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3.
Insect Sci ; 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33463036

RESUMO

Baculoviruses are natural enemies of agricultural and forest insect pests and play an important role in biological pest control. Oral infection by baculovirus in the insect midgut is necessary for establishing systemic infection and eventually killing the insect. Since the insect midgut continuously encounters microbiota, the gut microbiota could affect baculovirus infection. Here, we demonstrated that gut microbiota modulates immune responses and promotes baculovirus infection in the cotton bollworm, Helicoverpa armigera. After oral infection, numerous host immunity-related genes including genes encoding Toll and immune deficiency (IMD) pathway components were upregulated in the midgut. Elimination of the gut microbiota significantly increased the resistance to viral infection in H. armigera. Quantitative real-time reverse transcription polymerase chain reaction and proteomic analysis showed that downregulation of the antiviral factor prophenoloxidase (PPO) could be mediated by microbiota during infection. It implied that midgut microbiota diminishes the expression of PPO to facilitate viral infection in H. armigera. Our findings revealed that the microbiota plays an important role in modulating the resistance of H. armigera to baculovirus infection, providing new insights in applying biopesticide.

4.
J Psychiatr Res ; 135: 37-46, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33445059

RESUMO

Only a few studies investigated the impact of quarantine on anxiety of general population during a second wave of COVID-19 breakout. We aimed to compare anxiety levels of quarantined and non-quarantined people and investigate factors affecting anxiety during the second COVID-19 pandemic. A total of 1837 participants were included in this cross-sectional study. Anxiety was measured by the State-Trait Anxiety Inventory (STAI). Participants were divided into the quarantined group (QG) and non-quarantined group (Non-QG). The mean STAI-S score in the QG was significantly higher than Non-QG (41.8 ± 11.2 vs 40.01 ± 9.9), so was the proportion of severe state anxiety (11.6% vs 5.5%). Males in the QG were significantly more anxious than females evaluated by both STAI-S and STAI-T. High income was independent protective factors while moderate or bad health status and high trait anxiety level were independent risk factors for severe state anxiety. In conclusion, the COVID-19 confinement could significantly increase anxiety of quarantined people. Males were more vulnerable to the quarantine of COVID-19 with significantly increased anxiety level than females. The results suggest that attention should be paid to anxiety during a second round of quarantine due to COVID-19 and are of help in planning psychological interventions.

5.
Asian J Psychiatr ; 56: 102533, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33418283

RESUMO

AIM: This study aimed to investigate and monitor the mental health status of pregnant women during the COVID-19 pandemic. MATERIALS AND METHODS: The meta-analysis was used to study the literatures on the psychology of pregnant women in four databases until Sep 27, 2020. RESULTS: A total of 19 articles were included in the final meta-analysis. The overall prevalence of anxiety was 42 % (95 %CI 26 %-57 %) with substantial heterogeneity (I2 = 99.6 %). The overall prevalence of depression was 25 % (95 %CI 20 %-31 %) with substantial heterogeneity (I2 = 97.9 %). Age, family economic status, social support, and physical activity seem to correlate with the mental health status of pregnant women. CONCLUSION: The prevalence of anxiety and depression among pregnant women increased significantly during the COVID-19 epidemic. Pregnant women are more concerned about others than themselves during COVID-19, and younger pregnant women seem to be more prone to anxiety, while social support and physical activity can reduce the likelihood of anxiety and depression. It is necessary to take some psychological intervention measures for pregnant women to help them go through this special period safely and smoothly.


Assuntos
Ansiedade/epidemiologia , Depressão/epidemiologia , Complicações na Gravidez/epidemiologia , Fatores Etários , Ansiedade/psicologia , Depressão/psicologia , Status Econômico , Exercício Físico/psicologia , Feminino , Humanos , Gravidez , Complicações na Gravidez/psicologia , Gestantes/psicologia , Apoio Social
6.
J Gen Virol ; 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33459587

RESUMO

Baculoviruses are large DNA viruses that replicate within the nucleus of infected host cells. Therefore, many viral proteins must gain access to the nucleus for efficient viral genome replication, gene transcription and virion assembly. To date, the global protein localization pattern of baculoviral proteins is unknown. In this study, we systematically analysed the nuclear localization of 154 ORFs encoded by the prototypic baculovirus, Autographa californica multiple nucleopolyhedrovirus (AcMNPV), either during transient expression or with super-infection of the virus. By transient expression of vectors containing egfp-fused ORFs, we found that in the absence of virus infection, 25 viral proteins were localized in the nucleus. Most of these, which we called 'auto-nuclear localization' proteins, are related to virus replication, transcription or virion structure, and 20 of them contain predicted classical nuclear localization signal. Upon virus infection, 11 proteins, which originally localized in the cytoplasm or both cytoplasm and nucleus in the transfection assays, were completely translocated into the nucleus, suggesting that their nuclear import is facilitated by other viral or host proteins. Further co-transfection experiments identified that four of the 11 proteins, including P143, P33, AC73 and AC114, were imported into the nucleus with the assistance of the auto-nuclear localization proteins LEF-3 (for P143), TLP (for P33) and VP80 (for both AC73 and AC114). This study presents the first global nuclear localization profile of AcMNPV proteins and provides useful information for further elucidation of the mechanisms of baculovirus nuclear entry and gene functions.

7.
Cell Res ; 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33390587

RESUMO

Glioblastoma (GBM) is an incurable and highly heterogeneous brain tumor, originating from human neural stem/progenitor cells (hNSCs/hNPCs) years ahead of diagnosis. Despite extensive efforts to characterize hNSCs and end-stage GBM at bulk and single-cell levels, the de novo gliomagenic path from hNSCs is largely unknown due to technical difficulties in early-stage sampling and preclinical modeling. Here, we established two highly penetrant hNSC-derived malignant glioma models, which resemble the histopathology and transcriptional heterogeneity of human GBM. Integrating time-series analyses of whole-exome sequencing, bulk and single-cell RNA-seq, we reconstructed gliomagenic trajectories, and identified a persistent NSC-like population at all stages of tumorigenesis. Through trajectory analyses and lineage tracing, we showed that tumor progression is primarily driven by multi-step transcriptional reprogramming and fate-switches in the NSC-like cells, which sequentially generate malignant heterogeneity and induce tumor phenotype transitions. We further uncovered stage-specific oncogenic cascades, and among the candidate genes we functionally validated C1QL1 as a new glioma-promoting factor. Importantly, the neurogenic-to-gliogenic switch in NSC-like cells marks an early stage characterized by a burst of oncogenic alterations, during which transient AP-1 inhibition is sufficient to inhibit gliomagenesis. Together, our results reveal previously undercharacterized molecular dynamics and fate choices driving de novo gliomagenesis from hNSCs, and provide a blueprint for potential early-stage treatment/diagnosis for GBM.

9.
BMC Pregnancy Childbirth ; 20(1): 660, 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33129300

RESUMO

BACKGROUND: Delivery methods are associated with postpartum hemorrhage (PPH) both in nulliparous and multiparous women. However, few studies have examined the difference in this association between nulliparous and multiparous women. This study aimed to explore the difference of maternal and neonatal characteristics and delivery methods between Chinese nulliparous and multiparous women, and then examine the differential effects of different delivery methods on PPH between these two-type women. METHODS: Totally 151,333 medical records of women who gave birth between April 2013 to May 2016 were obtained from the electronic health records (EHR) in a northern province, China. The severity of PPH was estimated and classified into blood loss at the level of < 900 ml, 900-1500 ml, 1500-2100 ml, and > 2100 ml. Neonatal and maternal characteristics related to PPH were derived from the same database. Multiple ordinal logistic regression was used to estimate associations. RESULTS: Medical comorbidities, placenta previa and accreta were higher in the nulliparous group and the episiotomy rate was higher in the multiparous group. Compared with spontaneous vaginal delivery (SVD), the adjusted odds (aOR) for progression to severe PPH due to the forceps-assisted delivery was much higher in multiparous women (aOR: 9.32; 95% CI: 3.66-23.71) than in nulliparous women (aOR: 1.70; 95% CI: 0.91-3.18). The (aOR) for progression to severe PPH due to cesarean section (CS) compared to SVD was twice as high in the multiparous women (aOR: 4.32; 95% CI: 3.03-6.14) as in the nulliparous women (aOR: 2.04; 95% CI: 1.40-2.97). However, the (aOR) for progression to severe PPH due to episiotomy compared to SVD between multiparous (aOR: 1.24; 95% CI: 0.96-1.62) and nulliparous women (aOR: 1.55; 95% CI: 0.92-2.60) was not significantly different. The (aOR) for progression to severe PPH due to vacuum-assisted delivery compared to SVD in multiparous women (aOR: 2.41; 95% CI: 0.36-16.29) was not significantly different from the nulliparous women (aOR: 1.05; 95% CI: 0.40-2.73). CONCLUSIONS: Forceps-assisted delivery and CS methods were found to increase the risk of severity of the PPH. The adverse effects were even greater for multiparous women. Episiotomy and the vacuum-assisted delivery, and SVD were similar to the risk of progression to severe PPH in either nulliparous or multiparous women. Our findings have implications for the obstetric decision on the choice of delivery methods, maternal and neonatal health care, and obstetric quality control.

10.
J Clin Biochem Nutr ; 67(2): 146-152, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33041511

RESUMO

Our study was to understand the autophagy induce by different ratios and concentrations of LA/DHA on Raw264.7 cell, and then to investigate the effect of Raw264.7 autophagy on the clearance of Staphylococcus aureus. Raw264.7 cells was treated by LA/DHA in different concentrations (50/100 µmol/L) and ratios (4:1, 6:1, 8:1, 1:4, 1:6 and 1:8) for 6/12/24 h, cell viability assay was assessed by Cell Counting Kit-8, LC3B, p62, P-mTOR, P-Akt, P-PI3K and BECN 1 were detected by the Western blot. LA/DHA could induce autophagy of Raw264.7 cells through the PI3K-Akt-mTOR signaling pathway, the strong effect on autophagy by the concentration is 100 µmol/L, the ratio is 6:1 of LA/DHA, and the treatment time is 24 h. Compared with the images in the control group obtained by merging red and green fluorescence channels, the treatment of LA, DHA in a ratio of 6:1 at a concentration of 100 µmol/L for 24 h significantly lead to a substantial number of autophagosomes (yellow) as well as autolysosomes (red), enhancing autophagy flux. Autophagy induce by LA/DHA can devour and damage intracellular and extracellular Staphylococcus aureus. These results indicate that LA/DHA cloud induce autophagy and enhance the phagocytosis and killing ability of macrophages to intracellular parasitic bacteria.

11.
J Invertebr Pathol ; 177: 107481, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33035534

RESUMO

Ticks are considered to be the second most important vectors of human infectious diseases. The innate immune system is the key factor that affects its vector competence. Hyalomma asiaticum is the primary vector of Crimean-Congo hemorrhagic fever virus (CCHFV). However, the immune system of H. asiaticum remains virtually unknown. Here, a high throughput full-length mRNA sequencing method was adopted to define the immunotranscriptome of H. asiaticum infected with the fungal pathogen Beauveria bassiana and gram-negative bacterium Enterobacter cloacae. The analysis yielded 22,300 isoforms with an average length of 3233 bps. In total, 68 potential immunity-related genes were identified based on similarity to the homologs known to be involved in immunity. These included most members of the Toll and JAK/STAT signaling pathways, but not the IMD signaling pathway. Moreover, two copies of Dicer-2 and five copies of Argonaute-2 were detected. These genes are postulated to be involved in the RNA interference (RNAi) pathway, which is an important defense against RNA viruses. Overall, this study provides the foundation for understanding the immune response of H. asiaticum to CCHFV.

12.
Virol Sin ; 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32910347

RESUMO

The recent outbreak of novel coronavirus pneumonia (COVID-19) caused by a new coronavirus has posed a great threat to public health. Identifying safe and effective antivirals is of urgent demand to cure the huge number of patients. Virus-encoded proteases are considered potential drug targets. The human immunodeficiency virus protease inhibitors (lopinavir/ritonavir) has been recommended in the global Solidarity Trial in March launched by World Health Organization. However, there is currently no experimental evidence to support or against its clinical use. We evaluated the antiviral efficacy of lopinavir/ritonavir along with other two viral protease inhibitors in vitro, and discussed the possible inhibitory mechanism in silico. The in vitro to in vivo extrapolation was carried out to assess whether lopinavir/ritonavir could be effective in clinical. Among the four tested compounds, lopinavir showed the best inhibitory effect against the novel coronavirus infection. However, further in vitro to in vivo extrapolation of pharmacokinetics suggested that lopinavir/ritonavir could not reach effective concentration under standard dosing regimen [marketed as Kaletra®, contained lopinavir/ritonavir (200 mg/50 mg) tablets, recommended dosage is 400 mg/10 mg (2 tablets) twice daily]. This research concluded that lopinavir/ritonavir should be stopped for clinical use due to the huge gap between in vitro IC50 and free plasma concentration. Nevertheless, the structure-activity relationship analysis of the four inhibitors provided further information for de novel design of future viral protease inhibitors of SARS-CoV-2.

13.
ACS Infect Dis ; 6(9): 2524-2531, 2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32786284

RESUMO

The discovery of novel drug candidates with anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) potential is critical for the control of the global COVID-19 pandemic. Artemisinin, an old antimalarial drug derived from Chinese herbs, has saved millions of lives. Artemisinins are a cluster of artemisinin-related drugs developed for the treatment of malaria and have been reported to have multiple pharmacological activities, including anticancer, antiviral, and immune modulation. Considering the reported broad-spectrum antiviral potential of artemisinins, researchers are interested in whether they could be used to combat COVID-19. We systematically evaluated the anti-SARS-CoV-2 activities of nine artemisinin-related compounds in vitro and carried out a time-of-drug-addition assay to explore their antiviral mode of action. Finally, a pharmacokinetic prediction model was established to predict the therapeutic potential of selected compounds against COVID-19. Arteannuin B showed the highest anti-SARS-CoV-2 potential with an EC50 of 10.28 ± 1.12 µM. Artesunate and dihydroartemisinin showed similar EC50 values of 12.98 ± 5.30 µM and 13.31 ± 1.24 µM, respectively, which could be clinically achieved in plasma after intravenous administration. Interestingly, although an EC50 of 23.17 ± 3.22 µM was not prominent among the tested compounds, lumefantrine showed therapeutic promise due to high plasma and lung drug concentrations after multiple dosing. Further mode of action analysis revealed that arteannuin B and lumefantrine acted at the post-entry step of SARS-CoV-2 infection. This research highlights the anti-SARS-CoV-2 potential of artemisinins and provides leading candidates for anti-SARS-CoV-2 drug research and development.


Assuntos
Antivirais/farmacologia , Artemisininas/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Animais , Antimaláricos/farmacologia , Chlorocebus aethiops , Descoberta de Drogas , Reposicionamento de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Pandemias , Células Vero
14.
Cancer Gene Ther ; 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32632269

RESUMO

Tumor organoids recapitulate pathological properties and would serve as an excellent ex vivo model for drug discovery. Here, we performed an unbiased drug screening on drivers-defined tumor organoids from mouse endometrial cancer, the most prevalent gynecological malignancy in human, with a small molecule library targeting epigenetic factors. Among them, menin-MLL inhibitors MI-136 and MI-463 scored. The therapeutic capacity of MI-136 was further validated in tumor organoids in vitro and an orthotopic model in vivo. CRISPR/cas9-mediated mutations of major components of the menin-MLL complex, Men1, Kmt2a and Ash2l, inhibited the growth of tumor organoids, suggesting that the complex was the target of MI-136. Transcriptome analysis showed that the hypoxia-inducible factor (HIF) pathway was the most significantly downregulated pathway by MI-136 treatment. Consistently, Men1, Kmt2a, and Ash2l knockout also repressed the expressions of the HIF target genes. Loss of Hif1a or Hif1b partially phenocopied the inhibition of the menin-MLL complex by MI-136 or mutations in term of tumor organoid growth. Further, we found that MEN1 was upregulated in human endometrial cancers, which were tightly correlated with the expression levels of HIF1A, and associated with poor prognosis. Importantly, MI-136 also significantly inhibited the growth of endometrial cancer organoids derived from patients. Thus, our study identified MI-136 as a potential inhibitor for endometrial cancer through regulating the HIF pathway, a novel molecular mechanism distinguished from those in AML and prostate cancer.

15.
BMC Public Health ; 20(1): 681, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32404088

RESUMO

BACKGROUND: The respiratory infectious diseases (RID) threaten the health and life quality of school students. However, previous related studies were insufficient in research design and method applied. This study aimed to evaluate the effect of health education on the knowledge and behavior of students toward RID through difference-in-difference (DID) analysis in Gansu, China. METHODS: In 2015-2016, a one-year health education program in Gansu, China was conducted. The intervention group contained 1064 students before and 1001 students after the health education (2015 and 2016, respectively). The control group contained 1018 and 1001 students, respectively. The health education, including playing promotional cartoons, developing lectures, giving out handbook copies and making hand copy and blackboard newspapers, and publicity columns on RID, were conducted monthly from 2015 to 2016 in intervention group. The data were collected before and after the health education program with a questionnaire on the students' knowledge and preventive behaviors regarding RID. The ×2 and t tests were performed to compare the accuracy rate and scores for RID knowledge and behavior of the two groups. DID estimation was conducted to evaluate the effect of health education on RID knowledge and behavior while controlling the non- equilibrium variables. RESULTS: After the health education program, the accuracy rate and scores of most items in the intervention group were significantly higher than those in the control group (P < 0.05) except for item k9 "What methods can prevent flu?". The DID results wherein the demographics- age, nationality, and household register were controlled showed that health education significantly improved the accuracy rate of RID knowledge by 5.2-63.9% for most items, although the accuracy rates of items k2 "What's the transmission way of the mumps?" and k9 were significantly decreased by 36.8 and 12.0%. The health education significantly improved the score of knowledge by 155.2% (P < 0.001) and the accuracy rate of all items of RID behavior by 2.9-51.5% except for item b3 "If you have phlegm, how do you usually deal with it?". In addition, the health education also significantly improved the score of behavior toward RID of the sampled students by 138.2% (P < 0.001). CONCLUSION: The results of this study show that health education seemed to increase the RID knowledge and behavior of students. It is recommended that the health education should be enhanced and popularized in schools of China, and RID transmission routes and prevention methods should attract more attention.


Assuntos
Educação em Saúde/organização & administração , Conhecimentos, Atitudes e Prática em Saúde , Infecções Respiratórias/fisiopatologia , Serviços de Saúde Escolar/organização & administração , Adolescente , Criança , China , Feminino , Humanos , Masculino
16.
Front Immunol ; 11: 785, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32431706

RESUMO

Melanization is a prominent insect humoral response for encapsulation of and killing invading pathogens. It is mediated by a protease cascade composed of a modular serine protease (SP), and clip domain SPs (cSPs), which converts prophenoloxidase (PPO) into active phenoloxidase (PO). To date, melanization pathway in cotton bollworm Helicoverpa armigera, an important agricultural pest, remains largely unclear. To biochemically reconstitute the pathway in vitro, the putative proteases along with modified proteases containing the factor Xa cleavage site were expressed by Drosophila S2 cell expression system. Purified recombinant proteins were used to examine their role in activating PPO. It is revealed that cascade is initiated by a modular SP-SP41, followed by cSP1 and cSP6. The three-step SP41/cSP1/cSP6 cascade could further activate PPO, and the PO activity was significantly enhanced in the presence of two cSP homologs (cSPHs), cSPH11 and cSPH50, suggesting the latter are cofactors for PPO activation. Moreover, baculovirus infection was efficiently blocked by the reconstituted PPO activation cascade, and the effect was boosted by cSPH11 and cSPH50. Taken together, we unraveled a conserved PPO activation cascade in H. armigera, which is similar to that exists in lepidopteran biochemical model Manduca sexta and highlighted its role in antagonizing viral infection.

17.
J Virol ; 94(15)2020 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-32434885

RESUMO

Disulfide bonds are critical for the structure and function of many proteins. Some large DNA viruses encode their own sulfhydryl oxidase for disulfide bond formation. Previous studies have demonstrated that the baculovirus-encoded sulfhydryl oxidase P33 is necessary for progeny virus production, and its enzymatic activity is important for morphogenesis and oral infectivity of baculoviruses. However, the downstream substrates of P33 in the putative redox pathway of baculoviruses are unknown. In this study, we showed that PIF5, one of the per os infectivity factors (PIFs), contained intramolecular disulfide bonds and that the disulfide bond formation was interrupted in the absence of P33. In vivo pulldown and colocalization analyses revealed that PIF5 and P33 interacted with each other during virus infection. Further, in vitro assays validated that the reduced PIF5 proteins could be oxidized by P33. To understand the contribution of disulfide bonds to the function of PIF5, several cysteine-to-serine mutants were constructed, which all interfered with the disulfide bond formation of PIF5 to different extents. All the mutants lost their oral infectivity but had no impact on infectious budding virus (BV) production or virus morphogenesis. Taken together, our results indicated PIF5 as the first identified substrate of P33. Further, the disulfide bonds in PIF5 play an essential role in its function in oral infection.IMPORTANCE Similar to some large DNA viruses that encode their own disulfide bond pathway, baculovirus encodes a viral sulfhydryl oxidase, P33. Enzyme activity of P33 is related to infectious BV production, occlusion-derived virus (ODV) envelopment, occlusion body morphogenesis, and oral infectivity, suggesting that P33 is involved in disulfide bond formation of multiple proteins. A complete disulfide bond formation pathway normally contains a sulfhydryl oxidase, a disulfide-donating enzyme, and one or more substrates. In baculovirus, apart from P33, other components of the putative pathway remain unknown. In this study, we identified PIF5 as the first substrate of P33, which is fundamental for revealing the complete disulfide bond formation pathway in baculovirus. PIF5 is essential for oral infection and is absent from the PIF complex. Our study demonstrated that native disulfide bonds in PIF5 are required for oral infection, which will help us to reveal its mode of action.


Assuntos
Dissulfetos/metabolismo , Nucleopoliedrovírus/metabolismo , Oxirredutases/metabolismo , Proteínas Virais/metabolismo , Substituição de Aminoácidos , Mutação de Sentido Incorreto , Nucleopoliedrovírus/genética , Oxirredução , Oxirredutases/genética , Proteínas Virais/genética
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