derived from rice bran, and α-cyclodextrin (αCD) were prepared using a solvent-free three-dimensional (3D) ball milling method. Their physicochemical properties were examined using various techniques. Powder X-ray diffraction analysis of the ground mixture at a Ko/αCD ratio of 1/8 revealed the disappearance of diffraction peaks characteristic of Ko and the emergence of new peaks, indicating the formation of a distinct crystalline phase. Moreover, differential scanning calorimetry analysis showed the disappearance of the endothermic peaks corresponding to Ko, indicating molecular-level interactions with αCD. Near-infrared spectroscopy results suggested the formation of hydrogen bonds between the C–H groups of Ko and the O–H groups of αCD. Solid-state ¹³C CP/MAS NMR and T₁ relaxation time measurements indicated the formation of a pseudopolyrotaxane structure, while scanning electron microscopy images confirmed distinct morphological changes consistent with complex formation. These findings demonstrate that 3D ball milling facilitates the formation of Ko/αCD inclusion complexes with a supramolecular architecture, providing a novel approach to improve the formulation and bioavailability of poorly water-soluble lipophilic compounds. Full article

This study aims to evaluate eco-innovative solutions in the fertilizer industry that allow for waste valorization in the context of a resource-efficient circular economy. A comprehensive reuse strategy was developed for low-rank peat and post-cultivation horticultural mineral wool, involving the extraction of valuable humic substances from peat and residual nutrients from used mineral wool, followed by the use of both post-extraction residues to produce organic–mineral substrates. The resulting products/semifinished products were characterized in terms of their composition and properties, which met the requirements necessary to obtain the admission of this type of product to the market in accordance with the Regulation of the Minister for Agriculture and Rural Development of 18 June 2008 on the implementation of certain provisions of the Act on fertilizers and fertilization (Journal of Laws No 119, item 765). Elemental analysis, FTIR spectroscopy, and solid-state CP-MAS ¹³C NMR spectroscopy suggest that post-extraction peat has a relatively condensed structure with a high C content (47.4%) and a reduced O/C atomic ratio and is rich in alkyl-like matter (63.2%) but devoid of some functional groups in favor of extracted fulvic acids. Therefore, it remains a valuable organic biowaste, which, in combination with post-extraction waste mineral wool in a ratio of 60:40 and possibly the addition of mineral nutrients, allows us to obtain a completely new substrate with a bulk density of 264 g/m³, a salinity of 7.8 g/dm³ and a pH of 5.3, with an appropriate content of heavy metals and with no impurities, meeting the requirements of this type of product. A liquid fertilizer based on an extract containing previously recovered nutrients also meets the criteria in terms of quality and content of impurities and can potentially be used as a fertilizing product suitable for agricultural crops. This study demonstrates a feasible pathway for transforming specific waste streams into valuable agricultural inputs, contributing to environmental protection and sustainable production. The production of a new liquid fertilizer using nutrients recovered from post-cultivation mineral wool and the preparation of an organic–mineral substrate using post-extraction solid residue is a rational strategy for recycling hard-to-biodegrade end-of-life products. Full article

Background: Aquatic therapy (AT), immersion in hot water, and supported standing are frequently used to manage spasticity, contractures, and joint retractions in children with cerebral palsy (CP). Recently, the use of exoskeletons has been offering a new treatment option for severe CP. This study aimed to compare the post-immediate effects of four treatments on spasticity, range of motion, and the heart rate of children with severe CP. Methods: Three children with spastic CP (levels IV and V GMFCS) received a single 30-min session in consecutive weeks of robot-assisted gait training (RAGT), AT, supported standing, and immersion in hot water. Post-immediate assessments included knee flexor spasticity (modified Ashworth scale, MAS, and modified Tardieu scale, MTS); knee range of motion (ROM, in degrees (°)); and heart rate (HR). Results: AT and supported standing induced greater reductions in spasticity based on MAS scores. RAGT demonstrated superior spasticity reduction using MTS and yielded the greatest improvement in popliteal angle (mean increase: 27°). AT and RAGT induced a 14 beats-per-minute change in HR, indicating moderate cardiovascular engagement. Conclusions: RAGT appears particularly effective in improving spasticity and ROM in children with severe CP. Nonetheless, conventional treatments still offer an effective option when addressing spasticity. Full article

This study evaluated birch and oak ash extracts as alternative extractants for isolating humic substances (HSs) from peat and lignite. The effects of ultrasound intensity, extraction time, and temperature were optimized using a Box–Behnken design and validated statistically. The highest HSs yields were obtained from peat with oak ash extract (pH 13.18), compared to birch ash extract (pH 12.09). Optimal process parameters varied by variant, falling within 309–391 mW∙cm⁻², 116–142 min, and 67–79 °C. HSs extracted under optimal conditions were fractionated into humic acids (HAs) and fulvic acids (FAs), and then analyzed by elemental analysis, Fourier Transform Infrared Spectroscopy (FTIR), and Cross-Polarization Magic Angle Spinning Carbon-13 Nuclear Magnetic Resonance Spectroscopy (CP/MAS ¹³C NMR). The main differences in HSs quality were influenced by raw material and fraction type. However, the use of birch ash extract consistently resulted in a higher proportion of carboxylic structures across all fractions. Overall, wood ash extract, especially from oak, offers a sustainable and effective alternative to conventional extractants, particularly for HSs isolation from lignite. Notably, HSs yield from lignite with oak ash extract (29.13%) was only slightly lower than that achieved with 0.5 M NaOH (31.02%), highlighting its practical potential in environmentally friendly extraction technologies. Full article

Background/Objectives: Spasticity in children with cerebral palsy (CP) can impair motor-related functions. The objective of this exploratory, prospective study was to examine if transcutaneous electrical nerve stimulation (TENS) in a whole-body suit leads to changes in spasticity and other related effects. Methods: Thirty-one children with CP GMFCS III–V, with a median age of 11.0 years (age range of 7–17 years), were consecutively included, and they used the suit with TENS for 24 weeks. The primary outcome was spasticity measured using the Modified Ashworth Scale (MAS). Functional motor-related tasks were evaluated by the Goal Attainment Scale (SMART GAS). The Modified Tardieu Scale (MTS), passive Range of Motion (pROM), GMFM-66, and Posture and Postural Ability Scale (PPAS) assessments were performed. Results: Seventeen subjects (17/31) completed the 24 weeks. Dropout was due to difficulty in donning the suit. The level of overall spasticity, most pronounced in the proximal arms and legs, was reduced according to the MAS, but not the MTS or pROM. Subject-relevant motor-related goals improved significantly in standing/walking and hand/arm function. Changes in the GMFM-66 and PPAS were not significant. Conclusions: Although there were statistically significant but underpowered changes in the MAS after 24 weeks, there were no clinically relevant effects. Exploratorily, we found observer-reliant motor-related functional improvements, which, however, we were unable to detect when trying to quantify them. Donning the suit led to dropout throughout the study. Caregivers need to allocate time, mental capacity and have the physical skill set for donning the suit for long-term use. Full article

Overuse of antibiotics is a concern in ‘culture-negative sepsis’ but it is unclear whether this is due to infection with viruses, fungi or other microbes that are not easily cultured, or whether it results from inflammatory processes. In a prospective study, we enrolled 50 preterm neonates with culture-positive sepsis (CP), culture-negative sepsis (CN), and asymptomatic preterm controls (CO). The microbiome of stool, skin, and blood, including bacterial, viral and fungal components and serum cytokine profiles were evaluated. The microbiome alpha or beta diversity did not differ between CN and CO groups. A MaAsLin analysis revealed increased relative abundances of specific bacterial and fungal genera in stool and skin samples in the CN group compared to CO. The virome analysis identified 24 viruses from skin samples, but they were not statistically different among the three groups. The cytokine and chemokine biomarker profiles were elevated in the CP group but were not statistically different between the CN and CO groups. Although the CN group had a longer hospital stay and higher BPD rates than the controls in unadjusted analyses, these differences were not significant after adjusting for gestational age and birth weight. The CN infants demonstrated microbial shifts without systemic immune activation or significantly worse clinical outcomes, supporting the rationale for discontinuing antibiotics in the absence of positive cultures. Full article