Synthesis of tunable thickness-to-diameter ratio microcapsules via a diffusion-controlled process for temperature-responsive release.

Designing microcapsules with a complicated functionalized shell to respond to an external stimulus has attracted much attention for triggered release; however, simplifying the synthesis process remains a significant challenge. Herein, we initially propose a novel, simple synthesis strategy that utilizes a mixed solvent as the organic phase to control the diffusion of common monomers during interfacial polymerization, resulting in the successful preparation of microcapsules with tunable thickness-to-diameter ratios (T/D). The morphology of microcapsules is confirmed by scanning electron microscopy. We also observe that the T/D of the designed microcapsules progressively increases as the diffusion of monomers occurs, and the glass transition temperature of microcapsules is controlled. Furthermore, microcapsule-based crosslinking agents are applied to investigate the crosslinking reaction of poly(vinyl chloride). Rotational rheometer results indicate that the microcapsules exhibit an excellent external stimulus response, precisely triggering release at the predetermined temperature. This simple approach for the preparation of microcapsules with tunable physical properties has great potential for triggered release in diverse applications.

PlexinA1 promotes gastric cancer migration through preventing MICAL1 protein ubiquitin/proteasome-mediated degradation in a Rac1-dependent manner.

Metastasis promotes the development of tumors and is a significant cause of gastric cancer death. For metastasis to proceed, tumor cells must become mobile by modulating their cytoskeleton. MICAL1 (Molecule Interacting with CasL1) is known as an actin cytoskeleton regulator, but the mechanisms by which it drives gastric cancer cell migration are still unclear. Analysis of gastric cancer tissues revealed that MICAL1 expression is dramatically upregulated in stomach adenocarcinoma (STAD) samples as compared to noncancerous stomach tissues. Patients with high MICAL1 expression had shorter overall survival (OS), post-progression survival (PPS) and first-progression survival (FPS) compared with patients with low MICAL1 expression. RNAi-mediated silencing of MICAL1 inhibited the expression of Vimentin, a protein involved in epithelial-mesenchymal transition. This effect correlates with a significant reduction in gastric cancer cell migration. MICAL1 overexpression reversed these preventive effects. Immunoprecipitation experiments and immunofluorescence assays revealed that PlexinA1 forms a complex with MICAL1. Importantly, specific inhibition of PlexinA1 blocked the Rac1 activation and ROS production, which, in turn, impaired MICAL1 protein stability by accelerating MICAL1 ubiquitin/proteasome-dependent degradation. Overexpression of PlexinA1 enhanced Rac1 activation, ROS production, MICAL1 and Vimentin expressions, and favored cell migration. In conclusion, this study identified MICAL1 as an important facilitator of gastric cancer cell migration, at least in part, by affecting Vimentin expression and PlexinA1 promotes gastric cancer cell migration by binding to and suppressing MICAL1 degradation in a Rac1/ROS-dependent manner.

A Novel One-Step Reactive Extrusion Process for High-Performance Rigid Crosslinked PVC Composite Fabrication Using Triazine Crosslinking Agent@Melamine-Formaldehyde Microcapsules.

In this work, we propose, for the first time, a simple, fast, and efficient strategy to fabricate high-performance rigid crosslinked PVC composites by continuous extrusion. This strategy improves the poor processing fluidity of composites and solves the impossibility of conducting extrusion in one step via using microcapsule-type crosslinking agents prepared by in situ polymerization to co-extrude with PVC blends. The results demonstrate that the PVC/microcapsule composites were successfully prepared. Within the studied parameters, the properties of crosslinked PVC gradually increased with the addition of microcapsules, and its Vicat softening temperature increased from 79.3 °C to 86.2 °C compared with pure PVC. This study shows the possibility for the industrial scale-up of the extrusion process for rigid crosslinked PVC.

Prognostic impact of MICALL1 and associates with immune infiltration in liver hepatocellular carcinoma patients.

BACKGROUND: Liver hepatocellular carcinoma (LIHC) is one of the most malignancy over the world. Previous studies have proven that Molecules Interacting with CasL-Like 1 (MICALL1) participated in cellular trafficking cascades, while there has no study to explore the function and carcinogenic mechanism MICALL1 in LIHC. METHODS: We aimed to investigate the relationship between MICALL1 mRNA expression and LIHC using TCGA database. The expression of MICALL1 protein in clinic samples were examined by UALCAN database. Kaplan-Meier method was used for survival analysis. Logistic regression and Cox regression were performed to evaluate the prognostic significance of MICALL1. The MICALL1-binding protein were built by the STRING tool. Enrichment analysis by GO, KEGG and GSEA was used to explore possible function of MICALL1. The ssGSEA method was used to investigate the association between MICALL1 expression and the immune infiltration level in LIHC. RESULTS: The expression and prognostic value of different MICAL family members in LIHC were evaluated. The expression of MICALL1 was significantly increased at both the transcript and protein levels in LIHC tissues. Further, the LIHC patients with high MICALL1 levels showed a worse OS, DSS and PFI. Some clinicopathologic features were identified to be related to MICALL1 expression in LIHC included clinical T stage, pathologic stage, histologic grade and AFP concentration. Univariate and multivariate survival analysis showed that MICALL1 was an independent prognostic marker for OS and DSS. Further enrichment analysis revealed that the K-RAS, TNFα/NF-κB and inflammatory response were significantly enriched in the high MICALL1 expression group. Immune infiltration analysis showed that high MICALL1 expression was correlated with infiltration level of macrophage cells, Th2 cells and some other immune cell types, including TFH. CONCLUSIONS: MICALL1 expression was significantly associated with immune cell infiltration and may regarded as a promising prognostic biomarker for LIHC patients.

Synthesis of Acrylate Dual-Tone Resists and the Effect of Their Molecular Weight on Lithography Performance and Mechanism: An Investigation.

Acrylate photoresists have gained considerable attention in recent years owing to their high resolution, high sensitivity, and versality. In this work, a series of thermally stable copolymers are synthesized by introducing an isobornyl group, and well characterized using Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectra (1H-NMR). The effects of polymerization conditions on the molecular weight and their further influence on lithography are explored. By analyzing the thermal properties, film-forming capabilities, and the patterning behavior of these copolymers, a direct correlation between lithography performance and polymerization conditions is established via the molecular weight. In addition, the baking temperature of lithography is also optimized by atomic force microscopy (AFM), after which a line resolution of 0.1 µm is observed under the exposure of a 248 nm UV light and electron beam. Notably, our synthesized photoresist displays dual-tone resist characteristics when different developers are applied, and the reaction mechanism of acid-catalyzed hydrolysis is finally proposed by comparing the structural changes before and after exposure.

Synthesis of High-Molecular-Weight Biobased Aliphatic Polyesters by Acyclic Diene Metathesis Polymerization in Ionic Liquids.

Acyclic diene metathesis (ADMET) polymerization of an α,ω-diene monomer of bis(undec-10-enoate) with isosorbide (M1) using a RuCl2(IMesH2)(CH-2-O i Pr-C6H4) (HG2, IMesH2 = 1,3-bis(2,4,6-trimethylphenyl)imidazolin-2-ylidene) catalyst and conducted at 50 °C (in vacuo) in ionic liquids (ILs) afforded higher-molecular-weight polymers (P1, M n = 32 200-39 200) than those reported previously (M n = 5600-14700). 1-n-Butyl-3-methyl imidazolium hexafluorophosphate ([Bmim]PF6) and 1-n-hexyl-3-methyl imidazolium bis(trifluoromethanesulfonyl)imide ([Hmim]TFSI) were suitable as effective solvents among a series of imidazolium salts and the pyridinium salts. The polymerization of α,ω-diene monomers of bis(undec-10-enoate) with isomannide (M2), 1,4-cyclohexanedimethanol (M3), and 1,4-butanediol (M4) in [Bmim]PF6 and [Hmim]TFSI also afforded the higher-molecular-weight polymers. The M n values in the resultant polymers did not decrease even under the scale-up conditions (300 mg to 1.0 g scale, M1, M2, and M4) in the polymerizations in [Hmim]TFSI; the subsequent reaction of P1 with ethylene (0.8 MPa, 50 °C, and 5 h) gave oligomers (proceeded via depolymerization). Tandem hydrogenation of the resultant unsaturated polymers (P1) in a [Bmim]PF6-toluene biphasic system upon the addition of Al2O3 (1.0 MPa H2 at 50 °C) gave the corresponding saturated polymers (HP1), which waswere isolated by a phase separation in the toluene layer. The [Bmim]PF6 layer containing the ruthenium catalyst could be recycled without a decrease in the activity/selectivity of the olefin hydrogenation at least eight times.

Comprehensive Analysis of MICALL2 Reveals Its Potential Roles in EGFR Stabilization and Ovarian Cancer Cell Invasion.

Molecules interacting with CasL (MICALs) are critical mediators of cell motility that act by cytoskeleton rearrangement. However, the molecular mechanisms underlying the regulation of cancer cell invasion remain elusive. The aim of this study was to investigate the potential role of one member of MICALs, i.e., MICALL2, in the invasion and function of ovarian cancer cells. We showed by bioinformatics analysis that MICALL2 expression was significantly higher in tissues of advanced-stage ovarian cancer and associated with poor overall survival of patients. MICALL2 was strongly correlated with the infiltration of multiple types of immune cells and T-cell exhaustion markers. Moreover, enrichment analyses showed that MICALL2 was involved in the tumor-related matrix degradation pathway. Mechanistically, MMP9 was identified as the target gene of MICALL2 for the regulation of invadopodium formation and SKOV3, HO-8910PM cell invasion. In addition, EGFR-AKT-mTOR signaling was identified as the downstream pathway of MICALL2 in the regulation of MMP9 expression. Furthermore, MICALL2 silencing promoted EGFR degradation; however, this effect was abrogated by treatment with the autophagy inhibitors acadesine and chloroquine diphosphate. Silencing of MICALL2 resulted in a suppressive activity of Rac1 while suppressing Rac1 activation attenuated the pro-EGFR, pro-MMP9, and proinvasive effects induced by the overexpression of MICALL2. Collectively, our results indicated that MICALL2 participated in the process of immune infiltration and invasion by ovarian cancer cells. Moreover, MICALL2 prevented EGFR degradation in a Rac1-dependent manner, consequently leading to EGFR-AKT-mTOR-MMP9 signaling activation and invadopodia-mediated matrix degradation.

On the association of frustrated Lewis pairs in ionic liquids: a molecular dynamics simulation study.

Sterically hindered frustrated Lewis pairs (FLPs) have the ability to activate hydrogen molecules, and their reactivity is strongly determined by the geometric parameters of the Lewis acids and bases. A recent experimental study showed that ionic liquids (ILs) could largely improve the effective configuration of FLPs. However, the detailed mechanistic profile is still unclear. Herein, we performed molecular dynamics (MD) simulations to reveal the effects of ILs on the structures of FLPs, in particular, the association of Lewis acids and bases. For this purpose, mixed systems were adopted consisting of the ILs [Cnmim][NTf2] (n = 6, 10, 14), [C6mim][PF6] and [C6mim][CTf3] and the typical FLP (tBu)3P/B(C6F5)3 for MD simulations. Radial distribution functions (RDFs) results show that toluene competes with (tBu)3P to interact with B(C6F5)3, resulting in a relatively low effective (tBu)3P/B(C6F5)3 complex, while [C10mim][NTf2] shows less competition with (tBu)3P, which increases the amount of effective FLPs. Spatial distribution functions (SDFs) results show that toluene forms a continuum solvation-shell, which hinders the interactions between (tBu)3P and B(C6F5)3, while [C10mim][NTf2] leaves relatively large empty spaces, which are accessible for (tBu)3P or B(C6F5)3 molecules, resulting in higher probabilities of effective FLP structures. Lastly, we find that the longer alkyl chain length of [Cnmim]+ cations, the higher the amount of effective (tBu)3P/B(C6F5)3 pairs, and the anion [CTf3]- shows negative effects, for which even less effective (tBu)3P/B(C6F5)3 pairs have been found compared to those of toluene.

Effects of Ionic Liquids on the Thermodynamics of Hydrogen Activation by Frustrated Lewis Pairs: A Density Functional Theory Study*.

Nowadays, hydrogen activation by frustrated Lewis pairs (FLPs) and their applications are one of the emerging research topics in the field of catalysis. Previous studies have shown that the thermodynamics of this reaction is determined by electronic structures of FLPs and solvents. Herein, we investigated systems consisting of typical FLPs and ionic liquids (ILs), which are well known by their large number of types and excellent solvent effects. The density functional theory (DFT) calculations were performed to study the thermodynamics for H2 activation by both inter- and intra-molecular FLPs, as well as the individual components. The results show that the computed overall Gibbs free energies in ILs are more negative than that computed in toluene. Through the thermodynamics partitioning, we find that ILs favor the H-H cleavage elemental step over the elemental steps of proton attachment, hydride attachment and zwitterionic stabilization. Moreover, the results show that these effects are strongly dependent on the type of FLPs, where intra-molecular FLPs are more affected compared to the inter-molecular FLPs.

Highly active, thermally stable, ethylene-polymerisation pre-catalysts based on niobium/tantalum-imine systems.

The reactions of MCl5 or MOCl3 with imidazole-based pro-ligand L(1)H, 3,5-tBu2-2-OH-C6H2-(4,5-Ph2-1H-)imidazole, or oxazole-based ligand L(2)H, 3,5-tBu2-2-OH-C6H2 (1H-phenanthro[9,10-d])oxazole, following work-up, afforded octahedral complexes [MX(L(1,2))], where MX=NbCl4 (L(1), 1a; L(2), 2a), [NbOCl2(NCMe)] (L(1), 1b; L(2), 2b), TaCl4 (L(1), 1c; L(2), 2c), or [TaOCl2(NCMe)] (L(1), 1d). The treatment of α-diimine ligand L(3), (2,6-iPr2C6H3N=CH)2, with [MCl4(thf)2] (M=Nb, Ta) afforded [MCl4(L(3))] (M=Nb, 3a; Ta, 3b). The reaction of [MCl3(dme)] (dme=1,2-dimethoxyethane; M=Nb, Ta) with bis(imino)pyridine ligand L(4), 2,6-[2,6-iPr2C6H3N=(Me)C]2C5H3N, afforded known complexes of the type [MCl3(L(4))] (M=Nb, 4a; Ta, 4b), whereas the reaction of 2-acetyl-6-iminopyridine ligand L(5), 2-[2,6-iPr2C6H3N=(Me)C]-6-Ac-C5H3N, with the niobium precursor afforded the coupled product [({2-Ac-6-(2,6-iPr2C6H3N=(Me)C)C5H3N}NbOCl2)2] (5). The reaction of MCl5 with Schiff-base pro-ligands L(6)H-L(10)H, 3,5-(R(1))2-2-OH-C6H2CH=N(2-OR(2)-C6H4), (L(6)H: R(1)=tBu, R(2)=Ph; L(7)H: R(1)=tBu, R(2)=Me; L(8)H: R(1)=Cl, R(2)=Ph; L(9)H: R(1)=Cl, R(2)=Me; L(10)H: R(1)=Cl, R(2)=CF3) afforded [MCl4(L(6-10))] complexes (M=Nb, 6a-10a; M=Ta, 6b-9b). In the case of compound 8b, the corresponding zwitterion was also synthesised, namely [Ta(-)Cl5(L(8)H)(+)]·MeCN (8c). Unexpectedly, the reaction of L(7)H with TaCl5 at reflux in toluene led to the removal of the methyl group and the formation of trichloride 7c [TaCl3(L(7-Me))]; conducting the reaction at room temperature led to the formation of the expected methoxy compound (7b). Upon activation with methylaluminoxane (MAO), these complexes displayed poor activities for the homogeneous polymerisation of ethylene. However, the use of chloroalkylaluminium reagents, such as dimethylaluminium chloride (DMAC) and methylaluminium dichloride (MADC), as co-catalysts in the presence of the reactivator ethyl trichloroacetate (ETA) generated thermally stable catalysts with, in the case of niobium, catalytic activities that were two orders of magnitude higher than those previously observed. The effects of steric hindrance and electronic configuration on the polymerisation activity of these tantalum and niobium pre-catalysts were investigated. Spectroscopic studies ((1)H NMR, (13)C NMR and (1)H-(1)H and (1)H-(13)C correlations) on the reactions of compounds 4a/4b with either MAO(50) or AlMe3/[CPh3](+)[B(C6F5)4](-) were consistent with the formation of a diamagnetic cation of the form [L(4)AlMe2](+) (MAO(50) is the product of the vacuum distillation of commercial MAO at +50 °C and contains only 1 mol% of Al in the form of free AlMe3). In the presence of MAO, this cationic aluminium complex was not capable of initiating the ROMP (ring opening metathesis polymerisation) of norbornene, whereas the 4a/4b systems with MAO(50) were active. A parallel pressure reactor (PPR)-based homogeneous polymerisation screening by using pre-catalysts 1b, 1c, 2a, 3a and 6a, in combination with MAO, revealed only moderate-to-good activities for the homo-polymerisation of ethylene and the co-polymerisation of ethylene/1-hexene. The molecular structures are reported for complexes 1a-1c, 2b, 5, 6a, 6b, 7a, 8a and 8c.