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Marginal enamel fractures (MEF) are a common clinical concern in dentistry, particularly in anterior teeth. These fractures occur at the enamel margins and their etiopathogenesis involves a complex interplay of mechanical, chemical, and biological factors. The ongoing research focuses on an overview of MEF to improve the knowledge about this condition. Understanding the multifaceted nature of MEF is crucial for devising effective preventive and therapeutic strategies in contemporary restorative dentistry. Indeed, mechanical stresses, such as occlusal forces and parafunctional habits are primary contributors for MEF. Additionally, it can happen at the enamel-restoration interface due to expansion and contraction of restorative materials. Chemical degradation, including acid erosion and the breakdown of adhesive bonds, further exacerbates the vulnerability of enamel. Biological factors, such as enamel composition and the presence of micro-cracks also play a role in the development of MEF. Clinical management of MEF involves subtractive or additive techniques, repairing or replacing the compromised tooth structure using techniques to ensure the integration with the natural enamel.

Introduction: ctDNA is a useful tool for NGS molecular profiling in advanced NSCLC patients. Its clinical applicability in patients with gene rearrangements is still limited due to a lower detection rate of these types of alterations compared to single SNVs or small indels. To this purpose, we performed a study in two Italian centers to assess the concordance between tissue and plasma samples in the detection of genes fusions (ALK, ROS, RET) and METexon14 mutations in advanced NSCLC patients. Methods: Patients with a histological diagnosis of oncogene addicted (ALK, ROS1, RET positive or METexon14 mutated) advanced NSCLC were enrolled at the time of first line of TKI treatment. Plasma samples were harvested before the start of TKI treatment and NGS analysis on ctDNA samples using the AVENIO ctDNA Expanded kit was performed. The Positive Percent Agreement (PPA) between tissue and plasma was calculated. Results: Fifty-eight rearranged or METexon14 mutated NSCLC patients were included and 57 ctDNA samples were successfully sequenced. An overall PPA of 37% (21/57) was obtained, with a best performance for RET fusion (80%), intermediate for METexon14 skipping mutations (40%) and ALK rearranged (36%) and a worst one for ROS1 rearranged samples (18%). We found TP53, APC and SMAD4 as most prevalent co-mutated genes (21%, 12% and 10% of patients, respectively). Among different factors considered, increased driver detection rate in patients with extra-thoracic metastases (p = 0.0049) was observed. Significantly shorter survival was observed in patients harboring co-occurring KRAS/NRAS mutations in ctDNA. Conclusions: ctDNA testing to detect oncogenic fusions or METexon14 mutations in advanced NSCLC patients is useful, even if type of gene alterations and clinical characteristics could influence the driver detection rate. Liquid biopsy represents a complementary tool to tissue genotyping, however more sensitive approaches for gene fusions and METexon14 detection are needed to implement its strength and reliability.

The Andes region has an exceptional record of high-altitude settlements integrated within widespread regional chains of mobility and exchange. The Sierra de Aconquija (NW Argentina, south-central Andes) is an effective climatic barrier that has afforded an enduring indigenous approach to land use, mobility, and exchange over millennia. Despite this rich history, the Sierra has been largely considered marginal in pre-Columbian regional cultural developments. Today, the expansion of extractive industries threatens the region’s heritage and the sustainable futures of local communities. Innovative, integrative methodologies are needed for landscape characterisation, heritage assessment, and sustainable policy development. Building on earlier work, we undertook the first comprehensive mapping of archaeological features over 3800 sq. km of the Sierra using interpreter-led assessment of commercial and open-access satellite imagery and DSM data, to verify earlier assumptions and to identify previously unnoticed trends in the aggregation, distribution, and connectivity of archaeological features. The mapping identified 6794 features distributed unevenly but with clear tendencies towards maximising topographic, ecologic, and connectivity advantages expressed consistently across the study area. The outcomes confirm the important role the Sierra had in pre-Hispanic times, highlighting the significance of ancient indigenous practices for the sustainability of vulnerable upland landscapes both in the Andes and worldwide.

Mechanical forces control cell behavior, including cancer progression. Cells sense forces through actomyosin to activate YAP. However, the regulators of F-actin dynamics playing relevant roles during mechanostransduction in vitro and in vivo remain poorly characterized. Here we identify the Fascin1 F-actin bundling protein as a factor that sustains YAP activation in response to ECM mechanical cues. This is conserved in the mouse liver, where Fascin1 regulates YAP-dependent phenotypes, and in human cholangiocarcinoma cell lines. Moreover, this is relevant for liver tumorigenesis, because Fascin1 is required in the AKT/NICD cholangiocarcinogenesis model and it is sufficient, together with AKT, to induce cholangiocellular lesions in mice, recapitulating genetic YAP requirements. In support of these findings, Fascin1 expression in human intrahepatic cholangiocarcinomas strongly correlates with poor patient prognosis. We propose that Fascin1 represents a pro-oncogenic mechanism that can be exploited during intrahepatic cholangiocarcinoma development to overcome a mechanical tumor-suppressive environment.

A wide range of platinum(0)-η2-(E)-1,2-ditosylethene complexes bearing isocyanide, phosphine and N-heterocyclic carbene ancillary ligands have been prepared with high yields and selectivity. All the novel products underwent thorough characterization using spectroscopic techniques, including NMR and FT-IR analyses. Additionally, for some compounds, the solid-state structures were elucidated through X-ray diffractometry. The synthesized complexes were successively evaluated for their potential as anticancer agents against two ovarian cancer cell lines (A2780 and A2780cis) and one breast cancer cell line (MDA-MB-231). The majority of the compounds displayed promising cytotoxicity within the micromolar range against A2780 and MDA-MB-231 cells, with IC50 values comparable to or even surpassing those of cisplatin. However, only a subset of compounds was cytotoxic against cisplatin-resistant cancer cells (A2780cis). Furthermore, the assessment of antiproliferative activity on MRC-5 normal cells revealed certain compounds to exhibit in vitro selectivity. Notably, complexes 3d, 6a and 6b showed low cytotoxicity towards normal cells (IC50 > 100 µM) while concurrently displaying potent cytotoxicity against cancer cells.

IntroductionRearranged during transfection (RET) gene rearrangements occur in 1%–2% of non–small cell lung cancer (NSCLC). Because of the results of the study LIBRETTO-001, selpercatinib has been approved as the first-line treatment for patients with RET fusion–positive advanced NSCLC. Selpercatinib demonstrated to be well tolerated. Despite this, gastrointestinal adverse events (AEs) are frequently reported, and no clinical-radiological and endoscopic features and their impact in terms of treatment discontinuations, interruptions, and dose reductions have been described so far.Case reportA 37-year-old never-smoker woman was treated in our institution with selpercatinib for a RET fusion–positive NSCLC. After 9 months of treatment, the patient referred abdominal pain of grade (G) 2, associated with nausea of G2, bilious vomiting of G3, and weight loss of G1. At computed tomography scan, the presence of important bowel wall thickening, free ascitic fluid, mesenteric congestion, and stranding was detected. The patient underwent an anterograde enteroscopy extended to jejunum with detection of lymphocytic duodenitis with sub-mucosal edema. Selpercatinib treatment was temporary interrupted with complete resolution of the symptoms and then re-administered with dose reduction, without relapsed of the gastrointestinal toxicity after 120 days.ConclusionTo our knowledge, this is the first case report of a patient with NSCLC treated with selpercatinib outside a clinical study who developed severe gastrointestinal toxicity characterized by small bowel edema and lymphocytic duodenitis, leading to treatment interruption and dose reduction. The gastrointestinal AE has been described by a radiological, endoscopic, and histopathological point of view. Further investigations are needed to better identify pathological mechanisms of gastrointestinal toxicity for an appropriate AE management.

An original plasma assisted vapor phase route is proposed for the low-temperature fabrication of supported NiO nanostructures on conductive glasses. The sole deposition time variation enables to tailor material properties, modulating, in turn, the system wettability and functional performances in the photodegradation of recalcitrant pollutants. [ABSTRACT FROM AUTHOR]

Aqueous ammonia has been examined as a new weak base for the synthesis of [Au(NHC)Cl] complexes, as well as for the activation of C–H, S–H, and N–H bonds. Its low cost and mild operational conditions (in air and using technical grade solvents) make it an attractive alternative for producing gold-NHC complexes. Synthetic pathways have been investigated in silico, assessing the role of the deprotonation and metalation steps within the reaction mechanisms. [ABSTRACT FROM AUTHOR]

The discovery and optimisation of reaction conditions leading to the reduction of amides, a fundamental large-scale industrial reaction, is achieved using a machine learning (ML) platform and a platinum catalyst. The optimisation leads to the discovery of a new platinum-based catalytic system that displays unexpectedly high performance. The approach enables rapid and high conversions at ppm-level catalyst loadings. [ABSTRACT FROM AUTHOR]

The design and synthesis of low-cost oxygen evolution reaction (OER) photoelectrocatalysts endowed with high activity and durability is of utmost importance for sustainable energy generation via solar-assisted water splitting. In this regard, and in the framework of our recent activities, we have focused on the electrophoretic deposition of graphitic carbon nitride (gCN) specimens containing dispersed NiO nanoaggregates on carbon cloth substrates. In the present study, the attention is devoted to the x-ray photoelectron spectroscopy characterization of a representative gCN–NiO specimen. In particular, we provide an analysis of C 1s, N 1s, O 1s, and Ni 2p regions, discussing in detail the main spectral features. The obtained results, that provide evidence for a direct electronic interplay between the single material components, may serve as a useful comparison for additional research on analogous materials for energy and environmental applications. [ABSTRACT FROM AUTHOR]

Marginal enamel fractures (MEF) are a common clinical concern in dentistry, particularly in anterior teeth. These fractures occur at the enamel margins and their etiopathogenesis involves a complex interplay of mechanical, chemical, and biological factors. The ongoing research focuses on an overview of MEF to improve the knowledge about this condition. Understanding the multifaceted nature of MEF is crucial for devising effective preventive and therapeutic strategies in contemporary restorative dentistry. Indeed, mechanical stresses, such as occlusal forces and parafunctional habits are primary contributors for MEF. Additionally, it can happen at the enamel-restoration interface due to expansion and contraction of restorative materials. Chemical degradation, including acid erosion and the breakdown of adhesive bonds, further exacerbates the vulnerability of enamel. Biological factors, such as enamel composition and the presence of micro-cracks also play a role in the development of MEF. Clinical management of MEF involves subtractive or additive techniques, repairing or replacing the compromised tooth structure using techniques to ensure the integration with the natural enamel. [ABSTRACT FROM AUTHOR]

A new class of palladium–indenyl complexes characterized by the presence of one bulky alkyl isocyanide and one aryl phosphine serving as ancillary ligands has been prepared, presenting high yields and selectivity. All the new products were completely characterized using spectroscopic and spectrometric techniques (NMR, FT-IR, and HRMS), and, for most of them, it was also possible to define their solid-state structures via X-ray diffractometry, revealing that the indenyl fragment always binds to the metal centre with a hapticity intermediate between ƞ3 and ƞ5. A reactivity study carried out using piperidine as a nucleophilic agent proved that the indenyl moiety is the eligible site of attack rather than the isocyanide ligand or the metal centre. All complexes were tested as potential anticancer agents against three ovarian cancer cell lines (A2780, A2780cis, and OVCAR-5) and one breast cancer cell line (MDA-MB-231), displaying comparable activity with respect to cisplatin, which was used as a positive control. Moreover, the similar cytotoxicity observed towards A2780 and A2780cis cells (cisplatin-sensitive and cisplatin-resistant, respectively) suggests that our palladium derivatives presumably act with a mechanism of action different than that of the clinically approved platinum drugs. For comparison, we also synthesized Pd-ƞ3-allyl derivatives, which generally showed a slightly higher activity towards ovarian cancer cells and lower activity towards breast cancer cells with respect to their Pd-indenyl congeners.

An empirical study with different levels of soil pollution and a meta-analysis provide insight into the drivers of plant biomass partitioning under soil pollution stress.

Se dan a conocer los resultados de las investigaciones arqueológicas realizadas en el sitio La Reservada Bajo (Cafayate, Salta) cuyo objetivo consistió en la localización de un contexto cultural de la transición entre los períodos Formativo y Tardío de la secuencia histórica prehispánica. Para ello se realizaron tareas de registro de colecciones locales, prospecciones, recolecciones superficiales, relevamientos planimétricos y excavaciones. La investigación permitió identificar un establecimiento rural con una ocupación fechada a principios del segundo milenio de la E.C. Se reconstruyeron de manera parcial cuatro ollas cerámicas Ordinario Alisado y una tinaja Santa María Bicolor; además, se observó que el cuarzo fue la materia prima más utilizada para la talla y que el conjunto óseo está representado principalmente por camélidos. Finalmente, se discute la transición entre Formativo y Tardío a partir de las vinculaciones iconográficas en los estilos Guachipas Polícromo y Santa María y de la configuración arquitectónica del sitio.

Pocaterra et al. demonstrate that Fascin1 F-actin bundling protein sustains YAP activation in the tumour environment in response to extracellular matrix mechanical cues. This study highlights Fascin1 as a potential clinical target in intrahepatic cholangiocarcinoma development.

In this work, we describe the synthesis of heterobimetallic Fe(II)/Pd(II) complexes bearing different halides and halide‐substituted butadienyl ligands. The synthetic approach involves the preparation of suitable Pd(II)‐butadienyl precursors containing a thioquinoline moiety, followed by the substitution of this relatively labile ligand with dppf (dppf=1,1′‐bis(diphenylphosphino)ferrocene). With the exception of complexes containing at least one iodine atom, all compounds were synthesized in high yields and purity, and thoroughly characterized using spectroscopic and diffractometric methods. The investigation of the antiproliferative activity of the synthesized organometallic complexes against ovarian and breast cancer cell lines revealed that all compounds exhibit noteworthy cytotoxicity, with IC50 values in the micromolar range and generally comparable to those of cisplatin. Interestingly, significant differences of cytotoxicity among the analysed compounds were observed in the case of MRC‐5 normal cells. Of particular interest is the dichloride derivative 3 a, which is essentially inactive towards non‐cancerous cells (IC50>100 μM), thus demonstrating promising in vitro selectivity that we believe warrants further investigation in the future. [ABSTRACT FROM AUTHOR]

The development of low‐cost and high‐efficiency oxygen evolution reaction (OER) photoelectrocatalysts is a key requirement for H2 generation via solar‐assisted water splitting. In this study, we report on an amenable fabrication route to carbon cloth‐supported graphitic carbon nitride (gCN) nanoarchitectures, featuring a modular dispersion of NiO as co‐catalyst. The synergistic interaction between gCN and NiO, along with the tailoring of their size and spatial distribution, yield very attractive OER performances and durability in freshwater splitting, of great significance for practical end‐uses. The potential of gCN electrocatalysts containing ultra‐dispersed, i. e. "quasi‐atomic" NiO, exhibiting a higher activity than the ones containing nickel oxide nanoaggregates, is further highlighted by their activity even in real seawater. This work suggests that efficient OER catalysts can be designed through the construction of optimized interfaces between transition metal oxides and carbon nitride, yielding inexpensive and promising noble metal‐free systems for real‐world applications. [ABSTRACT FROM AUTHOR]

The Andes region has an exceptional record of high-altitude settlements integrated within widespread regional chains of mobility and exchange. The Sierra de Aconquija (NW Argentina, south-central Andes) is an effective climatic barrier that has afforded an enduring indigenous approach to land use, mobility, and exchange over millennia. Despite this rich history, the Sierra has been largely considered marginal in pre-Columbian regional cultural developments. Today, the expansion of extractive industries threatens the region's heritage and the sustainable futures of local communities. Innovative, integrative methodologies are needed for landscape characterisation, heritage assessment, and sustainable policy development. Building on earlier work, we undertook the first comprehensive mapping of archaeological features over 3800 sq. km of the Sierra using interpreter-led assessment of commercial and open-access satellite imagery and DSM data, to verify earlier assumptions and to identify previously unnoticed trends in the aggregation, distribution, and connectivity of archaeological features. The mapping identified 6794 features distributed unevenly but with clear tendencies towards maximising topographic, ecologic, and connectivity advantages expressed consistently across the study area. The outcomes confirm the important role the Sierra had in pre-Hispanic times, highlighting the significance of ancient indigenous practices for the sustainability of vulnerable upland landscapes both in the Andes and worldwide. [ABSTRACT FROM AUTHOR]

Already known molecules which exhibit good electrochemiluminescence (ECL) efficiencies and high photoluminescence quantum yields (PLQY) have been structurally modified in order to increase their performance. The followed strategy is to stiffen the structures to limit the rotational and vibrational freedom degrees and favour radiative decay processes once excited. Molecules under investigation consist of donor‐acceptor systems in which the acceptor fraction is a benzonitrile with an imidazole in para position, while the donor fraction consists of four diphenylamine (NPh2) or 3,6‐di(tert‐butyl)‐9H‐carbazole (t‐BuCz) groups in the remaining positions on the central benzene ring. Therefore, in order to stiffen these systems and restrict the intramolecular rotations (RIR), the imidazole in the para position has been replaced with more extended π‐systems, i. e., benzimidazole and phenanthro[9,10‐d]imidazole. The restriction of the intramolecular rotation can be clearly observed by 1H NMR analysis. We expected to observe an increase in ECL efficiency and PLQY with the rigidity. Surprisingly, we observed a generally opposite trend: molecules with the smallest imidazole fraction showed the best performance in ECL and higher PLQY. Notably, NPh2 derivatives with benzimidazole and phenanthro[9,10‐d]imidazole showed an hypsochromic shift of the emission spectra with concomitant increase of the PLQY as the solvent polarity increases. [ABSTRACT FROM AUTHOR]