Search Results (92)

De-sealing, or depaving, is increasingly adopted to restore soil permeability and support green infrastructure, yet its potential to recover soil functions remains insufficiently understood. This study reports one year of soil monitoring following the de-sealing of a brownfield site in Milan (Italy). It compares the evolution of pedoclimatic parameters in sealed and de-sealed soils and assesses the suitability of recycled aggregates (RAs) from demolition waste as a soil-forming material. Buried sensors continuously recorded pedoclimatic parameters, temperature, water content, and oxygen concentration, while periodic sampling was carried out to analyse soil chemical properties, bacterial community composition, and the quality of percolation water (heavy metal content). De-sealing immediately improved pedoclimatic conditions, enhancing soil aeration, water regulation, and heat exchange capacity. No significant variation was detected in soil chemical properties, apart from pH fluctuations linked to the leaching of alkaline ions from concrete-based RAs. The presence of RAs caused no adverse effects on either soil or percolation water. Bacterial community composition was strongly associated with soil organic carbon, C:N ratio, and soil water content, without showing clear temporal trends. Overall, the study demonstrates that de-sealing rapidly triggers soil functional recovery and that, when properly characterised for composition and contamination risk, RAs pose no evident threat to the surrounding environment. Full article

Colorectal carcinoma (CRC) is characterized by mutations in p53 and the Wnt signaling pathway, and immunotherapy has shown limited efficacy in microsatellite-stable CRC. Here, CEABP1, a binding protein for the CRC biomarker carcinoembryonic antigen (CEA), was designed de novo through the AI-based computational generation methods RFDiffusion/ProteinMPNN and stringent in silico selection, for targeted delivery of purified p53 protein and transcription factor T-cell factor (TCF)/lymphoid enhancer-binding factor (LEF) transcription factor decoy (TFD) DNA into CRC cells. The cell-penetrating peptide (CPP) p28 was employed to deliver the p28-p53-CEABP1 protein, which significantly enhanced p53’s inhibition of CRC cell proliferation and xenograft tumor growth. Codelivery of the p14ARF protein together with p53 prolonged the effective antitumor duration of p53. In addition, the DNA binding domain of Max was fused with CPP and CEABP1 to deliver TCF/LEF TFD DNA, comprising concatenated consensus binding motifs for TCF/LEF and Max, into CRC cells to inhibit Wnt target gene transcription, leading to marked suppression of CRC cell proliferation and xenograft tumor growth. These findings paved the way for the development of precision anticancer therapeutics using designed binding proteins of tumor biomarkers for targeted delivery of tumor suppressor proteins and TFD DNA. Full article

Neoadjuvant therapy has become the standard of care in early-stage triple-negative breast cancer (TNBC), providing both prognostic information and a platform for treatment individualization. The achievement of a pathological complete response (pCR) is strongly associated with excellent long-term outcomes, whereas the presence of residual disease (RD) indicates a markedly increased risk of recurrence. This dual prognostic value has established post-neoadjuvant treatment as a critical arena for risk-adapted strategies. In patients achieving pCR, de-escalation of adjuvant therapy is under active investigation, with several randomized trials assessing whether surveillance may safely replace prolonged immunotherapy. Conversely, the management of patients with RD has become increasingly complex, as clinicians must navigate between established options such as capecitabine, olaparib, and pembrolizumab, while antibody-drug conjugates are likely to emerge as future therapeutic options in this high-risk setting. In parallel, locoregional approaches are evolving, with trials evaluating axillary de-escalation and even the omission of surgery in highly selected cases. Looking forward, the integration of biomarkers such as circulating tumor DNA and tumor-infiltrating lymphocytes may help refine these strategies, paving the way toward truly personalized post-neoadjuvant care in TNBC. Full article

This paper evaluates Urban Heat Island (UHI) mitigation strategies in Florence’s historical centre, characterized by relevant cultural heritage value and significant tourist fluxes but increasingly susceptible to heatwaves. The research work focused on the evaluation of both current microclimate conditions and mitigation solutions for UHI-related issues, using ENVI-met microclimate modelling software as a simulation tool. Different models, featuring a 2 m grid resolution and detailed material properties, were produced to assess outdoor air temperature (Ta), mean radiant temperature (MRT), and Universal Thermal Climate Index (UTCI), chosen as reference parameters for human thermal sensation. Diversified conditions induced by the peculiarities of the urban layout were highlighted, with current Ta up to 32 °C and MRT exceeding 55 °C in paved open areas. Site-specific measures and their expected effectiveness were hence analyzed. De-paving and greening yield modest local cooling (Ta reduction up to −0.25 °C, MRT up to −1.75 °C), while tree installation ensures that MRT decreases by −7.50 °C to −12.00 °C. Most effectively, suspended shading fabrics preventing direct radiation can act on Ta (−0.09 °C to −0.25 °C) and provide substantial MRT reductions (−7.50 °C to −17.00 °C), significantly improving thermal comfort. The findings emphasize the potentialities of site-specific, reversible interventions in historic centres to combine climate adaptation and heritage preservation. Full article

The extraordinary diversity of protein sequences and structures gives rise to a vast protein functional universe with extensive biotechnological potential. Nevertheless, this universe remains largely unexplored, constrained by the limitations of natural evolution and conventional protein engineering. Substantial evidence further indicates that the known natural fold space is approaching saturation, with novel folds rarely emerging. AI-driven de novo protein design is overcoming these constraints by enabling the computational creation of proteins with customized folds and functions. This review systematically surveys the rapidly advancing field of AI-based de novo protein design, reviewing current methodologies and examining how cutting-edge computational frameworks accelerate discovery through three complementary vectors: (1) exploring novel folds and topologies; (2) designing functional sites de novo; (3) exploring sequence–structure–function landscapes. We highlight key applications across therapeutic, catalytic, and synthetic biology and discuss the persistent challenges. By fusing recent progress and the existing limitations, this review outlines how AI is not only accelerating the exploration of the protein functional universe but also fundamentally expanding the possibilities within protein engineering, paving the way for bespoke biomolecules with tailored functionalities. Full article

Laser-induced breakdown spectroscopy (LIBS) has been used to explore the chemistry of three regions of Mars on respective missions by NASA and CNSA, with CNES contributions. All three LIBS instruments use ~100 mm diameter telescopes projecting pulsed infrared laser beams of 10–14 mJ to enable LIBS at 2–10 m distances, eliminating the need to position the rover and instrument directly onto targets. Over 1.3 million LIBS spectra have been used to provide routine compositions for eight major elements and several minor and trace elements on >3000 targets on Mars. Onboard calibration targets common to all three instruments allow careful intercomparison of results. Operating over thirteen years, ChemCam on Curiosity has explored lacustrine sediments and diagenetic features in Gale crater, which was a long-lasting (>1 My) lake during Mars’ Hesperian period. SuperCam on Perseverance is exploring the ultramafic igneous floor, fluvial–deltaic features, and the rim of Jezero crater. MarSCoDe on the Zhurong rover investigated for one year the local blocks, soils, and transverse aeolian ridges of Utopia Planitia. The pioneering work of these three stand-off LIBS instruments paves the way for future space exploration with LIBS, where advantages of light-element (H, C, N, O) quantification can be used on icy regions. Full article

This study presents an algorithm for non-invasive blood pressure (BP) estimation in neonates using photoplethysmography (PPG), suitable for resource-constrained neonatal telecare platforms. Using the Windkessel model, the algorithm processes PPG signals from a MAX 30102 sensor, (Analog Devices (formerly Maxim Integrated), based in San Jose, CA, USA) filtering motion noise and extracting cardiac cycle time and systolic time (ST). These parameters inform a derived blood flow signal, the input for the Windkessel model. Calibration utilizes average parameters based on the newborn’s post-conceptional age, weight, and gestational age. Performance was validated against readings from a standard non-invasive BP cuff at SES Hospital Universitario de Caldas. Two parameter estimation methods were evaluated. The first yielded root mean square errors (RMSEs) of 24.14 mmHg for systolic and 19.13 mmHg for diastolic BP. The second method significantly improved accuracy, achieving RMSEs of 2.31 mmHg and 5.13 mmHg, respectively. The successful adaptation of the Windkessel model to single PPG signals allows for BP calculation alongside other physiological variables within the telecare program. A device analysis was conducted to determine the appropriate device based on computational capacity, availability of programming tools, and ease of integration within an Internet of Things environment. This study paves the way for future research that focuses on parameter variations due to cardiovascular changes in newborns during their first month of life. Full article

Implementing nature-based solutions (NbSs) for wildfire risk management and other hazards has been challenging in emerging economies due to the high costs, the lack of immediate returns on investment, and stringent inclusion criteria set by organizations like the IUCN and domain experts. To address these challenges, this exploratory study proposes a new concept: green/blue initiatives. These initiatives represent intermediate steps, encompassing small-scale, community-driven activities that can evolve into recognized NbSs over time. To explore this concept, experiences related to wildfire prevention in the Biobío region of Chile were analyzed through primary and secondary source reviews. The analysis identified three initiatives qualifying as green/blue initiatives: (1) goat grazing in Santa Juana to reduce fuel loads, (2) a restoration prevention farm model in Florida called Faro de Restauración Mahuidanche and (3) the Conservation Landscape Strategy in Nonguén. They were examined in detail using data collected from site visits and interviews. In contrast to Chile’s prevailing wildfire policies, which focus on costly, large-scale fire suppression efforts, these initiatives emphasize the importance of reframing wildfire as a manageable ecological process. Lastly, the challenges and enabling factors for adopting green/blue initiatives are discussed, highlighting their potential to pave the way for future NbS implementation in central Chile. Full article

Massively parallel or next-generation sequencing (NGS) has enabled the genetic characterization of cancer patients, allowing the identification of somatic and germline variants associated with their diagnosis, tumor classification, and therapy response. Despite its benefits, NGS testing is not yet available in the Chilean public health system, rendering it both costly and time-consuming for patients and clinicians. Using a retrospective cohort of 67 formalin-fixed, paraffin-embedded (FFPE) colorectal cancer (CRC) samples, we aimed to implement the identification, annotation, and prioritization of relevant actionable tumor somatic variants in our laboratory, as part of the public health system. We compared two different library preparation methodologies (amplicon-based and capture-based) and different bioinformatics pipelines for sequencing analysis to assess advantages and disadvantages of each one. We obtained 80.5% concordance between actionable variants detected in our analysis and those obtained in the Cancer Genomics Laboratory from the Universidad de Chile (62 out of 77 variants), a validated laboratory for this methodology. Notably, 98.4% (61 out of 62) of variants detected previously by the validated laboratory were also identified in our analysis. Then, comparing the hybridization capture-based library preparation methodology with the amplicon-based strategy, we found ~94% concordance between identified actionable variants across the 15 shared genes, analyzed by the TumorSec^TM bioinformatics pipeline, developed by the Cancer Genomics Laboratory. Our results demonstrate that it is entirely viable to implement an NGS-based analysis of actionable variant identification and prioritization in cancer samples in our laboratory, being part of the Chilean public health system and paving the way to improve the access to such analyses. Considering the economic realities of most Latin American countries, using a small NGS panel, such as TumorSec^TM, focused on relevant variants of the Chilean and Latin American population is a cost-effective approach to extensive global NGS panels. Furthermore, the incorporation of automated bioinformatics analysis in this streamlined assay holds the potential of facilitating the implementation of precision medicine in this geographic region, which aims to greatly support personalized treatment of cancer patients in Chile. Full article

2-Phenylethanol (2-PE), an aromatic alcohol with a rose-like fragrance, is widely used in the food, pharmaceutical, and high-end cosmetic industries. In this study, a high-yield 2-PE-producing strain was isolated and identified as Saccharomyces cerevisiae based on morphological characterization and taxonomic identification. Fermentation medium components (carbon and nitrogen sources) were optimized through single-factor experiments in shaking flasks, and fermentation medium with 40 g/L glucose, 5 g/L malt extract, 1.75 g/L corn steep liquor, 2.5 g/L yeast extract, 5 g/L malt extract, 1.75 g/L corn steep liquor was considered suitable for 2-PE production. RT-qPCR results indicated that corn steep liquor activates expression of genes related to the shikimate pathway and Ehrlich pathway (pha2, aro4, aro8, and aro9), thereby promoting the synthesis of 2-PE through these pathways. Excess yeast extract inhibited the expression of aro8 and aro9, while enhancing the expression of tdh3 and adh2, thus promoting the de novo synthesis of 2-PE. Furthermore, fermentation in a 5 L bioreactor was applied to investigate the effects of feeding strategies, inoculum proportion, and pH on 2-PE production. With a pH of 5.5 and10% inoculum proportion, the supplementation of the substrate L-Phe led to a 2-PE production of 4.81 g/L after 24 h of fermentation. Finally, in situ product recovery (ISPR) techniques was applied to alleviate 2-PE cytotoxicity, achieving a production of 6.41 g/L. This process offers a promising strategy for producing 2-PE efficiently and naturally, paving the way for further industrial applications in food, pharmaceutical, and cosmetic sectors. Full article

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a rising prevalence, driven by multifactorial genetic and environmental factors. Among the genetic contributors identified, SCN2A, a critical gene encoding the Nav1.2 sodium channel, has been implicated in ASD and other related neurological conditions. This systematic review aims to explore the relationship between SCN2A mutations and ASD phenotypes. Methods: This review systematically analyzed data from studies reporting SCN2A mutations in individuals diagnosed with ASD. The primary focus was on the characterization of mutation types, associated clinical features, and phenotypic variability. Results: The mutations identified were predominantly de novo missense mutations and were associated with a spectrum of neurological and developmental challenges, including seizures, intellectual disability, movement disorders, and repetitive behaviors. A notable finding was the significant phenotypic variability observed across individuals. Gender differences emerged, suggesting a potentially greater impact on females compared to trends typically seen in ASD genetic studies. Specific mutations, such as c.2919+4delT, and mosaicism were identified as novel contributors to the observed heterogeneity. Conclusions: The review highlights the clinical significance of SCN2A mutations in ASD and highlights their relevance in genetic counseling and the development of targeted therapies. Understanding the diverse genotype–phenotype correlations associated with SCN2A can drive progress in personalized medicine, paving the way for precision therapies tailored to individuals with SCN2A-related ASD. Full article

Two innovative dimeric derivatives of indolo[3,2,1-jk]carbazole (ICz), named 7,7′-biindolo[3,2,1-jk]carbazole (ICzDO) and 4,4′-biindolo[3,2,1-jk]carbazole (ICzDM), have been developed. Both dimers consist of two ICz units coupled through distinct ortho and meta positions. In the solution state, ICzDO and ICzDM exhibited photoluminescence (PL) maxima at 379 nm and 391 nm, demonstrating emission in the deep-blue region. These compounds show exceptionally narrow emission spectra, characterized by full width at half maximum (FWHM) of 28 nm for ICzDO and 26 nm for ICzDM. In the film state, ICzDM exhibited a photoluminescence (PL) maximum at 428 nm, whereas ICzDO showed a red-shifted emission at 507 nm with a broad full width at half maximum (FWHM) of 87 nm, indicating significant red-shifted excimer emission characteristics. This is attributed to its aggregation-enhanced excimer emission (AEEE) characteristics. When used as host materials for red phosphorescent OLEDs, both compounds enabled efficient energy transfer. Devices using ICzDM as the host attained highly efficient external quantum efficiency (EQE) values of 13.5%, coupled with remarkable color purity represented by Commission Internationale de l’Éclairage (CIE) coordinates of (0.685, 0.314). These findings emphasize how strategic variations in linking positions of identical chromophores can markedly enhance OLED device performance, paving the way for innovative material designs in next-generation organic semiconductor technologies. Full article

The persistent operational instability of all-inorganic cesium lead halide (CsPbX₃) perovskite nanocrystals (NCs) has hindered their integration into white-light-emitting diodes (WLEDs). This study introduces a transformative approach by engineering a phase transition from CsPbBr₃ NCs to zirconium bromide (ZrBr₄)-stabilized hexagonal nanocomposites (HNs) through a modified hot-injection synthesis. Structural analyses revealed that the ZrBr₄-mediated phase transformation induced a structurally ordered lattice with minimized defects, significantly enhancing charge carrier confinement and radiative recombination efficiency. The resulting HNs achieved an exceptional photoluminescence quantum yield (PLQY) of 92%, prolonged emission lifetimes, and suppressed nonradiative decay, attributed to effective surface passivation. The WLEDs with HNs enabled a breakthrough luminous efficiency of 158 lm/W and a record color rendering index (CRI) of 98, outperforming conventional CsPbX₃-based devices. The WLEDs exhibited robust thermal stability, retaining over 80% of initial emission intensity at 100 °C, and demonstrated exceptional operational stability with negligible PL degradation during 50 h of continuous operation at 100 mA. Commission Internationale de l’Éclairage (CIE) coordinates of (0.35, 0.32) validated pure white-light emission with high chromatic fidelity. This work establishes ZrBr₄-mediated HNs as a paradigm-shifting material platform, addressing critical stability and efficiency challenges in perovskite optoelectronics and paving the way for next-generation, high-performance lighting solutions. Full article

Background: Agitation is a frequent and challenging symptom in schizophrenia and bipolar disorder, characterized by heightened motor activity, emotional distress, and potential aggression. This symptom is most observed during acute episodes, representing a significant burden on patients, caregivers, and healthcare systems. Agitation is a leading cause of emergency department visits and psychiatric hospitalizations, necessitating prompt and effective interventions to ensure safety and mitigate its far-reaching impact. Traditional treatments, including high-potency antipsychotics and benzodiazepines, remain first-line options but are associated with significant drawbacks such as sedation, extrapyramidal symptoms, tolerance, and limited applicability in certain patient populations, especially those with respiratory or cardiac depression and the elderly. Non-pharmacologic strategies like de-escalation techniques and environmental modifications are invaluable but may be impractical in acute care settings, as speed and efficiency are critical in emergent settings. These limitations, including the onset of extrapyramidal symptoms with high-dose antipsychotics and the development of tolerance with benzodiazepines, highlight gaps in care, including the need for faster-acting, safer, and more patient-friendly alternatives that reduce reliance on physical restraints and invasive interventions. Methods: This review explores the evolution of treatments for agitation, focusing on alternative and innovative approaches. To highlight these treatments, an extensive review of the literature was conducted utilizing PubMed, Google Scholar, Embase.com, and other search engines. Results: Key developments include sublingual dexmedetomidine, recently FDA-approved, which offers sedation without respiratory depression and a non-invasive administration route. Similarly, subcutaneous olanzapine provides a more convenient alternative to intramuscular injections, reducing injection-related complications. Other emerging treatments such as gabapentin, pregabalin, and ketamine show promise in addressing agitation in specific contexts, including comorbid conditions and treatment-resistant cases. A comparative analysis of these therapies highlights their mechanisms of action, clinical evidence, and practical challenges. Conclusions: Future directions emphasize intranasal delivery systems, novel pharmacologic agents, and potential roles for cannabinoids in managing agitation. These innovations aim to balance rapid symptom control with improved patient safety and experience. The set back with these emerging techniques is a lack of standardized dosing and protocols. They also face ethical concerns, including the chance of misuse or abuse, as well as regulatory barriers, as they lack FDA approval and their legality changes between states. This review underscores the clinical, practical, and ethical considerations in advancing care for agitated patients, paving the way for more effective and compassionate management strategies in psychiatric settings. Full article

The red palm weevil, Rhynchophorus ferrugineus, is a destructive, invasive pest to a diverse range of palm plantations globally. Commonly used broad-range chemical insecticides for insect control pose high risks to non-target organisms, humans, and the environment. A bio-rational approach of screening natural small-molecule inhibitors that specifically target R. ferrugineus proteins critical to its life processes can pave the way for developing novel bioinsecticides. Digestive enzymes (DEs), which impair feeding on plants (herbivory), are promising targets. We generated de novo transcriptomes, annotated DE-related genes from the R. ferrugineus gut and abdomen, manually annotated the DE gene family from the recently available genome and our transcriptome data, and reported 34 glycosidases, 85 lipases, and 201 proteases. We identified several tandem duplicates and allelic variants from the lipase and protease families, notably, 10 RferLip and 21 RferPro alleles, which emerged primarily through indels and single-site substitution. These alleles may confer enhanced digestive lipolysis and proteolysis. Phylogenetic analyses identified and classified different subfamilies of DEs and revealed close evolutionary relationships with other coleopterans. We assessed select candidate DEs’ activity and the potential for inhibition in silico to better understand the herbivory arsenal. In silico analysis revealed that the selected enzymes exhibited similar ligand-binding affinity to their corresponding substrate, except for protease aminopeptidase N, RferPro40, which exhibited poorer affinity to the inhibitor bestatin. Overall, our study serves as a foundation for further functional analysis and offers a novel target for the development of a novel bio-rational insecticide for R. ferrugineus. Full article