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1.
Nat Commun ; 12(1): 4158, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34230497

RESUMO

Prenylated indole alkaloids featuring spirooxindole rings possess a 3R or 3S carbon stereocenter, which determines the bioactivities of these compounds. Despite the stereoselective advantages of spirooxindole biosynthesis compared with those of organic synthesis, the biocatalytic mechanism for controlling the 3R or 3S-spirooxindole formation has been elusive. Here, we report an oxygenase/semipinacolase CtdE that specifies the 3S-spirooxindole construction in the biosynthesis of 21R-citrinadin A. High-resolution X-ray crystal structures of CtdE with the substrate and cofactor, together with site-directed mutagenesis and computational studies, illustrate the catalytic mechanisms for the possible ß-face epoxidation followed by a regioselective collapse of the epoxide intermediate, which triggers semipinacol rearrangement to form the 3S-spirooxindole. Comparing CtdE with PhqK, which catalyzes the formation of the 3R-spirooxindole, we reveal an evolutionary branch of CtdE in specific 3S spirocyclization. Our study provides deeper insights into the stereoselective catalytic machinery, which is important for the biocatalysis design to synthesize spirooxindole pharmaceuticals.

3.
Gynecol Endocrinol ; : 1-7, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34232092

RESUMO

BACKGROUND: The aim of this case-control study was to document maternal, umbilical arterial metabolic levels and correlations in pregnancies with and without 25-hydroxyvitamin D [25(OH)D] deficiency, while, also investigating the expression of nuclear factor erythroid 2 related factor 2 (Nrf2) and carbonyl reductase 1 (CBR1) in the placenta. METHODS: One hundred participants, 50 deficient for 25(OH)D and 50 normal, were recruited from among hospitalized single-term pregnant women who had elected for cesarean section. Umbilical arterial and placental samples were collected during cesarean section. Metabolic levels were assessed for the 25(OH)D deficiency and control groups' maternal, umbilical arterial samples. Nrf2 and CBR1 expression levels were investigated in the placentas of 12 pregnant women with 25(OH)D deficiency and 12 controls. RESULTS: Compared with the control participants, the 25(OH)D deficient women had significantly higher triglyceride (TG) levels (3.80 ± 2.11 vs. 2.93 ± 1.16 mmol/L, 3.64 ± 1.84 vs. 2.81 ± 1.16 mmol/L, p < .01, .001); lower high density lipoprotein cholesterol (HDL-C) levels (1.54 ± 0.32 vs. 1.82 ± 0.63 mmol/L, 1.41 ± 0.72 vs. 2.44 ± 1.68 mmol/L, p < .001, .01) in both material blood and the umbilical artery. In addition, Nrf2 and CBR1 expression levels were lower in the maternal 25(OH)D deficient placenta. CONCLUSION: 25(OH)D deficient pregnant women have higher TG levels and lower HDL-C levels in both material blood and the umbilical artery. TG level is negatively correlated with 25(OH)D in both the maternal serum and infant umbilical artery. 25(OH)D deficiency also lowers placental expression of Nrf2 and CBR1.Supplemental data for this article is available online at here.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34236129

RESUMO

Compared with inorganic long-lasting luminescent materials, organic room temperature phosphorescent (RTP) ones show several advantages, such as flexibility, transparency, solubility and color adjustability. However, organic RTP materials close to commercialization are still to be developed. In this work, we developed a new host-guest doping system with stimulus-responsive RTP characteristics, in which triphenylphosphine oxide ( OPph 3 ) acted host and benzo(dibenzo)phenothiazine dioxide derivatives as guests. Turn-on RTP effect was realized by mixing them together through co-crystallization or grinding, in which the efficient energy transfer from host to guest and the strong intersystem crossing (ISC) ability of the guest have played significant role. Further on, multistage stimulus-responsive RTP characteristics from grinding to chemical stimulus were achieved via introducing pyridine group into the guest molecule. In addition, the anti-counterfeiting printings were realized for these materials through various methods, including stylus printing, thermal printing and inkjet printing, which brings RTP materials closer to commercialization.

5.
Mol Med Rep ; 23(4)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-34223631

RESUMO

Acute myelogenous leukemia (AML) is frequently accompanied by a poor prognosis. The majority of patients with AML will experience recurrence due to multiple drug resistance. Our previous study reported that targeting the mTOR pathway may increase cell sensitivity to doxorubicin (Doxo) and provide an improved therapeutic approach to leukemia. However, the effect and mechanism of action of NVP­BEZ235 (BEZ235), a dual inhibitor of PI3K/mTOR, on Doxo­resistant K562 cells (K562/A) is yet to be elucidated. Therefore, the aim of the present study was to investigate the effects of BEZ235 on K562/A cell proliferation. K562/A cells was investigated using CCK­8, flow cytometry and western blotting, following BEZ235 treatment. It was observed that BEZ235 significantly decreased the viability of K562/A cells. In addition, BEZ235 arrested K562/A cells at the G0/G1 phase, and reduced the protein expression levels of CDK4, CDK6 and cyclin D1. Apoptotic cells were more frequently detected in K562/A cells treated with BEZ235 compared with the control group (12.97±0.91% vs. 7.37±0.42%, respectively; P<0.05). Cells treated with BEZ235 exhibited downregulation of Bcl­2 and upregulation of Bax. Furthermore, BEZ235 treatment markedly decreased the activation of the PI3K/AKT/mTOR pathway and its downstream effectors. Thus, these results demonstrated that BEZ235 inhibited cell viability, induced G0/G1 arrest and increased apoptosis in K562/A cells, suggesting that BEZ235 may reverse Doxo resistance in leukemia cells. Therefore, targeting the PI3K/mTOR pathway may be of value as a novel therapeutic approach to leukemia.

6.
Neural Plast ; 2021: 6627507, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34257640

RESUMO

Recently, transcranial direct current stimulation (tDCS) has been applied to relieve symptoms in individuals with autism spectrum disorder (ASD). In this prospective, parallel, single-blinded, randomized study, we investigate the modulation effect of three-week tDCS treatment at the left dorsal lateral prefrontal cortex (DLPFC) in children with ASD. 47 children with ASD were enrolled, and 40 (20 in each group) completed the study. The primary outcomes are Childhood Autism Rating Scale (CARS), Aberrant Behavior Checklist (ABC), and the Repetitive Behavior Scale-Revised (RBS-R). We found that children with ASD can tolerate three-week tDCS treatment with no serious adverse events detected. A within-group comparison showed that real tDCS, but not sham tDCS, can significantly reduce the scores of CARS, Children's Sleep Habits Questionnaire (CSHQ), and general impressions in CARS (15th item). Real tDCS produced significant score reduction in the CSHQ and in CARS general impressions when compared to the effects of sham tDCS. The pilot study suggests that three-week left DLPFC tDCS is well-tolerated and may hold potential in relieving some symptoms in children with ASD.

8.
Polymers (Basel) ; 13(13)2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34279352

RESUMO

The mannose receptor (MAN-R)-targeted delivery system is commonly used to deliver antigens to macrophages or immature dendritic cells (DCs) to promote the efficiency of antigen presentation. To maximize the enhancement effects of chitosan (CS) and induce an efficient humoral and cellular immune response against an antigen, we encapsulated ovalbumin (OVA) in poly(lactic-co-glycolic acid) (PLGA) microspheres (MPs) and conjugated it with MAN-modified CS to obtain MAN-R-targeting nano-MPs (MAN-CS-OVA-PLGA-MPs). The physicochemical properties, drug loading rate, and immunomodulation activity of MAN-CS-OVA-PLGA-MPs were evaluated. In vitro, MAN-CS-OVA-PLGA-MPs (80 µg mL-1) could enhance the proliferation of DCs and increase their phagocytic efficiency. In vivo, MAN-CS-OVA-PLGA-MPs significantly increased the ratio of CD3+CD4+/CD3+CD8+ T cells, increased CD80+, CD86+, and MHC II expression in DCs, and improved OVA-specific IgG, IgG1, IgG2a, and IgG2b antibodies. Moreover, MAN-CS-OVA-PLGA-MPs promoted cytokine (IFN-γ, IL-4, and IL-6) production in mice. Taken together, our results show that MAN-CS-OVA-PLGA-MPs may act by activating the T cells to initiate an immune response by promoting the maturation of dendritic cells and improving their antigen presentation efficiency. The current study provides a basis for the use of MAN-CS-OVA-PLGA-MPs as an antigen and adjuvant delivery system targeting the MAN-R on the surface of macrophages and dendritic cells.

9.
IEEE Trans Med Imaging ; PP2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34224349

RESUMO

Pulmonary emphysema overlaps considerably with chronic obstructive pulmonary disease (COPD), and is traditionally subcategorized into three subtypes previously identified on autopsy. Unsupervised learning of emphysema subtypes on computed tomography (CT) opens the way to new definitions of emphysema subtypes and eliminates the need of thorough manual labeling. However, CT-based emphysema subtypes have been limited to texture-based patterns without considering spatial location. In this work, we introduce a standardized spatial mapping of the lung for quantitative study of lung texture location and propose a novel framework for combining spatial and texture information to discover spatially-informed lung texture patterns (sLTPs) that represent novel emphysema subtype candidates. Exploiting two cohorts of full-lung CT scans from the MESA COPD (n=317) and EMCAP (n=22) studies, we first show that our spatial mapping enables population-wide study of emphysema spatial location. We then evaluate the characteristics of the sLTPs discovered on MESA COPD, and show that they are reproducible, able to encode standard emphysema subtypes, and associated with physiological symptoms.

10.
Int J Lab Hematol ; 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34271589

RESUMO

INTRODUCTION: ß-thalassemia is a severe hereditary hemolytic anemia. Due to the diversity of mutations spectrum, ß-thalassemia manifests a highly heterogeneous clinical severity. We noted that a previous report characterized HBB:c.313delA, at the end of exon 2, as a ß-thalassemia trait rather than dominant ß-thalassemia, the classification given to similar mutations. We further explored the impact of this functional variant on globin structure through larger pedigree analysis and in vitro studies. METHODS: Hematological analysis and molecular genotyping were conducted on the proband and his family members. We evaluated functional effects of the variant on ß-globin gene in the proband's nucleated erythrocytes and transfected HEK-293T cells. Three-dimensional construction of protein structure was carried out in silico to demonstrate amino acid changes. RESULTS: The thalassemia major proband was identified as a compound heterozygote of HBB:c.313delA and HBB:c.126_129delCTTT. Three family members with heterozygotes of HBB:c.313delA displayed microcytic hypochromic anemia. Molecular characterization demonstrated that the frameshift mutation could give rise to retro-positioning of the termination codon, resulting in an elongated ß-globin chain with an extension of 10 amino acids. Clinical phenotype and functional experiments indicated that HBB:c.313delA led to ß0 -thalassemia phenotype. CONCLUSION: We concluded that the phenotype of HBB:c.313delA was mainly related to the stability of mutant mRNA, the degradation of mutant proteins, and production of inclusion bodies according to a systematic description of clinical phenotype and a series of molecular experiments.

11.
Phys Rev E ; 103(6-1): 063216, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34271707

RESUMO

An accurate understanding of ion-beam transport in plasmas is crucial for applications in inertial fusion energy and high-energy-density physics. We present an experimental measurement on the energy spectrum of a proton beam at 270 keV propagating through a gas-discharge hydrogen plasma. We observe the energies of the beam protons changing as a function of the plasma density and spectrum broadening due to a collective beam-plasma interaction. Supported by linear theory and three-dimensional particle-in-cell simulations, we attribute this energy modulation to a two-stream instability excitation and further saturation by beam ion trapping in the wave. The widths of the energy spectrum from both experiment and simulation agree with the theory.

12.
ACS Nano ; 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34269062

RESUMO

Although high-entropy alloys have been intensively studied in the past decade, there are still many requirements for manufacturing processes and application directions to be proposed and developed, but most techniques are focused on high-entropy bulk materials and surface coatings. We fabricated high-entropy ceramic (HEC) nanomaterials using simple pulsed laser irradiation scanning on mixed salt solutions (PLMS method) under low-vacuum conditions. This method, allowing simple operation, rapid manufacturing, and low cost, is capable of using various metal salts as precursors and is also suitable for both flat and complicated 3D substrates. In this work, we engineered this PLMS method to fabricate high-entropy ceramic oxides containing four to seven elements. To address the catalytic performance of these HEC nanomaterials, we focused on CoCrFeNiAl high-entropy oxides applied to the oxygen-evolution reaction (OER), which is considered a sluggish process in water. We performed systematic material characterization to solve the complicated structure of the CoCrFeNiAl HEC as a spinel structure, AB2O4 (A, B = Co, Cr, Fe, Ni, or Al). Atoms in A and B sites in the spinel structure can be replaced with other elements; either divalent or trivalent metals can occupy the spinel lattice using this PLMS process. We applied this PLMS method to manufacture electrocatalytic CoCrFeNiAl HEC electrodes for the OER reaction, which displayed state-of-the-art activity and stability.

13.
Food Funct ; 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34269784

RESUMO

The purpose of this study was to investigate the effect of starch-hydrocolloid (gum arabic, xanthan gum, and guar gum) complexes with heat-moisture treatment (HMT) on in vivo digestibility. In vivo digestibility experiments revealed that the body weight, liver weight, and fat index of mice in the intervention group were significantly reduced compared with those in the high-fat group. Glucose tolerance improved, and blood lipid levels, liver and adipose tissue morphology returned to normal. The results of mRNA expression levels showed that the intervention of corn starch-hydrocolloid complexes after HMT down-regulated the expression level of genes related to fat synthesis compared with the high-fat group, which could decrease lipid deposition and stabilize blood lipid levels. Results revealed that starch-xanthan gum complex (1 : 40 ratio) with HMT could markedly reduce the digestibility of starch. Overall, this study provides new ideas for the application of low-glycemic-index and functional foods.

14.
BMC Cancer ; 21(1): 786, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238242

RESUMO

BACKGROUND: The clinical pathologic stages (stage I, II, III-IV) of hepatocellular carcinoma (HCC) are closely linked to the clinical prognosis of patients. This study aims at investigating the gene expression and mutational profile in different clinical pathologic stages of HCC. METHODS: Based on the TCGA-LIHC cohort, we utilized a series of analytical approaches, such as statistical analysis, random forest, decision tree, principal component analysis (PCA), to identify the differential gene expression and mutational profiles. The expression patterns of several targeting genes were also verified by analyzing the Chinese HLivH060PG02 HCC cohort, several GEO datasets, HPA database, and diethylnitrosamine-induced HCC mouse model. RESULTS: We identified a series of targeting genes with copy number variation, which is statistically associated with gene expression. Non-synonymous mutations mainly existed in some genes (e.g.,TTN, TP53, CTNNB1). Nevertheless, no association between gene mutation frequency and pathologic stage distribution was detected. The random forest and decision tree modeling analysis data showed a group of genes related to different HCC pathologic stages, including GAS2L3 and SEMA3F. Additionally, our PCA data indicated several genes associated with different pathologic stages, including SNRPA and SNRPD2. Compared with adjacent normal tissues, we observed a highly expressed level of GAS2L3, SNRPA, and SNRPD2 (P = 0.002) genes in HCC tissues of our HLivH060PG02 cohort. We also detected the high expression pattern of GAS2L3, SEMA3F, SNRPA, and SNRPD2 in the datasets of GSE102079, GSE76427, GSE64041, GSE121248, GSE84005, and the qPCR assay using diethylnitrosamine-induced HCC mouse model. Moreover, SEMA3F and SNRPD2 protein were highly stained in the HCC tissues of the HPA database. The high expression level of these four genes was associated with the poor survival prognosis of HCC cases. CONCLUSIONS: Our study provides evidence regarding the gene expression and mutational profile in different clinical pathologic stages of TCGA HCC cases. Identifying four targeting genes, including GAS2L3, SNRPA, SNRPD2, and SEMA3F, offers insight into the molecular mechanisms associated with different prognoses of HCC.

15.
Nanoscale ; 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34263895

RESUMO

Interlayer engineering of graphite anodes in alkali metal ion (M = Li, Na, and K) batteries is carried out based on the first-principles calculations. By increasing the interlayer spacing of graphite, the specific capacity of Li or Na does not increase while that of K increases continuously (from 279 mA h g-1 at the equilibrium interlayer spacing to 1396 mA h g-1 at the interlayer spacing of 20.0 Å). As the interlayer spacing increases, the electrostatic potential of graphite becomes smoother, and the ability to buffer the electrostatic potential fluctuation becomes poorer in M ions. These two effects jointly lead to minima of the diffusion barrier of M ions on graphite (0.01-0.05 eV), instead of strictly monotonous declines with the increasing interlayer spacing. To perform the interlayer engineering of anode candidates more efficiently, a set of high-throughput programs has been developed and can be easily applied to other systems. Our research has guiding significance for achieving the optimal effect in interlayer engineering experimentally.

16.
IEEE Trans Biomed Eng ; PP2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34242159

RESUMO

Seizure prediction for drug-refractory epilepsy patients can improve their quality of life, reduce their anxiety, and help them take the necessary precautions. Nowadays, numerous deep learning algorithms have been proposed to predict seizure onset and obtain better performance than traditional machine learning methods. However, these methods require a large set of parameters and large hardware resources; they also have high energy consumption. Therefore, these methods cannot be implemented on compact, low-power wearable, or implantable medical devices. The devices should operate on a real-time basis to continually inform the epileptic patients. In this paper, we describe energy-efficient and hardware-friendly methods to predict the epileptic seizures. A model of only 45 kB was obtained by the neural architecture search and was evaluated across three datasets. The overall accuracy, sensitivity, false prediction rate, and area under receiver operating characteristic curve were 99.53%, 99.81%, 0.005/h, 1 and 93.60%, 93.48%, 0.063/h, 0.977 and 86.86%, 85.19%, 0.116/h, 0.933, respectively, for the CHB-MIT scalp, the AES and Melbourne University intracranial electroencephalography (EEG) datasets. This model was further reduced with network pruning, quantization, and compact neural networks. The performances for the model sizes less than 50 kB for scalp EEG data and less than 10 kB for intracranial EEG data outperformed all the other models of similar model sizes. In particular, the energy consumption estimation was less than 10 mJ per inference for scalp EEG signal and less than 0.5 mJ per inference for intracranial EEG signal, which meet the requirements for low-power wearable and implantable devices, respectively.

17.
Rev Sci Instrum ; 92(4): 043103, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-34243435

RESUMO

We present a velocity-map imaging (VMI) apparatus coupled with a magneto-optical trap (MOT) of 87Rb atoms designed for low-energy photo-ion spectroscopy. The VMI-electrode geometry uses a three-electrode configuration, and the focusing electric field is optimized based on systematic simulations of relatively low-energy ions. To calibrate the apparatus, we use resonant two-color two-photon ionization of rubidium atoms as Doppler-selected ions. This VMI system provides an accuracy of 0.15 m/s and a resolution of 7.5 m/s for photoions with speeds below 100 m/s. Finally, details of the design, construction, and testing of the VMI-MOT system are presented.

18.
Aging (Albany NY) ; 132021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34229300

RESUMO

Emerging evidence proves that exosomes contain specific microRNAs(miRNAs) contribute to osteogenic differentiation of bone marrow stem cells (BMSCs). However, the role and mechanism of bone marrow stem cells (BMSCs)-derived exosomes overexpressing miR-424-5p in osteoblasts remains unclear. Firstly, the BMSCs-derived exosomes were isolated, and identified by Western blot with the exosome surface markers CD9, CD81 and CD63. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the level of miR-424-5p in exosomes, and western blot was implemented to verify the WIF1/Wnt/ß-catenin expression. The binding association between miR-424-5p and WIF1 was determined by the dual-luciferase reporter gene assay. Functional enhancement experiments were adopted to determine the role of exosome-carried miR-424-5p and WIF1/Wnt/ß-catenin in osteogenic differentiation. ALP staining was adopted, and levels of RUNX2, OCN, and OPN were monitored using qRT-PCR to determine osteogenic differentiation. As a result, In vivo experiments showed that RUNX2, OCN and OPN levels decreased and the ALP activity was dampened after miR-424-5p overexpression in exosomes. Besides, exosomes overexpressing miR-424-5p attenuated osteogenic development via WIF1/Wnt/ß-catenin. Our findings may bring evidence for miR-424-5p as a new biomarker for the treatment of osteoporosis.

19.
Anal Chem ; 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34251808

RESUMO

A new strategy has been developed for the direct chirality fixation, which is induced by electrochemical polymerization, of macrocyclic hosts pillar[5]arene. Taking advantage of electrochemical polymerization, thiophene-modified pillar[5]arene monomers (Th-P[5]A) have been regularly arranged under the action of an electric field to form chiral nanofiber-like crystalline pillar[5]arene-based polymers (poly-Th-P[5]A), showing a significant circular dichroism (CD) signal. With the active photochemical properties, poly-Th-P[5]A is first used as a photoelectrochemical (PEC) chiral sensor for the identification and determination of l- and d-ascorbic acid (l-AA, d-AA) without adding any extra photoactive probes. Importantly, the chiral recognition between poly-Th-P[5]A and l-AA also triggers a polarity conversion for the photocurrent of the polymer, and it greatly results in a broad chiral detection range for l-AA, crossing 6 orders of magnitude. This work provides a promotional strategy for building a PEC chiral recognition platform based on pillararenes.

20.
Artigo em Inglês | MEDLINE | ID: mdl-34280090

RESUMO

Image smoothing is a fundamental procedure in applications of both computer vision and graphics. The required smoothing properties can be different or even contradictive among different tasks. Nevertheless, the inherent smoothing nature of one smoothing operator is usually fixed and thus cannot meet the various requirements of different applications. In this paper, we first introduce the truncated Huber penalty function which shows strong flexibility under different parameter settings. A generalized framework is then proposed with the introduced truncated Huber penalty function. When combined with its strong flexibility, our framework is able to achieve diverse smoothing natures where contradictive smoothing behaviors can even be achieved. It can also yield the smoothing behavior that can seldom be achieved by previous methods, and superior performance is thus achieved in challenging cases. These together enable our framework capable of a range of applications and able to outperform the state-of-the-art approaches in several tasks. In addition, an efficient numerical solution is provided and its convergence is theoretically guaranteed even the optimization framework is non-convex and non-smooth. A simple yet effective approach is further proposed to reduce the computational cost of our method while maintaining its performance. The effectiveness and superior performance of our approach are validated through comprehensive experiments in a range of applications.

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