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1.
Eur J Radiol ; 171: 111292, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38211395

RESUMO

INTRODUCTION: To compare the diagnostic performance of cone-beam breast computed tomography (CBBCT) and mammography (MG) in primary breast cancer. METHODS: PubMed, Embase, Web of Science, China National Knowledge Infrastructure, WanFang DATA, and China Science and Technology Journal databases were searched comprehensively from inception to March 2023. Sensitivity and specificity were calculated using bivariate random-effects models, and a summary receiver operating characteristic (SROC) curve was constructed. Bivariate I2 statistics and meta-regression analyses were also performed. The differences in diagnostic performance between CBBCT and MG were analysed using Z-test statistics. Clinical utility was explored using Fagan's nomogram, and quality assessment was conducted utilising the Quality Assessment of Diagnostic Accuracy Studies-2 checklist. RESULTS: The summary sensitivity and specificity for CBBCT in diagnosing primary breast cancer were 0.92 (95 % CI: 0.87-0.94) and 0.79 (95 % CI: 0.71-0.85), respectively, and the area under the curve (AUC) of the SROC was 0.93 (95 % CI: 0.90-0.95). For MG, the summary sensitivity and specificity were 0.77 (95 % CI: 0.69-0.83) and 0.75 (95 % CI: 0.66-0.82), respectively, with an AUC of 0.83 (95 % CI: 0.80-0.86). The Z-test revealed that the summary sensitivity of CBBCT was significantly higher than that of MG (P < 0.001). Additionally, the summary AUC of CBBCT was significantly higher than that of MG (P < 0.001). CONCLUSION: The diagnostic performance of CBBCT for primary breast cancer was better than that of MG. However, the results of both the CBBCT and MG are based on studies with small sample sizes. Further studies with larger sample sizes and more comprehensive designs are required to address this issue.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Reprodutibilidade dos Testes , Mama/diagnóstico por imagem , Mamografia/métodos , Tomografia Computadorizada de Feixe Cônico/métodos
2.
Bioorg Chem ; 144: 107114, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38224637

RESUMO

Acute myelogenous leukemia (AML) is the most common form of acute leukemia in adults. PDE1 (Phosphodiesterase 1) is a subfamily of the PDE super-enzyme families that can hydrolyze the second messengers cAMP and cGMP simultaneously. Previous research has shown that suppressing the gene expression of PDE1 can trigger apoptosis of human leukemia cells. However, no selective PDE1 inhibitors have been used to explore whether PDE1 is a potential target for treating AML. Based on our previously reported PDE9/PDE1 dual inhibitor 11a, a series of novel pyrazolopyrimidinone derivatives were designed in this study. The lead compound 6c showed an IC50 of 7.5 nM against PDE1, excellent selectivity over other PDEs and good metabolic stability. In AML cells, compound 6c significantly inhibited the proliferation and induced apoptosis. Further experiments indicated that the apoptosis induced by 6c was through a mitochondria-dependent pathway by decreasing the ratio of Bcl-2/Bax and increasing the cleavage of caspase-3, 7, 9, and PARP. All these results suggested that PDE1 might be a novel target for AML.


Assuntos
Leucemia Mieloide Aguda , Inibidores de Fosfodiesterase , Pirazóis , Pirimidinonas , Adulto , Humanos , Inibidores de Fosfodiesterase/farmacologia , Diester Fosfórico Hidrolases/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , GMP Cíclico/metabolismo
3.
J Colloid Interface Sci ; 646: 78-88, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37182261

RESUMO

The exploitation of high-performance electrode materials is significant to develop supercapacitors with satisfied energy and power output properties. In this study, a g-C3N4/Prussian-blue analogue (PBA)/Nickel foam (NF) with hierarchical micro/nano structures was developed by a simple salts-directed self-assembly approach. In this synthetic strategy, NF acted as both 3D macroporous conductive substrate and Ni source for PBA formation. Moreover, the incidental salt in molten salt-synthesized g-C3N4 nanosheets could regulate the combination mode between g-C3N4 and PBA to generate interactive networks of g-C3N4 nanosheets-covered PBA nano-protuberances on NF surfaces, which further expended the electrode/electrolyte interfaces. Based on the merits from this unique hierarchical structure and the synergy effect of PBA and g-C3N4, the optimized g-C3N4/PBA/NF electrode exhibited a maximum areal capacitance of 3366 mF cm-2 at current of 2 mA cm-2, as well as 2118 mF cm-2 even under large current of 20 mA cm-2. The solid-state asymmetric supercapacitor using g-C3N4/PBA/NF electrode possessed an extended working potential window of 1.8 V, prominent energy density of 0.195 mWh cm-2 and power density of 27.06 mW cm-2. Compared to the device with pure NiFe-PBA electrode, a better cyclic stability with capacitance retention rate of 80% after 5000 cycles was also achieved due to the protective effect of g-C3N4 shells on the etching of PBA nano-protuberances in electrolyte. This work not only builds a promising electrode material for supercapacitors, but also provide an effective way to apply molten salt-synthesized g-C3N4 nanosheet without purification.

5.
Front Cell Dev Biol ; 10: 1044198, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36420138

RESUMO

Placenta accreta spectrum disorders (PAS) are severe pregnancy complications that occur when extravillous trophoblast cells (EVTs) invade beyond the uterine inner myometrium and are characterized by hypervascularity on prenatal ultrasound and catastrophic postpartum hemorrhage. The potential mechanisms remain incompletely understood. With single-cell RNA-sequencing analysis on the representative invasive parts and the normal part obtained from the same PAS placenta, we profiled the pathological landscape of invasive PAS placenta and deciphered an intensified differentiation pathway from progenitor cytotrophoblasts (CTBs) to EVTs via LAMB4 + and KRT6A + CTBs. In the absence of the decidua, the invasive trophoblasts of various differentiation states interacted with ADIRF + and DES + maternal stromal cells. The PAS-associated hypervascularity might be due to the enhanced crosstalk of trophoblasts, stromal cells and vascular endothelial cells. Finally, we presented an immune microenvironmental landscape of invasive PAS. The pathogenesis of PAS could be further explored with current resources for future targeted translational studies.

6.
Front Immunol ; 13: 967356, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36211330

RESUMO

Alzheimer's disease (AD)-like cognitive impairment, a kind of Neuro-COVID syndrome, is a reported complication of SARS-CoV-2 infection. However, the specific mechanisms remain largely unknown. Here, we integrated single-nucleus RNA-sequencing data to explore the potential shared genes and pathways that may lead to cognitive dysfunction in AD and COVID-19. We also constructed ingenuity AD-high-risk scores based on AD-high-risk genes from transcriptomic, proteomic, and Genome-Wide Association Studies (GWAS) data to identify disease-associated cell subtypes and potential targets in COVID-19 patients. We demonstrated that the primary disturbed cell populations were astrocytes and neurons between the above two dis-eases that exhibit cognitive impairment. We identified significant relationships between COVID-19 and AD involving synaptic dysfunction, neuronal damage, and neuroinflammation. Our findings may provide new insight for future studies to identify novel targets for preventive and therapeutic interventions in COVID-19 patients.


Assuntos
Doença de Alzheimer , COVID-19 , Disfunção Cognitiva , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , COVID-19/complicações , COVID-19/genética , Disfunção Cognitiva/genética , Estudo de Associação Genômica Ampla , Humanos , Proteômica , RNA , SARS-CoV-2 , Análise de Sequência de RNA
7.
JAMA Netw Open ; 5(8): e2228002, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35994286

RESUMO

Importance: Placenta previa is widely acknowledged as a risk factor for placenta accreta spectrum (PAS) disorders, which are severe maternal complications; however, data are limited regarding whether placenta previa is associated with a higher risk of worse maternal outcomes among patients with PAS disorders. Objective: To examine the association between placenta previa and the risk of severe maternal morbidities (SMMs) and higher resource use among patients with PAS disorders. Design, Setting, and Participants: This retrospective cohort study extracted records of 3793 patients with PAS diagnosis and delivery indicators between October 1, 2015, and December 31, 2019, from the US National Inpatient Sample database. Exposures: Placenta previa. Main Outcomes and Measures: Data on 21 Centers for Disease Control and Prevention-defined SMMs and 25 study-defined surgical morbidities associated with PAS were extracted. Six surgical procedures (cystoscopy, intra-arterial balloon occlusion, cesarean delivery, hysterectomy, cystectomy, and oophorectomy), hospital length of stay, and inpatient costs were compared. Multivariable Poisson regression models built in the generalized estimating equation framework were used. Results: Among 3793 patients with PAS (median [IQR] age at admission, 33 [29-37] years), 621 women (16.4%) were Black, 765 (20.2%) were Hispanic, 1779 (46.9%) were White, 441 (11.6%) were of other races and/or ethnicities (47 [1.2%] were American Indian, 220 [5.8%] were Asian or Pacific Islander, and 174 [4.6%] were of multiple or other races and/or ethnicities), and 187 (4.9%) were of unknown race and ethnicity. A total of 1323 patients (34.9%) had placenta previa and 2470 patients (65.1%) did not; of those with placenta previa, 405 patients (30.6%) had invasive PAS. Patients with vs without placenta previa had a significantly higher rate and risk of any SMM (935 women [70.7%] vs 1087 women [44.0%]; P < .001; adjusted risk ratio [aRR], 1.19; 95% CI, 1.12-1.27) and any surgical morbidity (1170 women [88.4%] vs 1667 women [67.5%]; P < .001; aRR, 1.18; 95% CI, 1.13-1.23). With regard to specific outcomes, those with vs without placenta previa had a significantly higher rate of peripartum hemorrhage (878 patients [66.4%] vs 1217 patients [49.3%]; P < .001), blood product transfusion (413 patients [31.2%] vs 610 patients [24.7%]; P < .001), shock (83 patients [6.3%] vs 108 patients [4.4%]; P = .01), disseminated intravascular coagulation or other coagulopathy (77 patients [5.8%] vs 105 patients [4.3%]; P = .04), and urinary tract injury (44 patients [3.3%] vs 41 patients [1.7%]; P = .002). Patients with vs without placenta previa were more likely to undergo cesarean delivery (1292 patients [97.7%] vs 1787 patients [72.3%]; P < .001), hysterectomy (786 patients [59.4%] vs 689 patients [27.9%]; P < .001), cystoscopy (301 patients [22.8%] vs 203 patients [8.2%]; P < .001), cystectomy (157 patients [11.9%] vs 98 patients [4.0%]; P < .001), and intra-arterial balloon occlusion (121 patients [9.1%] vs 77 patients [3.1%]; P < .001) and to have significantly longer hospital length of stay (median [IQR], 5 [4-11] days vs 3 [3-5] days; P < .001) and total inpatient costs (median [IQR], $17 496 [$10 863-$30 619] vs $9728 [$6130-$16 790]; P < .001). Hypertensive disorder of pregnancy was associated with a decreased risk of placenta previa (aRR, 0.67; 95% CI, 0.46-0.96) among patients with PAS. Conclusions and Relevance: In this study, placenta previa was associated with an increased risk of maternal and surgical morbidities and higher resource use among women with PAS. These findings suggest that interventions to alleviate maternal and surgical morbidities are especially needed for patients with placenta previa-complicated PAS disorders.


Assuntos
Placenta Acreta , Placenta Prévia , Cesárea/efeitos adversos , Feminino , Humanos , Histerectomia/efeitos adversos , Placenta Acreta/diagnóstico , Placenta Acreta/epidemiologia , Placenta Acreta/etiologia , Placenta Prévia/epidemiologia , Placenta Prévia/etiologia , Placenta Prévia/cirurgia , Gravidez , Estudos Retrospectivos , Estados Unidos/epidemiologia
8.
Front Endocrinol (Lausanne) ; 13: 862785, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35663330

RESUMO

Background: It remained controversial whether women with multiple gestation are at higher risk of placenta accreta spectrum (PAS) disorders and large-scale studies are needed. This study aimed to assess whether PAS incidence is higher among women with multiple gestation than among singleton, as well as to compare the characteristics and outcomes of PAS in multiple and singleton gestation. Methods: Women who underwent cesarean section with live births at Peking University First Hospital from January 2015 to December 2020 were included. Demographic and clinical information was collected through chart review. Logistic regression models were used to analyze the associations between multiple gestation and PAS. The clinical characteristics and perioperative outcomes of PAS in multiple and singleton gestation were further compared. Results: Among the 14583 women included, 2.4% (352/14583) were diagnosed with PAS. PAS was slightly more prevalent among multiple gestations than among singletons (2.5% vs 2.4%, P=0.857). After adjusting for known risk factors and pregnancy complications, multiple gestation was associated with a higher risk of PAS (aOR=1.63, 95% CI 1.01-2.62). Among PAS patients, women who had multiple births had a significantly lower rate of previous cesarean deliveries (27.6% vs. 56.3%, P=0.003), placenta previa (17.2% vs. 56.3%, P<0.001) and invasive PAS (24.1% vs. 53.9, P=0.002) than singletons. There were no significant differences in perioperative outcomes between these two groups. Conclusion: Multiple gestation could be independently associated with an elevated risk of PAS. The clinical characteristics of PAS in the multiple and singleton gestation groups differed significantly in cesarean delivery history and placenta previa. The results of this study may inform guidelines on the screening, early detection and timely intervention of PAS patients among women with multiple births.


Assuntos
Placenta Acreta , Placenta Prévia , Cesárea , China/epidemiologia , Feminino , Humanos , Placenta Acreta/epidemiologia , Placenta Acreta/etiologia , Placenta Acreta/cirurgia , Placenta Prévia/epidemiologia , Placenta Prévia/etiologia , Gravidez , Estudos Retrospectivos
10.
J Med Chem ; 65(9): 6573-6592, 2022 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-35500243

RESUMO

EZH2 inhibitors that prevent trimethylation of histone lysine 27 (H3K27) are often limited to the treatment of a subset of hematological malignancies. In most solid tumors, EZH2 inhibitors induce reciprocal H3K27 acetylation that subsequently results in acquired drug resistance. The combination of EZH2 and BRD4 inhibitors to resensitize solid cancer cells to EZH2 inhibitors has proven to be effective, underlying the significance of developing dual inhibitors. Herein, we present the design, synthesis, and biological evaluation of first-in-class dual EZH2/BRD4 inhibitors. Our most promising compound, YM458, displays potent inhibitory activity against EZH2 and BRD4 and remarkable antiproliferative capacity against 11 solid cancer cell lines. Its in vivo therapeutic potential is validated in both lung cancer and pancreatic cancer xenograft tumor mice models, highlighting the potential of EZH2/BRD4 dual inhibitors to target a broad scope of EZH2 inhibitor-resistant solid tumors.


Assuntos
Neoplasias , Proteínas Nucleares , Animais , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proteína Potenciadora do Homólogo 2 de Zeste , Histonas , Humanos , Camundongos , Neoplasias/tratamento farmacológico , Fatores de Transcrição
11.
Clin Appl Thromb Hemost ; 28: 10760296211070580, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34994211

RESUMO

OBJECTIVES: To analyze the association between pre-operational coagulation indicators and the severity of placenta accreta spectrum (PAS), as well as blood loss volume during operation. METHODS: Hospitalized patients of the obstetric department in a major hospital from 2018 to 2020 who were clinically and/or pathologically diagnosed with invasive PAS were included. Univariate and multivariate logistic regression and Poisson regression models were used to quantify the association between each of the 6 coagulation indicators and PAS severity (measured by FIGO grade) as well as maternal outcomes. RESULTS: Ninety-five patients (46 FIGO grade 2 and 49 FIGO grade 3) were included. Higher PT [adjusted OR (aOR): 5.54; 95% CI, 1.80 to 17.07] and FDP (aOR: 1.19; 95% CI, 1.01-1.42) levels were associated with an increased risk of FIGO grade 3 after adjusting for covariates. D-dimer [incidence rate ratio (IRR): 1.19; 95% CI, 1.05 to 1.35)] and FDP (IRR: 1.03; 95% CI, 1.01-1.04) levels were significantly associated with higher blood loss volume after adjusting for covariates. CONCLUSION: Preoperative coagulation indicators, especially PT, D-dimer and FDP, are associated with disease severity and blood loss volume during operation of invasive PAS. The underlying mechanism for the coagulation profile of PAS patients warrants further analysis. SYNOPSIS: Preoperative coagulation indicators, especially PT, D-dimer and FDP, are associated with disease severity and blood loss volume during operation among invasive placenta accreta spectrum patients.


Assuntos
Coagulação Sanguínea/fisiologia , Perda Sanguínea Cirúrgica/prevenção & controle , Procedimentos Cirúrgicos em Ginecologia/métodos , Placenta Acreta/sangue , Cesárea , Feminino , Humanos , Recém-Nascido , Placenta Acreta/diagnóstico , Placenta Acreta/cirurgia , Gravidez , Período Pré-Operatório , Estudos Retrospectivos , Índice de Gravidade de Doença
12.
J Colloid Interface Sci ; 613: 796-805, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35066235

RESUMO

Developing the high-performance supercapacitors is overwhelmingly dependent on the composition design and structure tailoring of electrode materials. By a one-step solution method, the composite of carbon dots/Prussian blue analogues nanocubes-incorporated three-dimensional Ni foams was prepared and used as a self-standing positive electrode for hybrid electrochemical capacitors (HEC). Aside from the role of Ni source for Prussian blue analogues (PBA), Ni foams acts as 3D conductive supports, making electrolytes more accessible to the internal surface of electrode. Meanwhile, carbon dots can be absorbed for the formation of carbon dots/PBA nanocubes on Ni foams surfaces, offering optimized interfaces for the interactions between electrodes and electrolytes and relieving the decomposition of PBA in alkaline electrolyte. With these merits, the carbon dots/Prussian blue analogues nanocubes-Ni foams electrode in the hybrid electrolyte of 0.5 M KOH and 1.3 M Na2SO4 exhibits a maximum specific capacity of 659 C g-1 at current density of 0.5 A g-1 and 344 C g-1 even under large current density of 5 A g-1. An extended working potential window of 1.8 V, high energy density of 65 Wh kg-1 and high power density of 4.052 kW kg-1 as well as improved cyclic stability are also achieved in the assembled HEC. This study builds a boulevard to improve the application potential of PBA in HEC, which will be beneficial for the development of supercapacitors.

14.
J Cell Mol Med ; 25(2): 919-924, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33280245

RESUMO

YKL-40 was reported to be associated with the risk of hypertension. Whether the variants of CHI3L1 gene were associated with both YKL-40 levels and hypertension needs to be further elucidated. In a 1:1 matched case-control study of 507 pairs with available YKL-40 levels and DNA samples nested in a prospective cohort of Chinese subjects, the 15 tag single nucleotide polymorphisms (SNPs) of CHI3L1 gene were genotyped. The levels of YKL-40 among different genotypes of each SNP were compared after false discovery rate adjustment. Multivariable conditional logistic regression analyses were used to explore the association between the genotypes and the risk of hypertension. Subjects with the genetic variants for rs10399931, rs1538372, rs2071580, rs2297839 and rs4950928 had lower YKL-40 levels. The genetic variant for rs10399805 was associated with higher YKL-40 level. Subjects with the genotype of GA/AA of rs10399805 had a 1.34-fold risk of hypertension compared with those with GG genotype in the total population (P = .05). Subjects with heterozygote/rare homozygote genotype of rs4950928 and rs2297839 both had a significantly lower risk of hypertension compared with those with major homozygote genotype among men. The ORs (95% CIs) were 0.46 (0.23-0.89) and 0.49 (0.26-0.91), respectively. The above three SNPs could significantly improve the accuracy of risk prediction for hypertension based on the conventional factors. The genotypes of rs10399805, rs4950928 and rs2297839 may hopefully become stable biomarkers for predicting the risk of hypertension.


Assuntos
Proteína 1 Semelhante à Quitinase-3/genética , Predisposição Genética para Doença , Hipertensão/epidemiologia , Hipertensão/genética , Polimorfismo de Nucleotídeo Único/genética , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco
15.
Int J Biol Macromol ; 167: 10-22, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33249153

RESUMO

Antibacterial wound dressings can effectively avoid the residual of antibacterial nanomaterials for injection in vivo, reduce their biological toxicity to normal cells and tissues, making them be widely applied in biomedical field. Herein, an approach of combining ion-crosslinking, in-situ reduction and microwave-assisted methods was employed to prepare chitosan-copper-gallic acid nanocomposites (CS-Cu-GA NCs) with dual-functional nano-enzyme characteristics (oxidase- and peroxidase-like functions). The oxidase-like activity of CS-Cu-GA NCs can facilitate the production of hydrogen peroxide (H2O2) when it contacted with physiologically relevant antioxidants (AH2) in bacteria. Subsequently, H2O2 was catalyzed to generate hydroxyl radicals (OH) under the peroxidase-like activity of CS-Cu-GA NCs. Furthermore, CS-Cu-GA NCs integrate the inherent antibacterial properties of chitosan, Cu NPs and Cu2+. Animal experiments revealed that the antibacterial dressing incorporating CS-Cu-GA NCs exhibited its effective promotion of S. aureus-infected wounds healing, as well as no damage to normal tissues. Besides, the antibacterial dressing was prepared to a band aid with excellent water swelling and antibacterial properties, which was further fixed in a medical tape to construct a portable antibacterial product that can be applied to the surface of human skin and showed excellent waterproof performance, providing a new insight for the construction of clinical antibacterial wound healing products.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Bandagens , Quitosana/química , Cobre/química , Ácido Gálico/química , Nanocompostos/química , Animais , Catálise , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Nanocompostos/ultraestrutura , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
16.
Carbohydr Polym ; 247: 116739, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32829858

RESUMO

The bacterial infection is one of the most common but critical problems in the wound healing process due to the general antibiotic resistance of bacteria. Hence it is increasingly necessary and urgent to develop an advanced and efficient sterilization strategy. Herein, a chitosan-based aerogel embedded amino-functionalized molybdenum disulfide nanosheets (abbreviated to CS/NMNSs) was successfully constructed through amino modification and physical assembly. Scanning electron microscopy characterizations and swelling experiments indicated that freeze-dried chitosan aerogel is provided with extremely regular sponge-like structure, high porosity, and favorable swelling property. The CS aerogel can be used as an ideal bacterial adsorption agent ascribed to its inherent positive charge. The result of antibacterial studies showed that the CS/NMNSs exhibited efficient bacterial elimination capacity via capture ability of chitosan aerogel and near infrared induced photothermal sterilization. Therefore, the CS/NMNSs have great potential in developing as a photothermal antibacterial agent in future application.


Assuntos
Antibacterianos/farmacologia , Bactérias/crescimento & desenvolvimento , Infecções Bacterianas/prevenção & controle , Quitosana/química , Dissulfetos/química , Farmacorresistência Bacteriana/efeitos dos fármacos , Molibdênio/química , Fototerapia/métodos , Bactérias/efeitos dos fármacos , Infecções Bacterianas/microbiologia , Porosidade , Cicatrização
17.
iScience ; 23(7): 101307, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32634743

RESUMO

Cross-coupling reactions between aryl iodide and nucleophiles have been well developed. Iodoniums equipped with a reactive C-I(III) bond accelerate cross-coupling reactions of aryl iodide. Among them, cyclic diaryliodoniums are more atom economical; however; they are often in the trap of metal reliance and encounter regioselectivity issues. Now, we have developed a series of highly reactive cyclic monoaryl-vinyl iodoniums that can be tuned to construct C-N, C-O, and C-C bonds without metal catalysis. Under promotion of triethylamine, coupling reactions with aniline, phenol, aromatic acid, and indole proceed rapidly and regioselectively at room temperature. The carbene species is conceptualized as a key intermediate in our mechanism model. Furthermore, the coupling products enable diversity-oriented synthesis strategy to further build up a chemical library of diverse heterocyclic fragments that are in demand in the drug discovery field. Our current work provides a deep insight into the synthetic application of these highly reactive cyclic iodoniums.

18.
Biomater Sci ; 8(15): 4266-4274, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32588850

RESUMO

Bacterial infection has been recognized as one of the greatest threats to public health. In view of the continuous increase of bacterial resistance, constructing a collaborative bactericidal platform is a promising strategy to enhance the efficiency of antimicrobial agents. Herein, we report a facile, biocompatible and versatile nano-platform based on positively charged copper manganate nanoflakes (CuMnO2 NFs), which exhibits intrinsic peroxidase-like catalytic activity and excellent photothermal properties. The CuMnO2 NFs can bind with negatively charged bacteria via electrostatic interactions, and generate hydroxyl radicals (˙OH) through catalysis involving hydrogen peroxide (H2O2) to make bacteria more susceptible to temperature. Introducing near-infrared light generates hyperthermia to fight against bacteria and enhances the peroxidase-like catalytic activity of the CuMnO2 NFs, thus producing more ˙OH to combat bacteria. The PTT-enhanced ˙OH synergistic antibacterial strategy exerts desirable antibacterial efficiencies of 98.78% and 99.92% against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) at a controlled low temperature (below 50 °C), without damage to healthy tissues. Animal experiments indicate that this synergistic treatment has a better therapeutic effect on S. aureus-infected wounds in mice, compared with either treatment by itself. Therefore, this work holds great promise for developing new synergistic antimicrobial strategies to treat bacterial infections.


Assuntos
Hipertermia Induzida , Staphylococcus aureus , Animais , Antibacterianos/farmacologia , Catálise , Cobre , Escherichia coli , Peróxido de Hidrogênio , Camundongos
19.
BMC Med Genomics ; 13(1): 59, 2020 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-32252754

RESUMO

BACKGROUND: Escherichia coli are mostly commensals but also contain pathogenic lineages. It is largely unclear whether the commensal E. coli as the potential origins of pathogenic lineages may consist of monophyletic or polyphyletic populations, elucidation of which is expected to lead to novel insights into the associations of E. coli diversity with human health and diseases. METHODS: Using genomic sequencing and pulsed field gel electrophoresis (PFGE) techniques, we analyzed E. coli from the intestinal microbiota of three groups of healthy individuals, including preschool children, university students, and seniors of a longevity village, as well as colorectal cancer (CRC) patients, to probe the commensal E. coli populations for their diversity. RESULTS: We delineated the 2280 fresh E. coli isolates from 185 subjects into distinct genome types (genotypes) by PFGE. The genomic diversity of the sampled E. coli populations was so high that a given subject may have multiple genotypes of E. coli, with the general diversity within a host going up from preschool children through university students to seniors. Compared to the healthy subjects, the CRC patients had the lowest diversity level among their E. coli isolates. Notably, E. coli isolates from CRC patients could suppress the growth of E. coli bacteria isolated from healthy controls under nutrient-limited culture conditions. CONCLUSIONS: The coexistence of multiple E. coli lineages in a host may help create and maintain a microbial environment that is beneficial to the host. As such, the low diversity of E. coli bacteria may be associated with unhealthy microenvironment in the intestine and hence facilitate the pathogenesis of diseases such as CRC.


Assuntos
Neoplasias Colorretais/patologia , DNA Bacteriano/análise , Infecções por Escherichia coli/complicações , Escherichia coli/classificação , Escherichia coli/genética , Variação Genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , China/epidemiologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/microbiologia , DNA Bacteriano/genética , Infecções por Escherichia coli/microbiologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Microambiente Tumoral , Adulto Jovem
20.
Coron Artery Dis ; 31(4): 372-377, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31860558

RESUMO

OBJECTIVE: We aimed to detect the synergistic effect between alcohol drinking, smoking and obesity on incident cardiovascular disease (CVD) in a Chinese population- based cohort. METHODS: We performed this study based on a prospective cohort based on a Chinese population in Jiangsu, China. Logistic regression was employed to detect the interaction of smoking, drinking with obesity on susceptibility to CVD, and calculate the odds ratio (OR) of CVD and corresponding 95% confidence interval (CI). RESULTS: A total of 3598 subjects (1451 males and 2147 females) were enrolled, including 82 CVD patients (36 males and 46 females) who new developed CVD at the follow-up. We found a significant abdominal obesity-current smoking interaction on CVD risk. Compared to never-smokers with normal waist circumference, OR (95% CI) of CVD were 2.44 (1.56-3.81), 1.58 (0.93-2.69), and 5.37 (3.08-9.34) for smokers with normal waist circumference, abdominal obese nonsmokers and abdominal obese smokers, respectively. Synergy index for this interaction was 2.35 (1.05-4.50). We also found a significant abdominal obesity-alcohol drinking interaction on CVD. Compared to never-drinkers with normal waist circumference, OR (95% CI) of CVD were 1.57 (1.01-2.45), 1.84 (1.08-3.12), and 4.44 (2.55-7.72) for drinkers with normal waist circumference, abdominal obese non- drinkers and abdominal obese drinkers, respectively. Synergy index for this interaction was 2.44 (1.04-5.72). CONCLUSION: We found significant interactions between alcohol drinking and abdominal obesity, smoking and abdominal obesity on CVD risk, suggested that the effect of alcohol drinking or smoking on CVD susceptibility seems to be modified by abdominal obesity.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Doenças Cardiovasculares/etiologia , Obesidade/complicações , Fumar/efeitos adversos , Adulto , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , China/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Estudos Prospectivos , Fatores de Risco , Fumar/epidemiologia , Taxa de Sobrevida/tendências
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