Inkjet-Printed Bio-Based Melanin Composite Humidity Sensor for Sustainable Electronics.

A lack of sustainability in the design of electronic components contributes to the current challenges of electronic waste and material sourcing. Common materials for electronics are prone to environmental, economic, and ethical problems in their sourcing, and at the end of their life often contribute to toxic and nonrecyclable waste. This study investigates the inkjet printing of flexible humidity sensors and includes biosourced and biodegradable materials to improve the sustainability of the process. Humidity sensors are useful tools for monitoring atmospheric conditions in various fields. Here, an aqueous dispersion of black soldier fly melanin was optimized for printing with a cosolvent and deposited onto interdigitated silver electrodes on flexible substrates. Impedance spectroscopy demonstrated that adding choline chloride increased the ion concentration and AC conductivity by more than 3 orders of magnitude, resulting in a significant improvement in sensing performance and reduced hysteresis. The devices exhibit fast detection (0.8 ± 0.5 s) and recovery times (0.8 ± 0.3 s), with a 170 ± 40-fold decrease in impedance for relative humidity changes from 30% to 90%. This factor is lowered upon prolonged exposure to high humidity in tests over 72 h during which a stable operation is reached. The low embodied energy of the sensor, achieved through material-efficient deposition and the use of waste management byproducts, enhances its sustainability. In addition, approaches for reusability and degradability are presented, rendering the sensor suitable for wearable or agricultural applications.

Prevalence of Metabolic Syndrome in Vitiligo Patients and its Relation to Vitiligo Severity - A Cross-Sectional Study.

Background: In vitiligo, there is a significant decrease in melanocytes and melanin. The decrease in melanin causes oxidative stress, with a chance of causing metabolic syndrome. Hence, there is a need to look for metabolic syndrome in vitiligo. Aim and Objectives: To estimate the prevalence of metabolic syndrome in vitiligo patients and to evaluate the relationship between the severity and progression of vitiligo and metabolic syndrome. Materials and Methods: A hospital-based cross-sectional study was conducted on 178 vitiligo cases and 178 controls who were age- and sex-matched. The type of vitiligo, stability by vitiligo disease activity score (VIDA), and severity by vitiligo area severity index (VASI) were noted. The waist circumference, blood pressure, fasting lipid profile, and fasting blood sugar were measured for cases and controls. Metabolic syndrome was diagnosed based on Harmonization Asian criteria. Results: The mean age in cases was 34.38 years, and in controls, it was 35.67 years. The majority were females in both cases (52.2%) and controls (55.6%). Most have a VIDA score of 2+ (41.6%). The mean VASI score was 2.54. The percentage of metabolic syndrome was higher in cases (36%) compared to controls (24.2%) (P = 0.015). The mean age was lower in vitiligo cases with metabolic syndrome (38.83 years) compared to controls with metabolic syndrome (43.14 years). Metabolic syndrome was more frequent in the vitiligo vulgaris type (48.9%) than in acral and segmental vitiligo. Metabolic syndrome was more common in patients with high VIDA (45%) and VASI (52.3%) scores compared to patients with low VIDA (25%) and VASI (27.3%) scores. Limitation: It is a hospital-based study, so controls were not from the general population. Conclusion: The prevalence of metabolic syndrome was higher in vitiligo patients compared to controls, and it was higher in patients with active and severe disease. Screening and close monitoring of vitiligo patients help in the early diagnosis of metabolic syndrome and reduce the risk of cardiovascular disease.

Exploring monocyclic core: Discovery of pyrrol-2-one derivatives as a new series of potent MCHR1 antagonists with in vivo efficacy.

With an objective to improve the profiles of the 1st generation non-basic MCHR1 antagonists, a lean design approach of replacing the bicyclic thienopyrimidine core with a monocyclic pyrrol-2-one chemotype was examined in the context of reducing aromatic ring count, while also contemplating enhanced flexibility as a means of decreasing flat character. The new compounds exhibited potent antagonism up to the sub-nanomolar range, thereby implying that the monocyclic ring could effectively serve as an effective bioisostere of the bicyclic system. The prototype compound 2m offered benefits like improved potency, reduced half-life, and enhanced solubility, while also demonstrating >5% reduction in weight gain in rats, thereby providing proof-of-concept for this new class of compounds as anti-obesity agents.

Comparison between clinical and computerized methods for assessing gingival pigmentation.

Background and Objective: Digital computerized assessment can provide objective values for the measurement of gingival pigmentation. This study aims to compare the Commission Internationale de l'Eclairage Lab color space (CIELAB) values and the computerized intensity values (CIVs) from digital imaging with clinical evaluations using the Dummett-Gupta Oral Pigmentation Index (DOPI) for assessing gingival pigmentation in a multi-ethnic population. Methodology: Digital photographs of 188 participants were taken using standardized parameters. The buccal gingival pigmentation was evaluated using three methods (a) a clinical evaluation by two independent assessors using the DOPI, (b) the CIELAB values using the Adobe Photoshop® software (Version 23.1.1) and (c) the CIV calculated using the ImageJ software (Version 1.53k). A hierarchical clustering analysis was used to identify colour groups that clustered together. Agreement between the clinical and digital categorization of the pigmentation was carried out using weighted kappa analysis. Agreements between CIELAB and CIV were compared using intra-class correlation coefficient. Results: There was a statistically significant difference in the DOPI, the L*, a*, and b* coordinates, and the CIV between the different ethnic groups of the participants. Cluster analysis for the CIELAB and CIV both identified four clusters. The gingival pigmentation categorization using the L*, a*, and b* values moderately agreed with the clinical evaluation using the DOPI index while the categorization with the CIV was in slight agreement with the clinical evaluations. Conclusion: This study identified four clusters of gingival pigmentation in 188 multi-ethnic participants. The clusters, determined by CIELAB values, align with the clinical assessment of gingival pigmentation. Digital measurements derived from clinical photographs can serve as an effective means of pigmentation measurement in dental clinics.

Bioinspired Three-Component System to Prepare Full-Color Functional Biomimetic Pigments.

Nature provides a great source of inspiration for the development of sustainable materials with excellent properties, among which melanin with optical, electronic, and radiation protection properties are considered to be promising coloring materials. However, compared to chemical pigments, the single color, complex oxidation process, and poor solubility of natural melanin strongly limit their further applications. Here, we introduce a series of melanin-like polymeric pigments with amino acid-encoded physicochemical properties by a simple three-component reaction system. Our protocol enables artificial control of the chromophore structures through the rational design of the substrates and dopants, thereby combining the safety and functionality of biopigments with the color richness of chemical dyes. Similar to the photoprotective effect of natural melanin, the polymeric pigments showed excellent antioxidant activity in reducing free radicals and have the advantages of iridescent color, strong tinting strength, stability, and affordability. Furthermore, due to their ability to dye substrates, these biomimetic are expected to become new low-cost bioactive chromophores and find various biochemical applications such as in clothing and hair dyeing, food addition, and anticounterfeiting detection.

Gingivectomy-Gingivoplasty for Oral Physiological Melanosis Depigmentation: A Case Report Involving Human Papillomavirus.

Gingiva hyperpigmentation resulting from physiological melanosis causes aesthetic discomfort and is usually perceived as a disease by patients because healthy attached gingiva is typically characterized by coral pink coloring with stippling and scalloped contours. When physiological melanosis compromises the aesthetics of smiling, it may induce insecurity in patients, who usually seek out alternatives for reducing or eliminating hyperpigmentation. We present a case report of a surgical procedure combining gingivectomy with gingivoplasty for the management of physiological melanosis. The surgical procedure was performed on a 40-year-old female patient with bilateral pigmentation in both arches. The results of the histological analysis confirm the diagnoses of melanotic macula, with papillary hyperplasia and cytopathic changes being suggestive of HPV infection, which was verified using an immunohistochemistry analysis based on the detection of a major capsid protein of HPV. Acceptable functional and aesthetic results were obtained for the patient without major discomfort during the postoperative period. In cases when HPV infection is present, long-term follow-up becomes necessary.

Identification of candidate genes associated with primary feathers of tianfu nonghua ducks based on Genome-wide association studies.

The primary feathers of ducks have important economic value in the poultry industry. This study quantified the primary feather phenotype of Nonghua ducks, including the primary feathers' length, area, distribution of black spots, and feather symmetry. And genome-wide association analysis was used to screen candidate genes that affect the primary feather traits. The genome-wide association study (GWAS) results identified the genetic region related to feather length (FL) on chromosome 2. Through Linkage disequilibrium (LD) analysis, candidate regions (chr2: 115,246,393-116,501,448 bp) were identified and were further annotated to 5 genes: MRS2, GPLD1, ALDH5A1, KIAA0319, and ATP9B. Secondly, candidate regions related to feather black spots were identified on chromosome 21. Through LD analysis, the candidate regions (chr21: 163,552-2,183,853 bp) were screened and further annotated to 47 genes. Among them, STK4, CCN5, and YWHAB genes were related to melanin-related pathways or pigment deposition, which may be key genes affecting the distribution of black spots on feathers. In addition, we also screened 125 genes on multiple chromosomes that may be related to feather symmetry. Among them, significant SNPs on chromosome 1 were further identified as candidate regions (chr1: 142,118,209-142,223,605 bp) through LD analysis and annotated into 2 genes, TGFBRAP1 and LOC113839965. These results reported the genetic basis of the primary feather from multiple phenotypes, and offered valuable insights into the genetic basis for the growth and development of duck feathers and feather color pattern.

Electrospun fibrillary scaffold for electrochemical cell biomarkers detection.

A novel scaffold for in situ electrochemical detection of cell biomarkers was developed using electrospun nanofibers and commercial adhesive polymeric membranes. The electrochemical sensing of cell biomarkers requires the cultivation of the cells on/near the (bio)sensor surface in a manner to preserve an appropriate electroactive available surface and to avoid the surface passivation and sensor damage. This can be achieved by employing biocompatible nanofiber meshes that allow the cells to have a normal behavior and do not alter the electrochemical detection. For a better mechanical stability and ease of handling, nylon 6/6 nanofibers were collected on commercial polymeric membranes, at an optimal fiber density, obtaining a double-layered platform. To demonstrate the functionality of the fabricated scaffold, the screening of cellular stress has been achieved integrating melanoma B16-F10 cells and the (bio)sensor components on the transducer whereas the melanin exocytosis was successfully quantified using a commercial electrode. Either directly on the surface of the (bio)sensor or spatially detached from it, the integration of cell cultures in biosensing platforms based on electrospun nanofibers represents a powerful bioanalytical tool able to provide real-time information about the biomarker release, enzyme activity or inhibition, and monitoring of various cellular events.

Preparation and Evaluation of Nanoemulsion Formulation Containing Kojic Acid and Kojyl 3-aminopropylphosphonic Acid.

BACKGROUND: The kojyl 3-aminopropylphosphonic acid (KAP) was synthesized by kojic acid (KA) with a 3-aminopropylphosphonic acid. Which is more stable than KA and showed better skin penetration and anti-pigmentation efficacy in melanocytes. However, up till now, there have been no studies aimed at incorporating KAP into an emulsion system and evaluating its effectiveness. OBJECTIVE: We develop a novel skin-lightening agent using KAP as the active ingredient and a low-cytotoxic nanoemulsion as the delivery system in this study. METHOD: The sorbitan monooleate and polysorbate surfactants with polyethylene glycol (PEG) co-surfactant were used to generate a nanoemulsion system. RESULT: The transparency and particle size stability over various storage times indicate that the formulated nanoemulsions are suitable for long-term storage. Besides, results demonstrate that the anti-pigmentation function of KA and KAP-containing nanoemulsions (NE-KA and NEKAP) evidently outperformed that of the non-packed KA and KAP group. Despite having the lowest concentration among other treatments, NE-KAP was able to reduce melanin content to approximately 80% of the blank. CONCLUSION: Our findings suggest that this newly developed nanoemulsion containing KAP could potentially serve as a sustainable alternative to hydroquinone for treating dermal hyperpigmentation disorders in future applications.

Melanized root-associated fungi: key players in plant-soil systems.

Melanized root-associated fungi are a group of fungi that produce melanized structures and form root associations, including different mycorrhizal and endophytic symbioses with plants. They are pervasive across terrestrial ecosystems and play an important role in the prevailing soil carbon (C) and nutrient cycling syndromes through direct and indirect mechanisms, where they may strongly modulate plant-microbe interactions and structure root and soil microbiomes. Furthermore, melanized root-associated fungi can confer on plants an enhanced ability to tolerate abiotic and biotic stressors such as drought, extreme temperatures, heavy metals, and pathogen attacks. We propose that melanized root-associated fungi are a cohesive and ecologically relevant grouping that can be an indicator of plant-soil system functioning, and considering them will advance research on plant-soil interactions.

Exosomes Derived from Hypertrophic Scar Fibroblasts Suppress Melanogenesis in Normal Human Epidermal Melanocytes.

Post-burn hypertrophic scars often exhibit abnormal pigmentation. Exosomes play important roles in maintaining normal physiological homeostasis and in the pathological development of diseases. This study investigated the effects of the exosomes derived from hypertrophic scar fibroblasts (HTSFs) on melanocytes, which are pigment-producing cells. Normal fibroblasts (NFs) and HTSFs were isolated and cultured from normal skin and hypertrophic scar (HTS) tissue. Both the NF- and HTSF-exosomes were isolated from a cell culture medium and purified using a column-based technique. The normal human epidermal melanocytes were treated with both exosomes at a concentration of 100 µg/mL at different times. The cell proliferation, melanin content in the medium, apoptotic factors, transcription factors, melanin synthesis enzymes, signaling, signal transduction pathways, and activators of transcription factors (STAT) 1, 3, 5, and 6 were investigated. Compared with the Dulbecco's phosphate-buffered saline (DPBS)-treated controls and NF-exosomes, the HTSF-exosomes decreased the melanocyte proliferation and melanin secretion. The molecular patterns of apoptosis, proliferation, melanin synthesis, Smad and non-Smad signaling, and STATs were altered by the treatment with the HTSF-exosomes. No significant differences were observed between the DPBS-treated control and NF-exosome-treated cells. HTSF-derived exosomes may play a role in the pathological epidermal hypopigmentation observed in patients with HTS.

Anti-IgG Doped Melanin Nanoparticles Functionalized Quartz Tuning Fork Immunosensors for Immunoglobulin G Detection: In Vitro and In Silico Study.

The quartz tuning fork (QTF) is a promising instrument for biosensor applications due to its advanced properties such as high sensitivity to physical quantities, cost-effectiveness, frequency stability, and high-quality factor. Nevertheless, the fork's small size and difficulty in modifying the prongs' surfaces limit its wide use in experimental research. Our study presents the development of a QTF immunosensor composed of three active layers: biocompatible natural melanin nanoparticles (MNPs), glutaraldehyde (GLU), and anti-IgG layers, for the detection of immunoglobulin G (IgG). Frequency shifts of QTFs after MNP functionalization, GLU activation, and anti-IgG immobilization were measured with an Asensis QTF F-master device. Using QTF immunosensors that had been modified under optimum conditions, the performance of QTF immunosensors for IgG detection was evaluated. Accordingly, a finite element method (FEM)-based model was produced using the COMSOL Multiphysics software program (COMSOL License No. 2102058) to simulate the effect of deposited layers on the QTF resonance frequency. The experimental results, which demonstrated shifts in frequency with each layer during QTF surface functionalization, corroborated the simulation model predictions. A modelling error of 0.05% was observed for the MNP-functionalized QTF biosensor compared to experimental findings. This study validated a simulation model that demonstrates the advantages of a simulation-based approach to optimize QTF biosensors, thereby reducing the need for extensive laboratory work.

Differential Diagnosis of Pigmented Lesions in the Oral Mucosa: A Clinical Based Overview and Narrative Review.

This paper examines the clinical differentiation of pigmented lesions in the oral mucosa, which poses significant diagnostic challenges across dental and medical disciplines due to their spectrum from benign to potentially malignant conditions. Through a literature review and analysis of clinical cases, this study clarifies current diagnostic methodologies, with an emphasis on differential diagnosis, to provide a practical guide for clinicians. The classification of pigmented lesions, such as endogenous, focal melanocytic, and multifocal pigmentation, based on clinical and histological features, highlights the necessity for a structured and informed approach. A retrospective examination of cases from our oral medicine and pathology clinic, coupled with analysis of photographic and histological records, aids in classifying these lesions. This fosters a better understanding and promotes informed discussions among clinicians, ultimately aiming to enhance early and precise diagnosis, thus improving patient management and outcomes.

Bio-inspired multifunctional and reusable LiP@MFO-GO and LiP@MFO-Chit hybrid enzyme complexes for efficient degradation of melanin.

Melanin is a complex brown pigment, primarily responsible for the skin pigmentation. Therefore, cosmetic industries have always been in search of potent oxidative enzymes useful for melanin degradation, and to promise a fair complexion after using their products. In the present study, lignin peroxidase from Pseudomonas fluorescence LiP-RL5 isolate has been immobilized on super-paramagnetic nanoparticles to enhance its stability and reusability. The chitosan coated enzyme-nanomaterial complex (LiP@MFO-Chit) showed higher melanin decolorization (47.30 ± 2.3 %) compared to the graphene oxide coated nanoparticles (LiP@MFO-GO) (41.60 ± 1.6 %). Synthesized enzyme nanoparticle complexes showed microbicidal effect on skin infection causing pathogen, Pantoea agglomerans with an inhibitory zone of 6.0 ± 0.9 mm and 250 µg/100 µl minimum inhibitory concentration, and a 7.0 ± 1.5 mm zone and 170 µg/100 µl MIC for LiP@MFO-GO and LiP@MFO-Chit, respectively. Antioxidant potential of LiP@MFO-Chit and LiP@MFO-GO nano-conjugates showed a substantial DPPH scavenging activity of 75.7 % and 88.3 %, respectively. Therefore, LiP-nanoparticle hybrid complexes analyzed in this study are not only effective as skin whitening agents but they are potential molecules against various microbial skin infections as well as useful for different other biomedical applications like biorefinery, drug delivery, and dermatology, etc.

Occurrence and persistence of pseudo-tail spots in the barn swallow.

While numerous studies have confirmed sexual selection for ornamental traits in animals, it remains unclear about how animals exaggerate ornamentation across traits. I found that some Asian barn swallows Hirundo rustica gutturalis possessed "pseudo-tail spots" on their undertail coverts adjacent to a well-known sexual signal, the white tail spots. A close inspection showed their remarkable resemblance, and, as a consequence, pseudo-tail spots appear to add white spots to the uniformly black central tail feathers, increasing the total number and area of white spots when spread tails are viewed from below. Pseudo-tail spots on the undertail covers do not incur any flight cost, unlike the white tail spots on the tail itself, and thus presence of pseudo-tail spots can represent an initial stage of a deceptive elaboration as predicted by sexual selection theory (i.e., males can elaborate traits with no additional flight cost, uncoupling flight cost and trait expression). The frequency of pseudo-tail spots in the study population remained low even a decade after the first observation (ca. 7%), but was higher compared to other populations (e.g., 1% in another Japanese population). The slow progress of evolution, perhaps due to the low detectability of the trait, provides a unique opportunity to observe contemporary evolution of ornament exaggeration across traits. Further research with wider spatial and temporal coverage is needed to better understand the evolutionary and ecological importance of the trait.

Precise Serial Microregistration Enables Quantitative Microscopy Imaging Tracking of Human Skin Cells In Vivo.

We developed an automated microregistration method that enables repeated in vivo skin microscopy imaging of the same tissue microlocation and specific cells over a long period of days and weeks with unprecedented precision. Applying this method in conjunction with an in vivo multimodality multiphoton microscope, the behavior of human skin cells such as cell proliferation, melanin upward migration, blood flow dynamics, and epidermal thickness adaptation can be recorded over time, facilitating quantitative cellular dynamics analysis. We demonstrated the usefulness of this method in a skin biology study by successfully monitoring skin cellular responses for a period of two weeks following an acute exposure to ultraviolet light.

Investigation of the influence of pH and temperature on melanization and survival under oxidative stress in Cryptococcus neoformans.

Cryptococcus neoformans is an opportunistic pathogenic fungus that produces melanin during infection, an important virulence factor in Cryptococcal infections that enhances the ability of the fungus to resist immune defense. This fungus can synthesize melanin from a variety of substrates, including L-DOPA (L-3,4-dihydroxyphenylalanine). Since melanin protects the fungus from various stress factors such as oxidative, nitrosative, extreme heat and cold stress; we investigated the effects of environmental conditions on melanin production and survival. In this study, we investigated the effects of different pH values (5.6, 7.0 and 8.5) and temperatures (30 °C and 37 °C) on melanization and cell survival using a microtiter plate-based melanin production assay and an oxidative stress assay, respectively. In addition, the efficacy of compounds known to inhibit laccase involved in melanin synthesis, i.e., tunicamycin, ß-mercaptoethanol, dithiothreitol, sodium azide and caspofungin on melanization was evaluated and their sensitivity to temperature and pH changes was measured. The results showed that melanin content correlated with pH and temperature changes and that pH 8.5 and 30 °C, were best for melanin production. Besides that, melanin production protects the fungal cells from oxidative stress induced by hydrogen peroxide. Thus, changes in pH and temperature drastically alter melanin production in C. neoformans and it correlates with the fungal survival. Due to the limited antifungal repertoire and the development of resistance in cryptococcal infections, the investigation of environmental conditions in the regulation of melanization and survival of C. neoformans could be useful for future research and clinical phasing.

Melanin-Based Nanoparticles for Lymph Node Tattooing: Experimental, Histopathological and Ultrastructural Study.

In breast cancer, Targeted Axillary Dissection (TAD) allows for the selective excision of the sentinel lymph node (SLN) during primary tumor surgery. TAD consists of the resection of labelled SLNs prior to neoadjuvant chemotherapy (NACT). Numerous clinical and preclinical studies have explored the use of carbon-based colloids for SLN tattooing prior to NACT. However, carbon vectors show varying degrees of inflammatory reactions and, in about one fifth of cases, carbon particles migrate via the lymphatic pathway to other nodes, causing the SLN to mismatch the tattooed node. To overcome these limitations, in this study, we explored the use of melanin as a staining endogenous pigment. We synthesized and characterized melanin-loaded polymeric nanoparticles (Mel-NPs) and used them to tattoo lymph nodes in pig animal models given the similarity in the size of the human and pig nodes. Mel-NPs tattooed lymph nodes showed high identification rates, reaching 83.3% positive identification 16 weeks after tattooing. We did not observe any reduction in the identification as time increased, implying that the colloid is stable in the lymph node tissue. In addition, we performed histological and ultrastructural studies to characterize the biological behavior of the tag. We observed foreign-body-like granulomatous inflammatory responses associated with Mel-NPs, characterized by the formation of multinucleated giant cells. In addition, electron microscopy studies showed that uptake is mainly performed by macrophages, and that macrophages undergo cellular damage associated with particle uptake.

Deletion of the polyketide synthase-encoding gene pks1 prevents melanization in the extremophilic fungus Cryomyces antarcticus.

Cryomyces antarcticus, a melanized cryptoendolithic fungus endemic to Antarctica, can tolerate environmental conditions as severe as those in space. Particularly, its ability to withstand ionizing radiation has been attributed to the presence of thick and highly melanized cell walls, which-according to a previous investigation-may contain both 1,8-dihydroxynaphthalene (DHN) and L-3,4 dihydroxyphenylalanine (L-DOPA) melanin. The genes putatively involved in the synthesis of DHN melanin were identified in the genome of C. antarcticus. Most important is capks1 encoding a non-reducing polyketide synthase (PKS) and being the ortholog of the functionally characterized kppks1 from the rock-inhabiting fungus Knufia petricola. The co-expression of CaPKS1 or KpPKS1 with a 4'-phosphopantetheinyl transferase in Saccharomyces cerevisiae resulted in the formation of a yellowish pigment, suggesting that CaPKS1 is the enzyme providing the precursor for DHN melanin. To dissect the composition and function of the melanin layer in the outer cell wall of C. antarcticus, non-melanized mutants were generated by CRISPR/Cas9-mediated genome editing. Notwithstanding its slow growth (up to months), three independent non-melanized Δcapks1 mutants were obtained. The mutants exhibited growth similar to the wild type and a light pinkish pigmentation, which is presumably due to carotenoids. Interestingly, visible light had an adverse effect on growth of both melanized wild-type and non-melanized Δcapks1 strains. Further evidence that light can pass the melanized cell walls derives from a mutant expressing a H2B-GFP fusion protein, which can be detected by fluorescence microscopy. In conclusion, the study reports on the first genetic manipulation of C. antarcticus, resulting in non-melanized mutants and demonstrating that the melanin is rather of the DHN type. These mutants will allow to elucidate the relevance of melanization for surviving extreme conditions found in the natural habitat as well as in space.