Synthesis of Thiophene-Based Derivatives and the Effects of Their Molecular Structure on the Mesomorphic Behavior and Temperature Range of Liquid-Crystalline Blue Phases

The development of blue-phase liquid crystal (BPLC) materials with a wide temperature range is of great significance for practical applications in the optoelectronic field. In the study, bent-core derivatives with a 3-hexyl-2,5-disubstituted thiophene central ring in the λ-shaped molecular structure were designed and synthesized. Their mesomorphic behavior and effect on the blue-phase (BP) temperature range were investigated. Interestingly, a BP was achieved both during the heating and cooling processes by doping with a proper concentration of chiral compound into the thiophene bent-shaped molecule with high rigidity, while derivatives with fluorine atom substitution only exhibited cholesteric phase no matter how many chiral compounds were added. This result proved that BP is highly sensitive to the molecular structures of bent-shaped molecules. Moreover, the BP temperature range was broadened when adding these molecules into a BPLC host, which thus improved the BP temperature range from the initial value, no more than 4 °C, to as much as 24 °C. The experimental phenomena were reasonably explained through molecular simulation calculations. The study may provide some experimental basis and theoretical guidance for the design of novel bent-shaped molecules and BPLC material with a wide temperature range

Cross-Cultural Longitudinal Study on Cognitive Decline (CLoCODE) for Subjective Cognitive Decline in China and Germany: A Protocol for Study Design

Background: Subjective cognitive decline (SCD) is considered as the first symptomatic manifestation of Alzheimer's disease (AD), which is also affected by different cultural backgrounds. Establishing cross-cultural prediction models of SCD is challenging. Objective: To establish prediction models of SCD available for both the Chinese and European populations. Methods: In this project, 330 SCD from China and 380 SCD from Germany are intended to be recruited. For all participants, standardized assessments, including clinical, neuropsychological, apolipoprotein E (APOE) genotype, blood, and multi-parameter magnetic resonance imaging (MRI) at baseline will be conducted. Participants will voluntarily undergo amyloid positron emission tomography (PET) and are classified into amyloid-beta (A beta) positive SCD (SCD+) and A beta negative SCD (SCD-). First, baseline data of all SCD individuals between the two cohorts will be compared. Then, key features associated with brain amyloidosis will be extracted in SCD+ individuals, and the diagnosis model will be established using the radiomics method. Finally, the follow-up visits will be conducted every 12 months and the primary outcome is the conversion to mild cognitive impairment or dementia. After a 4-year follow-up, we will extract factors associated with the conversion risk of SCD using Cox regression analysis. Results: At present, 141 SCD from China and 338 SCD from Germany have been recruited. Initial analysis showed significant differences in demographic information, neuropsychological tests, and regional brain atrophy in SCD compared with controls in both cohorts. Conclusion: This project may be of great value for future implications of SCD studies in different cultural backgrounds

MARCH2 regulates autophagy by promoting CFTR ubiquitination and degradation and PIK3CA-AKT-MTOR signaling

<p>MARCH2 (membrane-associated RING-CH protein 2), an E3 ubiquitin ligase, is mainly associated with the vesicle trafficking. In the present study, for the first time, we demonstrated that MARCH2 negatively regulates autophagy. Our data indicated that overexpression of MARCH2 impaired autophagy, as evidenced by attenuated levels of LC3B-II and impaired degradation of endogenous and exogenous autophagic substrates. By contrast, loss of <i>MARCH2</i> expression had the opposite effects. In vivo experiments demonstrate that <i>MARCH2</i> knockout mediated autophagy results in an inhibition of tumorigenicity. Further investigation revealed that the induction of autophagy by <i>MARCH2</i> deficiency was mediated through the PIK3CA-AKT-MTOR signaling pathway. Additionally, we found that MARCH2 interacts with CFTR (cystic fibrosis transmembrane conductance regulator), promotes the ubiquitination and degradation of CFTR, and inhibits CFTR-mediated autophagy in tumor cells. The functional PDZ domain of MARCH2 is required for the association with CFTR. Thus, our study identified a novel negative regulator of autophagy and suggested that the physical and functional connection between the MARCH2 and CFTR in different conditions will be elucidated in the further experiments.</p