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1.
Mol Psychiatry ; 28(4): 1679-1691, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36670199

RESUMO

N6-methyladenosine (m6A) has been demonstrated to regulate learning and memory in mice. To investigate the mechanism by which m6A modification exerts its function through its reader proteins in the hippocampus, as well as to unveil the specific subregions of the hippocampus that are crucial for memory formation, we generated dentate gyrus (DG)-, CA3-, and CA1-specific Ythdf1 and Ythdf2 conditional knockout (cKO) mice, respectively. Surprisingly, we found that only the DG-specific Ythdf2 cKO mice displayed impaired memory formation, which is inconsistent with the previous report showing that YTHDF1 was involved in this process. YTHDF2 controls the stability of its target transcripts which encode proteins that regulate the elongation of mossy fibers (MF), the axons of DG granule cells. DG-specific Ythdf2 ablation caused MF overgrowth and impairment of the MF-CA3 excitatory synapse development and transmission in the stratum lucidum. Thus, this study identifies the m6A reader YTHDF2 in dentate gyrus as the only regulator that mediates m6A modification in hippocampus-dependent learning and memory.


Assuntos
Giro Denteado , Hipocampo , Camundongos , Animais , Giro Denteado/metabolismo , Neurônios/metabolismo , Axônios/metabolismo , Sinapses/metabolismo
2.
Chaos ; 34(6)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38885070

RESUMO

The robustness of interdependent networks against perturbations is an important problem for network design and operation. This paper focuses on establishing a cascading failure dynamics model and analyzing the robustness for interdependent networks, in which the states of the nodes follow certain failure probability and various connectivity patterns. First, to describe the removal mechanism of an overloaded node, the failure probability associated with the load distribution of components was proposed. Then, we present the node capacity cost and the average capacity cost of the network to investigate the propagation of cascading failures. Finally, to discuss the impact of the configuration parameters on robustness, some numerical examples are conducted, where the robustness was analyzed based on the proposed method and different interdependence types. Our results show that, the larger the overload parameter, the more robust the network is, but this also increases the network cost. Furthermore, we find that allocating more protection resources to the nodes with higher degree can enhance the robustness of the interdependent network. The robustness of multiple-to-multiple interdependent networks outperforms that of one-to-one interdependent networks under the same coupling pattern. In addition, our results unveil that the impact of coupling strategies on the robustness of multiple-to-multiple interdependent networks is smaller than that of one-to-one interdependent networks.

3.
Dev Dyn ; 252(2): 263-275, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36063149

RESUMO

BACKGROUND: In the zebrafish midbrain, GABAergic neurons develop from precursors located in the nucleus of the medial longitudinal fasciculus (nMLF). However, the precise mechanisms that underline generation of the nMLF GABAergic neuron are poorly understood. RESULTS: GABAergic neurons in the nMLF co-express transcription factors tal2, gata2a, gata3, and nkx1.2lb. The Nodal-related gene and shh signaling are required for differentiation of nMLF GABAergic neuron precursors. Tal2 is important for nMLF GABAergic neurogenesis. Disruption of Tal2, embryos completely lack the GABA-synthesizing enzyme glutamic acid decarboxylase 67 gene (gad67) expressing cells in the nMLF, and the whole nkx1.2lb expressing cells in the midbrain. Although almost all tal2-expressing cells in the diencephalon and/or nMLF are gata2a- and gata3-positive, simultaneous knockdown of gata2a and gata3 does not affect either tal2 or gad67 expression. CONCLUSIONS: In the zebrafish midbrain, expression of tal2, gata2a, and/or gata3 is independent of each other. The function of gata2a and gata3 is dispensable for generation of GABAergic neuron in the nMLF. This suggests that the functional connections of the regulatory genes leading to generation of nMLF GABAergic neurons have diverged between mouse and zebrafish.


Assuntos
Mesencéfalo , Peixe-Zebra , Camundongos , Animais , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Mesencéfalo/metabolismo , Neurônios GABAérgicos , Diferenciação Celular , Neurogênese/genética
4.
Angew Chem Int Ed Engl ; 63(3): e202314587, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37949836

RESUMO

Preventing the misfolding or aggregation of transactive response DNA binding protein with 43 kDa (TDP-43) is the most actively pursued disease-modifying strategy to treat amyotrophic lateral sclerosis and other neurodegenerative diseases. In this work, we provide proof of concept that native state stabilization of TDP-43 is a viable and effective strategy for treating TDP-43 proteinopathies. Firstly, we leveraged the Cryo-EM structures of TDP-43 fibrils to design C-terminal substitutions that disrupt TDP-43 aggregation. Secondly, we showed that these substitutions (S333D/S342D) stabilize monomeric TDP-43 without altering its physiological properties. Thirdly, we demonstrated that binding native oligonucleotide ligands stabilized monomeric TDP-43 and prevented its fibrillization and phase separation in the absence of direct binding to the aggregation-prone C-terminal domain. Fourthly, we showed that the monomeric TDP-43 variant could be induced to aggregate in a controlled manner, which enabled the design and implementation of a high-throughput screening assay to identify native state stabilizers of TDP-43. Altogether, our findings demonstrate that different structural domains in TDP-43 could be exploited and targeted to develop drugs that stabilize the native state of TDP-43 and provide a platform to discover novel drugs to treat TDP-43 proteinopathies.


Assuntos
Esclerose Lateral Amiotrófica , Doenças Neurodegenerativas , Proteinopatias TDP-43 , Humanos , Proteinopatias TDP-43/genética , Proteinopatias TDP-43/metabolismo , Esclerose Lateral Amiotrófica/metabolismo , Proteínas de Ligação a DNA/química
5.
J Struct Biol ; 215(3): 107991, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37451561

RESUMO

Cell recognition methods are in high demand in cell biology and medicine, and the method based on atomic force microscopy (AFM) shows a great value in application. The difference in mechanical properties or morphology of cells has been frequently used to detect whether cells are cancerous, but this detection method cannot be a general means for cancer cell detection, and the traditional artificial feature extraction method also has its limitations. In this work, we proposed an analytic method based on the physical properties of cells and deep learning method for recognizing cell types. The residual neural network used for recognition was modified by multi-scale convolutional fusion, attention mechanism and depthwise separable convolution, so as to optimize feature extraction and reduce operation costs. In the method, the collected cells were imaged by AFM, and the processed images were analyzed by the optimized convolutional neural network. The recognition results of two groups of cells (HL-7702 and SMMC-7721, SGC-7901 and GES-1) by this method show that the recognition rate of dataset with the combination of cell surface morphology, adhesion and Young's modulus is higher, and the recognition rate of the dataset with optimal resolution is higher. Our study indicated that the recognition of physical properties of cells using deep learning technology can serve as a universal and effective method for the automated analysis of cell information.


Assuntos
Comunicação Celular , Redes Neurais de Computação , Microscopia de Força Atômica/métodos , Módulo de Elasticidade
6.
Neurobiol Dis ; 184: 106193, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37295561

RESUMO

Dravet syndrome (DS) is a debilitating infantile epileptic encephalopathy characterized by seizures induced by high body temperature (hyperthermia), sudden unexpected death in epilepsy (SUDEP), cognitive impairment, and behavioral disturbances. The most common cause of DS is haploinsufficiency of the SCN1A gene, which encodes the voltage-gated sodium channel Nav1.1. In current mouse models of DS, the epileptic phenotype is strictly dependent on the genetic background and most mouse models exhibit drastically higher SUDEP rates than patients. Therefore, we sought to develop an alternative animal model for DS. Here, we report the generation and characterization of a Scn1a halploinsufficiency rat model of DS by disrupting the Scn1a allele. Scn1a+/- rats show reduced Scn1a expression in the cerebral cortex, hippocampus and thalamus. Homozygous null rats die prematurely. Heterozygous animals are highly susceptible to heat-induced seizures, the clinical hallmark of DS, but are otherwise normal in survival, growth, and behavior without seizure induction. Hyperthermia-induced seizures activate distinct sets of neurons in the hippocampus and hypothalamus in Scn1a+/- rats. Electroencephalogram (EEG) recordings in Scn1a+/- rats reveal characteristic ictal EEG with high amplitude bursts with significantly increased delta and theta power. After the initial hyperthermia-induced seizures, non-convulsive, and convulsive seizures occur spontaneously in Scn1a+/- rats. In conclusion, we generate a Scn1a haploinsufficiency rat model with phenotypes closely resembling DS, providing a unique platform for establishing therapies for DS.


Assuntos
Epilepsias Mioclônicas , Epilepsia , Convulsões Febris , Morte Súbita Inesperada na Epilepsia , Camundongos , Animais , Ratos , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Epilepsias Mioclônicas/genética , Convulsões/genética , Neurônios/metabolismo , Febre/complicações , Febre/genética , Modelos Animais de Doenças
7.
Anal Chem ; 95(2): 695-702, 2023 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-36598765

RESUMO

As the usage of long-chain perfluoroalkyl and polyfluoroalkyl substances (PFASs) may be gradually restricted, short-chain and even ultra-short-chain PFASs have been widely produced and used, which has put forward new requirements for the simultaneous analysis of the above substances. Using solid phase extraction two-fraction elution and ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), an experimental method was established for the simultaneous analysis of ultrashort-chain, short-chain, and long-chain PFASs and the precursor perfluorohexanesulfonamide (FHxSA) in low-concentration water, such as tap water and bottled water. By optimizing the volume of methanol in the first-fraction elution, the concentration of ammonia in the second-fraction elution, and the concentration of ammonium acetate in the mobile phase, the high recovery and low detection limit (0.01-3 ng/L) were obtained. In addition, this method was used to measure nine tap water samples and six bottled water samples for validation, and the results showed that the concentration of PFASs in bottled water was lower than that in tap water. This study first reported the trifluoroacetic acid concentration in bottled water (6.61 ± 9.60 ng/L), which was lower than that in tap water (1712 ± 174 ng/L). The main substances in tap water and bottled water are both ultrashort-chain PFASs (C2-C3), accounting for more than 50%. There are few reports on the simultaneous analysis of ultrashort-chain, short-chain, and long-chain PFASs (C2-C18) and the precursor FHxSA in low-concentration water samples, and the new method can be further developed for different environmental media.


Assuntos
Água Potável , Fluorocarbonos , Poluentes Químicos da Água , Água Potável/análise , Cromatografia Líquida , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Poluentes Químicos da Água/análise , Fluorocarbonos/análise , Extração em Fase Sólida/métodos
8.
Haematologica ; 108(1): 150-160, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-35443559

RESUMO

Somatic mutations are recognized as an important prognostic factor in chronic myelomonocytic leukemia (CMML). However, limited data are available regarding their impact on outcomes after allogeneic hematopoietic cell transplantation (HCT). In this registry analysis conducted in collaboration with the Center for International Blood and Marrow Transplantation Registry database/sample repository, we identified 313 adult patients with CMML (median age: 64 years, range, 28- 77) who underwent allogeneic HCT during 2001-2017 and had an available biospecimen in the form of a peripheral blood sample obtained prior to the start of conditioning. In multivariate analysis, a CMML-specific prognostic scoring system (CPSS) score of intermediate-2 (HR=1.46, P=0.049) or high (HR=3.22, P=0.0004) correlated significantly with overall survival. When the molecularly informed CPSS-Mol prognostic model was applied, a high CPSS-Mol score (HR=2 P=0.0079) correlated significantly with overall survival. The most common somatic mutations were in ASXL1 (62%), TET2 (35%), KRAS/NRAS (33% combined), and SRSF2 (31%). DNMT3A and TP53 mutations were associated with decreased overall survival (HR=1.70 [95% CI: 1.11-2.60], P=0.0147 and HR=2.72 [95% CI: 1.37-5.39], P=0.0042, respectively) while DNMT3A, JAK2, and TP53 mutations were associated with decreased disease-free survival (HR=1.66 [95% CI: 1.11-2.49], P=0.0138, HR=1.79 [95% CI: 1.06-3.03], P=0.0293, and HR=2.94 [95% CI: 1.50-5.79], P=0.0018, respectively). The only mutation associated with increased relapse was TP53 (HR=2.94, P=0.0201). Nonetheless, the impact of TP53 mutations specifically should be interpreted cautiously given their rarity in CMML. We calculated the goodness of fit measured by Harrell's C-index for both the CPSS and CPSS-Mol, which were very similar. In summary, via registry data we have determined the mutational landscape in patients with CMML who underwent allogeneic HCT, and demonstrated an association between CPSS-Mol and transplant outcomes although without major improvement in the risk prediction beyond that provided by the CPSS.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mielomonocítica Crônica , Adulto , Humanos , Pessoa de Meia-Idade , Medula Óssea , Leucemia Mielomonocítica Crônica/genética , Leucemia Mielomonocítica Crônica/terapia , Mutação , Prognóstico , Idoso
9.
Crit Rev Food Sci Nutr ; : 1-17, 2023 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-37068005

RESUMO

Fermented foods are important components of the human diet. There is increasing awareness of abundant nutritional and functional properties present in fermented foods that arise from the transformation of substrates by microbial communities. Thus, it is significant to unravel the microbial communities and mechanisms of characteristic flavor formation occurring during fermentation. There has been rapid development of high-throughput and other omics technologies, such as metaproteomics and metabolomics, and as a result, there is growing recognition of the importance of integrating these approaches. The successful applications of multi-omics approaches and bioinformatics analyses have provided a solid foundation for exploring the fermentation process. Compared with single-omics, multi-omics analyses more accurately delineate microbial and molecular features, thus they are more apt to reveal the mechanisms of fermentation. This review introduces fermented foods and an overview of single-omics technologies - including metagenomics, metatranscriptomics, metaproteomics, and metabolomics. We also discuss integrated multi-omics and bioinformatic analyses and their role in recent research progress related to fermented foods, as well as summarize the main potential pathways involved in certain fermented foods. In the future, multilayered analyses of multi-omics data should be conducted to enable better understanding of flavor formation mechanisms in fermented foods.

10.
PLoS Genet ; 16(6): e1008774, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32555736

RESUMO

Cranial neural crest (NC) contributes to the developing vertebrate eye. By multidimensional, quantitative imaging, we traced the origin of the ocular NC cells to two distinct NC populations that differ in the maintenance of sox10 expression, Wnt signalling, origin, route, mode and destination of migration. The first NC population migrates to the proximal and the second NC cell group populates the distal (anterior) part of the eye. By analysing zebrafish pax6a/b compound mutants presenting anterior segment dysgenesis, we demonstrate that Pax6a/b guide the two NC populations to distinct proximodistal locations. We further provide evidence that the lens whose formation is pax6a/b-dependent and lens-derived TGFß signals contribute to the building of the anterior segment. Taken together, our results reveal multiple roles of Pax6a/b in the control of NC cells during development of the anterior segment.


Assuntos
Segmento Anterior do Olho/metabolismo , Crista Neural/metabolismo , Neurogênese , Fator de Transcrição PAX6/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Animais , Segmento Anterior do Olho/citologia , Segmento Anterior do Olho/embriologia , Movimento Celular , Mutação , Crista Neural/citologia , Crista Neural/embriologia , Neurônios/citologia , Neurônios/metabolismo , Fator de Transcrição PAX6/genética , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Peixe-Zebra , Proteínas de Peixe-Zebra/genética
11.
Sensors (Basel) ; 23(19)2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37836911

RESUMO

With the development of deep fusion intelligent control technology and the application of low-carbon energy, the number of renewable energy sources connected to the distribution grid has been increasing year by year, gradually replacing traditional distribution grids with active distribution grids. In addition, as an important component of the distribution grid, substations have a complex internal environment and numerous devices. The problems of untimely defect detection and slow response during intelligent inspections are particularly prominent, posing risks and challenges to the safe and stable operation of active distribution grids. To address these issues, this paper proposes a high-performance and lightweight substation defect detection model called YOLO-Substation-large (YOLO-SS-large) based on YOLOv5m. The model improves lightweight performance based upon the FasterNet network structure and obtains the F-YOLOv5m model. Furthermore, in order to enhance the detection performance of the model for small object defects in substations, the normalized Wasserstein distance (NWD) and complete intersection over union (CIoU) loss functions are weighted and fused to design a novel loss function called NWD-CIoU. Lastly, based on the improved model mentioned above, the dynamic head module is introduced to unify the scale-aware, spatial-aware, and task-aware attention of the object detection heads of the model. Compared to the YOLOv5m model, the YOLO-SS-Large model achieves an average precision improvement of 0.3%, FPS enhancement of 43.5%, and parameter reduction of 41.0%. This improved model demonstrates significantly enhanced comprehensive performance, better meeting the requirements of the speed and precision for substation defect detection, and plays an important role in promoting the informatization and intelligent construction of active distribution grids.

12.
Entropy (Basel) ; 25(6)2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37372193

RESUMO

Community structure exists widely in real social networks. To investigate the effect of community structure on the spreading of infectious diseases, this paper proposes a community network model that considers both the connection rate and the number of connected edges. Based on the presented community network, a new SIRS transmission model is constructed via the mean-field theory. Furthermore, the basic reproduction number of the model is calculated via the next-generation matrix method. The results reveal that the connection rate and the number of connected edges of the community nodes play crucial roles in the spreading process of infectious diseases. Specifically, it is demonstrated that the basic reproduction number of the model decreases as the community strength increases. However, the density of infected individuals within the community increases as the community strength increases. For community networks with weak strength, infectious diseases are likely not to be eradicated and eventually will become endemic. Therefore, controlling the frequency and range of intercommunity contact will be an effective initiative to curb outbreaks of infectious diseases throughout the network. Our results can provide a theoretical basis for preventing and controlling the spreading of infectious diseases.

13.
Entropy (Basel) ; 25(10)2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37895558

RESUMO

This paper proposes a SIQRS epidemic model with birth and death on a complex network, considering individual alertness. In particular, we investigate the influence of the individual behavior in the transmission of epidemics and derive the basic reproduction number depending on birth rate, death rate, alertness rate, quarantine rate. In addition, the stabilities of the disease-free equilibrium point and endemic equilibrium point are analyzed via stability theory. It is found that the emergence of individual behavior can influence the process of transmission of epidemics. Our results show that individual alertness rate is negatively correlated with basic reproduction number, while the impact of individual alertness on infectious factor is positively correlated with basic reproduction number. When the basic reproduction number is less than one, the system is stable and the disease is eventually eradicated. Nevertheless, there is an endemic equilibrium point under the condition that the basic reproduction number is more than one. Finally, numerical simulations are carried out to illustrate theoretical results.

14.
Zhongguo Zhong Yao Za Zhi ; 48(11): 3074-3085, 2023 Jun.
Artigo em Zh | MEDLINE | ID: mdl-37381966

RESUMO

The tissue distribution of Qingfei Paidu Decoction was studied by HPLC-MS/MS in vivo. Hypersil GOLD C_(18) column(2.1 mm×50 mm, 1.9 µm) was used for gradient elution with acetonitrile as the mobile phase A and 0.1% formic acid solution as the mobile phase B. High-resolution liquid chromatography-mass spectrometry in both positive and negative ion scanning mode and multiple response monitoring(MRM) mode was employed to analyze the behaviors of the active components of Qingfei Paidu Decoction in diffe-rent tissues. The results showed that 19, 9, 17, 14, 22, 19, 24, and 2 compounds were detected in plasma, heart, liver, spleen, lung, kidney, large intestine, and brain, respectively. The compounds belonged to 8 groups, covering 14 herbs in the prescription. After administration with Qingfei Paidu Decoction, the compounds were rapidly distributed in various tissues, especially in the lung, liver, large intestine, and kidney. The majority of the compounds displayed secondary distribution. This study comprehensively analyzed the distribution rules of the main active components in Qingfei Paidu Decoction and provided a basis for the clinical application.


Assuntos
Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão , Distribuição Tecidual
15.
Development ; 146(4)2019 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-30760481

RESUMO

Specification of neurons in the spinal cord relies on extrinsic and intrinsic signals, which in turn are interpreted by expression of transcription factors. V2 interneurons develop from the ventral aspects of the spinal cord. We report here a novel neuronal V2 subtype, named V2s, in zebrafish embryos. Formation of these neurons depends on the transcription factors sox1a and sox1b. They develop from common gata2a- and gata3-dependent precursors co-expressing markers of V2b and V2s interneurons. Chemical blockage of Notch signalling causes a decrease in V2s and an increase in V2b cells. Our results are consistent with the existence of at least two types of precursor arranged in a hierarchical manner in the V2 domain. V2s neurons grow long ipsilateral descending axonal projections with a short branch at the ventral midline. They acquire a glycinergic neurotransmitter type during the second day of development. Unilateral ablation of V2s interneurons causes a delay in touch-provoked escape behaviour, suggesting that V2s interneurons are involved in fast motor responses.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Interneurônios/metabolismo , Neurônios Motores/metabolismo , Fatores de Transcrição SOXB1/metabolismo , Medula Espinal/metabolismo , Peixe-Zebra/embriologia , Animais , Comportamento Animal , Fator de Transcrição GATA2/metabolismo , Genótipo , Glicina/química , Proteínas de Fluorescência Verde/metabolismo , Proteínas de Homeodomínio/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos , Camundongos Transgênicos , Mutação , Receptores Notch/metabolismo , Transdução de Sinais , Especificidade da Espécie , Medula Espinal/embriologia , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/metabolismo
16.
J Virol ; 95(6)2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33328312

RESUMO

The Tembusu virus (TMUV) PS strain, derived by several passages and plaque purifications in BHK-21 cells, displays markedly lower virulence in Pekin ducklings relative to a natural isolate of TMUV, but the potential virulence determinants and the in vivo mechanisms for substantial virulence attenuation of the passage variant remain unknown. Here, we constructed a series of chimeric and mutant viruses and assessed their virulence using a 2-day-old Pekin duckling model. We showed that residue 304 in the envelope (E) protein is the molecular determinant of TMUV virulence. Further investigations with mutant and parental viruses demonstrated that acquisition of positive charges at E protein residue 304 plays a critical role in substantial attenuation of neurovirulence and neuroinvasiveness, which is linked to enhanced binding affinity for glycosaminoglycans (GAGs). In Pekin ducklings infected by subcutaneous inoculation, an Arg at residue 304 in the E protein was shown to contribute to more rapid virus clearance from the circulation, markedly reduced viremia, and significantly decreased viral growth in the extraneural tissues and the central nervous system, relative to a Met at the corresponding residue. These findings suggest that the in vivo mechanism of virulence attenuation of the TMUV passage variant closely resembles that proposed previously for GAG-binding variants of other flaviviruses. Overall, our study provides insight into the molecular basis of TMUV virulence and the in vivo consequences of acquisition of a GAG-binding determinant at residue 304 in the E protein of TMUV.IMPORTANCE TMUV-related disease emerged in 2010 and has a significant economic impact on the duck industry. Although the disease was originally recognized to affect adult ducks, increasing evidence has shown that TMUV also causes severe disease of young ducklings. It is, therefore, essential to investigate the pathogenesis of TMUV infection in a young duckling model. The significance of our studies is in identifying E protein residue Arg304 as the molecular determinant for TMUV virulence and in clarifying the crucial role of positive charges at E protein residue 304 in virulence attenuation of a TMUV passage variant. These data will greatly enhance our understanding of the pathogenesis of TMUV infection in ducklings and have implications for development of a safe and efficient vaccine.


Assuntos
Arginina/metabolismo , Infecções por Flavivirus/virologia , Flavivirus/patogenicidade , Proteínas do Envelope Viral/metabolismo , Animais , Arginina/genética , Linhagem Celular , Sistema Nervoso Central/virologia , Cricetinae , Patos , Glicosaminoglicanos/metabolismo , Mutação , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/genética , Viremia/virologia , Virulência/genética , Replicação Viral
17.
Radiol Med ; 127(2): 154-161, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35034318

RESUMO

BACKGROUND: Pulmonary embolism (PE) associated with Mycoplasma pneumoniae pneumonia (MPP) in children has already attracted more attention. CT pulmonary angiography (CTPA) has been the preferred method for diagnosing PE, but it has some limitations, especially for children. Dual-energy spectral CT has been used in diagnosing PE in adults. PURPOSE: To evaluate the application of dual-energy spectral CT in diagnosing PE in children with MPP. MATERIALS AND METHODS: Eighty-three children with MPP and highly suspected PE, underwent CTPA with spectral imaging mode, 25 children were diagnosis with PE. Noise, clot-to-artery contrast-to-noise ratio, image quality and diagnosis confidence were calculated and assessed on nine monochromatic image sets (40 to 80 keV). CTPA images were observed for the presence, localization and embolic degrees of PE. Clots were divided into intra- and extra-consolidation clots. For extra-consolidation clots, iodine concentration (IC) of perfusion defects and normal lung, perfusion defects of four children before and after the treatment were measured and compared. For intra-consolidation clots, IC of consolidation areas with clots and consolidation areas without clot were measured and compared. RESULTS: The optimal energy level for detecting PE in children was 55 keV. 116 clots (29 extra-consolidations) were found, IC of defect regions was 0.69 ± 0.28 mg/mL (extra-consolidations) and 0.90 ± 0.23 mg/mL (intra-consolidations), both significantly lower than the 2.76 ± 0.45 mg/mL in normal lungs and 10.25 ± 1.76 mg/mL in consolidations without clots (P < 0.001). Significant difference was found in the presence or absence of perfusion defects between occlusive clots and nonocclusive clots (P < 0.001). IC of the perfusion defects significantly increased after treatment (P < 0.001). CONCLUSIONS: In dual-energy spectral CTPA, 55 keV images optimize PE detection for children, and MD images quantify pulmonary blood flow of PE, and may help to detect small clots and quantify embolic degrees.


Assuntos
Pneumonia por Mycoplasma/complicações , Pneumonia por Mycoplasma/diagnóstico por imagem , Embolia Pulmonar/complicações , Embolia Pulmonar/diagnóstico por imagem , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos , Tomografia Computadorizada por Raios X/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Mycoplasma pneumoniae , Artéria Pulmonar/diagnóstico por imagem , Reprodutibilidade dos Testes
18.
Nano Lett ; 21(22): 9601-9608, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34766784

RESUMO

Flexoelectricity is an effective tool in modulating the crystallographic structures and properties of oxides for multifunctional applications. However, engineering the nonuniform strain to obtain tunable flexoelectric behaviors at the atomic scale remains an ongoing challenge in conventional substrate-imposed ferroelectric films. Here, the regulatable flexoelectric behaviors are demonstrated at atomic scale in [110]-oriented BiFeO3 thin films, which are triggered by the strain-field coupling of high-density interfacial dislocations. Using aberration-corrected scanning transmission electron microscopy, the asymmetric polarization rotation around the single dislocation is revealed, which is induced by the gradient strain fields of the single dislocation. These strain fields are highly correlated to generate huge strain gradients between neighboring dislocations, and thereby, serial flexoelectric responses are engineered as a function of dislocation spacings in thicker BiFeO3 films. This work opens a pathway for the modulation of flexoelectric responses in ferroelectrics, which could be extended to other functional materials to create exotic phenomena.

19.
Nano Lett ; 21(14): 6274-6281, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34252283

RESUMO

SrTiO3 is generally paraelectric with centrosymmetric structure exhibiting unique quantum fluctuation related ferroelectricity. Here we reveal highly polar and periodic polarization waves in SrTiO3 at room temperature, which is stabilized by periodic tensile strains in a sandwiched PbTiO3/SrTiO3/PbTiO3 structure. Scanning transmission electron microscopy reveals that periodic a/c domain structures in PbTiO3 layers exert unique periodic tensile strains in the ultrathin SrTiO3 layer and consequently make the highly polar and periodic states of SrTiO3. The as-received polar SrTiO3 layer features peak polar ion displacement of ∼0.01 nm and peak tetragonality of ∼1.07. These peak values are larger than previous results, which are comparable to that of bulk ferroelectric PbTiO3. Our results suggest that it is possible to integrate large and periodic strain state in oxide films with exotic properties, which in turn could be useful in optical applications and information addressing when used as memory unit.

20.
Nano Lett ; 21(13): 5586-5592, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34138575

RESUMO

Dislocations often exhibit unique physical properties distinct from those of the bulk material. However, functional applications of dislocations are challenging due to difficulties in the construction of high-performance devices of dislocations. Here we demonstrate unidirectional single-dislocation Schottky diode arrays in a Fe2O3 thin film on Nb-doped SrTiO3 substrates. Conductivity measurements using conductive atomic force microscopy indicate that a net current will flow through individual dislocation Schottky diodes under forward bias and disappear under reverse bias. Under cyclic bias voltages, the single-dislocation Schottky diodes exhibit a distinct resistive switching behavior containing low-resistance and high-resistance states with a high resistance ratio of ∼103. A combined study of transmission electron microscopy and first-principles calculations reveals that the Fe2O3 dislocations comprise mixed Fe2+ and Fe3+ ions due to O deficiency and exhibit a one-dimensional electrical conductivity. The single-dislocation Schottky diodes may find applications for developing ultrahigh-density electronic and memory devices.

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