Factors associated with pregnant women's willingness to receive maternal pertussis vaccination in Guizhou Province, China: An exploratory cross-sectional study.

The rise in pertussis incidence among infants in Guizhou, China underscores the need for maternal acellular pertussis vaccine (aP) immunization, a key strategy in protecting infants from severe health consequences. However, the willingness of pregnant women in Guizhou to receive this vaccine is not well-understood. This study aimed to explore pregnant women's intentions toward maternal pertussis vaccination in Guizhou and identify the associated factors. A questionnaire based on the health belief model, was administered in an exploratory cross-sectional study from January to February 2022. Data from 564 participants were collected and analyzed. The chi-square test, Mann-Whitney U test, and Poisson regression were used to identify potential factors associated with vaccination intentions. Participants' median age was 27 y (interquartile range (IQR): 24-31), and the median number of children per participant was one. The study found that only 36.0% of the participants intended to receive the aP vaccine while 64.0% were uncertain or negative in this regard. Significant factors associated with intentions to vaccinate included perceived barriers and cues for action and perceived benefits. The major barriers for low vaccination intentions were safety concerns for both the fetus and the mother, and family members' negative attitudes. Free vaccines, perceiving preventive benefits, observing other pregnant women getting vaccinated, and healthcare provider recommendations may facilitate vaccination intentions. Multiple immune strategies should be developed or optimized to cope with the resurgence of pertussis.

Recent trends in design of healthier fat replacers: Type, replacement mechanism, sensory evaluation method and consumer acceptance.

In recent years, with the increasing awareness of consumers about the relationship between excessive fat intake and chronic diseases, such as obesity, heart disease, diabetes, etc., the demand for low-fat foods has increased year by year. However, a simple reduction of fat content in food will cause changes in physical and chemical properties, physiological properties, and sensory properties of food. Therefore, developing high-quality fat replacers to replace natural fats has become an emerging trend, and it is still a technical challenge to completely simulate the special function of natural fat in low-fat foods. This review aims to provide an overview of development trends of fat replacers, and the different types of fat replacers, the potential fat replacement mechanisms, sensory evaluation methods, and their consumer acceptance are discussed and compared, which may provide a theoretical guidance to produce fat replacers and develop more healthy low-fat products favored by consumers.

The Effect of Ionic Strength on the Formation and Stability of Ovalbumin-Xanthan Gum Complex Emulsions.

Protein-polysaccharide complexes have been widely used to stabilize emulsions, but the effect of NaCl on ovalbumin-xanthan gum (OVA-XG) complex emulsions is unclear. Therefore, OVA-XG complex emulsions with different XG concentrations at pH 5.5 were prepared, and the effects of NaCl on them were explored. The results indicated that the NaCl significantly affected the interaction force between OVA-XG complexes. The NaCl improved the adsorption of proteins at the oil-water interface and significantly enhanced emulsion stability, and the droplet size and zeta potential of the emulsion gradually decreased with increasing NaCl concentrations (0-0.08 M). In particular, 0.08 M NaCl was added to the OVA-0.2% XG emulsion, which had a minimum droplet size of 18.3 µm. Additionally, XG as a stabilizer could improve the stability of the emulsions, and the OVA-0.3% XG emulsion also exhibited good stability, even without NaCl. This study further revealed the effects of NaCl on emulsions, which has positive implications for the application of egg white proteins in food processing.

Nanotopographical cues for regulation of macrophages and osteoclasts: emerging opportunities for osseointegration.

Nanotopographical cues of bone implant surface has direct influences on various cell types during the establishment of osseointegration, a prerequisite of implant bear-loading. Given the important roles of monocyte/macrophage lineage cells in bone regeneration and remodeling, the regulation of nanotopographies on macrophages and osteoclasts has arisen considerable attentions recently. However, compared to osteoblastic cells, how nanotopographies regulate macrophages and osteoclasts has not been properly summarized. In this review, the roles and interactions of macrophages, osteoclasts and osteoblasts at different stages of bone healing is firstly presented. Then, the diversity and preparation methods of nanotopographies are summarized. Special attentions are paid to the regulation characterizations of nanotopographies on macrophages polarization and osteoclast differentiation, as well as the focal adhesion-cytoskeleton mediated mechanism. Finally, an outlook is indicated of coordinating nanotopographies, macrophages and osteoclasts to achieve better osseointegration. These comprehensive discussions may not only help to guide the optimization of bone implant surface nanostructures, but also provide an enlightenment to the osteoimmune response to external implant.

Knowledge and Willingness toward Vaccination among Pregnant Women: Comparison between Pertussis and Influenza.

BACKGROUND: Our study sought to characterize the knowledge and willingness levels regarding vaccinations against pertussis and seasonal influenza (influenza) among pregnant women in Guizhou province, China, which have previously been unclear. METHODS: In total, 11 hospitals that carried out obstetrics and antenatal examination services were randomly included in the target organizations, and 564 questionnaires completed by the pregnant women were collected and analyzed in Guizhou province. The questionnaires contained questions addressing awareness and knowledge of pertussis and influenza, willingness to be vaccinated at different life stages, and the basic statuses of subjects. A two-paired McNemar test was used to compare the knowledge levels on pertussis and influenza. A Friedman test was used to compare the willingness to be vaccinated at different life stages. To explore the factors influencing knowledge levels, a chi-square test and binary logistic regression were used with stepwise backward regression. RESULTS: In total, 11.9 percent of the pregnant women had received influenza vaccines in the year prior to their pregnancy in Guizhou province. The pregnant women had poorer knowledge of pertussis than of influenza. Given a vaccine was available, the willingness of pregnant women to partake in the following vaccination-related actions could be ranked, from highest to lowest: free vaccination of babies, recommend vaccination to family members, postpartum vaccination, vaccination of babies at mothers' expense, and vaccination during pregnancy. Knowledge levels played different roles in the women's willingness to receive vaccinations at different life stages. Common knowledge of pertussis and influenza played a limited role in the willingness to receive maternal vaccinations. Among the pregnant women, the factors influencing the low levels of pertussis knowledge were occupation as nonmedical-institution staff, lower educational level, pregnancy stage past the first trimester, and not bearing children; for influenza, the factors were occupation as nonmedical-institution staff, lower educational level, denial of pregnancy-induced disease, and lower monthly household income per capita. CONCLUSIONS: Pregnant women have poorer levels of knowledge on pertussis than influenza, whereas there was no significant difference in their willingness to be vaccinated against these conditions. Health education on pertussis should be strengthened and we called for vaccines given at birth.

DeU-Net 2.0: Enhanced deformable U-Net for 3D cardiac cine MRI segmentation.

Automatic segmentation of cardiac magnetic resonance imaging (MRI) facilitates efficient and accurate volume measurement in clinical applications. However, due to anisotropic resolution, ambiguous borders and complicated shapes, existing methods suffer from the degradation of accuracy and robustness in cardiac MRI segmentation. In this paper, we propose an enhanced Deformable U-Net (DeU-Net) for 3D cardiac cine MRI segmentation, composed of three modules, namely Temporal Deformable Aggregation Module (TDAM), Enhanced Deformable Attention Network (EDAN), and Probabilistic Noise Correction Module (PNCM). TDAM first takes consecutive cardiac MR slices (including a target slice and its neighboring reference slices) as input, and extracts spatio-temporal information by an offset prediction network to generate fused features of the target slice. Then the fused features are also fed into EDAN that exploits several flexible deformable convolutional layers and generates clear borders of every segmentation map. A Multi-Scale Attention Module (MSAM) in EDAN is proposed to capture long range dependencies between features of different scales. Meanwhile, PNCM treats the fused features as a distribution to quantify uncertainty. Experimental results show that our DeU-Net achieves the state-of-the-art performance in terms of the commonly used evaluation metrics on the Extended ACDC dataset and competitive performance on other two datasets, validating the robustness and generalization of DeU-Net.

Positron emission tomography in the COVID-19 pandemic era.

Coronavirus disease 2019 (COVID-19) has become a major public health problem worldwide since its outbreak in 2019. Currently, the spread of COVID-19 is far from over, and various complications have roused increasing awareness of the public, calling for novel techniques to aid at diagnosis and treatment. Based on the principle of molecular imaging, positron emission tomography (PET) is expected to offer pathophysiological alternations of COVID-19 in the molecular/cellular perspectives and facilitate the clinical management of patients. A number of PET-related cases and research have been reported on COVID-19 over the past one year. This article reviews the current studies of PET in the diagnosis and treatment of COVID-19, and discusses potential applications of PET in the development of management strategy for COVID-19 patients in the pandemic era.

Insights into motor carrier crashes: A preliminary investigation of FMCSA inspection violations.

Many researchers have developed predictive models of crashes based on the safety scores of commercial truck companies, but these studies have been based on aggregated data at the truck company level-evaluating the total crashes and violations per company over a period of time. This level of aggregation obscures critical information. Here, a new approach to organizing non-aggregated data is taken, and logistic regression and random forest models are applied to non-aggregated FMCSA roadside inspection, violation, and crash data at the specific vehicle level. Resampling methods are used to improve model performance where there are relatively few events of interest-crashes. These results point not to specific "unsafe" drivers, but rather, patterns of unsafe behaviors or conditions that predict roadway crashes. Working toward reducing these behaviors systematically could save lives on US highways.

Structural, Functional, and Molecular Imaging of Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder associated with both genetic and environmental risks. Neuroimaging approaches have been widely employed to parse the neurophysiological mechanisms underlying ASD, and provide critical insights into the anatomical, functional, and neurochemical changes. We reviewed recent advances in neuroimaging studies that focused on ASD by using magnetic resonance imaging (MRI), positron emission tomography (PET), or single-positron emission tomography (SPECT). Longitudinal structural MRI has delineated an abnormal developmental trajectory of ASD that is associated with cascading neurobiological processes, and functional MRI has pointed to disrupted functional neural networks. Meanwhile, PET and SPECT imaging have revealed that metabolic and neurotransmitter abnormalities may contribute to shaping the aberrant neural circuits of ASD. Future large-scale, multi-center, multimodal investigations are essential to elucidate the neurophysiological underpinnings of ASD, and facilitate the development of novel diagnostic biomarkers and better-targeted therapy.

PET imaging of neural activity, ß-amyloid, and tau in normal brain aging.

Normal brain aging is commonly associated with neural activity alteration, ß-amyloid (Aß) deposition, and tau aggregation, driving a progressive cognitive decline in normal elderly individuals. Positron emission tomography (PET) with radiotracers targeting these age-related changes has been increasingly employed to clarify the sequence of their occurrence and the evolution of clinically cognitive deficits. Herein, we reviewed recent literature on PET-based imaging of normal human brain aging in terms of neural activity, Aß, and tau. Neural hypoactivity reflected by decreased glucose utilization with PET imaging has been predominately reported in the frontal, cingulate, and temporal lobes of the normal aging brain. Aß PET imaging uncovers the pathophysiological association of Aß deposition with cognitive aging, as well as the potential mechanisms. Tau-associated cognitive changes in normal aging are likely independent of but facilitated by Aß as indicated by tau and Aß PET imaging. Future longitudinal studies using multi-radiotracer PET imaging combined with other neuroimaging modalities, such as magnetic resonance imaging (MRI) morphometry, functional MRI, and magnetoencephalography, are essential to elucidate the neuropathological underpinnings and interactions in normal brain aging.

CRISPR/Cas9-edited triple-fusion reporter gene imaging of dynamics and function of transplanted human urinary-induced pluripotent stem cell-derived cardiomyocytes.

PURPOSE: To investigate the post-transplantation behaviour and therapeutic efficacy of human urinary-induced pluripotent stem cell-derived cardiomyocytes (hUiCMs) in infarcted heart. METHODS: We used clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (CRISPR/Cas9) technology to integrate a triple-fusion (TF) reporter gene into the AAVS1 locus in human urine-derived hiPSCs (hUiPSCs) to generate TF-hUiPSCs that stably expressed monomeric red fluorescent protein for fluorescence imaging, firefly luciferase for bioluminescence imaging (BLI) and herpes simplex virus thymidine kinase for positron emission tomography (PET) imaging. RESULTS: Transplanted cardiomyocytes derived from TF-hUiPSCs (TF-hUiCMs) engrafted and proliferated in the infarcted heart as monitored by both BLI and PET imaging and significantly improved cardiac function. Under ischaemic conditions, TF-hUiCMs enhanced cardiomyocyte (CM) glucose metabolism and promoted angiogenic activity. CONCLUSION: This study established a CRISPR/Cas9-mediated multimodality reporter gene imaging system that can determine the dynamics and function of TF-hUiCMs in myocardial infarction, which is helpful for investigating the application of stem cell therapy.

Resveratrol promotes the survival and neuronal differentiation of hypoxia-conditioned neuronal progenitor cells in rats with cerebral ischemia.

Hypoxia conditioning could increase the survival of transplanted neuronal progenitor cells (NPCs) in rats with cerebral ischemia but could also hinder neuronal differentiation partly by suppressing mitochondrial metabolism. In this work, the mitochondrial metabolism of hypoxia-conditioned NPCs (hcNPCs) was upregulated via the additional administration of resveratrol, an herbal compound, to resolve the limitation of hypoxia conditioning on neuronal differentiation. Resveratrol was first applied during the in vitro neuronal differentiation of hcNPCs and concurrently promoted the differentiation, synaptogenesis, and functional development of neurons derived from hcNPCs and restored the mitochondrial metabolism. Furthermore, this herbal compound was used as an adjuvant during hcNPC transplantation in a photothrombotic stroke rat model. Resveratrol promoted neuronal differentiation and increased the long-term survival of transplanted hcNPCs. 18-fluorine fluorodeoxyglucose positron emission tomography and rotarod test showed that resveratrol and hcNPC transplantation synergistically improved the neurological and metabolic recovery of stroke rats. In conclusion, resveratrol promoted the neuronal differentiation and therapeutic efficiency of hcNPCs in stroke rats via restoring mitochondrial metabolism. This work suggested a novel approach to promote the clinical translation of NPC transplantation therapy.

Systematic imaging in medicine: a comprehensive review.

Systematic imaging can be broadly defined as the systematic identification and characterization of biological processes at multiple scales and levels. In contrast to "classical" diagnostic imaging, systematic imaging emphasizes on detecting the overall abnormalities including molecular, functional, and structural alterations occurring during disease course in a systematic manner, rather than just one aspect in a partial manner. Concomitant efforts including improvement of imaging instruments, development of novel imaging agents, and advancement of artificial intelligence are warranted for achievement of systematic imaging. It is undeniable that scientists and radiologists will play a predominant role in directing this burgeoning field. This article introduces several recent developments in imaging modalities and nanoparticles-based imaging agents, and discusses how systematic imaging can be achieved. In the near future, systematic imaging which combines multiple imaging modalities with multimodal imaging agents will pave a new avenue for comprehensive characterization of diseases, successful achievement of image-guided therapy, precise evaluation of therapeutic effects, and rapid development of novel pharmaceuticals, with the final goal of improving human health-related outcomes.

Microbial community response to the toxic effect of pentachlorophenol in paddy soil amended with an electron donor and shuttle.

Understanding the degradation of pentachlorophenol (PCP) by indigenous microorganisms stimulated by an electron donor and shuttle in paddy soil, and the influences of PCP/electron donor/shuttle on the native microbial community are important for biodegradation and ecological and environmental safety. Previous studies focused on the kinetics and the microbial actions of PCP degradation, however, the effects of toxic and antimicrobial PCP and electron donor/shuttle on the microbial community diversity and composition in paddy soil are poorly understood. In this study, the effects of PCP, an electron donor (lactate), and the electron shuttle (anthraquinone-2, 6-disulfonate, AQDS) on the microbial community in paddy soil were investigated. The results showed that the presence of PCP reduced the microbial diversity compared to the control during PCP degradation, while increased the microbial diversity was observed in response to lactate and AQDS. The addition of PCP stimulated the microorganisms involved in PCP dechlorination, including Clostridium, Desulfitobacterium, Pandoraea, and unclassified Veillonellaceae, which were dormant in raw soil without PCP stress. In all of the treatments with PCP, the addition of lactate or AQDS enhanced PCP dechlorination by stimulating the growth of functional groups involved in PCP dechlorination and by changing the microbial community during dechlorination process. The microbial community tended to be uniform after complete PCP degradation (28 days). However, when lactate and AQDS were present simultaneously in PCP-contaminated soil, lactate acted as a carbon source or electron donor to promote the activities of microbial community, and AQDS changed the redox potential because of the production of reduced AQDS. These findings enhance our understanding of the effect of PCP and a biostimulation method for PCP biodegradation in soil ecosystems at the microbial community level, and suggest the appropriate selection of an electron donor/shuttle for accelerating the bioremediation of PCP-contaminated soils.

Diagnostic Value of Interferon-Gamma Release Assays Combined with Multiple Indicators for Tuberculous Peritonitis.

OBJECTIVE: To investigate the diagnostic value of interferon-gamma release assays combined with multiple indicators for tuberculous peritonitis. METHODS: Patients who were admitted to the hospital due to suspected tuberculous peritonitis were prospectively included during the 30-month study period. Moreover, healthy individuals were recruited and included in the control group. All the study participants were assessed using various indexes, such as interferon-gamma release assays. RESULTS: A total of 180 patients with suspected tuberculous peritonitis were enrolled, and 24 were excluded. 73 patients with a confirmed diagnosis of tuberculous peritonitis were included in the tuberculous peritonitis group, 83 patients with other diseases in the other-disease control group, and 52 healthy individuals in the control group. Moreover, 83 patients in the other-disease control group and 52 participants in the control group were identified as 135 nontuberculous peritonitis patients. The area under the receiver operating characteristics curve for the QuantiFERON-TB test was 0.851 (95% confidence interval: 0.799-0.903), and the optimal cutoff value was 0.55 IU/mL, which corresponds to a sensitivity and specificity of 86.30% and 80.00%, respectively. The receiver operating characteristic curves for the combination of the QuantiFERON-TB test and the use of erythrocyte sedimentation rate, serum adenosine deaminase level, serum cancer antigen 125 level, and hypersensitive C-reactive protein level had an area under the curve of 0.859 (95% confidence interval: 0.809-0.909), with a sensitivity and specificity of 97.26% and 62.96%, respectively. CONCLUSIONS: The combined use of the QuantiFERON-TB test and multiple indexes can significantly improve the accuracy of diagnosing tuberculous peritonitis.

A novel GSK-3ß inhibitor YQ138 prevents neuronal injury induced by glutamate and brain ischemia through activation of the Nrf2 signaling pathway.

AIM: To discover neuroprotective compounds and to characterize the discovered active compound YQ138 as a novel GSK-3ß inhibitor. METHODS: Primary rat cerebellar granule cells (CGCs) were treated with glutamate, and cell viability was analyzed with MTT assay, which was used as in vitro model for screening neuroprotective compounds. Active compound was further tested in OGD- or serum deprivation-induced neuronal injury models. The expression levels of GSK-3ß downstream proteins (Nrf2, HO-1, NQO1, Tau and ß-catenin) were detected with Western blotting. For evaluating the neuroprotective effects in vivo, adult male rats were subjected to transient middle cerebral artery occlusion (tMCAO), then treated with YQ138 (10 mg/kg, iv) at 2, 4 and 6 h after ischemia onset. RESULTS: From a compound library consisting of about 2000 potential kinase inhibitors, YQ138 was found to exert neuroprotective effects: pretreatment with YQ138 (0.1-40 µmol/L) dose-dependently inhibited glutamate-induced neuronal death. Furthermore, pretreatment with YQ138 (10 µmol/L) significantly inhibited OGD- or serum deprivation-induced neuronal death. Among a panel of seven kinases tested, YQ138 selectively inhibited the activity of GSK-3ß (IC50=0.52 nmol/L). Furthermore, YQ138 dose-dependently increased the expression of ß-catenin, and decreased the phosphorylation of Tau in CGCs. Moreover, YQ138 significantly increased the expression of GSK-3ß downstream antioxidative proteins Nrf2, HO-1, NQO1, GSH and SOD in CGCs. In rats with tMCAO, administration of YQ138 significantly decreased infarct volume, improved the neurological deficit, and increased the expression of Nrf2 and HO-1 and the activities of SOD and GSH in the cerebral cortex. CONCLUSION: A novel GSK-3ß inhibitor YQ138 effectively suppresses brain ischemic injury in vitro and in vivo.

Totarol prevents neuronal injury in vitro and ameliorates brain ischemic stroke: Potential roles of Akt activation and HO-1 induction.

The natural product totarol, a phenolic diterpenoid and a major constituent isolated from the sap of Podocarpus totara, has been reported to have a potent antimicrobial activity. In this study, we determined whether totarol possessed an additional neuroprotective activity in vitro and in vivo. We found that totarol prevented glutamate- and oxygen and glucose deprivation-induced neuronal death in primary rat cerebellar granule neuronal cells and cerebral cortical neurons. Totarol increased Akt and GSK-3ß phosphorylation, Nrf2 and heme oxygenase-1 (HO-1) protein expressions and suppressed oxidative stress by increasing GSH and SOD activities. The PI3K/Akt inhibitor LY294002 prevented totarol neuroprotective effect by suppressing the totarol-induced changes in HO-1 expression and the activities of GSH and SOD. The HO-1 inhibitor ZnPPIX also prevented totarol-increased GSH and SOD activities. In a model of acute cerebral ischemic injury in Sprague-Dawley rats, produced by occlusion of the middle cerebral artery for 2h followed by 22 h or 46 h of reperfusion, totarol significantly reduced infarct volume and improved the neurological deficit. In this model, totarol increased HO-1 expression and the activities of GSH and SOD. These observations suggest that totarol may be a novel activator of the Akt/HO-1 pathway protecting against ischemic stroke through reduction of oxidative stress.

Design, synthesis and biological evaluation of tricyclic diterpene derivatives as novel neuroprotective agents against ischemic brain injury.

Lead compound 7 has neuroprotective effects, and it was discovered by screening a small synthetic natural product-like (NPL) library. Based on the lead, a series of tricyclic diterpene derivatives was designed and synthesized, and their neuroprotective effects were further evaluated against glutamate-, oxygen and glucose deprivation (OGD)- and nutrient deprivation-induced neuronal injury using cell-based assays. To our delight, most of these synthetic compounds exhibited increased neuroprotective effects and blood-brain barrier (BBB) permeability without cellular toxicity. The most potent compound, compound 30, showed significantly improved neuroprotection against neuronal injury in primary neurons. Furthermore, compound 30 exhibited remarkable neuroprotection in transient middle cerebral artery occlusion (tMCAO) rats by reducing their infarct sizes and neurological deficit scores. A mechanistic exploration using in vitro and in vivo experiments showed that the neuroprotection of these compounds was at least partly mediated by improving the levels of glutathione (GSH), superoxide dismutase (SOD) and heme oxygenase-1 (HO-1) protein. Therefore, these tricyclic diterpene derivatives could be used as promising leads for the development of a new type of neuroprotective agents against ischemic brain injury.

Synthesis and biological evaluation of 3-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-4-(indol-3-yl)-maleimides as potent, selective GSK-3ß inhibitors and neuroprotective agents.

A series of novel 3-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-4-(indol-3-yl)-maleimides were designed, prepared and evaluated for their GSK-3ß inhibitory activities. Most compounds showed high potency to GSK-3ß inhibition with high selectivity. Among them, compounds 7c, 7f, 7h, 7l and 7m significantly reduced GSK-3ß substrate Tau phosphorylation at Ser396 in primary neurons, showing the inhibition of cellular GSK-3ß. In the in vitro neuronal injury models, compounds 7c, 7f, 7h, 7l and 7m prevented neuronal death against glutamate, oxygen-glucose deprivation and nutrient serum deprivation which are associated with cerebral ischemic stroke. In the in vivo cerebral ischemia animal model, compound 7f reduced infarct size by 15% and improved the neurological deficit following focal cerebral ischemia. These findings may provide new insights into the development of novel GSK-3ß inhibitors with potential neuroprotective activity.

Synthesis and Evaluation of 3-(furo[2,3-b]pyridin-3-yl)-4-(1H-indol-3-yl)-maleimides as Novel GSK-3ß Inhibitors and Anti-Ischemic Agents.

A series of novel 3-(furo[2,3-b]pyridin-3-yl)-4-(1H-indol-3-yl)-maleimides were designed, synthesized, and biologically evaluated for their GSK-3ß inhibitory activities. Most compounds showed favorable inhibitory activities against GSK-3ß protein. Among them, compounds 5n, 5o, and 5p significantly reduced GSK-3ß substrate tau phosphorylation at Ser396 in primary neurons, indicating inhibition of cellular GSK-3ß activity. In the in vitro neuronal injury models, compounds 5n, 5o, and 5p prevented neuronal death against glutamate, oxygen-glucose deprivation, and nutrient serum deprivation which are closely associated with cerebral ischemic stroke. In the in vivo cerebral ischemia animal model, compound 5o reduced infarct size by 10% and improved the neurological deficit. The results may provide new insights into the development of novel GSK-3ß inhibitors with potential neuroprotective activity against brain ischemic stroke.