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1.
Artigo em Inglês | MEDLINE | ID: mdl-34114304

RESUMO

Site-selective incorporation of deuterium into biologically active compounds is of high interest in pharmaceutical industry. We present a mild and environmentally benign metal-free method for the remote selective radical C-H monodeuteration of aliphatic C-H bonds in various amides with inexpensive heavy water (D2O) as the deuterium source. The method uses the easily installed N-allylsulfonyl moiety as N-radical precursor that generates the remote C-radical via site-selective 1,5- or 1,6-hydrogen atom transfer (HAT). Methyl thioglycolate, that readily exchanges its proton with D2O, serves as the radical deuteration reagent and as a chain-carrier. The highly site-selective monodeuteration has been applied to different types of unactivated sp3-C-H bonds and also to the deuteration of C-H bonds next to heteroatoms. The potential utility of this method is further demonstrated by the site-selective incorporation of deuterium into natural product derivatives and drugs.

2.
J Pharm Biomed Anal ; 203: 114176, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34098508

RESUMO

In this study, we identify the triterpene saponins (TSs) extracted from the leaves and buds of Aralia elata (Miq.) Seems using ultra-performance liquid chromatography and positive ionization electrospray quadrupole time-of-flight mass spectrometry (UPLC-ESI+-QTOF). The energy-resolved MSAll (erMSall) technique is applied in order to simultaneously collect the diverse precursors attributed to [M+H]+, [M + NH4]+ and [M + Na]+ ions. A practical and effective erMSall workflow is established to rapidly identify and compare the saponins in the analyzed samples. In total, 111 TSs of structure are estimated, including 44 new compounds that had not been identified previously in A. elata. Of the five aglycones detected in the samples, a sapogenin 3ß, 16α, 23-trihydroxyoleana-11,13-dien-28-oic acid (A5) that is identified for the first time in A. elata leaves. Compared to the buds, the leaves number twice as many hederagenin-type (A2) compounds. Although the number of other aglycones does not vary significantly between the buds and the leaves, A5 compounds are exclusively detected in the latter. Moreover, the C-3 sugar chains of TSs in A. elata leaves are mainly neutral (e.g., Hex+Hex, Hex+Hex+Hex and Hex+Hex+Hex+Hex), whereas those of bud TS compounds are primarily acidic (e.g., Pen+HexA, Hex+HexA and Hex+Pen+HexA). Some of the identified TS compounds, e.g., 27, 28, 32, 46, 54, 57, 71 and 105 can be used as indices to evaluate the quality of the plant leaves and buds. Overall, this study is of great significance for the comparative study of triterpenoid saponins in the leaves and buds of Aralia elata.

3.
Sci Rep ; 11(1): 11272, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34050207

RESUMO

O-GlcNAcylation, an energy-sensitive posttranslational modification, can regulate the activity of endothelial nitric oxide synthase (eNOS). Previous studies found that Thr866 is the key site for low-glucose-mediated regulation of eNOS O-GlcNAc. However, it is not known whether this activity functions through the Thr866 site concomitant with other physical and chemical factors. Therefore, we first explored the effects of physical and chemical factors on eNOS O-GlcNAc and its Thr866 site. In this study, hypertonic stress, hyperthermia and hydrogen peroxide all increased the expression levels of eNOS O-GlcNAc, whereas hypoxia and high levels of alcohol had no effect. on the expression levels of eNOS O-GlcNAc; by contrast, low pH led to a decrease in eNOS O-GlcNAc levels. Notably, eNOS O-GlcNAc protein levels were unchanged after Thr866 site mutation only under hypertonic conditions, suggesting that hypertonic stress may act through the Thr866 site. Upon exploring the mechanism of hypertonic stress on eNOS O-GlcNAc activity and function, we found that hypertonic stress can upregulate the expression of O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), which is dependent on AMPK. When AMPK was knocked out, the upregulation of OGT expression and increased O-GlcNAc modifications induced by hypertonic stress were reversed.

4.
Jpn J Infect Dis ; 2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34053954

RESUMO

Xpert Xpress Flu/RSV is a fast and automated real-time nucleic acid amplification tool for detecting influenza virus and respiratory syncytial virus (RSV). The aim of this study was to verify the accuracy of Xpert Xpress Flu/RSV in detecting influenza virus and RSV. PubMed, EMBASE, Cochrane Library, and Web of Science were searched up to October 2020. The quality of original research was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 guidelines. Meta-DiSc 1.4 software was used to analyze the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and Summary receiver operating characteristic curve. Deek's funnel plot asymmetry test was used to evaluate the publication bias by Stata 12.0. Ten studies with 25 fourfold tables were included in this analysis. The sensitivity of Xpert Xpress Flu/RSV in detecting influenza A, influenza B, and RSV was 0.97, 0.98, 0.96, respectively, and the specificity was 0.97, 1.00, 1.00, respectively. Compared with other common clinical real-time reverse transcriptase PCR (RT-PCR), Xpert Xpress Flu/RSV is a valuable tool for diagnosing influenza virus and RSV with high sensitivity and specificity.

5.
Curr Microbiol ; 78(6): 2231-2241, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33963446

RESUMO

Small non-coding RNAs (sRNAs) are a class of regulatory RNAs 20-500 nucleotides in length, which have recently been discovered in prokaryotic organisms. sRNAs are key regulators in many biological processes, such as sensing various environmental changes and regulating intracellular gene expression through binding target mRNAs or proteins. Bacterial sRNAs have recently been rapidly mined, thus providing new insights into the regulatory network of biological functions in prokaryotes. Although most bacterial sRNAs have been discovered and studied in Escherichia coli and other Gram-negative bacteria, sRNAs have increasingly been predicted and verified in Gram-positive bacteria in the past decade. The genus Streptococcus includes many commensal and pathogenic Gram-positive bacteria. However, current understanding of sRNA-mediated regulation in Streptococcus is limited. Most known sRNAs in Streptococcus are associated with the regulation of virulence. In this review, we summarize recent advances in understanding of the functions and mechanisms of sRNAs in Streptococcus, and we discuss the RNA chaperone protein and synthetic sRNA-mediated gene regulation, with the aim of providing a reference for the study of microbial sRNAs.


Assuntos
Pequeno RNA não Traduzido , Regulação Bacteriana da Expressão Gênica , RNA Bacteriano/genética , Pequeno RNA não Traduzido/genética , Streptococcus , Virulência
6.
J Sci Food Agric ; 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33937994

RESUMO

BACKGROUND: Streptococcus thermophilus, one of the most important lactic acid bacteria, is widely used in food fermentation, which is beneficial to improve food quality. However, the current genetic transformation systems are inefficient for S. thermophilus S-3, which hinders its further study. RESULTS: We developed three electroporation transformation methods for S. thermophilus S-3, and optimized various parameters to enhance the transformation efficiency up to 1.3 × 106 CFU/µg DNA, which was 32-fold higher than that of unoptimized. Additionally, transcriptional analysis showed that a series of competence genes in S. thermophilus S-3 were remarkedly up-regulated after optimization, indicating that improvement of transformation efficiency was attributed to the expression level of competence genes. Furthermore, to prove their potential, expression of competence genes (comEA, cbpD and comX) were employed to increase transformation efficiency. The maximum transformation efficiency was obtained by overexpression of comEA, which was 14-fold higher than that of control. CONCLUSION: This is the first report of competence gene expression for enhancing transformability in S. thermophilus, which exerts a positive effect on the development of desirable characteristics strains. © 2021 Society of Chemical Industry.

7.
FEBS Open Bio ; 2021 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-33993653

RESUMO

Endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) plays a crucial role in maintaining vascular homeostasis. As a hallmark of eNOS activation, phosphorylation of eNOS at Ser1177 induced by activated protein kinase B (PKB/Akt) is pivotal for NO production. The complete activation of Akt requires its phosphorylation of both Thr308 and Ser473. However, which site plays the main role in regulating phosphorylation of eNOS Ser1177 is still controversial. The purpose of the present study is to explore the specific regulatory mechanism of phosphorylated Akt in eNOS activation. Inhibition of Akt Thr308 phosphorylation by a specific inhibitor or by siRNA in vitro led to a decrease in eNOS phosphorylation at Ser1177 and to lower NO concentration in the cell culture medium of HUVECs. However, inhibiting p-Akt Ser473 had no effect on eNOS phosphorylation at Ser1177. Next, we administered mice with inhibitors to downregulate p-Akt Ser473 or Thr308 activity. Along with the inhibition of p-Akt Thr308, vascular p-eNOS Ser1177 protein was simultaneously downregulated in parallel with a decrease in plasma NO concentration. Additionally, we cultured HUVECs at various temperature conditions (37, 22, and 4 °C). The results showed that p-Akt Ser473 was gradually decreased in line with the reduction in temperature, accompanied by increased levels of p-Akt Thr308 and p-eNOS Ser1177. Taken together, our study indicates that the phosphorylation of Akt at Thr308, but not at Ser473, plays a more significant role in regulating p-eNOS Ser1177 levels under physiological conditions.

8.
Comput Methods Programs Biomed ; 206: 106142, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34004500

RESUMO

BACKGROUND AND OBJECTIVE: Automatic cardiac segmentation plays an utmost role in the diagnosis and quantification of cardiovascular diseases. METHODS: This paper proposes a new cardiac segmentation method in short-axis Magnetic Resonance Imaging (MRI) images, called attention U-Net architecture with input image pyramid and deep supervised output layers (AID), which can fully-automatically learn to pay attention to target structures of various sizes and shapes. During each training process, the model continues to learn how to emphasize the desired features and suppress irrelevant areas in the original images, effectively improving the accuracy of cardiac segmentation. At the same time, we introduce the Focal Tversky Loss (FTL), which can effectively solve the problem of high imbalance in the amount of data between the target class and the background class during cardiac image segmentation. In order to obtain a better representation of intermediate features, we add a multi-scale input pyramid to the attention network. RESULTS: The proposed cardiac segmentation technique is tested on the public Left Ventricle Segmentation Challenge (LVSC) dataset, which is shown to achieve 0.75, 0.87 and 0.92 for Jaccard Index, Sensitivity and Specificity, respectively. Experimental results demonstrate that the proposed method is able to improve the segmentation accuracy compared with the standard U-Net, and achieves comparable performance to the most advanced fully-automated methods. CONCLUSIONS: Given its effectiveness and advantages, the proposed method can facilitate cardiac segmentation in short-axis MRI images in clinical practice.


Assuntos
Imagem Cinética por Ressonância Magnética , Redes Neurais de Computação , Coração/diagnóstico por imagem , Ventrículos do Coração , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética
9.
Sleep Med ; 81: 375-381, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33813234

RESUMO

BACKGROUND: The co-occurrence of insomnia and hypersomnia symptoms in patients with major depressive disorder (MDD) is associated with suicidal ideation and functional impairment. The relationship between sleep disturbances and clinical features and outcomes may not be adequately studied. In this study, we measured the functional impairments and clinical features of co-occurring insomnia and hypersomnia symptoms in Chinese patients with MDD. METHODS: A post-hoc analysis was performed on data from the National Survey on Symptomatology of Depression (NSSD), which assessed the MDD patients in 32 hospitals by a clinician-rating questionnaire. The clinical features and outcomes were compared among the following four groups: insomnia symptom only, hypersomnia symptom only, both insomnia and hypersomnia symptoms, no sleep disturbance, respectively. RESULTS: Totally, 234 (7.15%) of 3275 participants with MDD co-occurred insomnia and hypersomnia symptoms. They had more depressive symptoms (27.41 ± 9.123), higher rate of suicide ideation (39.7%), more severe impairment in physical (58.1%), economic (32.9%), work (55.1%), and relationship with families (29.5%). Patients with both sleep disturbances were more likely to excessive worry about sleep, have suicidal ideation, the distress of social disharmony, more somatic symptoms, lack of energy, hyperphagia, loss of mood reactivity, and diurnal change, whereas less likely to have anxious mood. LIMITATIONS: Sleep disorders were not diagnosed by current standard diagnostic criteria. CONCLUSIONS: Patients co-occurring with both sleep disturbances are associated with a higher rate of suicide risk and poorer social function. Our study could provide implications for suicidal risk evaluation and the development of therapeutic strategies for depression.

10.
Nat Commun ; 12(1): 2047, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33824349

RESUMO

Human chromosome 9p21.3 is susceptible to inactivation in cell immortalization and diseases, such as cancer, coronary artery disease and type-2 diabetes. Although this locus encodes three cyclin-dependent kinase (CDK) inhibitors (p15INK4B, p14ARF and p16INK4A), our understanding of their functions and modes of action is limited to the latter two. Here, we show that in vitro p15INK4B is markedly stronger than p16INK4A in inhibiting pRb1 phosphorylation, E2F activity and cell-cycle progression. In mice, urothelial cells expressing oncogenic HRas and lacking p15INK4B, but not those expressing HRas and lacking p16INK4A, develop early-onset bladder tumors. The potency of CDKN2B/p15INK4B in tumor suppression relies on its strong binding via key N-terminal residues to and inhibition of CDK4/CDK6. p15INK4B also binds and inhibits enolase-1, a glycolytic enzyme upregulated in most cancer types. Our results highlight the dual inhibition of p15INK4B on cell proliferation, and unveil mechanisms whereby p15INK4B aberrations may underpin cancer and non-cancer conditions.


Assuntos
Ciclo Celular , Cromossomos de Mamíferos/genética , Inibidor de Quinase Dependente de Ciclina p15/metabolismo , Glicólise , Aerobiose , Sequência de Aminoácidos , Animais , Ligação Competitiva , Cruzamento , Carcinogênese/metabolismo , Carcinogênese/patologia , Linhagem Celular Tumoral , Proliferação de Células , Cruzamentos Genéticos , Inibidor de Quinase Dependente de Ciclina p15/química , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Quinases Ciclina-Dependentes/metabolismo , Regulação para Baixo , Feminino , Humanos , Ligação de Hidrogênio , Masculino , Camundongos Transgênicos , Modelos Moleculares , Oncogenes , Penetrância , Fosfopiruvato Hidratase/metabolismo , Domínios Proteicos , Proteínas Proto-Oncogênicas p21(ras) , Homologia Estrutural de Proteína , Neoplasias da Bexiga Urinária/patologia , Urotélio/metabolismo
11.
J Colloid Interface Sci ; 598: 419-429, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33930746

RESUMO

The development of zinc-ion storage cathode materials for aqueous zinc-ion batteries (AZIBs) is a necessary step for the construction of large-scale electrochemical energy conversion and storage devices. Iron-doped alpha-manganese dioxide (α-MnO2) nanocomposites were achieved in this study via pre-intercalation of Fe3+ during the formation of α-MnO2 crystals. A polypyrrole (PPy) granular layer was fabricated on the surface of α-MnO2 using acid-catalyzed polymerization of pyrroles. The pre-intercalation of Fe3+ effectively enlarges the lattice spacing of α-MnO2 and consequently decreases the hindrance for Zn2+ insertion/extraction in the iron-doped α-MnO2 coated by PPy (Fe/α-MnO2@PPy) composite. Meanwhile, the PPy buffer layer can ameliorate electron and ion conductivity and prevent dissolution of α-MnO2during the charge/discharge process. This unique structure makes the Fe/α-MnO2@PPy composite an efficient zinc-ion storage cathode for AZIBs. The targeted Fe/α-MnO2@PPy cathode achieves superior performance with reversible specific capacity (270 mA h g-1 at 100 mA g-1) and exhibits highdiffusioncoefficientof 10-10-10-14 cm-2 s-1. Therefore, a feasible approach is implemented on advanced electrode materials using in AZIBs for practical applications.

12.
Int J Med Microbiol ; 311(4): 151501, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33866091

RESUMO

BACKGROUND: Previous studies reported the prevalence of mcr-1 among clinical infected Salmonella isolates in China. However, the transmission dynamics of mcr-1 in different ecological niches were not well investigated. Our objective is to exhibit the transmission dynamics of mcr-1 in Salmonella. METHODS: 598 Salmonella isolates were recovered from ten hospitals; besides 936 pig faces and 167 pork samples were collected from January 2015 to December 2017 in Guangzhou, China. PCR and sequencing were used to identify mcr-1-positive Salmonella. Antimicrobial susceptibility testing was performed with 16 antimicrobials. Conjugation, S1-PFGE, and Southern blot were used to determine the transferability and location of mcr-1. Whole-genome sequencing was used to investigate pangenome, phylogeny, plasmid, and transposon. RESULTS: Eleven mcr-1-positive Salmonella isolates were identified from patients with infectious diarrhea. Five pig fecal samples and three pork samples contained mcr-1-positive Salmonella isolates. All isolates were multi-drug resistant. The mcr-1 genes were located on ∼210-250 kb IncHI2-pST3 plasmids, and 12 mcr-1 genes were transferable. All isolates were assigned to ST34 or its genetically closed STs. The distribution of the core-genome network was significantly correlated with source distributions. The accessory genes-based network demonstrated that the diverse clonal complexes could share highly similar accessory genomes. CONCLUSIONS: The prevalence of mcr-1-positive Salmonella among different sources was low. Clonal transmission could not be the main reason for the expansion of mcr-1-positive Salmonella, but be attributed to the horizontal transfer of IncHI2-pST3 plasmid. Continuous surveillance on Salmonella should be performed to investigate the response of colistin banning in food-producing animals by mcr-1-positive Salmonella populations.


Assuntos
Antibacterianos , Salmonella typhimurium , Animais , Antibacterianos/farmacologia , China/epidemiologia , Diarreia/epidemiologia , Genômica , Humanos , Plasmídeos/genética , Prevalência , Salmonella typhimurium/genética , Suínos
13.
Int J Biol Macromol ; 183: 193-202, 2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33905800

RESUMO

In this study, a novel two-dimensional correlation infrared spectroscopy (2DCOS-IR) is presented to rapidly characterize and discriminate polysaccharides in Panax ginseng (PGP), P. notoginseng (PNP), and P. quinquefolius (PQP) using attenuated total reflection Fourier transform infrared spectroscopy-based on single-characteristic temperature as the external disturbance (2D-sATR-FTIR). Compared with two existing 2DCOS-IR methods based on gradient heating pathways using KBr pellet (100 min; 2D-KBr-FTIR) and attenuated total reflection (30 min; 2D-gATR-FTIR), the new procedure took an average of just 2 min to finish a sample measurement, which resolved previously tedious and time-consuming dilemmas. It offered advantages in the quality evaluation of natural polysaccharides and featured nondestructive, high-throughput, and high-efficiency characteristics. An intuitive analysis of the 2D-sATR-FTIR demonstrated that PNP was first identified because it had fewer auto-peaks. Posteriorly, PGP and PQP were distinguished according to the ratio of the auto-peaks 6 and 9, with the former greater than 1 and the latter less than 1. Furthermore, characteristic auto-peaks 1, 5, and 6 were unambiguously determined as Quality-markers using PCA and PLS-DA for visualized identifications. LDA was successfully used to establish a predictive model of the PGP, PNP, and PQP based on the positions and intensity of these three characteristic auto-peaks.

14.
Cell Biochem Biophys ; 79(2): 289-299, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33811614

RESUMO

The present study aimed to investigate the impacts and underlying mechanisms of 14,15-DHETs on eNOS and vascular endothelial functions. Bovine aortic endothelial cells (BAECs) were treated with various concentrations of 14, 15-DHET. The expressions of eNOS protein and mRNA were observed at different time points. The eNOS expression and phosphorylation were subsequently detected administered with 8,9-DHET, 11,12-DHET, and 14,15-DHET, respectively. Meanwhile, 14,15-DHET action on tube formation was observed in human umbilical vein endothelial cells (HUVECs). Finally, the aorta of male C57BL/6 mice was injected with 14,15-DHET via the tail vein. The impacts of 14,15-DHET (0.4 mg/kg body weight) on the expressions of eNOS protein and mRNA and endothelium-dependent vasodilation (EDV) were detected following 24 h. The expression of eNOS was greatly improved with the 14,15-DHET treatment compared with the BAECs, and eNOS phosphorylation sites at Ser1179, Ser635, and Thr497 were elevated. However, no statistically significant difference was revealed on total eNOS among the 8,9-DHET, 11,12-DHET, and 14,15-DHET treatment groups. Based on the upregulation of eNOS protein, eNOS mRNA levels were increased in BAECs and thoracic aorta of the male C57BL/6 mice treated with 14,15-DHET, suggesting that transcriptional activation was achieved in vascular eNOS. Moreover, 14,15-DHET enhanced tube formation abilities in HUVECs and acetylcholine(ACh)-induced EDV. These findings indicated that 14,15-DHET could improve the vascular endothelial diastolic functions of male C57BL/6 mice, and enhance the ability of tube formation, which might be related to the increase of eNOS expression.

15.
Adv Mater ; 33(13): e2008194, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33645858

RESUMO

Oxygen-redox of layer-structured metal-oxide cathodes has drawn great attention as an effective approach to break through the bottleneck of their capacity limit. However, reversible oxygen-redox can only be obtained in the high-voltage region (usually over 3.5 V) in current metal-oxide cathodes. Here, we realize reversible oxygen-redox in a wide voltage range of 1.5-4.5 V in a P2-layered Na0.7 Mg0.2 [Fe0.2 Mn0.6 □0.2 ]O2 cathode material, where intrinsic vacancies are located in transition-metal (TM) sites and Mg-ions are located in Na sites. Mg-ions in the Na layer serve as "pillars" to stabilize the layered structure during electrochemical cycling, especially in the high-voltage region. Intrinsic vacancies in the TM layer create the local configurations of "□-O-□", "Na-O-□" and "Mg-O-□" to trigger oxygen-redox in the whole voltage range of charge-discharge. Time-resolved techniques demonstrate that the P2 phase is well maintained in a wide potential window range of 1.5-4.5 V even at 10 C. It is revealed that charge compensation from Mn- and O-ions contributes to the whole voltage range of 1.5-4.5 V, while the redox of Fe-ions only contributes to the high-voltage region of 3.0-4.5 V. The orphaned electrons in the nonbonding 2p orbitals of O that point toward TM-vacancy sites are responsible for reversible oxygen-redox, and Mg-ions in Na sites suppress oxygen release effectively.

16.
Catheter Cardiovasc Interv ; 97 Suppl 2: 988-995, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33734575

RESUMO

OBJECTIVES: This study sought to compare the efficacy and clinical safety of the LONGTY drug-coated balloon (DCB) with those of SeQuent Please DCB in patients with in-stent restenosis (ISR). BACKGROUND: Although DCB technologies have evolved, little is known about the clinical efficacy of the new-generation LONGTY DCB. METHODS: This was a prospective, multicenter, randomized, noninferiority trial comparing LONGTY DCB with SeQuent Please DCB in patients with ISR. The primary endpoint was target lesion late lumen loss at 9 months' follow-up. RESULTS: A total of 211 patients with ISR from 13 Chinese sites were included (LONGTY DCB, n = 105; SeQuent Please DCB, n = 106). Device success was achieved in all patients. At the 9 month angiographic follow-up, target lesion late lumen loss was 0.35 ± 0.42 mm with LONGTY and 0.38 ± 0.45 mm with SeQuent Please (p for noninferiority <.001). The target lesion revascularization rates at 1 year were similar in both DCB groups (15.24 vs. 13.21%; p = .673). Over an extended follow-up of 2 years, the clinical endpoints, including cardiac death, myocardial infarction, and thrombus rate, were extremely low and similar in both groups. CONCLUSIONS: In this multicenter, head-to-head, randomized trial, the new-generation LONGTY DCB was noninferior to the SeQuent Please DCB for the primary endpoint of target lesion late lumen loss at 9 months.

17.
Emerg Microbes Infect ; 10(1): 700-709, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33739229

RESUMO

Bloodstream infections (BSIs) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) are potentially life-threatening and an urgent threat to public health. The present study aims to clarify the characteristics of carbapenemase-encoding and virulent plasmids, and their interactions with the host bacterium. A total of 425 Kp isolates were collected from the blood of BSI patients from nine Chinese hospitals, between 2005 and 2019. Integrated epidemiological and genomic data showed that ST11 and ST307 Kp isolates were associated with nosocomial outbreak and transmission. Comparative analysis of 147 Kp genomes and 39 completely assembled chromosomes revealed extensive interruption of acrR by ISKpn26 in all Kp carbapenemase-2 (KPC-2)-producing ST11 Kp isolates, leading to activation of the AcrAB-Tolc multidrug efflux pump and a subsequent reduction in susceptibility to the last-resort antibiotic tigecycline and six other antibiotics. We described 29 KPC-2 plasmids showing diverse structures, two virulence plasmids in two KPC-2-producing Kp, and two novel multidrug-resistant (MDR)-virulent plasmids. This study revealed a multifactorial impact of KPC-2 plasmid on Kp, which may be associated with nosocomial dissemination of MDR isolates.

18.
Molecules ; 26(4)2021 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-33670007

RESUMO

A novel series of 4-(4-formamidophenylamino)-N-methylpicolinamide derivatives were synthesized and evaluated against different tumor cell lines. Experiments in vitro showed that these derivatives could inhibit the proliferation of two kinds of human cancer cell lines (HepG2, HCT116) at low micromolar concentrations and the most potent analog 5q possessed broad-spectrum antiproliferative activity. Experiments in vivo demonstrated that 5q could effectively prolong the longevity of colon carcinoma-burdened mice and slow down the progression of cancer cells by suppression of angiogenesis and the induction of apoptosis and necrosis.


Assuntos
Antineoplásicos/farmacologia , Ácidos Picolínicos/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Ácidos Picolínicos/síntese química , Ácidos Picolínicos/química , Células Tumorais Cultivadas
19.
Int Immunopharmacol ; 93: 107388, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33529913

RESUMO

Endothelial dysfunction is a typical characteristic of sepsis. Endothelial nitric oxide synthase (eNOS) is important for maintaining endothelial function. Our previous study reported that the NLRP3 inflammasome promoted endothelial dysfunction by enhancing inflammation. However, the effects of NLRP3 on eNOS require further investigation. Therefore, the present study aimed to investigate the role of NLRP3 on eNOS expression levels in cecal ligation and puncture-induced impaired endothelium-dependent vascular relaxation and to determine the protective effects of melatonin. eNOS expression levels were discovered to be downregulated in the mesenteric arteries of sepsis model mice. Inhibiting NLRP3 with 10 mg/ kg MCC950 or inhibiting IL-1ß with 100 mg diacerein rescued the eNOS expression and improved endothelium-dependent vascular relaxation. In vitro, IL-1ß stimulation downregulated eNOS expression levels in human aortic endothelial cells (HAECs) in a concentration- and time-dependent manner, while pretreatment with 1 µM of the proteasome inhibitor MG132 reversed this effect. In addition, treatment with 10 mg/kg MG132 also prevented the proteolysis of eNOS and improved endothelium-dependent vascular relaxation in vivo. Notably, treatment with 30 mg/kg melatonin downregulated NLRP3 expression levels and decreased IL-1ß secretion, subsequently increasing the expression of eNOS and improving endothelium-dependent vascular relaxation. In conclusion, the findings of the present study indicated that the NLRP3/IL-1ß axis may impair vasodilation by promoting the proteolysis of eNOS and melatonin may protect against sepsis-induced endothelial relaxation dysfunction by inhibiting the NLRP3/IL-1ß axis, suggesting its pharmacological potential in sepsis.


Assuntos
Interleucina-1beta/fisiologia , Melatonina/uso terapêutico , Proteína 3 que Contém Domínio de Pirina da Família NLR/fisiologia , Óxido Nítrico Sintase Tipo III/metabolismo , Sepse/tratamento farmacológico , Vasodilatação/fisiologia , Animais , Aorta/citologia , Células Cultivadas , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/fisiologia , Humanos , Masculino , Melatonina/farmacologia , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/fisiologia , Camundongos Endogâmicos C57BL , Proteólise , Sepse/metabolismo , Sepse/fisiopatologia , Vasodilatação/efeitos dos fármacos
20.
J Pharm Biomed Anal ; 197: 113929, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33618133

RESUMO

Plant saponins are important natural product with biologically active. However, the metabolism of these compounds has rarely been studied due to their low bioavailability and the complexity of their metabolite structures. In this study, ultra-performance liquid chromatography/Fusion Lumos Orbitrap mass spectrometry was used to analyze the metabolites of hederasaponin B in vivo, and its possible metabolic pathways were proposed. After oral administration of the parent drug, a total of 47 metabolites are identified in rat feces (42), urine (11), and plasma (9) samples. These metabolites resulted from the metabolic processes in phases I and II reactions involved in deglycosylation, hydroxylation, acetylation, oxidation, gluconalciation and glycosylations. Deglycosylation is the main metabolic pathway (accounts for 52.46 % of all metabolites in feces samples). Among the identified metabolites, four were glycosylated (deprotonated precursors at m/z = 1335.7, 1365.7, 1467.9, and 1379.6) with higher molecular weight than the parent drug . These glycosylated compounds account for 11.55 % of the metabolites in rat feces according to the semi-quantitative chromatographic peak areas. To sum up, the results of this study provide a basis for further understanding the metabolism of plant saponins in vivo.

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