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The diatom Phaeodactylum tricornutum, known for its high triacylglycerol (TAG) content and significant levels of n-3 long chain polyunsaturated fatty acids (LC-PUFAs), such as eicosapentaenoic acid (EPA), has a limited ability to utilize exogenous organic matter. This study investigates the enhancement of acetate utilization in P. tricornutum by introducing an exogenous acetate transport protein. The acetate transporter gene ADY2 from Saccharomyces cerevisiae endowed the organism with the capability to assimilate acetate and accelerating its growth. The transformants exhibited superior growth rates at an optimal NaAc concentration of 0.01 M, with a 1.7- to 2.0-fold increase compared to the wild-type. The analysis of pigments and photosynthetic activities demonstrated a decline in photosynthetic efficiency and maximum electron transport rate. This decline is speculated to result from the over-reduction of the electron transport components between photosystems due to acetate utilization. Furthermore, the study assessed the impact of acetate on the crude lipid content and fatty acid composition, revealing an increase in the crude lipid content and alterations in fatty acid profiles, particularly an increase in C16:1n-7 at the expense of EPA and a decrease in the unsaturation index. The findings provide insights into guiding the biomass and biologically active products production of P. tricornutum through metabolic engineering.
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Acetatos , Diatomeas , Fotosíntesis , Diatomeas/metabolismo , Diatomeas/genética , Acetatos/metabolismo , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Ácidos Grasos/metabolismo , Transporte de Electrón , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genéticaRESUMEN
In the evolving landscape of higher education, particularly in the post-pandemic era, it is crucial for college students to face societal challenges and achieve success by understanding and predicting psychological resilience. To deepen our understanding of psychological resilience, this study used a decision tree model to explore influencing factors. We surveyed 776 college students and collected data on demographic information, self-esteem, sense of school belonging, pro-environmental behavior, subjective well-being, internet game addiction, life autonomy, and academic procrastination using several scales. The decision tree model identified eight key predictors of psychological resilience, which are as follows in order of importance: self-esteem, sense of school belonging, pro-environmental behavior, subjective well-being, academic procrastination, life autonomy, internet game addiction, and academic achievement. This model's accuracy reached 73.985 %, emphasizing its potential utility in educational settings. The findings not only provide a novel and data-driven perspective to understand psychological resilience in college students compared to existing research but also provide practical guidance for educational practitioners and policymakers on how to develop psychological resilience in college students.
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BACKGROUND: Ultrapluse CO2 fractional laser technology has emerged as an effective treatment for scar management. However, one drawback of this modality is the pain caused during the procedure. This study aims to explore the efficacy and safety of dezocine (DZC) as preemptive analgesia for reduction of pain induced by ultrapulse CO2 fractional laser treatment for acne scars. METHODS: The study cohort included 78 outpatients with acne scars between February and April 2023. Patients were randomly assigned into three groups with intravenous injection (iv) of DZC prior to laser treatment: (1) control, iv of saline; (2) DZC group 1 (DZC_1), iv of DZC at 0.15 mg/kg; and (3) DZC_2, iv of DZC at 0.20 mg/kg. After 30 min, one session of ultrapulse CO2 fractional laser treatment on acne scars was performed. Hemodynamics, visual analogue scale (VAS), and anxiety visual analog test (AVAT) were monitored prior to, during, and after the procedure. RESULTS: Operative success rates for patients in the control, DZC_1, and DZC_2 groups were 34.6%, 84.6%, and 100%, respectively. DZC administered with either dosage significantly reduced the VAS and AVAT scores of patients in treatment groups as compared with the subjects in the control group during the course of ultrapulse CO2 fractional laser treatment. Patients in DZC_1 and DZC_2 groups did not show any significant difference in hemodynamic parameters, VAS, and AVAT scores. Temporary adverse effects such as nausea and dizziness were observed in some subjects after treatment; the symptoms were quickly dissolved after a rest in supine position. CONCLUSIONS: DZC as preemptive analgesia could effectively reduce pain and anxiety induced by ultrapulse CO2 fractional laser treatment in patients. This study provided an option of preemptive anesthesia to minimize the pain and discomforts associated with laser treatments in clinical practices.
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Acné Vulgar , Cicatriz , Láseres de Gas , Dimensión del Dolor , Tetrahidronaftalenos , Humanos , Acné Vulgar/complicaciones , Acné Vulgar/terapia , Láseres de Gas/efectos adversos , Láseres de Gas/uso terapéutico , Femenino , Adulto , Masculino , Adulto Joven , Cicatriz/etiología , Cicatriz/prevención & control , Cicatriz/terapia , Tetrahidronaftalenos/administración & dosificación , Tetrahidronaftalenos/efectos adversos , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Compuestos Bicíclicos Heterocíclicos con Puentes/efectos adversos , Dolor Asociado a Procedimientos Médicos/etiología , Dolor Asociado a Procedimientos Médicos/prevención & control , Dolor Asociado a Procedimientos Médicos/diagnóstico , Dolor Asociado a Procedimientos Médicos/terapia , Resultado del Tratamiento , Analgesia/métodosRESUMEN
Coxsackievirus A10 (CV-A10) infection, a prominent cause of childhood hand-foot-and-mouth disease (HFMD), frequently manifests with the intriguing phenomenon of onychomadesis, characterized by nail shedding. However, the underlying mechanism is elusive. Here, we found that CV-A10 infection in mice could suppress Wnt/ß-catenin signaling by restraining LDL receptor-related protein 6 (LRP6) phosphorylation and ß-catenin accumulation and lead to onychomadesis. Mechanistically, CV-A10 mimics Dickkopf-related protein 1 (DKK1) to interact with Kringle-containing transmembrane protein 1 (KRM1), the CV-A10 cellular receptor. We further found that Wnt agonist (GSK3ß inhibitor) CHIR99021 can restore nail stem cell differentiation and protect against nail shedding. These findings provide novel insights into the pathogenesis of CV-A10 and related viruses in onychomadesis and guide prognosis assessment and clinical treatment of the disease.
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Infecciones por Coxsackievirus , Péptidos y Proteínas de Señalización Intercelular , Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad , Uñas , Vía de Señalización Wnt , Animales , Humanos , Ratones , beta Catenina/metabolismo , Diferenciación Celular/efectos de los fármacos , Infecciones por Coxsackievirus/complicaciones , Infecciones por Coxsackievirus/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Enfermedad de Boca, Mano y Pie/virología , Enfermedad de Boca, Mano y Pie/metabolismo , Enfermedad de Boca, Mano y Pie/patología , Enfermedad de Boca, Mano y Pie/complicaciones , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Péptidos y Proteínas de Señalización Intercelular/genética , Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad/metabolismo , Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad/genética , Ratones Endogámicos C57BL , Enfermedades de la Uña/metabolismo , Enfermedades de la Uña/virología , Enfermedades de la Uña/patología , Uñas/metabolismo , Uñas/patología , Fosforilación/efectos de los fármacos , Piridinas/farmacología , Pirimidinas , Vía de Señalización Wnt/efectos de los fármacos , Enterovirus/metabolismo , Enterovirus/patogenicidadRESUMEN
Titanium alloys face challenges of high temperature oxidation during the service period when used as aircraft engine components. In this paper, the effect of Y2O3 addition on the oxidation behavior and the microstructural change of the Ti6Al4V alloy fabricated by selective laser melting (SLM) was comprehensively studied. The results show that the surface of the Ti6Al4V alloy is a dense oxide layer composed of TiO2 and Al2O3 compounds. The thickness of the oxide layer of the Ti6Al4V increased from 59.55 µm to 139.15 µm. In contrast, with the addition of Y2O3, the thickness of the oxide layer increased from 35.73 µm to 80.34 µm. This indicates that the thickness of the oxide layer formation was a diffusion-controlled process and, therefore, the thickness of the oxide layer increased with an increase in temperature. The Ti6Al4V-1.0 wt.% Y2O3 alloy exhibits excellent oxidation resistance, and the thickness is significantly lower than that of the Ti6Al4V alloy. The oxidation kinetics of the Ti6Al4V and Ti6Al4V-1.0 wt.% Y2O3 alloys at 600 °C and 800 °C follows a parabolic rule, whereas the oxidation of the Ti6Al4V and Ti6Al4V-1.0 wt.% Y2O3 alloys at 1000 °C follows the linear law. The average microhardness values of Ti6Al4V samples after oxidation increased to 818.9 ± 20 HV0.5 with increasing temperature, and the average microhardness values of the Ti6Al4V-1.0 wt.% Y2O3 alloy increases until 800 °C and then decreases at 1000 °C. The addition of Y2O3 shows a significant improvement in the microhardness during the different temperatures after oxidation.
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This study is a multiscale experimental investigation into the embrittlement of Al-Zn-Mg aluminum alloy (7075-T6) caused by liquid metal gallium. The results of the experiment demonstrate that the tensile strength of the 7075-T6 aluminum alloy significantly weakens with an increase in the embrittlement temperature and a prolonged embrittlement time, whereas it improves with an increase in the strain rate. On the basis of the analysis of the experimental data, the sensitivity of the embrittlement of 7075-T6 aluminum alloy by liquid gallium to the loading strain rate is significantly higher compared to other environmental factors. In addition, this study also includes several experiments for microscopic observation, such as Scanning Electron Microscope (SEM) observation, Energy-Dispersive Spectrometer (EDS) spectroscopy, and Electron Back Scatter Diffraction (EBSD) analysis. The experimental observations confirmed the following: (1) gallium is enriched in the intergranular space of aluminum; (2) the fracture mode of 7075-T6 aluminum alloy changes from ductile to brittle fracture; and (3) the infiltration of liquid gallium into aluminum alloys and its enrichment in the intergranular space result in the formation of new dislocation nucleation sites, in addition to the original dislocations cutting and entanglement. This reduces the material's ability to undergo plastic deformation, intensifies stress concentration at the dislocation nucleation point, and, ultimately, leads to the evolution of dislocations into cracks.
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MXene, renowned for its natural "quantum-confined-superfluidic" (QSF) channels, demonstrates superior electrical/thermal conductivity, favorable hydrophilicity, and remarkable mechanical strength, rendering it an ideal candidate for multiresponsive actuators, which are promising for soft electronics and robots. Currently, most MXene-based actuators are mainly prepared by combining an active layer and an inner layer, with only a few utilizing regulated QSF channels. However, tailoring QSF channels for multiresponsive actuators is extremely challenging. Herein, we introduce a multiresponsive graphene oxide (GO)&Fe3O4/MXene actuator that can respond to humidity, light, heat, electricity, and magnetic fields by constructing asymmetric QSF channels. The asymmetric water adsorption, transportation, and desorption behaviors, controlled by the different QSF channels between the GO&Fe3O4 layer and the MXene layer, enable the multiresponsiveness of the actuator. As proof-of-concept demonstrations, several smart devices, such as a bionic crab-like crawler, a transporting flower robot, and a smart gripper, are prepared, holding great potential for advancing future soft robotics.
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Calreticulin (CRT), a damage-associated molecular pattern molecule, is reported to translocate from the endoplasmic reticulum to the membrane in melanocytes under oxidative stress. To investigate the potential role of CRT in the pathogenesis of vitiligo, we analyzed the correlation between CRT and ROS in serum and lesions of vitiligo, detected CRT and protein kinase RNA-like endoplasmic reticulum kinase (PERK) expression in vitiligo lesions, and studied the production of CRT and mediators of unfolded protein response (UPR) pathway and then tested the chemotactic migration of CD8+ T cells or CD11c+ CD86+ cells. Initially, we verified the overexpression of CRT in perilesional epidermis that was positively correlated with the disease severity of vitiligo. Furthermore, the PERK branch of UPR was confirmed to be responsible for the overexpression and membranal translocation of CRT in melanocytes under oxidative stress. We also found that oxidative stress-induced membranal translocation of CRT promoted the activation and migration of CD8+ T cells in vitiligo. In addition, dendritic cells from patients with vitiligo were also prone to maturation with the coincubation of melanocytes harboring membranal CRT. CRT could be induced on the membrane of melanocytes through UPR and might play a role in oxidative stress-triggered CD8+ T-cell response in vitiligo.
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Autoinmunidad , Linfocitos T CD8-positivos , Calreticulina , Melanocitos , Estrés Oxidativo , Respuesta de Proteína Desplegada , Vitíligo , Vitíligo/inmunología , Vitíligo/metabolismo , Vitíligo/patología , Humanos , Melanocitos/metabolismo , Melanocitos/inmunología , Estrés Oxidativo/inmunología , Calreticulina/metabolismo , Respuesta de Proteína Desplegada/inmunología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Femenino , Masculino , Adulto , eIF-2 Quinasa/metabolismo , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Persona de Mediana Edad , Especies Reactivas de Oxígeno/metabolismo , Adulto Joven , Membrana Celular/metabolismo , Epidermis/inmunología , Epidermis/metabolismo , Epidermis/patologíaRESUMEN
LAY ABSTRACT: Preschool teachers can play a critical role in early detection of autism. Equipping preschool teachers with prerequisite knowledge and skills would allow them to identify children with probable autism and referral to diagnostic services. This study aimed to investigate the impact of an educational module (EMiASD) that prepared preschool teachers to identify autism symptoms. The sample included 144 preschool teachers, of which 120 were stratified and randomly assigned to an intervention arm receiving training in EMiASD (n = 60) or a comparison arm receiving standard training (n = 60) using a parallel mixed-methods design. Responses to open-ended questions about video case studies revealed improvement in the identification of autism symptoms in preschool teachers in the intervention arm, in contrast to preschool teachers in the comparison arm. Moreover, significant changes in knowledge, belief, and self-efficacy about autism favoured EMiASD. Overall, these results demonstrate the influence of EMiASD in the Yemeni cultural context.
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Trastorno del Espectro Autista , Trastorno Autístico , Preescolar , Humanos , Trastorno del Espectro Autista/diagnóstico , Trastorno Autístico/diagnóstico , Escolaridad , Maestros , Autoeficacia , Grabación de Cinta de VideoRESUMEN
Psoriasis is a common inflammatory skin disease, in which epidermal keratinocytes play a vital role in its pathogenesis by acting both as the responder and as the accelerator to the cutaneous psoriatic immune response. Advanced glycation end products (AGEs) are a class of proinflammatory metabolites that are commonly accumulating in cardiometabolic disorders. Recent studies have also observed the increased level of AGEs in the serum and skin of psoriasis patients, but the role of AGEs in psoriatic inflammation has not been well investigated. In the present study, we initially detected abnormal accumulation of AGEs in epidermal keratinocytes of psoriatic lesions collected from psoriasis patients. Furthermore, AGEs promoted the proliferation of keratinocytes via upregulated Keratin 17 (K17)-mediated p27KIP1 inhibition followed by accelerated cell cycle progression. More importantly, AGEs facilitated the production of interleukin-36 alpha (IL-36α) in keratinocytes, which could enhance T helper 17 (Th17) immune response. In addition, the induction of both K17 and IL-36α by AGEs in keratinocytes was dependent on the activation of signal transducer and activator of transcription 1/3 (STAT1/3) signaling pathways. At last, the effects of AGEs on keratinocytes were mediated by the receptor for AGEs (RAGE). Taken together, these findings support that AGEs potentiate the innate immune function of keratinocytes, which contributes to the formation of psoriatic inflammation. Our study implicates AGEs as a potential pathogenic link between psoriasis and cardiometabolic comorbidities.
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Enfermedades Cardiovasculares , Psoriasis , Humanos , Piel/patología , Queratinocitos , Inflamación/metabolismo , Inmunidad , Productos Finales de Glicación Avanzada/metabolismo , Productos Finales de Glicación Avanzada/farmacología , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/patologíaRESUMEN
This study aimed to investigate the geospatial distribution of normal reference values of Interleukin 4 (IL-4) in healthy Chinese adults and to provide a basis for the development of standard references. IL-4 values of 5,221 healthy adults from 64 cities in China were collected and analyzed for a potential correlation with 24 topographical, climatic and soil factors. Seven of these factors were extracted and used to build a back propagation (BP) neural network model that was used to predict IL-4 reference values in healthy individuals from 2,317 observation sites nationwide. The predicted values were tested for normality and geographic distribution by analytic Kriging interpolation to map the geographic distribution of IL-4 reference values in healthy Chinese subjects. The results showed that IL-4 values generally decreased and then increased from the South to the North. We concluded that the BP neural network model applies to this approach, where certain geographical factors determine levels of various biochemical and immunological standards in healthy adults in regions with different topography, climate and soil indices.
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Interleucina-4 , Redes Neurales de la Computación , Adulto , Humanos , China , Valores de Referencia , SueloRESUMEN
Obesity is associated with an increased risk of atopic dermatitis (AD) and may accelerate its development. Keratinocyte dysfunction has been observed in obesity-related skin diseases, including psoriasis and acanthosis nigricans, but is not fully understood in AD. In this study, we found that high-fat diet-induced obesity exacerbated AD-like dermatitis in mice, with elevated inflammatory molecules and increased CD36-SREBP1-related fatty acid accumulation in the lesional skin. Blocking CD36 or SREBP1 with chemical inhibitors effectively alleviated AD-like inflammation, decreased fatty acid accumulation, and downregulated TSLP expression in obese calcipotriol (MC903)-treated mice. Moreover, palmitic acid treatment induced TSLP overexpression in keratinocytes through the activation of the CD36-SREBP1 signaling pathway. The chromatin immunoprecipitation assay further revealed increased binding of SREBP1 to the TSLP promoter region. Our findings provide compelling evidence that obesity triggers the activation of the CD36-SREBP1-TSLP axis in keratinocytes, leading to epidermal lipid disorders and the aggravation of AD-like inflammation. By targeting CD36 or SREBP1, future combination therapies or modified treatment strategies could be developed to help manage patients with both obesity and AD.
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BACKGROUND: Previous studies have indicated an association between birth weight (BW) and type 2 diabetes mellitus (T2DM), but few studies have explored this relationship under different conditions of obesity in adulthood. METHODS: A total of 4,005 individuals from ten provinces of China were randomly selected to participate in this study. We used a questionnaire to collect age, BW, current weight, height, T2DM history, age at T2DM diagnosis, and other variables. The participants were divided into three groups were according to BW trisection (BW ≤ 2500 g for the lower BW group, 2500 g < BW ≤ 3500 g for the normal BW group, and BW > 3500 g for the higher BW group). The cutoff of overweight and obesity were 25 kg/m2 and 28 kg/m2, respectively. RESULTS: The prevalence rates of T2DM among women with lower BW, normal BW and higher BW were 5.2%, 3.6% and 2.0%, respectively. The obesity prevalence rates in the lower BW, normal BW and higher BW groups were 8.1%, 6.7% and 9.0%, respectively. In the obese population, we did not find a relationship between BW and T2DM, but in the nonobese population, we found that with increasing BW, the risk of developing T2DM was reduced. Obese status in adulthood modified the association between BW and the risk of T2DM. CONCLUSION: There is a "U" shape association between BW and risk of adulthood obesity in Chinese women, but this trend is not existed between BW and risk of developing T2DM. In non-overweight females, the risk of developing T2DM decreased with increasing BW, but this trend was not observed in overweight females.
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Diabetes Mellitus Tipo 2 , Humanos , Femenino , Adulto , Preescolar , Diabetes Mellitus Tipo 2/etiología , Diabetes Mellitus Tipo 2/complicaciones , Peso al Nacer , Obesidad/epidemiología , Obesidad/complicaciones , Sobrepeso/epidemiología , Sobrepeso/complicaciones , Aumento de Peso , China/epidemiologíaRESUMEN
Stimulator of interferon genes (STING) is an essential signaling protein that is located on the endoplasmic reticulum (ER) and triggers the production of type I interferons (IFN) and proinflammatory cytokines in response to pathogenic DNA. Aberrant activation of STING is linked to autoimmune diseases. The mechanisms underlying homeostatic regulation of STING are unclear. Here, we report that UNC13D, which is associated with familial hemophagocytic lymphohistiocytosis (FHL3), is a negative regulator of the STING-mediated innate immune response. UNC13D colocalizes with STING on the ER and inhibits STING oligomerization. Cellular knockdown and knockout of UNC13D promote the production of interferon-ß (IFN-ß) induced by DNA viruses, but not RNA viruses. Moreover, UNC13D deficiency also increases the basal level of proinflammatory cytokines. These effects are diminished by an inhibitor of STING signaling. Furthermore, the domains involved in the UNC13D/STING interaction on both proteins are mapped. Our findings provide insight into the regulatory mechanism of STING, the previously unknown cellular function of UNC13D and the potential pathogenesis of FHL3.
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Retículo Endoplásmico , Interferón Tipo I , Retículo Endoplásmico/metabolismo , Transducción de Señal , Inmunidad Innata , Interferón beta/genéticaRESUMEN
With the continuous development of network communication technology, the domestic network has covered the homes of ordinary people, but the indoor coverage system of the network cable network needs to be further improved. The optical fiber distribution system is a signal coverage system integrating GSM, TD-SCDMA, and other standards. It is mainly composed of system access unit, system expansion unit, and system remote unit. Wireless network is an important communication technology, which is easy to use and can be connected wirelessly over long distances. The purpose of this paper is to study an optical fiber distribution system for indoor coverage design of wireless networks, so as to achieve faster and more efficient coverage. In this paper, a wireless network signal processing algorithm is proposed, and a systematic method for designing the wireless network indoor coverage of the optical fiber distribution system is proposed, and the algorithms are compared and tested. The test results in this paper show that the signal strength obtained by the algorithm in this paper is -54.83 dB, while the traditional artificial design algorithm is only -45.97 dB. In addition, the wireless network base point of the algorithm in this paper is also 3 lower than the traditional one. Moreover, the coverage rate achieved by the algorithm in this paper is 3.17% higher than that of the network cable network base point layout given by the genetic algorithm, and the average received signal strength is 3.34 dB higher. In addition, the algorithm in this paper takes 9.1 s, 11.2 s, and 5.3 s for the three scenarios of underground parking lot, large shopping mall, and residential residential area, while the traditional manual design algorithm takes 87.9 s, 108.8 s, and 51.7 s, respectively. The algorithm in this paper is only about 1/10 of the traditional artificial design algorithm. Therefore, it can be concluded that the coverage effect of the wireless network indoor coverage system of the optical fiber distribution system designed in this paper is significantly improved.
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PURPOSE: Although mast cells (MCs) modulate the activity of effector cells during Candida albicans infection, their role in the pathogenesis of candidiasis remains unclear. Candidalysin, a C. albicans-derived peptide toxin, is a crucial factor in fungal infections. We aimed to investigate the effect of candidalysin on MC activation and the underlying molecular mechanism. METHODS: Serum from candidalysin-immunized mice was used to measure candidalysin expression in patients infected with C. albicans. MC degranulation and migration were evaluated by ß-hexosaminidase release assay and chemotaxis assay, respectively. EIA and ELISA were used to evaluate the production of eicosanoids and cytokines/chemokines, respectively. The production of nitric oxide (NO) was measured with a DAF-FM diacetate kit, while reactive oxygen species (ROS) production was analyzed by flow cytometry. MAPK activation was evaluated by Western blotting. RESULTS: We detected high candidalysin expression in the lesions of patients infected with C. albicans, and the MC number was increased in these lesions. LL-37 colocalized with MCs in the lesions of candidiasis patients. Candidalysin-enhanced MC accumulation in mice and treating LAD2 and HMC-1 cells with candidalysin induced their degranulation, migration, and production of pro- and anti-inflammatory cytokines/chemokines, eicosanoids, ROS, NO, and LL-37. Interestingly, C. albicans strains lacking candidalysin failed to induce MC activation. Moreover, candidalysin increased dectin-1 expression, and the inhibition of dectin-1 decreased MC activation. Downstream dectin-1 signaling involved the MAPK pathways. CONCLUSION: The finding that candidalysin causes cutaneous MC activation may improve our understanding of the role of MCs in the pathology of cutaneous C. albicans infection.
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Candida albicans , Candidiasis , Animales , Candida albicans/metabolismo , Citocinas/metabolismo , Eicosanoides/metabolismo , Proteínas Fúngicas , Humanos , Lectinas Tipo C , Mastocitos/metabolismo , Ratones , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Factores de Virulencia/metabolismoRESUMEN
Impaired keratinocyte functions are major factors that are responsible for delayed diabetic wound healing. In addition to its antimicrobial activity, the antimicrobial peptide derived from insulin-like growth factor-binding protein 5 (AMP-IBP5) activates mast cells and promotes keratinocyte and fibroblast proliferation and migration. However, its effects on diabetic wound healing remain unclear. Human keratinocytes were cultured in normal or high glucose milieus. The production of angiogenic growth factor and cell proliferation and migration were evaluated. Wounds in normal and streptozotocin-induced diabetic mice were monitored and histologically examined. We found that AMP-IBP5 rescued the high glucose-induced attenuation of proliferation and migration as well as the production of angiogenin and vascular endothelial growth factors in keratinocytes. The AMP-IBP5-induced activity was mediated by the epidermal growth factor receptor, signal transducer and activator of transcription 1 and 3, and mitogen-activated protein kinase pathways, as indicated by the inhibitory effects of pathway-specific inhibitors. In vivo, AMP-IBP5 markedly accelerated wound healing, increased the expression of angiogenic factors and promoted vessel formation in both normal and diabetic mice. Overall, the finding that AMP-IBP5 accelerated diabetic wound healing by protecting against glucotoxicity and promoting angiogenesis suggests that AMP-IBP5 might be a potential therapeutic target for treating chronic diabetic wounds.
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Diabetes Mellitus Experimental , Somatomedinas , Animales , Ratones , Péptidos Antimicrobianos , Movimiento Celular , Diabetes Mellitus Experimental/metabolismo , Glucosa/farmacología , Queratinocitos , Somatomedinas/metabolismo , Somatomedinas/farmacología , Cicatrización de HeridasRESUMEN
Colleges and universities are considered as one of the "main battlefields" of epidemic prevention and control, wherein, they have difficulty in clarifying and identifying the critical points for emergency management due to the complexity and multiplicity of influencing factors. Therefore, this study aims to identify the most effective Critical Success Factors (CSFs) for COVID-19 prevention and control in China. This study uses the Decision-Making Trial and Evaluation Laboratory (DEMATEL) method. This study has finally identified five Critical Success Factors (CSFs), which are 1) the training of emergency management professionals, 2) the cultivation of coordinating abilities, 3) the establishment of an epidemic prevention and control leadership team, 4) the development of corresponding responsibility awareness, and 5) the regulation of online public opinions. By focusing on these five CSFs, it can effectively facilitate colleges and universities to optimize their entire emergency management system in the process of normalization and professionalization of campus emergency management.
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Autophagy plays a protective role in oxidative stressâinduced melanocyte death. Dysregulated autophagy increases the sensitivity of melanocytes in response to oxidative damage and promotes melanocyte degeneration in vitiligo. However, the molecular mechanism underlying this process is not fully understood. In this study, using RNA-sequencing technology, we compared the transcriptome change between normal and vitiligo melanocytes with or without treatment of oxidative stress. We found that ATG5 and ATG12, the critical components for autophagosome formation, were significantly reduced in vitiligo melanocytes under oxidative stress. Mechanistically, HSF1 is the prime transcription factor for both ATG5 and ATG12, accounting for the reduced level of ATG5 and ATG12 in vitiligo melanocytes. Deficiency of HSF1 led to accumulation of intracellular ROS, imbalance of mitochondrion membrane potential, and apoptosis in melanocytes exposure to oxidative stress. Furthermore, overexpression of HSF1 could ameliorate oxidative stressâinduced melanocytes death through the activation of autophagy by upregulating ATG5 and ATG12. These findings suggested that targeting HSF1-ATG5/12 axis could prevent oxidative stressâinduced melanocyte death and may be used as a therapeutic strategy for vitiligo treatment.