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Synthesis of cationic polymers possessing significant therapeutic potential is of tremendous research interest. Here, we report a facile synthesis of poly(e-caprolactone) (PCL) based cationic polymers with controlled topological structures and tunable charge densities via postpolymerization modification using thio-bromo “click” chemistry. Three types of polymeric precursors were prepared by ring-opening polymerization (ROP) or combination of ROP and azide–alkyne click reaction, including linear homopolymer poly(α-bromo-e-caprolactone) (P(CL-Br)), block copolymer PCL-b-P(CL-Br), and bottlebrush polymer PCL-g-(PCL-b-P(CL-Br)), and then the P(CL-Br) blocks or segments were modified using the thio-bromo click reaction with a thiol bearing a tertiary amino group, yielding the corresponding cationic polymers, respectively. Size exclusion chromatography (SEC) and 1H NMR characterization demonstrated successful synthesis of the cationic polymers with controlled molecular weights and topological structures that may have great potential for biomedical applications.

Mechanochromic mechanophores have promising applications in stress sensing and damage detection. Here we report a simple mechanofluorochromic mechanophore based on aminothiomaleimide (ATM). Poly(methyl acrylate) containing this mechanophore (ATM-PMA) was synthesized by atom transfer radical polymerization (ATRP) using an ATM-derived difunctional initiator. To investigate its mechanofluorochromism, the solution of ATM-PMA was subjected to ultrasonication, and size exclusion chromatography (SEC) and fluorescence spectroscopy were employed to monitor the changes in molecular weight and fluorescence emission. The results showed that the molecular weight of ATM-PMA decreased upon ultrasonication, accompanied by a shift of fluorescence emission from bright yellow to light blue. This mechanophore of a simple functional group of ATM has great potential to be used in mechanochromic polymer materials.

Specification of the primary heart field in mouse embryos requires signaling from the anterior visceral endoderm (AVE). The nature of these signals is not known. We hypothesized that the TGFβ-activated kinase (TAK1/Map3k7) may act as a cardiogenic factor, based on its expression in heart-inducing endoderm and its requirement for cardiac differentiation of p19 cells. To test this, mouse embryonic stem (ES) cells overexpressing Map3k7 were isolated and differentiated as embryoid bodies (EBs). Map3k7-overexpressing EBs showed increased expression of AVE markers but interestingly, showed little effect on mesoderm formation and had no impact on overall cardiomyocyte formation. To test whether the pronounced expansion of endoderm masks an expansion of cardiac lineages, chimeric EBs were made consisting of Map3k7-overexpressing ES and wild type ES cells harboring a cardiac reporter transgene, MHCα::GFP, allowing cardiac differentiation to be assessed specifically in wild type ES cells. Wild type ES cells co-cultured with Map3k7-overexpressing cells had a 4-fold increase in expression of the cardiac reporter, supporting the hypothesis that Map3k7 increases the formation of cardiogenic endoderm. To further examine the role of Map3k7 in early lineage specification, other endodermal markers were examined. Interestingly, markers that are expressed in both the VE and later in gut development were expanded, whereas transcripts that specifically mark the early definitive (streak-derived) endoderm (DE) were not. To determine if Map3k7 is necessary for endoderm differentiation, EBs were grown in the presence of the Map3k7 specific inhibitor 5Z-7-oxozeaenol. Endoderm differentiation was dramatically decreased in these cells. Western blot analysis showed that known downstream targets of Map3k7 (Jnk, Nemo-like kinase (NLK) and p38 MAPK) were all inhibited. By contrast, transcripts for another TGFβ target, Sonic Hedgehog (Shh) were markedly upregulated, as were transcripts for Gli2 (but not Gli1 and Gli3). Together these data support the hypothesis that Map3k7 governs the formation, or proliferation of cardiogenic endoderm.

The stability of surface-tethered polyelectrolyte brushes has been investigated during the past few years. We have previously reported on the degrafting of poly(acrylic acid) (PAA) polymer brushes from flat silicon substrates. Here, we present a detailed study on the effects of NaCl concentration and the grafting density and molecular weight on the stability of PAA brushes during incubation in 0.1 M ethanolamine buffer (pH 9.0) solutions. Without NaCl in the buffer solution, the PAA brushes remain intact. Adding NaCl facilitates etching of the substrate due to accelerating dissolution of the top silica layer and promoting degrafting of the PAA chains. The PAA grafting density and molecular weight play an important role in the substrate etching by affecting the penetration barrier and local concentration of the etchants. We also tested the stability of self-assembled monolayers (SAMs) made of hydrophobic alkyltrichlorosilanes anchored on silicon substrates. The results demonstrated that the SAMs were too thin to protect the substrates from etching, in contrast to thick poly(methyl methacrylate) brushes. Our findings suggest that both polymer brushes (especially polyelectrolyte brushes) and SAMs anchored to silicon substrates may undergo erosion/etching on the substrates in basic environments, which compromises their stability and therefore jeopardizes their applications in coating, biosensing, and so forth.

Molecular bottlebrushes featuring brush-on-brush (BoB) architecture were prepared by combining azide-alkyne click chemistry, ring-opening polymerization (ROP), and atom transfer radical polymerization (ATRP). Primary side chains of diblock copolymers with a poly(ε-caprolactone) (PCL) block and a poly(α-bromo-ε-caprolactone) (P(CL-Br)) block were synthesized by ROP and then grafted onto PCL backbone by the click reaction. Then the secondary side chains of poly(oligo(ethylene glycol) acrylate) (POEGA) were grafted from the P(CL-Br) block by ATRP, yielding an amphiphilic core/shell structure. Imaging of individual macromolecules by atomic force microscopy (AFM) demonstrated dramatically thickened wormlike formation with distinct hairy side chains. Interestingly, for the BoB molecular bottlebrushes with enough long primary and secondary side chains, sufficient tension can be generated along the backbone and thus lead to its cleavage.

Background Chronic gastritis (CG) is an inflammatory disease which is one of the common diseases of the digestive system. To investigate the mechanisms of herbal pair Acoritataninowii Rhizoma(Shichangpu, AR) and Curcumae Radix༈Yujin, CR༉ in treatment of CG based on the network pharmacology. Methods The possible active ingredients and targets of AR-CR were obtained by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The UniProt database was used to query the human gene corresponding to each target protein. The genes related to CG were collected from the GeneCards database, the OMIM database, the DisGeNET database and the PharmGKB database. Intersected the target genes of AR-CR and CG, then protein-protein interaction(PPI) network was constructed by STRING website. The overlapped genes were subjected to gene ontology༈GO༉enrichment and Kyoto encyclopedia of genes and genomes༈KEGG༉pathway enrichment analyses by David. Results 45 intersection genes were obtained, and there were 40 targets in the PPI network for protein interaction, the kernel targets with Degree ≥ 10 included AKT1, TNF, JUN, MAPK3, MAPK8 and MAPK1. The Go enrichment analysis was mainly related to protein binding, enzyme binding, protein homodimerization activity, etc. The KEGG pathway enrichment analyses mainly involved the Pathways in cancer, TNF signaling pathway, Apoptosis, and VEGF signaling pathway. Conclusion AR-CR might delayed, blocked or reversed the atrophy, intestinal metaplasia, dysplasia and canceration of gastric mucosa by targeting key proteins and signal pathways,achieved the effect of the treatment of CG.

The heart is a large organ containing many cell types, each of which is necessary for normal function. Because of this, cardiac regenerative medicine presents many unique challenges. Because each of the many types of cells within the heart has unique physiological and electrophysiological characteristics, donor cells must be well matched to the area of the heart into which they are grafted to avoid mechanical dysfunction or arrhythmia. In addition, grafted cells must be functionally integrated into host tissue to effectively repair cardiac function. Because of its size and physiological function, the metabolic needs of the heart are considerable. Therefore grafts must contain not only cardiomyocytes but also a functional vascular network to meet their needs for oxygen and nutrition. In this article we review progress in the use of pluripotent stem cells as a source of donor cardiomyocytes and highlight current unmet needs in the field. We also examine recent tissue engineering approaches integrating cells with various engineered materials that should address some of these unmet needs.

In vivo, cardiomyocytes comprise a heterogeneous population of contractile cells defined by unique electrophysiologies, molecular markers and morphologies. The mechanisms directing myocardial cells to specific sub-lineages remain poorly understood. Here we report that overexpression of TGFβ-Activated Kinase (TAK1/Map3k7) in mouse embryonic stem (ES) cells faithfully directs myocardial differentiation of embryoid body (EB)-derived cardiac cells toward the sinoatrial node (SAN) lineage. Most cardiac cells in Map3k7-overexpressing EBs adopt markers, cellular morphologies, and electrophysiological behaviors characteristic of the SAN. These data, in addition to the fact that Map3k7 is upregulated in the sinus venous-the source of cells for the SAN-suggest that Map3k7 may be an endogenous regulator of the SAN fate.