Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 57
Filtrar
1.
Infect Immun ; 92(4): e0048323, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38501672

RESUMO

Aspergillus fumigatus (A. fumigatus) is one of the common pathogens of fungal keratitis. Fungal growth and invasion cause excessive inflammation and corneal damage, leading to severe vision loss. Neutrophils are the primary infiltrating cells critical for fungal clearance. Cathelicidin [LL-37 in humans and cathelicidin-related antimicrobial peptide (CRAMP) in mice], a natural antimicrobial peptide, can directly inhibit the growth of many pathogens and regulate immune responses. However, the role of cathelicidin and its effect on neutrophils in A. fumigatus keratitis remain unclear. By establishing A. fumigatus keratitis mouse models, we found that cathelicidin was increased in A. fumigatus keratitis. It could reduce fungal loads, lower clinical scores, and improve corneal transparency. Restriction of CRAMP on fungal proliferation was largely counteracted in CD18-/- mice, in which neutrophils cannot migrate into infected sites. When WT neutrophils were transferred into CD18-/- mice, corneal fungal loads were distinctly reduced, indicating that neutrophils are vital for CRAMP-mediated resistance. Furthermore, cathelicidin promoted neutrophils to phagocytose and degrade conidia both in vitro and in vivo. CXC chemokine receptor 2 (CXCR2) was reported to be a functional receptor of LL-37 on neutrophils. CXCR2 antagonist SB225002 or phospholipase C (PLC) inhibitor U73122 weakened LL-37-induced phagocytosis. Meanwhile, LL-37 induced PLC γ phosphorylation, which was attenuated by SB225002. SB225002 or the autophagy inhibitors Bafilomycin-A1 and 3-Methyladenine weakened LL-37-induced degradation of conidia. Transmission electron microscopy (TEM) observed that LL-37 increased autophagosomes in Aspergillus-infected neutrophils. Consistently, LL-37 elevated autophagy-associated protein expressions (Beclin-1 and LC3-II), but this effect was weakened by SB225002. Collectively, cathelicidin reduces fungal loads and improves the prognosis of A. fumigatus keratitis. Both in vitro and in vivo, cathelicidin promotes neutrophils to phagocytose and degrade conidia. LL-37/CXCR2 activates PLC γ to amplify neutrophils' phagocytosis and induces autophagy to eliminate intracellular conidia.


Assuntos
Aspergillus fumigatus , Ceratite , Compostos de Fenilureia , Humanos , Animais , Camundongos , Neutrófilos , Antifúngicos/metabolismo , Catelicidinas , Fosfolipase C gama/metabolismo , Ceratite/microbiologia , Prognóstico , Camundongos Endogâmicos C57BL
2.
Am J Gastroenterol ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38989871

RESUMO

INTRODUCTION: Postendoscopic submucosal dissection (ESD) coagulation syndrome (PECS) prevention is one of the common postoperative complications of colorectal ESD. Considering the increasing incidence of PECS, it is critical to investigate various prevention methods. The objective of this study was to evaluate the efficacy of transrectal drainage tubes (TDTs) in PECS prevention in patients following colorectal ESD. METHODS: From July 2022 to July 2023, a multicenter, randomized controlled clinical trial was conducted in 3 hospitals in China. Patients with superficial colorectal lesions ≥20 mm who had undergone ESD for a single lesion were enrolled. Initially, 229 patients were included in the study and 5 were excluded. Two hundred twenty-four were randomly assigned to the TDT and non-TDT group in the end. This open-label study utilized a parallel design with a 1:1 allocation ratio, and endoscopists and patients were not blind to the randomization, and a 24 Fr drainage tube was inserted approximately 10-15 cm above the anus after the ESD under the endoscopy and tightly attached to a drainage bag. The TDTs were removed in 1-3 days following the ESD. RESULTS: A total of 229 eligible patients were enrolled in this study, and 5 patients were excluded. Ultimately, 224 patients were assigned to the TDT group (n = 112) and non-TDT group (n = 112). The median age for the patients was 63.45 years (IQR 57-71; 59 men [52.68%]) in the TDT group and 60.95 years (IQR 54-68; 60 men [53.57%]) in the non-TDT group. Intention-to-treat analysis showed patients in the TDT group had a lower incidence of PECS than patients in the non-TDT group (7 [6.25%] vs 20 [17.86%]; relative risk, 0.350; 95% confidence interval [CI], 0.154-0.795; P = 0.008). In the subgroup analysis, TDTs were found to prevent PECS in patients of the female gender (odd ratio, 0.097; 95% CI, 0.021-0.449; P = 0.001), tumor size <4 cm (odd ratio, 0.203; 95% CI, 0.056-0.728; P = 0.011), tumor located in the left-sided colorectum (odd ratio, 0. 339 95% CI, 0.120-0.957; P = 0.035), and shorter procedure time (<45 minutes) (odd ratio, 0.316; 95% CI, 0.113-0.879; P = 0.023). The tube fell off in 1 case (0.89%) accidentally ahead of time. No TDT-related complication was observed. DISCUSSION: The results from this randomized clinical study indicate that the application of TDTs effectively reduced the incidence of PECS in patients after colorectal ESD ( chictr.org.cn Identifier: ChiCTR2200062164).

3.
Small ; 20(29): e2400093, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38353062

RESUMO

For large-size potassium accommodation, heterostructure usually suffers severe delamination and exfoliation at the interfaces due to different volume expansion of two-phase during charge/discharge process, resulting in the deconstruction of heterostructures and shortened lifespan of batteries. Here, an innovative strategy is proposed through constructing a microscopic heterostructure system containing copper quantum dots (Cu QDs) highly dispersed in the triphenyl-substituted triazine graphdiyne (TPTG) substrates (TPTG@CuQDs) to solve this problem. The copper quantum dots are uniformly anchored on TPTG substrates, generating a myriad of island-like heterogeneous structures, together with tandem toroidal built-in electric field (BIEF) between every micro heterointerface. The island-like heterostructure endows both benefits of exposed contact interface and robust architecture. Generated tandem toroidal BIEF provides efficient transport pathways with lower energy barriers, reducing the diffusion resistance and facilitating the reaction kinetics of potassium ions. When used as anode, the TPTG@CuQDs exhibit highly reversible capacity and low-capacity degradation (≈0.01% over 5560 cycles at 1 A g-1). Moreover, the TPTG@CuQDs-based full cell delivers an outstanding reversible capacity of ≈110 mAh g-1 over 800 cycles at 1 A g-1. This quantum-scale heterointerface construction strategy offers a new approach toward stable heterostructure design for the application of metal ion batteries.

4.
BMC Infect Dis ; 24(1): 569, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849747

RESUMO

BACKGROUND: Flies are acknowledged as vectors of diseases transmitted through mechanical means and represent a significant risk to human health. The study aimed to determine the prevalence of enteropathogens carried by flies in Pudong New Area to inform strategies for preventing and controlling flies. METHODS: Samples were collected from various locations in the area using cage trapping techniques between April and November 2021, encompassing various habitats such as parks, residential areas, restaurants, and farmers' markets. The main fly species were identified using cryomicrography and taxonomic enumeration, with 20 samples per tube collected from different habitats. Twenty-five enteropathogens were screened using GI_Trial v3 TaqManTM microbial arrays. RESULTS: A total of 3,875 flies were collected from 6,400 placements, resulting in an average fly density of 0.61 flies per cage. M. domestica were the most common species at 39.85%, followed by L. sericata at 16.57% and B. peregrina at 13.14%. Out of 189 samples, 93 tested positive for enteropathogens, with nine different pathogens being found. 12.70% of samples exclusively had parasites, a higher percentage than those with only bacteria or viruses. The study found that M. domestica had fewer enteropathogens than L. sericata and B. peregrina, which primarily harbored B. hominis instead of bacteria and viruses such as E. coli, Astrovirus, and Sapovirus. During spring testing, all three fly species exhibited low rates of detecting enteropathogens. M. domestica were found in residential areas with the highest number of pathogen species, totaling six. In contrast, L. sericata and B. peregrina were identified in farmers' markets with the highest number of pathogen species, totaling six and seven, respectively. CONCLUSIONS: Flies have the potential to serve as vectors for the transmission of enteropathogens, thereby posing a substantial risk to public health.


Assuntos
Insetos Vetores , Animais , Humanos , Insetos Vetores/microbiologia , Bactérias/isolamento & purificação , Bactérias/classificação , Bactérias/genética , China/epidemiologia , Dípteros/microbiologia , Vírus/isolamento & purificação , Vírus/classificação , Vírus/genética , Muscidae/microbiologia
5.
J Opt Soc Am A Opt Image Sci Vis ; 41(4): 606-614, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38568661

RESUMO

A liquid crystal variable retarder (LCVR) is the core device to realize fast and high-precision broadband polarization imaging, and its ability to suppress the noise will have an impact on the polarization measurement results. In order to obtain better imaging quality and measurement accuracy, it is crucial to solve the optimization problem of the LCVR. In this paper, the optimal objective function for solving the optimization problem of the LCVR is analytically derived and verified based on the genetic algorithm in the band range of 350-700 nm. Meanwhile, considering that the minimum number of four measurements at this time cannot achieve the optimal state, the relationship between the number of measurements and the overall performance relative to the error propagation (optimized conditions number) is discussed. The results show that a better optimal set of angles can be obtained by using the optimal objective function. In this paper, a set of the most favorable angles is obtained, and the optimized average of the CN is 2.0000, which is reduced by 0.32% compared with previous optimization results and is closer to the ideal value of the CN. In addition, in this paper, the noise immunity of the set of most favorable angles is simulated and analyzed, and the optimized system can effectively improve the measured performance of the wide-band liquid crystal variable retarder polarimeter.

6.
Exp Parasitol ; 262: 108788, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38759775

RESUMO

Giardiasis is a common waterborne zoonotic disease caused by Giardia intestinalis. Upon infection, Giardia releases excretory and secretory products (ESPs) including secreted proteins (SPs) and extracellular vesicles (EVs). Although the interplay between ESPs and intestinal epithelial cells (IECs) has been previously described, the functions of EVs in these interactions and their differences from those of SPs require further exploration. In the present study, EVs and EV-depleted SPs were isolated from Giardia ESPs. Proteomic analyses of isolated SPs and EVs showed 146 and 91 proteins, respectively. Certain unique and enriched proteins have been identified in SPs and EVs. Transcriptome analysis of Caco-2 cells exposed to EVs showed 96 differentially expressed genes (DEGs), with 56 upregulated and 40 downregulated genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) indicated that Caco-2 genes related to metabolic processes, the HIF-1 signaling pathway, and the cAMP signaling pathway were affected. This study provides new insights into host-parasite interactions, highlighting the potential significance of EVs on IECs during infections.


Assuntos
Vesículas Extracelulares , Giardia lamblia , Mucosa Intestinal , Humanos , Células CACO-2 , Giardia lamblia/genética , Giardia lamblia/metabolismo , Vesículas Extracelulares/metabolismo , Mucosa Intestinal/parasitologia , Mucosa Intestinal/metabolismo , Perfilação da Expressão Gênica , Células Epiteliais/parasitologia , Células Epiteliais/metabolismo , Proteômica , Interações Hospedeiro-Parasita , Expressão Gênica , Transcriptoma , Giardíase/parasitologia
7.
Memory ; 32(7): 874-888, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38805606

RESUMO

Peoples' recognition memory for pictorial stimuli is extremely good. Even complex scientific visualisations are recognised with a high degree of accuracy. The present research examined recognition memory for the branching structure of evolutionary trees. This is an educationally consequential topic due to the potential for contamination from students' misconceptions. The authors created six pairs of scientifically accurate and structurally identical evolutionary trees that differed in whether they included a taxon that cued a misconception in memory. As predicted, Experiment 1 found that (a) college students (N = 90) had better memory for each of the six tree structures when a neutral taxon (M = 0.73) rather than a misconception-cuing taxon (M = 0.64) was included in the tree, and (b) recognition memory was significantly above chance for both sets of trees. Experiment 2 ruled out an alternative hypothesis based on the possibility that 8-12 sec was not enough time for students to encode the relationships depicted in the trees. The authors consider implications of these results for using evolutionary trees to better communicate scientific information. This is important because these trees provide information that is relevant for everyday life.


Assuntos
Reconhecimento Psicológico , Estudantes , Humanos , Feminino , Masculino , Adulto Jovem , Estudantes/psicologia , Evolução Biológica , Adulto , Sinais (Psicologia) , Adolescente , Estimulação Luminosa
8.
J Craniofac Surg ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38861329

RESUMO

Reconstructive surgery plays a crucial role in addressing congenital defects, posttraumatic deformities, and related conditions, providing transformative solutions for patients. Its primary goal is to restore or enhance damaged tissue structures, improving both functionality and appearance, and empowering individuals to lead fulfilling lives. Take, for example, a female patient who experienced a nasal infection after a cat bite. Despite initial treatment, she developed severe scar contractures and excessive scar tissue within her nostrils, significantly impacting her quality of life. Seeking assistance, she consulted the authors' plastic and reconstructive surgery team. By utilizing various flap techniques, the authors embarked on the intricate journey of reconstructing her nasal framework, ultimately restoring both form and function.

9.
Beilstein J Org Chem ; 20: 155-161, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38292044

RESUMO

An efficient and practical method for the synthesis of C5-brominated 8-aminoquinoline amides via a copper-promoted selective bromination of 8-aminoquinoline amides with alkyl bromides was developed. The reaction proceeds smoothly in dimethyl sulfoxide (DMSO) under air, employing activated and unactivated alkyl bromides as the halogenation reagents without additional external oxidants. This method features outstanding site selectivity, broad substrate scope, and excellent yields.

10.
Future Oncol ; 19(40): 2641-2650, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38108112

RESUMO

Conventional laparoscopic-assisted right hemicolectomy requires a small abdominal incision to extract the specimen, which becomes an important source of postoperative complications and impairs perioperative experience. Transvaginal natural orifice specimen extraction surgery (NOSES VIIIA) avoids this small incision by extracting the specimen through the vagina. Here we describe the design of a multicenter, open-label, parallel, noninferior, phase III randomized controlled trial (NCT05495048). The aim of this study is to confirm that the NOSES VIIIA procedure is not inferior to small-incision assisted right hemicolectomy in long-term oncological efficacy. A total of 352 female patients with right colon adenocarcinoma/high-grade intraepithelial neoplasia will be randomly assigned to the NOSES VIIIA arm and the small-incision arm in a 1:1 ratio. The primary end point of this trial is 3 year disease-free survival. Clinical Trial Registration: NCT05495048 (ClinicalTrials.gov).


Assuntos
Adenocarcinoma , Neoplasias do Colo , Laparoscopia , Cirurgia Endoscópica por Orifício Natural , Feminino , Humanos , Adenocarcinoma/cirurgia , Ensaios Clínicos Fase III como Assunto , Colectomia/efeitos adversos , Neoplasias do Colo/cirurgia , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Estudos Multicêntricos como Assunto , Cirurgia Endoscópica por Orifício Natural/efeitos adversos , Cirurgia Endoscópica por Orifício Natural/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Estudos de Equivalência como Asunto
11.
Int J Mol Sci ; 25(1)2023 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-38203486

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease characterized by excessive deposition of fibrotic connective tissue in the lungs. Emerging evidence suggests that metabolic alterations, particularly glycolysis reprogramming, play a crucial role in the pathogenesis of IPF. Lactate, once considered a metabolic waste product, is now recognized as a signaling molecule involved in various cellular processes. In the context of IPF, lactate has been shown to promote fibroblast activation, myofibroblast differentiation, and extracellular matrix remodeling. Furthermore, lactate can modulate immune responses and contribute to the pro-inflammatory microenvironment observed in IPF. In addition, lactate has been implicated in the crosstalk between different cell types involved in IPF; it can influence cell-cell communication, cytokine production, and the activation of profibrotic signaling pathways. This review aims to summarize the current research progress on the role of glycolytic reprogramming and lactate in IPF and its potential implications to clarify the role of lactate in IPF and to provide a reference and direction for future research. In conclusion, elucidating the intricate interplay between lactate metabolism and fibrotic processes may lead to the development of innovative therapeutic strategies for IPF.


Assuntos
Fibrose Pulmonar Idiopática , Ácido Láctico , Humanos , Comunicação Celular , Glicólise , Pulmão
12.
Zhongguo Zhen Jiu ; 44(2): 221-223, 2024 Feb 12.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-38373771

RESUMO

The Elastic acupuncture needle, a set of clinical device used in randomized controlled trials of acupuncture is developed, which may potentially obtain the double-blind placebo control. This kind of acupuncture device consists of a real needle and a sham one (placebo needle) with a identical appearance. Either of the needle is composed of an integrated cap-type handle and needle body, and a sterile double-sided adhesive pad is designed on the bottom for fixation. A spring with miniature low profile is built in sham needle. During operation, the real needle can be normally inserted, while the sham one be retracted because of the elasticity generated by the pressure on the skin, but deqi can still be felt by patients whenever the force difference between the skin and the spring reaches a certain balance. The rubber pad designed in this acupuncture needle can simulate the "resistance" felt by operators during needle insertion so that the double blinding is actualized in terms of the appearance and sensations.


Assuntos
Terapia por Acupuntura , Acupuntura , Humanos , Sensação , Método Duplo-Cego , Agulhas , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
J Hazard Mater ; 469: 133971, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38471379

RESUMO

Microplastics are recognized as a new environmental pollutant. Researchers have detected their presence in waste incineration ash. However, traditional testing methods take a very long testing period. There is a lack of research on detecting microplastics in waste incineration ash. In this paper, a portable near-infrared spectra (NIRS) spectrometer was used for qualitative discrimination and quantitative prediction of microplastics in ash. A total of 84 sets of simulated ash samples containing different types (PP, PS, PE, and PVC) and contents (2.4 wt% - 20 wt%) of microplastics were used in the model. The results show the qualitative discrimination model using support vector machines (SVM) method with multiplicative scatter correction (MSC) preprocessing could effectively identify the microplastic types in the ash with 100% detection accuracy. Furthermore, the partial least squares regression (PLSR) model was effective in quantitatively predicting the content of microplastics in ash. The Rp2 of the PP, PS, PE, and PVC models are 0.95, 0.93, 0.89, and 0.95, respectively. The RPD of the PP, PS, PE, and PVC models are 3.97, 3.96, 2.89 and 5.02, respectively. This study shows that microplastics in ash can be detected rapidly and accurately using portable near-infrared spectrometers.

14.
Sci Total Environ ; 912: 169347, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38104822

RESUMO

Plastics account for a large proportion of domestic waste. However, micro-plastics will be produced after the plastic is incinerated. The purpose of this study is to find out the change rule of micro-plastics produced during incineration under different conditions. Combining micro-FTIR and PCA algorithm is a good tool to identify the micro-plastics. The PE, PP and PVC micro-plastics are distinguished using PCA-FTIR spectra. The results show different incineration conditions significantly affect the output of micro-plastics. The yield of micro-plastics increases with increasing temperature for both PP and PVC. And the yield of micro-plastics decreases with the increase in flow rate. The maximum amount of micro-plastics is produced by PE, which is 6.62 × 103 after 1 g PE incineration. The yield of micro-plastics in the co-incineration of PE and PP, as well as PE and PVC, significantly increased to 1.42 and 1.89 times of the calculated values, respectively. The nano-particles are also observed. The FTIR and EDS results show that the nano-particles are the products of incineration of plastics, including partly CH bond and unburned carbon, tar and ash.

15.
Hum Vaccin Immunother ; 20(1): 2364480, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38972854

RESUMO

Elderly individuals face a high risk of hospitalization and death related to influenza, thus prioritizing them for influenza vaccination. Due to variations in the influenza virus and waning protective antibodies, annual influenza vaccination is recommended. However, research on repeated influenza vaccination among elderly individuals in China is limited. From 2020 to 2022, the average influenza vaccination coverage among registered elderly individuals in Shanghai was 4.1%, showing a declining trend over time. In 2020, the rate of repeated influenza vaccination among elderly individuals was 28.35%, which rose to almost two-thirds both in 2021 and 2022. No increased risk of adverse events following immunization was observed after repeated influenza vaccination during this period. Our study also found that elderly individuals with Shanghai household registration, managed by community clinics, and older age tended to receive more doses of repeated influenza vaccination throughout the period from 2020 to 2022. Increasing influenza vaccine coverage among elderly individuals in Shanghai is both urgent and challenging. Health authorities should intensify educational and promotional campaigns to encourage uptake of annual repeated influenza vaccination among elderly individuals.


Assuntos
Vacinas contra Influenza , Influenza Humana , Cobertura Vacinal , Humanos , China , Vacinas contra Influenza/administração & dosagem , Idoso , Influenza Humana/prevenção & controle , Masculino , Feminino , Cobertura Vacinal/estatística & dados numéricos , Cobertura Vacinal/tendências , Idoso de 80 Anos ou mais , Vacinação/estatística & dados numéricos , Vacinação/tendências , Pessoa de Meia-Idade
16.
Viruses ; 16(2)2024 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-38400086

RESUMO

The CRISPR/Cas9 system is widely used to manipulate viral genomes. Although Alphaherpesvirinae genomes are large and complicated to edit, in recent years several Pseudorabies virus (PRV) mutants have been successfully generated using the CRISPR/Cas9 system. However, the application of CRISPR/Cas9 editing on another member of alpha herpesviruses, bovine herpesvirus-1 (BHV-1), is rarely reported. This paper reports a rapid and straightforward approach to manipulating herpesviruses genome using CRISPR/Cas9. The recombinant plasmids contained the left and right arm of the thymidine kinase (TK) gene of PRV or of the glycoprotein I (gI) and glycoprotein E (gE) of BHV-1. Upon the cleavage of the TK or gIgE gene by Cas9 protein, this was replaced by the enhanced green fluorescence protein (eGFP) by homologous recombination. With this approach, we generated recombinant TK-/eGFP+ PRV and gIgE-/eGFP+ BHV-1 mutants and then proceeded to characterize their biological activities in vitro and in vivo. In conclusion, we showed that alpha herpesvirus, including PRV and BHV-1, can be rapidly edited using the CRISPR/Cas9 approach paving the way to the development of animal herpesvirus vaccines.


Assuntos
Herpesvirus Bovino 1 , Herpesvirus Suídeo 1 , Pseudorraiva , Animais , Edição de Genes , Sistemas CRISPR-Cas , Herpesvirus Bovino 1/genética , Herpesvirus Bovino 1/metabolismo , Pseudorraiva/prevenção & controle , Glicoproteínas/genética
17.
Eur J Med Chem ; 274: 116538, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38823264

RESUMO

DNA methyltransferase 1 (DNMT1) is the primary enzyme responsible for maintaining DNA methylation patterns during cellular division, crucial for cancer development by suppressing tumor suppressor genes. In this study, we retained the phthalimide structure of N-phthaloyl-l-tryptophan (RG108) and substituted its indole ring with nitrogen-containing aromatic rings of varying sizes. We synthesized 3-(9H-carbazol-9-yl)-2-(1,3-dioxoisoindolin-2-yl)propanoic acids and confirmed them as DNMT1 inhibitors through protein affinity testing, radiometric method using tritium labeled SAM, and MTT assay. Preliminary structure-activity relationship analysis revealed that introducing substituents on the carbazole ring could enhance inhibitory activity, with S-configuration isomers showing greater activity than R-configuration ones. Notably, S-3-(3,6-di-tert-butyl-9H-carbazol-9-yl)-2-(1,3-dioxoisoindolin-2-yl)propanoic acid (7r-S) and S-3-(1,3,6-trichloro-9H-carbazol-9-yl)-2-(1,3-dioxoisoindolin-2-yl)propanoic acid (7t-S) exhibited significant DNMT1 enzyme inhibition activity, with IC50 values of 8.147 µM and 0.777 µM, respectively (compared to RG108 with an IC50 above 250 µM). Moreover, they demonstrated potential anti-proliferative activity on various tumor cell lines including A2780, HeLa, K562, and SiHa. Transcriptome analysis and KEGG pathway enrichment of K562 cells treated with 7r-S and 7t-S identified differentially expressed genes (DEGs) related to apoptosis and cell cycle pathways. Flow cytometry assays further indicated that 7r-S and 7t-S induce apoptosis in K562 cells and arrest them in the G0/G1 phase in a concentration-dependent manner. Molecular docking revealed that 7t-S may bind to the methyl donor S-adenosyl-l-methionine (SAM) site in DNMT1 with an orientation opposite to RG108, suggesting potential for deeper penetration into the DNMT1 pocket and laying the groundwork for further modifications.


Assuntos
Carbazóis , Proliferação de Células , DNA (Citosina-5-)-Metiltransferase 1 , Inibidores Enzimáticos , Humanos , Relação Estrutura-Atividade , Carbazóis/farmacologia , Carbazóis/química , Carbazóis/síntese química , DNA (Citosina-5-)-Metiltransferase 1/antagonistas & inibidores , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química , Proliferação de Células/efeitos dos fármacos , Estrutura Molecular , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Ensaios de Seleção de Medicamentos Antitumorais , Relação Dose-Resposta a Droga , Indóis/farmacologia , Indóis/química , Indóis/síntese química , Simulação de Acoplamento Molecular , Linhagem Celular Tumoral , Ftalimidas , Triptofano/análogos & derivados
18.
Neural Netw ; 179: 106554, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39096748

RESUMO

The success of the ClassSR has led to a strategy of decomposing images being used for large image SR. The decomposed image patches have different recovery difficulties. Therefore, in ClassSR, image patches are reconstructed by different networks to greatly reduce the computational cost. However, in ClassSR, the training of multiple sub-networks inevitably increases the training difficulty. Furthermore, decomposing images with overlapping not only increases the computational cost but also inevitably produces artifacts. To address these challenges, we propose an end-to-end general framework, named patches separation and artifacts removal SR (PSAR-SR). In PSAR-SR, we propose an image information complexity module (IICM) to efficiently determine the difficulty of recovering image patches. Then, we propose a patches classification and separation module (PCSM), which can dynamically select an appropriate SR path for image patches of different recovery difficulties. Moreover, we propose a multi-attention artifacts removal module (MARM) in the network backend, which can not only greatly reduce the computational cost but also solve the artifacts problem well under the overlapping-free decomposition. Further, we propose two loss functions - threshold penalty loss (TP-Loss) and artifacts removal loss (AR-Loss). TP-Loss can better select appropriate SR paths for image patches. AR-Loss can effectively guarantee the reconstruction quality between image patches. Experiments show that compared to the leading methods, PSAR-SR well eliminates artifacts under the overlapping-free decomposition and achieves superior performance on existing methods (e.g., FSRCNN, CARN, SRResNet, RCAN and CAMixerSR). Moreover, PSAR-SR saves 53%-65% FLOPs in computational cost far beyond the leading methods. The code will be made available: https://github.com/dywang95/PSAR-SR.

19.
Coron Artery Dis ; 35(3): 221-230, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38299258

RESUMO

BACKGROUND: Evidence about the association between albumin combined with neutrophil-to-lymphocyte ratio score (ANS) and survival outcomes in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) is rare. This study aimed to evaluate the prognostic value of ANS in patients with ACS undergoing PCI by propensity score matching (PSM) analysis. PATIENTS AND METHODS: Patients with ACS undergoing PCI were consecutively enrolled in this prospective cohort study from January 2016 to December 2018. The albumin and neutrophil-to-lymphocyte ratio cutoff values for predicting major adverse cardiovascular events (MACEs) were calculated using receiver operating characteristic curves. Survival analysis was performed using Kaplan-Meier estimates, the Cox proportional hazard regression models and PSM. The study endpoint was the occurrence of a MACE, which included all-cause mortality and rehospitalization for severe heart failure during follow-up. RESULTS: Overall, 1549 patients with adequate specimens were identified and assigned into different groups for comparison. Before and after PSM, the Kaplan-Meier curves showed that a higher ANS value was associated with a higher risk of MACEs (all P  < 0.001). The multivariate Cox proportional hazard regression model showed that the ANS (per 1 score increase) [hazard ratio (HR), 2.016; 95% confidence interval (CI), 1.329-3.057; P  = 0.001 vs. HR, 2.166; 95% CI, 1.344-3.492; P  = 0.002] was an independent predictor for MACEs. CONCLUSION: This study tentatively confirms that ANS may be a valuable clinical indicator to identify high-risk ACS patients after PCI. More high-quality prospective studies are needed in the future.


Assuntos
Síndrome Coronariana Aguda , Infarto do Miocárdio , Intervenção Coronária Percutânea , Humanos , Infarto do Miocárdio/epidemiologia , Estudos Prospectivos , Intervenção Coronária Percutânea/efeitos adversos , Neutrófilos , Albuminas , Fatores de Risco , Estudos Retrospectivos
20.
Clin Cardiol ; 47(3): e24246, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38425231

RESUMO

BACKGROUND: Lipid metabolism related factors, such as angiopoietin-like protein 3 (ANGPTL3), angiopoietin-like 4 (ANGPTL4), fatty acid-binding protein 4 (FABP4) are newly discovered factors that can affect coronary artery disease (CAD). In this study, we aimed to investigate the relationship between CAD and these lipid metabolism factors. HYPOTHESIS: ANGPTL3, ANGPTL4, and FABP4 may provide a new method for the control of CAD risk factors and the prevention and treatment of CAD. METHODS: We enrolled 284 consecutive inpatients with suspected CAD and divided them into CAD and non-CAD groups based on the coronary angiography results. Serum ANGPTL3, ANGPTL4, FABP4, and tumor necrosis factor-α (TNF-α) levels were estimated using the enzyme-linked immunosorbent assay. Multivariate logistic regression was used to assess the risk factors for CAD. The receiver operating characteristic curve was used to determine the cutoff and diagnostic values. RESULTS: The serum TNF-α, FABP4, ANGPTL3, and ANGPTL4 values showed a significant difference between the CAD and non-CAD groups (p < .05). After adjusting for confounding factors, the FABP4, ANGPTL3, and ANGPTL4 levels were independently associated with CAD (p < .05). The ANGPTL3 expression level was an independent risk factor for CAD in patients with hypertension, but not in those without hypertension. The ANGPTL3 > 67.53 ng/mL, ANGPTL4 > 29.95 ng/mL, and FABP4 > 1421.25 ng/L combination had the highest diagnostic value for CAD. CONCLUSION: ANGPTL3, ANGPTL4, and FABP4 were identified as independent risk factors for CAD and have valuable clinical implications for the diagnosis and treatment of CAD.


Assuntos
Doença da Artéria Coronariana , Hipertensão , Humanos , Proteína 3 Semelhante a Angiopoietina , Proteínas Semelhantes a Angiopoietina/metabolismo , Doença da Artéria Coronariana/diagnóstico por imagem , Proteína 4 Semelhante a Angiopoietina/metabolismo , Fator de Necrose Tumoral alfa , Proteínas de Ligação a Ácido Graxo
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa