Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.588
Filtrar
1.
Eur J Neurol ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33065758

RESUMO

BACKGROUND: Autoantibodies targeting the GluN1(NR1) subunit of the anti-N-methyl-D-aspartate receptor (NMDAR) cause encephalitis. Although it has been shown that anti-NMDAR encephalitis is associated with human leukocyte antigen (HLA) loci, susceptibility genes for the disease outside the HLA loci remain unidentified. In this study, we aimed to explore the association of anti-NMDAR encephalitis with non-HLA genes. METHODS: Two Chinese anti-NMDAR encephalitis cohorts from Han populations were recruited in this study. The North Chinese case-control set consisted 98 patients and 460 controls while the South Chinese case-control set included 78 patients and 541 controls. All subjects were genotyped for 28 single nucleotide polymorphisms which are associated with autoimmune disorders or infectious diseases. RESULTS: With two independent case-control sets, we identified significant association of anti-NMDAR encephalitis with IRF7 rs1131665 (OR=3.34, 95% CI: 1.99-5.63, P<0.000001, Padjusted =0.00004), BANK1 rs4522865 (OR=1.44, 95% CI: 1.15-1.82, P=0.0017, Padjusted =0.0149), and TBX21 rs17244587 (OR=2.03, 95% CI: 1.35-3.05, P=0.00051, Padjusted =0.0066). Furthermore, analysis of the three polymorphisms with clinical features of the disease revealed that the IRF7 rs1131665 is associated with the status of tumour. CONCLUSION: The current study has for the first time identified non-HLA susceptibility genes for anti-NMDAR encephalitis. The association of IRF7, BANK1 and TBX21 with anti-NMDAR encephalitis suggests that B cells activation, Th1 responses, virus infection and type I IFN signaling pathway are involved in the pathogenesis of the diseases.

2.
Apoptosis ; 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33068199

RESUMO

Blockade of hypoxia-caused nonmyocytes apoptosis helps improve survival and mitigate ventricular remodeling and dysfunction during the chronic stage of myocardial infarction. But tools affecting nonmyocyte apoptosis are very rare. Sphingosylphosphorylcholine (SPC), a naturally occurring bioactive sphingolipid in plasma, was proved to protect cardiomyocyte against apoptosis in an ischemic model in our previous study. Here, we showed that SPC also inhibited hypoxia-induced apoptosis in myofibroblasts, an important type of nonmyocytes in the heart. Calmodulin (CaM) is an identified receptor of SPC. We clarified that SPC inhibited myofibroblast apoptosis through CaM as evidenced by decreased cleaved caspase 3, PARP1 and condensed nucleus. Furthermore, the employment of inhibitor and agonist of p38 and STAT3 suggests that SPC inhibits myofibroblast apoptosis by regulating the phosphorylation of p38 and STAT3, and they act as downstream of CaM. The present work may provide new evidence on the regulation of myofibroblasts apoptosis by SPC and a novel target for heart remodeling after hypoxia.

3.
J Neural Eng ; 17(5): 056017, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33055386

RESUMO

OBJECTIVE: Automatic sleep staging models suffer from an inherent class imbalance problem (CIP), which hinders the classifiers from achieving a better performance. To address this issue, we systematically studied sleep electroencephalogram data augmentation (DA) approaches. Furthermore, we modified and transferred novel DA approaches from related research fields, yielding new efficient ways to enhance sleep datasets. APPROACH: This study covers five DA methods, including repeating minority classes, morphological change, signal segmentation and recombination, dataset-to-dataset transfer, as well as generative adversarial network (GAN). We evaluated these mentioned DA methods by a sleep staging model on two datasets, the Montreal archive of sleep studies (MASS) and Sleep-EDF. We used a classification model with a typical convolutional neural network architecture to evaluate the effectiveness of the mentioned DA approaches. We also conducted a comprehensive analysis of these methods. MAIN RESULTS: The classification results showed that DA methods, especially DA by GAN, significantly improved the total classification performance in comparison with the baseline. The improvement of accuracy, F1 score and Cohen Kappa coefficient range from 0.90% to 3.79%, 0.73% to 3.48%, 2.61% to 5.43% on MASS and 1.36% to 4.79%, 1.47% to 4.23%, 2.22% to 4.04% on Sleep-EDF, respectively. DA methods improved the classification performance in most cases, whereas the performance of class N1 showed a subtle degradation in the F1 scores. SIGNIFICANCE: Overall, our study proved that DA approaches are efficient in alleviating CIP lying in sleep staging tasks. Meanwhile, this study provided avenues for further improving the sleep staging accuracy using DA methods.

4.
J Food Sci ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33063315

RESUMO

To identify the key aroma compounds in Yunnan goat milk cake, seven varieties of milk cake samples were subjected to sensory analysis and gas chromatography-mass spectrometry (GC-MS), gas chromatography-olfactometry (GC-O), aroma recombination, omission, and addition tests. The GC-MS results revealed 53 compounds with aroma characteristics in all the samples. A further comparison of odor activity values and aroma intensities (AI) revealed 25 of these compounds as the initial key aroma compounds. The contributions of these key aroma compounds to the sensory attributes were determined using a partial least squares regression. Of these compounds, 2-heptanone and 2-nonanone were closely related to the "milky" and "cheesy" attributes and were highly abundant in the samples from Kunming. Fatty acids, including butanoic acid, hexanoic acid, octanoic acid, and decanoic acid, were the most abundant compounds detected in the milk cakes. These fatty acids were closely related to the "rancid" and "animalic (goat)" attributes and were largely detected in the samples from Dali Dengchuan and Dali Xiaguan. Sensory-directed aroma recombination, omission, and addition tests further validated the important contributions of ethyl butyrate, benzaldehyde, 3-methyl-1-butanol, 2-heptanone, hexanoic acid, and octanoic acid to the overall sensory properties. Moreover, ethyl butyrate, benzaldehyde, and 2-heptanone, when added, had evident inhibitory or masking effects on the AI of "sour," "rancid," and "animalic (goat)" attributes. PRACTICAL APPLICATION: Goat milk cake is a popular acid-curd cheese in Yunnan, China, however, our limited knowledge to its key aroma compounds restricts its development and industrial production. In this study, a sensory-directed flavor analysis was used to characterized the key aroma compounds of Yunnan goat milk cake, which will help to enhance our understanding on the flavor profile of Yunnan goat milk cake and provide a reference for optimizing the flavor feature and organoleptic quality of this fresh goat cheese.

5.
Front Immunol ; 11: 1801, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013831

RESUMO

A recently developed humanized mouse has been used to assess the immune response evoked against the isolated attenuated C9 parasite clone (C9-M; carrying a single insertion disrupting the open reading frame (ORF) of PF3D7_1305500) of Plasmodium falciparum. Significant human RBC engraftment was achieved by ameliorating the residual non-adaptive immune response using clodronate-loaded liposome treatment. Controlled reactive professional phagocytic leukocytes in immunodeficient mice allowed for sizeable human blood chimerism and injected huRBCs acted as bona fide host cells for P. falciparum. huRBC-reconstituted immunodeficient mice received infectious challenge with attenuated P. falciparum C9 parasite mutants (C9-M), complemented (C9-C), and wild type (NF54) progenitors to study the role of immune effectors in the clearance of the parasite from mouse circulation. C9-M and NF54 parasites grew and developed in the huRBC-reconstituted humanized NSG mice. Further, the presence of mutant parasites in deep-seated tissues suggests the escape of parasites from the host's immune responses and thus extended the survival of the parasite. Our results suggest an evasion mechanism that may have been employed by the parasite to survive the mouse's residual non-adaptive immune responses. Collectively, our data suggest that huRBCs reconstituted NSG mice infected with attenuated P. falciparum is a valuable tool to explore the role of C9 mutation in the growth and survival of parasite mutants and their response to the host's immune responses. This mouse might help in identifying novel chemotherapeutic targets to develop new anti-malarial drugs.

6.
J Am Chem Soc ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33021373

RESUMO

This work describes a strategy to produce circularly polarized thermally activated delayed fluorescence (CP-TADF). A set of two structurally similar organic emitters SFST and SFOT are constructed, whose spiro architectures containing asymmetric donors result in chirality. Upon grafting within the spiro frameworks, the donor and acceptor are fixed proximally in a face-to-face manner. This orientation allows intramolecular through-space charge transfer (TSCT) to occur in both emitters, leading to TADF properties. The donor units in SFST and SFOT have a sulfur and oxygen atom, respectively; such a subtle difference has great impacts on their photophysical, chiroptical, and electroluminescence (EL) properties. SFOT exhibits greatly enhanced EL performance in doped organic light-emitting diodes, with external quantum efficiency (EQE) up to 23.1%, owing to the concurrent manipulation of highly photoluminescent quantum efficiency (PLQY, ∼90%) and high exciton utilization. As a comparison, the relatively larger sulfur atom in SFST introduces heavy atom effects and leads to distortion of the molecular backbone that lengthens the donor-acceptor distance. SFST thus has lower PLQY and faster nonradiative decay rate. The collective consequence is that the EQE value of SFST, i.e., 12.5%, is much lower than that of SFOT. The chirality of these two spiro emitters results in circularly polarized luminescence. Because SFST has a more distorted molecular architecture than SFOT, the luminescence dissymmetry factor (|glum|) of circularly polarized luminescence of one enantiomer of the former, namely, either (S)-SFST or (R)-SFST, is almost twice that of (S)-SFOT/(R)-SFOT. Moreover, the CP organic light-emitting diodes (CP-OLEDs) show obvious circularly polarized electroluminescence (CPEL) signals with gEL of 1.30 × 10-3 and 1.0 × 10-3 for (S)-SFST and (S)-SFOT, respectively.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32998320

RESUMO

This study, using the method of economic quantitative analysis, studied the land use changes of Qilihai Wetland from 2008 to 2017, and the effects of these changes on the ES (ecosystem service) values of the wetland. This article benchmarked the 2030 Agenda for Sustainable Development, based on the systematic analysis and analysis of current ecological service function value evaluation methods. The research results show that the total values of the wetland ecosystem services in 2008, 2011, 2014, and 2017 were 317 million yuan, 299 million yuan, 283 million yuan, and 321 million yuan, respectively. In 2008 and 2011, the ES of the Wetland was mainly based on supply and support services, and in 2014 and 2017, it was mainly based on supply and regulation services. Changes in human utilization, natural conditions, and social economy will all lead to changes in the ES value of the whole Wetland. This research can enable decision makers to intuitively understand its ecological changes and plan the use of land and formulate ecological protection measures in a reasonable and effective manner. Finally, the article puts forward relevant suggestions for sustainable development based on the resource and environmental foundation and characteristics of Qilihai Wetland.

8.
Sci Adv ; 6(43)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33087363

RESUMO

Progranulin (PGRN) is a secreted pleiotropic glycoprotein associated with the development of common neurodegenerative diseases. Understanding the pathophysiological role of PGRN may help uncover biological underpinnings. We performed a genome-wide association study to determine the genetic regulators of cerebrospinal fluid (CSF) PGRN levels. Common variants in region of FAM171A2 were associated with lower CSF PGRN levels (rs708384, P = 3.95 × 10-12). This was replicated in another independent cohort. The rs708384 was associated with increased risk of Alzheimer's disease, Parkinson's disease, and frontotemporal dementia and could modify the expression of the FAM171A2 gene. FAM171A2 was considerably expressed in the vascular endothelium and microglia, which are rich in PGRN. The in vitro study further confirmed that the rs708384 mutation up-regulated the expression of FAM171A2, which caused a decrease in the PGRN level. Collectively, genetic, molecular, and bioinformatic findings suggested that FAM171A2 is a key player in regulating PGRN production.

9.
J Environ Manage ; 277: 111395, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33038671

RESUMO

The multi-sectoral metabolisms of substance and energy in rural areas are complex, whose optimization is the key to realize resource recycling and energy cascade utilization. Through Substance Flow Analysis (SFA), we establish a Multi-sectoral Metabolism Analysis Model specific to rural areas (MMAM-rural), and investigated the multi-sectoral metabolisms of Liujiadian Town in Beijing city. We simulate the water, energy and nutrients (carbon, nitrogen and phosphorus) metabolisms of a total of five sectors (water, waste management, livestock husbandry, forestry, and residential sectors), and identify the key metabolic flows significant for improving regional metabolism performance of Liujiadian Town. For further technical path optimization, we construct an index system made up of resource utilization efficiency, environmental burden of production and recycling efficiency, and adopt Scenario Analysis to evaluate the water-energy-nutrient metabolism performance under multiple technical scenarios different from disposals of agricultural waste, livestock and poultry manure, and domestic waste. Results show that, for agricultural wastes disposal, the combination scenario of edible fungi cultivation, anaerobic fermentation and aerobic composting is optimal. For livestock and poultry manure, all pig manure should be composted after anaerobic fermentation. For domestic wastes, food wastes require anaerobic fermentation and composting for optimization. Our study provides a model to evaluate metabolism performance of water-energy-nutrient nexus in rural areas, and raises solutions for optimization in the process of eco-town construction.

10.
Aging (Albany NY) ; 122020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33104518

RESUMO

Blood-based biomarkers are ideal candidates for dementia prediction. This systematic review and meta-analysis aimed to evaluate longitudinal relationships of blood hormones and hormone-binding proteins in hypothalamic-pituitary (HP) axes with dementia or cognitive decline. PubMed, MEDLINE, EMBASE, PsycINFO, and BIOSIS were systematically searched from 1919 to June 2020. Fifteen types of hormones and four types of hormone-binding proteins were measured in 48 prospective studies. Increased risk of dementia or cognitive decline could be predicted by elevated blood concentrations of free-thyroxine (free-T4, RR = 1.06, p = 0.001) and sex hormone-binding globulin (SHBG, RR = 1.10, p = 0.025). Lower thyroid-stimulating hormone (TSH) levels within (RR = 1.28, p < 0.001) and below (RR = 1.27, p = 0.004) the normal range were both risky. Current evidence suggests the alterations of multiple blood molecules in HP axes, especially TSH, free-T4, and SHBG precede the incidence of dementia or cognitive decline. The underpinning etiology remains to be elucidated in the future.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33081253

RESUMO

Overuse of antibiotics has caused a series of global problems, especially in the underdeveloped western regions where healthcare systems are fragile. We used antibiotic procurement data of all healthcare institutions to analyze the total amount, patterns and trends of antibiotic use in Shaanxi Province, western China between 2015 and 2018. Antibiotic utilization was quantified using the standard Anatomical Therapeutic Chemical (ATC)/Defined daily dose (DDD) methodology. The World Health Organization's "Access, Watch and Reserve" (AWaRe) classification and European Surveillance of Antimicrobial Consumption (ESAC) drug-specific quality indicators were also adopted to evaluate the appropriateness and quality of antibiotic utilization. Overall, antibiotic consumption decreased from 11.20 DID in 2015 to 10.13 DID (DDDs per 1000 inhabitants per day) in 2016, then increased to 12.99 DID in 2018. The top three antibiotic categories consumed in 2018 were J01C (penicillins) 33.58%, J01D (cephalosporins) 29.76%, and J01F (macrolides) 19.14%. Parenteral antibiotics accounted for 27.41% of the total consumption. The largest proportion of antibiotic use was observed in primary healthcare institutions in rural areas, which accounts for 51.67% of total use. Consumption of the Access group, the Watch group, the Reserve group of antibiotics was 40.31%, 42.28% and 0.11%, respectively. Concurrently, the consumption of J01D and the percentage of J01 (DD + DE) (third and fourth generation cephalosporins) were at a poor level according to the evaluation of ESAC quality indicators. The total antibiotic consumption in Shaanxi Province had been on an upward trend, and the patterns of antibiotic use were not justified enough to conclude that it was rational. This is partly because there was high preference for the third and fourth generation cephalosporins and for the Watch group antibiotics.

12.
J Org Chem ; 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33085889

RESUMO

Although the best-known examples of synthetic polymers are derived from carbon-based monomers, there exists another large and growing family of macromolecules based on the chemistry of phosphorus. These are the poly(organophosphazenes): polymers with a backbone of alternating phosphorus and nitrogen atoms and with two organic side groups attached to each phosphorus. The methods of synthesis of these polymers allow access to property combinations not found in all-organic counterparts, and this provides pathways to new materials that are important in biomedical research, energy generation and storage, aerospace materials, and numerous other specialized applications.

13.
Clin Infect Dis ; 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33086379

RESUMO

Intra-host analysis of SARS-CoV-2 genomic sequences identified two viral haplotypes that comprised of three genetically linked mutations from the respiratory and intestinal tracts of a patient with COVID-19. Spatiotemporal data suggest that this patient initially had dual-infection of two SARS-CoV-2 variants, which subsequently re-distributed into the two systems.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33086429

RESUMO

Polypill is a fixed-dose combination of medications with proven benefits for the prevention of cardiovascular disease (CVD). Its role in CVD prevention has been extensively debated since the inception of this concept in 2003. There are two major kinds of polypills in clinical studies. The first is polypill that combines multiple low-dose medications for controlling only one CVD risk factor (such as high blood pressure or high serum cholesterol). These "single-purpose" polypills were mostly developed from original producers and have higher cost. The polypill that combines 3-4 pharmaceutical components, each with potential to reduce one major cardiovascular risk factors is "multi-purpose" or "cardiovascular" polypill. Using data from various clinical trials and from meta-analysis, Wald and Law claimed that this "cardiovascular" polypill when administered to every individual older than 55 years could reduce the incidence of CVD by more than 80%. Several short and intermediate to long-term studies with different cardiovascular polypills in phase II and III trials showed that they could provide better adherence, equivalent, or better risk factor control and quality of life among users as compared to usual care. One recently published randomized controlled clinical trial demonstrated the effectiveness and safety of a four-component polypill for both primary and secondary CVD prevention with acceptable number needed to treat (NNT) to prevent one major cardiovascular event. Considering the slow achievement of CVD prevention in many poor- and middle-income Asian countries and also the need to further improve compliance of antihypertensive and lipid lowering medications in many high-income Asian countries, the concept of "cardiovascular polypill" could be very useful. With further support from ongoing polypill cardiovascular outcome trials, polypill could be the foundation of the population-based strategies for CVD prevention.

15.
Occup Environ Med ; 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097674

RESUMO

OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) is an increasing public health concern worldwide. The objective of this study was to calculate a summary odds ratio (OR) of livestock-associated MRSA colonisation and infection in humans, and to determine specific risk factors in livestock production contributing to MRSA colonisation. METHODS: We screened PubMed and Embase for studies published from 2005 to 2019 inclusive, reporting livestock-associated (LA)-MRSA colonisation and infection among livestock workers/veterinarians, their families, and community members not regularly exposed to livestock. The primary outcome of interest was the OR of LA-MRSA colonisation comparing exposed and control groups. Quality was assessed according to the Newcastle-Ottawa quality assessment scale. A meta-analysis using a random-effects model was conducted to calculate a pooled OR. The heterogeneity in the meta-analysis was assessed using the I² method, and publication bias was evaluated using funnel plots. RESULTS: A total of 3490 studies were identified by the search, with 37 studies including 53 matched exposed-control groups and 14 038 participants eligible for the meta-analysis. The pooled OR for LA-MRSA among livestock workers and veterinarians is 9.80 (95% CI 6.89 to 13.95; p=0.000; I2 =73.4), with no significant publication bias (Egger's p=0.66). The OR for swine workers was highest at 15.41 (95% CI 9.24 to 25.69), followed by cattle workers (11.62, 95% CI 4.60 to 29.36), veterinarians (7.63, 95% CI 3.10 to 18.74), horse workers (7.45, 95% CI 2.39 to 23.25), livestock workers (5.86, 95% CI 1.14 to 30.16), poultry workers (5.70, 95% CI 1.70 19.11), and industrial slaughterhouse workers (4.69, 95% CI 1.10 to 20.0). CONCLUSIONS: Livestock workers, particularly swine farmers, are at significantly higher risk for LA-MRSA colonisation and subsequent infection. These results support the need for preventive practices to reduce LA-MRSA risk among those who handle and treat livestock. TRIAL REGISTRATION NUMBER: CRD42019120403.

16.
Chem Biodivers ; 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33098214

RESUMO

Chemical investigation of the secondary metabolites of the whole plant of bryophyte Hypnum plumaeforme Wilson led to the isolation of a new pimarane-type diterpenoid (1), along with seventeen known compounds (2-18). Their chemical structures were elucidated based on massive spectroscopic data. The allelopathic and antifungal properties were evaluated. Among them, compounds 1 to 4 showed significant allelopathic activity against Samolus parviflorus Raf., and Lactuca sativa L. var. angustana Irish , as well as selected antifungal property against crop pathogenic fungi strains. On the other hand, compound 8 exhibited strong promoting activity on the growth of L. sativa L. var. angustana Irish. The present investigation provided new insights for developing of H. plumaeforme for further application as a potential agricultural tool.

17.
Cancer Sci ; 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33007133

RESUMO

Stromal invasion is considered an important prognostic factor in patients with lung adenocarcinoma. The mechanisms underlying the formation of tumor stroma and stromal invasion have been studied in the lung; however, they are still unclear. CD109 is a glycosylphosphatidylinositol-anchored glycoprotein highly expressed in several types of human malignant tumors including lung cancers. In this study, we investigated the in vivo functions of CD109 protein in malignant lung tumors. Initially, we identified an association between higher expression of CD109 protein in human lung adenocarcinoma and a significantly worse prognosis, according to immunohistochemical analysis. We also showed that CD109 deficiency significantly reduced the area of stromal invasive lesions in a genetically engineered CD109-deficient lung adenocarcinoma mouse model, which correlated with the results observed in human lung adenocarcinoma. Furthermore, we identified latent TGF-ß binding protein-1 (LTBP1) as a CD109-interacting protein using mass spectrometry and confirmed their interaction by co-immunoprecipitation. Importantly, increased CD109 expression enhanced stromal TGF-ß activation in the presence of LTBP1. Therefore, these data suggest the significance of the regulation of TGF-ß signaling through CD109 and LTBP1 interaction in tumor stroma and also reveal the importance of CD109 expression levels in promoting lung cancer cell proliferation, migration, and invasion, and thus predicting the outcome of patients suffering from lung adenocarcinoma. Therefore, CD109 protein could be a potential therapeutic target for this disease.

18.
Bioresour Technol ; 318: 124202, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33035945

RESUMO

Pilot-scale saturated vertical flow constructed wetlands (VF-CWs) were established to identify whether T. tubifex has the similar performance in saturated VF-CWs to that in surface flow CWs in improving pollutant removal efficiency (RE). The saturated VF-CWs with T. tubifex achieved REs of 67.3% total nitrogen (TN) and 39.8% chemical oxygen demand (COD), which were significantly higher than treatments without T. tubifex (42.2% TN and 31.4% COD). There existed significant interactions between macrophytes and T. tubifex. T. tubifex greatly improved the dissolved oxygen by increasing the connectivity between layers, and enhanced dehydrogenase activity and fluorescein diacetate. Adding T. tubifex improved the bacterial diversity and relative abundance of both N-cycle bacteria and fermentation bacteria in the biofilms. The improvements of ammonia oxidation and anammox were the main pathways for the increased nitrogen removal by T. tubifex. Therefore, T. tubifex is a useful tool for improving pollutant REs in saturated VF-CWs.

19.
Stem Cell Res ; 49: 102027, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33059129

RESUMO

Parkinson's disease (PD) is the second most common neurodegenerative disease affecting millions of elder people due to the degeneration of dopamine neurons in the striatum and substantia nigra. The clinical manifestations of PD include tremor, rigidity, bradykinesia and postural instability. Studying PD is challenging due to two obstacles: 1) disease models such as primary neurons or animal models usually couldn't recapitulate the disease phenotype, and 2) accessibility of human autopsied brain samples is very limited if not impossible. Induced pluripotent stem cells (iPSCs)-derived neuronal cells from patients emerge as an ideal in vitro model for disease modeling and drug development. Here we describe a cell density-dependent method for preparing functional hiPSC-derived dopamine neurons (iDAs) with ~90% purity (TH-positive cells). iDAs derived from PD patient exhibit the disease-related phenotypes, for example, slowed morphogenesis, reduced dopamine release, impaired mitochondrial function, and α-synuclein accumulation as early as 35 days after induction. Furthermore, we found that the effects of cell density are different between iDA development stages, whereas high cell density increases stress for early neural progenitor cells (NPCs), but are neural-protective for mature iDAs, high density also favors morphogenesis. Hence, using stage and density-dependent strategies we can obtain high quality iDAs, which are critical for disease modeling, drug development and cell replacement therapy.

20.
Virol J ; 17(1): 155, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33076966

RESUMO

BACKGROUND: This study aims to screen the male human papillomavirus (HPV) infection status and genotyping in Qingcheng District, Qingyuan City, Guangdong Province, China to provide a reference basis for formulating prevention strategies for HPV infection. METHODS: The present study collected urethral epithelium or scraped penile epidermis from high-risk male patients in Qingyuan People's Hospital during the last five years, extracted DNA fragments using the boiling method, and detected 23 types of HPV genotypes by PCR-reverse blot hybridization. RESULTS: The positive detection rate was 54.31% of 1044 males with high risk of HPV (567/1044). Among these males, the positive detection rate of HPV was the highest in patients initially diagnosed with warts, and the rate was 66.47%. Five main HPV types are identified as follows: HPV6 18.87% (197/1044), HPV11 10.25% (107/1044), HPV52 8.81% (92/1044), HPV16 6.90% (72/1044), and HPV51 5.08% (53/1044). Among these HPV-infected patients, single infection mainly by low-risk HPV6 and HPV11 accounted for 56.61% (321/567); high- and low-risk combined HPV co-infections accounted for 29.10% (165/567). The HPV infected patients was mainly between 21 and 40 years old, and the HPV infection rate was higher with increased age. CONCLUSIONS: The HPV infection rate in the Qingyuan area is higher than in other areas and the main infection is single infection. Furthermore, HPV52, HPV16, and HPV51 are the main high-risk infection types, while HPV6 and HPV11 are the main low-risk infection types.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA