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1.
Phys Rev Lett ; 126(11): 110502, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33798351

RESUMO

Principal component analysis (PCA) is a widely applied but rather time-consuming tool in machine learning techniques. In 2014, Lloyd, Mohseni, and Rebentrost proposed a quantum PCA (qPCA) algorithm [Lloyd, Mohseni, and Rebentrost, Nat. Phys. 10, 631 (2014)NPAHAX1745-247310.1038/nphys3029] that still lacks experimental demonstration due to the experimental challenges in preparing multiple quantum state copies and implementing quantum phase estimations. Here, we propose a new qPCA algorithm using the hybrid classical-quantum control, where parameterized quantum circuits are optimized with simple measurement observables, which significantly reduces the experimental complexity. As one important PCA application, we implement a human face recognition process using the images from the Yale Face Dataset. By training our quantum processor, the eigenface information in the training dataset is encoded into the parameterized quantum circuit, and the quantum processor learns to recognize new face images from the test dataset with high fidelities. Our work paves a new avenue toward the study of qPCA applications in theory and experiment.

2.
J Cosmet Dermatol ; 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33825341

RESUMO

BACKGROUND: The incidence of hyaluronic acid (HA) embolism has increased markedly in recent years. HA embolism can lead to serious complications such as blindness, eye and eyelid movement disorders, skin necrosis, and cerebral embolism. However, there is a lack of robust clinical evidence regarding the benefits of treatment of HA embolism with intra-arterial thrombolytic therapy (IATT). METHODS: In the present study, we enrolled 45 patients with decreased visual acuity, including 40 patients with symptoms of vision loss, and 8 patients with symptoms of intracranial embolism. The patients underwent emergency IATT via hyaluronidase and papaverine injections, followed by conventional sequential therapy. RESULTS: In the 45 patients with symptoms of vision loss, 16 (36%) exhibited improvements in final visual acuity, even when the clinical application of the thrombolytic treatments was performed beyond the recommended window for optimal treatment. The facial skin necrosis of all patients was restored to near normal appearance. Notably, for 8 patients with suspected symptoms of intracranial infarction we performed cerebral angiography and IATT, and in 2 patients obtained partial recanalization of the obstruction,the symptoms of heavy headache and binocular distension pain was improved in 1 patient with intracranial embolism after IATT treatment. CONCLUSION: Our results indicate that IATT is feasible for patients with vision loss induced by HA embolism. IATT combined with conventional sequential therapy was beneficial in the recovery from other serious HA embolism complications. Nevertheless, the underlying pathophysiological mechanism needs to be clarified in future animal experiments.

3.
Malar J ; 20(1): 160, 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33743705

RESUMO

BACKGROUND: Accumulating evidence suggest that compromised CYP2D6 enzyme activity caused by gene mutation could contribute to primaquine failure for the radical cure of vivax malaria. The current study aims to preliminarily reveal the association between the recurrence of vivax malaria in Yunnan Province and CYP2D6 gene mutation by analysing polymorphisms in the entire coding region of human CYP2D6 gene. METHODS: Blood samples were collected from patients with vivax malaria, who received "chloroquine and 8-day course of primaquine therapy" in Yunnan Province. The suspected relapsed cases were determined by epidemiological approaches and gene sequence alignment. PCR was conducted to amplify the CYP2D6 gene in the human genome, and the amplified products were then sequenced to compare with the non-mutation "reference" sequence, so as to ensure correct sequencing results and to determine 9 exon regions. Subsequently, the DNA sequences of 9 exons were spliced into the coding DNA sequence (CDS), which, by default, is known as maternal CDS. The paternal CDS was obtained by adjusting the bases according to the sequencing peaks. The mutation loci, haplotypes (star alleles), genotypes and odds ratios (OR) of all the CDSs were analysed. RESULTS: Of the119 maternal CDS chains in total with 1491 bp in length, 12 mutation sites in the 238 maternal and paternal CDS chains were detected. The c.408G > C mutation was most frequently detected in both suspected relapsed group (SR) and non-relapsed group (NR), reaching 85.2% (75/88) and 76.0% (114/150), respectively. The c.886C > T mutation was most closely related to the recurrence of vivax malaria (OR = 2.167, 95% CI 1.104-4.252, P < 0.05). Among the 23 haplotypes (Hap_1 ~ Hap_23), Hap_3 was non-mutant, and the sequence structure of Hap_9 was the most complicated one. Five star alleles, including *1, *2, *4, *10 and *39, were confirmed by comparison, and CYP2D6*10 allele accounted for the largest percentage (45.4%, 108/238). The frequency of CYP2D6*2 allele in the SR group was significantly higher than that in the NR group (Χ2 = 16.177, P < 0.05). Of the defined 24 genotypes, 8 genotypes, including *4/*4, *4/*o, *2/*39, *39/*m, *39/*x, *1/*r, *1/*n, and *v/*10, were detected only in the SR group. CONCLUSION: Mutation of CYP2D6*10 allele accounts for the highest proportion of vivax malaria cases in Yunnan Province. The mutations of c. 886C > T and CYP2D6*2 allele, which correspond to impaired PQ metabolizer phenotype, are most closely related to the relapse of vivax malaria. In addition, the genotype *4/*4 with null CYP2D6 enzyme function was only detected in the SR group. These results reveal the risk of defected CYP2D6 enzyme activity that diminishes the therapeutic effect of primaquine on vivax malaria.

4.
Spectrochim Acta A Mol Biomol Spectrosc ; 254: 119626, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33677207

RESUMO

Curcumae Radix (Yujin) is a multi-origin herbal medicine with excellent clinical efficacy. For fast discrimination and quantification analysis of Yujin from four botanical origins (Guiyujin, Huangyujin, Lvyujin and Wenyujin), near infrared (NIR) spectroscopy combined with chemometrics tools was employed in this study. Based on NIR data, principal component analysis (PCA) could only realize the separation between Guiyujin and Wenyujin samples, and the partial least squares-discrimination analysis (PLS-DA), support vector machine (SVM) and k-nearest neighbors (KNN) models achieved the complete discrimination of the four species of Yujin with 100% accuracy. Moreover, the method for the simultaneous determination of six bioactive compounds in Yujin was developed by HPLC. Germacrone, curdione and curcumenol could be found in all samples, and curcumin, demethoxycurcumin and bisdemethoxycurcumin were only observed in Huangyujin samples. Then, the support vector machine regression (SVMR) model for the prediction of germacrone content was successfully constructed. And the coefficients of determination were 0.88 and 0.89 for calibration and validation sets, respectively. The present work proposes a quick, economic and reliable method for the discrimination of Yujin from four botanical origins and the prediction of germacrone content, which will contribute to its quality control researches.

5.
Huan Jing Ke Xue ; 42(2): 819-830, 2021 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-33742876

RESUMO

Periphytic algae are often used as an indicator to evaluate water quality. Here, the community structure of periphytic algae and its relationship with environment factors were analyzed in the main stream of the Songhua River during the summers of 2014 to 2019. The status and trends in ecological water quality were also evaluated based on bioassessments. Phytoplankton species belonging to 4 phyla and 58 genera were recorded, including 28 Bacillariophyta genera, 17 Chlorophyta genera, 10 Cyanophyta genera, and 3 Euglenophyta genera; Bacillariophyta, Chlorophyta, and Cyanophyta accounted for 48.28%, 29.31%, and 17.24% of the community, respectively. Cell densities varied between 1.29×104 and 8.42×104 ind·cm-3, with an average of 4.35×104 ind·cm-3. The dominant genera were Cyclotella, Melosira, Asterionella, Cymbella, Synedra, Pinnularia, Navicula, and Scenedesmus. The physicochemical water quality showed notable changes during the past six-year monitoring period. Specifically, the dissolved oxygen content increased year on year; ammonia nitrogen, total phosphorus, and total nitrogen first increased and then decreased; and, overall, water quality significantly improved in 2019. Relationship between periphytic algae and environmental factors was further examined using redundancy analysis (RDA), which showed that time was the main factor driving the succession of algal community structure. Dissolved oxygen (DO), ammonia nitrogen (NH4+-N), total nitrogen (TN), total phosphorus (TP), five-day biochemical oxygen demand (BOD), and chemical oxygen demand (COD) were also important environmental variables affecting algal community structure.


Assuntos
Diatomáceas , Rios , China , Monitoramento Ambiental , Nitrogênio/análise , Fósforo/análise , Fitoplâncton , Estações do Ano , Qualidade da Água
6.
Acta Pharmacol Sin ; 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33654217

RESUMO

Idiopathic pulmonary fibrosis (IPF) is an aging-associated disease with a poor prognosis. Emerging evidence has revealed that targeting senescent cells may be a potential treatment for IPF. In this study, we aimed to explore whether roxithromycin (RXM) can improve lung fibrosis by targeting senescent cells. First, we confirmed the ability of RXM to selectively kill senescent cells by inducing apoptosis and inhibiting the expression of senescence-associated secretory phenotype (SASP) factors, suggesting the potential role of RXM as a "senolytic" and "senomorphic" drug. Next, we observed that TGF-ß- and senescent cell-induced lung fibroblast activation was inhibited by RXM treatment, which prompted us to further investigate its effect in vivo. In a mouse model of bleomycin (BLM)-induced pulmonary fibrosis, RXM was shown to attenuate lung injury, inflammation, and fibrosis. Furthermore, the senescent phenotype of lung tissues induced by BLM was significantly diminished after RXM administration, indicating the potential of RXM as an antifibrotic and antisenescent agent. Interestingly, NADPH oxidase 4 (NOX4), implicated in lung fibrosis and cell senescence, was shown to be inhibited by RXM treatments. The antifibroblast activation and antisenescent effects of RXM were abolished in NOX4 knockdown cells, demonstrating that RXM may ameliorate BLM-induced pulmonary fibrosis by targeting senescent cells mediated by the NOX4 pathway. Collectively, these data demonstrated that RXM may be a potential clinical agent for IPF and further supported the notion that targeting cellular senescence is a promising treatment for progressive age-related disease.

7.
J Food Biochem ; : e13680, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33646616

RESUMO

High-fat diet (HFD)-induced obesity is caused by the imbalance between energy intake and expenditure. Here, we studied the inhibitory effects of aqueous extracts of fermented barley with Lactobacillus plantarum dy-1 (LFBE) and beta-glucan (BGL) on the obesity induced by HFD. Both LFBE and BGL significantly decreased body weight, suppressed visceral lipid accumulation, improved blood lipid profile, and glucose tolerance in HFD rats. BGL showed no thermogenic capacity, while LFBE enhanced the expression of Uncoupling Protein 1 (UCP1), and brown-specific mRNA (PRDM16, PGC1-α, and CIDEA) levels in brown adipose tissue (BAT) and white adipose tissues (WAT) of HFD rats. In addition, LFBE increased the expression of key genes involved in mitochondria biosynthesis and the mitochondrial respiration function. Further, we demonstrated that proteins extracted from LFBE (LFBE-P) were responsible for triggering brown markers to some extent. In conclusion, LFBE alleviates HFD-induced obesity by activating thermogenic fat bioenergetics and mitochondria biosynthesis. PRACTICAL APPLICATIONS: Barley is one of the most productive crops with pretty low utilization. Our group committed to exploring the application and nutritional value of barley. This work aimed to explore improvements in nutritional function of barley after fermentation by Lactobacillus plantarum dy-1. Our study found that oral administration of LFBE help turning white adipose tissue into a thermogenesis state and activate heat generation function of brown adipose tissue. Its characteristics mentioned above significantly inhibited the body weight and blood lipid of high-fat diet rats. Further, we evidenced that LFBE-P were responsible for triggering brown markers in 3T3-L1 cells. We believe our research plays a great part to relieving high-fat diet-induced obesity and type 2 diabetes with functional diet supplementation.

8.
Biomed Pharmacother ; 138: 111403, 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33714782

RESUMO

Gu-Ben-Fang-Xiao decoction (GBFXD), derived from the traditional Chinese medicine Yu-Ping-Feng-San, is widely used in clinical settings and has obvious curative effects in respiratory diseases. GBFXD regulates cholesterol transport and lipid metabolism in chronic persistent asthma. There is evidence for its beneficial effects in the remission stage of asthma; however, its metabolic regulatory effects and underlying mechanisms during asthma remission are unclear. In the present study, we used liquid chromatography-mass spectrometry (LC-MS) to analyse the metabolic profile of mouse serum during asthma remission. The acquired LC-MS data were subjected to a multivariate analysis for identification of significantly altered metabolites. In total, 42 metabolites were significantly differentially expressed among the control, model, and GBFXD groups. In particular, levels of fatty acids, acylcarnitines, phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositols, triglycerides, and diacylglycerols were altered during asthma remission. GBFXD may maintain lipid homeostasis on the lung surface by modulating lipid metabolism and may thereby alleviate asthma. We further quantified hypogeic acid (FA 16:1) based on targeted metabolomics and found that GBFXD may regulate fatty acid metabolism by activating the AMP-activated protein kinase (AMPK) pathway. These results support the use of GBFXD in patients with asthma remission.

9.
J Hum Hypertens ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33785906

RESUMO

Recently, the contribution of both insufficient sleep duration and gut microbiome dysbiosis to hypertension (HTN) have been revealed, yet the profile of gut flora in hypertensive patients with insufficient sleep duration remains unknown. To examine this condition, the specific shifts in the fecal microbiome of 53 participants with or without HTN were investigated. The patients were divided into those who slept short (≤6 h) or optimal (6-9 h) duration per day. Comprehensive metagenomic sequencing analysis of fecal specimens was performed in healthy controls with sufficient sleep (s-CTR, n = 10), healthy controls with insufficient sleep (ins-CTR, n = 6), hypertensive patients with sufficient sleep (s-HTN, n = 25), and HTNs complicated by short sleep duration (ins-HTN, n = 12). We found that the α-diversity and ß-diversity were quite similar between s-HTN and ins-HTN. Similarities were also observed in the enterotype distribution between s-HTN and ins-HTN subjects. In addition, the enrichment of gut bacteria was evident, such as Fusobacterium mortiferum and Roseburia inulinivorans in ins-HTN subjects. Several functional modules that were distinct between s-HTN and ins-HTN subjects were identified, which were unique to hypertensive patients with insufficient sleep duration. Overall, the data demonstrated that the gut microbial features were largely maintained in hypertensive participants with insufficient sleep duration.

10.
Cell Tissue Res ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33783609

RESUMO

The occurrence of osteoarthritis is closely related to chondrocyte dysfunction caused by cellular inflammatory response and matrix degradation, which seriously affect the quality of life of patients. Therefore, this study aimed to investigate the role of potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (KCNQ1OT1), a member of the lncRNA voltage-gated channel subfamily Q, in the development of osteoarthritis. In this study, RT-qPCR results showed that KCNQ1OT1 expression was downregulated in osteoarthritic chondrocytes compared with normal chondrocytes. In addition, upregulation of KCNQ1OT1 significantly enhanced the viability of osteoarthritic chondrocytes, inhibited cell apoptosis, and reduced the release of inflammatory cytokines and metal matrix enzymes. Next, bioinformatics analysis and luciferase reporter gene analysis predicted and validated the targeting relationship between KCNQ1OT1 and miR-218-5p. We found that the expression of miR-218-5p was significantly upregulated in osteoarthritic chondrocytes, and knockdown of miR-218-5p significantly enhanced the viability of osteoarthritic chondrocytes, inhibited apoptosis, and decreased the abundance of inflammatory cytokines and metal matrix enzymes. Furthermore, the targeting relationship between miR-218-5p and recombinant phosphoinositide-3-kinase class-2-alpha polypeptide (PIK3C2A) was identified, and overexpression of PIK3C2A enhanced cell viability, and reduced apoptosis and secretion of inflammatory factors. Finally, we found that miR-218-5p overexpression reversed the protective effect of overexpression of KCNQ1OT1 or PIK3C2A on osteoarthritic chondrocytes. In conclusion, our results demonstrated that KCNQ1OT1 upregulated PIK3C2A and activated the PI3K/AKT/mTOR pathway to reduce chondrocyte dysfunction by targeting miR-218-5p, providing new insights into the pathogenesis of osteoarthritis.

11.
J Clin Lab Anal ; : e23740, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33616216

RESUMO

BACKGROUND: Preeclampsia (PE) prediction has been shown to improve the maternal and fetal outcomes in pregnancy. We aimed to evaluate the PE prediction values of a series of serum biomarkers. METHODS: The singleton pregnant women (20-36 gestational weeks) with PE-related clinical and/or laboratory presentations were recruited and had the blood drawn at their first visits. The following markers were tested with the collected serum samples: soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), thrombomodulin (TM), tissue plasminogen activator inhibitor complex (tPAI-C), complement factors C1q, B, H, glycosylated fibronectin (GlyFn), pregnancy-associated plasma protein-A2 (PAPP-A2), blood urea nitrogen (BUN), creatinine (Cre), uric acid (UA), and cystatin C (Cysc). RESULTS: Of the 196 recruited subjects, 25% (n = 49) developed preeclampsia before delivery, and 75% remained preeclampsia negative (n = 147). The serum levels of sFlt-1, BUN, Cre, UA, Cysc, and PAPP-A2 were significantly elevated, and the PlGF level was significantly decreased in the preeclampsia-positive patients. In the receiver operating characteristics (ROC) analyses, the area under the curves were listed in the order of decreasing values: 0.73 (UA), 0.67 (sFlt-1/PlGF), 0.66 (Cysc), 0.65 (GlyFn/PlGF), 0.64 (PAPP-A2/PlGF), 0.63 (BUN), 0.63 (Cre), and 0.60 (PAPP-A2). The positive predictive values of these serum markers were between 33.1% and 58.5%, and the negative predictive values were between 80.9% and 89.5%. CONCLUSIONS: The serum markers investigated in current study showed better performance in ruling out than ruling in PE. Absence of pre-defined latency period between blood draw and the onset of PE limits the clinical utility of these markers.

12.
Plant Dis ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33616433

RESUMO

Yunmuxiang (Aucklandia lappa) is a tall, perennial herbaceous plant in the compositae family, occurring mainly in Asia and Europe. Yunmuxiang originated in India and was introduced into China in approximately 1940. Since then it has been widely cultivated in the southwest region of China for medicinal uses; it is included in the Chinese Pharmacopoeia. Yunmuxiang is used primarily as a sedative, including for anesthesia (Ting et al. 2012). Severely stunted and withered Yunmuxiang plants with rotted and galled roots were observed in a field in near the city of Lijiang (N 99°46'; E 27°18') in October 2019. These symptoms were typical of infection by root-knot nematodes.The second-stage juveniles (J2) were collected from the soil in the root zone, and adult females were dissected from roots. Population densities of J2 ranged from 325 to 645 per 100 cm3. Morphological analysis and species-specific PCR were performed on the second stage (J2) and females. Morphological characteristics are as follows: for J2 (n=20) , body length = 360.5 ± 23.4 µm, tail length = 47.2 ± 6.1 µm, and stylet length = 10.4 ± 1.9 µm, distance from dorsal esophageal gland opening to the stylet knot (DGO) = 3.96 ± 0.42 µm; females (n = 20) were pear-shaped, body length = 565.23 ± 86.68 µm, maximum body width = 407.24 ± 60.21 µm, stylet length = 9.93 ± 0.88 µm, DGO = 4.76 ± 0.32 µm, stylet median bulb width (MBW) = 29.67 ± 3.61 µm, perineum morphology is low and low dorsal arch round, with a typical inferior protrusion near the anus. These morphological characteristics are consistent with Meloidogyne hapla as described by Hunt and Handoo (2009). To confirm species identification, DNA was extracted from females (Blok, et al. 1997) and ITS region was amplified using the primers 18S/26S (Vrain et al. 1992). Furthermore, species-specific SCAR primers JMV1/JMV hapla were used as described by Adam et al. (2007). PCR produced 768 bp and 419 bp sequences. Fragments were sequenced (MW512922and MW228371, respectively) and compared with available sequences on NCBI. Sequences were 99.48% identical to the MT249016, KJ572385, and 100% identical to the GQ395574, GQ395569 M. hapla sequences, respectively. Morphological and molecular characterization supports the identification of the isolate found on Aucklandia lappa as M. hapla. Yunmuxiang seed were planted in 20 cm diameter, 10 cm deep plastic pots containing 1000 cm3 sterilized soil. Seedlings were thinned to one per pot. At the 2-3 leaf stage 10 pots were infested with 1500 M. hapla J2 per seedling, using a sterilized micropipette. Plants were maintained at 20-25°C in a greenhouse. Control plants received sterile water, and the pathogenicity test was repeated three times. After 30 days, plants were removed from pots and soil gently removed from the roots. A large number of galls (95.6 ± 2.5) and egg masses (33.5 ± 0.5) were found on each root system. Yunmuxiang was considered a good host for M. hapla in Lijiang. M. hapla is a major plant parasitic nematode with a wide geographic distribution and range of host plants and causes severe yield losses (Azevedo de Oliveira et al. 2018). Through investigation, this is the first report worldwide of M. hapla infecting Aucklandia lappa.

13.
Am J Emerg Med ; 43: 97-102, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33550105

RESUMO

BACKGROUND: The association between body mass index (BMI) and all-cause mortality of patients with Cardiogenic Shock (CS) is still controversial. The objective of this analysis is to summarize the available evidence of this association and perform meta-analysis using adjusted estimates. METHODS: PubMed, Embase and Cochrane databases were systematically searched for eligible studies up to July 2020. Studies were considered eligible if they described the association between BMI and all-cause mortality of patients with CS, and those reporting adjusted estimates were included in the meta-analysis. RESULTS: Three studies were identified and included total 345,281 participants. The pooled hazard ratio of all-cause mortality was 0.88(95% confidence interval (CI): 0.71-1.08, P = 0.23) when compared obesity with non-obese. In subgroup analysis, A subgroup analysis based on geographic region showed that obese patients had lower mortality compared with non-obese patients (OR = 0.71,95% CI 0.65-0.77, P < 0.00001) in USA, developed country and the retrospective study. Heterogeneity was not explained in pre-specified subgroups analysis. CONCLUSION: Obesity was associated with increased adjusted all-cause mortality of patients with Cardiogenic Shock when compared to non-obese. Unexplained heterogeneity and suboptimal quality of studies limit the strength of the results. This seemingly paradoxical finding needs to be confirmed with further research.

14.
Cell Rep ; 34(7): 108713, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33596428

RESUMO

AMP-activated protein kinase (AMPK) is an energy sensor that plays roles in multiple biological processes beyond metabolism. Several studies have suggested that AMPK is involved in the DNA damage response (DDR), but the mechanisms remain unclear. Herein, we demonstrate that AMPK promotes classic non-homologous end joining (c-NHEJ) in double-strand break (DSB) repair through recruiting a key chromatin-based mediator named p53-binding protein 1 (53BP1), which facilitates the end joining of distal DNA ends during DDR. We find that the interaction of AMPK and 53BP1 spatially occurs under DSB stress. In the context of DSBs, AMPK directly phosphorylates 53BP1 at Ser1317 and promotes 53BP1 recruitment during DDR for an efficient c-NHEJ, thus maintaining genomic stability and diversity of the immune repertoire. Taken together, our study demonstrates that AMPK is a regulator of 53BP1 and controls c-NHEJ choice by phospho-regulation.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33607295

RESUMO

AMP-activated protein kinase (AMPK) is a conservative energy sensor that plays roles in diverse biologic processes via direct phosphorylation on various substrates. Emerging studies have demonstrated the regulatory roles of AMPK in DNA repair, but the underlying mechanisms remain to be fully understood. Herein, using mass spectrometry-based proteomic technologies, we systematically investigate the regulatory network of AMPK in DNA damage response (DDR). Our system-wide phosphoproteome study uncovers a variety of newly-identified potential substrates involved in diverse biologic processes, whereas our system-wide histone modification analysis reveals a linkage between AMPK and histone acetylation. Together with these findings, we discover that AMPK promotes apoptosis by phosphorylating apoptosis-stimulating of p53 protein 2 (ASPP2) in irradiation (IR)-dependent way and regulates histone acetylation by phosphorylating histone deacetylase 9 (HDAC9) in IR-independent way. Besides, we reveal that disturbing the histone acetylation by the bromodomain BRD4 inhibitor JQ-1 enhances the sensitivity of AMPK-deficient cells to IR. Therefore, our studies provided a source to study the phosphorylation and histone acetylation underlying the regulatory network of AMPK, which could be beneficial to understand the exact role of AMPK in DDR.

16.
Virol Sin ; 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33534086

RESUMO

Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus, which causes the most commonly diagnosed viral encephalitis named Japanese encephalitis (JE) in the world with an unclear pathogenesis. Axl, a receptor tyrosine kinase from TAM family, plays crucial role in many inflammatory diseases. We have previously discovered that Axl deficiency resulted in more severe body weight loss in mice during JEV infection, which we speculate is due to the anti-inflammatory effect of Axl during JE. Currently, the role of Axl in regulating the neuroinflammation and brain damage during JE has not been investigated yet. In this study, by using Axl deficient and heterozygous control mice, we discovered that Axl deficient mice displayed accelerated JE progression and exacerbated brain damage characterized by increased neural cell death, extended infiltration of inflammatory cells, and enhanced production of pro-inflammatory cytokines, in comparison to control mice. Additionally, consistent with our previous report, Axl deficiency had no impact on the infection and target cell tropism of JEV in brain. Taken together, our results suggest that Axl plays an anti-inflammatory and neuroprotective role during the pathogenesis of JE.

17.
Biosci Trends ; 15(1): 61-63, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33504739

RESUMO

With the implementation of the two-child policy in China, an increased number of women of advanced maternal age (AMA) have been giving birth. Formulating evidence-based guidance for the clinical management of this population is crucial. This retrospective study aimed to explore factors influencing the mode of delivery in women of AMA. Data on 350 women of AMA who delivered at Shanghai Putuo Maternity & Infant Health Hospital from January to June of 2016 were collected. Results indicated that most (114/134, 85%) of the multiparae chose delivery via cesarean section (CS) because of uterine scarring. There were significant differences in the body mass index (BMI) before pregnancy, BMI at delivery, gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), and placenta previa between the CS and vaginal delivery groups (P < 0.05 for all). The current results suggest that vaginal delivery is recommended for the first delivery whenever reasonable. Moreover, management of metabolic disorders during pregnancy is essential to effectively reduce the rate of CS among women of AMA.

18.
BMC Infect Dis ; 21(1): 57, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33435865

RESUMO

BACKGROUND: In December 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, Hubei, China. Moreover, it has become a global pandemic. This is of great value in describing the clinical symptoms of COVID-19 patients in detail and looking for markers which are significant to predict the prognosis of COVID-19 patients. METHODS: In this multicenter, retrospective study, 476 patients with COVID-19 were enrolled from a consecutive series. After screening, a total of 395 patients were included in this study. All-cause death was the primary endpoint. All patients were followed up from admission till discharge or death. RESULTS: The main symptoms observed in the study included fever on admission, cough, fatigue, and shortness of breath. The most common comorbidities were hypertension and diabetes mellitus. Patients with lower CD4+T cell level were older and more often male compared to those with higher CD4+T cell level. Reduced CD8+T cell level was an indicator of the severity of COVID-19. Both decreased CD4+T [HR:13.659; 95%CI: 3.235-57.671] and CD8+T [HR: 10.883; 95%CI: 3.277-36.145] cell levels were associated with in-hospital death in COVID-19 patients, but only the decrease of CD4+T cell level was an independent predictor of in-hospital death in COVID-19 patients. CONCLUSIONS: Reductions in lymphocytes and lymphocyte subsets were common in COVID-19 patients, especially in severe cases of COVID-19. It was the CD8+T cell level, not the CD4+T cell level, that reflected the severity of the patient's disease. Only reduced CD4+T cell level was independently associated with increased in-hospital death in COVID-19 patients. TRIAL REGISTRATION: Prognostic Factors of Patients With COVID-19, NCT04292964 . Registered 03 March 2020. Retrospectively registered.


Assuntos
Linfócitos T CD4-Positivos/citologia , /imunologia , Adulto , Idoso , Linfócitos T CD8-Positivos/citologia , /mortalidade , Comorbidade , Feminino , Seguimentos , Hospitalização , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Alta do Paciente , Prognóstico , Estudos Retrospectivos , /genética
19.
Food Res Int ; 139: 109808, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33509451

RESUMO

Fermentation has been considered as effective tools to promote the functional properties of cereals. In this paper, barley flour was fermented with Lactobacillus plantarum dy-1 (L. plantarum dy-1) and the main components in the fermented barley aqueous extracts were identified using by ultra-high performance liquid chromatography tandem with high resolution mass spectrometry (UPLC-HRMS), and investigated by metabolomics strategy involved on chemometrics. The barley extracts were prepared at the fermentation time of 0, 4, 8, 12, 16, 20, 24, 28 h, respectively and a total of 124 compounds were detected in the samples. Principal component analysis (PCA) was performed and the results indicated that the fermentation process became to slow down from 16 h until terminated. During fermentation, saccharides, amino acids, nucleosides, and some organic acids decreased, while lipids and bioactive molecules in barley were released and metabolites were accumulated by L. plantarum dy-1. Meanwhile, partial least squares discrimination analysis (PLS-DA) was performed for revealing the characteristic components in fermented barley aqueous extracts, including some functional molecules such as indole-3-lactic acid, phenyllactic acid, homovanillic acid and cafestol, etc., which provided the roles of them and the basis for further investigation on the functional bioactivities and application.

20.
Ann Clin Transl Neurol ; 8(3): 558-570, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33465303

RESUMO

OBJECTIVE: Rasmussen's encephalitis (RE) is a rare and severe progressive epileptic syndrome with unknown etiology. Infection by viruses such as human cytomegalovirus (HCMV) has been hypothesized to be a potential trigger for RE. Interferon-induced transmembrane protein-3 (IFITM3) single-nucleotide polymorphism (SNP) rs12252 is associated with the severity of viral infection disease. This study aimed to address the possibility that HCMV infection and IFITM3 rs12252 might be associated with RE disease progression. METHODS: The expression of HCMV and IFITM3 was detected with immunohistochemical staining, in situ hybridization and immunofluorescence double staining. The genotype of IFITM3 rs12252 was detected using the Sanger sequencing method. A genetic association analysis was carried out for this SNP and HCMV antigen expression. The relationship between this SNP and the clinical characteristics of these patients was further analyzed. In in vitro study, HCMV replication in SH-SY5Y cells with overexpressed IFITM3 variant was detected by immunofluorescence and real-time RT-PCR. RESULTS: Elevated expression of HCMV and IFITM3 was observed in the brain tissue of RE patients. Moreover, the IFITM3 polymorphism rs12252-C was found to associate with HCMV high detection and rapid disease progression in RE patients with the IFITM3 rs12252-CC genotype. In vitro study showed the overexpressed IFITM3 variant was associated with HCMV high infection level. CONCLUSION: These results suggest that the IFITM3 rs12252-C is associated with the disease progression of RE patients via facilitating persistent HCMV infection in brain tissue and provides new insight into understanding the pathogenesis of RE.

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