A Highly Translatable Dual-arm Local Delivery Strategy To Achieve Widespread Therapeutic Coverage in Healthy and Tumor-bearing Brain Tissues.

Drug delivery nanoparticles (NPs) based entirely on materials generally recognized as safe that provide widespread parenchymal distribution following intracranial administration via convection-enhanced delivery (CED) are introduced. Poly(lactic-co-glycolic acid) (PLGA) NPs are coated with various poloxamers, including F68, F98, or F127, via physical adsorption to render particle surfaces non-adhesive, thereby resisting interactions with brain extracellular matrix. F127-coated PLGA (F127/PLGA) NPs provide markedly greater distribution in healthy rat brains compared to uncoated NPs and widespread coverage in orthotopically-established brain tumors. Distribution analysis of variously-sized F127/PLGA NPs determines the average rat brain tissue porosity to be between 135 and 170 nm while revealing unprecedented brain coverage of larger F127/PLGA NPs with an aid of hydraulic pressure provided by CED. Importantly, F127/PLGA NPs can be lyophilized for long-term storage without compromising their ability to penetrate the brain tissue. Further, 65- and 200-nm F127/PLGA NPs lyophilized-reconstituted and administered in a moderately hyperosmolar infusate solution show further enhance particle dissemination in the brain via osmotically-driven enlargement of the brain tissue porosity. Combination of F127/PLGA NPs and osmotic tissue modulation provides a means with a clear regulatory path to maximize the brain distribution of large NPs that enable greater drug loading and prolong drug release.

Learning motivations and effort beliefs in Confucian cultural context: A dual-mode theoretical framework of achievement goal.

For decades, results of international academic assessments have shown that students in the Confucian cultural circle performed outstandingly well. However, many studies also showed that East Asian students often experienced high pressure and had low interest in academic learning. The "high achievement but low interest" phenomenon has aroused great interest in psychologists and educators. From the emic perspective of cultural psychology, this theoretical article aims to propose (1) a dual-mode framework of achievement goals to conceptualize the motivation for academic learning and (2) two kinds of effort beliefs (obligation-oriented and improvement-oriented belief about effort) students may develop when pursuing academic achievement in societies influenced by Confucian heritage culture. Moreover, a series of empirical studies based on the framework are presented in this article to show that (1) Chinese students' academic striving is motivated not only by their interest but also by role obligation or virtue of effort, (2) students' effort beliefs could predict their learning emotion and behavioral tendency, and (3) students' effort beliefs could be influenced by their parents' and teachers' effort beliefs. The theoretical and practical implications of the framework are discussed.

Non-adhesive and highly stable biodegradable nanoparticles that provide widespread and safe transgene expression in orthotopic brain tumors.

Several generations of poly(ß-amino ester) (PBAE) polymers have been developed for efficient cellular transfection. However, PBAE-based gene vectors, similar to other cationic materials, cannot readily provide widespread gene transfer in the brain due to adhesive interactions with the extracellular matrix (ECM). We thus engineered eight vector candidates using previously identified lead PBAE polymer variants but endowed them with non-adhesive surface coatings to facilitate their spread through brain ECM. Specifically, we screened for the ability to provide widespread gene transfer in tumor spheroids and healthy mouse brains. We then confirmed that a lead formulation provided widespread transgene expression in orthotopically established brain tumor models with an excellent in vivo safety profile. Lastly, we developed a method to store it long-term while fully retaining its brain-penetrating property. This new platform provides a broad utility in evaluating novel genetic targets for gene therapy of brain tumors and neurological disorders in preclinical and clinical settings. Graphical abstract We engineered biodegradable DNA-loaded brain-penetrating nanoparticles (DNA-BPN) possessing small particle diameters (< 70 nm) and non-adhesive surface coatings to facilitate their spread through brain tumor extracellular matrix (ECM). These DNA-BPN provide widespread gene transfer in models recapitulating the ECM barrier, including three-dimensional multicellular tumor spheroids and mice with orthotopically established brain tumor.

Rethinking dependent personality disorder: comparing different human relatedness in cultural contexts.

We argue that the Diagnostic and Statistical Manual of Mental Disorders dependent personality disorder is a culturally related concept reflecting deeply rooted values, beliefs, and assumptions of American individualistic convictions about self and interpersonal relationship. This article integrates social psychology concepts into the exploration of psychopathology. Beginning with the construct of individualism and collectivism, we demonstrate the limitations of this commonly used framework. The indigenous Chinese concept of Confucianism and Chinese Relationalism is introduced to highlight that a well-differentiated self is not a universal premise of human beings, healthy existence. In East Asian Confucianism the manifestation of dependence and submission may be considered individuals' proper behavior and required for their social obligation, rather than a direct display of individuals' personality. Thus, the complexity of dependent personality disorder is beyond the neo-Kraepelinian approach assumed by the Diagnostic and Statistical Manual of Mental Disorders system.

Taiwanese students' self-attributions for two types of achievement goals.

Previous studies of achievement motivations have focused on the patterns of self-attribution with little consideration of the effects of achievement goals. In the present study, the authors investigated Taiwanese students' self-attribution for achievement goals mainly on the basis of autonomous interest (i.e., personal goals) and on social expectation (i.e., vertical goals). The authors administered self-developed scenario simulation questionnaires to undergraduate and graduate participants in 2 studies. The results showed that (a) in pursuit of personal goals, participants tended to attribute success to internal factors and failure to external factors and (b) in pursuit of vertical goals, participants tended to attribute their failure to lack of effort. The authors further discuss the theoretical implications of these findings under a cultural context.

The Mediating Role of Self-Exertion on the Effects of Effort on Learning Virtues and Emotional Distress in Academic Failure in a Confucian Context.

Previous studies have found that in East Asian Confucian societies, hardworking students are often trapped in a dilemma of enjoying a positive moral image while suffering from emotional distress due to academic failure. This study intends to further explore whether the cultural-specific belief in self-exertion acts as a psychological mechanism to lessen these students' negative emotions. A group of 288 college students in Taiwan were administered a questionnaire to record their responses to past academic failures. The results from structural equation modeling showed that self-exertion functioned as a mediator between the effects of effort on learning virtues and emotional distress. Self-exertion to fulfill one's duty to oneself positively mediated the effect of effort on learning virtues, whereas self-exertion to fulfill one's duty to one's parents negatively mediated the effect of effort on emotional distress. Theoretical and cultural implications are further discussed.

High-School Teachers' Beliefs about Effort and Their Attitudes toward Struggling and Smart Students in a Confucian Society.

Previous studies conducted in Western societies showed that instructors' beliefs about intellectual ability affected their attitudes toward students. However, in many East Asian societies influenced by Confucian culture, teachers not only hold beliefs of ability but also two kinds of beliefs about effort: obligation-oriented belief (i.e., believing that effort-making is a student's role obligation) and improvement-oriented belief (i.e., believing that effort can conquer the limitations of one's ability). This study aimed to investigate the relationships between teachers' effort beliefs and their attitudes toward favoritism, praise, and expectations toward struggling and smart students. The participants were 151 Taiwanese high-school teachers. Results of Structure Equation Modeling showed that (1) teachers' obligation-oriented belief about effort was positively correlated with their favoritism, praise, short-term and long-term expectations of struggling students, but negatively correlated with their favoritism and praise of smart students, (2) teachers' improvement-orientated belief about effort was negatively correlated with their short-term expectation of smart students and favoritism of struggling students, but positively correlated with their praise of smart students, and (3) the entity theory of intelligence was negatively correlated with favoritism and praise of struggling students, but positively correlated with favoritism of smart students. The theoretical and cultural implications are discussed.