Probing Temperature-Induced Plasmonic Nonlinearity: Unveiling Opto-Thermal Effects on Light Absorption and Near-Field Enhancement.

Precise measurement and control of local heating in plasmonic nanostructures are vital for diverse nanophotonic devices. Despite significant efforts, challenges in understanding temperature-induced plasmonic nonlinearity persist, particularly in light absorption and near-field enhancement due to the absence of suitable measurement techniques. This study presents an approach allowing simultaneous measurements of light absorption and near-field enhancement through angle-resolved near-field scanning optical microscopy with iterative opto-thermal analysis. We revealed gold thin films exhibit sublinear nonlinearity in near-field enhancement due to nonlinear opto-thermal effects, while light absorption shows both sublinear and superlinear behaviors at varying thicknesses. These observations align with predictions from a simple harmonic oscillation model, in which changes in damping parameters affect light absorption and field enhancement differently. The sensitivity of our method was experimentally examined by measuring the opto-thermal responses of three-dimensional nanostructure arrays. Our findings have direct implications for advancing plasmonic applications, including photocatalysis, photovoltaics, photothermal effects, and surface-enhanced Raman spectroscopy.

Inhibitory effect of γ-ray-modified hydroxymethylated baicalins on NO production.

Baicalin, a glucuronic flavone, is the major active component in the medicinal plant Scutellaria baicalensis. Herein, baicalin was irradiated by γ-rays to afford four unusual flavanones, baicalinols A (2), B (3), and C (4) and peroxybaicaleinol (5), and two known flavones, oroxylin A (6) and baicalein (7). The structures of the hydroxymethylated products were elucidated using nuclear magnetic resonance spectroscopy and mass spectrometry, and their absolute configuration was established using electronic circular dichroism spectroscopy. Novel hydroxymethylated flavanones 2 and 3 suppressed both nitric oxide (NO) production and the expression of inducible NO synthase and showed significantly higher anti-inflammatory activities in lipopolysaccharide-stimulated macrophages than the parent compound. These newly generated hydroxymethylated flavanones can be potentially used for treating inflammatory diseases.

Label-free detection of single nanoparticles with disordered nanoisland surface plasmon sensor.

We report sensing of single nanoparticles using disordered metallic nanoisland substrates supporting surface plasmon polaritons (SPPs). Speckle patterns arising from leakage radiation of elastically scattered SPPs provide a unique fingerprint of the scattering microstructure at the sensor surface. Experimental measurements of the speckle decorrelation are presented and shown to enable detection of sorption of individual gold nanoparticles and polystyrene beads. Our approach is verified through bright-field and fluorescence imaging of particles adhering to the nanoisland substrate.

Urine-Derived Stem Cell-Secreted Klotho Plays a Crucial Role in the HK-2 Fibrosis Model by Inhibiting the TGF-ß Signaling Pathway.

Renal fibrosis is an irreversible and progressive process that causes severe dysfunction in chronic kidney disease (CKD). The progression of CKD stages is highly associated with a gradual reduction in serum Klotho levels. We focused on Klotho protein as a key therapeutic factor against CKD. Urine-derived stem cells (UDSCs) have been identified as a novel stem cell source for kidney regeneration and CKD treatment because of their kidney tissue-specific origin. However, the relationship between UDSCs and Klotho in the kidneys is not yet known. In this study, we discovered that UDSCs were stem cells that expressed Klotho protein more strongly than other mesenchymal stem cells (MSCs). UDSCs also suppressed fibrosis by inhibiting transforming growth factor (TGF)-ß in HK-2 human renal proximal tubule cells in an in vitro model. Klotho siRNA silencing reduced the TGF-inhibiting ability of UDSCs. Here, we suggest an alternative cell source that can overcome the limitations of MSCs through the synergetic effect of the origin specificity of UDSCs and the anti-fibrotic effect of Klotho.

Machine learning-based leaky momentum prediction of plasmonic random nanosubstrate.

In this work, we explore the use of machine learning for constructing the leakage radiation characteristics of the bright-field images of nanoislands from surface plasmon polariton based on the plasmonic random nanosubstrate. The leakage radiation refers to a leaky wave of surface plasmon polariton (SPP) modes through a dielectric substrate which has drawn interest due to its possibility of direct visualization and analysis of SPP propagation. A fast-learning two-layer neural network has been deployed to learn and predict the relationship between the leakage radiation characteristics and the bright-field images of nanoislands utilizing a limited number of training samples. The proposed learning framework is expected to significantly simplify the process of leaky radiation image construction without the need of sophisticated equipment. Moreover, a wide range of application extensions can be anticipated for the proposed image-to-image prediction.

Super-resolved Raman microscopy using random structured light illumination: Concept and feasibility.

In this article, we report the use of randomly structured light illumination for chemical imaging of molecular distribution based on Raman microscopy with improved image resolution. Random structured basis images generated from temporal and spectral characteristics of the measured Raman signatures were superposed to perform structured illumination microscopy (SIM) with the blind-SIM algorithm. For experimental validation, Raman signatures corresponding to Rhodamine 6G (R6G) in the waveband of 730-760 nm and Raman shift in the range of 1096-1634 cm-1 were extracted and reconstructed to build images of R6G. The results confirm improved image resolution using the concept and hints at super-resolution by almost twice better than the diffraction-limit.

Surface Plasmon Localization-Based Super-resolved Raman Microscopy.

We investigate label-free measurement of molecular distribution by super-resolved Raman microscopy using surface plasmon (SP) localization. Localized SP was formed with plasmonic nanopost arrays (PNAs) for measurement of the molecular distribution in HeLa cells. Compared with conventional Raman microscopy on gold thin films, PNAs induce a localized near-field, which allows for the enhancement of the peak signal-to-noise ratio by as much as 4.5 dB in the Raman shifts. Super-resolved distributions of aromatic amino acids and lipids (C-C stretching and C-H2 twist mode) as targets in HeLa cells were obtained after image reconstruction. Results show almost 4-fold improvement on average in the lateral precision over conventional diffraction-limited Raman microscopy images. Combined with axial imaging in an evanescent field, the results suggest an improvement in optical resolution due to superlocalized light volume by more than an order of magnitude over that of conventional diffraction-limited Raman microscopy.

Pharmacokinetic/Pharmacodynamic Modeling To Predict the Antiplatelet Effect of the Ticagrelor-Loaded Self-Microemulsifying Drug Delivery System in Rats.

Ticagrelor (TCG) has been used as an antiplatelet agent for acute coronary syndrome patients. The aim of this research was to establish a population pharmacokinetic/pharmacodynamic (PK/PD) model of TCG and to apply the model for predicting the PD response of the TCG-loaded self-microemulsifying drug delivery system (TCG-SME) in rats. Pure TCG and TCG-SME (2, 5, and 10 mg/kg of TCG) were orally administered to male Sprague-Dawley rats. Plasma samples were collected at scheduled time-points and then analyzed for TCG plasma concentrations and antiplatelet effects. The inhibition of platelet aggregation of TCG was measured as a PD response. The PK profiles of pure TCG and TCG-SME could be well-explained with a two-compartment PK model. The accuracy of the PK model was assessed with a goodness-of-fit plot and conditional weight residual error (CWRES). Also, the visual predictive check was investigated based on the predictions. A population PK/PD model for pure TCG was established as an indirect response Emax model linked to the two-compartment PK model of pure TCG. The PK/PD model proposed a suitable fitting to link the plasma concentration of TCG simultaneously with platelet aggregation. Based on the PK data of TCG-SME, as well as the established PK/PD model of pure TCG, the PD profiles of TCG-SME were simulated. TCG-SME was more effective in inducing the antiplatelet effect than pure TCG at equivalent doses of TCG. The accuracy of the simulation was verified by comparing the simulated PD profile with the profile observed in rats. The observations were close to the model simulations. In addition, the values of CWRES were almost within ±2. In conclusion, the PK/PD modeling approach can provide a way for predicting mathematically the PD responses from PK profiles of other TCG formulations and a conceptual prediction for future clinical assessment.

Consensus on Current Injectable Treatment Strategies in the Asian Face.

BACKGROUND: The desire for and use of nonsurgical injectable esthetic facial treatments are increasing in Asia. The structural and anatomical features specific to the Asian face, and differences from Western populations in facial aging, necessitate unique esthetic treatment strategies, but published recommendations and clinical evidence for injectable treatments in Asians are scarce. METHODS: The Asian Facial Aesthetics Expert Consensus Group met to discuss current practices and consensus opinions on the cosmetic use of botulinum toxin and hyaluronic acid (HA) fillers, alone and in combination, for facial applications in Southeastern and Eastern Asians. Consensus opinions and statements on treatment aims and current practice were developed following discussions regarding pre-meeting and meeting survey outcomes, peer-reviewed literature, and the experts' clinical experience. RESULTS: The indications and patterns of use of injectable treatments vary among patients of different ages, and among Asian countries. The combination use of botulinum toxin and fillers increases as patients age. Treatment aims in Asians and current practice regarding the use of botulinum toxin and HA fillers in the upper, middle, and lower face of patients aged 18 to[55 years are presented. CONCLUSIONS: In younger Asian patients, addressing proportion and structural features and deficiencies are important to achieve desired esthetic outcomes. In older patients, maintaining facial structure and volume and addressing lines and folds are essential to reduce the appearance of aging. This paper provides guidance on treatment strategies to address the complex esthetic requirements in Asian patients of all ages. LEVEL OF EVIDENCE V: This journal requires that the authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

An EGF- and Curcumin-Co-Encapsulated Nanostructured Lipid Carrier Accelerates Chronic-Wound Healing in Diabetic Rats.

Nanostructured lipid carriers (NLC) are capable of encapsulating hydrophilic and lipophilic drugs. The present study developed an NLC containing epidermal growth factor (EGF) and curcumin (EGF-Cur-NLC). EGF-Cur-NLC was prepared by a modified water-in-oil-in-water (w/o/w) double-emulsion method. The EGF-Cur-NLC particles showed an average diameter of 331.8 nm and a high encapsulation efficiency (81.1% and 99.4% for EGF and curcumin, respectively). In vitro cell studies were performed using two cell types, NIH 3T3 fibroblasts and HaCaT keratinocytes. The results showed no loss of bioactivity of EGF in the NLC formulation. In addition, EGF-Cur-NLC improved in vitro cell migration, which mimics the wound healing process. Finally, EGF-Cur-NLC was evaluated in a chronic wound model in diabetic rats. We found that EGF-Cur-NLC accelerated wound closure and increased the activity of antioxidant enzymes. Overall, these results reveal the potential of the NLC formulation containing EGF and curcumin to promote healing of chronic wounds.

Bioanalytical Method Development and Validation of Veratraldehyde and Its Metabolite Veratric Acid in Rat Plasma: An Application for a Pharmacokinetic Study.

A simple, sensitive, and rapid UHPLC-MS/MS method was developed for the simultaneous determination of veratraldehyde and its metabolite veratric acid in rat plasma. Cinnamaldehyde was used as an internal standard (IS) and the one-step protein precipitation method with 0.2% formic acid in acetonitrile (mobile phase B) was used for the sample extraction. Reversed C18 column (YMC-Triart C18 column, 50 mm × 2.0 mm, 1.9 µm) was used for chromatographic separation and was maintained at 30 °C. The total run time was 4.5 min and the electrospray ionization in positive mode was used with the transition m/z 167.07 → 139.00 for veratraldehyde, m/z 183.07 → 139.00 for veratric acid, and m/z 133.00 → 55.00 for IS. The developed method exhibited good linearity (r2 ≥ 0.9977), and the lower limits of quantification ranged from 3 to 10 ng/mL for the two analytes. Intra-day precision and accuracy parameters met the criteria (within ±15%) during the validation. The bioanalytical method was applied for the determination of veratraldehyde and veratric acid in rat plasma after oral and percutaneous administration of 300 and 600 mg/kg veratraldehyde. Using the analytical methods established in this study, we can confirm the absorption and metabolism of veratraldehyde in rats for various routes.

Deep Learning Approach for Enhanced Detection of Surface Plasmon Scattering.

A deep learning approach has been taken to improve detection characteristics of surface plasmon microscopy (SPM) of light scattering. Deep learning based on the convolutional neural network algorithm was used to estimate the effect of scattering parameters, mainly the number of scatterers. The improvement was assessed on a quantitative basis by applying the approach to SPM images formed by coherent interference of scatterers. It was found that deep learning significantly improves the accuracy over conventional detection: the enhancement in the accuracy was shown to be significantly higher by almost 6 times and useful for scattering by polydisperse mixtures. This suggests that deep learning can be used to find scattering objects effectively in the noisy environment. Furthermore, deep learning can be extended directly to label-free molecular detection assays and provide considerably improved detection in imaging and microscopy techniques.

Experimental confirmation of plasmonic field cancellation under specific conditions of trapezoidal nanopatterns.

In this study, we investigated plasmonic field localization with trapezoidal nanopatterns under normal incident light excitation to find optimum structures for sensing and imaging. A finite element method was used to calculate the fundamental characteristics of the localized surface plasmon with varied trapezoidal nanopatterns. First, we describe how to localize the plasmonic fields on the trapezoidal patterns and then report our results from the investigation of the optimum properties of the nanopatterns for maximized field intensity. Initially, we expected that maximized field localization would lead to enhancement of the sensing sensitivity or imaging resolution in plasmon-based sensing and imaging systems. However, more interestingly, we found a field cancellation effect under specific modality conditions through the simulation. Thus, we thoroughly investigated the principle of the effect and extracted the modality conditions that induced field cancellation. In addition, specific modality conditions of nanopatterns that could be fabricated with conventional lithographic methods were numerically determined. Then, the field cancellation effect was experimentally verified using scanning nearfield optical microscopy. The results indicate that trapezoidal nanopatterns bring about enhanced field localization at the shaper edge of nanopatterns than do conventional rectangular nanopatterns and that plasmonic field cancellation can be observed under specific modality conditions of nanopatterns, even for conventional rectangular nanopatterns. Thus, it is suggested that careful fabrication and maintenance are needed to obtain strong plasmonic localization. Finally, the feasibility of providing a novel sensing platform using the field cancellation effect is suggested.

Hybrid polymeric microspheres for enhancing the encapsulation of phenylethyl resorcinol.

Phenylethyl resorcinol (PR) has been known to allow the whitening effect by inhibiting formation of tyrosinase. PR has solubility of 4.05 ± 0.02 mg/g for water and log P of 3.017, proposed an amphiphilic substance. Hybrid PLGA microspheres with oil (HPMSs) have been used to improve encapsulation efficiency (EE) of hydrophilic molecules and control the release of them. The solubility (618.3 ± 22.29 mg/g) of PR was the highest in CapryolTM 90. The formulations (F6 and F`6) were selected after evaluation with EE and the released % (w/w) at 8 h. HPMSs showed 40% (w/w) increase of EE compared to that in CPMSs. Retention study on rat skin at 12 h resulted in that PR of HPMSs was remained more than that of CPMSs in dermal layer forming the melanin. HPMSs showed 1.4-fold increase of tyrosinase inhibition significantly in melanoma cells than that of the PR solution at 24 h.

PCGF2 negatively regulates arsenic trioxide-induced PML-RARA protein degradation via UBE2I inhibition in NB4 cells.

Arsenic trioxide (ATO) is a therapeutic agent for acute promyelocytic leukemia (APL) which induces PML-RARA protein degradation via enhanced UBE2I-mediated sumoylation. PCGF2, a Polycomb group protein, has been suggested as an anti-SUMO E3 protein by inhibiting the sumoylation of UBE2I substrates, HSF2 and RANGAP1, via direct interaction. Thus, we hypothesized that PCGF2 might play a role in ATO-induced PML-RARA degradation by interacting with UBE2I. PCGF2 protein was down-regulated upon ATO treatment in human APL cell line, NB4. Knockdown of PCGF2 in NB4 cells, in the absence of ATO treatment, was sufficient to induce sumoylation-, ubiquitylation- and PML nuclear body-mediated degradation of PML-RARA protein. Moreover, overexpression of PCGF2 protected ATO-mediated degradation of ectopic and endogenous PML-RARA in 293T and NB4 cells, respectively. In 293T cells, UBE2I-mediated PML-RARA degradation was reduced upon PCGF2 co-expression. In addition, UBE2I-mediated sumoylation of PML-RARA was reduced upon PCGF2 co-expression and PCGF2-UBE2I interaction was confirmed by co-immunoprecipitation. Likewise, endogenous PCGF2-UBE2I interaction was detected by co-immunoprecipitation and immunofluorescence assays in NB4 cells. Intriguingly, upon ATO-treatment, such interaction was disrupted and UBE2I was co-immunoprecipitated or co-localized with its SUMO substrate, PML-RARA. Taken together, our results suggested a novel role of PCGF2 in ATO-mediated degradation of PML-RARA that PCGF2 might act as a negative regulator of UBE2I via direct interaction.

Consensus on Current Injectable Treatment Strategies in the Asian Face.

BACKGROUND: The desire for and use of nonsurgical injectable esthetic facial treatments are increasing in Asia. The structural and anatomical features specific to the Asian face, and differences from Western populations in facial aging, necessitate unique esthetic treatment strategies, but published recommendations and clinical evidence for injectable treatments in Asians are scarce. METHOD: The Asian Facial Aesthetics Expert Consensus Group met to discuss current practices and consensus opinions on the cosmetic use of botulinum toxin and hyaluronic acid (HA) fillers, alone and in combination, for facial applications in Southeastern and Eastern Asians. Consensus opinions and statements on treatment aims and current practice were developed following discussions regarding pre-meeting and meeting survey outcomes, peer-reviewed literature, and the experts' clinical experience. RESULTS: The indications and patterns of use of injectable treatments vary among patients of different ages, and among Asian countries. The combination use of botulinum toxin and fillers increases as patients age. Treatment aims in Asians and current practice regarding the use of botulinum toxin and HA fillers in the upper, middle, and lower face of patients aged 18 to >55 years are presented. CONCLUSIONS: In younger Asian patients, addressing proportion and structural features and deficiencies are important to achieve desired esthetic outcomes. In older patients, maintaining facial structure and volume and addressing lines and folds are essential to reduce the appearance of aging. This paper provides guidance on treatment strategies to address the complex esthetic requirements in Asian patients of all ages. LEVEL OF EVIDENCE V: This journal requires that the authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Anatomical and histological study of the arterial distribution in the columellar area, and the clinical implications.

PURPOSE: The aim of this study was to elucidate the distribution of the columellar artery (CoA) in the mobile nasal septum by means of detailed dissection and histological observation. METHODS: Fifteen Korean cadavers were examined; five specimens were dissected to observe the ramification pattern of the CoA from the superior labial artery (SLA), and the noses of ten specimens were quick-frozen in isopropanol cooled with liquid nitrogen and then cryosectioned at a thickness of 40 µm. RESULTS: The arterial vasculature of the CoA in the columella was supplied by the SLA and entered the columella via the columellolabial junction. The vessels of the CoA proceeded anteriorly, inferior to the medial crus of the lower lateral cartilage (MC) at the midline, at the basal and posterior portions of the septum. The vessels traveled closer to the MC than the epidermis. There were very few vessels in the area between the left and right MCs, which was usually packed only with loose connective tissue. More anteriorly, there were more abundant vessels between the MC and the epidermis, with a dispersed distribution. In axial sections, multiple vessels were dispersed in front of the MC, with the pattern varying among the specimens. Furthermore, tiny vessels were also detected in the vicinity of the septal cartilage posterior to the MC. The microdistribution near to the MC was almost consistent. CONCLUSION: The anatomical findings of the CoA in this study will be useful for safe manipulations during various medical interventions in the columella.

Development of in vitro model of exosome transport in microfluidic gut-brain axis-on-a-chip.

The gut communicates with the brain in a variety of ways known as the gut-brain axis (GBA), which is known to affect neurophysiological functions as well as neuronal disorders. Exosomes capable of passing through the blood-brain-barrier (BBB) have received attention as a mediator of gut-brain signaling and drug delivery vehicles. In conventional well plate-based experiments, it is difficult to observe the exosome movement in real time. Here, we developed a microfluidic-based GBA chip for co-culturing gut epithelial cells and neuronal cells and simultaneously observing exosome transport. The GBA-chip is aimed to mimic the in vivo situation of convective flow in blood vessels and convective and diffusive transport in the tissue interstitium. Here, fluorescence-labeled exosome was produced by transfection of HEK-293T cells with CD63-GFP plasmid. We observed in real time the secretion of CD63-GFP-exosomes by the transfected HEK-293T cells in the chip, and transport of the exosomes to neuronal cells and analyzed the dynamics of GFP-exosome movement. Our model is expected to enhance understanding of the roles of exosome in GBA.

Super resolution label-free dark-field microscopy by deep learning.

Dark-field microscopy (DFM) is a powerful label-free and high-contrast imaging technique due to its ability to reveal features of transparent specimens with inhomogeneities. However, owing to the Abbe's diffraction limit, fine structures at sub-wavelength scale are difficult to resolve. In this work, we report a single image super resolution DFM scheme using a convolutional neural network (CNN). A U-net based CNN is trained with a dataset which is numerically simulated based on the forward physical model of the DFM. The forward physical model described by the parameters of the imaging setup connects the object ground truths and dark field images. With the trained network, we demonstrate super resolution dark field imaging of various test samples with twice resolution improvement. Our technique illustrates a promising deep learning approach to double the resolution of DFM without any hardware modification.

Fabrication and evaluation of chitosan-coated nanostructured lipid carriers for co-delivery of paclitaxel and PD-L1 siRNA.

This study aimed to develop a nanostructured lipid carrier (NLC) capable of co-delivering paclitaxel (PTX) and programmed death-ligand 1 (PD-L1) small interfering RNA (siRNA) to enhance PTX bioavailability and bolster immunity through PD-L1 knockdown. We prepared a PTX-loaded NLC (P-NLC) and coated it with positively charged chitosan (Chi) to create P-NLC-Chi, which was subsequently conjugated to siRNA (P-NLC-Chi-siRNA). The P-NLC-Chi formulation was optimized using the Box-Behnken design. P-NLC-Chi measured 123.8 ± 0.52 nm (zeta potential, 22.71 ± 0.49 mV). By verifying the gel retardation assay and observing changes in the zeta potential, the optimal binding ratio of NLC to PD-L1 siRNA was identified as 50:1. The P-NLC-Chi-siRNA particle size was 181.97 ± 0.67 nm, with a zeta potential of 18.66 ± 0.23 mV. siRNA stability was observed in serum over a 24-h period. Enhanced cytotoxicity and intracellular uptake of the complex were evident in breast cancer cells and breast cancer-resistant cells (MCF-7 and MCF-7/ADR cells, respectively). Evaluation of P-glycoprotein-mediated efflux demonstrated that NLC mitigated drug efflux in MCF-7/ADR cells. Subcutaneous injection of P-NLC-Chi-siRNA into tumor-bearing BALB/c nude mice injected with MCF-7/ADR cells revealed a reduction in tumor size. In vitro and in vivo experiments indicated a significant reduction in PD-L1 mRNA expression levels. Additionally, an in vivo study revealed tumor-specific CD4 + and CD8 + T cell responses within the tumor tissue following the injection of P-NLC-Chi-siRNA. Our findings suggest that Chi-coated NLC for the co-delivery of PTX and PD-L1 siRNA has great potential as an innovative delivery system for chemoimmunotherapy.