Optical Quantification of Metal Ions Using Plasmonic Nanostructured Microbeads Coated with Metal-Organic Frameworks and Ion-Selective Dyes.

Herein, we designed and synthesized a hybrid material comprising polystyrene submicrobeads coated with silver nanospheres. This material provides a dense collection of electromagnetic hot spots upon illumination with visible light. The subsequent coating with a metal-framework and the adsorption of bathocuproine on it yield an optical sensor for SERS that can specifically detect Cu(II) in a variety of aqueous samples at the ultratrace level. Detection limits with this method are superior to those of induced coupled plasma or atomic absorption and comparable with those obtained with induced coupled plasma coupled with a mass detector.

Association between metabolic syndrome components and gingival bleeding is women-specific: a nested cross-sectional study.

BACKGROUND: Metabolic syndrome (MetS) is a cluster of atherosclerotic risk factors that increases cardiovascular risk. MetS has been associated with periodontitis, but the contribution of single MetS components and any possible sexual dimorphism in this relation remain undetermined. METHODS: Using the third National Health and Nutrition Examination Survey (NHANES III), we performed a nested cross-sectional study to test whether individuals aged > 30 years undergoing periodontal evaluation (population) exposed to ≥ 1 MetS component (exposure) were at increased risk of bleeding/non-bleeding periodontal diseases (outcome) compared to nonexposed individuals, propensity score matched for sex, age, race/ethnicity, and income (controls). The association between MetS components combinations and periodontal diseases was explored overall and across subgroups by sex and smoking. Periodontal health status prediction based on MetS components was assessed. RESULTS: In total, 2258 individuals (n. 1129/group) with nested clinical-demographic features were analyzed. Exposure was associated with gingival bleeding (+ 18% risk for every unitary increase in MetS components, and triple risk when all five were combined), but not with stable periodontitis; the association was specific for women, but not for men, irrespective of smoking. The only MetS feature with significant association in men was high BP with periodontitis. CRP levels significantly increased from health to disease only among exposed women. MetS components did not substantially improve the prediction of bleeding/non-bleeding periodontal disease. CONCLUSION: The observed women-specific association of gingival bleeding with single and combined MetS components advances gender and precision periodontology. Further research is needed to validate and expand these findings.

Design and fabrication of bimetallic plasmonic colloids through cold nanowelding.

The integration of Au and Ag into nanoalloys has emerged as an intriguing strategy to further tailor and boost the plasmonic properties of optical substrates. Conventional approaches for fabricating these materials via chemical reductions of metal salts in solution suffer from some limitations, such as the possibility of retaining the original morphology of the monometallic substrate. Spontaneous nanowelding at room temperature has emerged as an alternative route to tailor Au/Ag nanomaterials. Herein, we perform a thorough study on the cold-welding process of silver nanoparticles onto gold substrates to gain a better understanding of the role of different variables in enabling the formation of well-defined bimetallic structures that retain the original gold substrate morphology. To this end, we systematically varied the size of silver nanoparticles, dimensions and geometries of gold substrates, solvent polarity and structural nature of the polymeric coating. A wide range of optical and microscopy techniques have been used to provide a complementary and detailed description of the nanowelding process. We believe this extensive study will provide valuable insights into the optimal design and engineering of bimetallic plasmonic Ag/Au structures for application in nanodevices.

Plasmonic Azobenzene Chemoreporter for Surface-Enhanced Raman Scattering Detection of Biothiols.

Low molecular weight thiols (biothiols) are highly active compounds extensively involved in human physiology. Their abnormal levels have been associated with multiple diseases. In recent years, major efforts have been devoted to developing new nanosensing methods for the low cost and fast quantification of this class of analytes in minimally pre-treated samples. Herein, we present a novel strategy for engineering a highly efficient surface-enhanced Raman scattering (SERS) spectroscopy platform for the dynamic sensing of biothiols. Colloidally stable silver nanoparticles clusters equipped with a specifically designed azobenzene derivative (AzoProbe) were generated as highly SERS active substrates. In the presence of small biothiols (e.g., glutathione, GSH), breakage of the AzoProbe diazo bond causes drastic spectral changes that can be quantitatively correlated with the biothiol content with a limit of detection of ca. 5 nM for GSH. An identical response was observed for other low molecular weight thiols, while larger macromolecules with free thiol groups (e.g., bovine serum albumin) do not produce distinguishable spectral alterations. This indicates the suitability of the SERS sensing platform for the selective quantification of small biothiols.

Targets and Tools: Nucleic Acids for Surface-Enhanced Raman Spectroscopy.

Surface-enhanced Raman spectroscopy (SERS) merges nanotechnology with conventional Raman spectroscopy to produce an ultrasensitive and highly specific analytical tool that has been exploited as the optical signal read-out in a variety of advanced applications. In this feature article, we delineate the main features of the intertwined relationship between SERS and nucleic acids (NAs). In particular, we report representative examples of the implementation of SERS in biosensing platforms for NA detection, the integration of DNA as the biorecognition element onto plasmonic materials for SERS analysis of different classes of analytes (from metal ions to microorgniasms) and, finally, the use of structural DNA nanotechnology for the precise engineering of SERS-active nanomaterials.

Surface-Enhanced Raman Scattering (SERS) Spectroscopy for Sensing and Characterization of Exosomes in Cancer Diagnosis.

Exosomes are emerging as one of the most intriguing cancer biomarkers in modern oncology for early cancer diagnosis, prognosis and treatment monitoring. Concurrently, several nanoplasmonic methods have been applied and developed to tackle the challenging task of enabling the rapid, sensitive, affordable analysis of exosomes. In this review, we specifically focus our attention on the application of plasmonic devices exploiting surface-enhanced Raman spectroscopy (SERS) as the optosensing technique for the structural interrogation and characterization of the heterogeneous nature of exosomes. We summarized the current state-of-art of this field while illustrating the main strategic approaches and discuss their advantages and limitations.

Surface-Enhanced Raman Scattering Sensing of Transition Metal Ions in Waters.

In this mini-review, we provide a coherent discussion on the sensing schemes exploited in the surface-enhanced Raman scattering (SERS) analysis of transition metal ions in waters. A critical approach was used where illustrative examples are selected to discuss key drawbacks and challenges associated with various experimental configurations and the employed enhancing substrates.

Structural Recognition of Triple-Stranded DNA by Surface-Enhanced Raman Spectroscopy.

Direct, label-free analysis of nucleic acids via surface-enhanced Raman spectroscopy (SERS) has been continuously expanding its range of applications as an intriguing and powerful analytical tool for the structural characterization of diverse DNA structures. Still, interrogation of nucleic acid tertiary structures beyond the canonical double helix often remains challenging. In this work, we report for the first time the structural identification of DNA triplex structures. This class of nucleic acids has been attracting great interest because of their intriguing biological functions and pharmacological potential in gene therapy, and the ability for precisely engineering DNA-based functional nanomaterials. Herein, structural discrimination of the triplex structure against its duplex and tertiary strand counterparts is univocally revealed by recognizing key markers bands in the intrinsic SERS fingerprint. These vibrational features are informative of the base stacking, Hoogsteen hydrogen bonding and sugar-phosphate backbone reorganization associated with the triple helix formation. This work expands the applicability of direct SERS to nucleic acids analysis, with potential impact on fields such as sensing, biology and drug design.

Positively-charged plasmonic nanostructures for SERS sensing applications.

Surface-enhanced Raman (SERS) spectroscopy has been establishing itself as an ultrasensitive analytical technique with a cross-disciplinary range of applications, which scientific growth is triggered by the continuous improvement in the design of advanced plasmonic materials with enhanced multifunctional abilities and tailorable surface chemistry. In this regard, conventional synthetic procedures yield negatively-charged plasmonic materials which can hamper the adhesion of negatively-charged species. To tackle this issue, metallic surfaces have been modified via diverse procedures with a broad array of surface ligands to impart positive charges. Cationic amines have been preferred because of their ability to retain a positive zeta potential even at alkaline pH as well as due to their wide accessibility in terms of structural features and cost. In this review, we will describe and discuss the different approaches for generating positively-charged plasmonic platforms and their applications in SERS sensing.

Surface-Enhanced Raman Scattering Detection of Nucleic Acids Exhibiting Sterically Accessible Guanines Using Ruthenium-Polypyridyl Reagents.

Here, we report the application of surface-enhanced Raman scattering (SERS) spectroscopy as a rapid and practical tool for assessing the formation of coordinative adducts between nucleic acid guanines and ruthenium polypyridyl reagents. The technology provides a practical approach for the wash-free and quick identification of nucleic acid structures exhibiting sterically accessible guanines. This is demonstrated for the detection of a quadruplex-forming sequence present in the promoter region of the c-myc oncogene, which exhibits a nonpaired, reactive guanine at a flanking position of the G-quartets.

Mucoadhesive Buccal Films for Local Delivery of Lactobacillus brevis.

The aim of this work was to prepare mucoadhesive buccal films for local release of Lactobacillus brevis CD2, which shows interesting anti-inflammatory properties due to its high levels of arginine deiminase. Hydroxypropylmethylcellulose-based films were prepared by means of a modified casting method, which allowed L. brevis CD2 loading on one side of the film, before its complete drying. Three batches of films were prepared, stored at +2-8 °C and +23-25 °C for 48 weeks and characterized in terms of physico-chemical and functional properties. For each batch, the L. brevis viable count and arginine deiminase activity were evaluated at different time points in order to assess functional property maintenance over time. Moreover, the mucoadhesive properties and ability of the films to release L. brevis CD2 were evaluated. A good survival of L. brevis CD2 was observed, particularly at the storage temperature of +2-8 °C, while the activity of arginine deiminase was maintained at both temperature values. Films showed good mucoadhesive properties and guaranteed a prolonged release of viable lactobacilli, which can be directed towards the whole buccal cavity or specific mucosa lesions. In conclusion, the proposed preparative method can be successfully employed for the production of buccal films able to release viable L. brevis CD2 cells that maintain the anti-inflammatory enzymatic activity.

Fabrication of Hybrid Silver Microstructures from Vermiculite Templates as SERS Substrates.

There is great interest in developing complex, 3D plasmonic materials with unusual structural properties. This can be achieved via template-assisted approaches exploiting scaffold elements to engineer unique plasmonic substrates, which would be otherwise impossible to synthesize. Herein, we present a novel, simple, and low-cost template-assisted method for producing interconnected 3-D silver microstructures by utilizing vermiculite, a well-known silicate, as both in-situ reductant and template for silver growth. The silicate network of the vermiculite can be easily removed by dissolution with hydrofluoric acid, which, simultaneously, leads to the formation of a magnesium fluoride skeleton supporting a plasmonically active silver film. Optical, morphological, and chemical properties of the materials were extensively investigated, revealing, for example, that hybrid silver microstructures can be exploited as valuable SERS substrates over a broad spectral range of excitation wavelengths.

Type I Collagen Suspension Induces Neocollagenesis and Myodifferentiation in Fibroblasts In Vitro.

The ability of a collagen-based matrix to support cell proliferation, migration, and infiltration has been reported; however, the direct effect of an aqueous collagen suspension on cell cultures has not been studied yet. In this work, the effects of a high-concentration aqueous suspension of a micronized type I equine collagen (EC-I) have been evaluated on a normal mouse fibroblast cell line. Immunofluorescence analysis showed the ability of EC-I to induce a significant increase of type I and III collagen levels, parallel with overexpression of crucial proteins in collagen biosynthesis, maturation, and secretion, prolyl 4-hydroxylase (P4H) and heat shock protein 47 (HSP47), as demonstrated by western blot experiments. The treatment led, also, to an increase of α-smooth muscle actin (α-SMA) expression, evaluated through western blot analysis, and cytoskeletal reorganization, as assessed by phalloidin staining. Moreover, scanning electron microscopy analysis highlighted the appearance of plasma membrane extensions and blebbing of extracellular vesicles. Altogether, these results strongly suggest that an aqueous collagen type I suspension is able to induce fibroblast myodifferentiation. Moreover, our findings also support in vitro models as a useful tool to evaluate the effects of a collagen suspension and understand the molecular signaling pathways possibly involved in the effects observed following collagen treatment in vivo.

Surface-enhanced Raman spectroscopy (SERS) characterisation of abasic sites in DNA duplexes.

In this study, direct surface-enhanced Raman scattering (SERS) spectroscopy is used as an exquisite nano-optical tool for ultrasensitive structural characterisation of abasic sites in DNA. In addition, the conformational discrimination (intra- vs. extra-helical) of the nucleobase opposite to the abasic site was also achieved.

Correction: Metabolic pathway for the universal fluorescent recognition of tumor cells.

[This corrects the article DOI: 10.18632/oncotarget.18551.].

Multiplex SERS Chemosensing of Metal Ions via DNA-Mediated Recognition.

The combination of molecular sensors and plasmonic materials is emerging as one of the most promising approaches for ultrasensitive SERS-based detection of metal ions in complex fluids. However, only a very small fraction of the large pool of potential chemosensors described in classical analytical chemistry has been successfully implemented into viable SERS platforms for metal ion determination. This is due to the molecular restrictions that require the chemosensor to adhere onto the plasmonic surface while retaining the capability to undergo large structural alterations upon metal ion binding. In this work, we demonstrate that the structural and functional plasticity of DNA for interacting with small aromatic molecules can be exploited to this end. DNA coating of silver nanoparticles modulates the interaction of the commercially available alizarin red S (ARS) chemosensor with the nanomaterial, translating its recognition capabilities from bulk solution onto the plasmonic surface, while simultaneously directing the particle assembling into highly efficient SERS clusters. The sensing approach was successfully applied to the multiplex, quantitative determination of Al(III) and Fe(III) in tap water in the subppb level.

Surface-Enhanced Raman Spectroscopy in Cancer Diagnosis, Prognosis and Monitoring.

As medicine continues to advance our understanding of and knowledge about the complex and multifactorial nature of cancer, new major technological challenges have emerged in the design of analytical methods capable of characterizing and assessing the dynamic heterogeneity of cancer for diagnosis, prognosis and monitoring, as required by precision medicine. With this aim, novel nanotechnological approaches have been pursued and developed for overcoming intrinsic and current limitations of conventional methods in terms of rapidity, sensitivity, multiplicity, non-invasive procedures and cost. Eminently, a special focus has been put on their implementation in liquid biopsy analysis. Among optical nanosensors, those based on surface-enhanced Raman scattering (SERS) have been attracting tremendous attention due to the combination of the intrinsic prerogatives of the technique (e.g., sensitivity and structural specificity) and the high degree of refinement in nano-manufacturing, which translate into reliable and robust real-life applications. In this review, we categorize the diverse strategic approaches of SERS biosensors for targeting different classes of tumor biomarkers (cells, nucleic acids and proteins) by illustrating key recent research works. We will also discuss the current limitations and future research challenges to be addressed to improve the competitiveness of SERS over other methodologies in cancer medicine.

Extraordinarily transparent compact metallic metamaterials.

The design of achromatic optical components requires materials with high transparency and low dispersion. We show that although metals are highly opaque, densely packed arrays of metallic nanoparticles can be more transparent to infrared radiation than dielectrics such as germanium, even when the arrays are over 75% metal by volume. Such arrays form effective dielectrics that are virtually dispersion-free over ultra-broadband ranges of wavelengths from microns up to millimeters or more. Furthermore, the local refractive indices may be tuned by altering the size, shape, and spacing of the nanoparticles, allowing the design of gradient-index lenses that guide and focus light on the microscale. The electric field is also strongly concentrated in the gaps between the metallic nanoparticles, and the simultaneous focusing and squeezing of the electric field produces strong 'doubly-enhanced' hotspots which could boost measurements made using infrared spectroscopy and other non-linear processes over a broad range of frequencies.

Modular assembly of plasmonic core-satellite structures as highly brilliant SERS-encoded nanoparticles.

Herein, we present a fabrication approach that produces homogeneous core-satellite SERS encoded particles with minimal interparticle gaps (<2-3 nm) and maximum particle loading, while positioning the encoding agents at the gaps. Integration of plasmonic building blocks of different sizes, shapes, compositions, surface chemistries or encoding agents is achieved in a modular fashion with minimal modification of the general synthetic protocol. These materials present an outstanding optical performance with homogeneous enhancement factors over 4 orders of magnitude as compared with classical SERS encoded particles, which allows their use as single particle labels.

Delay Cournot duopoly models revisited.

In considering economic dynamics, it has been known that time delays are inherent in economic phenomena and could be crucial sources for oscillatory behavior. The main aim of this study is to shed light on what effects the delays can generate. To this end, different models of Cournot duopoly with different delays are built in a continuous time framework and their local and global dynamics are analytically and numerically examined. Three major findings are obtained. First, the stability switching conditions are analytically constructed. Second, it is numerically demonstrated that different lengths of the delays are sources for the birth of simple and complicated dynamics. Third, the delay for collecting information on the competitors' output alone does not affect stability.