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1.
Neural Regen Res ; 16(1): 150-157, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32788470

RESUMO

Acrylamide has been shown to be neurotoxic. Brain-derived neurotrophic factor (BDNF) can alleviate acrylamide-induced synaptic injury; however, the underlying mechanism remains unclear. In this study, dibutyryl-cyclic adenosine monophosphate-induced mature human neuroblastoma (NB-1) cells were exposed with 0-100 µg/mL acrylamide for 24-72 hours. Acrylamide decreased cell viability and destroyed synapses. Exposure of co-cultured NB-1 cells and Schwann cells to 0-100 µg/mL acrylamide for 48 hours resulted in upregulated expression of synapsin I and BDNF, suggesting that Schwann cells can activate self-protection of neurons. Under co-culture conditions, activation of the downstream TrkB-MAPK-Erk1/2 pathway strengthened the protective effect. Exogenous BDNF can increase expression of TrkB, Erk1/2, and synapsin I, while exogenous BDNF or the TrkB inhibitor K252a could inhibit these changes. Taken together, Schwann cells may act through the BDNF-TrkB-MAPK-Erk1/2 signaling pathway, indicating that BDNF plays an important role in this process. Therefore, exogenous BDNF may be an effective treatment strategy for acrylamide-induced nerve injury. This study was approved by the Laboratory Animal Welfare and Ethics Committee of the National Institute of Occupational Health and Poison Control, a division of the Chinese Center for Disease Control and Prevention (approval No. EAWE-2017-008) on May 29, 2017.

2.
Mol Med Rep ; 22(5): 4227-4235, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000205

RESUMO

A number of studies have reported that diabetic retinopathy (DR) is the major cause of blindness. Berberine (BBR) is a bioactive constituent that displays effects on blood glucose; however, the mechanism underlying the role of BBR during the development of DR is not completely understood. In the present study, a rat model of DR was successfully established. The eye tissues were removed and subsequently assessed by hematoxylin and eosin staining and the TUNEL assay. The catalase, malondialdehyde, reactive oxygen species, glutathione and superoxide dismutase contents of the eye tissues were measured. Müller cells were chosen for further in vitro experiments. Cell apoptosis was examined by Annexin V­FITC apoptosis detection and Hoechst staining, and the mitochondrial membrane potential was assessed by JC­1 mitochondrial membrane potential detection. BBR decreased ganglion cell layer, cell apoptosis, reduced diabetic­induced oxidative stress and deactivated the NF­κB signaling pathway in the rat model of DR. High glucose enhanced oxidative stress and induced mitochondria­dependent cell apoptosis in Müller cells by activating the NF­κB signaling pathway. BBR reversed the high glucose­induced effects by decreasing the phosphorylation of IκB, inhibiting NF­κB nuclear translocation and deactivating the NF­κB signaling pathway. The results suggested that BBR protected against DR by inhibiting oxidative stress and cell apoptosis via deactivation of the NF­κB signaling pathway; therefore, suggesting that BBR may serve as a promising therapeutic agent for DR.

3.
Bone ; : 115666, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33007528

RESUMO

Glucocorticoid (or steroid) induced osteoporosis (GIOP) is the leading form of secondary osteoporosis, affecting up to 50% of patients receiving chronic glucocorticoid therapy. Bone quantity (bone mass) changes in GIOP patients alone are inadequate to explain the increased fracture risk, and bone material changes (bone quality) at multiple levels have been implicated in the reduced mechanics. Quantitative analysis of specific material-level changes is limited. Here, we combined multiscale experimental techniques (scanning small/wide-angle X-ray scattering/diffraction, backscattered electron imaging, and X-ray radiography) to investigate these changes in a mouse model (Crh-120/+) with chronic endogenous steroid production. Nanoscale degree of orientation, the size distribution of mineral nanocrystals in the bone matrix, the spatial map of mineralization on the femoral cortex, and the microporosity showed significant changes between GIOP and the control, especially in the endosteal cortex. Our work can provide insight into the altered structure-property relationship leading to lowered mechanical properties in GIOP. SIGNIFICANCE STATEMENT: As a natural nanocomposite with a hierarchical structure, bone undergoes a staggered load transfer mechanism at the nanoscale. Disease and age-related deterioration of bone mechanics are caused by changes in bone structure at multiple length scales. Although clinical tools such as dual-energy X-ray absorptiometry (DXA) can be used to assess the reduction of bone quantity in these cases, little is known about how altered bone quality in diseased bone can increase fracture risk. It is clear that high-resolution diagnostic techniques need to be developed to narrow the gap between the onset and diagnosis of fracture-related changes. Here, by combining several scanning probe methods on a mouse model (Crh-120/+) of glucocorticoid-induced osteoporosis (GIOP), we developed quantitative and spatially resolved maps of ultrastructural changes in collagen fibrils and mineral nanocrystals, mineralization distribution (microscale), and morphology (macroscale) across femoral osteoporotic bone. Our results indicate that the altered bone remodelling in GIOP leads to 1) heterogeneous bone structure and mineralization, 2) reduced degree of orientation of collagen fibrils and mineral nanocrystals, and 3) reduced length and increased thickness of mineral nanocrystals, which contribute to mechanical abnormalities. The combined multiscale experimental approach presented here will be used to understand musculoskeletal degeneration in aging and osteoporosis.

4.
Mol Autism ; 11(1): 75, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023636

RESUMO

BACKGROUND: Both de novo variants and recessive inherited variants were associated with autism spectrum disorder (ASD). This study aimed to use exome data to prioritize recessive inherited genes (RIGs) with biallelically inherited variants in autosomes or X-linked inherited variants in males and investigate the functional relationships between RIGs and genes with de novo variants (DNGs). METHODS: We used a bioinformatics pipeline to analyze whole-exome sequencing data from 1799 ASD quads (containing one proband, one unaffected sibling, and their parents) from the Simons Simplex Collection and prioritize candidate RIGs with rare biallelically inherited variants in autosomes or X-linked inherited variants in males. The relationships between RIGs and DNGs were characterized based on different genetic perspectives, including genetic variants, functional networks, and brain expression patterns. RESULTS: Among the biallelically or hemizygous constrained genes that were expressed in the brain, ASD probands carried significantly more biallelically inherited protein-truncating variants (PTVs) in autosomes (p = 0.038) and X-linked inherited PTVs in males (p = 0.026) than those in unaffected siblings. We prioritized eight autosomal, and 13 X-linked candidate RIGs, including 11 genes already associated with neurodevelopmental disorders. In total, we detected biallelically inherited variants or X-linked inherited variants of these 21 candidate RIGs in 26 (1.4%) of 1799 probands. We then integrated previously reported known or candidate genes in ASD, ultimately obtaining 70 RIGs and 87 DNGs for analysis. We found that RIGs were less likely to carry multiple recessive inherited variants than DNGs were to carry multiple de novo variants. Additionally, RIGs and DNGs were significantly co-expressed and interacted with each other, forming a network enriched in known functional ASD clusters, although RIGs were less likely to be enriched in these functional clusters compared with DNGs. Furthermore, although RIGs and DNGs presented comparable expression patterns in the human brain, RIGs were less likely to be associated with prenatal brain regions, the middle cortical layers, and excitatory neurons than DNGs. LIMITATIONS: The RIGs analyzed in this study require functional validation, and the results should be replicated in more patients with ASD. CONCLUSIONS: ASD RIGs were functionally associated with DNGs; however, they exhibited higher heterogeneity than DNGs.

5.
ACS Nano ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33034451

RESUMO

Determining multiscale, concurrent strain, and deformation mechanisms in hierarchical biological materials is a crucial engineering goal, to understand structural optimization strategies in Nature. However, experimentally characterizing complex strain and displacement fields within a 3D hierarchical composite, in a multiscale full-field manner, is challenging. Here, we determined the in situ strains at the macro-, meso-, and molecular-levels in stomatopod cuticle simultaneously, by exploiting the anisotropy of the 3D fiber diffraction coupled with sample rotation. The results demonstrate the method, using the mineralized 3D α-chitin fiber networks as strain sensors, can capture submicrometer deformation of a single lamella (mesoscale), can extract strain information on multiple constituents concurrently, and shows that α-chitin fiber networks deform elastically while the surrounding matrix deforms plastically before systematic failure under compression. Further, the results demonstrate a molecular-level prestrain gradient in chitin fibers, resulting from different mineralization degrees in the exo- and endo cuticle.

6.
Dalton Trans ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33034595

RESUMO

Two five-coordinate mononuclear Co(ii) complexes [Co(12-TMC)X][B(C6H5)4] (L = 1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclododecane (12-TMC), X = Cl- (1), Br- (2)) have been studied by X-ray single crystallography, magnetic measurements, high-frequency and -field EPR (HF-EPR) spectroscopy and theoretical calculations. Both complexes have a distorted square pyramidal geometry with the Co(ii) ion lying above the basal plane constrained by the rigid tetradentate macrocyclic ligand. In contrast to the reported five-coordinate Co(ii) complex [Co(12-TMC)(NCO)][B(C6H5)4] (3) exhibiting easy-axis anisotropy, an easy-plane magnetic anisotropy was found for 1 and 2 via the analyses of the direct-current magnetic data and HF-EPR spectroscopy. Frequency- and temperature-dependent alternating-current magnetic susceptibility measurements demonstrated that complexes 1 and 2 show slow magnetic relaxation at an applied dc field. Ab initio calculations were performed to reveal the impact of the terminal ligands on the nature of the magnetic anisotropies of this series of five-coordinate Co(ii) complexes.

7.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5378-5381, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33019197

RESUMO

This paper investigates the association between consecutive ambient air pollution and Chronic Obstructive Pulmonary Disease (COPD) hospitalization in Chengdu China. The three-year (2015-2017) time series data for both ambient air pollutant concentrations and COPD hospitalizations in Chengdu are approved for the study. The big data statistic analysis shows that Air Quality Index (AQI) exceeded the lighted air polluted level in Chengdu region are mainly attributed to particulate matters (i.e., PM2.5 and PM10). The time series study for consecutive ambient air pollutant concentrations reveal that AQI, PM2.5, and PM10 are significantly positive correlated, especially when the number of consecutive polluted days is greater than nine days. The daily COPD hospitalizations for every 10 µg/m3 increase in PM2.5 and PM10 indicate that consecutive ambient air pollution can lead to an appearance of an elevation of COPD admissions, and also present that dynamic responses before and after the peak admission are different. Support Vector Regression (SVR) is then used to describe the dynamics of COPD hospitalizations to consecutive ambient air pollution. These findings will be further developed for region specific, hospital early notifications of COPD in responses to consecutive ambient air pollution.

8.
Dalton Trans ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33020782

RESUMO

The reactions of LnIII ions with a versatile pyridyl-decorated dicarboxylic acid ligand lead to the formation of a series of novel three-dimensional (3D) Ln-MOFs, [Ln3(pta)4(Hpta)(H2O)]·xH2O (Ln = Dy (1), Eu (2), Gd (3), Tb (4), H2pta = 2-(4-pyridyl)-terephthalic acid, x = 6 for 1, 2.5 for 2, 1.5 for 3 and 2 for 4). The Ln3+ ions act as nine-coordinated muffin spheres, linking to each other to generate trinuclear {Ln3(OOC)6N2} SBUs, which are further extended to be interesting 3D topological architectures. To the best of our knowledge, the Dy-MOF exhibits zero-field single-molecule magnet (SMM) behaviour with the largest effective energy barrier among the previously reported 3D MOF-based Dy-SMMs. The combined analyses of a diluted sample (1@Y) and ab initio calculations demonstrate that the thermally assisted slow relaxation is mainly attributed to the single-ion magnetism. Furthermore, fluorescence measurements reveal that H2pta can sensitize EuIII and TbIII characteristic luminescence.

9.
Gut Liver ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33028744

RESUMO

Background/Aims: Single-balloon enteroscopy (SBE) has been widely used in diagnosing small bowel disease. We conducted this study to systematically appraise its technical and clinical performance. Methods: Studies on SBE published by September 2018 were systematically searched. Technical and clinical performance data were collected and analyzed with descriptive or meta-analysis methods. Results: In total, 54 articles incorporating 4,592 patients (6,036 procedures) were included. Regarding technical parameters, the pooled insertion depths (IDs) for anterograde and retrograde SBE were 209.2 cm and 98.1 cm, respectively. The pooled retrograde ID in Asian countries was significantly greater than that in Western countries (129.0 cm vs 81.1 cm, p<0.001). The pooled anterograde and retrograde procedure times were 57.6 minutes and 65.1 minutes, respectively. The total enteroscopy rate was 21.9%, with no significant difference between Asian and Western countries. Clinically, the pooled diagnostic yield of SBE was 62.3%. Obscure gastrointestinal bleeding (OGIB) was the most common indication (50.0%), with a diagnostic yield of 59.5%. Vascular lesions were the most common findings in Western OGIB patients (76.9%) but not in Asian ones (31.0%). The rates of severe and mild adverse events were 0.5% and 2.5%, respectively. Conclusions: SBE is technically efficient and is clinically effective and safe, but total enteroscopy is relatively difficult to achieve with this technique. Etiologies of OGIB in Asian countries differ from those in Western countries.

10.
Chem Biodivers ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33022147

RESUMO

Two novel epimerized andrographolides, 8,17-dihydro-7,8-dehydroandrographolide and 10ß-8,17-dihydro-7,8-dehydroandrographolide, were isolated from andrographolide sulfonates. Their structures were elucidated by detailed NMR analysis, single-crystal X-ray diffraction and quantum chemical ECD calculations. In addition, these compounds exhibited suppression of NO production in LPS-stimulated RAW264.7 cells over the range of 1.564 to 25.000 µg/mL.

11.
J Immunother Cancer ; 8(2)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33023981

RESUMO

BACKGROUND: Tumor relapse due to mutation in CD19 can hinder the efficacy of chimeric antigen receptor (CAR)-T cell therapy. Herein, we focused on lymphoma patients whose B cells exhibited a point mutation in CD19 of B cells after CAR-T cell infusion. METHODS: The CAR-T and CD19+ B cells from peripheral blood or bone marrow were assessed using flow cytometry. Genome sequencing was conducted to identify the molecular characteristics of CAR-T and CD19+ B cells from pre-relapse and postrelapse samples. CD19 in CARs comprising single chain fragments variable (scFV) antibody with FMC63 or 21D4 was constructed. The cytotoxic efficacy of CAR-T cells was also evaluated via in vitro and in vivo experiments. RESULTS: A patient with high-grade B cell lymphoma exhibited complete response, but the lymphoma relapsed in her left breast at 6 months after CD19 CAR (FMC63)-T cell infusion. A mutation was found in exon 3 of CD19 (p.163. R-L) in malignant B cells of the patient. In two lymphoma patients who exhibited resistance to CAR-T cell therapy, a mutation was detected in exon 3 of CD19 (p.174. L-V). Functional analysis revealed that FMC63 CAR-T cells exhibited antitumor ability against wild-type CD19+ cells but were unable to eradicate these two types of mutated CD19+ cells. Interestingly, 21D4 CAR-T cells were potentially capable of eradicating these mutated CD19+ cells and exhibiting high antitumor capacity against CD19+ cells with loss of exon 1, 2, or 3. CONCLUSIONS: These findings suggest that point mutation can facilitate immune escape from CAR-T cell therapy and that alternative CAR-T cells can effectively eradicate the mutated B cells, providing an individualized therapeutic approach for lymphoma patients showing relapse.

12.
Dalton Trans ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33026012

RESUMO

Six dimetallic lanthanide complexes, [Ln2(L')(acac)4] (1Dy-3Gd) (Ln = Dy (1Dy), Tb (2Tb) and Gd (3Gd)) and [Ln2(L')(tfac)4] (4Dy-6Gd) (Ln = Dy (4Dy), Tb (5Tb) and Gd (6Gd)) (H2L' = 1,9-dichloro-3,7,11,15-tetraaza-1,9(1,3)-dibenzenacyclohexadecaphane-2,10-diene-1,9-diol), have been synthesized by the reaction of lanthanide nitrates with the HL ligand in the presence of acetylacetonate (acac) (or trifluoroacetylacetonate (tfac) and triethylamine (HL = 4-chloro-2,6-bis(-((3-((3-(dimethylamino)propyl)amino)propyl)imino)methyl)phenol). Ln-Assisted modification of the Schiff base HL occurred and led to the formation of a new macrocyclic ligand (H2L'). X-ray crystallographic analysis revealed that the LnIII ions of complexes 1Dy-6Gd are all eight-coordinated in a square antiprismatic geometry with D4d local symmetry. Magnetic measurements of these complexes revealed that 1Dy and 4Dy show single-molecule magnet behaviour with energy barriers of 66.7 and 79.0 K, respectively, under a zero direct magnetic field. The orientations of the magnetic axes and crystal field parameters were obtained from theoretical calculations and an electrostatic model. The magneto-structural correlations of SMMs 1Dy and 4Dy are further discussed in detail.

13.
J Integr Med ; 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33069626

RESUMO

OBJECTIVE: Traditional Chinese medicine plays a significant role in the treatment of the pandemic of coronavirus disease 2019 (COVID-19). Tanreqing Capsule (TRQC) was used in the treatment of COVID-19 patients in the Shanghai Public Health Clinical Center. This study aimed to investigate the clinical efficacy of TRQC in the treatment of COVID-19. METHODS: A retrospective cohort study was conducted on 82 patients who had laboratory-confirmed mild and moderate COVID-19; patients were treated with TRQC in one designated hospital. The treatment and control groups consisted of 25 and 57 cases, respectively. The treatment group was given TRQC orally three times a day, three pills each time, in addition to conventional Western medicine treatments which were also administered to the control group. The clinical efficacy indicators, such as the negative conversion time of pharyngeal swab nucleic acid, the negative conversion time of fecal nucleic acid, the duration of negative conversion of pharyngeal-fecal nucleic acid, and the improvement in the level of immune indicators such as T-cell subsets (CD3, CD4 and CD45) were monitored. RESULTS: COVID-19 patients in the treatment group, compared to the control group, had a shorter negative conversion time of fecal nucleic acid (4 vs. 9 days, P = 0.047) and a shorter interval of negative conversion of pharyngeal-fecal nucleic acid (0 vs. 2 days, P = 0.042). The level of CD3+ T cells increased in the treatment group compared to the control group ([317.09 ± 274.39] vs. [175.02 ± 239.95] counts/µL, P = 0.030). No statistically significant differences were detected in the median improvement in levels of CD4+ T cells (173 vs. 107 counts/µL, P = 0.208) and CD45+ T cells (366 vs. 141 counts/µL, P = 0.117) between the treatment and control groups. CONCLUSION: Significant reductions in the negative conversion time of fecal nucleic acid and the duration of negative conversion of pharyngeal-fecal nucleic acid were identified in the treatment group as compared to the control group, illustrating the potential therapeutic benefits of using TRQC as a complement to conventional medicine in patients with mild and moderate COVID-19. The underlying mechanism may be related to the improved levels of the immune indicator CD3+ T cells.

14.
Mol Nutr Food Res ; : e2000353, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33002297

RESUMO

SCOPE: Huangjinya is a light-sensitive tea mutant containing low levels of tea polyphenols. Currently, most studies focused on characteristics formation, free amino acid metabolism and phytochemical purification. The biological activity of Huangjinya black tea (HJBT) on metabolic syndrome regarding fecal metabolome modulation is unavailable and is studied herein. METHODS AND RESULTS: High-fat diet (HFD)-fed mice are treated with HJBT for 9 weeks, various metabolic biomarkers and fecal metabolites are determined. HJBT reduces adipogenic and lipogenic gene expression, enhances lipolytic gene expression, decreases adipocyte expansion, and prevents the development of obesity. HJBT reduces lipogenic gene expression, increases fatty acid oxidation-related genes expression, which alleviates liver steatosis. HJBT enhances glucose/insulin tolerance, increases insulin/Akt signaling, attenuates hyperlipidemia and hyperglycemia, prevents the onset of insulin resistance. HJBT modulates bile acid metabolism, promotes secondary/primary bile acid ratio; increases short-chain fatty acids production, promotes saturated and polyunsaturated fatty acids content; reduces carnitines and phosphocholines, but increases myo-inositol content; decreases branched-chain and aromatic amino acids content; increases the metabolite content related to pentose phosphate pathway. CONCLUSION: This study reported the association between fecal metabolome modulation and metabolism improvement due to HJBT administration, proposes HJBT as a dietary intervention for preventing obesity and metabolic disorders.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33007478

RESUMO

OBJECTIVES: Use of corticosteroids is common in the treatment of coronavirus disease 2019, but the clinical effectiveness was controversial. We aimed to investigate the association of corticosteroids therapy with clinical outcomes of hospitalized COVID-19 patients. METHODS: In this single center, retrospective cohort study, adult patients with confirmed coronavirus disease 2019 and dead or discharged between December 29, 2019 and February 15, 2020 were studied. 1:1 propensity score matchings were performed between patients with or without corticosteroids treatment. Multivariable COX proportional hazards model was used to estimate the association between corticosteroids treatment and in-hospital mortality by taking corticosteroids as a time-varying covariate. RESULTS: Among 646 patients, in-hospital death rate was higher in 158 patients with corticosteroids administration (72/158, 45.6% vs 56/488, 11.5%, p<0.0001). After propensity score-match analysis, no significant differences were observed in in-hospital death between patients with and without corticosteroids treatment (47/124, 37.9% vs 47/124, 37.9%, p=1.000). When patients received corticosteroids before they required nasal high-flow oxygen therapy or mechanical ventilation, in-hospital death rate was lower than that in patients who were not administered with corticosteroids (17/86, 19.8% vs. 26/86, 30.2%, log rank p=0.0102), whereas time from admission to clinical improvement was longer (13 [IQR, 10∼17] days vs 10 [IQR, 8∼13] days; p<0.001). Using Cox proportional hazards regression model accounting for time varying exposures in matched pairs, corticosteroid therapy was not associated with mortality difference (HR=0.98, 95%CI: 0.93-1.03, p=0.4694). CONCLUSIONS: Corticosteroids use in COVID-19 patients may not be associated with in-hospital mortality.

16.
J Neural Eng ; 17(5): 056011, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33043903

RESUMO

OBJECTIVE: Removal of common mode noise and artifacts from extracellularly measured action potentials, herein referred to as spikes, recorded with multi-electrode arrays (MEAs) which included severe noise and artifacts generated by an ultrahigh field (UHF) 16.4 Tesla magnetic resonance imaging (MRI) scanner. APPROACH: An adaptive virtual referencing (AVR) algorithm is used to remove artifacts and thus enable extraction of neural spike signals from extracellular recordings in anesthetized rat brains. A 16-channel MEA with 150-micron inter-site spacing is used, and a virtual reference is created by spatially averaging the 16 signal channels which results in a reference signal without extracellular spiking activity while preserving common mode noise and artifacts. This virtual reference signal is then used as the input to an adaptive FIR filter which optimally scales and time-shifts the reference to each specific electrode site to remove the artifacts and noise. MAIN RESULTS: By removing artifacts and reducing noise, the neural spikes at each electrode site can be well extracted, even from data originally recorded with a high noise floor due to electromagnetic interference and artifacts generated by a 16.4T MRI scanner. The AVR method enables many more spikes to be detected than would otherwise be possible. Further, the filtered spike waveforms can be well separated from each other using PCA feature extraction and semi-supervised k-means clustering. While data in a 16.4T MRI scanner contains significantly more noise and artifacts, the developed AVR method enables similar data quality to be extracted as recorded on benchtop experiments outside the MRI scanner. SIGNIFICANCE: AVR of extracellular spike signals recorded with MEAs has not been previously reported and fills a technical need by enabling low-noise extracellular spike extraction in noisy and challenging environments such as UHF MRI that will enable further study of neuro-vascular coupling at UHF.

17.
Cereb Cortex ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33037819

RESUMO

The biological mediators that support cognitive-control and long-term weight-loss after laparoscopic sleeve gastrectomy (LSG) remain unclear. We measured peripheral appetitive hormones and brain functional-connectivity (FC) using magnetic-resonance-imaging with food cue-reactivity task in 25 obese participants at pre, 1 month, and 6 month after LSG, and compared with 30 normal weight controls. We also used diffusion-tensor-imaging to explore whether LSG increases brain structural-connectivity (SC) of regions involved in food cue-reactivity. LSG significantly decreased BMI, craving for high-calorie food cues, ghrelin, insulin, and leptin levels, and increased self-reported cognitive-control of eating behavior. LSG increased FC between the right dorsolateral prefrontal cortex (DLPFC) and the pregenual anterior cingulate cortex (pgACC) and increased SC between DLPFC and ACC at 1 month and 6 month after LSG. Reduction in BMI correlated negatively with increased FC of right DLPFC-pgACC at 1 month and with increased SC of DLPFC-ACC at 1 month and 6 month after LSG. Reduction in craving for high-calorie food cues correlated negatively with increased FC of DLPFC-pgACC at 6 month after LSG. Additionally, SC of DLPFC-ACC mediated the relationship between lower ghrelin levels and greater cognitive control. These findings provide evidence that LSG improved functional and structural connectivity in prefrontal regions, which contribute to enhanced cognitive-control and sustained weight-loss following surgery.

18.
J Int Med Res ; 48(10): 300060520960317, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33044102

RESUMO

OBJECTIVE: To explore a method for evaluating the bioequivalence of acarbose based on pharmacodynamic parameters using a single-dose, randomized-sequence, three-way crossover study of acarbose test (T) and reference (R) formulations. METHODS: Baseline-adjusted, pre-dose value deduction, and direct comparison methods were used to evaluate the geometric T/R ratios and 90% confidence intervals (CIs) of the ln-transformed pharmacodynamic parameters to identify the most suitable evaluation system. Twelve participants were randomly divided into three groups to receive treatment in the following sequences: TRR, RTR, and RRT, each including a 7-day washout period between treatment periods. The serum glucose concentration (baseline) was determined. Pharmacodynamic parameters, including the maximum reduction in serum glucose concentrations (ΔCSG,max) and difference of the AUC of glucose between before and after acarbose exposure (ΔAUEC), were tested. RESULTS: Using the direct comparison method, the geometric mean ratios of CSG,max, AUEC(0-2h), and AUEC(0-4h) were 94.13%, 97.82% and 99.76%, respectively. The 90% CIs of the geometric T/R ratios for CSG,max, AUEC(0-2h), and AUEC(0-4h) all fell between 80% and 125%. Conversely, ΔCSG,max and ΔAUEC(0-4h) were less reliable measures of acarbose bioequivalence. CONCLUSIONS: Pre-dose value deduction and direct comparison methods can be initially considered suitable for assessing acarbose bioequivalence.

19.
J Mol Med (Berl) ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33047154

RESUMO

Epidemiological studies have shown an increased prevalence of cancer in some patients with neurodevelopmental disorder (NDD); however, the genetic mechanisms regarding how cancer-related genes (CRGs) contribute to NDD remain unclear. We performed bioinformatic analyses on 219 CRGs from OMIM and de novo mutations (DNMs) from 16,498 patients with different NDDs and 3391 controls. Our results showed that autism spectrum disorder, undiagnosed neurodevelopmental disorder, congenital heart disease and intellectual disability, but not epileptic encephalopathy and schizophrenia, harboured significantly more putative functional DNMs in CRGs, compared with controls, providing genetic evidence supporting previous epidemiological surveys. We further detected 26 CRGs with recurrent putative functional DNMs that showed high expression in the human brain during the prenatal stage and in non-brain organs in adults. The proteins coded by the 26 CRGs and known NDD candidate genes formed a functional network that is involved in brain development and tumorigenesis. Overall, we proposed 39 cancer-targeting drugs that could be investigated for treating patients with NDD, which would be potentially cost-effective. In conclusion, DNMs contribute to specific NDDs and there may be a shared genetic basis between NDDs and cancer, highlighting the importance of considering cancer-targeting drugs with potential curative effects in patients with NDDs. KEY MESSAGES: • The contribution of DNMs in NDD is consistent with epidemiological surveys. • We highlighted 26 CRGs, including nine genes with more than five functional DNMs. • Specific expression patterns underlie the genetic mechanism of CRGs in NDD. • Specific functional networks underlie the genetic mechanism of CRGs in NDD. • The shared genetic aetiology suggests potential mutual treatment strategies.

20.
Crit Rev Biotechnol ; : 1-18, 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33012193

RESUMO

Adenosine triphosphate (ATP), the universal energy currency of life, has a central role in numerous biochemical reactions with potential for the synthesis of numerous high-value products. ATP can be regenerated by three types of mechanisms: substrate level phosphorylation, oxidative phosphorylation, and photophosphorylation. Current ATP regeneration methods are mainly based on substrate level phosphorylation catalyzed by one enzyme, several cascade enzymes, or in vitro synthetic enzymatic pathways. Among them, polyphosphate kinases and acetate kinase, along with their respective phosphate donors, are the most popular approaches for in vitro ATP regeneration. For in vitro artificial pathways, either ATP-free or ATP-balancing strategies can be implemented via smart pathway design by choosing ATP-independent enzymes. Also, we discuss some remaining challenges and suggest perspectives, especially for industrial biomanufacturing. Development of ATP regeneration systems featuring low cost, high volumetric productivity, long lifetime, flexible compatibility, and great robustness could be one of the bottom-up strategies for cascade biocatalysis and in vitro synthetic biology.

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