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Keloids are a type of fibrotic disease characterized by excessive collagen production and extracellular matrix (ECM) deposition. The symptoms of pain and itching and frequent recurrence after treatment significantly impact the quality of life and mental health of patients. A deeper understanding of the pathogenesis of keloids is crucial for the development of an effective therapeutic approach. Fibroblasts play a central role in the pathogenesis of keloids by producing large amounts of collagen fibers. Recent evidence indicates that keloids exhibit high immune cell infiltration, and these cells secrete cytokines or growth factors to support keloid fibroblast proliferation. This article provides an update on the knowledge regarding the keloid microenvironment based on recent single-cell sequencing literature. Many inflammatory cells gathered in keloid lesions, such as macrophages, mast cells, and T lymphocytes, indicate that keloids may be an inflammatory skin disease. In this review, we focus on the communication from immune cells to the fibroblasts and the potential of immunotherapy for keloids. We hope that this review will trigger interest in investigating keloids as an inflammatory disease, which may open up new avenues for drug development by targeting immune mediators.
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Queloide , Humanos , Queloide/metabolismo , Calidad de Vida , Colágeno/metabolismo , Fibroblastos/metabolismo , Células Cultivadas , Inmunoterapia , ComunicaciónRESUMEN
BACKGROUND: To measure volumetric bone mineral density (vBMD) with quantitative computed tomography (QCT) in the proximal femur of ankylosing spondylitis (AS) patients with hip involvement and analyze their correlations with radiographic and clinical parameters. METHODS: Sixty-five AS inpatients were enrolled in this study. The bone mineral density was measured by QCT and dual-energy x-ray absorptiometry (DXA), respectively. The morphological parameters of the proximal femur were measured on digital anteroposterior (AP) radiographs of the pelvis. The correlations between them were analyzed by SPSS software. RESULTS: The average trabecular vBMD measured at the femoral neck was 136.38 ± 25.58 mg/cm3. According to the BASRI-Hip score, group A consisted of 39 hips (0-2 score) and group B consisted of 26 hips (3-4 score). There were significant differences regarding trabecular CTXA equivalent T-score between group A and B at the femoral neck (p = 0.004); intertrochanteric region (p < 0.001) and greater trochanter (p = 0.001). The trabecular CTXA equivalent T-score at femoral neck had a negative correlation with disease duration (r = - 0.311, p = 0.012) and with CBR (r = - 0.319, p = 0.010). CONCLUSIONS: The low trabecular bone density at the site of the hip was associated with the duration of disease progression and degree of hip involvement. Meanwhile, it had a correlation with hip function status although we failed to confirm a significant relationship between hip vBMD and disease activity.
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Densidad Ósea , Espondilitis Anquilosante , Absorciometría de Fotón , Fémur/diagnóstico por imagen , Cuello Femoral , Humanos , Espondilitis Anquilosante/diagnóstico por imagenRESUMEN
Recently, flexible metacomposites with negative permittivity have triggered extensive interest owing largely to their promising applications in areas such as sensors, cloaking, and wearable and flexible electronic devices. In this paper, flexible silver nanowire/carbon fiber felt (AgNW/CFF) metacomposites with weakly negative permittivity were fabricated by adjusting their composition and microstructure. Along with the formation of a conductive AgNW network, the resulting composites gradually presented metal-like behavior. Interestingly, weakly negative permittivity with a small absolute value (as low as about 6.4) and good flexibility were observed in the composites with 3.7 wt% AgNWs. The one-dimensional silver nanowires contribute to reducing the overall electron density of the resulting composites, which is responsible for the weakly negative permittivity. As the AgNWs increased, the Drude-like negative permittivity got stronger owing to the enhancement of the electron density. Further investigation from the perspective of microelectronics revealed that the negative permittivity is dependent on the inductive characteristic. The proposed design strategy for AgNW/CFF composites with tunable negative permittivity opens up a new approach to flexible metacomposites.
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BACKGROUND: Delayed first medical consultation (patient's delay) is quite common in cases of penile carcinoma (PC), but its reasons and impacts remain unclear. We conducted this study to ascertain risk factors resulting in delayed treatment seeking and evaluate its influence on prognosis. METHODS: From 2004 to 2010 at 4 centers, 254 patients were enrolled into this study from 262 consecutive PC cases. Patients' sexual performance was investigated using the International Index of Erectile Function (IIEF)-15 at the sixth-month end after treatment. Data for prognostic analyses was obtained via a 5-year follow-up. RESULTS: A multivariate model ascertained 4 risk factors (single, living in rural areas, heavy drinking alcohol, and aspecific initial symptoms) and 1 protective factor (history of condyloma) significantly associated with patient's delay. Delay >3 months led to significant risks for adverse clinical characteristics, low penis-sparing rate, and poor sexual function restoration. Although patient's delay was not found to impact on postoperative relapses and 5-year overall survival (OS), patients with delay >6 months had significantly inferior 2-year OS. CONCLUSIONS: Single, living in rural areas, heavy drinking alcohol, and aspecific initial symptoms are significant risk factors of PC associated with patient's delay. Delay >3 months will lead to significantly inferior clinical consequences. Minimizing patient's delay is the key to avoid amputation and retain superior sexual potency. Improving patient education on initial symptoms of PC is necessary in men of >40 years old.
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Adenocarcinoma/complicaciones , Diagnóstico Tardío/psicología , Eccema/etiología , Eritema/etiología , Neoplasias del Pene/complicaciones , Adenocarcinoma/diagnóstico , Adenocarcinoma/psicología , Adulto , Anciano , Eccema/diagnóstico , Eritema/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias del Pene/diagnóstico , Neoplasias del Pene/psicología , Pronóstico , Derivación y Consulta , Factores de Riesgo , Factores de TiempoRESUMEN
PURPOSE: We evaluated whether glans preserving surgery would be more helpful for patients to regain satisfactory sexual competency postoperatively than conventional partial amputation. MATERIALS AND METHODS: From 2004 to 2012 at 4 centers a total of 135 men treated with glans preserving surgery and 36 treated with partial amputation were selected for evaluation from a total of 273 consecutive patients with penile cancer. Subjective evaluation for patient sexual performance was investigated using the IIEF-15. Objective evaluation was done using the audiovisual sexual stimulation test with the RigiScan® Plus. The degree of satisfaction with penile appearance, and patient confidence and partner acceptability for intercourse were evaluated by 5-point scales. RESULTS: Patients treated with glans preserving surgery had better performance in 4 IIEF-15 domains (erectile function, orgasmic function, intercourse satisfaction and overall satisfaction) and 1 RigiScan parameter (tip rigidity) (each p <0.01). They also had significantly higher appearance satisfaction (64.4% vs 13.9%) and intercourse confidence (55.6% vs 5.6%) than men who underwent partial amputation. Sexual partners in the glans preserving group also showed significantly higher appearance satisfaction (51.1% vs 5.6%) and intercourse acceptability (37.8% vs 16.7%) than in the partial amputation group. CONCLUSIONS: Glans preserving surgery effectively preserves the functional anatomy and cosmetic appearance of the glans penis. Glans preservation contributes to minimizing postoperative erectile dysfunction and negative psychological impediments, and promotes return to satisfactory sexual performance. Patients treated with glans preservation have more advantages in obtaining sexual acceptance from their partners than those who undergo amputation.
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Pene/cirugía , Procedimientos de Cirugía Plástica/métodos , Sexualidad/fisiología , Procedimientos Quirúrgicos Urológicos Masculinos , Adulto , Anciano , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Erección Peniana/fisiología , Periodo Posoperatorio , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Background: Atopic dermatitis (AD) is a common chronic inflammatory skin diseases that seriously affects life quality of the patients. Staphylococcus aureus (S. aureus) colonization on the skin plays an important role in the pathogenesis of AD; however, the mechanism of how it modulates skin immunity to exacerbate AD remains unclear. MicroRNAs are short non-coding RNAs that act as post-transcriptional regulators of genes. They are involved in the pathogenesis of various inflammatory skin diseases. Methods: In this study, we established miRNA expression profiles for keratinocytes stimulated with heat-killed S. aureus (HKSA). The expression of miR-939 in atopic dermatitis patients was analyzed by fluorescence in situ hybridization (FISH). miR-939 mimic was transfected to human primary keratinocyte to investigate its impact on the expression of matrix metalloproteinase genes (MMPs) in vitro. Subsequently, miR-939, along with Polyplus transfection reagent, was administered to MC903-induced atopic dermatitis skin to assess its function in vivo. Results: MiR-939 was highly upregulated in HKSA-stimulated keratinocytes and AD lesions. In vitro studies revealed that miR-939 increased the expression of matrix metalloproteinase genes, including MMP1, MMP3, and MMP9, as well as the cell adhesion molecule ICAM1 in human primary keratinocytes. In vivo studies indicated that miR-939 increased the expression of matrix metalloproteinases to promote the colonization of S. aureus and exacerbated S. aureus-induced AD-like skin inflammation. Conclusions: Our work reveals miR-939 is an important regulator of skin inflammation in AD that could be used as a potential therapeutic target for AD.
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Dermatitis Atópica , Queratinocitos , Metaloproteinasas de la Matriz , MicroARNs , Staphylococcus aureus , Dermatitis Atópica/inmunología , Dermatitis Atópica/genética , Humanos , MicroARNs/genética , Queratinocitos/metabolismo , Queratinocitos/inmunología , Animales , Ratones , Metaloproteinasas de la Matriz/genética , Metaloproteinasas de la Matriz/metabolismo , Infecciones Estafilocócicas/inmunología , Infecciones Estafilocócicas/genética , Femenino , Masculino , Modelos Animales de Enfermedad , Piel/microbiología , Piel/patología , Piel/inmunología , Células CultivadasRESUMEN
When wood is used as a stressed component of building materials, the parts most prone to failure are the upper and lower surfaces which can be called the weak structure. In a hydrothermal environment, lignin and hemicellulose in wood readily soften and dissolve, thus leading to their designation as the weak structure. The weak structures results in the wood having a low strength. In this paper, the sandwich beam material can be obtained by two steps from the skin self-reinforcement method, whereby the weak structure of the wood surface was removed by the delignification, and then the wood surface was densified. The authenticity of the sandwich structure is proved by a scanning electron microscope (SEM) and density profile analysis. When the moisture content (MC) is 10 %-12 % and the mass loss ratio is 23.04 %, the optimal resilience of the sandwich beam is only 1 %, the maximum modulus of rupture (MOR) and modulus of elasticity (MOE) are 1.42 and 2.1 times greater than those of natural wood, respectively. This finding shows that our method strengthens the weak structure of natural wood, which has good flexural performance and springback ratio.
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Lignina , Madera , Lignina/química , Madera/química , Polisacáridos/química , Fenómenos FísicosRESUMEN
B cells are central players in the immune system, responsible for producing antibodies and modulating immune responses. This review explores the intricate relationship between aberrant B cell activation and the development of autoimmune diseases, emphasizing the essential role of B cells in these conditions. We also summarize B cell receptor signaling and Toll-like receptor signaling in B cell activation, as well as their association with autoimmune diseases, shedding light on the molecular mechanisms behind these associations. Additionally, we explore the clinical observations involving B cell activation and their significance in autoimmune disease management. Various clinical studies related to B cell-targeted therapies are also discussed, offering insights into potential avenues for improving treatment strategies. Overall, this review serves as a resource for researchers and clinicians in the field of immunology and autoimmune diseases, providing a general view of B cell signaling and its role in autoimmunity.
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INTRODUCTION: This is the first study to analyze the associations between the radiological severity of hip involvement with clinical characteristics and sagittal spinopelvic balance in patients with ankylosing spondylitis (AS). METHOD: We evaluated 182 patients with AS who were referred to outpatient clinics. Patient demographic data and clinical and radiographic parameters were collected. Patients were divided into three groups based on the Bath Ankylosing Spondylitis Radiology Hip Index. Clinical characteristics and spinopelvic parameters acquired by a low-dose biplanar imaging system were evaluated among these groups. RESULTS: Patients with more severe hip involvement were older and had longer disease duration and diagnostic delay, with lower Harris Hip Score (p < 0.001) and 12-item Short Form Health Survey Physical Component Score (p < 0.001) and higher Bath Ankylosing Spondylitis Disease Activity Index (p = 0.030) and Functional Index (p < 0.001). Patients with more severe hip involvement had significantly higher sacroiliac grade (p < 0.001) and higher modified Stoke Ankylosing Spondylitis Spinal Score (p < 0.001). Patients with moderate and severe hip involvement had similar lumbar lordosis and spino-sacral angle, whereas patients with severe hip involvement had lower pelvic tilt, pelvic femoral angle, higher sacral slope, and sagittal vertical axis. CONCLUSIONS: The severity of hip involvement is associated with physical function and is not consistent with the severity of spinal involvement. Severe hip involvement impairs the ability to retrovert the pelvis to accommodate the sagittal deformity, and spinopelvic parameters should be concretely evaluated in preoperative counseling of patients with AS waiting for total hip arthroplasty. Key Points ⢠The severity of hip involvement in patients with AS is associated with physical function. ⢠Severe hip involvement impairs the ability to retrovert the pelvis to accommodate the sagittal deformity.
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Radiología , Espondilitis Anquilosante , Humanos , Espondilitis Anquilosante/complicaciones , Espondilitis Anquilosante/diagnóstico por imagen , Diagnóstico Tardío , Sacro , RadiografíaRESUMEN
Leprosy ulcer is a chronic and recurrent disease resulting from nerve injury. While existing treatments partially facilitate ulcer healing, they exhibit limited ability to address localized nerve repair, leading to a risk of recurrence. Moreover, there is a dearth of animal models to evaluate the preclinical efficacy and safety of novel therapeutic approaches. Over the years, adipose-derived mesenchymal stem cells have been extensively employed in regenerative medicine as an optimal cell therapy source for fostering skin ulcer healing. They have also demonstrated the capacity to enhance nerve regeneration in in vitro experiments and clinical trials. In this study, we established a NU/NU mouse foot pad leprosy ulcer model, transplanted human adipose-derived stem cells (hADSCs) into leprosy ulcers via local injection, and conducted subsequent follow-up. Our findings revealed that hADSCs persisted in the leprosy ulcer and facilitated the healing process. In this respect, gross observation and histological analysis revealed increased granular formation, collagen synthesis, and re-epithelialization in the local ulcer area. RNA-Seq data revealed that the upregulated differential genes resulting from the transplantation intervention were not only enriched in pathways related to re-epithelialization and collagen synthesis but also contributed to local nerve regeneration. Furthermore, immunofluorescence assays revealed the increased expression of angiogenesis markers-CD31 and VEGFa, cell proliferation markers-Ki67 and TGF-ß, and nerve regeneration markers-ß3-tubulin, SOX10, NGF, and NT-3. These results underscore the potential of hADSCs in promoting the healing of leprosy ulcers and offer valuable preclinical data for their prospective clinical application.
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Lepra , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Cicatrización de Heridas , Humanos , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Lepra/terapia , Lepra/patología , Animales , Trasplante de Células Madre Mesenquimatosas/métodos , Ratones , Tejido Adiposo/citología , Neovascularización Fisiológica , Ratones Desnudos , Modelos Animales de EnfermedadRESUMEN
With the development of high-rise and large-scale modern structures, traditional concrete has become a design limitation due to its excessive dead weight. High-strength lightweight concrete is being emphasized. Lightweight concrete has low density and the characteristics of a brittle material. This is an important factor affecting the strength and ductility of the lightweight concrete. To improve these shortcomings and proffer solutions, a three-phase composite lightweight concrete was prepared using a combination of tumbling and molding methods. This paper investigates the various influencing factors such as the stacking volume fraction of GFR-EMS, the type of fiber, and the content and length of fiber in the matrix. Studies have shown that the addition of fibers significantly increases the compressive strength of the concrete. The compressive strength of concrete with a 12 mm basalt fiber (BF) (1.5%) admixture is 9.08 MPa, which is 62.43% higher than that of concrete without the fiber admixture. The compressive strength was increased by 27.53 and 21.88% compared to concrete containing 3 mm BF (1.5%) and 0.5% BF (12 mm), respectively. Fibers can fill the pore defects within the matrix. Mutually overlapping fibers easily form a network structure to improve the bond between the cement matrix and the aggregate particles. The compressive strength of lightweight concrete with the addition of BF was 16.71% higher than that with the addition of polypropylene fiber (PPF) with the same length and content of fibers. BF has been shown to be more effective in improving the mechanical properties of concrete. In this work, the compressive mechanism and optimum preparation parameters of a three-phase composite lightweight concrete were analyzed through compression tests. This provides some insights into the development of lightweight concrete.
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We present the first case of phaeohyphomycosis caused by Rhinocladiella basitona (R. basitona) in China and describe the mycological characteristics of this pathogen. A 11-year-old girl was presented with plaque on her face for 3 years. Diagnosis was based on histopathology, mycology, and molecular identification. The patient was treated with terbinafine and itraconazole. This case is the second of phaeohyphomycosis caused by R. basitona in the world (previously belonging to Geniculosporium).
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Ascomicetos/clasificación , Ascomicetos/aislamiento & purificación , Feohifomicosis/diagnóstico , Feohifomicosis/microbiología , Antifúngicos/uso terapéutico , Niño , China , ADN de Hongos/química , ADN de Hongos/genética , ADN Ribosómico/química , ADN Ribosómico/genética , ADN Espaciador Ribosómico/química , ADN Espaciador Ribosómico/genética , Cara/patología , Femenino , Histocitoquímica , Humanos , Itraconazol/uso terapéutico , Técnicas Microbiológicas , Técnicas de Diagnóstico Molecular , Datos de Secuencia Molecular , Naftalenos/uso terapéutico , Feohifomicosis/tratamiento farmacológico , Feohifomicosis/patología , Análisis de Secuencia de ADN , TerbinafinaRESUMEN
For glulam bonding performance assessment, the traditional method of manually measuring the wood failure percentage (WFP) is insufficient. In this paper, we developed a rapid assessment approach to predicate the WFP based on deep-learning (DL) techniques. bamboo/Larch laminated wood composites bonded with either phenolic resin (PF) or methylene diphenyl diisocyanate (MDI) were used for this sample analysis. Scanning of bamboo/larch laminated wood composites that have completed shear failure tests using an electronic scanner allows a digital image of the failure surface to be obtained, and this image is used in the training process of a deep convolutional neural networks (DCNNs).The result shows that the DL technique can predict the accurately localized failures of wood composites. The findings further indicate that the UNet model has the highest values of MIou, Accuracy, and F1 with 98.87%, 97.13%, and 94.88, respectively, compared to the values predicted by the PSPNet and DeepLab_v3+ models for wood composite failure predication. In addition, the test conditions of the materials, adhesives, and loadings affect the predication accuracy, and the optimal conditions were identified. The predicted value from training images assessed by DL techniques with the optimal conditions is 4.3%, which is the same as the experimental value measured through the traditional manual method. Overall, this advanced DL method could significantly facilitate the quality identification process of the wood composites, particularly in terms of measurement accuracy, speed, and stability, through the UNet model.
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Systemic lupus erythematosus (SLE) is an autoimmune illness marked by the loss of immune tolerance and the production of autoantibodies against nucleic acids and other nuclear antigens (Ags). B lymphocytes are important in the immunopathogenesis of SLE. Multiple receptors control abnormal B-cell activation in SLE patients, including intrinsic Toll-like receptors (TLRs), B-cell receptors (BCRs), and cytokine receptors. The role of TLRs, notably TLR7 and TLR9, in the pathophysiology of SLE has been extensively explored in recent years. When endogenous or exogenous nucleic acid ligands are recognized by BCRs and internalized into B cells, they bind TLR7 or TLR9 to activate related signalling pathways and thus govern the proliferation and differentiation of B cells. Surprisingly, TLR7 and TLR9 appear to play opposing roles in SLE B cells, and the interaction between them is still poorly understood. In addition, other cells can enhance TLR signalling in B cells of SLE patients by releasing cytokines that accelerate the differentiation of B cells into plasma cells. Therefore, the delineation of how TLR7 and TLR9 regulate the abnormal activation of B cells in SLE may aid the understanding of the mechanisms of SLE and provide directions for TLR-targeted therapies for SLE.
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Lupus Eritematoso Sistémico , Ácidos Nucleicos , Humanos , Receptor Toll-Like 7 , Receptor Toll-Like 9 , Linfocitos B , Diferenciación Celular , Receptores de Antígenos de Linfocitos B , Proliferación CelularRESUMEN
Lightweight concrete is one of the effective means to solve the problems of structural component weight, energy efficiency, and fire safety in modern civil engineering. Heavy calcium carbonate-reinforced epoxy composite spheres (HC-R-EMS) were prepared by the ball milling method, and HC-R-EMS, cement, and hollow glass microspheres (HGMS) were mixed into the mold by the molding method to prepare composite lightweight concrete. The relationship between the HC-R-EMS volumetric fraction, the initial inner diameter of the HC-R-EMS, the number of layers of HC-R-EMS, the HGMS volume ratio, the basalt fiber length and content, and the multi-phase composite lightweight concrete density and compressive strength was studied. The experimental results show that the density of the lightweight concrete ranges between 0.953-1.679 g/cm3 and the compressive strength ranges between 1.59-17.26 MPa, where the volume fraction of HC-R-EMS is 90%, the initial internal diameter is 8-9 mm, and the number of layers of HC-R-EMS is three. The lightweight concrete can meet the requirements of high strength (12.67 MPa) and low density (0.953 g/cm3). In addition, the addition of basalt fiber (BF) can effectively improve the compressive strength of the material without changing the density of the material. From a micro-level perspective, HC-R-EMS is closely combined with the cement matrix, which is conducive to increasing the compressive strength of concrete. Basalt fibers connect the matrix into a network, improving the maximum limit force of the concrete.
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Damage-associated molecular patterns (DAMPs) are typically derived from the endogenous elements of necrosis cells and can trigger inflammatory responses by activating DAMPs-sensing receptors on immune cells. Failure to clear DAMPs may lead to persistent inflammation, thereby contributing to the pathogenesis of immunological diseases. This review focuses on a newly recognized class of DAMPs derived from lipid, glucose, nucleotide, and amino acid metabolic pathways, which are then termed as metabolite-derived DAMPs. This review summarizes the reported molecular mechanisms of these metabolite-derived DAMPs in exacerbating inflammation responses, which may attribute to the pathology of certain types of immunological diseases. Additionally, this review also highlights both direct and indirect clinical interventions that have been explored to mitigate the pathological effects of these DAMPs. By summarizing our current understanding of metabolite-derived DAMPs, this review aims to inspire future thoughts and endeavors on targeted medicinal interventions and the development of therapies for immunological diseases.
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Insulin-like growth factor-1 receptor (IGF-1R) has been made an attractive anticancer target due to its overexpression in cancers. However, targeting it has often produced the disappointing results as the role played by cross talk with numerous downstream signalings. Here, we report a disobliging IGF-1R signaling which promotes growth of cancer through triggering the E3 ubiquitin ligase MEX3A-mediated degradation of RIG-I. The active ß-arrestin-2 scaffolds this disobliging signaling to talk with MEX3A. In response to ligands, IGF-1Rß activated the basal ßarr2 into its active state by phosphorylating the interdomain domain on Tyr64 and Tyr250, opening the middle loop (Leu130âCys141) to the RING domain of MEX3A through the conformational changes of ßarr2. The models of ßarr2/IGF-1Rß and ßarr2/MEX3A could interpret the mechanism of the activated-IGF-1R in triggering degradation of RIG-I. The assay of the mutants ßarr2Y64A and ßarr2Y250A further confirmed the role of these two Tyr residues of the interlobe in mediating the talk between IGF-1Rß and the RING domain of MEX3A. The truncated-ßarr2 and the peptide ATQAIRIF, which mimicked the RING domain of MEX3A could prevent the formation of ßarr2/IGF-1Rß and ßarr2/MEX3A complexes, thus blocking the IGF-1R-triggered RIG-I degradation. Degradation of RIG-I resulted in the suppression of the IFN-I-associated immune cells in the TME due to the blockade of the RIG-I-MAVS-IFN-I pathway. Poly(I:C) could reverse anti-PD-L1 insensitivity by recovery of RIG-I. In summary, we revealed a disobliging IGF-1R signaling by which IGF-1Rß promoted cancer growth through triggering the MEX3A-mediated degradation of RIG-I.
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Lightweight concrete is widely used in the construction industry due to its low density and high strength. In this paper, lightweight concrete was prepared by a simple two-step method. Firstly, the light calcium carbonate reinforced epoxy macrospheres (LCR-EMS) material was obtained by adhering calcium lighter carbonate powder to the expanded polystyrene foam spheres (EPS) material using the "balling method". In the second step, the LCR-EMS was mixed with water, cement, and the hollow glass microspheres (HGMS) material using the "molding method" to obtain lightweight concrete. The combination of macroscopic photographs and microscopic morphology shows that the LCR-EMS material itself is uniformly encapsulated and well bonded to the matrix. Test results show that the density of the lightweight concrete decreases with an increase in the volume fraction of stacked LCR-EMS, the diameter, and the proportion of HGMS in the matrix, but it decreases with a decrease in the number of layers of LCR-EMS. The compressive strength of lightweight concrete exhibits a completely opposite trend. When three layers of LCR-EMS were used as filler material, the density and compressive strength of the concrete were 1.246 g/cm3 and 8.19 MPa, respectively. The density and maximum compressive strength of lightweight concrete were 1.146 g/cm3 and 6.37 Mpa, respectively, when filled with 8-9 mm-2L-90 svol% of LCR-EMS and 40 wt% of HGMS in the matrix. Compared with lightweight concrete filled with 90% EPS, the density increased by 20% while the compressive strength increased by 300%.
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The well-known insulin-like growth factor 1 (IGF1)/IGF-1 receptor (IGF-1R) signaling pathway is overexpressed in many tumors, and is thus an attractive target for cancer treatment. However, results have often been disappointing due to crosstalk with other signals. Here, we report that IGF-1R signaling stimulates the growth of hepatocellular carcinoma (HCC) cells through the translocation of IGF-1R into the ER to enhance sarco-endoplasmic reticulum calcium ATPase 2 (SERCA2) activity. In response to ligand binding, IGF-1Rß is translocated into the ER by ß-arrestin2 (ß-arr2). Mass spectrometry analysis identified SERCA2 as a target of ER IGF-1Rß. SERCA2 activity is heavily dependent on the increase in ER IGF-1Rß levels. ER IGF-1Rß phosphorylates SERCA2 on Tyr990 to enhance its activity. Mutation of SERCA2-Tyr990 disrupted the interaction of ER IGF-1Rß with SERCA2, and therefore ER IGF-1Rß failed to promote SERCA2 activity. The enhancement of SERCA2 activity triggered Ca2+ER perturbation, leading to an increase in autophagy. Thapsigargin blocked the interaction between SERCA2 and ER IGF-1Rß and therefore SERCA2 activity, resulting in inhibition of HCC growth. In conclusion, the translocation of IGF-1R into the ER triggers Ca2+ER perturbation by enhancing SERCA2 activity through phosphorylating Tyr990 in HCC.