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1.
Infect Dis Poverty ; 10(1): 18, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33648599

RESUMO

BACKGROUND: Vaccination is crucial for human immunodeficiency virus (HIV)-exposed children because of their increased risk of morbidity and mortality from various vaccine-preventable diseases. However, studies have shown that they are at high risk of incomplete vaccination. Although China has developed prevention of mother-to-child transmission (PMTCT) of HIV programs substantially over the past decades, few studies have investigated the immunization levels of Chinese HIV-exposed children. Therefore, we aimed to evaluate vaccination coverage and its associated factors among HIV-exposed children in China during 2016‒2018. METHODS: We conducted a retrospective cohort review of all cases of Chinese HIV-exposed children born between July 1, 2016 and June 30, 2018 recorded in the Chinese information system on PMTCT. The vaccination coverage indicators refer to the percentage of children who received recommended basic vaccines, including Bacillus Calmette-Guérin (BCG), hepatitis B (HepB), polio, measles-containing vaccine (MCV), and diphtheria-tetanus-pertussis-containing (DTP) vaccine. Univariate and multivariate logistic regression analyses expressed as crude odds ratios (cORs) and adjusted odds ratios (aORs), each with 95% confidence intervals (95% CI), were performed to compare the proportional differences of factors associated with vaccine coverage. RESULTS: Among the enrolled 10 033 children, the vaccination rate was 54.1% for BCG, 84.5% for complete HepB vaccination, 54.5% for complete polio vaccination, 51.3% for MCV, and 59.5% for complete DTP vaccination. Children with perinatally acquired HIV (PHIV) were 2.46‒3.82 times less likely to be vaccinated than HIV-exposed uninfected children. Multivariate logistic regression indicated that children of Han ethnicity (aOR = 1.33‒2.04), children with early infant diagnosis (EID) of HIV (aOR = 1.86‒3.17), and children whose mothers had better education (college or above, aOR = 1.63‒2.51) had higher odds of being vaccinated. Most of the deceased children (aOR = 4.28‒21.55) missed vaccination, and PHIV (aOR = 2.46‒3.82) significantly affected immunization. CONCLUSIONS: Chinese HIV-exposed children had low vaccination coverage, which is a serious health challenge that needs to be addressed thoroughly. Interventions should be developed with a focus on minority HIV-exposed children whose mothers do not have formal education. Particularly, more attention should be paid to EID to increase access to immunization.

3.
JACC Cardiovasc Interv ; 14(3): 247-257, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33541535

RESUMO

OBJECTIVES: The aim of this study was to explore the difference in target vessel failure (TVF) 3 years after intravascular ultrasound (IVUS) guidance versus angiographic guidance among all comers undergoing second-generation drug-eluting stent (DES) implantation. BACKGROUND: The multicenter randomized ULTIMATE (Intravascular Ultrasound Guided Drug Eluting Stents Implantation in "All-Comers" Coronary Lesions) trial showed a lower incidence of 1-year TVF after IVUS-guided DES implantation among all comers compared with angiographic guidance. However, the 3-year clinical outcomes of the ULTIMATE trial remain unknown. METHODS: A total of 1,448 all comers undergoing DES implantation who were randomly assigned to either IVUS guidance or angiographic guidance in the ULTIMATE trial were followed for 3 years. The primary endpoint was the risk for TVF at 3 years. The safety endpoint was definite or probable stent thrombosis (ST). RESULTS: At 3 years, TVF occurred in 47 patients (6.6%) in the IVUS-guided group and in 76 patients (10.7%) in the angiography-guided group (p = 0.01), driven mainly by the decrease in clinically driven target vessel revascularization (4.5% vs. 6.9%; p = 0.05). The rate of definite or probable ST was 0.1% in the IVUS-guided group and 1.1% in the angiography-guided group (p = 0.02). Notably, the IVUS-defined optimal procedure was associated with a significant reduction in 3-year TVF relative to that with the suboptimal procedure. CONCLUSIONS: IVUS-guided DES implantation was associated with significantly lower rates of TVF and ST during 3-year follow-up among all comers, particularly those who underwent the IVUS-defined optimal procedure compared with those with angiographic guidance. (Intravascular Ultrasound Guided Drug Eluting Stents Implantation in "All-Comers" Coronary Lesions; NCT02215915).

4.
Clin Biochem ; 90: 1-7, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33476578

RESUMO

INTRODUCTION: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is diagnosed by molecular-based detection of SARS-CoV-2 RNA. Serologic testing detects antibodies specific to SARS-CoV-2 and IgM specifically may serve as an adjunct test to PCR early in disease. We evaluated the Abbott anti-SARS-CoV-2 IgM and IgG assays along with DiaSorin anti-SARS-CoV-2 IgG and Roche anti-SARS-CoV-2 Total. METHODS: Specimens from 175 PCR-positive patients and 107 control specimens were analyzed using Abbott IgM and IgG, DiaSorin IgG, and Roche Total (IgA, IgG, IgM) assays. Sensitivity, specificity, cross-reactivity, concordance between assays, trends over time, positive predictive value (PPV), and negative predictive value (NPV) were determined. RESULTS: Abbott IgM sensitivity was 63.6% at 0 days post-PCR positivity, 76.5% at 1-5d, 76.3% at 6-14d, 85.2% at 15-30d, and 63.6% at > 30d. All assays exhibited highest sensitivity 15-30d post-PCR positivity (83.3-85.2%). Combining Abbott IgM and IgG improved sensitivity by 22.7% compared to IgG alone when tested 0d post-PCR positivity. All assays had a specificity of 100% and only Abbott IgG exhibited cross-reactivity (anti-dsDNA). Cohen's kappa varied between 0.86 and 0.93. Time to seroconversion from PCR positivity was lowest for Abbott IgM and highest for Abbott IgG. NPV was highest for Abbott IgM < 14 days post-PCR positivity and Abbott IgG ≥ 14 days. CONCLUSION: The Abbott IgM assay exhibited the earliest response and greatest signal in most patients evaluated for serial sampling and had the highest NPV < 14 days post-PCR positivity, suggesting its potential utility as an adjunct test to PCR early in disease course.


Assuntos
Anticorpos Antivirais/sangue , /imunologia , Imunoglobulina M/sangue , /imunologia , /diagnóstico , Reações Cruzadas , Humanos , Imunoensaio/métodos , Imunoglobulina G , Reação em Cadeia da Polimerase/métodos , Valor Preditivo dos Testes , RNA Viral , Sensibilidade e Especificidade
5.
Anal Chem ; 93(5): 2959-2967, 2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33506679

RESUMO

In this work, a low triggered potential electrochemiluminescence strategy based on gold-filled photonic crystals (GPCs) electrodes composed of photonic crystals self-assembled with polystyrene spheres and gold nanoparticles embedded in the gaps of the photonic crystals was proposed. The GPCs electrodes served as the detection platform to bind antigen, and Ru(bpy)32+-COOH as a luminophore was labeled on the antibody (Ab). Then, Ru(bpy)32+-COOH/Ab was connected to the immobilized antigen on the surface of the photonic crystals by the immunoreaction to avoid direct contact with the gold nanoparticles surface. ECL emission can only be initiated by electrochemical oxidation of tripropylamine (TPrA) since Ru(bpy)32+-COOH cannot be oxidized directly on the electrode surface. The TPrA·+ and TPrA· radicals generated by the oxidation of TPrA can spread to the vicinity of Ru(bpy)32+-COOH over a short distance and react with the Ru(bpy)32+-COOH, eventually producing ECL emission. The potential of ECL emission caused by TPrA oxidation was about 300 mV lower than that caused by Ru(bpy)32+-COOH oxidation because the oxidation potential of TPrA (0.95 V vs SCE) was lower than Ru(bpy)32+-COOH (1.25 V vs SCE). Furthermore, the photonic crystals nanomembrane has the capability to enhance electrochemiluminescence. Thereafter, tetracycline antibiotic as a model compound was successfully detected via competitive immunoassay on GPCs electrodes with a detection limit of 0.075 pg/mL (S/N = 3), which has broad application prospects in the field of analysis and detection.

6.
Anal Chim Acta ; 1147: 15-22, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33485573

RESUMO

Rapid, sensitive, and user-friendly nucleic acid detection is of growing importance in early clinical diagnosis. Here, we construct a simple, one-pot and ultrasensitive DNA sensor via exonuclease III (Exo III)-assisted target recycling amplification (ERA) combined with 3D DNA walker cascade amplification. In the presence of single-stranded DNA target, the ERA process is activated to generate numerous walker strands (WS). Thereafter, Exo III-powered WSs autonomously move along magnetic bead (MB)-based 3D track to release numerous AgNCs into the supernatant as an amplified signal output. This biosensor had a low detection limit of 18 fM and an analytical range of 40 fM to 1 pM. Furthermore, the practical application potential of this biosensor was also confirmed by the spiking experiments of p53 into human serum and urine samples.

7.
Talanta ; 221: 121668, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33076174

RESUMO

Rapid and sensitive diagnosis of bacterial infections at early stage is of great significance for food safety monitoring as well as clinical treatment. Herein, we construct a surface-enhanced Raman scattering (SERS) nanoprobe based on M13 phages for the selective detection and inactivation of Staphylococcus aureus (S. aureus). M13 phage with specific S. aureus-binding heptapeptide displayed on the N-terminal of pIII protein is selected from phage display peptide library. The S. aureus-specific SERS probe is thus constructed by in situ growth of gold nanoparticles (AuNPs) on M13 phage surface, followed by modification with 5,5-dithiobis-(2-nitrobenzoic acid) (DTNB) as SERS active molecule. Upon the addition of this SERS probe, M13 phage selectively binds with S. aureus to induce anchoring of AuNPs on S. aureus surface, and the SERS probe-labeled S. aureus cells are collected by centrifugation for SERS detection. For the quantification of S. aureus, a linear range of 10-106 cfu mL-1 is achieved in aqueous medium. It is further demonstrated by spiking recovery in soft drinks. Furthermore, this SERS probe exhibits bactericidal capabilities towards S. aureus, which shows promising potential to serve as a multifunctional platform for simultaneous detection and inactivation of S. aureus.

8.
Biomed Environ Sci ; 33(10): 745-749, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33228833

RESUMO

Objective: To calculate the number of pregnant women who receive standardized prevention of mother-to-child transmission (PMTCT) services for HIV annually. Methods: HIV-positive pregnant women in six counties of Liangshan Prefecture in 2017 were selected as study subjects. The entire process, from when the subjects first received the PMTCT of HIV services to the end, was divided into four stages, which were further divided into 25 phases. The equivalent coefficient was used to indicate the weight of workload in each phase. Seven experts were invited to score the equivalent coefficient; the number of pregnant women who received standardized services to prevent the transmission of HIV was calculated. Results: A total of 663 HIV-positive pregnant women were registered in six Liangshan Prefecture counties in 2017. This figure was converted into 7,780 person-months devoted to HIV-positive pregnant women, with 260 person-months (3.34%) spent on the first antenatal care, 1,510 person-months (19.41%) during pregnancy, 378 person-months (4.86%) on delivery, and 5,632 person-months (72.39%) on post-partum period. The equivalent coefficient calculation showed that 314 HIV-positive pregnant women received standardized PMTCT services. Conclusion: The number of pregnant women receiving standardized services for the PMTCT of HIV can be calculated accurately using the equivalent method to identify the gap between the level of PMTCT of HIV intervention services needed and the actual workload.

9.
Plant Dis ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33200971

RESUMO

Sugarcane (Saccharum officinarum L.) is the main sugar crop in China. Yunnan is the second largest sugarcane production province in China. In December 2018, leaf blight was first observed on almost every leaf of sugarcane on 'Huanan 54-11', 'Baimei' and 'Chongan' in Kaiyuan (103°27' E, 23°72' N), Yunnan. In October 2019, during our survey in the field in Lingcang (100°08' E, 23°88' N), Yunnan, this disease was also observed on 'ROC 25'. Symptoms of the disease initially appeared as wilted, which seemed to be cause by water stress. As the disease progressed, irregular straw-yellow and blighted lesion ran throughout the leaf lamina from leaf tip to entire leaf sheath, many small black conidia formed in the dead leaf tissue under humid conditions. Symptomatic leaf tissues were surface-sterilized with 70% ethanol for 30 s, 0.1% HgCl2 for 1 min, and rinsed with sterilized water three times, air dried on sterile filter paper, and plated on potato dextrose agar (PDA). Six isolates were obtained from six symptomatic leaf samples and were transferred onto potato carrot agar (PCA). Colonies on PDA were white with loose aerial hyphae at first, then turned to dark olive or dark. Colonies on PCA were grayish with sparse hyphae, then turned to dark gray. Conidiophores were brown, simple or branched, and produced numerous conidia in short chains. Conidia (n = 50) were obclavate to obpyriform or ellipsoid, brown to dark brown, with a cylindrical short beak at the tip (2.3 to 17.3 µm in length), and 15.3 to 46.6 µm × 4.2 to 17.9 µm, 2 to 7 transverse septa and 0 to 3 longitudinal septa. Morphologically, the isolates were identified as Alternaria tenuissima (Simmons 2007). Two representative isolates C4 and C5 were selected for molecular identification. The internal transcribed spacers (ITS), Histone 3 genes and plasma membrane ATPase were amplified with primer pairs ITS1/ITS4, H3-1a/H3-1b and ATPDF1/ATPDR1, respectively (Glass et al. 1995; Lawrence et al. 2013). The sequences were deposited in GenBank (ITS, MT679707-MT679708; Histone 3, MT710929-MT710930; ATPase, MT833928-MT833929). BLAST searches showed ≥99% nucleotide identity to the sequence of A. tenuissima (ITS, 100% to MN822571; Histone 3, 100% to MN481955; ATPase, 99% to JQ671875, 100% to MH492703, respectively). Thus, the fungus was identified as A. tenuissima based on morphological and molecular characteristics. For pathogenicity tests, five healthy 2-month-old potted sugarcane leaves were wounded with one sterile needle and inoculated with 20 µl of suspension of 106 conidia/ mL, and five plants were inoculated with distilled water as the controls. Plants were placed in a greenhouse at 25 to 35°C. After two months, the leaf wound inoculated with the putative pathogen displayed blighted as those observed in the field whereas the controls remained symptomless. The fungus was reisolated from symptomatic leaves with the same morphological and molecular traits as the original isolates. The fungus was not isolated from the control plants. Pathogenicity tests were repeated two times. A. tenuissima causing leaf blight on barley in China was reported in 2008 (Luo et al. 2008). Leaf spot disease of sugarcane caused by A. tenuis has been recorded in Maharashtra (Patil et al. 1974). To our knowledge, this is the first report on A. tenuissima affecting leaf blight on sugarcane in Yunnan Province, China. Identification of the causes of the disease is important to develop effective disease management strategies. The author(s) declare no conflict of interest. Funding: This research was supported by Sugar Crop Research System (CARS-170303), the Yunling Industry and Technology Leading Talent Training Program "Prevention and Control of Sugarcane Pests" (2018LJRC56), and the Yunnan Province Agriculture Research System. References: Glass, N. L., et al. 1995. Appl. Environ. Microbiol. 61:1323. Lawrence, D. P., et al. 2013. Mycologia 105:530. Luo, Z., et al. 2008. Acta Phytophy. Sin. 35(5): 469-470. Patil, A.O., et al. 1974. Res. J. Mahatma Phule Agric. Univ. 5(2): 122-123. Simmons, E. G. 2007. Alternaria: An Identification Manual. CBS Fungal Biodiversity Centre, Utrecht, The Netherlands. Caption for supplementary Figure 1 Supplementary Figure S1. Disease symptoms of sugarcane leaf blight disease and morphological characteristics of Alternaria tenuissima. (A) Typical straw-yellow and blighted lesions on naturally-infected leaves of sugarcane; (B) Infected symptoms on wounded leaves of sugarcane two months after artificial infection with A. tenuissima; (C) Colony of A. tenuissima on PDA; (D) Colony of A. tenuissima on PCA; and (E-F) Sporulation and conidia of A. tenuissima on PCA. (Scale bars = 100 µm; 20 µm).

10.
World J Clin Cases ; 8(18): 3934-3941, 2020 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-33024750

RESUMO

Coronavirus disease-2019 (COVID-19) has so far caused hundreds of mortalities worldwide. Although respiratory symptoms are the main complication in COVID-19 patients, the disease is also associated with gastrointestinal problems, with diarrhea, nausea, and vomiting being primary COVID-19 symptoms. Thus, cancer and inflammatory bowel disease (IBD) management, stool viral tests, and virus exposure are major concerns in the context of COVID-19 epidemic. In patients with colorectal cancer and IBD, the colonic mucosa exhibits elevated angiotensin-converting enzyme 2 receptor levels, enhancing COVID-19 susceptibility. In some cases, positive viral stool tests may be the only indicator of infection at admission or after leaving quarantine. Without supplemental stool tests, the risk of undetected COVID-19 transmission is high. Moreover, viral exposure during the regular or emergency endoscopic examination should be avoided. We carefully discuss key gastrointestinal concerns with regard to COVID-19 and call for more attention to such problems.

11.
Toxicol Res (Camb) ; 9(4): 467-473, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32905277

RESUMO

Lidocaine is one of the most common local anesthetics (LA) used in clinical practice and it is neurotoxic. Recent studies suggested that LA, including lidocaine, could exert protective effect over neurotoxicity by promoting autophagy. However, the underlying mechanism was not sufficiently elucidated. This study aimed to explore the mechanism behind. Human neuroblastoma cell line SH-SY5Y was used throughout the whole study. The effect of lidocaine on viability, toxicity of SH-SY5Y cells were analyzed by MTT and lactate dehydrogenase (LDH) assays, respectively. The relative expression of miR-145 was assessed by quantitative reverse transcription-polymerase chain reaction. The impact which lidocaine brought on PI3K/AKT/mTOR pathway and autophagy-related proteins were examined by the western blot assay. LC3B was assessed by immunofluorescence staining. The interaction between miR-145 and AKT3 was conducted by the dual-luciferase reporting assay. Lidocaine inhibited viability of SH-SY5Y cells in a time and dose dependent manner and enhanced the release of LDH in SH-SY5Y cells. Furthermore, the expression of miR-145 and autophagy were enhanced by lidocaine. Transfection with miR-145 inhibitor inhibited the release of LDH and autophagy. miR-145 targeted AKT3 to inhibit PI3K/AKT/mTOR pathway. Finally, lidocaine inactivated PI3K/AKT/mTOR pathways via upregulation of miR-145, and it subsequently promoted autophagy of SH-SY5Y cells. However, silence of miR-145 could reverse the promotion of the autophagy of SH-SY5Y cells. Our results showed that lidocaine promoted autophagy of nerve cells via regulating miR-145 expression and further inactivation of PI3K/AKT/mTOR signaling pathway.

12.
Math Biosci Eng ; 17(4): 3052-3061, 2020 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-32987516

RESUMO

The novel coronavirus disease 2019 (COVID-19) infection broke out in December 2019 in Wuhan, and rapidly overspread 31 provinces in mainland China on 31 January 2020. In the face of the increasing number of daily confirmed infected cases, it has become a common concern and worthy of pondering when the infection will appear the turning points, what is the final size and when the infection would be ultimately controlled. Based on the current control measures, we proposed a dynamical transmission model with contact trace and quarantine and predicted the peak time and final size for daily confirmed infected cases by employing Markov Chain Monte Carlo algorithm. We estimate the basic reproductive number of COVID-19 is 5.78 (95%CI: 5.71-5.89). Under the current intervention before 31 January, the number of daily confirmed infected cases is expected to peak on around 11 February 2020 with the size of 4066 (95%CI: 3898-4472). The infection of COVID-19 might be controlled approximately after 18 May 2020. Reducing contact and increasing trace about the risk population are likely to be the present effective measures.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Modelos Biológicos , Pandemias/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Algoritmos , Número Básico de Reprodução/estatística & dados numéricos , China/epidemiologia , Simulação por Computador , Busca de Comunicante/estatística & dados numéricos , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Epidemias/prevenção & controle , Epidemias/estatística & dados numéricos , Mapeamento Geográfico , Humanos , Cadeias de Markov , Conceitos Matemáticos , Método de Monte Carlo , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão , Quarentena/estatística & dados numéricos
13.
Chin J Dent Res ; 23(3): 199-204, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32974620

RESUMO

OBJECTIVE: To investigate the bilateral symmetry of double root canals, variation in root canal bifurcation and position of canal orifices in mandibular incisors in a Chinese population. METHODS: A total of 149 subjects with mandibular incisors with two canals were selected from 866 patients based on CBCT images and divided into three groups: group 1 (< 21 years), group 2 (21-40 years) and group 3 (> 40 years). The prevalence of bilateral symmetry of double root canals (type III and type V), the distance between the cementoenamel junction (CEJ) and the bifurcation (D1) and the distance between the two canal orifices (D2) were calculated and analysed. RESULTS: The bilateral symmetry of type III for mandibular central incisors (MCIs) (44.4%) was significantly lower than that for mandibular lateral incisors (MLIs) (63.4%). D1 was greater in group 1 (4.63 ± 1.35mm) than in group 2 (3.99 ± 1.02 mm) and group 3 (3.90 ± 1.95 mm). D2 was shorter in in MCIs (0.65 ± 0.20 mm) than in MLIs (0.74 ± 0.22 mm). CONCLUSION: Special attention is required in the root canal treatment of mandibular incisors, especially in patients aged above 21 years.


Assuntos
Cavidade Pulpar/diagnóstico por imagem , Incisivo , Adulto , Tomografia Computadorizada de Feixe Cônico , Humanos , Mandíbula/diagnóstico por imagem , Raiz Dentária , Adulto Jovem
14.
Chin J Dent Res ; 23(3): 205-214, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32974621

RESUMO

This report describes the cases of two patients with a maxillary lateral incisor with palatogingival groove and extensive endodontic-periodontal lesions. Although it is reported that acceptable periodontal status is of great importance in case selection in intentional replantation, it is suggested in this report that intentional replantation could be chosen instead of immediate extraction if extensive endodontic-periodontal lesions exist in a tooth with palatogingival groove. The gingival margin position and gingival papilla were well preserved and the bone defect was almost completely repaired. This was beneficial to the aesthetic prosthodontic treatment and implantation, although external root resorption was observed.


Assuntos
Reimplante Dentário , Raiz Dentária/cirurgia , Gengiva/cirurgia , Humanos , Incisivo/cirurgia , Tratamento do Canal Radicular
15.
Biochem Biophys Res Commun ; 532(3): 329-335, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-32977944

RESUMO

Drug resistance remains the unresolved obstacle for gastric cancer (GC) treatment. Recently more and more studies have shown that microRNAs are involved in cancer resistance and could apply to drug resistance therapy in tumors. The relationship between miR-149 and 5-fluorouracil (5-FU) resistance in GC remains unclear. Here we detected miR-149 expression in 5-FU resistance tumor tissues and cell lines, and found that miR-149 expression is upregulated in AGS/5-FU cells compared with AGS cells. Further experiments indicated that overexpression of miR-149 can alleviate 5-FU-induced apoptosis and proliferation inhibition by targeting TREM2. It was also confirmed that TREM2 regulated 5-FU resistance through ß-catenin pathway. Generally speaking, our results indicated that miR-149 contributes to resistance of 5-FU in gastric cancer via targeting TREM2 and regulating ß-catenin pathway.

16.
Nat Commun ; 11(1): 4857, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32978402

RESUMO

Characterization of the dynamic conformational changes in membrane protein signaling complexes by nuclear magnetic resonance (NMR) spectroscopy remains challenging. Here we report the site-specific incorporation of 4-trimethylsilyl phenylalanine (TMSiPhe) into proteins, through genetic code expansion. Crystallographic analysis revealed structural changes that reshaped the TMSiPhe-specific amino-acyl tRNA synthetase active site to selectively accommodate the trimethylsilyl (TMSi) group. The unique up-field 1H-NMR chemical shift and the highly efficient incorporation of TMSiPhe enabled the characterization of multiple conformational states of a phospho-ß2 adrenergic receptor/ß-arrestin-1(ß-arr1) membrane protein signaling complex, using only 5 µM protein and 20 min of spectrum accumulation time. We further showed that extracellular ligands induced conformational changes located in the polar core or ERK interaction site of ß-arr1 via direct receptor transmembrane core interactions. These observations provided direct delineation and key mechanism insights that multiple receptor ligands were able to induce distinct functionally relevant conformational changes of arrestin.


Assuntos
Arrestina/química , Arrestina/genética , Arrestina/metabolismo , Ligantes , Espectroscopia de Prótons por Ressonância Magnética/métodos , Sítios de Ligação , Cristalografia por Raios X , Humanos , Modelos Moleculares , Fenilalanina , Ligação Proteica , Conformação Proteica , Receptores Adrenérgicos beta 2/metabolismo , Transdução de Sinais , beta-Arrestina 1/química , beta-Arrestina 1/genética , beta-Arrestina 1/metabolismo
17.
Materials (Basel) ; 13(19)2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32987819

RESUMO

The as-cast alloy of nickel-based single-crystal superalloy was used as the research object. After four hours of solution treatment at 1315 °C, four cooling rates (water cooling (WC), air cooling (AC) and furnace cooling (FC1/FC2)) were used to reduce the alloy to room temperature. Four different microstructures of nickel-based superalloy material were prepared. A high-temperature tensile test at 980 °C was carried out to study the influence of various rates on the formation of the material's microstructure and to further obtain the influence of different microstructures on the high-temperature mechanical properties of the materials. The results show that an increase of cooling rate resulted in a larger γ' phase nucleation rate, formation of a smaller γ' phase and a greater number. When air cooling was used, the uniformity of the γ' phase and the coherence relationship between the γ' phase and the γ phase were the best. At the same time, the test alloy had the best high-temperature tensile properties, and the material showed a certain degree of plasticity. TEM test results showed that the test alloy mainly blocked dislocations from traveling in the material through the strengthening effect of γ', and that AC had the strongest hindering effect on γ' dislocation movement.

18.
Chem Biol Drug Des ; 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32915501

RESUMO

In an effort to discover new agents with high anti-inflammatory activity, 22 new 4-sulfonyloxy/alkoxy benzoxazolone derivatives were synthesized, characterized, and evaluated for their anti-inflammatory activities against lipopolysaccharide (LPS)-induced nitric oxide (NO) production and TNF-α expression in RAW 264.7 cells in vitro. Most of these compounds displayed greater inhibitory ability against NO production than the lead compound 4-o-methyl-benzenesulfonyl benzoxazolone, and the most active compound 2h exhibited the strongest inhibitory activity against NO, IL-1ß, and IL-6 production with IC50 values 17.67, 20.07, and 8.61 µΜ, respectively. The effects of 2h were comparable or stronger than those of the positive control celecoxib. Compound 2h also displayed higher activity in vivo than celecoxib in a mouse model of xylene-induced ear edema, based on their inhibitory rates of 42.69% and 30.87%, respectively. Further molecular analysis revealed that compound 2h significantly reduced the iNOS levels in cell supernatant and suppressed the protein expression of iNOS, p-p38, p-ERK, and nuclear NF-κB. The results indicated that the anti-inflammatory effect of 2h might be realized through the regulation of ERK- and p38-mediated mitogen-activated protein kinase (MAPK)-NF-κB/iNOS signaling, thereby reducing the excessive release of NO, IL-1ß, and IL-6. Our findings demonstrated that compound 2h, a new benzoxazolone derivative, could inhibit activation of the MAPK-NF-κB/iNOS pathway, supporting its potential as a novel anti-inflammatory agent.

19.
Talanta ; 218: 121065, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32797863

RESUMO

It is of significance to elucidate or understand the intracellular transformation & migration behaviors of heavy metals in specific cells. Herein, we report the fast and efficient separation of cadmium-metallothioneins (Cd-MTs) and Cd2+in cell lysate by a short column capillary electrophoresis (SC-CE), followed by coupling with inductively coupled plasma mass spectrometry (ICP-MS) to facilitate the speciation of intracellular cadmium species. The incorporation of sodium dodecyl sulfate (SDS) in running buffer significantly reduces the peak width of Cd2+from 170 s to 26 s in the electrophoretogram, causing a 5.3-fold improvement on the sensitivity. Linear ranges of 0.5-50 mg L-1,0.056-5.6 mg L-1 and 0.1-10 mg L-1 are achieved for MTs, Cd-MTs (Cd) and Cd2+, respectively, along with detection limits of 0.013 mg L-1 for Cd-MTs (Cd) and 0.020 mg L-1 for Cd2+. The transformation of cadmium in HepG2 and MCF-7 cells is evaluated after their incubation with Cd2+ reinforced culture medium. Intracellular free Cd2+ cation and Cd-MTs are identified, along with Cd2+ transformation to Cd-glutathione (GSH) adduct/complex, as further demonstrated by ESI-MS.

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