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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 245: 118928, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32950857

RESUMO

An aggregation-induced emission enhancement (AIEE)-active fluorescent sensor has been successfully designed and synthesized, combining the AIE effect of tetraphenylethylene (TPE) with the cyanide acceptor of phenanthro[9,10-d]imidazole. The sensor exhibits not only the property of AIEE in DCM/n-hexane or THF/H2O, but also the phenomenon of mechanofluorochromic (MFC). It displays large Stokes shift (107 nm) due to the intramolecular charge transfer (ICT) process. The cation of CN- boosts the ICT process to make the greater Stokes shift (184 nm) with the fluorescent color vary from blue-green to sodium-yellow and visually turning from light yellow to dark yellow in the naked eyes. The results of Job's plot, ESI-MS and the DFT calculations provide the stoichiometric ratio and electronic properties of the sensor. Furthermore, the sensor could be applied to qualitative and quantitative detection of CN- on test paper strips.

2.
Medicine (Baltimore) ; 99(45): e23001, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33157943

RESUMO

BACKGROUND: In recent years, platelet-rich plasma (PRP) has been used in burn wound repair, plastic surgery, bone and tendon ligament injury repair and other treatment at home and abroad. Clinical studies indicate that PRP has a good curative effect on repairing burn wounds. The residual wounds formed after large area severe burns are difficult to cure and have recurrent attacks. Because the action mechanism of PRP is unclear, its clinical efficacy of PRP in repairing severe burn wounds is controversial. And there is no relevant systematic evaluation of PRP in repairing severe burn wounds now. OBJECTIVE: Meta analysis was used to evaluate the efficacy and safety of PRP in repairing severe burn wounds. METHODS: Randomized controlled clinical trial of using PRP to repair severe burn wounds were retrieved by computer WanFang, China National Knowledge Infrastructure, China Science and Technology Journal Database, China Biology Medicine disc, Embase, PubMed, Web of Science and Cochrane Library from the establishment of the database to September 2020. Two researchers independently extract data and assess the quality of the included literature, and Meta analysis of the included literature is carried out by using RevMan5.3 software. RESULTS: In this study, the efficacy and safety of PRP in repairing severe burn wounds are evaluated from the aspects of wound healing rate, wound healing time, scar index, visual simulation score, the number of layers of dressing, the number of times of changing gauze, frequency of dressing change, the positive rate of wound bacterial culture and the incidence of inflammatory reaction. CONCLUSIONS: PRP has a good curative effect on the repair of severe burn wounds. This study provides reliable evidence for the clinical use of PRP in the clinical repair of severe burn wounds. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/FG682.

3.
Cell Death Dis ; 11(11): 953, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33159035

RESUMO

p66Shc, a master regulator of mitochondrial reactive oxygen species (mtROS), is a crucial mediator of hepatocyte oxidative stress. However, its functional contribution to acetaminophen (APAP)-induced liver injury and the mechanism by which it is modulated remain unknown. Here, we aimed to assess the effect of p66Shc on APAP-induced liver injury and to evaluate if circular RNA (circRNA) functions as a competitive endogenous RNA (ceRNA) to mediate p66Shc in APAP-induced liver injury. p66Shc-, miR-185-5p-, and circ-CBFB-silenced mice were injected with APAP. AML12 cells were transfected with p66Shc, miR-185-5p, and circ-CBFB silencing or overexpression plasmids or siRNAs prior to APAP stimulation. p66Shc was upregulated in liver tissues in response to APAP, and p66Shc silencing in vivo protected mice from APAP-induced mitochondrial dynamics perturbation and liver injury. p66Shc knockdown in vitro attenuated mitochondrial dynamics and APAP-induced hepatocyte injury. Mechanically, p66Shc perturbs mitochondrial dynamics partially by inhibiting OMA1 ubiquitination. miR-185-5p, which directly suppressed p66Shc translation, was identified by microarray and bioinformatics analyses, and its overexpression attenuated mitochondrial dynamics and hepatocyte injury in vitro. Furthermore, luciferase, pull-down and RNA immunoprecipitation assays demonstrated that circ-CBFB acts as a miRNA sponge of miR-185-5p to mediate p66Shc in APAP-induced liver injury. circ-CBFB knockdown also alleviated APAP-induced mitochondrial dynamics perturbation and hepatocyte injury. More importantly, we found that the protective effects of circ-CBFB knockdown on p66Shc, mitochondrial dynamics and liver injury were abolished by miR-185-5p inhibition both in vivo and in vitro. In conclusion, p66Shc is a key regulator of APAP-induced liver injury that acts by triggering mitochondrial dynamics perturbation. circ-CBFB functions as a ceRNA to regulate p66Shc during APAP-induced liver injury, which may provide a potential therapeutic target.

4.
Zhongguo Zhong Yao Za Zhi ; 45(18): 4519-4527, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-33164383

RESUMO

In this paper, the name, origin and producing area of Sojae Semen Nigrum were studied to provide the basis for the selection of medicinal varieties of Sojae Semen Nigrum. The textual research of this herbal was carried out through the textual research of ancient and modern literature and the comparative study of botany, combined with agricultural archaeology and the investigation of adulterant products. Before Qin Dynasty, the Sojae Semen Nigrums had not been selected, and the edible beans should only be Glycine soja. From Qin to the Northern and Southern dynasties, the Sojae Semen Nigrums G. max were selected,but the medicinal Sojae Semen Nigrum was G. soja. After Tang Dynasty, Sojae Semen Nigrums were recorded more, the medicinal Sojae Semen Nigrums referred to G. soja,G. max and G. gracilis. In modern times, G. soja was hardly to use as the medicine. The harvest time is August or September, and there are many processing methods, such as frying, making tofu, making Semen Sojae Praeparatum, boiling, boiling with auxiliary materials, germination, etc. The quality evaluation of Sojae Semen Nigrum was consistent in past dynasties, and it was considered that "it is better for those who are tight and small". Before Tang Dynasty, the better should only be G. soja. After the Qing Dynasty, the better should be green cotyledon varieties of G. max,which are recommended. In addition, there are many varieties of Sojae Semen Nigrum. It is hoped that that the scientific researchers of traditional Chinese medicine can use modern technology to distinguish the efficacy of Sojae Semen Nigrum with green and yellow cotyledon, and make a comparison between large and small Sojae Semen Nigrum. The results provide scientific basis for the selection of medicinal varieties of Sojae Semen Nigrum.


Assuntos
Medicamentos de Ervas Chinesas , China , Medicina Tradicional Chinesa , Sementes , Sêmen , Soja
5.
Pathogens ; 9(10)2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33036450

RESUMO

Recently developed nanopore sequencing technologies offer a unique opportunity to rapidly close the genome and to identify complete sequences of mobile genetic elements (MGEs). In this study, 17 isolates of Listeria monocytogenes (Lm) epidemic clone II (ECII) from seven ready-to-eat meat or poultry processing facilities, not known to be associated with outbreaks, were shotgun sequenced, and among them, five isolates were further subjected to long-read sequencing. Additionally, 26 genomes of Lm ECII isolates associated with three listeriosis outbreaks in the U.S. and South Africa were obtained from the National Center for Biotechnology Information (NCBI) database and analyzed to evaluate if MGEs may be used as a high-resolution genetic marker for identifying and sourcing the origin of Lm. The analyses identified four comK prophages in 11 non-outbreak isolates from four facilities and three comK prophages in 20 isolates associated with two outbreaks that occurred in the U.S. In addition, three different plasmids were identified among 10 non-outbreak isolates and 14 outbreak isolates. Each comK prophage and plasmid was conserved among the isolates sharing it. Different prophages from different facilities or outbreaks had significant genetic variations, possibly due to horizontal gene transfer. Phylogenetic analysis showed that isolates from the same facility or the same outbreak always closely clustered. The time of most recent common ancestor of the Lm ECII isolates was estimated to be in March 1816 with the average nucleotide substitution rate of 3.1 × 10-7 substitutions per site per year. This study showed that complete MGE sequences provide a good signal to determine the genetic relatedness of Lm isolates, to identify persistence or repeated contamination that occurred within food processing environment, and to study the evolutionary history among closely related isolates.

6.
Lancet Infect Dis ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33035474

RESUMO

BACKGROUND: Middle East respiratory syndrome (MERS) remains of global public health concern. Dromedary camels are the source of zoonotic infection. Over 70% of MERS coronavirus (MERS-CoV)-infected dromedaries are found in Africa but no zoonotic disease has been reported in Africa. We aimed to understand whether individuals with exposure to dromedaries in Africa had been infected by MERS-CoV. METHODS: Workers slaughtering dromedaries in an abattoir in Kano, Nigeria, were compared with abattoir workers without direct dromedary contact, non-abattoir workers from Kano, and controls from Guangzhou, China. Exposure to dromedaries was ascertained using a questionnaire. Serum and peripheral blood mononuclear cells (PBMCs) were tested for MERS-CoV specific neutralising antibody and T-cell responses. FINDINGS: None of the participants from Nigeria or Guangdong were MERS-CoV seropositive. 18 (30%) of 61 abattoir workers with exposure to dromedaries, but none of 20 abattoir workers without exposure (p=0·0042), ten non-abattoir workers or 24 controls from Guangzhou (p=0·0002) had evidence of MERS-CoV-specific CD4+ or CD8+ T cells in PBMC. T-cell responses to other endemic human coronaviruses (229E, OC43, HKU-1, and NL-63) were observed in all groups with no association with dromedary exposure. Drinking both unpasteurised camel milk and camel urine was significantly and negatively associated with T-cell positivity (odds ratio 0·07, 95% CI 0·01-0·54). INTERPRETATION: Zoonotic infection of dromedary-exposed individuals is taking place in Nigeria and suggests that the extent of MERS-CoV infections in Africa is underestimated. MERS-CoV could therefore adapt to human transmission in Africa rather than the Arabian Peninsula, where attention is currently focused. FUNDING: The National Science and Technology Major Project, National Institutes of Health.

7.
Mol Ther ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33091613

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest forms of cancer with very few available therapeutic options. We previously reported that an engineered human enzyme, cyst(e)inase, which degrades L-cysteine (L-Cys) and cystine, inhibits growth of multiple cancer cells, including PDAC both in vitro and in vivo. Here, we show that cyst(e)inase treatment leads to increased clustered oxidative DNA damage, DNA single-strand breaks, apurinic/apyrimidinic sites, and DNA double-strand breaks (DSBs) in PDAC cells sensitive to intracellular depletion of L-Cys that is associated with reduced survival. BRCA2-deficient PDAC cells exhibited increased DSBs and enhanced sensitivity to cyst(e)inase. The blocking of a second antioxidant pathway (thioredoxin/thioredoxin reductase) using auranofin or inhibiting DNA repair using the poly (ADP-ribose) polymerase (PARP) inhibitor, olaparib, led to significant increases in DSBs following cyst(e)inase treatment in all PDAC cells examined. Cyst(e)inase plus olaparib also synergistically inhibited growth of sensitive and resistant PDAC cells in both xenograft and allograft tumor models. Collectively, these results demonstrate an important role for oxidative DNA damage and ultimately DNA DSBs in the anticancer action of cyst(e)inase. The data further show the potential for combining agents that target alternate antioxidant pathways or by targeting DNA repair pathways or genetic liabilities in DNA repair pathways to enhance the therapeutic action of cyst(e)inase for PDAC.

8.
J Org Chem ; 85(21): 13567-13578, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33112605

RESUMO

An approach to access functionalized 3,4-dihydro-1,3-oxazin-2-ones has been developed by reacting semicyclic N,O-acetals 5 and 6 with ynamides 7 or terminal alkynes 8 in a one-pot fashion. The reaction went through a formal [4 + 2] cycloaddition process to generate a number of functionalized 3,4-dihydro-1,3-oxazin-2-ones 9a-9ak and 10a-10bc in yields of 34-97%. In addition, the utility of this transformation was demonstrated by the synthesis of (±)-sedamine 13.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32941096

RESUMO

Seven surfactants were selected as candidate agents for in situ soil column flushing. Column flushing lacks the interaction between surfactants and contaminants, so efficiency is not easy to improve. Microbubbles generated in situ may adhere to the contaminant diesel. Thereafter, the bubbles were mobilized to lift the multi-system oil to the top layer. This process must be attributed to the increased column flushing efficiency of diesel removal. Compared with a single solution, using randomly methylated beta-cyclodextrin (RAMEB) and microbubble enhancement, the diesel removal of column flushing increased by 30.7%. Compared with the existing conditions (5.25 × 10-4 cm s-1), the hydraulic conductivity of loam soil (3.74 × 10-3 cm s-1) increased by 7.1 times after the continued operation of the two processes. The oil layer was collected for further reuse. After three treatments, the effluent for the RAMEB was more than 85%. The collected effluent was treated with a synthetic absorbent and then qualifiedly discharged with a TOC value of only 2.6 mg L-1. By combining surfactant flushing with microbubbles and other equipment, not only can the reaction time be effectively saved, but organic pollutants could be concentrated and reused in the soil, so no additional treatment was required.

10.
BMC Genomics ; 21(1): 631, 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32928108

RESUMO

BACKGROUND: We benchmarked the hybrid assembly approaches of MaSuRCA, SPAdes, and Unicycler for bacterial pathogens using Illumina and Oxford Nanopore sequencing by determining genome completeness and accuracy, antimicrobial resistance (AMR), virulence potential, multilocus sequence typing (MLST), phylogeny, and pan genome. Ten bacterial species (10 strains) were tested for simulated reads of both mediocre- and low-quality, whereas 11 bacterial species (12 strains) were tested for real reads. RESULTS: Unicycler performed the best for achieving contiguous genomes, closely followed by MaSuRCA, while all SPAdes assemblies were incomplete. MaSuRCA was less tolerant of low-quality long reads than SPAdes and Unicycler. The hybrid assemblies of five antimicrobial-resistant strains with simulated reads provided consistent AMR genotypes with the reference genomes. The MaSuRCA assembly of Staphylococcus aureus with real reads contained msr(A) and tet(K), while the reference genome and SPAdes and Unicycler assemblies harbored blaZ. The AMR genotypes of the reference genomes and hybrid assemblies were consistent for the other five antimicrobial-resistant strains with real reads. The numbers of virulence genes in all hybrid assemblies were similar to those of the reference genomes, irrespective of simulated or real reads. Only one exception existed that the reference genome and hybrid assemblies of Pseudomonas aeruginosa with mediocre-quality long reads carried 241 virulence genes, whereas 184 virulence genes were identified in the hybrid assemblies of low-quality long reads. The MaSuRCA assemblies of Escherichia coli O157:H7 and Salmonella Typhimurium with mediocre-quality long reads contained 126 and 118 virulence genes, respectively, while 110 and 107 virulence genes were detected in their MaSuRCA assemblies of low-quality long reads, respectively. All approaches performed well in our MLST and phylogenetic analyses. The pan genomes of the hybrid assemblies of S. Typhimurium with mediocre-quality long reads were similar to that of the reference genome, while SPAdes and Unicycler were more tolerant of low-quality long reads than MaSuRCA for the pan-genome analysis. All approaches functioned well in the pan-genome analysis of Campylobacter jejuni with real reads. CONCLUSIONS: Our research demonstrates the hybrid assembly pipeline of Unicycler as a superior approach for genomic analyses of bacterial pathogens using Illumina and Oxford Nanopore sequencing.

11.
BMC Nephrol ; 21(1): 396, 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32928127

RESUMO

BACKGROUND: Minimal change disease (MCD) is one of the major causes of nephrotic syndrome (NS). A confirmed MCD diagnosis mainly depends on renal biopsy at present, which is an invasive procedure with many potential risks. The overall incidence of complications caused by renal biopsy procedures has been reported as approximately 11 and 6.6% outside and within China, respectively. Unfortunately, there is currently no noninvasive procedure or practical classification method for distinguishing MCD from other primary glomerular diseases available. METHOD: A total of 1009 adult patients who underwent renal biopsy between January 2017 and November 2019 were enrolled in this study. Twenty-five parameters extracted from patient demographics, clinical manifestations, and laboratory test results were statistically analysed. LASSO regression analysis was further performed on these parameters. The parameters with the highest area under the curve (AUC) were selected and used to establish a logistic diagnostic prediction model. RESULTS: Of the 25 parameters, 14 parameters were significantly different (P < 0.05). MCD patients were mostly younger (36 (22, 55) vs. 41 (28.75, 53)) and male (59% vs. 52%) and had lower levels of diastolic blood pressure (DBP) (79 (71, 85.5) vs. 80 (74, 89)) and IgG (5.42 (3.17, 6.36) vs. 9.38 (6.79, 12.02)) and higher levels of IgM (1.44 (0.96, 1.88) vs. 1.03 (0.71, 1.45)) and IgE (160 (46.7, 982) vs. 47.3 (19, 126)) than those in the non-MCD group. Using the LASSO model, we established a classifier for adults based on four parameters: DBP and the serum levels of IgG, IgM, IgE. We were able to clinically classify adult patients with NS into MCD and non-MCD using this model. The validation accuracy of the logistic regression model was 0.88. A nomogram based on these four classifiers was developed for clinical use that could predict the probability of MCD in adult patients with NS. CONCLUSIONS: A LASSO model can be used to distinguish MCD from other primary glomerular diseases in adult patients with NS. Combining the model and the nomogram potentially provides a novel and valuable approach for nephrologists to diagnose MCD, avoiding the complications caused by renal biopsy.

12.
Phys Chem Chem Phys ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32996507

RESUMO

CoIII(salen)-X (X = Cl-, OAc-, and OTs-) mediated hydration of propylene oxide (PO) to propylene glycol has been investigated in detail using density functional theory (DFT) calculations. Two kinds of reaction mechanisms, the concerted and stepwise pathways, were scrutinized. For the eight concerted routes, the cooperative bimetallic route in which the middle carbon atom is attacked by the nucleophilic oxygen atom (route VI-m) was calculated to be the most favorable, and among the three catalysts examined H2O-CoIII-OTs was found to be the most active, due to the strong hydrogen bonding between the nucleophilic H2O and the ring oxygen atom in the epoxides as well as the extra π-π stacking interaction. For the stepwise mechanism which consists of the formation of H2O-CoIII-OH, the ring-opening of PO and propylene glycol formation, our studies reveal that different H2O-CoIII-Xs behave kinetically very similarly in the course of propylene glycol formation, but show a notable difference in the rate of H2O-CoIII-OH formation with Cl- > OAc- > OTs-. The rate ordering with which we rationalize the experimental phenomena well is disclosed to be consistent with the nucleophilicity of the counterions by molecular electrostatic potential, condensed Fukui function and condensed local softness. We show that the nucleophilicity of the counterion determines the favorable mechanism that PO hydration follows.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32902085

RESUMO

Optical chirality sensing has attracted a lot of interest due to its potential in high-throughput screening in chirality analysis. A molecular sensor is required to convert the chirality of analytes into optical signals. Although many molecular sensors have been reported, sensors with wide substrate scope remain to be developed. Herein, we report that the amide naphthotube-based chirality sensors have an unprecedented wide scope for chiroptical sensing of organic molecules. The substrates include, but are not limited to common organic products in asymmetric catalysis, chiral molecules with inert groups or remote functional groups from their chiral centers, natural products and their derivatives, and chiral drugs. The effective chirality sensing is based on biomimetic recognition in water and on effective chirality transfer through guest-induced formation of a chiral conformation of the sensors. Furthermore, the sensors can be used in real-time monitoring on reaction kinetics in water and in determining absolute configurations and ee values of the products in asymmetric catalysis.

14.
Chin J Integr Med ; 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32915425

RESUMO

OBJECTIVE: To evaluate the effect of Guilu Erxian Glue (, GEG) on cyclophosphamide (CTX)-induced bone marrow hematopoietic stem cells (HSCs) senescence in mice and explore the underlying mechanism. METHODS: The H22 liver cancer ascites lump model was established in male Kunming mice by injecting intraperitoneally (i.p.) with 5 × 106/mL H22 cells per mouse. Fifty tumor-bearing mice were divided into the control, model, pifithrin-α, GEG, and GEG+pifithrin-α groups using a random number table, 10 mice in each group. CTX (100 mg/kg i.p.) was administrated to mice from day 1 to day 3 (d1-d3) continuously except for the control group. The mice in the pifithrin-α, GEG and GEG+pifithrin-α groups were treated with pifithrin-α (2.2 mg/(kg·d) i.p.) for 6 consecutive days (d4-d9), GEG (9.5 g/(kg·d) i.p.) for 9 consecutive days (d1-d9), and GEG plus pifithrin-α, respectively. HSCs were collected after 9-d drug treatment. The anti-aging effect of GEG was studied by cell viability, cell cycle, and ß -galactosidase (ß -gal) assays. The mRNA and protein expressions of cyclin-dependent kinase 2 (CDK2), CDK4, inhibitor of cyclin-dependent kinase 4a encoding the tumor suppressor protein p16 (p16INK4a), p21Cip1/Waf1, p53, and phosphorylated retinoblastoma (pRb) were evaluated by quantitative real-time reverse transcription-polymerase chain reaction and semi-quantitative Western blot, respectively. RESULTS: Compared with the model group, GEG increased cell viability as well as proliferation (P<0.05 or P<0.01) and reduced ß -gal expression. Furthermore, GEG significantly decreased the expressions of p16INK4a, p53 and p21Cip1/Waf1 proteins, and increased the expressions of CDK2, CDK4 and pRb proteins compared with the model group (P<0.05 or P<0.01). CONCLUSION: GEG can alleviate CTX-induced HSCs senescence in mice, and the p16INK4a-Rb signaling pathway might be the underlying mechanism.

15.
Ann Neurol ; 88(6): 1132-1143, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32939785

RESUMO

OBJECTIVE: A recessive biallelic repeat expansion, (AAGGG)exp , in the RFC1 gene has been reported to be a frequent cause of late-onset ataxia. For cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS), the recessive biallelic (AAGGG)exp genotype was present in ~92% of cases. This study aimed to examine whether the pentanucleotide repeat (PNR) was related to multiple system atrophy (MSA), which shares a spectrum of symptoms with CANVAS. METHODS: In this study, we screened the pathogenic (AAGGG)exp repeat and 5 other PNRs in 104 Chinese sporadic adult-onset ataxia of unknown aetiology (SAOA) patients, 282 MSA patients, and 203 unaffected individuals. Multiple molecular genetic tests were used, including long-range polymerase chain reaction (PCR), repeat-primed PCR (RP-PCR), Sanger sequencing, and Southern blot. Comprehensive clinical assessments were conducted, including neurological examination, neuroimaging, nerve electrophysiology, and examination of vestibular function. RESULTS: We identified biallelic (AAGGG)exp in 1 SAOA patient and 3 MSA patients. Additionally, 1 MSA patient had the (AAGGG)exp /(AAAGG)exp genotype with uncertain pathogenicity. We also described the carrier frequency for different PNRs in our cohorts. Furthermore, we summarized the distinct phenotypes of affected patients, suggesting that biallelic (AAGGG)exp in RFC1 could be associated with MSA and should be screened routinely in the MSA diagnostic workflow. INTERPRETATION: Our results expanded the clinical phenotypic spectrum of RFC1-related disorders and raised the possibility that MSA might share the same genetic background as CANVAS, which is crucial for re-evaluating the current CANVAS and MSA diagnostic criteria. ANN NEUROL 2020;88:1132-1143.

16.
Artigo em Inglês | MEDLINE | ID: mdl-32931437

RESUMO

Digital histopathology image segmentation can facilitate computer-assisted cancer diagnostics. Given the difficulty of obtaining manual annotations, weak supervision is more suitable for the task than full supervision is. However, most weakly supervised models are not ideal for handling severe intra-class heterogeneity and inter-class homogeneity in histopathology images. Therefore, we propose a novel end-to-end weakly supervised learning framework named WESUP. With only sparse point annotations, it performs accurate segmentation and exhibits good generalizability. The training phase comprises two major parts, hierarchical feature representation and deep dynamic label propagation. The former uses superpixels to capture local details and global context from the convolutional feature maps obtained via transfer learning. The latter recognizes the manifold structure of the hierarchical features and identifies potential targets with the sparse annotations. Moreover, these two parts are trained jointly to improve the performance of the whole framework. To further boost test performance, pixel-wise inference is adopted for finer prediction. As demonstrated by experimental results, WESUP is able to largely resolve the confusion between histological foreground and background. It outperforms several state-of-the-art weakly supervised methods on a variety of histopathology datasets with minimal annotation efforts. Trained by very sparse point annotations, WESUP can even beat an advanced fully supervised segmentation network.

17.
Mov Disord ; 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32991004

RESUMO

BACKGROUND: In polyglutamine (polyQ) disease, the investigation of the prediction of a patient's age at onset (AAO) facilitates the development of disease-modifying intervention and underpins the delay of disease onset and progression. Few polyQ disease studies have evaluated AAO predicted by machine-learning algorithms and linear regression methods. OBJECTIVE: The objective of this study was to develop a machine-learning model for AAO prediction in the largest spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) population from mainland China. METHODS: In this observational study, we introduced an innovative approach by systematically comparing the performance of 7 machine-learning algorithms with linear regression to explore AAO prediction in SCA3/MJD using CAG expansions of 10 polyQ-related genes, sex, and parental origin. RESULTS: Similar prediction performance of testing set and training set in each models were identified and few overfitting of training data was observed. Overall, the machine-learning-based XGBoost model exhibited the most favorable performance in AAO prediction over the traditional linear regression method and other 6 machine-learning algorithms for the training set and testing set. The optimal XGBoost model achieved mean absolute error, root mean square error, and median absolute error of 5.56, 7.13, 4.15 years, respectively, in testing set 1, with mean absolute error (4.78 years), root mean square error (6.31 years), and median absolute error (3.59 years) in testing set 2. CONCLUSION: Machine-learning algorithms can be used to predict AAO in patients with SCA3/MJD. The optimal XGBoost algorithm can provide a good reference for the establishment and optimization of prediction models for SCA3/MJD or other polyQ diseases. © 2020 International Parkinson and Movement Disorder Society.

18.
Theranostics ; 10(23): 10680-10696, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32929374

RESUMO

Background: Oxidative stress has emerged as an essential factor in the pathogenesis of intestinal ischemia/reperfusion (I/R) injury. The adaptor protein p66Shc is a key regulator of reactive oxygen species (ROS) generation and a mediator of I/R damage in the intestine, but the upstream mechanisms that directly regulate p66Shc expression during intestinal I/R remain largely unknown. Recent studies have suggested that noncoding RNAs, such as circular RNAs (circRNAs), are important players in physiological and pathological processes based on their versatile regulatory roles in gene expression. The aim of this study was to elucidate the contribution of p66Shc to oxidative damage in intestinal I/R and to investigate the regulation of p66Shc by circRNA sponges. Methods: Intestinal I/R was induced in mice via superior mesenteric artery (SMA) occlusion. A miR-339-5p agomir or circ-protein kinase C beta (PRKCB) siRNA was injected intravenously before I/R challenge. In addition, Caco-2 cells were subjected to hypoxia/reoxygenation (H/R) in vitro to simulate an in vivo I/R model. Results: In vitro, p66Shc deficiency significantly reduced H/R-induced ROS overproduction by attenuating mitochondrial superoxide anion (O2 -) levels, suppressing NADPH oxidase activity and enhancing antioxidant enzyme expression. Moreover, miR-339-5p was identified to directly regulate p66Shc expression in the intestine. Furthermore, we found that a circRNA transcribed from the PRKCB gene, named circ-PRKCB, acted as an endogenous miR-339-5p sponge to regulate p66Shc expression. circ-PRKCB silencing or miR-339-5p overexpression significantly downregulated p66Shc expression and attenuated oxidative stress levels and I/R injury in vivo and in vitro. Notably, the increased circ-PRKCB levels and decreased miR-339-5p levels associated with murine intestinal I/R were consistent with those in patients with intestinal infarction. Conclusions: Our findings reveal a crucial role for the circ-PRKCB/miR-339-5p/p66Shc signaling pathway in regulating oxidative stress in the I/R intestine. This pathway may be a potential therapeutic target for intestinal I/R injury.

19.
Neurobiol Aging ; 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32768149

RESUMO

Recent studies have identified an expanded GGC repeat in the 5' untranslated region of the NOTCH2NLC gene as a possible pathogenic genetic cause of neuronal intranuclear inclusion disease. Converging evidence verifying the presence of the same GGC repeat expansion in patients with Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases has also received increased attention. Inspired by some of the clinical similarities between neuronal intranuclear inclusion disease and multiple system atrophy (MSA), we used repeat-primed PCR to explore the occurrence of GGC repeats in 328 patients with MSA in mainland China. Our result failed to detect any GGC repeat expansion in these patients with MSA, indicating that the NOTCH2NLC gene may not be involved in the pathogenesis of MSA.

20.
Waste Manag ; 117: 42-47, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32805600

RESUMO

Poultry litter is used as soil amendment or organic fertilizer. While poultry litter is enriched with organic matter suitable for land, the presence of pathogens such as Salmonella in poultry litter is a concern. To investigate the effect of gaseous ozone on pathogen reductions in poultry litter, this study conducted a series of experiments that involved understanding of Salmonella Typhimurium and Escherichia coli O157:H7 inactivation at various doses of Ozone (O3) in wet and dry poultry litter conditions. Previously, ozone treatment has been shown to disinfect the surface of foods and plant materials including fruits, juices, and wastewater, however, additional research are needed to better understand the impacts of ozone on treatment of soil amendments. Sanitizing methods capable of eliminating pathogens of soil amendments are crucial to mitigate disease outbreaks related with litter/manure-based fertilizers. In this study, a bench scale continuous ozone treatment system was designed to produce O3 gas, with a range O3 concentrations (7.15-132.46 mg·L-1), monitor ozone concentrations continuously, and control the ozone exposure time (15 to 90 mins) to understand the effectiveness of O3 in eliminating S. Typhimurium and E. coli O157:H7 in poultry litter. Results showed that 7.15 mg·L-1 did not reduce the counts of S. Typhimurium until exposure to O3 for 90 min. The O3 concentrations of 43.26 ~ 132.46 mg·L-1 exposure reduced the bacterial counts. Furthermore, the moisture content of poultry litter was found to be an influencing factor for pathogen reduction. The pathogen reduction rates were reduced when the moisture content was increased. At higher moisture content, high concentrations of O3 (132.46 mg·L-1) were needed for pathogen reductions. The moisture content of 30% or lower was found to be more effective for controlling pathogen levels in poultry litter. Our study demonstrates that gaseous O3 treatment could be used as an additional decontamination technique to ensure the certain degree of microbiological safety of poultry litter based soil amendment.


Assuntos
Escherichia coli O157 , Ozônio , Animais , Microbiologia de Alimentos , Esterco , Aves Domésticas , Salmonella typhimurium
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