Heterochiral π-stacking dimerization of helical secondary structures with emerging supramolecular chirality.

In this work, we report a new type of interface modes between helical secondary structures by noncovalent assembly along the helical axis. The dimerization of helical secondary structures mediated by aromatic π-stacking leads to discrete heterochiral dimeric helical rods consisting of left-handed helix and right-handed helix, which has been demonstrated by single-crystal X-ray diffraction. We conduct chiral induction studies on discrete heterochiral dimers to regulate the preference of the helical sense. Surprisingly, we found a novel supramolecular chirality potentially occurring inside the super-secondary structure of chirality-induced heterochiral helical dimers, rather than the racemization of helical chirality. Furthermore, chirality-induced heterochiral helical dimers can exhibit unique chiral switches when formed or not formed. In order to identify the emerging supramolecular chirality of discrete heterochiral dimeric helix, we covalently synthesized meso-helix structures with opposite helical handedness. The chirality of aromatic chromophore linker was confirmed by chiral induction despite competition from opposite handed helices, which strongly demonstrates the occurrence of emerging supramolecular chirality in heterochiral dimeric helix. This study not only reports the heterochiral π-stacking dimerization of helical secondary structures for the first time, but also discovers novel supramolecular chirality hidden in the structure of noncovalent and even covalent meso-helices.

A biomimetic ion channel shortens the QT interval of type 2 long QT syndrome through efficient transmembrane transport of potassium ions.

Potassium ion transport across myocardial cell membrane is essential for type 2 long QT syndrome (LQT2). However, the dysfunction of potassium ion transport due to genetic mutations limits the therapeutic effect in treating LQT2. Biomimetic ion channels that selectively and efficiently transport potassium ions across the cellular membranes are promising for the treatment of LQT2. To corroborate this, we synthesized a series of foldamer-based ion channels with different side chains, and found a biomimetic ion channel of K+ (BICK) with the highest transport activity among them. The selected BICK can restore potassium ion transport and increase transmembrane potassium ion current, thus shortening phase 3 of action potential (AP) repolarization and QT interval in LQT2. Moreover, BICK does not affect heart rate and cardiac rhythm in treating LQT2 model induced by E4031 in isolated heart as well as in guinea pigs. By restoring ion transmembrane transport tactic, biomimetic ion channels, such as BICK, will show great potential in treating diseases related to ion transport blockade. STATEMENT OF SIGNIFICANCE: Type 2 long QT syndrome (LQT2) is a disease caused by K+ transport disorder, which can cause malignant arrhythmia and even death. There is currently no radical cure, so it is critical to explore ways to improve K+ transmembrane transport. In this study, we report that a small-molecule biomimetic ion channel BICK can efficiently simulate natural K+ channel proteins on the cardiomyocyte and cure E4031-induced LQT2 in guinea pig by restoring K+ transport function for the first time. This study found that the potassium transmembrane transport by BICK significantly reduced the QT interval, which provides a conceptually new strategy for the treatment of LQT2 disease.

CEO-TMT overseas experience differences and firm performance: A self-categorization theory perspective.

Based on upper echelons and self-categorization theories, this study empirically examines the relationship between CEO-top management team (TMT) overseas experience differences and firm performance and the moderating effects of hometown connectedness, ownership nature, and environmental dynamics. We use data on Chinese manufacturing listed companies from 2012 to 2021. The results show that CEO-TMT overseas experience differences significantly and negatively affect firm performance. Hometown connectedness positively moderates this relationship; as CEO-TMT hometown connectedness increases, the negative impact of CEO-TMT overseas experience differences on firm performance decreases. Finally, state ownership and higher environmental dynamics mitigate the negative relationship between CEO-TMT's overseas experiences and firm performance.

A Revised Approach to Orthodontic Treatment Monitoring From Oralscan Video.

Research on orthodontic treatment monitoring from oralscan video is a new direction in dental digitalization. We designed an approach to reconstruct, segment, and estimate the pose of individual teeth to measure orthodontic treatment. To handle the semantic gap in heterogeneous data on the condition that they are combined linearly, we present a multimedia interaction network (MIN) to combine heterogeneous information in point cloud segmentation by extending the graph attention mechanism. Moreover, a structure-aware quadruple loss is designed to explore the relation between multiple and diverse unmatched points in point cloud registration. The performance of our approach is evaluated on multiple tooth registration datasets, and extensive experiments show that our approach improves the accuracy by a margin of 1.4% in the inlier ratio on the Aoralscan3 dataset when it is compared with prevailing approaches.