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Refinery filtration processes often face challenges related to rapidly increasing permeate pressure differentials and the consequent need for frequent back-flushing. This study investigates the impact of high-intensity immersed sonotrode ultrasound device on flow patterns to address these issues, both numerically and experimentally. Numerical simulations reveal that ultrasound promotes axial circular mixing of the bulk fluid, increasing average flow velocities around the filter tube from 5.11 × 10-5 m/s to 8.76 × 10-3-6.09 × 10-2 m/s, thereby facilitating cleansing of filter tube surfaces. Additionally, high-frequency pressure fluctuations contribute to enhancing the filtration process during positive pressure phases, while robust online back-flushing effects are generated during negative pressure phases. Although the wire-wrapped filter tube attenuates ultrasound energy as it penetrates the tube gaps, ultrasound still induces turbulent mixing inside and outside the filter tubes, aiding in the removal of impurities from the gaps. The utilization of ultrasound is demonstrated to not inflict harm on upstream and downstream facilities. Experimental results demonstrate that ultrasound-assisted filtration with 600 W and 1000 W power inputs reduces filtration pressure differences by 18 % and 73 %, respectively, affirming ultrasound's effectiveness in mitigating and preventing blockages, highlighting its significance for industrial applicability.
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Purpose: Intravitreal injection of anti-VEGF antibodies remains the primary therapy for exudative age-related macular degeneration (exAMD), although its efficacy is limited. Previous research has demonstrated that both a loss-of-function mutation of srr and the intravenous injection of a serine racemase inhibitor, L-aspartic acid ß-hydroxamate (L-ABH), significantly inhibit laser-induced choroidal neovascularization (CNV) in mice. Given that L-ABH is a small molecule, this study investigated the effects of L-ABH administered via eye drops on CNV, aiming to develop a noninvasive treatment strategy for exAMD. Methods: CNV models in mice and rhesus macaques were established through laser photocoagulation. Seven monkeys were randomly assigned to receive either saline solution or L-ABH eye drops. Intraperitoneal or intravenous injection of fluorescein characterized CNV in both mice and monkeys. Fluorescein fundus angiography was used to assess leakage, whereas optical coherence tomography measured retinal thickness in the monkeys. Results: L-ABH eye drops significantly reduced fluorescein leakage in laser-injured mice (P < 0.001 compared to saline). In laser-injured rhesus macaques, the average percent changes in leakage areas treated with L-ABH were 2.5% ± 25.8% (P = 0.004) and 1.5% ± 75.7% (P = 0.023 compared to saline solution) on day 14 and day 28, respectively. However, L-ABH eye drops did not significantly affect the number of grade IV laser spots or retinal thickness, whereas bevacizumab did. Conclusions: This study demonstrates the potential efficacy of an SRR inhibitor in two animal models of laser-induced CNV. Translational Relevance: This represents the first investigation into the effects of topical delivery of an SRR inhibitor on CNV.
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Neovascularización Coroidal , Modelos Animales de Enfermedad , Angiografía con Fluoresceína , Macaca mulatta , Ratones Endogámicos C57BL , Tomografía de Coherencia Óptica , Animales , Neovascularización Coroidal/tratamiento farmacológico , Neovascularización Coroidal/patología , Ratones , Racemasas y Epimerasas/antagonistas & inhibidores , Racemasas y Epimerasas/genética , Racemasas y Epimerasas/metabolismo , Coagulación con Láser/efectos adversos , Soluciones Oftálmicas , Masculino , Coroides/efectos de los fármacos , Coroides/patología , Coroides/diagnóstico por imagen , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/uso terapéutico , Ácidos Hidroxámicos/administración & dosificación , Ácidos Hidroxámicos/farmacología , Ácidos Hidroxámicos/uso terapéuticoRESUMEN
Despite impressive advances in the construction of enantioenriched silacarbocycles featuring silicon-stereogenic centers via a selection of well-defined sila-synthons, the development of a more convenient and economic method with readily available starting materials is significantly less explored and remains a considerable challenge. Herein, we report the first example of copper-catalyzed sequential hydrosilylation of readily accessible methylenecyclopropanes (MCPs) and primary silanes, affording an efficient and convenient route to a wide range of chiral silacyclopentanes bearing consecutive silicon- and carbon-stereogenic centers with excellent enantio- and diastereoselectivities (generally ≥98% ee, > 25:1 dr). Mechanistic studies reveal that these reactions combine copper-catalyzed intermolecular ring-opening hydrosilylation of aryl MCPs and intramolecular asymmetric hydrosilylation of the resultant Z/E mixture of homoallylic silanes.
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We herein describe the first example of ligand-controlled, copper-catalyzed regiodivergent asymmetric difunctionalization of terminal alkynes through a cascade hydroboration and hydroallylation process. The catalytic system, consisting of (R)-DTBM-Segphos and CuBr, could efficiently achieve asymmetric 1,1-difunctionalization of aryl terminal alkynes, while ligand switching to (S,S)-Ph-BPE could result in asymmetric 1,2-difunctionalization exclusively. In addition, alkyl substituted terminal alkynes, especially industrially relevant acetylene and propyne, were also valid feedstocks for asymmetric 1,1-difunctionalization. This protocol is characterized by good functional group tolerance, a broad scope of substrates (> 150 examples), and mild reaction conditions. We also showcase the value of this method in the late-stage functionalization of complicated bioactive molecules and simplifying the synthetic routes toward the key intermediacy of natural product (bruguierol A). Mechanistic studies combined with DFT calculations provide insight into the mechanism and origins of this ligand-controlled regio- and stereoselectivity.
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MAIN CONCLUSION: PLDα1 promoted H2S production by positively regulating the expression of LCD. Stomatal closure promoted by PLDα1 required the accumulation of H2S under drought stress. Phospholipase Dα1 (PLDα1) acting as one of the signal enzymes can respond to drought stress. It is well known that hydrogen sulfide (H2S) plays an important role in plant responding to biotic or abiotic stress. In this study, the functions and relationship between PLDα1 and H2S in drought stress resistance in Arabidopsis were explored. Our results indicated that drought stress promotes PLDα1 and H2S production by inducing the expression of PLDα1 and LCD genes. PLDα1 and LCD enhanced plant tolerance to drought by regulating membrane lipid peroxidation, proline accumulation, H2O2 content and stomatal closure. Under drought stress, the H2O2 content of PLDα1-deficient mutant (pldα1), L-cysteine desulfhydrase (LCD)-deficient mutant (lcd) was higher than that of ecotype (WT), the stomatal aperture of pldα1 and lcd was larger than that of WT. The transcriptional and translational levels of LCD were lower in pldα1 than that in WT. Exogenous application of the H2S donor NaHS or GYY reduced the stomatal aperture of WT, pldα1, PLDα1-CO, and PLDα1-OE lines, while exogenous application of the H2S scavenger hypotaurine (HT) increased the stomatal aperture. qRT-PCR analysis of stomatal movement-related genes showed that the expression of CAX1, ABCG5, SCAB1, and SLAC1 genes in pldα1 and lcd were down-regulated, while ACA1 and OST1 gene expression was significantly up-regulated. Thus, PLDα1 and LCD are required for stomatal closure to improve drought stress tolerance.
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Proteínas de Arabidopsis , Arabidopsis , Sequías , Regulación de la Expresión Génica de las Plantas , Sulfuro de Hidrógeno , Fosfolipasa D , Estomas de Plantas , Arabidopsis/genética , Arabidopsis/fisiología , Estomas de Plantas/fisiología , Estomas de Plantas/genética , Fosfolipasa D/metabolismo , Fosfolipasa D/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Sulfuro de Hidrógeno/metabolismo , Peróxido de Hidrógeno/metabolismo , Estrés Fisiológico/genética , Prolina/metabolismo , Cistationina gamma-Liasa/genética , Cistationina gamma-Liasa/metabolismo , Peroxidación de LípidoRESUMEN
Lead-free electrocaloric (EC) ferroelectrics are considered ideal for the next generation of environmentally friendly solid-state refrigeration materials. However, their inferior performance compared to lead-based materials significantly restricts their potential application. According to phase-field simulations, it is predicted that the pinning effect of a moderate number of defects can effectively enhance the reversible polarization response associated with the entropy change. Herein, sodium-bismuth titanate (BNT) ceramics with high spontaneous polarization are selected to construct B-site defects by introducing Li+ and Nb5+. Under an electric field of 6 kV mm-1, ultrahigh EC temperature changes of ΔTpos = 1.77 and ΔTneg = 1.49 K are achieved at 65 °C by direct measurement (ΔTneg > 1 K over 55-120 °C). Furthermore, ΔTneg remains above 0.70 K in the temperature range from 25 to 130 °C, exhibiting immense potential for practical applications. This study offers a promising direction for optimizing the EC response in defect systems.
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Targeting tumor angiogenesis is an important approach in advanced tumor therapy. Here we investigated the effect of the suppressor of variegation 3-9 homolog 1 (SUV39H1) on tumor angiogenesis in oral squamous cell carcinoma (OSCC). The GEPIA database was used to analyze the expression of SUV39H1 in various cancer tissues. The expression of SUV39H1 in OSCC was detected by immunohistochemistry, and the correlation between SUV39H1 and Notch1 and microvascular density (MVD) was analyzed. The effect of SUV39H1 inhibition on OSCC was investigated in vivo by chaetocin treatment. The migration and tube formation of vascular endothelial cells by conditioned culture-medium of different treatments of oral squamous cell cells were measured. The transcriptional level of SUV39H1 is elevated in various cancer tissues. The transcription level of SUV39H1 in head and neck squamous cell carcinoma was significantly higher than that in control. Immunohistochemistry result showed increased SUV39H1 expression in OSCC, which was significantly correlated with T staging. The expression of SUV39H1 was significantly correlated with Notch1 and CD31. In vivo experiment chaetocin treatment significantly inhibit the growth of tumor, and reduce SUV39H1, Notch1, CD31 expression. The decreased expression of SUV39H1 in OSCC cells lead to the decreased expression of Notch1 and VEGF proteins, as well as the decreased migration and tube formation ability of vascular endothelial cells. Inhibition of Notch1 further enhance this effect. Our results suggest inhibition of SUV39H1 may affect angiogenesis by regulating Notch1 expression. This study provides a foundation for SUV39H1 as a potential therapeutic target for OSCC.
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Carcinoma de Células Escamosas , Metiltransferasas , Neoplasias de la Boca , Neovascularización Patológica , Receptor Notch1 , Proteínas Represoras , Humanos , Receptor Notch1/metabolismo , Receptor Notch1/genética , Neoplasias de la Boca/patología , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/irrigación sanguínea , Neovascularización Patológica/metabolismo , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/patología , Animales , Proteínas Represoras/metabolismo , Proteínas Represoras/genética , Metiltransferasas/metabolismo , Metiltransferasas/antagonistas & inhibidores , Metiltransferasas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/irrigación sanguínea , Línea Celular Tumoral , Ratones , Movimiento Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , AngiogénesisRESUMEN
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with an overall 5-year survival rate of <12% due to the lack of effective treatments. Novel treatment strategies are urgently needed. Here, PKMYT1 is identified through genome-wide CRISPR screens as a non-mutant, genetic vulnerability of PDAC. Higher PKMYT1 expression levels indicate poor prognosis in PDAC patients. PKMYT1 ablation inhibits tumor growth and proliferation in vitro and in vivo by regulating cell cycle progression and inducing apoptosis. Moreover, pharmacological inhibition of PKMYT1 shows efficacy in multiple PDAC cell models and effectively induces tumor regression without overt toxicity in PDAC cell line-derived xenograft and in more clinically relevant patient-derived xenograft models. Mechanistically, in addition to its canonical function of phosphorylating CDK1, PKMYT1 functions as an oncogene to promote PDAC tumorigenesis by regulating PLK1 expression and phosphorylation. Finally, TP53 function and PRKDC activation are shown to modulate the sensitivity to PKMYT1 inhibition. These results define PKMYT1 dependency in PDAC and identify potential therapeutic strategies for clinical translation.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Proteínas Serina-Treonina Quinasas , Proteínas Tirosina Quinasas , Animales , Humanos , Ratones , Apoptosis/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/patología , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/antagonistas & inhibidores , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas/genética , Proteínas de la Membrana , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Proteínas Tirosina Quinasas/genética , Proteínas Tirosina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Sistemas CRISPR-CasRESUMEN
Vascular calcification (VC) is an accurate risk factor and predictor of adverse cardiovascular events; however, there is currently no effective therapy to specifically prevent VC progression. Capsaicin (Cap) is a bioactive alkaloid isolated from Capsicum annuum L., a traditional medicinal and edible plant that is beneficial for preventing cardiovascular diseases. However, the effect of Cap on VC remains unclear. This study aimed to explore the effects and related mechanisms of Cap on aortic calcification in a mouse and on Pi-induced calcification in vascular smooth muscle cells (VSMCs). First, we established a calcification mouse model with vitamin D3 and evaluated the effects of Cap on calcification mice using von Kossa staining, calcium content, and alkaline phosphatase activity tests. The results showed that Cap significantly improved calcification in mice. VSMCs were then cultured in 2.6 mM Na2HPO4 and 50 µg/mL ascorbic acid for 7 days to obtain a calcification model, and we investigated the effects and mechanisms of Cap on VSMCs calcification by assessing the changes of calcium deposition, calcium content, and subsequent VC biomarkers. These results showed that Cap alleviated VSMCs calcification by upregulating the expressions of TRPV1. Moreover, Cap reduced the expression of Wnt3a and ß-catenin, whereas DKK1 antagonised the inhibitory effect of Cap on VSMC calcification. This study is the first to offer direct evidence that Cap inhibits the Wnt/ß-catenin signaling pathway by upregulating the expression of the TRPV1 receptor, resulting in the decreased expression of Runx2 and BMP-2, thereby reducing VSMC calcification. Our study may provide novel strategies for preventing the progression of VC. This could serve as a theoretical basis for clinically treating VC with spicy foods.
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Wetlands export large amounts of dissolved organic carbon (DOC) downstream, which is sensitive to water-table fluctuations (WTFs). While numerous studies have shown that WTFs may decrease wetland DOC via enhancing DOC biodegradation, an alternative pathway, i.e., retention of dissolved organic matter (DOM) by soil minerals, remains under-investigated. Here, we conducted a water-table manipulation experiment on intact soil columns collected from three wetlands with varying contents of reactive metals and clay to examine the potential retention of DOM by soil minerals during WTFs. Using batch sorption experiments and Fourier transform ion cyclotron resonance mass spectrometry, we showed that mineral (bentonite) sorption mainly retained lignin-, aromatic- and humic-like compounds (i.e., adsorbable compounds), in contrast to the preferential removal of protein- and carbohydrate-like compounds during biodegradation. Seven cycles of WTFs significantly decreased the intensity of adsorbable compounds in DOM (by 50 ± 21% based on fluorescence spectroscopy) and DOC adsorbability (by 2-20% and 1.9-12.7 mg L-1 based on batch sorption experiment), to a comparable extent compared with biodegradable compounds (by 11-32% and 1.6-15.2 mg L-1). Furthermore, oxidation of soil ferrous iron [Fe(II)] exerted a major control on the magnitude of potential DOM retention by minerals, while WTFs increased mineral-bound lignin phenols in the Zoige soil with the highest content of lignin phenols and Fe(II). Collectively, these results suggest that DOM retention by minerals likely played an important role in DOC decrease during WTFs, especially in soils with high contents of oxidizable Fe. Our findings support the 'iron gate' mechanism of soil carbon protection by newly-formed Fe (hydr)oxides during water-table decline, and highlight an underappreciated process (mineral-DOM interaction) leading to contrasting fate (i.e., preservation) of DOC in wetlands compared to biodegradation. Mineral retention of wetland DOC hence deserves more attention under changing climate and human activities.
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Materia Orgánica Disuelta , Suelo , Humanos , Suelo/química , Humedales , Lignina , Minerales/química , Hierro/análisis , Agua/análisis , Fenoles/análisis , Compuestos Ferrosos , Carbono/químicaRESUMEN
The development of high-performance lead-free K0.5Na0.5NbO3-based piezoceramics for replacing commercial lead-containing counterparts is crucial for achieving environmentally sustainable society. Although the proposed new phase boundaries (NPB) can effectively improve the piezoelectricity of KNN-based ceramics, the difficulty of achieving saturated poling and the underlying multiscale structures resolution of their complex microstructures are urgent issues. Here, we employ a medium entropy strategy to design NPB and utilize texture engineering to induce crystal orientation. The developed K0.5Na0.5NbO3-based ceramics enjoys both prominent piezoelectric performance and satisfactory Curie temperature, thus exhibiting an ultrahigh energy harvesting performance as well as excellent transducer performance, which is highly competitive in both lead-free and lead-based piezoceramics. Comprehensive structural analysis have ascertained that the field-induced efficient multiscale polarization configurations irreversible transitions greatly encourages high saturated poling. This study demonstrates a strategy for designing high-performance piezoceramics and establishes a close correlation between the piezoelectricty and the underlying multiscale structures.
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Microplastic contamination has become increasingly aggravated in coastal environments, further affecting biogeochemical processes involved with microbial community shifts. As a key biogeochemical process mainly driven by microbiota in coastal wetland sediments, litter decomposition contributes greatly to the global greenhouse gas (GHG) budget. However, under microplastic pollution, the relationship between microbial alterations and GHG emissions during litter decomposition in coastal wetlands remains largely unknown. Here, we explored the microbial mechanism by which polyethylene microplastic (PE-MP) influenced greenhouse gas (i.e., CH4, CO2 and N2O) emissions during litter decomposition in coastal sediments through a 75-day microcosm experiment. During litter decomposition, PE-MP exposure significantly decreased cumulative CH4 and CO2 emissions by 41.07% and 25.79%, respectively. However, there was no significant change in cumulative N2O emissions under PE-MP exposure. The bacterial, archaeal, and fungal communities in sediments exhibited varied responses to PE-MP exposure over time, as reflected by the altered structure and changed functional groups of the microbiota. The altered microbial functional groups ascribed to PE-MP exposure and sediment property changes might contribute to suppressing CH4 and CO2 emissions during litter decomposition. This study yielded valuable information regarding the effects of PE-MP on GHG emissions during litter decomposition in coastal wetland sediments.
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Gases de Efecto Invernadero , Humedales , Gases de Efecto Invernadero/análisis , Microplásticos , Plásticos , Polietileno , Dióxido de Carbono , Metano/análisis , Óxido Nitroso/análisis , SueloRESUMEN
Human umbilical cord mesenchymal stem cells (UC-MSCs)-derived hepatocyte-like cells (HLCs) have shown great promise in the treatment of liver diseases. However, most current induction protocols yield hepatocyte-like cells with limited function as compared with primary hepatocytes. Schisandrin B (Sch B) is one of the main components of Schisandra chinensis, which can prevent fibrosis progression and promote liver cell regeneration. Herein, we investigated the effects of Sch B on hepatic differentiation of UC-MSCs. We found that treatment with 10 µM Sch B from the second stage of the differentiation process increased hepatic marker levels and hepatic function. Additionally, RNA-seq analysis revealed that Sch B promoted hepatic differentiation via activating the JAK2/STAT3 pathway. When transplanted HLCs into mice with CCL4-induced liver fibrosis, Sch B-treated HLCs exhibited significant therapeutic effects. This study provides an optimized hepatic differentiation protocol for UC-MSCs based on Sch B, yielding functioning cells for liver disease treatment.
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BACKGROUND: The aim of this study was to investigate whether ischemia/hypoxia conditions induce fatty acid transport from neurons to astrocytes and whether this mechanism is affected by ApoE isoforms. METHODS AND RESULTS: A neonatal rat model of hypoxic-ischemic brain damage was established. Excessive accumulation of lipid droplets and upregulation of ApoE expression occurred in the hippocampus and cerebral cortex after hypoxia-ischemia, which implied the occurrence of abnormal fatty acid metabolism. Lipid peroxidation was induced in an oxygen-glucose deprivation and reperfusion (OGDR) model of ApoE-/- primary neurons. The number of BODIPY 558/568 C12-positive particles (fatty acid markers) transferred from neurons to astrocytes was significantly increased with the addition of human recombinant ApoE compared with that in the OGDR group, which significantly increased the efficiency of fatty acid transport from neurons to astrocytes and neuronal viability. However, ApoE4 was found to be associated with lower efficiency in fatty acid transport and less protective effects in OGDR-induced neuronal cell death than both ApoE2 and ApoE3. COG133, an ApoE-mimetic peptide, partially compensated for the adverse effects of ApoE4. FABP5 and SOD1 gene and protein expression levels were upregulated in astrocytes treated with BODIPY 558/568 C12 particles. CONCLUSIONS: In conclusion, ApoE plays an important role in mediating the transport of fatty acids from neurons to astrocytes under ischemia/hypoxia conditions, and this transport mechanism is ApoE isoform dependent. ApoE4 has a low transfer efficiency and may be a potential target for the clinical treatment of neonatal hypoxic-ischemic encephalopathy.
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Apolipoproteína E4 , Astrocitos , Compuestos de Boro , Animales , Humanos , Ratas , Apolipoproteína E4/genética , Astrocitos/metabolismo , Proteínas de Unión a Ácidos Grasos , Ácidos Grasos/metabolismo , Hipoxia/metabolismo , Isquemia , Neuronas/metabolismoRESUMEN
Transparent dielectric ceramics are splendid candidates for transparent pulse capacitors (TPCs) due to splendid cycle stability and large power density. However, the performance and service life of TPCs at present are threatened by overheating damage caused by dielectric loss. Here, a cooperative optimization strategy of microstructure control and superparaelectric regional regulation is proposed to simultaneously achieve excellent energy storage performance and real-time temperature monitoring function in NaNbO3-based ceramics. By introducing aliovalent ions and oxides with large bandgap energy, the size of polar nanoregions is continuously reduced. Due to the combined effect of increased relaxor behavior and fine grains, excellent comprehensive performances are obtained through doping appropriate amounts of Bi, Yb, Tm, and Zr, Ta, Hf in A- and B-sites of the NaNbO3 matrix, including recoverable energy storage density (5.39 J cm-3), extremely high energy storage efficiency (91.97%), ultra-fast discharge time (29 ns), and superior optical transmittance (≈47.5% at 736 nm). Additionally, the phenomenon of abnormal fluorescent negative thermal expansion is realized due to activation mechanism of surface phonon at high temperatures that can promote the formation of [Yb···O]-Tm3+ pairs, showing great potential in real-time temperature monitoring of TPCs. This research provides ideas for developing electronic devices with multiple functionalities.
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Metastasis is an important factor that causes ovarian cancer (OC) to become the most lethal malignancy of the female reproductive system, but its molecular mechanism is not fully understood. In this study, through bioinformatics analysis, as well as analysis of tissue samples and clinicopathological characteristics and prognosis of patients in our centre, it was found that Forkhead box Q1 (FOXQ1) was correlated with metastasis and prognosis of OC. Through cell function experiments and animal experiments, the results show that FOXQ1 can promote the progression of ovarian cancer in vivo and in vitro. Through RNA-seq, chromatin immunoprecipitation sequencing (ChIP-seq), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), Western blotting (WB), quantitative real-time polymerase chain reaction (qRTâPCR), immunohistochemistry (IHC), luciferase assay, and ChIP-PCR, it was demonstrated that FOXQ1 can mediate the WNT/ß-catenin pathway by targeting the LAMB promoter region. Through coimmunoprecipitation (Co-IP), mass spectrometry (MS), ubiquitination experiments, and immunofluorescence (IF), the results showed that PARP1 could stabilise FOXQ1 expression via the E3 ubiquitin ligase Hsc70-interacting protein (CHIP). Finally, the whole mechanism pathway was verified by animal drug combination experiments and clinical specimen prognosis analysis. In summary, our results suggest that PARP1 can promote ovarian cancer progression through the LAMB3/WNT/ß-catenin pathway by stabilising FOXQ1 expression.
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Neoplasias Ováricas , beta Catenina , Animales , Humanos , Femenino , beta Catenina/genética , beta Catenina/metabolismo , Línea Celular Tumoral , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Vía de Señalización Wnt/genética , Regulación Neoplásica de la Expresión Génica , Proliferación Celular , Poli(ADP-Ribosa) Polimerasa-1/genéticaRESUMEN
BACKGROUND: Presently, a consistent strategy for determining the stability of unruptured intracranial aneurysms (UIAs) in elderly patients is lacking, primarily due to the unique characteristics of this demographic. Our objective was to assess the risk factors contributing to aneurysm instability (growth or rupture) within the elderly population. METHODS: In this study, we compiled data from follow-up patients with UIAs spanning from November 2016 to August 2021. We specifically focused on patients aged ≥ 60 years. Clinical histories were gathered, and morphological parameters of aneurysms were measured. The growth of aneurysms was determined using the computer-assisted semi-automated measurement (CASAM). Growth and rupture rates of UIAs were calculated, and both univariate and multivariate Cox regression analyses were conducted. Additionally, Kaplan-Meier survival curves were plotted. RESULTS: A total of 184 patients with 210 aneurysms were enrolled in the study. The follow-up period encompasses 506.6 aneurysm-years and 401.4 patient-years. Among all the aneurysms, 23 aneurysms exhibited growth, with an annual aneurysm growth rate of 11.0%, and 1 (4.5%) experienced rupture, resulting in an annual aneurysm rupture rate of 0.21%. Multivariate Cox analysis identified poorly controlled hypertension (P = 0.011) and high-risk aneurysms (including anterior cerebral artery (ACA), anterior communicating artery (AcoA), posterior communicating artery aneurysm (PcoA), posterior circulation (PC) > 4 mm or distal internal carotid artery (ICAd), middle cerebral artery (MCA), and PC > 7 mm) (P = 0.006) as independent risk factors for the development of unstable aneurysms. CONCLUSIONS: In the elderly, poorly controlled hypertension and high-risk aneurysms emerge as significant risk factors for aneurysm instability. This underscores the importance of rigorous surveillance or timely intervention in patients presenting with these risk factors.
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Aneurisma Roto , Hipertensión , Aneurisma Intracraneal , Humanos , Anciano , Adulto , Niño , Aneurisma Intracraneal/epidemiología , Factores de Riesgo , Aneurisma Roto/epidemiología , Arteria Cerebral AnteriorRESUMEN
Organic small-molecule compounds have become promising cathode materials for high-performance lithium-ion batteries (LIBs) due to their high theoretical capacity, efficient utilization of active sites, low cost, and sustainability. However, severe dissolution and poor electronic conductivity limit their further practical applications. Herein, we have synthesized an insoluble organic small molecule, ferrocenyl-3-(λ1-azazyl) pyrazinyl [2,3-f] [1,10] phenanthrolino-2-amine (FCPD), by grafting ferrocene onto pyrazino[2,3-f] [1,10] phenanthroline-2,3-diamine (PPD). The combination of ferrocene (p-type Fe2+ moiety) and PPD (n-type C[double bond, length as m-dash]N groups) in a bipolar manner endows the target FCPD cathode with an increased theoretical capacity and a wide voltage window. The highly conjugated π-π aromatic skeleton inside enhances FCPD's electron delocalization and promotes strong interaction between FCPD units. Additionally, the mesoporous structure within the FCPD can provide numerous electroactive sites, contact area, and ion diffusion channels. Benefiting from the bipolar feature, aromatic, and mesoporous structure, the FCPD cathode demonstrates a large capacity of 250 mA h g-1 at 0.1 A g-1, a long lifespan of 1000 cycles and a high-rate capability of 151 mA h g-1 at 5 A g-1 along with a wide voltage window (1.2-3.8 V). Additionally, in situ synchrotron FT-IR and ex situ XPS reveal its dual ion storage mechanism in depth. Our findings provide essential insights into exploring the molecular design of advanced organic small molecules.
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BACKGROUND: Although stent-assisted coiling embolization (SAC) has been associated with a higher risk of ischemic and hemorrhagic complications, the use of SAC continues to rise for treating ruptured intracranial aneurysms (RIAs). This study aims to assess the safety and effectiveness of dual antiplatelet therapy (DAPT) in the context of RIAs. METHODS: We conducted a retrospective analysis at a single center, involving patients with aneurysmal subarachnoid hemorrhage (aSAH) between May 1, 2017 and December 31, 2021. Patients were categorized into two groups: the SAC group and the non-SAC (NSC) group. Patients in the SAC group received DAPT. We compared modified Rankin Scale (mRS) score, along with hemorrhagic and ischemic complications, between the two groups to evaluate the safety and efficacy of DAPT for SAC. RESULTS: The study included a total of 541 patients, of whom 38 (7.0%) experienced hemorrhagic complications and 48 (8.9%) developed ischemic complications. Additionally, 99 (18.3%) and 84 (15.5%) had poor clinical outcomes at discharge and 6 months, respectively. However, no statistically significant differences were observed between the two groups. Our analysis revealed that aneurysm location in the posterior circulation was a significant risk factor for an unfavorable prognosis when antiplatelet drugs were used following SAC (p = 0.025). CONCLUSIONS: Administering antiplatelet drugs after SAC for RIAs has demonstrated both safety and effectiveness. However, caution should be exercised when considering this treatment strategy for RIAs located in the posterior circulation due to the potentially elevated risk.
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BACKGROUND: Predicting breast cancer molecular subtypes can help guide individualised clinical treatment of patients who need the rational preoperative treatment. This study aimed to investigate the efficacy of preoperative prediction of breast cancer molecular subtypes by contrast-enhanced mammography (CEM) radiomic features. METHODS: This retrospective two-centre study included women with breast cancer who underwent CEM preoperatively between August 2016 and May 2022. We included 356 patients with 386 lesions, which were grouped into training (n = 162), internal test (n = 160) and external test sets (n = 64). Radiomics features were extracted from low-energy (LE) images and recombined (RC) images and selected. Three dichotomous tasks were established according to postoperative immunohistochemical results: Luminal vs. non-Luminal, human epidermal growth factor receptor (HER2)-enriched vs. non-HER2-enriched, and triple-negative breast cancer (TNBC) vs. non-TNBC. For each dichotomous task, the LE, RC, and LE+RC radiomics models were built by the support vector machine classifier. The prediction performance of the models was assessed by the area under the receiver operating characteristic curve (AUC). Then, the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were calculated for the models. DeLong's test was utilised to compare the AUCs. RESULTS: Radiomics models based on CEM are valuable for predicting breast cancer molecular subtypes. The LE+RC model achieved the best performance in the test set. The LE+RC model predicted Luminal, HER2-enriched, and TNBC subtypes with AUCs of 0.93, 0.89, and 0.87 in the internal test set and 0.82, 0.83, and 0.69 in the external test set, respectively. In addition, the LE model performed more satisfactorily than the RC model. CONCLUSION: CEM radiomics features can effectively predict breast cancer molecular subtypes preoperatively, and the LE+RC model has the best predictive performance.