Crosstalk and complexity within signaling pathways and their perturbation by oncogenes limit component-by-component approaches to understanding human disease. Network analysis of how normal and ...oncogenic signaling can be rewired by drugs may provide opportunities to target tumors with high specificity and efficacy. Using targeted inhibition of oncogenic signaling pathways, combined with DNA-damaging chemotherapy, we report that time-staggered EGFR inhibition, but not simultaneous coadministration, dramatically sensitizes a subset of triple-negative breast cancer cells to genotoxic drugs. Systems-level analysis—using high-density time-dependent measurements of signaling networks, gene expression profiles, and cell phenotypic responses in combination with mathematical modeling—revealed an approach for altering the intrinsic state of the cell through dynamic rewiring of oncogenic signaling pathways. This process converts these cells to a less tumorigenic state that is more susceptible to DNA damage-induced cell death by reactivation of an extrinsic apoptotic pathway whose function is suppressed in the oncogene-addicted state.
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► The efficacy of combination treatments for cancer depends on drug order and timing ► Dynamic rewiring of signaling networks by drugs can provide therapeutic benefit ► Sustained EGFR inhibition sensitizes triple-negative breast cancer cells to DNA damage ► EGFR activity, but not EGFR expression, is a biomarker of response to this treatment
The effectiveness of combination therapy for triple-negative breast cancer may be increased by delivering the drugs sequentially. Inhibiting EGFR dynamically rewires tumor cell signaling networks to enhance subsequent susceptibility to DNA-damaging agents, an effect not seen when the drugs are applied simultaneously.
Propylene/propane separation is one of the most challenging separations, currently achieved by energy-intensive cryogenic distillation. Despite the great potential for energy-efficient membrane-based ...separations, no commercial membranes are currently available due to the limitations of current polymeric materials. Zeolitic imidazolate framework, ZIF-8, with the effective aperture size of ∼4.0 Å, has been shown to be very promising for propylene/propane separation. Despite the extensive research on ZIF-8 membranes, only a few reported ZIF-8 membranes have displayed good propylene/propane separation performances presumably due to the challenges of controlling the microstructures of polycrystalline membranes. Here we report the first well-intergrown membranes of ZIF-67 (Co-substituted ZIF-8) by heteroepitaxially growing ZIF-67 on ZIF-8 seed layers. The ZIF-67 membranes exhibited impressively high propylene/propane separation capabilities. Furthermore, when a tertiary growth of ZIF-8 layers was applied to heteroepitaxially grown ZIF-67 membranes, the membranes exhibited unprecedentedly high propylene/propane separation factors of ∼200 possibly due to enhanced grain boundary structure.
The interaction energy of base–acid plays a key role in acid retention of phosphoric acid (PA)-doped polymer electrolytes under fuel cell operating conditions. Here, we investigate the energetics of ...proton-accepting and hydroxide-donating organic bases using density functional theory calculations. Because of their weak basicity, proton-accepting organic bases such as benzimidazole have relatively low interaction energy with the acid in the absence of water (15.3–28.0 kcal mol–1). Energetics of the proton-accepting base–PA complex increases by adding water, indicating that the interactions in the base–acid complex strengthen in the presence of water. On the other hand, hydroxide-donating organic bases, such as tetramethylammonium hydroxide, have high interaction energy with PA (∼110 kcal mol–1), which remains high in the presence of water. The chemical shifts of 31P NMR support the energetics of the base–acid complexes. This study further discusses the benefit of incorporating hydroxide-donating organic bases into the polymeric structure over proton-accepting bases as a way to increase acid retention.
Modern electrochemical energy conversion devices require more advanced proton conductors for their broad applications. Phosphonated polymers have been proposed as anhydrous proton conductors for fuel ...cells. However, the anhydride formation of phosphonic acid functional groups lowers proton conductivity and this prevents the use of phosphonated polymers in fuel cell applications. Here, we report a poly(2,3,5,6-tetrafluorostyrene-4-phosphonic acid) that does not undergo anhydride formation and thus maintains protonic conductivity above 200 °C. We use the phosphonated polymer in fuel cell electrodes with an ion-pair coordinated membrane in a membrane electrode assembly. This synergistically integrated fuel cell reached peak power densities of 1,130 mW cm
at 160 °C and 1,740 mW cm
at 240 °C under H
/O
conditions, substantially outperforming polybenzimidazole- and metal phosphate-based fuel cells. Our result indicates a pathway towards using phosphonated polymers in high-performance fuel cells under hot and dry operating conditions.
The durability of alkaline anion exchange membrane (AEM) electrolyzers is a critical requirement for implementing this technology in cost-effective hydrogen production. Here, we report that the ...electrochemical oxidation of the adsorbed phenyl group (found in the ionomer) on oxygen evolution catalysts produces phenol, which may cause performance deterioration in AEM electrolyzers. In-line 1H NMR kinetic analyses of phenyl oxidation in a model organic cation electrolyte shows that catalyst type significantly impacts the phenyl oxidation rate at an oxygen evolution potential. Density functional theory calculations show that the phenyl adsorption is a critical factor determining the phenyl oxidation. This research provides a path for the development of more durable AEM electrolyzers with components that can minimize the adverse impact induced by the phenyl group oxidation, such as the development of novel ionomers with fewer phenyl moieties or catalysts with less phenyl-adsorbing character.
Transient receptor potential vanilloid channel 3 (TRPV3), a member of the thermosensitive TRP (thermoTRPV) channels, is activated by warm temperatures and serves as a key regulator of normal skin ...physiology through the release of pro-inflammatory messengers. Mutations in trpv3 have been identified as the cause of the congenital skin disorder, Olmsted syndrome. Unlike other members of the thermoTRPV channel family, TRPV3 sensitizes upon repeated stimulation, yet a lack of structural information about the channel precludes a molecular-level understanding of TRPV3 sensitization and gating. Here, we present the cryo-electron microscopy structures of apo and sensitized human TRPV3, as well as several structures of TRPV3 in the presence of the common thermoTRPV agonist 2-aminoethoxydiphenyl borate (2-APB). Our results show α-to-π-helix transitions in the S6 during sensitization, and suggest a critical role for the S4-S5 linker π-helix during ligand-dependent gating.
Very recently, MXene‐based wearable hydrogels have emerged as promising candidates for epidermal sensors due to their tissue‐like softness and unique electrical and mechanical properties. However, it ...remains a challenge to achieve MXene‐based hydrogels with reliable sensing performance and prolonged service life, because MXene inevitably oxidizes in water‐containing system of the hydrogels. Herein, catechol‐functionalized poly(vinyl alcohol) (PVA‐CA)‐based hydrogels is proposed to inhibit the oxidation of MXene, leading to rapid self‐healing and superior strain sensing behaviors. Sufficient interaction of hydrophobic catechol groups with the MXene surface reduces the oxidation‐accessible sites in the MXene for reaction with water and eventually suppresses the oxidation of MXene in the hydrogel. Furthermore, the PVA‐CA‐MXene hydrogel is demonstrated for use as a strain sensor for real‐time motion monitoring, such as detecting subtle human motions and handwriting. The signals of PVA‐CA‐MXene hydrogel sensor can be accurately classified using deep learning models.
This study provides an avenue for the synthesis of oxidation‐resistant MXene‐based catechol‐grafted poly (vinyl alcohol) hydrogels (PVA‐CA‐MXene hydrogel) with prolonged service life intended for strain sensors in real‐time motion monitoring, such as detecting subtle human motions and handwriting. The signals of PVA‐CA‐MXene hydrogel sensor are further accurately classified using deep learning models.
Through fine-tuning of the myriad of reaction conditions for an aqueous base-catalyzed hydrolysis–polycondensation reaction, a facile synthesis of structurally controlled polyphenylsilsesquioxanes ...was developed. Mechanism and kinetic studies indicated that the condensation reaction proceeded through a T 1 structured dimer, which was quantitatively and in situ formed through mild hydrolysis of a phenyltrimethoxysilane (PTMS) monomer, to give either the cage-structured polyhedral oligomeric silsesquioxanes (POSS) or the corresponding ladderlike silsesquioxane (LPSQ) with excellent yields. Ladderlike and POSS materials were selectively achieved at higher and lower initial concentrations of PTMS, respectively, and an in-depth spectroscopic analysis of both compounds clearly revealed their structural differences with different molecular weights.
Improving water flux is a crucial objective of research in forward osmosis (FO) technology. A structural parameter is the property of the support layer of the membrane that determines the internal ...concentration polarization, which is determined by the bulk porosity, tortuosity, and thickness of the support layer. Surface porosity, i.e., porosity at the interface between the active and support layers, has recently been recognized as another critical factor in determining the water flux behavior and the structural parameter. In this study, the relative importance of the surface porosity, bulk porosity, and pore geometry of the support layer on water flux behavior is investigated using a recently developed pore-scale CFD simulator. To this end, various straight-like pore geometries with different combinations of surface and bulk porosities are studied. An increase in bulk porosity reduces internal concentration polarization, thereby increasing effective osmotic pressure. However, for the same magnitude of increase, an increase in surface porosity leads to a significantly larger increase in water flux. We show that water flux is most sensitive to surface porosity, and inconsistency in the structural parameter can be resolved by introducing surface porosity into the FO modeling framework.
•The impact of surface porosity on water flux behavior is fundamentally investigated.•Water flux is more sensitive to surface porosity than bulk porosity or pore geometry.•Inconsistency in structural parameter is resolved by properly considering surface porosity.
Background
Tai chi, also called taiji or tai chi chuan, is a form of mind–body exercise that originated from China. It combines Chinese martial arts and meditative movements that promote balance and ...healing of the mind and body, involving a series of slowly performed, dance-like postures that flow into one another. As it comprises mental concentration, physical balance, muscle relaxation, and relaxed breathing, tai chi shows great potential for becoming widely integrated into the prevention and rehabilitation of a number of medical and psychological conditions.
Purpose
A growing body of clinical research has begun to evaluate the efficacy of tai chi as a therapy for a variety of health issues. A systematic review and meta-analysis were carried out on randomized controlled trials (RCTs) and quasi-experimental (Q-E) trials that studied the effects of tai chi on psychological well-being.
Method
Drawn from English and Chinese databases, 37 RCTs and 5 Q-E studies published up to May 31, 2013 were included in the systematic review. The methodological quality of the RCTs was evaluated based on the following criteria: adequate sequence generation, allocation concealment, blinding, completeness of outcome data, selective reporting, and other potential biases. Statistical analyses were performed using Review Manager version 5.0.
Results
The studies in this review demonstrated that tai chi interventions have beneficial effects for various populations on a range of psychological well-being measures, including depression, anxiety, general stress management, and exercise self-efficacy. Meta-analysis was performed on three RCTs that used depression as an outcome measure (ES = −5.97; 95 % CI −7.06 to −4.87), with
I
2
= 0 %.
Conclusion
In spite of the positive outcomes, the studies to date generally had significant methodological limitations. More RCTs with rigorous research design are needed to establish the efficacy of tai chi in improving psychological well-being and its potential to be used in interventions for populations with various clinical conditions.
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