RESUMEN
Early embryogenesis is a conserved and self-organized process. In the mammalian embryo, the potential for self-organization is manifested in its extraordinary developmental plasticity, allowing a correctly patterned embryo to arise despite experimental perturbation. The underlying mechanisms enabling such regulative development have long been a topic of study. In this Review, we summarize our current understanding of the self-organizing principles behind the regulative nature of the early mammalian embryo. We argue that geometrical constraints, feedback between mechanical and biochemical factors, and cellular heterogeneity are all required to ensure the developmental plasticity of mammalian embryo development.
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Embrión de Mamíferos/fisiología , Mamíferos/embriología , Animales , Blastocisto/citología , Tipificación del Cuerpo , Linaje de la Célula , Embrión de Mamíferos/citología , Desarrollo EmbrionarioRESUMEN
Nuclear architecture has never been carefully examined during early mammalian development at the stages leading to establishment of the embryonic and extra-embryonic lineages. Heterogeneous activity of the methyltransferase CARM1 during these stages results in differential methylation of histone H3R26 to modulate establishment of these two lineages. Here we show that CARM1 accumulates in nuclear granules at the 2- to 4-cell stage transition in the mouse embryo, with the majority corresponding to paraspeckles. The paraspeckle component Neat1 and its partner p54nrb are required for CARM1's association with paraspeckles and for H3R26 methylation. Conversely, CARM1 also influences paraspeckle organization. Depletion of Neat1 or p54nrb results in arrest at the 16- to 32-cell stage, with elevated expression of transcription factor Cdx2, promoting differentiation into the extra-embryonic lineage. This developmental arrest occurs at an earlier stage than following CARM1 depletion, indicating that paraspeckles act upstream of CARM1 but also have additional earlier roles in fate choice.
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Blastocisto/metabolismo , Diferenciación Celular , Linaje de la Célula , Desarrollo Embrionario , Proteínas Asociadas a Matriz Nuclear/metabolismo , Proteína-Arginina N-Metiltransferasas/metabolismo , ARN Largo no Codificante/metabolismo , Proteínas de Unión al ARN/metabolismo , Animales , Blastocisto/citología , Puntos de Control del Ciclo Celular , Ratones , Proteínas Asociadas a Matriz Nuclear/genética , Proteína-Arginina N-Metiltransferasas/genética , ARN Largo no Codificante/genética , Proteínas de Unión al ARN/genéticaRESUMEN
Antiferromagnetic spintronics1-16 is a rapidly growing field in condensed-matter physics and information technology with potential applications for high-density and ultrafast information devices. However, the practical application of these devices has been largely limited by small electrical outputs at room temperature. Here we describe a room-temperature exchange-bias effect between a collinear antiferromagnet, MnPt, and a non-collinear antiferromagnet, Mn3Pt, which together are similar to a ferromagnet-antiferromagnet exchange-bias system. We use this exotic effect to build all-antiferromagnetic tunnel junctions with large nonvolatile room-temperature magnetoresistance values that reach a maximum of about 100%. Atomistic spin dynamics simulations reveal that uncompensated localized spins at the interface of MnPt produce the exchange bias. First-principles calculations indicate that the remarkable tunnelling magnetoresistance originates from the spin polarization of Mn3Pt in the momentum space. All-antiferromagnetic tunnel junction devices, with nearly vanishing stray fields and strongly enhanced spin dynamics up to the terahertz level, could be important for next-generation highly integrated and ultrafast memory devices7,9,16.
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Splicing quantitative trait loci (sQTLs) have been demonstrated to contribute to disease etiology by affecting alternative splicing. However, the role of sQTLs in the development of non-small-cell lung cancer (NSCLC) remains unknown. Thus, we performed a genome-wide sQTL study to identify genetic variants that affect alternative splicing in lung tissues from 116 individuals of Chinese ancestry, which resulted in the identification of 1,385 sQTL-harboring genes (sGenes) containing 378,210 significant variant-intron pairs. A comprehensive characterization of these sQTLs showed that they were enriched in actively transcribed regions, genetic regulatory elements, and splicing-factor-binding sites. Moreover, sQTLs were largely distinct from expression quantitative trait loci (eQTLs) and showed significant enrichment in potential risk loci of NSCLC. We also integrated sQTLs into NSCLC GWAS datasets (13,327 affected individuals and 13,328 control individuals) by using splice-transcriptome-wide association study (spTWAS) and identified alternative splicing events in 19 genes that were significantly associated with NSCLC risk. By using functional annotation and experiments, we confirmed an sQTL variant, rs35861926, that reduced the risk of lung adenocarcinoma (rs35861926-T, OR = 0.88, 95% confidence interval [CI]: 0.82-0.93, p = 1.87 × 10-5) by promoting FARP1 exon 20 skipping to downregulate the expression level of the long transcript FARP1-011. Transcript FARP1-011 promoted the migration and proliferation of lung adenocarcinoma cells. Overall, our study provided informative lung sQTL resources and insights into the molecular mechanisms linking sQTL variants to NSCLC risk.
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Adenocarcinoma del Pulmón , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Sitios de Carácter Cuantitativo/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Estudio de Asociación del Genoma Completo/métodos , Neoplasias Pulmonares/genética , Empalme Alternativo/genética , Adenocarcinoma del Pulmón/genética , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
Elevated circulating levels of growth differentiation factor 15 (GDF15) have been shown to reduce food intake and lower body weight through activation of hindbrain receptor glial-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL) in rodents and nonhuman primates, thus endogenous induction of this peptide holds promise for obesity treatment. Here, through in silico drug-screening methods, we found that small molecule Camptothecin (CPT), a previously identified drug with potential antitumor activity, is a GDF15 inducer. Oral CPT administration increases circulating GDF15 levels in diet-induced obese (DIO) mice and genetic ob/ob mice, with elevated Gdf15 expression predominantly in the liver through activation of integrated stress response. In line with GDF15's anorectic effect, CPT suppresses food intake, thereby reducing body weight, blood glucose, and hepatic fat content in obese mice. Conversely, CPT loses these beneficial effects when Gdf15 is inhibited by a neutralizing antibody or AAV8-mediated liver-specific knockdown. Similarly, CPT failed to reduce food intake and body weight in GDF15's specific receptor GFRAL-deficient mice despite high levels of GDF15. Together, these results indicate that CPT is a promising anti-obesity agent through activation of GDF15-GFRAL pathway.
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Camptotecina/farmacología , Receptores del Factor Neurotrófico Derivado de la Línea Celular Glial/genética , Factor 15 de Diferenciación de Crecimiento/genética , Obesidad/prevención & control , Animales , Peso Corporal/efectos de los fármacos , Peso Corporal/genética , Camptotecina/farmacocinética , Línea Celular , Línea Celular Tumoral , Dieta Alta en Grasa/efectos adversos , Ingestión de Alimentos/efectos de los fármacos , Ingestión de Alimentos/genética , Regulación de la Expresión Génica/efectos de los fármacos , Receptores del Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Factor 15 de Diferenciación de Crecimiento/metabolismo , Células HEK293 , Células HL-60 , Humanos , Células MCF-7 , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Obesos , Obesidad/etiología , Obesidad/genética , Células PC-3RESUMEN
The importance of highly siderophile elements (HSEs; namely, gold, iridium, osmium, palladium, platinum, rhenium, rhodium and ruthenium) in tracking the late accretion stages of planetary formation has long been recognized. However, the precise nature of the Moon's accretional history remains enigmatic. There is a substantial mismatch in the HSE budgets of the Earth and the Moon, with the Earth seeming to have accreted disproportionally more HSEs than the Moon1. Several scenarios have been proposed to explain this conundrum, including the delivery of HSEs to the Earth by a few big impactors1, the accretion of pebble-sized objects on dynamically cold orbits that enhanced the Earth's gravitational focusing factor2, and the 'sawtooth' impact model, with its much reduced impact flux before about 4.10 billion years ago3. However, most of these models assume a high impactor-retention ratio (the fraction of impactor mass retained on the target) for the Moon. Here we perform a series of impact simulations to quantify the impactor-retention ratio, followed by a Monte Carlo procedure considering a monotonically decaying impact flux4, to compute the impactor mass accreted into the lunar crust and mantle over their histories. We find that the average impactor-retention ratio for the Moon's entire impact history is about three times lower than previously estimated1,3. Our results indicate that, to match the HSE budgets of the lunar crust and mantle5,6, the retention of HSEs should have started 4.35 billion years ago, when most of the lunar magma ocean was solidified7,8. Mass accreted before this time must have lost its HSEs to the lunar core, presumably during lunar mantle crystallization9. The combination of a low impactor-retention ratio and a late retention of HSEs in the lunar mantle provides a realistic explanation for the apparent deficit of the Moon's late-accreted mass relative to that of the Earth.
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The proportion of lung cancer in never smokers is rising, especially among Asian women, but there is no effective early detection tool. Here, we developed a polygenic risk score (PRS), which may help to identify the population with higher risk of lung cancer in never-smoking women. We first performed a large GWAS meta-analysis (8595 cases and 8275 controls) to systematically identify the susceptibility loci for lung cancer in never-smoking Asian women and then generated a PRS using GWAS datasets. Furthermore, we evaluated the utility and effectiveness of PRS in an independent Chinese prospective cohort comprising 55 266 individuals. The GWAS meta-analysis identified eight known loci and a novel locus (5q11.2) at the genome-wide statistical significance level of P < 5 × 10-8 . Based on the summary statistics of GWAS, we derived a polygenic risk score including 21 variants (PRS-21) for lung cancer in never-smoking women. Furthermore, PRS-21 had a hazard ratio (HR) per SD of 1.29 (95% CI = 1.18-1.41) in the prospective cohort. Compared with participants who had a low genetic risk, those with an intermediate (HR = 1.32, 95% CI: 1.00-1.72) and high (HR = 2.09, 95% CI: 1.56-2.80) genetic risk had a significantly higher risk of incident lung cancer. The addition of PRS-21 to the conventional risk model yielded a modest significant improvement in AUC (0.697 to 0.711) and net reclassification improvement (24.2%). The GWAS-derived PRS-21 significantly improves the risk stratification and prediction accuracy for incident lung cancer in never-smoking Asian women, demonstrating the potential for identification of high-risk individuals and early screening.
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Neoplasias Pulmonares , Humanos , Femenino , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/genética , Puntuación de Riesgo Genético , Predisposición Genética a la Enfermedad , Estudios de Cohortes , Estudios Prospectivos , Estudio de Asociación del Genoma Completo , Factores de Riesgo , Fumar/genética , Fumar/epidemiología , ChinaRESUMEN
BACKGROUND: Although the associations between genetic variations and lung cancer risk have been explored, the epigenetic consequences of DNA methylation in lung cancer development are largely unknown. Here, the genetically predicted DNA methylation markers associated with non-small cell lung cancer (NSCLC) risk by a two-stage case-control design were investigated. METHODS: The genetic prediction models for methylation levels based on genetic and methylation data of 1595 subjects from the Framingham Heart Study were established. The prediction models were applied to a fixed-effect meta-analysis of screening data sets with 27,120 NSCLC cases and 27,355 controls to identify the methylation markers, which were then replicated in independent data sets with 7844 lung cancer cases and 421,224 controls. Also performed was a multi-omics functional annotation for the identified CpGs by integrating genomics, epigenomics, and transcriptomics and investigation of the potential regulation pathways. RESULTS: Of the 29,894 CpG sites passing the quality control, 39 CpGs associated with NSCLC risk (Bonferroni-corrected p ≤ 1.67 × 10-6 ) were originally identified. Of these, 16 CpGs remained significant in the validation stage (Bonferroni-corrected p ≤ 1.28 × 10-3 ), including four novel CpGs. Multi-omics functional annotation showed nine of 16 CpGs were potentially functional biomarkers for NSCLC risk. Thirty-five genes within a 1-Mb window of 12 CpGs that might be involved in regulatory pathways of NSCLC risk were identified. CONCLUSIONS: Sixteen promising DNA methylation markers associated with NSCLC were identified. Changes of the methylation level at these CpGs might influence the development of NSCLC by regulating the expression of genes nearby. PLAIN LANGUAGE SUMMARY: The epigenetic consequences of DNA methylation in lung cancer development are still largely unknown. This study used summary data of large-scale genome-wide association studies to investigate the associations between genetically predicted levels of methylation biomarkers and non-small cell lung cancer risk at the first time. This study looked at how well larotrectinib worked in adult patients with sarcomas caused by TRK fusion proteins. These findings will provide a unique insight into the epigenetic susceptibility mechanisms of lung cancer.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Adulto , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Metilación de ADN , Neoplasias Pulmonares/genética , Estudio de Asociación del Genoma Completo , Epigénesis Genética , Biomarcadores , Islas de CpGRESUMEN
Tissue development is mediated by a combination of mechanical and biological signals. Currently, there are many reports on biological signals regulating repair. However, insufficient attention is paid to the process of mechanical regulation, especially the active mechanical regulation in vivo, which has not been realized. Herein, a novel dynamically regulated repair system for both in vitro and in vivo applications is developed, which utilizes magnetic nanoparticles as non-contact actuators to activate hydrogels. The magnetic hydrogel can be periodically activated and deformed to different amplitudes by a dynamic magnetic system. An in vitro skin model is used to explore the impact of different dynamic stimuli on cellular mechano-transduction signal activation and cell differentiation. Specifically, the effect of mechanical stimulation on the phenotypic transition of fibroblasts to myofibroblasts is investigated. Furthermore, in vivo results verify that dynamic massage can simulate and enhance the traction effect in skin defects, thereby accelerating the wound healing process by promoting re-epithelialization and mediating dermal contraction.
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Vendajes , Masaje , Cicatrización de Heridas , Animales , Masaje/métodos , Fibroblastos , Humanos , Hidrogeles/química , Diferenciación Celular , Piel , Ratones , Miofibroblastos/citologíaRESUMEN
N6 -methyladenosine (m6 A) modification has been identified as one of the most important epigenetic regulation mechanisms in the development of human cancers. However, the association between m6 A-associated single-nucleotide polymorphisms (m6 A-SNPs) and lung cancer risk remains largely unknown. Here, we identified m6 A-SNPs and examined the association of these m6 A-SNPs with lung cancer risk in 13,793 lung cancer cases and 14,027 controls. In silico functional annotation was used to identify causal m6 A-SNPs and target genes. Furthermore, methylated RNA immunoprecipitation and quantitative real-time polymerase chain reaction (MeRIP-qPCR) assay was performed to assess the m6 A modification level of different genotypes of the causal SNP. In vitro assays were performed to validate the potential role of the target gene in lung cancer. A total of 8794 m6 A-SNPs were detected, among which 397 SNPs in nine susceptibility loci were associated with lung cancer risk, including six novel loci. Bioinformatics analyses indicated that rs1321328 in 6q21 was located around the m6 A modification site of AK9 and significantly reduced AK9 expression (ß = -0.15, p = 2.78 × 10-8 ). Moreover, AK9 was significantly downregulated in lung cancer tissues than that in adjacent normal tissues of samples from the Cancer Genome Atlas and Nanjing Lung Cancer Cohort. MeRIP-qPCR assay suggested that C allele of rs1321328 could significantly decrease the m6 A modification level of AK9 compared with G allele. In vitro assays verified the tumor-suppressing role of AK9 in lung cancer. These findings shed light on the pathogenic mechanism of lung cancer susceptibility loci linked with m6 A modification.
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Adenina , Neoplasias Pulmonares , Polimorfismo de Nucleótido Simple , Humanos , Adenina/análogos & derivados , Epigénesis Genética , Genes Supresores de Tumor , Neoplasias Pulmonares/genética , Adenilato Quinasa/metabolismoRESUMEN
Atherosclerosis is one of the leading causes of death worldwide. miR-26 is a potential biomarker of atherosclerosis. Standardized diagnostic tests for miR-26 (MIR26-DX) have been developed, but the fastest progress has been in predicting the efficacy of IFN-α therapy for hepatocellular carcinoma (HCC, phase 3). MiR-26 slows atherosclerosis development by suppressing ACC1/2, ACLY, ACSL3/4, ALDH3A2, ALPL, BMP2, CD36, COL1A1, CPT1A, CTGF, DGAT2, EHHADH, FAS, FBP1, GATA4, GSK3ß, G6PC, Gys2, HMGA1, HMGB1, LDLR, LIPC, IL-1ß, IL-6, JAG2, KCNJ2, MALT1, ß-MHC, NF-κB, PCK1, PLCß1, PYGL, RUNX2, SCD1, SMAD1/4/5/7, SREBF1, TAB3, TAK1, TCF7L2, and TNF-α expression. Many agents targeting these genes, such as the ACC1/2 inhibitors GS-0976, PF-05221304, and MK-4074; the DGAT2 inhibitors IONIS-DGAT2Rx, PF-06427878, PF-0685571, and PF-07202954; the COL1A1 inhibitor HT-100; the stimulants 68Ga-CBP8 and RCT-01; the CPT1A inhibitors etomoxir, perhexiline, and teglicar; the FBP1 inhibitors CS-917 and MB07803; and the SMAD7 inhibitor mongersen, have been investigated in clinical trials. Interestingly, miR-26 better reduced intima-media thickness (IMT) than PCSK9 or CT-1 knockout. Many PCSK9 inhibitors, including alirocumab, evolocumab, inclisiran, AZD8233, Civi-007, MK-0616, and LIB003, have been investigated in clinical trials. Recombinant CT-1 was also investigated in clinical trials. Therefore, miR-26 is a promising target for agent development. miR-26 promotes foam cell formation by reducing ABCA1 and ARL4C expression. Multiple materials can be used to deliver miR-26, but it is unclear which material is most suitable for mass production and clinical applications. This review focuses on the potential use of miR-26 in treating atherosclerosis to support the development of agents targeting it.
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Aterosclerosis , MicroARNs , Humanos , Factores de Ribosilacion-ADP , Grosor Intima-Media Carotídeo , Diacilglicerol O-Acetiltransferasa , MicroARNs/genética , Proproteína Convertasa 9 , Proteína smad7 , Aterosclerosis/genéticaRESUMEN
OBJECTIVE: Health care overuse is pervasive in countries with advanced health care delivery systems. We hypothesize that effective interventions to reduce low-value care that targets patients or clinicians are mediated by psychological and cognitive processes that change behaviors and that interventions targeting these processes are varied. Thus, we performed a scoping review of experimental studies of interventions, including the interventions' objectives and characteristics, to reduce low-value care that targeted psychological and cognitive processes. METHODS: We systematically searched databases for experimental studies of interventions to change cognitive orientations and affective states in the setting of health care overuse. Outcomes included observed overuse or a stated intention to use services. We used existing frameworks for behavior change and mechanisms of change to categorize the interventions and the mediating processes. RESULTS: Twenty-seven articles met the inclusion criteria. Sixteen studied the provision of information to patients or clinicians, with most providing cost information. Six studies used educational interventions, including the provision of feedback about individual practice. Studies rarely used counseling, behavioral nudges, persuasion, and rewards. Mechanisms for behavior change included gain in knowledge or confidence and motivation by social norms. CONCLUSIONS: In this scoping review, we found few experiments testing interventions that directly target the psychological and cognitive processes of patients or clinicians to reduce low-value care. Most studies provided information to patients or clinicians without measuring or considering mediating factors toward behavior change. These findings highlight the need for process-driven experimental designs, including trials of behavioral nudges and persuasive language involving a trusting patient-clinician relationship, to identify effective interventions to reduce low-value care.
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Atención a la Salud , Uso Excesivo de los Servicios de Salud , Humanos , Motivación , Uso Excesivo de los Servicios de Salud/prevención & controlRESUMEN
BACKGROUND: There is unclear added benefit of intravenous thrombolysis (IVT) with endovascular thrombectomy (EVT). We performed a cost-effectiveness analysis to assess the cost-effectiveness of comparing EVT with IVT versus EVT alone. METHODS: We used a decision tree to examine the short-term costs and outcomes at 90 days after the occurrence of index stroke to compare the cost-effectiveness of EVT alone with EVT plus IVT for patients with stroke. Subsequently, we developed a Markov state transition model to assess the costs and outcomes over 1-year, 5-year, and 20-year time horizons. We estimated total and incremental cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio. RESULTS: The average costs per patient were estimated to be $47,304, $49,510, $59,770, and $76,561 for EVT-only strategy and $55,482, $57,751, $68,314, and $85,611 for EVT with IVT over 90 days, 1 year, 5 years, and 20 years, respectively. The cost saving of EVT-only strategy was driven by the avoided medication costs of IVT (ranging from $8,178 to $9,050). The additional IVT led to a slight decrease in QALY estimate during the 90-day time horizon (loss of 0.002 QALY), but a small gain over 1-year and 5-year time horizons (0.011 and 0.0636 QALY). At a willingness-to-pay threshold of $50,000 per QALY gained, the probabilities of EVT only being cost-effective were 100%, 100%, and 99.3% over 90-day, 1-year, and 5-year time horizons. CONCLUSION: Our cost-effectiveness model suggested that EVT only may be cost-effective for patients with acute ischemic stroke secondary to large vessel occlusion.
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Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/cirugía , Terapia Trombolítica , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/cirugía , Análisis de Costo-Efectividad , Trombectomía , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/cirugía , Resultado del Tratamiento , Análisis Costo-BeneficioRESUMEN
It's urgent to discover new antibiotics along with the increasing emergence and dissemination of multidrug resistant (MDR) bacterial pathogens. In the present investigation, morusin exhibited rapid bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) by targeting the phospholipid of bacterial inner membrane, increasing membrane rigidity and disrupting bacterial homeostasis together with the membrane permeability, which caused fundamental metabolic disorders. Furthermore, morusin can also accumulate ROS, suppress H2S production, and aggravate oxidative damage in bacteria. Importantly, morusin also inhibited the spread of wounds and reduced the bacterial burden in the mouse model of skin infection caused by MRSA. It's a chance to meet the challenge of existing antibiotic resistance and avoid the development of bacterial resistance, given the multiple targets of morusin.
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Staphylococcus aureus Resistente a Meticilina , Morus , Animales , Ratones , Antibacterianos/farmacología , Pruebas de Sensibilidad MicrobianaRESUMEN
Cancer-associated fibroblasts (CAFs) are an important component of the tumor microenvironment (TME) and can induce functional polarization of tumor macrophages. This study aimed to explore the effect of CAFs-derived exosome LINC01833 on the malignant biological behavior of non-small cell lung cancer (NSCLC) cells and its mechanism. Tumor tissues (n = 3) and adjacent noncancerous tissues (n = 3) were collected from patients with NSCLC, and fibroblasts (CAF, NF) were isolated from the two tissues. Expression of LINC01833/miR-335-5p/VAPA in NSCLC clinical tissues and cell lines was detected by RT-qPCR. Exosomes of CAFs and NFs were isolated by ultracentrifugation. Cell proliferation, migration, invasion, and M2 macrophage polarization were detected by MTT, transwell, wound-healing assay, and flow cytometry assay, while western blot was used to verify the expression of M2 macrophage polarization-related proteins. Tumor volume weight and M2 macrophage polarization were detected by tumor xenografts in nude mice. LINC01833 was highly expressed in NSCLC tumor tissues and cells. Knockdown of LINC01833 exosomes could significantly inhibit proliferation, migration, invasion of NSCLC cells, and M2 macrophage polarization of THP-1 cells, while simultaneous knockdown of miR-335-5p on the above basis could reverse the effect of knockdown of LINC01833. In vivo experiments also indicated that knockdown of LINC01833 exosomes suppressed tumor growth and M2 macrophage polarization. CAF-derived LINC01833 exosomes can promote the proliferation, migration and invasion of NSCLC cells and M2 macrophage polarization by inhibiting miR-335-5p and regulating VAPA activity.
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Fibroblastos Asociados al Cáncer , Carcinoma de Pulmón de Células no Pequeñas , Exosomas , Neoplasias Pulmonares , Ratones Desnudos , MicroARNs , ARN Largo no Codificante , MicroARNs/genética , MicroARNs/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/genética , Humanos , Exosomas/metabolismo , Exosomas/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Animales , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Ratones , Proliferación Celular , Masculino , Femenino , Línea Celular Tumoral , Movimiento Celular , Células A549 , Ratones Endogámicos BALB CRESUMEN
This corrects the article DOI: 10.1038/nature24675.
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The study investigated the influence of additives on the fabrication of mixed matrix membranes comprising polyethersulfone (PES), with a specific focus on hydrophilicity, flux, morphology, and antifouling properties. Carboxymethyl modified ß-cyclodextrin (CMß-CD) was used to enhance the dispersion and hydrophilicity of graphene oxide (GO), leading to the formation of a hydrophilic and stable composite nanoparticle (CMCD@GO). The hydrophilicity (WCA <51.5°) and water flux (32.6 L m-2.h-1) of the modified PES membranes (MCDGO-x) were improved by the incorporation of CMCD@GO nanoparticles, while that of PES membrane was 79.7° and 10.6 L m-2.h-1. The rate of backscattered light intensity (ΔBS) of MCDGO-x suspensions remains stable, suggesting stable dispersion of CMCD@GO in organic solvents. Compared to the bare PES membrane, the MCDGO-x membrane exhibits a thinner active layer and a finger-like structure. The MCDGO-x membrane exhibited excellent naphthenic acids (NAs) rejection (>93.2%) due to reduced roughness and higher hydrophilicity, while the GO-modified PES membrane (MGO-5) exhibited lower NAs rejection (87.2%). Furthermore, the MCDGO-5 membrane showed higher flux recovery ratio (FRR) of 79.3% compared to MGO-5 membrane (68.5%) after three cycles, indicating the antifouling performance of MCDGO-x for NAs was significantly improved. The combination of CMß-CD and GO enhance the flux and antifouling properties of PES ultrafiltration membranes, suggesting significant potential for applications in the purification of oil sands process water and the treatment of oily wastewater.
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Incrustaciones Biológicas , Grafito , Membranas Artificiales , Ultrafiltración , Purificación del Agua , beta-Ciclodextrinas , beta-Ciclodextrinas/química , Grafito/química , Purificación del Agua/métodos , Ultrafiltración/métodos , Incrustaciones Biológicas/prevención & control , Interacciones Hidrofóbicas e Hidrofílicas , Sulfonas/química , PolímerosRESUMEN
Oil/water separation has become a global concern due to the increasing discharge of multi-component harmful oily wastewater. Super wetting membranes have been shown to be an effective material for oil/water separation. Ultra-high flux stainless-steel meshes (SSM) with superhydrophilicity and underwater superoleophobicity were fabricated by tannic acid (TA) modified ZIF-8 nanoparticles (TZIF-8) and two-dimensional MXene materials for oil/water separation. The TZIF-8 increased the interlayer space of MXene, enhancing the flux permeation (69,093 L m-2h-1) and rejection of the composite membrane (TZIF-8@MXene/SSM). The TZIF-8@MXene/SSM membrane showed an underwater oil contact angle of 154.2°. The membrane maintained underwater superoleophobic after stability and durability tests, including various pH solutions, organic solvents, reusability, etc. In addition, the oil/water separation efficiency of TZIF-8@MXene/SSM membranes was higher than 99% after treatment in harsh conditions and recycling. The outstanding anti-fouling, stability, durability, and recyclability properties of TZIF-8@MXene/SSM membrane highlight the remarkable potential of membranes for complex oil/water separation process.
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Nanopartículas , Polifenoles , Elementos de Transición , Membranas , Nitritos , Acero InoxidableRESUMEN
Optical systems with extended depth of field (EDOF) are crucial for observation and measurement applications, where achieving compactness and a substantial depth of field (DOF) presents a considerable challenge with conventional optical elements. In this paper, we propose an innovative solution for the miniaturization of EDOF imaging systems by introducing an ultra-thin annular folded lens (AFL). To validate the practical feasibility of the theory, we design an annular four-folded lens with an effective focal length of 80.91 mm and a total thickness of only 8.50 mm. Simulation results show that the proposed folded lens has a DOF of 380.55 m. We further developed an AFL-based test system exhibiting a resolution of 0.11 mrad across a wide wavelength range of 486-656 nm. Additionally, we present experimental results from a miniature compact prototype, which further highlights the promising potential of folded lenses for long-range EDOF imaging.
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Haematopoietic Stem cells (HSCs) have the potential for self-renewal and multilineage differentiation, and their behaviours are finely tuned by the microenvironment. HSC transplantation (HSCT) is widely used in the treatment of haematologic malignancies while limited by the quantity of available HSCs. With the development of tissue engineering, hydrogels have been deployed to mimic the HSC microenvironment in vitro. Engineered hydrogels influence HSC behaviour by regulating mechanical strength, extracellular matrix microstructure, cellular ligands and cytokines, cell-cell interaction, and oxygen concentration, which ultimately facilitate the acquisition of sufficient HSCs. Here, we review recent advances in the application of hydrogel-based microenvironment engineering of HSCs, and provide future perspectives on challenges in basic research and clinical practice.