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1.
Elife ; 92020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33044170

RESUMO

This study examined records of 2,566 consecutive COVID-19 patients at five Massachusetts hospitals and sought to predict level-of-care requirements based on clinical and laboratory data. Several classification methods were applied and compared against standard pneumonia severity scores. The need for hospitalization, ICU care, and mechanical ventilation were predicted with a validation accuracy of 88%, 87%, and 86%, respectively.ICU care and ventilation. When predictions are limited to patients with more complex disease, the accuracy of the ICU and ventilation prediction models achieved accuracy of 83% and 82%, respectively. Vital signs, age, BMI, dyspnea, and comorbidities were the most important predictors of hospitalization. Opacities on chest imaging, age, admission vital signs and symptoms, male gender, admission laboratory results, and diabetes were the most important risk factors for ICU admission and mechanical ventilation. The factors identified collectively form a signature of the novel COVID-19 disease.

2.
Microb Pathog ; : 104526, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33010364

RESUMO

Cryptosporidium spp. and Enterocytozoon bieneusi are two important zoonotic pathogens that can cause diarrhea and other gastrointestinal illnesses in humans and animals. However, the prevalence and genotype of the parasites in Longjiang Wagyu cattle in Heilongjiang Province, Northeast China have not been reported. In the present study, a total of 423 fecal samples of Longjiang Wagyu cattle collected from different farms in Heilongjiang Province, Northeast China, were examined for Cryptosporidium spp. and E. bieneusi using nested PCR. The overall infection rates for Cryptosporidium spp. and E. bieneusi were 6.38% (n = 27) and 7.09% (n = 30), respectively. The prevalence in different age groups ranged from 3.80% (95% confidence interval (CI) 1.01-6.59) to 8.36% (95% CI 4.83-11.90) for Cryptosporidium spp. and 5.97% (95% CI 2.52-9.43) to 7.94% (95% CI 4.49-11.40) for E. bieneusi. By analyzing the DNA sequences of the small subunit (SSU) rRNA gene, two Cryptosporidium species were detected in this study, namely C. parvum (n = 25) and C. ryanae (n = 2). The IIdA20G1 subtype was further identified by using the 60-kDa glycoprotein (gp60) gene of C. parvum. E. bieneusi was identified using three known sequences through the analysis of internal transcribed spacer (ITS) sequences: J (n = 23), I (n = 5), and BEB4 (n = 2), and all belonged to group 2. The results indicated that some of the Cryptosporidium species and E. bieneusi genotypes identified in Longjiang Wagyu cattle in the study areas might have zoonotic potential.

3.
Brief Bioinform ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33048110

RESUMO

MOTIVATION: The functional changes of the genes, RNAs and proteins will eventually be reflected in the metabolic level. Increasing number of researchers have researched mechanism, biomarkers and targeted drugs by metabolites. However, compared with our knowledge about genes, RNAs, and proteins, we still know few about diseases-related metabolites. All the few existed methods for identifying diseases-related metabolites ignore the chemical structure of metabolites, fail to recognize the association pattern between metabolites and diseases, and fail to apply to isolated diseases and metabolites. RESULTS: In this study, we present a graph deep learning based method, named Deep-DRM, for identifying diseases-related metabolites. First, chemical structures of metabolites were used to calculate similarities of metabolites. The similarities of diseases were obtained based on their functional gene network and semantic associations. Therefore, both metabolites and diseases network could be built. Next, Graph Convolutional Network (GCN) was applied to encode the features of metabolites and diseases, respectively. Then, the dimension of these features was reduced by Principal components analysis (PCA) with retainment 99% information. Finally, Deep neural network was built for identifying true metabolite-disease pairs (MDPs) based on these features. The 10-cross validations on three testing setups showed outstanding AUC (0.952) and AUPR (0.939) of Deep-DRM compared with previous methods and similar approaches. Ten of top 15 predicted associations between diseases and metabolites got support by other studies, which suggests that Deep-DRM is an efficient method to identify MDPs. CONTACT: liangcheng@hrbmu.edu.cn. AVAILABILITY AND IMPLEMENTATION: https://github.com/zty2009/GPDNN-for-Identify-ing-Disease-related-Metabolites.

4.
Aging (Albany NY) ; 12(19): 19083-19094, 2020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33041262

RESUMO

BACKGROUND: Apathy is common in Alzheimer's disease (AD) patients. However, its relation with other clinical symptoms in AD and brain structural changes in magnetic resonance imaging is unclear. RESULTS: Compared with AD with no apathy group, cognitive function and activities of daily living were significantly impaired and neuropsychiatric symptoms were obviously presented in AD with apathy group (P<0.05). The frequency of Apolipoprotein E genotypes was not significantly different (P>0.05). Correlation analyses and multiple linear analyses revealed that thickness of left temporal pole and volume of posterior corpus callosum were significantly and negatively correlated with Modified Apathy Estimation Scale score in AD patients (P<0.05). CONCLUSIONS: Apathy with AD is positively correlated with cognitive impairment, neuropsychiatric symptoms and poor activities of daily living. Atrophy of left temporal pole and posterior corpus callosum presented by MRI is positively related with apathy of AD. METHODS: In this study, 137 AD patients were recruited and divided into AD with apathy group and AD with no apathy group according to Modified Apathy Estimation Scale score. We evaluated patients' cognitive function, neuropsychiatric symptoms and activities of daily living, detected the frequency of Apolipoprotein E genotypes and measured cortical thickness and volume by magnetic resonance imaging (MRI).

5.
Biochim Biophys Acta Mol Basis Dis ; : 165991, 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33080346

RESUMO

Our previous study demonstrated that IL-10 secreting B (B10) cells alleviate inflammation and bone loss in experimental periodontitis. The purpose of this study is to determine whether antigen-specificity is required for the local infiltration of B10 cells. Experimental periodontitis was induced in the recipient mice by placement of silk ligature with or without the presence of live Porphyromonas gingivalis (P. gingivalis). Donor mice were pre-immunized by intraperitoneal (IP) injection of formalin-fixed P. gingivalis, or PBS as non-immunized control. Spleen B cells were purified and treated with LPS and CpG for 48 hours to expand the B10 population in vitro. Fluorescence-labeled B10 cells were transferred into the recipient mice by tail vein injection and were tracked on day 0, 3, 5 and 10 using IVIS Spectrum in vivo imaging system. The number of B10 cells and P. gingivalis-binding B cells were significantly increased after in vitro treatment of LPS and CpG. On day 5, the fluorescence intensity in gingival tissues was the highest in mice transferred with B10 cells from pre-immunized donor mice. Gingival expression of IL-6, TNF-α, RANKL/OPG ratio and periodontal bone loss in recipient mice were significantly reduced, and the expression of IL-10 and the number of CD19+ B cells were significantly increased after pre-immunized B10 cell transfer in the presence of antigen, compared to those with non-immunized B10 cell transfer or no antigen presence. This study suggests that antigen specificity dictate the local infiltration of B10 cells into periodontal tissue and these antigen-specific B10 cells promote anti-inflammatory responses.

6.
Hortic Res ; 7: 158, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33082965

RESUMO

Chinese pepper, mainly including Zanthoxylum bungeanum and Zanthoxylum armatum, is an economically important crop popular in Asian countries due to its unique taste characteristics and potential medical uses. Numerous cultivars of Chinese pepper have been developed in China through long-term domestication. To better understand the population structure, demographic history, and speciation of Chinese pepper, we performed a comprehensive analysis at a genome-wide level by analyzing 38,395 genomic SNPs that were identified in 112 cultivated and wild accessions using a high-throughput genome-wide genotyping-by-sequencing (GBS) approach. Our analysis provides genetic evidence of multiple splitting events occurring between and within species, resulting in at least four clades in Z. bungeanum and two clades in Z. armatum. Despite no evidence of recent admixture between species, we detected substantial gene flow within species. Estimates of demographic dynamics and species distribution modeling suggest that climatic oscillations during the Pleistocene (including the Penultimate Glaciation and the Last Glacial Maximum) and recent domestication events together shaped the demography and evolution of Chinese pepper. Our analyses also suggest that southeastern Gansu province is the most likely origin of Z. bungeanum in China. These findings provide comprehensive insights into genetic diversity, population structure, demography, and adaptation in Zanthoxylum.

7.
Addict Biol ; : e12974, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33084195

RESUMO

Obese individuals exhibit brain functional abnormalities in multiple regions implicated in reward/motivation, emotion/memory, homeostatic regulation, and executive control when exposed to food cues and during rest. However, it remains unclear whether abnormal brain responses to food cues might account for or relate to their abnormal activity in resting state. This information would be useful for understanding the neural mechanisms behind hyperactive responses to food cues, a critical marker of obesity. Resting-state functional magnetic resonance imaging (RS-fMRI) and a cue-reactivity fMRI task with high- (HiCal) and low-caloric (LoCal) food cues were employed to investigate brain baseline activity and food cue-induced activation differences in 44 obese participants (OB), in 37 overweight participants (OW), and in 37 normal weight (NW) controls. One-way analyses of variance showed there was a group difference in the left hippocampus/amygdala activity during resting state and during food-cue stimulation (pFWE < 0.05); post-hoc tests showed the OB group had both greater basal activity and greater food cue-induced activation than the OW and NW groups; OW had higher activity in the hippocampus/amygdala than the NW group, which was only significant during resting state. In the OB group, resting-state activity in the left hippocampus/amygdala was positively correlated with activation induced by HiCal food cues, and both of these measures correlated with body mass index (BMI). Mediation analysis showed that the relationship between BMI and hippocampus/amygdala response to HiCal food cues was mediated by their resting-state activity. These findings suggest a close association between obesity and brain functional abnormality in the hippocampus/amygdala. They also indicate that resting-state activity in the hippocampus/amygdala may impact these regions' responses to food cues.

8.
Mol Pharm ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33064009

RESUMO

Nanocarriers (NCs) are promising tools to improve drug delivery across the blood-brain barrier (BBB) for more effective treatment of brain disorders, although there is a scarcity of clinical translation of brain-directed NCs. In order to drive the development of brain-oriented NCs toward clinical success, it is essential to understand the prerequisites for nanodelivery to be successful in brain treatment. In this Perspective, we present how pharmacokinetic/pharmacodynamic (PK/PD), formulation and nanotoxicity factors impact the therapeutic success of brain-specific nanodelivery. Properties including high loading efficiency, slow in vivo drug release, long systemic circulation, an increase in unbound brain-to-plasma concentration/exposure ratio (Kp,uu,brain), high drug potency, and minimal nanotoxicity are prerequisites that should preferably be combined to maximize the therapeutic potential of a brain-targeted NC. The PK of brain-directed NCs needs to be evaluated in a more therapeutically relevant manner, focusing on the released, unbound drug. It is more crucial to increase the Kp,uu,brain than to improve the ability of the NC to cross the BBB in its intact form. Brain-targeted NCs, which are mostly developed for treating brain tumors, including metastases, should aim to enhance drug delivery not just to tumor regions with disrupted BBB, but equally important to regions with intact BBB where the drugs themselves have problems reaching. This article provides critical insights into how a brain-targeted nanoformulation needs to be designed and optimized to achieve therapeutic success in the brain.

9.
Biochem Genet ; 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33098307

RESUMO

Retinoblastoma (Rb) is the most common pediatric malignant tumor of the eyes. Previous studies demonstrated that miR-491-3p is downregulated in various cancers. However, its function in Rb remains unknown. A total of 15 pairs of primary Rb tissues and adjacent noncancerous tissues were collected. Quantitative real-time PCR (qRT-PCR) was used to investigate the expression profiles of miR-491-3p. qRT-PCR, western blotting and in situ immunocytochemistry were performed to investigate the expression profiles of epithelial-mesenchymal transition-related proteins (E-cadherin, Vimentin and N-cadherin) in Rb tissues and Rb cell lines as well as cell morphology. Cell proliferation was estimated by MTS and colony formation assays. Apoptosis was determined by FACS, cell migration and invasion were analyzed using transwell chambers. MiR-491-3p's target genes were predicted using target gene prediction databases. The interplay between miR-491-3p and SNN was evaluated through dual luciferase reporter gene assay. MiR-491-3p was significantly downregulated in mixed collection of 15 pairs of Rb tissues and Rb cell lines. Overexpression of miR-491-3p enhanced apoptosis, and significantly suppressed proliferation, migration and invasion of Rb cells. In contrast, the present of miR-491-3p inhibitor showed reversed results which apoptosis decreased, while cell proliferation of ARPE-19 cells increased. In addition, miR-491-3p increased the expression of E-cadherin, and dramatically decreased the expression of Vimentin and N-cadherin in Rb tissues and Rb cell lines, noticeable changes in morphology, too, as cells became less cohesive and more adhering. We found out that SNN was the pairing target of miR-491-3p and result showed that miR-491-3p and SNN interacted with each other. We also found out that the effects of miR-491-3p were in Rb cells were almost entirely canceled out at the overexpression of SNN. Our findings collectively suggest that miR-491-3p is an important tumor suppressor in Rb, which inhibits tumor growth and metastasis in Rb. These implicate it may be explored as a new therapeutic target in Rb.

10.
Neurogastroenterol Motil ; : e13992, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33073892

RESUMO

BACKGROUND: Functional constipation (FCon) is a common functional gastrointestinal disorder (FGID) with a high prevalence in clinical practice. Previous studies have identified that FCon is associated with functional and structural alterations in the primary brain regions involved in emotional arousal processing, sensory processing, somatic/motor-control, and self-referential processing. However, whether FCon is associated with abnormal structural connectivity (SC) among these brain regions remains unclear. METHODS: We selected the brain regions with functional and structural abnormalities as seed regions and employed diffusion tensor imaging (DTI) with probabilistic tractography to investigate SC changes in 29 patients with FCon and 31 healthy controls (HC). KEY RESULTS: Results showed lower fractional anisotropy (FA) in the fibers connecting the thalamus, a region involved in sensory processing, with the amygdala (AMY), hippocampal gyrus (HIPP), precentral (PreCen) and postcentral gyrus (PostCen), supplementary motor area (SMA) and precuneus in patients with FCon compared with HC. FCon had higher mean diffusivity (MD) and radial diffusivity (RD) in the thalamus connected to the AMY and HIPP. In addition, FCon had significantly increased RD of the thalamus-SMA tract. Sensation of incomplete evacuation was negatively correlated with FA of the thalamus-PostCen and thalamus-HIPP tracts, and there was a negative correlation between difficulty of defecation and FA of the thalamus-SMA tract. CONCLUSIONS AND INFERENCES: These findings reflected that FCon is associated with alterations in SC between the thalamus and limbic/parietal cortex, highlighting the integrative role of the thalamus in brain structural network.

11.
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.

12.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 812-815, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018109

RESUMO

The incidence of fall-related injuries in older adults is high. Given the significant and adverse outcomes that arise from injurious falls in older adults, it is of the utmost importance to identify older adults at greater risk for falls as early as possible. Given that balance dysfunction provides a significant risk factor for falls, an automated and objective identification of balance dysfunction in community dwelling older adults using wearable sensor data when walking may be beneficial. In this study, we examine the feasibility of using wearable sensors, when walking, to identify older adults who have trouble with balance at an early stage using state-of-the-art machine learning techniques. We recruited 21 community dwelling older women. The experimental paradigm consisted of two tasks: Normal walking with a self-selected comfortable speed on an instrumented treadmill and a test of reflexive postural response, using the motor control test (MCT). Based on the MCT, identification of older women with low or high balance function was performed. Using short duration accelerometer data from sensors placed on the knee and hip while walking, supervised machine learning was carried out to classify subjects with low and high balance function. Using a Gradient Boosting Machine (GBM) algorithm, we classified balance function in older adults using 60 seconds of accelerometer data with an average cross validation accuracy of 91.5% and area under the receiver operating characteristic curve (AUC) of 0.97. Early diagnosis of balance dysfunction in community dwelling older adults through the use of user friendly and inexpensive wearable sensors may help in reducing future fall risk in older adults through earlier interventions and treatments, and thereby significantly reduce associated healthcare costs.


Assuntos
Vida Independente , Equilíbrio Postural , Acelerometria , Acidentes por Quedas/prevenção & controle , Idoso , Feminino , Humanos , Aprendizado de Máquina
13.
World J Gastroenterol ; 26(31): 4589-4606, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32884219

RESUMO

BACKGROUND: Effective endoscopic management is fundamental for the treatment of extrahepatic cholangiocarcinoma (ECC). However, current biliary stents that are widely used in clinical practice showed no antitumor effect. Drug-eluting stents (DESs) may achieve a combination of local chemotherapy and biliary drainage to prolong stent patency and improve prognosis. AIM: To develop novel DESs coated with gemcitabine (GEM) and cisplatin (CIS)-coloaded nanofilms that can maintain the continuous and long-term release of antitumor agents in the bile duct to inhibit tumor growth and reduce systemic toxicity. METHODS: Stents coated with different drug-eluting components were prepared by the mixed electrospinning method, with poly-L-lactide-caprolactone (PLCL) as the drug-loaded nanofiber membrane and GEM and/or CIS as the antitumor agents. Four different DESs were manufactured with four drug-loading ratios (5%, 10%, 15%, and 20%), including bare-loaded (PLCL-0), single-drug-loaded (PLCL-GEM and PLCL-CIS), and dual-drug-loaded (PLCL-GC) stents. The drug release property, antitumor activity, and biocompatibility were evaluated in vitro and in vivo to confirm the feasibility and efficacy of this novel DES for ECC. RESULTS: The in vitro drug release study showed the stable, continuous release of both GEM and CIS, which was sustained for over 30 d without an obvious initial burst, and a higher drug-loaded content induced a lower release rate. The drug-loading ratio of 10% was used for further experiments due to its ideal inhibitory efficiency and relatively low toxicity. All drug-loaded nanofilms effectively inhibited the growth of EGI-1 cells in vitro and the tumor xenografts of nude mice in vivo; in addition, the dual-loaded nanofilm (PLCL-GC) had a significantly better effect than the single-drug-loaded nanofilms (P < 0.05). No significant differences in the serological analysis (P > 0.05) or histopathological changes were observed between the single-loaded and drug-loaded nanofilms after stent placement in the normal porcine biliary tract. CONCLUSION: This novel PLCL-GEM and CIS-eluting stent maintains continuous, stable drug release locally and inhibits tumor growth effectively in vitro and in vivo. It can also be used safely in normal porcine bile ducts. We anticipate that it might be considered an alternative strategy for the palliative therapy of ECC patients.

15.
BMC Neurol ; 20(1): 342, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917165

RESUMO

BACKGROUND: Aspergillosis infection of central nervous system (CNS) is rare and fatal. Diagnosis of invasive aspergillosis remains difficult. Aspergillosis of CNS can be an acute, subacute, or chronic onset, and the longest course of the disease was currently reported to be 4 years. Here, we report a case with recurrent headache over 20 years. CASE PRESENTATION: A 54-year-old man was admitted to our neurological disease ward due to intermittent throbbing headache lasting for more than 20 years that had grown notably worse over the past week. The headache was localized to the side of his head blown by a cold wind. He also experienced nausea and vomiting when the headache became severe. The headache usually lasted for 3-4 h after he was blown by the cold wind, though he had no fever. The neurological examination was normal. Magnetic resonance imaging (MRI) of the brain was negative for parenchymal and meningeal lesions. However, the case had increased intracranial pressure (ICP), and elevated protein level in the cerebrospinal fluid (CSF). Aspergillus fumigatus was found in CSF by nanopore targeted sequencing (NTS) and in blood by enzyme-linked immunosorbent assay (ELISA). Aspergillus fumigatus-specific antibody IgG was 104.62 AU/mL, aspergillus galactomannan (GM) antigen was 3.27 µg/L, D-dimer was 3.25 mg/L and fibrinogen degradation product was 11.50 mg/L, which were markedly higher than the normal levels. The patient was prescribed by voriconazole. After the treatment of 14 days, the ICP, CSF protein level, Aspergillus fumigatus-specific antibody IgG, GM antigen, D-dimer and fibrinogen degradation product returned normal. Aspergillus was disappeared by NTS test of CSF. His headache has never occurred again after blowing by a cold wind. CONCLUSIONS: This report reveals that aspergillosis infection of CNS can last for more than 20 years and the major symptom is only intermittent throbbing headache in an immunocompetent patient. Vascular invasion is probably the mechanism of headache in our case with CNS aspergillosis infection. Performing high-throughput gene sequencing technology in CSF is important when the pathogen is not determined for the patients with suspected CNS infection.

16.
Neuropharmacology ; 180: 108301, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32910952

RESUMO

Social anxiety disorder (SAD) usually onsets in childhood or adolescence and is associated with brain development and chronic family stress during this period. As an information hub, the thalamus plays a crucial role in the development of emotion processing and stress regulation. Its structural and functional lateralization have been related to mental disorders. This study examined the age-dependent asymmetry of the thalamic volume in children and adolescents with SAD. We further examined the role of the thalamic asymmetry in moderating the relationships between parental alienation, which is a main source of familial stress for children and adolescents, and anxiety symptoms in this population. Fifty-three medication-free children and adolescents with SAD and 53 typical developing controls (age: 8-17) were included. Anxiety severity was measured using the Screen for Child Anxiety-Related Emotional Disorders (SCARED). We estimated the bilateral thalamic volume and examined diagnosis effect and age-group difference on the thalamic asymmetry. We further examined the moderation of the thalamic asymmetry on the associations between scores on the parental alienation, social phobia, and total SCARED. Compared with controls, the SAD group exhibited significantly abnormal asymmetry in thalamic volume. This asymmetry became more evident in the older age group. Furthermore, this asymmetry significantly weakened the relationships between parental attachment and total SCARED score. The asymmetry of the thalamic volume and its age-group difference provide novel evidence to support brain developmental abnormalities in children and adolescents with SAD. The findings further revealed interactions between physiological and chronic stress in children and adolescents with SAD.

17.
Acta Pharm Sin B ; 10(8): 1347-1359, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32963936

RESUMO

Gene therapy is rapidly emerging as a powerful therapeutic strategy for a wide range of neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). Some early clinical trials have failed to achieve satisfactory therapeutic effects. Efforts to enhance effectiveness are now concentrating on three major fields: identification of new vectors, novel therapeutic targets, and reliable of delivery routes for transgenes. These approaches are being assessed closely in preclinical and clinical trials, which may ultimately provide powerful treatments for patients. Here, we discuss advances and challenges of gene therapy for neurodegenerative disorders, highlighting promising technologies, targets, and future prospects.

18.
Ultrason Sonochem ; 70: 105326, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32906063

RESUMO

Surimi from silver carp with different salt contents (0-5%) was obtained treated by high intensity ultrasound (HIU, 100 kHz 91 W·cm-2). The gelation properties of samples were evaluated by puncture properties, microstructures, water-holding capacity, dynamic rheological properties and intermolecular interactions. As the salt content increased from 0 to 5%, gel properties of surimi without HIU significantly improved. For samples with low-salt (0-2% NaCl) content, HIU induced obvious enhancement in breaking force and deformation. HIU promoted the protein aggregation linked by SS bonds, hydrophobic interactions and non-disulfide covalent bonds in surimi gels with low-salt content. Moreover, microstructures of HIU surimi gels with low-salt content were more compact than those of the corresponding control samples. HIU also improved the gelation properties of surimi with 3% NaCl to an extent. However, for high-salt (4-5% NaCl) samples, HIU decreased the breaking force and deformation of surimi gels due to the degradation of proteins suggested by increased TCA-soluble peptides. In conclusion, HIU effectively improved the gelation properties of surimi with low-salt content (0-2% NaCl), but was harmful for high-salt (4-5% NaCl) surimi. This might provide the theoretical basis for the production of low-salt surimi gels.

19.
Atherosclerosis ; 309: 56-64, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32882641

RESUMO

BACKGROUND AND AIMS: Angiogenesis is a key process for establishing functional vasculature during embryogenesis and involves different signaling mechanisms. The RNA binding protein Zfp36l1 was reported to be involved in various diseases in different species, including cardiovascular diseases. However, whether Zfp36l1b, one of the 2 paralogs of Zfp36l1 in zebrafish, works like mammalian Zfp36l1, and if the molecular mechanisms are different remains unclear. Here, we show that Zfp36l1b plays a crucial protective role in angiogenesis of zebrafish embryos. METHODS: We used transparent transgenic and wild-type zebrafish larvae to dynamically investigate the early stage of angiogenesis with confocal in vivo, after the knockdown of Zfp36l1b by morpholinos (MOs). In situ hybridization and fluorescence-activated cell sorting were performed to detect Zfp36l1b expression. mRNA rescue and CRISPR/Cas9 knockdown, and luciferase reporter experiments were performed to further explore the role of Zfp36l1b in angiogenesis. RESULTS: We found that knockdown of Zfp36l1b led to defected angiogenesis in intersomitic vessels and sub-intestinal veins (SIVs), which could be rescued by the addition of Zfp36l1b mRNA. Moreover, knockdown of Zfp36l1b suppressed Notch1b expression, while knockdown of Notch1b resulted in a partial relief of angiogenesis defects induced by Zfp36l1b down-regulation. Besides, Zfp36l1b knockdown alleviated the excessive branch of SIVs caused by Vegfa over-expression. CONCLUSIONS: Our results show that Zfp36l1b is responsible for establishing normal vessel circuits by affecting the extension of endothelial tip cells filopodia and the proliferation of endothelial cells partly through Notch1b/Fll4 suppression and synergistic function with Vegfa.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32935966

RESUMO

Precise and efficient detection of solvents with similar refractive index is highly desired but remains a big challenge for the conventional opal because the shift of its reflection wavelength only depends on the refractive index of the solvent to be detected. Here, homologues (alcohols, acids, alkalis, esters, and aromatic hydrocarbons), isomers, and other solvents with similar refractive index and structures were precisely distinguished through the dynamic swelling reflection spectrum (DSRS) pattern based on the different swelling behavior of swellable photonic paper in solvents. The one reflection signal of photonic paper will split into two reflection peaks, which then tend to merge together during the swelling process. The variation of the reflection signals and merging time are highly sensitive to the polarity and refractive index of the solvent, and the differences can be significantly amplified in DSRS, resulting in the distinction of the solvent from its unique geometric pattern. Moreover, the variation tendency of the reflectance provides an additional parameter in recognition of the solvent, which can be explained by calculation and comparison of the practical volume ratio of the solvent swelled into the photonic paper and the corresponding critical volume ratio of the solvent determined by its refractive index.

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