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Universal and equitable access to affordable safely managed drinking water (SMDW) is a significant challenge and is highlighted by the United Nations' Sustainable Development Goals-6.1. However, SMDW coverage by 2030 is estimated to reach only 81% of the global population. Solar water evaporation (SWE) represents one potential method to ensure decentralized water purification, but its potential for addressing the global SMDW challenge remains unclear. We use a condensation-enhanced strategy and develop a physics-guided machine learning model for assessing the global potential of SWE technology to meet SMDW demand for unserved populations without external electricity input. We find that a condensation-enhanced SWE device (1 m2) can supply enough drinking water (2.5 L day-1) to 95.8% of the population lacking SMDW. SWE can help fulfill universal SMDW coverage by 2030 with an annual cost of 10.4 billion U.S. dollars, saving 66.7% of the current investment and fulfilling the SDG-6.1 goal.
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Electrochemical growth of metal nanocrystals is pivotal for material synthesis, processing, and resource recovery. Understanding the heterogeneous interface between electrolyte and electrode is crucial for nanocrystal nucleation, but the influence of this interaction is still poorly understood. This study employs advanced in situ measurements to investigate the heterogeneous nucleation of metals on solid surfaces. By observing the copper nanocrystal electrodeposition, an interphase interaction-induced nucleation mechanism highly dependent on substrate surface energy is uncovered. It shows that a high-energy (HE) electrode tended to form a polycrystalline structure, while a low-energy (LE) electrode induced a monocrystalline structure. Raman and electrochemical characterizations confirmed that HE interface enhances the interphase interaction, reducing the nucleation barrier for the sturdy nanostructures. This leads to a 30.92-52.21% reduction in the crystal layer thickness and a 19.18-31.78% increase in the charge transfer capability, promoting the formation of a uniform and compact film. The structural compactness of the early nucleated crystals enhances the deposit stability for long-duration electrodeposition. This research not only inspires comprehension of physicochemical processes correlated with heterogeneous nucleation, but also paves a new avenue for high-quality synthesis and efficient recovery of metallic nanomaterials.
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BACKGROUND: Limited research has explored the associations of gestational age (GA) and breastfeeding practices with growth and nutrition in term infants. METHODS: This multicenter cross-sectional study recruited 7299 singleton term infants from well-child visits in Shandong, China, between March 2021 and November 2022. Data on GA, gender, ethnicity, birth weight, parental heights, gestational diabetes and hypertension, age at visit, breastfeeding practices (point-in-time data at visit for infants < 6 months and retrospective data at 6 months for infants ≥ 6 months), complementary foods introduction, infant length and weight, were collected. 7270 infants were included in the analysis after excluding outliers with Z-scores of length (LAZ), weight or weight for length (WLZ) <-4 or > 4. Linear regression models adjused for covariates explored the impact of GA and breastfeeding practices on LAZ and WLZ, while logistic regression models evaluated their effect on the likelihood of moderate and severe stunting (MSS, LAZ<-2), moderate and severe acute malnutrition (MSAM, WLZ<-2) and overweight/obesity (WLZ > 2). Sensitivity analysis was conducted on normal birth weight infants (2.5-4.0 kg). RESULTS: Infants born early-term and exclusively breastfed accounted for 31.1% and 66.4% of the sample, respectively. Early-term birth related to higher WLZ (< 6 months: ß = 0.23, 95% confidence interval (CI): 0.16, 0.29; ≥6 months: ß = 0.12, 95% CI: 0.04, 0.20) and an increased risk of overweight/obesity throughout infancy (< 6 months: OR: 1.41, 95% CI 1.08, 1.84; ≥6 months: OR: 1.35, 95% CI 1.03, 1.79). Before 6 months, early-term birth correlated with lower LAZ (ß=-0.16, 95% CI: -0.21, -0.11) and an increased risk of MSS (OR: 1.01, 95%CI 1.00, 1.02); Compared to exclusive breastfeeding, exclusive formula-feeding and mixed feeding linked to lower WLZ (ß=-0.15, 95%CI -0.30, 0.00 and ß=-0.12, 95%CI -0.19, -0.05, respectively) and increased risks of MSAM (OR: 5.57, 95%CI 1.95, 15.88 and OR: 3.19, 95%CI 1.64, 6.19, respectively). Sensitivity analyses confirmed these findings. CONCLUSIONS: The findings emphasize the health risks of early-term birth and the protective effect of exclusive breastfeeding in singleton term infants, underscoring the avoidance of nonmedically indicated delivery before 39 weeks and promoting exclusive breastfeeding before 6 months.
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Lactancia Materna , Humanos , Lactancia Materna/estadística & datos numéricos , Estudios Transversales , Femenino , Masculino , Recién Nacido , Lactante , China/epidemiología , Edad Gestacional , Fenómenos Fisiológicos Nutricionales del Lactante , Nacimiento a Término , Estudios Retrospectivos , Adulto , Estado NutricionalRESUMEN
With the increasing demand of recycling disposal of industrial wastewater, oil-in-water (O/W) emulsion has been paid much attention in recent years owing to its high oil content. However, due to the presence of surfactant and salt, the emulsion was usually stable with complex physicochemical interfacial properties leading to increased processing difficulty. Herein, a novel flow-through electrode-based demulsification reactor (FEDR) was well designed for the treatment of saline O/W emulsion. In contrast to 53.7% for electrical demulsification only and 80.3% for filtration only, the COD removal efficiency increased to 92.8% under FEDR system. Moreover, the pore size of electrode and the applied voltage were two key factors that governed the FEDR demulsification performance. By observing the morphology of oil droplets deposited layer after different operation conditions and the behavior of oil droplets at the electrode surface under different voltage conditions, the mechanism was proposed that the oil droplets first accumulated on the surface of flow-through electrode by sieving effect, subsequently the gathered oil droplets could further coalesce with the promoting effect of the anode, leading to a high-performing demulsification. This study offers an attractive option of using flow-through electrode to accomplish the oil recovery with simultaneous water purification.
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Electrodos , Filtración , Eliminación de Residuos Líquidos , Purificación del Agua , Purificación del Agua/métodos , Filtración/métodos , Eliminación de Residuos Líquidos/métodos , Aceites/química , Aguas Residuales/química , Contaminantes Químicos del Agua/química , Emulsiones/química , Técnicas Electroquímicas/métodos , Técnicas Electroquímicas/instrumentaciónRESUMEN
The mechanism and function of the expression of Schwann characteristics by nevus cells in the mature zone of the dermis are unknown. Early growth response 3 (EGR3) induces Schwann cell-like differentiation of melanoma cells by simulating the process of nevus maturation, which leads to a strong phenotypic transformation of the cells, including the formation of long protrusions and a decrease in cell motility, proliferation, and melanin production. Meanwhile, EGR3 regulates the levels of myelin protein zero (MPZ) and collagen type I alpha 1 chain (COL1A1) through SRY-box transcription factor 10 (SOX10)-dependent and independent mechanisms, by binding to non-strictly conserved motifs, respectively. Schwann cell-like differentiation demonstrates significant benefits in both in vivo and clinical studies. Finally, a CD86-P2A-EGR3 recombinant mRNA vaccine is developed which leads to tumor control through forced cell differentiation and enhanced immune infiltration. Together, these data support further development of the recombinant mRNA as a treatment for cancer.
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The Yangtze River Basin is an important area for organophosphate esters (OPEs) consumption and emission. Studies proved high OPE detection in Yangtze River water, but there is limited information about the spatiotemporal distribution and transport flux of OPEs in sediment. The present study investigated 16 OPEs in sediment from upstream to mid-downstream of the Yangtze River. The mean concentration of OPEs was 84.30 ng/g, and alkyl-OPEs was the primary component. Great specific surface area and high content of organic carbon significantly increased OPE concentration in Three Gorges Reservoir (TGR) by physical adsorption and chemical bonds (p < 0.05), making TGR the most contaminated area in mainstream. No significant differences in OPE constituents were found in seasonal distribution. Four potential sources of OPEs were identified by principal component analysis and self-organizing maps, and traffic emissions were the dominant source for OPEs. The hazard quotient model results indicated that aryl-OPEs showed moderate risks in the mainstream of Yangtze River, alkyl-OPEs and Cl-OPEs showed low risks. TGR was a significant sink of OPEs in Yangtze River and buried 7.41 tons of OPEs in 2020, a total of 14.87 tons of OPE were transported into the sea by sediment.
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Regulation on denitrifying microbiomes is crucial for sustainable industrial biotechnology and ecological nitrogen cycling. The holistic genetic profiles of microbiomes can be provided by meta-omics. However, precise decryption and further applications of highly complex microbiomes and corresponding meta-omics data sets remain great challenges. Here, we combined optogenetics and geometric deep learning to form a discover-model-learn-advance (DMLA) cycle for denitrification microbiome encryption and regulation. Graph neural networks (GNNs) exhibited superior performance in integrating biological knowledge and identifying coexpression gene panels, which could be utilized to predict unknown phenotypes, elucidate molecular biology mechanisms, and advance biotechnologies. Through the DMLA cycle, we discovered the wavelength-divergent secretion system and nitrate-superoxide coregulation, realizing increasing extracellular protein production by 83.8% and facilitating nitrate removal with 99.9% enhancement. Our study showcased the potential of GNNs-empowered optogenetic approaches for regulating denitrification and accelerating the mechanistic discovery of microbiomes for in-depth research and versatile applications.
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The inhibition of return (IOR) is a phenomenon where response times (RTs) to a target appearing at a previously cued location are slower than those for an uncued location. IOR can improve visual search efficiency. This study aimed to investigate IOR in badminton athletes at different cue depths using a cue-target paradigm in three-dimensional (3-D) static and dynamic scenarios. The study involved 28 badminton athletes (M age = 21.29, SD = 2.39, 14 males) and 25 non-athletes (M age = 21.56, SD = 2.38, 11 males). In the static scenario (Experiment 1), no significant difference between IOR in cueing near and far conditions. IOR was showed both in cueing the near and far condition. Badminton athletes had a speed advantage than non-athletes. In the dynamic scenario (Experiment 2), only badminton athletes showed IOR in cueing the far-to-near condition, but not for the near-to-far. The present study showed that depth information influenced the IOR only in far-to-near condition. Badminton athletes showed more sensitivity to depth information than non-athletes. Additionally, the study expands the object-based IOR in 3-D dynamic scenario.
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In infants with severe bronchopulmonary dysplasia (sBPD), severe pulmonary lobar emphysema may occur as a complication, contributing to significant impairment in ventilation. Clinical management of these infants is extremely challenging and some may require lobectomy to improve ventilation. However, prior to the lobectomy, it is very difficult to assess whether the remaining lung parenchyma would be able to sustain adequate ventilation postoperatively. In addition, preoperative planning and perioperative management are also quite challenging in these patients. This paper reports the utility of selective bronchial occlusion in assessing the safety and efficacy of lobectomy in a case of sBPD complicated by severe right upper lobar emphysema. Since infants with sBPD already have poor lung development and significant lung injury, lobectomy should be viewed as a non-traditional therapy and be carried out with extreme caution. Selective bronchial occlusion test can be an effective tool in assessing the risks and benefits of lobectomy in cases with sBPD and lobar emphysema. However, given the technical difficulty, successful application of this technique requires close collaboration of an experienced interdisciplinary team.
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Displasia Broncopulmonar , Recien Nacido Prematuro , Enfisema Pulmonar , Humanos , Enfisema Pulmonar/cirugía , Displasia Broncopulmonar/etiología , Recién Nacido , Bronquios , Masculino , Neumonectomía , FemeninoRESUMEN
Elastic cartilage constitutes a major component of the external ear, which functions to guide sound to the middle and inner ears. Defects in auricle development cause congenital microtia, which affects hearing and appearance in patients. Mutations in several genes have been implicated in microtia development, yet, the pathogenesis of this disorder remains incompletely understood. Here, we show that Prrx1 genetically marks auricular chondrocytes in adult mice. Interestingly, BMP-Smad1/5/9 signaling in chondrocytes is increasingly activated from the proximal to distal segments of the ear, which is associated with a decrease in chondrocyte regenerative activity. Ablation of Bmpr1a in auricular chondrocytes led to chondrocyte atrophy and microtia development at the distal part. Transcriptome analysis revealed that Bmpr1a deficiency caused a switch from the chondrogenic program to the osteogenic program, accompanied by enhanced protein kinase A activation, likely through increased expression of Adcy5/8. Inhibition of PKA blocked chondrocyte-to-osteoblast transformation and microtia development. Moreover, analysis of single-cell RNA-seq of human microtia samples uncovered enriched gene expression in the PKA pathway and chondrocyte-to-osteoblast transformation process. These findings suggest that auricle cartilage is actively maintained by BMP signaling, which maintains chondrocyte identity by suppressing osteogenic differentiation.
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Condrocitos , Microtia Congénita , Proteínas Quinasas Dependientes de AMP Cíclico , Transducción de Señal , Animales , Condrocitos/metabolismo , Microtia Congénita/genética , Microtia Congénita/metabolismo , Ratones , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/genética , Proteínas Morfogenéticas Óseas/metabolismo , Proteínas Morfogenéticas Óseas/genética , Humanos , Receptores de Proteínas Morfogenéticas Óseas de Tipo 1/metabolismo , Receptores de Proteínas Morfogenéticas Óseas de Tipo 1/genética , Condrogénesis/genética , Proteínas de Homeodominio/metabolismo , Proteínas de Homeodominio/genéticaRESUMEN
Esophageal squamous cell carcinoma (ESCC) is a poor-prognostic cancer type with extensive intra- and inter-patient heterogeneity in both genomic variations and tumor microenvironment (TME). However, the patterns and drivers of spatial genomic and microenvironmental heterogeneity of ESCC remain largely unknown. Here, we generated a spatial multi-omic atlas by whole-exome, transcriptome, and methylome sequencing of 507 tumor samples from 103 patients. We identified a novel tumor suppressor PREX2, accounting for 22% of ESCCs with frequent somatic mutations or hyper-methylation, which promoted migration and invasion of ESCC cells in vitro. Analysis of the TME and quantification of subclonal expansion indicated that ESCCs undergo spatially directed evolution, where subclones mostly originated from the tumor center but had a biased clonal expansion to the upper direction of the esophagus. Interestingly, we found upper regions of ESCCs often underwent stronger immunoediting with increased selective fitness, suggesting more stringent immune selection. In addition, distinct TMEs were associated with variable genomic and clinical outcomes. Among them, hot TME was associated with high immune evasion and subclonal heterogeneity. We also found that immunoediting, instead of CD8+ T cell abundance, acts as an independent prognostic factor of ESCCs. Importantly, we found significant heterogeneity in previously considered potential therapeutic targets, as well as BRCAness characteristics in a subset of patients, emphasizing the importance of focusing on heterogeneity in ESCC targeted therapy. Collectively, these findings provide novel insights into the mechanisms of the spatial evolution of ESCC and inform precision therapeutic strategies.
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BACKGROUND: Myeloid-derived suppressor cells (MDSCs) promote tumor growth, metastasis, and lead to immunotherapy resistance. Studies revealed that miRNAs are also expressed in MDSCs and promote the immunosuppressive function of MDSCs. Currently, few studies have been reported on inducible cellular microvesicle delivery of nucleic acid drugs targeting miRNA in MDSCs for the treatment of malignant tumors. RESULTS AND CONCLUSION: In this study, we designed an artificial DNA named G-quadruplex-enhanced circular single-stranded DNA-9 (G4-CSSD9), that specifically adsorbs the miR-9 sequence. Its advanced DNA folding structure, rich in tandem repeat guanine (G-quadruplex), also provides good stability. Mesenchymal stem cells (MSCs) were prepared into nanostructured vesicles by membrane extrusion. The MSC microvesicles-encapsulated G4-CSSD9 (MVs@G4-CSSD9) was delivered into MDSCs, which affected the downstream transcription and translation process, and reduced the immunosuppressive function of MDSCs, so as to achieve the purpose of treating melanoma. In particular, it provides an idea for the malignant tumor treatment.
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ADN de Cadena Simple , G-Cuádruplex , Células Madre Mesenquimatosas , MicroARNs , Células Supresoras de Origen Mieloide , Animales , Células Supresoras de Origen Mieloide/metabolismo , Ratones , ADN de Cadena Simple/química , Línea Celular Tumoral , Ratones Endogámicos C57BL , Micropartículas Derivadas de Células/química , Micropartículas Derivadas de Células/metabolismo , ADN Circular/química , Humanos , Melanoma/tratamiento farmacológicoRESUMEN
Industrial hypersaline wastewaters contain diverse pollutants that harm the environment. Recovering clean water, alkali and acid from these wastewaters can promote circular economy and environmental protection. However, current electrochemical and advanced oxidation processes, which rely on hydroxyl radicals to degrade organic compounds, are inefficient and energy intensive. Here we report a flow-through redox-neutral electrochemical reactor (FRER) that effectively removes organic contaminants from hypersaline wastewaters via the chlorination-dehalogenation-hydroxylation route involving radical-radical cross-coupling. Bench-scale experiments demonstrate that the FRER achieves over 75% removal of total organic carbon across various compounds, and it maintains decontamination performance for over 360 h and continuously treats real hypersaline wastewaters for two months without corrosion. Integrating the FRER with electrodialysis reduces operating costs by 63.3% and CO2 emissions by 82.6% when compared with traditional multi-effect evaporation-crystallization techniques, placing our system at technology readiness levels of 7-8. The desalinated water, high-purity NaOH (>95%) and acid produced offset industrial production activities and thus support global sustainable development objectives.
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BACKGROUND AND STUDY AIMS: There are limited data regarding indeterminate acute liver failure (ALF). The study aims to perform a post hoc analysis using genetic methods for the ALF cases with indeterminate etiology. PATIENTS AND METHODS: Stored blood samples from these patients with indeterminate ALF were collected. Whole-exome sequencing (WES) was used to evaluate the pathogenesis of indeterminate ALF. RESULTS: A total of 16 samples from 11 adult patients and 5 pediatric patients with indeterminate ALF were available. Among the adult patients, one female patient was identified with two heterozygous variants (c.2333G > T (p.Arg778Leu) and c.2310C > G (p.Leu770 = )) in the adenosine triphosphatase copper-transporting beta (ATP7B) gene, and two male patients were found to harbor heterozygous and homozygous variants (c.686C > A (p.Pro229Gln) plus homozygousvariantA(TA)6TAAinsTA (-), andc.1456 T > G (p.Tyr486Asp) plus c.211G > A (p.Gly71Arg)) in the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene. For the pediatric patients, single heterozygous variant (c.2890C > T (p.Arg964Cys)) in the polymerase gamma (POLG) gene was found in 1 male child, and two heterozygous variants (c.1909A > G (p.Lys637Glu) and c.3646G > A (p.Val1216Ile)) in the tetratricopeptide repeat domain 37 (TTC37) gene were found in 1 female child. No variants clinically associated with known liver diseases were revealed in the remaining patients. CONCLUSION: These results expand the knowledge of ALF with indeterminate etiology. WES is helpful to reveal possible candidate genes for indeterminate ALF, but incomplete consistency between the genotype and phenotype in some cases still challenge the accurate diagnosis.
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ATPasas Transportadoras de Cobre , Secuenciación del Exoma , Glucuronosiltransferasa , Fallo Hepático Agudo , Humanos , Fallo Hepático Agudo/genética , Fallo Hepático Agudo/diagnóstico , Masculino , Femenino , Adulto , Glucuronosiltransferasa/genética , Niño , ATPasas Transportadoras de Cobre/genética , Heterocigoto , Adolescente , Persona de Mediana Edad , Preescolar , Adulto Joven , Mutación , HomocigotoRESUMEN
Although Z. mioga flower buds are popular among consumers for its unique spicy flavor, high nutritional and medicinal value, there are few reports on the formation and changes of the flavor during its growth and maturation process. The understanding of the profile of volatile compounds would help to unravel the flavor formation for Z. mioga flower buds during growth. The volatile changes in Z. mioga flower buds were analyzed by GC-MS and a total of 182 volatile compounds identified, and the terpenoids accounted for the most abundant volatile substances. Almost all the identified volatiles presented an intuitive upward trend throughout the growth period and reached the maximum at the later stage of development (DS3 or DS4). Regarding the PCA and HCA results, there were significant differences found among the four stages, and the DS3 was the critical node. The top 50 differential volatiles screened by OPLS-DA and PLS-DA were all up-regulated, and the correlation analysis indicated that terpenoids might synergize with other chemical types of volatiles to jointly affect the flavor formation of Z. mioga flower buds during growth. The association network for flavor omics revealed that the most important sensory flavor for Z. mioga flower buds were woody and sweet, and the main contribution compounds for the unique flavor contained ß-guaiene, ß-farnesene, δ-cadinene and citronellyl isobutanoate. Taken together, the results of this study provided a reference for flavor quality evaluation of flower buds and determination of the best harvest period.
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Flores , Cromatografía de Gases y Espectrometría de Masas , Compuestos Orgánicos Volátiles , Flores/crecimiento & desarrollo , Flores/metabolismo , Compuestos Orgánicos Volátiles/análisis , Compuestos Orgánicos Volátiles/metabolismo , Gusto , Terpenos/metabolismo , Terpenos/análisisRESUMEN
Drinking water with micropollutants is a notable environmental concern worldwide. Membrane separation is one of the few methods capable of removing micropollutants from water. However, existing membranes face challenges in the simultaneous and efficient treatment of small-molecular and ionic contaminants because of their limited permselectivity. Here, we propose a high-efficiency water purification method using a low-pressure Janus membrane with electro-induced multi-affinity. By virtue of hydrophobic and electrostatic interactions between the functional interfaces and contaminants, the Janus membrane achieves simultaneous separation of diverse types of organics and heavy metals from water via single-pass filtration, with an approximately 100% removal efficiency, high water flux (>680 liters m-2 hour-1), and 98% lower energy consumption compared with commercial nanofiltration membranes. The electro-induced switching of interfacial affinity enables 100% regeneration of membrane performance; thus, our work paves a sustainable avenue for drinking water purification by regulating the interfacial affinity of membranes.
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Exosomes are emerging mediators of cell-cell communication, which are secreted from cells and may be delivered into recipient cells in cell biological processes. Here, we examined microRNA (miRNA) expression in esophageal squamous cell carcinoma (ESCC) cells. We performed miRNA sequencing in exosomes and cells of KYSE150 and KYSE450 cell lines. Among these differentially expressed miRNAs, 20 of the miRNAs were detected in cells and exosomes. A heat map indicated that the level of miR-451a was higher in exosomes than in ESCC cells. Furthermore, miRNA pull-down assays and combined exosomes proteomic data showed that miR-451a interacts with YWHAE. Over-expression of YWHAE leads to miR-451a accumulation in the exosomes instead of the donor cells. We found that miR-451a was sorted into exosomes. However, the biological function of miR-451a remains unclear in ESCC. Here, Dual-luciferase reporter assay was conducted and it was proved that CAB39 is a target gene of miR-451a. Moreover, CAB39 is related to TGF-ß1 from RNA-sequencing data of 155 paired of ESCC tissues and the matched tissues. Western Blot and qPCR revealed that CAB39 and TGF-ß1 were positively correlated in ESCC. Over-expression of CAB39 were cocultured with PBMCs from the blood from healthy donors. Flow cytometry assays showed that apoptotic cells were significantly reduced after CAB39 over-expression and significantly increased after treated with TGF-ß1 inhibitors. Thus, our data indicate that CAB39 weakens antitumor immunity through TGF-ß1 in ESCC. In summary, YWHAE selectively sorted miR-451a into exosomes and it can weaken antitumor immunity promotes tumor progression through CAB39.
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Progresión de la Enfermedad , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Exosomas , MicroARNs , Animales , Femenino , Humanos , Masculino , Ratones , Proteínas 14-3-3/genética , Proteínas 14-3-3/metabolismo , Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/metabolismo , Exosomas/metabolismo , Exosomas/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , MicroARNs/metabolismoRESUMEN
BACKGROUND: Psoriasis is a common chronic inflammatory disease with an unclear aetiology. Keratinocytes in psoriasis are susceptible to exogenous triggers that induce inflammatory cell death. OBJECTIVES: To investigate whether gasdermin E (GSDME)-mediated pyroptosis in keratinocytes contributes to the pathogenesis of psoriasis. METHODS: Skin samples from patients with psoriasis and from healthy controls were collected to evaluate the expression of GSDME, cleaved caspase-3 and inflammatory factors. We then analysed the data series GSE41662 to further compare the expression of GSDME between lesional and nonlesional skin samples in those with psoriasis. In vivo, a caspase-3 inhibitor and GSDME-deficient mice (Gsdme-/-) were used to block caspase-3/GSDME activation in an imiquimod-induced psoriasis model. Skin inflammation, disease severity and pyroptosis-related proteins were analysed. In vitro, tumour necrosis factor (TNF)-α-induced caspase-3/GSDME-mediated pyroptosis in the HACAT cell line was explored. RESULTS: Our analysis of the GSE41662 data series found that GSDME was upregulated in psoriasis lesions vs. normal skin. High levels of inflammatory cytokines such as interleukin (IL)-1ß, IL-6 and TNF-α were also found in psoriasis lesions. In mice in the Gsdme-/- and caspase-3 inhibitor groups, the severity of skin inflammation was attenuated and GSDME and cleaved caspase-3 levels decreased after imiquimod treatment. Similarly, IL-1ß, IL-6 and TNF-α expression was decreased in the Gsdme-/- and caspase-3 inhibitor groups. In vitro, TNF-α induced HACAT cell pyroptosis through caspase-3/GSDME pathway activation, which was suppressed by blocking caspase-3 or silencing Gsdme. CONCLUSIONS: Our study provides a novel explanation of TNF-α/caspase-3/GSDME-mediated keratinocyte pyroptosis in the initiation and -acceleration of skin inflammation and the progression of psoriasis.
Psoriasis is chronic and autoinflammatory common skin disease that affects 23% of the world's population. The disease is characterized by persistent inflammation in various body systems, including the skin and joints. However, the exact cause of the disease is unclear. In this study from China, we found that in people with psoriasis a protein called 'gasdermin E' (or 'GSDME') is increased in a type of skin cell called keratinocytes. In psoriasis, these keratinocytes are susceptible to a type of cell death called 'pyroptosis'. We aimed to find out whether pyroptosis caused by GSDME in keratinocytes contributes to the development of psoriasis. To do this, we looked at samples of skin from people with psoriasis and compared these to samples from healthy controls (those without psoriasis). Firstly, we investigated the levels of GSDME, another protein called caspase-3 and other inflammatory factors in the skin lesions from patients with psoriasis. Secondly, we analysed previously published data from 24 patients with psoriasis. Finally, we carried out a range of experiments to confirm our findings. We found that keratinocyte pyroptosis was mediated by the messenger proteins TNF-α/caspase-3, and that GSDME played a key role in the initiation and acceleration of skin inflammation and the progression of psoriasis. Targeting the GSDME pathway may be a novel strategy in treating psoriasis.