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1.
Nano Lett ; 23(14): 6449-6457, 2023 Jul 26.
Article in English | MEDLINE | ID: mdl-37379096

ABSTRACT

Spin obit torque (SOT) driven magnetization switching has been used widely for encoding consumption-efficient memory and logic. However, symmetry breaking under a magnetic field is required to realize the deterministic switching in synthetic antiferromagnets with perpendicular magnetic anisotropy (PMA), which limits their potential applications. Herein, we report all electric-controlled magnetization switching in the antiferromagnetic Co/Ir/Co trilayers with vertical magnetic imbalance. Besides, the switching polarity could be reversed by optimizing the Ir thickness. By using the polarized neutron reflection (PNR) measurements, the canted noncollinear spin configuration was observed in Co/Ir/Co trilayers, which results from the competition of magnetic inhomogeneity. In addition, the asymmetric domain walls demonstrated by micromagnetic simulations result from introducing imbalance magnetism, leading to the deterministic magnetization switching in Co/Ir/Co trilayers. Our findings highlight a promising route to electric-controlled magnetism via tunable spin configuration, improve our understanding of physical mechanisms, and significantly promote industrial applications in spintronic devices.

2.
Small ; 19(38): e2300122, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37144423

ABSTRACT

As a clean and effective approach, the introduction of external magnetic fields to improve the performance of catalysts has attracted extensive attention. Owing to its room-temperature ferromagnetism, chemical stability, and earth abundance, VSe2 is expected to be a promising and cost-effective ferromagnetic electrocatalyst for the accomplishment of high-efficient spin-related OER kinetics. In this work, a facile pulsed laser deposition (PLD) method combined with rapid thermal annealing (RTA) treatment is used to successfully confine monodispersed 1T-VSe2 nanoparticles in amorphous carbon matrix. As expected, with external magnetic fields of 800 mT stimulation, the confined 1T-VSe2 nanoparticles exhibit highly efficient oxygen evolution reaction (OER) catalytic activity with an overpotential of 228 mV for 10 mA cm-2 and remarkable durability without deactivation after >100 h OER operation. The experimental results together with theoretical calculations illustrate that magnetic fields can facilitate the surface charge transfer dynamics of 1T-VSe2 , and modify the adsorption-free energy of *OOH, thus finally improving the intrinsic activity of the catalysts. This work realizes the application of ferromagnetic VSe2 electrocatalyst in highly efficient spin-dependent OER kinetics, which is expected to promote the application of transition metal chalcogenides (TMCs) in external magnetic field-assisted electrocatalysis.

3.
BMC Musculoskelet Disord ; 24(1): 46, 2023 Jan 19.
Article in English | MEDLINE | ID: mdl-36658540

ABSTRACT

BACKGROUND: Bone mineral density (BMD) and prevalence of osteoporosis may differ between urban and rural populations. This study aimed to investigate the differences in BMD characteristics between urban and rural populations in Jiangsu, China. METHODS: A total of 2,711 participants aged 20 years and older were included in the cross-sectional study. Multistage and stratified cluster random sampling was used as the sampling strategy. BMD was measured by the method of dual-energy x-ray absorptiometry (DXA). Data were collected through questionnaires/interview. BMD values at the lumbar spine (L1-L4), femoral neck, total hip, and greater trochanter were collected. Descriptive statistics were used to demonstrate the characteristics of urban and rural participants. Multivariate logistic regression analysis was utilized to analyze the factors that may be associated with osteoporosis in urban and rural populations. RESULTS: Of these participants, 1,540 (50.49%) were females and 1,363 (42.14%) were from urban. The prevalence of osteoporosis in urban and rural populations was 5.52% and 10.33%, respectively. In terms of gender, the prevalence of osteoporosis was 2.68% in males and 13.82% in females. For menopausal status, the prevalence of osteoporosis was 30.34% in postmenopausal females and 4.78% in premenopausal females. In urban populations, older age [adjusted odds ratio (AOR) = 2.36, 95%CI, 2.35-2.36), hypertension (AOR = 1.37, 95%CI, 1.36-1.37), unmarried (AOR = 4.04, 95%CI, 3.99-4.09), smoking everyday (AOR = 2.26, 95%CI, 2.23-2.28), family history of osteoporosis (AOR = 1.66, 95%CI, 1.65-1.67), dyslipidemia (AOR = 1.05, 95%CI, 1.04-1.05), and higher ß-crosslaps (ß-CTX) level (AOR = 1.02, 95%CI, 1.02-1.02) were associated with an increased risk of osteoporosis, while males (AOR = 0.04, 95%CI, 0.04-0.04), higher education level (AOR = 0.95, 95%CI, 0.95-0.95), and aquatic product intake (AOR = 0.99, 95%CI, 0.99-0.99) were related to decreased risk of osteoporosis. Similar results were also observed in rural populations, and (all P < 0.05). CONCLUSION: The prevalence of osteoporosis in rural populations was higher than that in urban populations, and the factors associated with the risk of osteoporosis were similar in urban and rural populations.


Subject(s)
Osteoporosis, Postmenopausal , Osteoporosis , Female , Humans , Male , Absorptiometry, Photon , Bone Density , Cross-Sectional Studies , Osteoporosis/diagnostic imaging , Osteoporosis/epidemiology , Prevalence , Risk Factors , Rural Population , China
4.
Int J Mol Sci ; 24(4)2023 Feb 20.
Article in English | MEDLINE | ID: mdl-36835648

ABSTRACT

The indispensable role of the SARS-CoV-2 main protease (Mpro) in the viral replication cycle and its dissimilarity to human proteases make Mpro a promising drug target. In order to identify the non-covalent Mpro inhibitors, we performed a comprehensive study using a combined computational strategy. We first screened the ZINC purchasable compound database using the pharmacophore model generated from the reference crystal structure of Mpro complexed with the inhibitor ML188. The hit compounds were then filtered by molecular docking and predicted parameters of drug-likeness and pharmacokinetics. The final molecular dynamics (MD) simulations identified three effective candidate inhibitors (ECIs) capable of maintaining binding within the substrate-binding cavity of Mpro. We further performed comparative analyses of the reference and effective complexes in terms of dynamics, thermodynamics, binding free energy (BFE), and interaction energies and modes. The results reveal that, when compared to the inter-molecular electrostatic forces/interactions, the inter-molecular van der Waals (vdW) forces/interactions are far more important in maintaining the association and determining the high affinity. Given the un-favorable effects of the inter-molecular electrostatic interactions-association destabilization by the competitive hydrogen bond (HB) interactions and the reduced binding affinity arising from the un-compensable increase in the electrostatic desolvation penalty-we suggest that enhancing the inter-molecular vdW interactions while avoiding introducing the deeply buried HBs may be a promising strategy in future inhibitor optimization.


Subject(s)
Coronavirus 3C Proteases , Protease Inhibitors , SARS-CoV-2 , Humans , COVID-19 , Molecular Docking Simulation , SARS-CoV-2/drug effects , Coronavirus 3C Proteases/antagonists & inhibitors
5.
Nano Lett ; 21(14): 5920-5930, 2021 07 28.
Article in English | MEDLINE | ID: mdl-34279108

ABSTRACT

The disease caused by SARS-CoV-2 infection threatens human health. In this study, we used high-pressure homogenization technology not only to efficiently drive the bacterial membrane to produce artificial vesicles but also to force the fusion protein ClyA-receptor binding domain (RBD) to pass through gaps in the bacterial membrane to increase the contact between ClyA-RBD and the membrane. Therefore, the load of ClyA-RBD on the membrane is substantially increased. Using this technology, we constructed a "ring-like" bacterial biomimetic vesicle (BBV) loaded with polymerized RBD (RBD-BBV). RBD-BBVs injected subcutaneously can accumulate in lymph nodes, promote antigen uptake and processing, and elicit SARS-CoV-2-specific humoral and cellular immune responses in mice. In conclusion, we evaluated the potential of this novel bacterial vesicle as a vaccine delivery system and provided a new idea for the development of SARS-CoV-2 vaccines.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , Animals , COVID-19 Vaccines , Humans , Mice , Protein Binding , SARS-CoV-2
6.
Acta Pharmacol Sin ; 42(9): 1507-1515, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33311599

ABSTRACT

Astroglioma is the most common primary tumor in the central nervous system without effective treatment strategies. Temozolomide (TMZ) is a chemotherapeutic drug to treat astroglioma but exhibits low potency and has side effects. Therefore, there is an urgent need to develop new compounds to treat astroglioma. Dalbergia sissoo Roxb was the source of Dalbergia odorifera in traditional Chinese medicine (TCM) and has been clinically used as an anti-tumor medicine. 4-Methoxydalbergione (4MOD) is purified from Dalbergia sissoo Roxb., and shows an inhibitory effect on osteosarcoma, but its effects on astroglioma have not been reported. Here, we evaluate its anti-astroglioma effects on both in vitro and in vivo models. In cultured astroglioma U87 cells, 4MOD inhibited cell proliferation and induced cell apoptosis in a time- and concentration-dependent manner. Compared with TMZ, 4MOD exhibited a tenfold greater potency of anti-astroglioma effects. 4MOD effectively stalled the cell cycle in G2 phase. Transcriptome sequencing (RNA-seq) showed that 4MOD upregulated 158 genes and downregulated 204 genes that are mainly enriched in cell membrane, cell division, cell cycle, p53, TNF, and MAPK signaling pathways, which may underlie its anti-tumor mechanisms. In a nude mouse xenograft model transplanted with U87 cells, 10 mg/kg 4MOD slowed down tumor growth rate, while at 30 mg/kg dose, it reduced tumor size. Collectively, this study demonstrates that 4MOD is a potent native compound that remarkably inhibits U87 astroglioma growth in both in vitro and in vivo models.


Subject(s)
Astrocytoma/drug therapy , Astrocytoma/metabolism , Benzoquinones/pharmacology , Animals , Apoptosis/drug effects , Astrocytoma/genetics , Astrocytoma/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Dalbergia , Drug Resistance, Neoplasm/drug effects , Gene Expression , Heterografts , Humans , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Nude
7.
Acta Pharmacol Sin ; 40(3): 410-417, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30202013

ABSTRACT

We recently reported that a CB2R agonist, GW405833 (GW), reduced both the ACh-induced Ca2+ oscillations and the L-arginine-induced Ca2+ signal enhancement in mouse pancreatic acinar cells, suggesting that GW-induced inhibition may prevent the pathogenesis of acute pancreatitis. In this study, we aim to evaluate the effects of other cannabinoid ligands on Ca2+ signaling in acinar cells. Patch-clamp whole-cell recordings were applied to measure ACh-induced intracellular Ca2+ oscillations in pancreatic acinar cells acutely dissociated from wild-type (WT), CB1R knockout (KO), and CB2R KO mice, and the pharmacological effects of various cannabinoid ligands on the Ca2+ oscillations were examined. We found that all the 8 CB2R agonists tested inhibited ACh-induced Ca2+ oscillations. Among them, GW, JWH133, and GP1a caused potent inhibition with IC50 values of 5.0, 6.7, and 1.2 µmol/L, respectively. In CB2R KO mice or in the presence of a CB2R antagonist (AM630), the inhibitory effects of these 3 CB2R agonists were abolished, suggesting that they acted through the CB2Rs. The CB1R agonist ACEA also induced inhibition of Ca2+ oscillations that existed in CB1R KO mice and in the presence of a CB1R antagonist (AM251), suggesting a non-CB1R effect. In WT, CB1R KO, and CB2R KO mice, a nonselective CBR agonist, WIN55,212-2, inhibited Ca2+ oscillations, which was not mediated by CB1Rs or CB2Rs. The endogenous cannabinoid substance, 2-arachidonoylglycerol (2-AG), did not show an inhibitory effect on Ca2+ oscillations. In conclusion, CB2R agonists play critical roles in modulating Ca2+ signals in mouse pancreatic acinar cells, while other cannabinoid ligands modulate Ca2+ oscillations in a heterogeneous manner through a CB receptor or non-CB-receptor mechanism.


Subject(s)
Acinar Cells/drug effects , Calcium/metabolism , Cannabinoid Receptor Agonists/pharmacology , Receptor, Cannabinoid, CB1/agonists , Receptor, Cannabinoid, CB2/agonists , Animals , Ligands , Male , Mice, Knockout , Pancreas/cytology
8.
PLoS Genet ; 12(8): e1006244, 2016 08.
Article in English | MEDLINE | ID: mdl-27541266

ABSTRACT

Cancer-associated fibroblasts (CAFs), the most common constituent of the tumor stoma, are known to promote tumor initiation, progression and metastasis. However, the mechanism of how cancer cells transform normal fibroblasts (NFs) into CAFs is largely unknown. In this study, we determined the contribution of miRNAs in the transformation of NFs into CAFs. We found that miR-1 and miR-206 were down-regulated, whereas miR-31 was up-regulated in lung CAFs when compared with matched NFs. Importantly, modifying the expression of these three deregulated miRNAs induced a functional conversion of NFs into CAFs and vice versa. When the miRNA-reprogrammed NFs and CAFs were co-cultured with lung cancer cells (LCCs), a similar pattern of cytokine expression profiling were observed between two groups. Using a combination of cytokine expression profiling and miRNAs algorithms, we identified VEGFA/CCL2 and FOXO3a as direct targets of miR-1, miR-206 and miR-31, respectively. Importantly, systemic delivery of anti-VEGFA/CCL2 or pre-miR-1, pre-miR-206 and anti-miR-31 significantly inhibited tumor angiogenesis, TAMs accumulation, tumor growth and lung metastasis. Our results show that miRNAs-mediated FOXO3a/VEGF/CCL2 signaling plays a prominent role in LCCs-mediated NFs into CAFs, which may have clinical implications for providing novel biomarker(s) and potential therapeutic target(s) of lung cancer in the future.


Subject(s)
Chemokine CCL2/biosynthesis , Lung Neoplasms/genetics , MicroRNAs/biosynthesis , Vascular Endothelial Growth Factor A/biosynthesis , Cancer-Associated Fibroblasts/metabolism , Cancer-Associated Fibroblasts/pathology , Cell Line, Tumor , Cellular Reprogramming/genetics , Chemokine CCL2/genetics , Forkhead Box Protein O3/biosynthesis , Forkhead Box Protein O3/genetics , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/pathology , MicroRNAs/genetics , Neoplasm Metastasis , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/pathology , Signal Transduction/genetics , Vascular Endothelial Growth Factor A/genetics
9.
Acta Pharmacol Sin ; 35(12): 1514-20, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25345744

ABSTRACT

AIM: Congo red, a secondary diazo dye, is usually used as an indicator for the presence of amyloid fibrils. Recent studies show that congo red exerts neuroprotective effects in a variety of models of neurodegenerative diseases. However, its pharmacological profile remains unknown. In this study, we investigated the effects of congo red on ACh-induced Ca(2+) oscillations in mouse pancreatic acinar cells in vitro. METHODS: Acutely dissociated pancreatic acinar cells of mice were prepared. A U-tube drug application system was used to deliver drugs into the bath. Intracellular Ca(2+) oscillations were monitored by whole-cell recording of Ca(2+)-activated Cl(-) currents and by using confocal Ca(2+) imaging. For intracellular drug application, the drug was added in pipette solution and diffused into cell after the whole-cell configuration was established. RESULTS: Bath application of ACh (10 nmol/L) induced typical Ca(2+) oscillations in dissociated pancreatic acinar cells. Addition of congo red (1, 10, 100 µmol/L) dose-dependently enhanced Ach-induced Ca(2+) oscillations, but congo red alone did not induce any detectable response. Furthermore, this enhancement depended on the concentrations of ACh: congo red markedly enhanced the Ca(2+) oscillations induced by ACh (10-30 nmol/L), but did not alter the Ca(2+) oscillations induced by ACh (100-10000 nmol/L). Congo red also enhanced the Ca(2+) oscillations induced by bath application of IP3 (30 µmol/L). Intracellular application of congo red failed to alter ACh-induced Ca(2+) oscillations. CONCLUSION: Congo red significantly modulates intracellular Ca(2+) signaling in pancreatic acinar cells, and this pharmacological effect should be fully considered when developing congo red as a novel therapeutic drug.


Subject(s)
Acetylcholine/pharmacology , Calcium Signaling/drug effects , Congo Red/pharmacology , Pancreas, Exocrine/drug effects , Animals , Calcium Channel Blockers/pharmacology , Dose-Response Relationship, Drug , Inositol 1,4,5-Trisphosphate/pharmacology , Male , Membrane Potentials , Mice , Pancreas, Exocrine/cytology , Pancreas, Exocrine/metabolism , Time Factors
10.
Comput Biol Med ; 177: 108610, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38820776

ABSTRACT

Accurately quantifying the height of central serous chorioretinopathy (CSCR) lesion is of great significance for assisting ophthalmologists in diagnosing CSCR and evaluating treatment efficacy. The manual measurement results dominated by single optical coherence tomography (OCT) B-scan image in clinical practice face the dilemma of weak reference, poor reproducibility, and experience dependence. In this context, this paper constructs two schemes: Scheme Ⅰ draws on the idea of ensemble learning, namely, integrating multiple models for locating starting key point in the height direction of lesion in the inference stage, which appropriately improves the performance of a single model. Scheme Ⅱ designs an adaptive gradient threshold (AGT) technique, followed by the construction of cascading strategy, which involves preliminary location of starting key point through deep learning, and then employs AGT for precise adjustment. This strategy not only achieves effective location for starting key point, but also significantly reduces the large appetite of deep learning model for training samples. Subsequently, AGT continues to play a crucial role in locating the terminal key point in the height direction of lesion, further demonstrating its feasibility and effectiveness. Quantitative and qualitative key point location experiments in the height direction of lesion on 1152 samples, as well as the final height measurement display, consistently conveys the superiority of the constructed schemes, especially the cascading strategy, expanding another potential tool for the comprehensive analysis of CSCR.


Subject(s)
Central Serous Chorioretinopathy , Deep Learning , Tomography, Optical Coherence , Humans , Central Serous Chorioretinopathy/diagnostic imaging , Tomography, Optical Coherence/methods , Image Interpretation, Computer-Assisted/methods , Algorithms
11.
Front Public Health ; 12: 1361911, 2024.
Article in English | MEDLINE | ID: mdl-38347931

ABSTRACT

Objective: This study aims to investigate the relationship between exposure to air pollution and adverse meteorological factors, and the risk of osteoporosis. Methods: We diagnosed osteoporosis by assessing bone mineral density through Dual-Energy X-ray absorptiometry in 2,361 participants from Jiangsu, China. Additionally, we conducted physical examinations, blood tests, and questionnaires. We evaluated pollution exposure levels using grid data, considering various lag periods (ranging from one to five years) based on participants' addresses. We utilized logistic regression analysis, adjusted for temperature, humidity, and individual factors, to examine the connections between osteoporosis and seven air pollutants: PM1, PM2.5, PM10, SO2, NO2, CO, and O3. We assessed the robustness of our study through two-pollutant models and distributed lag non-linear models (DLNM) and explored susceptibility using stratified analyses. Results: In Jiangsu, China, the prevalence of osteoporosis among individuals aged 40 and above was found to be 15.1%. A consistent association was observed between osteoporosis and the five-year average exposure to most pollutants, including PM2.5, PM10, CO, and O3. The effects of PM10 and CO remained stable even after adjusting for the presence of a second pollutant. However, the levels of PM1 and PM2.5 were significantly influenced by O3 levels. Individuals aged 60 and above, those with a BMI of 25 or higher, and males were found to be more susceptible to the effects of air pollution. Interestingly, males showed a significantly higher susceptibility to PM1 and PM2.5 compared to females. This study provides valuable insights into the long-term effects of air pollution on osteoporosis risk among the adult population in China. Conclusion: This study indicates a potential association between air pollutants and osteoporosis, particularly with long-term exposure. The risk of osteoporosis induced by air pollution is found to be higher in individuals aged 60 and above, those with a BMI greater than 25, and males. These findings underscore the need for further research and public health interventions to mitigate the impact of air pollution on bone health.


Subject(s)
Air Pollutants , Air Pollution , Environmental Pollutants , Osteoporosis , Adult , Male , Female , Humans , Particulate Matter/adverse effects , Particulate Matter/analysis , Environmental Exposure/adverse effects , Air Pollution/analysis , Air Pollutants/adverse effects , Air Pollutants/analysis , Osteoporosis/epidemiology , Osteoporosis/etiology , China/epidemiology , Temperature , Environmental Pollutants/analysis
12.
Biochem Pharmacol ; 225: 116279, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38740221

ABSTRACT

Berberine, a natural isoquinoline alkaloid, exhibits a variety of pharmacological effects, but the pharmacological targets and mechanisms remain elusive. Here, we report a novel finding that berberine inhibits acetylcholine (ACh)-induced intracellular Ca2+ oscillations, mediated through an inhibition of the muscarinic subtype 3 (M3) receptor. Patch-clamp recordings and confocal Ca2+ imaging were applied to acute dissociated pancreatic acinar cells prepared from CD1 mice to examine the effects of berberine on ACh-induced Ca2+ oscillations. Whole-cell patch-clamp recordings showed that berberine (from 0.1 to 10 µM) reduced ACh-induced Ca2+ oscillations in a concentration-dependent manner, and this inhibition also depended on ACh concentrations. The inhibitory effect of berberine neither occurred in intracellular targets nor extracellular cholecystokinin (CCK) receptors, chloride (Cl-) channels, and store-operated Ca2+ channels. Together, the results demonstrate that berberine directly inhibits the muscarinic M3 receptors, further confirmed by evidence of the interaction between berberine and M3 receptors in pancreatic acinar cells.


Subject(s)
Acinar Cells , Berberine , Calcium Signaling , Receptor, Muscarinic M3 , Animals , Berberine/pharmacology , Receptor, Muscarinic M3/metabolism , Receptor, Muscarinic M3/antagonists & inhibitors , Mice , Acinar Cells/drug effects , Acinar Cells/metabolism , Calcium Signaling/drug effects , Calcium Signaling/physiology , Pancreas/drug effects , Pancreas/metabolism , Male , Acetylcholine/metabolism , Calcium/metabolism , Dose-Response Relationship, Drug
13.
Guang Pu Xue Yu Guang Pu Fen Xi ; 33(2): 448-53, 2013 Feb.
Article in Zh | MEDLINE | ID: mdl-23697130

ABSTRACT

In order to automatically detect hemorrhages in fundus images, and develop an automated diabetic retinopathy screening system, a novel algorithm named locally adaptive region growing based on multi-template matching was established and studied. Firstly, spectral signature of major anatomical structures in fundus was studied, so that the right channel among RGB channels could be selected for different segmentation objects. Secondly, the fundus image was preprocessed by means of HSV brightness correction and contrast limited adaptive histogram equalization (CLAHE). Then, seeds of region growing were founded out by removing optic disc and vessel from the resulting image of normalized cross-correlation (NCC) template matching on the previous preprocessed image with several templates. Finally, locally adaptive region growing segmentation was used to find out the exact contours of hemorrhages, and the automated detection of the lesions was accomplished. The approach was tested on 90 different resolution fundus images with variable color, brightness and quality. Results suggest that the approach could fast and effectively detect hemorrhages in fundus images, and it is stable and robust. As a result, the approach can meet the clinical demands.


Subject(s)
Algorithms , Diabetic Retinopathy/diagnosis , Fundus Oculi , Image Processing, Computer-Assisted , Retinal Hemorrhage/diagnosis , Humans , Photography
14.
Comput Biol Med ; 155: 106648, 2023 03.
Article in English | MEDLINE | ID: mdl-36805213

ABSTRACT

The lesion boundary of central serous chorioretinopathy (CSCR) is the guarantee to guide the ophthalmologist to accurately arrange the laser spots, so as to enable this ophthalmopathy to be treated precisely. Currently, the accuracy and rapidity of manually locating CSCR lesion boundary in clinic based on single-modal fundus image are limited by imaging quality and ophthalmologist experience, which is also accompanied by poor repeatability, weak reliability and low efficiency. Consequently, a multi-modal fundus image-based lesion boundary auxiliary location method is developed. Firstly, the initial location module (ILM) is employed to achieve the preliminary location of key boundary points of CSCR lesion area on the optical coherence tomography (OCT) B-scan image, then followed by the joint location module (JLM) created based on reinforcement learning for further enhancing the location accuracy. Secondly, the scanning line detection module (SLDM) is constructed to realize the location of lesion scanning line on the scanning laser ophthalmoscope (SLO) image, so as to facilitate the cross-modal mapping of key boundary points. Finally, a simple yet effective lesion boundary location module (LBLM) is designed to assist the automatic cross-modal mapping of key boundary points and enable the final location of lesion boundary. Extensive experiments show that each module can perform well on its corresponding sub task, such as JLM, which makes the correction rate (CR) of ILM increase to 92.11%, comprehensively indicating the effectiveness and feasibility of this method in providing effective lesion boundary guidance for assisting ophthalmologists to precisely arrange the laser spots, and also opening a new research idea for the automatic location of lesion boundary of other fundus diseases.


Subject(s)
Central Serous Chorioretinopathy , Humans , Central Serous Chorioretinopathy/diagnosis , Reproducibility of Results , Fluorescein Angiography/methods , Fundus Oculi , Tomography, Optical Coherence/methods , Lasers
15.
Comput Intell Neurosci ; 2023: 1839387, 2023.
Article in English | MEDLINE | ID: mdl-36818580

ABSTRACT

Accurately and rapidly measuring the diameter of central serous chorioretinopathy (CSCR) lesion area is the key to judge the severity of CSCR and evaluate the efficacy of the corresponding treatments. Currently, the manual measurement scheme based on a single or a small number of optical coherence tomography (OCT) B-scan images encounters the dilemma of incredibility. Although manually measuring the diameters of all OCT B-scan images of a single patient can alleviate the previous issue, the situation of inefficiency will thus arise. Additionally, manual operation is subject to subjective factors of ophthalmologists, resulting in unrepeatable measurement results. Therefore, an automatic image processing method (i.e., a joint framework) based on artificial intelligence (AI) is innovatively proposed for locating the key boundary points of CSCR lesion area to assist the diameter measurement. Firstly, the initial location module (ILM) benefiting from multitask learning is properly adjusted and tentatively achieves the preliminary location of key boundary points. Secondly, the location task is formulated as a Markov decision process, aiming at further improving the location accuracy by utilizing the single agent reinforcement learning module (SARLM). Finally, the joint framework based on the ILM and SARLM is skillfully established, in which ILM provides an initial starting point for SARLM to narrow the active region of agent, and SARLM makes up for the defect of low generalization of ILM by virtue of the independent exploration ability of agent. Experiments reveal the AI-based method which joins the multitask learning, and single agent reinforcement learning paradigms enable agents to work in local region, alleviating the time-consuming problem of SARLM, performing location task in a global scope, and improving the location accuracy of ILM, thus reflecting its effectiveness and clinical application value in the task of rapidly and accurately measuring the diameter of CSCR lesions.


Subject(s)
Central Serous Chorioretinopathy , Humans , Central Serous Chorioretinopathy/pathology , Artificial Intelligence , Image Processing, Computer-Assisted , Tomography, Optical Coherence/methods , Learning
16.
RSC Adv ; 13(9): 6274-6286, 2023 Feb 14.
Article in English | MEDLINE | ID: mdl-36825290

ABSTRACT

Different HIV-1 strains have different antibody neutralization phenotypes (or CD4-dependencies). However, the molecular mechanisms underlying these differences remain to be elucidated. In this study, we constructed gp120 structural models from the CD4-dependent, neutralization-resistant JR-FL strain and the CD4-independent, neutralization-sensitive R2 strain and carried out several conventional molecular dynamics (MD) simulations and free energy landscape (FEL) constructions. Comparative analyses of the MD simulations and FELs indicated that R2 gp120 had higher global structural flexibility and greater conformational diversity than JR-FL gp120. This provides the preconditions for R2 gp120 to adopt a more open conformation than JR-FL gp120. Essential dynamics (ED) analysis showed that the collective motions of R2 gp120 tend towards an open state while those of JR-FL gp120 tend to retain a closed state. Based on conformational selection theory, R2 gp120's more readily sampled open state makes it more sensitive to neutralizing antibodies (or more CD4-independent) than JR-FL gp120, which may explain why the HIV-1 R2 and JR-FL strains show CD4-independent and -dependent phenotypes, respectively. Our study provides thermodynamic and kinetic insights into the CD4-dependent and -independent molecular mechanisms of HIV-1 gp120 and helps shed light on HIV-1 immune evasion.

17.
BMC Neurosci ; 13: 155, 2012 Dec 29.
Article in English | MEDLINE | ID: mdl-23272676

ABSTRACT

BACKGROUND: ß-amyloid (Aß) accumulation is described as a hallmark of Alzheimer's disease (AD). Aß perturbs a number of synaptic components including nicotinic acetylcholine receptors containing α7 subunits (α7-nAChRs), which are abundantly expressed in the hippocampus and found on GABAergic interneurons. We have previously demonstrated the existence of a novel, heteromeric α7ß2-nAChR in basal forebrain cholinergic neurons that exhibits high sensitivity to acute Aß exposure. To extend our previous work, we evaluated the expression and pharmacology of α7ß2-nAChRs in hippocampal interneurons and their sensitivity to Aß. RESULTS: GABAergic interneurons in the CA1 subregion of the hippocampus expressed functional α7ß2-nAChRs, which were characterized by relatively slow whole-cell current kinetics, pharmacological sensitivity to dihydro-ß-erythroidine (DHßE), a nAChR ß2* subunit selective blocker, and α7 and ß2 subunit interaction using immunoprecipitation assay. In addition, α7ß2-nAChRs were sensitive to 1 nM oligomeric Aß. Similar effects were observed in identified hippocampal interneurons prepared from GFP-GAD mice. CONCLUSION: These findings suggest that Aß modulation of cholinergic signaling in hippocampal GABAergic interneurons via α7ß2-nAChRs could be an early and critical event in Aß-induced functional abnormalities of hippocampal function, which may be relevant to learning and memory deficits in AD.


Subject(s)
Amyloid beta-Peptides/pharmacology , CA1 Region, Hippocampal/metabolism , GABAergic Neurons/metabolism , GABAergic Neurons/physiology , Interneurons/metabolism , Interneurons/physiology , Peptide Fragments/pharmacology , Receptors, Nicotinic/physiology , Animals , CA1 Region, Hippocampal/drug effects , CA1 Region, Hippocampal/physiology , Cells, Cultured , Dihydro-beta-Erythroidine/pharmacology , Gene Knock-In Techniques/methods , Interneurons/drug effects , Male , Membrane Potentials/drug effects , Membrane Potentials/physiology , Mice , Mice, Inbred C57BL , Mice, Inbred ICR , Mice, Knockout , Nicotinic Antagonists/pharmacology , Receptors, Nicotinic/biosynthesis , Receptors, Nicotinic/genetics , Receptors, Nicotinic/metabolism , alpha7 Nicotinic Acetylcholine Receptor
18.
Guang Pu Xue Yu Guang Pu Fen Xi ; 32(3): 760-4, 2012 Mar.
Article in Zh | MEDLINE | ID: mdl-22582648

ABSTRACT

The technology of automated detection of diabetic retinopathy (DR) on fundus retinal images can not only make mass screening possible, but also offer a powerful adjunct for early diagnosis, treatment of diabetic retinopathy, and scientific research on human vision. For this purpose, an algorithm based on mathematical morphology for automated detection of diabetic retinopathy was proposed. Firstly, the optic disc was segmented by mathematical morphology and threshold in order to find candidate regions possibly containing lesions. Secondly, some methods such as morphological reconstruction were applied to find the exact contours of lesions. Finally, the true lesions were found out exactly. Experimental results showed that the algorithm was fast and effective in detecting diabetic retinopathy of fundus retinal images.


Subject(s)
Diabetic Retinopathy/diagnosis , Fundus Oculi , Algorithms , Automation , Humans
19.
Guang Pu Xue Yu Guang Pu Fen Xi ; 32(7): 1795-800, 2012 Jul.
Article in Zh | MEDLINE | ID: mdl-23016327

ABSTRACT

The structure features and spatial characteristics of the two kinds of micro-machined membrane deformable mirrors, OKO 37-element and BMC 140-element, which work in the NIR based human eye aberration correction system, are compared and analyzed. At same time, the principal component analysis was carried out for the influence function of the mirror, the voltage control model was established and the optimal control mode of deformable mirror can be determined by adjusting the control parameter d. Finally, the simulation experiments for fitting aberration of unit Zernike mode and human eye aberration of Thibos model were carried out. The experiment results show that the capability for fitting the each Zernike mode of BMC 140-element mirror is twice more than the OKO 37-element mirror at least. When correcting the Thibos model human eye aberration whose average RMS error is 0.638 lambda (lambda=0.785 microm), the residual RMS error of BMC mirror is 0.063 lambda which achieves the diffraction limit (lambda/14) of the optical system, but the correction capability of OKO mirror is far less than BMC mirror due to the large cross-linked value between actuators, small density distribution of actuators and some other influencing factors, and the residual wave-front RMS error is 0.168 lambda. The methodology can also be used for other types of deformable mirror performance evaluation.


Subject(s)
Models, Theoretical , Optical Devices , Vision Disorders , Humans , Principal Component Analysis
20.
Article in Zh | MEDLINE | ID: mdl-22403997

ABSTRACT

The precise estimation of blood vessel centerline and width is a prerequisite condition for the quantitative and visualized diagnosis of blood vessel disease in fundus images. In this paper, a retinal blood vessel segmentation algorithm based on centerline extraction is proposed. According to the characteristics of the fundus image and retinal blood vessels, the image is convoluted with the masks of discrete Gaussian partial derivative kernels. The centerline is determined by differential geometric properties of the blood vessels and the width is also calculated. The precision of our method can reach sub-pixel level with a fast computation speed. The experiments on several kinds of fundus images showed that the method worked quickly and accurately.


Subject(s)
Algorithms , Image Enhancement/methods , Retinal Vessels/anatomy & histology , Fundus Oculi , Humans
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