Three-dimensional shape of natural riblets in the white shark: relationship between the denticle morphology and swimming speed of sharks.

The ridges of the dermal denticles of migratory sharks have inspired riblets to reduce the frictional drag of a fluid. In particular, the dermal denticles of white sharks (Carcharodon carcharias) are characterized by a high middle ridge and low side ridges. The detailed morphology of their denticles and their variation along the body, however, have never been investigated. Moreover, the hydrodynamic function of high-low combinations of ridges is unknown. In this article, the ridge spacings and heights of the white shark denticles were three-dimensionally quantified using microfocus X-ray computed tomography. Then, the swimming speed at which the ridges would reduce drag was hydrodynamically calculated with a flat plate body model and previous riblet data. High ridges with a large spacing were found to effectively reduce drag at a migration speed of 2.3 m s-1, while adjacent high and low ridges with a small spacing reduced drag at a burst hunting speed of 5.1 m s-1. Moreover, the above hydrodynamic calculation method was also applied to the shortfin mako shark and an extinct giant shark (called megalodon) with known ridge spacings, resulting in the estimated hunting speeds of 10.5 m s-1and 5.9 m s-1, respectively.

Molecular characteristics of rhesus macaque interferon-lambda receptor 1 (mmuIFNLR1): Sequence identity, distribution and alteration after simian-human immunodeficiency virus infection in the skin and buccal mucosa.

Interferon-lambda receptor 1 (IFNLR1) is the key to interferon-lambda's biological activities. Rhesus macaques (Macaca mulatta) are supposedly more suitable for translational studies on interferon lambda-associated human diseases, yet little is known about their IFNLR1 (mmuIFNLR1). In this study, we cloned the coding sequence of mmuIFNLR1, examined its variants, and determined the distribution of mmuIFNLR1 mRNA and immunoreactivity in the buccal mucosa and arm skin of normal and immunodeficiency virus (SHIV/SIV) infected rhesus macaques. It was found that mmuIFNLR1 has 93.1% amino acid sequence identity to that of humans; all the amino acid residues of mmuIFNLR1 signal peptide, transmembrane region, PxxLxF motif and those essential for ligand binding are identical to that of humans; 6 variants of mmuIFNLR1, including the ones corresponding to that of humans were detected; IFNLR1 immunoreactivity was localized in primarily the epithelia of buccal mucosa and arm skin; SHIV/SIV infection could affect the levels of mmuIFNLR1 mRNA and immunoreactivity. These data expanded our knowledge on mmuIFNLR1 and provided a scientific basis for rational use of rhesus macaques in studies of IFN-λ associated human diseases like AIDS. Future studies testing IFNLR1-targeting therapeutics in rhesus macaques were warranted.

Direct immunofluorescence on plucked hair outer root sheath can predict relapse in pemphigus vulgaris.

BACKGROUND: Prospective research is lacking on the utility of plucked hair outer root sheath direct immunofluorescence (ORS DIF) in the prediction of relapse in pemphigus vulgaris (PV) and the correlation of ORS DIF positivity with serum desmoglein antibody titers. METHODS: We performed a prospective cohort study enrolling 80 PV patients in complete clinical remission at a tertiary care center in North India. Study participants underwent ORS DIF at baseline, which was repeated every 3 months. Skin biopsy DIF was done at study inclusion, repeated at 3 months, and upon clinical relapse. An antidesmoglein antibody titer was assessed concurrently with ORS DIF in a subset of patients. Patients on adjuvant therapy had their adjuvant therapy withdrawn either at the initial visit, at 3 months, or at a 6-month follow-up. Our objectives were to determine the association between positive ORS DIF and clinical relapse, the correlation between positive ORS DIF and skin biopsy DIF, and between positive ORS DIF and positive antidesmoglein antibody titers (when concurrently done). RESULTS: Twenty-two patients (27.5%) had a clinical relapse. Baseline immunological markers significantly associated with relapse are ORS DIF positivity with IgG (16/36 [45.44%] P = 0.005) and C3 (12/29 [41.37%] P = 0.047) and greater intensity of baseline IgG and C3 positivity in ORS DIF (IgG, P = 0.002; C3, P = 0.033). Notably, a significant correlation was observed between baseline positive ORS DIF and skin biopsy DIF (IgG, ρ = 0.695; C3, ρ = 0.498). Positive ORS DIF strongly correlated with positive anti-Dsg3 antibody titers (φs = 0.815; P < 0.01). Early withdrawal of adjuvant immunosuppressant (within 3 months) (P = 0.007) and positive ORS DIF were also associated with relapse (P = 0.017). CONCLUSION AND RELEVANCE: ORS DIF is a reliable predictor of PV clinical relapse and demonstrated robust correlations with skin biopsy DIF and antidesmoglein antibody titers. Periodic assessment of ORS DIF aids in determining new-onset positivity that heralds clinical relapse.

Revisiting X-linked congenital ichthyosis.

X-linked recessive ichthyosis (XLI) is a hereditary skin disease characterized by generalized dryness and scaling of the skin, with frequent extracutaneous manifestations. It is the second most common type of ichthyosis, with a prevalence of 1/6,000 to 1/2,000 in males and without any racial or geographical differences. The causative gene for XLI is the steroid sulfatase gene (STS), located on Xp22.3. STS deficiency causes an abnormal cholesterol sulfate (CS) accumulation in the stratum corneum (SC). Excess CS induces epidermal permeability barrier dysfunction and scaling abnormalities. This review summarizes XLI's genetic, clinical, and pathological features, pathogenesis, diagnosis and differential diagnoses, and therapeutic perspectives. Further understanding the role of the STS gene pathogenic variants in XLI may contribute to a more accurate and efficient clinical diagnosis of XLI and provide novel strategies for its treatment and prenatal diagnosis.

Facial pore refining by targeting dermal and epidermal functions: Assessment across age and gender.

BACKGROUND: Conspicuous facial pores are benign but represent a cosmetic concern for men and women. Recent works described dermal and epidermal impairments as clinical causes of enlarged pores. Morphological modifications of skin at the site of pores were associated with collagen density loss, possible alteration of extracellular matrix and abnormal differentiation of keratinocytes. AIMS: A composition containing mannose-6-phosphate (Active Complex) was designed to address these different aspects of pore enlargement. In vitro and ex vivo evaluations were conducted in different models mimicking disturbance of dermal and epidermal functions. The pore refining activity of Active Complex was assessed in two clinical trials studying a Caucasian women cohort and an Asian men cohort. RESULTS: At the dermal level, Active Complex upregulated collagen I and decorin synthesis, and genes encoding collagens I, III, V, VII, XVII; suggesting its ability to favor collagen fiber organization and anchorage. The downregulation of matrix metalloprotease, involved in extracellular matrix degradation, reinforced the protective effect of Active Complex in the dermis. Active Complex down modulated differentiation markers in keratinocytes as well as genes involved in cell renewal. Study of reconstructed human epidermis modeling keratinocyte hyperproliferation revealed that Active Complex mitigated two markers of this state: number of nuclei in the stratum corneum and involucrin expression. Clinical trials confirmed the pore refining activity of Active Complex on men and women of different ages and ethnicities; -24% total skin pore area after 56 days of application on women, and -30.2% on men after 7 days. CONCLUSIONS: This work demonstrates the interest to target dermal and epidermal modifications described in conspicuous pore area, especially dermis fiber organization, to address this cosmetic concern.

Enkephalin-mediated modulation of basal somatic sensitivity by regulatory T cells in mice.

CD4+CD25+Foxp3+ regulatory T cells (Treg) have been implicated in pain modulation in various inflammatory conditions. However, whether Treg cells hamper pain at steady state and by which mechanism is still unclear. From a meta-analysis of the transcriptomes of murine Treg and conventional T cells (Tconv), we observe that the proenkephalin gene (Penk), encoding the precursor of analgesic opioid peptides, ranks among the top 25 genes most enriched in Treg cells. We then present various evidence suggesting that Penk is regulated in part by members of the Tumor Necrosis Factor Receptor (TNFR) family and the transcription factor Basic leucine zipper transcription faatf-like (BATF). Using mice in which the promoter activity of Penk can be tracked with a fluorescent reporter, we also show that Penk expression is mostly detected in Treg and activated Tconv in non-inflammatory conditions in the colon and skin. Functionally, Treg cells proficient or deficient for Penk suppress equally well the proliferation of effector T cells in vitro and autoimmune colitis in vivo. In contrast, inducible ablation of Penk in Treg leads to heat hyperalgesia in both male and female mice. Overall, our results indicate that Treg might play a key role at modulating basal somatic sensitivity in mice through the production of analgesic opioid peptides.

Agarose-collagen composite microsphere implants: A biocompatible and robust approach for skin tissue regeneration.

Photoaged skin, a consequence of UV radiation-induced collagen degradation, presents a significant challenge for skin rejuvenation. Synthetic polymer microspheres, while offering collagen regeneration potential, carry risks like granulomas. To overcome this, we developed a novel agarose-collagen composite microsphere implant for skin tissue regeneration. Fabricated using an emulsification-crosslinking method, these microspheres exhibited excellent uniformity and sphericity (with a diameter of ~38.5 µm), as well as attractive injectability. In vitro studies demonstrated their superior biocompatibility, promoting cell proliferation, adhesion, and migration. Further assessments revealed favorable biosafety and blood compatibility. In vivo experiments in photoaged mice showed that implantation of these microspheres effectively reduced wrinkles, increased skin density, and improved elasticity by stimulating fibroblast encapsulation and collagen regeneration. These findings highlight the potential of agarose-collagen microspheres in dermatological and tissue engineering applications, offering a safer alternative for skin rejuvenation.

Chondroitin/dermatan sulphate proteoglycan, desmosealin, showing affinity to desmosomes.

INTRODUCTION: Complexities of robotic distal gastrectomy (RDG) give reason to assess physician's surgical skill. Varying levels in surgical skill affect patient outcomes. We aim to investigate how a novel artificial intelligence (AI) model can be used to evaluate surgical skill in RDG by recognizing surgical instruments. METHODS: Fifty-five consecutive robotic surgical videos of RDG for gastric cancer were analyzed. We used Deeplab, a multi-stage temporal convolutional network, and it trained on 1234 manually annotated images. The model was then tested on 149 annotated images for accuracy. Deep learning metrics such as Intersection over Union (IoU) and accuracy were assessed, and the comparison between experienced and non-experienced surgeons based on usage of instruments during infrapyloric lymph node dissection was performed. RESULTS: We annotated 540 Cadiere forceps, 898 fenestrated bipolars, 359 suction tubes, 307 Maryland bipolars, 688 harmonic scalpels, 400 staplers, and 59 large clips. The average IoU and accuracy were 0.82 ± 0.12% and 87.2 ± 11.9% respectively. Moreover, the percentage of each instrument's usage to overall infrapyloric lymphadenectomy duration predicted by AI were compared. The use of stapler and large clip were significantly shorter in the experienced group compared to the non-experienced group. CONCLUSIONS: This study is the first to report that surgical skill can be successfully and accurately determined by an AI model for RDG. Our AI gives us a way to recognize and automatically generate instance segmentation of the surgical instruments present in this procedure. Use of this technology allows unbiased, more accessible RDG surgical skill.

OBJECTIF: Les desmosomes sont les jonctions inter­kératinocytaires les plus proéminentes. Le fonctionnement appropriée des épithéliums stratifiés comme épiderme dépend de leur expression. La composition moléculaire et les propriétés physico­chimiques des desmosomes évoluent au cours de la différenciation épidermique. La desquamation de cornéocytes la surface du stratum corneum depend de la dégradation ordonnée des desmosomes par les enzymes endogènes. Ce processus peut être régulé par les molécules glycosylées. Notre travail consistait en détection et caractérisation de l'un des acteurs potentiellement impliqués, portant des chaînes carbohydrate. METHODES: Les approches d'analyse biochimique s'appuyant sur un anticorps monoclonal original (immunotransfert mono­et bi­dimensionnel, immunoprécipitation­immunodétection croisées, digestions enzymatiques, tests de déglycosylation et d'inhibition de synthèse) nous ont permis la caractérisation partielle d'un protéoglycanne sécrété dans les espaces inter­kératinocytaires. Cette molécule s'intègre aux desmosomes en quantités proportionnelles au stade de différenciation des kératinocytes, comme le démontrent les marquages ultrastructuraux à l'or colloïdal sur des cryocoupes et tissus enrobés en résines acryliques. RESULTATS: Cet antigène, que nous avons appelé desmosealine, est clairement distinct des éléments constitutifs de desmosomes décrits jusqu'alors. Contrairement aux protéoglycannes épidermiques connus, il porte exclusivement les chaînes glycosaminoglycannes de type chondroïtine/dermatane sulfate. La desmosealine est présente dans les parties extracellulaires de desmosomes, dans la portion supérieure de l'épiderme vivant et le début du stratum corneum. CONCLUSION: L'intégration massive d'un protéoglycanne dans des parties intercellulaires de desmosomes revêt vraisemblablement une importance fonctionnelle. De par son profile biochimique, sa distribution dans l'épiderme et son affinité pour les desmosomes, le desmosealine peut s'avérer être un élément clé dans la régulation de la cohésion interkératinocytaire et la formation de la barrière de perméabilité épidermique.

A Mendelian randomization analysis reveals the multifaceted role of the skin microbiota in liver cancer.

Background: Hepatocellular carcinoma (HCC, or hepatic cancer, HC) and cholangiocarcinoma (CCA, or hepatic bile duct cancer, HBDC) are two major types of primary liver cancer (PLC). Previous studies have suggested that microbiota can either act as risk factors or preventive factors in PLC. However, no study has reported the relationship between skin microbiota and PLC. Therefore, we conducted a two-sample Mendelian randomization (MR) study to assess the causality between skin microbiota and PLC. Methods: Data from the genome-wide association study (GWAS) on skin microbiota were collected. The GWAS summary data of GCST90018803 (HBDC) and GCST90018858 (HC) were utilized in the discovery and verification phases, respectively. The inverse variance weighted (IVW) method was utilized as the principal method in our MR study. The MR-Egger intercept test, Cochran's Q-test, MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and leave-one-out analysis were conducted to identify the heterogeneity and pleiotropy. Results: The results showed that Veillonella (unc.) plays a protective role in HBDC, while the family Neisseriaceae has a positive association with HBDC risk. The class Betaproteobacteria, Veillonella (unc.), and the phylum Bacillota (Firmicutes) play a protective role in HC. Staphylococcus epidermidis, Corynebacterium (unc.), the family Neisseriaceae, and Pasteurellaceae sp. were associated with an increased risk of HC. Conclusion: This study provided new evidence regarding the association between skin microbiota and PLC, suggesting that skin microbiota plays a role in PLC progression. Skin microbiota could be a novel and effective way for PLC diagnosis and treatment.

Dovetailing skin incision design of radial forearm free flap for forearm wound closure and maxillofacial reconstruction.

Object: This study aimed to examine the feasibility of the dovetailing skin incision design of radial forearm free flap (RFFF) for closing forearm wounds and performing maxillofacial reconstruction. Method: A total of 27 patients were divided into two groups. In the dovetail group (n = 16), forearm wounds were closed primarily and maxillofacial defects were reconstructed by dovetail RFFF. In the conventional group (n = 11), forearm wounds were closed by skin grafts from the abdomen or mattress suturing, and maxillofacial defects were reconstructed by conventional RFFF. Information on the healing time of the forearm wound, length of postsurgical hospitalization, esthetic assessments, and complications associated with the forearm wound and the maxillofacial region was collected at least 6 months postoperatively. Result: The average size of the flap in the dovetail group was smaller than that in the conventional group (p = 0.134), and average healing time of the forearm wound in dovetail group was significantly shorter than that in conventional group (p = 0.000). Comparing with the conventional group, there were more cases in the dovetail group demonstrating decreased sensitivity (p = 1.000). Esthetic assessments of forearm wound and maxillofacial reconstructions in the dovetail group were significantly higher than that in the conventional group (p = 0.000). Conclusion: Closure of forearm wounds and maxillofacial defects using dovetail design was found to be a feasible alternative to the conventional design.

Lichenoid Drug Eruption Secondary to Adalimumab: A Case Report.

Adalimumab, an anti-tumor necrosis factor-α (TNF-α), is widely prescribed for many autoimmune diseases and chronic inflammatory skin diseases such as hidradenitis suppurative, psoriasis, etc. We report a case of lichenoid drug eruption secondary to adalimumab, a rare side effect, in a 62-year-old female with ulcerative colitis. The skin eruption appeared two weeks after initiating adalimumab. A skin biopsy was taken, and the histopathological findings correlated with a lichenoid drug eruption. Although rare, drug-induced lichen planus has been associated with adalimumab. Early recognition and a high index of suspicion are key in the prompt management of these cases. The discontinuation of adalimumab must be carefully weighed against its therapeutic benefits, as the discontinuation might trigger a severe form of inflammation in the primary autoimmune disease being treated. Extreme caution, early intervention, and a multidisciplinary approach are best for the overall well-being and optimal care of the individual.

A Dermatological Dilemma: The Importance of Recognizing Dermatologic Manifestations of Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) in Skin of Color Patients.

Many dermatologic conditions that are seen in medical literature are typically on lighter skin tones making it easier to identify. This can pose a difficult problem in the care of skin of color patients. The purpose of this paper is to highlight the importance of dermatologic manifestations in skin of color patients and the disparities that exist in the medical field. Here, we present the case of a 51-year-old African American male who was hospitalized on a prolonged course of antibiotics found to have drug reaction with eosinophilia and systemic symptoms (DRESS). Although the initial diagnosis was not made at symptom onset due to the atypical presentation in darker skin tones, the patient improved when the diagnosis was eventually made with cessation of the offending agent and steroid therapy. There is a vital need for continued awareness of the disparities that exist within medical literature and the medical field in regard to skin of color patients.

Progress in the application of artificial intelligence in skin wound assessment and prediction of healing time.

Since the 1970s, artificial intelligence (AI) has played an increasingly pivotal role in the medical field, enhancing the efficiency of disease diagnosis and treatment. Amidst an aging population and the proliferation of chronic disease, the prevalence of complex surgeries for high-risk multimorbid patients and hard-to-heal wounds has escalated. Healthcare professionals face the challenge of delivering safe and effective care to all patients concurrently. Inadequate management of skin wounds exacerbates the risk of infection and complications, which can obstruct the healing process and diminish patients' quality of life. AI shows substantial promise in revolutionizing wound care and management, thus enhancing the treatment of hospitalized patients and enabling healthcare workers to allocate their time more effectively. This review details the advancements in applying AI for skin wound assessment and the prediction of healing timelines. It emphasizes the use of diverse algorithms to automate and streamline the measurement, classification, and identification of chronic wound healing stages, and to predict wound healing times. Moreover, the review addresses existing limitations and explores future directions.

Synthesis of some polyphenolics from contents of onion skin and discovery of the promoter effect on barley germination.

Facile synthesis and characterisation of three natural compounds and their two synthetic analogues based on onion skin content were performed. Both OSE and 2,4,6-trihydroxyphenylglyoxylic acid was induced effect on cell proliferation during barley germination with a difference of approximately %4 compared to the control group.

Understanding sex differences in extinction retention: Pre-extinction stress and sex hormone status.

Difficulties in fear regulation can sometimes result in maladaptive fear responses. To better understand how to improve fear regulation, it is important to determine how known factors, such as sex hormone status and stress, might interact to influence fear memory. Research has shown that women with high estradiol levels (mid-cycle) and men exhibit better extinction retention compared to women with low estradiol levels (women in the early follicular cycle or using oral contraceptives). Stress has also been demonstrated to affect both the learning and retention of extinction. Despite documented interactions between stress and sex hormones, their combined effects have not been thoroughly studied. This study aims to examine the impact of stress as a function of sex hormone status on extinction learning and retention. A total of 168 non-clinical participants were studied, including men (n = 46), women using oral contraceptives (n = 38), women in the early follicular phase (n = 40), and women in mid-cycle (n = 44). On Day 1, fear acquisition training was performed. On day 2, prior to extinction training, half of the participants were exposed to a psychosocial stressor, while the other half performed a non-stressful control task. On day 3, extinction retention was tested. Fear was quantified using skin conductance responses, while stress hormones were quantified through saliva samples. Exposure to stress prior to extinction training did not affect extinction learning, regardless of sex hormone status. In contrast, pre-extinction stress exposure had different effects on extinction retention depending on hormone status. Stressed men showed impairment in extinction retention compared to controls, while the experimental condition had no effect on naturally cycling women. Regardless of stress exposure, early follicular women exhibited a deficit in fear regulation, while mid-cycle women showed effective fear regulation. Among women using oral contraceptives, the stress group demonstrated better extinction retention compared to the control group. These results demonstrate the importance of considering sex hormone status and stress exposure during extinction learning, as both components may modulate extinction retention. These results could help identifying hormonal conditions that may enhance the effectiveness of extinction-based psychological therapies used in the treatment of fear-related disorders.

Bacterial infection-biased abundance of proteins in the skin mucus of obscure puffer (Takifugu Obscurus).

The skin mucus of fish is equipped with immunological and antimicrobial peptides that confer protection against invading pathogens. The skin mucus has been studied in fish however information regarding its immunological roles in bacterial infection is rare. This study highlighted the proteins and peptides in the skin mucus of Obscure puffer Takifugu obscurus that quantitatively altered against Aeromonas hydrophila infection. We infected the fish through bath immersion, intraperitonially, and treated with PBS (control) then compared the level of proteins in the skin mucus among the groups using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The Tandem Mass Tag (TMT) based quantification showed that 4896 proteins were Deferentially Quantified Proteins (DQPs), based on 19,751 unique peptides. Of which 170 were depleted (decreased in abundance) and 69 were abundant in comparison of Bath Treated (BT) vs Control (C) groups. Similarly, 76 DQPs were depleted and 70 were abundant in comparison of Treated (T) vs BT groups. Further, 126 DQPs were depleted, and 34 were abundant in comparison to T vs C groups. The DQPs we report were mostly immunological and were involved in unique biological functions and pathways. The interesting protein we report, where some of the proteins are for the first time in fish, shows the protein-rich structure of the mucus of fish, which may act as a biomarker to be targeted for bacterial disease therapy in fish and ultimately hint to the way of making resistance in fish against bacterial pathogens.