Guard Cell-Inspired Ion Channels: Harnessing the Photomechanical Effect via Supramolecular Assembly of Cross-Linked Azobenzene/Polymers.

Stimuli-responsive ion nanochannels have attracted considerable attention in various fields because of their remote controllability of ionic transportation. For photoresponsive ion nanochannels, however, achieving precise regulation of ion conductivity is still challenging, primarily due to the difficulty of programmable structural changes in confined environments. Moreover, the relationship between noncontact photo-stimulation in nanoscale and light-induced ion conductivity has not been well understood. In this work, a versatile design for fabricating guard cell-inspired photoswitchable ion channels is presented by infiltrating azobenzene-cross-linked polymer (AAZO-PDAC) into nanoporous anodic aluminum oxide (AAO) membranes. The azobenzene-cross-linked polymer is formed by azobenzene chromophore (AAZO)-cross-linked poly(diallyldimethylammonium chloride) (PDAC) with electrostatic interactions. Under UV irradiation, the trans-AAZO isomerizes to the cis-AAZO, causing the volume compression of the polymer network, whereas, in darkness, the cis-AAZO reverts to the trans-AAZO, leading to the recovery of the structure. Consequently, the resultant nanopore sizes can be manipulated by the photomechanical effect of the AAZO-PDAC polymers. By adding ionic liquids, the ion conductivity of the light-driven ion nanochannels can be controlled with good repeatability and fast responses (within seconds) in multiple cycles. The ion channels have promising potential in the applications of biomimetic materials, sensors, and biomedical sciences.

Boosting Ion Conductivities: Light-Modulated Azobenzene-Based Ionic Liquids in Vertical Nanochannels.

Exploring stimuli-responsive ion-conductive materials is a challenging task, but it has gained increasing attention because of their enormous potential applications in actuators, sensors, and smart electronics. Here, we demonstrate a distinctive photoresponsive ion-conductive device that utilizes azobenzene-based ionic liquids ([AzoCnMIM][Br], where n = 2, 6, and 10), confined in nanochannels of anodic aluminum oxide (AAO) templates for photoisomerization. The structure of [AzoCnMIM][Br] comprises photoresponsive and hydrophobic azobenzene moieties, hydrophilic imidazolium cations, and negatively charged bromide ions. Therefore, [AzoCnMIM][Br] can form micelles and exhibit photoresponsive ion conductivities. The nanochannels of AAO templates exhibit a confinement effect on the formation of azobenzene-based ionic liquid micelles due to the pore size, thereby preventing the formation of larger micelles that could lead to a decrease in conductivity. Consequently, the ion conductivities of the azobenzene-based ionic liquids are higher in the nanochannels of the AAO templates. The effects of the length of carbon chains on the azobezene-based ionic liquids and the pore size of the AAO templates have also been investigated. Additionally, through irradiation with UV/vis light, [AzoCnMIM][Br] can undergo reversible isomerization, thereby reversibly changing the sizes of the micelles and subsequently altering the ion conductivities.

Smart Temperature-Gating and Ion Conductivity Control of Grafted Anodic Aluminum Oxide Membranes.

Over the past few decades, stimuli-responsive materials have been widely applied to porous surfaces. Permeability and conductivity control of ions confined in nanochannels modified with stimuli-responsive materials, however, have been less investigated. In this work, the permeability and conductivity control of ions confined in nanochannels of anodic aluminum oxide (AAO) templates modified with thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) brushes are demonstrated. By surface-initiated atom transfer radical polymerization (SI-ATRP), PNIPAM brushes are successfully grafted onto the hexagonally packed cylindrical nanopores of AAO templates. The surface hydrophilicities of the membranes can be reversibly altered because of the lower critical solution temperature (LCST) behavior of the PNIPAM polymer brushes. From electrochemical impedance spectroscopy (EIS) analysis, the temperature-gating behaviors of the AAO-g-PNIPAM membranes exhibit larger impedance changes than those of the pure AAO membranes at higher temperatures because of the aggregation of the grafted PNIPAM chains. The reversible surface properties caused by the extended and collapsed states of the polymer chains are also demonstrated by dye release tests. The smart thermo-gated and ion-controlled nanoporous membranes are suitable for future smart membrane applications.

Photoswitchable and Solvent-Controlled Directional Actuators: Supramolecular Assembly and Crosslinked Polymers.

Untethered small actuators have drawn tremendous interest owing to their reversibility, flexibility, and widespread applications in various fields. For polymer actuators, however, it is still challenging to achieve programmable structural changes under different stimuli caused by the intractability and single-stimulus responses of most polymer materials. Herein, multi-stimuli-responsive polymer actuators that can respond to light and solvent via structural changes are developed. The actuators are based on bilayer films of polydimethylsiloxane (PDMS) and azobenzene chromophore (AAZO)-crosslinked poly(diallyldimethylammonium chloride) (PDAC). Upon UV light irradiation, the AAZO undergoes trans-cis-trans photoisomerization, causing the bending of the bilayer films. When the UV light is off, a shape recovery toward an opposite direction occurs spontaneously. The reversible deformation can be repeated at least 20 cycles. Upon solvent vapor annealing, one of the bilayer films can be selectively swollen, causing the bending of the bilayer films with the directions controlled by the solvent vapors. The effects of different parameters, such as the weight ratios of AAZO and film thicknesses, on the bending angles and curvatures of the polymer films are also analyzed. The results demonstrate that multi-stimuli-responsive actuators with fast responses and high reproducibility can be fulfilled.

Informing plasmid compatibility with bacterial hosts using protein-protein interaction data.

The compatibility of plasmids with new host cells is significant given their role in spreading antimicrobial resistance (AMR) and virulence factor genes. Evaluating this using in vitro screening is laborious and can be informed by computational analyses of plasmid-host compatibility through rates of protein-protein interactions (PPIs) between plasmid and host cell proteins. We identified large excesses of such PPIs in eight important plasmids, including pOXA-48, using most known bacteria (n = 4363). 23 species had high rates of interactions with four blaOXA-48-positive plasmids. We also identified 48 species with high interaction rates with plasmids common in Escherichia coli. We found a strong association between one plasmid and the fimbrial adhesin operon pil, which could enhance host cell adhesion in aqueous environments. An excess rate of PPIs could be a sign of host-plasmid compatibility, which is important for AMR control given that plasmids like pOXA-48 move between species with ease.

Aberrant calcium signalling downstream of mutations in TP53 and the PI3K/AKT pathway genes promotes disease progression and therapy resistance in triple negative breast cancer.

Triple-negative breast cancer (TNBC) is characterized as an aggressive form of breast cancer (BC) associated with poor patient outcomes. For the majority of patients, there is a lack of approved targeted therapies. Therefore, chemotherapy remains a key treatment option for these patients, but significant issues around acquired resistance limit its efficacy. Thus, TNBC has an unmet need for new targeted personalized medicine approaches. Calcium (Ca2+) is a ubiquitous second messenger that is known to control a range of key cellular processes by mediating signalling transduction and gene transcription. Changes in Ca2+ through altered calcium channel expression or activity are known to promote tumorigenesis and treatment resistance in a range of cancers including BC. Emerging evidence shows that this is mediated by Ca2+ modulation, supporting the function of tumour suppressor genes (TSGs) and oncogenes. This review provides insight into the underlying alterations in calcium signalling and how it plays a key role in promoting disease progression and therapy resistance in TNBC which harbours mutations in tumour protein p53 (TP53) and the PI3K/AKT pathway.

Effects of endogenous sex hormones on lung function and symptom control in adolescents with asthma.

BACKGROUND: Although pre-puberty asthma is more prevalent in males, after puberty through middle-age, asthma is more prevalent in females. The surge of sex hormones with puberty might explain this gender switch. METHODS: To examine the effects of sex hormones on lung function and symptoms with puberty, Tanner stage was assessed in 187 children 6-18 years of age (59% severe) enrolled in the NIH/NHLBI Severe Asthma Research Program (SARP). The effects of circulating sex hormones (n = 68; testosterone, dehydroepiandrosterone sulfate (DHEA-S), estrogen, and progesterone) on lung function and 4 week symptom control (ACQ6) in cross-section were tested by linear regression. RESULTS: From pre-/early to late puberty, lung function did not change significantly but ACQ6 scores improved in males with severe asthma. By contrast females had lower post-BD FEV1% and FVC% and worse ACQ6 scores with late puberty assessed by breast development. In males log DHEA-S levels, which increased by Tanner stage, associated positively with pre- and post-BD FEV1%, pre-BD FVC %, and negatively (improved) with ACQ6. Patients treated with high-dose inhaled corticosteroids had similar levels of circulating DHEA-S. In females, estradiol levels increased by Tanner stage, and associated negatively with pre-BD FEV1% and FVC %. CONCLUSIONS: These results support beneficial effects of androgens on lung function and symptom control and weak deleterious effects of estradiol on lung function in children with asthma. Longitudinal data are necessary to confirm these cross-sectional findings and to further elucidate hormonal mechanisms informing sex differences in asthma features with puberty. TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT01748175 .

A polymorphism in the interleukin-4 receptor affects the ability of interleukin-4 to regulate Th17 cells: a possible immunoregulatory mechanism for genetic control of the severity of rheumatoid arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) is now suspected to be driven by pathogenic Th17 cells that secrete interleukin (IL)-17 and can be regulated by IL-4. A single-nucleotide polymorphism (SNP), I50V, in the coding region of the human IL-4 receptor (IL-4R) is associated with rapid development of erosive disease in RA. The present study was undertaken to determine whether this SNP renders the IL-4R less able to transduce signals that regulate IL-17 production. METHODS: Peripheral blood mononuclear cells were activated under Th17-stimulating conditions in the presence or absence of IL-4, and IL-17 production was measured by both enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Serum IL-17 was also measured by ELISA. Paired comparisons were performed using the two-tailed t-test. IL-4 receptor gene alleles were determined by polymerase chain reaction. RESULTS: In healthy individuals, IL-4 significantly inhibited IL-17 production by cells from subjects with the I/I genotype (P = 0.0079) and the I/V genotype (P = 0.013), but not the V/V genotype (P > 0.05). In a cross-sectional sample of patients with established RA, the magnitude of the in vitro effect of IL-4 was lower and was not associated with a specific IL-4R allele. Serum IL-17 levels were higher in RA patients than in healthy individuals, as was the percentage of CD4+ cells that produced IL-17. CONCLUSIONS: These results indicate that an inherited polymorphism of the IL-4R controls the ability of the human immune system to regulate the magnitude of IL-17 production. However, in established RA, this pattern may be altered, possibly due to secondary effects of both RA itself as well as immunomodulatory medications. Ineffective control of Th17 immune responses is a potential mechanism to explain why IL-4R is an important severity gene in RA, but this issue will require careful study of a cohort of new-onset RA patients.

Antioxidant and hepatoprotective activities of Cirsium setidens Nakai against CCl4-induced liver damage.

The antioxidant activity and hepatoprotective potential of Cirsium setidens Nakai, a widely used medicinal plant, were investigated. The n-butanol (n-BuOH) fraction of leaves and roots of C. setidens had a higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity than the other soluble fractions. The n-BuOH fraction of roots of C. setidens had a significant hepatoprotective activity at a dose of 500 mg/kg compared to that of a standard agent. The biochemical results were confirmed by histological observations indicating that C. setidens extract decreased ballooning degeneration in response to CCl(4) treatment. The n-BuOH fraction reduced CCl(4)-induced liver injury in rats, and transcript levels of genes encoding antioxidant enzymes such as glutathione peroxidase 1 (GPO1), glutathione peroxidase 3 (GPO3) and superoxide dismutase (SOD1) were elevated in the livers of rats treated with this fraction (500 mg/kg). Based on these results, we suggest that the C. setidens extract has hepatoprotective effect related to its antioxidant activity.