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1.
BMC Plant Biol ; 24(1): 633, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38971752

RESUMEN

BACKGROUND: Alfalfa (Medicago sativa L.) experiences many negative effects under salinity stress, which may be mediated by recurrent selection. Salt-tolerant alfalfa may display unique adaptations in association with rhizobium under salt stress. RESULTS: To elucidate inoculation effects on salt-tolerant alfalfa under salt stress, this study leveraged a salt-tolerant alfalfa population selected through two cycles of recurrent selection under high salt stress. After experiencing 120-day salt stress, mRNA was extracted from 8 random genotypes either grown in 0 or 8 dS/m salt stress with or without inoculation by Ensifer meliloti. Results showed 320 and 176 differentially expressed genes (DEGs) modulated in response to salinity stress or inoculation x salinity stress, respectively. Notable results in plants under 8 dS/m stress included upregulation of a key gene involved in the Target of Rapamycin (TOR) signaling pathway with a concomitant decrease in expression of the SNrK pathway. Inoculation of salt-stressed plants stimulated increased transcription of a sulfate-uptake gene as well as upregulation of the Lysine-27-trimethyltransferase (EZH2), Histone 3 (H3), and argonaute (AGO, a component of miRISC silencing complexes) genes related to epigenetic and post-transcriptional gene control. CONCLUSIONS: Salt-tolerant alfalfa may benefit from improved activity of TOR and decreased activity of SNrK1 in salt stress, while inoculation by rhizobiumstimulates production of sulfate uptake- and other unique genes.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Medicago sativa , Tolerancia a la Sal , Medicago sativa/genética , Medicago sativa/fisiología , Medicago sativa/microbiología , Tolerancia a la Sal/genética , Estrés Salino/genética , Salinidad , Sinorhizobium meliloti/fisiología , Plantas Tolerantes a la Sal/genética , Plantas Tolerantes a la Sal/fisiología
2.
3.
N Biotechnol ; 83: 56-65, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38945523

RESUMEN

Chinese hamster ovary (CHO) cells represent the most preferential host cell system for therapeutic monoclonal antibody (mAb) production. Enhancing mAb production in CHO cells can be achieved by adding chemical compounds that regulate the cell cycle and cell survival pathways. This study investigated the impact of ectoine supplementation on mAb production in CHO cells. The results showed that adding ectoine at a concentration of 100 mM on the 3rd day of cultivation improved mAb production by improving cell viability and extending the culture duration. RNA sequencing analysis revealed differentially expressed genes associated with cell cycle regulation, cell proliferation, and cellular homeostasis, in particular promotion of cell cycle arrest, which was then confirmed by flow cytometry analysis. Ectoine-treated CHO cells exhibited an increase in the number of cells in the G0/G1 phase. In addition, the cell diameter was also increased. These findings support the hypothesis that ectoine enhances mAb production in CHO cells through mechanisms involving cell cycle arrest and cellular homeostasis. Overall, this study highlights the potential of ectoine as a promising supplementation strategy to enhance mAb production not only in CHO cells but also in other cell lines.

4.
Clin Exp Pharmacol Physiol ; 51(8): e13872, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38886134

RESUMEN

Atherosclerosis, a lipid-driven chronic inflammatory disorder, is a significant global health concern associated with high rates of morbidity and mortality, imposing a substantial societal burden. The purpose of this study is to investigate the possible molecular mechanisms of atherosclerosis and identify potential therapeutic targets. We conducted an integrated bioinformatics analysis using data from peripheral blood mononuclear cell and TISSUE databases obtained from the Gene Expression Omnibus, to identify key genes associated with the progression of atherosclerosis. Here, IRF8 was found to be a key gene in atherosclerosis patients. Silencing IRF8 with small interfering RNA reduced inflammation in endothelial cells. This suggests IRF8 is a crucial biomarker for immune infiltration in atherosclerosis advance.


Asunto(s)
Aterosclerosis , Biomarcadores , Biología Computacional , Factores Reguladores del Interferón , Humanos , Aterosclerosis/genética , Aterosclerosis/inmunología , Biología Computacional/métodos , Factores Reguladores del Interferón/genética , Biomarcadores/metabolismo , Inflamación/genética , Inflamación/inmunología
5.
Entropy (Basel) ; 26(6)2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38920463

RESUMEN

Modern concepts in irreversible thermodynamics are applied to system transformation and degradation analyses. Phenomenological entropy generation (PEG) theorem is combined with the Degradation-Entropy Generation (DEG) theorem for instantaneous multi-disciplinary, multi-scale, multi-component system characterization. A transformation-PEG theorem and space materialize with system and process defining elements and dimensions. The near-100% accurate, consistent results and features in recent publications demonstrating and applying the new TPEG methods to frictional wear, grease aging, electrochemical power system cycling-including lithium-ion battery thermal runaway-metal fatigue loading and pump flow are collated herein, demonstrating the practicality of the new and universal PEG theorem and the predictive power of models that combine and utilize both theorems. The methodology is useful for design, analysis, prognostics, diagnostics, maintenance and optimization.

6.
Genes Genomics ; 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38922499

RESUMEN

BACKGROUND: The genes involved in cephalopod development and their association with hatching and survival during early life stages have been extensively studied. However, few studies have investigated the paralarvae transcriptome of the East Asian common octopus (Octopus sinen sis). OBJECTIVE: This study aimed to identify the genes related to embryonic development and hatching in O. sinensis using RNA sequencing (RNA-seq) and verify the genes most relevant to different embryonic stages. METHODS: RNA samples from hatched and 25 days post-hatching (dph) O. sinensis paralarvae were used to construct cDNA libraries. Clean reads from individual samples were aligned to the reference O. sinensis database to identify the differentially expressed genes (DEGs) between the 0- and 25-dph paralarvae libraries. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to supplement the RNA-seq data for embryogenic developmental stages. RESULTS: A total of 12,597 transcripts were annotated and 5,468 DEGs were identified between the 0- and 25-dph O. sinensis paralarvae, including 2,715 upregulated and 2,753 downregulated transcripts in the 25-dph paralarvae. Several key DEGs were related to transmembrane transport, lipid biosynthesis, monooxygenase activity, lipid transport, neuropeptide signaling, transcription regulation, and protein-cysteine S-palmitoyltransferase activity during the post-hatching development of O. sinensis paralarvae. RT-qPCR analysis further revealed that SLC5A3A, ABCC12, and NPC1 transcripts in 20 and/or 30 days post-fertilization (dpf) embryos were significantly higher (p < 0.05) than those in 10-dpf embryos. CONCLUSION: Transcriptome profiles provide molecular targets to understand the embryonic development, hatching, and survival of O. sinensis paralarvae, and enhance octopus production.

7.
Curr Vasc Pharmacol ; 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38910465

RESUMEN

BACKGROUND: Alzheimer's disease (AD) plays a prominent role as the most common form of dementia. Moreover, the traditional mechanism of AD does not explain the microvascular damage observed in about 25-30 years between the onset of AD, which results in late application treatment that inhibits or delays neurodegeneration. OBJECTIVE: Our objective was to identify differentially expressed genes in human brain samples associated with vascular disruption in AD. METHODS: We analyzed 1633 post-mortem brain samples in the GEO to database and, after applying clinical and bioinformatic exclusion criteria, worked with 581 prefrontal and frontal samples. All datasets were analyzed using GEO2R from NCBI. We identified common genes using the Venny tool, and their metabolic relevance associated with AD and the vascular system was analyzed using MetaboAnalyst tools. RESULTS: Our bioinformatic analysis identified PRKCB, MAP2K2, ADCY1, GNA11, GNAQ, PRKACB, KCNMB4, CALD1, and GNAS as potentially involved in AD pathogenesis. These genes are associated with signal transductions, cell death signaling, and cytoskeleton, suggesting potential modulation of cellular physiology, including endoplasmic reticulum and mitochondrial activity. CONCLUSION: This study generates hypotheses regarding the roles of novel genes over critical pathways relevant to AD and its relation with vascular dysfunction. These findings suggest potential new targets for further investigation into the pathogenesis of dementia and AD.

8.
Genes Genomics ; 46(7): 743-749, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38733519

RESUMEN

BACKGROUND: Exposure to particulate matter (PM) and house dust mite (HDM) can change the expression patterns of inflammation-, oxidative stress-, and cell death-related genes. We investigated the changes in gene expression patterns owing to PM exposure. OBJECTIVE: This study examined the changes in gene expression patterns following PM exposure. METHODS: We searched for differentially expressed genes (DEGs) following PM exposure using five cell line-based RNA-seq or microarray datasets and six human-derived datasets. The enrichment terms of the DEGs were assessed. RESULTS: DEG analysis yielded two gene sets. Thus, enrichment analysis was performed for each gene set, and the enrichment terms related to respiratory diseases were presented. The intersection of six human-derived datasets and two gene sets was obtained, and the expression patterns following PM exposure were observed. CONCLUSIONS: Two gene sets were obtained for cells treated with PM and their expression patterns were presented following verification in human-derived cells. Our findings suggest that exposure to PM2.5 and HDM may reveal changes in genes that are associated with diseases, such as allergies, highlighting the importance of mitigating PM2.5 and HDM exposure for disease prevention.


Asunto(s)
Material Particulado , Material Particulado/efectos adversos , Material Particulado/toxicidad , Humanos , Pyroglyphidae , Transcriptoma , Animales , Línea Celular , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica/efectos de los fármacos
9.
ACS Appl Mater Interfaces ; 16(20): 26915-26921, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38717847

RESUMEN

Multifunctional integration in a single device has always been a hot research topic, especially for contradictory phenomena, one of which is the coexistence of ferroelectricity and metallicity. The complex oxide heterostructures, as symmetric breaking systems, provide a great possibility to incorporate different properties. Moreover, finding a series of oxide heterostructures to achieve this goal remains as a challenge. Here, taking the advantage of different physical phenomena, we use H2 plasma to pretreat the SrTiO3 (STO) substrate and then fabricate HfO2/STO heterostructures with it. The novel, well-repeatable metallic two-dimensional electron gas (2DEG) is directly obtained at the heterointerfaces without any further complex procedures, while the obvious ferroelectric-like behavior and Rashba spin-orbit coupling are also observed. The understanding of the mechanism, as well as the modified facile preparation procedure, would be meaningful for further development of ferroelectric metal in complex oxide heterostructures.

10.
BMC Psychiatry ; 24(1): 369, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38755543

RESUMEN

BACKGROUND: Patients with major depressive disorder (MDD) have an increased risk of breast cancer (BC), implying that these two diseases share similar pathological mechanisms. This study aimed to identify the key pathogenic genes that lead to the occurrence of both triple-negative breast cancer (TNBC) and MDD. METHODS: Public datasets GSE65194 and GSE98793 were analyzed to identify differentially expressed genes (DEGs) shared by both datasets. A protein-protein interaction (PPI) network was constructed using STRING and Cytoscape to identify key PPI genes using cytoHubba. Hub DEGs were obtained from the intersection of hub genes from a PPI network with genes in the disease associated modules of the Weighed Gene Co-expression Network Analysis (WGCNA). Independent datasets (TCGA and GSE76826) and RT-qPCR validated hub gene expression. RESULTS: A total of 113 overlapping DEGs were identified between TNBC and MDD. The PPI network was constructed, and 35 hub DEGs were identified. Through WGCNA, the blue, brown, and turquoise modules were recognized as highly correlated with TNBC, while the brown, turquoise, and yellow modules were similarly correlated with MDD. Notably, G3BP1, MAF, NCEH1, and TMEM45A emerged as hub DEGs as they appeared both in modules and PPI hub DEGs. Within the GSE65194 and GSE98793 datasets, G3BP1 and MAF exhibited a significant downregulation in TNBC and MDD groups compared to the control, whereas NCEH1 and TMEM45A demonstrated a significant upregulation. These findings were further substantiated by TCGA and GSE76826, as well as through RT-qPCR validation. CONCLUSIONS: This study identified G3BP1, MAF, NCEH1 and TMEM45A as key pathological genes in both TNBC and MDD.


Asunto(s)
Trastorno Depresivo Mayor , Mapas de Interacción de Proteínas , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/genética , Trastorno Depresivo Mayor/genética , Femenino , Mapas de Interacción de Proteínas/genética , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Bases de Datos Genéticas , Transcriptoma/genética
11.
Front Plant Sci ; 15: 1387427, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38817928

RESUMEN

Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is one of the most destructive fungal diseases threatening global wheat production. Exploring powdery mildew resistance (Pm) gene(s) and dissecting the molecular mechanism of the host resistance are critical to effectively and reasonably control this disease. Durum wheat (Triticum turgidum L. var. durumDesf.) is an important gene donor for wheat improvement against powdery mildew. In this study, a resistant durum wheat accession W762 was used to investigate its potential resistance component(s) and profile its expression pattern in responding to Bgt invasion using bulked segregant RNA-Seq (BSR-Seq) and further qRT-PCR verification. Genetic analysis showed that the powdery mildew resistance in W762 did not meet monogenic inheritance and complex genetic model might exist within the population of W762 × Langdon (susceptible durum wheat). After BSR-Seq, 6,196 consistently different single nucleotide polymorphisms (SNPs) were called between resistant and susceptible parents and bulks, and among them, 763 SNPs were assigned to the chromosome arm 7B. Subsequently, 3,653 differentially expressed genes (DEGs) between resistant and susceptible parents and bulks were annotated and analyzed by Gene Ontology (GO), Cluster of Orthologous Groups (COG), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. The potential regulated genes were selected and analyzed their temporal expression patterns following Bgt inoculation. As a result, nine disease-related genes showed distinctive expression profile after Bgt invasion and might serve as potential targets to regulate the resistance against powdery mildew in W762. Our study could lay a foundation for analysis of the molecular mechanism and also provide potential targets for the improvement of durable resistance against powdery mildew.

12.
Biosystems ; 238: 105200, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38565418

RESUMEN

One of the prime reasons of increasing breast cancer mortality is metastasizing cancer cells. Owing to the side effects of clinically available drugs to treat breast cancer metastasis, it is of utmost importance to understand the underlying biogenesis of breast cancer tumorigenesis. In-silico identification of potential RNAs might help in utilizing the miR-27 family as a therapeutic target in breast cancer. The experimentally verified common interacting mRNAs for miR27 family are retrieved from three publicly available databases- TargetScan, miRDB and miRTarBase. Finally on comparing the common genes with HCMDB and GEPIA data, four breast cancer-associated differentially expressed metastatic mRNAs (GATA3, ENAH, ITGA2 and SEMA4D) are obtained. Corresponding to the miR27 family and associated mRNAs, interacting drugs are retrieved from Sm2mir and CTDbase, respectively. The interaction network-based approach was utilized to obtain the hub RNAs and triad modules by employing the 'Cytohubba' and 'MClique' plugins, respectively in Cytoscape. Further, sample-, subclass- and promoter methylation-based expression analyses reveals GATA3 and ENAH to be the most significant mRNAs in breast cancer metastasis having >10% genetic alteration in both METABRIC Vs TCGA datasets as per their oncoprint analysis via cBioPortal. Additionally, survival analysis in Oncolnc reveals SEMA4D as survival biomarker. Interactions among the miR27 family, their target mRNAs and drugs interacting with miRNAs and mRNAs can be extensively explored in both in-vivo and in-vitro setups to assess their therapeutic potential in the diminution of breast cancer.


Asunto(s)
Neoplasias de la Mama , MicroARNs , Humanos , Femenino , Neoplasias de la Mama/genética , Perfilación de la Expresión Génica , Redes Reguladoras de Genes/genética , Biomarcadores de Tumor/genética , MicroARNs/genética , ARN Mensajero/genética
13.
Nanotechnology ; 35(32)2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38684144

RESUMEN

Semiconductor nanowires (NWs) are promising candidates for use in electronic and optoelectronic applications, offering numerous advantages over their thin film counterparts. Their performance relies heavily on the quality of the contacts to the NW, which should exhibit ohmic behavior with low resistance and should be formed in a reproducible manner. In the case of heterostructure NWs for high-mobility applications that host a two-dimensional electron gas, ohmic contacts are particularly challenging to implement since the NW core constituting the conduction channel is away from the NW surface. We investigated contact formation to modulation-doped GaAs/(Al,Ga)As core/shell NWs using scanning transmission electron microscopy, energy dispersive x-ray spectroscopy and electron tomography to correlate microstructure, diffusion profile and chemical composition of the NW contact region with the current-voltage (I-V) characteristics of the contacted NWs. Our results illustrate how diffusion, alloying and phase formation processes essential to the effective formation of ohmic contacts are more intricate than in planar layers, leading to reproducibility challenges even when the processing conditions are the same. We demonstrate that the NW geometry plays a crucial role in the creation of good contacts. Both ohmic and rectifying contacts were obtained under nominally identical processing conditions. Furthermore, the presence of Ge in the NW core, in the absence of Au and Ni, was found as the key factor leading to ohmic contacts. The analysis contributes to the current understanding of ohmic contact formation to heterostructure core/shell NWs offering pathways to enhance the reproducibility and further optimization of such NW contacts.

14.
Front Neurosci ; 18: 1359631, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38516314

RESUMEN

Background: Alzheimer's disease (AD) is a common, refractory, progressive neurodegenerative disorder in which cognitive and memory deficits are highly correlated with abnormalities in hippocampal brain regions. There is still a lack of hippocampus-related markers for AD diagnosis and prevention. Methods: Differently expressed genes were identified in the gene expression profile GSE293789 in the hippocampal brain region. Enrichment analyses GO, KEGG, and GSEA were used to identify biological pathways involved in the DEGs and AD-related group. WGCNA was used to identify the gene modules that are highly associated with AD in the samples. The intersecting genes of the genes in DEGs and modules were extracted and the top ten ranked hub genes were identified. Finally GES48350 was used as a validation cohort to predict the diagnostic efficacy of hub genes. Results: From GSE293789, 225 DEGs were identified, which were mainly associated with calcium response, glutamatergic synapses, and calcium-dependent phospholipid-binding response. WGCNA analysis yielded dark green and bright yellow modular genes as the most relevant to AD. From these two modules, 176 genes were extracted, which were taken to be intersected with DEGs, yielding 51 intersecting genes. Then 10 hub genes were identified in them: HSPA1B, HSPB1, HSPA1A, DNAJB1, HSPB8, ANXA2, ANXA1, SOX9, YAP1, and AHNAK. Validation of these genes was found to have excellent diagnostic performance. Conclusion: Ten AD-related hub genes in the hippocampus were identified, contributing to further understanding of AD development in the hippocampus and development of targets for therapeutic prevention.

15.
ACS Nano ; 18(12): 9221-9231, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38488287

RESUMEN

We investigate the direction-dependent switching current in a flux-tunable four-terminal Josephson junction defined in an InAs/Al two-dimensional heterostructure. The device exhibits the Josephson diode effect with switching currents that depend on the sign of the bias current. The superconducting diode efficiency, reaching a maximum of |η| ≈ 34%, is widely tunable─both in amplitude and sign─as a function of magnetic fluxes and gate voltages. Our observations are supported by a circuit model of three parallel Josephson junctions with nonsinusoidal current-phase relation. With respect to conventional Josephson interferometers, phase-tunable multiterminal Josephson junctions enable large diode efficiencies in structurally symmetric devices, where local magnetic fluxes generated on the chip break both time-reversal and spatial symmetries. Our work presents an approach for developing Josephson diodes with wide-range tunability that do not rely on exotic materials.

16.
J Biomol Struct Dyn ; : 1-17, 2024 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-38459947

RESUMEN

Endometrial carcinoma is a frequent cancer of the female genital tract. Endometrial carcinoma accounts for 97% of all uterine malignancies and 3 % of sarcomas that develop from the endometrium's glands. Endometrial cancer is frequently found in its early stages since most women quickly report postmenopausal vaginal hemorrhage. The need for more advanced medications to improve survival in such situations is still unfulfilled. As a result, there is growing interest in employing an herbal treatment to treat endometriosis, which seems to be an effective strategy. We have discovered a few unintended targets (ligands) in our investigation that are active components of common therapeutic herbs. The differentially expressed genes (DEG - target protein) for endometrial cancer were found using the NCBI and CIViC databases. In our investigation, the protein used for docking and simulation was PDB ID: 3THW. Using the Cytoscape server, the gene-encoding protein network has been identified. It was discovered that the Protein 3THW's binding energy to the bioactive substance (Asarone) was -7.15 Kcal/mol. It was discovered that the crucial interacting amino acid residues were ILE648, PHE650, ILE651, VAL802, TYR815, VAL817. The properties of the pharmaceutical target are further investigated by employing a molecular simulation study for 100 ns with NAMD software. Low RMSD and SASA (Solvent accessible surface area), high RMSF, High hydrogen bonds, between Asarone and MSH2 demonstrated their potency as endometrial cancer inhibitor compounds. Based on these analyses we infer that the bioactive substances originating from medicinal plants may be an effective treatment for endometrial cancer.Communicated by Ramaswamy H. Sarma.

17.
Heliyon ; 10(3): e24963, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38318069

RESUMEN

Background: Pulmonary hypertension (PH) is characterized with vascular remodeling, which is intiated by vascular endothelial dysfunction. N6-methyladenosine (m6A) modification mediates gene expression in many ways including mediating RNA degradation, splicing, nuclear export et al. m6A modification have been found to be associated with the development of PH. However, the role of m6A regulators in pulmonary artery endothelial cells (PAECs) dysfunction of PH is still under research. Methods: The expression levels of m6A regulators in PAECs were analyzed with the single-cell sequencing Data(scRNA). Next, the target differentially expressed genes (DEGs) of m6A regulators in PAECs were functionally annotated. The analysis of cellular interactions included the examination of receptor-ligand pairs regulated by m6A regulators. Pseudo-time trajectory analyses and a ceRNA network involving lncRNAs, miRNAs, and mRNAs were conducted in PAECs. Furthermore, microarray data (GSE180169) for Sugen Hypoxia PH (SuHx PH) mouse models was screened for DEGs and m6A regulators in PAECs. Moreover, the expression of YTHDC1 in the lung samples of SuHx PH models was determined using immunofluorescence. In vitro, the mRNA expression of YTHDC1 in HPAECs under hypoxia conditions was detected. The effect of YTHDC1 recombinant protein on HPAEC proliferation was detected by Cell Counting Kit-8 (CCK8). Results: Dysregulation of m6A regulators was observed in mouse PAECs. The m6A reader of YTHDC1 was decreased in PAECs in scRNA data and RNAseq data of isolated PAECs of SuHx PH models. Downregulation of YTHDC1 was caused by hypoxia in PAECs in vitro and similar results was observed in PAECs of SuHx PH mouse models. Next, YTHDC1 recombinant protein was found to inhibit HPAECs proliferation. The DEGs targeted by YTHDC1 were enriched in angiogenesis, endothelial cell migration, fluid shear stress, and stem cell maintenance. Analysis indicates that interactions among endothelial cells, smooth muscle cells, fibroblasts, and immune cells, mediated by specific YTHDC1 target genes (e.g., PTPRC-MRC1, ITBG2-ICAM1, COL4A1-CD44), contribute to PH development. Also, the YTHDC1 expression were consistent with Thioredoxin interacting protein (TXNIP). What's more, the predicted transcription factors showed that NFKB1, Foxd3 may be involved in the regulation of YTHDC1. Lastly, our data suggest that YTHDC1 may be involved in regulating PAECs dysfunction through lncRNA/miRNA/mRNA network. Conclusion: For the first time, we analyzed changes in the expression and biological functions of m6A regulators in SuHx PH mouse models. We causatively linked YTHDC1 to PAECs dysfunction, providing novel insight into and opportunities to diagnose and treat PH.

18.
Int J Mol Sci ; 25(4)2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38396790

RESUMEN

Platelet-activating factor (PAF) is a phospholipid-derived inflammatory mediator that triggers various inflammatory conditions, including eosinophil activation and recruitment. This study aimed to evaluate the expressions of PAF-metabolism-associated genes, namely genes coding the enzymes involved in PAF synthesis (LPCAT1, LPCAT2, LPCAT3, and LPCAT4), PAF degradation (PAFAH1B2, PAFAH1B3, and PAFAH2), and the gene for the PAF receptor (PTAFR) in subtypes of CRSwNP classified by clinical- or hierarchal-analysis-based classifications. Transcriptomic analysis using bulk RNA barcoding and sequencing (BRB-seq) was performed with CRSwNP, including eosinophilic CRS (ECRS) (n = 9), nonECRS (n = 8), ECRS with aspirin-exacerbated respiratory disease (Asp) (n = 3), and controls with a normal uncinate process mucosa (n = 6). PTAFR was only upregulated in ECRS and nonECRS. In the hierarchical cluster analysis with clusters 1 and 2 reflecting patients with low-to-moderate and high levels of type 2 inflammation, respectively, cluster 1 exhibited a significant downregulation of LPCAT2 and an upregulation of PTAFR expression, while cluster 2 showed an upregulation of LPCAT1, PAFAH1B2, and PTAFR and downregulation of PAFAH2 expression. Understanding this strong PAF-associated pathophysiology in the severe type 2 inflammation group could provide valuable insights into the treatment and management of CRSwNP.


Asunto(s)
Pólipos Nasales , Rinitis , Rinosinusitis , Sinusitis , Humanos , Rinitis/patología , Factor de Activación Plaquetaria/genética , Factor de Activación Plaquetaria/metabolismo , Mucosa Nasal/metabolismo , ARN/metabolismo , Pólipos Nasales/patología , Sinusitis/metabolismo , Inflamación/metabolismo , Enfermedad Crónica , Análisis por Conglomerados , Eosinófilos/metabolismo
19.
Skin Res Technol ; 30(2): e13608, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38314944

RESUMEN

BACKGROUND: Frontal fibrosis alopecia (FFA) is a primary cicatricial alopecia and has received increasing attention in recent years. However, the pathogenesis of FFA has not been fully elucidated. METHODS AND RESULTS: Herein, we collected the transcriptome data of scalp lesions of seven patients with FFA and seven healthy controls. The differential expression analysis and weighted gene co-expression network analysis were conducted and we identified 458 differentially expressed genes (DEGs) in two key modules. Later, we performed functional enrichment analysis and functional modules identification, revealing the participation of immune response and fatty acid metabolism. Based on the results, we processed further studies. On the one hand, we analyzed the infiltrating immune cells of FFA through CIBERSORT algorithm, indicating the activation of M1 macrophage and CD8+ T cell. On the other hand, considering lipid metabolism of FFA and oxidative stress of hair follicle cells in alopecia, we explored the potential ferroptosis of FFA. By intersection of DEGs and ferroptosis-related genes from FerrDb database, 19 genes were identified and their expression was validated in an external dataset containing 36 FFA cases and 12 controls. Then, we used LASSO algorithms to construct a four-gene diagnostic model, which achieved an AUC of 0.924 in validation dataset. Additionally, the immune cells were found to be related to ferroptosis in FFA. CONCLUSION: Taken together, this study contributed to reveal the molecular mechanisms of FFA and is expected to inspire future research on treatment.


Asunto(s)
Ferroptosis , Humanos , Ferroptosis/genética , Alopecia/genética , Alopecia/patología , Fibrosis , Cuero Cabelludo/patología , Perfilación de la Expresión Génica
20.
ACS Appl Mater Interfaces ; 16(9): 11595-11604, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38381554

RESUMEN

Dielectric elastomer generator (DEG), which consists of a dielectric elastomer (DE) film sandwiched between two flexible electrodes (FEs), has the advantages of lightweight, high energy density, and high energy conversion efficiency, providing a simple and feasible solution for harvesting energy from human motion or nature. As crucial constituents of DEG, FEs are expected to possess excellent conductivity and compliance. Nevertheless, there is currently no quantitative characterization method for FE compliance. In addition, the impact mechanism of FE compliance on the energy harvesting performance and fatigue life of the DEG remains unclear. In this study, the dynamic mechanical property (DMP) was used to assess the compliance of FEs, and the quantitative characterization method of FE compliance was proposed. A series of silicone rubber electrodes (SREs) with different DMPs and compliance were designed and prepared, and the impact mechanism of FE compliance on the energy harvesting stability and fatigue life of the DEG was investigated. The results indicate that the key to achieving excellent FE compliance lies in reducing the difference in the magnitude of the complex modulus and phase angle between the FEs and DE, which can significantly reduce interfacial friction and extend the fatigue life of DEG. Benefiting from the enhanced FE compliance, the fatigue life and full-life energy density of the DEG device increase by 20.3 times and 26.4 times, respectively, compared with those of the commonly used carbon-based electrodes.

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