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1.
J Chem Inf Model ; 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33955748

RESUMO

NAD(P)H:quinone oxidoreductase 1 (NQO1) has been shown to be a potential therapeutic target for various human diseases, such as cancer and neurodegenerative disorders. Recent advances in computational methods, especially network-based methods, have made it possible to identify novel compounds for a target with high efficiency and low cost. In this study, we designed a workflow combining network-based methods and identification of privileged substructures to discover new compounds targeting NQO1 from a natural product library. According to the prediction results, we purchased 56 compounds for experimental validation. Without the assistance of privileged substructures, 31 compounds (31/56 = 55.4%) showed IC50 < 100 µM, and 11 compounds (11/56 = 19.6%) showed IC50 < 10 µM. With the assistance of privileged substructures, the two success rates were increased to 61.8 and 26.5%, respectively. Seven natural products further showed inhibitory activity on NQO1 at the cellular level, which may serve as lead compounds for further development. Moreover, network analysis revealed that osthole may exert anticancer effects against multiple cancer types by inhibiting not only carbonic anhydrases IX and XII but also NQO1. Our workflow and computational methods can be easily applied in other targets and become useful tools in drug discovery and development.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33945255

RESUMO

Slippery lubricant-infused porous surface (SLIPS) is a promising solution to undesired adhesion. Unfortunately, the complicated fabrication process and limited coating area block its practical applications. Herein, we report a one-step strategy to fabricate polypropylene-based SLIPS coatings through thermally induced phase separation, in which the lubricant is in situ infiltrated within a polymer network formed during cooling. The solid-liquid-phase separation process was monitored by an in situ hot-stage microscope. Such coating performs outstanding self-cleaning, anti-corrosion, and anti-bacterial performance, as well as enhanced stability of the lubricant layer because the lubricant is well adapted in the structure.

3.
J Immunol ; 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33941659

RESUMO

The detection of intracellular nucleic acids is a fundamental mechanism of host defense against infections. The dysregulated nucleic acid sensing, however, is a major cause for a number of autoimmune diseases. In this study, we report that GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is critical for both intracellular DNA- and RNA-induced immune responses. We found that in both human and mouse cells, the deletion of G3BP1 led to the dampened cGAS activation by DNA and the insufficient binding of RNA by RIG-I. We further found that resveratrol (RSVL), a natural compound found in grape skin, suppressed both intracellular DNA- and RNA-induced type I IFN production through inhibiting G3BP1. Importantly, using experimental mouse models for Aicardi-Goutières syndrome, an autoimmune disorder found in humans, we demonstrated that RSVL effectively alleviated intracellular nucleic acid-stimulated autoimmune responses. Thus, our study demonstrated a broader role of G3BP1 in sensing different kinds of intracellular nucleic acids and presented RSVL as a potential treatment for autoimmune conditions caused by dysregulated nucleic acid sensing.

4.
Aging (Albany NY) ; 132021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33819186

RESUMO

Oxaliplatin resistance can develop in colorectal cancer (CRC), which may involve inhibition of ferroptosis, although further research is needed to understand this potential mechanism. We evaluated CRC cells with acquired oxaliplatin resistance (HCT116-Or) or congenital resistance (H716) to determine whether a ferroptosis inducer (RSL3) or inhibitor (liproxstatin-1) could modulate the effects of oxaliplatin. The results suggested that induction of ferroptosis could significantly reverse the oxaliplatin resistance of the CRC cells. Bioinformatic and cytobiological searches also revealed that KIF20A was highly expressed in the oxaliplatin-resistant cell lines and was strongly correlated with survival among CRC patients. Silencing KIF20A enhanced cellular sensitivity to oxaliplatin both in vivo and in vitro, and silencing KIF20A also suppressed NUAK1 activation, while a NUAK1 agonist (ETC-1002) could reverse the oxaliplatin sensitivity of KIF20A-silenced cells. Moreover, silencing NUAK1 up-regulated the expression of PP1ß, down-regulated the phosphorylation of downstream GSK3ßSer9, suppressed the nuclear import of Nrf2, inhibited the expression of a ferroptosis key negative regulatory protein (GPX4), and blocked cellular resistance. Applying a Nrf2 agonist (oltipraz) also reversed the oxaliplatin sensitivity of NUAK1-silenced cells. Therefore, cellular ferroptosis may be inhibited via the KIF20A/NUAK1/PP1ß/GPX4 pathway in CRC cells, which may underly the resistance of CRC to oxaliplatin.

5.
Ecotoxicol Environ Saf ; 216: 112183, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33812209

RESUMO

Flurochloridone (FLC), a selective herbicide used on a global scale, has been reported to have male reproductive toxicity which underlying mechanism is still largely unknown. The present study was conducted to determine the effects of FLC on Sertoli cell and explore its mechanism by using normal mouse Sertoli (TM4) cell line. Our data indicate that FLC suppressed proliferation of TM4 cells in a dose- and time-dependent manner. Further studies confirmed that FLC induced apoptosis in TM4 cells, accompanied by reactive oxygen species (ROS) accumulation, intracellular calcium increase, opening of mitochondrial permeability transition pore, depolarization of the mitochondrial membrane potential (MMP) and decrease of adenosine triphosphate (ATP) level. Meanwhile, changes of B-cell lymphoma-2 (Bcl-2) family proteins expression, release of cytochrome c and the activation of caspase-9 and caspase-3 were also confirmed. These results indicate that FLC induces TM4 cells apoptosis through the mitochondrial apoptotic pathway. In addition, pretreatment with ROS scavenger N-acetyl-L-cysteine (NAC), could significantly alleviate FLC-induced TM4 cells apoptosis and MMP depolarization. In conclusion, our results suggested that FLC induced TM4 cells apoptosis and it was regulated by mitochondrial dysfunction and oxidative stresses.

6.
IEEE Trans Cybern ; PP2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33878007

RESUMO

This article considers the distributed bipartite adaptive event-triggered fault-tolerant consensus tracking issue for linear multiagent systems in the presence of actuator faults based on the output feedback control protocol. Both time-varying additive and multiplicative actuator faults are taken into account in the meantime. And the upper/lower bounds of actuator faults are not required to be known. First, the state observer is designed to settle the occurrence of unmeasurable system states. Two kinds of event-triggered mechanisms are then developed to schedule the interagent communication and controller updates. Next, with the developed event-triggered mechanisms, a novel observer-based bipartite adaptive control strategy is proposed such that the fault-tolerant control problem can be addressed. Compared with some related works on this topic, our control scheme can achieve the intermittent communication and intermittent controller updates, and the more general actuator faults and network topology are considered. It is proved that the exclusion of Zeno behavior can be realized. Finally, three illustrative examples are given to demonstrate the feasibility of the main theoretical findings.

7.
J Chem Inf Model ; 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33884878

RESUMO

Human cytochrome P450 3A4 (CYP3A4) is responsible for the metabolism of ∼50% clinically used drugs. Midazolam (MDZ) is a commonly used sedative drug and serves as a marker substrate for the CYP3A4 activity assessment. MDZ is metabolized by CYP3A4 to two hydroxylation products, 1'-OH-MDZ and 4-OH-MDZ. It has been reported that the ratio of 1'-OH-MDZ and 4-OH-MDZ is dependent on the MDZ concentration, which reflects the homotropic cooperative behavior in MDZ metabolism by CYP3A4. Here, we used quantum chemistry (QC), molecular docking, conventional molecular dynamics (cMD), and Gaussian accelerated molecular dynamics (GaMD) approaches to investigate the mechanism of the interactions between CYP3A4 and MDZ. QC calculations suggest that C1' is less reactive for hydroxylation than C4, which is a pro-chirality carbon. However, the 4-OH-MDZ product is likely to be racemic due to the chirality inversion in the rebound step. The MD simulation results indicate that MDZ at the peripheral allosteric site is not stable and the binding modes of the MDZ molecules at the productive site are in line with the experimental observations.

8.
Nat Commun ; 12(1): 2114, 2021 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-33837182

RESUMO

Lack of detailed knowledge of SARS-CoV-2 infection has been hampering the development of treatments for coronavirus disease 2019 (COVID-19). Here, we report that RNA triggers the liquid-liquid phase separation (LLPS) of the SARS-CoV-2 nucleocapsid protein, N. By analyzing all 29 proteins of SARS-CoV-2, we find that only N is predicted as an LLPS protein. We further confirm the LLPS of N during SARS-CoV-2 infection. Among the 100,849 genome variants of SARS-CoV-2 in the GISAID database, we identify that ~37% (36,941) of the genomes contain a specific trio-nucleotide polymorphism (GGG-to-AAC) in the coding sequence of N, which leads to the amino acid substitutions, R203K/G204R. Interestingly, NR203K/G204R exhibits a higher propensity to undergo LLPS and a greater effect on IFN inhibition. By screening the chemicals known to interfere with N-RNA binding in other viruses, we find that (-)-gallocatechin gallate (GCG), a polyphenol from green tea, disrupts the LLPS of N and inhibits SARS-CoV-2 replication. Thus, our study reveals that targeting N-RNA condensation with GCG could be a potential treatment for COVID-19.


Assuntos
Substituição de Aminoácidos/efeitos dos fármacos , Catequina/análogos & derivados , Proteínas do Nucleocapsídeo/genética , Replicação Viral/efeitos dos fármacos , /virologia , Catequina/farmacologia , Genoma Viral/genética , Humanos , Extração Líquido-Líquido , Proteínas do Nucleocapsídeo/metabolismo , RNA Viral/genética , RNA Viral/metabolismo , Replicação Viral/genética
9.
J Chem Inf Model ; 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33900090

RESUMO

Identification of drug-pathway associations plays an important role in pathway-based drug repurposing. However, it is time-consuming and costly to uncover new drug-pathway associations experimentally. The drug-induced transcriptomics data provide a global view of cellular pathways and tell how these pathways change under different treatments. These data enable computational approaches for large-scale prediction of drug-pathway associations. Here we introduced DPNetinfer, a novel computational method to predict potential drug-pathway associations based on substructure-drug-pathway networks via network-based approaches. The results demonstrated that DPNetinfer performed well in a pan-cancer network with an AUC (area under curve) = 0.9358. Meanwhile, DPNetinfer was shown to have a good capability of generalization on two external validation sets (AUC = 0.8519 and 0.7494, respectively). As a case study, DPNetinfer was used in pathway-based drug repurposing for cancer therapy. Unexpected anticancer activities of some nononcology drugs were then identified on the PI3K-Akt pathway. Considering tumor heterogeneity, seven primary site-based models were constructed by DPNetinfer in different drug-pathway networks. In a word, DPNetinfer provides a powerful tool for large-scale prediction of drug-pathway associations in pathway-based drug repurposing. A web tool for DPNetinfer is freely available at http://lmmd.ecust.edu.cn/netinfer/.

10.
Nanomaterials (Basel) ; 11(3)2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33801017

RESUMO

The nepenthes-inspired lubricant-infused surface (LIS) is emerging as a novel repellent surface with self-healing, self-cleaning, pressure stability and ultra-slippery properties. Recently, stimuli-responsive materials to construct a smart LIS have broadened the application of LIS for droplet manipulation, showing great promise in microfluidics. This review mainly focuses on the recent developments towards the droplet manipulation on LIS with different mechanisms induced by various external stimuli, including thermo, light, electric, magnetism, and mechanical force. First, the droplet condition on LIS, determined by the properties of the droplet, the lubricant and substrate, is illustrated. Droplet manipulation via altering the droplet regime realized by different mechanisms, such as varying slipperiness, electrostatic force and wettability, is discussed. Moreover, some applications on droplet manipulation employed in various filed, including microreactors, microfluidics, etc., are also presented. Finally, a summary of this work and possible future research directions for the transport of droplets on smart LIS are outlined to promote the development of this field.

11.
Brain ; 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33876815

RESUMO

Recent studies in cognitively unimpaired elderly individuals suggest that the APOE ε4 allele exerts a dosage-dependent effect on brain tau deposition. The aim of this study was to investigate sex differences in APOE ε4 gene dosage effects on brain tau deposition in cognitively impaired individuals using quantitative 18F-flortaucipir PET. Preprocessed 18F-flortaucipir tau PET images, T1-weighted structural MRI images, demographic information, global cortical amyloid-ß burden measured by 18F-florbetapir PET, CSF total tau and phosphorylated tau measurements were obtained from the Alzheimer's Disease Neuroimaging Initiative database. Two hundred and sixty-eight cognitively impaired individuals with 146 APOE ε4 non-carriers and 122 carriers (85 heterozygotes and 37 homozygotes) were included in the study. An iterative reblurred Van Cittert iteration partial volume correction method was applied to all downloaded PET images. MRI images were used for PET spatial normalization. Twelve regional standardized uptake value ratios relative to the cerebellum were computed in standard space. APOE ε4 dosage by sex interaction effect on 18F-flortaucipir standardized uptake value ratios was assessed using generalized linear models and sex-stratified analysis. We observed a significant APOE ε4 dosage by sex interaction effect on tau deposition in the lateral temporal, posterior cingulate, medial temporal, inferior temporal, entorhinal cortex, amygdala, parahippocampal gyrus regions after adjusting for age and education level (P < 0.05). The medial temporal, entorhinal cortex, amygdala and parahippocampal gyrus regions retained a significant APOE ε4 dosage by sex interaction effect on tau deposition after adjusting for global cortical amyloid-ß (P < 0.05). In sex-stratified analysis, there was no significant difference in tau deposition between female homozygotes and heterozygotes (P > 0.05). In contrast, male homozygotes standardized uptake value ratios were significantly greater than heterozygotes or non-carriers throughout all twelve regions of interest (P < 0.05). Female heterozygotes exhibited significantly increased tau deposition compared to male heterozygotes in the orbitofrontal, posterior cingulate, lateral temporal, inferior temporal, entorhinal cortex, amygdala and parahippocampal gyrus (P < 0.05). Results from voxelwise analysis were similar to the ones obtained from regions of interest analysis. Our findings suggest that an APOE ε4 dosage effect on brain region-specific tau deposition exists in males, but not females. These results have important clinical implications towards developing sex and genotype-guided therapeutics in Alzheimer's disease and uncovers a potential explanation underlying differential apolipoprotein E ε4-associated Alzheimer's risk in males and females.

12.
Eur Radiol ; 2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33893857

RESUMO

OBJECTIVES: This study was to investigate clinical applicability of diffusion spectrum imaging (DSI) for quantitative detection of visual pathway abnormalities to predict the degree of visual field defects (VFD) in patients with pituitary adenomas. METHODS: Sixty-five patients with pituitary adenomas and 33 healthy controls underwent conventional MRI and DSI scanning that allowed high-angular-resolution fiber tracking. Optic chiasmal compression and VFD were confirmed in all patients via radiological and neuro-ophthalmological examinations. Quantitative assessments of chiasmal lift, VFD, and DSI parameters from the optic nerve, optic tract, and optic radiation were performed. Group comparisons and correlation analyses were conducted in patients and controls. Using the 5-fold cross-validation method, the support vector machine classifiers were constructed to predict the degree of visual defects. RESULTS: The mean values of quantitative anisotropy and generalized fractional anisotropy in optic nerve and optic tract showed significant differences between patients and controls (p < 0.05). These parameters were also significantly correlated with the chiasmal lift distance and degree of visual defects (p < 0.05). All patients were divided into mild (n = 42) and severe (n = 23) VFD groups, using the mean deviation value of -8 dB as the threshold. The classifiers achieved an accuracy of 0.83, sensitivity of 0.78, and specificity of 0.86 to discriminate patients with mild and severe visual defects. CONCLUSIONS: Using high-angular-resolution fiber tracking, DSI may provide quantitative information to detect visual pathway abnormalities and be a potential diagnostic tool for determining the degree of visual field defects in pituitary adenomas. KEY POINTS: • Abnormal QA and GFA values of optic nerve and optic tract in adenoma patients • Close relationship between DSI parameters and VFD degree in adenoma patients • The classifiers achieved an accuracy of 0.83, sensitivity of 0.78, and specificity of 0.86 to discriminate patients with mild and severe VFD.

13.
Reprod Biol Endocrinol ; 19(1): 64, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33902598

RESUMO

BACKGROUND: Fluorochloridone (FLC), a selective pyrrolidone herbicide, has been recognized as a potential endocrine disruptor and reported to induce male reproductive toxicity, but the underlying mechanism is unclear. The aim of this study was to investigate the mechanism of FLC-induced reproductive toxicity on male mice with particular emphasis on the role of autophagy in mice' TM4 Sertoli cells. METHODS: Adult C57BL/6 mice were divided into one control group (0.5% sodium carboxymethyl cellulose), and four FLC-treated groups (3,15,75,375 mg/kg). The animals (ten mice per group) received gavage for 28 days. After treatment, histological analysis, sperm parameters, the microstructure of autophagy and the expression of autophagy-associated proteins in testis were evaluated. Furthermore, to explore the autophagy mechanism, TM4 Sertoli cells were treated with FLC (0,40,80,160 µM) in vitro for 24 h. Cell activity and cytoskeletal changes were measured by MTT assay and F-actin immunofluorescence staining. The formation of autophagosome, accumulation of reactive oxygen species (ROS), expression of autophagy marker proteins (LC3, Beclin-1 and P62) and AKT-related pathway proteins (AKT, mTOR) were observed. The ROS scavenger N-acetylcysteine (NAC) and AKT agonist (SC79) were used to treat TM4 cells to observe the changes of AKT-mTOR pathway and autophagy. RESULTS: In vivo, it showed that FLC exposure caused testicular injuries, abnormality in epididymal sperm. Moreover, FLC increased the formation of autophagosomes, the accumulation of LC3II/LC3I, Beclin-1 and P62 protein, which is related to the degradation of autophagy. In vitro, FLC triggered TM4 cell autophagy by increasing the formation of autophagosomes and upregulating of LC3II/LC3I, Beclin-1 and P62 levels. In addition, FLC induced ROS production and inhibited the activities of AKT and mTOR kinases. The Inhibition of AKT/mTOR signaling pathways and the activation of autophagy induced by FLC could be efficiently reversed by pretreatment of NAC. Additionally, decreased autophagy and increased cell viability were observed in TM4 cells treated with SC79 and FLC, compared with FLC alone, indicating that FLC-induced autophagy may be pro-death. CONCLUSION: Taken together, our study provided the evidence that FLC promoted autophagy in TM4 Sertoli cells and that this process may involve ROS-mediated AKT/mTOR signaling pathways.

14.
Sci Total Environ ; 768: 145466, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33736345

RESUMO

The distribution of bacterial community in an actual landfill was analyzed and the bioprocess involved in refuse degradation was clarified. The results showed that the degradation degree of refuse showed great differences with the landfill age, in which the contents of organic matter (OM) and total Kjeldahl nitrogen (TKN) in refuse as well as the chemical oxygen demand (COD) in leachate presented decreasing trends with increasing landfill age. The diversity of bacterial community increased first and then decreased with increasing landfill age. The main bacterial phyla involved in refuse degradation were Proteobacteria, Firmicutes and Bacteroidetes, among which, Proteobacteria had an absolute advantage with a relative abundance ranging of 66-78%. With increasing landfill age, the abundance of Firmicutes decreased gradually, while that of Bacteroidetes increased. Pseudomonas, Thiopseudomonas, Psychrobacter and Desemzia were the main genera. The distribution of bacterial community in samples with landfill ages of 0-1 and 1-3 years were greatly influenced by TKN and pH, respectively. Amino acid and carbohydrate metabolism were the main biological pathways according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and the biodegradation of xenobiotics as well as terpenoids and polyketides also accounted relatively high frequencies in the landfill. These results provide a better understanding of landfill microbiology and bioprocesses for landfill stabilization.


Assuntos
Eliminação de Resíduos , Poluentes Químicos da Água , Biodegradação Ambiental , Análise da Demanda Biológica de Oxigênio , Instalações de Eliminação de Resíduos
15.
ISA Trans ; 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33766452

RESUMO

Run-to-failure experiment is efficient and effective to investigate bearing deterioration process. Periodic transient waveform carries rich information of health conditions of bearings but the transient waveform matching is a challenging problem for evaluating bearing fatigue life because the shapes and parameters of the waveform vary with the evolution of the bearing degradation. A wavelet function such as a Morlet wavelet is able to extract essential features from the transient waveform but limited to a single transient component. The multi-wavelet may provide a solution to fit a variety of primary components in the transient waveform, so as to track the degradation trend of the bearing; however, very limited work has been done to address this issue. To bridge the research gap in the transient waveform matching, a novel ascension multi-wavelet method is proposed in this paper for diagnosing the undergoing degradation state and predicting the remaining useful life (RUL) of the bearings. Firstly, the transient waveform was matched using the combination of multiple wavelets. Then, the entropy of the multiple-wavelet signal was calculated to quantify the periodic transients to generate a monotone trend of the bearing degradation. The degradation state of the bearing was identified using the entropy. Lastly, the ensemble learning method was employed to establish an RUL predictor. Both simulation and experiments were carried out to evaluate the proposed method. The analysis results demonstrate satisfactory diagnostics and prognostics performance of the proposed method. The RUL prediction accuracy of the multi-wavelet matching is better than that of the single-wavelet matching.

16.
Environ Pollut ; 280: 116998, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33780840

RESUMO

Naturally present aquatic microorganisms play an important role in water purification systems, such as the self-purification of surface waters. In this study, two water sources representing polluted surface water (Olympic Green; OG) and unpolluted surface water (Jingmi river; JM), were used to explore the self-purification of surface water by bacteria under different environmental conditions. The dominant bacterial community of OG and JM waters (both are Firmicutes and Proteobacteria) were isolated, cultured, and then used to carry out flocculation tests. Results showed that the flocculation ability of the dominant bacteria and extracellular polymeric substances (EPS) obtained from OG isolation was significantly greater than that from JM. Further examination illustrated that the main components of EPS were polysaccharides, which played an important role in improving the flocculation ability of bacteria. EPS from dominant cultural bacteria strains (OG1 and JM3) isolated from the two different sources lacked hydrophilic groups (e.g. COOH) and had a networked structure which are the main reasons to enhance the flocculation ability. The bacterial diversity and redundancy analysis (RDA) results also showed that microbial community composition is determined by water quality (SS, TOC, and NH4+), and different Bacteroidetes, Actinobacteria and Proteobacteria community structures can improve the water body's ability to remove environmental pollutants (such as SS, humic acid and fulvic acid). These findings provide new information showing how bacterial communities change with environmental factors while maintaining the purity of surface water.

17.
PLoS One ; 16(3): e0247500, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33657150

RESUMO

Thrips and thrips-transmitted tospoviruses cause significant losses in crop yields worldwide. The melon thrips (Thrips palmi) is not only a pest of cucurbit crops, but also a vector that transmits tospoviruses, such as the watermelon silver mottle virus (WSMoV). Vector transmission of tospoviruses has been well studied in the tomato spotted wilt virus (TSWV)-Frankliniella occidentalis model system; however, until now the transmission mode of WSMoV by T. palmi has not been sufficiently examined. The results of the transmission assays suggest that T. palmi transmits WSMoV in a persistent manner, and that the virus is mainly transmitted by adults, having been ingested at the first-instar larval stage. Complementary RNAs corresponding to the NSm and NSs genes of WSMoV were detected in viruliferous thrips by reverse transcription-polymerase chain reaction; NSs protein was also detected in viruliferous thrips by western blotting, verifying the replication of WSMoV in T. palmi. Furthermore, we demonstrated that in thrips infected with WSMoV at the first-instar larval stage, the virus eventually infected various tissues of the adult thrips, including the primary salivary glands. Taken together, these results suggest that T. palmi transmits WSMoV in a persistent-propagative mode. The results of this study make a significant contribution to the understanding of the transmission biology of tospoviruses in general.

18.
Insects ; 12(2)2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33672688

RESUMO

Viruses that cause tomato yellow leaf curl disease are part of a group of viruses of the genus Begomovirus, family Geminiviridae. Tomato-infecting begomoviruses cause epidemics in tomato crops in tropical, subtropical, and Mediterranean climates, and they are exclusively transmitted by Bemisia tabaci in the field. The objective of the present study was to examine the transmission biology of the tomato yellow leaf curl Thailand virus (TYLCTHV) by B. tabaci, including virus-infected tissues, virus translocation, virus replication, and transovarial transmission. The results demonstrated that the virus translocates from the alimentary gut to the salivary glands via the hemolymph, without apparent replication when acquired by B. tabaci. Furthermore, the virus was detected in 10% of the first-generation progeny of viruliferous females, but the progeny was unable to cause the viral infection of host plants. There was no evidence of transovarial transmission of TYLCTHV in B. tabaci. When combined with the current literature, our results suggest that B. tabaci transmits TYLCTHV in a persistent-circulative mode. The present study enhances our understanding of virus-vector interaction and the transmission biology of TYLCTHV in B. tabaci.

19.
Stem Cell Res Ther ; 12(1): 168, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33691753

RESUMO

BACKGROUND: Retina diseases may lead to blindness as they often afflict both eyes. Stem cell transplantation into the affected eye(s) is a promising therapeutic strategy for certain retinal diseases. Human peripheral blood mononuclear cells (hPBMCs) are a good source of stem cells, but it is unclear whether pre-induced hPBMCs can migrate from the injected eye to the contralateral eye for bilateral treatment. We examine the possibility of bilateral cell transplantation from unilateral cell injection. METHODS: One hundred and sixty-one 3-month-old retinal degeneration 1 (rd1) mice were divided randomly into 3 groups: an untreated group (n = 45), a control group receiving serum-free Dulbecco's modified Eagle's medium (DMEM) injection into the right subretina (n = 45), and a treatment group receiving injection of pre-induced hPBMCs into the right subretina (n = 71). Both eyes were examined by full-field electroretinogram (ERG), immunofluorescence, flow cytometry, and quantitative real-time polymerase chain reaction (qRT-PCR) at 1 and 3 months post-injection. RESULTS: At both 1 and 3 months post-injection, labeled pre-induced hPBMCs were observed in the retinal inner nuclear layer of the contralateral (left untreated) eye as well as the treated eye as evidenced by immunofluorescence staining for a human antigen. Flow cytometry of fluorescently label cells and qRT-PCR of hPBMCs genes confirmed that transplanted hPBMCs migrated from the treated to the contralateral untreated eye and remained viable for up to 3 months. Further, full-field ERG showed clear light-evoked a and b waves in both treated and untreated eyes at 3 months post-transplantation. Labeled pre-induced hPBMCs were also observed in the contralateral optic nerve but not in the blood circulation, suggesting migration via the optic chiasm. CONCLUSION: It may be possible to treat binocular eye diseases by unilateral stem cell injection.

20.
BMC Health Serv Res ; 21(1): 237, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731096

RESUMO

BACKGROUND: Many studies suggest that patient satisfaction is significantly negatively correlated with the waiting time. A well-designed healthcare system should not keep patients waiting too long for an appointment and consultation. However, in China, patients spend notable time waiting, and the actual time spent on diagnosis and treatment in the consulting room is comparatively less. METHODS: We developed an artificial intelligence (AI)-assisted module and name it XIAO YI. It could help outpatients automatically order imaging examinations or laboratory tests based on their chief complaints. Thus, outpatients could get examined or tested before they went to see the doctor. People who saw the doctor in the traditional way were allocated to the conventional group, and those who used XIAO YI were assigned to the AI-assisted group. We conducted a retrospective cohort study from August 1, 2019 to January 31, 2020. Propensity score matching was used to balance the confounding factor between the two groups. And waiting time was defined as the time from registration to preparation for laboratory tests or imaging examinations. The total cost included the registration fee, test fee, examination fee, and drug fee. We used Wilcoxon rank-sum test to compare the differences in time and cost. The statistical significance level was set at 0.05 for two sides. RESULTS: Twelve thousand and three hundred forty-two visits were recruited, consisting of 6171 visits in the conventional group and 6171 visits in the AI-assisted group. The median waiting time was 0.38 (interquartile range: 0.20, 1.33) hours for the AI-assisted group compared with 1.97 (0.76, 3.48) hours for the conventional group (p < 0.05). The total cost was 335.97 (interquartile range: 244.80, 437.60) CNY (Chinese Yuan) for the AI-assisted group and 364.58 (249.70, 497.76) CNY for the conventional group (p < 0.05). CONCLUSIONS: Using XIAO YI can significantly reduce the waiting time of patients, and thus, improve the outpatient service process of hospitals.

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