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1.
Ecol Lett ; 27(5): e14415, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38712683

RESUMO

The breakdown of plant material fuels soil functioning and biodiversity. Currently, process understanding of global decomposition patterns and the drivers of such patterns are hampered by the lack of coherent large-scale datasets. We buried 36,000 individual litterbags (tea bags) worldwide and found an overall negative correlation between initial mass-loss rates and stabilization factors of plant-derived carbon, using the Tea Bag Index (TBI). The stabilization factor quantifies the degree to which easy-to-degrade components accumulate during early-stage decomposition (e.g. by environmental limitations). However, agriculture and an interaction between moisture and temperature led to a decoupling between initial mass-loss rates and stabilization, notably in colder locations. Using TBI improved mass-loss estimates of natural litter compared to models that ignored stabilization. Ignoring the transformation of dead plant material to more recalcitrant substances during early-stage decomposition, and the environmental control of this transformation, could overestimate carbon losses during early decomposition in carbon cycle models.


Assuntos
Folhas de Planta , Ciclo do Carbono , Carbono/metabolismo
2.
Immunology ; 172(4): 533-546, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38561001

RESUMO

Radiation-induced fibrosis (RIF) is a severe chronic complication of radiotherapy (RT) manifested by excessive extracellular matrix (ECM) components deposition within the irradiated area. The lung, heart, skin, jaw, pelvic organs and so on may be affected by RIF, which hampers body functions and quality of life. There is accumulating evidence suggesting that the immune microenvironment may play a key regulatory role in RIF. This article discussed the synergetic or antagonistic effects of immune cells and mediators in regulating RIF's development. Several potential preventative and therapeutic strategies for RIF were proposed based on the immunological mechanisms to provide clinicians with improved cognition and clinical treatment guidance.


Assuntos
Microambiente Celular , Fibrose , Lesões por Radiação , Radioterapia , Humanos , Animais , Lesões por Radiação/imunologia , Radioterapia/efeitos adversos , Matriz Extracelular/metabolismo , Matriz Extracelular/imunologia , Matriz Extracelular/efeitos da radiação
3.
Anal Chem ; 96(19): 7497-7505, 2024 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-38687987

RESUMO

Redox potential plays a key role in regulating intracellular signaling pathways, with its quantitative analysis in individual cells benefiting our understanding of the underlying mechanism in the pathophysiological events. Here, a metal organic framework (MOF)-functionalized SERS nanopotentiometer has been developed for the dynamic monitoring of intracellular redox potential. The approach is based on the encapsulation of zirconium-based MOF (Uio-66-F4) on a surface of gold-silver nanorods (Au-Ag NRs) that is modified with the newly synthesized redox-sensitive probe ortho-mercaptohydroquinone (HQ). Thanks to size exclusion of MOF as the chemical protector, the nanopotentiometer can be adapted to long-term use and possess high anti-interference ability toward nonredox species. Combining the superior fingerprint identification of SERS with the electrochemical activity of the quinone/hydroquinone, the nanopotentiometer shows a reversible redox responsivity and can quantify redox potential with a relatively wide range of -250-100 mV. Furthermore, the nanopotentiometer allows for dynamic visualization of intracellular redox potential changes induced by drugs' stimulation in a high-resolution manner. The developed approach would be promising for offering new insights into the correlation between redox potential and tumor proliferation-involved processes such as oxidative stress and hypoxia.


Assuntos
Ouro , Estruturas Metalorgânicas , Oxirredução , Prata , Zircônio , Estruturas Metalorgânicas/química , Humanos , Ouro/química , Prata/química , Zircônio/química , Análise Espectral Raman , Nanotubos/química , Hidroquinonas/química , Nanopartículas Metálicas/química
4.
Lupus ; 33(4): 387-396, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38305218

RESUMO

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disorder. When SLE occurs in individuals under the age of 18, it is referred to as childhood-onset SLE (cSLE). Currently, there is a dearth of bibliometric research pertaining to cSLE. METHOD: Relevant studies in the field of cSLE from 2000 to 2022 were screened from the Web of Science Core Collection (WoSCC). CiteSpace and VOSviewer software were used to visualize the annual publications, countries, institutions, authors, journals, keywords, and references, after which the authors conducted the scientific analysis. RESULTS: A total of 2857 articles were included in this study, and the number of articles published in the past 20 years showed an overall upwards trend. The most prolific countries are the United States, China, and Brazil; however, the United States, Canada, and the United Kingdom are clearly superior in terms of literary influence, and there is more cooperation between them and their institutions. LUPUS (n = 389) contributed the most to the variance. Brunner, HI's contribution in the field of cSLE is outstanding. The words related to 'lupus nephritis' and 'antibodies' are important words reflected in the keyword network diagram. The keywords included 'evidence-based recommendation', 'validation', 'diagnosis' and 'adult' from 2019, and 'continuous bursts' to the present. CONCLUSION: This study examined the research status of cSLE patients, discussed and analysed the research hotspots and trends in this field, and provided a reference for further research in this field to promote the development of cSLE research.


Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Anticorpos , Bibliometria , Brasil
5.
Microb Cell Fact ; 23(1): 64, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38402158

RESUMO

Phosphate solubilizing fungi Penicillium oxalicum (POX) and Red yeast Rhodotorula mucilaginosa (Rho) have been applied in Pb remediation with the combination of fluorapatite (FAp), respectively. The secretion of oxalic acid by POX and the production of extracellular polymers (EPS) by Rho dominate the Pb remediation. In this study, the potential of Pb remediation by the fungal combined system (POX and Rho) with FAp was investigated. After six days of incubation, the combination of POX and Rho showed the highest Pb remove ratio (99.7%) and the lowest TCLP-Pb concentration (2.9 mg/L). The EPS combined with POX also enhanced Pb remediation, which has a 99.3% Pb removal ratio and 5.5 mg/L TCLP-Pb concentration. Meanwhile, Rho and EPS can also stimulate POX to secrete more oxalic acid, which reached 1510.1 and 1450.6 mg/L in six days, respectively. The secreted oxalic acid can promote FAp dissolution and the formation of lead oxalate and pyromorphite. Meanwhile, the EPS produced by Rho can combine with Pb to form EPS-Pb. In the combined system of POX + Rho and POX + EPS, all of the lead oxalate, pyromorphite, and EPS-Pb were observed. Our findings suggest that the combined application of POX and Rho with FAp is an effective approach for enhancing Pb remediation.


Assuntos
Apatitas , Produtos Biológicos , Minerais , Penicillium , Chumbo , Fosfatos , Ácido Oxálico
6.
Phys Chem Chem Phys ; 26(19): 14364-14373, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38712391

RESUMO

Using density functional theory calculations we investigate the formation, structure and electronic properties of gh-C3N4-supported Ni-Co (Ni-Co/gh-C3N4) dual-atom catalysts and Ni1(Co1) single-metal catalysts, as a paradigmatic example of single-atom versus few-atom catalysts. An inverted mold assumption is proposed to identify the factors determining the number, shape and packing manner of metal atoms inside the pores of gh-C3N4. The area matching between virtual fragments and metal fillers and lattice inheritance from N coordination and metal aggregates allow for a stable Ni-Co/gh-C3N4, which would possess more active sites and a more complex structure-activity relation than single-atom doping. The hydrogen production behavior and catalytic activity of this catalyst are comprehensively discussed. Ni-Co/gh-C3N4 exhibits higher hydrogen evolution activity than Ni1(Co1)/gh-C3N4 at an appropriate H coverage, which is comparable to Pt under analogous conditions. This strategy, derived from the inverted mold assumption, is deemed to be a simple and easy-to-operate method for designing and building metal aggregates confined inside the pores of two-dimensional materials and in the cavities of nanoparticles for few-atom catalysts.

7.
Appl Microbiol Biotechnol ; 108(1): 289, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587649

RESUMO

Rumen microbial urease inhibitors have been proposed for regulating nitrogen emission and improving nitrogen utilization efficiency in ruminant livestock industry. However, studies on plant-derived natural inhibitors of rumen microbial urease are limited. Urease accessory protein UreG, plays a crucial role in facilitating urease maturation, is a new target for design of urease inhibitor. The objective of this study was to select the potential effective inhibitor of rumen microbial urease from major protoberberine alkaloids in Rhizoma Coptidis by targeting UreG. Our results showed that berberine chloride and epiberberine exerted superior inhibition potential than other alkaloids based on GTPase activity study of UreG. Berberine chloride inhibition of UreG was mixed type, while inhibition kinetics type of epiberberine was uncompetitive. Furthermore, epiberberine was found to be more effective than berberine chloride in inhibiting the combination of nickel towards UreG and inducing changes in the second structure of UreG. Molecular modeling provided the rational structural basis for the higher inhibition potential of epiberberine, amino acid residues in G1 motif and G3 motif of UreG formed interactions with D ring of berberine chloride, while interacted with A ring and D ring of epiberberine. We further demonstrated the efficacy of epiberberine in the ruminal microbial fermentation with low ammonia release and urea degradation. In conclusion, our study clearly indicates that epiberberine is a promising candidate as a safe and effective inhibitor of rumen microbial urease and provides an optimal strategy and suitable feed additive for regulating nitrogen excretion in ruminants in the future. KEY POINTS: • Epiberberine is the most effective inhibitor of rumen urease from Rhizoma Coptidis. • Urease accessory protein UreG is an effective target for design of urease inhibitor. • Epiberberine may be used as natural feed additive to reducing NH3 release in ruminants.


Assuntos
Berberina , Berberina/análogos & derivados , Animais , Berberina/farmacologia , Urease , Amônia , Cloretos , Rúmen , Inibidores Enzimáticos/farmacologia , Nitrogênio , Ruminantes
8.
J Nanobiotechnology ; 22(1): 414, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39010059

RESUMO

Staphylococcus aureus (SA) poses a serious risk to human and animal health, necessitating a low-cost and high-performance analytical platform for point-of-care diagnostics. Cellulose paper-based field-effect transistors (FETs) with RNA-cleaving DNAzymes (RCDs) can fulfill the low-cost requirements, however, its high hydrophilicity and lipophilicity hinder biochemical modification and result in low sensitivity, poor mechanical stability and poor fouling performance. Herein, we proposed a controllable self-cleaning FET to simplify biochemical modification and improve mechanical stability and antifouling performance. Then, we constructed an RCD-based DNA nanotree to significantly enhance the sensitivity for SA detection. For controllable self-cleaning FET, 1 H,1 H,2 H,2 H-perfluorodecyltrimethoxysilane based-polymeric nanoparticles were synthesized to decorate cellulose paper and whole carbon nanofilm wires. O2 plasma was applied to regulate to reduce fluorocarbon chain density, and then control the hydrophobic-oleophobic property in sensitive areas. Because negatively charged DNA affected the sensitivity of semiconducting FETs, three Y-shaped branches with low-cost were designed and applied to synthesize an RCD-based DNA-Nanotree based on similar DNA-origami technology, which further improved the sensitivity. The trunk of DNA-Nanotree was composed of RCD, and the canopy was self-assembled using multiple Y-shaped branches. The controllable self-cleaning FET biosensor was applied for SA detection without cultivation, which had a wide linear range from 1 to 105 CFU/mL and could detect a low value of 1 CFU/mL.


Assuntos
Técnicas Biossensoriais , DNA Catalítico , Staphylococcus aureus , DNA Catalítico/química , DNA Catalítico/metabolismo , Técnicas Biossensoriais/métodos , Transistores Eletrônicos , RNA/metabolismo , Limite de Detecção , Celulose/química , Papel , Nanopartículas/química , Humanos
9.
Clin Exp Pharmacol Physiol ; 51(4): e13848, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38423007

RESUMO

In this research, we aimed to observe the changes in myocardial fibrosis indices in patients with chronic heart failure before and after treatment and to evaluate the anti-chronic heart failure and ventricular remodelling effects of Trichosanthis peel (TP) injection. This study was a single-center, open, single-blind, randomized controlled study with an optimal efficacy design. Patients were consecutively and randomly divided into two groups, with 36 patients in the TP injection group and 36 patients in the conventional treatment group. ELISA was used to measure changes in myocardial fibrosis indices before and after discharge, including transforming growth factor ß (TGF-ß), serum hyaluronic acid (HA), type I procollagen (PCI), laminin (LN) and type III procollagen (PCIII). There was no significant difference between the two groups in clinical data or baseline level of myocardial fibrosis before treatment. After treatment, compared with the conventional treatment group, the myocardial fibrosis index was significantly decreased following TP injection. Our findings indicate that TP injection combined with conventional medicine can attenuate myocardial fibrosis by reducing angiotensin II, aldosterone, TGFß, HA, PCI, metallomatrix proteinase 2, connective tissue growth factor and LN and promote ventricular remodelling in patients with chronic heart failure.


Assuntos
Líquidos Corporais , Insuficiência Cardíaca , Humanos , Método Simples-Cego , Remodelação Ventricular , Insuficiência Cardíaca/tratamento farmacológico , Angiotensina II , Doença Crônica
10.
Oral Dis ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38696357

RESUMO

OBJECTIVE: This study aimed to clarify the relationship between FADD amplification and overexpression and the tumor immune microenvironment. METHODS: Immunohistochemical staining and bioanalysis were used to analyze the association between FADD expression in tumor cells and cells in tumor microenvironment. RNA-seq analysis was used to detect the differences in gene expression upon FADD overexpression. Flow cytometry and multicolor immunofluorescence staining (mIHC) were used to detect the differences in CD8+ T-cell infiltration in FADD-overexpressed cells or tumor tissues. RESULTS: Overexpression of FADD significantly promoted tumor growth. Cells with high FADD expression presented high expression of CD276 and FGFBP1 and low expression of proinflammatory factors (such as IFIT1-3 and CXCL8), which reduced the percentage of CD8+ T cells and created a "cold tumor" immune microenvironment, thus promoting tumor progression. In vivo and in vitro experiment confirmed that tumor tissues with excessive FADD expression exhibited CD8+ T-cell exclusion in the microenvironment. CONCLUSION: Our preliminary investigation has discovered the association between FADD expression and the immunosuppressive microenvironment in HNSCC. Due to the high frequent amplification of the chromosomal region 11q13.3, where FADD is located, targeting FADD holds promise for improving the immune-inactive state of tumors, subsequently inhibiting HNSCC tumor progression.

11.
Nanomedicine ; 55: 102723, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38007064

RESUMO

OBJECTIVE: Osteoarthritis (OA) is characterized by progressive cartilage degeneration and absence of curative therapies. Therefore, more efficient therapies are compellingly needed. Both mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) and Icariin (ICA) are promising for repair of cartilage defect. This study proposes that ICA may be combined to potentiate the cartilage repair capacity of MSC-EVs. MATERIALS AND METHODS: MSC-EVs were isolated from sodium alginate (SA) and hyaluronic acid (HA) composite hydrogel (SA-HA) cell spheroid culture. EVs and ICA were combined in SA-HA hydrogel to test therapeutic efficacy on cartilage defect in vivo. RESULTS: EVs and ICA were synergistic for promoting both proliferation and migration of MSCs and inflammatory chondrocytes. The combination therapy led to strikingly enhanced repair on cartilage defect in rats, with mechanisms involved in the concomitant modulation of both cartilage degradation and synthesis makers. CONCLUSION: The MSC-EVs-ICA/SA-HA hydrogel potentially constitutes a novel therapy for cartilage defect in OA.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , Osteoartrite , Animais , Ratos , Hidrogéis/farmacologia , Ácido Hialurônico/farmacologia , Ácido Hialurônico/metabolismo , Cartilagem , Condrócitos/metabolismo , Osteoartrite/tratamento farmacológico , Regeneração , Vesículas Extracelulares/metabolismo
12.
Artigo em Inglês | MEDLINE | ID: mdl-39010846

RESUMO

This study investigates the role of lactate in the genesis and progression of ovarian cancer (OV) and explores the underlying mechanisms. Serum lactate levels show a positive correlation with tumor grade and poor prognosis in patients with OV. Bioinformatics analysis identifies CCL18 as a lactate-related gene in OV. CCL18 is up-regulated in cancerous tissues and positively related to serum lactate levels in OV patients. THP-1 cells are exposed to phorbol-12-myristate-13-acetate for M0 macrophage induction. The results of RT-qPCR and ELISA for M1/M2 macrophage-related markers and inflammatory cytokines show that the exposure of lactate to macrophages induces M2 polarization. Based on the coculture of OV cells with macrophages, lactate-treated macrophages induces a significant increase in the proliferation and migration of OV cells. However, these effects can be reversed by silencing of Gpr132 in macrophages or treatment with anti-CCL18 antibody. Experiments using the xenograft model verify that the oncogenic role of lactate in tumor growth and metastasis relies on Gpr132 and CCL18. ChIP-qPCR and luciferase reporter assays reveal that lactate regulates CCL18 expression via H3K18 lactylation. In conclusion, lactate is a potential therapeutic target for OV. It is involved in tumorigenesis by activating CCL18 expression via H3K18 lactylation in macrophages.

13.
Ecotoxicol Environ Saf ; 269: 115835, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38100850

RESUMO

Implementing an external magnetic field of suitable strength has been reported to increase Cd uptake by Noccaea caerulescence. However, only a few mechanisms promoting this efficiency have been reported. A series of culture experiments was conducted to explore how Cd subcellular distribution and speciation vary within the tissue of N. caerulescens when subjected to external magnetic fields of different intensities. Without a magnetic field, over 80% of the Cd was deposited in the cell wall and cytoplasm, indicating that cell wall retention and cytoplasm isolation are significant mechanisms for the detoxification of Cd. An external magnetic field (120 mT) increased the Cd concentrations deposited in the cytoplasm and water-soluble inorganic Cd in the roots, increasing the cell wall-bound Cd and undissolved Cd phosphate in the shoots. Meanwhile, the magnetic field increased carbonic anhydrase activity in plant shoots, except at 400 mT. These results indicated that an external field can elevate the Cd decontamination capacity of N. caerulescens by changing the subcellular compartmentalization and speciation of Cd in different tissues.


Assuntos
Brassicaceae , Poluentes do Solo , Cádmio/análise , Biodegradação Ambiental , Poluentes do Solo/análise , Campos Magnéticos , Raízes de Plantas/química
14.
Ecotoxicol Environ Saf ; 277: 116376, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38657453

RESUMO

The application of an external magnetic field has been shown to improve the Cd phytoremediation efficiency of F. arundinacea by leaf harvesting. However, the influencing mechanisms of the promoting effect have not yet been revealed. This study evaluated variations in the Cd subcellular allocation and fractions in various F. arundinacea leaves, with or without magnetized water irrigation. Over 50 % of the metal were sequestered within the cell wall in all tissues under all treatments, indicating that cell wall binding was a critical detoxification pathway for Cd. After magnetized water treatment, the metal stored in the cytoplasm of roots raised from 33.1 % to 45.3 %, and the quantity of soluble Cd in plant roots enhanced from 53.4 % to 59.0 %. The findings suggested that magnetized water mobilized Cd in the roots, and thus drove it into the leaves. In addition, the proportion of Cd in the organelles, and the concentration of ethanol-extracted Cd in emerging leaves, decreased by 13.0 % and 47.1 %, respectively, after magnetized water treatment. These results explained why an external field improved the phytoextraction effect of the plant through leaf harvesting.


Assuntos
Biodegradação Ambiental , Cádmio , Festuca , Folhas de Planta , Raízes de Plantas , Folhas de Planta/metabolismo , Cádmio/toxicidade , Cádmio/metabolismo , Raízes de Plantas/metabolismo , Festuca/metabolismo , Festuca/efeitos dos fármacos , Irrigação Agrícola/métodos , Poluentes do Solo/metabolismo , Poluentes do Solo/toxicidade , Água/química
15.
J Asian Nat Prod Res ; 26(9): 1033-1040, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38835269

RESUMO

Phytochemical studies on cigar tobacco leaves led to the isolation of 18 ionone-type compounds, including previously undescribed cigatobanes E (1) and F (2). Additionally, compounds vomifoliol acetate (3), dehydrovomifoliol (4), 8,9-dihydromegastigmane-4,6-diene-3-one (5), 7α,8α-epoxyblumenol B (6), 3-oxoactinidol (12), and loliolide acetate (15), 4ß-hydroxy-dihydroactinidiolide (17), were found in tobacco leaves for the first time. The structural elucidation of all compounds was accomplished through rigorous spectral analysis.


Assuntos
Nicotiana , Folhas de Planta , Folhas de Planta/química , Estrutura Molecular , Nicotiana/química , Norisoprenoides/química
16.
Women Health ; 64(5): 440-449, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38755523

RESUMO

Female-specific reproductive factors might contribute to increased risk of cardiovascular disease, and the American Heart Association (AHA) recently proposed Life's Essential 8 (LE8) score to quantify cardiovascular health (CVH). The study aimed to examine the relationships between reproductive factors and the LE8 score among post-menopause women in the United States. We enrolled 3223 post-menopause women from National Health and Nutrition Examination Survey (NHANES). CVH groups based on LE8 score were low (0-49), moderate (50-79), and high good CVH levels (80-100). Multivariate ordinal logistic regressions were applied to estimate the associations between reproductive factors and the LE8 score. In multivariate model, early menarche (OR: 0.69, 95 percent CI: 0.51-0.93) and early menopause (OR: 0.57, 95 percent CI: 0.43-0.77) were associated with LE8 score compared with normal menarche and menopause; Meanwhile, ages at menarche and menopause were positively correlated with LE8 score. The number of pregnancies and full-term pregnancies were negatively associated with LE8 (OR for per pregnancy increase and 95 percent CI, 0.93 (0.88, 0.98), 0.93 (0.87, 0.99), separately). Overall, natural menopausal women with early age at menarche and menopause, and a higher number of pregnancies may have a high risk of lower CVH, and need to focus on their CVH.


Assuntos
Doenças Cardiovasculares , Menarca , Menopausa , Inquéritos Nutricionais , Pós-Menopausa , Humanos , Feminino , Pessoa de Meia-Idade , Doenças Cardiovasculares/epidemiologia , Pós-Menopausa/fisiologia , Estados Unidos/epidemiologia , Menopausa/fisiologia , Fatores de Risco , Idoso , Estudos Transversais , História Reprodutiva , Gravidez , Modelos Logísticos , Fatores Etários
17.
Int J Mol Sci ; 25(4)2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38396677

RESUMO

Urokinase plasminogen activator receptor (uPAR) encoded by the PLAUR gene is known as a clinical marker for cell invasiveness in glioblastoma multiforme (GBM). It is additionally implicated in various processes, including angiogenesis and inflammation within the tumor microenvironment. However, there has not been a comprehensive study that depicts the overall functions and molecular cooperators of PLAUR with respect to intra-tumoral subtypes of GBM. Using single-cell RNA sequencing data from 37 GBM patients, we identified PLAUR as a marker gene for two distinct subtypes in GBM. One subtype is featured by inflammatory activities and the other subtype is marked by ECM remodeling processes. Using the whole-transcriptome data from single cells, we are able to uncover the molecular cooperators of PLAUR for both subtypes without presuming biological pathways. Two protein networks comprise the molecular context of PLAUR, with each of the two subtypes characterized by a different dominant network. We concluded that targeting PLAUR directly influences the mechanisms represented by these two protein networks, regardless of the subtype of the targeted cell.


Assuntos
Glioblastoma , Receptores de Ativador de Plasminogênio Tipo Uroquinase , Humanos , Glioblastoma/metabolismo , Receptores de Ativador de Plasminogênio Tipo Uroquinase/genética , Receptores de Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Análise de Sequência de RNA , Transdução de Sinais , Microambiente Tumoral/genética , Análise da Expressão Gênica de Célula Única , Biomarcadores Tumorais
18.
Entropy (Basel) ; 26(7)2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-39056950

RESUMO

Graph representation learning aims to map nodes or edges within a graph using low-dimensional vectors, while preserving as much topological information as possible. During past decades, numerous algorithms for graph representation learning have emerged. Among them, proximity matrix representation methods have been shown to exhibit excellent performance in experiments and scale to large graphs with millions of nodes. However, with the rapid development of the Internet, information interactions are happening at the scale of billions every moment. Most methods for similarity matrix factorization still focus on static graphs, leading to incomplete similarity descriptions and low embedding quality. To enhance the embedding quality of temporal graph learning, we propose a temporal graph representation learning model based on the matrix factorization of Time-constrained Personalize PageRank (TPPR) matrices. TPPR, an extension of personalized PageRank (PPR) that incorporates temporal information, better captures node similarities in temporal graphs. Based on this, we use Single Value Decomposition or Nonnegative Matrix Factorization to decompose TPPR matrices to obtain embedding vectors for each node. Through experiments on tasks such as link prediction, node classification, and node clustering across multiple temporal graphs, as well as a comparison with various experimental methods, we find that graph representation learning algorithms based on TPPR matrix factorization achieve overall outstanding scores on multiple temporal datasets, highlighting their effectiveness.

19.
Apoptosis ; 28(7-8): 1060-1075, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37060507

RESUMO

The aberrantly up-regulated CDK9 can be targeted for cancer therapy. The CDK inhibitor dinaciclib (Dina) has been found to drastically sensitizes cancer response to TRAIL-expressing extracellular vesicle (EV-T). However, the low selectivity of Dina has limited its application for cancer. We propose that CDK9-targeted siRNA (siCDK9) may be a good alternative to Dina. The siCDK9 molecules were encapsulated into EV-Ts to prepare a complexed nanodrug (siEV-T). It was shown to efficiently suppress CDK9 expression and overcome TRAIL resistance to induce strikingly augmented apoptosis in lung cancer both in vitro and in vivo, with a mechanism related to suppression of both anti-apoptotic factors and nuclear factor-kappa B pathway. Therefore, siEV-T potentially constitutes a novel, highly effective and safe therapy for cancers.


Assuntos
Neoplasias Pulmonares , NF-kappa B , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , Apoptose , Linhagem Celular Tumoral , RNA Interferente Pequeno/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/genética , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genética , Quinase 9 Dependente de Ciclina/genética
20.
Anal Chem ; 95(6): 3507-3515, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36724388

RESUMO

ATP and reactive oxygen species (ROS) are considered significant indicators of cell apoptosis. However, visualizing the interplay between apoptosis-related ATP and ROS is challenging. Herein, we developed a metal-organic framework (MOF)-based nanoprobe for an apoptosis assay using duplex imaging of cellular ATP and ROS. The nanoprobe was fabricated through controlled encapsulation of gold nanorods with a thin zirconium-based MOF layer, followed by modification of the ROS-responsive molecules 2-mercaptohydroquinone and 6-carboxyfluorescein-labeled ATP aptamer. The nanoprobe enables ATP and ROS visualization via fluorescence and surface-enhanced Raman spectroscopy, respectively, avoiding the mutual interference that often occurs in single-mode methods. Moreover, the dual-modal assay effectively showed dynamic imaging of ATP and ROS in cancer cells treated with various drugs, revealing their apoptosis-related pathways and interactions that differ from those under normal conditions. This study provides a method for studying the relationship between energy metabolism and redox homeostasis in cell apoptosis processes.


Assuntos
Apoptose , Ouro , Espécies Reativas de Oxigênio/metabolismo , Ouro/química , Trifosfato de Adenosina
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