Interplay of chain dynamics and ion transport on mechanical behavior and conductivity in ionogels.

Understanding the interplay among the mechanical behavior, ionic conductivity and chain dynamics of ionogels is essential for designing flexible conductors that exhibit both high conductivity and excellent mechanical properties. In this study, ionogels were synthesized the radical polymerization of ,'-dimethylacrylamide (DMAA) and methacrylic acid (MAAc) monomers in the presence of ionic liquid 1-ethyl-3-methylimidazolium trifluoromethane sulfonate ([EMIM][OTf]). By varying the mass content of ionic liquid within ionogels, we investigated the mechanical behavior and ionic conductivity at the macroscopic scale using tensile, rheological testing and electrochemical impedance spectroscopy, as well as the dynamic behavior of chain segments and ions within the network at the microscopic scale using broadband dielectric relaxation spectroscopy (BDS) over a broad temperature range.

CD47 masks pro-phagocytic ligands in cis on tumor cells to suppress antitumor immunity.

Cancer cells often overexpress CD47, which triggers the inhibitory receptor SIRPα expressed on macrophages, to elude phagocytosis and antitumor immunity. Pharmacological blockade of CD47 or SIRPα is showing promise as anticancer therapy, although CD47 blockade has been associated with hematological toxicities that may reflect its broad expression pattern on normal cells. Here we found that, in addition to triggering SIRPα, CD47 suppressed phagocytosis by a SIRPα-independent mechanism.

Skeletal Network Enabling New-Generation Thermoplastic Vulcanizates.

Upcycling of cross-linked rubbers is pressing. The introduction of dynamic covalent bonds into the networks is a popular tactic for recycling thermosetting polymers, but it is very challenging to integrate engineering performance and continuous yet stable reprocessability. Based on traditional rubber formulations, herein, a straightforward strategy is presented for constructing a skeletal network (SN) through interfacial crosslinking and percolation of rubbery granules in a rubber matrix.

Cis interactions between CD2 and its ligands on T cells are required for T cell activation.

CD2 is largely described to promote T cell activation when engaged by its ligands, CD48 in mice and CD58 in humans, that are present on antigen-presenting cells (APCs). However, both CD48 and CD58 are also expressed on T cells. By generating new knockout mouse strains lacking CD2 or CD48 in the C57BL/6 background, we determined that whereas CD2 was necessary on T cells for T cell activation, its ligand CD48 was not required on APCs.

Inflammatory macrophages exploit unconventional pro-phagocytic integrins for phagocytosis and anti-tumor immunity.

Blockade of the inhibitory checkpoint SIRPα-CD47 promotes phagocytosis of cancer cells by macrophages and is a promising avenue in anti-cancer therapy. Productive phagocytosis is strictly predicated on co-engagement of pro-phagocytic receptors-namely, Fc receptors (FcRs), integrin CD11b, or SLAMF7-by their ligands on cancer cells. Here, we examine whether additional pro-phagocytic receptors could be harnessed to broaden the scope of phagocytosis.

Generic Method to Create Segregated Structures toward Robust, Flexible, Highly Conductive Elastomer Composites.

Electrically and thermally conductive polymer composites are extensively used in our daily life. It is of great significance to fulfill the conductivity requirement while maintaining desirable mechanical performance. An efficient solution to achieve this goal is to construct segregated structures in polymer composites by confining fillers into the interstitial areas among polymer domains.

Engineering Segregated Structures in a Cross-Linked Elastomeric Network Enabled by Dynamic Cross-Link Reshuffling.

Construction of segregated structures in polymer composites is an efficient way to improve the electrical conductivity and reduce the percolation threshold by confining conductive fillers into the interstitial areas between polymer domains. Yet, it remains a great challenge to engineer segregated structures into thermosets as the cross-linked structure prohibits the "sintering" of polymer domains into a coherent material. Thus far, the state of art approaches to create segregated network in cross-linked polymers involve tedious procedures and are limited to latex mixing technology.

Catalyst-Free Metathesis of Cyclic Acetals and Spirocyclic Acetal Covalent Adaptable Networks.

Due to the exchangeability of dynamic covalent bonds in the covalent adaptable networks (CANs) at elevated temperature, they possess recyclability while still maintaining many of the superior properties of thermosets. The exploration of dynamic covalent chemistry is of great significance to the expansion of CANs library and hence the sustainable development of thermosets. In this work, we discovered that, in absence of catalyst, the direct metathesis of the cyclic acetals proceeds while the acyclic acetals cannot.

Activation of notch 3/c-MYC/CHOP axis regulates apoptosis and promotes sensitivity of lung cancer cells to mTOR inhibitor everolimus.

The mammalian target of rapamycin (mTOR) pathway converges diverse environmental cues to support the lung cancer growth and survival. However, the mTOR-targeted mono-therapy does not achieve expected therapeutic effect. Here, we revealed that fangchinoline (FCL), an active alkaloid that purified from the traditional Chinese medicine Stephania tetrandra S.

Facile Strategy for the Biomimetic Heterogeneous Design of Elastomers with Mechanical Robustness, Malleability, and Functionality.

It remains challenging to simultaneously realize mechanical robustness, malleability, and functionality in elastomers via facile yet efficient methods. Herein, a simple strategy for the biomimetic heterogeneous design is proposed to achieve mechanically strong, malleable, and functionalized elastomers. We demonstrate the strategy by straightforward mechanical mixing of a highly cross-linked vitrimeric elastomer with a homogeneous gum and subsequent curing, resulting in heterogeneous vitrimeric elastomers (hetero-VEs).

Uniaxial Stretching-Induced Alignment of Carbon Nanotubes in Cross-Linked Elastomer Enabled by Dynamic Cross-Link Reshuffling.

The fascinating properties of carbon nanotubes (CNTs) make them highly promising in fabricating polymer composites. Yet, the property enhancements of polymer/CNTs composites remain far behind the theoretical predictions. A critical issue to resolve this dilemma is to align CNTs in polymer matrices.

Elastomer Reinforced with Innate Sulfur-Based Cross-Links as Ligands.

Although the incorporation of sacrificial bonds into an elastomer is an effective way to provide a combination of high strength and high fracture toughness, this method normally involves complicated chemical processes. The coordination between metal ions and polysulfides has been documented. However, the potential of polysulfide structures in vulcanizates as ligands has long been neglected.

Integrating Sacrificial Bonds into Dynamic Covalent Networks toward Mechanically Robust and Malleable Elastomers.

Vitrimers are a class of covalently cross-linked polymers that have drawn great attention due to their fascinating properties such as malleability and reprocessability. The state of art approach to improve their mechanical properties is the addition of fillers, which, however, greatly restricts the chain mobility and impedes network topology rearrangement, thereby deteriorating the dynamic properties of vitrimer composites. Here, we demonstrate that the integration of sacrificial bonds into a vitrimeric network can remarkably enhance the overall mechanical properties while facilitating network rearrangement.

Toughening Elastomers Using a Mussel-Inspired Multiphase Design.

It is a challenge to simultaneously achieve high stretchability, high modulus, and recoverability of polymers. Inspired by the multiphase structure of mussel byssus cuticles, we circumvent this dilemma by introducing a deformable microphase-separated granule with rich coordination into a ductile rubber network. The granule can serve as an additional cross-link to improve the modulus, while the sacrificial, reversible coordination can dissociate and reconstruct continuously during stretching to dissipate energy.

Covalently Cross-Linked Elastomers with Self-Healing and Malleable Abilities Enabled by Boronic Ester Bonds.

Covalently cross-linked rubbers are renowned for their high elasticity that play an indispensable role in various applications including tires, seals, and medical implants. Development of self-healing and malleable rubbers is highly desirable as it allows for damage repair and reprocessability to extend the lifetime and alleviate environmental pollution. Herein, we propose a facile approach to prepare permanently cross-linked yet self-healing and recyclable diene-rubber by programming dynamic boronic ester linkages into the network.

Osimertinib resistance in non-small cell lung cancer: Mechanisms and therapeutic strategies.

Given the successful identification of epidermal growth factor receptor EGFR T790M, the third-generation EGFR tyrosine kinase inhibitor (TKI), osimertinib (OSI, AZD9291), was developed to target EGFR T790M mutation. OSI was approved for the treatment of patients with non-small cell lung cancer (NSCLC) harboring EGFR T790M mutation. However, the disease would progress after the patient received OSI treatment for approximately 10 months.

Engineering of β-Hydroxyl Esters into Elastomer-Nanoparticle Interface toward Malleable, Robust, and Reprocessable Vitrimer Composites.

Rubbers are strategically important due to their indispensable applications in the daily life and high-tech fields. For their real-world applications, the covalent cross-linking, reinforcement, and malleability of rubbers are three important issues because they are closely related to the elasticity, mechanical properties, and recycling of the rubber materials. Herein, we demonstrate a simple way to prepare covalently cross-linked yet recyclable and robust elastomeric vitrimer composites by incorporating exchangeable β-hydroxyl ester bonds into the elastomer-nanoparticle interface using epoxy group-functionalized silica (Esilica) as both cross-linker and reinforcement in carboxyl group-grafted styrene-butadiene rubber (CSBR).

Identification of a novel autophagic inhibitor cepharanthine to enhance the anti-cancer property of dacomitinib in non-small cell lung cancer.

Inhibition of autophagy is a promising strategy for non-small cell lung cancer (NSCLC) treatment, which is in the clinical trials. However, only chloroquine is used in clinic as an autophagic inhibitor and the inhibitory effect of chloroquine on autophagy is finite. Therefore, the development of an alternative autophagic inhibitor for NSCLC therapy becomes necessary.

Baicalein protects tert‑butyl hydroperoxide‑induced hepatotoxicity dependent of reactive oxygen species removal.

Baicalein (BA), one of the major bioactive flavonoids isolated from Scutellariae Radix, possesses various pharmacological activities. The present study aimed to investigate the protective effects of BA on tert‑butyl hydroperoxide (t‑BHP)‑induced hepatotoxicity, and to investigate the potential mechanisms in LO2 cells. BA was demonstrated to possess protective properties against t‑BHP injury in LO2 cells, as evidenced by MTT and lactate dehydrogenase assays.

Increased Expression of IRE1α Associates with the Resistant Mechanism of Osimertinib (AZD9291)-resistant non-small Cell Lung Cancer HCC827/OSIR Cells.

Background: Osimertinib (OSI), also known as AZD9291, is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of non-small cell lung cancer (NSCLC) patients.

Objective: Establishment of the OSI-resistant HCC827/OSIR cell line and study of its resistant mechanism.

Method: The anti-proliferative effect was studied through MTT and colony formation assays.

Induction of reactive oxygen species-stimulated distinctive autophagy by chelerythrine in non-small cell lung cancer cells.

Chelerythrine (CHE), a natural benzo[c]phenanthridine alkaloid, shows anti-cancer effect through a number of mechanisms. Herein, the effect and mechanism of the CHE-induced autophagy, a type II programmed cell death, in non-small cell lung cancer (NSCLC) cells were studied for the first time. CHE induced cell viability decrease, colony formation inhibition, and apoptosis in a concentration-dependent manner in NSCLC A549 and NCI-H1299 cells.