Prenatal anxiety and the associated factors among Chinese pregnant women during the COVID-19 pandemic--a smartphone questionnaire survey study.

BACKGROUNDS: The uncertainty of the pandemic of Coronavirus Disease 2019 (COVID-19) brought about tremendous psychological harm for pregnant women, causing their high rates of prenatal anxiety. The impacts of COVID-19 pandemic and symptoms of pregnant status are highly linked with prenatal anxiety. Whereas, self-efficacy and support from family and friends could attenuate the development of prenatal anxiety. Thus, the purpose of the study is to evaluate the prevalence of prenatal anxiety and its influence factors among pregnant women during the pandemic of COVID-19 in Shenyang, China. METHODS: A cross-sectional study with face-to-face interview between April 24, 2020 and May 3, 2020 during the COVID-19 pandemic was applied among pregnant women in Shenyang Women's and Children's Hospital. Chi-square tests were calculated to determine the differences in prenatal anxiety among categorical variables. Multivariable logistic regression was employed to investigate the risk factors of prenatal anxiety. RESULTS: The percentage of prenatal anxiety (GAD-7 score ≥ 7) among pregnant women during the pandemic of COVID-19 was 34/304 (11.18%). Logistic regression indicated that vomiting (OR 4.454, 95% CI 1.113-17.821) and feeling susceptible to SARS-CoV-2 infection (OR 2.966, 95% CI 1.151-7.642) increased the odds of prenatal anxiety. Satisfaction with medical care (OR 0.303, 95% CI 0.113-0.813) and self-efficacy (OR 0.253, 95% CI 0.100-0.639) decreased the odds of prenatal anxiety. High monthly income (OR 0.246, 95% CI 0.078 ~ 0.780) reduced the chances of suffering from prenatal anxiety. CONCLUSION: The pregnant women in China exerted a higher prevalence of prenatal anxiety during the COVID-19 pandemic than that without COVID-19 pandemic. Effective management on symptoms of pregnant status should be delivered to relieve prenatal anxiety for the pregnant women. Furthermore, interventions on self-efficacy enhancement and high-quality medical prenatal care should be provided to prevent from the susceptibility of SARS-CoV-2 infection and reduce prenatal anxiety.

A tacrine-tetrahydroquinoline heterodimer potently inhibits acetylcholinesterase activity and enhances neurotransmission in mice.

Cholinergic neurons are ubiquitous and involved in various higher brain functions including learning and memory. Patients with Alzheimer's disease exhibit significant dysfunction and loss of cholinergic neurons. Meanwhile, such cholinergic deficits can be potentially relieved pharmacologically by increasing acetylcholine. Acetylcholinesterase (AChE) inhibitors have been used to improve cholinergic transmission in the brain for two decades and have proven effective for alleviating symptoms in the early stages of Alzheimer's disease. Therefore, the search for AChE inhibitors for drug development is ongoing. The enzymatic pocket of AChE has long been the target of several drug designs over the last two decades. The peripheral and catalytic sites of AChE are simultaneously bound by several dimeric molecules, enabling more-efficient inhibition. Here, we used 6-chlorotacrine and the tetrahydroquinolone moiety of huperzine A to design and synthesize a series of heterodimers that inhibit AChE at nanomolar potency. Specifically, compound 7b inhibits AChE with an IC50 < 1 nM and spares butyrylcholinesterase. Administration of 7b to mouse brain slices restores synaptic activity impaired by pirenzepine, a muscarinic M1-selective antagonist. Moreover, oral administration of 7b to C57BL/6 mice enhances hippocampal long-term potentiation in a dose-dependent manner and is detectable in the brain tissue. All these data supported that 7b is a potential cognitive enhancer and is worth for further exploration.

Resilience mediates the effect of self-efficacy on symptoms of prenatal anxiety among pregnant women: a nationwide smartphone cross-sectional study in China.

BACKGROUND: Prenatal anxiety is one of the most prevalent mental disorders during pregnancy. This study assessed the prevalence of prenatal anxiety and examined whether resilience could play the mediating role in the association between self-efficacy and symptoms of prenatal anxiety among pregnant women in China. METHODS: A nationwide smartphone cross-sectional study was carried out in three cities (Shenyang of Liaoning Province, Zhengzhou of Henan Province and Chongqing Municipality) in China from July 2018 to July 2019. The questionnaire consisted of questions on demographic characteristics, the Generalized Anxiety Disorder Scale (GAD-7), the Chinese version of General Self-efficacy Scale (GSES), and the 14-item Wagnild and Young Resilience Scale (RS-14). A total of 665 pregnant women were recruited in this study. A hierarchical multiple regression model was employed to explore the associate factors and mediators of symptoms of prenatal anxiety. A structural equation model was employed to test the hypothesis that resilience mediates the association between self-efficacy and symptoms of prenatal anxiety. RESULTS: The prevalence of symptoms of prenatal anxiety was 36.4% in this study. Self-efficacy was negatively correlated with symptoms of prenatal anxiety (r = -0.366, P < 0.01). Resilience had a significant positive correlation with self-efficacy (r = 0.612, P < 0.01) and had a negative correlation with symptoms of prenatal anxiety (r = -0.427, P < 0.01). The hierarchical multiple regression model indicated that self-efficacy and resilience were the main factors associated with symptoms of prenatal anxiety and contributed to 11.9% and 6.3% to the variance of symptoms of prenatal anxiety, respectively. Resilience served as a mediator between self-efficacy and symptoms of prenatal anxiety (a*b = -0.198, Bias-corrected and accelerated bootstrap 95% Confidence interval: -0.270, -0.126). CONCLUSIONS: Self-efficacy was a negative predictor of symptoms of prenatal anxiety among pregnant women. Moreover, resilience mediated the relation between self-efficacy and symptoms of prenatal anxiety among pregnant women in China. It was observed in this study that psychological interventions might be beneficial for pregnant women to relieve symptoms of prenatal anxiety through improved self-efficacy and resilience.

Resilience as the Mediating Factor in the Relationship Between Sleep Disturbance and Post-stroke Depression of Stroke Patients in China: A Structural Equation Modeling Analysis.

Background: Stroke patients may suffer from a variety of symptoms which can result in sleep disturbance and post-stroke depression (PSD). Whereas, resilience can alleviate sleep disturbance and help maintain well-being after stroke. Objective: The aim of this study is to explore whether resilience plays a mediating role in the relationship between sleep disturbance and PSD of stroke patients in China. Methods: A cross-sectional study with a multi-stage sampling was carried out in Liaoning Rehabilitation Center and the Third People's Hospital of Chongqing in China from May to September 2019. A total of 353 stroke patients were enrolled in this study. Structural equation model (SEM) was used to test the mediating effect of resilience on the relationship between sleep disturbance and PSD. Results: The prevalence of PSD of stroke patients was 34.56%. Sleep disturbance contributed most to the variance of PSD and had a significantly positive association with PSD among stroke patients (P < 0.01). Resilience was negatively associated with PSD, and acted as a mediator between sleep disturbance and PSD (a * b = 0.201, BCa 95% CI: 0.156~0.254). Conclusions: The prevalence of PSD was high among the Chinese stroke patients. Sleep disturbance was highly associated with PSD, resulting in the increased risk of PSD. Furthermore, resilience has a mediating effect on the relationship between sleep disturbance and PSD, and could reduce the negative effect of sleep disturbance on the development of PSD.

Increased quality of life in patients with stroke during the COVID-19 pandemic: a matched-pair study.

Patients with stroke are likely to experience impaired health-related quality of life (QOL), especially during the COVID-19 pandemic. This study aimed to evaluate the QOL of Chinese patients with stroke during the pandemic and explore the associated variables. A matched-pair, multicenter survey was conducted before and during the COVID-19 pandemic. Questionnaires including the 36-item Short-Form Health Survey (SF-36), the Activities of Daily Living (ADL) scale, and the Questionnaire about the Process of Recovery (QPR) were used. A total of 172 matched pairs (344 patients) were recruited in this study. Hierarchical multiple regression analysis was performed to analyze variables associated with QOL. Physical and mental component scores (PCS and MCS) were higher among the stroke patients during the pandemic (44.20 ± 18.92 and 54.24 ± 19.08) than before the pandemic (37.98 ± 14.52 and 43.50 ± 20.94). Pandemic stress, demographic and clinical characteristics were negative variables associated with PCS and MCS. QPR was positively associated with PCS and MCS. The QOL of Chinese stroke patients was higher during than before the COVID-19 pandemic. Pandemic stress aggravated stroke patients' QOL, while personal recovery could alleviate the detrimental effect of pandemic stress on QOL for stroke patients.

Factors Influencing Anxiety Among WeChat Users During the Early Stages of the COVID-19 Pandemic in Mainland China: Cross-sectional Survey Study.

BACKGROUND: The rapid outbreak of COVID-19 around the world has adversely affected the mental health of the public. The prevalence of anxiety among the public has increased dramatically during the COVID-19 pandemic. However, there are few studies evaluating the effects of positive psychological responses and information-seeking behaviors on anxiety experienced among social media users during the COVID-19 pandemic. OBJECTIVE: This study evaluated the prevalence of anxiety and its associated factors among WeChat users in mainland China during the early stages of the COVID-19 pandemic. METHODS: From February 10 to February 24, 2020, a nationwide, web-based cross-sectional survey study was carried out using convenience sampling. Participants' levels of anxiety, positive psychological responses, and information-seeking behaviors were assessed. The survey was distributed among WeChat users via the WeChat smartphone platform. Chi-square tests and multivariable logistic regression analyses were performed to examine the factors associated with anxiety. RESULTS: This study found that the prevalence of anxiety (Generalized Anxiety Disorder 7-item [GAD-7] scale score ≥7) among WeChat users in China was 17.96% (446/2483) during the early stages of the COVID-19 pandemic. Results of multivariable logistic regression analysis showed that information-seeking behaviors such as cannot stop searching for information on COVID-19, being concerned about the COVID-19 pandemic, and spending more than 1 hour per day consuming information about the pandemic were found to be associated with increased levels of anxiety. Additionally, participants who chose social media and commercial media as the primary sources to obtain information about the COVID-19 pandemic were found more likely to report anxiety. Conversely, participants who were confident or rational about the COVID-19 pandemic were less likely to report anxiety. CONCLUSIONS: This study found that positive psychological responses and information-seeking behaviors were closely associated with anxiety among WeChat users during the COVID-19 pandemic in China. It might be paramount to enhance mental well-being by helping people respond to the COVID-19 pandemic more rationally and positively in order to decrease symptoms of anxiety.

Positive effects of resilience and self-efficacy on World Health Organization Quality of Life Instrument score among caregivers of stroke inpatients in China.

AIM: Stroke is one of the major health challenges affecting life expectancy and quality of life around the world. However, there is limited reporting on the status of some caregivers, including Chinese caregivers of stroke inpatients. Limited information is available on evaluations using the World Health Organization Quality of Life Instrument (WHOQOL) and the effects of resilience and self-efficacy on WHOQOL score. Therefore, we conducted research to assess the role of resilience on the WHOQOL and to investigate the role of self-efficacy as a mediator between resilience and WHOQOL score among Chinese caregivers of stroke inpatients. METHODS: This cross-sectional study to gather data from north-east and south-east China was conducted from June 2019 to October 2019. Over 380 caregivers of stroke inpatients at two general public hospitals were interviewed face-to-face. About 305 caregivers (80.26%) completed the questionnaire, which included the Ego Resilience Scale, the General Self-Efficacy Scale, and the brief version of the WHOQOL and asked about demographic characteristics. This study also examined factors associated with WHOQOL score and used linear regression analysis and structure equation modelling to construct direct and indirect models, respectively. RESULTS: After adjustment for demographic characteristics, both resilience and self-efficacy were positively associated with all WHOQOL domains. Structure equation modelling revealed that self-efficacy mediated the relationship between resilience and WHOQOL score among caregivers of stroke inpatients. CONCLUSION: Chinese caregivers of stroke inpatients exhibited good social health but poor physical, psychological, and environmental health. It is necessary for promoting resilience and improving WHOQOL score through the mediating effect of self-efficacy. These results suggest that interventions in health care focused on both enhancing resilience and providing self-efficacy training could effectively improve WHOQOL score.

Sleep Quality as a Mediator in the Relationship Between Perceived Stress and Job Burnout Among Chinese Nurses: A Structural Equation Modeling Analysis.

Background: Job burnout has become an increasing prevailing phenomenon among nurses in both developed and developing countries. There is a paucity of research exploring the relationship between perceived stress (i.e., the level of one's perception or appraisal of stress rather than objective stressful events) and job burnout and no existing literature examining the mediating role of sleep quality in the relationship between these two constructs. The objective of the study was to examine if sleep quality mediates the relationship between perceived stress and job burnout. Methods: Cross-sectional data were collected from a total of 1,013 nurses working in six public tertiary hospitals in China. The self-administered questionnaire included demographic information, the Maslach Burnout Inventory-General Scale, the Pittsburgh Sleep Quality Index and the Perceived Stress Scale. Hierarchical multiple regression (HMR) analyses were performed to examine the contribution of each covariate to the prediction of job burnout. Structural equation modeling (SEM) was employed to test whether the proposed relationships between variables involved existed. Results: Both perceived stress and poor sleep quality exhibited strong positive associations with job burnout among Chinese nurses. The SEM analysis confirmed the direct pathway from perceived stress to burnout and the indirect pathway mediated by sleep quality. The direct effect of perceived stress on job burnout was found to be statistically significant and positive (ß = 0.69, p < 0.05). There existed statistically significant effects of sleep quality on both perceived stress (ß = 0.48) and job burnout (ß = 0.29). The path coefficients of perceived stress on job burnout were significantly reduced (ß = 0.56) when sleep quality was modeled as a mediator. The bias-corrected and accelerated bootstrap test revealed that sleep quality had a significant mediating effect on the relationship between perceived stress and job burnout (a * b = 0.139, BCa 95%, CI: 0.110~0.174). Conclusion: Perceived stress might exert significant effects on burnout both directly and indirectly through the mediating role of sleep quality. Efforts to reduce burnout among nurses in clinical settings may benefit from interventions for coping with perceived stress and practices for promoting healthy sleep.

Recovery Experience: A Concept for Maintaining Quality of Life and Its Mediating Effect Among Female Nurses in China.

PURPOSE: Nurses are high-risk groups for job burnout, which affect their quality of life (QOL). Recovery experience, a conceptualization of positive psychological resources, can combat the negative impacts of job burnout on health and QOL. The aim of this study was to examine the mediating effect of recovery experience on the relationship between job burnout and QOL among female nurses in China. PARTICIPANTS AND METHODS: QOL information was captured from 1068 female nurses from December 2017 to February 2018 in tertiary hospitals in Shenyang, Liaoning Province of China. A structural equation model was employed to examine the mediating effect of recovery experience on the relationship between job burnout and QOL. RESULTS: Job burnout had a significant impact on both the mental component summary and the physical component summary of a 36-item Short-Form Health Survey. However, mental component summary scores were significantly lower than physical component summary scores in female nurses. Recovery experience played a mediating role in the relationship between job burnout and QOL. CONCLUSION: Job burnout could result in a reduction in QOL among Chinese female nurses. Recovery experience, as a mediating factor, could alleviate the impact of job burnout on QOL. Recovery experience should be strengthened to attenuate job burnout and enhance QOL.

Depression and Psychological-Behavioral Responses Among the General Public in China During the Early Stages of the COVID-19 Pandemic: Survey Study.

BACKGROUND: The COVID-19 pandemic has recently spread dramatically worldwide, raising considerable concerns and resulting in detrimental effects on the psychological health of people who are vulnerable to the disease. Therefore, assessment of depression in members of the general public and their psychological and behavioral responses is essential for the maintenance of health. OBJECTIVE: This study aimed to assess the prevalence of depression and the associated factors among the general public during the early stages of the COVID-19 pandemic in China. METHODS: A cross-sectional survey with convenience sampling was conducted from February 11 to 16, 2020, in the early stages of the COVID-19 outbreak in China. A self-administrated smartphone questionnaire based on the Patient Health Questionnaire-9 (PHQ-9) and psychological and behavioral responses was distributed to the general public. Hierarchical multiple regression analysis and multivariate logistic regression analysis were conducted to explore the associated factors of depression.aA cross-sectional survey with convenience sampling was conducted from February 11 to 16, 2020, in the early stages of the COVID-19 outbreak in China. A self-administrated smartphone questionnaire based on the Patient Health Questionnaire-9 (PHQ-9) and psychological and behavioral responses was distributed to the general public. Hierarchical multiple regression analysis and multivariate logistic regression analysis were conducted to explore the associated factors of depression. RESULTS: The prevalence of depression (PHQ-9 score ≥10) among the general public during the COVID-19 pandemic was 182/1342 (13.6%). Regression analysis indicated that feeling stressed, feeling helpless, persistently being worried even with support, never feeling clean after disinfecting, scrubbing hands and items repeatedly, hoarding food, medicine, or daily supplies, and being distracted from work or study were positively associated with depression, while social support and being calm were negatively associated with depression. CONCLUSIONS: The general public suffered from high levels of depression during the early stages of the COVID-19 pandemic. Thus, COVID-19-related mood management and social support should be provided to attenuate depression in the general public.

Prevalence of Prenatal Depression Among Pregnant Women and the Importance of Resilience: A Multi-Site Questionnaire-Based Survey in Mainland China.

BACKGROUND: Prenatal depression is associated with adverse maternal and fetal health consequences, yet it has not raised sufficient concerns in China. Psychological worries and stress may lead to prenatal depression, but resilience could relieve some of the negative effects of worries and stress and mitigate prenatal depression. AIMS: This study aimed to assess the prevalence of prenatal depression and explore its associated factors. METHOD: A multisite cross-sectional study was conducted that included 605 pregnant women from three hospitals in two provincial capitals (Shenyang and Zhengzhou) and one municipality (Chongqing). A smartphone questionnaire was employed to assess prenatal depression using the Center for Epidemiologic Studies Depression Scale (CES-D). Multivariate logistic regression analysis was performed to explore factors associated with prenatal depression. RESULTS: The prevalence of prenatal depression (CES-D≥16) among Chinese pregnant women was 28.4%. Logistic regression analyses revealed that prenatal depression was positively associated with worries about appearance (odds ratio [OR] 1.666, 95% confidence interval [CI] 1.043-2.661) and perceived stress (OR 1.156, 95% CI 1.104-1.211) and negatively associated with monthly income, relationship with mother (OR 0.287, 95% CI 0.103-0.796), and resilience (OR 0.935, 95% CI 0.918-0.953). CONCLUSION: These findings revealed that Chinese pregnant women suffered from high levels of prenatal depression (28.4%). Worries about appearance and perceived stress were risk factors for prenatal depression, whereas a pregnant woman's harmonious relationship with her own mother and resilience could relieve the negative impacts of pregnancy that can lead to prenatal depression. Improving resilience and maintaining harmonious relationships with mothers should be emphasized in order to reduce the detrimental effects of pregnancy and improve the mental well-being of pregnant women.

Recovery Experience as the Mediating Factor in the Relationship Between Sleep Disturbance and Depressive Symptoms Among Female Nurses in Chinese Public Hospitals: A Structural Equation Modeling Analysis.

PURPOSE: Nurses are suffering from considerable work-related stress, which can result in disturbed sleep and depressive symptoms. Whereas, recovery experience can alleviate sleep disturbance and help maintain well-being in the working environment. The aim of this study was to examine whether recovery experiences play a mediating role in the relationship between sleep disturbance and depressive symptoms of female nurses in Chinese public hospitals. METHODS: From December 2017 to May 2018, the study with proportional sampling of cross-sectional design was carried out in the public tertiary hospitals from Shenyang of Liaoning Province in China. A total of 1500 female nurses who had been working for one or more years participated in this study. A structural equation model (SEM) was applied to test the assumption that recovery experiences might function as a mediator in the relationship between sleep disturbance and symptoms of depression. RESULTS: Sleep disturbance contributed most to the variance (32.9%) of depressive symptoms and had a significantly positive correlation with depressive symptoms (P<0.01) among nurses. Psychological detachment in recovery experience had a significantly positive correlation with sleep disturbance (P<0.01) and depressive symptoms (P<0.01). Whereas, relaxation, mastery experience, and control in recovery experience were significantly and negatively correlated with sleep disturbance (P<0.01) and depressive symptoms (P<0.01). Recovery experience served as a mediator between sleep disturbance and depressive symptoms (a * b = 0.066, BCa 95% CI: 0.045, 0.095). CONCLUSION: Sleep disturbance was the predictor of depressive symptoms for female nurses. Moreover, recovery experience could combat the detrimental impacts of sleep disturbances on symptoms of depression. This study suggested that nurses might benefit from interventions on improving sleep quality to relieve depressive symptoms through mediating path of recovery experience.

Optimizing quality of life among Chinese physicians: the positive effects of resilience and recovery experience.

BACKGROUND: The physicians in Chinese public tertiary hospitals are exposed to considerable work-related stress because of the imperfections in hierarchical diagnosis and treatment systems, such as the imperfections in referral system and low quality in diagnosis and treatment outcomes in community hospitals, for which most patients visit tertiary hospitals firstly in order to access a higher quality health care service. As a consequence, the health-related quality of life (HRQOL) for Chinese physicians is compromised. However, there is a paucity of research exploring physicians' physical and mental health and positive psychological resource factors such as resilience and recovery experience (RE) which can help maintain well-being. Thus, this study aims to assess HRQOL of Chinese physicians and explore the relationship between HRQOL, resilience, and RE. METHODS: A cross-sectional study with proportional sampling was conducted in Shenyang, China from February to October 2018. A total of 642 physicians in five public tertiary hospitals were enrolled in this study. They completed the smartphone questionnaire including the 36-item Short-Form Health Survey (SF-36), the EGO Resilience Scale, and Recovery Experience Questionnaire (REQ). Linear regression analysis was conducted to explore the factors associated with HRQOL. Structural equation modeling (SEM) was used to evaluate the mediating effect of RE on the relationship between resilience and HRQOL. RESULTS: Regression analysis indicated that resilience and RE were the most important contributors to both physical and mental component summary scores. SEM showed that RE partially mediated the relationship between resilience and HRQOL in these physicians. CONCLUSION: Chinese physicians exhibited good physical health, but poor mental health. Resilience could help maintain and improve HRQOL through the partial mediating effect of RE. Resilience and RE enhancement should be provided to effectively manage work-related stress and improve both physical and mental health for the long-term well-being of physicians.

Investigation of stereoisomeric bisarylethenesulfonic acid esters for discovering potent and selective PTP1B inhibitors.

Protein tyrosine phosphatase 1B (PTP1B) has been considered as a promising therapeutic target for type 2 diabetes mellitus (T2DM) and obesity due to its key regulating effects in insulin signaling and leptin receptor pathways. In this work, a series of cis- and trans-pyrrolidine bisarylethenesulfonic acid esters were prepared and their PTP1B inhibitory potency, selectivity and membrane permeability were evaluated. These novel stereoisomeric molecules especially trans-isomers exhibited remarkable inhibitory activity, significant selectivity as well as good membrane permeability (e.g. compound 28a, IC50 = 120, 1940 and 2670 nM against PTP1B, TCPTP and SHP2 respectively, and Papp = 1.74 × 10-6 cm/s). Molecular simulations indicated that trans-pyrrolidine bisarylethenesulfonic acid esters yielded the stronger binding affinity than their cis-isomers by constructing more interactions with non-catalytic sites of PTP1B. Further biological activity studies revealed that compound 28a could enhance insulin-stimulated glucose uptake and insulin-mediated insulin receptor ß (IRß) phosphorylation with no significant cytotoxicity.

Y-shaped bis-arylethenesulfonic acid esters: Potential potent and membrane permeable protein tyrosine phosphatase 1B inhibitors.

Known PTP1B inhibitors with bis-anionic moieties exhibit potent inhibitory activity, good selectivity, however, they are incapable of penetrating cellular membranes. Based upon our finding of a new pharmacophoric group in inhibition of PTP1B and the structural characteristics of the binding pocket of PTP1B, a series of bis-arylethenesulfonic acid ester derivatives were designed and synthesized. These novel molecules, particularly Y-shaped bis-arylethenesulfonic acid ester derivatives, exhibited high PTP1B inhibitory activity, moderate selectivity, and great potential in penetrating cellular membranes (compound 7p, CLogP=9.73, Papp=9.6×10-6cm/s; IC50=140, 1290 and 920nM on PTP1B, TCPTP and SHP2, respectively). Docking simulations suggested that these Y-shaped inhibitors might interact with multiple secondary binding sites in addition to the catalytic site of PTP1B.

Antiproliferative activity and SARs of caffeic acid esters with mono-substituted phenylethanols moiety.

A series of CAPE derivatives with mono-substituted phenylethanols moiety were synthesized and evaluated by MTT assay on growth of 4 human cancer cell lines (Hela, DU-145, MCF-7 and ECA-109). The substituent effects on the antiproliferative activity were systematically investigated for the first time. It was found that electron-donating and hydrophobic substituents at 2'-position of phenylethanol moiety could significantly enhance CAPE's antiproliferative activity. 2'-Propoxyl derivative, as a novel caffeic acid ester, exhibited exquisite potency (IC50=0.4±0.02 & 0.6±0.03µM against Hela and DU-145 respectively).

A cascade of acid-promoted C-O bond cleavage and redox reactions: from oxa-bridged benzazepines to benzazepinones.

A sequence of C-O bond cleavage and redox reactions in oxa-bridged azepines was realized under acid promoted conditions. This protocol provides an atom-economical and straightforward approach to access benzo[b]azepin-5(2H)-ones in high yields. The formal synthesis of tolvaptan was achieved by exploiting this new transformation.

Synthesis of hexahydrobenzo[b]pyrimido[4,5-h][1,6]naphthyridines via an intramolecular hetero-Diels-Alder reaction.

Method development was completed for a strategy to access a novel pyrimidine-fused heterocyclic scaffold. The key step for this synthetic route entails an intramolecular inverse electron demand hetero-Diels-Alder reaction of imines or iminiums formed in situ from allylaminopyrimidinealdehydes 3 and anilines. The reactions provided exclusively cis-configuration products 6. Products 6 were readily precipitated in the reaction solution in good to excellent yields. Further transformations of the phenylthio group were demonstrated by an oxidation and subsequent nucleophilic substitution sequence. The synthetic strategy provides an efficient way to access libraries of the tetracyclic pyrimidine-fused heterocycles that can be explored for potential pharmaceutical or biological activities.

A cascade reaction with iminium ion isomerization as the key step leading to tetrahydropyrimido[4,5-d]pyrimidines.

A novel cascade reaction of aminopyrimidines 1 with N-alkyl amino acids or analogues was investigated. The keys to this cascade are the isomerization of an iminium ion formed between the aldehyde group in pyrimidine and the secondary amine of an amino acid, and subsequent cyclization to the neighboring amino group. This sequence could be useful in the synthesis of novel tetrahydropyrimido[4,5-d]pyrimidine libraries.