Van der Waals materials as dielectric layers for tailoring the near-field photonic response of surfaces.

Epsilon near-zero photonics and surface polariton nanophotonics have become major fields within optics, leading to unusual and enhanced light-matter interaction. Specific dielectric responses are required in both cases, which can be achieved, e.g., via operation near a material's electronic or phononic resonance. However, this condition restricts operation to a specific, narrow frequency range. It has been shown that using a thin dielectric layer can adjust the dielectric response of a surface and, therefore, the operating frequency for achieving specific photonic excitations. Here, we show that a surface's optical properties can be tuned via the deposition/transference of ultra-thin layered van der Waals (vdW) crystals, the thicknesses of which can easily be adjusted to provide the desired response. In particular, we experimentally and theoretically show that the surface phonon resonance of a silica surface can be tuned by ∼50 cm-1 through the simple deposition of nanometer-thick exfoliated flakes of black phosphorus. The surface properties were probed by infrared nanospectroscopy, and results show a close agreement with the theory. The black phosphorus-silica layered structure effectively acts as a surface with a tunable effective dielectric constant that presents an infrared response dependent on the black phosphorus thickness. In contrast, with a lower dielectric constant, hexagonal boron nitride does not significantly tune the silica surface phonon polariton. Our approach also applies to epsilon near-zero surfaces, as theoretically shown, and to polaritonic surfaces operating at other optical ranges.

Finding the perfect match between nanoparticles and microfluidics to respond to cancer challenges.

The clinical translation of new cancer theranostic has been delayed by inherent cancer's heterogeneity. Additionally, this delay has been enhanced by the lack of an appropriate in vitro model, capable to produce accurate data. Nanoparticles and microfluidic devices have been used to obtain new and more efficient strategies to tackle cancer challenges. On one hand, nanoparticles-based therapeutics can be modified to target specific cells, and/or molecules, and/or modified with drugs, releasing them over time. On the other hand, microfluidic devices allow the exhibition of physiologically complex systems, incorporation of controlled flow, and control of the chemical environment. Herein, we review the use of nanoparticles and microfluidic devices to address different cancer challenges, such as detection of CTCs and biomarkers, point-of-care devices for early diagnosis and improvement of therapies. The future perspectives of cancer challenges are also addressed herein.

Microfluidic Devices and Three Dimensional-Printing Strategies for in vitro Models of Bone.

Bone is a complex and highly dynamic tissue, which has been worldwide studied, from fundamental biology to tissue engineering fields. Even so, current in vitro models do not truly replicate the native bone tissue environment. For so, new and improved in vitro tissue models are necessary to obtain more reliable data, not only in a development point of view, but also to fasten the translation of new drugs into the clinics. In this reasoning, tissue-engineering strategies were applied to develop mimetic and three-dimensional (3D) microenvironments, which were associated with microfluidic devices for the development of more complex and realistic systems. Such devices mimic blood vessels that are present in the native tissue, thus enabling the study of complex biological mechanism as such as bone angiogenesis. More recently, 3D printing has been pursued to produce more intricate microfluidic devices and engineered tissues in a single step. The ability to print spatially controlled structures composed of different biomaterials, growth factors and cells caught the attention of scientists for the development of more efficient in vitro models. Additionally, it allows obtaining microfluidic devices and/or engineered tissues with the desired architecture within a small amount of time and with reduced costs. Recently, the use of high-resolution scanning boosted the production of patient-specific implants. Despite the difficulties associated with 3D printed structures that still need to be overcome, it has been proven to be a valuable tool to accomplish a new generation of 3D bioprinted bone-on-a-chip platforms.

Nanoparticles and Microfluidic Devices in Cancer Research.

Cancer is considered the disease of the century, which can be easily understood considering its increasing incidence worldwide. Over the last years, nanotechnology has been presenting promising theranostic approaches to tackle cancer, as the development of nanoparticle-based therapies. But, regardless of the promising outcomes within in vitro settings, its translation into the clinics has been delayed. One of the main reasons is the lack of an appropriate in vitro model, capable to mimic the true environment of the human body, to test the designed nanoparticles. In fact, most of in vitro models used for the validation of nanoparticle-based therapies do not address adequately the complex barriers that naturally occur in a tumor scenario, as such as blood vessels, the interstitial fluid pressure or the interactions with surrounding cells that can hamper the proper delivery of the nanoparticles into the desired site. In this reasoning, to get a step closer to the in vivo reality, it has been proposed of the use of microfluidic devices. In fact, microfluidic devices can be designed on-demand to exhibit complex structures that mimic tissue/organ-level physiological architectures. Even so, despite microfluidic-based in vitro models do not compare with the reality and complexity of the human body, the most complex systems created up to now have been showing similar results to in vivo animal models. Microfluidic devices have been proven to be a valuable tool to accomplish more realistic tumour's environment. The recent advances in this field, and in particular, the ones enabling the rapid test of new therapies, and show great promise to be translated to the clinics will be overviewed herein.

Fractal morphology, imaging and mass spectrometry of single aerosol particles in flight.

The morphology of micrometre-size particulate matter is of critical importance in fields ranging from toxicology to climate science, yet these properties are surprisingly difficult to measure in the particles' native environment. Electron microscopy requires collection of particles on a substrate; visible light scattering provides insufficient resolution; and X-ray synchrotron studies have been limited to ensembles of particles. Here we demonstrate an in situ method for imaging individual sub-micrometre particles to nanometre resolution in their native environment, using intense, coherent X-ray pulses from the Linac Coherent Light Source free-electron laser. We introduced individual aerosol particles into the pulsed X-ray beam, which is sufficiently intense that diffraction from individual particles can be measured for morphological analysis. At the same time, ion fragments ejected from the beam were analysed using mass spectrometry, to determine the composition of single aerosol particles. Our results show the extent of internal dilation symmetry of individual soot particles subject to non-equilibrium aggregation, and the surprisingly large variability in their fractal dimensions. More broadly, our methods can be extended to resolve both static and dynamic morphology of general ensembles of disordered particles. Such general morphology has implications in topics such as solvent accessibilities in proteins, vibrational energy transfer by the hydrodynamic interaction of amino acids, and large-scale production of nanoscale structures by flame synthesis.

Tissue Engineering Strategies for Osteochondral Repair.

Tissue engineering strategies have been pushing forward several fields in the range of biomedical research. The musculoskeletal field is not an exception. In fact, tissue engineering has been a great asset in the development of new treatments for osteochondral lesions. Herein, we overview the recent developments in osteochondral tissue engineering. Currently, the treatments applied in a clinical scenario have shown some drawbacks given the difficulty in regenerating a fully functional hyaline cartilage. Among the different strategies designed for osteochondral regeneration, it is possible to identify cell-free strategies, scaffold-free strategies, and advanced strategies, where different materials are combined with cells. Cell-free strategies consist in the development of scaffolds in the attempt to better fulfill the requirements of the cartilage regeneration process. For that, different structures have been designed, from monolayers to multilayered structures, with the intent to mimic the osteochondral architecture. In the case of scaffold-free strategies, they took advantage on the extracellular matrix produced by cells. The last strategy relies in the development of new biomaterials capable of mimicking the extracellular matrix. This way, the cell growth, proliferation, and differentiation at the lesion site are expedited, exploiting the self-regenerative potential of cells and its interaction with biomolecules. Overall, despite the difficulties associated with each approach, tissue engineering has been proven a valuable tool in the regeneration of osteochondral lesions and together with the latest advances in the field, promises to revolutionize personalized therapies.

Biological performance of a promising Kefiran-biopolymer with potential in regenerative medicine applications: a comparative study with hyaluronic acid.

Kefiran from kefir grains, an exopolysaccharide (EPS) produced by lactic acid bacteria (LAB), has received an increasing interest because of its safe status. This natural biopolymer is a water-soluble glucogalactan with probed health-promoting properties. However, its biological performance has yet to be completely recognized and properly exploited. This research was carried out to evaluate the in vitro antioxidant and the in vitro anti-inflammatory properties of Kefiran biopolymer. Regarding antioxidant activity, the results demonstrated that the Kefiran extract possessed the strongest reducing power and superoxide radical scavenging, over hyaluronic acid (HA, gold standard viscosupplementation treatment). This exopolysaccharide showed a distinct antioxidant performance in the majority of in vitro working mechanisms of antioxidant activity comparing to HA. Moreover, Kefiran presented an interesting capacity to scavenge nitric oxide radical comparing to the gold standard that did not present any potency. Finally, the cytotoxic effects of Kefiran extracts on hASCs were also performed and demonstrated no cytotoxic response, ability to improve cellular function of hASCs. This study demonstrated that Kefiran represented a great scavenger for reactive oxygen and nitrogen species and showed also that it could be an excellent candidate to promote tissue repair and regeneration.

Tooth loss in middle-aged adults with diabetes and hypertension: Social determinants, health perceptions, oral impact on daily performance (OIDP) and treatment need.

BACKGROUND: This study aimed to explore the association between tooth loss and social determinants, health self-perceptions, OIDP and self-concept of dental treatment need in middle-aged adults with diabetes and hypertension. MATERIAL AND METHODS: A cross-sectional study was developed with 212 hypertensive and diabetic middle-aged adults (50-65 years). Data were collected from clinical examinations (DMFT) and a questionnaire regarding socioeconomic status, dental health assistance, self-perceptions of oral and general health, OIDP, and the self-concept of dental treatment need. Tooth loss was dichotomized considering the cutoff point of 12 (Model I) or 24 missing teeth (Model II). Data were analyzed using Chi-square, Fisher's exact test and logistic regression (p≤0.05). RESULTS: Tooth loss was significantly associated with variables such as last dental visit, reason for dental visit, OIDP, perception of dental treatment need, and general self-perception (Model I). Schooling, last dental visit, oral health self-perception and perception of dental treatment need were significantly associated with tooth loss in the Model II. When Model 1 and 2 were adjusted, they demonstrated that last dental visit and perception of dental treatment need were predictor variables. CONCLUSIONS: The annual dental visit and the self-concept of dental treatment need were associated with tooth loss, demonstrating that these variables reduce the tooth loss prevalence.

Stroke in systemic lupus erythematosus and antiphospholipid syndrome: risk factors, clinical manifestations, neuroimaging, and treatment.

Neurologic disorders are among the most common and important clinical manifestations associated with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), mainly those that affect the central nervous system (CNS). Risk of cerebrovascular events in both conditions is increased, and stroke represents one of the most severe complications, with an incidence rate between 3% and 20%, especially in the first five years of diagnosis. This article updates the data regarding the risk factors, clinical manifestations, neuroimaging, and treatment of stroke in SLE and APS.

Physiological effects of temperature do not explain prevalence of females in populations of gynodioecious Lobelia siphilitica growing in warmer climates.

PREMISE OF THE STUDY: Gynodioecy is a sexual polymorphism whereby female and hermaphroditic plants co-occur within populations. In many gynodioecious species, stressful abiotic environments are associated with higher frequencies of females. This association suggests that abiotic stress affects the relative fitness of females and hermaphrodites and, thus, the maintenance of gynodioecy. METHODS: To test whether abiotic stress affects the fitness of females and hermaphrodites, we grew open-pollinated Lobelia siphilitica families in temperature regimes characteristic of the southern portion of the species' range (where females are common) and the northern portion of the range (where females are rare). We measured physiological and phenological traits that are indicative of heat stress, and fitness components of females and hermaphrodites that could affect the maintenance of gynodioecy. KEY RESULTS: Contrary to expectations if growth at high temperatures is stressful, we found that the hot treatment increased leaf chlorophyll content, decreased the percentage of plants that delayed flowering initiation, and did not affect the quantum efficiency of photosystem II. Growth at high temperatures did not affect the magnitude of the difference in rosette size (a correlate of flower number) between females and hermaphrodites, or the variance in pollen viability among hermaphrodites. CONCLUSIONS: We found that growing-season temperatures typical of high female L. siphilitica populations were not stressful and did not affect either the fitness of females compared to hermaphrodites or variation in fitness among hermaphrodites. Consequently, further research is necessary to explain correlations between abiotic environmental factors and the frequency of females in this and other gynodioecious species.

Cuticular signature in the development of Polistes versicolor.

Wasps belong to societies that are highly complex and diverse, especially considering social organization and parental care. They use chemicals in their daily communication, and act incisively in recognition of mates and non-nest mates, and can even identify individuals of different castes. In this study, cuticle composition was examined during the development of Polistes versicolor from the egg stage to adulthood, with the aim to assess changes in the chemical signature of the species, using gas chromatography. Linear alkanes and branched alkanes were identified that were important to distinguish the various developmental stages of P. versicolor. The variation in the linear alkanes and branched alkanes was quantitative, since most of them are present in all stages, with the exception of some linear alkanes that uniquely characterized the egg stage. At the egg stage, differences were predominant for linear alkanes C8, C24, C27, and C29. For the larval instars, there was a predominance of linear alkanes C8, C22 and C24 to C30. In the pre-pupae, pupae and adult stages, C8, C22, C24, and C26 to C30 showed a higher abundance during later developmental stages. The addition to branched alkanes increased their abundance from the egg (13.52%) to adult (22.96%) stages.

Hydroxyapatite/alginate/gellan gum inks with osteoconduction and osteogenic potential for bioprinting bone tissue analogues.

There is a growing demand for engineered bone tissues custom-designed to match the patient-specific defect size and in vitro models for studying bone diseases and/or drug screening. Herein, we propose a bioprinted bone tissue construct using SaOs-2 cells within alginate/gellan gum/hydroxyapatite inks. Different ink formulations were developed with varying hydroxyapatite content and then evaluated for viscoelasticity, printability, biomineralization properties, post-printing viability, proliferation, metabolic activity, and osteogenic phenotype of SaOs-2-encapsulated cells. Results indicate that ink formulations exhibit non-Newtonian shear-thinning behaviour, maintaining shape integrity and structural stability post-printing. Ink mineralization rates increase with the hydroxyapatite content, rendering them suitable for bone defect strategies. Post-printed cells in the developed constructs remain live, spreading, and metabolically active but do not proliferate. Osteogenic gene and protein expression, both early and late, show upregulation at day 7 relative to day 1, followed by downregulation at day 14. Lower hydroxyapatite content inks demonstrate up to fourfold upregulation in genes and proteins at most time points. Additionally, these constructs release calcium and phosphate at levels conducive to mineralization. Overall, the tissue-engineered miniaturized constructs not only meet the criteria for early-stage bone defect/fracture regeneration but also serve as a promising platform for drug screening and evaluating potential therapeutic treatments.

The extraction of single-particle diffraction patterns from a multiple-particle diffraction pattern.

The structures of biological molecules may soon be determined with X-ray free-electron lasers without crystallization by recording the coherent diffraction patterns of many identical copies of a molecule. Most analysis methods require a measurement of each molecule individually. However, current injection methods deliver particles to the X-ray beam stochastically and the maximum yield of single particle measurements is 37% at optimal concentration. The remaining 63% of pulses intercept no particles or multiple particles. We demonstrate that in the latter case single particle diffraction patterns can be extracted provided the particles are sufficiently separated. The technique has the potential to greatly increase the amount of data available for three-dimensional imaging of identical particles with X-ray lasers.

Impact of wave front and coherence optimization in coherent diffractive imaging.

We present single shot nanoscale imaging using a table-top femtosecond soft X-ray laser harmonic source at a wavelength of 32 nm. We show that the phase retrieval process in coherent diffractive imaging critically depends on beam quality. Coherence and image fidelity are measured from single-shot coherent diffraction patterns of isolated nano-patterned slits. Impact of flux, wave front and coherence of the soft X-ray beam on the phase retrieval process and the image quality are discussed. After beam improvements, a final image reconstruction is presented with a spatial resolution of 78 nm (half period) in a single 20 fs laser harmonic shot.

Nanocontainer-based corrosion sensing coating.

The present paper reports on the development of new sensing active coating on the basis of nanocontainers containing pH-indicating agent. The coating is able to detect active corrosion processes on different metallic substrates. The corrosion detection functionality based on the local colour change in active cathodic zones results from the interaction of hydroxide ions with phenolphthalein encapsulated in mesoporous nanocontainers which function as sensing nanoreactors. The mesoporous silica nanocontainers are synthesized and loaded with pH indicator phenolphthalein in a one-stage process. The resulting system is mesoporous, which together with bulkiness of the indicator molecules limits their leaching. At the same time, penetration of water molecules and ions inside the container is still possible, allowing encapsulated phenolphthalein to be sensitive to the pH in the surrounding environment and outperforming systems when an indicator is directly dispersed in the coating layer.The performed tests demonstrate the pH sensitivity of the developed nanocontainers being dispersed in aqueous solutions. The corrosion sensing functionality of the protective coatings with nanocontainers are proven for aluminium- and magnesium-based metallic substrates. As a result, the developed nanocontainers show high potential to be used in a new generation of active protective coatings with corrosion-sensing coatings.

Development of Conjugated Kefiran-Chondroitin Sulphate Cryogels with Enhanced Properties for Biomedical Applications.

Hydrogels based on natural polysaccharides can have unique properties and be tailored for several applications, which may be mainly limited by the fragile structure and weak mechanical properties of this type of system. We successfully prepared cryogels made of newly synthesized kefiran exopolysaccharide-chondroitin sulfate (CS) conjugate via carbodiimide-mediated coupling to overcome these drawbacks. The freeze-thawing procedure of cryogel preparation followed by lyophilization is a promising route to fabricate polymer-based scaffolds with countless and valuable biomedical applications. The novel graft macromolecular compound (kefiran-CS conjugate) was characterized through 1H-NMR and FTIR spectroscopy-which confirmed the structure of the conjugate, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA)-which mirrored good thermal stability (degradation temperature of about 215 °C) and, finally, gel permeation chromatography-size exclusion chromatography (GPC-SEC)-which proved an increased molecular weight due to chemical coupling of kefiran with CS. At the same time, the corresponding cryogels physically crosslinked after the freeze-thawing procedure were investigated by scanning electron microscopy (SEM), Micro-CT, and dynamic rheology. The results revealed a prevalent contribution of elastic/storage component to the viscoelastic behavior of cryogels in swollen state, a micromorphology with micrometer-sized open pores fully interconnected, and high porosity (ca. 90%) observed for freeze-dried cryogels. Furthermore, the metabolic activity and proliferation of human adipose stem cells (hASCs), when cultured onto the developed kefiran-CS cryogel, was maintained at a satisfactory level over 72 h. Based on the results obtained, it can be inferred that the newly freeze-dried kefiran-CS cryogels possess a host of unique properties that render them highly suitable for use in tissue engineering, regenerative medicine, drug delivery, and other biomedical applications where robust mechanical properties and biocompatibility are crucial.

Extremely aggressive course in a poorly differentiated thyroid carcinoma presenting a double mutation of the TERT promoter.

BRAF and TERT oncogenes hotspot mutations are associated with a more aggressive outcome in thyroid carcinomas (TC). TERT promoter (pTERT) mutations (C228T and C250T) are related to cancer growth and reduced overall- and disease-free survivals in TC. We report a patient followed up for 8 years with a poorly differentiated thyroid carcinoma (PDTC) presenting an extremely aggressive course, who developed a large volume of metastases in a short period. Molecular analysis of the primary tumor revealed two pTERT mutations (C228T and C250T), and no BRAF V600E mutation. pTERT mutations C228T and C250T have been described as mutually exclusive, indicating that one mutation is enough for telomerase activation and exerts its action in thyroid tumorigenesis. This report describes both pTERT hotspot mutations in the same PDTC patient presenting a very aggressive course, even for PDTC, suggesting a relationship between the two events. However, more studies are needed to prove this causality.

Femtosecond dark-field imaging with an X-ray free electron laser.

The emergence of femtosecond diffractive imaging with X-ray lasers has enabled pioneering structural studies of isolated particles, such as viruses, at nanometer length scales. However, the issue of missing low frequency data significantly limits the potential of X-ray lasers to reveal sub-nanometer details of micrometer-sized samples. We have developed a new technique of dark-field coherent diffractive imaging to simultaneously overcome the missing data issue and enable us to harness the unique contrast mechanisms available in dark-field microscopy. Images of airborne particulate matter (soot) up to two microns in length were obtained using single-shot diffraction patterns obtained at the Linac Coherent Light Source, four times the size of objects previously imaged in similar experiments. This technique opens the door to femtosecond diffractive imaging of a wide range of micrometer-sized materials that exhibit irreproducible complexity down to the nanoscale, including airborne particulate matter, small cells, bacteria and gold-labeled biological samples.

Recent approaches towards bone tissue engineering.

Bone tissue engineering approaches have evolved towards addressing the challenges of tissue mimetic requirements over the years. Different strategies have been combining scaffolds, cells, and biologically active cues using a wide range of fabrication techniques, envisioning the mimicry of bone tissue. On the one hand, biomimetic scaffold-based strategies have been pursuing different biomaterials to produce scaffolds, combining with diverse and innovative fabrication strategies to mimic bone tissue better, surpassing bone grafts. On the other hand, biomimetic scaffold-free approaches mainly foresee replicating endochondral ossification, replacing hyaline cartilage with new bone. Finally, since bone tissue is highly vascularized, new strategies focused on developing pre-vascularized scaffolds or pre-vascularized cellular aggregates have been a motif of study. The recent biomimetic scaffold-based and scaffold-free approaches in bone tissue engineering, focusing on materials and fabrication methods used, are overviewed herein. The biomimetic vascularized approaches are also discussed, namely the development of pre-vascularized scaffolds and pre-vascularized cellular aggregates.

Uranium retention in a Callovo-Oxfordian clay rock formation: From laboratory-based models to in natura conditions.

For the performance assessment of radioactive waste disposal, it is critical to predict the mobility of radionuclides in the geological barrier that hosts it. A key challenge consists of assessing the transferability of current knowledge on the retention properties deduced from model systems to in natura situations. The case of the redox-sensitive element uranium in the Callovo-Oxfordian clay formation (COx) is presented herein. Extensive experimental work was carried out with respect to parameters affecting uranium speciation (pH, PCO2, [Ca] and redox potential) with illite, COx clay fraction and raw COx claystone. The "bottom-up" approach implemented, with illite and montmorillonite as reactive phases, quantitatively explains the adsorption results of U(VI) and U(IV) on COx. While retention is high for U(IV) (Rd∼104 L kg-1), it remains very low for U(VI) (Rd∼4 L kg-1) due to the formation of soluble ternary Ca(Mg)-U(VI)-carbonate complexes. The applicability of the sorption model was then assessed by comparing predictive analyses with data characterizing the behavior of naturally-occurring U (<3 mg kg-1). The COx clay phase is the largest reservoir of naturally-occurring U (∼65%) but only a small fraction appears to be adsorbed (∼1%). Under representative site conditions (especially with respect to reducing conditions), we have concluded that ternary U(VI) complexes control U speciation in solution while U(IV) surface species dominate U adsorption, with Rd values > 70 L kg-1.