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1.
Front Plant Sci ; 15: 1364086, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39114465

RESUMO

As an upright tree with multifunctional economic application, Machilus pauhoi is an excellent choice in modern forestry from Lauraceae. The growth characteristics is of great significance for its molecular breeding and improvement. However, there still lack the information of WUSCHEL-related homeobox (WOX) and Auxin response factor (ARF) gene family, which were reported as specific transcription factors in plant growth as well as auxin signaling. Here, a total of sixteen MpWOX and twenty-one MpARF genes were identified from the genome of M. pauhoi. Though member of WOX conserved in the Lauraceae, MpWOX and MpARF genes were unevenly distributed on 12 chromosomes as a result of region duplication. These genes presented 45 and 142 miRNA editing sites, respectively, reflecting a potential post-transcriptional restrain. Overall, MpWOX4, MpWOX13a, MpWOX13b, MpARF6b, MpARF6c, and MpARF19a were highly co-expressed in the vascular cambium, forming a working mode as WOX-ARF complex. MpWOXs contains typical AuxRR-core and TGA-element cis-acting regulatory elements in this auxin signaling linkage. In addition, under IAA and NPA treatments, MpARF2a and MpWOX1a was highly sensitive to IAA response, showing significant changes after 6 hours of treatment. And MpWOX1a was significantly inhibited by NPA treatment. Through all these solid analysis, our findings provide a genetic foundation to growth mechanism analysis and further molecular designing breeding in Machilus pauhoi.

2.
Foot Ankle Surg ; 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39107216

RESUMO

BACKGROUND: Chronic ankle instability (CAI) is a common and highly disabling condition. Although several studies have evaluated and analyzed prevention and treatment strategies for CAI, an unbiased and systematic synthesis of evidence is required to provide the most powerful and comprehensive evidence-based measures for the its prevention and treatment of CAI. This study aimed to synthesize evidence from the existing literature addressing the treatment and prevention of CAI. METHODS: The PubMed, Embase, Cochrane, and Web of Science databases were systematically searched for relevant studies from inception to December 12, 2023. Data on effect sizes and corresponding 95 % confidence intervals for selected intervention measures were extracted. Systematic reviews were assessed for quality of included studies using a measurement tool (i.e., "AMSTAR 2"). RESULTS: In total, 37 studies were included, among which 21 (57 %) were of high or moderate quality. Strong evidence suggested that lower weight (P < 0.001), lower body mass index (P = 0.002), and non-stability defects (P = 0.04) significantly reduced the risk of developing CAI. Strong evidence supported exercise and moderate evidence supported manual therapy, acupuncture, and surgery for improving CAI. Additionally, external support plays an active role in the treatment process of CAI. CONCLUSION: This is the first study synthesizing evidence supporting interventions for the treatment and prevention of CAI. Low body weight and body mass index were effective preventive measures against CAI. Exercise, manual therapy, acupuncture, and surgery can improve ankle function in patients with CAI. Plantar sensory treatment and neuromuscular training may be good therapeutic options for patients with CAI. LEVEL OF EVIDENCE: Level I.

3.
Nanomaterials (Basel) ; 14(15)2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39120404

RESUMO

In this work, ß-NiS nanoparticles (NPs) were efficiently prepared by a straightforward hydrothermal process. The difference in morphology between these NiS NPs was produced by adding different amounts of thiourea, and the corresponding products were denoted as NiS-15 and NiS-5. Through electrochemical tests, the specific capacity (Cs) of NiS-15 was determined to be 638.34 C g-1 at 1 A g-1, compared to 558.17 C g-1 for NiS-5. To explore the practical application potential of such ß-NiS NPs in supercapacitors, a hybrid supercapacitor (HSC) device was assembled with activated carbon (AC) as an anode. Benefitting from the high capacity of the NiS cathode and the large voltage window of the device, the NiS-15//AC HSC showed a high energy density (Ed) of 43.57 W h kg-1 at 936.92 W kg-1, and the NiS-5//AC HSC provided an inferior Ed of 37.89 W h kg-1 at 954.79 W kg-1. Both HSCs showed excellent cycling performance over 6000 cycles at 10 A g-1. The experimental findings suggest that both NiS-15 and NiS-5 in this study can serve as potential cathodes for high-performance supercapacitors. This current synthesis method is simple and can be extended to the preparation of other transition metal sulfide (TMS)-based electrode materials with exceptional electrochemical properties.

4.
Animals (Basel) ; 14(15)2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39123803

RESUMO

Avian pathogenic E. coli (APEC) causes localized and systemic infections and are a threat to human health. microRNAs (miRNAs) play critical roles in inflammation and immune regulation following pathogen invasion. However, the related regulatory mechanism remains unclear. This study aimed to elucidate the involvement of chicken microRNA-20a-5p (gga-miR-20a-5p) in host defense against APEC in chickens and the underlying mechanisms. We evaluated the expression levels of gga-miR-20a-5p in chicken tissues and cells and observed a significant decrease in expression following APEC infection. Dual luciferase reporter assays showed that gga-miR-20a-5p directly targeted transforming growth factor-beta receptor 2 (TGFBR2), specifically by binding to the 3'-untranslated region (3'UTR) of TGFBR2. Overexpression of gga-miR-20a-5p markedly reduced both the mRNA and protein levels of TGFBR2, whereas inhibition of gga-miR-20a-5p significantly increased expression. Mechanistic investigations revealed that overexpression of gga-miR-20a-5p also attenuated the expression levels of the pro-inflammatory cytokines IL8, TNFα, IL6, and IL1ß, whereas inhibition of gga-miR-20a-5p had the opposite effects. Collectively, our findings suggest that gga-miR-20a-5p regulates the immune response during APEC infection by targeting TGFBR2, thereby suppressing inflammatory cytokine production. This study provides valuable insights into the role of gga-miR-20a-5p in the host defense against APEC.

5.
Cereb Cortex ; 34(7)2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-39042033

RESUMO

We aimed to evaluate the potential causal relationship between brain imaging-derived phenotypes and cognitive functions via Mendelian randomization analyses. Genetic instruments for 470 brain imaging-derived phenotypes were selected from a genome-wide association study based on the UK Biobank (n = 33,224). Statistics for cognitive functions were obtained from the genome-wide association study based on the UK Biobank. We used the inverse variance weighted Mendelian randomization method to investigate the associations between brain imaging-derived phenotypes and cognitive functions, and reverse Mendelian randomization analyses were performed for significant brain imaging-derived phenotypes to examine the reverse causation for the identified associations. We identified three brain imaging-derived phenotypes to be associated with verbal-numerical reasoning, including cortical surface area of the left fusiform gyrus (beta, 0.18 [95% confidence interval, 0.11 to 0.25], P = 4.74 × 10-7), cortical surface area of the right superior temporal gyrus (beta, 0.25 [95% confidence interval, 0.15 to 0.35], P = 6.30 × 10-7), and orientation dispersion in the left superior longitudinal fasciculus (beta, 0.14 [95% confidence interval, 0.09 to 0.20], P = 8.37 × 10-7). The reverse Mendelian randomization analysis indicated that verbal-numerical reasoning had no effect on these three brain imaging-derived phenotypes. This Mendelian randomization study identified cortical surface area of the left fusiform gyrus, cortical surface area of the right superior temporal gyrus, and orientation dispersion in the left superior longitudinal fasciculus as predictors of verbal-numerical reasoning.


Assuntos
Encéfalo , Cognição , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Fenótipo , Humanos , Cognição/fisiologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Masculino , Feminino , Neuroimagem/métodos , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética/métodos , Idoso
6.
Clin Proteomics ; 21(1): 50, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39004717

RESUMO

BACKGROUND: Estrogen receptor-positive (ER+) breast cancer accounts for two-thirds of all breast cancers, and its early and late recurrences still threaten patients' long-term survival and quality of life. Finding candidate tumor antigens and potential therapeutic targets is critical to addressing these unmet needs. METHOD: The isobaric tags for relative and absolute quantitation (iTRAQ) proteomic analysis was employed to identify the differentially expressed proteins (DEPs) between ER + breast cancer and corresponding adjacent normal tissue. Candidate DEPs were screened by bioinformatic analyses, and their expression was confirmed by immunohistochemical (IHC) staining and western blot. A series of in vitro experiments, including wound healing assay, colony formation, and cell cycle assay, were performed to reveal the functions of selected DEPs. Additionally, their clinical significances were further analyzed. RESULT: A total of 369 DEPs (fold change ≥ 2.0 or ≤ 0.66, P < 0.05) were discovered. Compared with normal tissue, 358 proteins were up-regulated and 11 proteins were down-regulated in ER + breast cancer. GO and KEGG enrichment analysis showed that DEPs were closely associated with RNA regulation and metabolic pathways. STRING analysis found ESF1 and MIPEP were the hub genes in breast cancer, whose increased expressions were verified by the IHC staining and western blot. Knocking down ESF1 and MIPEP inhibited colony formation and increased cell apoptosis. Besides, knocking down ESF1 inhibited wound healing but not MIPEP. In addition, ESF1 and MIPEP expression were negatively associated with patient prognosis. CONCLUSION: The upregulation of ESF1 and MIPEP promoted ER + breast cancer proliferation, which might provide novel targets for the development of new therapies.

7.
Plants (Basel) ; 13(13)2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38999689

RESUMO

The low nutrient content of soil in desert ecosystems results in unique physiological and ecological characteristics of plants under long-term water and nutrient stress, which is the basis for the productivity and stability maintenance of the desert ecosystem. However, the relationship between the soil and the plant nutrient elements in the desert ecosystem and its mechanism for maintaining ecosystem stability is still unclear. In this study, 35 sampling sites were established in an area with typical desert vegetation in the Qaidam Basin, based on a drought gradient. A total of 90 soil samples and 100 plant samples were collected, and the soil's physico-chemical properties, as well as the nutrient elements in the plant leaves, were measured. Regression analysis, redundancy analysis (RDA), the Theil-Sen Median and Mann-Kendall methods, the structural equation model (SEM), and other methods were employed to analyze the distribution characteristics of the soil and plant nutrient elements along the drought gradient and the relationship between the soil and leaf nutrient elements and its impact on ecosystem stability. The results provided the following conclusions: Compared with the nutrient elements in plant leaves, the soil's nutrient elements had a more obvious regularity of distribution along the drought gradient. A strong correlation was observed between the soil and leaf nutrient elements, with soil organic carbon and alkali-hydrolyzed nitrogen identified as important factors influencing the leaf nutrient content. The SEM showed that the soil's organic carbon had a positive effect on ecosystem stability by influencing the leaf carbon, while the soil's available phosphorus and the mean annual temperature had a direct positive effect on stability, and the soil's total nitrogen had a negative effect on stability. In general, the soil nutrient content was high in areas with a low mean annual temperature and high precipitation, and the ecosystem stability in the area distribution of typical desert vegetation in the Qaidam Basin was low. These findings reveal that soil nutrients affect the stability of desert ecosystems directly or indirectly through plant nutrients in the Qaidam Basin, which is crucial for maintaining the stability of desert ecosystems with the background of climate change.

8.
iScience ; 27(6): 110113, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38952681

RESUMO

The gut epithelium is subject to constant renewal, a process reliant upon intestinal stem cell (ISC) proliferation that is driven by Wnt/ß-catenin signaling. Despite the importance of Wnt signaling within ISCs, the relevance of Wnt signaling within other gut cell types and the underlying mechanisms that modulate Wnt signaling in these contexts remain incompletely understood. Using challenge of the Drosophila midgut with a non-lethal enteric pathogen, we examine the cellular determinants of ISC proliferation, harnessing kramer, a recently identified regulator of Wnt signaling pathways, as a mechanistic tool. We find that Wnt signaling within Prospero-positive cells supports ISC proliferation and that kramer regulates Wnt signaling in this context by antagonizing kelch, a Cullin-3 E3 ligase adaptor that mediates Dishevelled polyubiquitination. This work establishes kramer as a physiological regulator of Wnt/ß-catenin signaling in vivo and suggests enteroendocrine cells as a new cell type that regulates ISC proliferation via Wnt/ß-catenin signaling.

9.
Gene ; 928: 148783, 2024 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-39033937

RESUMO

Ammonia acts as a detrimental atmospheric pollutant, posing a sever threat to respiratory tract health and causing lung injury in humans and animals. Circular RNAs (circRNAs) are a distinctive class of non-coding RNA generated by back-splicing of linear RNA, implicated in various biological processes. However, their role in the immune response of chicken lungs to ammonia exposure remains unclear. In this study, we examined the expression profiles of circRNAs in chicken lungs under ammonia stimulation. In total, 61 differentially expressed (DE) circRNAs were identified between the ammonia exposure and control groups, including 17 up-regulated and 44 down-regulated circRNAs. The source genes of these DE circRNAs were predominantly enriched in Influenza A, SNARE interactions in vesicular transport, and Notch signaling pathway. Notably, nine DE circRNAs (circNBAS, circMTIF2, circXPO1, circSNX24, circRAB11A, circARID3B, circUSP54, circPPARA, and circERG) were selected for validation the reliability and authenticity of RNA-seq data. Results showed the back-splicing circular structure, as well as the reliability and accuracy of RNA-seq data in quantifying circRNA expression, as the RT-qPCR results were in agreement with the RNA-seq data. Moreover, we constructed the circRNA-miRNA-mRNA regulatory networks and identified several regulatory networks in chicken lungs under ammonia stimulation, including circRAB11A-gga-miR-191b-3p-BRD2 and circARID3B-gga-miR-1696-CKS2. Taken together, our study delineates the circRNA expression profile and their potential roles in the immune response of chicken lungs to ammonia exposure. These findings offer insights into molecular mechanisms that may mitigate diseases associated with ammonia induced respiratory tract pollution in humans and animals.


Assuntos
Amônia , Galinhas , Pulmão , RNA Circular , RNA Circular/genética , Animais , Galinhas/genética , Amônia/toxicidade , Amônia/metabolismo , Pulmão/metabolismo , Pulmão/efeitos dos fármacos , Redes Reguladoras de Genes , MicroRNAs/genética , Perfilação da Expressão Gênica , Transcriptoma , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos
10.
Fish Shellfish Immunol ; 152: 109784, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39067495

RESUMO

Exocyst, a protein complex, plays a crucial role in various cellular functions, including cell polarization, migration, invasion, cytokinesis, and autophagy. Sec3, known as Exoc1, is a key subunit of the Exocyst complex and can be involved in cell survival and apoptosis. In this study, two subtypes of Sec3 were isolated from Epinephelus coioides, an important marine fish in China. The role of E. coioides Sec3 was explored during Singapore grouper iridovirus (SGIV) infection, an important pathogen of marine fish which could induce 90 % mortality. E. coioides Sec3 sequences showed a high similarity with that from other species, indicating the presence of a conserved Sec3 superfamily domain. E. coioides Sec3 mRNA could be detected in all examined tissues, albeit at varying expression levels. SGIV infection could upregulate E. coioides Sec3 mRNA. Upregulated Sec3 significantly promoted SGIV-induced CPE, and the expressions of viral key genes. E. coioides Sec3 could inhibit the activation of NF-κB and AP-1, as well as SGIV-induced cell apoptosis. The results illustrated that E. coioides Sec3 promotes SGIV infection by regulating the innate immune response.


Assuntos
Bass , Infecções por Vírus de DNA , Doenças dos Peixes , Proteínas de Peixes , Imunidade Inata , Filogenia , Ranavirus , Animais , Doenças dos Peixes/imunologia , Doenças dos Peixes/virologia , Infecções por Vírus de DNA/imunologia , Infecções por Vírus de DNA/veterinária , Imunidade Inata/genética , Bass/imunologia , Ranavirus/fisiologia , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Proteínas de Peixes/química , Regulação da Expressão Gênica/imunologia , Alinhamento de Sequência/veterinária , Sequência de Aminoácidos , Perfilação da Expressão Gênica/veterinária
11.
J Cancer ; 15(13): 4386-4405, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38947398

RESUMO

Background: TMEM132A is a transmembrane protein that regulates gastric cancer cell malignancy and overall survival in bladder cancer patients. However, while some studies have investigated the involvement of TMEM132A in specific cancers, further systematic studies are required to elucidate its specific mechanisms of action in different cancer types. Methods: We investigated the pan-cancer role of TMEM132A using several databases. We analyzed TMEM132A expression and its correlation with clinical survival, immune checkpoints, tumor stemness score, prognostic value, immunomodulators, genomic profiles, immunological characteristics, immunotherapy and functional enrichment. Results: First, it was observed that TMEM132A expression levels were higher in the majority of tumors compared to non-tumor tissues. In addition, high TMEM132A expression may have a higher prognostic value in some cancers. Furthermore, TMEM132A was significantly associated with immune checkpoints, immunomodulators, prognosis, immunomodulatory genes, tumor stemness score, cell function status and immune infiltration in most tumors. Further analysis of TMEM132A-related gene enrichment, mutation sites and types, RNA modification and genomic heterogeneity showed that the major mutations of TMEM132A were missense mutations and that TMEM132A plays a very important role in UCEC, LUAD and LIHC. Finally, these results suggest that high TMEM132A expression may be associated with a better response to specific immunotherapies. Conclusion: This comprehensive study uncovers an important function for TMEM132A in different types of cancer. It also has the potential to identify TMEM132A as a potential biomarker for predicting treatment response. This may help us to better understand how TMEM132A plays a role in cancer and provide valuable insights for developing personalised treatments.

12.
Adv Sci (Weinh) ; : e2402838, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38896788

RESUMO

Chemoselective modification of specific residues within a given protein poses a significant challenge, as the microenvironment of amino acid residues in proteins is variable. Developing a universal molecular platform with tunable chemical warheads can provide powerful tools for precisely labeling specific amino acids in proteins. Cysteine and lysine are hot targets for chemoselective modification, but current cysteine/lysine-selective warheads face challenges due to cross-reactivity and unstable reaction products. In this study, a versatile fluorescent platform is developed for highly selective modification of cysteine/lysine under biocompatible conditions. Chloro- or phenoxy-substituted NBSe derivatives effectively labeled cysteine residues in the cellular proteome with high specificity. This finding also led to the development of phenoxy-NBSe phototheragnostic for the diagnosis and activatable photodynamic therapy of GSH-overexpressed cancer cells. Conversely, alkoxy-NBSe derivatives are engineered to selectively react with lysine residues in the cellular environment, exhibiting excellent anti-interfering ability against thiols. Leveraging a proximity-driven approach, alkoxy-NBSe probes are successfully designed to demonstrate their utility in bioimaging of lysine deacetylase activity. This study also achieves integrating a small photosensitizer into lysine residues of proteins in a regioselective manner, achieving photoablation of cancer cells activated by overexpressed proteins.

13.
Small Methods ; : e2400155, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38781604

RESUMO

Microfluidic Paper-based Analytical Devices (µPADs) have emerged as a new class of microfluidic systems, offering numerous advantages over traditional microfluidic chips. These advantages include simplicity, cost-effectiveness, stability, storability, disposability, and portability. As a result, various designs for different types of assays are developed and investigated. In recent years, µPADs are combined with conventional detection methods to enable rapid on-site detection, providing results comparable to expensive and sophisticated large-scale testing methods that require more time and skilled personnel. The application of µPAD techniques is extensive in environmental quality control/analysis, clinical diagnosis, and food safety testing, paving the way for on-site real-time diagnosis as a promising future development. This review focuses on the recent research advancements in the design, fabrication, material selection, and detection methods of µPADs. It provides a comprehensive understanding of their principles of operation, applications, and future development prospects.

14.
Clin Interv Aging ; 19: 939-951, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38807637

RESUMO

Age-related macular degeneration (AMD) is a degenerative ocular disease primarily affecting central vision in the elderly. Its pathogenesis is complex, involving cellular senescence and immune homeostasis dysregulation. This review investigates the interaction between these two critical biological processes in AMD pathogenesis and their impact on disease progression. Initially, cellular senescence is analyzed, with particular emphasis on retinal damage induced by senescent retinal pigment epithelial cells. Subsequently, the occurrence of immune homeostasis dysregulation within the retina and its mechanistic role in AMD areis explored. Furthermore, the paper also discusses in detail the interplay between cellular senescence and immune responses, forming a vicious cycle that exacerbates retinal damage and may influence treatment outcomes. In summary, a deeper understanding of the interrelation between cellular senescence and immune dysregulation is vital for the developing innovative therapeutic strategies for AMD.


Assuntos
Senescência Celular , Homeostase , Degeneração Macular , Epitélio Pigmentado da Retina , Humanos , Degeneração Macular/imunologia , Epitélio Pigmentado da Retina/imunologia , Progressão da Doença , Retina/imunologia
15.
Clin Epigenetics ; 16(1): 72, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38812044

RESUMO

Lactic acid, traditionally considered as a metabolic waste product arising from glycolysis, has undergone a resurgence in scientific interest since the discovery of the Warburg effect in tumor cells. Numerous studies have proved that lactic acid could promote angiogenesis and impair the function of immune cells within tumor microenvironments. Nevertheless, the precise molecular mechanisms governing these biological functions remain inadequately understood. Recently, lactic acid has been found to induce a posttranslational modification, lactylation, that may offer insight into lactic acid's non-metabolic functions. Notably, the posttranslational modification of proteins by lactylation has emerged as a crucial mechanism by which lactate regulates cellular processes. This article provides an overview of the discovery of lactate acidification, outlines the potential "writers" and "erasers" responsible for protein lactylation, presents an overview of protein lactylation patterns across different organisms, and discusses the diverse physiological roles of lactylation. Besides, the article highlights the latest research progress concerning the regulatory functions of protein lactylation in pathological processes and underscores its scientific significance for future investigations.


Assuntos
Processamento de Proteína Pós-Traducional , Humanos , Ácido Láctico/metabolismo , Animais , Histonas/metabolismo , Histonas/genética , Código das Histonas/genética , Neoplasias/genética , Neoplasias/metabolismo , Epigênese Genética/genética
16.
Front Endocrinol (Lausanne) ; 15: 1382896, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38800474

RESUMO

Background: Proliferative diabetic retinopathy (PDR), a major cause of blindness, is characterized by complex pathogenesis. This study integrates single-cell RNA sequencing (scRNA-seq), Non-negative Matrix Factorization (NMF), machine learning, and AlphaFold 2 methods to explore the molecular level of PDR. Methods: We analyzed scRNA-seq data from PDR patients and healthy controls to identify distinct cellular subtypes and gene expression patterns. NMF was used to define specific transcriptional programs in PDR. The oxidative stress-related genes (ORGs) identified within Meta-Program 1 were utilized to construct a predictive model using twelve machine learning algorithms. Furthermore, we employed AlphaFold 2 for the prediction of protein structures, complementing this with molecular docking to validate the structural foundation of potential therapeutic targets. We also analyzed protein-protein interaction (PPI) networks and the interplay among key ORGs. Results: Our scRNA-seq analysis revealed five major cell types and 14 subcell types in PDR patients, with significant differences in gene expression compared to those in controls. We identified three key meta-programs underscoring the role of microglia in the pathogenesis of PDR. Three critical ORGs (ALKBH1, PSIP1, and ATP13A2) were identified, with the best-performing predictive model demonstrating high accuracy (AUC of 0.989 in the training cohort and 0.833 in the validation cohort). Moreover, AlphaFold 2 predictions combined with molecular docking revealed that resveratrol has a strong affinity for ALKBH1, indicating its potential as a targeted therapeutic agent. PPI network analysis, revealed a complex network of interactions among the hub ORGs and other genes, suggesting a collective role in PDR pathogenesis. Conclusion: This study provides insights into the cellular and molecular aspects of PDR, identifying potential biomarkers and therapeutic targets using advanced technological approaches.


Assuntos
Retinopatia Diabética , Aprendizado de Máquina , Humanos , Retinopatia Diabética/genética , Retinopatia Diabética/metabolismo , Retinopatia Diabética/patologia , Simulação de Acoplamento Molecular , Análise de Célula Única/métodos , Análise de Sequência de RNA/métodos , RNA-Seq , Mapas de Interação de Proteínas , Feminino , Masculino , Estresse Oxidativo , Estudos de Casos e Controles , Análise da Expressão Gênica de Célula Única
17.
Brief Bioinform ; 25(3)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38725156

RESUMO

Protein acetylation is one of the extensively studied post-translational modifications (PTMs) due to its significant roles across a myriad of biological processes. Although many computational tools for acetylation site identification have been developed, there is a lack of benchmark dataset and bespoke predictors for non-histone acetylation site prediction. To address these problems, we have contributed to both dataset creation and predictor benchmark in this study. First, we construct a non-histone acetylation site benchmark dataset, namely NHAC, which includes 11 subsets according to the sequence length ranging from 11 to 61 amino acids. There are totally 886 positive samples and 4707 negative samples for each sequence length. Secondly, we propose TransPTM, a transformer-based neural network model for non-histone acetylation site predication. During the data representation phase, per-residue contextualized embeddings are extracted using ProtT5 (an existing pre-trained protein language model). This is followed by the implementation of a graph neural network framework, which consists of three TransformerConv layers for feature extraction and a multilayer perceptron module for classification. The benchmark results reflect that TransPTM has the competitive performance for non-histone acetylation site prediction over three state-of-the-art tools. It improves our comprehension on the PTM mechanism and provides a theoretical basis for developing drug targets for diseases. Moreover, the created PTM datasets fills the gap in non-histone acetylation site datasets and is beneficial to the related communities. The related source code and data utilized by TransPTM are accessible at https://www.github.com/TransPTM/TransPTM.


Assuntos
Redes Neurais de Computação , Processamento de Proteína Pós-Traducional , Acetilação , Biologia Computacional/métodos , Bases de Dados de Proteínas , Software , Algoritmos , Humanos , Proteínas/química , Proteínas/metabolismo
18.
J Colloid Interface Sci ; 667: 350-361, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38640654

RESUMO

Herein, porous MnCo2O4 with disc-like (MnCo2O4-discs) and ring-like (MnCo2O4-rings) microstructures were respectively synthesized using an initial hydrothermal method at different temperatures and a calcination treatment in air. The electrochemical properties of these MnCo2O4 materials were investigated in three-electrode and two-electrode systems, and as such, MnCo2O4 presented a battery-like electrochemical response. The specific capacity of MnCo2O4-discs was determined to be 296.1C/g at 1 A/g, superior to 246.3C/g for MnCo2O4-rings. An asymmetric supercapacitor (ASC) was assembled with MnCo2O4 as the cathode and activated carbon (AC) as the anode to evaluate the potential for practical application. The MnCo2O4-discs//AC ASC exhibited an energy density (Ed) of 35.8 W h kg-1 at a power density (Pd) of 927.5 W kg-1. For the MnCo2O4-rings//AC ASC, an inferior Ed of 31.4 W h kg-1 under 890.9 W kg-1 was achieved. Furthermore, the two ASCs presented outstanding cyclic performance after 5000 cycles at 6 A/g. The exceptional properties of MnCo2O4 microstructures can be applied to the assembly of ASC devices, which can have promising potential for application in electrochemical energy storage. This synthetic method is straightforward, cost-effective, and can be extended to fabricate similar electrode materials with superior electrochemical performance.

19.
ACS Appl Mater Interfaces ; 16(19): 24341-24350, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38687629

RESUMO

Magnetic micro/nanorobots are promising platforms for targeted drug delivery, and their construction with soft and flexible features has received extensive attention for practical applications. Despite significant efforts in this field, facile fabrication of magnetic microrobots with flexible structures and versatility in targeted therapy remains a big challenge. Herein, we proposed a novel universal strategy to fabricate a biohybrid flexible sperm-like microrobot (BFSM) based on a Chlorella (Ch.) cell and artificial flagella, which showed great potential for targeted chemo-photothermal therapy for the first time. In this approach, microspherical Ch. cells were utilized to construct the microrobotic heads, which were intracellularly deposited with core-shell Pd@Au, extracellularly magnetized with Fe3O4, and further loaded with anticancer drug. The magnetic heads with excellent photothermal and chemotherapeutic capability were further assembled with flexible polypyrrole nanowires via biotin-streptavidin bonding to construct the BFSMs. Based on the exquisite head-to-tail structures, the BFSMs could be effectively propelled under precessing magnetic fields and move back and forth without a U-turn. Moreover, in vitro chemo-photothermal tests were conducted to verify their performance of targeted drug delivery toward localized HeLa cells. Due to this superior versatility and facile fabrication, the BFSMs demonstrated great potential for targeted anticancer therapy.


Assuntos
Terapia Fototérmica , Humanos , Células HeLa , Robótica , Sistemas de Liberação de Medicamentos , Antineoplásicos/química , Antineoplásicos/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacologia , Polímeros/química , Nanofios/química , Ouro/química
20.
Cell Death Discov ; 10(1): 160, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561355

RESUMO

Steroid receptor RNA activator (SRA)-like non-coding RNA (SLNCR1) has been implicated in various tumorigenic processes, but the precise regulatory role in melanoma progression remains uncertain. We performed a comprehensive analysis to investigate the prognostic value of SLNCR1 expression in patients with melanoma by TCGA database and melanoma tissue samples via the Kaplan-Meier method. Subsequently, we conducted qRT-PCR and Fluorescence in Situ Hybridization (FISH) assays to identify SLNCR1 expression levels and localization in tissues and cells, respectively. Loss-of-function assays utilizing shRNAs vectors were used to investigate the potential impact of SLNCR1. Our data showed that SLNCR1 is significantly up-regulated in human malignant melanoma tissues and cell lines and functions as an oncogene. Silencing of SLNCR1 suppressed melanoma cell proliferation, migration, invasion, and inhibited tumorigenesis in a mouse xenograft model. Additionally, we employed bioinformatic predictive analysis, combined with dual-luciferase reporter analysis and functional rescue assays, to elucidate the mechanistic target of the SLNCR1/SOX5 axis in melanoma. Mechanistically, we discovered that SLNCR1 promotes EMT of human melanoma by targeting SOX5, as downregulation of SLNCR1 expression leads to a decrease in SOX5 protein levels and inhibits melanoma tumorigenesis. Our research offers promising insights for more precise diagnosis and treatment of human melanoma.

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