Construction and Functionalization of Highly Strained N-Doped Zigzag Hydrocarbon Belts

Recent years have witnessed breakthroughs in the study of zigzag hydrocarbon belts.However,the synthesis of heterocycle-containing zigzag molecular belts remains very rare and challenging despite their interesting structures and potential applications in chemistry and materials science.Here,we report the expeditious construction of a highly strained belt[4]arene[4](1,4-dihydropyridine)structure using the fjords-stitching strategy.The synthesis comprised four-fold abnormal m-bromination of four Npivaloylaniline units and Pd_(2)(dba)_(3)/4-Me_(2)NC_(6)H_(4)Pt Bu_(2)-catalyzed intramolecular C-N bond-forming reactions.Subsequent functionalization through Narylations produced a variety of tetraza-embedded octahydrobelt[8]arenes.Further oxidation of p-methoxyphenyl-substituted belt[4]arene[4](1,4-dihydropyridine)with Ag[Al(O^(t)Bu^(F))^(4)]yielded a singlet diradical dication N-doped zigzag belt.

Consistent apparent Young’s modulus of human embryonic stem cells and derived cell types stabilized by substrate stiffness regulation promotes lineage specificity maintenance

Background:Apparent Young’s modulus(AYM),which reflects the fundamental mechanical property of live cells measured by atomic force microscopy and is determined by substrate stiffness regulated cytoskeletal organization,has been investigated as potential indicators of cell fate in specific cell types.However,applying biophysical cues,such as modulating the substrate stiffness,to regulate AYM and thereby reflect and/or control stem cell lineage specificity for downstream applications,remains a primary challenge during in vitro stem cell expansion.Moreover,substrate stiffness could modulate cell heterogeneity in the single-cell stage and contribute to cell fate regulation,yet the indicative link between AYM and cell fate determination during in vitro dynamic cell expansion(from single-cell stage to multi-cell stage)has not been established.Results:Here,we show that the AYM of cells changed dynamically during passaging and proliferation on substrates with different stiffness.Moreover,the same change in substrate stiffness caused different patterns of AYM change in epithelial and mesenchymal cell types.Embryonic stem cells and their derived progenitor cells exhibited distinguishing AYM changes in response to different substrate stiffness that had significant effects on their maintenance of pluripotency and/or lineage-specific characteristics.On substrates that were too rigid or too soft,fluctuations in AYM occurred during cell passaging and proliferation that led to a loss in lineage specificity.On a substrate with‘optimal’stiffness(i.e.,3.5 kPa),the AYM was maintained at a constant level that was consistent with the parental cells during passaging and proliferation and led to preservation of lineage specificity.The effects of substrate stiffness on AYM and downstream cell fate were correlated with intracellular cytoskeletal organization and nuclear/cytoplasmic localization of YAP.Conclusions:In summary,this study suggests that optimal substrate stiffness regulated consistent AYM during passaging and proliferation reflects and contributes to hESCs and their derived progenitor cells lineage specificity maintenance,through the underlying mechanistic pathways of stiffness-induced cytoskeletal organization and the downstream YAP signaling.These findings highlighted the potential of AYM as an indicator to select suitable substrate stiffness for stem cell specificity maintenance during in vitro expansion for regenerative applications.

A Cleavable Self-Inclusion Conjugate with Enhanced Biocompatibility and Antitumor Bioactivity

The effective encapsulation of antitumor drugs by dynamic host–guest interactions at the submicromolar level remains a challenge.Herein,we report a cleavable self-inclusion camptothecin-cucurbit[7]uril(CPT-CB[7])conjugate.The binding affinity of CB[7]to CPT is greatly enhanced owing to the intramolecular self-inclusion,demonstrating a concentrationindependent encapsulation efficiency of nearly 100%.The disulfide linker of CPT-CB[7]conjugate can be cleaved in the reductive tumor microenvironment,transforming the self-inclusion into a binary host–guest complexation pattern,thus releasing the CPT thoroughly.The enhanced biocompatibility and antitumor bioactivity of the cleavable self-inclusion conjugate have been confirmed by in vitro and in vivo experiments.This line of research will open new horizons for supramolecular drug delivery systems operating in diluted and competitive conditions.

An orally-available monovalent SMAC mimetic compound as a broad-spectrum antiviral

DearEditor,The coronavirus disease 2019(COVID-19)pandemic caused great global morbidity and mortality concurrent with astronomical socioeconomic damages and losses.Until now,the culpable pathogen,SARS-CoV-2,has infected over 6 hundred million people resulting in more than 6 million deaths worldwide(WHO SARSCoV-2 cases).There is an urgent need for rapid development of effective and affordable therapeutics for COVID-19 patients.

Ultrastable Near-Infrared Aggregation-Induced Emission Nanoparticles as a Fluorescent Probe:Long-Term Tumor Monitoring and Lipid Droplet Tracking

Effective real-time tumor monitoring and cell tracking are of great importance for precise diagnosis and therapy of tumors,and also for the surveillance of biological processes.In this study,a new organic fluorescent nanoprobe(named TPATBT NPs)with unique aggregation-induced emission(AIE)characteristics has been obtained for the first time via facile synthesis to achieve real-time and long-term monitoring in living cells.The advantages of TPATBT NPs include small size(∼80 nm),a large Stokes shift(∼150 nm),high stability,good dispersibility in aqueous media,and biocompatibility.In addition,such NPs have showed excellent bioimaging performance and unusual long-term tumor monitoring properties.The red fluorescence signals inside MDA-MB-231 cells last for longer than 10 generations(18 days).Moreover,the cellular uptake of TPATBT NPs has been found to highly rely on energy-dependent endocytosis and clathrin-mediated endocytosis,and to primarily accumulate in lipid droplets(LDs),which can lead to targeted LD cellular imaging and therapy.Thus,TPATBT NPs can work as an excellent fluorescent nanoprobe for long-term monitoring of malignant tumor growth and dynamic biological processes.