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1.
Adv Sci (Weinh) ; : e2310239, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582519

RESUMO

Rationally designed organic redox-active materials have attracted numerous interests due to their excellent electrochemical performance and reasonable sustainability. However, they often suffer from poor cycling stability, intrinsic low operating potential, and poor rate performance. Herein, a novel Donor-Acceptor (D-A) bipolar polymer with n-type pyrene-4,5,9,10-tetraone unit storing Li cations and p-type carbazole unit which attracts anions and provides polymerization sites is employed as a cathode for lithium-ion batteries through in situ electropolymerization. The multiple redox reactions and boosted kinetics by the D-A structure lead to excellent electrochemical performance of a high discharge capacity of 202 mA h g-1 at 200 mA g-1, impressive working potential (2.87 and 4.15 V), an outstanding rate capability of 119 mA h g-1 at 10 A g-1 and a noteworthy energy density up to 554 Wh kg-1. This strategy has significant implications for the molecule design of bipolar organic cathode for high cycling stability and high energy density.

2.
Ecotoxicol Environ Saf ; 275: 116250, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38552387

RESUMO

Forests emit a large amount of biogenic volatile organic compounds (BVOCs) in response to biotic and abiotic stress. Despite frequent occurrence of large forest fires in recent years, the impact of smoke stress derived from these forest fires on the emission of BVOCs is largely unexplored. Thus, the aims of the study were to quantify the amount and composition of BVOCs released by two sub-tropical tree species, Cunninghamia lanceolata and Schima superba, in response to exposure to smoke. Physiological responses and their relationship with BVOCs were also investigated. The results showed that smoke treatments significantly (p < 0.001) promoted short-term release of BVOCs by C. lanceolata leaves than S. superba; and alkanes, olefins and benzene homologs were identified as major classes of BVOCs. Both C. lanceolata and S. superba seedlings showed significant (p < 0.005) physiological responses after being smoke-stressed where photosynthetic rate remained unaffected, chlorophyll content greatly reduced and Activities of anti-oxidant enzymes and the malondialdehyde content generally increased with the increase in smoke concentration. Activities of anti-oxidant enzymes showed mainly positive correlations with the major BVOCs. In conclusion, the release of BVOCs following smoke stress is species-specific and there exists a link between activities of antioxidant enzymes and BVOCs released. The findings provide insight about management of forest fires in order to control excessive emission of smoke that would trigger increased release of BVOCs.

3.
Front Psychol ; 15: 1217106, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38425554

RESUMO

Time course analysis of eye movements during free exploration of real-world scenes often reveals an increase in fixation durations together with a decrease in saccade amplitudes, which has been explained within the two visual systems approach, i.e., a transition from ambient to focal. Short fixations and long saccades during early viewing periods are classified as ambient mode of vision, which is concerned with spatial orientation and is related to simple visual properties such as motion, contrast, and location. Longer fixations and shorter saccades during later viewing periods are classified as focal mode of vision, which is concentrated in the foveal projection and is capable of object identification and its semantic categorization. While these findings are mainly obtained in the context of image exploration, the present study endeavors to investigate whether the same pattern of interplay between ambient and focal visual attention is deployed when people work on complex real-world tasks-and if so, when? Based on a re-analysis of existing data that integrates concurrent think aloud and eye tracking protocols, the present study correlated participants' internal thinking models to the parameters of their eye movements when they planned solutions to an open-ended design problem in a real-world setting. We hypothesize that switching between ambient and focal attentional processing is useful when solvers encounter difficulty compelling them to shift their conceptual direction to adjust the solution path. Individuals may prefer different attentional strategies for information-seeking behavior, such as ambient-to-focal or focal-to-ambient. The observed increase in fixation durations and decrease in saccade amplitudes during the periods around shifts in conceptual direction lends support to the postulation of the ambient-to-focal processing; however, focal-to-ambient processing is not evident. Furthermore, our data demonstrate that the beginning of a shift in conceptual direction is observable in eye movement behavior with a significant prolongation of fixation. Our findings add to the conclusions drawn from laboratory settings by providing preliminary evidence for ambient and focal processing characteristics in real-world problem-solving.

4.
Am J Pathol ; 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38403164

RESUMO

Polycystic ovary syndrome (PCOS) is a highly heterogeneous and genetically complex endocrine disorder. Although the etiology remains mostly elusive, growing evidence suggested abnormal changes of DNA methylation correlate well with systemic and tissue-specific dysfunctions in PCOS. A dehydroepiandrosterone-induced PCOS-like mouse model was generated, which has a similar metabolic and reproductive phenotype as human patients with PCOS, and was used to experimentally validate the potential role of aberrant DNA methylation in PCOS in this study. Integrated DNA methylation and transcriptome analysis revealed the potential role of genomic DNA hypomethylation in transcription regulation of PCOS and identified several key candidate genes, including BMP4, Adcy7, Tnfaip3, and Fas, which were regulated by aberrant DNA hypomethylation. Moreover, i.p. injection of S-adenosylmethionine increased the overall DNA methylation level of PCOS-like mice and restored expression of the candidate genes to similar levels as the control, alleviating reproductive and metabolic abnormalities in PCOS-like mice. These findings provided direct evidence showing the importance of normal DNA methylation in epigenetic regulation of PCOS and potential targets for diagnosis and treatment of the disease.

5.
J Cell Mol Med ; 28(4): e18145, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38332517

RESUMO

Base editors are emerging as powerful tools to correct single-nucleotide variants and treat genetic diseases. In particular, the adenine base editors (ABEs) exhibit robust and accurate adenine-to-guanidine editing capacity and have entered the clinical stage for cardiovascular therapy. Despite the tremendous progress using ABEs to treat heart diseases, a standard technical route toward successful ABE-based therapy remains to be fully established. In this study, we harnessed adeno-associated virus (AAV) and a mouse model carrying the cardiomyopathy-causing Lmna c.1621C > T mutation to demonstrate key steps and concerns in designing a cardiac ABE experiment in vivo. We found DeepABE as a reliable deep-learning-based model to predict ABE editing outcomes in the heart. Screening of sgRNAs for a Cas9 mutant with relieved protospacer adjacent motif (PAM) allowed the reduction of bystander editing. The ABE editing efficiency can be significantly enhanced by modifying the TadA and Cas9 variants, which are core components of ABEs. The ABE systems can be delivered into the heart via either dual AAV or all-in-one AAV vectors. Together, this study showcased crucial technical considerations in designing an ABE system for the heart and pointed out major challenges in further improvement of this new technology for gene therapy.


Assuntos
Adenina , Edição de Genes , Animais , Camundongos , Terapia Genética , Mutação/genética , RNA Guia de Sistemas CRISPR-Cas
6.
Int J Biol Sci ; 20(3): 1042-1044, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38322120

RESUMO

Disulfidptosis occurs as a result of the accumulation of intracellular cystine followed by disulfide stress in actin cytoskeleton proteins due to a reduction of NADPH produced through the pentose phosphate pathway in cells with high expression of SLC7A11. It is a cell death caused by the redox imbalance resulting from the disruption of amino acid metabolism and glucose metabolism. The discovery of disulfidptosis has sparked immense enthusiasm, but there are numerous unresolved issues that need to be addressed. Solutions to these riddles will provide insights into the detailed mechanisms and the pathophysiological relevance of disulfidptosis and utilizing disulfidptosis as an actionable therapeutic target.


Assuntos
Dissulfetos , Proteínas dos Microfilamentos , Morte Celular , NADP
7.
Biomacromolecules ; 25(2): 1246-1261, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38305191

RESUMO

Preserving stable tooth-periodontal tissue integration is vital for maintaining alveolar bone stability under physiological conditions. However, tooth extraction compromises this integration and impedes socket healing. Therefore, it becomes crucial to provide early stage coverage of the socket to promote optimal healing. Drawing inspiration from the periodontium, we have developed a quaternized methacryloyl chitosan/dopamine-grafted oxidized sodium alginate hydrogel, termed the quaternized methacryloyl chitosan/dopamine-grafted oxidized sodium alginate hydrogel (QDL hydrogel). Through blue-light-induced cross-linking, the QDL hydrogel serves as a comprehensive wound dressing for socket healing. The QDL hydrogel exhibits remarkable efficacy in closing irregular tooth extraction wounds. Its favorable mechanical properties, flexible formability, and strong adhesion are achieved through modifications of chitosan and sodium alginate derived from biomass sources. Moreover, the QDL hydrogel demonstrates a superior hemostatic ability, facilitating swift blood clot formation. Additionally, the inherent antibacterial properties of the QDL hydrogel effectively inhibit oral microorganisms. Furthermore, the QDL hydrogel promotes angiogenesis, which facilitates the nutrient supply for subsequent tissue regeneration. Notably, the hydrogel accelerates socket healing by upregulating the expression of genes associated with wound healing. In conclusion, the periodontium-mimicking multifunctional hydrogel exhibits significant potential as a clinical tooth extraction wound dressing.


Assuntos
Quitosana , Hidrogéis , Hidrogéis/farmacologia , Biomassa , Quitosana/farmacologia , Dopamina , Periodonto , Alginatos/farmacologia , Antibacterianos/farmacologia
8.
J Gene Med ; 26(1): e3647, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38084655

RESUMO

Breast cancer is the most commonly diagnosed cancer among women. The primary treatment options include surgery, radiotherapy, chemotherapy, targeted therapy and hormone therapy. The effectiveness of breast cancer therapy varies depending on the stage and aggressiveness of the cancer, as well as individual factors. Advances in early detection and improved treatments have significantly increased survival rates for breast cancer patients. Nevertheless, specific subtypes of breast cancer, particularly triple-negative breast cancer, still lack effective treatment strategies. Thus, novel and effective therapeutic targets for breast cancer need to be explored. As substrates of protein synthesis, amino acids are important sources of energy and nutrition, only secondly to glucose. The rich supply of amino acids enables the tumor to maintain its proliferative competence through participation in energy generation, nucleoside synthesis and maintenance of cellular redox balance. Amino acids also play an important role in immune-suppressive microenvironment formation. Thus, the biological effects of amino acids may change unexpectedly in tumor-specific or oncogene-dependent manners. In recent years, there has been significant progress in the study of amino acid metabolism, particularly in their potential application as therapeutic targets in breast cancer. In this review, we provide an update on amino acid metabolism and discuss the therapeutic implications of amino acids in breast cancer.


Assuntos
Aminoácidos , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Imunoterapia , Neoplasias de Mama Triplo Negativas/metabolismo , Microambiente Tumoral
9.
Adv Healthc Mater ; : e2303293, 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38060135

RESUMO

Invasion of bacteria and continuous oozing of exudate are significant causes of interference with the healing of infected wounds. Therefore, an exudate-induced gelatinizable and near-infrared (NIR)-responsive nanofiber membrane composed of polyvinyl alcohol (PVA), carboxymethyl chitosan (CMC), and Fe-doped phosphomolybdic acid (Fe-PMA) with exceptional exudate absorption capacity and potent bactericidal efficacy is developed and denoted as the PVA-FP-CMC membrane. After absorbing exudate, the fiber membrane can transform into a hydrogel membrane, forming coordination bonds between the Fe-PMA and CMC. The unique exudate-induced gelation process imparts the membrane with high exudate absorption and retention capability, and the formed hydrogel also traps the bacteria that thrive in the exudate. Moreover, it is discovered for the first time that the Fe-PMA exhibits an enhanced photothermal conversion capability and photocatalytic activity compared to the PMA. Therefore, the presence of Fe-PMA provides the membrane with a photothermal and photodynamic therapeutic effect for killing bacteria. The PVA-FP-CMC membrane is proven with a liquid absorption ratio of 520.7%, a light-heat conversion efficiency of 41.9%, high-level generation of hydroxyl radical (•OH) and singlet oxygen (1 O2 ), and a bacterial killing ratio of 100% for S. aureus and 99.6% for E. coli. The treatment of infected wounds on the backs of rats further confirms the promotion of wound healing by the PVA-FP-CMC membrane with NIR irradiation. Overall, this novel functional dressing for the synergistic management of bacteria-infected wounds presents a promising therapeutic strategy for tissue repair and regeneration.

10.
bioRxiv ; 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38106146

RESUMO

Z-lines are core ultrastructural organizers of cardiomyocytes that modulate many facets of cardiac pathogenesis. Yet a comprehensive proteomic atlas of Z-line-associated components remain incomplete. Here, we established an adeno-associated virus (AAV)-delivered, cardiomyocyte-specific, proximity-labeling approach to characterize the Z-line proteome in vivo. We found palmdelphin (PALMD) as a novel Z-line-associated protein in both adult murine cardiomyocytes and human pluripotent stem cell-derived cardiomyocytes. Germline and cardiomyocyte-specific palmd knockout mice were grossly normal at baseline but exhibited compromised cardiac hypertrophy and aggravated cardiac injury upon long-term isoproterenol treatment. By contrast, cardiomyocyte-specific PALMD overexpression was sufficient to mitigate isoproterenol-induced cardiac injury. PALMD ablation perturbed transverse tubules (T-tubules) and their association with sarcoplasmic reticulum, which formed the Z-line-associated junctional membrane complex (JMC) essential for calcium handling and cardiac function. These phenotypes were associated with disrupted localization of T-tubule markers caveolin-3 (CAV3) and junctophilin-2 (JPH2) and the reduction of nexilin (NEXN) protein, a crucial Z-line-associated protein that is essential for both Z-line and JMC structures and functions. PALMD was found to interact with NEXN and enhance its protein stability while the Nexn mRNA level was not affected. Together, this study discovered PALMD as a potential target for myocardial protection and highlighted in vivo proximity proteomics as a powerful approach to nominate novel players regulating cardiac pathogenesis. Highlights: In vivo proximity proteomics uncover novel Z-line components that are undetected in in vitro proximity proteomics in cardiomyocytes.PALMD is a novel Z-line-associated protein that is dispensable for baseline cardiomyocyte function in vivo.PALMD mitigates cardiac dysfunction and myocardial injury after repeated isoproterenol insults.PALMD stabilizes NEXN, an essential Z-line-associated regulator of the junctional membrane complex and cardiac systolic function.

11.
Genes (Basel) ; 14(12)2023 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-38136994

RESUMO

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Although immunotherapy is effective for some patients, most find it difficult to benefit from it. This study aims to explore the impact of specific immune pathways and their regulated molecular mechanisms in TNBC. The gene expression data of breast cancer patients were obtained from the TCGA and METABRIC databases. Gene set variation analysis (GSVA) revealed specific upregulation or abnormal expression of immunodeficiency pathways in TNBC patients. Multi-omics data showed significant differential expression of Primary Immunodeficiency Genes (PIDGs) in TNBC patients, who are prone to genomic-level variations. Consensus clustering was used in two datasets to classify patients into two distinct molecular subtypes based on PIDGs expression patterns, with each displaying different biological features and immune landscapes. To further explore the prognostic characteristics of PIDGs-regulated molecules, we constructed a four-gene prognostic PIDG score model and a nomogram using least absolute shrinkage and selection operator (LASSO) regression analysis in combination with clinicopathological parameters. The PIDG score was closely associated with the immune therapy and drug sensitivity of TNBC patients, providing potential guidance for clinical treatment. Particularly noteworthy is the close association of this scoring with RNA modifications; patients with different scores also exhibited different mutation landscapes. This study offers new insights for the clinical treatment of TNBC and for identifying novel prognostic markers and therapeutic targets in TNBC.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/terapia , Prognóstico , Nomogramas , Regulação para Cima , RNA
12.
Pharmacol Res ; 198: 107017, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38006979

RESUMO

Sorafenib, a multi-targeted tyrosine kinase inhibitor, is a first-line treatment for advanced solid tumors, but it induces many adverse cardiovascular events, including myocardial infarction and heart failure. These cardiac defects can be mediated by alternative splicing of genes critical for heart function. Whether alternative splicing plays a role in sorafenib-induced cardiotoxicity remains unclear. Transcriptome of rat hearts or human cardiomyocytes treated with sorafenib was analyzed and validated to define alternatively spliced genes and their impact on cardiotoxicity. In rats, sorafenib caused severe cardiotoxicity with decreased left ventricular systolic pressure, elongated sarcomere, enlarged mitochondria and decreased ATP. This was associated with alternative splicing of hundreds of genes in the hearts, many of which were targets of a cardiac specific splicing factor, RBM20. Sorafenib inhibited RBM20 expression in both rat hearts and human cardiomyocytes. The splicing of RBM20's targets, SLC25A3 and FHOD3, was altered into fetal isoforms with decreased function. Upregulation of RBM20 during sorafenib treatment reversed the pathogenic splicing of SLC25A3 and FHOD3, and enhanced the phosphate transport into mitochondria by SLC25A3, ATP synthesis and cell survival.We envision this regulation may happen in many drug-induced cardiotoxicity, and represent a potential druggable pathway for mitigating sorafenib-induced cardiotoxicity.


Assuntos
Processamento Alternativo , Cardiotoxicidade , Ratos , Animais , Humanos , Sorafenibe , Cardiotoxicidade/genética , Cardiotoxicidade/metabolismo , Sarcômeros/metabolismo , Genes Mitocondriais , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Miócitos Cardíacos/metabolismo , Trifosfato de Adenosina/metabolismo , Forminas/genética , Forminas/metabolismo
13.
Circulation ; 148(23): 1887-1906, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-37905452

RESUMO

BACKGROUND: The importance of mitochondria in normal heart function are well recognized and recent studies have implicated changes in mitochondrial metabolism with some forms of heart disease. Previous studies demonstrated that knockdown of the mitochondrial ribosomal protein S5 (MRPS5) by small interfering RNA (siRNA) inhibits mitochondrial translation and thereby causes a mitonuclear protein imbalance. Therefore, we decided to examine the effects of MRPS5 loss and the role of these processes on cardiomyocyte proliferation. METHODS: We deleted a single allele of MRPS5 in mice and used left anterior descending coronary artery ligation surgery to induce myocardial damage in these animals. We examined cardiomyocyte proliferation and cardiac regeneration both in vivo and in vitro. Doxycycline treatment was used to inhibit protein translation. Heart function in mice was assessed by echocardiography. Quantitative real-time polymerase chain reaction and RNA sequencing were used to assess changes in transcription and chromatin immunoprecipitation (ChIP) and BioChIP were used to assess chromatin effects. Protein levels were assessed by Western blotting and cell proliferation or death by histology and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays. Adeno-associated virus was used to overexpress genes. The luciferase reporter assay was used to assess promoter activity. Mitochondrial oxygen consumption rate, ATP levels, and reactive oxygen species were also analyzed. RESULTS: We determined that deletion of a single allele of MRPS5 in mice results in elevated cardiomyocyte proliferation and cardiac regeneration; this observation correlates with improved cardiac function after induction of myocardial infarction. We identified ATF4 (activating transcription factor 4) as a key regulator of the mitochondrial stress response in cardiomyocytes from Mrps5+/- mice; furthermore, ATF4 regulates Knl1 (kinetochore scaffold 1) leading to an increase in cytokinesis during cardiomyocyte proliferation. The increased cardiomyocyte proliferation observed in Mrps5+/- mice was attenuated when one allele of Atf4 was deleted genetically (Mrps5+/-/Atf4+/-), resulting in the loss in the capacity for cardiac regeneration. Either MRPS5 inhibition (or as we also demonstrate, doxycycline treatment) activate a conserved regulatory mechanism that increases the proliferation of human induced pluripotent stem cell-derived cardiomyocytes. CONCLUSIONS: These data highlight a critical role for MRPS5/ATF4 in cardiomyocytes and an exciting new avenue of study for therapies to treat myocardial injury.


Assuntos
Células-Tronco Pluripotentes Induzidas , Miócitos Cardíacos , Humanos , Camundongos , Animais , Miócitos Cardíacos/metabolismo , Doxiciclina , Células Cultivadas , Células-Tronco Pluripotentes Induzidas/metabolismo , RNA Interferente Pequeno/metabolismo , Biossíntese de Proteínas , Proliferação de Células , Regeneração , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo
14.
Technol Health Care ; 2023 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37781823

RESUMO

BACKGROUND: Although cone beam computed tomography (CBCT) plays an important role in the diagnosis and treatment of oral diseases, its image segmentation method needs to be further improved, and there are still objections about the clinical application effect of general anesthesia (GA) on children's dental fear (CDF). OBJECTIVE: This study aimed to investigate the application value of CBCT based on intelligent computer segmentation model in oral diagnosis and treatment of children in the context of biomedical signals, and to analyze the alleviating effect of GA on CDF. METHODS: Based on the regional level set (CV) algorithm, the local binary fitting (LBF) model was introduced to optimize it, and the tooth CBCT image segmentation model CV-LBF was established to compare the segmentation accuracy (SA), maximum symmetric surface distance (MSSD), average symmetric surface distance (ASSD), over segmentation rate (OR), and under segmentation rate (UR) between these model and other algorithms. 82 children with CDF were divided into general anesthesia group (GAG) (n= 38) and controls (n= 44) according to the voluntary principle of their families. Children in GAG were treated with GA and controls with protective fixed intervention. Children's fear survey schedule-dental subscale (CFSS-DS) and Venham scores were counted before intervention in the two groups. CFSS-DS scores were recorded at 2 hours after intervention and after recovery in children in GAG. CFSS-DS and Venham scores were performed in all children 1 week after surgery. RESULTS: The results showed that the S⁢A value of CV-LBF algorithm was higher than that of region growing algorithm (P< 0.05). OR, UR, MSSD, and ASSD values of CV-LBF algorithm were evidently lower than those of other algorithms (P< 0.05). CFSS-DS scores were lower in GAG than in controls 2 hours after intervention and at return visits after 1 week of intervention (P< 0.001), and Venham scores were lower in GAG than in controls after intervention (P< 0.001). After intervention, the proportion of children with Venham grade 0, 1, 2, and 3 was obviously higher in GAG than in controls (P< 0.001), while the proportion of children with Venham grade 4 and 5 was clearly higher in controls than in GAG (P< 0.001). CONCLUSION: The results revealed that the computer intelligent segmentation model CV-LBF has potential application value in CBCT image segmentation of children's teeth, and GA can effectively alleviate anxiety of children with CDF and can be used as biomedical signals.

17.
Medicina (Kaunas) ; 59(6)2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37374362

RESUMO

Background: The maturation of cardiomyocytes is a rapidly evolving area of research within the field of cardiovascular medicine. Understanding the molecular mechanisms underlying cardiomyocyte maturation is essential to advancing our knowledge of the underlying causes of cardiovascular disease. Impaired maturation can lead to the development of cardiomyopathy, particularly dilated cardiomyopathy (DCM). Recent studies have confirmed the involvement of the ACTN2 and RYR2 genes in the maturation process, facilitating the functional maturation of the sarcomere and calcium handling. Defective sarcomere and electrophysiological maturation have been linked to severe forms of cardiomyopathy. This report presents a rare case of DCM with myocardial non-compaction, probably resulting from allelic collapse of both the ACTN2 and RYR2 genes. Case Presentation: The proband in this case was a four-year-old male child who presented with a recurrent and aggressive reduction in activity tolerance, decreased ingestion volume, and profuse sweating. Electrocardiography revealed significant ST-T segment depression (II, III, aVF V3-V6 ST segment depression >0.05 mV with inverted T-waves). Echocardiography showed an enlarged left ventricle and marked myocardial non-compaction. Cardiac magnetic resonance imaging revealed increased left ventricular trabeculae, an enlarged left ventricle, and a reduced ejection fraction. Whole exome sequencing revealed a restricted genomic depletion in the 1q43 region (chr1:236,686,454-237,833,988/Hg38), encompassing the coding genes ACTN2, MTR, and RYR2. The identified variant resulted in heterozygous variations in these three genes, with the ACTN2 g.236,686,454-236,764,631_del and RYR2 g.237,402,134-237,833,988_del variants being the dominant contributors to the induction of cardiomyopathy. The patient was finally diagnosed with DCM and left ventricular myocardial non-compaction. Conclusions: This study reports a rare case of DCM with myocardial non-compaction caused by the allelic collapse of the ACTN2 and RYR2 genes. This case provides the first human validation of the critical role of cardiomyocyte maturation in maintaining cardiac function and stability and confirms the key findings of previous experimental research conducted by our group. This report emphasizes the connection between genes involved in regulating the maturation of cardiomyocytes and the development of cardiomyopathy.


Assuntos
Cardiomiopatia Dilatada , Masculino , Criança , Humanos , Pré-Escolar , Cardiomiopatia Dilatada/patologia , Miócitos Cardíacos/patologia , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Miocárdio/patologia , Ventrículos do Coração
18.
Macromol Rapid Commun ; 44(15): e2300160, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37194471

RESUMO

Dielectric elastomers based on commercial acrylic dielectric elastomers (VHB adhesive films) are widely investigated for soft actuators due to their large electrically driven actuation strain and high work density. However, the VHB films require prestretching to overcome electromechanical instability, which adds fabrication complexity. In addition, their high viscoelasticity leads to a low response speed. Interpenetrated polymer networks (IPNs) are developed to lock the prestrain in VHB films, resulting in free-standing films that are capable of large-strain actuation. In this work, a prestrain-locked high-performance dielectric elastomer thin film (VHB-IPN-P) by introducing 1,6-hexanediol diacrylate to create an IPN in the VHB network and a plasticizer to enhance the actuation speed is reported. VHB-IPN-P based actuators exhibit stable actuation at 60% strain up to 10 Hz and reach a peak energy density of 102 J kg⁻1 . In addition, a hybrid process is also developed for the fabrication of multilayer stacks of VHB-IPN-P with strong inter-layer bonding and structural integrity. Four-layer stacks fabricated preserve the strain and energy density of single-layer VHB-IPN-P films but with linearly scaled force and work output.


Assuntos
Elastômeros , Polímeros , Elastômeros/química , Polímeros/química , Eletricidade
19.
RSC Adv ; 13(19): 12685-12694, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37101530

RESUMO

Two-dimensional (2D) materials are a very promising material family. The two-dimensional inorganic metal network called BlueP-Au network is rapidly attracting the attention of researchers due to its customizable architecture, adjustable chemical functions and electronic properties. Herein, manganese (Mn) was successfully doped on a BlueP-Au network for the first time, then the doping mechanism and electronic structure evolution was studied by in situ X-ray photoelectron spectroscopy (XPS) based on synchrotron radiation, X-ray absorption spectroscopy (XAS), Scanning Tunneling Microscopy (STM), Density functional theory (DFT), Low-energy electron diffraction (LEED), Angle resolved photoemission spectroscopy (ARPES), etc. Mn atoms tend to be stably adsorbed on two sites of the BlueP-Au network. It was the first observation that atoms can absorb on the two sites stably simultaneously. It is different from the previous adsorption models of BlueP-Au networks. The band structure was also successfully modulated, and overall down about 0.25 eV relative to the Fermi edge. It provided a new strategy for customizing the functional structure of the BlueP-Au network, which has provided new insights into monatomic catalysis, energy storage and nano electronic devices.

20.
Dev Cell ; 58(10): 898-914.e7, 2023 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-37071996

RESUMO

Cardiomyocyte differentiation continues throughout murine gestation and into the postnatal period, driven by temporally regulated expression changes in the transcriptome. The mechanisms that regulate these developmental changes remain incompletely defined. Here, we used cardiomyocyte-specific ChIP-seq of the activate enhancer marker P300 to identify 54,920 cardiomyocyte enhancers at seven stages of murine heart development. These data were matched to cardiomyocyte gene expression profiles at the same stages and to Hi-C and H3K27ac HiChIP chromatin conformation data at fetal, neonatal, and adult stages. Regions with dynamic P300 occupancy exhibited developmentally regulated enhancer activity, as measured by massively parallel reporter assays in cardiomyocytes in vivo, and identified key transcription factor-binding motifs. These dynamic enhancers interacted with temporal changes of the 3D genome architecture to specify developmentally regulated cardiomyocyte gene expressions. Our work provides a 3D genome-mediated enhancer activity landscape of murine cardiomyocyte development.


Assuntos
Elementos Facilitadores Genéticos , Miócitos Cardíacos , Animais , Camundongos , Cromatina , Regiões Promotoras Genéticas , Transcriptoma
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