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Histone 2B ubiquitination (H2Bub) and trimethylation of H3 at lysine 4 (H3K4me3) are associated with transcription activation. However, the function of these modifications in transcription in plants remains largely unknown. Here, we report that coordination of H2Bub and H3K4me3 deposition with the binding of the RNA polymerase-associated factor VERNALIZATION INDEPENDENCE2 (VIP2) to FLOWERING LOCUS C (FLC) modulates flowering time in Arabidopsis. We found that RING domain protein HISTONE MONOUBIQUITINATION1 (HUB1) and HUB2 (we refer as HUB1/2), which are responsible for H2Bub, interact with ARABIDOPSIS TRITHORAX1 (ATX1), which is required for H3K4me3 deposition, to promote the transcription of FLC and repress the flowering time. The atx1-2 hub1-10 hub2-2 triple mutant in FRIGIDIA (FRI) background displayed early flowering like FRI hub1-10 hub2-2 and overexpression of ATX1 failed to rescue the early flowering phenotype of hub1-10 hub2-2. Mutations in HUB1 and HUB2 reduced the ATX1 enrichment at FLC, indicating that HUB1 and HUB2 are required for ATX1 recruitment and H3K4me3 deposition at FLC. We also found that the VIP2 directly binds to HUB1, HUB2, and ATX1 and that loss of VIP2 in FRI hub1-10 hub2-2 and FRI atx1-2 plants resulted in early flowering like that observed in FRI vip2-10. Loss of function of HUB2 and ATX1 impaired VIP2 enrichment at FLC, and reduced the transcription initiation and elongation of FLC. In addition, mutations in VIP2 reduced HUB1 and ATX1 enrichment and H2Bub and H3K4me3 levels at FLC. Together, our findings revealed that HUB1/2, ATX1, and VIP2 coordinately modulate H2Bub and H3K4me3 deposition, FLC transcription, and flowering time.
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Proteínas de Arabidopsis , Arabidopsis , Regulación de la Expresión Génica de las Plantas , Histonas , Arabidopsis/genética , Arabidopsis/fisiología , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Flores/genética , Flores/fisiología , Flores/crecimiento & desarrollo , Flores/metabolismo , N-Metiltransferasa de Histona-Lisina/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , Histonas/metabolismo , Proteínas de Dominio MADS/genética , Proteínas de Dominio MADS/metabolismo , Mutación , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Factores de Elongación Transcripcional/metabolismo , Factores de Elongación Transcripcional/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , UbiquitinaciónRESUMEN
The development of heterogeneous asymmetric catalysts has attracted increasing interest in synthetic chemistry but mostly relies on the immobilization of homogeneous chiral catalysts. Herein, a series of chiral metal-organic frameworks (MOFs) have been fabricated by anchoring similar chiral hydroxylated molecules (catalytically inactive) with different lengths onto Zr-oxo clusters in achiral PCN-222(Cu). The resulting chiral MOFs exhibit regulated enantioselectivity up to 83 % ee in the asymmetric ring-opening of cyclohexene oxide. The chiral molecules furnished onto the catalytic Lewis sites in the MOF create multilevel microenvironment, including the hydrogen interaction between the substrate and the chiral -OH group, the steric hindrance endowed by the benzene ring on the chiral molecules, and the proximity between the catalytic sites and chiral molecules confined in the MOF pores, which play crucial roles and synergistically promote chiral catalysis. This work nicely achieves heterogeneous enantioselective catalysis by chiral microenvironment modulation around Lewis acid sites.
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Photoelectrochemical overall water splitting has been considered as a promising approach for producing chemical energy from solar energy. Although many photoelectrochemical cells have been developed for overall water splitting by coupling two semiconductor photoelectrodes, inefficient charge transfer between the light-harvesters and electron acceptor/donor severely restricts the solar energy conversion efficiency. Inspired by natural photosynthesis, we assembled a photoelectrochemical platform with multimediator modulation to achieve unassisted overall water splitting. Photogenerated electrons are transferred in order through multimediators driven by the electrochemical potential gradient, resulting in efficient charge separation and transportation with enhanced charge transfer rate and reduced charge recombination rate. The integrated system composed of inorganic oxide-based photoanode (BiVO4) and organic polymer-based photocathode (PBDB-T:ITIC:PC71BM) with complementary light absorption, exhibits a solar-to-hydrogen conversion efficiency as high as 4.3%. This work makes a rational design possible by constructing an efficient charge-transfer chain in artificial photosynthesis systems for solar fuel production.
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BACKGROUND: Mitochondria play a role in the occurrence, development, drug resistance, metastasis, and other functions of cancer and thus are a drug target. An acid-activated mitochondria-targeting drug nanocarrier with redox-responsive function was constructed in the present study. However, whether this vector can precisely delivery paclitaxel (PTX) to enhance therapeutic efficacy in drug-resistant lung cancer is unknown. RESULTS: Acid-cleavable dimethylmaleic anhydride (DA) was used to modify pluronic P85-conjugated mitochondria-targeting triphenylphosphonium (TPP) using disulfide bonds as intermediate linkers (DA-P85-SS-TPP and DA-P-SS-T). The constructed nanocarriers demonstrated enhanced cellular uptake and selective mitochondrial targeting at extracellular pH characteristic for a tumor (6.5) and were characterized by extended circulation in the blood. TPP promoted the targeting of the DA-P-SS-T/PTX nanomicelles to the mitochondrial outer membrane to decrease the membrane potential and ATP level, resulting in inhibition of P-glycoprotein and suppression of drug resistance and cancer metastasis. PTX was also rapidly released in the presence of high glutathione (GSH) levels and directly diffused into the mitochondria, resulting in apoptosis of drug-resistant lung cancer cells. CONCLUSIONS: These promising results indicated that acid-activated mitochondria-targeting and redox-responsive nanomicelles potentially represent a significant advancement in cancer treatment. GRAPHIC ABSTARCT.
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Antineoplásicos/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Micelas , Mitocondrias/metabolismo , Nanopartículas/química , Paclitaxel/metabolismo , Células A549 , Apoptosis , Sistemas de Liberación de Medicamentos/métodos , Resistencia a Antineoplásicos/efectos de los fármacos , Humanos , Concentración de Iones de Hidrógeno , Mitocondrias/efectos de los fármacos , Membranas Mitocondriales/efectos de los fármacos , Nanopartículas/uso terapéutico , Oxidación-Reducción , Paclitaxel/química , PoloxalenoRESUMEN
3D measurement methods based on fringe projection have attracted extensive research. However, it is a challenge to deal with overshooting on a high-reflection or specular surface. To eliminate the saturated pixels caused by overshooting, we propose a projection intensity adaptive adjustment method. First, we project three uniform gray-level images and estimate the projection intensity of the measured surface through the captured uniform gray-level images. Then we can obtain the optimal projection fringes in the camera coordinate system. Second, a set of horizontal and vertical gray-coded patterns are used to establish a coordinate matching relationship between the projected image and the captured image. To check the decoding result of the gray-coded patterns, a set of horizontal and vertical sinusoidal fringes are used to calculate the high-reflection mapping area (HRMA) in the projector coordinate system. Through the distribution of HRMA, we can check whether the decoding is reliable or not. Finally, we project the optimal intensity fringes and obtain the measurement results. We develop a measurement system to verify the validity of the proposed method. Experimental results show that the proposed method can effectively avoid overshooting and obtain measurement results with a minimum rms error.
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Decidualization is essential to the establishment of pregnancy in rodents and primates. Laminin A5 (encoding by Laminin α5) is a member of the laminin family, which is mainly expressed in the basement membranes. Although laminins regulate cellular phenotype maintenance, adhesion, migration, growth, and differentiation, the expression, function, and regulation of laminin A5 during early pregnancy are still unknown. Therefore, we investigated the expression and role of laminin A5 during mouse and human decidualization. Laminin A5 is highly expressed in mouse decidua and artificially induced deciduoma. Laminin A5 is significantly increased under in vitro decidualization. Laminin A5 knockdown significantly inhibits the expression of Prl8a2, a marker for mouse decidualization. Progesterone stimulates the expression of laminin A5 in ovariectomized mouse uterus and cultured mouse stromal cells. We also show that progesterone regulates laminin A5 through the PKA-CREB-C/EBPß pathway. Laminin A5 is also highly expressed in human pregnant decidua and cultured human endometrial stromal cells during in vitro decidualization. Laminin A5 knockdown by siRNA inhibits human in vitro decidualization. Collectively, our study reveals that laminin A5 may play a pivotal role during mouse and human decidualization via the PKA-CREB-C/EBPß pathway.
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Decidua/metabolismo , Laminina/metabolismo , Adulto , Animales , Proteína beta Potenciadora de Unión a CCAAT/metabolismo , AMP Cíclico/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Decidua/efectos de los fármacos , Femenino , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Humanos , Laminina/genética , Masculino , Ratones Endogámicos ICR , Modelos Biológicos , Embarazo , Progesterona/farmacología , Transducción de Señal/efectos de los fármacos , Células del Estroma/efectos de los fármacos , Células del Estroma/metabolismoRESUMEN
Sigma-1 (σ-1) receptor agonists are considered as potential treatment for stroke. TS-157 is an alkoxyisoxazole-based σ-1 receptor agonist previously discovered in our group. The present study describes TS-157 profile in a battery of tests for cerebral ischemia. Initial evaluation demonstrated the compound's safety profile and blood-brain barrier permeability, as well as its ability to induce neurite outgrowth in vitro. The neurite outgrowth was shown to be mediated via σ-1 receptor agonism and involves upregulation of ERK phosphorylation (pERK). In particular, TS-157 also significantly accelerated the recovery of motor function in rats with transient middle cerebral artery occlusion (tMCAO). Overall, the results herein support the notion that σ-1 receptor agonists are potential therapeutics for stroke and further animal efficacy studies are warranted.
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Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Actividad Motora/efectos de los fármacos , Proyección Neuronal/efectos de los fármacos , Oxazoles/farmacología , Receptores sigma/agonistas , Recuperación de la Función/efectos de los fármacos , Animales , Infarto de la Arteria Cerebral Media/metabolismo , Masculino , Estructura Molecular , Oxazoles/síntesis química , Oxazoles/química , Fosforilación/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Receptor Sigma-1RESUMEN
Ferrihydrite (Fh) has been demonstrated as an effective interfacial layer for photoanodes to achieve outstanding photoelectrochemical (PEC) performance for water oxidation reaction owing to its unique hole-storage function. However, it is unknown whether such a hole-storage layer can be used to construct highly efficient photocathodes for hydrogen evolution reaction (HER). In this work, we report Fh interfacial engineering of amorphous silicon photocathode (with nickel as HER cocatalyst) achieving a photocurrent density of 15.6â mA cm-2 at 0â V vs. the reversible hydrogen electrode and a half-cell energy conversion efficiency of 4.08 % in alkaline solution, outperforming most of reported a-Si based photocathodes including multi-junction configurations integrated with noble metal cocatalysts in acid solution. Besides, the photocurrent density is maintained above 14â mA cm-2 for 175â min with 100 % Faradaic efficiency for HER in alkaline solution. Our results demonstrate a feasible approach to construct efficient photocathodes via the application of a hole-storage layer.
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Chemotherapeutic drugs frequently encounter multidrug resistance. ATP from mitochondria helps overexpression of drug efflux pumps to induce multidrug resistance, so mitochondrial delivery as a means of "repurposing'' chemotherapeutic drugs currently used in the clinic appears to be a worthwhile strategy to pursue for the development of new anti-drug-resistant cancer agents. TPP-Pluronic F127-hyaluronic acid (HA) (TPH), with a mitochondria-targeting triphenylphosphine (TPP) head group, was first synthesized through ester bond formation. Paclitaxel (PTX)-loaded TPH (TPH/PTX) nanomicelles exhibited excellent physical properties and significantly inhibited A549/ADR cells. After TPH/PTX nanomicelles entered acidic lysosomes through macropinocytosis, the positively charged TP/PTX nanomicelles that resulted from degradation of HA by hyaluronidase (HAase) in acidic lysosomes were exposed and completed lysosomal escape at 12 h, finally localizing to mitochondria over a period of 24 h in A549/ADR cells. Subsequently, TPH/PTX caused mitochondrial outer membrane permeabilization (MOMP) by inhibiting antiapoptotic Bcl-2, leading to cytochrome C release and activation of caspase-3 and caspase-9. In an A549/ADR xenograft tumor model and a drug-resistant breast cancer-bearing mouse model with lung metastasis, TPH/PTX nanomicelles exhibited obvious tumor targeting and significant antitumor efficacy. This work presents the potential of a single, nontoxic nanoparticle (NP) platform for mitochondria-targeted delivery of therapeutics for diverse drug-resistant cancers.
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Apoptosis , Resistencia a Antineoplásicos , Neoplasias Pulmonares/tratamiento farmacológico , Mitocondrias/metabolismo , Nanopartículas/química , Células A549 , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Endocitosis/efectos de los fármacos , Femenino , Humanos , Ácido Hialurónico/síntesis química , Ácido Hialurónico/química , Concentración 50 Inhibidora , Lisosomas/efectos de los fármacos , Lisosomas/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones Endogámicos BALB C , Micelas , Mitocondrias/efectos de los fármacos , Membranas Mitocondriales/efectos de los fármacos , Membranas Mitocondriales/metabolismo , Nanopartículas/ultraestructura , Compuestos Organofosforados/síntesis química , Compuestos Organofosforados/química , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Poloxámero/síntesis química , Poloxámero/química , Espectroscopía de Protones por Resonancia Magnética , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
In a broad range of taxa, genes can duplicate through an RNA intermediate in a process mediated by retrotransposons (retroposition). In mammals, L1 retrotransposons drive retroposition, but the elements responsible for retroposition in other animals have yet to be identified. Here, we examined young retrocopies from various animals that still retain the sequence features indicative of the underlying retroposition mechanism. In Drosophila melanogaster, we identified and de novo assembled 15 polymorphic retrocopies and found that all retroposed loci are chimeras of internal retrocopies flanked by discontinuous LTR retrotransposons. At the fusion points between the mRNAs and the LTR retrotransposons, we identified shared short similar sequences that suggest the involvement of microsimilarity-dependent template switches. By expanding our approach to mosquito, zebrafish, chicken, and mammals, we identified in all these species recently originated retrocopies with a similar chimeric structure and shared microsimilarities at the fusion points. We also identified several retrocopies that combine the sequences of two or more parental genes, demonstrating LTR-retroposition as a novel mechanism of exon shuffling. Finally, we found that LTR-mediated retrocopies are immediately cotranscribed with their flanking LTR retrotransposons. Transcriptional profiling coupled with sequence analyses revealed that the sense-strand transcription of the retrocopies often lead to the origination of in-frame proteins relative to the parental genes. Overall, our data show that LTR-mediated retroposition is highly conserved across a wide range of animal taxa; combined with previous work from plants and yeast, it represents an ancient and ongoing mechanism continuously shaping gene content evolution in eukaryotes.
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Duplicación de Gen , Perfilación de la Expresión Génica/métodos , ARN Mensajero/genética , Secuencias Repetidas Terminales , Animales , Pollos/genética , Culicidae/genética , Drosophila melanogaster/genética , Evolución Molecular , Humanos , Mamíferos/genética , Ratones , Retroelementos , Duplicaciones Segmentarias en el Genoma , Pez Cebra/genéticaRESUMEN
Sulfur mustard (SM) is a chemical warfare agent that was applied in a series of military conflicts and still poses a severe threat to civilians and military personnel. Although the cellular and molecular mechanisms of SM toxicity are still not fully understood, oxidative stress has been considered as the initial vital process for damage. Polydatin, the product of resveratrol and glucose, is a promising candidate for the treatment of oxidative stress-related diseases. However, its effects on SM-induced hepatic injury remain unknown. Thus, we investigated the protective effects of polydatin against SM-induced hepatic injury and its possible mechanism. We found that treatment with polydatin remarkably improved the survival rate of mice bear subcutaneously injected with SM. Polydatin decreased the SM-induced increase of serum aminotransferase levels and ameliorated hepatic pathological damage. We also found that indexes of oxidative stress were improved in mouse liver samples and L02 cells. Meanwhile, changes in the Sirtuin family after treatment with SM were explored in mice and cells since polydatin is a potent activator of Sirt1 and Sirt3. Polydatin significantly increased the expression of Sirt1, HO-1, and NQO1; and the nuclear translocation of Nrf2 in mouse liver and L02 cells. Furthermore, we also observed that either Sirt1 or Nrf2 knockdown abolished the protective effect of polydatin. Our data indicated that polydatin could provide protection against SM-induced hepatic injury through the Sirt1/Nrf2 pathway, suggesting that polydatin is a novel potential antidote for sulfur mustard.
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Antioxidantes/farmacología , Sustancias para la Guerra Química/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Glucósidos/farmacología , Hepatocitos/efectos de los fármacos , Hígado/efectos de los fármacos , Gas Mostaza/toxicidad , Estrés Oxidativo/efectos de los fármacos , Estilbenos/farmacología , Animales , Línea Celular , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Hepatocitos/metabolismo , Hepatocitos/patología , Humanos , Hígado/metabolismo , Hígado/patología , Masculino , Ratones Endogámicos ICR , Factor 2 Relacionado con NF-E2/metabolismo , Transducción de Señal/efectos de los fármacos , Sirtuina 1/metabolismoRESUMEN
Several mitochondrial tRNA mutations have been associated with hypertension, but their pathophysiology remains poorly understood. In this report, we identified a novel homoplasmic 3253TâC mutation in the mitochondrial tRNALeu(UUR) gene in a Han Chinese family with maternally inherited hypertension. The m.3253TâC mutation affected a highly conserved uridine at position 22 at the D-stem of tRNALeu(UUR), introducing a G-C base pairing (G13-C22) at the D-stem and a tertiary base pairing (C22-G46) between the D-stem and the variable loop. We therefore hypothesized that the m.3253TâC mutation altered both the structure and function of tRNALeu(UUR) Using cytoplasmic hybrid (cybrid) cell lines derived from this Chinese family, we demonstrated that the m.3253TâC mutation perturbed the conformation and stability of tRNALeu(UUR), as suggested by faster electrophoretic mobility of mutated tRNA relative to the wild-type molecule. Northern blot analysis revealed an â¼45% decrease in the steady-state level of tRNALeu(UUR) in the mutant cell lines carrying the m.3253TâC mutation, as compared with control cell lines. Moreover, an â¼35% reduction in aminoacylation efficiency of tRNALeu(UUR) was observed in the m.3253TâC mutant cells. These alterations in tRNALeu(UUR) metabolism impaired mitochondrial translation, especially for those polypeptides with a high proportion of Leu(UUR) codons, such as ND6. Furthermore, we demonstrated that the m.3253TâC mutation decreased the activities of mitochondrial complexes I and V, markedly diminished mitochondrial ATP levels and membrane potential, and increased the production of reactive oxygen species in the cells. In conclusion, our findings may provide new insights into the pathophysiology of maternally inherited hypertension.
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ADN Mitocondrial/metabolismo , Hipertensión/genética , Linfocitos/metabolismo , Herencia Materna , Modelos Moleculares , Mutación , ARN de Transferencia de Leucina/metabolismo , Adulto , Pueblo Asiatico , Emparejamiento Base , Línea Celular , Células Cultivadas , China , Análisis Mutacional de ADN , ADN Mitocondrial/química , Ensayo de Cambio de Movilidad Electroforética , Femenino , Humanos , Células Híbridas , Hipertensión/sangre , Hipertensión/metabolismo , Hipertensión/patología , Linfocitos/inmunología , Linfocitos/patología , Masculino , Conformación de Ácido Nucleico , Estabilidad del ARN , ARN de Transferencia de Leucina/química , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Vasculogenic mimicry (VM) gives rise to tumor neovascularization that is critical for tumor growth and metastasis. Long non-coding RNAs (lncRNAs) have been implicated in diverse and fundamental biological processes. LINC00312 is associated with lung adenocarcinoma. In this study, we found that LINC00312 induced migration, invasion and VM of lung cancer cells by direct binding to the transcription factor Y-Box Binding Protein 1 (YBX1). Moreover, we demonstrated that YBX1 is associated with different fragments within 0-2410 nt 5'region of LINC00312. In addition, LINC00312 is associated with VM in 124 lung adenocarcinoma clinical specimens. The results suggest that LINC00312 is a promising therapeutic and diagnostic target for lung adenocarcinoma.
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Adenocarcinoma del Pulmón/irrigación sanguínea , Adenocarcinoma del Pulmón/genética , Neoplasias Pulmonares/irrigación sanguínea , Neoplasias Pulmonares/genética , ARN Largo no Codificante/genética , Proteína 1 de Unión a la Caja Y/genética , Adenocarcinoma del Pulmón/patología , Diferenciación Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Humanos , Neoplasias Pulmonares/patología , Neovascularización Patológica/genética , Neovascularización Patológica/patologíaRESUMEN
Lung cancer is the leading cause of cancer-related mortality worldwide. Approximately 80% of lung cancer cases are non-small cell lung carcinoma (NSCLC). However current diagnostic and therapeutic modalities against NSCLC are ineffective due to incomplete understanding of molecular pathogenesis of NSCLC. Emerging evidence shows that long non-coding RNAs (lncRNAs) can function as biomarkers for diagnosis and prognosis. LncRNAs can control transcription, translation, and protein function via diverse mechanisms although they lack the protein coding potential. LncRNAs have attracted intense investigations on their roles in cancer. Mounting evidence indicates that lncRNAs are promising biomarkers in diagnosis and prognosis for NSCLC, especially their presence in body fluids. Herein we will review recent advances in the research that explores the diagnostic and prognostic potentials of lncRNAs in NSCLC. We will also discuss emerging evidence that suggested lncRNAs as therapeutic targets in NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Neoplasias Pulmonares/diagnóstico , ARN Largo no Codificante/sangre , Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Pronóstico , ARN Largo no Codificante/metabolismo , Esputo/metabolismoRESUMEN
Protein persulfidation is a newly defined oxidative posttranslational modification and plays important roles in many biological processes. Detection of protein persulfidation in living systems is urgently needed to advance the study of H2S/H2Sn-based signalling and cellular redox regulation. Here, we developed a novel off-on fluorescent probe for the detection of persulfidation using a chemical sensor, HQO-SSH, in biological systems. HQO-SSH features fast reaction, good selectivity and high sensitivity. Due to the distinctive features of HQO-SSH, this probe was successfully applied to image protein persulfidation changes in pulmonary cells. We also demonstrated that the probe is suitable for imaging protein persulfidation in lung tissues. In addition, confocal imaging with this method revealed that sulfur mustard, a commonly used chemical warfare agent, decreased mitochondrial protein persulfidation in living lung cells and tissues. Due to these results, this probe holds great promise for exploring the role of protein persulfidation in a variety of pathophysiological conditions.
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Colorantes Fluorescentes/metabolismo , Proteínas Mitocondriales/metabolismo , Sulfuros/metabolismo , Células A549 , Animales , Gliceraldehído-3-Fosfato Deshidrogenasa (Fosforilante)/metabolismo , Humanos , Cinética , Masculino , Ratones , Imagen ÓpticaRESUMEN
INTRODUCTION: Treatment of complex anterior circulation aneurysms with flow diverters (FDs) has become common practice in neurovascular centers. However, this treatment method for posterior circulation aneurysms (PCAs) still remains controversial. METHODS: Through searches for reports on the treatment of PCAs with FDs, we conducted a systematic review of the literature on its clinical efficacy and safety using random-effect binomial meta-analysis. RESULTS: We included 14 studies, which reported on a total of 225 PCAs in 220 patients. Procedure-related good outcome rate was 79% (95% confidence interval (CI), 72-84), with significantly lower odds among patients with ruptured aneurysms and basilar artery aneurysms. Procedure-related mortality rate was 15% (95% CI 10-21), with significantly higher rates among patients with giant aneurysms and basilar artery aneurysms. The rate of complete aneurysm occlusion at 6-month digital subtraction angiography (DSA) was 84%. Ischemic stroke rate was 11%. Perforator infarction rate was 7%. Postoperative subarachnoid hemorrhage (SAH) rate was 3%. Intraparenchymal hemorrhage (IPH) rate was 4%. CONCLUSIONS: Flow diverter treatment of PCAs is an effective method, which provides a high rate of complete occlusion at 6-month DSA. However, compared with anterior circulation aneurysms, patients with PCAs are at significantly higher risk of mortality, ischemic stroke and perforator infarction. Our findings indicate that, in most clinical centers, flow diverter treatment of PCAs should be conducted in carefully selected patients with poor natural history and no optimal treatment strategy. For ruptured and giant basilar artery aneurysms, there is still no good treatment option.
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Prótesis Vascular , Procedimientos Endovasculares , Aneurisma Intracraneal/terapia , Stents , HumanosRESUMEN
The precise regulation of synaptic growth is critical for the proper formation and plasticity of functional neural circuits. Identification and characterization of factors that regulate synaptic growth and function have been under intensive investigation. Here we report that brain tumor (brat), which was identified as a translational repressor in multiple biological processes, plays a crucial role at Drosophila neuromuscular junction (NMJ) synapses. Immunohistochemical analysis demonstrated that brat mutants exhibited synaptic overgrowth characterized by excess satellite boutons at NMJ terminals, whereas electron microscopy revealed increased synaptic vesicle size but reduced density at active zones compared with wild-types. Spontaneous miniature excitatory junctional potential amplitudes were larger and evoked quantal content was lower at brat mutant NMJs. In agreement with the morphological and physiological phenotypes, loss of Brat resulted in reduced FM1-43 uptake at the NMJ terminals, indicating that brat regulates synaptic endocytosis. Genetic analysis revealed that the actions of Brat at synapses are mediated through mothers against decapentaplegic (Mad), the signal transduction effector of the bone morphogenetic protein (BMP) signaling pathway. Furthermore, biochemical analyses showed upregulated levels of Mad protein but normal mRNA levels in the larval brains of brat mutants, suggesting that Brat suppresses Mad translation. Consistently, knockdown of brat by RNA interference in Drosophila S2 cells also increased Mad protein level. These results together reveal an important and previously unidentified role for Brat in synaptic development and endocytosis mediated by suppression of BMP signaling.
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Proteínas de Unión al ADN/metabolismo , Proteínas de Drosophila/metabolismo , Endocitosis/fisiología , Unión Neuromuscular/metabolismo , Plasticidad Neuronal/fisiología , Sinapsis/metabolismo , Factores de Transcripción/metabolismo , Animales , Proteínas de Unión al ADN/genética , Proteínas de Drosophila/genética , Drosophila melanogaster , Femenino , Colorantes Fluorescentes/farmacocinética , Masculino , Microscopía Electrónica , Mutagénesis , Unión Neuromuscular/ultraestructura , Compuestos de Piridinio/farmacocinética , Compuestos de Amonio Cuaternario/farmacocinética , ARN Interferente Pequeño/genética , Transducción de Señal/fisiología , Sinapsis/ultraestructura , Vesículas Sinápticas/fisiología , Vesículas Sinápticas/ultraestructura , Factores de Transcripción/genéticaRESUMEN
Objective: This study aimed to investigate the factors influencing nurses' ability to respond to public health emergencies and understand the relationship between nurses' ability to respond to emergencies and workplace resilience. Methods: A cross-sectional study of 361 nurses from military hospitals was conducted from January 18 to September 6, 2022, using an online survey. The Infectious Diseases Emergency Response Capacity (IDERC) questionnaire and the Workplace Resilience Scale (WRS) were utilized, and sociodemographic information was also collected. Data were analyzed using descriptive statistics and frequency analysis. Differences between groups were identified by one-way analysis of variance, and linear regression was used to analyze the main factors influencing the infectious emergency response capacity. Results: The average infectious emergency response capacity score on the IDERC questionnaire and workplace resilience, measured by WRS, were 4.01 (SD = 0.76) and 3.85 (SD = 0.71), respectively, on a scale of 1-5, indicating high performance. Factors such as degree of education, nurses' service years and experience in epidemic prevention participation were found to be the main influencing factors of the score of IDERC. The level of workplace resilience showed a positive correlation with the capacity to respond to infectious disease, the score of WRS and the service year accounted for 63.6% of the variance in emergency response capabilities. Conclusion: The results indicate an urgent need to strengthen the training of nurses with lower degree of education, shorter service years, no prior work, or no experience of epidemic prevention participation, and hospitals should also prioritize improving nurses' workplace resilience through targeted interventions, enhancing their abilities in infectious disease prevention, preparation, first aid, and subsequent critical patient care.
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Background: Hospital resilience is essential in responding to disasters, but current research focuses mainly on frameworks and models rather than the protection of resilience and analysis of risk factors during public health emergencies. This study aims to examine the development of resilience in Chinese frontline hospitals during the initial COVID-19 outbreak in 2020, providing insights for future disaster response efforts. Objectives: We conducted interviews with 26 hospital staff members who were involved in the initial response to the COVID-19 outbreak in China. We used a semi-structured interview approach and employed purposive sampling and snowball sampling techniques. The interview outline was guided by the 'Action Framework' proposed by the World Health Organization (WHO) for responding to infectious disease emergencies. This framework includes dimensions such as command, surveillance, risk communication, medical response, and public health response. We analyzed the collected data using Colaizzi's seven-step data analysis method and the template analysis method. Results: WHO's 'action framework' effectively highlights the factors that contribute to hospital resilience. While medical response, including the availability of materials and facilities, the use of information technology, and the capacity for infectious disease diagnosis and treatment, remains crucial, other important aspects include awareness and beliefs about infections, treatment experience, interdisciplinary collaboration, and more. Additionally, it is essential to establish an intelligent command system, foster trusting partnerships between teams, improve monitoring capabilities for infectious disease agents, enhance risk communication through information synchronization and transparency, strengthen infection control planning, and improve environmental disinfection capabilities for effective public health emergency response. These contradictions significantly impact the enhancement of hospital resilience in dealing with major infectious disease outbreaks. Conclusion: In responding to sudden major infectious diseases, hospitals play a vital role within the healthcare system. Enhancing hospital resilience involves more than just improving treatment capabilities. It also requires effective command coordination at the hospital level, infection control planning, and the deployment of intelligent equipment. Additionally, planning for effective communication and coordination between hospitals, communities, and the national healthcare system can further enhance hospital resilience.
Asunto(s)
COVID-19 , Enfermedades Transmisibles , Desastres , Resiliencia Psicológica , Humanos , Urgencias Médicas , Hospitales , COVID-19/epidemiología , COVID-19/prevención & controlRESUMEN
Developing high-performance electrocatalysts for alkaline hydrogen oxidation reaction (HOR) is crucial for the commercialization of anion exchange membrane fuel cells (AEMFCs). Here, boron interstitially inserted ruthenium (B-Ru/C) is synthesized and used as an anode catalyst for AEMFC, achieving a peak power density of 1.37 W cm-2 , close to the state-of-the-art commercial PtRu catalyst. Unexpectedly, instead of the monotonous decline of HOR kinetics with pH as generally believed, an inflection point behavior in the pH-dependent HOR kinetics on B-Ru/C is observed, showing an anomalous behavior that the HOR activity under alkaline electrolyte surpasses acidic electrolyte. Experimental results and density functional theory calculations reveal that the upshifted d-band center of Ru after the intervention of interstitial boron can lead to enhanced adsorption ability of OH and H2 O, which together with the reduced energy barrier of water formation, contributes to the outstanding alkaline HOR performance with a mass activity of 1.716 mA µgPGM -1 , which is 13.4-fold and 5.2-fold higher than that of Ru/C and commercial Pt/C, respectively.