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1.
Brain Imaging Behav ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31898088

RESUMO

Recent studies have demonstrated sex-specific differences in etiology, course and brain dysfunction that are associated with cigarette smoking. However, little is known about sex-specific differences in subcortical structure and function. In this study, structural and resting-state functional magnetic resonance imaging (fMRI) data were collected from 60 cigarette smokers (25 females) and 67 nonsmokers (28 females). The structural MRI was applied to identify deficits in sex-specific subcortical volume. Using resting-state fMRI, sex-related alterations in resting-state functional connectivity (rsFC) were investigated in subcortical nuclei with volume deficits as seed regions. Compared to nonsmokers, male but not female smokers demonstrated a significantly smaller volume in the left caudate, while female but not male smokers showed a smaller volume in the right amygdala. Resting-state FC analysis revealed that male but not female smokers had increased rsFC between the left caudate and the left prefrontal cortex but decreased rsFC within the bilateral caudate and between the right amygdala and right orbitofrontal cortex (OFC). Furthermore, the right amygdala volume was negatively correlated with the impulsivity score in female but not male smokers. The rsFC of the right amygdala-OFC circuit was negatively associated with the craving score in male but not female smokers. These findings indicate that cigarette smoking may have differential effects on the caudate and amygdala volumes as well as rsFC between men and women, contributing to our knowledge of sex-specific effects of nicotine addiction. Such sex-specific differences in subcortical structure and function may provide a methodological framework for the development of sex-specific relapse prevention therapies.

3.
Cancer Res ; 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31948942

RESUMO

Mutations in Sonic hedgehog (SHH) signaling promote aberrant proliferation and tumor growth. SHH medulloblastoma (MB) is among the most frequent brain tumors in children less than three years of age. While key components of the SHH pathway are well-known, we hypothesized that new disease-modifying targets of SHH MB might be identified from large-scale bioinformatics and systems biology analyses. Using a data-driven systems biology approach, we built a medulloblastoma-specific interactome. The ATP-binding cassette transporter ABCC4 was identified as a modulator of SHH-MB. Accordingly, increased ABCC4 expression correlated with poor overall survival in SHH MB patients. Knockdown of ABCC4 expression markedly blunted the constitutive activation of the SHH pathway secondary to Ptch1 or Sufu insufficiency. In human tumor cell lines, ABCC4 knockdown and inhibition reduced full-length GLI3 levels. In a clinically relevant murine SHH MB model, targeted ablation of Abcc4 in primary tumors significantly reduced tumor burden and extended the lifespan of tumor-bearing mice. These studies reveal ABCC4 as a potent SHH pathway regulator and a new candidate to target with the potential to improve SHH MB therapy.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31903759

RESUMO

With the rapid development of biotechnological industry, there is an urgent need for exploiting new materials to immobilize enzymes to improve the performance of biocatalysts. In this paper, hierarchically porous magnetic microspheres (PFMMs) were prepared through solvothermal method and rapidly grafted with a novel rigid-flexible dendrimer first synthesized from monomers of trimesoyl chloride (TMC) and 1,6-hexanediamine (HDA) via interfacial polymerization process for covalent immobilization of Pseudomonas fluorescens lipase (PFL). The maximum PFL loading of the synthesized support reaches 87.5 mgprotein/gsupport, and 864% activity recovery of PFMMs-G3.0-PFL can be achieved at pH 9.0. Then, it was used to catalyze the resolution of (R,S)-1-phenylethanol with vinyl acetate. Under the optimized conditions, 50.0% conversion with 99.0% ees can be reached within 1.5 h. In addition, a conversion of 49.2% and ees of 96.9% can be retained after 10 batches of running, displaying an excellent operational stability. Importantly, a further investigation shows that the obviously improved reusability of the immobilized PFL is ascribed to the increased rigidity in comparison to fully flexible dendrimer. Thus, the newly constructed protocol for lipase immobilization exhibits a great prospect in biochemical engineering.

5.
Chemistry ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31943406

RESUMO

Coordination preference of different metal ions and ligands push forward immense influence on the constructions of functional MOF materials. In this work, two new monometallic complexes, namely [Ag(HL)(bipy)0.5] (1), and {[Tb(L)1.5(H2O)]∙4H2O}n (2) (bipy = 4,4-bipyridine), have been firstly synthesized successfully by employing a bifunctional 2-(imidazol-1-yl)terephthalic acid (H2L) ligand. After that, two new different heterometallic-organic frameworks (HMOFs), namely {[TbAg(L)2(H2O)3]∙H2O}n (3), and [TbAg(L)2(H2O)]n (4), were obtained by complexes 1 and 2 as the precursors based on the rational stepwise construction strategy and theory of hard and soft acids and bases (HSAB principle), respectively. The HMOFs bearing dual metallic catalytic sites (Tb and Ag) can be used as heterogeneous catalysts without losing performance for the chemical fixation of CO2 with epoxides including the sterically hindered epoxides, demonstrating some of the highest reported catalytic activity values. This work may build up a new synthetic route toward tailoring more new HMOFs with excellent catalytic activity.

6.
Vet Microbiol ; 241: 108540, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31928695

RESUMO

Urinary tract infections (UTIs), many of which are caused by bacterial pathogens, are some of the most common infections in dogs. To effectively treat UTIs, it is important to identify the predominant bacterial pathogens and their susceptibility to antimicrobial agents. In this study, we collected 326 samples from cases with UTIs or other urinary system diseases at the China Agricultural University Veterinary Teaching Hospital, Beijing, from 2016-2018. In total, 129 non-duplicate bacterial isolates were recovered from 103 clinical samples. The proportion of positive female samples was higher than that of males. The predominant Gram-negative bacteria were Escherichia coli and Klebsiella spp., while Staphylococcus spp. were the predominant Gram-positive bacteria. Broth microdilution-based antimicrobial susceptibility testing showed that 39 % of E. coli and 51.5 % of Staphylococcus spp. isolates were multidrug-resistant. Specifically, E. coli isolates showed high rates of resistance to ampicillin (40.5 %), ceftazidime (59.5 %), and florfenicol (42.9 %), but limited resistance to amikacin (2.38 %), meropenem (7.14 %), and polymyxin E (7.14 %). In comparison, Staphylococcus spp. showed high rates of resistance to erythromycin (60.6 %), trimethoprim-sulfamethoxazole (54.6 %), and penicillin (45. 5 %), but low resistance rates to vancomycin (6.06 %) and nitrofurantoin (6.06 %). Pulsed-field gel electrophoresis (PFGE)-based typing identified 31 PFGE patterns among the 43 E. coli isolates. These results suggested that multiple bacterial strains, many of which are multidrug-resistant, can cause UTIs in dogs. Thus, basic antimicrobial susceptibility tests should be performed to provide guidance for the selection of first-line clinical therapeutics, and to help prevent the occurrence and spread of induced antimicrobial resistance.

7.
Dalton Trans ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31930274

RESUMO

Reversible single crystal-to-single crystal transformations from [FeL2(NCS)2]·3MeOH (1·3MeOH, L = 2-(anthracen-10-yl)-1H-imidazo[4,5-f][1,10]phenanthroline) to 1 and 1·2H2O were reported, which were accompanied by on-off switching of the spin-crossover properties.

8.
Muscle Nerve ; 2020 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-31930519

RESUMO

INTRODUCTION: Number of small segments (NSS) and activity analysis is a mature method for electromyographic automatic interference pattern analysis (IPA), but there are few reports on the application of this technique. Our objective was to establish normal reference values of NSS-activity clouds. METHODS: The NSS and activity data of the sternocleidomastoid, deltoid, biceps brachii (long head), extensor digitorum communis, abductor digiti minimi, vastus medialis, tibialis anterior, and gastrocnemius (lateral head) muscles were obtained from 34 men and 25 women, aged 15-80 years, using concentric needle electrodes. A linear regression of log(NSS) versus log(activity) was performed and the slope, intercept and standard deviation were calculated for each muscle. These variables were transformed back to the original parameters to yield clouds. RESULTS: Normal NSS-activity clouds for the above eight muscles were obtained. DISCUSSION: Normal reference values of NSS-activity may facilitate detection of early and mild neurogenic and myogenic abnormalities. This article is protected by copyright. All rights reserved.

9.
Diabetes Res Clin Pract ; 160: 108004, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31911250

RESUMO

Cardiovascular disease is a major chronic complication of obesity and diabetes. Due to several patients with obesity and diabetes, it is necessary to urgently explore early diagnostic biomarkers and innovative therapeutic strategies to prevent the progression of cardiovascular diseases. Recently, microRNAs (also known as miRNAs) have emerged as important players in heart disease and energy regulation. MiRNAs are a group of small, highly conserved non-coding RNA molecules that regulate gene expression by suppressing the translation of messenger RNA of target genes or by promoting mRNA degradation. These act as a class of potential biomarkers and may provide key information in diagnosing common diseases such as tumors, tissue damage, and autoimmune diseases. Among all the known miRNAs, microRNA-208 (miR-208) is specifically expressed in myocardial cells and showed close association with the development of cardiac diseases, such as myocardial hypertrophy, cardiac fibrosis, myocardial infarction, arrhythmia, and heart failure. However, the functions and underlying mechanisms of miR-208 in heart are still unclear. In this review, we highlighted the novel insights of miR-208 functions and associated mechanisms in the regulation of cardiac diseases.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31935122

RESUMO

Left bundle branch (LBB) pacing was first reported by Huang et al in 2017 and following studies demonstrated that LBB pacing could provide favorable left ventricular (LV) electrical and mechanical synchrony. However, the mechanism of LV activation during LBB pacing is not fully understood. This study aimed to elucidate the detailed LV endocardial activation during LBB pacing in a swine model using an ultra-high density electroanatomic mapping system.

11.
Org Lett ; 22(1): 230-233, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31859511

RESUMO

An unprecedented method that enables the direct transformation of unprotected secondary aliphatic amines into functionalized N-heterocycles in the absence of transition metals was developed. The activation of these NH-free amines by the iodonium ylide induces a site-selective ß-C-H malonylation process, allowing the construction of three σ-bonds and one π-bond in a simple operation.

12.
ACS Appl Mater Interfaces ; 12(2): 3080-3085, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31854960

RESUMO

The poor stability of perovskite nanocrystals (NCs) is one of the major obstacles for their application in optoelectronic devices. Herein, we develop an easy in situ strategy for preparing polyimide (PI)-coated single-particle CsPbBr3 NCs in a continuous stirred-tank reactor system. Benefiting from the protection of the thick polyimide layer, these PI-coated CsPbBr3 NCs show excellent stability against severe environments such as water, heat, oxygen, and light. Meanwhile, time-resolved photoluminescence and ultrafast transient absorption spectroscopy revealed that the polyimide (PI) polymer contributes to passivating the surface defects of the CsPbBr3 NCs, giving CsPbBr3/PI NCs a higher photoluminescence quantum yield. Thanks to the performances of high luminescent efficiency and stability, these green-emitting perovskite CsPbBr3/PI NCs show promising potentials in the fields of solid-state lighting and display.

13.
Nat Genet ; 52(1): 95-105, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31844322

RESUMO

Around implantation, the epiblast (Epi) transits from naïve to primed pluripotency, before giving rise to the three germ layers. How chromatin is reconfigured during this developmental window remains poorly understood. We performed a genome-wide investigation of chromatin landscapes during this period. We find that enhancers in ectoderm are already pre-accessible in embryonic day 6.5 (E6.5) Epi when cells enter a primed pluripotent state. Unexpectedly, strong trimethylation of histone H3 at lysine 4 (H3K4me3) emerges at developmental gene promoters in E6.5 Epi and positively correlates with H3K27me3, thus establishing bivalency. These genes also show enhanced spatial interactions. Both the strong bivalency and spatial clustering are virtually absent in preimplantation embryos and are markedly reduced in fate-committed lineages. Finally, we show that KMT2B is essential for establishing bivalent H3K4me3 at E6.5 but becomes partially dispensable later. Its deficiency leads to impaired activation of developmental genes and subsequent embryonic lethality. Thus, our data characterize lineage-specific chromatin reconfiguration and a unique chromatin state for primed pluripotency.

14.
Chin Med J (Engl) ; 133(2): 141-147, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31868806

RESUMO

BACKGROUND: Super-responders (SRs) to cardiac resynchronization therapy (CRT) regain near-normal or normal cardiac function. The extent of cardiac synchrony of SRs and whether continuous biventricular (BIV) pacing is needed remain unknown. The aim of this study was to evaluate the cardiac electrical and mechanical synchrony of SRs. METHODS: We retrospectively analyzed CRT recipients between 2008 and 2016 in 2 centers to identify SRs, whose left ventricular (LV) ejection fraction was increased to ≥50% at follow-up. Cardiac synchrony was evaluated in intrinsic and BIV-paced rhythms. Electrical synchrony was estimated by QRS duration and LV mechanical synchrony by single-photon emission computed tomography myocardial perfusion imaging. RESULTS: Seventeen SRs were included with LV ejection fraction increased from 33.0 ±â€Š4.6% to 59.3 ±â€Š6.3%. The intrinsic QRS duration after super-response was 148.8 ±â€Š30.0 ms, significantly shorter than baseline (174.8 ±â€Š11.9 ms, P = 0.004, t = -3.379) but longer than BIV-paced level (135.5 ±â€Š16.7 ms, P = 0.042, t = 2.211). Intrinsic LV mechanical synchrony significantly improved after super-response (phase standard deviation [PSD], 51.1 ±â€Š16.5° vs. 19.8 ±â€Š8.1°, P < 0.001, t = 5.726; phase histogram bandwidth (PHB), 171.7 ±â€Š64.2° vs. 60.5 ±â€Š22.9°, P < 0.001, t = 5.376) but was inferior to BIV-paced synchrony (PSD, 19.8 ±â€Š8.1° vs. 15.2 ±â€Š6.4°, P = 0.005, t = 3.414; PHB, 60.5 ±â€Š22.9° vs. 46.0 ±â€Š16.3°, P = 0.009, t = 3.136). CONCLUSIONS: SRs had significant improvements in cardiac electrical and LV mechanical synchrony. Since intrinsic synchrony of SRs was still inferior to BIV-paced rhythm, continued BIV pacing is needed to maintain longstanding and synchronized contraction.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31885247

RESUMO

Polymeric nanovehicles have been widely applied in many fields, but during the process of preparation, it is still hard to reach the balance between precise structure control and mass production. In the present work, using industrial pixel grids as the macroscopic template, we applied dual effects of confinement and dielectric difference to speed up the self-assembly of polymeric nanovehicles, even to regulate the generated mesostructures and cargo loading. Within 2 min, a poly(ethylene glycol)-block-poly(d,l-lactide acid) (PEG-b-PDLLA) amphiphilic block copolymer layer was rapidly pushed off and broken down into uniform nanoparticles at 40 V. Hereinto, increasing volume of the outer aqueous phase in pixel grids favored the architectonic transformation of the generated nanovehicles from solid micelles with a diameter of 95 nm to hollow vesicles with a diameter of 232 nm. In particular, all the elements from the confinement cells to the preparation process can be completed via wet printing. Electric-field-induced pixel template technology is facile, cheap, controllable, and recyclable, and it is anticipated to promote continuous and bulk production of polymeric nanovehicles.

16.
Biotechnol Biofuels ; 12: 273, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31832096

RESUMO

Background: Fed-batch fermentation has been conventionally implemented for the production of lactic acid with a high titer and high productivity. However, its operation needs a complicated control which increases the production cost. Results: This issue was addressed by simplifying the production scheme. Escherichia coli was manipulated for its glycerol dissimilation and d-lactate synthesis pathways and then subjected to adaptive evolution under high crude glycerol. Batch fermentation in the two-stage mode was performed by controlling the dissolved oxygen (DO), and the evolved strain deprived of poxB enabled production of 100 g/L d-lactate with productivity of 1.85 g/L/h. To increase productivity, the producer strain was further evolved to improve its growth rate on crude glycerol. The fermentation was performed to undergo the aerobic growth with low substrate, followed by the anaerobic production with high substrate. Moreover, the intracellular redox of the strain was balanced by fulfillment of the anaerobic respiratory chain with nitrate reduction. Without controlling the DO, the microbial fermentation resulted in the homofermentative production of d-lactate (ca. 0.97 g/g) with a titer of 115 g/L and productivity of 3.29 g/L/h. Conclusions: The proposed fermentation strategy achieves the highest yield based on crude glycerol and a comparable titer and productivity as compared to the approach by fed-batch fermentation. It holds a promise to sustain the continued development of the crude glycerol-based biorefinery.

17.
Cancer Lett ; 471: 38-48, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31811909

RESUMO

The biological functions of circular RNAs (circRNAs) in gastric cancer (GC) remain largely unexplored. Here, we identified that circ-RanGAP1 was significantly upregulated in both GC tissues and exosomes from the plasma of GC patients. High circ-RanGAP1 expression was closely associated with an advanced TNM stage, lymph node metastases, and worse survival. Inhibition of circ-RanGAP1 decreased GC cell invasion and migration in vitro. Overexpression of circ-RanGAP1 had the opposite effect. Additionally, circ-RanGAP1 silencing remarkably suppressed tumor growth and metastasis of GC in vivo. Mechanistically, circ-RanGAP1 sponged miR-877-3p to upregulate VEGFA expression. Overexpression of miR-877-3p reversed the biological functions mediated by circ-RanGAP1 in GC cells. Interestingly, we demonstrated that circ-RanGAP1 was upregulated in plasma exosomes from preoperative GC patients. More importantly, the plasma exosomes derived from these patients enhanced the migration and invasion potential of GC cells. Overall, the circ-RanGAP1-mediated miR-877-3p/VEGFA axis promotes GC progression. Our findings suggest that circ-RanGAP1 might act as a potential prognostic biomarker and therapeutic target for GC treatment.

18.
Ther Clin Risk Manag ; 15: 1305-1318, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31814726

RESUMO

Thyroid eye disease (TED) is a complex, debilitating autoimmune disease that causes orbital inflammation and tissue remodeling, resulting in proptosis, diplopia, and in severe cases, loss of vision. TED can lead to facial disfigurement and severely impact patients' quality of life. Although the course of TED was identified over 60 years ago, effective treatment options have proved to be challenging. Current treatments such as glucocorticoid therapy and orbital radiation focus on reducing orbital inflammation. However, these therapies fail to modify the disease outcomes, including proptosis and diplopia. Recent advances in the understanding of the molecular basis of TED have facilitated the development of targeted molecular therapies such as teprotumumab, an insulin-like growth factor-1 receptor inhibiting monoclonal antibody. In recent phase 2 and phase 3 randomized placebo-controlled trials, teprotumumab rapidly achieved improvement in clinical endpoints defining TED, including improved proptosis and diplopia. Dramatic improvement in clinical outcomes achieved after teprotumumab therapy during active TED are heretofore singular and comparable only to surgical therapies achieved during the inactive phase of TED. The advent of effective medical therapy can lead to a paradigm shift in the clinical management of TED. This review will provide an overview of TED, its epidemiology, insight into the molecular biology of the disease, clinical characteristics and diagnosis, and current and emerging treatment modalities.

19.
PLoS One ; 14(12): e0225705, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31815951

RESUMO

INTRODUCTION: Neuregulin 4 (Nrg4) was proven as a brown fat-enriched secreted factor that can regulate glucose and lipid metabolism. However, the association between circulating Nrg4 levels and diabetes mellitus (DM) in human remains unclear. We conducted a meta-analysis to investigate association of circulating Nrg4 with DM. METHODS: Observational studies comparing circulating Nrg4 levels in diabetes patients and health controls were included. Circulating Nrg4, correlation coefficients of clinical indices and circulating Nrg4 were pooled by meta-analysis. RESULTS: Seven studies were included. The pooled results indicated there were no significant difference in the circulating Nrg4 between diabetes patients and controls (SMD = 0.18, 95%CI = -0.06 to 0.42, P = 0.143). However, diabetes patients had higher circulating Nrg4 than their controls in cross-sectional studies (SMD = 0.55, 95%CI = 0.36 to 0.73, P<0.001). None of the renal function and metabolic syndrome markers were correlated with circulating Nrg4, whereas the HbA1c and BMI were positively correlated (rs = 0.09, 95%CI = 0.03 to 0.16, P = 0.005; rs = 0.20, 95%CI = 0.07 to 0.34, P = 0.003; respectively). CONCLUSION: Our findings suggested circulating Nrg4 may play a role in in the development of DM in cross-sectional studies and circulating Nrg4 might be associated with imbalance in glucose metabolism and obesity.

20.
J Hematol Oncol ; 12(1): 128, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31783889

RESUMO

The approval of two chimeric antigen receptor-modified T cell types by the US Food and Drug Administration (FDA) for the treatment of hematologic malignancies is a milestone in immunotherapy; however, the application of CAR-T cells has been limited by antigen escape and on-target, off-tumor toxicities. Therefore, it may be a potentially effective strategy to select appropriate targets and to combine multi-antigen-targeted CAR-T cells with "OR", "AND" and "NOT" Boolean logic gates. We summarize the current limitations of CAR-T cells as well as the efficacy and safety of logic-gated CAR-T cells in antitumor therapy. This review will help to explore more optimized strategies to expand the CAR-T cell therapeutic window.

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