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1.
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.

2.
J Bioenerg Biomembr ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067739

RESUMO

Overexpression of Actin-like 6A (ACTL6A) has been observed in a wide spectrum of tumors and exerts an outstanding oncogenic function throughout cancer progression. However, the detailed relevance of ACTL6A for laryngeal squamous cell carcinoma (LSCC) is not fully understood. In this work, we aimed to elucidate the precise role of ACTL6A in LSCC. Here, we show that ACTL6A expression was significantly upregulated in LSCC versus normal tissues. In vitro functional assays demonstrated that silencing of ACTL6A significantly diminished the capacity of LSCC cells to proliferate and invade, whilst up-regulation of ACTL6A drove proliferation and invasion in LSCC cells. Further investigation revealed that knockdown of ACTL6A repressed the activation of Yes-associated protein (YAP)-mediated signaling in LSCC cells, while reactivation of YAP markedly reversed ACTL6A-silencing-mediated inhibition of proliferation and invasion in LSCC cells. Moreover, suppression of YAP markedly diminished ACTL6A-overexpression-induced promotion of tumor formation in LSCC. In addition, ACTL6A silencing diminished the tumorigenicity of LSCC cells in vivo. To summarize, our work indicates that ACTL6A may enhance LSCC progression via potentiating the activation of YAP signaling. Thus, ACTL6A may be an attractive anticancer target for the treatment of LSCC.

3.
BJOG ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33021043

RESUMO

OBJECTIVE: This study aimed to investigate the incidence and associated predictors of adverse pregnancy outcomes (APOs) among pregnant women infected with syphilis. DESIGN: Cox regression analysis. SETTING: China. POPULATION OR SAMPLE: Pregnant women who were tested and diagnosed with syphilis during the index pregnancy and delivered at a gestational age ≥28 weeks between 2016 and 2019. METHODS: Data were extracted from China's Information System of Prevention of Mother-to-Child Transmission (PMTCT) of Syphilis Management. Descriptive analysis provided profiles and pregnant outcomes of maternal syphilis, as well as the incidence of APOs. Log-rank tests and cox proportional hazard models were used to investigate factors influencing APOs in infected mothers with singleton births. MAIN OUTCOME MEASURES: The incidence of APOs; the Hazard Ratios (HRs) of associated predictors using cox proportional hazard model. RESULTS: Syphilis treatment data was available from 83.86% of diagnosed women. Including deliveries from the total study population, 13.33% experienced APOs. Cox regression indicated that APOs were more likely in women tested and diagnosed in the late trimester, delivery or postpartum. Women who accepted non-standardized treatment and who received standardized treatment had less risk of APOs . CONCLUSIONS: China has made huge progress over the last decades in PMTCT of syphilis, but the incidence of APOs among pregnant women infected with syphilis remains high. It is extremely essential to further strengthen access to early detection and standardized treatment of infected women to reduce the risk of APOs.

4.
Eur Radiol ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33021702

RESUMO

OBJECTIVES: Currently, the main challenge in tumour-induced osteomalacia (TIO) is the difficulty in locating culprit tumours for definitive diagnosis and surgical therapy. Herein, we retrospectively evaluate the efficiency of 68Ga-DOTANOC PET/CT in the localisation and diagnosis of TIO, and compared with 18F-FDG. METHODS: Twenty-four consecutive patients with hypophosphataemic osteomalacia (HO) and suspicion of TIO who were referred to our centre for 68Ga-DOTANOC PET/CT scanning were retrospectively reviewed. The images were evaluated qualitatively as well as semi-quantitatively, and imaging results were compared with the final diagnoses. RESULTS: Among the total of 21 patients who were included in the final analyses, 17 were diagnosed with TIO, while four were proven to have other causes of HO. 68Ga-DOTANOC PET/CT produced positive results in 16 of the 17 patients with TIO, representing a sensitivity of 94.1%. Moreover, the 68Ga-DOTANOC PET/CT results were negative in 3 of the 4 patients without TIO, representing a specificity of 75.0%. The overall accuracy of 68Ga-DOTANOC PET/CT in locating the tumours responsible for TIO is 90.5%. In particular, 68Ga-DOTANOC PET/CT detected the culprit tumours in 4 out of 10 patients with negative results on previous 18F-FDG PET/CT and showed a significantly higher T/M ratio of tumours than 18F-FDG PET/CT in the same patients (n = 10; 4.76 ± 3.08 vs 1.95 ± 1.33, p < 0.05). CONCLUSIONS: 68Ga-DOTANOC PET/CT is an accurate imaging modality in the localisation of tumours for TIO. It is superior to 18F-FDG PET/CT and may be useful in the differential diagnosis of HO. KEY POINTS: • TIO should be considered a possible cause for patients diagnosed with HO, which usually needs to be differentiated from other aetiologies. • 68Ga-DOTANOC PET/CT is an accurate imaging modality in locating culprit tumours for TIO, superior to 18F-FDG PET/CT.

5.
Vet Microbiol ; 251: 108870, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33053451

RESUMO

Tembusu virus (TMUV) infection most commonly affects breeder and layer ducks during laying period, and can also affect young ducks below 7 weeks of age. Here, we report our investigation of a TMUV-caused fatal disease of Jingding ducklings (Anas platyrhynchos domesticus) in Northeast China. The disease resulted in mortalities of up to 40 % in 2 to 4-week-old ducks, up to 25 % in 5 to 6-week-old ducks, and less than 10 % in 7 to 8-week-old ducks. Using a TMUV-specific reverse transcription-PCR assay, all 44 ducks collected from 10 different farms were found positive for TMUV. Phylogenetic analysis of the E nucleotide sequence revealed that five of the six TMUV strains detected from three young ducks and three laying ducks were grouped within cluster 2.1. Inoculation of the liver sample of a 40-day-old sick duck in BHK-21 cells resulted in isolation of cluster 2.1 TMUV strain H. In experimental infections performed using 3-week-old Pekin ducklings (Anas platyrhynchos domesticus) (n = 30; 10 birds/group), high mortality (60 %) was caused by strain H, in sharp contrast with a very low mortality (10 %) caused by strain Y which was isolated during outbreaks of the TMUV-related disease of young Jinding ducks in 2014 in the same region. These findings clearly demonstrated that the cluster 2.1 TMUV strain H is more pathogenic for 3-week-old ducklings as compared to the cluster 2.2 TMUV strain Y. The present study may enhance our understanding of pathogenicity of TMUV in young ducks, and will stimulate further studies on the pathogenesis of TMUV infection.

6.
Int J Chron Obstruct Pulmon Dis ; 15: 2005-2013, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061338

RESUMO

Background: COPD exacerbations occur more frequently with disease progression and are associated with worse prognosis and higher healthcare expenditure. Purpose: To utilize a networked system, optimized with statistical process control (SPC), for remote patient monitoring (RPM) and to identify potential predictors of COPD exacerbations. Methods: Seventeen subjects, mean (SD) age of 69.7 (7.2) years, with moderate to severe COPD received RPM. Over 2618 patient-days (7.17 patient-years) of monitoring, we obtained daily symptom scores, treatment adherence, self-reported activity levels, daily spirometry (SVC, FEV1, FVC, PEF), inspiratory capacity (IC), and oxygenation (SpO2). These data were used to identify predictors of exacerbations defined using Anthonisen and other criteria. Results: After implementation of SPC, concordance analysis showed substantial agreement between FVC (decrease below the 7-day rolling average minus 1.645 SD) and self-reported healthcare utilization events (κ=0.747, P<0.001) as well as between increased use of inhaled short-acting bronchodilators and exacerbations defined by two Anthonisen criteria (κ=0.611, P<0.001) or modified Anthonisen criteria (κ=0.622, P<0.001). There was a moderate agreement between FEV1 (decrease >1.645 SD below the 7-day rolling average) and self-reported healthcare utilization events (κ=0.475, P<0.001) and between SpO2 less than 90% and exacerbations defined by two Anthonisen criteria (κ=0.474, P<0.001) or modified Anthonisen criteria (κ=0.564, P<0.001). Conclusion: Exacerbations were best predicted by FVC and FEV1 below the one-sided 95% confidence interval derived from SPC but also by increased use of inhaled short-acting bronchodilators and fall in oxygen saturation. An RPM program that captures these parameters may be used to guide appropriate interventions aimed at reducing healthcare utilization in COPD patients.

7.
Clin Exp Rheumatol ; 38 Suppl 126(4): 253-260, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33025881

RESUMO

The advent of immune checkpoint inhibitor (ICI) therapy for treatment of cancers is unfortunately coupled with a broad panoply of side effects, related to non-specific activation of the immune system. One such side effect is the development of sicca complaints. This culminates in a proportion of patients who, according to the ACR-EULAR 2016 criteria, can be classified as suffering from the autoimmune disease primary Sjögren's syndrome (pSS). Although salivary gland (SG) loss of function is often seen after ICI therapy, the similarities with 'classical' pSS patients would appear to end there. Despite the presence of focal lymphocytic sialadenitis typical for SS in salivary gland biopsies from patients receiving ICI therapy, the nature of the immune infiltration (foci) following ICI use (T-cell dominated) is starkly different to that in pSS (B-cell dominated). The SG parenchyma post-ICI use does not present with germinal centres, lymphoepithelial lesions or IgG plasma cells, which are frequently found in the SG in pSS. Here we review the functional deterioration of SGs following ICI use, the SG parenchyma phenotype associated with this, and ultrasound abnormalities. We conclude by suggesting that ICI-induced SG dysfunction may represent a new interferonopathy, driven by IFNγ, and that this 'pSS' patient cohort may require a different management than classical pSS patients.

8.
Clin Exp Rheumatol ; 38 Suppl 126(4): 261-270, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33095136

RESUMO

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterised by dysfunction and inflammatory lymphocytic infiltration of exocrine glands, namely the salivary and lacrimal glands. pSS patients often suffer from sicca (dry mouth) complaints, including dental caries, and difficulties in eating, sleeping and speaking. A large body of literature points to a central role for salivary gland (SG) epithelial cells in the development of this pathology. Here we summarise recent studies concerning the role of SG epithelial cells in pSS, which strongly indicate their intrinsic activation and early involvement during the disease process. Based on that, we propose possible future interventions targeting SG epithelial cells, to treat SG dysfunction pSS.

9.
Radiother Oncol ; 154: 207-213, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33035622

RESUMO

BACKGROUND AND PURPOSE: The optimal dose for prostate stereotactic body radiotherapy (SBRT) is still unknown. This study evaluated the dose-response relationships for prostate-specific antigen (PSA) decay and biochemical recurrence (BCR) among 4 SBRT dose regimens. MATERIALS AND METHODS: In 1908 men with low-risk (50.0%), favorable intermediate-risk (30.9%), and unfavorable intermediate-risk (19.1%) prostate cancer treated with prostate SBRT across 8 institutions from 2003 to 2018, we examined 4 regimens (35 Gy/5 fractions [35/5, n = 265, 13.4%], 36.25 Gy/5 fractions [36.25/5, n = 711, 37.3%], 40 Gy/5 fractions [40/5, n = 684, 35.8%], and 38 Gy/4 fractions [38/4, n = 257, 13.5%]). Between dose groups, we compared PSA decay slope, nadir PSA (nPSA), achievement of nPSA ≤0.2 and ≤0.5 ng/mL, and BCR-free survival (BCRFS). RESULTS: Median follow-up was 72.3 months. Median nPSA was 0.01 ng/mL for 38/4, and 0.17-0.20 ng/mL for 5-fraction regimens (p < 0.0001). The 38/4 cohort demonstrated the steepest PSA decay slope and greater odds of nPSA ≤0.2 ng/mL (both p < 0.0001 vs. all other regimens). BCR occurred in 6.25%, 6.75%, 3.95%, and 8.95% of men treated with 35/5, 36.25/5, 40/5, and 38/4, respectively (p = 0.12), with the highest BCRFS after 40/5 (vs. 35/5 hazard ratio [HR] 0.49, p = 0.026; vs. 36.25/5 HR 0.42, p = 0.0005; vs. 38/4 HR 0.55, p = 0.037) including the entirety of follow-up, but not for 5-year BCRFS (≥93% for all regimens, p ≥ 0.21). CONCLUSION: Dose-escalation was associated with greater prostate ablation and PSA decay. Dose-escalation to 40/5, but not beyond, was associated with improved BCRFS. Biochemical control remains excellent, and prospective studies will provide clarity on the benefit of dose-escalation.

10.
Sci Rep ; 10(1): 16848, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033318

RESUMO

Paraoxonase 1(PON1) is an HDL-associated protein, which metabolizes inflammatory, oxidized lipids associated with atherosclerotic plaque development. Because oxidized lipid mediators have also been implicated in the pathogenesis of rheumatoid arthritis (RA), we evaluated the role of PON1 in murine inflammatory arthritis. K/BxN serum transfer (STIA) or collagen antibody transfer (CAIA) was used for arthritis induction in B6 mice homozygous for the PON1 human transgene [PON1Tg], PON1 knock-out mice [PON1KO], and wild type littermate control mice [WT]. Experiments were also performed in K/BxN mice with chronic arthritis, and in RA patients and healthy controls. Arthritis activity in K/BxN mice was associated with a marked dyslipidemia, lower PON1 activity and higher bioactive lipid mediators (BLM), as well as a dysregulated hepatic lipid gene expression profile. Higher serum PON1 activity correlated with lower BLM and lower arthritis activity in both K/BxN mice and RA patients. Overexpression of the human PON1 transgene was associated with reduced inflammatory arthritis, which correlated strongly with higher circulating PON1 activity, upregulation of the hepatic glutathione pathway, and reduction of circulating BLM. These results implicate PON1 as a potential novel therapeutic target for joint disease in RA with potential for vascular benefit, which warrants further investigation.

11.
Cell Death Differ ; 2020 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-33100324

RESUMO

Transcription factor EB (TFEB) is a master regulator of autophagy and lysosomal biogenesis. The post-translational phosphorylation modulations of TFEB by mTOR and ERK signaling can determine its nucleocytoplasmic shuttling and activity in response to nutrient availability. However, regulations of TFEB at translational level are rarely known. Here, we found that programmed cell death 4 (PDCD4), a tumor suppressor, decreased levels of nuclear TFEB to inhibit lysosome biogenesis and function. Mechanistically, PDCD4 reduces global pool of TFEB by suppressing TFEB translation in an eIF4A-dependent manner, rather than influencing mTOR- and ERK2-dependnet TFEB nucleocytoplasmic shuttling. Both of MA3 domains within PDCD4 are required for TFEB translation inhibition. Furthermore, TFEB is required for PDCD4-mediated lysosomal function suppression. In the tumor microenvironment, PDCD4 deficiency promotes the anti-tumor effect of macrophage via enhancing TFEB expression. Our research reveals a novel PDCD4-dependent TFEB translational regulation and supports PDCD4 as a potential therapeutic target for lysosome dysfunction related diseases.

12.
Orthop Surg ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33073501

RESUMO

OBJECTIVE: To study the distribution of sympathetic nerves of the ligamentum flavum (LF), confirm its existence by histological observation and nuclear magnetic resonance spectroscopy, and analyze the relationship between sympathetic nerve fibers and the biomechanical structure of the LF. METHODS: Randomly controlled scientific research selected 15 cases of posterior surgery in the affiliated hospital of Qingdao University from January 2013 to December 2019. The average age was 67.5 ± 14.5 years old, eight males and seven females. The LF specimens (completely separated fresh tissue) of different segments (C3-7 ) were taken during the operation. Two pages of LF specimens on the left and right sides of the same segment are randomly allocated by the pairing method for formalin fixation and cryopreservation in liquid nitrogen. LF specimens extracted from seven other adult cadaver specimens (average age at death of about 56.8 ± 4.0 years, three males and four females) were used as a control group; together with formalin- fixed specimens obtained during surgery, 3D slices were given layer by layer. The distribution of sympathetic nerves in different parts of the LF was analyzed by glyoxylic acid-induced biological monoamine fluorescent technique (SPG) and hematoxylin-eosin (HE) staining. Fifteen liquid nitrogen storage specimens were divided into the back of the LF and the spinal canal through frozen sections, and were analyzed by nuclear magnetic resonance spectroscopy-hydrogen spectrum (1 H -NMR) for neurotransmitters and neurometabolites. RESULTS: There were type C sympathetic nerve fibers in the LF, which were divided into linear shape (α) and wave shape (ß). Experimental group (χ2 = 1.705, P > 0.05) and control group (χ2 = 0.879, P > 0.05) can detect no difference in fluorescence units. Nerve fiber transmitter metabolites choline (Cho), creator (Cr), γ-aminobutyric acid (GABA) also indicate that the sympathetic nerve is present in the LF. LF sympathetic nerve fibers were mainly distributed in the proximal spinal canal surface, nerve fibers on the medial belt (area II) were fewer than the lateral belt (area I) (W = 210, P < 0.05). The 1 HNMR spectrum of LF spinal canal PG / Cho (t = 8.721, P < 0.05), GABA (t = 16.01, P < 0.05) value increased, lactic acid (Lac) / Cr (t = 4.213, P < 0.05), Cho / Cr (t = 2.402, P < 0.05) value decreased, indicating that nerve fibers are actively metabolized on the surface of the spinal canal, mainly distributed in tube surface. ßtype fibers were more often distributed around microvessels. A small amount of α type fibers went next to the vascular structures, while α type fibers and ß type fibers go cross within LF. Two patients with vertebral artery dissection had no recurrence of sympathetic symptoms within a total of 12 follow-ups 2 years after discharge. CONCLUSIONS: There are many sympathetic nerve fibers distributed on LF, and their distribution may be correlated with histological and mechanical characteristics of LF. It may also be the anatomical basis of cervical vertigo.

13.
J Comp Eff Res ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33073605

RESUMO

Aim: PD-1 inhibitors have a leading role among immunotherapy while its efficacy on colorectal cancer (CRC) patients did not reach consensus and the small sample size remains as a limitation. Therefore, we undertook a meta-analysis on the effects of the monotherapy anti-PD-1 inhibitors in treating metastatic colorectal cancer (mCRC). Materials & methods: We searched databases to identify studies on efficacy of anti-PD-1 inhibitor on CRC. Objectives were objective response rate, progression-free survival rate, disease control rate and overall survival rate with their 95% CI. Results: The overall survival rate at 1-year was 64.2% (95% CI: 0.46-0.83). Disease control rate was 56.5% (CI: 0.27-0.86) and the objective response rate as 19.7% (CI: 0.08-0.32). The 1-year-progression-free survival rate was 38.4% (CI: 0.12-0.66). Sensitivity analysis and subgroup analysis were also conducted. Conclusion: The monotherapy anti-PD-1 inhibitors are effective in treating mCRC and could be a new option for dMMR mCRC patient in first-line treatment.

14.
J Mater Chem B ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33043939

RESUMO

Acute lung injury (ALI) is a diffuse inflammatory pulmonary damage caused by excessive ROS that break the coordination of normal physiological structures and functions. Hypochlorous acid (HOCl), one kind of ROS, is a hopeful biological marker for inflammation-related diseases. Therefore, the excessive generation of HOCl might be a significant reason for oxidative injury in ALI. Herein, we developed a fluorescent probe, namely BCy-HOCl, for quantitatively monitoring and visualizing HOCl in living cells and in vivo. The probe BCy-HOCl displayed a significant fluorescence signal enhancement towards HOCl with excellent selectivity and sensitivity. The variation of HOCl in the ALI cell model and ALI mouse model was evaluated with BCy-HOCl to clarify the relationship between ALI and HOCl. Our results verified that the HOCl levels conspicuously increased with the severity of the ALI. Thus, HOCl is likely to play a crucial part in the process of ALI, which will probably provide a new strategy for its treatment.

15.
Sensors (Basel) ; 20(20)2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33081374

RESUMO

A silicon photonic polarization multiplexing (PM) sensor featuring both a large range and a high resolution is proposed and experimentally demonstrated. The sensor includes a Fabry-Pérot (FP) resonator and a microring resonator (MRR) functioning as the sensing parts. With PM technology, the FP resonator only works on the transverse-electric mode while the MRR only on the transverse-magnetic mode. Thus, the proposed sensor can simultaneously achieve a large range with a short FP resonator and a high resolution with a high-Q MRR. Measured results show a range of 113 °C and a resolution of 0.06 °C for temperature sensing, and a range of 0.58 RIU (refractive index unit) with the resolution of 0.002 RIU for analyte refractive index sensing.

16.
Genomics ; 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33022357

RESUMO

Tubby-like protein genes (TULPs), present in the form of large multigene families, play important roles in environmental stress. However, little is known regarding the TULP family genes in cotton. In this study, we systematically identified and analyzed the membership, characterization, and evolutionary relationship of TULPs in four species of cotton. Transcriptome analysis indicated that GhTULPs participate in environmental stress and cotton tissue development. At the same time, we also predicted and analyzed the potential molecular regulatory mechanisms and functions of TULPs. GhTULP34, as a candidate gene, significantly reduced the germination rate of transgenic Arabidopsis plants under salt stress, and inhibited root development and stomatal closure under mannitol stress. The yeast two-hybrid and luciferase (LUC) systems showed that GhTULP34 can interact with GhSKP1A, a subunit of the SCF-type (Skp1-Cullin-1-F-box) complex. This study will provide a basis and reference for future research on their roles in stress tolerance.

17.
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
18.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(7): 988-994, 2020 Jul 30.
Artigo em Chinês | MEDLINE | ID: mdl-32895166

RESUMO

OBJECTIVE: To study the anti- fibrotic effect of human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-EXOs) and explore the mechanism. METHODS: Twenty-four C57 BL/6 mice were divided into 4 groups (n=6), including the control group treated with intratracheal injection of saline (3 mg/kg); lung fibrosis model group with intratracheal injection of 1.5 mg/mL bleomycin solution (prepared with saline, 3 mg/kg); EXOs1 group with intratracheal injection of 1.5 mg/mL bleomycin solution (3 mg/kg) and hUCMSC-EXOs (100 µg/250 µL, given by tail vein injection on the next day after modeling); and EXOs2 group with intratracheal injection of 1.5 mg/mL bleomycin solution (3 mg/kg) and hUCMSC-EXOs (100 µg/250 µL, given by tail vein injection on the 10th day after modeling). At 21 days after modeling, pulmonary index, lung tissue pathology and collagen deposition in the mice were assessed using HE staining and Masson staining. The expression level of TGF-ß1 was detected using ELISA, and vimentin, E-cadherin and phosphorylated Smad2/3 (p-Smad2/3) were detected using immunohistochemical staining. CCK8 assay was used to evaluate the effect of hUCMSCEXOs on the viability of A549 cells, and Western blotting was used to detect the expression levels of p-Smad2/3, vimentin, and E-cadherin in the cells. RESULTS: Compared with those in the model group, the mice treated with hUCMSC-EXOs showed significantly reduced the pulmonary index (P < 0.05), collagen deposition, lung tissue pathologies, lowered expressions of TGF-ß1 (P < 0.05), vimentin, and p-Smad2/3 and increased expression of E-cadherin. hUCMSC-EXOs given on the second day produced more pronounced effect than that given on the 11th day (P < 0.05). CCK8 assay results showed that hUCMSC-EXOs had no toxic effects on A549 cells (P > 0.05). Western blotting results showed that hUCMSC-EXOs treatment significantly increased the expression of E-cadherin and decreased the expressions of p-Smad2/3 and vimentin in the cells. CONCLUSIONS: hUCMSC-EXOs can alleviate pulmonary fibrosis in mice by inhibiting epithelialmesenchymal transition activated by the TGF-ß1/Smad2/3 signaling pathway, and the inhibitory effect is more obvious when it is administered on the second day after modeling.


Assuntos
Exossomos , Células-Tronco Mesenquimais , Fibrose Pulmonar , Animais , Transição Epitelial-Mesenquimal , Humanos , Camundongos , Fator de Crescimento Transformador beta1 , Cordão Umbilical
19.
Electron Commer Res Appl ; : 101007, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32989378

RESUMO

Internet platform enterprises have become one of the dominant organizational forms for internet-based businesses. Despite the strategically crucial role that openness decision plays for Internet platform enterprises, the results of existing research on the relationship between platform openness and platform performance are not conclusive. As to the nature of platform, its transaction attribute has been overemphasized while its innovation attribute is mostly neglected. Through decomposing platform openness into supply-side openness and demand-side openness, as well as introducing demand diversity and knowledge complexity as contextual variables, this study attempts to understand the impact of both types of attributes on performance by considering their configuration. Using fuzzy sets qualitative comparative analysis (fsQCA) method, we find that high demand diversity of platform users and high supply-side openness will lead to better platform performance. Moreover, the high knowledge complexity required for platform innovation together with high supply-side and demand-side openness will contribute to a high level of platform performance.

20.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(5): 501-506, 2020 May 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-32879097

RESUMO

OBJECTIVES: To establish a system for control of cross-infection and workflow for preventing severe acute respiratory syndrome coronavirus 2 spread and ensuring the safety of medical staffs and patients in endoscopy center during the pandemic of the coronavirus disease 2019 (COVID-19). METHODS: Based on the national publication of relevant documents and relevant guidance of Digestive Endoscopy Branch of Chinese Medical Association, we explored and optimized the workflow, staff protection and sterilization of endoscope in digestive endoscopy center during the pandemic of the COVID-19. RESULTS: The prevention system of cross-infection and workflow in endoscopy during the pandemic of the COVID-19 were developed. The optimized workflow in endoscopy was conducted in 106 patients with necessary endoscopy from the Department of Gastroenterology, Third Xiangya Hospital, Central South University between January 24, 2020 and February 26, 2020, and no case of cross-infection was presented among the medical staffs, patients and family members. CONCLUSIONS: Measures on control of cross-infection and workflow in digestive endoscopy center during the pandemic of the COVID-19 are effective, which are beneficial to preventing cross-infection in hospital and provide a scientific guidance for the general work in the digestive endoscopy centers during the pandemic of the COVID-19.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecção Hospitalar/prevenção & controle , Endoscopia , Gastroenterologia/organização & administração , Pneumonia Viral/epidemiologia , Fluxo de Trabalho , Betacoronavirus , China , Infecções por Coronavirus/prevenção & controle , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle
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