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1.
J Neurochem ; 168(3): 303-311, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38316937

RESUMO

Controversial findings regarding the association between serum cholesterol levels and Alzheimer's disease (AD) have been identified through observational studies. The genetic basis shared by both factors and the causality between them remain largely unknown. The objective of this study is to examine the causal impact of maternal history of AD on changes in serum cholesterol levels in adult offspring. By retrieving genetic variants from summary statistics of large-scale genome-wide association study of maternal history of AD (European-based: Ncase = 27 696, Ncontrol = 260 980). The causal association between genetically predicted maternal history of AD and changes in serum cholesterol levels in adult offspring was examined using the two-sample Mendelian randomization (MR) method. Causal impact estimates were calculated using single-nucleotide polymorphisms in both univariable MR (UMR) and multivariable MR (MVMR) analyses. Additionally, other approaches, such as Cochran's Q test and leave-one-out variant analysis, were employed to correct for potential biases. The results of UMR presented that genetically predicted maternal history of AD was positively associated with hypercholesterolemia (OR = 1.014; 95% CI: 1.009-1.018; p < 0.001), total cholesterol (OR = 1.29; 95% CI: 1.134-1.466; p < 0.001) and low-density lipoprotein (OR = 1.525; 95% CI: 1.272-1.828; p < 0.001) among adult offspring. Genetic predisposition for maternal history of AD to be negatively associated with high-density lipoprotein (OR = 0.889; 95% CI: 0.861-0.917; p < 0.001). The MVMR analysis remained robust and significant after adjusting for diabetes and obesity in offspring. Sufficient evidence was provided in this study to support the putative causal impact of maternal history of AD on the change of serum cholesterol profile in adult offspring. In clinical practice, priority should be given to the detection and monitoring of cholesterol levels in individuals with a maternal history of AD, particularly in the early stages.


Assuntos
Filhos Adultos , Doença de Alzheimer , Adulto , Humanos , Doença de Alzheimer/genética , Estudo de Associação Genômica Ampla , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Colesterol
2.
J Virol ; 97(5): e0045923, 2023 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-37097154

RESUMO

Numerous studies have illustrated that the Seneca Valley virus (SVV) shows sufficient oncolytic efficacy targeting small cell lung cancer (SCLC). However, the therapeutics of nonsmall cell lung carcinoma (NSCLC, accounts for 85% of lung cancer cases) using oncolytic virus have been resisting due to the filtration of neutralizing antibody and limited reproduction capacity. Here, we employed structural biology and reverse genetics to optimize novel oncolytic SVV mutants (viral receptor-associated mutant SVV-S177A and viral antigenic peptide-related variant SVV-S177A/P60S) with increased infectivity and lower immunogenicity. The results of the NSCLC-bearing athymic mouse model demonstrated that wild-type (wt) SVV-HB extended the median overall survival (mOS) from 11 days in the PBS group to 19 days. Notably, the newly discovered mutations significantly (P < 0.001) prolonged the mOS from 11 days in the control cohort to 23 days in the SVV-S177A cohort and the SVV-S177A/P60S cohort. Taken together, we present a structure-guided genetic modification strategy for oncolytic SVV optimization and provide a candidate for developing oncolytic viral therapy against nonsensitive NSCLC. IMPORTANCE Nonsmall cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases (more than 1.85 million cases with 1.48 million deaths in 2020). In the present study, two novel oncolytic SVV mutants modified based on structural biology and reverse genetics (viral receptor-associated mutant SVV-S177A and viral antigenic peptide-related mutant SVV-S177A/P60S) with increased infectivity or lower immunogenicity significantly (P < 0.001) prolonged the mOS from 11 days in the control cohort to 23 days in the SVV-S177A cohort and the SVV-S177A/P60S cohort in the NSCLC-bearing athymic mouse model, which may provide the direction for modifying SVV to improve the effect of oncolysis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Picornaviridae , Animais , Camundongos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Pulmão , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Camundongos Nus , Picornaviridae/genética
3.
Clin Chem Lab Med ; 60(5): 748-755, 2022 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-35212492

RESUMO

OBJECTIVES: Platelet clumps present in anticoagulant specimens may generate a falsely decreased platelet count and lead to an incorrect diagnosis. A clear understanding of the ability of a haematology analyser (HA) to detect platelet clumps is important for routine work in the clinical laboratory. METHODS: Citrate-anticoagulated whole-blood samples were collected from various patients as a negative group. Adenosine diphosphate (ADP)-induced platelet aggregation was performed on those negative samples to mimic platelet-clump-containing (positive) samples. The 'platelet clumps' and 'platelet abnormal' flags generated by the Sysmex XN-10 instrument were used to assess the flagging performance of this HA and demonstrate its flagging features. The complete blood count (CBC) results of paired negative and positive samples were compared to evaluate the impact of platelet clumps on the CBC parameters. RESULTS: A total of 187 samples were eligible for this study. The total accuracy, sensitivity, and specificity of the platelet clumps flag were 0.786, 0.626, and 0.947, respectively. The total accuracy, sensitivity, and specificity of the platelet abnormal flag were 0.631, 0.348, and 0.914, respectively. A separate assessment focusing on the positive samples with low platelet counts showed that the total sensitivities of the platelet clumps and platelet abnormal flags were 0.801 and 1.000, respectively. Platelet clumps may interfere with the leukocyte count and with platelet and erythrocyte indices. CONCLUSIONS: Platelet clumps can influence not only platelet indices but also leukocyte and erythrocyte counts. The Sysmex XN-10 instrument is sensitive to positive samples with low platelet counts but insensitive to those with high platelet counts.


Assuntos
Hematologia , Leucócitos , Contagem de Células Sanguíneas/métodos , Hematologia/métodos , Humanos , Contagem de Leucócitos , Contagem de Plaquetas
4.
Clin Chem Lab Med ; 59(7): 1289-1297, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-33660491

RESUMO

OBJECTIVES: A sample with a blood clot may produce an inaccurate outcome in coagulation testing, which may mislead clinicians into making improper clinical decisions. Currently, there is no efficient method to automatically detect clots. This study demonstrates the feasibility of utilizing machine learning (ML) to identify clotted specimens. METHODS: The results of coagulation testing with 192 clotted samples and 2,889 no-clot-detected (NCD) samples were retrospectively retrieved from a laboratory information system to form the training dataset and testing dataset. Standard and momentum backpropagation neural networks (BPNNs) were trained and validated using the training dataset with a five-fold cross-validation method. The predictive performances of the models were then assessed based on the testing dataset. RESULTS: Our results demonstrated that there were intrinsic distinctions between the clotted and NCD specimens regarding differences in the testing results and the separation of the groups (clotted and NCD) in the t-SNE analysis. The standard and momentum BPNNs could identify the sample status (clotted and NCD) with areas under the ROC curves of 0.966 (95% CI, 0.958-0.974) and 0.971 (95% CI, 0.9641-0.9784), respectively. CONCLUSIONS: Here, we have described the application of ML algorithms in identifying the sample status based on the results of coagulation testing. This approach provides a proof-of-concept application of ML algorithms to evaluate the sample quality, and it has the potential to facilitate clinical laboratory automation.


Assuntos
Laboratórios Clínicos , Doenças não Transmissíveis , Algoritmos , Testes de Coagulação Sanguínea , Humanos , Aprendizado de Máquina , Estudos Retrospectivos
5.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(3): 362-366, 2019 May.
Artigo em Zh | MEDLINE | ID: mdl-31631604

RESUMO

OBJECTIVE: To determine the association between daily particulate matter 2.5 (PM 2.5) mass and emergency calls for help with respiratory diseases. METHODS: Semi-parametric generalized additive model was established to determine the association between daily PM 2.5 and emergency calls for help with respiratory diseases in 2017 in Chengdu, after adjustments for time trend and variations in the days of the week and weather conditions. RESULTS: In 2017, a total of 9 309 emergency calls for help with respiratory diseases were recorded in Chengdu: on average 26 calls a day. Over the year, Chengdu reported a mean PM 2.5 mass concentration of 53.6 µg/m 3, an average temperature of 16.6 ℃, and an average relative humidity of 81.2%. The single pollutant model with lag time effect showed that a 10 µg/m 3 increase in PM 2.5 was associated with an increase of 1.26% (95% confidence interval ( CI) 0.56%-1.97%) emergency calls for help with respiratory diseases. The exposure-response was almost in a direct line. The dual pollutant model found that O 3 8-hour sliding average (O 3-8 h) enhanced the effect of PM 2.5 on emergency calls for help with respiratory diseases. CONCLUSION: Outdoor PM 2.5 is a significant predictor of emergency calls for help with respiratory diseases in Chengdu.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Serviços Médicos de Emergência/estatística & dados numéricos , Material Particulado/efeitos adversos , Doenças Respiratórias/epidemiologia , China , Humanos , Temperatura
6.
J Magn Reson Imaging ; 39(5): 1327-37, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24123542

RESUMO

PURPOSE: To automatically and robustly detect the arterial input function (AIF) with high detection accuracy and low computational cost in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). MATERIALS AND METHODS: In this study, we developed an automatic AIF detection method using an accelerated version (Fast-AP) of affinity propagation (AP) clustering. The validity of this Fast-AP-based method was proved on two DCE-MRI datasets, i.e., rat kidney and human head and neck. The detailed AIF detection performance of this proposed method was assessed in comparison with other clustering-based methods, namely original AP and K-means, as well as the manual AIF detection method. RESULTS: Both the automatic AP- and Fast-AP-based methods achieved satisfactory AIF detection accuracy, but the computational cost of Fast-AP could be reduced by 64.37-92.10% on rat dataset and 73.18-90.18% on human dataset compared with the cost of AP. The K-means yielded the lowest computational cost, but resulted in the lowest AIF detection accuracy. The experimental results demonstrated that both the AP- and Fast-AP-based methods were insensitive to the initialization of cluster centers, and had superior robustness compared with K-means method. CONCLUSION: The Fast-AP-based method enables automatic AIF detection with high accuracy and efficiency.


Assuntos
Algoritmos , Artérias/fisiologia , Compostos Heterocíclicos/farmacocinética , Angiografia por Ressonância Magnética/métodos , Modelos Biológicos , Compostos Organometálicos/farmacocinética , Reconhecimento Automatizado de Padrão/métodos , Animais , Artérias/anatomia & histologia , Velocidade do Fluxo Sanguíneo/fisiologia , Simulação por Computador , Humanos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Rim/irrigação sanguínea , Ratos , Circulação Renal/fisiologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
7.
Environ Toxicol ; 29(5): 526-33, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-22489048

RESUMO

Aphis gossypii (Glover) has been found to possess multiple mutations in the acetylcholinesterase (AChE) gene (Ace) that might involve target site insensitivity. In vitro functional expression of AChEs reveals that the resistant Ace1 (Ace1R) and Ace2 (Ace2R) were significantly less inhibited by eserine, omethoate, and malaoxon than the susceptible Ace1 (Ace1S) and Ace2 (Ace2S). Furthermore, in both the mutant and susceptible AChEs, Ace2 was significantly less sensitive to eserine, omethoate, and malaoxon than Ace1. These results suggested that both the mutant Ace1 and Ace2 were responsible for omethoate resistance, while the mutant Ace2 played a major role in insecticide resistance. The DNA copy number and transcription level of Ace2 were 1.52- and 1.88-fold higher in the ORR strain than in the OSS strain. Furthermore, the DNA copy number and transcription level of Ace2 were significantly higher than that of Ace1 in either OSS or ORR strains, demonstrating the involvement of Ace2 gene duplication in resistance. Thus, the authors conclude that omethoate resistance in cotton aphids appears to have evolved through a combination of multiple mutations and extensive Ace2R gene duplication.


Assuntos
Acetilcolinesterase/genética , Afídeos/genética , Duplicação Gênica , Resistência a Inseticidas/genética , Mutação , Acetilcolinesterase/metabolismo , Animais , Afídeos/enzimologia , Linhagem Celular , Variações do Número de Cópias de DNA , DNA Complementar/genética , Dimetoato/análogos & derivados , Malation/análogos & derivados , Fisostigmina , Análise de Sequência de DNA
8.
Front Psychol ; 15: 1332523, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38659682

RESUMO

Objective: To systematically evaluate and explore the factors influencing depressive symptoms in female breast cancer patients in China through meta-analysis. Methods: Relevant data were retrieved from cross-sectional studies or cohort studies on depressive symptoms of Chinese breast cancer within the following databases: PubMed, Embase, Cohrane Library, Web of 105 Science, Database of Medical Literature (CBM), Wan Fang Data, CNKI, and VIP databases. The literature screening, data extraction and literature quality evaluation were performed by two researchers by carefully reading the title, abstract and full text, and meta-analysis was performed using Stata 1.5 software after extracting relevant data. Results: Fourteen papers were finally included, with a cumulative total of 3,071 people surveyed, and a total of 1,298 breast cancer patients were detected with depression, with a detection rate of depressive symptoms of 42.26%; meta analysis showed that age less than 40 years old, unmarried, less than undergraduate education, monthly income <5,000 yuan, advanced breast cancer, radical breast cancer surgery, family history, living in rural areas, underlying disease stage and chemotherapy were associated with an increased incidence of depression in breast cancer patients. Conclusion: The detection rate of depressive symptoms in female breast cancer patients is high, and there is a need to strengthen depression-related psychological screening of breast cancer patients and provide them with individualized interventions to reduce the incidence of depression in breast cancer patients and to lower the level of depression already present in the patients.

9.
Foods ; 13(12)2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38928750

RESUMO

This study aimed to investigate the aroma effects of key volatile compounds in a new type of mulberry leaf Fu brick teas (MTs) and traditional Fu brick teas (FTs). Headspace solid-phase microextraction (HS-SPME), gas chromatography-mass spectrometry (GC-MS), sensory evaluation, and chemometrics were used to determine the differences in key flavour qualities between the two. The results showed that a total of 139 volatile components were identified, with aldehydes, ketones, and alcohols dominating. Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) combined with the odour activity value (OAV) showed that seven aroma compounds had an OAV > 10, including 2-(4-methylcyclohex-3-en-1-yl) propan-2-ol with floral and fruity aroma and green attributes, 6-methylhept-5-en-2-one, (E)-6,10-dimethyl-5,9-Undecadien-2-one, (3E,5E)-octa-3,5-dien-2-one, Benzaldehyde, and (E)-3,7,11,15-tetramethylhexadec-2-en-1-ol, which were more abundant in MTs than FTs; Cedrol with sweet aroma attributes was more consistent in MTs than FTs, and we suggest that these odour compounds are important aroma contributors to MTs. Taken together, these findings will provide new insights into the mechanism of formation of the characteristic attributes of aroma in MTs.

10.
Nurs Open ; 11(1): e2064, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38268260

RESUMO

AIM: The number of breast cancer patients is increasing, but there are insufficient sources of information for their family caregivers. The purpose of this systematic review was to elaborate the psychologically realistic experiences and corresponding needs of family members of patients with breast cancer in the course of their experience in the disease which may provide them with effective, targeted intervention strategies to improve their quality of life. DESIGN: Protocol for a meta-synthesis. METHODS: We will search the Chinese databases (i.e., China National Knowledge Infrastructure, VIP Database and Wanfang Database) and the English databases (i.e., PubMed, Embase, Web of Science, the Cochrane Library, CINAHL and PsycINFO). Qualitative studies from the above databases, studying the psychological experiences of family members of patients with breast cancer, will be searched comprehensively. The quality of the study will be evaluated by two reviewers independently using the Joanna Briggs Institute (JBI) critical appraisal tools for qualitative study, and any disagreements will be discussed and judged by the third reviewer. Data will be extracted using JBI standardized data extraction tool. Then, the literature will be compared and analysed, and the raw results summarized using the JBI meta-aggregation tool. The reliability and credibility of the overall quality of the included studies will be assessed by using the JBI ConQual approach. RESULTS: N/A. No Patient or Public Contribution. PROSPERO REGISTRATION NUMBER: REDACTED.


Assuntos
Neoplasias da Mama , Cuidadores , Feminino , Humanos , Qualidade de Vida , Revisões Sistemáticas como Assunto
11.
Ann Clin Biochem ; 60(2): 126-135, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36653307

RESUMO

BACKGROUND: Mainstream haematology analysers (HAs) are reported to have low detection sensitivity for platelet clumps. In this study, a deep learning (DL) algorithm, convolutional neural network (CNN), was implemented to detect platelet clumps. METHODS: Adenosine diphosphate (ADP) was used to induce platelet aggregation to mimic platelet clumps detected (PCD) samples. Six types of leukocyte scattergrams were collected from the Sysmex XN-10. Then, multiple CNNs were trained and validated by scattergrams in a fivefold cross-validation (CV) method. Finally, the CNN model with the best CV accuracy was tested with practical routine work samples. RESULTS: A total of 386 samples (190 PCD and 196 negative samples) and 4253 samples (150 PCD and 4103 negative samples) were eligible for CNN training and practical test, respectively. The CNN with the highest CV accuracy was trained by using scattergrams of side scatter (SSC) vs. forward scatter (FSC) from the white count and nucleated red blood cells (WNR) channel, whose mean area under the curve (AUC), accuracy, specificity and sensitivity were 0.968, 0.940, 0.937 and 0.942, respectively, in the CV. In the practical test, the AUC, accuracy, specificity and sensitivity of the CNN were 0.916, 0.961, 0.860 and 0.965, respectively. The dispersed spots presenting around the leucocytes in the WNR channel may be a sign of platelet clumping. CONCLUSIONS: This study demonstrates that the CNN algorithms can identify platelet clumps based on optical information from dedicated leukocyte channels and has a higher ability to detect platelet clumps than the XN-10 device's internal algorithm under practical circumstances.


Assuntos
Hematologia , Humanos , Hematologia/métodos , Algoritmos
12.
Front Psychiatry ; 14: 1148838, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36993922

RESUMO

Objectives: To translate 20-item Meaningful and Enjoyable Activities Scale into Chinese and evaluate its psychometric properties amongst Chinese with mild dementia. Methods: A cross-sectional study of 450 people with mild dementia recruited from a memory disorders clinic was conducted with the C-MEAS. Raw data were randomly divided into two parts for exploratory factor analysis and confirmatory factor analysis, to evaluate the construct validity. Content validity and reliability were tested by content validity index and Cronbach's α coefficients, respectively. Results: Adaptation results showed that the Chinese version of the scale is adequate for linguistic and content validation. Confirmatory factor analysis indicated a significantly good fit for a three-factor model. Cronbach's alpha coefficient was 0.84 for the overall scale. Conclusion: The C-MEAS for people with mild dementia is a reliable and valid instrument with satisfactory psychometric properties. Future studies should recruit a more representative sample of people with mild dementia in China to verify the applicability of the scale.

13.
J Agric Food Chem ; 71(17): 6541-6551, 2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-37058441

RESUMO

The rice water weevil (RWW), Lissorhoptrus oryzophilus Kuschel (Coleoptera: Curculionidae), is a destructive rice pest that threatens the rice industry worldwide. Odorant receptors (ORs) and odorant receptor coreceptors (Orcos) play an important role in the process of insects' whole life activities; however, there are no related functional studies on RWW. On this basis, a heterologous study of LoryOR20/LoryOrco in Xenopus laevis oocytes was performed to detect the effects of certain natural compounds on RWWs and four active compounds were found. Electroantennogram (EAG) recordings and a behavior test showed that RWWs exhibited a significant response to phenylacetaldehyde (PAA) and an EAG measurement of dsRNA-LoryOR20-treated RWWs revealed a significant decrease in response to PAA. Our results revealed an olfactory molecular mechanism for the recognition of PAA by RWWs, thus providing a potential genetic target at the peripheral olfactory sensing level, contributing to the development of novel control strategies for pest management.


Assuntos
Besouros , Oryza , Receptores Odorantes , Gorgulhos , Animais , Receptores Odorantes/genética , Água
14.
J Mater Sci Mater Med ; 23(2): 375-84, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22139537

RESUMO

Oleoyl-carboxymethy chitosan (OCMCS) nanoparticles based on chitosan with different molecular weights (50, 170 and 820 kDa) were prepared by self-assembled method. The nanoparticles had spherical shape, positive surface charges and the mean diameters were 157.4, 274.1 and 396.7 nm, respectively. FITC-labeled OCMCS nanoparticles were internalized via the intestinal mucosa and observed in liver, spleen, intestine and heart following oral deliverance to carps (Cyprinus carpio). Extracellular products (ECPs) of Aeromonas hydrophila as microbial antigen was efficiently loaded to form OCMCS-ECPs nanoparticles and shown to be sustained release in PBS. Significantly higher (P < 0.05) antigen-specific antibodies were detected in serum after orally immunized with OCMCS-ECPs nanoparticles than that immunized with ECPs alone and non-immunized in control group in carps. These results implied that amphiphilic modified chitosan nanoparticles had great potential to be applied as carriers for the oral administration of protein drugs.


Assuntos
Quitosana/análogos & derivados , Nanopartículas/química , Nanotecnologia/métodos , Administração Oral , Aeromonas/metabolismo , Animais , Anti-Infecciosos/farmacologia , Antígenos/química , Materiais Biocompatíveis/química , Carpas , Quitosana/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Luz , Teste de Materiais , Microscopia Eletrônica de Transmissão/métodos , Peso Molecular , Solubilidade , Estresse Mecânico , Água/química
15.
Front Vet Sci ; 9: 853044, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464348

RESUMO

Porcine reproductive and respiratory syndrome virus (PRRSV) remains a major threat to the swine industry in China and has caused enormous losses every year. To monitor the epidemiological and genetic characteristics of PRRSV in South China, 6,795 clinical samples from diseased pigs were collected between 2017 and 2021, and 1,279 (18.82%) of them were positive for PRRSV by RT-PCR detecting the ORF5 gene. Phylogenetic analysis based on 479 ORF5 sequences revealed that a large proportion of them were highly-pathogenic PRRSVs (409, 85.39%) and PRRSV NADC30-like strains (66, 13.78%). Furthermore, 93.15% of these highly-pathogenic strains were found to be MLV-derived. We next recovered 11 PRRSV isolates from the positive samples and generated the whole genome sequences of them. Bioinformatic analysis showed that seven isolates were MLV-derived. Besides, six isolates were found to be recombinant strains. These eleven isolates contained different types of amino acid mutations in their GP5 and Nsp2 proteins compared to those of the PRRSVs with genome sequences publicly available in GenBank. Taken together, our findings contribute to understanding the prevalent status of PRRSV in South China and provide useful information for PRRS control especially the use of PRRSV MLV vaccines.

16.
Insects ; 13(10)2022 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-36292815

RESUMO

Trehalase is the only enzyme known for the irreversible splitting of trehalose and plays a major role in insect growth and development. In this report, we describe a basic study of the trehalase gene fragment encoding a soluble trehalase from Lissorhoptrus oryzophilus (LoTRE1). Sequence alignment and phylogenetic analysis suggested that LoTRE1 was similar to some known insect trehalases and belongs to the Coleoptera trehalase group. Additionally, LoTRE1 was expressed mainly in the fat body. Purified protein was obtained using heterologous expression of LoTRE1 in Escherichia coli, and the recombinant protein exhibited the ability to decompose trehalose. Enzyme-substrate docking indicated the potential involvement of other residues in the catalytic activity, in addition to Asp 333. Moreover, feeding of adults on LoTRE1 dsRNA silenced the transcription of LoTRE1 and thereby reduced the activity of trehalase and increased the trehalose content; it also led to a 12% death rate. This study reveals essential molecular features of trehalase and offers insights into the structural aspects of this enzyme, which might be related to its function. Taken together, the findings demonstrate that LoTRE1 is indispensable for adults of this pest and provide a new target for the control of L. oryzophilus.

17.
Vaccines (Basel) ; 9(1)2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33451123

RESUMO

Protein-based self-assembling nanoplatforms exhibit superior immunogenicity compared with soluble antigens. Here, we present a comprehensive vaccine strategy for displaying classical swine fever virus (CSFV) E2 glycoprotein on the surface of ferritin (fe) nanocages. An E2-specific blocking antibody assay showed that the blocking rates in pE2-fe/Gel02 (84.3%) and a half-dose cohort of E2-fe/Gel02 (81.9%) were significantly higher (p < 0.05) than that in a ferritin-free cohort of pE2/Gel02 (62.7%) at 21 days post immunization (dpi) in vivo. Furthermore, quantitation of neutralizing potency revealed that a highly significant difference (p < 0.001) was observed between the pE2-fe/Gel02 cohort (1:32, equivalent to live-attenuated strain C at 1:32) and the pE2/Gel02 cohort (1:4) at 21 dpi. Moreover, the innate immune cytokines of IL-4 and IFN-γ activated by the half-dose (20 µg) cohort of E2-fe/Gel02 were equivalent to those elicited by the full dose (40 µg) of purified E2 in the pE2/Gel02 cohort at most time points. In conclusion, we successfully obtained an antigen-displaying E2-ferritin nanoplatform and confirmed high ferritin-assisted humoral and cellular immunities. Our results provided a novel paradigm of self-assembling nanovaccine development for the defense and elimination of potentially pandemic infectious viral pathogens.

18.
Viruses ; 12(4)2020 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-32230737

RESUMO

Pseudorabies (PR), caused by pseudorabies virus (PRV), is an acute and febrile infectious disease in swine. To eradicate PR, a more efficacious vaccine needs to be developed. Here, the gE/gI- and TK/gE/gI-gene-deleted recombinant PRV (rGXΔgE/gI and rGXΔTK/gE/gI) are constructed through CRISPR/Cas9 and Cre/Lox systems. We found that the rGXΔTK/gE/gI was safer than rGXΔgE/gI in mice. Additionally, the effects of rGXΔgE/gI and rGXΔTK/gE/gI were further evaluated in swine. The rGXΔgE/gI and rGXΔTK/gE/gI significantly increased numbers of IFN-γ-producing CD4+ and CD8+ T-cells in swine, whereas there was no difference between rGXΔgE/gI and rGXΔTK/gE/gI. Moreover, rGXΔgE/gI and rGXΔTK/gE/gI promoted a PRV-specific humoral immune response. The PRV-specific humoral immune response induced by rGXΔgE/gI was consistent with that caused by rGXΔTK/gE/gI. After the challenge, swine vaccinated with rGXΔgE/gI and rGXΔTK/gE/gI showed no clinical signs and viral shedding. However, histopathological detection revealed that rGXΔgE/gI, not rGXΔTK/gE/gI, caused pathological lesions in brain and lung tissues. In summary, these results demonstrate that the TK/gE/gI-gene-deleted recombinant PRV was safer compared with rGXΔgE/gI in swine. The data imply that the TK/gE/gI-gene-deleted recombinant PRV may be a more efficacious vaccine candidate for the prevention of PR.


Assuntos
Sistemas CRISPR-Cas , Deleção de Genes , Herpesvirus Suídeo 1/genética , Herpesvirus Suídeo 1/imunologia , Recombinação Homóloga , Integrases/metabolismo , Vacinas contra Pseudorraiva/genética , Vacinas contra Pseudorraiva/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Antivirais/imunologia , Feminino , Marcação de Genes , Engenharia Genética , Genoma Viral , Células HEK293 , Herpesvirus Suídeo 1/isolamento & purificação , Humanos , Camundongos , Suínos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Virulência
19.
Vaccine ; 38(29): 4574-4583, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32417139

RESUMO

Classical swine fever (CSF) remains one of the most important highly contagious and fatal viral disease of swine with high morbidity and mortality. CSF is caused by classical swine fever virus (CSFV), a small, enveloped RNA virus of the genus Pestivirus. The aim of this study was to construct the a novel CSFV Fc-fusion recombinant protein and evaluate the efficacy as a vaccine against CSFV. Here, we obtained a novel subunit vaccine expressing CSFV E2 recombinant fusion protein in CHO-S cells. Functional analysis revealed that CSFV Fc-fusion recombinant protein (CSFV-E2-Fc) could bind to FcγRI on antigen-presenting cells (APCs) and significantly increase IgA levels in serum and feces, inducing stronger mucosal immune response in swine. Additionally, CSFV-E2-Fc immunization enhanced CSFV-specific T cell immune response with a Th1-like pattern of cytokine secretion, remarkably stimulated the Th1-biased cellular immune response and humoral immune response. Further, the protective effects of CSFV-E2-Fc subunit vaccines were confirmed. The data suggest that CSFV E2-Fc recombinant fusion protein may be a promising candidate subunit vaccine to elicit immune response and protect against CSFV.


Assuntos
Vírus da Febre Suína Clássica , Peste Suína Clássica , Vacinas Virais , Animais , Anticorpos Antivirais , Peste Suína Clássica/prevenção & controle , Antígenos de Histocompatibilidade Classe I , Receptores Fc , Suínos , Vacinação , Proteínas do Envelope Viral/genética
20.
Curr Protein Pept Sci ; 20(7): 696-704, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30678617

RESUMO

Numerous experimental studies have demonstrated that a series of remodeling processes occurred in the adipose tissue during the weaning, such as differentiation. Fibroblasts in the breast at weaning stage could re-differentiate into mature adipocytes. Many transcriptional factors were involved in these processes, especially the PPARγ, C/EBP, and SREBP1. There is cell apoptosis participating in the breast tissue degeneration and secretory epithelial cells loss during weaning. In addition, hormones, especially the estrogen and pituitary hormone, play a vital role in the whole reproductive processes. In this review, we mainly focus on the underlying regulated mechanisms of differentiation of adipose tissue and apoptosis of breast cell to provide a specific insight into the physiological changes during weaning.


Assuntos
Adipócitos/citologia , Apoptose , Mama/citologia , Diferenciação Celular , Desmame , Animais , Mama/metabolismo , Humanos , Fatores de Transcrição/metabolismo
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