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1.
World J Gastroenterol ; 30(9): 1164-1176, 2024 Mar 07.
Article En | MEDLINE | ID: mdl-38577177

BACKGROUND: Diffusion-weighted imaging (DWI) has been developed to stage liver fibrosis. However, its diagnostic performance is inconsistent among studies. Therefore, it is worth studying the diagnostic value of various diffusion models for liver fibrosis in one cohort. AIM: To evaluate the clinical potential of six diffusion-weighted models in liver fibrosis staging and compare their diagnostic performances. METHODS: This prospective study enrolled 59 patients suspected of liver disease and scheduled for liver biopsy and 17 healthy participants. All participants underwent multi-b value DWI. The main DWI-derived parameters included Mono-apparent diffusion coefficient (ADC) from mono-exponential DWI, intravoxel incoherent motion model-derived true diffusion coefficient (IVIM-D), diffusion kurtosis imaging-derived apparent diffusivity (DKI-MD), stretched exponential model-derived distributed diffusion coefficient (SEM-DDC), fractional order calculus (FROC) model-derived diffusion coefficient (FROC-D) and FROC model-derived microstructural quantity (FROC-µ), and continuous-time random-walk (CTRW) model-derived anomalous diffusion coefficient (CTRW-D) and CTRW model-derived temporal diffusion heterogeneity index (CTRW-α). The correlations between DWI-derived parameters and fibrosis stages and the parameters' diagnostic efficacy in detecting significant fibrosis (SF) were assessed and compared. RESULTS: CTRW-D (r = -0.356), CTRW-α (r = -0.297), DKI-MD (r = -0.297), FROC-D (r = -0.350), FROC-µ (r = -0.321), IVIM-D (r = -0.251), Mono-ADC (r = -0.362), and SEM-DDC (r = -0.263) were significantly correlated with fibrosis stages. The areas under the ROC curves (AUCs) of the combined index of the six models for distinguishing SF (0.697-0.747) were higher than each of the parameters alone (0.524-0.719). The DWI models' ability to detect SF was similar. The combined index of CTRW model parameters had the highest AUC (0.747). CONCLUSION: The DWI models were similarly valuable in distinguishing SF in patients with liver disease. The combined index of CTRW parameters had the highest AUC.


Diffusion Magnetic Resonance Imaging , Liver Diseases , Humans , Prospective Studies , Diffusion Magnetic Resonance Imaging/methods , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/pathology , Diffusion Tensor Imaging/methods
2.
CNS Neurosci Ther ; 30(2): e14573, 2024 02.
Article En | MEDLINE | ID: mdl-38421101

AIMS: Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive dysfunction and memory impairment. AD pathology involves protein acetylation. Previous studies have mainly focused on histone acetylation in AD, however, the roles of nonhistone acetylation in AD are less explored. METHODS: The protein acetylation and expression levels were detected by western blotting and co-immunoprecipitation. The stoichiometry of acetylation was measured by home-made and site-specific antibodies against acetylated-CaM (Ac-CaM) at K22, K95, and K116. Hippocampus-dependent learning and memory were evaluated by using the Morris water maze, novel object recognition, and contextual fear conditioning tests. RESULTS: We showed that calmodulin (CaM) acetylation is reduced in plasma of AD patients and mice. CaM acetylation and its target Ca2+ /CaM-dependent kinase II α (CaMKIIα) activity were severely impaired in AD mouse brain. The stoichiometry showed that Ac-K22, K95-CaM acetylation were decreased in AD patients and mice. Moreover, we screened and identified that lysine deacetylase 9 (HDAC9) was the main deacetylase for CaM. In addition, HDAC9 inhibition increased CaM acetylation and CaMKIIα activity, and hippocampus-dependent memory in AD mice. CONCLUSIONS: HDAC9-mediated CaM deacetylation induces memory impairment in AD, HDAC9, or CaM acetylation may become potential therapeutic targets for AD.


Alzheimer Disease , Neurodegenerative Diseases , Mice , Humans , Animals , Alzheimer Disease/metabolism , Calmodulin , Mice, Transgenic , Memory Disorders/etiology , Hippocampus/metabolism , Disease Models, Animal , Histone Deacetylases/metabolism , Repressor Proteins/metabolism
3.
Sci Rep ; 13(1): 12555, 2023 08 02.
Article En | MEDLINE | ID: mdl-37532757

This study associated the liver proton density fat fraction (PDFF), measured by multi-echo Dixon (ME-Dixon) and breath-hold single-voxel high-speed T2-corrected multi-echo 1H magnetic resonance spectroscopy (HISTO) at 1.5 T, with serum biomarkers and liver fibrosis stages. This prospective study enrolled 75 patients suspected of liver fibrosis and scheduled for liver biopsy and 23 healthy participants with normal liver function. The participant underwent ME-Dixon and HISTO scanning. The agreement of PDFF measured by ME-Dixon (PDFF-D) and HISTO (PDFF-H) were compared. Correlations between PDFF and serum fat biomarkers (total cholesterol, triglyceride, and high- and low-density lipoproteins) and the liver fibrosis stages were assessed. PDFF were compared among the liver fibrosis stages (F0-F4) based on clinical liver biopsies. The Bland-Altman plot showed agreement between PDFF-D and PDFF-H(LoA, - 4.44 to 6.75), which have high consistency (ICC 0.752, P < 0.001). The correlations with the blood serum markers were mild to moderate (PDFF-H: r = 0.261-0.410, P < 0.01; PDFF-D: r = 0.265-0.367, P < 0.01). PDFF-D, PDFF-H, and steatosis were distributed similarly among the liver fibrosis stages. PDFF-H showed a slight negative correlation with the liver fibrosis stages (r = - 0.220, P = 0.04). Both ME-Dixon and HISTO sequences measured liver fat content noninvasively. Liver fat content was not directly associated with liver fibrosis stages.


Fatty Liver , Non-alcoholic Fatty Liver Disease , Humans , Magnetic Resonance Imaging/methods , Prospective Studies , Liver/diagnostic imaging , Liver/pathology , Fatty Liver/pathology , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/pathology , Protons , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Non-alcoholic Fatty Liver Disease/pathology
4.
Sci Bull (Beijing) ; 68(19): 2180-2189, 2023 Oct 15.
Article En | MEDLINE | ID: mdl-37558535

Chemical transformation strategy is capable of fabricating nanomaterials with well-defined structures and fascinating performance via controllable crystallization kinetics in the phase transformation. V2CTx MXene has been used as precursors to fabricate vanadium porphyrin metal-organic frameworks (V-PMOFs) via the coordination of deprotonated carboxylic acid ligands. However, the rational and in-depth exploration of synthesis mechanism with the aim of enriching the variety of MXene (i.e., Ti3C2Tx) and organic ligands (i.e., catechol-based) to design new MOFs is rarely reported. Herein, we have first developed a metal ion assistant transformation strategy to synthesize three-dimensional catechol-based TiCu-HHTP (HHTP = 2,3,6,7,10,11-hexahydroxytriphenylene) MOFs with a non-interpenetrating SrSi2 (srs) framework using two-dimensional Ti3C2Tx as precursors. The unique synergetic transformation mechanism involves the electron transfer from Ti3C2Tx to electrostatically adsorbed Cu2+ ion for redox reaction, the subsequent Ti-C bond rupture for Ti4+ ion release, and the continuous chelation coordination between Ti4+/Cu2+ and HHTP. Ti3C2Tx precursors and auxiliary metal ion could be rationally substituted by V2CTx and Mn+ (e.g., Ni2+, Co2+, Mn2+, and Zn2+), respectively. This strategy lays the foundation for the design and synthesis of innovative and multifarious MOFs derived from MXene or other unconventional metal precursors.

5.
Trop Med Infect Dis ; 8(5)2023 May 06.
Article En | MEDLINE | ID: mdl-37235315

OBJECTIVES: Schistosomiasis is a zoonotic infectious disease that seriously harms people's physical and mental health. As early as 1985, the WHO suggested that health education and health promotion should be the focus of schistosomiasis prevention work. This study aimed to explore the effect of health education on controlling the risk of schistosomiasis transmission after schistosomiasis blocking and to provide a scientific basis for the further improvement of intervention strategies after schistosomiasis interruption in China and other endemic countries. METHODS: In Jiangling County, Hubei Province, China, one severe, one moderate, and one mildly endemic village were selected as the intervention group; two severe, two moderate, and two mildly endemic villages were selected as the control group. In towns with different epidemic types, a primary school was randomly selected for intervention. In September 2020, a baseline survey was carried out through a questionnaire survey to understand the knowledge, attitudes, and practices (KAP) of adults and students concerning schistosomiasis control. Next, two rounds of health education interventions for schistosomiasis control were carried out. The evaluation survey was conducted in September 2021 and the follow-up survey conducted in September 2022. RESULTS: Compared with the baseline survey, the qualified rate of the KAP on schistosomiasis prevention of the control group in the follow-up survey increased from 79.1% (584/738) to 81.0% (493/609) (p > 0.05); in the intervention group, the qualified rate of the KAP on schistosomiasis control increased from 74.9% (286/382) to 88.1% (260/295) (p < 0.001). In the baseline survey, the qualified rate of the KAP of the intervention group was lower than that of the control group, and in the follow-up survey, the qualified rate of the KAP of the intervention group was 7.2% higher than that of the control group (p < 0.05). Compared with the baseline survey, the accuracy rates of the KAP of the intervention group's adults were higher than those of the control group, with statistical significance (p < 0.001). Compared with the baseline survey, the qualified rate of the students' KAP in the follow-up survey increased from 83.8% (253/302) to 97.8% (304/311) (p < 0.001). In the follow-up survey, the accuracy rate of the knowledge, attitudes, and practices of the students was significantly different from the baseline accuracy (p < 0.001). CONCLUSION: a health education-led risk control model of schistosomiasis can significantly improve schistosomiasis control knowledge among adults and students, establishing correct attitudes and leading to the development of correct hygiene habits.

6.
Front Pharmacol ; 14: 1124845, 2023.
Article En | MEDLINE | ID: mdl-36909184

Background: Major depression is one of the most common psychiatric disorders worldwide, inflicting suffering, significant reduction in life span, and financial burdens on families and society. Mounting evidence implicates that exposure to chronic stress can induce the dysregulation of the immune system, and the activation of brain-resident innate immune cells, microglia, leading to depression-like symptoms. However, the specific mechanisms need to be further elucidated. Method: Animal models of depression were established by chronic restraint stress (CRS), and depression-like behavior was assessed by sucrose preference test (SPT), open field test (OFT), tail suspension test (TST) and forced swimming test (FST). Microglial activation was visualized by immunofluorescent and immunohistochemical staining, and microglial morphological changes were further analyzed by skeleton analysis. The levels of inflammatory cytokines were detected by western blotting and qPCR. Result: Microglial Dlg1 knockout ameliorates CRS-induced mice depression-like behavior. In contrast to the effect of Dlg1 in the LPS-induced mouse model, Dlg1 knockout had little effect on microglial density, but significantly decreased the number of activated microglia and reversed microglia morphological changes in mice challenged with CRS. Moreover, the upregulation of inflammatory cytokines following CRS exposure was partially reversed by Dlg1 deletion. Conclusion: Our study provides the evidence that Dlg1 ablation in microglia remarkedly reverses microglial activation and depression-like behavior in mice exposed to CRS, implicating a potential target for the treatment of clinical depression.

7.
Nat Commun ; 14(1): 278, 2023 Jan 17.
Article En | MEDLINE | ID: mdl-36650125

Flexible titanium carbide (Ti3C2) antenna offers a breakthrough in the penetration of information communications for the spread of Internet of Things (IoT) applications. Current configurations are constrained to multi-layer complicated designs due to the limited conformal integration of the dielectric substrate and additive-free Ti3C2 inks. Here, we report the flexible ultrawideband Ti3C2 monopole antenna by combining strategies of interfacial modification and advanced extrusion printing technology. The polydopamine, as molecular glue nano-binder, contributes the tight adhesion interactions between Ti3C2 film and commercial circuit boards for high spatial uniformity and mechanical flexibility. The bandwidth and center frequency of Ti3C2 antenna can be well maintained and the gain differences fluctuate within ±0.2 dBi at the low frequency range after the bent antenna returns to the flat state, which conquers the traditional inelastic Cu antenna. It also achieves the demo instance for the fluent and stable real-time wireless transmission in bending states.

8.
Comput Struct Biotechnol J ; 21: 940-955, 2023.
Article En | MEDLINE | ID: mdl-38213887

Advances in transcriptomic technologies have deepened our understanding of the cellular gene expression programs of multicellular organisms and provided a theoretical basis for disease diagnosis and therapy. However, both bulk and single-cell RNA sequencing approaches lose the spatial context of cells within the tissue microenvironment, and the development of spatial transcriptomics has made overall bias-free access to both transcriptional information and spatial information possible. Here, we elaborate development of spatial transcriptomic technologies to help researchers select the best-suited technology for their goals and integrate the vast amounts of data to facilitate data accessibility and availability. Then, we marshal various computational approaches to analyze spatial transcriptomic data for various purposes and describe the spatial multimodal omics and its potential for application in tumor tissue. Finally, we provide a detailed discussion and outlook of the spatial transcriptomic technologies, data resources and analysis approaches to guide current and future research on spatial transcriptomics.

9.
PLoS One ; 17(9): e0273804, 2022.
Article En | MEDLINE | ID: mdl-36107957

With the continuous development of deep learning, more and more domains use deep learning technique to solve key problems. The security issues of deep learning models have also received more and more attention. Nowadays, malware has become a huge security threat in cyberspace. Traditional signature-based malware detection methods are not adaptable to the current large-scale malware detection. Thus many deep learning-based malware detection models are widely used in real malware detection scenarios. Therefore, we need to secure the deep learning-based malware detection models. However, model testing currently focuses on image and natural language processing models. There is no related work to test deep learning-based malware detection models specifically. Therefore, to fill this gap, we propose MalFuzz. MalFuzz uses the idea of coverage-guided fuzzing to test deep learning-based malware detection models. To solve the model state representation problem, MalFuzz uses the first and last layer neuron values to approximately represent the model state. To solve the new coverage calculation problem, MalFuzz uses the fast approximate nearest neighbor algorithm to compute the new coverage. The mutation strategy and seed selection strategy in image model or natural language processing model testing is not appropriate in deep learning-based malware detection model testing. Hence MalFuzz designs the seed selection strategy and seed mutation strategy for malware detection model testing. We performed extensive experiments to demonstrate the effectiveness of MalFuzz. Based on MalConv, Convnet, and CNN 2-d, we compared the modified TensorFuzz and MAB-malware with MalFuzz. Experiment results show that MalFuzz can detect more model classification errors. Likewise, the mutation operation of MalFuzz can retain the original functionality of malware with high probability. Moreover, the seed selection strategy of MalFuzz can help us explore the model state space quickly.


Deep Learning , Algorithms , Natural Language Processing
10.
Scanning ; 2022: 1544440, 2022.
Article En | MEDLINE | ID: mdl-36177155

In order to solve the problem of the difference in the diagnostic effect of different sequences of magnetic resonance imaging (MRI) examinations for anterior and posterior cruciate ligament injuries, the author proposes an MRI rehabilitation method to relieve anterior cruciate ligament injury in dancers. This method retrospectively analyzed the clinical data of 60 patients with knee anterior and posterior cruciate ligament injuries in our hospital, and all patients were diagnosed with knee anterior and posterior cruciate ligament injuries. All patients underwent MRI 3D sequence and 2D sequence examination successively to compare anatomical measurements. This study aimed at comparing the measurements of the posterior cruciate ligament (PCL) and anterior cruciate ligament (ACL) between the two examination sequences; comparing the diagnosis; comparing the grading and judgment of the anterior and posterior cruciate ligament injuries of the knee joint between the two inspection sequences; and comparing the diagnostic coincidence rates of the two examination sequences in the complete tear of the anterior and posterior cruciate ligaments of the knee. Experimental results show that, in terms of PCL and ACL, the angle, thickness, and length of two-dimensional MRI examination were significantly different from those of MRI examination and anatomical measurement (P < 0.05); for PCL and ACL, the angle, thickness, and length of 3D MRI were not significantly different from anatomical measurements (P > 0.05). The diagnostic accuracy of 2D MRI was 83.33%, which was lower than 95.00% of 3D MRI (P < 0.05). There was no significant difference in the grading of anterior and posterior cruciate ligament injuries between the two examination sequences (P > 0.05). The diagnostic coincidence rates of 3D MRI and 2D MRI for complete tear of the anterior and posterior cruciate ligaments were 95.55% and 80.00%, respectively (P < 0.05). In conclusion, three-dimensional MRI examination can obtain higher diagnostic value for patients with knee joint anterior and posterior cruciate ligament injury.


Anterior Cruciate Ligament Injuries , Posterior Cruciate Ligament , Anterior Cruciate Ligament/diagnostic imaging , Anterior Cruciate Ligament/pathology , Anterior Cruciate Ligament Injuries/diagnostic imaging , Anterior Cruciate Ligament Injuries/pathology , Humans , Magnetic Resonance Imaging , Posterior Cruciate Ligament/diagnostic imaging , Posterior Cruciate Ligament/injuries , Posterior Cruciate Ligament/pathology , Retrospective Studies
11.
Infect Dis Poverty ; 11(1): 48, 2022 May 03.
Article En | MEDLINE | ID: mdl-35505361

BACKGROUND: The One Health (OH) concept has been promoted widely around the globe. OH framework is expected to be applied as an integrated approach to support addressing zoonotic diseases as a significant global health issue and to improve the efficiency and effectiveness of zoonosis prevention and control. This review is intended to overview the social impact of the implementation of OH on zoonosis prevention and control. METHODS: A scoping review of studies in the past 10 years was performed to overview the integration feature of OH in zoonosis prevention and control and the social impacts of OH. PubMed and Web of Science were searched for studies published in English between January 2011 and June 2021. The included studies were selected based on predefined criteria. RESULTS: Thirty-two studies were included in this review, and most of them adopted qualitative and semi-qualitative methods. More than 50% of the studies focused on zoonosis prevention and control. Most studies were conducted in low- and middle-income countries in Africa and Asia. Applying OH approach in diseases control integrates policymakers, stakeholders, and academics from various backgrounds. The impact of OH on economic is estimated that it may alleviate the burden of diseases and poverty in the long term, even though more financial support might be needed at the initial stage of OH implementation. OH implementation considers social and ecological factors related to zoonosis transmission and provides comprehensive strategies to assess and address related risks in different communities according to regions and customs. CONCLUSIONS: Based on reviewed literature, although there seems to be a lack of guidelines for assessing and visualizing the outcomes of OH implementation, which may limit the large-scale adoption of it, evidence on the contributions of implementing OH concepts on zoonosis prevention and control indicates long-term benefits to society, including a better integration of politics, stakeholders and academics to improve their cooperation, a potential to address economic issues caused by zoonosis, and a comprehensive consideration on social determinants of health during zoonosis prevention and control.


One Health , Animals , Global Health , Income , Poverty , Zoonoses/prevention & control
12.
J Vis ; 22(5): 3, 2022 04 06.
Article En | MEDLINE | ID: mdl-35412556

Stereopsis is an important depth cue for normal people, but a subset of people suffer from stereoblindness and cannot use binocular disparity as a cue to depth. Does this experience of stereoblindness modulate use of other depth cues? We investigated this question by comparing perception of 3D slant from texture for stereoblind people and stereo-normal people. Subjects performed slant discrimination and slant estimation tasks using both monocular and binocular stimuli. We found that two groups had comparable ability to discriminate slant from texture information and showed similar mappings between texture information and slant perception (biased perception toward frontal surface with texture information indicating low slants). The results suggest that the experience of stereoblindness did not change the use of texture information for slant perception. In addition, we found that stereoblind people benefitted from binocular viewing in the slant estimation task, despite their inability to use binocular disparity information. These findings are generally consistent with the optimal cue combination model of slant perception.


Depth Perception , Vision Disparity , Cues , Humans , Vision, Binocular
14.
Vision Res ; 196: 108029, 2022 07.
Article En | MEDLINE | ID: mdl-35248890

Reaches guided using monocular versus binocular vision have been found to be equally fast and accurate only when optical texture was available projected from a support surface across which the reach was performed. We now investigate what property of optical texture elements is used to perceive relative distance: image width, image height, or image shape. Participants performed reaches to match target distances. Targets appeared on a textured surface on the left and participants reached to place their hand at target distance along a surface on the right. A perturbation discriminated which texture property was being used. The righthand surface was higher than the lefthand one by either 2, 4 or 6 cm. Participants should overshoot if they matched texture image width at the target, undershoot if they matched image shape, and undershoot far distances and, depending on the overall eye height, overshoot near distances if they matched image height. In Experiment 1, participants reached by moving a joystick to control a hand avatar in a virtual environment display. Their eye height was 15 cm. For each texture property, distances were predicted from the viewing geometry. Results ruled out image width in favor of image height or shape. In Experiment 2, participants at a 50 cm eye height reached in an actual environment with the same manipulations. Results supported use of image shape (or foreshortening), consistent with findings of texture properties used in slant perception. We discuss implications for models of visually guided reaching.


Depth Perception , Vision, Binocular , Distance Perception , Humans , Vision, Monocular
15.
China CDC Wkly ; 4(8): 153-156, 2022 Feb 25.
Article En | MEDLINE | ID: mdl-35356593
16.
J Biol Chem ; 297(3): 101044, 2021 09.
Article En | MEDLINE | ID: mdl-34358562

Protein acetylation is a reversible posttranslational modification, which is regulated by lysine acetyltransferase (KAT) and lysine deacetyltransferase (KDAC). Although protein acetylation has been shown to regulate synaptic plasticity, this was mainly for histone protein acetylation. The function and regulation of nonhistone protein acetylation in synaptic plasticity and learning remain largely unknown. Calmodulin (CaM), a ubiquitous Ca2+ sensor, plays critical roles in synaptic plasticity such as long-term potentiation (LTP). During LTP induction, activation of NMDA receptor triggers Ca2+ influx, and the Ca2+ binds with CaM and activates calcium/calmodulin-dependent protein kinase IIα (CaMKIIα). In our previous study, we demonstrated that acetylation of CaM was important for synaptic plasticity and fear learning in mice. However, the KAT responsible for CaM acetylation is currently unknown. Here, following an HEK293 cell-based screen of candidate KATs, steroid receptor coactivator 3 (SRC3) is identified as the most active KAT for CaM. We further demonstrate that SRC3 interacts with and acetylates CaM in a Ca2+ and NMDA receptor-dependent manner. We also show that pharmacological inhibition or genetic downregulation of SRC3 impairs CaM acetylation, synaptic plasticity, and contextual fear learning in mice. Moreover, the effects of SRC3 inhibition on synaptic plasticity and fear learning could be rescued by 3KQ-CaM, a mutant form of CaM, which mimics acetylation. Together, these observations demonstrate that SRC3 acetylates CaM and regulates synaptic plasticity and learning in mice.


Brain/metabolism , Calmodulin/metabolism , Fear , Learning , Nuclear Receptor Coactivator 3/metabolism , Acetylation , Animals , Calcium/metabolism , Calmodulin/genetics , Male , Mice , Mice, Inbred C57BL , Neuronal Plasticity , Nuclear Receptor Coactivator 3/genetics
17.
J Biol Chem ; 297(3): 101034, 2021 09.
Article En | MEDLINE | ID: mdl-34339735

Synaptic plasticity is critical for brain function, including learning and memory. It is regulated by gene transcription and protein synthesis as well as posttranslational modifications at synapses. Although protein acetylation has been shown to be involved in the regulation of synaptic plasticity, this was mainly for histone protein acetylation. To investigate whether acetylation of nonhistone proteins is important for synaptic plasticity, we analyzed mouse brain acetylome and found that calmodulin (CaM), a ubiquitous Ca2+ sensor, was acetylated on three lysine residues, which were conserved across species. NMDA receptor-dependent long-term potentiation (LTP) is considered the most compelling form of synaptic plasticity. During LTP induction, activation of NMDA receptor triggers Ca2+ influx, and the Ca2+ binds with CaM and activates calcium/calmodulin-dependent protein kinase IIα (CaMKIIα), which is essential for LTP induction. By using home-generated and site-specific antibodies against acetylated CaM, we show that CaM acetylation is upregulated by neural activities in an NMDA receptor-dependent manner. Moreover, mutation of acetyllysines in CaM1 proteins disrupts synaptic plasticity and fear learning in a mouse model. We further demonstrate that acetylation of CaM reduces the binding free energy and increases the binding affinity toward CaMKIIα, a protein kinase pivotal to synaptic plasticity and learning. Taken together, our results demonstrate importance of CaM acetylation in regulating synaptic plasticity and learning.


Calmodulin/metabolism , Fear , Learning , Neuronal Plasticity , Acetylation , Animals , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Calmodulin/genetics , Hippocampus/enzymology , Hippocampus/metabolism , Hippocampus/physiology , In Vitro Techniques , Long-Term Synaptic Depression , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic
18.
Neurosci Bull ; 37(12): 1645-1657, 2021 Dec.
Article En | MEDLINE | ID: mdl-34228315

Steroid hormones play important roles in brain development and function. The signaling of steroid hormones depends on the interaction between steroid receptors and their coactivators. Although the function of steroid receptor coactivators has been extensively studied in other tissues, their functions in the central nervous system are less well investigated. In this study, we addressed the function of steroid receptor coactivator 3 (SRC3) - a member of the p160 SRC protein family that is expressed predominantly in the hippocampus. While hippocampal development was not altered in Src3+/- mice, hippocampus-dependent functions such as short-term memory and spatial memory were impaired. We further demonstrated that the deficient learning and memory in Src3+/- mice was strongly associated with the impairment of long-term potentiation (LTP) at Schaffer Collateral-CA1 synapses. Mechanistic studies indicated that Src3+/- mutation altered the composition of N-methyl-D-aspartate receptor subunits in the postsynaptic densities of hippocampal neurons. Finally, we showed that SRC3 regulated synaptic plasticity and learning mainly dependent on its lysine acetyltransferase activity. Taken together, these results reveal previously unknown functions of SRC3 in the hippocampus and thus may provide insight into how steroid hormones regulate brain function.


Hippocampus , Nuclear Receptor Coactivator 3 , Animals , Long-Term Potentiation , Mice , Neuronal Plasticity , Nuclear Receptor Coactivator 3/genetics , Synapses
19.
Kaohsiung J Med Sci ; 37(5): 379-391, 2021 May.
Article En | MEDLINE | ID: mdl-33502823

Cholangiocarcinoma (CCA) is a highly aggressive and malignant tumor. In this study, the effect and molecular mechanism of nuclear enriched abundant transcript 1 (NEAT1) in CCA were elucidated. The expressions of NEAT1, microRNA-186-5p (miR-186-5p), and PTP4A1 were measured by quantitative real-time PCR. The protein levels were measured by Western blotting. Kaplan-Meier analysis was performed to create survival curves. The interactions between NEAT1, miR-186-5p, and PTP4A1 were assessed through the dual luciferase reporter assay. Additionally, the cell proliferation, apoptosis, migration, and invasion were measured by colony formation, flow cytometry, the Transwell assay, and the wound healing assay, respectively. NEAT1 and PTP4A1 were significantly upregulated in CCA tissues and cells, but miR-186-5p was downregulated. NEAT1 expression was negatively correlated with the survival of CCA patients and has remarkable correlation with serum CA199 levels and lymph node metastasis. Besides, NEAT1 could act as a molecular sponge for miR-186-5p to upregulate PTP4A1 expression. More importantly, the knockdown of NEAT1 or overexpression of miR-186-5p inhibited the proliferation, migration and invasion of CCA cells, and the inhibition of miR-186-5p reversed the effects of the knockdown of NEAT1. In addition, NEAT1 could also activate the PI3K/AKT signaling pathway and regulate the epithelial-mesenchymal transition (EMT) through the miR-186-5p/PTP4A1 axis. In conclusion, NEAT1 was involved in cell proliferation, migration and invasion in CCA, and the NEAT1/miR-186-5p/PTP4A1/PI3K/AKT axis indicated novel regulatory mechanisms and therapeutics for the treatment of CCA.


Cell Cycle Proteins/metabolism , Cholangiocarcinoma/metabolism , Gene Expression Regulation , Membrane Proteins/metabolism , MicroRNAs/genetics , Protein Tyrosine Phosphatases/metabolism , RNA, Long Noncoding/metabolism , Aged , Antigens, Tumor-Associated, Carbohydrate/biosynthesis , Apoptosis , Cell Line, Tumor , Cell Movement , Cell Proliferation , Epithelial-Mesenchymal Transition , Female , Gene Expression Regulation, Neoplastic , HEK293 Cells , Humans , Kaplan-Meier Estimate , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , RNA, Long Noncoding/genetics , Signal Transduction , Wound Healing
20.
J Neurophysiol ; 124(3): 856-867, 2020 09 01.
Article En | MEDLINE | ID: mdl-32783573

Previous research has shown that both perception and oculomotor control are affected by visual illusions. While these findings appear to suggest a common code of visual processing for perception and oculomotor control, there remains the possibility that the perceptual and the oculomotor effects emerge through partially different processes. In three experiments, we replicated the previous finding that perception and saccades were both biased by the typical Müller-Lyer configurations. However, using a non-Müller-Lyer setup in which the perceptual illusion effect was much restrained, we did not observe a comparable reduction in the saccadic effect. Instead, the saccadic effect by Müller-Lyer configuration could be partially due to the center-of-gravity (CoG) effect (i.e., the tendency for saccades to land at the center of gravity of the stimuli). These results indicate that the influence of the Müller-Lyer configuration on saccadic eye movements is a mixed effect of perceptual representation and CoG, rather than exclusively due to the illusory perception. We further found that the saccadic and perceptual effects were not correlated at the trial-by-trial level, which suggest that there could be largely independent sources of noise for perception and saccadic control.NEW & NOTEWORTHY The Müller-Lyer illusion affects both perception and oculomotor control, but it is unknown whether these effects arise from the same or different underlying mechanisms. We developed a modified version of the Müller-Lyer configuration, which largely reduced the perceptual illusion effect compared with the typical configuration but reduced the saccadic effect to a much less extent. Such difference indicates that influence of the Müller-Lyer configuration on saccadic eye movements is not fully mediated by illusory perception.


Optical Illusions/physiology , Saccades/physiology , Space Perception/physiology , Visual Perception/physiology , Adult , Female , Humans , Male , Young Adult
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