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Brain microvascular endothelial cells (BMECs) dysfunction is related to the pathogenesis of neurovascular complication of diabetes mellitus that adversely lead to various CNS disorders. Mitoquinone (MitoQ) is a mitochondria targeted antioxidant that exerts multiple protective effects in many oxidative damage-related diseases. In this study, we determined the protective effects of MitoQ on high glucose (HG)-induced BMECs injury and investigated the underlying mechanism. We found that HG significantly reduced the expression of Nrf2 and HO-1, decreased mitochondrial membrane potential, increased intracellular and mitochondrial reactive oxygen species (ROS) generation, induced cytoskeletal damage and apoptosis in BMECs. In addition, Mito tempol, a mitochondrial ROS scavenger, significantly reduced HG-induced mitochondrial ROS production and attenuated cytoskeletal damage and cell apoptosis, suggesting MtROS production was involved in HG-induced BMECs injury. Moreover, we found that MitoQ treatment significantly upregulated the expression of Nrf2 and HO-1 in HG-induced BMECs, which is accompanied by improved mitochondrial membrane potential and decreased MtROS production. Meanwhile, MitoQ treatment also remarkably attenuated HG-induced cytoskeletal damage and cell apoptosis in BMECs. However, inhibitor of Nrf2 with ML385 impaired the protective effects of MitoQ in HG-induced BMECs. In conclusion, our results suggest that MitoQ exerts protective effect on HG-induced BMECs injury via activating Nrf2/HO-1 pathway.
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Encéfalo/citologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Heme Oxigenase-1/metabolismo , Proteínas de Membrana/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Compostos Organofosforados/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Ubiquinona/análogos & derivados , Animais , Antioxidantes , Apoptose/efeitos dos fármacos , Células Cultivadas , Glucose/efeitos adversos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ubiquinona/farmacologiaRESUMO
OBJECTIVE: To investigate the influence of home nurture environment on language development and social emotion in children with developmental language disorder (DLD). METHODS: The 1-3 Years Child Home Nurture Environment Scale, Gesell Developmental Scale, and Infant-Toddler Social and Emotional Assessment Scale were used for the evaluation of 125 children with DLD. A total of 130 children with normal language development matched for age and sex were enrolled as control group. RESULTS: Compared with the control group, the DLD group had a significantly higher proportion of children in a bad home nurture environment and significantly lower scores of all domains of home nurture environment (P<0.05). In children with DLD, the home nurture environment score was positively correlated with the level of language development (r=0.536, P<0.01) and the score of ability domain in social emotion (r=0.397, P<0.01) and was negatively correlated with the scores of the domains of explicit behavior, covert behavior, and imbalance in social emotion (r=-0.455, -0.438, and -0.390 respectively, P<0.01). Home nurture environment had direct influence on language development in children with DLD and affected their language development via the mediating effect of social emotion. CONCLUSIONS: Home nurture environment influences language development and social emotion in children with DLD, and social emotion has a partial mediating effect between home nurture environment and language development.
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Emoções , Transtornos do Desenvolvimento da Linguagem/psicologia , Desenvolvimento da Linguagem , Pré-Escolar , Meio Ambiente , Feminino , Humanos , Lactente , Masculino , Comportamento SocialRESUMO
Background: Preeclampsia (PE) is a hypertensive disorder of pregnancy characterized by widespread maternal endothelial dysfunction. Although clinical signs subside following delivery, long-term risks associated with PE include hypertension, stroke, and cardiovascular disease. MicroRNAs (miRNAs) are emerging as critical regulators of biological function, and while alterations to the miRNAs have been described in the context of pregnancy and PE, the postpartum implications of PE on miRNA expression are unknown. In the present study, we aimed to determine the clinical performance of miR-296 in PE. Methods: First, the clinical information and outcomes of all the participants were collected and analyzed. Afterward, the miR-296 expressions in the serum samples from healthy pregnant women and women with PE at different periods were detected using quantitative real-time polymerase chain reaction (qRT-PCR). Then, the receive operation characteristic (ROC) curve was used to determine the diagnostic value of miR-296 in PE. Finally, the at-term placentals were collected, the expressions of miR-296 in different groups were compared at first blood collection and at delivery. Results: In this study, we found that miR-296 expression was significantly increased in the placenta samples from PE patients compared with that in healthy controls both in early onset group (EOPE, p < 0.01) and late onset group (LOPE, p < 0.01). Furthermore, results of ROC analysis showed miR-296 might be a putative biomarker for early onset preeclampsia and late onset preeclampsia diagnosis with an area under the curve (AUC) of 0.84 (95% confidence interval 0.75-0.92) and 0.85 (95% confidence interval 0.77-0.93). Last but not the least, the expressions of miR-296 were significantly increased (p < 0.05) in serum samples of EOPE and LOPE patients (p < 0.001), and serum and placental levels of the miR-296 was positively correlated for EOPE (r = 0.5574, p < 0.001) and LOPE (r = 0.6613, p < 0.001) patients, respectively. Meanwhile, compared with those at first blood collection, the expression of miR-296 in EOPE (p = 0.05) and LOPE (p = 0.01) were significantly decreased at delivery. Conclusion: miR-296 may function as a putative diagnostic biomarker for PE and contribute to identifying at-risk mothers in pregnancy.
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MicroRNAs , Pré-Eclâmpsia , Humanos , Gravidez , Feminino , Placenta/metabolismo , Pré-Eclâmpsia/genética , MicroRNAs/metabolismo , Biomarcadores/metabolismoRESUMO
This is the protocol for a Campbell systematic review. The objectives are as follows. We will solve the following questions: (1) What are the characteristics of skills training services for individuals experiencing or at risk of homelessness? (2) How effectively do the different skills training programs improve employment status, work and life skills, or housing stability? (3) What factors are associated with the variation in the effectiveness of skills training services?
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Gut microbiota has been identified as a unique endocrine organ linked to the development of cardiovascular disease and other illnesses, especially deteriorated in overweight and obese postmenopausal women. The object of this systematic review and meta-analysis aimed to assess the effects of oral supplementation with probiotics for overweight and obese postmenopausal women. We performed a systematic search for randomized controlled trials (RCTs) from inception to April 2022 in MEDLINE, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov. We also performed a hand search by reviewing reference lists to identify trials. The risk of bias in individual studies was assessed with the Cochrane risk of bias tool for randomized trials (RoB). Two reviewers independently selected studies and collected data. There were 6 studies from 5 RCTs with 281 participants in this systematic review. Compared with the placebo, the probiotics supplementation group had reductions in insulin (MD - 4.20 IU/L (95% CI - 8.11 to - 0.30 IU/L), I2 = 54%), HOMA-IR (MD - 1.25 (95% CI - 2.49 to - 0.01), I2 = 50%), and TNF-α (MD - 0.12 pg/mL (95% CI - 0.22 to - 0.01 pg/mL), I2 = 44%). Improvements were also shown in body adiposity and lipid profile, but these effects were nonsignificant. In addition to body adiposity and cardiovascular risk markers, one trial showed the administration of probiotics also had an effect on iron metabolism. In conclusion, probiotics have a potential benefit on glucose metabolism and inflammatory process in overweight and obese postmenopausal women, but this effect is mild. It demonstrates that oral probiotics supplementation can be a complementary treatment for improving the fitness of postmenopausal women with overweight and obesity.
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Sobrepeso , Probióticos , Feminino , Humanos , Sobrepeso/tratamento farmacológico , Pós-Menopausa , Ensaios Clínicos Controlados Aleatórios como Assunto , Obesidade/tratamento farmacológicoRESUMO
Background: The debate over the impact of vitamin D in assisted reproduction continues. The purpose of our study was to assess embryo quality and pregnancy outcomes among groups with different levels of vitamin D after the first in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycle in patients with normal ovarian reserve (NOR). Methods: Patients in this retrospective cohort study were divided into three groups: severe vitamin D deficiency group (25OH-D < 10 ng/ml), vitamin D deficiency group (10 ng/ml ≤ 25OH-D < 20 ng/ml), and non-vitamin D deficiency group (25OH-D ≥ 20 ng/ml). The primary outcome was clinical pregnancy, while the secondary outcomes were mature oocytes, oocyte fertilization, available cleavage embryos, available blastocysts, biochemical pregnancy, early abortion, and embryo implantation. A modified Poisson regression model and multiple linear regression analysis were conducted for the multivariate analysis. Results: 264 NOR patients undergoing the first IVF/ICSI cycles were included. For the primary outcome, there was no significant difference in clinical pregnancy between the severe vitamin D deficiency group and the other two groups (vitamin D deficiency group: adjusted RR = 1.026; 0.780 - 1.350; P = 0.854; non-vitamin D deficiency group: adjusted RR = 1.092; 0.743 - 1.605; P = 0.652). For all secondary outcomes, no significant differences were observed among the severe vitamin D deficiency, vitamin D deficiency, and non-vitamin D deficiency groups (P > 0.05). Exploratory subgroup analyses concerning the season of embryo transfer, phase of embryo transferred, and endometrial thickness, as well as the sensitivity analysis using logistic regression models for the primary outcome, revealed comparable clinical pregnancy rates among the groups (P > 0.05). Subgroup analysis concerning ovarian stimulation protocol indicated that in the subgroup of gonadotrophin-releasing hormone (GnRH) antagonist protocol, the clinical pregnancy rate of the non-vitamin D deficiency group was significantly higher than that of the other two groups (P < 0.05). Conclusion: Serum vitamin D level was not associated with embryo quality and pregnancy outcomes for patients with NOR. Further studies with greater sample sizes and a longer follow-up period are needed to elucidate the relationships between vitamin D levels and IVF outcomes.
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Reserva Ovariana , Vitamina D , Masculino , Feminino , Gravidez , Humanos , Estudos Retrospectivos , Injeções de Esperma Intracitoplásmicas , Sêmen , Vitaminas , Fertilização in vitro , Antagonistas de HormôniosRESUMO
This is the protocol for an evidence and gap map. The objectives are as follows: To map available randomized control trials, economic evaluations, and systematic reviews that assess the effectiveness and cost-effectiveness of non-pharmacological interventions for older people with a diagnosis of depression and identify any existing gaps in the evidence that can inform future research.
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AIM: Although Cognitive behavioural therapy (CBT) potentially holds efficacy in addressing functional abdominal pain disorders (FAPDs) amongst children and adolescents, the persistent efficacy is uncertain. METHODS: We searched three databases to identify related randomized controlled trials (RCTs). Meta-analysis was performed using RevMan and Stata. Subgroup analyses were mainly conducted based on follow-up time. The GRADE approach was used to evaluate the certainty of the evidence. RESULTS: A total of 14 RCTs evaluating 858 patients were included. All RCTs were rated as having a high risk of bias. Compared with control groups, CBT was associated with improvement of general functional impairment (standardized mean difference (SMD) = -0.77, 95% CI [-1.12, -0.42], p < 0.05), higher treatment success (relative risk (RR) = 2.35, 95% CI [1.50, 3.69], p < 0.05), improvement of abdominal pain symptoms (SMD = -0.48, 95% CI [-0.73, -0.23], p < 0.05), QoL (SMD = 0.42, 95% CI [0.20, 0.64], p < 0.05), and psychological states (SMD = -0.95, 95% CI [-1.62, -0.27], p < 0.05). CONCLUSION: This meta-analysis provides low to moderate quality evidence that CBT could significantly improve clinical outcomes and QoL for children and adolescents with FAPDs with improvement persisting until short-term follow-up. However, there were discrepancies regarding CBT's effects at mid- and long-term follow-up across different outcomes. More high-quality and longer-duration studies are thus warranted to explore the effectiveness of CBT in the future. SYSTEMATIC REVIEW REGISTRATION ON PROSPERO: CRD42022369353.
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Terapia Cognitivo-Comportamental , Criança , Adolescente , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Viés , Dor Abdominal/terapiaRESUMO
This is the protocol for a Campbell systematic review. The objectives are as follows: (1) To evaluate the reporting quality of systematic reviews published in Chinese social science journals against the PRISMA and MOOSE standards; (2) To evaluate the methodology quality of systematic reviews published in Chinese social science journals against the AMSTAR-2 and DART standards; and (3) To analyze other characteristics of systematic reviews published in Chinese social science journals using content analysis.
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BACKGROUND: This study aims to investigate the expression of galectin-1 and vascular mimicry (VM) in rectal cancer tissues, and to assess their predictive value in the prognostic evaluation of patients with rectal cancer. METHODS: Immunohistochemistry (IHC) and CD34-periodic acid solution (PAS) double staining were used to detect galectin-1 expression and the formation of VM in rectal cancer tissues from 94 patients with stage I-III rectal cancer and their corresponding paracancerous tissues. We also analyzed the relationship between the expression of galectin-1, VM, various clinicopathological parameters, and the prognosis of rectal cancer patients, as well as their influence on the overall survival (OS) of rectal cancer patients. RESULTS: Among the 94 tissue specimens from rectal cancer patients, 43 had positive expression of galectin-1 and 19 had positive expression of VM. There was a positive correlation between VM and galectin-1 expression in rectal cancer tissue. Galectin-1 expression in rectal cancer tissue and the formation of VM were related to tumor differentiation, staging, lymph node metastasis, and intravascular tumor thrombus (P<0.05). Kaplan-Meier analysis showed that the OS time of rectal cancer patients in the galectin-1 positive expression group was shorter than the galectin-1 negative expression patients, and the difference between the 2 groups was statistically significant (P=0.003). The OS time of patients with rectal cancer in the VM positive expression group was shorter than the VM negative expression group, and the difference between the two groups was statistically significant (P<0.001). The OS time of the galectin-1 and VM negative expression group was 57.33±1.13 months, and the OS time of the galectin-1 and VM positive expression group was 43.21±3.97 months, while the OS time of the galectin-1 positive expression and VM negative expression group was 55.42±2.23 months, and the difference between the three groups was statistically significant (P<0.001). Multi-factor analysis results indicated that invasion depth and VM expression were independent risk factors that affected the OS of patients with rectal cancer. CONCLUSIONS: Galectin-1 and VM expression in rectal cancer tissues may predict poor prognosis in patients after radical surgery. Galectin-1 and VM may therefore become potential new targets for rectal cancer treatment.
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Indoleamine 2,3-dioxygenase1(IDO1) is one of the most important proteins in protect the embryos from the mother's immune system during pregnancy. However, the regulation of the protein expression at the maternal-foetal interface is not fully known. We aimed to study the regulation of IDO1 expression by progesterone in villi and decidua of in early pregnancy. Fifty cases of early pregnancy women's villi and decidua were collected. Tissue explants of chorionic villi and the decidua were cultured in media containing in different concentrations of progesterone, in the presence or absence of mifepristone. Western blot analysis and immunofluorescence were used to detect the expression of IDO1 in chorionic villi and decidua in cultured tissues. IDO1 protein was identified in chorionic villi and decidua tissues of normal pregnant women, and the expression of IDO1in the decidua was significantly higher than those in chorionic villi. Progesterone decreased IDO1 expression in early pregnancy chorionic villi and decidua, and mifepristone, as the progesterone inhibitor, reverted this effect. In normal physiological state of pregnancy, progesterone may be involved in the regulation of immune tolerance by negative regulation of IDO1 expression at maternal foetal interface. Progesterone may down-regulate IDO1 expression during early pregnancy.
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Vilosidades Coriônicas/metabolismo , Decídua/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Progesterona/metabolismo , Adulto , Feminino , Humanos , GravidezRESUMO
BACKGROUND: Hand hygiene is one of the ways to prevent the spread of diseases. Our aim was to explore the relationship between hand washing frequency and the impact on disease, and give recommendations on the number of times to wash hands. METHODS: We searched seven electronic databases from their inception to April 11, 2020, and reference lists of related reviews for all studies on hand washing frequency and disease prevention. The Review Manager 5.3. software was used to conduct a meta-analysis. We assessed the risk of bias of included studies, and quality of evidence of the main findings. RESULTS: A total of eight studies were included. The results of the meta-analysis showed that there was no statistical significance between the effect of disease prevention and washing more than 4 times/day compared to not [odds ratio (OR) =0.61, 95% confidence interval (CI): 0.37 to 1.01]. The results of a case-control study showed that compared with hand washing ≤4 times/day, hand washing 5-10 times/day (OR =0.75, 95% CI: 0.63 to 0.91) and hand washing >10 times/day (OR =0.65, 95% CI 0.53 to 0.80) could reduce the risk of disease infection. There was no statistical significance advantage to hand washing more than 10 times/day compared to 5-10 times/day (OR =0.86, 95% CI: 0.70 to 1.06). Comparing hand washing ≤10 times/day with hand washing >10 times/day, increased hand washing was a protective factor against infection (OR =0.59, 95% CI: 0.36 to 0.97). CONCLUSIONS: The more frequently hands were washed, the lower risk of disease. So far however, there is no high-quality evidence indicating the best range of hand washing frequency for disease prevention.
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PROBLEM: Indoleamine 2,3-dioxygenase (IDO) is a key protein that participates in the protection of embryos against the mother's immune system during pregnancy. How the expression of this protein is regulated at the maternal-fetal interface remains largely unknown. METHOD OF STUDY: The chorionic villi and decidua of women in early pregnancy were collected. Tissue explants of the chorionic villi and decidua were cultured in media containing varying concentrations of 17ß-estradiol and estriol with or without fulvestrant. Western blot analysis and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were used to detect the expression of IDO and the suppressors of cytokine signaling 3 (SOCS3) in the cultured tissues from chorionic villi and decidua. RESULTS: Both IDO and SOCS3 were expressed in chorionic villi and decidua. The expression of IDO was increased in tissue explants from chorionic villi and decidua cultured in medium containing different concentrations of 17ß-estradiol or estriol, and this increase was reversed when fulvestrant was added to the medium. The expression of IDO was upregulated, and SOCS3 expression was downregulated the most in tissue explants from chorionic villi and decidua that were cultured in medium containing 17ß-estradiol at a concentration of 10 ng/mL or estriol at a concentration of 1 µg/mL. This increase in IDO and decrease in SOCS3 were reversed when fulvestrant was added to the medium at a concentration of 10 µg/mL. CONCLUSION: At a concentration similar to that present during pregnancy, estrogen may upregulate the expression of IDO via downregulating SOCS3, which implies that estrogen may contribute to the prevention of allogeneic fetal rejection, and further studies may strengthen the possibility of using estrogen as an immune modulator.
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Vilosidades Coriônicas/efeitos dos fármacos , Decídua/efeitos dos fármacos , Estradiol/farmacologia , Estriol/farmacologia , Estrogênios/farmacologia , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Adulto , Vilosidades Coriônicas/metabolismo , Decídua/metabolismo , Feminino , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Gravidez , Proteína 3 Supressora da Sinalização de Citocinas/genética , Adulto JovemRESUMO
Indoleamine 2,3dioxygenase (IDO) is one of the most important proteins protecting the embryos from the mother's immune system during pregnancy; however, little is known about the regulation of expression of this protein at the maternalfetal interface. In the current study, chorionic villi and decidua were collected from women at early stages of pregnancy. Samples of chorionic villi and decidua were cultured in medium containing different concentrations of 17ßestradiol and estriol respectively, with or without fulvestrant. Western blot analysis and/or immunofluorescent staining were used to detect the expression of transforming growth factor ß (TGFß) and IDO in chorionic villi and decidua tissues. Both TGFß and IDO were expressed in chorionic villi and decidua. The expression levels of these two proteins increased the most in samples of chorionic villi and decidua cultured in medium containing 17ßestradiol at the concentration of 10 ng/ml, or estriol at the concentration of 1 µg/ml. This increase could be reversed when fulvestrant was added in the medium at the concentration of 10 µg/ml. IDO expression increased in a dosedependent manner in tissue samples cultured in medium containing TGFß. The results of the current study revealed that administration of estrogen at doses similar to those observed in healthy pregnant women may upregulate the expression of IDO by TGFß, suggesting that estrogen may prevent allogeneic fetal rejection and may be used as an immunomodulator.
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Vilosidades Coriônicas/metabolismo , Decídua/metabolismo , Estrogênios/farmacologia , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Adulto , Vilosidades Coriônicas/efeitos dos fármacos , Estradiol/farmacologia , Feminino , Humanos , Técnicas In Vitro , Gravidez , Primeiro Trimestre da GravidezRESUMO
All-inorganic cesium lead halide perovskite nanocrystals (CsPbX3, X = Cl, Br, or I) present broad applications in the field of optoelectronics due to their excellent photoluminescence (PL), narrow spectral bandwidth, and wide spectral tunability. However, their poor stability limits their practical application. In this work, we successfully use an in situ crystallization strategy for growing and cladding CsPbBr3 perovskite nanocrystals in poly(vinylidene difluoride) (PVDF). The CsPbBr3 nanocrystals in the as-fabricated CsPbBr3@PVDF composites have an average diameter of 16-18 nm and a strong PL emission (537 nm), with a photoluminescence quantum yield exceeding 30%. In addition, the fabricated CsPbBr3@PVDF composites present improved resistance to heat and water preserving with remarkable optical performance, owing to the effective protection of PVDF. Moreover, the CsPbBr3 nanocrystals generated in PVDF can withstand temperatures up to 170 °C and can be completely immersed in water for 60 days while still retaining high PL intensity, which facilitate the practical application of CsPbBr3 perovskite nanocrystals. These CsPbBr3@PVDF composite films with remarkable optical performances and superior anti-interference ability have broad application prospects in optoelectronics as well as good potential as temperature sensors in mechanical engineering.
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Alzheimer's disease is a neurodegenerative disorder characterized by deposition of ß-amyloid (Aß) fibrils accompanied with progressive neurite loss. None of the clinically approved anti-Alzheimer's agents target both pathological processes. We hypothesized that conjugation of a metal chelator to destabilize Aß fibrils (fAßs) and a long-chain fatty alcohol to induce neurite outgrowth may generate a novel molecular scaffold that targets both pathologies. The hydroxyalkylquinoline J2326 was designed and synthesized by joining an 11-carbon alcohol to 5-chloro-8-methoxyquinoline at the 2-position and its anti-neurodegenerative potentials in vitro and in vivo were characterized. It attenuated fAß formation and disaggregated the existing fAß zinc-dependently as well as zinc-independently. It also triggered extracellular signal-regulated kinase-dependent neurite outgrowth and increased synaptic activity in neuronal cells. In fAß-driven neurodegeneration in vitro, J2326 reversed neurite collapse and neurotoxicity. These roles of J2326 were also demonstrated in vivo and were pivotal to the observed improvement in memory of mice with hippocampal fAß lesions. These results show that the effectiveness of J2326 on fAß-driven neurodegeneration is ascribed to its novel scaffold. This might give clues to evolving attractive therapy for future clinical trials.