Catalytic Asymmetric oxa-Michael−Michael Cascade for Facile Construction of Chiral Chromans via an Aminal Intermediate

An unprecedented highly enantioselective cascade oxa-Michael−Michael reaction has been developed. The simple and practical process, efficiently catalyzed by chiral diphenylprolinol TMS ether, affords a powerful access to highly functionalized synthetically useful chiral chromans. Moreover, notably a new activation mode involving an aminal is disclosed for the first time

Catalytic Asymmetric oxa-Michael−Michael Cascade for Facile Construction of Chiral Chromans via an Aminal Intermediate

An unprecedented highly enantioselective cascade oxa-Michael−Michael reaction has been developed. The simple and practical process, efficiently catalyzed by chiral diphenylprolinol TMS ether, affords a powerful access to highly functionalized synthetically useful chiral chromans. Moreover, notably a new activation mode involving an aminal is disclosed for the first time

Direct and indirect effects and 95% confidence intervals for the mediation model.

<p>Direct and indirect effects and 95% confidence intervals for the mediation model.</p

Experiential Avoidance Mediates the Association between Emotion Regulation Abilities and Loneliness

<div><p>Experiential avoidance (EA) involves the unwillingness to remain in contact with aversive experiences such as painful feelings, thoughts, and emotions. EA is often associated with the development and maintenance of emotional problems. Since loneliness is characterized by negative emotions such as sadness and pessimism, which is often linked to emotional problems, this study aims to test the mediating effects of EA on the relationship between emotion regulation abilities (ERA) and loneliness in a sample of Chinese adults. Five hundred undergraduates completed questionnaires measuring EA (Acceptance and Action Questionnaire; AAQ-Ⅱ), ERA (Failure-relate action orientation; Action Control Scale, ACS-90) and loneliness (UCLA Loneliness Scale). Structural equation modeling showed that EA fully-mediated the relationship between ERA and loneliness. The findings suggest EA is a key mechanism in explaining why people with high ERA are prone to feeling lower levels of loneliness. In particular, these findings have important implications for designing effective psychological interventions for loneliness.</p></div

Organocatalytic Enantioselective Friedel−Crafts Reactions of 1-Naphthols with Aldimines

An organocatalytic enantioselective Friedel−Crafts reaction of 1-naphthols with aldimines has been developed. The method affords a direct access to chiral aminoarylnaphthols in good yields and with good to high enantioselectivities

Organocatalytic Enantioselective Friedel−Crafts Reactions of 1-Naphthols with Aldimines

An organocatalytic enantioselective Friedel−Crafts reaction of 1-naphthols with aldimines has been developed. The method affords a direct access to chiral aminoarylnaphthols in good yields and with good to high enantioselectivities

Structural modeling of HLA-B*1502/peptide/carbamazepine/T-cell receptor complex architecture: implication for the molecular mechanism of carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis

<p>Drug-induced adverse reactions are a significant problem in healthcare worldwide and are estimated to cost billions of dollars annually in the United States. A portion of such reactions is observed to strongly associate with certain human leukocyte antigen (HLA) alleles; one of the strongest associations is the HLA-B*1502 protein with carbamazepine (CBZ)-induced Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) – the odds ratio value can even be higher than one thousand. The particularly strong association in CBZ-induced SJS/TEN suggests that the HLA-B*1502 is not only a genetic marker but also a participant in the pathogenesis of the disease. In the current study, we attempt to computationally model the atomic-level structure of the complete HLA-B*1502/peptide/CBZ/T-cell receptor (TCR) complex architecture based on prior knowledge obtained from epidemiological investigations as well as <i>in vitro</i> and <i>in vivo</i> assays. The model tells a different story about the molecular mechanism of CBZ-induced SJS/TEN from that previously reported for abacavir (ABC)-induced hypersensitivity (HSR); the CBZ molecule is located at the interface between HLA-B*1502/peptide and TCR, directly contacts the P3–P6 residues of antigen peptide, and bound within a pocket region encompassed by two TCR CDR3 fingers. Molecular dynamics simulation and binding energy analysis further reveal that the CBZ shows considerably high affinity to TCR over HLA-B*1502/peptide, which can tightly interact with the former rather than the latter. From the model, two hypotheses are proposed that can well explain most previous observations and are expected to guide next wet-lab experiments. This study could help to promote our understanding of the molecular mechanism and pathological implication underlying CBZ-induced SJS/TEN.</p

Final structural model (n = 500, standardized path coefficients).

<p><i>Note</i>: <i>ERA</i> = emotion regulation abilities; <i>EA</i> = experiential avoidance; <i>L</i> = loneliness (<i>L1–L4</i> four parcels of loneliness). *<i>p</i><0.05; **<i>p</i><0.01.</p

Correlations, means, and standard deviations for study variables.

<p>Correlations, means, and standard deviations for study variables.</p

Construction of a Hierarchical Micro-/Submicro-/Nanostructured 3D-Printed Ti6Al4V Surface Feature to Promote Osteogenesis: Involvement of Sema7A through the ITGB1/FAK/ERK Signaling Pathway

Constructing hierarchical hybrid structures is considered a facile method to improve the osseointegration of implants. Herein, a hierarchical micro-/submicro-/nanostructured surface feature of Ti6Al4V implants (3DAT group) was successfully constructed by combining the inherently formed three-dimensional (3D)-printed microscale topography, acid-etched sub-micropits, and anodized nanotubes. Compared with the classical SLA surface, the microscale topography and sub-micropits increased the three-dimensional space for the cell growth and mechanical stability of implants, while the modification of nanotubes dramatically improved the surface hydrophilicity, protein adsorption, and biomineralization. Most importantly, the 3DAT surface feature possessed excellent osteogenic performance in vitro and in vivo, with the involvement of semaphorin 7A (Sema7A) as revealed by RNA-seq through the ITGB1/FAK/ERK signaling pathway. The present study suggested that the hierarchically structured surface design strategy could accelerate the osseointegration rate of 3D-printed Ti6Al4V implants, promising personalized reconstruction of bone defects