Across adolescence, individuals enrich their concrete, empathic, context-specific interpretations of social-world happenings with abstract, situation-transcending, system-level considerations-invoking values, bigger implications and broader emotional perspectives. To investigate neural mechanisms involved in abstract construals vs concrete construals and the effects of emotional engagement on these mechanisms, 65 mid-adolescents aged 14-18 years reacted to compelling video mini-documentaries during private, open-ended interviews and again during functional magnetic resonance imaging. Following calls to diversify samples, participants were ethnically diverse low-socioeconomic status (SES) urban adolescents performing well in school. Participants spontaneously produced both concrete and abstract construals in the interview, and tendencies to produce each varied independently. As hypothesized, participants who made more abstract construals showed a greater subsequent default mode network (DMN) activity; those who made more concrete construals showed greater executive control network (ECN) activity. Findings were independent of IQ, SES, age and gender. Within individuals, DMN activation, especially when individuals were reporting strong emotional engagement, and ECN deactivation together predicted an abstract construal to a trial. Additionally, brief ECN activation early in the trial strengthened the DMN-abstraction relationship. Findings suggest a neural mechanism for abstract social thought in adolescence. They also link adolescents' natural construals of social situations to distinct networks' activity and suggest separable sociocognitive traits that may vary across youths.

Objectives: The objective of this study was to gain insight into how Chinese special education teachers1 conceptualize individual education plan (IEP) and how IEP is implemented in their daily work. Method: Fourteen administrators and teachers from several special education schools in three metropolitan cities in China were interviews about their perspective of IEP and IEP practice at their work. Results: The results suggested that despite remaining concerns about the implementation of IEP Chinese teachers highly commit to the value of IEP. It is noted that the IEP process in Chinese schools is quite similar to that of US schools in terms of some major requirements and yet some adaptions are made given the different social-cultural context and that the IEP practice is influenced by a variety of factors such as schools policy, curriculum, and the paucity of educational resources. Conclusion: There is a need for developing a systematic guideline of IEP considering inconsistency of implementing IEP in schools. Improving teachers professional competence is critical to the effectiveness of IEP practice in China, and local governments should put in more efforts in ensuring adequate resource being provided to schools and teachers regarding the implementation of IEPs.

Developmental scientists have long described mid-adolescents emerging capacities to make deep meaning about the social world and self, here called transcendent thinking, as a hallmark developmental stage. In this 5-years longitudinal study, sixty-five 14-18 years-old youths proclivities to grapple psychologically with the ethical, systems-level and personal implications of social stories, predicted future increases in the coordination of two key brain networks: the default-mode network, involved in reflective, autobiographical and free-form thinking, and the executive control network, involved in effortful, focused thinking; findings were independent of IQ, ethnicity, and socioeconomic background. This neural development predicted late-adolescent identity development, which predicted young-adult self-liking and relationship satisfaction, in a developmental cascade. The findings reveal a novel predictor of mid-adolescents neural development, and suggest the importance of attending to adolescents proclivities to engage agentically with complex perspectives and emotions on the social and personal relevance of issues, such as through civically minded educational approaches.

Renal fibrosis is an unavoidable end result of all forms of progressive chronic kidney diseases (CKD). Discovery of efficacious drugs against renal fibrosis is in crucial need. In a preliminary study we found that a derivative of artemisinin, dihydroartemisinin (DHA), exerted strong renoprotection, and reversed renal fibrosis in adenine-induced CKD mouse model. In this study we investigated the anti-fibrotic mechanisms of DHA, particularly its specific target in renal cells. Renal fibrosis was induced in mice by unilateral ureteral obstruction (UUO) or oral administration of adenine (80 mg · kg-1), the mice received DHA (30 mg · kg-1 · d-1, i.g.) for 14 or 21 days, respectively. We showed that DHA administration markedly attenuated the inflammation and fibrotic responses in the kidneys and significantly improved the renal function in both the renal fibrosis mouse models. In adenine-treated mice, DHA was more effective than 5-azacytidine against renal fibrosis. The anti-fibrotic effects of DHA were also observed in TGF-β1-treated HK-2 cells. In order to determine the target protein of DHA, we conducted pull-down technology coupled with shotgun proteomics using a small-molecule probe based on the structure of DHA (biotin-DHA). As a results, DNA methyltransferase 1 (DNMT1) was identified as the anti-fibrotic target of DHA in 3 different types of renal cell lines (HK-2, HEK293 and 3T3). We demonstrated that DHA directly bound to Asn 1529 and Thr 1528 of DNMT1 with a Kd value of 8.18 μM. In primary mouse renal tubular cells, we showed that DHA (10 μM) promoted DNMT1 degradation via the ubiquitin-proteasome pathway. DHA-reduced DNMT1 expression effectively reversed Klotho promoter hypermethylation, which led to the reversal of Klotho protein loss in the kidney of UUO mice. This subsequently resulted in inhibition of the Wnt/β-catenin and TGF-β/Smad signaling pathways and consequently conferred renoprotection in the animals. Knockdown of Klotho abolished the renoprotective effect of DHA in UUO mice. Our study reveals a novel pharmacological activity for DHA, i.e., renoprotection. DHA exhibits this effect by targeting DNMT1 to reverse Klotho repression. This study provides an evidence for the possible clinical application of DHA in the treatment of renal fibrosis.

Hair follicle stem cells are regulated by dermal papilla fibroblasts, their principal signaling niche. Overactivation of Hedgehog signaling in the niche dramatically accelerates hair growth and induces follicle multiplication in mice. On single-cell RNA sequencing, dermal papilla fibroblasts increase heterogeneity to include new Wnt5a^high states. Transcriptionally, mutant fibroblasts activate regulatory networks for Gli1, Alx3, Ebf1, Hoxc8, Sox18, and Zfp239. These networks jointly upregulate secreted factors for multiple hair morphogenesis and hair-growth-related pathways. Among these is non-conventional TGF-β ligand Scube3. We show that in normal mouse skin, Scube3 is expressed only in dermal papillae of growing, but not in resting follicles. SCUBE3 protein microinjection is sufficient to induce new hair growth, and pharmacological TGF-β inhibition rescues mutant hair hyper-activation phenotype. Moreover, dermal-papilla-enriched expression of SCUBE3 and its growth-activating effect are partially conserved in human scalp hair follicles. Thus, Hedgehog regulates mesenchymal niche function in the hair follicle via SCUBE3/TGF-β mechanism.