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1.
Proc Natl Acad Sci U S A ; 121(25): e2314314121, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38865262

RESUMEN

Pyruvate lies at a pivotal node of carbon metabolism in eukaryotes. It is involved in diverse metabolic pathways in multiple organelles, and its interorganelle shuttling is crucial for cell fitness. Many apicomplexan parasites harbor a unique organelle called the apicoplast that houses metabolic pathways like fatty acid and isoprenoid precursor biosyntheses, requiring pyruvate as a substrate. However, how pyruvate is supplied in the apicoplast remains enigmatic. Here, deploying the zoonotic parasite Toxoplasma gondii as a model apicomplexan, we identified two proteins residing in the apicoplast membranes that together constitute a functional apicoplast pyruvate carrier (APC) to mediate the import of cytosolic pyruvate. Depletion of APC results in reduced activities of metabolic pathways in the apicoplast and impaired integrity of this organelle, leading to parasite growth arrest. APC is a pyruvate transporter in diverse apicomplexan parasites, suggesting a common strategy for pyruvate acquisition by the apicoplast in these clinically relevant intracellular pathogens.


Asunto(s)
Apicoplastos , Ácido Pirúvico , Toxoplasma , Apicoplastos/metabolismo , Toxoplasma/metabolismo , Ácido Pirúvico/metabolismo , Proteínas Protozoarias/metabolismo , Proteínas Protozoarias/genética , Animales , Proteínas de Transporte de Membrana/metabolismo , Proteínas de Transporte de Membrana/genética , Transporte Biológico , Redes y Vías Metabólicas
2.
Exp Cell Res ; 435(2): 113932, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38246397

RESUMEN

RNA binding protein RBM10 participates in various RNA metabolism, and its decreased expression or loss of function by mutation has been identified in many human cancers. However, how its dysregulation contributes to human cancer pathogenesis remains to be determined. Here, we found that RBM10 expression was decreased in breast tumors, and breast cancer patients with low RBM10 expression presented poorer survival rates. RBM10 depletion in breast cancer cells significantly promotes the cellular proliferation and migration. We further demonstrated that RBM10 forms a triple complex with YBX1 and phosphatase 1B (PPM1B), in which PPM1B serves as the phosphatase of YBX1. RBM10 knock-down markedly attenuated association between YBX1 and PPM1B, leading to elevated levels of YBX1 phosphorylation and its nuclear translocation. Furthermore, cancer cells with RBM10 depletion had a significantly accelerated tumor growth in nude mice. Importantly, these enhanced tumorigenic phenotypes can be reversed by overexpression of PPM1B. Our findings provide the mechanistic bases for functional loss of RBM10 in promoting tumorigenicity, and are potentially useful in the development of combined therapeutic strategies for cancer patients with defective RBM10.


Asunto(s)
Neoplasias de la Mama , Carcinogénesis , Animales , Ratones , Humanos , Femenino , Ratones Desnudos , Carcinogénesis/genética , Fosforilación , Proliferación Celular/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Monoéster Fosfórico Hidrolasas/genética , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral , Proteína 1 de Unión a la Caja Y/genética , Proteína 1 de Unión a la Caja Y/metabolismo , Proteínas de Unión al ARN/metabolismo , Proteína Fosfatasa 2C/genética , Proteína Fosfatasa 2C/metabolismo
3.
Plant J ; 115(5): 1277-1297, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37235696

RESUMEN

Plant embryogenic calli (ECs) can undergo somatic embryogenesis to regenerate plants. This process is mediated by regulatory factors, such as transcription factors and specifically expressed genes, but the precise molecular mechanisms underlying somatic embryogenesis at the single-cell level remain unclear. In this study, we performed high-resolution single-cell RNA sequencing analysis to determine the cellular changes in the EC of the woody plant species Dimocarpus longan (longan) and clarify the continuous cell differentiation trajectories at the transcriptome level. The highly heterogeneous cells in the EC were divided into 12 putative clusters (e.g., proliferating, meristematic, vascular, and epidermal cell clusters). We determined cluster-enriched expression marker genes and found that overexpression of the epidermal cell marker gene GDSL ESTERASE/LIPASE-1 inhibited the hydrolysis of triacylglycerol. In addition, the stability of autophagy was critical for the somatic embryogenesis of longan. The pseudo-timeline analysis elucidated the continuous cell differentiation trajectories from early embryonic cell division to vascular and epidermal cell differentiation during the somatic embryogenesis of longan. Moreover, key transcriptional regulators associated with cell fates were revealed. We found that ETHYLENE RESPONSIVE FACTOR 6 was characterized as a heat-sensitive factor that negatively regulates longan somatic embryogenesis under high-temperature stress conditions. The results of this study provide new spatiotemporal insights into cell division and differentiation during longan somatic embryogenesis at single-cell resolution.


Asunto(s)
Sapindaceae , Transcriptoma , Transcriptoma/genética , Sapindaceae/genética , Perfilación de la Expresión Génica , Análisis de Secuencia de ARN , Desarrollo Embrionario , Técnicas de Embriogénesis Somática de Plantas , Regulación de la Expresión Génica de las Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
4.
Curr Issues Mol Biol ; 46(3): 2514-2527, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38534775

RESUMEN

There has been debate about whether individuals with different color phenotypes should have different taxonomic status. In order to determine whether the different color phenotypes of Nedyopus patrioticus require separate taxonomic status or are simply synonyms, here, the complete mitochondrial genomes (mitogenomes) of two different colored N. patrioticus, i.e., red N. patrioticus and white N. patrioticus, are presented. The two mitogenomes were 15,781 bp and 15,798 bp in length, respectively. Each mitogenome contained 13 PCGs, 19 tRNAs, 2 rRNAs, and 1 CR, with a lack of trnI, trnL2, and trnV compared to other Polydesmida species. All genes were located on a single strand in two mitogenomes. Mitochondrial DNA analyses revealed that red N. patrioticus and white N. patrioticus did not show clear evolutionary differences. Furthermore, no significant divergence was discovered by means of base composition analysis. As a result, we suggest that white N. patrioticus might be regarded as a synonym for red N. patrioticus. The current findings confirmed the existence of color polymorphism in N. patrioticus, which provides exciting possibilities for future research. It is necessary to apply a combination of molecular and morphological methods in the taxonomy of millipedes.

5.
Small ; : e2403934, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38982940

RESUMEN

Achieving both robust adhesion to arbitrary surfaces and thermal-switchable/recyclable properties has proven challenging, particularly for commodity polyolefins. Herein, a simple and effective route is reported to transform polyolefins elastomer (POE) into a fully recycled epoxy-functionalized POE vitrimers (E-POE vit) with ultra-high, universal, stable, and switchable adhesion via facile free radical grafting and dynamic cross-linking. The resultant E-POE vit exhibits increase in adhesion strength on glass exceeding three to ten times compared to those commonly used polymers, due to the synergy of dense hydrogen (H)-bonds and strong interfacial affinity. In addition, E-POE vit also displays strong adhesion on diverse surfaces ranging from inorganic to organic while maintaining good stability in various harsh environments. More importantly, temperature-sensitive H-bonds allow E-POE vit to switch between attachment-detachment at alternating temperatures, resulting in reversible adhesion without adhesion loss, even after 10 cycles. Moreover, E-POE vit is able to be fully recycled and reused more than ten times via thermo-activated transesterification reactions with negligible change in structure and performance. This work may unlock strategies to fabricate high-performance commercial polymer-based adhesives with adhesion and recyclable features for intelligent and sustainable applications.

6.
Small ; 20(34): e2401706, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38602199

RESUMEN

In frigid regions, it is imperative to possess functionality materials that are ultrastrong, reusable, and economical, providing self-generated heat and electricity. One promising solution is a solar‒thermal‒electric (STE) generator, composed of solar‒thermal conversion phase change composites (PCCs) and temperature-difference power-generation-sheets. However, the existing PCCs face challenges with conflicting requirements for solar‒thermal conversion efficiency and mechanical robustness, mainly due to monotonous functionalized aerogel framework. Herein, a novel starch vitrimer aerogel is proposed that incorporates orientational distributed carboxylated carbon nanotubes (CCNT) to create PCC. This innovative design integrates large through-holes, mechanical robustness, and superior solar‒thermal conversion. Remarkably, PCC with only 0.8 wt.% CCNT loading achieves 85.8 MPa compressive strength, 102.4 °C at 200 mW cm-2 irradiation with an impressive 92.9% solar-thermal conversion efficiency. Noteworthy, the STE generator assembled with PCC harvests 99.1 W m-2 output power density, surpassing other reported STE generators. Strikingly, even under harsh conditions of -10 °C and 10 mW cm‒2 irradiation, the STE generator maintains 20 °C for PCC with 325 mV output voltage and 45 mA current, showcasing enhanced electricity generation in colder environments. This study introduces a groundbreaking STE generator, paving the way for self-sufficient heat and electricity supply in cold regions.

7.
J Transl Med ; 22(1): 880, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39350123

RESUMEN

BACKGROUND: Patients with glioblastoma (GBM) have a poor prognosis and limited treatment options. The mRNA decapping enzyme scavenger (DCPS) is a cap-hydrolyzing enzyme. The DCPS inhibitor RG3039 exhibited excellent central nervous system bioavailability in vivo and was safe and well tolerated in healthy volunteers in a phase 1 clinical trial. In this study, we investigated the expression of DCPS in GBM and the anti-tumor activity of RG3039 in various preclinical models of GBM. METHODS: DCPS expression was examined in human GBM and paired peritumoral tissues. Its prognostic role was evaluated together with clinicopathological characteristics of patients. The anti-GBM effect of RG3039 was determined using GBM cell lines, patient-derived organoids, and orthotopic mouse models. The therapeutic mechanisms of DCPS inhibition were explored. RESULTS: DCPS is overexpressed in GBM and is associated with poor survival of patients with GBM. The DCPS inhibitor RG3039 exhibited robust anti-GBM activities in GBM cell lines, patient-derived organoids and orthotopic mouse models, with drug exposure achievable in humans. Mechanistically, RG3039 downregulated STAT5B expression, thereby suppressing proliferation, survival and colony formation of GBM cells. CONCLUSIONS: DCPS is a promising target for GBM. Inhibition of DCPS with RG3039 at doses achievable in humans downregulates STAT5B expression and reduces proliferation, survival and colony formation of GBM cells. Given the excellent anti-cancer activity and central nervous system bioavailability in vivo and good tolerance in humans, RG3039 warrants further study as a potential GBM therapy.


Asunto(s)
Glioblastoma , Humanos , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Glioblastoma/genética , Glioblastoma/metabolismo , Animales , Línea Celular Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto , Endorribonucleasas/metabolismo , Endorribonucleasas/antagonistas & inhibidores , Proliferación Celular/efectos de los fármacos , Femenino , Masculino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Ratones Desnudos , Ratones , Organoides/efectos de los fármacos , Organoides/metabolismo , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , ARN Mensajero/metabolismo , ARN Mensajero/genética , Persona de Mediana Edad
8.
Plant Physiol ; 192(3): 1799-1820, 2023 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-36930572

RESUMEN

Plant somatic embryogenesis (SE) is an in vitro biological process wherein bipolar structures are induced to form somatic cells and regenerate into whole plants. MicroRNA (miRNA) is an essential player in plant SE. However, the mechanism of microRNA408 (miR408) in SE remains elusive. Here, we used stable transgenic technology in longan (Dimocarpus longan) embryogenic calli to verify the mechanism by which miR408 promotes cell division and differentiation of longan early SE. dlo-miR408-3p regulated riboflavin biosynthesis by targeting nudix hydrolase 23 (DlNUDT23), a previously unidentified gene mediating N6-methyladenosine (m6A) modification and influencing RNA homeostasis and cell cycle gene expression during longan early SE. We showed that DlMIR408 overexpression (DlMIR408-OE) promoted 21-nt miRNA biosynthesis. In DlMIR408-OE cell lines, dlo-miR408-3p targeted and downregulated DlNUDT23, promoted riboflavin biosynthesis, decreased flavin mononucleotide (FMN) accumulation, promoted m6A level, and influenced miRNA homeostasis. DNA replication, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, the pentose phosphate pathway, and taurine and hypotaurine metabolism were also closely associated with riboflavin metabolism. In a riboflavin feeding assay, dlo-miR408-3p and pre-miR408 were upregulated and DlNUDT23 was downregulated, increasing the m6A level and cell division and differentiation in longan globular embryos. When riboflavin biosynthesis was inhibited, dlo-miR408-3p was downregulated and DlNUDT23 was upregulated, which decreased m6A modification and inhibited cell division but did not inhibit cell differentiation. FMN artificial demethylated m6A modification affected the homeostasis of precursor miRNA and miRNA. Our results revealed a mechanism underlying dlo-miR408-3p-activated riboflavin biosynthesis in which DlNUDT23 is targeted, m6A modification is dynamically mediated, and cell division is affected, promoting early SE in plants.


Asunto(s)
MicroARNs , Sapindaceae , Perfilación de la Expresión Génica , Sapindaceae/genética , Sapindaceae/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Riboflavina/metabolismo
9.
Plant Physiol ; 193(1): 555-577, 2023 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-37313777

RESUMEN

Somatic embryogenesis (SE), like zygotic embryo development, is a progressive process. Early SE is the beginning of a switch from a somatic to an embryogenic state and is an important stage for initiating chromatin reprogramming of SE. Previous studies suggest that changes in chromatin accessibility occur during early SE, although information on the 3D structure of chromatin is not yet available. Here, we present a chromosome-level genome assembly of longan (Dimocarpus longan) using PacBio combined with high-through chromosome conformation capture scaffolding, which resulted in a 446 Mb genome assembly anchored onto 15 scaffolds. During early SE, chromatin was concentrated and then decondensed, and a large number of long terminal repeat retrotransposons (LTR-RTs) were enriched in the local chromatin interaction region, suggesting LTR-RTs were involved in chromatin reorganization. Early SE was accompanied by the transformation from A to B compartments, and the interactions between B compartments were enhanced. Results from chromatin accessibility, monomethylation of histone H3 at lysine 4 (H3K4me1) modification, and transcription analyses further revealed a gene regulatory network for cell wall thickening during SE. Particularly, we found that the H3K4me1 differential peak binding motif showed abnormal activation of ethylene response factor transcription factors and participation in SE. The chromosome-level genomic and multiomics analyses revealed the 3D conformation of chromatin during early SE, providing insight into the molecular mechanisms underlying cell wall thickening and the potential regulatory networks of TFs during early SE in D. longan. These results provide additional clues for revealing the molecular mechanisms of plant SE.


Asunto(s)
Cromosomas de las Plantas , Técnicas de Embriogénesis Somática de Plantas , Sapindaceae , Biomarcadores/metabolismo , Pared Celular , Cromatina , Redes Reguladoras de Genes , Genoma de Planta , Código de Histonas , Anotación de Secuencia Molecular , Sapindaceae/citología , Sapindaceae/crecimiento & desarrollo , Sapindaceae/metabolismo , Transcriptoma
10.
J Acoust Soc Am ; 156(2): 1252-1268, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39162419

RESUMEN

This paper introduces two-dimensional (2D) and 3D acoustic modeling and modal analysis using the wavelet finite-element method (WFEM). Governed by the Helmholtz equation, the acoustic domain is parameterized and analyzed using the scaling functions of B-spline wavelets, which facilitates the construction of elements with varying numbers of nodes via multi-resolution analysis. The wavelet-based shape functions provide a semi-orthogonal basis that enables rapid searching for approximate solutions in Lebesgue spaces, thereby offering significantly reduced interpolation errors and computational burden. Numerical examples are considered using WFEM, comprising a 2D acoustic problem involving a tube for predicting acoustic pressure and eigenfrequency investigations, and 3D acoustic problems involving a cubic room and an L-shaped room for capturing acoustic characteristics. The results are compared with those of (i) standard FEM with the same mesh and (ii) analytical solutions. Importantly, WFEM demonstrates stability by being insensitive to internal mesh size variations, indicating that B-spline wavelet elements have minimal effects on the numerical results. Furthermore, B-spline wavelet elements effectively control the pollution (dispersion) error of numerical methods when imposing Neumann boundary conditions in the high-frequency range, and they reduce interpolation errors caused by polynomial interpolation in the low-frequency domain.

11.
J Acoust Soc Am ; 155(1): 156-170, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38180152

RESUMEN

Piezoelectric composite materials (PCMs) with shunt damping circuits are used widely in hydroacoustics because of the flexible adjustability of their parameters. PCMs offer good underwater sound absorption, but shortcomings remain, such as poor low-frequency sound absorption, narrow bandwidth, and a single dissipation mechanism. In this paper, the tunable underwater sound absorption of a 0-3 PCM combined with a cavity structure and shunt circuit (PCMC) is studied systematically. First, the equivalent material parameters of 0-3 PCM are derived based on the Yamada model, and then a theoretical electroacoustic model is established for solving the absorption coefficient and is mutually verified with the numerical simulation method. On this basis, the tunable absorption characteristics of the structure are analyzed. The results show that coupling the energy dissipation mechanism of 0-3 PCM with the acoustic mechanism of the cavity structure not only achieves strong absorption at lower frequencies but also enriches the absorption mode in the mid-high frequencies by connecting the shunt circuits. Moreover, the influence of piezoelectric control variables and acoustic cavity morphology characteristics on structural sound absorption performance is further explored. Finally, the acoustic performance of PCMC is improved further via shape optimization and parameter optimization.

12.
Angew Chem Int Ed Engl ; 63(17): e202318568, 2024 04 22.
Artículo en Inglés | MEDLINE | ID: mdl-38433368

RESUMEN

ATR has emerged as a promising target for anti-cancer drug development. Several potent ATR inhibitors are currently undergoing various stages of clinical trials, but none have yet received FDA approval due to unclear regulatory mechanisms. In this study, we discovered a potent and selective ATR degrader. Its kinase-independent regulatory functions in acute myeloid leukemia (AML) cells were elucidated using this proteolysis-targeting chimera (PROTAC) molecule as a probe. The ATR degrader, 8 i, exhibited significantly different cellular phenotypes compared to the ATR kinase inhibitor 1. Mechanistic studies revealed that ATR deletion led to breakdown in the nuclear envelope, causing genome instability and extensive DNA damage. This would increase the expression of p53 and triggered immediately p53-mediated apoptosis signaling pathway, which was earlier and more effective than ATR kinase inhibition. Based on these findings, the in vivo anti-proliferative effects of ATR degrader 8 i were assessed using xenograft models. The degrader significantly inhibited the growth of AML cells in vivo, unlike the ATR inhibitor. These results suggest that the marked anti-AML activity is regulated by the kinase-independent functions of the ATR protein. Consequently, developing potent and selective ATR degraders could be a promising strategy for treating AML.


Asunto(s)
Antineoplásicos , Leucemia Mieloide Aguda , Humanos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Proteínas de la Ataxia Telangiectasia Mutada/uso terapéutico , Línea Celular Tumoral , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/metabolismo , Proteolisis , Proteína p53 Supresora de Tumor/metabolismo
13.
BMC Genomics ; 24(1): 138, 2023 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-36944911

RESUMEN

Longan (Dimocarpus longan Lour.) is an economically important subtropical fruit tree. Its fruit quality and yield are affected by embryo development. As a plant seed germination marker gene, the germin-like protein (GLP) gene plays an important role in embryo development. However, the mechanism underlying the role of the GLP gene in somatic embryos is still unclear. Therefore, we conducted genome-wide identification of the longan GLP (DlGLP) gene and preliminarily verified the function of DlGLP1-5-1. Thirty-five genes were identified as longan GLP genes and divided into 8 subfamilies. Based on transcriptome data and qRT‒PCR results, DlGLP genes exhibited the highest expression levels in the root, and the expression of most DlGLPs was upregulated during the early somatic embryogenesis (SE) in longan and responded to high temperature stress and 2,4-D treatment; eight DlGLP genes were upregulated under MeJA treatment, and four of them were downregulated under ABA treatment. Subcellular localization showed that DlGLP5-8-2 and DlGLP1-5-1 were located in the cytoplasm and extracellular stroma/chloroplast, respectively. Overexpression of DIGLP1-5-1 in the globular embryos (GEs) of longan promoted the accumulation of lignin and decreased the H2O2 content by regulating the activities of ROS-related enzymes. The results provide a reference for the functional analysis of DlGLPs and related research on improving lignin accumulation in the agricultural industry through genetic engineering.


Asunto(s)
Lignina , Sapindaceae , Lignina/metabolismo , Perfilación de la Expresión Génica/métodos , Peróxido de Hidrógeno/metabolismo
14.
Anal Chem ; 95(15): 6227-6234, 2023 04 18.
Artículo en Inglés | MEDLINE | ID: mdl-37027009

RESUMEN

Bisphenol chemicals (BPs) represent a complexity of halogenated and nonhalogenated substances sharing a common structure of two phenol functionalities, some of which exhibit ubiquitous environmental distributions and endocrine-disrupting activities. However, environmental monitoring of complex BP-like chemicals has faced analytical challenges arising from the lack of commercially available reference standards and efficient screening strategies. In the present study, we developed a strategy based on dansyl chloride (DnsCl) derivatization in combination with in-source fragmentation (D-ISF) during high-resolution mass spectrometry analysis to screen for bisphenol chemicals in complex environmental samples. The strategy contains three steps, including DnsCl derivatization to enhance the detection sensitivity by one to more than four orders of magnitude, in-source fragmentation to produce characteristic loss of 234.0589, 63.9619, and 298.0208 Da for the identification of DnsCl-derivatized compounds, and data processing and annotation. The D-ISF strategy was further validated and then applied to identify BPs in six types of particular matters as representative environmental samples, including settled dust from an electronic waste dismantling site, homes, offices, and vehicles, and airborne particles from indoor and outdoor environments. A total of six halogenated and fourteen nonhalogenated BPs were identified in the particles, including several chemicals that had rarely or never been identified in environmental samples. Our strategy offers a powerful tool for the environmental monitoring of bisphenol chemicals and assessment of human exposure risks.


Asunto(s)
Monitoreo del Ambiente , Fenoles , Humanos , Monitoreo del Ambiente/métodos , Espectrometría de Masas , Compuestos de Dansilo , Fenoles/análisis , Compuestos de Bencidrilo/análisis
15.
Langmuir ; 39(37): 13068-13075, 2023 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-37678181

RESUMEN

We present a facile chemical method for fabricating bioinspired microadhesives with significant improved reversible adhesion strength. Four kinds of polysiloxane with gradient varying phenyl contents were synthesized and used to fabricate microadhesives. The chemical structures and mechanical properties, as well as surface properties of the four microadhesives, were confirmed and characterized by ATR-FTIR, DSC, XPS, low-field NMR, tensile tests, and SEM, respectively. The macroadhesion test results revealed that phenyl contents showed remarkable and positive impacts on the macroadhesion performance of microadhesives. The pull-off adhesion strength of microadhesives with 90% phenyl content (0.851 N/cm2) was nearly 300% higher than that of pure PDMS (0.309 N/cm2). The macroadhesion mechanism analysis demonstrates that a larger bulk energy dissipation caused by massive π-π interaction, as well as the hydrophobic interaction and van der Waals forces at the interface synergistically resulted in a significant enhancement of the adhesion performance. Our results demonstrate the remarkable impact of chemical structures on the adhesion of microadhesives, and it is conducive to the further improvement of adhesion properties of bioinspired microadhesives.

16.
Eur Radiol ; 33(2): 1353-1363, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35997838

RESUMEN

OBJECTIVE: To investigate the feasibility of b-value threshold (bThreshold) map in preoperative evaluation of tumor budding (TB) in patients with locally advanced rectal cancer (LARC). METHODS: Patients with LARC were enrolled and underwent diffusion-weighted imaging (DWI). Contrast-to-noise ratio (CNR) between the lesions and normal tissues was assessed using DWI and bThreshold maps. TB was counted and scored using hematoxylin and eosin staining. Reproducibility for the apparent diffusion coefficient (ADC), bThreshold values, and region-of-interest (ROI) sizes were compared. Differences in ADC and bThreshold values with low-intermediate and high TB grades and the correlations between mean ADC and bThreshold values with TB categories were analyzed. Diagnostic performance of ADC and bThreshold values was assessed using area under the curve (AUC) and decision curve analysis. RESULTS: Fifty-one patients were evaluated. The CNR on bThreshold maps was significantly higher than that on DW images (9.807 ± 4.811 vs 7.779 ± 3.508, p = 0.005). Reproducibility was excellent for the ADC (ICC 0.933; CV 8.807%), bThreshold values (ICC 0.958; CV 7.399%), and ROI sizes (ICC 0.934; CV 8.425%). Significant negative correlations were observed between mean ADC values and TB grades and positive correlations were observed between mean bThreshold values and TB grades (p < 0.05). bThreshold maps showed better diagnostic performance than ADC maps (AUC, 0.914 vs 0.726; p = 0.048). CONCLUSIONS: In LARC patients, bThreshold values could distinguish different TB grades better than ADC values, and bThreshold maps may be a preoperative, non-invasive approach to evaluate TB grades. KEY POINTS: • Compared with diffusion-weighted images, bThreshold maps improved visualization and detection of rectal tumors. • Agreement and diagnostic performance of bThreshold values are superior to apparent diffusion coefficient in assessing tumor budding grades in patients with locally advanced rectal cancer. • bThreshold maps could be used to evaluate tumor budding grades non-invasively before operation.


Asunto(s)
Adenocarcinoma , Neoplasias Primarias Secundarias , Neoplasias del Recto , Humanos , Reproducibilidad de los Resultados , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/patología , Imagen de Difusión por Resonancia Magnética/métodos , Recto/patología , Adenocarcinoma/diagnóstico por imagen
17.
Bioorg Med Chem ; 91: 117404, 2023 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-37429211

RESUMEN

A series of novel substituted 4-anilinoquinazolines and their related compounds were designed and prepared by 3D modeling as potential inhibitors of VEGFR-2. Evaluation of VEGFR inhibitory activities suggested that compound I10 was a more potent (IC50 = 0.11 nM) VEGFR-2 inhibitor than most of the listed drugs. Kinase panel assays demonstrated that compound I10 was the selective VEGFR-2 inhibitor. The prediction of 3D modeling unveiled a unique binding mode of this lead compound to VEGFR-2. Compound I10 exhibited remarkable anti-angiogenesis and anti-proliferation in HUVEC at low nanomolar concentrations. PK studies indicated that the lead compound possessed adequate oral bioavailability in various species. In vivo subcutaneous tumor model demonstrated that oral administration of I10 demonstrated potent efficacy in inhibiting tumor growth and angiogenesis. All these results suggested compound I10 is a potential drug candidate for cancer treatment.


Asunto(s)
Antineoplásicos , Neoplasias , Humanos , Receptor 2 de Factores de Crecimiento Endotelial Vascular , Neoplasias/tratamiento farmacológico , Fosforilación , Inhibidores de Proteínas Quinasas/química , Proliferación Celular , Antineoplásicos/química , Relación Estructura-Actividad , Ensayos de Selección de Medicamentos Antitumorales , Simulación del Acoplamiento Molecular , Estructura Molecular
18.
BMC Pediatr ; 23(1): 73, 2023 02 11.
Artículo en Inglés | MEDLINE | ID: mdl-36765306

RESUMEN

BACKGROUND: To investigate health-related quality of life (HRQOL) in children with postoperative delirium (POD) after surgical repair of ventricular septal defects (VSDs). METHODS: A total of 109 patients were enrolled and assigned to the POD group (n = 47) and the non-POD group (n = 62). HRQOL was assessed by the PedsQLTM 3.0 Cardiac Module at discharge, and at the three- and six-month postoperative follow. RESULTS: Significant differences were detected in age, operation time, CPB time, mechanical ventilation duration, and length of ICU stay between the two groups, whereas sex and the VSD size did not significantly differ between groups. In terms of "cardiac heart problems and treatment" and "treatment-II", the HRQOL scores of the non-POD group were significantly better than those of the POD group. In terms of "perceived physical appearance" and "treatment anxiety", the POD group had significantly higher scores than the non-POD group at discharge and at the three-month postoperative follow-up. In terms of "cognitive problems" and "communication", the occurrence of POD still affected HRQOL at three months postoperatively, but the effect was significantly reduced at six months postoperatively. In terms of "total scores", both groups scored increasingly higher over time. The non-POD group had higher scores at discharge and three months postoperatively than the POD group, but no significant difference persisted at six months postoperatively. CONCLUSION: During the follow-up period, the HRQOL of the children with POD after surgical repair of VSD was inferior to that of the children without POD at discharge and three months postoperatively. However, the HRQOL did not differ between the two groups at six months postoperatively.


Asunto(s)
Delirio del Despertar , Defectos del Tabique Interventricular , Humanos , Niño , Calidad de Vida/psicología , Estudios de Seguimiento , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Defectos del Tabique Interventricular/cirugía
19.
J Acoust Soc Am ; 153(1): 643, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36732220

RESUMEN

Simultaneous perturbation stochastic approximation (SPSA) algorithm, an algorithm without secondary path modeling, has been applied to active noise control by some researchers. Some extended versions of this algorithm have been also developed to improve its performance. However, these existing algorithms are mostly dedicated to controlling the periodic noise instead of the broadband noise. In particular, background noise is not taken into account when SPSA algorithms are applied to control broadband noise. In this paper, an algorithm combining the cost function with the SPSA algorithm to control broadband noise has been proposed. The suggested cost function is an inner product of the estimated cross-correlation function between a reference vector and the error signal. The elements of the reference vector are composed of the reference signals at different times. Moreover, the algorithm analysis is performed and the numerical simulations are carried out to demonstrate the validity of the proposed algorithm. The results illustrate that the proposed algorithm can effectively reduce broadband noise when interference noise exists in the control system. Furthermore, the proposed algorithm has better convergence performance than other SPSA algorithms.

20.
Cardiol Young ; 33(7): 1165-1171, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35912615

RESUMEN

BACKGROUND: This study aimed to evaluate the efficacy and safety of high-frequency oscillation ventilation combined with intermittent mandatory ventilation in infants with acute respiratory distress syndrome after congenital heart surgery. METHODS: We retrospectively analysed the clinical data of 32 infants who were ventilated due to acute respiratory distress syndrome after congenital heart surgery between January, 2020 and January, 2022. We adopted high-frequency oscillation ventilation combined with intermittent mandatory ventilation as the rescue ventilation mode for infants who were failing conventional mechanical ventilation. RESULTS: After rescue high-frequency oscillation ventilation combined with intermittent mandatory ventilation, the dynamic compliance (Cdyn), PaO2 and PaO2/FiO2 ratio of the infants improved compared with conventional mechanical ventilation (p < 0.05). Moreover, high-frequency oscillation ventilation combined with intermittent mandatory ventilation resulted in a significant decrease in arterial-alveolar oxygen difference (AaDO2), FiO2, and oxygenation index (p < 0.05). No significant effect on haemodynamic parameters was observed. Moreover, no serious complications occurred in the two groups. CONCLUSION: Rescue high-frequency oscillation ventilation combined with intermittent mandatory ventilation significantly improved oxygenation in infants who failed conventional mechanical ventilation for acute respiratory distress syndrome after congenital heart surgery. Thus, this strategy is considered safe and feasible. However, further studies must be conducted to confirm the efficacy and safety of high-frequency oscillation ventilation combined with intermittent mandatory ventilation as a rescue perioperative respiratory support strategy for CHD.


Asunto(s)
Cardiopatías Congénitas , Ventilación de Alta Frecuencia , Síndrome de Dificultad Respiratoria , Humanos , Lactante , Estudios Retrospectivos , Respiración Artificial/métodos , Cardiopatías Congénitas/cirugía
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