Ultrasound-Assisted CRISPRi-Exosome for Epigenetic Modification of α-Synuclein Gene in a Mouse Model of Parkinson's Disease.

Currently, there is a lack of effective treatment for Parkinson's disease (PD). In PD patients, aberrant methylation of SNCA (α-synuclein gene) has been reported and may be a potential therapeutic target. In this study, we established an epigenetic regulation platform based on an exosomal CRISPR intervention system. With the assist of focused ultrasound (FUS) opening the blood-brain barrier, engineered exosomes carrying RVG (rabies viral glycoprotein) targeting peptide, sgRNA (single guide RNA), and dCas9-DNMT3A (named RVG-CRISPRi-Exo) were efficiently delivered into the brain lesions and induced specific methylation of SNCA. In vivo, FUS combined with RVG-CRISPRi-Exo significantly improved motor performance, balance coordination, and neurosensitivity in PD mice, greatly down-regulated the elevation of α-synuclein (α-syn) caused by modeling, rescued cell apoptosis, and alleviated the progression of PD in mice. [18F]-FP-DTBZ imaging suggested that the synaptic function of the nigrostriatal pathway could be restored, which was conducive to the control of motor behavior in PD mice. Pyrosequencing results showed that RVG-CRISPRi-Exo could methylate CpG at specific sites of SNCA, and this fine-tuned editing achieved good therapeutic effects in PD model mice. In vitro, RVG-CRISPRi-Exo down-regulated SNCA transcripts and α-syn expression and relieved neuronal cell damage. Collectively, our findings provide a proof-of-principle for the development of targeted brain nanodelivery based on engineered exosomes and provide insights into epigenetic regulation of brain diseases.

Mental health profiles and the related socio-demographic predictors in Hong Kong university students under the COVID-19 pandemic: A latent class analysis.

While the COVID-19 pandemic has brought about significant challenges to mental health of university students, there is limited research in this area. Particularly, few studies examined the person-centered mental health symptom profiles such as depression and anxiety and the related socio-demographic predictors. Using Latent Class Analysis (LCA), this study investigated the symptom profiles of depression and anxiety in university students in Hong Kong under the COVID-19 pandemic and the socio-demographic predictors. A total of 978 undergraduate students completed an online questionnaire including socio-demographic factors and measures of depression and anxiety during the summer of 2022. The LCA identified three latent classes: "normal" group, "moderate comorbid depression and anxiety" group and "severe comorbid depression and anxiety" group. Multinominal logistic regression showed that comparing with the "normal" group and the "moderate symptom" group, the "severe symptom" group had higher personal financial difficulties and individual/family member unemployment during the pandemic. In contrast, other socio-demographic factors (age, gender, year of study, living status, and COVID-19 infection status) had no significant association with group status. The study contributes to understanding of person-centered depression and anxiety symptom profiles and the risk role of personal financial difficulty in mental health of university students under the pandemic.

Psychosocial correlates of mental health of university students in Hong Kong under COVID-19.

Although the COVID-19 pandemic has caused many problems for university students, there are several research gaps in the study of psychological well-being of Hong Kong university students. First, few studies have examined different ecological correlates of mental health in a single study. Second, few studies have used both psychological morbidity and positive well-being as indicators of mental health. Third, we know little about the relationships between university students' perceived need satisfaction, difficulties, service utilization, and their mental health. Hence, we conducted a study (N = 1,020 university students) in the later stage of the COVID-19 pandemic in Hong Kong. For mental health, we included measures of negative mental health (psychological morbidity) and positive mental health. We addressed several research questions in this study: (1) what is the mental health status of Hong Kong university students? (2) what is the relationship between COVID-19 stress and student mental health? (3) what are the intrapersonal correlates of student mental health? (4) are interpersonal factors related to student mental health? (5) are need satisfaction, difficulties encountered, and service utilization related to students' mental health? (6) are there gender differences in the effects of correlates in different ecological systems? Analyses using structural equation modeling showed several observations. First, the prevalence of mental health symptoms among university students was alarming. Second, COVID-19 related socio-economic stress positively predicted psychological morbidity but negatively predicted well-being. Third, beliefs about adversity, resilience, and emotional competence predicted mental health. Fourth, family functioning was related to psychological morbidity negatively but connected with well-being positively. Fifth, while need satisfaction predicted psychological morbidity negatively, difficulties encountered showed the opposite direction. Besides, the perceived usefulness of university services positively predicted mental health. Finally, there were no gender differences in the effects of different predictors. The present findings enable public health researchers to formulate theoretical models on different ecological determinants of university students' mental health under the pandemic. For public health practitioners, the study highlights the importance of reducing COVID-19 associated stress, strengthening internal and external developmental assets, and meeting the psychosocial needs of university students as strategies to promote their mental health under the pandemic.

Socio-demographic and mental health correlates of internet addiction amongst Hong Kong university students under COVID-19.

Introduction: Regarding the problem of Internet addiction (IA) amongst university students under the pandemic, there are several research gaps. Firstly, few studies have examined IA of university students in Hong Kong, which is a Chinese society heavily influenced by Western values. In addition, findings on the socio-demographic correlates and psychological well-being predictors of IA in university students are unclear. Finally, researchers have not systematically examined the interaction effects of socio-demographic factors (particularly gender and personal infection of COVID-19) and psychological morbidity on IA. This pioneer study aimed to investigate the predictive role of socio-demographic factors and psychological morbidity in IA, and the moderating effects of gender and personal infection of COVID-19 on the relationship between psychological morbidity and IA. Methods: We conducted an online survey (N = 1,020 university students) during the ending phase of Wave 5 of the pandemic in Hong Kong (late 2022 to early 2023). Socio-demographic correlates included age, gender, living status, personal and family financial situation, student status, personal and family infection of COVID-19. Participants responded to validated measures of psychological morbidity, including depression, suicidal behavior, and hopelessness. Hierarchical regression and simple slope analyses were used to examine the predictive role of socio-demographic variables and psychological morbidity in IA and the interactive effect of gender and personal infection of COVID-19 with psychological morbidity on IA. Results: Personal financial difficulty was a significant socio-demographic predictor of IA. Depression, suicidal behavior, and hopelessness positively predicted IA. We also found a significant interaction effect of gender and psychological morbidity on IA. While the predictive relationship between depression and IA was stronger in males than in females, hopelessness was more strongly related to IA in females than in males. Finally, there was a significant interaction effect of personal infection of COVID-19 and suicidal behavior on IA. Conclusion: Personal financial difficulty was a socio-economic correlate of IA. Psychological morbidity also predicted IA. Gender and personal infection of COVID-19 moderated the linkage between psychological morbidity and IA. The findings of the study enhance our understanding of individual differences in IA in university students during the pandemic, particularly concerning different ecological risk factors.

Profiles and predictors of mental health of university students in Hong Kong under the COVID-19 pandemic.

This study investigated the mental health problems of university students in Hong Kong and related sociodemographic and psychosocial predictors under the pandemic. A total of 978 undergraduate students (mean age = 20.69 ± 1.61) completed an online questionnaire measuring sociodemographic factors, psychological morbidity, positive well-being, COVID-19 related stress and self-efficacy, and positive psychosocial attributes. Psychosocial risk factors included psychological morbidity, COVID-19 related stress, and difficulties encountered under the pandemic, whereas protective factors comprised pandemic related self-efficacy, positive psychological attributes, positive environmental factors, need satisfaction and positive perception toward service. Results showed that psychological morbidity in the participants was widespread, and it was related to sociodemographic factors, particularly family financial difficulties. While pandemic related stress positively predicted psychological morbidity and negatively predicted well-being indicators, COVID-19 self-efficacy showed an opposite effect. Besides, positive psychological attributes (resilience, emotional competence, and positive beliefs related to adversity) and environmental factors (healthy family functioning, peer support, and supportive community atmosphere) negatively predicted psychological morbidity and positively predicted well-being. Furthermore, need satisfaction and positive perception toward service were negatively associated with psychological morbidity and positively associated with well-being, while perceived difficulties showed an opposite effect.

Risk Factors and Protective Factors of Internet Addiction in University Students during the Pandemic: Implications for Prevention and Treatment.

While the prevalence rates of Internet addiction (IA) amongst young people during the pandemic are disturbing, few studies have investigated the risk and protective factors of IA in Hong Kong university students under COVID-19. In this study, we examined the relationship between COVID-19-related stress and IA and the role of psychological morbidity and positive psychological attributes in the relationship. In summer 2022, 978 university students completed a survey assessing pandemic-related stress, psychological morbidity, and positive psychological attributes. While psychological morbidity was indexed by depression, post-traumatic stress disorder, and suicidal behavior, positive psychological attributes included life satisfaction, flourishing, adversity beliefs, emotional competence, resilience, and family functioning measures. Results showed that stress and psychological morbidity positively predicted IA, and psychological morbidity mediated the association between stress and IA. Positive psychological attributes negatively predicted stress and IA, and mediated the connection between stress and IA. Positive psychological attributes moderated the mediating effect of psychological morbidity on the relationship between stress and IA. In addition to theoretical contributions, this study contributes to IA prevention and treatment: reducing psychological morbidity and promoting positive psychological attributes are promising strategies to address IA issues in young people.

Stress and depressive symptoms in university students in Hong Kong under the pandemic: Moderating effect of positive psychological attributes.

Introduction: There are very few studies examining the psychological well-being of university students in Hong Kong under the COVID-19 pandemic. Besides COVID-19-related stress, the "social event" in 2019-2020 has caused significant stress in young people. As such, we attempted to answer several research questions in this paper. First, what are the relationships between stresses (COVID-19 and "social event" related stresses) and psychological well-being indexed by depressive symptoms? Based on the stress and coping perspective, we predicted that there would be positive relationships between both types of stress and depression. Second, what are the relationships between different positive psychological factors (including life satisfaction, resilience and emotional management, flourishing, and beliefs about adversity) and depression? Based on different theoretical models of positive psychology, we hypothesized that negative relationships would exist between positive psychological factors and depressive symptoms. Third, do positive psychological attributes moderate the associations between stresses (COVID-19 and "social event" related stresses) and depressive symptoms? Based on the positive psychology literature, we hypothesized that positive psychological attributes would buffer the negative impact of stresses on depression. Methods: We recruited university students roughly one year after the first wave of the pandemic (N = 1,648) in early 2021. We used 25 items to measure COVID-19-related stress and "social event" related stress. For psychological well-being indexed by depressive symptoms, we used the "Centre for Epidemiologic Studies Depression Scale Revised (CESD-R)". For positive psychological attributes, we employed established measures of life satisfaction, resilience and emotional management, flourishing, and beliefs about adversity. Results: Regarding the relationship between stress and depression, we found positive relationships between both types of stress and depressive symptoms. As predicted, negative relationships existed between all positive psychological attributes and depressive symptoms. Besides, the positive psychological attributes significantly moderated the effects of stresses on depression, suggesting that these factors can reduce the negative impacts of stresses on depression. The present findings provide support for those models, highlighting the importance of positive psychological attributes as protective factors for university students' depression. Discussion: The findings of this study underscore the important role of positive psychological attributes in the stress-depression relationship in university students under the pandemic. The findings also generalize the positive youth development theory in the Chinese context. In terms of practice, university administrators and service providers should consider cultivating positive psychological attributes in university students with the purpose of promoting their psychological well-being.

Ultrasound nanotheranostics: Toward precision medicine.

Ultrasound (US) is a mechanical wave that can penetrate biological tissues and trigger complex bioeffects. The mechanisms of US in different diagnosis and treatment are different, and the functional application of commercial US is also expanding. In particular, recent developments in nanotechnology have led to a wider use of US in precision medicine. In this review, we focus on US in combination with versatile micro and nanoparticles (NPs)/nanovesicles for tumor theranostics. We first introduce US-assisted drug delivery as a stimulus-responsive approach that spatiotemporally regulates the deposit of nanomedicines in target tissues. Multiple functionalized NPs and their US-regulated drug-release curves are analyzed in detail. Moreover, as a typical representative of US therapy, sonodynamic antitumor strategy is attracting researchers' attention. The collaborative efficiency and mechanisms of US and various nano-sensitizers such as nano-porphyrins and organic/inorganic nanosized sensitizers are outlined in this paper. A series of physicochemical processes during ultrasonic cavitation and NPs activation are also discussed. Finally, the new applications of US and diagnostic NPs in tumor-monitoring and image-guided combined therapy are summarized. Diagnostic NPs contain substances with imaging properties that enhance US contrast and photoacoustic imaging. The development of such high-resolution, low-background US-based imaging methods has contributed to modern precision medicine. It is expected that the integration of non-invasive US and nanotechnology will lead to significant breakthroughs in future clinical applications.

The relationship between anxiety and depression under the pandemic: The role of life meaning.

Introduction: COVID-19 is a stressor creating much anxiety for the general public, such as anxiety related to possible infection, social distancing, financial strain and uncertainty. As the scientific literature shows that there is an intimate relationship between anxiety and depression, it is important to ask whether anxiety is related to depression under the pandemic and whether spirituality indexed by life meaning can moderate the relationship between anxiety and depression. According to theories highlighting the importance of life meaning, relative to people with a higher level of life meaning, the relationship between anxiety and depression would be stronger in people with a lower level of life meaning. Methods: Empirically, we collected data in two waves (i.e., before and after the first wave of COVID-19, respectively) from 4,981 adolescents recruited in Sichuan, China. Then, the 41-item "Screen for Child Anxiety Related Emotional Disorders" was employed to measure anxiety symptoms, 20-item "Center for Epidemiological Studies-Depression Scale" was utilized to examine depression symptoms, and the "Spirituality Subscale of the Chinese Positive Youth Development Scale" for assessing life meaning. Results: We found that anxiety significantly predicted depression at each wave and across time. Second, controlling for Wave 1 depression scores, results showed that a drop in Wave 1 anxiety predicted a drop in depressive symptoms over time. Regarding the relationship between meaning in life and depression, spirituality indexed by meaning in life negatively predicted depression at each wave and over time, and predicted change in depression across time. Finally, multiple regression analyses showed that life meaning moderated the predictive effect of anxiety on depression. Discussion: The findings support the thesis that spirituality serves as a protective factor for psychological morbidity in Chinese adolescents. The study also suggests the importance of helping adolescents to develop life meaning under COVID-19.

The Effectiveness of a Leadership Subject Using a Hybrid Teaching Mode during the Pandemic: Objective Outcome and Subjective Outcome Evaluation.

Positive youth development (PYD) is an innovative approach to protect students from mental health problems and promote their positive and holistic development. Although there are many studies on the beneficial effects of PYD programs on youth in high school and community contexts, it is not clear whether subjects adopting PYD principles can promote positive development for university students. Moreover, it is unclear whether such subjects are effective under COVID-19, where subjects are commonly taught via the "hybrid" mode (i.e., face-to-face plus online teaching). The present study examined students' changes in the PYD, wellbeing, and desired graduate attributes after they had taken a leadership subject utilizing PYD principles taught by the "hybrid" mode (N = 630). Adopting the one-group pre-test and post-test design (i.e., objective outcome evaluation), we found that students showed significant positive improvement in PYD indicators, wellbeing, as well as desired graduate attributes. Additionally, students had high satisfaction with the course design and teaching staff, and perceived many benefits from this subject based on the subjective outcome evaluation conducted at the end of the subject. Results also showed that students' satisfaction with the curriculum significantly and positively predicted their positive change in PYD indicators, indicating the convergence of subjective outcome evaluation and objective outcome evaluation. The results highlight the positive impacts of the hybrid mode leadership subject with PYD principles in higher education.

Promotion of Meaning in Life and Wellbeing Among University Students During the COVID-19 Pandemic via a Service-Learning Subject.

Utilizing the principle of "learning by doing," service-learning (SL) course provides a platform for university students to apply academic knowledge in serving the community, reflecting on the serving experiences, deepening their understanding of the knowledge, and further improving their competence, responsibility, wellbeing, and meaning in life (MIL). This study reported university students' changes in psychological wellbeing (positive youth development attributes), subjective wellbeing (life satisfaction), and MIL after taking a SL subject during the COVID-19 pandemic through a one-group pretest-posttest design. Based on the data collected from 229 students (mean age = 20.86 ± 1.56 years, 48.0% females), repeated-measures multivariate general linear model (GLM) analyses revealed that students showed significant positive changes in wellbeing and MIL. In addition, pretest MIL scores positively predicted posttest scores of the two wellbeing measures but not vice versa. As predicted, improvement in MIL among students was closely associated with the positive changes in both psychological and subjective wellbeing measures. These findings suggest that SL participation during the pandemic may promote students' life meaning and foster their wellbeing. Furthermore, MIL and wellbeing may improve simultaneously, and MIL enhancement may further contribute to improvement in psychological and subjective wellbeing. The findings further prove that SL is an effective pedagogy in higher education settings in promoting youth positive development.

The Impact of Positive Youth Development Attributes and Life Satisfaction on Academic Well-Being: A Longitudinal Mediation Study.

While research studies revealed that positive youth development (PYD) attributes have beneficial impact on adolescent developmental outcomes, whether and how PYD qualities are related to academic well-being (such as academic stress and academic satisfaction) are unclear. Based on a longitudinal study (N = 2,312 secondary school students; Mage = 12.54 ± 0.68; 51% female) in Hong Kong, the present study tested a longitudinal mediation model in which it was hypothesized that PYD qualities predicted life satisfaction, academic stress, and academic satisfaction, with satisfaction with life mediating the influence of PYD qualities on academic well-being. Results showed that PYD qualities positively predicted academic satisfaction but negatively predicted academic stress over time. While life satisfaction partially mediated the influence of PYD attributes on academic satisfaction, it fully mediated the influence of PYD attributes on academic stress. The present study supports the proposed conceptual model and underscores the role of PYD qualities in academic well-being through the mediation of life satisfaction.

Influence of Family Factors on Substance Use in Early Adolescents: A Longitudinal Study in Hong Kong.

The present study examined the concurrent and longitudinal influences of paternal and maternal factors on the levels of and changes in substance use among early adolescents. Based on three waves of data collected from 2,669 junior high school Chinese students in Hong Kong, we found that fathers' and mothers' behavioral control and the quality of parent-adolescent relationship were negative predictors of the initial levels of substance use. Higher levels of maternal behavioral control and quality of mother-adolescent relationship predicted a slower rate of increase in adolescent substance use. Parental psychological control was not a significant predictor of the growth rate of adolescent substance use. While fathers' behavioral control and mother-adolescent relationship were stable concurrent predictors, the mother-adolescent relationship was a robust longitudinal predictor of adolescent substance use. The findings underline the critical roles of parents in influencing adolescent substance use.

Positive youth development: current perspectives.

This review outlines the current perspectives on positive youth development (PYD). Besides presenting the diverse theoretical roots contributing to PYD approaches, this review also introduces several PYD perspectives, including Benson's 40 developmental assets, Lerner's 5Cs and 6Cs conceptions, Catalano's 15 PYD constructs, social-emotional learning (SEL) and the "being" perspective (character and spirituality). A comparison of the different PYD models in terms of theoretical orientation, the role of community, spirituality, character/morality, thriving, "being" versus "doing" and origin is also presented. The review suggests three future research directions, including the development of spirituality and character approaches to PYD, differentiating the role of "being" versus "doing" in PYD and construction of PYD models as well as conducting related research in non-Western contexts.

Child abuse and suicidal ideation among adolescents in China.

The present study examined the relationship among physical abuse, psychological abuse, perceived family functioning and adolescent suicidal ideation in Shanghai, China. Perceived family functioning was investigated as a possible moderator between physical abuse, psychological abuse and suicidal ideation. A cross sectional survey using convenience sampling was conducted. A total of 560 valid self-administered questionnaires were completed by the students aged from 12 to 17 in Shanghai. Descriptive statistical analyses, Pearson correlations analyses, and hierarchical regression analyses were adopted as methods of data analyses. Results indicated that physical abuse was significantly associated with greater adolescent suicidal ideation, while a higher level of perceived family functioning was significantly associated with lower suicidal ideation. However, psychological abuse was not associated with suicidal ideation. Perceived family functioning was shown to be a moderator between physical abuse and suicidal ideation. Specifically, mutuality and family communication moderated the relationship between physical abuse and suicidal ideation. To decrease adolescent suicidal ideation, measures are suggested to prevent physical abuse and enhance family functioning. First, it is important to increase the parents' awareness of the meaning and boundaries of physical abuse, as well as the role it plays in contributing to adolescent suicidal ideation. Second, parents should be taught appropriate parenting skills and knowledge and be guided to treat the children as individuals with their unique personality, rights and privileges. Third, it is important to promote family harmony, effective communication as well as mutual trust, concern and understanding among family members.

Synthesis of polyisoprene terpenoid dendrons and their applications in oligo(phenylene ethynylene)s as "shells".

The novel double-stage convergent synthesis of a new class of polyisoprene terpenoid (PIPTP) dendrons is described. PIPTP dendrons bear a highly branched aliphatic hydrocarbon skeleton and a hydrophilic hydroxy focal point functionality. These dendrons have the specific formula C((5×2)(G+1)(-5))H((5×2)(G+2)(-8))O, and each dendritic layer is constructed from an isoprene unit. The key branching steps involve a double alkyl-metal addition to an ester functionality, followed by deoxygenation of the resulting tertiary alcohol by triethylsilane and trifluoroacetic acid, then hydrogenation or hydrogenolysis. The dendrons were also attached to oligo(phenylene ethynylene)s (OPEs) so as to function as protective shells to allow fine tuning of the nanoscopic environment around the OPE moiety, and to exert precise control of the packing density and intermolecular interaction between the OPE cores. Fluorescence quantum yield data reveal that the OPE core is better encapsulated by the PIPTP dendrons than by Fréchet dendrons.

Novel synthesis of amphiphilic dendrons by the double-stage convergent method.

A series of amphiphilic dendrons (G1-G4) have been designed and synthesized, which have a highly branched aliphatic hydrocarbon skeleton and a hydrophilic hydroxyl functionality to enable conjugation with other substrates. The higher generation dendrons (G3 and G4) were synthesized by a double-stage convergent method, which shortened the synthetic route significantly and provided the products in an efficient manner. The key branching step involved a double alkyl-metal addition to an ester functionality followed by deoxygenation of a resulting tertiary alcohol by triethylsilane.