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1.
J Biol Chem ; : 107672, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39128723

RESUMO

The ubiquitin-proteasome system (UPS), which involves E3 ligases and deubiquitinases (DUBs), is critical for protein homeostasis. The epigenetic reader ZMYND8 (zinc finger MYND-type containing 8) has emerged as an oncoprotein, and its protein levels are elevated in various types of cancer, including breast cancer. However, the mechanism by which ZMYND8 protein levels are increased in cancer remains elusive. Although ZMYND8 has been reported to be regulated by the E3 ligase FBXW7, it is still unknown whether ZMYND8 could be modulated by DUBs. Here, we identified USP7 (ubiquitin carboxyl-terminal hydrolase 7) as a bona fide DUB for ZMYND8. Mechanically, USP7 directly binds to the PBP (PHD-BRD-PWWP) domain of ZMYND8 via its TRAF (tumor necrosis factor receptor-associated factor) domain and UBL (ubiquitin-like) domain and removes F-box and WD repeat domain containing 7 (FBXW7)-catalyzed poly-ubiquitin chains on lysine residue 1034 (K1034) within ZMYND8, thereby stabilizing ZMYND8 and stimulating the transcription of ZMYND8 target genes ZEB1 (zinc finger E-box binding homeobox 1) and VEGFA (Vascular Endothelial Growth Factor A). Consequently, USP7 enhances the capacity of breast cancer cells for migration and invasion through antagonizing FBXW7-mediated ZMYND8 degradation. Importantly, the protein levels of USP7 positively correlates with those of ZMYND8 in breast cancer tissues. These findings delineate an important layer of migration and invasion regulation by the USP7-ZMYND8 axis in breast cancer cells.

2.
Int J Biol Macromol ; 276(Pt 1): 133780, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38992525

RESUMO

The properties and structure of gluten protein with different deacetylation degrees of konjac glucomannan (KGM) were investigated, in an attempt to improve the quality of gluten protein in flour products. Results showed that deacetylated KGM (DKGM) could improve the textural properties and enhance the thermal stability of gluten protein. DKGM increased the water holding capacity and shortened the T2 relaxation time of gluten after removing some acetyl groups. As the deacetylation degree increased, the hardness and adhesiveness of gluten gels gradually increased, while the springiness decreased. In addition, the presence of DKGM promoted the conversion from free sulfhydryl to disulfide bonds and increased the ß-sheet content in gluten protein. The low-deacetylation KGM decreased the surface hydrophobicity and fluorescence intensity of gluten protein, and the microstructures of gluten gels became more compact. Compared with gluten protein-KGM complex gel, the degradation temperature of gluten protein-DKGM complex gels was observed to increase by >3 °C. Overall, the low-deacetylation KGM was beneficial for improving the physicochemical properties and maintaining the network structure of gluten protein. This study provides valuable references and practical insights to improve gluten quality in the flour industry.

3.
Front Oncol ; 14: 1332314, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39026974

RESUMO

In locally advanced esophageal cancer, the controversy over the two traditional treatment modalities, neoadjuvant radiotherapy and neoadjuvant chemotherapy, has been unending and also challenged by the addition of neoadjuvant immunotherapy. Neoadjuvant immunotherapy has led to an increasing diversity of neoadjuvant combination treatment modalities, among which neoadjuvant immunochemotherapy has emerged, with current clinical studies initially demonstrating its efficacy and safety. We report a case of a patient with locally advanced esophageal cancer who underwent two cycles of neoadjuvant immunochemotherapy and successful surgery and achieved a pathological complete response (pCR). A 73-year-old elderly female patient presented with progressive dysphagia for more than 1 month with an Eastern Cooperative Oncology Group (ECOG) score of 1. After completing gastroscopy + pathological biopsy, chest enhanced CT, barium esophageal meal, PET-CT, and other related examinations, the clinical diagnosis was thoracic segmental esophageal poorly differentiated squamous carcinoma cT2N2M0 stage III. After a multidisciplinary discussion of the comprehensive treatment plan, two cycles of neoadjuvant therapy were given on February 16, 2023, and March 9, 2023, and the treatment plan was as follows: cisplatin 30 mg d1-3 + albumin paclitaxel 200 mg d1 and 100 mg d8 + sintilimab 200 mg d4, q3w. After the neoadjuvant therapy, the patient underwent an imaging examination. The chest enhanced CT suggested that the lesion range was significantly reduced compared with the previous scan, and mediastinal lymph nodes were partially reduced. Then, thoracoscopic radical esophageal cancer surgery was performed on April 23, 2023. pCR was achieved by pathological evaluation, and the postoperative diagnosis was thoracic segmental esophageal hypofractionated squamous carcinoma ypT0N0M0. Two cycles of adjuvant immunochemotherapy were performed after surgery on May 30, 2023, and June 21, 2023, and the regimen was as follows: cisplatin 30 mg d1-3 + albumin paclitaxel 200 mg d1 and 100 mg d8 + sindilizumab 200 mg d4, q3w. As of the latest review on March 20, 2024, the patient was not seen to have any significant postoperative complications and remains in a state of complete response (CR). Neoadjuvant immunochemotherapy has positive significance for the treatment of patients with locally advanced esophageal cancer. Whether neoadjuvant immunochemotherapy can replace neoadjuvant synchronous radiotherapy is a future direction of research, which needs to be further verified by more reliable clinical trials.

4.
Food Chem ; 459: 140429, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39024880

RESUMO

The ideal physicochemical properties of bigels are important for food applications. Therefore, a new bigel was prepared based on mixed beef tallow and soybean oil oleogel and deacetylated konjac glucomannan (KGM) hydrogel. The effect of the deacetylation degree of KGM on the physicochemical properties and microstructure of bigels was studied. The bigel containing moderate deacetylation degree of KGM had better rheological properties and hardness (319.84 g) than that with low and high deacetylation degrees of KGM. The interactions among the bigel components were analyzed by Fourier transform infrared spectroscopy and molecular dynamics simulation, indicating that the formation of the bigels was dominated by electrostatic interactions. Overall, the bigels containing moderate deacetylation degree of KGM had better physical properties, which may provide a theoretical foundation to develop bigels with low cholesterol, trans and saturated fats levels to replace traditional solid fats in food industry.

5.
BMC Genomics ; 25(1): 727, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39060939

RESUMO

BACKGROUND: Acinetobacter baumannii (A. baumannii) is a common opportunistic pathogen in hospitals that causes nosocomial infection. In order to understand the phenotypic and genotypic characteristics of A. baumannii isolates, we sequenced and analyzed 62 A. baumannii isolates from a hospital in Gansu province. RESULTS: Non-repeated 62 A. baumannii isolates were collected from August 2015 to November 2021. Most isolates (56/62) were resistant to multiple drugs. All the 62 A. baumannii isolates were resistant to aztreonam and contained blaADC-25 gene which exists only on chromosome contigs. The 62 isolates in this study were not clustered in a single clade, but were dispersed among multiple clades in the common genome. Seven sequence types were identified by Multilocus sequence type (MLST) analysis and most isolates (52/62) belonged to ST2. The plasmids were grouped into 11 clusters by MOB-suite. CONCLUSIONS: This study furthers the understanding of A. baumannii antimicrobial-resistant genotypes, and may aid in prevention and control nosocomial infection caused by drug-resistant A. baumannii.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Genótipo , Tipagem de Sequências Multilocus , Fenótipo , Acinetobacter baumannii/genética , Acinetobacter baumannii/isolamento & purificação , Acinetobacter baumannii/efeitos dos fármacos , Humanos , China , Infecções por Acinetobacter/microbiologia , Infecções por Acinetobacter/epidemiologia , Antibacterianos/farmacologia , Hospitais , Farmacorresistência Bacteriana Múltipla/genética , Infecção Hospitalar/microbiologia , Testes de Sensibilidade Microbiana , Filogenia , Plasmídeos/genética , Masculino , Feminino , Pessoa de Meia-Idade , Adulto
6.
Int J Biol Macromol ; 275(Pt 1): 133403, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38917926

RESUMO

Nasopharyngeal carcinoma (NPC), a malignant cancer originating from the epithelial cells of the nasopharynx, presents diagnostic challenges with current methods such as plasma Epstein-Barr virus (EBV) DNA testing showing limited efficacy. This study focused on identifying small extracellular vesicle (sEV) proteins as potential noninvasive biomarkers to enhance NPC diagnostic accuracy. We isolated sEVs from plasma and utilized 4D label-free proteomics to identify differentially expressed proteins (DEPs) among healthy controls (NC = 10), early-stage NPC (E-NPC = 10), and late-stage NPC (L-NPC = 10). Eighteen sEV proteins were identified as potential biomarkers. Subsequently, parallel reaction monitoring (PRM) proteomic analysis preliminarily confirmed sEV carbonic anhydrase 1 (CA1) as a highly promising biomarker for NPC, particularly in early-stage diagnosis (NC = 15; E-NPC = 10; L-NPC = 15). To facilitate this, we developed an automated, high-throughput and highly sensitive CA1 immune-chemiluminescence chip technology characterized by a broad linear detection range and robust controls. Further validation in an independent retrospective cohort (NC = 89; E-NPC = 39; L-NPC = 172) using this technology confirmed sEV CA1 as a reliable diagnostic biomarker for NPC (AUC = 0.9809) and E-NPC (AUC = 0.9893), independent of EBV-DNA testing. Notably, sEV CA1 exhibited superior diagnostic performance compared to EBV-DNA, with a significant incremental net reclassification improvement of 27.61 % for NPC and 72.11 % for E-NPC detection. Thus, this study identifies sEV CA1 as an innovative diagnostic biomarker for NPC and E-NPC independent of EBV-DNA. Additionally, it establishes an immune-chemiluminescence chip technology for the detection of sEV CA1 protein, paving the way for further validation and clinical application.


Assuntos
Biomarcadores Tumorais , Vesículas Extracelulares , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/sangue , Carcinoma Nasofaríngeo/virologia , Biomarcadores Tumorais/sangue , Vesículas Extracelulares/metabolismo , Masculino , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/virologia , Feminino , Pessoa de Meia-Idade , Adulto , Proteômica/métodos , Idoso
7.
Genes (Basel) ; 15(6)2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38927664

RESUMO

Chilling stress is one of the main abiotic factors affecting rice growth and yield. In rice, chlorophyllide a oxygenase encoded by OsCAO1 is responsible for converting chlorophyllide a to chlorophyllide b, playing a crucial role in photosynthesis and thus rice growth. However, little is known about the function of OsCAO1 in chilling stress responses. The presence of the cis-acting element involved in low-temperature responsiveness (LTR) in the OsCAO1 promoter implied that OsCAO1 probably is a cold-responsive gene. The gene expression level of OsCAO1 was usually inhibited by low temperatures during the day and promoted by low temperatures at night. The OsCAO1 knockout mutants generated by the CRISPR-Cas9 technology in rice (Oryza sativa L.) exhibited significantly weakened chilling tolerance at the seedling stage. OsCAO1 dysfunction led to the accumulation of reactive oxygen species and malondialdehyde, an increase in relative electrolyte leakage, and a reduction in antioxidant gene expression under chilling stress. In addition, the functional deficiency of OsCAO1 resulted in more severe damage to chloroplast morphology, such as abnormal grana thylakoid stacking, caused by low temperatures. Moreover, the rice yield was reduced in OsCAO1 knockout mutants. Therefore, the elevated expression of OsCAO1 probably has the potential to increase both rice yield and chilling tolerance simultaneously, providing a strategy to cultivate chilling-tolerant rice varieties with high yields.


Assuntos
Temperatura Baixa , Regulação da Expressão Gênica de Plantas , Oryza , Proteínas de Plantas , Plântula , Oryza/genética , Oryza/crescimento & desenvolvimento , Plântula/genética , Plântula/crescimento & desenvolvimento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Oxigenases/genética , Oxigenases/metabolismo , Resposta ao Choque Frio/genética , Técnicas de Inativação de Genes , Espécies Reativas de Oxigênio/metabolismo , Clorofila/metabolismo , Fotossíntese/genética
8.
Cell Death Dis ; 15(6): 446, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914543

RESUMO

Protein homeostasis is predominantly governed through post-translational modification (PTM). UBE3B, identified as an oncoprotein, exhibits elevated protein levels in breast cancer. However, the impact of PTM on UBE3B remains unexplored. In this study, we show that VHL is a bona fide E3 ligase for UBE3B. Mechanistically, VHL directly binds to UBE3B, facilitating its lysine 48 (K48)-linked polyubiquitination at K286 and K427 in a prolyl hydroxylase (PHD)-independent manner. Consequently, this promotes the proteasomal degradation of UBE3B. The K286/427R mutation of UBE3B dramatically abolishes the inhibitory effect of VHL on breast tumor growth and lung metastasis. Additionally, the protein levels of UBE3B and VHL exhibit a negative correlation in breast cancer tissues. These findings delineate an important layer of UBE3B regulation by VHL.


Assuntos
Neoplasias da Mama , Ubiquitina-Proteína Ligases , Ubiquitinação , Proteína Supressora de Tumor Von Hippel-Lindau , Animais , Feminino , Humanos , Camundongos , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Células HEK293 , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Camundongos Nus , Metástase Neoplásica , Ligação Proteica , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Proteína Supressora de Tumor Von Hippel-Lindau/genética
9.
Cell Death Dis ; 15(6): 392, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834617

RESUMO

Keratinocyte proliferation and differentiation in epidermis are well-controlled and essential for reacting to stimuli such as ultraviolet light. Imbalance between proliferation and differentiation is a characteristic feature of major human skin diseases such as psoriasis and squamous cell carcinoma. However, the effect of keratinocyte metabolism on proliferation and differentiation remains largely elusive. We show here that the gluconeogenic enzyme fructose-1,6-bisphosphatase 1 (FBP1) promotes differentiation while inhibits proliferation of keratinocyte and suppresses psoriasis development. FBP1 is identified among the most upregulated genes induced by UVB using transcriptome sequencing and is elevated especially in upper epidermis. Fbp1 heterozygous mice exhibit aberrant epidermis phenotypes with local hyperplasia and dedifferentiation. Loss of FBP1 promotes proliferation and inhibits differentiation of keratinocytes in vitro. Mechanistically, FBP1 loss facilitates glycolysis-mediated acetyl-CoA production, which increases histone H3 acetylation at lysine 9, resulting in enhanced transcription of proliferation genes. We further find that the expression of FBP1 is dramatically reduced in human psoriatic lesions and in skin of mouse imiquimod psoriasis model. Fbp1 deficiency in mice facilitates psoriasis-like skin lesions development through glycolysis and acetyl-CoA production. Collectively, our findings reveal a previously unrecognized role of FBP1 in epidermal homeostasis and provide evidence for FBP1 as a metabolic psoriasis suppressor.


Assuntos
Diferenciação Celular , Proliferação de Células , Frutose-Bifosfatase , Histonas , Queratinócitos , Psoríase , Animais , Humanos , Camundongos , Acetilcoenzima A/metabolismo , Acetilação , Modelos Animais de Doenças , Frutose-Bifosfatase/metabolismo , Frutose-Bifosfatase/genética , Glicólise , Histonas/metabolismo , Queratinócitos/metabolismo , Queratinócitos/patologia , Camundongos Endogâmicos C57BL , Psoríase/patologia , Psoríase/metabolismo , Psoríase/genética
10.
Am J Otolaryngol ; 45(5): 104373, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38838480

RESUMO

BACKGROUND: With advancements in medicine and economy, it would be expected that there will be changes in the clinical characteristics of upper respiratory papillomatosis. The aim of this study was to examine the current clinical characteristics of upper respiratory papillomatosis, as there are no recent data in the literature. METHODS: The medical records of 1894 patients with upper respiratory papillomatosis were retrospectively reviewed. Data extracted included clinical features, laryngoscopy images, and surgical procedure data. RESULTS: The upper frequency of upper respiratory papillomatosis in the oropharynx was 69.1 %, and in the larynx was held 28.9 %. The overall postoperative relapse rate was 2.4 %. The relapse rate of laryngeal papillomatosis was 6.5 %. Approximately 2.6 % of cases were in children. All postoperative recurrences in children were laryngeal, and the recurrence rate was 30.4 %. CONCLUSION: The oropharynx has the highest frequency of upper respiratory papillomatosis. The larynx, however, has the highest rate of postoperative recurrence. Compared to adults, children are more likely to experience a postoperative recurrence.

11.
Research (Wash D C) ; 7: 0379, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38779490

RESUMO

Cement-based materials are the foundation of modern buildings but suffer from intensive energy consumption. Utilizing cement-based materials for efficient energy storage is one of the most promising strategies for realizing zero-energy buildings. However, cement-based materials encounter challenges in achieving excellent electrochemical performance without compromising mechanical properties. Here, we introduce a biomimetic cement-based solid-state electrolyte (labeled as l-CPSSE) with artificially organized layered microstructures by proposing an in situ ice-templating strategy upon the cement hydration, in which the layered micropores are further filled with fast-ion-conducting hydrogels and serve as ion diffusion highways. With these merits, the obtained l-CPSSE not only presents marked specific bending and compressive strength (2.2 and 1.2 times that of traditional cement, respectively) but also exhibits excellent ionic conductivity (27.8 mS·cm-1), overwhelming most previously reported cement-based and hydrogel-based electrolytes. As a proof-of-concept demonstration, we assemble the l-CPSSE electrolytes with cement-based electrodes to achieve all-cement-based solid-state energy storage devices, delivering an outstanding full-cell specific capacity of 72.2 mF·cm-2. More importantly, a 5 × 5 cm2 sized building model is successfully fabricated and operated by connecting 4 l-CPSSE-based full cells in series, showcasing its great potential in self-energy-storage buildings. This work provides a general methodology for preparing revolutionary cement-based electrolytes and may pave the way for achieving zero-carbon buildings.

12.
Food Chem ; 453: 139599, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-38788640

RESUMO

In this study, oxidized deacetylated konjac glucomannans with different degrees of oxidation were prepared by a combination of deacetylation and ozone oxidation. Carboxyl groups were found to be introduced into the modified konjac glucomannan while acetyl groups were removed. The backbone, branched chains, and crystal structure of modified konjac glucomannan were not significantly affected. The whiteness was enhanced to 97-99 % and the thermal degradation temperature was up to 250 °C after modification. The solubility of the modified konjac glucomannan (oxidized for 60 min) was significantly increased to 84.56 % (p < 0.05), while its viscosity and swelling power were notably decreased owing to the changes in molecular weight (from 106 to 104) and functional groups. Rheological analysis showed that oxidized deacetylated konjac glucomannan has the ability to form soft-textured gels and the potential to develop dysphagia foods. Future studies should focus on the gelation mechanisms of oxidized deacetylated konjac glucomannan.


Assuntos
Géis , Mananas , Oxirredução , Ozônio , Reologia , Mananas/química , Viscosidade , Ozônio/química , Géis/química , Acetilação , Peso Molecular , Solubilidade , Amorphophallus/química
13.
BMC Plant Biol ; 24(1): 387, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38724946

RESUMO

BACKGROUND: Woody bamboos are the only diverse large perennial grasses in mesic-wet forests and are widely distributed in the understory and canopy. The functional trait variations and trade-offs in this taxon remain unclear due to woody bamboo syndromes (represented by lignified culm of composed internodes and nodes). Here, we examined the effects of heritable legacy and occurrence site climates on functional trait variations in leaf and culm across 77 woody bamboo species in a common garden. We explored the trade-offs among leaf functional traits, the connection between leaf nitrogen (N), phosphorus (P) concentrations and functional niche traits, and the correlation of functional traits between leaves and culms. RESULTS: The Bayesian mixed models reveal that the combined effects of heritable legacy (phylogenetic distances and other evolutionary processes) and occurrence site climates accounted for 55.10-90.89% of the total variation among species for each studied trait. The standardized major axis analysis identified trade-offs among leaf functional traits in woody bamboo consistent with the global leaf economics spectrum; however, compared to non-bamboo species, the woody bamboo exhibited lower leaf mass per area but higher N, P concentrations and assimilation, dark respiration rates. The canonical correlation analysis demonstrated a positive correlation (ρ = 0.57, P-value < 0.001) between leaf N, P concentrations and morphophysiology traits. The phylogenetic principal components and trait network analyses indicated that leaf and culm traits were clustered separately, with leaf assimilation and respiration rates associated with culm ground diameter. CONCLUSION: Our study confirms the applicability of the leaf economics spectrum and the biogeochemical niche in woody bamboo taxa, improves the understanding of woody bamboo leaf and culm functional trait variations and trade-offs, and broadens the taxonomic units considered in plant functional trait studies, which contributes to our comprehensive understanding of terrestrial forest ecosystems.


Assuntos
Nitrogênio , Folhas de Planta , Folhas de Planta/fisiologia , Folhas de Planta/genética , Nitrogênio/metabolismo , Sasa/genética , Sasa/fisiologia , Poaceae/genética , Poaceae/fisiologia , Fósforo/metabolismo , Filogenia , Teorema de Bayes
14.
Antioxidants (Basel) ; 13(5)2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38790697

RESUMO

High temperature is a significant environmental stress that limits plant growth and agricultural productivity. GDSL lipase is a hydrolytic enzyme with a conserved GDSL sequence at the N-terminus, which has various biological functions, such as participating in plant growth, development, lipid metabolism, and stress resistance. However, little is known about the function of the GDSL lipase gene in the heat tolerance of rice. Here, we characterized a lipase family protein coding gene HTA1, which was significantly induced by high temperature in rice. Rice seedlings in which the mutant hta1 was knocked out showed enhanced heat tolerance, whereas the overexpressing HTA1 showed more sensitivity to heat stress. Under heat stress, hta1 could reduce plant membrane damage and reactive oxygen species (ROS) levels and elevate the activity of antioxidant enzymes. Moreover, real-time quantitative PCR (RT-qPCR) analysis showed that mutant hta1 significantly activated gene expression in antioxidant enzymes, heat response, and defense. In conclusion, our results suggest that HTA1 negatively regulates heat stress tolerance by modulating the ROS accumulation and the expression of heat-responsive and defense-related genes in rice seedlings. This research will provide a valuable resource for utilizing HTA1 to improve crop heat tolerance.

15.
Food Chem ; 449: 139114, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38581782

RESUMO

L-Tryptophan (L-Trp) is essential for the human body and can only be obtained externally. It is important to develop a method to efficiently detect L-Trp in food. In this work, ionic liquid (IL) modified poly(3,4-ethylendioxythiophene)/ Titanium carbide (PEDOT/Ti3C2TX) was used as a substrate material to improve detection sensitivity. Molecular imprinted polymers (MIP) film for specific recognition of L-Trp was fabricated on the surface of modified electrodes using electrochemical polymerization. The monitoring results showed that the molecularly imprinted electrochemical sensors (MIECS) exhibited good linearity ranges (10-6 - 0.1 µM and 0.1-100 µM) with a low detection limit (LOD) of 2.09 × 10-7 µM. In addition, the MIECS exhibited remarkable stability, reproducibility, and immunity to interference. A good recovery (93.54-99.59%) was demonstrated in the detection of milk. The sensor was expected to be developed as a highly selective and sensitive portable assay, and applied to the detection of L-Trp in food.


Assuntos
Técnicas Eletroquímicas , Líquidos Iônicos , Limite de Detecção , Leite , Impressão Molecular , Polímeros , Titânio , Triptofano , Leite/química , Líquidos Iônicos/química , Polímeros/química , Animais , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Triptofano/análise , Triptofano/química , Titânio/química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Polímeros Molecularmente Impressos/química , Contaminação de Alimentos/análise , Eletrodos , Reprodutibilidade dos Testes
16.
J Control Release ; 369: 746-764, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38599547

RESUMO

Acute respiratory distress syndrome (ARDS) is a critical illness characterized by severe lung inflammation. Improving the delivery efficiency and achieving the controlled release of anti-inflammatory drugs at the lung inflammatory site are major challenges in ARDS therapy. Taking advantage of the increased pulmonary vascular permeability and a slightly acidic-inflammatory microenvironment, pH-responsive mineralized nanoparticles based on dexamethasone sodium phosphate (DSP) and Ca2+ were constructed. By further biomimetic modification with M2 macrophage membranes, hybrid mineralized nanovesicles (MM@LCaP) were designed to possess immunomodulatory ability from the membranes and preserve the pH-sensitivity from core nanoparticles for responsive drug release under acidic inflammatory conditions. Compared with healthy mice, the lung/liver accumulation of MM@LCaP in inflammatory mice was increased by around 5.5 times at 48 h after intravenous injection. MM@LCaP promoted the polarization of anti-inflammatory macrophages, calmed inflammatory cytokines, and exhibited a comprehensive therapeutic outcome. Moreover, MM@LCaP improved the safety profile of glucocorticoids. Taken together, the hybrid mineralized nanovesicles-based drug delivery strategy may offer promising ideas for enhancing the efficacy and reducing the toxicity of clinical drugs.


Assuntos
Anti-Inflamatórios , Dexametasona , Glucocorticoides , Pulmão , Nanopartículas , Síndrome do Desconforto Respiratório , Animais , Glucocorticoides/administração & dosagem , Glucocorticoides/farmacocinética , Glucocorticoides/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/farmacocinética , Dexametasona/uso terapêutico , Dexametasona/análogos & derivados , Distribuição Tecidual , Nanopartículas/química , Camundongos , Síndrome do Desconforto Respiratório/tratamento farmacológico , Pulmão/metabolismo , Pulmão/efeitos dos fármacos , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacocinética , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Liberação Controlada de Fármacos , Pneumonia/tratamento farmacológico , Pneumonia/induzido quimicamente , Células RAW 264.7 , Sistemas de Liberação de Medicamentos , Cálcio/metabolismo , Citocinas/metabolismo
17.
J Biomed Inform ; 154: 104627, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38561170

RESUMO

OBJECTIVE: Designing a new clinical trial entails many decisions, such as defining a cohort and setting the study objectives to name a few, and therefore can benefit from recommendations based on exhaustive mining of past clinical trial records. This study proposes an approach based on knowledge graph embeddings and semantics-driven inductive inference for generating such recommendations. METHOD: The proposed recommendation methodology is based on neural embeddings trained on first-of-its-kind knowledge graph constructed from clinical trials data. The methodology includes design of a knowledge graph for clinical trial data, evaluation of various knowledge graph embedding techniques for it, application of a novel inductive inference method using these embeddings, and generation of recommendations for clinical trial design. The study uses freely available data from clinicaltrials.gov and related sources. RESULTS: The proposed approach for recommendations obtained relevance scores ranging from 70% to 83%. These scores were determined by evaluating the text similarity of recommended elements to actual elements used in clinical trials that are in progress. Furthermore, the most pertinent recommendations were consistently located towards the top of the list, indicating the effectiveness of our method. CONCLUSION: Our study suggests that inductive inference using node semantics is a viable approach for generating recommendations using graphs neural embeddings, and that there is a potential for improvement in training graph embeddings using node semantics.


Assuntos
Ensaios Clínicos como Assunto , Semântica , Humanos , Mineração de Dados/métodos , Algoritmos , Redes Neurais de Computação , Projetos de Pesquisa
18.
Angew Chem Int Ed Engl ; 63(24): e202403827, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38589299

RESUMO

Organic radicals with narrow energy gaps are highly sought-after for the production of near-infrared (NIR) fluorophores. However, the current repertoire of developed organic radicals is notably limited, facing challenges related to stability and low fluorescence efficiency. This study addresses these limitations by achieving stable radicals in nonconjugated poly(diphenylmethane) (PDPM). Notably, PDPM exhibits a well-balanced structural flexibility and rigidity, resulting in a robust intra-/inter-chain through-space conjugation (TSC). The stable radicals within PDPM, coupled with strong TSC, yield a remarkable full-spectrum emission spanning from blue to NIR beyond 900 nm. This extensive tunability is achieved through careful adjustments of concentration and excitation wavelength. The findings highlight the efficacy of polymerization in stabilizing radicals and introduce a novel approach for developing nonconjugated NIR emitters based on triphenylmethane subunits.

19.
Biosens Bioelectron ; 257: 116332, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38677016

RESUMO

In situ detection of dopamine (DA) at single-cell level is critical for exploring neurotransmitter-related biological processes and diseases. However, the low content of DA and a variety of distractors with similar oxidation potentials as DA in cells brought great challenges. Here, a sensitive and specific electrochemical nanosensor was proposed for in situ detection of DA in single living cells based on nanodiamond (ND) and molecularly imprinted polymer (MIP)-functionalized carbon fiber nanoelectrode (ND/MIP/CFNE). Due to its excellent electrocatalytic property, ND was modified to the surface of CFNE based on amide bonding. Compared with bare CFNE, ND-modified CFNE can enhance oxidation currents of DA by about 4-fold, improving signal-to-noise ratio and detection sensitivity. MIP was further electropolymerized on the surface of nanoelectrodes to achieve specific capture and recognition of DA, which could avoid the interference of complex matrix and analogs in cells. Taking advantage of the precise positioning capability of a single-cell analyzer and micromanipulator, ND/MIP/CFNE could be precisely inserted into different locations of single cells and monitor oxidation signal of DA. The concentration of DA in the cytoplasm of single pheochromocytoma (PC12) cell was measured to be about 0.4 µM, providing a sensitive and powerful method for single-cell detection. Furthermore, the nanoelectrodes can monitor the fluctuation of intracellular DA under drug stimulation, providing new ideas and methods for new drug development and efficacy evaluation.


Assuntos
Técnicas Biossensoriais , Dopamina , Técnicas Eletroquímicas , Polímeros Molecularmente Impressos , Análise de Célula Única , Dopamina/análise , Dopamina/química , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Células PC12 , Técnicas Eletroquímicas/métodos , Polímeros Molecularmente Impressos/química , Animais , Ratos , Nanodiamantes/química , Eletrodos , Fibra de Carbono/química , Impressão Molecular/métodos , Limite de Detecção , Polímeros/química
20.
Polymers (Basel) ; 16(8)2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38674999

RESUMO

The branched structures of dendronized polymers can provide good steric stabilization for metal nanoparticle catalysts. In this work, an amphiphilic dendronized copolymer containing hydrophilic branched triethylene glycol moieties and hydrophobic branched ferrocenyl moieties is designed and prepared by one-pot ring-opening metathesis polymerization, and is used as the stabilizer for metal (Au, Ag and Pd) nanoparticles. These metal nanoparticles (Au nanoparticles: 3.5 ± 3.0 nm; Ag nanoparticles: 7.2 ± 4.0 nm; Pd nanoparticles: 2.5 ± 1.0 nm) are found to be highly active in both the 4-nitrophenol reduction and Suzuki-Miyaura reactions. In the 4-nitrophenol reduction, Pd nanoparticles have the highest catalytic ability (TOF: 2060 h-1). In addition, Pd nanoparticles are also an efficient catalyst for Suzuki-Miyaura reactions (TOF: 1980 h-1) and possess good applicability for diverse substrates. The amphiphilic dendronized copolymer will open a new door for the development of efficient metal nanoparticle catalysts.

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