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1.
Cell ; 186(5): 1026-1038.e20, 2023 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-36868208

RESUMEN

Down syndrome (DS) is a neurological disorder with multiple immune-related symptoms; however, crosstalk between the CNS and peripheral immune system remains unexplored. Using parabiosis and plasma infusion, we found that blood-borne factors drive synaptic deficits in DS. Proteomic analysis revealed elevation of ß2-microglobulin (B2M), a major histocompatibility complex class I (MHC-I) component, in human DS plasma. Systemic administration of B2M in wild-type mice led to synaptic and memory defects similar to those observed in DS mice. Moreover, genetic ablation of B2m or systemic administration of an anti-B2M antibody counteracts synaptic impairments in DS mice. Mechanistically, we demonstrate that B2M antagonizes NMDA receptor (NMDAR) function through interactions with the GluN1-S2 loop; blocking B2M-NMDAR interactions using competitive peptides restores NMDAR-dependent synaptic function. Our findings identify B2M as an endogenous NMDAR antagonist and reveal a pathophysiological role for circulating B2M in NMDAR dysfunction in DS and related cognitive disorders.


Asunto(s)
Síndrome de Down , Receptores de N-Metil-D-Aspartato , Microglobulina beta-2 , Animales , Humanos , Ratones , Microglobulina beta-2/metabolismo , Microglobulina beta-2/farmacología , Disfunción Cognitiva/metabolismo , Reacciones Cruzadas , Parabiosis , Proteómica , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Síndrome de Down/sangre , Síndrome de Down/metabolismo
2.
Cell ; 184(22): 5527-5540.e18, 2021 10 28.
Artículo en Inglés | MEDLINE | ID: mdl-34644527

RESUMEN

To secure phosphorus (P) from soil, most land plants use a direct phosphate uptake pathway via root hairs and epidermis and an indirect phosphate uptake pathway via mycorrhizal symbiosis. The interaction between these two pathways is unclear. Here, we mapped a network between transcription factors and mycorrhizal symbiosis-related genes using Y1H. Intriguingly, this gene regulatory network is governed by the conserved P-sensing pathway, centered on phosphate starvation response (PHR) transcription factors. PHRs are required for mycorrhizal symbiosis and regulate symbiosis-related genes via the P1BS motif. SPX-domain proteins suppress OsPHR2-mediated induction of symbiosis-related genes and inhibit mycorrhizal infection. In contrast, plants overexpressing OsPHR2 show improved mycorrhizal infection and are partially resistant to P-mediated inhibition of symbiosis. Functional analyses of network nodes revealed co-regulation of hormonal signaling and mycorrhizal symbiosis. This network deciphers extensive regulation of mycorrhizal symbiosis by endogenous and exogenous signals and highlights co-option of the P-sensing pathway for mycorrhizal symbiosis.


Asunto(s)
Redes Reguladoras de Genes , Micorrizas/genética , Micorrizas/fisiología , Fosfatos/deficiencia , Simbiosis/genética , Simbiosis/fisiología , Secuencia de Bases , Regulación de la Expresión Génica de las Plantas , Mutación/genética , Oryza/genética , Oryza/microbiología , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regiones Promotoras Genéticas/genética , Saccharomyces cerevisiae/metabolismo , Técnicas del Sistema de Dos Híbridos
3.
Nature ; 618(7967): 992-999, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37316666

RESUMEN

In the ongoing debates about eukaryogenesis-the series of evolutionary events leading to the emergence of the eukaryotic cell from prokaryotic ancestors-members of the Asgard archaea play a key part as the closest archaeal relatives of eukaryotes1. However, the nature and phylogenetic identity of the last common ancestor of Asgard archaea and eukaryotes remain unresolved2-4. Here we analyse distinct phylogenetic marker datasets of an expanded genomic sampling of Asgard archaea and evaluate competing evolutionary scenarios using state-of-the-art phylogenomic approaches. We find that eukaryotes are placed, with high confidence, as a well-nested clade within Asgard archaea and as a sister lineage to Hodarchaeales, a newly proposed order within Heimdallarchaeia. Using sophisticated gene tree and species tree reconciliation approaches, we show that analogous to the evolution of eukaryotic genomes, genome evolution in Asgard archaea involved significantly more gene duplication and fewer gene loss events compared with other archaea. Finally, we infer that the last common ancestor of Asgard archaea was probably a thermophilic chemolithotroph and that the lineage from which eukaryotes evolved adapted to mesophilic conditions and acquired the genetic potential to support a heterotrophic lifestyle. Our work provides key insights into the prokaryote-to-eukaryote transition and a platform for better understanding the emergence of cellular complexity in eukaryotic cells.


Asunto(s)
Archaea , Eucariontes , Filogenia , Archaea/clasificación , Archaea/citología , Archaea/genética , Eucariontes/clasificación , Eucariontes/citología , Eucariontes/genética , Células Eucariotas/clasificación , Células Eucariotas/citología , Células Procariotas/clasificación , Células Procariotas/citología , Conjuntos de Datos como Asunto , Duplicación de Gen , Evolución Molecular
4.
Proc Natl Acad Sci U S A ; 120(38): e2303466120, 2023 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-37695920

RESUMEN

Low-grade wind with airspeed Vwind < 5 m/s, while distributed far more abundantly, is still challenging to extract because current turbine-based technologies require particular geography (e.g., wide-open land or off-shore regions) with year-round Vwind > 5 m/s to effectively rotate the blades. Here, we report that low-speed airflow can sensitively enable directional flow within nanowire-anchored ionic liquid (IL) drops. Specifically, wind-induced air/liquid friction continuously raises directional leeward fluid transport in the upper portion, whereas three-phase contact line (TCL) pinning blocks further movement of IL. To remove excessive accumulation of IL near TCL, fluid dives, and headwind flow forms in the lower portion, as confirmed by microscope observation. Such stratified circulating flow within single drop can generate voltage output up to ~0.84 V, which we further scale up to ~60 V using drop "wind farms". Our results demonstrate a technology to tap the widespread low-grade wind as a reliable energy resource.

5.
Mol Biol Evol ; 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39041196

RESUMEN

Cyanobacteriota, the sole prokaryotes capable of oxygenic photosynthesis (OxyP), occupy a unique and pivotal role in Earth's history. While the notion that OxyP may have originated from Cyanobacteriota is widely accepted, its early evolution remains elusive. Here, by using both metagenomics and metatranscriptomics, we explore 36 metagenome-assembled genomes (MAGs) from hot spring ecosystems, belonging to two deep-branching cyanobacterial orders: Thermostichales and Gloeomargaritales. Functional investigation reveals that Thermostichales encode the crucial thylakoid membrane biogenesis protein, Vipp1. Based on the phylogenetic results, we infer that the evolution of the thylakoid membrane predates the divergence of Thermostichales from other cyanobacterial groups and that Thermostichales may be the most ancient lineage known to date to have inherited this feature from their common ancestor. Apart from OxyP, both lineages are potentially capable of sulfide-driven anoxygenic photosynthesis (AnoxyP) by linking sulfide oxidation to the photosynthetic electron transport chain. Unexpectedly, this AnoxyP capacity appears to be an acquired feature, as the key gene sqr was horizontally transferred from later-evolved cyanobacterial lineages. The presence of two D1 protein variants in Thermostichales suggests the functional flexibility of photosystems, ensuring their survival in fluctuating redox environments. Furthermore, all MAGs feature streamlined phycobilisomes with a preference for capturing longer-wavelength light, implying a unique evolutionary trajectory. Collectively, these results reveal the photosynthetic flexibility in these early-diverging cyanobacterial lineages, shedding new light on the early evolution of Cyanobacteriota and their photosynthetic processes.

6.
Biochem Biophys Res Commun ; 733: 150421, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39047426

RESUMEN

Retinoic acid receptor-related orphan receptor alpha (RORα), an essential tumor suppressor in a range of human malignancies, is classified as a member of the orphan nuclear receptor family. The most prevalent form of oral cancer, tongue squamous cell carcinoma (TSCC) is characterized by its severe malignancy and unfavorable prognosis. However, the extent to which its tumorigenesis mechanisms are associated with RORα expression levels is still not fully understood. The objective of this study was to examine the molecular mechanisms by which RORα is involved in TSCC. Through the use of immunohistochemistry (IHC), it was discovered that the expression level of RORα was significantly downregulated in TSCC tissues when compared to adjacent normal tissues in this study. To further investigate the role of RORα in TSCC, we activated the expression of RORα in human TSCC cell line (SCC9 cells) by transfecting RORα cDNA and using the selective RORα agonist SR1078. The results show that RORα can significantly inhibit the invasion, migration, proliferation, and adhesion of TSCC cells and induce cell apoptosis. In addition, xenograft models confirmed the conclusion that stable activation or treatment with SR1078 to increase RORα content significantly inhibited tumor growth and development. Taken together, this study provides solid evidence for the inhibitory role of RORα in the progression of TSCC. In addition, the preliminary application results of SR1078 in TSCC show that SR1078 is expected to be a potential therapeutic medication for TSCC. These findings provide innovative perspectives on the development of potential biomarkers and agents for TSCC therapy. The objective is to introduce novel strategy and alternatives for the prevention and treatment of TSCC.

7.
BMC Cancer ; 24(1): 580, 2024 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-38735973

RESUMEN

BACKGROUND: SRSF1, a member of Serine/Arginine-Rich Splicing Factors (SRSFs), has been observed to significantly influence cancer progression. However, the precise role of SRSF1 in osteosarcoma (OS) remains unclear. This study aims to investigate the functions of SRSF1 and its underlying mechanism in OS. METHODS: SRSF1 expression level in OS was evaluated on the TCGA dataset, TAGET-OS database. qRT-PCR and Western blotting were employed to assess SRSF1 expression in human OS cell lines as well as the interfered ectopic expression states. The effect of SRSF1 on cell migration, invasion, proliferation, and apoptosis of OS cells were measured by transwell assay and flow cytometry. RNA sequence and bioinformatic analyses were conducted to elucidate the targeted genes, relevant biological pathways, and alternative splicing (AS) events regulated by SRSF1. RESULTS: SRSF1 expression was consistently upregulated in both OS samples and OS cell lines. Diminishing SRSF1 resulted in reduced proliferation, migration, and invasion and increased apoptosis in OS cells while overexpressing SRSF1 led to enhanced growth, migration, invasion, and decreased apoptosis. Mechanistically, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis (GSEA) revealed that the biological functions of SRSF1 were closely associated with the dysregulation of the protein targeting processes, location of the cytosolic ribosome, extracellular matrix (ECM), and proteinaceous extracellular matrix, along with the PI3K-AKT pathway, Wnt pathway, and HIPPO pathway. Transcriptome analysis identified AS events modulated by SRSF1, especially (Skipped Exon) SE events and (Mutually exclusive Exons) MXE events, revealing potential roles of targeted molecules in mRNA surveillance, RNA degradation, and RNA transport during OS development. qRT-PCR confirmed that SRSF1 knockdown resulted in the occurrence of alternative splicing of SRRM2, DMKN, and SCAT1 in OS. CONCLUSIONS: Our results highlight the oncogenic role of high SRSF1 expression in promoting OS progression, and further explore the potential mechanisms of action. The significant involvement of SRSF1 in OS development suggests its potential utility as a therapeutic target in OS.


Asunto(s)
Apoptosis , Neoplasias Óseas , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Osteosarcoma , Factores de Empalme Serina-Arginina , Humanos , Empalme Alternativo , Apoptosis/genética , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Neoplasias Óseas/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Progresión de la Enfermedad , Osteosarcoma/genética , Osteosarcoma/patología , Osteosarcoma/metabolismo , Factores de Empalme Serina-Arginina/genética , Factores de Empalme Serina-Arginina/metabolismo , Regulación hacia Arriba
8.
Environ Sci Technol ; 58(27): 11923-11934, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38918172

RESUMEN

Chlorinated anthracenes (Cl-Ants), persistent organic pollutants, are widely detected in the environment, posing potential lung toxicity risks due to frequent respiratory exposure. However, direct evidence and a comprehensive understanding of their toxicity mechanisms are lacking. Building on our prior findings of Cl-Ants' immunotoxic risks, this study developed a three-dimensional coculture spheroid model mimicking the lung's immune microenvironment. The objective is to explore the pulmonary immunotoxicity and comprehend its mechanisms, taking into account the heightened immune reactivity and frequent lung exposure of Cl-Ants. The results demonstrated that Cl-Ants exposure led to reduced spheroid size, increased macrophage migration outward, lowered cell viability, elevated 8-OHdG levels, disturbed anti-infection balance, and altered cytokine production. Specifically, the chlorine substituent number correlates with the extent of disruption of spheroid indicators caused by Cl-Ants, with stronger immunotoxic effects observed in dichlorinated Ant compared to those in monochlorinated Ant. Furthermore, we identified critical regulatory genes associated with cell viability (ALDOC and ALDOA), bacterial response (TLR5 and MAP2K6), and GM-CSF production (CEBPB). Overall, this study offers initial in vitro evidence of low-dose Cl-PAHs' pulmonary immunotoxicity, advancing the understanding of Cl-Ants' structure-related toxicity and improving external toxicity assessment methods for environmental pollutants, which holds significance for future monitoring and evaluation.


Asunto(s)
Pulmón , Pulmón/efectos de los fármacos , Antracenos/toxicidad , Humanos , Técnicas de Cocultivo , Supervivencia Celular/efectos de los fármacos
9.
Echocardiography ; 41(8): e15895, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39073188

RESUMEN

Malignant melanoma (MM) is notorious for its high metastatic potential, with cardiac metastasis being particularly severe as it involves cardiac structures and can lead to significant cardiac functional issues. While there is no standardized treatment approach, early detection and intervention can improve prognosis.


Asunto(s)
Ecocardiografía , Neoplasias Cardíacas , Neoplasias Intestinales , Melanoma , Humanos , Melanoma/secundario , Neoplasias Cardíacas/secundario , Neoplasias Cardíacas/diagnóstico por imagen , Ecocardiografía/métodos , Neoplasias Intestinales/secundario , Neoplasias Intestinales/diagnóstico por imagen , Masculino , Intestino Delgado , Persona de Mediana Edad
10.
Echocardiography ; 41(7): e15874, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38924187

RESUMEN

The combination of the right aortic arch and aberrant left subclavian artery (ALSA) with Kommerell's diverticulum (KD) is rare to coexist with the left innominate vein (LINV) beneath the aortic arch. It escalates the surgical risk undoubtedly and increases the difficulty of clinical procedures. We report one case diagnosed by Ultrasound and Computed Tomography Angiography (CTA).


Asunto(s)
Aorta Torácica , Venas Braquiocefálicas , Divertículo , Arteria Subclavia , Humanos , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/anomalías , Divertículo/diagnóstico por imagen , Divertículo/complicaciones , Venas Braquiocefálicas/anomalías , Venas Braquiocefálicas/diagnóstico por imagen , Arteria Subclavia/anomalías , Arteria Subclavia/diagnóstico por imagen , Angiografía por Tomografía Computarizada/métodos , Masculino , Femenino , Ecocardiografía/métodos , Anomalías Múltiples , Aneurisma/complicaciones , Aneurisma/diagnóstico por imagen , Anomalías Cardiovasculares/complicaciones , Anomalías Cardiovasculares/diagnóstico por imagen
11.
Echocardiography ; 41(2): e15763, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38411366

RESUMEN

Cardiac myxoma is the most common primary benign cardiac tumors, mostly found in the left atrium. It was previously reported that the main component of myxoma was myxoid stroma riched in acid-mucopolysaccharide, the blood vessels in which were sparsely distributed, being characterized as hypovascular tumor by contrast echocardiography (CE) and computed tomography angiography (CTA). There are few reports of myxoma with rich blood supply and we report one in the left atrium.


Asunto(s)
Neoplasias Cardíacas , Mixoma , Humanos , Neoplasias Cardíacas/diagnóstico por imagen , Angiografía , Ecocardiografía , Atrios Cardíacos/diagnóstico por imagen , Mixoma/diagnóstico por imagen
12.
Echocardiography ; 41(5): e15826, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38678584

RESUMEN

This case report describes a 35-year-old female patient who presented with palpitations and shortness of breath. Imaging findings suggested a cardiac tumor, histopathology confirmed primary cardiac angiosarcoma. This tumor is highly aggressive, usually occurs in the right atrium, lacks specificity in clinical presentation, is prone to early metastasis, and has a poor prognosis. Echocardiography is the method of choice for early detection and is important in assessing tumor size, location, mode of attachment and whether cardiac function is impaired.


Asunto(s)
Ecocardiografía , Neoplasias Cardíacas , Hemangiosarcoma , Humanos , Neoplasias Cardíacas/diagnóstico por imagen , Neoplasias Cardíacas/diagnóstico , Femenino , Hemangiosarcoma/diagnóstico por imagen , Hemangiosarcoma/diagnóstico , Adulto , Ecocardiografía/métodos , Atrios Cardíacos/diagnóstico por imagen , Diagnóstico Diferencial
13.
Echocardiography ; 41(4): e15810, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38555578

RESUMEN

The aortic short axis view demonstrated the widening of the pulmonary artery and the membrane-like echo in the pulmonary artery divided it into true lumen and false lumen. And the flow of the ruptured openings on the band-like echo was clearly revealed by Color Doppler.


Asunto(s)
Disección Aórtica , Defectos del Tabique Interventricular , Estenosis de la Válvula Pulmonar , Humanos , Ecocardiografía , Arteria Pulmonar/diagnóstico por imagen , Defectos del Tabique Interventricular/complicaciones , Defectos del Tabique Interventricular/diagnóstico por imagen , Estenosis de la Válvula Pulmonar/complicaciones , Estenosis de la Válvula Pulmonar/diagnóstico por imagen
14.
J Clin Nurs ; 33(7): 2438-2455, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38345136

RESUMEN

AIMS: The clinical significance of cancer-related stigma on patients' well-being has been widely established. Stigma can be perceived and internalised by cancer patients or implemented by the general population and healthcare workers. Various interventions have been carried out to reduce cancer-related stigma, but their effectiveness is not well-understood. This review aims to synthesise evidence on the effectiveness of interventions to reduce cancer-related stigma. DESIGN: An integrative review. METHODS: This integrative review combined both qualitative and quantitative studies and followed five steps to identify problems, search for the literature, appraise the literature quality, analyse data, and present data. Mixed Methods Appraisal Tool (version 2018) was applied to evaluate the quality of the included studies. DATA SOURCES: Databases included Web of Science, MEDLINE, SpringerLink, Wiley Online Journals, Cochrane Library, ScienceDirect, OVID, and China National Knowledge Infrastructure (from the inception of each database to 30 April 2021). RESULTS: Eighteen quantitative, six qualitative, and five mixed-methods studies were included in this review. Cultural factors should be considered when conducting interventions to reduce cancer-related stigma. For cancer patients, multi-component interventions have demonstrated a positive effect on their perceived stigma. For general population, interactive interventions show promise to reduce their implemented stigma towards cancer patients. For healthcare workers, there is a paucity of studies to reduce their implemented stigma. Existing studies reported inconclusive evidence, partially due to the lack of a robust study design with an adequate sample size. CONCLUSIONS: Multi-component and interactive interventions show promise to relieve cancer-related stigma. More methodologically robust studies should be conducted in different cultures to elucidate the most appropriate interventions for different populations to reduce cancer-related stigma. IMPLICATION FOR THE PROFESSION AND PATIENT CARE: These findings will facilitate healthcare workers to design and implement interventions to reduce cancer-related stigma, thus improving the quality of life for cancer patients. PATIENT AND PUBLIC CONTRIBUTION: No patient and public contribution.


Asunto(s)
Neoplasias , Estigma Social , Humanos , Neoplasias/psicología , Personal de Salud/psicología
15.
J Clin Ultrasound ; 52(5): 635-637, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38532653

RESUMEN

Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumor in children, and botryoid rhabdomyosarcoma (BRMS) represents a subtype of RMS. BRMS primarily occurs in infants, young children, and adolescent females, with a predilection for mucosa-lined hollow organs such as the bladder, vagina, bile duct, and so on. Its occurrence in the biliary tract is extremely rare. Due to the high malignancy and rapid metastasis of biliary botryoid rhabdomyosarcoma, early diagnosis and treatment are crucial for improving prognosis.


Asunto(s)
Rabdomiosarcoma , Humanos , Rabdomiosarcoma/diagnóstico por imagen , Femenino , Niño , Masculino , Neoplasias del Sistema Biliar/diagnóstico por imagen , Diagnóstico Diferencial , Ultrasonografía/métodos
16.
J Clin Ultrasound ; 52(4): 435-436, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38168063

RESUMEN

During the fetal period, the pulmonary artery bifurcation revealed the absence of the left pulmonary artery. Instead, an anomalous artery originated from the right pulmonary artery, coursing posteriorly the trachea to the left lung. The diagnosis of PAS was established following prenatal ultrasound screening, which was subsequently confirmed by postnatal echocardiography and CT after delivery.


Asunto(s)
Arteria Pulmonar , Ultrasonografía Prenatal , Humanos , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/anomalías , Arteria Pulmonar/embriología , Ultrasonografía Prenatal/métodos , Femenino , Embarazo , Recién Nacido , Adulto , Ecocardiografía/métodos , Tomografía Computarizada por Rayos X/métodos
17.
J Clin Ultrasound ; 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38840562

RESUMEN

Non-Hodgkin lymphoma (NHL) is a highly aggressive malignant tumor arising in lymph nodes or extra-nodal lymphoid tissues, with an incidence of 8.3 per million. It accounts for approximately 7% of childhood and adolescent malignancies, second only to leukemia and brain tumors. Despite the gastrointestinal tract being the most common extra-nodal site involved by lymphoma, primary intestinal lymphoma (PIL) is rare and typically affects middle-aged men without specific clinical symptoms. Here, we present the case of a 2-year-old child indicative of PIL with the informed consent of the parents.

18.
Fetal Pediatr Pathol ; 43(2): 111-122, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38213180

RESUMEN

Background: We evaluated CD30 and CD56 expression in lymphoblastic lymphoma (LBL) and correlated the results with clinicopathological features and prognosis. Methods: Immunohistochemical (IHC) staining was performed on 85 formalin-fixed paraffin-embedded LBL specimens using two CD30 clones and one CD56 antibody clone. Results: Weak and diffuse expression of CD30 was expressed in 4.7% (clone Ber-H2) or 14.1% (clone EPR4102) in LBL, while CD56 was expressed in 24.7%. CD30 and CD56 expression correlated with lactate dehydrogenase levels. CD56-positive expression was closely associated with an unfavorable prognosis. Although CD30 expression exhibited a trend toward poorer overall survival, it did not reach statistical significance. Conclusion: CD56 is a potential negative prognostic marker. These findings suggest that CD30 and CD56 targeted therapies could be potential therapeutic targets for LBL patients.


Asunto(s)
Relevancia Clínica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Inmunohistoquímica , Adhesión en Parafina , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Estudios Retrospectivos , Antígeno Ki-1
19.
Angew Chem Int Ed Engl ; 63(16): e202319247, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38381931

RESUMEN

Binding water molecules to polar sites in covalent organic frameworks (COFs) is inevitable, but the corresponding solvent effects in electrocatalytic process have been largely overlooked. Herein, we investigate the solvent effects on COFs for catalyzing the oxygen reduction reaction (ORR). Our designed COFs incorporated different kinds of nitrogen atoms (imine N, pyridine N, and phenazine N), enabling tunable interactions with water molecules. These interactions play a crucial role in modulating electronic states and altering the catalytic centers within the COFs. Among the synthesized COFs, the one with pyridine N atoms exhibits the highest activity, with characterized by a half-wave potential of 0.78 V and a mass activity of 0.32 A mg-1, which surpass those from other metal-free COFs. Theoretical calculations further reveal that the enhanced activity can be attributed to the stronger binding ability of *OOH intermediates to the carbon atoms adjacent to the pyridine N sites. This work sheds light on the significance of considering solvent effects on COFs in electrocatalytic systems, providing valuable insights into their design and optimization for improved performance.

20.
Cancer Sci ; 114(12): 4747-4762, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37817462

RESUMEN

Osteosarcoma (OS) is one of the most aggressive bone tumors worldwide. Emerging documents have shown that long noncoding RNAs (lncRNAs) elicit crucial regulatory functions in the process of tumorigenesis. LncRNA DLGAP1-AS2 is recognized as a regulator in several types of cancers, but its biological functions and molecular mechanisms in OS remain to be elucidated. RT-qPCR and In situ hybridization (ISH) were used to evaluate DLGAP1-AS2 expression in OS samples. Western blotting was used for the measurement of the protein levels of hexokinase 2 (HK2) and epithelial-mesenchymal transition (EMT)-related markers. The proliferation of OS cells was determined using a CCK-8 assay and EdU assay. TUNEL assay and flow cytometry were performed to assess OS cell apoptosis. Glucose metabolism in vitro assays were used. The binding relations among miR-451a, HK2, and DLGAP1-AS2 were validated by luciferase reporter assay. The cellular distribution of DLGAP1-AS2 in OS cells was determined by FISH and subcellular fractionation assays. Mouse xenograft models were established to perform the experiments in vivo. We found that DLGAP1-AS2 expression was upregulated in OS tissues and cells. Downregulation of DLGAP1-AS2 expression suppressed the malignancy of OS cells by restraining cell proliferation, the EMT process, invasiveness, migration, and aerobic glycolysis and accelerating apoptotic behaviors. Of note, silenced DLGAP1-AS2 restrained tumor growth and metastasis in vivo. However, DLGAP1-AS2 overexpression accelerated the progression of OS. We further found that DLGAP1-AS2 upregulation was induced by hypoxia and low glucose. Additionally, DLGAP1-AS2 bound to miR-451a to upregulate HK2 expression. Rescue assays revealed that the DLGAP1-AS2/miR-451a/HK2 axis contributed to OS cell malignancy by promoting aerobic glucose metabolism. Overall, these findings revealed a new regulatory pathway where DLGAP1-AS2 upregulated HK2 expression by sponging miR-451a to accelerate OS development.


Asunto(s)
Osteosarcoma , ARN Largo no Codificante , Efecto Warburg en Oncología , Humanos , Línea Celular Tumoral , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica/genética , Técnicas de Silenciamiento del Gen , Hexoquinasa/metabolismo , Ratones Endogámicos BALB C , MicroARNs/metabolismo , Osteosarcoma/genética , Osteosarcoma/fisiopatología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo
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