Design, synthesis and biological evaluation of indoline-maleimide conjugates as potential antitumor agents for the treatment of colorectal cancer.

An efficient protocol for direct coupling of maleimides and indolines at the C7-position was achieved under Rh(III) catalysis. Thirty four novel indoline-maleimide conjugates were prepared in good to excellent yields using this method. All compounds were evaluated for their anti-proliferative effect against colorectal cell lines. Among them, compound 3ab showed the most potent anti-proliferative activity against the CRC cells, and displayed low toxicity in the normal cell. Further investigation indicated that 3ab could effectively suppress the proliferation and migration of CRC cells, along with inducing cell cycle arrest and apoptosis. Mechanistic studies revealed that compound 3ab inhibited the proliferation of CRC cells via suppressing the AKT/GSK-3ß pathway. In vivo evaluation demonstrated remarkable antitumor effect of 3ab (10 mg/kg) in the HCT116 xenograft model with no obvious toxicity, which is superior to that of 5-Fluorouracil (20 mg/kg). Therefore, conjugate 3ab could be considered as a potential CRC therapy agent for further development.

Metal-Free Radical [3 + 2] Annulation of Tetraalkylthiuram Disulfide with Alkynes/Alkenes: An Approach of Synthesizing 1,3-Dithiole and 1,3-Ditholane Derivatives.

A novel and metal-free [3 + 2] annulation of tetraalkylthiuram disulfide with alkynes/alkenes has been developed using Selectfluor at room temperature. The formed 1,3-dithiol-2-ylium/1,3-dithiolan-2-ylium salts can be easily transformed into the corresponding 1,3-dithiol-2-ylidenes/1,3-ditholan-2-ylidenes by one-pot subsequent condensation with malononitrile. The present protocol features the use of easily accessible starting materials, mild reaction conditions, good tolerance with diverse functional groups, easy scale-up, and a wide substrate scope, affording the desired products in good yields. Importantly, this method is suitable for the late-stage modification of bioactive molecules. Furthermore, 1,3-dithiol-2-ylium salt can also be easily converted into various 1,3-dithiole derivatives by condensation, reduction, or hydrolysis. Mechanism studies show that this transformation involves radical annulation. Of note, this method presented a novel example using tetraalkylthiuram disulfide as a sulfur synthon in annulation, which greatly enriches the application of tetraalkylthiuram disulfides in organic synthesis. Biological evaluation indicates that these prepared compounds are promising candidates in terms of their antitumor activity.

Metal-Free Oxidative Dearomatization-Alkoxylation/Acyloxylation of Indoles: Synthesis of 2-Monosubstituted Indolin-3-ones.

A metal-free route for the preparation of 2-monosubstituted indolin-3-ones, including 2-alkoxyindolin-3-ones and 2-acyloxyindolin-3-ones from commercially available indoles, has been developed employing (bis(trifluoroacetoxy)iodo)benzene (PIFA) as an oxidant. The present protocol features mild reaction conditions, good tolerance with diverse functional groups, and a wide substrate scope, affording the desired products in good yields. This transformation is easy to scale up, and the desired products can be further modified. Most importantly, this method is suitable for the late-stage modification of bioactive molecules. Mechanism studies show that this transformation involves metal-free radical dearomatization and oxygenation. Furthermore, this method also provides a practical and efficient way to prepare indolin-3-ones from commercially available reagents in one step.

Metal-Free Thiocarbamation of Quinolinones: Direct Access to 3,4-Difunctionalized Quinolines and Quinolinonyl Thiocarbamates at Room Temperature.

A novel and practical method for the preparation of difunctionalized quinolines, bearing a thiocarbamate group at the C3-position and an acyloxyl group at the C4-position, and quinolinonyl thiocarbamates from quinolinones, tetraalkylthiuram disulfides, and hypervalent iodine(III) reagents has been developed via thiocarbamation of quinolinones at room temperature. The present method features mild reaction conditions, good tolerance with diverse functional groups, and a wide substrate scope, providing the desired products in good yields. Furthermore, this transformation is easy to scale up, and the desired products can be readily converted to heterocyclic thiols. Most importantly, this protocol allows for the late-stage thiocarbamation of bioactive compounds. Mechanistic studies show that radicals may be involved in this transformation, water is probably the oxygen source of thiocarbamates, and difunctionalized quinolines are possibly formed via nucleophilic attack of carboxylic anions, which derive from hypervalent iodine(III) reagents.

Corrigendum: Risk Perception and PTSD Symptoms of Medical Staff Combating Against COVID-19: A PLS Structural Equation Model.

[This corrects the article DOI: 10.3389/fpsyt.2021.607612.].

Posttraumatic stress symptoms among health care workers during the COVID-19 epidemic: The roles of negative coping and fatigue.

Healthcare workers (HCWs) exposed to Coronavirus disease 2019 (COVID-19) are not immune to stressors. This study aimed to explore the prevalence of posttraumatic stress symptoms (PTSS) among HCWs during the COVID-19 epidemic and investigate the associations among negative coping, fatigue and PTSS. A total of 507 HCWs from Anhui province enrolled in the study and completed the cross-sectional survey including demographic data, Simplified Coping Style Questionnaire (SCSQ), 14-item Fatigue Scale (FS-14), and PTSD Checklist-civilian Version (PCL-C). Univariate linear regression, Pearson correlation and Mackinnon's four-step procedure were performed in the statistical analysis. Results indicated that the prevalence of PTSS among HCWs during the pandemic was 24%. Univariate linear regression showed HCWs aged 31-40 years exhibited significantly higher scores of PTSS than those aged 51-60 (ß = 0.20, 95% CI: 0.59 to 9.41). Having at least one child was associated with a higher risk of developing PTSS (ß = 0.01, 95% CI: 0.36 to 5.45). Negative coping and fatigue were positively correlated with all three PTSS (all P < 0.001), including re-experiencing, avoidance and hyper-arousal. Fatigue has mediated the association between negative coping and PTSS among HCWs during the pandemic (ab = 0.09, SE = 0.03, bootstrap 95% CI: 0.04 to 0.14). A considerable proportion of HCWs was traumatized during the COVID-19 outbreak. Hence, the institutions should screen out and pay close attention to HCWs who tend to use negative coping (e.g., withdrawal thinking, distraction and blaming others) and arrange work scientifically to avoid overfatigue and PTSS amid the public health crisis.

Risk Perception and PTSD Symptoms of Medical Staff Combating Against COVID-19: A PLS Structural Equation Model.

Medical staff were battling against coronavirus disease 2019 (COVID-19) at the expense of their physical and mental health, particularly at risk for posttraumatic stress disorder (PTSD). In this case, intervening PTSD of medical staff and preparing them for future outbreaks are important. Previous studies showed that perceived stress was related to the development of PTSD. Hence, in this study, the association between risk perception of medical staff and PTSD symptoms in COVID-19 and the potential links were explored. Three hundred four medical staff's exposure to COVID-19 patients, risk perception for working during COVID-19, PTSD symptoms, anxiety, and sleep quality were measured. Mediation analysis tested the indirect effects of anxiety and sleep quality on the relationship between risk perceptions and PTSD symptoms; 27.6% of participants were deemed as having probable PTSD diagnosis. Mediation analysis showed a significant chain-mediating effect of anxiety and sleep quality on the relationships between risk perceptions and PTSD symptoms; higher risk perceptions were related to increased anxiety, worsened sleep quality, and severe PTSD symptoms. Conclusively, medical staff have a high prevalence of PTSD symptoms after 3 months of COVID-19. Their PTSD symptoms were associated with the perceived risk level through the potential links with anxiety and sleep quality. Therefore, risk perception could be critical for our medical staff's responses to public health emergencies. It could be plausible to intervene in the perceived stress to alleviate aroused anxiety and improve sleep quality and thereby deter the development of PTSD.

Self-efficacy and fatigue among non-frontline health care workers during COVID-19 outbreak: A moderated mediation model of posttraumatic stress disorder symptoms and negative coping.

PURPOSES: Since a considerable number of health care workers (HCWs) were sent to Wuhan to aid COVID-19 control during the epidemic, non-frontline HCWs who stayed in local hospitals had to work overload to provide daily health care services for other health issues, which makes them more vulnerable to experience fatigue. Self-efficacy is suggested as a protective factor for fatigue. Nonetheless, less is known regarding the underlying mechanisms. This research aimed to explore the prevalence of fatigue among non-frontline HCWs during the pandemic, investigate the mediating effect of posttraumatic stress disorder (PTSD) symptoms and moderating effect of negative coping in the association between self-efficacy and fatigue. METHODS: General Self-Efficacy Scale, PTSD Checklist-Civilian Version, Simplified Coping Style Questionnaire and 14-item Fatigue Scale were administrated to 527 non-frontline HCWs from Anhui Province, China. The mediating effect was examined by Mackinnon's four-step procedure, while Hayes PROCESS macro was used to test the moderated mediation model. RESULTS: The prevalence of fatigue among non-frontline HCWs was 56.7%. The effect of self-efficacy on fatigue was partially mediated by PTSD symptoms (ab = -0.146, SE = 0.030, 95% CI = [-0.207, -0.095]). Additionally, negative coping moderated both the direct effect of self-efficacy on fatigue (ß = -0.158, P<0.001) and the mediating effect of PTSD symptoms (ß = 0.077, P = 0.008). When the standard score of negative coping increased to 1.49 and over, the direct association between self-efficacy and fatigue became insignificant. Likewise, the effect of self-efficacy on PTSD symptoms had no statistical significance when the standard score of negative coping was -1.40 and lower. CONCLUSIONS: More than half non-frontline HCWs suffered from fatigue during COVID-19. For those who tend to use negative coping, it might be crucial to design programs combining the enhancement of self-efficacy, preventions for PTSD symptoms and interventions for fatigue.

The influence of social anxiety on interpersonal information processing in a military-life environment: A cross-sectional study.

Although social anxiety as a ubiquitous emotion impacting people's social behaviors has aroused much researchers' interest in exploring its cognitive behavioral model, no previous study has focused on soldiers with different social anxiety within the context of the specific military environment.To explore the associations between social anxiety and interpersonal information processing concerted on interpretation and judgment, the study may provide an intervention point for soldiers to ameliorate social anxiety and accommodate to the military-life environment.A self-reported questionnaire and 2 behavioral tasks were conducted in the cross-section study to explore the associations.Seventy-four soldiers were randomly recruited from a naval base. The Interpersonal Anxiety Scale was used to assess social anxiety of soldiers. Two behavioral tasks were designed to test the characteristics of interpersonal information processing, one for interpretation bias and the other for judgment bias.This cross-sectional study showed social anxiety had a significant negative correlation with interpretation bias and abidance (as judgment bias), signaling that soldiers with higher levels of social anxiety had a stronger tendency to negative interpretation bias and showed lower abidance. The mediating effect analysis showed the interpretation bias could indirectly affect the soldier's abidance through social anxiety. Notably, none of the interaction effects of social anxiety and social information types were statistically significant; therefore, the level of social anxiety predetermined the abidance of soldiers.Soldiers' social anxiety has an influence on processing military-life interpersonal information, and it plays a certain intermediary role in the associations between low abidance and negative interpretation bias. The stronger negative interpretation bias than positive bias of soldiers, the higher social anxiety they could show with the less possibility to abide, which might result in behaviors against the military collective requirements. Social anxiety has the primary effect on the abidance of soldiers; hence, in the future, the interpretation bias modification could be a plausible cognitive-behavior therapy to help soldiers ameliorate social anxiety, thus contributing to enhancing their sense of belonging to the troops and accommodation to military life.

A cross-sectional study on mental health among health care workers during the outbreak of Corona Virus Disease 2019.

The spread of Corona Virus Disease 2019 (COVID-19) has become a global major public health event, threatening people's physical and mental health and even life safety. This study is to investigate the psychological abnormality in health care workers battling the COVID-19 epidemic and to explore the associations among social support, resilience and mental health. A total of 1521 health care workers, of whom 147 had public health emergency experience while 1374 showed no experience, completed the Symptom Check-List-90 (SCL-90), Chinese version of Connor-Davidson resilience scale (CD-RISC) and Social Support Rating Scale (SSRS). χ2 test, t test and multiple regression analyses were used in statistical analysis. The results showed that people without public health emergency treatment experience showed worse performance in mental health, resilience and social support, and tended to suffer from psychological abnormality on interpersonal sensitivity and photic anxiety. This finding suggested that high levels of training and professional experience, resilience and social support were necessary to health care workers who are first taking part in public health emergence.

Social support and mental health among health care workers during Coronavirus Disease 2019 outbreak: A moderated mediation model.

PURPOSES: During the outbreak of Coronavirus Disease 2019 (COVID-19) all over the world, the mental health conditions of health care workers are of great importance to ensure the efficiency of rescue operations. The current study examined the effect of social support on mental health of health care workers and its underlying mechanisms regarding the mediating role of resilience and moderating role of age during the epidemic. METHODS: Social Support Rating Scale (SSRS), Connor-Davidson Resilience scale (CD-RISC) and Symptom Checklist 90 (SCL-90) were administrated among 1472 health care workers from Jiangsu Province, China during the peak period of COVID-19 outbreak. Structural equation modeling (SEM) was used to examine the mediation effect of resilience on the relation between social support and mental health, whereas moderated mediation analysis was performed by Hayes PROCESS macro. RESULTS: The findings showed that resilience could partially mediate the effect of social support on mental health among health care workers. Age group moderated the indirect relationship between social support and mental health via resilience. Specifically, compared with younger health care workers, the association between resilience and mental health would be attenuated in the middle-aged workers. CONCLUSIONS: The results add knowledge to previous literature by uncovering the underlying mechanisms between social support and mental health. The present study has profound implications for mental health services for health care workers during the peak period of COVID-19.

Risk factors for PTSD of Shidu parents who lost the only child in a rapid aging process: a cross-sectional study.

BACKGROUND: The elderly population is rising globally, especially in China where a large population base causes the largest number of older adults in the world. Notably, Shidu people who are over the age of 60 and have lost their only child have drawn great public attentions as they become more elderly, medically unstable and worse mentally unhealthy. Posttraumatic stress disorder (PTSD) is one of the most common consequences resulted from the loss of the only child. However, few previous studies have examined PTSD in Shidu older aldults, and the risk factors are a relatively understudied area. Our study aims to estimate the prevalence and potential risk factors of PTSD and improve the possibility of early identifying the high-risk Shidu parents with PTSD, and successively provide timely and effective interventions. METHOD: Based on the register of population statistic information provided by the health family planning commission, 149 participants were enrolled randomly. Data was collected by interviews and questionnaires. Socio-demographic and bereavement-related information and physical health outcomes were obtained. PTSD Checklist-Civilian Version was used to screen for bereavement-related PTSD. RESULT: The morbidity of PTSD reached 30.9%, while in the group of age over 60 the morbidity reached 31.6%. Stratified by potential demographic risk factors, SDPs have significant between-group differences of PTSD. Specially, being women, higher income, losing the single child at older age, more serious medical conditions and being Shidu for a shorter period indicated higher severity of PTSD in SDPs. The single child dying at a older age and from accidence were also significant indicators. Regression analysis showed the gender of SDPs, hospital visits, and the cause of child death significantly predicted the severity of PTSD. CONCLUSION: With the accelerate process of aging, especially in China, Shidu older adults become a group deserved more attentions. PTSD is clearly a possible reaction to the loss of the only child. The gender and hospital visits of the Shidu older adults and the causes of their child's death significantly related to the prevalence of PTSD, which could help to improve the possibility of early intervening.