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1.
Sci Rep ; 14(1): 12687, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830988

RESUMO

Underwater object detection based on side-scan sonar (SSS) suffers from a lack of finely annotated data. This study aims to avoid the laborious task of annotation by achieving unsupervised underwater object detection through domain-adaptive object detection (DAOD). In DAOD, there exists a conflict between feature transferability and discriminability, suppressing the detection performance. To address this challenge, a domain collaborative bridging detector (DCBD) including intra-domain consistency constraint (IDCC) and domain collaborative bridging (DCB), is proposed. On one hand, previous static domain labels in adversarial-based methods hinder the domain discriminator from discerning subtle intra-domain discrepancies, thus decreasing feature transferability. IDCC addresses this by introducing contrastive learning to refine intra-domain similarity. On the other hand, DAOD encourages the feature extractor to extract domain-invariant features, overlooking potential discriminative signals embedded within domain attributes. DCB addresses this by complementing domain-invariant features with domain-relevant information, thereby bolstering feature discriminability. The feasibility of DCBD is validated using unlabeled underwater shipwrecks as a case study. Experiments show that our method achieves accuracy comparable to fully supervised methods in unsupervised SSS detection (92.16% AP50 and 98.50% recall), and achieves 52.6% AP50 on the famous benchmark dataset Foggy Cityscapes, exceeding the original state-of-the-art by 4.5%.

3.
Nat Commun ; 15(1): 4586, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811589

RESUMO

Stark effect, the electric-field analogue of magnetic Zeeman effect, is one of the celebrated phenomena in modern physics and appealing for emergent applications in electronics, optoelectronics, as well as quantum technologies. While in condensed matter it has prospered only for excitons, whether other collective excitations can display Stark effect remains elusive. Here, we report the observation of phonon Stark effect in a two-dimensional quantum system of bilayer 2H-MoS2. The longitudinal acoustic phonon red-shifts linearly with applied electric fields and can be tuned over ~1 THz, evidencing giant Stark effect of phonons. Together with many-body ab initio calculations, we uncover that the observed phonon Stark effect originates fundamentally from the strong coupling between phonons and interlayer excitons (IXs). In addition, IX-mediated electro-phonon intensity modulation up to ~1200% is discovered for infrared-active phonon A2u. Our results unveil the exotic phonon Stark effect and effective phonon engineering by IX-mediated mechanism, promising for a plethora of exciting many-body physics and potential technological innovations.

4.
Front Neurol ; 15: 1357476, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38654739

RESUMO

Objectives: Spinal muscular atrophy (SMA) is an autosomal recessive disease that is one of the most common in childhood neuromuscular disorders. Our screenings are more meaningful programs in preventing birth defects, providing a significant resource for healthcare professionals, genetic counselors, and policymakers involved in designing strategies to prevent and manage SMA. Method: We screened 39,647 participants from 2020 to the present by quantitative real-time PCR, including 7,231 pre-pregnancy participants and 32,416 pregnancy participants, to detect the presence of SMN1 gene EX7 and EX8 deletion in the DNA samples provided by the subjects. To validate the accuracy of our findings, we also utilized the Multiplex Ligation-dependent Probe Amplification (MLPA) to confirm the reliability of screening results obtained by quantitative real-time PCR. Result: Among the 39,647 participants who were screened, 726 participants were the carriers of SMN1. The overall carrier rate was calculated to be 1.83% (95% confidence interval: 0.86-2.8%). After undergoing screening, a total of 592 pregnancy carriers were provided with genetic counseling and only 503 of their spouses (84.97, 95% confidence interval: 82.09-87.85%) voluntarily underwent SMA screening. Conclusion: This study provides crucial insights into the prevalence and distribution of SMA carriers among the female population. The identification of 726 asymptomatic carriers highlights the necessity of comprehensive screening programs to identify at-risk individuals and ensure appropriate interventions are in place to minimize the impact of SMA-related conditions.

5.
Exp Cell Res ; 438(2): 114056, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38663475

RESUMO

It was reported that within the head and neck cancer (HNC) cell line CAL21 the epithelial-mesenchymal transition (EMT) and cell proliferation were promoted by Urokinase-Type Plasminogen Activator (PLAU) proteinase through TNFRSF12A. Additionally, in this paper HNC cell lines refer to Fadu and Tu686. A novel PLAU-STAT3 axis was found to be involved in HNC cell line proliferation and metastasis. PLAU expression in HNC samples was upregulated, besides, the elevated expression of PLAU was linked to the lower overall survival (OS) and disease-free survival (DFS). Ectopic PLAU expression promoted cell proliferation and migration, while PLAU knockdown exhibited opposite results. RNA-seq data identified the JAK-STAT signaling pathway, confirmed by western blotting. A recovery assay using S3I-201, a selective inhibitor of signal transducer and activator of transcription 3 (STAT3), indicated that PLAU promoted HNC cell line progression via STAT3 signaling in vitro. The oncogenic role of PLAU in HNC tumor growth in vivo was confirmed using xenograft models. In summary, we identified the tumorigenic PLAU function in the HNC progress. PLAU may represent a potential prognostic biomarker of HNC and the PLAU-STAT3 pathway might be considered a therapeutic target of HNC.


Assuntos
Movimento Celular , Proliferação de Células , Neoplasias de Cabeça e Pescoço , Fator de Transcrição STAT3 , Transdução de Sinais , Ativador de Plasminogênio Tipo Uroquinase , Animais , Feminino , Humanos , Masculino , Camundongos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/genética , Camundongos Endogâmicos BALB C , Camundongos Nus , Receptores de Ativador de Plasminogênio Tipo Uroquinase , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/genética , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Genes (Basel) ; 15(4)2024 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-38674435

RESUMO

In gene quantification and expression analysis, issues with sample selection and processing can be serious, as they can easily introduce irrelevant variables and lead to ambiguous results. This study aims to investigate the extent and mechanism of the impact of sample selection and processing on ribonucleic acid (RNA) sequencing. RNA from PBMCs and blood samples was investigated in this study. The integrity of this RNA was measured under different storage times. All the samples underwent high-throughput sequencing for comprehensive evaluation. The differentially expressed genes and their potential functions were analyzed after the samples were placed at room temperature for 0h, 4h and 8h, and different feature changes in these samples were also revealed. The sequencing results showed that the differences in gene expression were higher with an increased storage time, while the total number of genes detected did not change significantly. There were five genes showing gradient patterns over different storage times, all of which were protein-coding genes that had not been mentioned in previous studies. The effect of different storage times on seemingly the same samples was analyzed in this present study. This research, therefore, provides a theoretical basis for the long-term consideration of whether sample processing should be adequately addressed.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , RNA , Análise de Sequência de RNA , Humanos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de RNA/métodos , RNA/genética , RNA/sangue , Leucócitos Mononucleares/metabolismo , Perfilação da Expressão Gênica/métodos , Masculino , Manejo de Espécimes/métodos , Coleta de Amostras Sanguíneas/métodos , Feminino
7.
Carbohydr Polym ; 333: 121951, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38494216

RESUMO

Passive daytime radiative cooling (PDRC) as a zero-energy-consumption cooling technique offers rich opportunities in reducing global energy consumption and mitigating CO2 emissions. Developing high-performance PDRC coolers with practical applicability based on sustainable materials is of great significance, but remains a big challenge. Herein, polyvinyl alcohol (PVA) and esterified cellulose (EC) extracted from sawdust were used as raw materials to construct foams by using a dual-crosslinking assisted-unidirectional freeze-drying strategy followed by hydrophobic surface modification. The resultant PVA/EC (PEC) foams with ideal hierarchical macropore structure displayed various excellent features, such as low thermal conductivity (26.2 mW·m-1·K-1), high solar reflectance (95 %) and infrared emissivity (0.97), superhydrophobicity as well as high mechanical properties. The features allowed the PEC foams to be used as radiative coolers with excellent PDRC performance and thermal insulating materials. A maximum sub-ambient temperature drops of 10.2 °C could be achieved for optimal PEC foams. Building simulations indicated that PEC foams could save 55.8 % of the energy consumption for Xi'an. Our work would give inspiration for designing various types of PDRC coolers, including but certainly not limited to foams-based radiative coolers.

8.
RSC Adv ; 14(10): 7215-7220, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38419680

RESUMO

Polymer electrodes are drawing widespread attention to the future generation of lithium-ion battery materials. However, weak electrochemical performance of organic anode materials still exists, such as low capacity, low rate performance, and low cyclability. Herein, we successfully constructed a donor-acceptor thiophene-based polymer (PBT-1) by introducing an organoboron unit. The charge delocalization and lower LUMO energy level due to the unique structure enabled good performance in electrochemical tests with a reversible capacity of 405 mA h g-1 at 0.5 A g-1 and over 10 000 cycles at 1 A g-1. Moreover, electron paramagnetic resonance (EPR) spectra revealed that the unique stable spin system in the PBT-1 backbone during cycling provides a fundamental explanation for the highly stable electrochemical performance. This work offers a reliable reference for the design of organic anode materials and expands the potential application directions of organoboron chemistry.

9.
Anal Chim Acta ; 1296: 342331, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38401939

RESUMO

BACKGROUND: The cell-free RNA (cf-RNA) of spent embryo medium (SEM) has aroused a concern of academic and clinical researchers for its potential use in non-invasive embryo screening. However, comprehensive characterization of cf-RNA from SEM still presents significant technical challenges, primarily due to the limited volume of SEM. Hence, there is urgently need to a small input liquid volume and ultralow amount of cf-RNA library preparation method to unbiased cf-RNA sequencing from SEM. (75) RESULT: Here, we report a high sensitivity agarose amplification-based cf-RNA sequencing method (SEM-Acf) for human preimplantation SEM cf-RNA analysis. It is a cf-RNA sequencing library preparation method by adding agarose amplification. The agarose amplification sensitivity (0.005 pg) and efficiency (105.35 %) were increased than that of without agarose addition (0.45 pg and 96.06 %) by âˆ¼ 90 fold and 9.29 %, respectively. Compared with SMART sequencing (SMART-seq), the correlation of gene expression was stronger in different SEM samples by using SEM-Acf. The cf-RNA number of detected and coverage uniformity of 3' end were significantly increased. The proportion of 5' end adenine, alternative splicing events and short fragments (<400 bp) were increased. It is also found that 4-mer end motifs of cf-RNA fragments was significantly differences between different embryonic stage by day3 spent cleavage medium and day5/6 spent blastocyst medium. (141) SIGNIFICANCE: This study established an efficient SEM amplification and library preparation method. Additionally, we successfully described the characterizations of SEM cf-RNA in preimplantation embryo using SEM-Acf, including expression features and fragment lengths. SEM-Acf facilitates the exploration of cf-RNA as a noninvasive embryo screening biomarker, and opens up potential clinical utilities of small input liquid volume and ultralow amount cf-RNA sequencing. (59).


Assuntos
Ácidos Nucleicos Livres , Diagnóstico Pré-Implantação , Gravidez , Feminino , Humanos , Diagnóstico Pré-Implantação/métodos , Sefarose , Blastocisto/metabolismo , RNA/genética , RNA/metabolismo
10.
Mol Ther ; 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38414241

RESUMO

In chronic liver diseases, hepatic stellate cells (HSCs) are induced to form the myofibroblasts responsible for scar formation, leading to liver fibrosis and cirrhosis. Here, single-cell RNA sequencing with in vivo lineage tracing in nonalcoholic steatohepatitis (NASH) model mice reveals a subpopulation of HSCs transitioning back to a state resembling their developmental precursors, mesothelial cells (MCs), after liver injury. These damage-associated intermediates between HSCs and MCs (DIHMs) can be traced with a dual recombinase system by labeling Krt19-expressing cells within prelabeled Pdgfrb+ HSCs, and DIHMs highly express inflammation- and fibrosis-associated genes. Cre and Dre-inducible depletion of DIHMs by administering diphtheria toxin reduces liver fibrosis and alleviates liver damage in NASH model mice. Importantly, knockdown of Osr1, a zinc finger transcription factor of the OSR gene family, can block DIHM induction in vitro. Conditional knockout Osr1 in Pdgfrb-expressing mesenchymal cells in NASH model mice can reduce liver fibrosis in vivo. Our study collectively uncovers an injury-induced developmental reversion process wherein HSCs undergo what we call a mesenchymal-to-mesothelial transition, which can be targeted to develop interventions to treat chronic liver diseases.

11.
Phys Chem Chem Phys ; 26(6): 5141-5146, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38259223

RESUMO

The tunable structure and other properties of organic materials suggest that they can potentially solve the shortcomings of traditional anodes such as graphite. We successfully introduced an organoboron unit into the thiophene-based polymer PBT-2 to construct a donor-acceptor polymer anode. The charge delocalization and LUMO energy level resulting from the unique structure of this material enabled good redox activity and a very stable electrochemical performance in electrochemical tests, with a reversible capacity of 262 mA h g-1 at 0.5 A g-1 and >10 000 cycles at 1 A g-1 with a decay of 0.056‰ per cycle. Accordingly, targeted structural design to overcome the shortcomings of active units such as thiophene can effectively regulate their electrochemical performance, providing a solution for the development of high-performance anode materials for use in lithium ion batteries.

12.
J Cardiovasc Pharmacol ; 83(1): 116-125, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37755435

RESUMO

ABSTRACT: Sepsis-induced cardiac dysfunction represents a major cause of high mortality in intensive care units with limited therapeutic options. Golgi protein 73 (GP73) has been implicated in various diseases. However, the role of GP73 in lipopolysaccharide (LPS)-induced cardiac dysfunction is unclear. In this study, we established a sepsis-induced cardiac dysfunction model by LPS administration in wild-type and GP73 knockout ( GP73-/- ) mice. We found that GP73 was increased in LPS-treated mouse hearts and LPS-cultured neonatal rat cardiomyocytes (NRCMs). Knockout of GP73 alleviated myocardial injury and improved cardiac dysfunction. Moreover, depletion of GP73 in NRCMs relieved LPS-induced cardiomyocyte apoptosis and activated myocardial autophagy. Therefore, GP73 is a negative regulator in LPS-induced cardiac dysfunction by promoting cardiomyocyte apoptosis and inhibiting cardiomyocyte autophagy.


Assuntos
Cardiopatias , Sepse , Ratos , Camundongos , Animais , Lipopolissacarídeos/toxicidade , Camundongos Knockout , Cardiopatias/induzido quimicamente , Cardiopatias/genética , Apoptose , Autofagia , Sepse/metabolismo
13.
ACS Appl Mater Interfaces ; 16(1): 1451-1460, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38112199

RESUMO

Hydrogels with excellent mechanical flexibility are widely used in flexible electronic devices. However, it is difficult to meet further applications of high-power integrated flexible electronics as a result of their low thermal conductivity. Herein, highly thermally conductive composite hydrogels with a solid-liquid interpenetrating thermal conductivity network are constructed by aromatic polyamide nanofibers (ANF) and fluorinated graphene (FG) reinforced poly(vinyl alcohol) (PVA) and cross-linked by tannic acid (TA) solution immersion to obtain a hydrogel with a double cross-linked network. The PVA-ANF-FG3T-11.1% composite hydrogel exhibits good mechanical properties compared to PVA-ANFT, with a tensile modulus of up to 0.89 MPa, a tensile strength of up to 1.23 MPa, and an energy of rupture of up to 3.45 MJ cm-3, which is mainly attributed to the multihydrogen bonding interactions in the composite hydrogel. In addition, the friction coefficient of the PVA-ANF-FG3T-11.1% composite hydrogel is 0.178, making it suitable for use in high-friction coefficient applications. The thermal conductivity of the PVA-ANF-FG3T-11.1% composite hydrogel is 1.42 W m-1 K-1, which is attributed to the synergistic effect of the solid thermal conductivity network and the liquid convection network, resulting in a high thermal conductivity of the composite hydrogel. The high thermal conductivity of the PVA-ANF-FG3T-11.1% composite hydrogel shows great potential for flexible wearable electronics and cooling paste applications.

14.
iScience ; 26(12): 108532, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38144457

RESUMO

In prolonged liver injury, hepatocytes undergo partial identity loss with decreased regenerative capacity, resulting in liver failure. Here, we identified a five compound (5C) combination that could restore hepatocyte identity and reverse the damage-associated phenotype (e.g., dysfunction, senescence, epithelial to mesenchymal transition, growth arrest, and pro-inflammatory gene expression) in damaged hepatocytes (dHeps) from CCl4-induced mice with chronic liver injury, resembling a direct chemical reprogramming approach. Systemic administration of 5C in mice with chronic liver injury promoted hepatocyte regeneration, improved liver function, and ameliorated liver fibrosis. The hepatocyte-associated transcriptional networks were reestablished with chemical treatment as revealed by motif analysis of ATAC-seq, and a hepatocyte-enriched transcription factor, Foxa2, was found to be essential for hepatocyte revitalization. Overall, our findings indicate that the phenotype and transcriptional program of dHeps can be reprogrammed to generate functional and regenerative hepatocytes by using only small molecules, as an alternative approach to liver repair and regeneration.

15.
Brief Bioinform ; 24(6)2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37930031

RESUMO

Reconstructing the full-length sequence of extrachromosomal circular DNA (eccDNA) from short sequencing reads has proved challenging given the similarity of eccDNAs and their corresponding linear DNAs. Previous sequencing methods were unable to achieve high-throughput detection of full-length eccDNAs. Herein, a novel algorithm was developed, called Full-Length eccDNA Detection (FLED), to reconstruct the sequence of eccDNAs based on the strategy that combined rolling circle amplification and nanopore long-reads sequencing technology. Seven human epithelial and cancer cell line samples were analyzed by FLED and over 5000 full-length eccDNAs were identified per sample. The structures of identified eccDNAs were validated by both Polymerase Chain Reaction (PCR) and Sanger sequencing. Compared to other published nanopore-based eccDNA detectors, FLED exhibited higher sensitivity. In cancer cell lines, the genes overlapped with eccDNA regions were enriched in cancer-related pathways and cis-regulatory elements can be predicted in the upstream or downstream of intact genes on eccDNA molecules, and the expressions of these cancer-related genes were dysregulated in tumor cell lines, indicating the regulatory potency of eccDNAs in biological processes. The proposed method takes advantage of nanopore long reads and enables unbiased reconstruction of full-length eccDNA sequences. FLED is implemented using Python3 which is freely available on GitHub (https://github.com/FuyuLi/FLED).


Assuntos
DNA Circular , DNA , Humanos , DNA/genética , Reação em Cadeia da Polimerase , Linhagem Celular
16.
J Gastrointest Oncol ; 14(5): 2006-2017, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37969842

RESUMO

Background: Esophageal cancer (EC) is a highly lethal malignancy with a grim prognosis and high mortality rates, primarily treated through surgery and radiotherapy. Herbal remedies are emerging as complementary approaches in cancer therapy. Here, we explore the potential therapeutic benefits of Chinese medicine raw Pinellia ternata (RP) in EC using web-based pharmacological methods and cellular experiments. Methods: The chemical components of RP were obtained by data mining via searches of the systematic pharmacology database, analysis platform, and literature on traditional Chinese medicine (TCM). The properties of the main components of RP were calculated using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The potential targets of the components were mined and collected through multiple databases, and the relevant potential targets of efficacy were imported into Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database to obtain protein interactions. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway enrichment analysis of the potential targets were performed through Metascape. A target-pathway network was established using Cytoscape, and topological analysis was performed on the network so as to obtain the relevant targets and pathways of RP in the treatment of EC. The inhibitory effect of RP on human EC cells was verified by cell experiments. Results: Thirteen bioactive components of RP were screened, 87 related targets were obtained by construction, and 68 co-targets were obtained after taking intersection with EC related genes. The results of the protein-protein interaction (PPI) network analysis of the targets showed that the pharmacodynamic targets of hemicellulose might be closely related to the signaling pathways such as PI3K-Akt, FOS/JUN, and HIF-1. Meanwhile, GO and KEGG enrichment analysis showed that PI3K-Akt was also significantly enriched. The in vitro cellular experiments further indicated that raw hemicrania could inhibit EC through the PI3K-Akt signaling pathway. Conclusions: The pharmacodynamic mechanism of RP in the treatment of esophageal carcinoma was preliminarily revealed, which provided ideas and the basis for further experimental study of RP in the treatment of esophageal carcinoma.

17.
Analyst ; 149(1): 148-160, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-37987554

RESUMO

Extrachromosomal circular DNA (eccDNA) was discovered several decades ago, but little is known about its function. With the development of sequencing technology, several library preparation methods have been developed to elucidate the biogenesis and function of eccDNA. However, different treatment methods have certain biases that can lead to their erroneous interpretation. To address these issues, we compared the performance of different library preparation methods. Our investigation revealed that the utilization of rolling-circle amplification (RCA) and restriction enzyme linearization of mitochondrial DNA (mtDNA) significantly enhanced the efficiency of enriching extrachromosomal circular DNA (eccDNA). However, it also introduced certain biases, such as an unclear peak in ∼160-200 bp periodicity and the absence of a typical motif pattern. Furthermore, given that RCA can lead to a disproportionate change in copy numbers, eccDNA quantification using split and discordant reads should be avoided. Analysis of the genomic and elements distribution of the overall population of eccDNA molecules revealed a high correlation between the replicates, and provided a possible stability signature for eccDNA, which could potentially reflect different cell lines or cell states. However, we found only a few eccDNA with identical junction sites in each replicate, showing a high degree of heterogeneity of eccDNA. The emergence of different motif patterns flanking junctional sites in eccDNAs of varying sizes suggests the involvement of multiple potential mechanisms in eccDNA generation. This study comprehensively compares and discusses various essential approaches for eccDNA library preparation, offering valuable insights and practical advice to researchers involved in characterizing eccDNA.


Assuntos
DNA Circular , DNA , DNA Circular/genética , DNA/genética , Cromossomos , Genoma , Biblioteca Gênica
18.
Int Immunopharmacol ; 125(Pt A): 111074, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37879229

RESUMO

Sepsis-induced myocardial dysfunction (SIMD) is the main cause of mortality in sepsis. In this study, we identified Polo-like kinase 1 (Plk-1) is a promoter of SIMD. Plk-1 expression was increased in lipopolysaccharide (LPS)-treated mouse hearts and neonatal rat cardiomyocytes (NRCMs). Inhibition of Plk-1 either by heterozygous deletion of Plk-1 or Plk-1 inhibitor BI 6727 alleviated LPS-induced myocardial injury, inflammation, cardiac dysfunction, and thereby improved the survival of LPS-treated mice. Plk-1 was identified as a kinase of inhibitor of kappa B kinase alpha (IKKα). Plk-1 inhibition impeded NF-κB signal pathway activation in LPS-treated mouse hearts and NRCMs. Augmented Plk-1 is thus essential for the development of SIMD and is a druggable target for SIMD.


Assuntos
Cardiomiopatias , Sepse , Ratos , Camundongos , Animais , Miocárdio/metabolismo , NF-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , Cardiomiopatias/etiologia , Cardiomiopatias/metabolismo , Sepse/metabolismo , Quinase 1 Polo-Like
19.
Nat Commun ; 14(1): 5327, 2023 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-37723137

RESUMO

Little is known about circular RNAs (circRNAs) in specific brain cells and human neuropsychiatric disease. Here, we systematically identify over 11,039 circRNAs expressed in vulnerable dopamine and pyramidal neurons laser-captured from 190 human brains and non-neuronal cells using ultra-deep, total RNA sequencing. 1526 and 3308 circRNAs are custom-tailored to the cell identity of dopamine and pyramidal neurons and enriched in synapse pathways. 29% of Parkinson's and 12% of Alzheimer's disease-associated genes produced validated circRNAs. circDNAJC6, which is transcribed from a juvenile-onset Parkinson's gene, is already dysregulated during prodromal, onset stages of common Parkinson's disease neuropathology. Globally, addiction-associated genes preferentially produce circRNAs in dopamine neurons, autism-associated genes in pyramidal neurons, and cancers in non-neuronal cells. This study shows that circular RNAs in the human brain are tailored to neuron identity and implicate circRNA-regulated synaptic specialization in neuropsychiatric diseases.


Assuntos
Doença de Parkinson , RNA Circular , Humanos , RNA Circular/genética , Dopamina , Encéfalo , Neurônios Dopaminérgicos
20.
Comput Struct Biotechnol J ; 21: 4432-4445, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37731598

RESUMO

Highly transcribed noncoding elements (HTNEs) are critical noncoding elements with high levels of transcriptional capacity in particular cohorts involved in multiple cellular biological processes. Investigation of HTNEs with persistent aberrant expression in abnormal tissues could be of benefit in exploring their roles in disease occurrence and progression. Breast cancer is a highly heterogeneous disease for which early screening and prognosis are exceedingly crucial. In this study, we developed a HTNE identification framework to systematically investigate HTNE landscapes in breast cancer patients and identified over ten thousand HTNEs. The robustness and rationality of our framework were demonstrated via public datasets. We revealed that HTNEs had significant chromatin characteristics of enhancers and long noncoding RNAs (lncRNAs) and were significantly enriched with RNA-binding proteins as well as targeted by miRNAs. Further, HTNE-associated genes were significantly overexpressed and exhibited strong correlations with breast cancer. Ultimately, we explored the subtype-specific transcriptional processes associated with HTNEs and uncovered the HTNE signatures that could classify breast cancer subtypes based on the properties of hormone receptors. Our results highlight that the identified HTNEs as well as their associated genes play crucial roles in breast cancer progression and correlate with subtype-specific transcriptional processes of breast cancer.

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