Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 600
Filtrar
1.
BMC Cancer ; 24(1): 572, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720306

RESUMO

BACKGROUND: Postoperative central diabetes insipidus (CDI) is commonly observed in craniopharyngioma (CP) patients, and the inflammatory response plays an important role in CPs. We aimed to evaluate the predictive value of preoperative peripheral inflammatory markers and their combinations regarding CDI occurrence in CPs. METHODS: The clinical data including preoperative peripheral inflammatory markers of 208 CP patients who underwent surgical treatment were retrospectively collected and analyzed. The preoperative peripheral white blood cells (WBC), neutrophils, lymphocytes, monocytes, platelet (PLT), neutrophil-to-lymphocyte ratio (NLR), derived-NLR (dNLR), monocyte-to-lymphocyte ratio (MLR) and PLT-to-lymphocyte ratio (PLR) were assessed in total 208 CP patients and different age and surgical approach CP patient subgroups. Their predictive values were evaluated by the receiver operator characteristic curve analysis. RESULTS: Preoperative peripheral WBC, neutrophils, NLR, dNLR, MLR, and PLR were positively correlated and lymphocyte was negatively associated with postoperative CDI occurrence in CP patients, especially when WBC ≥ 6.66 × 109/L or lymphocyte ≤ 1.86 × 109/L. Meanwhile, multiple logistic regression analysis showed that WBC > 6.39 × 109/L in the > 18 yrs age patients, WBC > 6.88 × 109/L or lymphocytes ≤ 1.85 × 109/L in the transcranial approach patients were closely associated with the elevated incidence of postoperative CDI. Furthermore, the area under the curve obtained from the receiver operator characteristic curve analysis showed that the best predictors of inflammatory markers were the NLR in total CP patients, the MLR in the ≤ 18 yrs age group and the transsphenoidal group, the NLR in the > 18 yrs age group and the dNLR in the transcranial group. Notably, the combination index NLR + dNLR demonstrated the most valuable predictor in all groups. CONCLUSIONS: Preoperative peripheral inflammatory markers, especially WBC, lymphocytes and NLR + dNLR, are promising predictors of postoperative CDI in CPs.


Assuntos
Craniofaringioma , Diabetes Insípido Neurogênico , Neoplasias Hipofisárias , Complicações Pós-Operatórias , Humanos , Craniofaringioma/cirurgia , Craniofaringioma/sangue , Craniofaringioma/complicações , Feminino , Masculino , Estudos Retrospectivos , Adulto , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/complicações , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico , Adolescente , Pessoa de Meia-Idade , Criança , Adulto Jovem , Diabetes Insípido Neurogênico/sangue , Diabetes Insípido Neurogênico/etiologia , Neutrófilos , Biomarcadores/sangue , Linfócitos , Inflamação/sangue , Contagem de Leucócitos , Período Pré-Operatório , Pré-Escolar , Prognóstico , Curva ROC
2.
Aging (Albany NY) ; 162024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38771130

RESUMO

Immunotherapy has been a remarkable clinical advancement in cancer treatment, but only a few patients benefit from it. Metabolic reprogramming is tightly associated with immunotherapy efficacy and clinical outcomes. However, comprehensively analyzing their relationship is still lacking in lung adenocarcinoma (LUAD). Herein, we evaluated 84 metabolic pathways in TCGA-LUAD by ssGSEA. A matrix of metabolic pathway pairs was generated and a metabolic pathway-pair score (MPPS) model was established by univariable, LASSO, multivariable Cox regression analyses. The differences of metabolic reprogramming, tumor microenvironment (TME), tumor mutation burden and drug sensitivity in different MPPS groups were further explored. WGCNA and 117 machine learning algorithms were performed to identify MPPS-related genes. Single-cell RNA sequencing and in vitro experiments were used to explore the role of C1QTNF6 on TME. The results showed MPPS model accurately predicted prognosis and immunotherapy efficacy of LUAD patients regardless of sequencing platforms. High-MPPS group had worse prognosis, immunotherapy efficacy and lower immune cells infiltration, immune-related genes expression and cancer-immunity cycle scores than low-MPPS group. Seven MPPS-related genes were identified, of which C1QTNF6 was mainly expressed in fibroblasts. High C1QTNF6 expression in fibroblasts was associated with more infiltration of M2 macrophage, Treg cells and less infiltration of NK cells, memory CD8+ T cells. In vitro experiments validated silencing C1QTNF6 in fibroblasts could inhibit M2 macrophage polarization and migration. The study depicted the metabolic landscape of LUAD and constructed a MPPS model to accurately predict prognosis and immunotherapy efficacy. C1QTNF6 was a promising target to regulate M2 macrophage polarization and migration.

3.
Cell Death Dis ; 15(5): 335, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744853

RESUMO

PTENα/ß, two variants of PTEN, play a key role in promoting tumor growth by interacting with WDR5 through their N-terminal extensions (NTEs). This interaction facilitates the recruitment of the SET1/MLL methyltransferase complex, resulting in histone H3K4 trimethylation and upregulation of oncogenes such as NOTCH3, which in turn promotes tumor growth. However, the molecular mechanism underlying this interaction has remained elusive. In this study, we determined the first crystal structure of PTENα-NTE in complex with WDR5, which reveals that PTENα utilizes a unique binding motif of a sequence SSSRRSS found in the NTE domain of PTENα/ß to specifically bind to the WIN site of WDR5. Disruption of this interaction significantly impedes cell proliferation and tumor growth, highlighting the potential of the WIN site inhibitors of WDR5 as a way of therapeutic intervention of the PTENα/ß associated cancers. These findings not only shed light on the important role of the PTENα/ß-WDR5 interaction in carcinogenesis, but also present a promising avenue for developing cancer treatments that target this pathway.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular , PTEN Fosfo-Hidrolase , PTEN Fosfo-Hidrolase/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/química , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/química , Animais , Camundongos , Neoplasias/genética , Neoplasias/patologia , Neoplasias/metabolismo , Proliferação de Células/genética , Progressão da Doença , Ligação Proteica , Linhagem Celular Tumoral , Camundongos Nus , Histona-Lisina N-Metiltransferase/metabolismo , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/química , Domínios Proteicos , Motivos de Aminoácidos
4.
Plant Cell ; 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38581430

RESUMO

Lateral branches are important components of shoot architecture and directly affect crop yield and production cost. Although sporadic studies have implicated abscisic acid (ABA) biosynthesis in axillary bud outgrowth, the function of ABA catabolism and its upstream regulators in shoot branching remain elusive. Here, we showed that the MADS-box transcription factor AGAMOUS-LIKE 16 (CsAGL16) is a positive regulator of axillary bud outgrowth in cucumber (Cucumis sativus). Functional disruption of CsAGL16 led to reduced bud outgrowth, whereas overexpression of CsAGL16 resulted in enhanced branching. CsAGL16 directly binds to the promoter of the ABA 8'-hydroxylase gene CsCYP707A4 and promotes its expression. Loss of CsCYP707A4 function inhibited axillary bud outgrowth and increased ABA levels. Elevated expression of CsCYP707A4 or treatment with an ABA biosynthesis inhibitor largely rescued the Csagl16 mutant phenotype. Moreover, cucumber General Regulatory Factor 1 (CsGRF1) interacts with CsAGL16 and antagonizes CsAGL16-mediated CsCYP707A4 activation. Disruption of CsGRF1 resulted in elongated branches and decreased ABA levels in the axillary buds. The Csagl16 Csgrf1 double mutant exhibited a branching phenotype resembling that of the Csagl16 single mutant. Therefore, our data suggest that the CsAGL16-CsGRF1 module regulates axillary bud outgrowth via CsCYP707A4-mediated ABA catabolism in cucumber. Our findings provide a strategy to manipulate ABA levels in axillary buds during crop breeding to produce desirable branching phenotypes.

5.
Oncogene ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654107

RESUMO

Lung adenocarcinoma is a malignant tumor with high morbidity and mortality. ZBTB16 plays a double role in various tumors; however, the potential mechanism of ZBTB16 in the pathophysiology of lung adenocarcinoma has yet to be elucidated. We herein observed a decreased expression of ZBTB16 mRNA and protein in lung adenocarcinoma and a significantly increased DNA methylation level of ZBTB16 in patients with lung adenocarcinoma. Analysis of public databases and patients' clinical data indicated a close association between ZBTB16 and patient survival. Ectopic expression of ZBTB16 in lung adenocarcinoma cells significantly inhibited cell proliferation, invasion, and migration. It also induced cell cycle arrest in the S phase. Meanwhile, mitotic catastrophe was induced, and DNA damage and apoptosis occurred. In line with these findings, the overexpression of ZBTB16 in xenograft mice resulted in the inhibition of tumor growth. Comprehensive analysis showed that WDHD1 was a potential target for ZBTB16. The overexpression of both isoforms of WDHD1 significantly reversed the ZBTB16-mediated inhibition of lung adenocarcinoma proliferation and cell cycle. These studies suggest that ZBTB16 impedes the progression of lung adenocarcinoma by interfering with WDHD1 transcription, making it a potential novel therapeutic target in the management of lung adenocarcinoma.

6.
Environ Int ; 187: 108689, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38688236

RESUMO

Endocrine-disrupting chemicals (EDCs) are ubiquitous in ecological environments and have become a great issue of public health concern since the 1990 s. There is a deep scientific understanding of the toxicity of EDCs. However, recent studies have found that the abnormal physiological functions of the parents caused by EDCs could be transmitted to their unexposed offspring, leading to intergenerational toxicity. We questioned whether sustained epigenetic changes occur through the male germline. In this review, we (1) systematically searched the available research on the intergenerational impacts of EDCs in aquatic and mammal organisms, including 42 articles, (2) summarized the intergenerational genetic effects, such as decreased offspring survival, abnormal reproductive dysfunction, metabolic disorders, and behavioral abnormalities, (3) summarized the mechanisms of intergenerational toxicity through paternal interactions, and (4) propose suggestions on future research directions to develop a deeper understanding of the ecological risk of EDCs.


Assuntos
Disruptores Endócrinos , Epigênese Genética , Exposição Paterna , Disruptores Endócrinos/toxicidade , Epigênese Genética/efeitos dos fármacos , Exposição Paterna/efeitos adversos , Animais , Masculino , Humanos , Reprodução/efeitos dos fármacos , Feminino , Poluentes Ambientais/toxicidade
7.
Nat Commun ; 15(1): 3172, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609373

RESUMO

Hydrotreating renewable oils over sulfided metal catalysts is commercially applied to produce green diesel, but it requires a continuous sulfur replenishment to maintain catalyst activity, which inevitably results in sulfur contamination and increases production costs. We report a robust P-doped NiAl-oxide catalyst with frustrated Lewis pairs (i.e., P atom bonded with the O atom acts as an electron donor, while the spatially separated Ni atom acts as an electron acceptor) that allows efficient green diesel production without sulfur replenishment. The catalyst runs more than 500 h at a weight hourly space velocity (WHSV) of 28.3 h-1 without deactivation (methyl laurate as a model compound), and is able to completely convert a real feedstock of soybean oil to diesel-range hydrocarbons with selectivity >90% during 500 h of operation. This work is expected to open up a new avenue for designing non-sulfur catalysts that can make the green diesel production greener.

8.
Genes (Basel) ; 15(4)2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38674409

RESUMO

The wheat head blight disease caused by Fusarium graminearum is a major concern for food security and the health of both humans and animals. As a pathogenic microorganism, F. graminearum produces virulence factors during infection to increase pathogenicity, including various macromolecular and small molecular compounds. Among these virulence factors, secreted proteins and deoxynivalenol (DON) are important weapons for the expansion and colonization of F. graminearum. Besides the presence of virulence factors, sexual reproduction is also crucial for the infection process of F. graminearum and is indispensable for the emergence and spread of wheat head blight. Over the last ten years, there have been notable breakthroughs in researching the virulence factors and sexual reproduction of F. graminearum. This review aims to analyze the research progress of sexual reproduction, secreted proteins, and DON of F. graminearum, emphasizing the regulation of sexual reproduction and DON synthesis. We also discuss the application of new gene engineering technologies in the prevention and control of wheat head blight.


Assuntos
Fusarium , Doenças das Plantas , Tricotecenos , Triticum , Fusarium/genética , Fusarium/patogenicidade , Fusarium/metabolismo , Tricotecenos/metabolismo , Triticum/microbiologia , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Fatores de Virulência/genética , Regulação Fúngica da Expressão Gênica , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Virulência/genética , Reprodução/genética
9.
J Proteome Res ; 23(5): 1571-1582, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38594959

RESUMO

Reproducibility is a "proteomic dream" yet to be fully realized. A typical data analysis workflow utilizing extracted ion chromatograms (XICs) often treats the information path from identification to quantification as a one-way street. Here, we propose an XIC-centric approach in which the data flow is bidirectional: identifications are used to derive XICs whose information is in turn applied to validate the identifications. In this study, we employed liquid chromatography-mass spectrometry data from glycoprotein and human hair samples to illustrate the XIC-centric concept. At the core of this approach was XIC-based monoisotope repicking. Taking advantage of the intensity information for all detected isotopes across the whole range of an XIC peak significantly improved the accuracy and uncovered misidentifications originating from monoisotope assignment mistakes. It could also rescue non-top-ranked glycopeptide hits. Identification of glycopeptides is particularly susceptible to precursor mass errors for their low abundances, large masses, and glycans differing by 1 or 2 Da easily confused as isotopes. In addition, the XIC-centric strategy significantly reduced the problem of one XIC peak associated with multiple unique identifications, a source of quantitative irreproducibility. Taken together, the proposed approach can lead to improved identification and quantification accuracy and, ultimately, enhanced reproducibility in proteomic data analyses.


Assuntos
Cabelo , Proteômica , Proteômica/métodos , Humanos , Cromatografia Líquida/métodos , Cabelo/química , Reprodutibilidade dos Testes , Glicoproteínas/análise , Glicoproteínas/química , Glicopeptídeos/análise , Glicopeptídeos/química , Análise de Dados , Espectrometria de Massas/métodos , Espectrometria de Massas em Tandem/métodos
10.
Angew Chem Int Ed Engl ; 63(17): e202318800, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38443316

RESUMO

Organic small-molecule fluorophores, characterized by flexible chemical structure and adjustable optical performance, have shown tremendous potential in biosensing. However, classical organic fluorophore motifs feature large overlap between excitation and emission spectra, leading to the requirement of advanced optical set up to filter desired signal, which limits their application in scenarios with simple settings. Here, a series of wavelength-tunable small-molecule fluorescent dyes (PTs) bearing simple organic moieties have been developed, which exhibit Stokes shift up to 262 nm, molar extinction coefficients ranged 30,000-100,000 M-1 cm-1, with quantum yields up to 54.8 %. Furthermore, these dyes were formulated into fluorescent nanoparticles (PT-NPs), and applied in lateral flow assay (LFA). Consequently, limit of detection for SARS-CoV-2 nucleocapsid protein reached 20 fM with naked eye, a 100-fold improvement in sensitivity compared to the pM detection level for colloidal gold-based LFA. Besides, combined with loop-mediated isothermal amplification (LAMP), the LFA system achieved the visualization of single copy level nucleic acid detection for monkeypox (Mpox).


Assuntos
Nanopartículas , Ácidos Nucleicos , Corantes Fluorescentes/química , Nanopartículas/química , Técnicas de Amplificação de Ácido Nucleico
11.
Comput Biol Med ; 173: 108325, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38513389

RESUMO

Rapid discovery of target information for protein-protein interactions (PPIs) is significant in drug design, diagnostics, vaccine development, antibody therapy, etc. Peptide microarray is an ideal tool for revealing epitope information of PPIs. In this work, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) and the host cell receptor angiotensin-converting enzyme 2 (ACE2) were introduced as a model to study the epitope information of RBD-specific binding to ACE2 via a combination of theoretical calculations and experimental validation. Through dock and molecular dynamics simulations, it was found that among the 22 peptide fragments that consist of RBD, #14 (YNYLYRLFRKSNLKP) has the highest binding strength. Subsequently, the experiments of peptide microarray constructed based on plasmonic materials chip also confirmed the theoretical calculation data. Compared to other methods, such as phage display technology and surface plasmon resonance (SPR), this method is rapid and cost-effective, providing insights into the investigation of pathogen invasion processes and the timely development of peptide drugs and other fields.


Assuntos
Enzima de Conversão de Angiotensina 2 , Simulação de Dinâmica Molecular , Peptídeos , Desenho de Fármacos , Epitopos , SARS-CoV-2 , Ligação Proteica
12.
iScience ; 27(3): 109220, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38433921

RESUMO

LncRNA associated with immune cell infiltration in tumor microenvironment (TME) may be a potential therapeutic target for lung adenocarcinoma. We established a machine learning (ML) model based on 3896 samples characterized by the degree of immune cell infiltration, and further screened the key lncRNA. In vitro experiments were applied to validate the prediction. Treg is the key immune cell in the TME of lung adenocarcinoma, and the degree of infiltration is negatively correlated with the prognosis. PCBP1-AS1 may affect the infiltration of Tregs by regulating the TGF-ß pathway, which is a potential predictor of clinical response to immunotherapy. PCBP1-AS1 regulates cell proliferation, cell cycle, invasion, migration, and apoptosis in lung adenocarcinoma. The results of clinical sample staining and in vitro experiments showed that PCBP1-AS1 was negatively correlated with Treg infiltration and TGF-ß expression. Tregs and related lncRNA PCBP1-AS1 can be used as targets for the diagnosis and treatment of lung adenocarcinoma.

13.
Plants (Basel) ; 13(5)2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38475438

RESUMO

The vegetable plug seedling plays an important role in improving vegetable production. The process of plug seedling contributes to high-quality vegetable seedlings. The substrate composition and chemical fertilizer are widely studied to promote seedling growth. However, little is known about the effect of beneficial bacteria in the rhizosphere microbial community and vegetables' growth during plug seedling. The use of beneficial microbes to promote vegetable seedling growth is of great potential. In this study, we showed that the Serratia marcescens strain LYGN1 enhanced the growth of cucumber and pepper seedlings in plug seedling cultivation. The treatment with LYGN1 significantly increased the biomass and the growth-related index of cucumber and pepper, improving the seedling quality index. Specifically, LYGN1 also improved the cucumber and pepper root system architecture and increased the root diameter. We applied high-throughput sequencing to analyze the microbial community of the seedlings' rhizosphere, which showed LYGN1 to significantly change the composition and structure of the cucumber and pepper rhizosphere microbial communities. The correlation analysis showed that the Abditibacteriota and Bdellovibrionota had positive effects on seedling growth. The findings of this study provide evidence for the effects of Serratia marcescens LYGN1 on the cucumber and pepper rhizosphere microbial communities, which also promoted seedling quality in plug seedling cultivation.

14.
Cell Mol Life Sci ; 81(1): 128, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38472451

RESUMO

Epigenetic dysregulation that leads to alterations in gene expression and is suggested to be one of the key pathophysiological factors of Parkinson's disease (PD). Here, we found that α-synuclein preformed fibrils (PFFs) induced histone H3 dimethylation at lysine 9 (H3K9me2) and increased the euchromatic histone methyltransferases EHMT1 and EHMT2, which were accompanied by neuronal synaptic damage, including loss of synapses and diminished expression levels of synaptic-related proteins. Furthermore, the levels of H3K9me2 at promoters in genes that encode the synaptic-related proteins SNAP25, PSD95, Synapsin 1 and vGLUT1 were increased in primary neurons after PFF treatment, which suggests a linkage between H3K9 dimethylation and synaptic dysfunction. Inhibition of EHMT1/2 with the specific inhibitor A-366 or shRNA suppressed histone methylation and alleviated synaptic damage in primary neurons that were treated with PFFs. In addition, the synaptic damage and motor impairment in mice that were injected with PFFs were repressed by treatment with the EHMT1/2 inhibitor A-366. Thus, our findings reveal the role of histone H3 modification by EHMT1/2 in synaptic damage and motor impairment in a PFF animal model, suggesting the involvement of epigenetic dysregulation in PD pathogenesis.


Assuntos
Transtornos Motores , Doença de Parkinson , Animais , Camundongos , Histonas/metabolismo , Metilação , Neurônios/metabolismo , alfa-Sinucleína/metabolismo
15.
Sci Signal ; 17(829): eadk8249, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38530880

RESUMO

Mutations in the gene encoding the lysosomal enzyme glucocerebrosidase (GCase) are responsible for Gaucher disease (GD) and are considered the strongest genetic risk factor for Parkinson's disease (PD) and Lewy body dementia (LBD). GCase deficiency leads to extensive accumulation of glucosylceramides (GCs) in cells and contributes to the neuropathology of GD, PD, and LBD by triggering chronic neuroinflammation. Here, we investigated the mechanisms by which GC accumulation induces neuroinflammation. We found that GC accumulation within microglia induced by pharmacological inhibition of GCase triggered STING-dependent inflammation, which contributed to neuronal loss both in vitro and in vivo. GC accumulation in microglia induced mitochondrial DNA (mtDNA) leakage to the cytosol to trigger STING-dependent inflammation. Rapamycin, a compound that promotes lysosomal activity, improved mitochondrial function, thereby decreasing STING signaling. Furthermore, lysosomal damage caused by GC accumulation led to defects in the degradation of activated STING, further exacerbating inflammation mediated by microglia. Thus, limiting STING activity may be a strategy to suppress neuroinflammation caused by GCase deficiency.


Assuntos
Doença de Gaucher , Doença de Parkinson , Animais , Camundongos , alfa-Sinucleína/metabolismo , Doença de Gaucher/genética , Doença de Gaucher/patologia , Glucosilceramidas/metabolismo , Inflamação/metabolismo , Lisossomos/metabolismo , Microglia/metabolismo , Doenças Neuroinflamatórias , Doença de Parkinson/metabolismo
16.
J Proteome Res ; 23(4): 1443-1457, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38450643

RESUMO

We report the comparison of mass-spectral-based abundances of tryptic glycopeptides to fluorescence abundances of released labeled glycans and the effects of mass and charge state and in-source fragmentation on glycopeptide abundances. The primary glycoforms derived from Rituximab, NISTmAb, Evolocumab, and Infliximab were high-mannose and biantennary complex galactosylated and fucosylated N-glycans. Except for Evolocumab, in-source ions derived from the loss of HexNAc or HexNAc-Hex sugars are prominent for other therapeutic IgGs. After excluding in-source fragmentation of glycopeptide ions from the results, a linear correlation was observed between fluorescently labeled N-glycan and glycopeptide abundances over a dynamic range of 500. Different charge states of human IgG-derived glycopeptides containing a wider variety of abundant attached glycans were also investigated to examine the effects of the charge state on ion abundances. These revealed a linear dependence of glycopeptide abundance on the mass of the glycan with higher charge states favoring higher-mass glycans. Findings indicate that the mass spectrometry-based bottom-up approach can provide results as accurate as those of glycan release studies while revealing the origin of each attached glycan. These site-specific relative abundances are conveniently displayed and compared using previously described glycopeptide abundance distribution spectra "GADS" representations. Mass spectrometry data are available from the MAssIVE repository (MSV000093562).


Assuntos
Imunoglobulina G , Espectrometria de Massas em Tandem , Humanos , Glicosilação , Glicopeptídeos/análise , Polissacarídeos/química , Íons
17.
J Inflamm Res ; 17: 737-754, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38348277

RESUMO

Background: In recent years, the immunotherapy of lung adenocarcinoma has developed rapidly, but the good therapeutic effect only exists in some patients, and most of the current predictors cannot predict it very well. Tumor-infiltrating macrophages have been reported to play a crucial role in lung adenocarcinoma (LUAD). Thus, we want to build novel molecular markers based on macrophages. Methods: By non-negative matrix factorization (NMF) algorithm and Cox regression analysis, we constructed macrophage-related subtypes of LUAD patients and built a novel gene signature consisting of 12 differentially expressed genes between two subtypes. The gene signature was further validated in Gene-Expression Omnibus (GEO) datasets. Its predictive effect on prognosis and immunotherapy outcome was further evaluated with rounded analyses. We finally explore the role of TRIM28 in LUAD with a series of in vitro experiments. Results: Our research indicated that a higher LMS score was significantly correlated with tumor staging, pathological grade, tumor node metastasis stage, and survival. LMS was identified as an independent risk factor for OS in LUAD patients and verified in GEO datasets. Clinical response to immunotherapy was better in patients with low LMS score compared to those with high LMS score. TRIM28, a key gene in the gene signature, was shown to promote the proliferation, invasion and migration of LUAD cell. Conclusion: Our study highlights the significant role of gene signature in predicting the prognosis and immunotherapy efficacy of LUAD patients, and identifies TRIM28 as a potential biomarker for the treatment of LUAD.

18.
Small Methods ; 8(5): e2300910, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38415973

RESUMO

Rational morphology control of inorganic microarchitectures is important in diverse fields, requiring precise regulation of nucleation and growth processes. While wet chemical methods have achieved success regarding the shape-controlled synthesis of micro/nanostructures, accurately controlling the growth behavior in real time remains challenging. Comparatively, the electrodeposition technique can immediately control the growth behavior by tuning the overpotential, whereas it is rarely used to design complex microarchitectures. Here, the electrochemical design of complex Cu2O microarchitectures step-by-step by precisely controlling the growth behavior is demonstrated. The growth modes can be switched between the thermodynamic and kinetic modes by varying the overpotential. Cl- ions preferably adhered to {100} facets to modulate growth rates of these facets is proved. The discovered growth modes to prepare Cu2O microarchitectures composed of multiple building units inaccessible with existing methods are employed. Polyvinyl alcohol (PVA) additives can guarantee all pre-electrodeposits simultaneously evolve into uniform microarchitectures, instead of forming undesired microstructures on bare electrode surfaces in following electrodeposition processes is discovered. The designed Cu2O microarchitectures can be converted into noble metal microstructures with shapes unchanged, which can be used as surface-enhanced Raman scattering substrates. An electrochemical avenue toward rational design of complex inorganic microarchitectures is opened up.

19.
Artigo em Chinês | MEDLINE | ID: mdl-38297867

RESUMO

Objective:Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) play important roles in the poor prognosis of different inflammatory and neoplastic diseases, but their effects on postoperative recurrence of chronic rhinosinusitis(CRS) are unknown. The aim of this study was to investigate the correlation between preoperative NLR and PLR and the risk of postoperative recurrence in CRS. Methods:Clinical data were collected from patients with CRS who underwent initial functional endoscopic sinus surgery from October 2018 to February 2022 at our institution. Follow-up was until February 2023, and the study endpoint was defined as patient postoperative recurrence or follow-up time up to date. The optimal preoperative NLR and PLR threshold values were obtained based on subject work curve analysis, and they were divided into high and low level subgroups, respectively, and the clinical characteristics and postoperative recurrence rates of patients were compared between groups; patients were divided into non-recurrent CRS and recurrent CRS according to their postoperative recurrence, and Kaplan-Meier survival curves and logistic regression analysis were performed to explore the correlation between NLR and PLR and CRS The correlation between NLR and PLR and postoperative recurrence was investigated by Kaplan-Meier survival curve and logistic regression analysis. Results:A total of 630 patients with CRS were included, including 382 and 140 patients with high NLR and high PLR, respectively. The postoperative recurrence rates of CRS patients in the high NLR and high PLR groups were significantly higher than those in the low NLR and low PLR groups(P<0.05). The recurrent CRS had higher NLR and PLR levels and higher proportion of high NLR and high PLR than the non-recurrent CRS(P<0.05), and similarly the duration of recurrent CRS and the rate of allergic rhinitis with recurrence were significantly higher than the non-recurrent CRS(P<0.05). Kaplan-Meier survival curves showed that postoperative CRS was significantly higher in the high NLR and high PLR groups compared with the low NLR and low PLR groups. recurrence was significantly higher(P<0.05). In addition, logistic regression analysis showed that high NLR, high PLR, disease duration, and combined allergic rhinitis were significantly associated with an increased risk of postoperative recurrence of CRS(P<0.05). Conclusion:Both high preoperative NLR and high PLR are independent risk factors for postoperative recurrence of CRS, and they are expected to be new indicators for postoperative prognostic assessment and risk stratification of CRS patients. In addition, disease duration and comorbid allergic rhinitis were significantly associated with the risk of postoperative recurrence of CRS.


Assuntos
Rinite Alérgica , Rinossinusite , Humanos , Neutrófilos , Contagem de Plaquetas , Plaquetas , Linfócitos , Prognóstico , Estudos Retrospectivos
20.
Opt Lett ; 49(3): 530-533, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38300051

RESUMO

In this Letter, we have proposed a particle manipulation system based on a polarization-dependent dielectric metasurface (PDM), which enables far-field trapping and 2D arbitrary transporting. Based on flexible phase manipulation, by tuning the size and angle of meta-atoms, polarization-selective focusing in different modules of the metasurface can be realized. Then, when those regional focuses are continuously lighted in a relay way, the trapped particle at the focus could be delivered to the next one. When six different characteristic polarization states are tuned in order, the trapped particle could be transported to any adjacent hot spots so that 2D manipulation can be realized in an extended range. With the consideration of the Brownian motion, our simulation results show that the success rate of the particle transport can reach more than 96.0%, even after 20 periods when excited at the wavelength of 1064 nm with a power density of 0.15 mW/µm2. We believe that our research provides a new and promising method for particle manipulation and furthers on-chip optofluidic applications.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA