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Pancreatic ductal adenocarcinoma (PDAC) shows pronounced epithelial and mesenchymal cancer cell populations1-4. Cellular heterogeneity in PDAC is an important feature in disease subtype specification3-5, but how distinct PDAC subpopulations interact, and the molecular mechanisms that underlie PDAC cell fate decisions, are incompletely understood. Here we identify the BMP inhibitor GREM16,7 as a key regulator of cellular heterogeneity in pancreatic cancer in human and mouse. Grem1 inactivation in established PDAC in mice resulted in a direct conversion of epithelial into mesenchymal PDAC cells within days, suggesting that persistent GREM1 activity is required to maintain the epithelial PDAC subpopulations. By contrast, Grem1 overexpression caused an almost complete 'epithelialization' of highly mesenchymal PDAC, indicating that high GREM1 activity is sufficient to revert the mesenchymal fate of PDAC cells. Mechanistically, Grem1 was highly expressed in mesenchymal PDAC cells and inhibited the expression of the epithelial-mesenchymal transition transcription factors Snai1 (also known as Snail) and Snai2 (also known as Slug) in the epithelial cell compartment, therefore restricting epithelial-mesenchymal plasticity. Thus, constant suppression of BMP activity is essential to maintain epithelial PDAC cells, indicating that the maintenance of the cellular heterogeneity of pancreatic cancer requires continuous paracrine signalling elicited by a single soluble factor.
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Transição Epitelial-Mesenquimal , Peptídeos e Proteínas de Sinalização Intercelular , Neoplasias Pancreáticas , Animais , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Células Epiteliais/patologia , Transição Epitelial-Mesenquimal/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/deficiência , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Mesoderma/patologia , Camundongos , Neoplasias Pancreáticas/patologia , Fatores de Transcrição da Família SnailRESUMO
Tubular epithelia are a basic building block of organs and a common site of cancer occurrence1-4. During tumorigenesis, transformed cells overproliferate and epithelial architecture is disrupted. However, the biophysical parameters that underlie the adoption of abnormal tumour tissue shapes are unknown. Here we show in the pancreas of mice that the morphology of epithelial tumours is determined by the interplay of cytoskeletal changes in transformed cells and the existing tubular geometry. To analyse the morphological changes in tissue architecture during the initiation of cancer, we developed a three-dimensional whole-organ imaging technique that enables tissue analysis at single-cell resolution. Oncogenic transformation of pancreatic ducts led to two types of neoplastic growth: exophytic lesions that expanded outwards from the duct and endophytic lesions that grew inwards to the ductal lumen. Myosin activity was higher apically than basally in wild-type cells, but upon transformation this gradient was lost in both lesion types. Three-dimensional vertex model simulations and a continuum theory of epithelial mechanics, which incorporate the cytoskeletal changes observed in transformed cells, indicated that the diameter of the source epithelium instructs the morphology of growing tumours. Three-dimensional imaging revealed that-consistent with theory predictions-small pancreatic ducts produced exophytic growth, whereas large ducts deformed endophytically. Similar patterns of lesion growth were observed in tubular epithelia of the liver and lung; this finding identifies tension imbalance and tissue curvature as fundamental determinants of epithelial tumorigenesis.
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Fenômenos Biomecânicos , Polaridade Celular , Transformação Celular Neoplásica , Morfogênese , Ductos Pancreáticos/patologia , Neoplasias Pancreáticas/patologia , Animais , Humanos , Camundongos , Organoides/patologia , Estresse MecânicoRESUMO
The association of Helicobacter pylori to several gastric diseases, such as chronic gastritis, peptic ulcer disease, and gastric cancer, and its high prevalence worldwide, raised the necessity to use methods for a proper and fast diagnosis and monitoring the pathogen eradication. Available diagnostic methods can be classified as invasive or non-invasive, and the selection of the best relies on the clinical condition of the patient, as well as on the sensitivity, specificity, and accessibility of the diagnostic test. This review summarises all diagnostic methods currently available, including the invasive methods: endoscopy, histology, culture, and molecular methods, and the rapid urease test (RUT), as well as the non-invasive methods urea breath test (UBT), serological assays, biosensors, and microfluidic devices and the stool antigen test (SAT). Moreover, it lists the diagnostic advantages and limitations, as well as the main advances for each methodology. In the end, research on the development of new diagnostic methods, such as bacteriophage-based H. pylori diagnostic tools, is also discussed.
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Infecções por Helicobacter , Helicobacter pylori , Humanos , Helicobacter pylori/genética , Sensibilidade e Especificidade , Infecções por Helicobacter/diagnóstico , Urease , FezesRESUMO
Helicobacter pylori is the major component of the gastric microbiome of infected individuals and one of the aetiological factors of chronic gastritis, peptic ulcer disease and gastric cancer. The increasing resistance to antibiotics worldwide has made the treatment of H. pylori infection a challenge. As a way to overhaul the efficacy of currently used H. pylori antibiotic-based eradication therapies, alternative treatment strategies are being devised. These include probiotics and prebiotics as adjuvants in H. pylori treatment, antimicrobial peptides as alternatives to antibiotics, photodynamic therapy ingestible devices, microparticles and nanoparticles applied as drug delivery systems, vaccines, natural products, and phage therapy. This review provides an updated synopsis of these emerging H. pylori control strategies and discusses the advantages, hurdles, and challenges associated with their development and implementation. An effective human vaccine would be a major achievement although, until now, projects regarding vaccine development have failed or were discontinued. Numerous natural products have demonstrated anti-H. pylori activity, mostly in vitro, but further clinical studies are needed to fully disclose their role in H. pylori eradication. Finally, phage therapy has the potential to emerge as a valid alternative, but major challenges remain, namely the isolation of more H. pylori strictly virulent bacterio(phages).
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Produtos Biológicos , Infecções por Helicobacter , Helicobacter pylori , Probióticos , Antibacterianos/farmacologia , Produtos Biológicos/farmacologia , Infecções por Helicobacter/tratamento farmacológico , Humanos , Probióticos/uso terapêuticoRESUMO
Helicobacter pylori, a significant human gastric pathogen, has been demonstrating increased antibiotic resistance, causing difficulties in infection treatment. It is therefore important to develop alternatives or complementary approaches to antibiotics to tackle H. pylori infections, and (bacterio)phages have proven to be effective antibacterial agents. In this work, prophage isolation was attempted using H. pylori strains and UV radiation. One phage was isolated and further characterized to assess potential phage-inspired therapeutic alternatives to H. pylori infections. HPy1R is a new podovirus prophage with a genome length of 31,162 bp, 37.1% GC, encoding 36 predicted proteins, of which 17 were identified as structural. Phage particles remained stable at 37 °C, from pH 3 to 11, for 24 h in standard assays. Moreover, when submitted to an in vitro gastric digestion model, only a small decrease was observed in the gastric phase, suggesting that it is adapted to the gastric tract environment. Together with its other characteristics, its capability to suppress H. pylori population levels for up to 24 h post-infection at multiplicities of infection of 0.01, 0.1, and 1 suggests that this newly isolated phage is a potential candidate for phage therapy in the absence of strictly lytic phages.
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Bacteriófagos , Infecções por Helicobacter , Helicobacter pylori , Antibacterianos , Bacteriófagos/genética , Genômica , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/terapia , Humanos , Prófagos/genéticaRESUMO
Seven-coordinate, pentagonal-bipyramidal (PBP) complexes [Ln(bbpen)Cl] and [Ln(bbppn)Cl], in which Ln = Tb3+ (products I and II), Eu3+ (III and IV), and Gd3+ (V and VI), with bbpen2- = N,N'-bis(2-oxidobenzyl)-N,N'-bis(pyridin-2-ylmethyl)ethylenediamine and bbppn2- = N,N'-bis(2-oxidobenzyl)-N,N'-bis(pyridin-2-ylmethyl)-1,2-propanediamine, were synthesized and characterized by single-crystal X-ray diffraction analysis, alternating-current magnetic susceptibility measurements, and photoluminescence (steady-state and time-resolved) spectroscopy. Under a static magnetic field of 0.1 T, the Tb3+ complexes I and II revealed single-ion-magnet behavior. Also, upon excitation at 320 nm at 300 K, I and II presented very high absolute emission quantum yields (0.90 ± 0.09 and 0.92 ± 0.09, respectively), while the corresponding Eu3+ complexes III and IV showed no photoluminescence. Detailed theoretical calculations on the intramolecular energy-transfer rates for the Tb3+ products indicated that both singlet and triplet ligand excited states contribute efficiently to the overall emission performance. The expressive quantum yields, QLnL, measured for I and II in the solid state and a dichloromethane solution depend on the excitation wavelength, being higher at 320 nm. Such a dependence was rationalized by computing the intersystem crossing rates (WISC) and singlet fluorescence lifetimes (τS) related to the population dynamics of the S1 and T1 levels. Thin films of product II showed high air stability and photostability upon continuous UV illumination, which allowed their use as downshifting layers in a green light-emitting device (LED). The prototypes presented a luminous efficacy comparable with those found in commercial LED coatings, without requiring encapsulation or dispersion of II in host matrixes. The results indicate that the PBP environment determined by the ethylenediamine (en)-based ligands investigated in this work favors the outstanding optical properties in Tb3+ complexes. This work presents a comprehensive structural, chemical, and spectroscopic characterization of two Tb3+ complexes of mixed-donor, en-based ligands, focusing on their outstanding optical properties. They constitute good molecular examples in which both triplet and singlet excited states provide energy to the Tb3+ ion and lead to high values of QLnL.
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Two discrete mononuclear complexes, [Tb(bbpen)(NO3)] (I) and [Tb(bbppn)(NO3)] (II), for which H2bbpen = N,N'-bis(2-hydroxybenzyl)-N,N'-bis(pyridin-2-ylmethyl)ethylenediamine and H2bbppn = N,N'-bis(2-hydroxylbenzyl)-N,N'-bis(pyridin-2-ylmethyl)-1,2-propanediamine, were synthesized and characterized by FTIR, Raman, and photoluminescence (PL, steady-state and time-resolved modes) spectroscopy. The attachment of a methyl group to the ethylenediamine portion of the ligand backbone differentiates II from I and acts as a determining feature to both the structural and optical properties of the former. The single-crystal X-ray structure of H2bbppn is described here for the first time, while that of complex II has been redetermined in the monoclinic C2 space group in light of new diffraction data. In II, selective crystallization leads to spontaneous resolution of enantiomeric molecules in different crystals. Absolute emission quantum yields (Ï) and luminescence excited-state lifetimes (at room temperature and 11 K) were measured for both complexes. Despite their similar molecular structures, I and II exhibit remarkably different Ï values of 21 ± 2% and 67 ± 7%, respectively, under UV excitation at room temperature. Results of quantum-mechanical (DFT and TD-DFT) calculations and experimental PL measurements also performed for H2bbpen and H2bbppn confirmed that both ligands are suitable to work as "antennas" for TbIII. Considering the 5D4 lifetime profiles and the significantly higher absolute quantum yield of II, it appears that thermally active nonradiative pathways present in I are minimized in II due to differences in the conformation of the ethylenediamine bridge.
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The evidence for surface crystallization in ionic liquids is scarce. The existing reports seem to be contradictory as for its driving forces, since in the two compounds investigated in the literature, the contribution of coloumbic and van der Waals forces is very different. In this work 1-dodecyl-3-methylimidazolium tetrafluoroborate was studied and its surface crystallization characterized by surface tension, ellipsometry and optical microscopy. The results obtained seem to reconcile previous observations, and it was further shown, using the same techniques, that this phenomenon is prevalent in other ionic liquids. MD simulation results illustrate the different possibilities of organization, providing reasonable models to rationalize the experimental observations.
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The variety of H bond (HB) interactions is a source of inspiration for bottom-up molecular engineering through self-aggregation. Non-conventional intermolecular HBs between N,N'-disubstituted urea and thiourea are studied in detail by vibrational spectroscopies and ab initio calculations. Raman and IR mode assignments are given. We show that it is possible to study selectively the different intermolecular bifurcated intra- and inter-dimer HBs with the two types of HB acceptors. Through the ab initio calculation, the thioamide I mode, a specific marker of N-HS[double bond, length as m-dash]C HB interactions, is unambiguously identified.
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The development of portable low-cost integrated optics-based biosensors for photonics-on-a-chip devices for real-time diagnosis are of great interest, offering significant advantages over current analytical methods. We report the fabrication and characterization of an optical sensor based on a Mach-Zehnder interferometer to monitor the growing concentration of bacteria in a liquid medium. The device pattern was imprinted on transparent self-patternable organic-inorganic di-ureasil hybrid films by direct UV-laser, reducing the complexity and cost production compared with lithographic techniques or three-dimensional (3D) patterning using femtosecond lasers. The sensor performance was evaluated using, as an illustrative example, E. coli cell growth in an aqueous medium. The measured sensitivity (2 × 10-4 RIU) and limit of detection (LOD = 2 × 10-4) are among the best values known for low-refractive index contrast sensors. Furthermore, the di-ureasil hybrid used to produce this biosensor has additional advantages, such as mechanical flexibility, thermal stability, and low insertion losses due to fiber-device refractive index mismatch (~1.49). Therefore, the proposed sensor constitutes a direct, compact, fast, and cost-effective solution for monitoring the concentration of lived-cells.
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Óptica e Fotônica , Técnicas Biossensoriais , Escherichia coli , Interferometria , RefratometriaRESUMO
Two complexes comprising 9-coordinate capped square antiprismatic [Ln(NO3)3(OH2)2(MeOH)] units [Ln(III) = Dy 6; Tb 7] are reported in which the metal complexes are hydrogen-bonded to 15C5 (15-crown-5) macrocycles to form supramolecular chains, {[Ln(NO3)3(OH2)2(MeOH)]·(15C5)}n. Alternating current magnetic susceptibility measurements supported by ab initio studies show field-induced SMM (single-molecule magnet) behavior for 6, but rapid relaxation of the magnetization for 7 because of the presence of dominant quantum tunneling processes as evidenced by the presence of a significant calculated tunnel splitting within the ground-state multiplet. Modeling the high-resolution emission spectra for 6 afforded energies of 37 ± 5 and 28 ± 5 cm-1 for the first-excited-state Stark sublevels of the two crystallographically independent Dy1 and Dy2 ions, in excellent agreement with the calculated values of 31 and 21 cm-1 for ΔE1 derived from ab initio studies.
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The light emission properties of silicon crystalline nanoparticles (SiNPs) have been investigated using steady-state and time-resolved photoluminescence measurements carried out at 12 K and at room temperature. To enable a comparative study of the role of surface terminal groups on the optical properties, we investigated SiNPs-H ensembles with the same mean NP diameter but differing on the surface termination, namely organic-functionalized with 1-dodecene (SiNPs-C12) and H-terminated (SiNPs-H). We show that although the spectral dependence of the light emission is rather unaffected by surface termination, characterized by a single broad band peaking at â¼1.64 eV, both the exciton recombination lifetimes and quantum yields display a pronounced dependence on the surface termination. Exciton lifetimes and quantum yields are found to be significantly lower in SiNPs-H compared SiNPs-C12. This difference is due to distinct non-radiative recombination probabilities resulting from inter-NP exciton migration, which in SiNPs-C12 is inhibited by the energy barriers imposed by the bulky surface groups. The surface groups of organic-terminated SiPs are responsible for the inhibition of inter-NP exciton transfer, yielding a higher quantum yield compared to SiNPs-H. The surface oxidation of SiNPs-C12 leads to the appearance of a phenomenon of an exciton transference from to the Si core to oxide-related states that contribute to light emission. These excitons recombine radiatively, explaining why the emission quantum of the organic-terminated SiNPs is the same after surface oxidation of SiNPs-C12.
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This manuscript reports the synthesis and characterization of the first organic-inorganic hybrid material exhibiting efficient multimodal spectral converting properties. The nanocomposite, made of Er(3+), Yb(3+) codoped zirconia nanoparticles (NPs) entrapped in a di-ureasil d-U(600) hybrid matrix, is prepared by an easy two-step sol-gel synthesis leading to homogeneous and transparent materials that can be very easily processed as monolith or film. Extensive structural characterization reveals that zirconia nanocrystals of 10-20 nm in size are efficiently dispersed into the hybrid matrix and that the local structure of the di-ureasil is not affected by the presence of the NPs. A significant enhancement in the refractive index of the di-ureasil matrix with the incorporation of the ZrO2 nanocrystals is observed. The optical study demonstrates that luminescent properties of both constituents are perfectly preserved in the final hybrid. Thus, the material displays a white-light photoluminescence from the di-ureasil component upon excitation at UV/visible radiation and also intense green and red emissions from the Er(3+)- and Yb(3+)-doped NPs after NIR excitation. The dynamics of the optical processes were also studied as a function of the lanthanide content and the thickness of the films. Our results indicate that these luminescent hybrids represent a low-cost, environmentally friendly, size-controlled, easily processed and chemically stable alternative material to be used in light harvesting devices such as luminescent solar concentrators, optical fibres and sensors. Furthermore, this synthetic approach can be extended to a wide variety of luminescent NPs entrapped in hybrid matrices, thus leading to multifunctional and versatile materials for efficient tuneable nonlinear optical nanodevices.
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Multifunctional molecular ferroelectrics are exciting materials synthesized using molecular chemistry concepts, which may combine a spontaneous electrical polarization, switched upon applying an electric field, with another physical property. A high-temperature ferroelectric material is presented that is based on a chiral Zn(2+) /Dy(3+) complex exhibiting Dy(3+) luminescence, optical activity, and magnetism. We investigate the correlations between the electric polarization and the crystal structure as well as between the low-temperature magnetic slow relaxation and the optical properties.
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Building integrated photovoltaics is a promising strategy for solar technology, in which luminescent solar concentrators (LSCs) stand out. Challenges include the development of materials for sunlight harvesting and conversion, which is an iterative optimization process with several steps: synthesis, processing, and structural and optical characterizations before considering the energy generation figures of merit that requires a prototype fabrication. Thus, simulation models provide a valuable, cost-effective, and time-efficient alternative to experimental implementations, enabling researchers to gain valuable insights for informed decisions. We conducted a literature review on LSCs over the past 47 years from the Web of ScienceTM Core Collection, including published research conducted by our research group, to gather the optical features and identify the material classes that contribute to the performance. The dataset can be further expanded systematically offering a valuable resource for decision-making tools for device design without extensive experimental measurements.
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Compounds with the general formula RE3MO7 (RE = rare earth ions; M = Ta, Nb, Sb, Ru, Ir, Os, Re, etc.), crystallize as a fluorite-related structure, forming polymorphs with different space groups. The space group strongly depends on the RE3+ and M5+ ionic radii and processing conditions. Structural characterization is well-established for the lanthanide series, but literature studies have divergent views about how to attribute yttrium tantalate (Y3TaO7) space groups-some authors have described the Y3TaO7 structure as orthorhombic and belonging to space group C2221 or Ccmm, whereas others have assigned a cubic Fm3Ìm structure to it. Here, we have characterized the structure of undoped and Eu3+-doped Y3TaO7 (0.1 to 50 mol% of Eu3+) samples synthesized by the sol-gel method that crystallized as a cubic disordered fluorite-type structure, space group Fm3Ìm. Their powder X-ray diffraction measurements, Rietveld analyzes and Raman spectra were used as a conclusive technique of the structural properties. We have also investigated whether a secondary phase (M'-YTaO4) emerged in the samples and compared the phase composition of each sample to their Raman spectra. Low-temperature photoluminescence measurements (â¼15 K) using Eu3+ as a structural probe helped us analyze the inhomogeneous broadening observed in the emission spectra. These measurements can be used as an important tool to attribute the crystalline phases of rare earth tantalates and niobates.
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Building-integrated photovoltaics (BIPV) is an emerging technology in the solar energy field. It involves using luminescent solar concentrators to convert traditional windows into energy generators by utilizing light harvesting and conversion materials. This study investigates the application of machine learning (ML) to advance the fundamental understanding of optical material design. By leveraging accessible photoluminescent measurements, ML models estimate optical properties, streamlining the process of developing novel materials, offering a cost-effective and efficient alternative to traditional methods, and facilitating the selection of competitive materials. Regression and clustering methods were used to estimate the optical conversion efficiency and power conversion efficiency. The regression models achieved a Mean Absolute Error (MAE) of 10%, which demonstrates accuracy within a 10% range of possible values. Both regression and clustering models showed high agreement, with a minimal MAE of 7%, highlighting the efficacy of ML in predicting optical properties of luminescent materials for BIPV.
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The growing prevalence of Internet of Things (IoT) devices hinges on resolving the challenge of powering sensors and transmitters. Addressing this, supply-less IoT devices are gaining traction by integrating energy harvesters. This study introduces a temperature sensor devoid of external power sources, achieved through a novel luminescent solar concentrator (LSC) device based on a stretchable, adhesive elastomer. Leveraging a lanthanide-doped styrene-ethylene-butylene-styrene matrix, the LSC yielded 0.09% device efficiency. The resultant temperature sensor exhibits a thermal sensitivity of 2.1%°C-1 and a 0.06 °C temperature uncertainty, autonomously transmitting real-time data to a server for user visualization via smartphones. Additionally, the integration of LED-based lighting enables functionality in low-light conditions, ensuring 24 h cycle operation and the possibility of having four distinct thermometric parameters without changing the device configuration, stating remarkable robustness and reliability of the system.
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Correction for 'Carbon dots on LAPONITE® hybrid nanocomposites: solid-state emission and inter-aggregate energy transfer' by Bruno S. D. Onishi et al., Nanoscale, 2024, https://doi.org/10.1039/d3nr06336d.
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This study delves into the photoluminescent characteristics of solid-state hybrid carbon dots/LAPONITE® (CDLP). These hybrid materials were synthesized using the hydrothermal method with a precise pH control set at 8.5. The LAPONITE® structure remains intact without structural collapse, and we detected the possible deposition of carbon dots (CDs) aggregates on the clay mineral's edges. The use of different concentrations of citric acid (10-, 6-, 2- and 1-times weight/weight of LAPONITE® mass, maintaining the 1 : 1 molar ratio with ethylenediamine) during synthesis results in different CDs concentrations in CDLP-A (low precursors concentration) and CDLP-D (high concentration) with an amorphous structure and average size around 2.8-3.0 nm. The CDLP displayed visible photoluminescence emission in aqueous and powder, which the last underwent quenching according to lifetimes and quantum yield measurements. Low-temperature measurements revealed an enhancement of the non-radiative pathways induced by aggregation. Energy transfer modelling based on Förster-Dexter suggests an approximate mean distance of 9.5 nm between clusters of CDs.