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1.
Biomed Res Int ; 2021: 8814843, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33954199

RESUMO

Objective: This study is aimed at exploring the regulatory mechanism of 73HOXC-AS1 overexpression plasmid-activated Wntß-catenin classic signaling pathway and eukaryotic initiation factor 4A (eIF4AIII) expression increased by lentivirus-eIF4AIII-RNAi (44682-1) (LV-eIF4AIII-RNAi (44682-1)). Methods: Focusing on the occurrence and progression of gastric cancer, the human gastric cancer cell line BGC823 (University Experimental Center) was taken as the research object and was transfected after subculture. According to the different ways of transfection, the cells were divided into the P1 group (LV-eIF4AIII-RNAi (44682-1) overexpressed plasmid), the P2 group (pcDNA-HOXC-AS1 overexpressed plasmid), the P3 group (LV-eIF4AIII-RNAi (44682-1) + pcDNA-HOXC-AS1), and the P4 group (no transfection, control group). Cell proliferation was detected by CCK-8 (Cell Counting Kit-8) assay, Western blotting was adopted to detect Wnt3a and P-GSK3ß proteins, Transwell assay was adopted to detect the ability of cell migration and invasion, and cell cycle and apoptosis were detected by flow cytometry. Results: The results show that the protein expression levels of Wnt3a and P-GSK3ß (glycogen synthase kinase-3ß) in the P1 and P4 groups were lower than those in the P2 and P3 groups (P < 0.05). The cell activity and clone number of BGC823 in the P3 group were higher than those in the P1, P2, and P4 groups (P < 0.05). The apoptosis rate of BGC823 cells in the P3 group was significantly higher than those in the P1, P2, and P4 groups (P < 0.05). The proportion of BGC823 cells in the P3 group at the S phase was significantly higher than those in the P1, P2, and P4 groups, while the proportion in the G2 phase was significantly lower than those in the P1, P2, and P4 groups (P < 0.05). The number of migrating and invading BGC823 cells in the P3 group was significantly higher than those in the P1, P2, and P4 groups, while the number of migrating BGC823 cells in the P4 group was significantly lower than those in the P1 and P2 groups (P < 0.05). Conclusion: The 73HOXC-AS1 overexpression plasmid-activated Wntß-catenin classic signaling pathway and eIF4AIII expression increased by LV-eIF4AIII-RNAi (44682-1) could act together on BGC823 cells to improve cell proliferation activity, migration, and invasion; inhibit cell apoptosis; and prevent cells from entering the S phase.

2.
BMC Plant Biol ; 21(1): 199, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33902454

RESUMO

BACKGROUND: Electrical impedance tomography (EIT) has rarely been applied in plant science, particularly to study plant resistance to abiotic and biotic stresses. In this study, we evaluated the freezing resistance of floribunda roses (Rosa Floribunda) during frost dehardening using the EIT technique to identify a new method for rapid and non-destructive measurement of plant freezing resistance. RESULTS: The current was the excitation source, the boundary voltage value was measured, and then the boundary voltage reconstructed value was formed. Using an imaging algorithm, the two-dimensional (2D) distribution of impedance or impedance variation was reconstructed. The EIT reconstructed values decreased obviously with the decline in freezing temperatures. The EIT reconstructed values of stems had the best fit to the logistic equation, and subsequently, the semi-lethal temperatures were calculated. The freezing resistance results evaluated using EIT reconstructed values were linearly correlated with the results of the traditional electrolyte leakage (EL) method (r = 0.93, P < 0.01). CONCLUSIONS: In conclusion, after freezing tests, the reconstructed values of EIT images could be used to quantitatively evaluate the freezing resistance of floribunda rose stems. The present study provides a reference for the further application of the EIT technique for non-destructive and rapid detection of plant freezing resistance.

3.
Nanoscale ; 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33885113

RESUMO

Most materials that feature nontrivial band topology are spin-degenerate and three dimensional, strongly restricting them from application in spintronic nanodevices. Hence, two-dimensional (2D) intrinsically spin-polarized systems with rich topological elements are still in extreme scarcity. Here, 2D A3C2 (A = Ti, Zr, and Hf) materials with the P6[combining macron]m2 type structure are reported as new ferromagnetic materials with intrinsic magnetism and good stability. Unlike the Weyl nodal lines existing in nonmagnetic 2D systems, A3C2 hosts time-reversal-breaking Weyl nodal rings (two Γ-centered, one K-centered, and one K'-centered) without spin-orbit coupling (SOC). These nodal rings still remained under SOC with magnetization along the z direction (easy magnetization axis). More interestingly, the Curie temperatures (TC) of A3C2 were determined based on the Monte Carlo simulation. Ti3C2 features an extraordinary TC (above 800 K), and those of Zr3C2 and Hf3C2 are above room temperature. Therefore, A3C2 materials are excellent platforms to study magnetic Weyl nodal lines in high TC ferromagnetic 2D materials.

4.
Nanoscale ; 13(14): 6934-6943, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33885495

RESUMO

Polymer nanocomposites with high thermal conductivity have been increasingly sought after in the electronic industry. Based on molecular dynamics simulations, this work assesses the thermal transport in polyethylene (PE) nanocomposites with the presence of a new one-dimensional nanofiller-a carbon nanothread (NTH). It is found that the axial thermal conductivity of PE nanocomposites increases linearly with the content of regularly aligned NTH fillers, while the aggregated pattern suppresses the enhancement effect. This phenomenon is explained by a stronger filler-filler interaction that reduces the intrinsic thermal conductivity of the NTH. Results show that the randomly dispersed NTHs can hardly promote heat transfer because effective heat transfer channels are lacking. Strikingly, surface functionalization has an adverse effect on the thermal conductivity due to the presence of additional voids. The presence of voids answers a long-standing open question that functionalization of the heat conductive filler only slightly improves the thermal conductivity of the polymer composite. Additionally, the transverse thermal conductivity degrades in the presence of the NTH and exhibits no clear correlation with the filler content or the distribution pattern. Overall, this study provides an in-depth understanding of the heat transfer within the polymer nanocomposites, which opens up possibilities for the preparation of highly conductive polymers.

5.
Nanotechnology ; 32(26): 265603, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33843659

RESUMO

Core-shell nanocomposites with a catalytic metal-organic framework (MOF) shell are more effective and stable than bare MOF. We have successfully designed an effective heterogeneous catalyst for the synthesis of benzimidazole by integrating acidic catalytic activity, and promoted the aerobic oxidation and magnetic recyclability of core-shell nanocomposite Fe3O4@SiO2@UiO-66. The Fe3O4@SiO2 core is encapsulated by the in situ-grown UiO-66 shell, and the UiO-66 shell retains the porous structure and crystallinity of UiO-66 with abundant exposed Lewis acid sites. It shows high catalytic ability for the synthesis of various benzimidazoles through the acid-catalyzed condensation and aerobic oxidation with in situ oxygen. The Fe3O4@SiO2 core provides magnetic recyclability of Fe3O4@SiO2@UiO-66, and maintains high catalytic ability and stability over six cycles.

6.
Eur J Med Chem ; 219: 113446, 2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33873056

RESUMO

ATPases Associated with Diverse Cellular Activity (AAA ATPase) are essential enzymes found in all organisms. They are involved in various processes such as DNA replication, protein degradation, membrane fusion, microtubule serving, peroxisome biogenesis, signal transduction, and the regulation of gene expression. Due to the importance of AAA ATPases, several researchers identified and developed small-molecule inhibitors against these enzymes. We discuss six AAA ATPases that are potential drug targets and have well-developed inhibitors. We compare available structures that suggest significant differences of the ATP binding pockets among the AAA ATPases with or without ligand. The distances from ADP to the His20 in the His-Ser-His motif and the Arg finger (Arg353 or Arg378) in both RUVBL1/2 complex structures bound with or without ADP have significant differences, suggesting dramatically different interactions of the binding site with ADP. Taken together, the inhibitors of six well-studied AAA ATPases and their structural information suggest further development of specific AAA ATPase inhibitors due to difference in their structures. Future chemical biology coupled with proteomic approaches could be employed to develop variant specific, complex specific, and pathway specific inhibitors or activators for AAA ATPase proteins.

7.
Int J Biochem Cell Biol ; 135: 105982, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33894356

RESUMO

The hypoxia-inducible factor (HIF) prolyl hydroxylases (PHDs) are dioxygenases using oxygen and 2-oxoglutarate as co-substrates. Under normoxia, PHDs hydroxylate the conserved prolyl residues of HIFα, leading to HIFα degradation. In hypoxia PHDs are inactivated, which results in HIFα accumulation. The accumulated HIFα enters nucleus and initiates gene transcription. Many studies have shown that PHDs have substrates other than HIFα, implying that they have HIF-independent non-canonical functions. Besides modulating protein stability, the PHDs-mediated prolyl hydroxylation affects protein-protein interaction and protein activity for alternative substrates. Increasing evidence indicates that PHDs also have hydroxylase-independent functions. They influence protein stability, enzyme activity, and protein-protein interaction in a hydroxylase-independent manner. These findings highlight the functional diversity and complexity of PHDs. Due to having inhibitory activity on HIFα, PHDs are proposed to act as tumor suppressors. However, research shows that PHDs exert either tumor-promoting or tumor-suppressing features. Here, we try to summarize the current understanding of PHDs hydroxylase-dependent and -independent functions and their roles in cancer.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33921256

RESUMO

The loss of hematopoietic stem cell donation (HSCD) volunteers is widespread worldwide. This study analyzed the distribution characteristics of volunteer retention between the swab sampling approach and blood sampling approach. The Shanghai branch of the China Bone Marrow Donation Program conducted a telephone follow-up with 18,963 volunteers to understand volunteer retention. Multiple logistic regression was used to analyze the distribution characteristics of volunteer retention between two different sampling approaches, and a forest plot was used to observe the distribution trend. Only 32.37% of the volunteers could be contacted, and the loss of volunteers was severe. The volunteer retention is influenced by sampling approaches and demographic characteristics, and Shanghai natives, the highly educated, and students had better retention. The volunteer retention of the swab group was better among young people and technicians, while the volunteer retention of the blood sample group was lower among public officials and workers, and the volunteer retention in the blood sample group was more significantly affected by changes in population characteristics. To enhance the stability of volunteers, managers should improve the contact channels and frequency, expand the ratio of stable volunteers, strengthen volunteer education in the process of collecting blood samples, and respect individuals' willingness.

9.
BMC Pediatr ; 21(1): 209, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33926407

RESUMO

BACKGROUND: Centronuclear myopathy (CNM), a subtype of congenital myopathy (CM), is a group of clinical and genetically heterogeneous muscle disorders. Since the discovery of the SPEG gene and disease-causing variants, only a few additional patients have been reported. CASE PRESENTATION: The child, a 13-year-old female, had delayed motor development since childhood, weakness of both lower extremities for 10 years, gait swinging, and a positive Gower sign. Her distal muscle strength of both lower extremities was grade IV. The electromyography showed myogenic damage and electromyographic changes. Her 11-year-old sister had a similar muscle weakness phenotype. Gene sequencing revealed that both sisters had SPEG compound heterozygous mutations, and the mutation sites were c.3715 + 4C > T and c.3588delC, which were derived from their parents. These variant sites have not been reported before. The muscle biopsy showed the nucleic (> 20% of fibers) were located in the center of the cell, the average diameter of type I myofibers was slightly smaller than that of type II myofibers, and the pathology of type I myofibers was dominant, which agreed with the pathological changes of centronuclear myopathy. CONCLUSIONS: The clinical phenotypes of CNM patients caused by mutations at different sites of the SPEG gene are also different. In this case, there was no cardiomyopathy. This study expanded the number of CNM cases and the mutation spectrum of the SPEG gene to provide references for prenatal diagnosis and genetic counseling.

11.
Behav Brain Res ; 409: 113327, 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33930469

RESUMO

BACKGROUND AND PURPOSE: Different atrophy of hippocampus subregions is a valuable indicator of patients with Alzheimer's disease (AD). To explore the relationship among the hippocampal subregions of patients with AD, altered gray matter structural covariance of hippocampal subregions in patients with AD was studied. MATERIALS AND METHODS: Participants were selected from the Open Access Series of Imaging Studies Database. Pearson correlations among the volume of the hippocampal subregions were generated as structural covariance network. Topological metrics for all selected sparsity ranges were calculated in the healthy controls (HCs) and patients with AD by using the GRETNA software package. Spearman correlation analysis was performed to statistically analyze the volume and Mini-mental State Examination (MMSE) scores of the hippocampal subregions of the patients with AD, with age and gender as interference covariates and corrected for false discovery rate (FDR) (p < 0.05). RESULTS: The structural covariance network properties of the hippocampal subregions of patients with AD changed. The clustering coefficient (Cp) and network efficiency (Ne) decreased, characteristic path length (Lp) increased, and the hub nodes changed. The volumes of left parasubiculum, right granule cell layer of dentate gyrus (GC-DG), right molecular layer of the hippocampus (molecular_layer_HP), right Cornu Ammonis (CA) regions CA1 of the hippocampus proper, right fimbria and right CA4 were significantly correlated with the MMSE scores. CONCLUSIONS: The structural covariance network of the hippocampal subregions of patients with AD was reorganized, and the transmission efficiency was weakened. This study explored the changes in these subregions from the network level, which may provide a new perspective and theoretical basis for the neurobiological mechanisms of patients with AD.

12.
Nanotechnology ; 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33652419

RESUMO

In this work, we predict a new polymorph of two-dimensional (2D) monolayer arsenic. This structure, named as δ-As, consists of a centrosymmetric monolayer, which is thermodynamically and kinetically stable. Distinctly different from the previously predicted monolayer arsenic with indirect band gap, the new allotrope exhibits direct band gap characteristic. Moreover, while keeping the direct band gap unchanged, the band gap of monolayer δ-As can be adjusted from 1.83 eV to 0 eV by applying zigzag-direction tensile strain, which is pronounced advantage for solar cell and photodetector applications.

13.
Mol Cancer ; 20(1): 44, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33648511

RESUMO

BACKGROUND: Although mRNA vaccines have been effective against multiple cancers, their efficacy against pancreatic adenocarcinoma (PAAD) remains undefined. Accumulating evidence suggests that immunotyping can indicate the comprehensive immune status in tumors and their immune microenvironment, which is closely associated with therapeutic response and vaccination potential. The aim of this study was to identify potent antigens in PAAD for mRNA vaccine development, and further distinguish immune subtypes of PAAD to construct an immune landscape for selecting suitable patients for vaccination. METHODS: Gene expression profiles and clinical information of 239 PAAD datasets were extracted from ICGC, and RNA-Seq data of 103 samples were retrieved from TCGA. GEPIA was used to calculate differential expression levels and prognostic indices, cBioPortal program was used to compare genetic alterations, and TIMER was used to explore correlation between genes and immune infiltrating cells. Consensus cluster was used for consistency matrix construction and data clustering, DAVID was used for functional annotation, and graph learning-based dimensional reduction was used to depict immune landscape. RESULTS: Six overexpressed and mutated tumor antigens associated with poor prognosis and infiltration of antigen presenting cells were identified in PAAD, including ADAM9, EFNB2, MET, TMOD3, TPX2, and WNT7A. Furthermore, five immune subtypes (IS1-IS5) and nine immune gene modules of PAAD were identified that were consistent in both patient cohorts. The immune subtypes showed distinct molecular, cellular and clinical characteristics. IS1 and IS2 exhibited immune-activated phenotypes and correlated to better survival compared to the other subtypes. IS4 and IS5 tumors were immunologically cold and associated with higher tumor mutation burden. Immunogenic cell death modulators, immune checkpoints, and CA125 and CA199, were also differentially expressed among the five immune subtypes. Finally, the immune landscape of PAAD showed a high degree of heterogeneity between individual patients. CONCLUSIONS: ADAM9, EFNB2, MET, TMOD3, TPX2, and WNT7A are potent antigens for developing anti-PAAD mRNA vaccine, and patients with IS4 and IS5 tumors are suitable for vaccination.

14.
Arch Microbiol ; 2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33677636

RESUMO

This study was aimed to investigate whether host plant species and lifestyles, and environmental conditions in the desert affect endophytic fungi composition. Endophytic fungal communities from parasitic plant Cynomorium songaricum and its host Nitraria tangutorum were investigated from three sites including Tonggu Naoer, Xilin Gaole, and Guazhou in Tengger and Badain Jaran Deserts in China using the next-generation sequencing of a ribosomal RNA gene region. Similarity and difference in endophytic fungal composition from different geographic locations were evaluated through multivariate statistical analysis. It showed that plant genetics was a deciding factor affecting endophytic fungal composition even when C. songaricum and N. tangutorum grow together tightly. Not only that, the fungal composition was also greatly affected by the local environment and rainfall. However, the distribution and richness of fungal species indicated that the geographical distance exerted little influence on characterizing the fungal composition. Overall, the findings suggested that plant species, parasitic or non-parasitic lifestyles of the plant, and local environment strongly affected the number and diversity of the endophytic fungal species, which may provide valuable insights into the microbe ecology, symbiosis specificity, and the tripartite relationship among parasitic plant, host, and endophytic fungi, especially under desert environment.

15.
Int J Mol Med ; 47(3)2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33655338

RESUMO

MicroRNAs (miRNAs or miRs) play important roles in osteoporosis and exhibit high potential in the therapeutic treatment of this condition. The present study aimed to explore the effects of miR­146a on bone loss noted in the jawbones of ovariectomized (OVX) rats and the interaction of miR­146a with the Wnt/ß­catenin signaling pathway. OVX Sprague­Dawley female rats were used to establish the animal model of osteoporosis (OP). Bone mineral density (BMD) was measured via dual­energy X­ray and the miR­146a levels were detected by reverse transcription­quantitative PCR. miR­146a antagonist (miR­146a­A) and negative control (miR­146a­NC) were used to examine the effects of miR­146a on OVX rats. The contents of osteocalcin and tartrate resistant phosphatase (TRAP) were detected via ELISA. Hematoxylin and eosin, and TRAP staining were used to observe the pathological changes and the number of osteoclasts in the jawbone, respectively. In addition, the expression levels of the nuclear factor of activated T cells c1 (NFATc1), c­Fos and cathepsin K (CTK) in the jawbone were detected by immunohistochemistry, whereas the expression levels of osteoprotegerin, TRAP, dickkopf1, Wnt2 and ß­catenin in the same tissues were assessed by western blot analysis. The Wnt2 activator (DKK2­C2) and inhibitor (endostatin) were used to examine the effects of miR­146a on the Wnt/ß­catenin pathway. The results indicated that the BMD was increased, whereas the contents of osteocalcin and TRAP were decreased in the miR­146a­A group compared with those noted in the OP or negative control groups (P<0.05). Although the trabecular bone area of the OP group was decreased, the conditions were improved in the miR­146a­A group. The number of osteoclasts was decreased in the miR­146a­A group compared with that noted in the OP group (P<0.05). The expression levels of NFATc1, c­Fos and CTK in the miR­146a­A group were decreased compared with those noted in the OP or negative control groups (P<0.05). Similar results were found following the comparison of the miR­146a­A group with the DKK2­C2 group. Taken together, these data demonstrated that miR­146a downregulation inhibited OP of the jawbone in OVX rats by activating the Wnt/ß­catenin signaling pathway.

16.
Artigo em Inglês | MEDLINE | ID: mdl-33689280

RESUMO

Composite solid electrolytes (CSEs) hold great promise toward safe lithium metal batteries with high energy density, due to integration of the merits of polymer matrixes and fillers. Rational design of filler nanostructures has attracted increasing attention for improving the ionic transport of CSEs in solid batteries. In this work, we fabricated open-structured Li0.33La0.557TiO3 (LLTO) nanotubes (NTs) as ion-conductive fillers in CSEs by a gradient electrospinning method for the first time. Different from nanoparticles (NPs) and nanowires (NWs), our nanotubes are composed of connected small NPs, which offer three-dimensional (3D) Li+-accessible pathways, large polymer/filler interfacial ionic conduction regions, and enhanced wettability against the polymer matrix. As a result, the solid electrolytes based on LLTO NTs and polyacrylonitrile (PAN) can display a high ionic conductivity of up to 3.6 × 10-4 S cm-1 and a wide electrochemical window of 5 V at room temperature (RT). Furthermore, Li-Li symmetric cells using the LLTO NTs/PAN CSE can work stably over 1000 h with a polarization of 20 mV. LiFePO4-Li full cells exhibit a high capacity of 142.5 mAh g-1 with a capacity retention of 90% at 0.5 C after 100 cycles. All of these results demonstrate that the design of open-structured nanotubes as fillers is a promising strategy for high-performance solid electrolytes.

17.
Nanotechnology ; 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33725669

RESUMO

The core-shell nanocomposite with catalytic metal-organic framework (MOF) shell is more effective and stable than bare MOF. We have successfully designed an effective heterogeneous catalyst for the synthesis of benzimidazole by integrating acidic catalytic activity, promoted aerobic oxidation and magnetic recyclability into core-shell nanocomposite Fe3O4@SiO2@UiO-66. Fe3O4@SiO2 core is encapsulated by the in-situ growing UiO-66 shell, and the UiO-66 shell retains the porous structure and crystallinity of UiO-66 with abundant exposed Lewis acid sites, which shows high catalytic ability for the synthesis of various benzimidazole through the acid-catalyzed condensation and aerobic oxidation with in-situ oxygen. The Fe3O4@SiO2 core provides magnetic recyclability of Fe3O4@SiO2@UiO-66, which maintains high catalytic ability and stability for 6 cycles.

18.
Mol Cancer ; 20(1): 50, 2021 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-33685460

RESUMO

BACKGROUND: The mRNA-based cancer vaccine has been considered a promising strategy and the next hotspot in cancer immunotherapy. However, its application on cholangiocarcinoma remains largely uncharacterized. This study aimed to identify potential antigens of cholangiocarcinoma for development of anti-cholangiocarcinoma mRNA vaccine, and determine immune subtypes of cholangiocarcinoma for selection of suitable patients from an extremely heterogeneous population. METHODS: Gene expression profiles and corresponding clinical information were collected from GEO and TCGA, respectively. cBioPortal was used to visualize and compare genetic alterations. GEPIA2 was used to calculate the prognostic index of the selected antigens. TIMER was used to visualize the correlation between the infiltration of antigen-presenting cells and the expression of the identified antigens. Consensus clustering analysis was performed to identify the immune subtypes. Graph learning-based dimensionality reduction analysis was conducted to visualize the immune landscape of cholangiocarcinoma. RESULTS: Three tumor antigens, such as CD247, FCGR1A, and TRRAP, correlated with superior prognoses and infiltration of antigen-presenting cells were identified in cholangiocarcinoma. Cholangiocarcinoma patients were stratified into two immune subtypes characterized by differential molecular, cellular and clinical features. Patients with the IS1 tumor had immune "hot" and immunosuppressive phenotype, whereas those with the IS2 tumor had immune "cold" phenotype. Interestingly, patients with the IS2 tumor had a superior survival than those with the IS1 tumor. Furthermore, distinct expression of immune checkpoints and immunogenic cell death modulators was observed between different immune subtype tumors. Finally, the immune landscape of cholangiocarcinoma revealed immune cell components in individual patient. CONCLUSIONS: CD247, FCGR1A, and TRRAP are potential antigens for mRNA vaccine development against cholangiocarcinoma, specifically for patients with IS2 tumors. Therefore, this study provides a theoretical basis for the anti-cholangiocarcinoma mRNA vaccine and defines suitable patients for vaccination.

19.
Biomed Pharmacother ; 137: 111322, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33761592

RESUMO

Autism spectrum disorder (ASD) is a sort of mental disorder marked by deficits in cognitive and communication abilities. To date no effective cure for this pernicious disease has been available. Valproic acid (VPA) is a broad-spectrum, antiepileptic drug, and it is also a potent teratogen. Epidemiological studies have shown that children exposed to VPA are at higher risk for ASD during the first trimester of their gestational development. Several animal and human studies have demonstrated important behavioral impairments and morphological changes in the brain following VPA treatment. However, the mechanism of VPA exposure-induced ASD remains unclear. Several factors are involved in the pathological phase of ASD, including aberrant excitation/inhibition of synaptic transmission, neuroinflammation, diminished neurogenesis, oxidative stress, etc. In this review, we aim to outline the current knowledge of the critical pathophysiological mechanisms underlying VPA exposure-induced ASD. This review will give insight toward understanding the complex nature of VPA-induced neuronal toxicity and exploring a new path toward the development of novel pharmacological treatment against ASD.

20.
Plant Cell ; 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33630095

RESUMO

Ca2+/calmodulin (CaM)-dependent protein kinase (CCaMK) is an important positive regulator of abscisic acid (ABA) and abiotic stress signaling in plants and is believed to act upstream of mitogen-activated protein kinase (MAPK) in ABA signaling. However, it is unclear how CCaMK activates MAPK in ABA signaling. Here, we show that OsDMI3, a rice (Oryza sativa) CCaMK, directly interacts with and phosphorylates OsMKK1, a MAPK kinase (MKK) in rice, in vitro and in vivo. OsDMI3 was found to directly phosphorylate Thr-25 in the N-terminus of OsMKK1, and this Thr-25 phosphorylation is OsDMI3-specific in ABA signaling. The activation of OsMKK1 and its downstream kinase OsMPK1 is dependent on Thr-25 phosphorylation of OsMKK1 in ABA signaling. Moreover, ABA treatment induces phosphorylation in the activation loop of OsMKK1, and the two phosphorylations, in the N-terminus and in the activation loop, are independent. Further analyses revealed that OsDMI3-mediated phosphorylation of OsMKK1 positively regulates ABA responses in seed germination, root growth, and tolerance to both water stress and oxidative stress. Our results indicate that OsMKK1 is a direct target of OsDMI3, and OsDMI3-mediated phosphorylation of OsMKK1 plays an important role in activating the MAPK cascade and ABA signaling.

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