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Malassezia, the most abundant fungal commensal on the mammalian skin, has been linked to several inflammatory skin diseases such as atopic dermatitis, seborrheic dermatitis and psoriasis. This study reveals that epicutaneous application with Malassezia globosa (M. globosa) triggers skin inflammation in mice. RNA-sequencing of the resulting mouse lesions indicates activation of Interleukin-17 (IL-17) signaling and T helper 17 (Th17) cells differentiation pathways by M. globosa. Furthermore, our findings demonstrate a significant upregulation of IL-23, IL-23R, IL-17A, and IL-22 expressions, along with an increase in the proportion of Th17 and pathogenic Th17 cells in mouse skin exposed to M. globosa. In vitro experiments illustrate that M. globosa prompts human primary keratinocytes to secrete IL-23 via TLR2/MyD88/NF-κB signaling. This IL-23 secretion by keratinocytes is shown to be adequate for inducing the differentiation of pathogenic Th17 cells in the skin. Overall, these results underscore the significant role of Malassezia in exacerbating skin inflammation by stimulating IL-23 secretion by keratinocytes and promoting the differentiation of pathogenic Th17 cells.
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Diferenciación Celular , Interleucina-23 , Queratinocitos , Malassezia , Células Th17 , Malassezia/inmunología , Queratinocitos/microbiología , Queratinocitos/inmunología , Queratinocitos/metabolismo , Células Th17/inmunología , Animales , Interleucina-23/metabolismo , Humanos , Ratones , Transducción de Señal , FN-kappa B/metabolismo , Receptor Toll-Like 2/metabolismo , Interleucina-17/metabolismo , Piel/microbiología , Piel/patología , Piel/inmunología , Modelos Animales de Enfermedad , Factor 88 de Diferenciación Mieloide/metabolismo , Factor 88 de Diferenciación Mieloide/genética , Células Cultivadas , Ratones Endogámicos C57BL , Interleucina-22RESUMEN
Benvitimod has been successfully used in the treatment of psoriasis and atopic dermatitis (AD). However, the mechanism remains to be clarified. We aim to assess the effects of benvitimod on MC903-induced dermatitis in mice and to investigate the effects of benvitimod on filaggrin (FLG), involucrin (IVL), and loricrin (LOR) expressions and possible mechanism. MC903-induced mouse AD model was used to evaluate the effects of benvitimod. Filaggrin, involucrin, and loricrin protein and mRNA expressions in lesions of mice dermatitis were measured by Western blot and quantitative real-time PCR. In vitro, normal human epidermal keratinocytes (NHEKs) were cultured and benvitimod was used to treat NHEKs primed with IL-4 and IL-13. Then AHR and OVOL1 in NHEKs were knocked down to evaluate the role of AHR and OVOL1 in the effects of benvitimod. Topical treatment of benvitimod repaired skin barrier and alleviated skin inflammation in mouse AD model. This effect was inhibited by pretreatment with an AHR antagonist. Benvitimod upregulated the filaggrin, involucrin, and loricrin expressions in lesions of mouse AD model. In addition, benvitimod upregulated the filaggrin, involucrin, and loricrin expressions in NHEKs. Knockdown of AHR or OVO-like (OVOL)1 abrogated the upregulation of filaggrin, involucrin, and loricrin induced by benvitimod. Benvitimod attenuated MC903-induced mouse dermatitis and upregulated filaggrin, involucrin, and loricrin expressions via AHR-OVOL1 axis.
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Dermatitis Atópica , Modelos Animales de Enfermedad , Proteínas Filagrina , Proteínas de Filamentos Intermediarios , Queratinocitos , Precursores de Proteínas , Receptores de Hidrocarburo de Aril , Regulación hacia Arriba , Proteínas Filagrina/metabolismo , Animales , Precursores de Proteínas/metabolismo , Precursores de Proteínas/genética , Ratones , Humanos , Queratinocitos/metabolismo , Queratinocitos/efectos de los fármacos , Proteínas de Filamentos Intermediarios/metabolismo , Proteínas de Filamentos Intermediarios/genética , Dermatitis Atópica/metabolismo , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/patología , Regulación hacia Arriba/efectos de los fármacos , Receptores de Hidrocarburo de Aril/metabolismo , Receptores de Hidrocarburo de Aril/genética , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Células Cultivadas , Piel/patología , Piel/metabolismo , Piel/efectos de los fármacos , Ratones Endogámicos BALB C , Transducción de Señal/efectos de los fármacos , Proteínas de Unión al ADN , Factores de TranscripciónRESUMEN
Rubber concrete has been applied to a certain extent in fatigue-resistant structures due to its good durability. Based on a cohesive model of rubber composed of a five-phase material containing mortar, aggregate, rubber, aggregate-mortar interfacial transition zone (ITZ), and rubber-mortar ITZ, this paper studies the influence of the cohesive parameters in the rubber-mortar ITZ on the fatigue problem of rubber concrete on the mesoscopic scale. As the weak part of cement-based composite materials, the ITZ has a great influence on the mechanical properties and durability of concrete, but the performance of the ITZ is difficult to test in macro experiments, resulting in difficulties in determining its simulation parameters. Based on the cohesive model with a rubber content of 5%, this study uses Monofactor analysis and the Plackett-Burman test to quickly and effectively determine the primary and secondary influences of the cohesive model parameters in the rubber-mortar ITZ; further, the response surface method is used to optimize the cohesive parameters in the rubber-mortar ITZ, and the numerical simulation results after optimizing the cohesive parameters are compared and analyzed with the simulation results before optimization. The results show that, under the setting of the optimized parameters, the simulation results of each item of the optimal cohesive model parameters in the rubber-mortar ITZ are in line with the reality and closer to the experimental data, and they are also applicable to rubber concrete models with different rubber dosing.
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The incorporation of rubber can enhance concrete's durability and effectively reduce the damage caused by freeze-thaw cycling (FTC). Still, there has been only limited research on the damage mechanism of RC at the fine view level. To gain insight into the expansion process of uniaxial compression damage cracks in rubber concrete (RC) and summarize the internal temperature field distribution law during FTC, a fine RC thermodynamic model containing mortar, aggregate, rubber, water, and interfacial transition zone (ITZ) is established in this paper, and the cohesive element is selected for the ITZ part. The model can be used to study the mechanical properties of concrete before and after FTC. The validity of the calculation method was verified by comparing the calculated results of the compressive strength of concrete before and after FTC with the experimental results. On this basis, this study analyzed the compressive crack extension and internal temperature distribution of RC at 0, 5, 10, and 15% replacement rates before and after 0, 50, 100, and 150 cycles of FTC. The results showed that the fine-scale numerical simulation method can effectively reflect the mechanical properties of RC before and after FTC, and the computational results verify the applicability of the method to rubber concrete. The model can effectively reflect the uniaxial compression cracking pattern of RC before and after FTC. Incorporating rubber can impede temperature transfer and reduce the compressive strength loss caused by FTC in concrete. The FTC damage to RC can be reduced to a greater extent when the rubber incorporation is 10%.
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Rubber concrete (RC) exhibits high durability due to the rubber admixture. It is widely used in a large number of fatigue-resistant structures. Mesoscale studies are used to study the composition of polymers, but there is no method for fatigue simulation of RC. Therefore, this paper presents a finite element modeling approach to study the fatigue problem of RC on the mesoscale, which includes the random generation of the main components of the RC mesoscale structure. We also model the interfacial transition zone (ITZ) of aggregate mortar and the ITZ of rubber mortar. This paper combines the theory of concrete damage to plastic with the method of zero-thickness cohesive elements in the ITZ, and it is a new numerical approach. The results show that the model can simulate reasonably well the random damage pattern after RC beam load damage. The damage occurred in the middle of the beam span and tended to follow the ITZ. The model can predict the fatigue life of RC under various loads.
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The addition of rubber to concrete improves resistance to chloride ion attacks. Therefore, rapidly determining the chloride permeability coefficient (DCI) of rubber concrete (RC) can contribute to promotion in coastal areas. Most current methods for determining DCI of RC are traditional, which cannot account for multi-factorial effects and suffer from low prediction accuracy. Machine learning (ML) techniques have good non-linear learning capabilities and can consider the effects of multiple factors compared with traditional methods. However, ML models easily fall into the local optimum due to their parameters' influence. Therefore, a mixed whale optimization algorithm (MWOA) was developed in this paper to optimize ML models. The main strategies are to introduce Tent mapping to expand the search range of the algorithm, to use an adaptive t-distribution dimension-by-dimensional variation strategy to perturb the optimal fitness individual to thereby improve the algorithm's ability to jump out of the local optimum, and to introduce adaptive weights and adaptive probability threshold values to enhance the adaptive capacity of the algorithm. For this purpose, data were collected from the published literature. Three machine learning models, Extreme Learning Machine (ELM), Random Forest (RF), and Elman Neural Network (ELMAN), were built to predict the DCI of RC, and the three models were optimized using MWOA. The calculations show that the MWOA is effective with the optimized ELM, RF, and ELMAN models improving the prediction accuracy by 54.4%, 62.9%, and 36.4% compared with the initial model. The MWOA-ELM model was found to be the optimal model after a comparative analysis. The accuracy of the multiple linear regression model (MRL) and the traditional mathematical model is calculated to be 87.15% and 85.03%, which is lower than that of the MWOA-ELM model. This indicates that the ML model that is optimized using the improved whale optimization algorithm has better predictive ability than traditional models, providing a new option for predicting the DCI of RC.
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Background: Disseminated fusariosis is a rare and fatal infection in immunocompromised patients. Objectives: We report a case of disseminated amphotericin-resistant fusariosis in a paediatric patient with acute lymphoblastic leukaemia and review the features of reported disseminated fusariosis in China. Materials & Methods: Case reports of disseminated fusariosis were searched from the Chinese literature over the last two decades. Results: The presented case is a 15-year-old female who developed fever and multiple painful purple plaques with black necrotic centres and blood blisters. Fusarium was detected in blood and skin lesions with a high minimum inhibitory concentration (MIC) of amphotericin B (AMB) (>32 µg/mL) and a low MIC of voriconazole (VRC) (0.25 µg/mL). The Fusarium fujikuroi species complex was finally identified by rRNA gene analysis. Combination therapy of VRC and terbinafine (TRF) successfully resolved the disease after more than four months of treatment. Based on the review, the most common manifestations of disseminated fusariosis were fever, skin lesions and positive blood cultures, comprising nine cases (64.3%). Other sites of infection, including the lungs, eyes, sinuses or bone marrow, occurred in eight cases (57.1%). Seven patients (50%) were cured after monotherapy or combination therapy with AMB and VRC. Conclusion: In view of this case and the review of the literature, early identification of Fusarium infection and the appropriate antifungal drugs are critical for successful treatment. Primary therapy should consist of VRC or liposomal amphotericin B (L-AMB), with salvage therapy consisting of posaconazole (PSC). The combination of antifungals is probably necessary and more effective.
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Fusariosis , Leucemia-Linfoma Linfoblástico de Células Precursoras , Femenino , Humanos , Niño , Adolescente , Fusariosis/tratamiento farmacológico , Anfotericina B/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Antifúngicos/uso terapéutico , Terbinafina/uso terapéutico , FiebreRESUMEN
Cutaneous metastases are rare and often portend the aggressive malignancy and poor prognosis. We report a case of a 62-year-old man with a rapidly growing nodule on the left back for 2 months. The patient was diagnosed with lung adenocarcinoma shortly before the skin lesion presented. Physical examination showed a dome-shaped purplish red nodule, with ulceration and hemorrhagic crust. Excision of the skin lesion was performed, and the histopathology showed tumor cells infiltrate with immunohistochemistry (TTF-1+CK7+CD20-) favoring primary lung adenocarcinoma.
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Conventional neural networks tend to fall into local extremum on large datasets, while the research on the strength of rubber concrete using intelligent algorithms to optimize artificial neural networks is limited. Therefore, to improve the prediction accuracy of rubber concrete strength, an artificial neural network model with hybrid algorithm optimization was developed in this study. The main strategy is to mix the simulated annealing (SA) algorithm with the particle swarm optimization (PSO) algorithm, using the SA algorithm to compensate for the weak global search capability of the PSO algorithm at a later stage while changing the inertia factor of the PSO algorithm to an adaptive state. For this purpose, data were first collected from the published literature to create a database. Next, ANN and PSO-ANN models are also built for comparison while four evaluation metrics, MSE, RMSE, MAE, and R2, were used to assess the model performance. Finally, compared with empirical formulations and other neural network models, the result shows that the proposed optimized artificial neural network model successfully improves the accuracy of predicting the strength of rubber concrete. This provides a new option for predicting the strength of rubber concrete.
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Mycobacterium smegmatis is an acid-fast bacillus of rapidly growing mycobacteria (RGM) of nontuberculous mycobacteria (NTM). M. smegmatis was considered nonpathogenic to humans until 1986, when the first patient was linked to the infection. To date, fewer than 100 cases have been reported in the literature, mainly related to various surgical procedures. Herein, we report two immunocompetent patients who acquired M. smegmatis infection following cosmetic procedures. Due to the rarity of M. smegmatis infection in routine clinical practice, it is challenging for medical providers to diagnose and treat patients with M. smegmatis infection. M. smegmatis infection should be considered for patients with chronic skin and soft tissue infections at the injection site or surgical site following cosmetic procedures. Histological findings, pathogen identification by molecular testing or bacterial culture are required to make a definitive diagnosis. Medical providers should raise awareness of M. smegmatis infection for patients with chronic skin and soft tissue infections after cosmetic procedures. Stringent sterile procedures for surgical instruments, supplies, and environments should be enforced.
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Lichen sclerosis (LS) is an insidious, chronic, relapsing skin disease characterized by atrophic, porcelain-appearing plaques. It usually arises in the anogenital area, but some cases can present in extragenital regions with a variety of presentations, including a bullous variant. Topical corticosteroids are a first-line therapy and are usually the most effective treatment to induce remission of LS. However, there is a subset of patients that does not respond well to topical steroids. Herein, we report an extragenital bullous LS case successfully treated with a fractional CO2 laser (FxCO2) and subsequent wet dressing of halcinonide solution.
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Small-scale studies offer conflicting evidence regarding the relationship/association between psoriasis and insulin resistance by HOMA-IR (homeostasis model assessment of insulin resistance). The purpose of this study was to assess the association between baseline HOMA-IR and psoriasis incidence in a large-scale longitudinal cohort of postmenopausal women. The analysis included 21,789 postmenopausal women from the Women's Health Initiative. Psoriasis diagnosis was defined by fee-for-service Medicare ICD-9-CM codes assigned by dermatologists or rheumatologists, and a 2-year lookback period to exclude prevalent cases. Baseline HOMA-IR was calculated using the updated HOMA2 model. Hazard rates from the Cox regression models were stratified by age (10-year intervals), on WHI component (Clinical Trial or Observational Study), and on randomization status within each of the WHI clinical trials. The complete model also adjusted for ethnicity, waist-hip-ratio, and smoking and alcohol habits. Among participants free of psoriasis at entry, those with high baseline HOMA-IR (≥ 2) compared to low (< 1.4) had significantly higher risk for psoriasis over 21-year cumulative follow-up (HR: 1.39, 95% CI 1.08-1.79, P-trend: 0.011). In postmenopausal women, higher baseline HOMA-IR levels were significantly associated with higher incidence of psoriasis over 21-year cumulative follow-up. Results from this time-to-event analysis indicate that insulin resistance can precede and is associated with an increased risk of psoriasis. Study is limited by Medicare diagnostic code accuracy and cohort age.
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Resistencia a la Insulina , Psoriasis , Anciano , Estudios de Cohortes , Femenino , Humanos , Incidencia , Insulina , Medicare , Psoriasis/epidemiología , Factores de Riesgo , Estados Unidos/epidemiología , Salud de la MujerRESUMEN
The Siberian Traps large igneous province (STLIP) is commonly invoked as the primary driver of global environmental changes that triggered the end-Permian mass extinction (EPME). Here, we explore the contributions of coeval felsic volcanism to end-Permian environmental changes. We report evidence of extreme Cu enrichment in the EPME interval in South China. The enrichment is associated with an increase in the light Cu isotope, melt inclusions rich in copper and sulfides, and Hg concentration spikes. The Cu and Hg elemental and isotopic signatures can be linked to S-rich vapor produced by felsic volcanism. We use these previously unknown geochemical data to estimate volcanic SO2 injections and argue that this volcanism would have produced several degrees of rapid cooling before or coincident with the more protracted global warming. Large-scale eruptions near the South China block synchronous with the EPME strengthen the case that the STLIP may not have been the sole trigger.
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Mucormycosis is an opportunistic fungal infection driven by subphylum Mucormycotina. Cutaneous mucormycosis is the third most common presentation of mucormycosis, and its characterized presentation is an indurated plaque that rapidly evolves to necrosis. Trichophyton rubrum is one of the most common dermatophytes that mainly cause superficial infections and seldom induce deep infections. The present report presents a case of cutaneous fungal infection, in which two kinds of fungus were isolated, and the skin lesion mimicked pyoderma gangrenosum. Trichophyton rubrum was isolated from the crust and hyphae of subphylum Mucormycotina were found in dermal tissue. The irregular systemic and topical use of steroid therapy is the possible cause of the mixed fungal infection in this patient, suggesting the importance of regular steroid therapy.
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Background: Acral vitiligo often responses poorly to treatments. Objective: To observe whether pretreatment with ablative fractional CO2 laser aiding penetration of compound betamethasone solution plus NB-UVB could improve the response of refractory acral vitiligo. Methods: Subjects with symmetrical and stable acral vitiligo were enrolled in this study. The symmetrical lesions were randomly allocated to experimental and control sides in a subject. The experimental side underwent five sessions, one month apart, of ablative fractional CO2 laser followed by once of a topical painting of compound betamethasone solution, the control side applied topical betamethasone cream once a day; both sides underwent NB-UVB three times per week. The assessment was performed one month following each of the 1st, 2nd, 3rd, and 5th treatment sessions. Results: Two hundred eighty-nine subjects entered the clinical trial and 126 subjects completed the study. The experiment side showed better improvement in repigmentation. Overall response rate (repigmentation percentage ≥10%) of experiment sides was 51.6%, in contrast, that of control side was 35.8%. There were no severe adverse events in all subjects during the trial. Conclusions: A triple method of ablative fractional CO2 laser, topical compound betamethasone solution plus NB-UVB provided an alternative choice for acral vitiligo with remarkable safety profile. Cinical trial registration: This clinical trial has been registered at Chinese Clinical Trial Registry (Registration number: ChiCTR-TRC-12002593).