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1.
Exp Cell Res ; 438(1): 114037, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38631545

RESUMO

Anoikis plays a crucial role in the progression, prognosis, and immune response of lung adenocarcinoma (LUAD). However, its specific impact on LUAD remains unclear. In this study, we investigated the intricate interplay of nesting apoptotic factors in LUAD. By analyzing nine key nesting apoptotic factors, we categorized LUAD patients into two distinct clusters. Further examination of immune cell profiles revealed that Cluster A exhibited greater infiltration of innate immune cells than did Cluster B. Additionally, we identified two genes closely associated with prognosis and developed a predictive model to differentiate patients based on molecular clusters. Our findings suggest that the loss of specific anoikis-related genes could significantly influence the prognosis, tumor microenvironment, and clinical features of LUAD patients. Furthermore, we validated the expression and functional roles of two pivotal prognostic genes, solute carrier family 2 member 1 (SLC2A1) and sphingosine kinase 1 (SPHK1), in regulating tumor cell viability, migration, apoptosis, and anoikis. These results offer valuable insights for future mechanistic investigations. In conclusion, this study provides new avenues for advancing our understanding of LUAD, improving prognostic assessments, and developing more effective immunotherapy strategies.

2.
Breast Cancer Res ; 26(1): 70, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654332

RESUMO

BACKGROUND: Basal-like breast cancer (BLBC) is the most aggressive subtype of breast cancer due to its aggressive characteristics and lack of effective therapeutics. However, the mechanism underlying its aggressiveness remains largely unclear. S-adenosylmethionine decarboxylase proenzyme (AMD1) overexpression occurs specifically in BLBC. Here, we explored the potential molecular mechanisms and functions of AMD1 promoting the aggressiveness of BLBC. METHODS: The potential effects of AMD1 on breast cancer cells were tested by western blotting, colony formation, cell proliferation assay, migration and invasion assay. The spermidine level was determined by high performance liquid chromatography. The methylation status of CpG sites within the AMD1 promoter was evaluated by bisulfite sequencing PCR. We elucidated the relationship between AMD1 and Sox10 by ChIP assays and quantitative real-time PCR. The effect of AMD1 expression on breast cancer cells was evaluated by in vitro and in vivo tumorigenesis model. RESULTS: In this study, we showed that AMD1 expression was remarkably elevated in BLBC. AMD1 copy number amplification, hypomethylation of AMD1 promoter and transcription activity of Sox10 contributed to the overexpression of AMD1 in BLBC. AMD1 overexpression enhanced spermidine production, which enhanced eIF5A hypusination, activating translation of TCF4 with multiple conserved Pro-Pro motifs. Our studies showed that AMD1-mediated metabolic system of polyamine in BLBC cells promoted tumor cell proliferation and tumor growth. Clinically, elevated expression of AMD1 was correlated with high grade, metastasis and poor survival, indicating poor prognosis of breast cancer patients. CONCLUSION: Our work reveals the critical association of AMD1-mediated spermidine-eIF5A hypusination-TCF4 axis with BLBC aggressiveness, indicating potential prognostic indicators and therapeutic targets for BLBC.


Assuntos
Neoplasias da Mama , Proliferação de Células , 60599 , Regulação Neoplásica da Expressão Gênica , Lisina/análogos & derivados , Fatores de Iniciação de Peptídeos , Proteínas de Ligação a RNA , Espermidina , Fator de Transcrição 4 , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Fatores de Iniciação de Peptídeos/metabolismo , Fatores de Iniciação de Peptídeos/genética , Camundongos , Animais , Espermidina/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Fator de Transcrição 4/metabolismo , Fator de Transcrição 4/genética , Linhagem Celular Tumoral , Regiões Promotoras Genéticas , Adenosilmetionina Descarboxilase/metabolismo , Adenosilmetionina Descarboxilase/genética , Movimento Celular/genética , Metilação de DNA , Prognóstico , Fatores de Transcrição SOXE/metabolismo , Fatores de Transcrição SOXE/genética
3.
Artigo em Inglês | MEDLINE | ID: mdl-38447648

RESUMO

Gelsemium elegans (GE), also known as Duanchangcao, is a plant associated with toxic symptoms related to the abdomen; however, the toxicity caused by GE remains unknown. Gelsemine (GEL) is an alkaloid extracted from GE and is one of the most toxic alkaloids. This study used zebrafish as an animal model and employed high-throughput gene sequencing to identify genes and signaling pathways related to GEL toxicity. Exposure to GEL negatively impacted heart rate, swim bladder development, and activity in zebrafish larvae. Transcriptomics data revealed the enrichment of inflammatory and phagocyte signaling pathways. RT-PCR analysis revealed a decrease in the expression of pancreas-related genes, including the pancreatic coagulation protease (Ctr) family, such as Ctrl, Ctrb 1, and Ctrc, due to GEL exposure. Furthermore, GEL exposure significantly reduced Ctrb1 protein expression while elevating trypsin and serum amylase activities in zebrafish larvae. GEL also resulted in a decrease in pancreas-associated fluorescence area and an increase in neutrophil-related fluorescence area in transgenic zebrafish. This study revealed that GEL toxicity in zebrafish larvae is related to acute pancreatic inflammation.


Assuntos
Alcaloides , Gelsemium , Animais , Peixe-Zebra/metabolismo , Gelsemium/metabolismo , Larva/metabolismo
4.
Bull Environ Contam Toxicol ; 112(2): 39, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38353786

RESUMO

Acetaminophen (N-acetyl-p-aminophenol; APAP) is one of the most widely used analgesics. To examine the toxicity of APAP, we used zebrafish embryos as model animals to detect the effect of APAP on the thyroid system of zebrafish embryos. The zebrafish embryos were exposed to APAP from 4 h post fertilization (4 hpf) until observation. The experimental results showed that APAP caused pericardial edema and decreased pigmentation in the zebrafish embryos or larvae. The APAP treatment caused a decrease in the expression of tpo and thrß in the zebrafish at 36 and 72 hpf. The transcriptomic analysis found that APAP affected retinol metabolism, the metabolism of xenobiotics by cytochrome P450, and the tyrosine metabolism pathway. The harmful effect of APAP on zebrafish embryos might be due to its disrupting effect on the functional regulation of the thyroid hormone system.


Assuntos
Acetaminofen , Perciformes , Animais , Acetaminofen/toxicidade , Peixe-Zebra , Tiroxina , Pigmentação , Glândula Tireoide
5.
Crit Rev Eukaryot Gene Expr ; 34(3): 27-36, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38305286

RESUMO

This study aimed to investigate the T cell immunoreceptor with ITIM and Ig domains (TIGIT) expression in lung adenocarcinoma (LUAD). TIGIT expression was measured by western blot, reverse transcription quantitative polymerase chain reaction. Seventy-two paired surgical specimens were collected from patients with stage I-IV LUAD. The expression of TIGIT in surgical specimens was determined using immunohistochemistry. TIGIT was overexpressed in LUAD tissues. Moreover, overexpressed TIGIT was significantly associated with advanced clinical staging, lymph node metastasis, distant metastasis, and TP53 mutations in LUAD. Moreover, high expression of TIGIT was negatively correlated with purity of CD4+ T cells. High rations of TIGIT+CD4+ T cells predicted poor overall survival of LUAD patients. Additionally, high ratios of TIGIT+CD4+ T cells is closely related to CD4+ T cell depletion. Taken together, TIGIT was overexpressed in LUAD patients. High levels of TIGIT induced the alteration of CD4+ T cell based immunomodulation and predicted poor prognosis of LUAD patients. Therefore, TIGIT can be potential biomarker for LUAD.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Relevância Clínica , Expressão Ectópica do Gene , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Neoplasias Pulmonares/metabolismo
6.
Cancer Lett ; 582: 216527, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38048842

RESUMO

Basal-like breast cancer (BLBC) is the most aggressive subtype with poor prognosis; however, the mechanisms underlying aggressiveness in BLBC remain poorly understood. In this study, we showed that in contrast to other subtypes, inositol monophosphatase 2 (IMPA2) was dramatically increased in BLBC. Mechanistically, IMPA2 expression was upregulated due to copy number amplification, hypomethylation of IMPA2 promoter and MYC-mediated transcriptional activation. IMPA2 promoted MI-PI cycle and IP3 production, and IP3 then elevated intracellular Ca2+ concentration, leading to efficient activation of NFAT1. In turn, NFAT1 up-regulated MYC expression, thereby fulfilling a positive feedback loop that enhanced aggressiveness of BLBC cells. Knockdown of IMPA2 expression caused the inhibition of tumorigenicity and metastasis of BLBC cells in vitro and in vivo. Clinically, high IMPA2 expression was strongly correlated with large tumor size, high grade, metastasis and poor survival, indicating poor prognosis in breast cancer patients. These findings suggest that IMPA2-mediated MI-PI cycle allows crosstalk between metabolic and oncogenic pathways to promote BLBC progression.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Retroalimentação , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Regiões Promotoras Genéticas
7.
BMC Oral Health ; 23(1): 557, 2023 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-37573308

RESUMO

BACKGROUND: Many scholars have proven cervical vertebral maturation (CVM) method can predict the growth and development and assist in choosing the best time for treatment. However, assessing CVM is a complex process. The experience and seniority of the clinicians have an enormous impact on judgment. This study aims to establish a fully automated, high-accuracy CVM assessment system called the psc-CVM assessment system, based on deep learning, to provide valuable reference information for the growth period determination. METHODS: This study used 10,200 lateral cephalograms as the data set (7111 in train set, 1544 in validation set and 1545 in test set) to train the system. The psc-CVM assessment system is designed as three parts with different roles, each operating in a specific order. 1) Position Network for locating the position of cervical vertebrae; 2) Shape Recognition Network for recognizing and extracting the shapes of cervical vertebrae; and 3) CVM Assessment Network for assessing CVM according to the shapes of cervical vertebrae. Statistical analysis was conducted to detect the performance of the system and the agreement of CVM assessment between the system and the expert panel. Heat maps were analyzed to understand better what the system had learned. The area of the third (C3), fourth (C4) cervical vertebrae and the lower edge of second (C2) cervical vertebrae were activated when the system was assessing the images. RESULTS: The system has achieved good performance for CVM assessment with an average AUC (the area under the curve) of 0.94 and total accuracy of 70.42%, as evaluated on the test set. The Cohen's Kappa between the system and the expert panel is 0.645. The weighted Kappa between the system and the expert panel is 0.844. The overall ICC between the psc-CVM assessment system and the expert panel was 0.946. The F1 score rank for the psc-CVM assessment system was: CVS (cervical vertebral maturation stage) 6 > CVS1 > CVS4 > CVS5 > CVS3 > CVS2. CONCLUSIONS: The results showed that the psc-CVM assessment system achieved high accuracy in CVM assessment. The system in this study was significantly consistent with expert panels in CVM assessment, indicating that the system can be used as an efficient, accurate, and stable diagnostic aid to provide a clinical aid for determining growth and developmental stages by CVM.


Assuntos
Aprendizado Profundo , Humanos , Determinação da Idade pelo Esqueleto/métodos , Cefalometria/métodos , Vértebras Cervicais/diagnóstico por imagem , Radiografia
8.
J Org Chem ; 88(7): 4264-4272, 2023 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-36916510

RESUMO

Disclosed herein is the first protocol for the electrochemically oxidative phosphating of aldehydes and ketones to generate α-hydroxyphosphine oxides with diphenylphosphine as the phosphine source. Various phosphating products containing P-C bonds are basically assembled in modest to excellent yields. This electrochemical phosphating was achieved by utilizing a simple undivided cell with foam nickel electrodes at room temperature without the addition of any oxidant or metal catalyst. The prepared α-hydroxyphosphine oxides possess potential application in pharmacological research.

9.
Animals (Basel) ; 13(5)2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36899642

RESUMO

Early weaning is an effective strategy to improve cow feed utilization and shorten postpartum intervals in cows; however, this may lead to poor performance of the weaned calves. This study was conducted to test the effects of supplementing milk replacer with Bacillus licheniformis and a complex of probiotics and enzyme preparations on body weight (BW), size, and serum biochemical parameters and hormones in early-weaned grazing yak calves. Thirty two-month-old male grazing yaks (38.89 ± 1.45 kg body weight) were fed milk replacer at 3% of their BW and were randomly assigned to three treatments (n = 10, each): T1 (supplementation with 0.15 g/kg Bacillus licheniformis), T2 (supplementation with a 2.4 g/kg combination of probiotics and enzymes), and a control (without supplementation). Compared to the controls, the average daily gain (ADG) from 0 to 60 d was significantly higher in calves administered the T1 and T2 treatments, and that from 30 to 60 d was significantly higher in calves administered the T2 treatment. The ADG from 0 to 60 d was significantly higher in the T2- than in the T1-treated yaks. The concentration of serum growth hormone, insulin growth factor-1, and epidermal growth factor was significantly higher in the T2-treated calves than in the controls. The concentration of serum cortisol was significantly lower in the T1 treatment than in the controls. We concluded that supplementation with probiotics alone or a combination of probiotics and enzymes can improve the ADG of early-weaned grazing yak calves. Supplementation with the combination of probiotics and enzymes had a stronger positive effect on growth and serum hormone levels, compared to the single-probiotic treatment with Bacillus licheniformis, providing a basis for the application of a combination of probiotics and enzymes.

10.
Environ Health Perspect ; 131(1): 17009, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36719213

RESUMO

BACKGROUND: Recurrent miscarriage (RM) affects 1%-3% of pregnancies. However, in almost 50% of cases, the cause is unknown. Increasing evidence have shown that benzo(a)pyrene [B(a)P], a representative of polycyclic aromatic hydrocarbons (PAHs), is correlated with miscarriage. However, the underlying mechanisms of B(a)P/benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE)-induced trophoblast cell dysfunctions and miscarriage remain largely unknown. OBJECTIVE: The objective was to discover the role(s) of a novel lncRNA, lnc-HZ09, in the regulation of BPDE-inhibited migration and invasion of trophoblast cells and the occurrence of miscarriage. METHOD: Human trophoblast cells were treated with 0, 0.25, 0.5, 1.0, or 1.5µM BPDE with or without corresponding lnc-HZ09 silencing or overexpression. Using these cells, we evaluated cell migration and invasion, the mRNA and protein levels of members of the PLD1/RAC1/CDC42 pathway, the regulatory roles of lnc-HZ09 in PLD1 transcription and mRNA stability, and lnc-HZ09 transcription and stability. Human villous tissues were collected from RM (n=15) group and their matched healthy control (HC, n=15) group. We evaluated the levels of BPDE-DNA adducts, lnc-HZ09, and the mRNA and protein expression of members of the PLD1/RAC1/CDC42 pathway, and correlated their relative expression levels. We further constructed 0, 0.05 or 0.2mg/kg B(a)P-induced mouse miscarriage model (each n=6), in which the mRNA and protein expression of members of the Pld1/Rac1/Cdc42 pathway were measured. RESULTS: We identified a novel lnc-HZ09. Human trophoblast cells treated with lnc-HZ09 exhibited less cell migration and invasion. In addition, the levels of this lncRNA were higher in villous tissues from women with recurrent miscarriage than those from healthy individuals. SP1-mediated PLD1 mRNA levels were lower, and HuR-mediated PLD1 mRNA stability was less in trophoblast cells overexpressing lnc-HZ09. However, trophoblast cells treated with MSX1 had higher levels of lnc-HZ09, and METTL3-mediated m6A methylation on lnc-HZ09 resulted in greater lnc-HZ09 RNA stability. In BPDE-treated human trophoblast cells and in RM villous tissues, MSX1-mediated lnc-HZ09 transcription and METTL3-mediated lnc-HZ09 stability were both greater. In our mouse miscarriage model, B(a)P-treated mice had lower mRNA and protein levels of members of the Pld1/Rac1/Cdc42 pathway. DISCUSSION: These results suggest that in human trophoblast cells, BPDE exposure up-regulated lnc-HZ09 level, suppressed PLD1/RAC1/CDC42 pathway, and inhibited migration and invasion, providing new insights in understanding the causes and mechanisms of unexplained miscarriage. https://doi.org/10.1289/EHP10477.


Assuntos
Aborto Habitual , RNA Longo não Codificante , Gravidez , Humanos , Feminino , Camundongos , Animais , Trofoblastos , 7,8-Di-Hidro-7,8-Di-Hidroxibenzo(a)pireno 9,10-óxido/metabolismo , 7,8-Di-Hidro-7,8-Di-Hidroxibenzo(a)pireno 9,10-óxido/farmacologia , RNA Longo não Codificante/genética , Benzo(a)pireno/metabolismo , Aborto Habitual/genética , Aborto Habitual/metabolismo , RNA Mensageiro/metabolismo , Metiltransferases/metabolismo
11.
Foods ; 11(17)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36076847

RESUMO

Effects of ball milling (BM) on the structure and physicochemical properties of three types of citrus fibers were investigated. With the extension of the grinding time, the particle size of citrus fibers significantly decreased. Fourier transform infrared spectroscopy (FTIR) showed that the three citrus fibers had similar chemical groups, and more -OH and phenolic acid groups were exposed after BM, and pectin and lignin were not degraded. Scanning electron microscope (SEM) results showed that the appearance of particles changed from spherical to fragmented, irregular shapes. The water holding capacity (WHC), oil holding capacity (OHC), and water swelling capacity (WSC) of citrus fibers LM, JK, and FS reached the maximum value after BM of 2 h (increasing by 18.5%), 4 h (increasing by 46.1%), and 10 h (increasing by 38.3%), respectively. After 10 h BM, citrus fibers FS and JK had the highest adsorption capacity of cholesterol and sodium cholate, increasing by 48.3% and 48.6%, respectively. This indicates that BM transforms the spatial structure of citrus fibers and improves their physicochemical properties.

12.
ACS Omega ; 7(33): 28985-28993, 2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-36033652

RESUMO

This article systematically examines the physical characteristics, group composition characteristics, and geochemical characteristics of heavy oil in the Western Sag of the Liaohe Basin. The examination is based on the separation and quantitative analysis of crude oil and rock samples, as well as the analysis of test results from gas chromatography with saturated hydrocarbons and aromatic hydrocarbons. It also analyzes the generation mechanism and main controlling factors of heavy oil. The results show that heavy oil has low wax content (1.8-9.2%), a low freezing point (-19-38 °C), low sulfur content (0.28-0.5%), high colloid and asphaltene content, high density (0.926-1.008 g/cm3), and high viscosity (328-231910 mPa·s). The physical properties of the heavy oil in the same formation decrease from the depression's edge toward its center and within the same area, and the physical properties in different formations also have an inverse relationship with burial depth. Biodegradation is the main reason for the formation of heavy oil. Based on the biodegradation degree, there are four types of heavy oil: undegraded, weakly degraded, moderately degraded, and severely degraded. The main controlling factors of biodegradation are temperature and the water environment. This study provides a method for studying the genetic mechanism of heavy oil, an approach for discovering similar genetic oil and gas, and a basis for the transformation of heavy oil field development.

13.
Environ Sci Pollut Res Int ; 29(59): 89156-89167, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35849232

RESUMO

Electrochemical advanced oxidation processes (EAOPs) is considered to be an efficacious method to degrade antibiotics. However, the performance of the anode has become the main limiting factor of this technology. In this study, due to the electron-deficient characteristics and the improvement of OER performance of Mo, we chose to use thermal decomposition to incorporate Mo into IrO2 to prepare anodes with industrial applicability. Under the optimal ratio of Ir to Mo is 7:3, (Ir0.7Mo0.3)Ox electrode's particular pore structure can expose more active sites and create a channel for the transportation of electrons, thereby promoting the formation of free radicals and degrading pollutants more efficiently. (Ir0.7Mo0.3)Ox electrode also has a higher mass activity (6.332 A g-1, three times that of the IrO2 electrode) and a larger electrochemical active area (ECSA, 375.43 cm2, seven times that of the IrO2 electrode). In addition, the optimal conditions of (Ir0.7Mo0.3)Ox electrode for degrading sulfadiazine(SDZ) were explored, which achieved a higher removal than traditional electrodes (90% removal within 4 h) when the Ti plate was the substrate. Through the intermediate products of SDZ degradation and related literatures, two possible degradation pathways of SDZ were speculated. This research provides a new type of anode catalyst for the degradation of sulfonamide antibiotics, which is possible for industrial application.


Assuntos
Sulfadiazina , Poluentes Químicos da Água , Poluentes Químicos da Água/análise , Eletrodos , Catálise , Oxirredução , Antibacterianos , Titânio
14.
Sci Rep ; 12(1): 9680, 2022 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-35690643

RESUMO

Traditional cleaning processes may be banned in the near future because of the hazards they pose to the environment. In this study, a water jet was used to clean grease residues from steel wires for the first time. The EDS and SEM results of the steel wire rope surfaces and supplementary water jet impact experiments on galvanized steel plates revealed that when the pressure was lower than 50 MPa and the traverse speed was higher than 600 mm/min, the water jet caused minimal damage to the coating. When the pressure was 5 MPa, the cleaning ratio was between 45 and 60%, and the level of cleaning increased with increasing pressure. Two proposed concepts of exposure ratio and nonexposed area were applied to quantitatively analyze the theoretical upper and lower limits for grease that could be cleaned from two typical structures. The results showed that the lower and upper cleaning limits for structure 7 × 3 were 38.1% and 83.3%, while the lower and upper limits for structure 1 × 3 + 5 × 7 were 35.5% and 59.2%, respectively. This result explains why the grease content of structure 7 × 3 was lower than that of structure 1 × 3 + 5 × 7 after cleaning. In addition, the adhesion test results showed that adhesion to the two kinds of steel wire ropes after cleaning was increased by 126% and 145.71%, respectively, which means that additional processes for improving adhesion could be omitted after using a water jet for cleaning. This is an advantage that traditional cleaning processes do not offer.

15.
ACS Appl Mater Interfaces ; 14(25): 28706-28715, 2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35695736

RESUMO

Evaluating the structural and electronic-state characteristics of long-range disordered amorphous iridium (Ir)-based oxides is still unsatisfying. Compared with the benchmark IrO2, the higher oxygen evolution reaction (OER) performance brought by IrOxOHy was normally considered to be associated with the pristine IrIII-containing species. However, such a conclusion conflicts with the opinion that high-valence metals can create excellent OER activity. To resolve such contradictions, we synthesized a pure amorphous Lu1.25IrOxOHy (Lu = lutetium) catalyst in this work. In combination with the comprehensive electrochemical evaluation in alkaline and acidic media, ex situ Ir L3-edge and O K-edge X-ray absorption spectroscopy and theoretical calculations revealed that the ultrahigh OER performance of reconstructed IrOx/Lu1.25IrOxOHy in acidic media was identified to be driven by the more d-hole-containing electronic state of IrV created by cationic vacancies. The pristine properties of IrIII-containing Lu1.25IrOxOHy conversely inhibit the OER activity in alkaline media. Additionally, the high edge-shared [IrOx]-[IrOx] motif proportion structure in amorphous Lu1.25IrOxOHy achieves a stable OER process, which exhibits a high S-number stability index similar to IrO2. We demonstrate that the key factor of the edge-shared [IrOx]-[IrOx] motif with cationic vacancies in IrVOxOHy could rationally reveal the source for most of the high-performance Ir-based materials.

16.
J Exp Clin Cancer Res ; 41(1): 169, 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35526049

RESUMO

BACKGROUND: Basal-like breast cancer (BLBC) is the most aggressive subtype of breast cancer because of its aggressive biological characteristics and no effective targeted agents. However, the mechanism underlying its aggressive behavior remain poorly understood. ß1,3-N-acetylglucosaminyltransferase V (B3GNT5) overexpression occurs specifically in BLBC. Here, we studied the possible molecular mechanisms of B3GBT5 promoting the aggressiveness of BLBC. METHODS: The potential effects of B3GNT5 on breast cancer cells were tested by colony formation, mammosphere formation, cell proliferation assay, flow cytometry and Western blotting. The glycosylation patterns of B3GNT5 and associated functions were determined by Western blotting, quantitative real-time PCR and flow cytometry. The effect of B3GNT5 expression on BLBC was assessed by in vitro and in vivo tumorigenesis model. RESULTS: In this study, we showed that B3GNT5 copy number amplification and hypomethylation of B3GNT5 promoter contributed to the overexpression of B3GNT5 in BLBC. Knockout of B3GNT5 strongly reduced surface expression of SSEA-1 and impeded cancer stem cell (CSC)-like properties of BLBC cells. Our results also showed that B3GNT5 protein was heavily N-glycosylated, which is critical for its protein stabilization. Clinically, elevated expression of B3GNT5 was correlated with high grade, large tumor size and poor survival, indicating poor prognosis of breast cancer patients. CONCLUSIONS: Our work uncovers the critical association of B3GNT5 overexpression and glycosylation with enhanced CSCs properties in BLBC. These findings suggest that B3GNT5 has the potential to become a prognostic marker and therapeutic target for BLBC.


Assuntos
Antineoplásicos , Neoplasias da Mama , Antineoplásicos/uso terapêutico , Neoplasias da Mama/patologia , Feminino , Glicosilação , Humanos , Células-Tronco Neoplásicas/patologia
17.
Front Microbiol ; 13: 899578, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35558116

RESUMO

Directed evolution is a widely-used engineering strategy for improving the stabilities or biochemical functions of proteins by repeated rounds of mutation and selection. A protein of interest is selected as the template and expressed on a molecular display platform such as a bacteriophage for engineering. Initially, the surface-displayed protein template needs to be checked against the desired target via ELISA to examine whether the functions of the displayed template remain intact. The ELISA signal is subject to the protein-target binding affinity. A low-affinity results in a weak ELISA signal which makes it difficult to determine whether the weak signal is because of low affinity or because of poor expression of the protein. Using a methyllysine-binding chromodomain protein Cbx1 that weakly binds to the histone H3K9me3 peptide, we developed and compared three different approaches to increase the signal-to-background ratio of ELISA measurements. We observed that the specific peptide-binding signal was enhanced by increasing the Cbx1 phage concentration on the ELISA plate. The introduction of previously known gain-of-function mutations to the Cbx1 protein significantly increased the ELISA signals. Moreover, we demonstrated that the H3K9me3-specific binding signal was enhanced by fusing Cbx1 with a high-affinity phosphotyrosine-binding protein and by coating the ELISA plate with a mixture of H3K9me3 and phosphotyrosine peptides. This approach also worked with binding to a lower affinity momomethyllysine peptide H3K9me1. These approaches may help improve ELISA experiments when dealing with low-affinity ligand-protein interactions.

18.
Environ Sci Pollut Res Int ; 29(46): 69450-69461, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35576034

RESUMO

Activated carbon was one of the main adsorptions utilized in elemental mercury (Hg0) removal from coal combustion flue gas. However, the high cost and low physical adsorption efficiency of activated carbon injection (ACI) limited its application. In this study, an ultra-high efficiency (nearly 100%) catalyst sorbent-Sex/Activated carbon (Sex/AC) was synthesized and applied to remove Hg0 in the simulated flue gas, which exhibited 120 times outstanding adsorption performance versus the conventional activated carbon. The Sex/AC reached 17.98 mg/g Hg0 adsorption capacity at 160 °C under the pure nitrogen atmosphere. Moreover, it maintained an excellent mercury adsorption tolerance, reaching the efficiency of Hg0 removal above 85% at the NO and SO2 conditions in a bench-scale fixed-bed reactor. Characterized by the multiple methods, including BET, XRD, XPS, kinetic and thermodynamic analysis, and the DFT calculation, we demonstrated that the ultrahigh mercury removal performance originated from the activated Se species in Sex/AC. Chemical adsorption plays a dominant role in Hg0 removal: Selenium anchored on the surface of AC would capture Hg0 in the flue gas to form an extremely stable substance-HgSe, avoiding subsequent Hg0 released. Additionally, the oxygen-containing functional groups in AC and the higher BET areas promote the conversion of Hg0 to HgO. This work provided a novel and highly efficient carbon-based sorbent -Sex/AC to capture the mercury in coal combustion flue gas. Graphical abstract Selenium-modified porous activated carbon and the interface functional group promotes the synergistic effect of physical adsorption and chemical adsorption to promote the adsorption capacity of Hg0.


Assuntos
Poluentes Atmosféricos , Mercúrio , Selênio , Adsorção , Poluentes Atmosféricos/análise , Carvão Vegetal/análise , Carvão Mineral/análise , Mercúrio/análise , Nitrogênio/análise , Oxigênio/química , Selênio/análise
19.
Ecotoxicol Environ Saf ; 237: 113564, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35483139

RESUMO

Human trophoblast cell apoptosis may induce miscarriage. Trophoblast cells are sensitive to environmental BaP-7,8-dihydrodiol-9,10-epoxide (BPDE). However, how BPDE induces human trophoblast cell apoptosis is still largely elusive. In this work, we used BPDE-treated human trophoblast cells and villous tissues collected from recurrent miscarriage and health control groups to explore the underlying mechanism of BPDE-induced human trophoblast cell apoptosis. Continued with our recent work, we found that lncRNA HZ01 (lnc-HZ01) could induce human trophoblast cell apoptosis. In mechanism, lnc-HZ01 up-regulated p53 expression level by suppressing its MDM2-mediated proteasomal degradation. Meanwhile, we found that p53 acted as lnc-HZ01 transcription factor and promoted lnc-HZ01 transcription. Thus, lnc-HZ01 and p53 composed a positive feedback loop in human trophoblast cells. In normal trophoblast cells, relatively low levels of lnc-HZ01 and p53 suppressed p53/caspase-3 apoptosis pathway, giving normal pregnancy. Upon BPDE exposure, BPDE up-regulated the expression levels of lnc-HZ01 and p53, triggered this positive feedback loop, activated the p53/caspase-3 apoptosis pathway, and then induced miscarriage. Collectively, we discovered new mechanism by which lnc-HZ01 regulated BPDE-induced human trophoblast cell apoptosis, providing scientific basis for the diagnosis and treatment of unexplained recurrent miscarriage.


Assuntos
Aborto Habitual , RNA Longo não Codificante , 7,8-Di-Hidro-7,8-Di-Hidroxibenzo(a)pireno 9,10-óxido/metabolismo , 7,8-Di-Hidro-7,8-Di-Hidroxibenzo(a)pireno 9,10-óxido/toxicidade , Aborto Habitual/induzido quimicamente , Aborto Habitual/metabolismo , Apoptose , Caspase 3/metabolismo , Retroalimentação , Feminino , Humanos , Gravidez , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Trofoblastos/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
20.
ACS Appl Mater Interfaces ; 14(13): 15205-15213, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35343674

RESUMO

Efficient and stable electrocatalytic water splitting plays a critical role in energy storage and conversion but is strongly restricted by the low activity and stability of catalysts associated with the complicated oxygen evolution reaction (OER). This work provides a strategy to fabricate an advanced NiFe-based catalyst to steadily speed up the OER based on a strong amorphous-amorphous coupling effect generated through amorphous CuS that induces the formation of amorphous NiFe layered double hydroxide (LDH) nanosheets (A-NiFe NS/CuS). The presence of the strong coupling effect not only modifies the electronic structure of catalytic sites to accelerate the reaction kinetics but also enhances the binding between the catalyst and substrate to strengthen the durability. In comparison to well-grown core-shell crystalline NiFe LDH on CuO, the as-synthesized amorphous A-NiFe NS/CuS gives a low overpotential of 240 mV to achieve 100 mA cm-2 and shows robust stability under 100 h of operation at the same current density. Therefore, amorphous-amorphous coupling between catalyst-substrate by elaborate and rational engineering yields an opportunity to design efficient and robust NiFe-based OER catalysts.

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