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1.
J Cell Biochem ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38616655

RESUMO

This study aimed to explore the effects of peroxisome proliferator-activated receptor γ (PPARγ) inhibition on fracture healing of nonunion and the underlying mechanisms. Bone marrow mesenchymal stem cells (BMSCs) were treated with PPARγ antagonist GW9662 (5 µM, 10 µM). Alkaline phosphatase (ALP) staining and Alizarin Red S was used to assess early stage of osteogenesis and osteogenic differentiation. GW9662 (1 mg/kg/day) were administered intraperitoneally into the rats with bone fracture. Bone healing processes in the rat femur fracture model were recorded and assessed by radiographic methods on Weeks 8, 14, and 20 postoperation. Osteogenesis and angiogenesis at the fracture sites were evaluated by radiographic and histological methods on postoperative Week 20. GW9662 treatment increased ALP activity and Alp mRNA expression in rat BMSCs. Moreover, GW9662 administration increased matrix mineralization and mRNA and protein levels of Bmp2 and Runx2 in the BMSCs. In addition, GW9662 treatment improved radiographic score in the fracture rats and increased osteogenesis-related proteins, including type I collagen, osteopontin, and osteoglycin, in the bone tissues of the fracture sites. In conclusion, PPARγ inhibition promotes osteogenic differentiation of rat BMSCs, as well as improves the fracture healing of rats through Bmp2/Runx2 signaling pathway in the rat model of bone fracture.

2.
Appl Opt ; 63(10): A86-A97, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38568515

RESUMO

Pulsed light detecting and ranging (Lidar) is capable of acquiring comprehensive target information within a single pulse, including distance and intensity data. Intensity data reflects the target's backscattered intensity and is commonly regarded as a crucial observational parameter associated with target reflectivity information. Multiple studies have indicated the potential of intensity data in various applications within pulsed Lidar contexts. However, the intensity data is influenced by the incident angle and distance; hence it cannot directly manifest target characteristics. Consequently, a prerequisite for its usage is the implementation of intensity calibration. This paper presents a target intensity correction method based on an improved tail model, designed for preprocessing intensity data. First, the pulse echo signal equation is derived by incorporating the improved tail model with the detected target. On this foundation, a target echo intensity correction model is established to correct the intensities at various incident angles to those at the normal direction. Lastly, the derived approach is validated through simulation analysis, and practical experiments are conducted on a constructed pulsed Lidar system. These experiments meticulously investigate the influences of incident angle and distance, two prominent factors, on echo intensity. In the context of incident angle correction experiments, the mean absolute errors (MAEs) in calibrated values for diverse targets all remain within 0.04 V. Prior to correction, the maximum MAE for the cystosepiment is 0.505 V; after the correction it is reduced to merely 0.02 V, indicating a 96% reduction in error. Furthermore, all discrepancies exhibit an error standard deviation (ESD) of 0.03 V or less, showcasing favorable stability. For distance correction, under normal incidence conditions, a diverse set of targets is measured at different distances to achieve corrected MAE and ESD within 0.05 V. Consequently, the proposed method effectively achieves intensity correction concerning incident angles and distances. To achieve this, a reflectivity lookup table for the relevant targets was established. Combining this with the corrected intensity information enabled target identification in the three-dimensional imaging of pulsed Lidar.

3.
Front Immunol ; 15: 1344805, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38440722

RESUMO

Background: Acute lung injury (ALI)/severe acute respiratory distress syndrome (ARDS) is a serious clinical syndrome characterized by a high mortality rate. The pathophysiological mechanisms underlying ALI/ARDS remain incompletely understood. Considering the crucial role of immune infiltration and macrophage polarization in the pathogenesis of ALI/ARDS, this study aims to identify key genes associated with both ALI/ARDS and M1 macrophage polarization, employing a combination of bioinformatics and experimental approaches. The findings could potentially reveal novel biomarkers for the diagnosis and management of ALI/ARDS. Methods: Gene expression profiles relevant to ALI were retrieved from the GEO database to identify co-upregulated differentially expressed genes (DEGs). GO and KEGG analyses facilitated functional annotation and pathway elucidation. PPI networks were constructed to identify hub genes, and differences in immune cell infiltration were subsequently examined. The expression of hub genes in M1 versus M2 macrophages was evaluated using macrophage polarization datasets. The diagnostic utility of CD274 (PD-L1) for ARDS was assessed by receiver operating characteristic (ROC) analysis in a validation dataset. Experimental confirmation was conducted using two LPS-induced M1 macrophage models and an ALI mouse model. The role of CD274 (PD-L1) in M1 macrophage polarization and associated proinflammatory cytokine production was further investigated by siRNA-mediated silencing. Results: A total of 99 co-upregulated DEGs were identified in two ALI-linked datasets. Enrichment analysis revealed that these DEGs were mainly involved in immune-inflammatory pathways. The following top 10 hub genes were identified from the PPI network: IL-6, IL-1ß, CXCL10, CD274, CCL2, TLR2, CXCL1, CCL3, IFIT1, and IFIT3. Immune infiltration analysis revealed a significantly increased abundance of M1 and M2 macrophages in lung tissue from the ALI group compared to the control group. Subsequent analysis confirmed that CD274 (PD-L1), a key immunological checkpoint molecule, was highly expressed within M1 macrophages. ROC analysis validated CD274 (PD-L1) as a promising biomarker for the diagnosis of ARDS. Both in vitro and in vivo experiments supported the bioinformatics analysis and confirmed that the JAK-STAT3 pathway promotes CD274 (PD-L1) expression on M1 macrophages. Importantly, knockdown of CD274 (PD-L1) expression potentiated M1 macrophage polarization and enhanced proinflammatory cytokines production. Conclusion: This study demonstrates a significant correlation between CD274 (PD-L1) and M1 macrophages in ALI/ARDS. CD274 (PD-L1) functions as a negative regulator of M1 polarization and the secretion of proinflammatory cytokines in macrophages. These findings suggest potential new targets for the diagnosis and treatment of ALI/ARDS.


Assuntos
Lesão Pulmonar , Síndrome do Desconforto Respiratório , Animais , Camundongos , Antígeno B7-H1 , Biologia Computacional , Citocinas
4.
Sci Rep ; 14(1): 1386, 2024 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-38228673

RESUMO

Osteosarcoma (OS) is one of the most prevalent bone tumors in adolescents, and the correlation between aging and OS remains unclear. Currently, few accurate and reliable biomarkers have been determined for OS prognosis. To address this issue, we carried out a detailed bioinformatics analysis based on OS with data from the Cancer Genome Atlas data portal and Human Aging Genomic Resources database, as well as in vitro experiments. A total of 88 OS samples with gene expression profiles and corresponding clinical characteristics were obtained. Through univariate Cox regression analysis and survival analysis, 10 aging-associated survival lncRNAs (AASRs) were identified to be associated with the overall survival of OS patients. Based on the expression levels of the 10 AASRs, the OS patients were classified into two clusters (Cluster A and Cluster B). Cluster A had a worse prognosis, while Cluster B had a better prognosis. Then, 5 AASRs were ultimately included in the signature through least absolute shrinkage and selection operator-Cox regression analysis. Kaplan‒Meier survival analysis verified that the high-risk group exhibited a worse prognosis than the low-risk group. Furthermore, univariate and multivariate Cox regression analyses confirmed that the riskScore was an independent prognostic factor for OS patients. Subsequently, we discovered that the risk signature was correlated with the properties of the tumor microenvironment and immune cell infiltration. Specifically, there was a positive association between the risk model and naïve B cells, resting dendritic cells and gamma delta T cells, while it was negatively related to CD8+ T cells. Finally, in vitro experiments, we found that UNC5B-AS1 inhibited OS cells from undergoing cellular senescence and apoptosis, thereby promoting OS cells proliferation. In conclusion, we constructed and verified a 5 AASR-based signature, that exhibited excellent performance in evaluating the overall survival of OS patients. In addition, we found that UNC5B-AS1 might inhibit the senescence process, thus leading to the development and progression of OS. Our findings may provide novel insights into the treatment of OS patients.


Assuntos
Neoplasias Ósseas , Osteossarcoma , RNA Longo não Codificante , Adolescente , Humanos , RNA Longo não Codificante/genética , Linfócitos T CD8-Positivos , Prognóstico , Osteossarcoma/genética , Envelhecimento , Neoplasias Ósseas/genética , Microambiente Tumoral/genética , Receptores de Netrina
5.
Nat Commun ; 15(1): 512, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38218949

RESUMO

Tuning CO2 hydrogenation product distribution to obtain high-selectivity target products is of great significance. However, due to the imprecise regulation of chain propagation and hydrogenation reactions, the oriented synthesis of a single product is challenging. Herein, we report an approach to controlling multiple sites with graphene fence engineering that enables direct conversion of CO2/H2 mixtures into different types of hydrocarbons. Fe-Co active sites on the graphene fence surface present 50.1% light olefin selectivity, while the spatial Fe-Co nanoparticles separated by graphene fences achieve liquefied petroleum gas of 43.6%. With the assistance of graphene fences, iron carbides and metallic cobalt can efficiently regulate C-C coupling and olefin secondary hydrogenation reactions to achieve product-selective switching between light olefins and liquefied petroleum gas. Furthermore, it also creates a precedent for CO2 direct hydrogenation to liquefied petroleum gas via a Fischer-Tropsch pathway with the highest space-time yields compared to other reported composite catalysts.

6.
Environ Pollut ; 344: 123269, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38159627

RESUMO

The removal and recovery of uranium [U(VI)] from organic containing wastewater has been a challenging in radioactive wastewater purification. Here, we designed a polyamine/amidoxime polyacrylonitrile fiber (PAN-AO-A) with high removal efficiency, excellent selectivity, excellent organic resistance and low cost by combining the anti-organic properties of amidoxime polyacrylonitrile fiber (PAN-AO-A) with the high adsorption capacity of polyamine polyacrylonitrile fiber, which is used to extract U(VI) from low-level uranium-containing wastewater with high ammonia nitrogen and organic content. PAN-AO-A adsorbent with high grafting rate (86.52%), high adsorption capacity (qe = 618.8 mg g-1), and strong resistance to organics and impurity interference is achieved. The adsorption rate of U(VI) in both real organic and laundry wastewater containing uranium is as high as 99.7%, and the partition coefficients (Kd) are 7.61 × 105 mL g-1 and 9.16 × 106 mL g-1, respectively. The saturated adsorption capacity of PAN-AO-A in the continuous system solution can reach up to 505.5 mg g-1, and the concentration of U(VI) in the effluent is as low as 1 µg L-1. XPS analysis and Density functional theory (DFT) studies the coordination form between U(VI) and PAN-AO-A, where the most stable structure is η2-AO(UO2)(CO3)2. The -NH-/-NH2 and -C(NH2)N-OH groups of PAN-AO-A exhibit a synergistic complex effect in the U(VI) adsorption process. PAN-AO-A is a material with profound influence and limitless potential that can be used for wastewater containing U(VI) and organic matter.


Assuntos
Urânio , Águas Residuárias , Urânio/análise , Poliaminas , Oximas/química , Adsorção
7.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 40(5): 982-988, 2023 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-37879928

RESUMO

Radiopharmaceutical dynamic imaging typically necessitates intravenous injection via the bolus method. However, manual bolus injection carries the risk of handling errors as well as radiological injuries. Hence, there is potential for automated injection devices to replace manual injection methods. In this study, the effect of micro-bolus pulse injection technology was compared and verified by radioactive experiments using a programmable injection pump, and the overall bubble recognition experiment and rat tail vein simulation injection verification were performed using the piezoelectric sensor preloading method. The results showed that at the same injection peak speed, the effective flushing volume of micro-bolus pulse flushing (about 83 µL/pulse) was 49.65% lower than that of uniform injection and 25.77% lower than that of manual flushing. In order to avoid the dilution effect of long pipe on the volume of liquid, the use of piezoelectric sensor for sealing preloading detection could accurately predict the bubbles of more than 100 µL in the syringe. In the simulated injection experiment of rat tail vein, when the needle was placed in different tissues by preloading 100 µL normal saline, the piezoelectric sensor fed back a large difference in pressure attenuation rate within one second, which was 2.78% in muscle, 17.28% in subcutaneous and 54.71% in vein. Micro-bolus pulse injection method and piezoelectric sensor sealing preloading method have application potential in improving the safety of radiopharmaceutical automatic bolus injection.


Assuntos
Compostos Radiofarmacêuticos , Animais , Ratos , Compostos Radiofarmacêuticos/administração & dosagem
8.
PLoS One ; 18(9): e0290869, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37656682

RESUMO

We investigate the roles of liquidity and delay in financial markets through our proposed optimal forecasting model. The efficiency and liquidity of the financial market are examined using stochastic models that incorporate information delay. Based on machine learning, we estimate the in-sample and out-of-sample forecasting price performances of the six proposed methods using the likelihood function and Bayesian methods, and the out-of-sample prediction performance is compared with the benchmark model ARIMA-GARCH. We discover that the forecasting price performance of the proposed simplified delay stochastic model is superior to that of the benchmark methods by the test methods of a variety of loss function, superior predictive ability test (SPA), Akaike information criterion (AIC), and Bayesian information criterion (BIC). Using data from the Chinese stock market, the best forecasting model assesses the efficiency and liquidity of the financial market while accounting for information delay and trade probability. The rise in trade probability and delay time affects the stability of the return distribution and raises the risk, according to stochastic simulation. The empirical findings show that empirical and best forecasting approaches are compatible, that company size and liquidity (delay time) have an inverse relationship, and that delay time and liquidity have a nonlinear relationship. The most efficient have optimal liquidity.


Assuntos
Comércio , Previsões , Modelos Econômicos , Teorema de Bayes , Benchmarking , Funções Verossimilhança , Previsões/métodos , China , Processos Estocásticos , Aprendizado de Máquina , Comércio/economia , Comércio/tendências
9.
Angew Chem Int Ed Engl ; 62(46): e202311786, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37735097

RESUMO

The conversion of CO2 into ethanol with renewable H2 has attracted tremendous attention due to its integrated functions of carbon elimination and chemical synthesis, but remains challenging. The electronic properties of a catalyst are essential to determine the adsorption strength and configuration of the key intermediates, therefore altering the reaction network for targeted synthesis. Herein, we describe a catalytic system in which a carbon buffer layer is employed to tailor the electronic properties of the ternary ZnOx -Fe5 C2 -Fe3 O4 , in which the electron-transfer pathway (ZnOx →Fe species or carbon layer) ensures the appropriate adsorption strength of -CO* on the catalytic interface, facilitating C-C coupling between -CHx * and -CO* for ethanol synthesis. Benefiting from this unique electron-transfer buffering effect, an extremely high ethanol yield of 366.6 gEtOH kgcat -1 h-1 (with CO of 10 vol % co-feeding) is achieved from CO2 hydrogenation. This work provides a powerful electronic modulation strategy for catalyst design in terms of highly oriented synthesis.

10.
Molecules ; 28(18)2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37764410

RESUMO

The direct selective conversion of ethanol to butadiene (ETB) is a competitive and environmentally friendly process compared to the traditional crude cracking route. The acid-base properties of catalysts are crucial for the direct ETB process. Herein, we report a rationally designed multifunctional lignin-derived carbon-modulated ZnZr/SiO2 (L-ZnZr/SiO2) catalyst with suitable acid-base properties for the direct ETB reaction. A variety of characterization techniques are employed to investigate the relationship between the acid-base properties and catalytic performance of the multifunctional lignin-modulated ZnZr/SiO2 catalysts. The results revealed that the rationally additional lignin-modulated carbon enhances both the acidity and basicity of the ZnZr/SiO2 catalysts, providing a suitable acid-base ratio that boosts the direct ETB reactivity. Meanwhile, the 1% L-ZnZr/SiO2 catalyst possessed ethanol conversion and butadiene selectivity as high as 98.4% and 55.5%, respectively, and exhibited excellent catalytic stability.

11.
Adv Sci (Weinh) ; 10(28): e2302756, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37532671

RESUMO

Natural materials are composed of a limited number of molecular building blocks and their exceptional properties are governed by their hierarchical structure. However, this level of precision is unattainable with current state-of-the-art materials for 3D printing. Herein, new self-assembled printable materials based on block copolymers (BCPs) enabling precise control of the nanostructure in 3D are presented. In particular, well-defined BCPs consisting of poly(styrene) (PS) and a polymethacrylate-based copolymer decorated with printable units are selected as suitable self-assembled materials and synthesized using controlled radical polymerization. The synthesized library of BCPs are utilized as printable formulations for the fabrication of complex 3D microstructures using two-photon laser printing. By fine-tuning the BCP composition and solvent in the formulations, the fabrication of precise 3D nano-ordered structures is demonstrated for the first time. A key point of this work is the achievement of controlled nano-order within the entire 3D structures. Thus, imaging of the cross-sections of the 3D printed samples is performed, enabling the visualization also from the inside. The presented versatile approach is expected to create new avenues for the precise design of functional polymer materials suitable for high-resolution 3D printing exhibiting tailor-made nanostructures.

12.
Materials (Basel) ; 16(13)2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37445117

RESUMO

Discharged slag not only occupies a large amount of land for disposal, but also causes serious environmental pollution. The use of alkali-activated slag (AAS) instead of cement as a soil-stabilization agent is beneficial for industrial waste disposal and energy conservation, which complies with the concept of green and low-carbon sustainable development in the construction industry. In this study, the compressive strength, water permeability coefficient, chloride migration coefficient and sulfate resistance of alkali-activated slag-stabilized soil (AASS) were evaluated, and compared with those of cement-stabilized soil (CSS). The hydrated crystalline phases and microscopic pore structures were analyzed by X-ray diffraction, electrochemical impedance spectroscopy (EIS) and mercury intrusion porosimetry (MIP) tests, respectively. The results indicate that, compared with CSS, AASS exhibits a higher compressive strength, lower water permeability, chloride migration coefficient and better resistance to sulfate attack, with the optimum dosage higher than 10 wt.%. The results of the MIP analysis show that the addition of AAS reduces the porosity by 6.47%. The combined use of soil and AAS proves to be a viable and sustainable method of waste utilization and carbon emission reduction in the construction industry, which provides a practical path towards carbon peaking and carbon neutrality.

13.
Comput Biol Med ; 163: 107160, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37321099

RESUMO

BACKGROUND: Orthosiphon stamineus Benth is a dietary supplement and traditional Chinese herb with widespread clinical applications, but a comprehensive understanding of its active compounds and polypharmacological mechanisms is lacking. This study aimed to systematically investigate the natural compounds and molecular mechanisms of O. stamineus via network pharmacology. METHODS: Information on compounds from O. stamineus was collected via literature retrieval, while physicochemical properties and drug-likeness were evaluated using SwissADME. Protein targets were screened using SwissTargetPrediction, while the compound-target networks were constructed and analyzed via Cytoscape with CytoHubba for seed compounds and core targets. Enrichment analysis and disease ontology analysis were then carried out, generating target-function and compound-target-disease networks to intuitively explore potential pharmacological mechanisms. Lastly, the relationship between active compounds and targets was confirmed via molecular docking and dynamics simulation. RESULTS: A total of 22 key active compounds and 65 targets were identified and the main polypharmacological mechanisms of O. stamineus were addressed. The molecular docking results suggested that nearly all core compounds and their targets possess good binding affinity. In addition, the separation of receptor and ligands was not observed in all dynamics simulation processes, whereas complexes of orthosiphol Z-AR and Y-AR performed best in simulations of molecular dynamics. CONCLUSION: This study successfully identified the polypharmacological mechanisms of the main compounds in O. stamineus, and predicted five seed compounds along with 10 core targets. Moreover, orthosiphol Z, orthosiphol Y, and their derivatives can be utilized as lead compounds for further research and development. The findings here provide improved guidance for subsequent experiments, and we identified potential active compounds for drug discovery or health promotion.


Assuntos
Orthosiphon , Extratos Vegetais , Extratos Vegetais/farmacologia , Orthosiphon/química , Simulação de Acoplamento Molecular
14.
Reprod Biol ; 23(3): 100783, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37336146

RESUMO

Infertility affects roughly 8-12 % of couples worldwide, and in above 50 % of couples, male factors are the primary or contributing cause. Many long noncoding RNAs (lncRNAs) are detected in the testis, but their functions are not well understood. CIRBIL was 862 nucleotides in length and was found to be localized mostly in the cytosol of Leydig cell, a small portion was positioned inside the seminiferous tubules. Loss of CIRBIL in mice resulted in male subfertility, characterized by smaller testis and increased germ cell apoptosis. Deletion of CIRBIL significant decreased the number of sperm and impaired the integrity of sperm head and tail. In CIRBIL KO mice, testosterone levels in serum and expression of testosterone biosynthesis genes (STAR and 3ß-HSD) were both reduced. Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were primarily enriched in steroid synthesis process in CIRBIL-binding proteins. Protein-protein (PPI) interaction networks revealed that both cis- and trans-regulated target genes of CIRBIL were associated with testosterone synthesis. Collectively, our results strongly suggest that CIRBIL is a regulator of steroid hormone synthesis.


Assuntos
RNA Longo não Codificante , Masculino , Camundongos , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Espermatogênese , Testosterona , Sêmen/metabolismo , Testículo/metabolismo , Esteroides/metabolismo
15.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 40(2): 320-326, 2023 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-37139764

RESUMO

In clinical practice, radiopharmaceutical dynamic imaging technology requires the bolus injection method to complete injection. Due to the failure rate and radiation damage of manual injection, even experienced technicians still bear a lot of psychological burden. This study combined the advantages and disadvantages of various manual injection modes to develop the radiopharmaceutical bolus injector, and explored the application of automatic injection in the field of bolus injection from four aspects: radiation protection, occlusion response, sterility of injection process and effect of bolus injection. Compared with the current mainstream manual injection method, the bolus manufactured by the radiopharmaceutical bolus injector based on the automatic hemostasis method had a narrower full width at half maximum and better repeatability. At the same time, radiopharmaceutical bolus injector had reduced the radiation dose of the technician's palm by 98.8%, and ensured more efficient vein occlusion recognition performance and sterility of the entire injection process. The radiopharmaceutical bolus injector based on automatic hemostasis has application potential in improving the effect and repeatability of bolus injection.


Assuntos
Mãos , Compostos Radiofarmacêuticos , Injeções
16.
Mater Horiz ; 10(5): 1865-1874, 2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-36892431

RESUMO

Graphene aerogels (GAs) possess workable deformation and sensing properties at extreme temperatures. However, their poor tensile properties have restricted their applications in stretchable electronic devices, smart soft robots, and aerospace. Herein, an ultra-stretchable and elastic graphene aerogel with record elongation from -95% to 400% was achieved by constructing a highly crimped and crosslinked graphene network using a microbubble-filled GA precursor by a simple compress-annealing process. This conductive aerogel with near zero Poisson's ratio showed rubber-like but temperature-invariant elasticity from 196.5 °C to 300 °C, and special strain insensitivity from 50% to 400% tensile strain and high sensitivity below 50% tensile strain. Therefore, it can be used as a highly stretchable but strain-insensitive conductor under extreme environments, in which these polymer-based stretchable conductive materials are not workable. Moreover, this work provides new thoughts on constructing inorganic ultra-stretchable materials.

18.
Circ Res ; 132(2): 208-222, 2023 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-36656967

RESUMO

OBJECTIVE: ASPP1 (apoptosis stimulating of p53 protein 1) is critical in regulating cell apoptosis as a cofactor of p53 to promote its transcriptional activity in the nucleus. However, whether cytoplasmic ASPP1 affects p53 nuclear trafficking and its role in cardiac diseases remains unknown. This study aims to explore the mechanism by which ASPP1 modulates p53 nuclear trafficking and the subsequent contribution to cardiac ischemia/reperfusion (I/R) injury. METHODS AND RESULTS: The immunofluorescent staining showed that under normal condition ASPP1 and p53 colocalized in the cytoplasm of neonatal mouse ventricular cardiomyocytes, while they were both upregulated and translocated to the nuclei upon hypoxia/reoxygenation treatment. The nuclear translocation of ASPP1 and p53 was interdependent, as knockdown of either ASPP1 or p53 attenuated nuclear translocation of the other one. Inhibition of importin-ß1 resulted in the cytoplasmic sequestration of both p53 and ASPP1 in neonatal mouse ventricular cardiomyocytes with hypoxia/reoxygenation stimulation. Overexpression of ASPP1 potentiated, whereas knockdown of ASPP1 inhibited the expression of Bax (Bcl2-associated X), PUMA (p53 upregulated modulator of apoptosis), and Noxa, direct apoptosis-associated targets of p53. ASPP1 was also increased in the I/R myocardium. Cardiomyocyte-specific transgenic overexpression of ASPP1 aggravated I/R injury as indicated by increased infarct size and impaired cardiac function. Conversely, knockout of ASPP1 mitigated cardiac I/R injury. The same qualitative data were observed in neonatal mouse ventricular cardiomyocytes exposed to hypoxia/reoxygenation injury. Furthermore, inhibition of p53 significantly blunted the proapoptotic activity and detrimental effects of ASPP1 both in vitro and in vivo. CONCLUSIONS: Binding of ASPP1 to p53 triggers their nuclear cotranslocation via importin-ß1 that eventually exacerbates cardiac I/R injury. The findings imply that interfering the expression of ASPP1 or the interaction between ASPP1 and p53 to block their nuclear trafficking represents an important therapeutic strategy for cardiac I/R injury.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Traumatismo por Reperfusão , Proteína Supressora de Tumor p53 , Animais , Camundongos , Apoptose/fisiologia , Hipóxia/metabolismo , Isquemia/metabolismo , Carioferinas , Miócitos Cardíacos/metabolismo , Traumatismo por Reperfusão/metabolismo , Proteína Supressora de Tumor p53/genética , Proteínas Adaptadoras de Transdução de Sinal/genética
19.
Zootaxa ; 5357(3): 423-433, 2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-38220638

RESUMO

The exuviae of Anotogaster chaoi Zhou, 1998 and Neallogaster annandalei (Fraser, 1923) are described and illustrated for the first time from Erhai Lake Basin, Yunnan Province, China, based on the final stage larvae reared in a laboratory. Diagnostic differences between the larvae of congeneric A. chaoi, A. gregoryi Fraser, 1923, as well as N. annandalei and N. hermionae (Fraser, 1927) are discussed, and notes on their habitats are provided.


Assuntos
Odonatos , Animais , Larva , Lagos , China , Ecossistema
20.
Materials (Basel) ; 15(23)2022 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-36499933

RESUMO

This study investigated the effect of layered double hydroxides (LDHs) on the deterioration process of cement paste in the sulfate environment. Cement pastes with the addition of original and calcined LDHs at 2.5 wt.% and 5.0 wt.% of cement were exposed to Na2SO4 solution for 360 days. The macroscopic performance of the cement paste was assessed based on mass variation, porosity, compressive strength, and content of sulfate ions. Furthermore, the microhardness, microstructures, and composition of the degraded pastes were examined using Vickers hardness (HV), mercury intrusion porosimetry (MIP), scanning electron microscope (SEM), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The results indicate that cement paste incorporated with LDHs can mitigate the corrosion caused by sulfate effectively, especially in the case of calcined LDHs (C-LDHs), which primarily increase the adsorption of sulfate. Compared with the control specimen, the 180 d compressive strength loss ratio of specimens with 2.5 wt.% and 5.0 wt.% of C-LDHs decreased by 63.66% and 80.51%, respectively. Moreover, LDHs can reduce the amount of ettringite crystals, densify the microstructure, and refine the pore structure to mitigate the cement paste's sulfate corrosion significantly. Compared with the control specimen, the 180 d harmful pore volume fraction of specimens laced with 2.5 wt.% and 5.0 wt.% C-LDHs decreased by 43.77% and 54.51%, respectively. In terms of the content of C-LDHs, an optimal content of C-LDHs could ensure the dominant effect of adsorption, while excessive C-LDHs could refine pores. In addition, Vickers hardness has an excellent correlation with compressive strength, which could precisely predict the compressive strength. Moreover, by combining the Vickers hardness distribution and content distribution of sulfate ions, the cross-section of the paste could be classified into four regions to evaluate the deterioration process accurately: the degraded zone, the strengthened zone, the invaded zone, and the intact zone.

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