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Ras GTPases, well characterized for their role in oncogenesis, are the cells' molecular switches that signal to maintain immune homeostasis through cellular development, proliferation, differentiation, survival, and apoptosis. In the immune system, T cells are the central players that cause autoimmunity if dysregulated. Antigen‐specific T‐cell receptor (TCR) stimulation activates Ras‐isoforms, which exhibit isoform‐specific activator and effector requirements, functional specificities, and a selective role in T‐cell development and differentiation. Recent studies show the role of Ras in T‐cell‐mediated autoimmune diseases; however, there is a scarcity of knowledge about the role of Ras in T‐cell development and differentiation. To date, limited studies have demonstrated Ras activation in response to positive and negative selection signals and Ras isoform‐specific signaling, including subcellular signaling, in immune cells. The knowledge of isoform‐specific functions of Ras in T cells is essential, but still inadequate to develop the T‐cell‐targeted Ras isoform‐specific treatment strategies for the diseases caused by altered Ras‐isoform expression and activation in T cells. In this review, we discuss the role of Ras in T‐cell development and differentiation, critically analyzing the isoform‐specific functions. [ABSTRACT FROM AUTHOR]

Abstract The dicatechol ester ligand 2-H4 forms the compressed helicate Li4[(2)3 Ti2] which upon removal of the internally bound lithium cations expands. In the compressed form, the chiral diol units control the stereochemistry of the complex which is lost upon expansion of the system.

Direct synthesis of previously undescribed 5‐aryl‐substituted pyrrol‐2‐one derivatives containing a butadienetricarbonitrile (BDTC) acceptor was carried out. The kinetics of their reversible interaction with morpholine accompanied with high‐contrast color changes in acetonitrile solution was studied for the first time. It was found that the electronic effects of substituents in aromatic ring had a direct effect on the reaction rate and extent, that was supported by the observed linearity between the estimated equilibrium constants and the electrophilic Hammett constants. [ABSTRACT FROM AUTHOR]

Background: Despite the increasing number of research endeavors dedicated to investigating the relationship between colorectal carcinoma (CRC) and hepatocellular carcinoma (HCC), the underlying pathogenic mechanism remains largely elusive. The aim of this study is to shed light on the molecular mechanism involved in the development of this comorbidity. Methods: The gene expression profiles of CRC (GSE90627) and HCC (GSE45267) were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the common differentially expressed genes (DEGs) of psoriasis and atherosclerosis, three kinds of analyses were performed, namely, functional annotation, protein-protein interaction (PPI) network and module construction, and hub gene identification, survival analysis and co-expression analysis. Results: A total of 150 common downregulated differentially expressed genes and 148 upregulated differentially expressed genes were selected for subsequent analyses. The significance of chemokines and cytokines in the pathogenesis of these two ailments is underscored by functional analysis. Seven gene modules that were closely connected were identified. Moreover, the lipopolysaccharidemediated signaling pathway is intricately linked to the development of both diseases. Finally, 10 important hub genes were identified using cytoHubba, including CDK1, KIF11, CDC20, CCNA2, TOP2A, CCNB1, NUSAP1, BUB1B, ASPM, and MAD2L1. Conclusion: Our study reveals the common pathogenesis of colorectal carcinoma and hepatocellular carcinoma. These common pathways and hub genes may provide new ideas for further mechanism research. [ABSTRACT FROM AUTHOR]

Controlling the number of molecular switches and their relative positioning within porous materials is critical to their functionality and properties. The proximity of many molecular switches to one another can hinder or completely suppress their response. Herein, a synthetic strategy involving mixed linkers is used to control the distribution of spiropyran-functionalized linkers in a covalent organic framework (COF). The COF contains a spiropyran in each pore which exhibits excellent reversible photoswitching behavior to its merocyanine form in the solid state in response to UV/Vis light. The spiro-COF possesses an urchin-shaped morphology and exhibits a morphological transition to 2D nanosheets and vesicles in solution upon UV light irradiation. The merocyanine-equipped COFs are extremely stable and possess a more ordered structure with enhanced photoluminescence. This approach to modulating structural isomerization in the solid state is used to develop inkless printing media, while the photomediated polarity change is used for water harvesting applications. Controlling the number of molecular switches and their relative positioning within porous materials is critical to their functionality and properties. Here the authors systematically control the number of spiropyran units in a covalent organic framework using a mixed-linker synthetic strategy which resulted in one photoresponsive unit per pore. [ABSTRACT FROM AUTHOR]

Sensitively monitoring the concentration change of lipocalin 1 (LCN1) can provide data support for accurately diagnosing diabetic retinopathy and efficacy of treatment. Using a new aptamer triplex switch (ATS) probe and catalytic hairpin assembly (CHA) and hybridization chain reaction (HCR) dual signal amplifications, a highly sensitive electrochemical and enzyme-free biosensor for detecting LCN1 is reported. The ATS probes recognize and bind LCN1 to change its structure and release ssDNA sequences, which trigger the capture of methylene blue (MB)-tagged DNA on the sensor electrode via the CHA and HCR reactions. These MB tags are then subjected to electrochemical measurements to obtain highly amplified current outputs to sensitively detect LCN1 from 5 pM to 1 nM with a detection limit of 0.85 pM. This sensor also exhibits high interfering protein discrimination capability and can be employed to monitor low levels of LCN1 in diluted tear samples. Our established sensor significantly outperforms current major LCN1 detection methods based on immunoassays and thus holds promising potential for evaluating the severity of diabetic retinopathy and monitoring treatment response. [ABSTRACT FROM AUTHOR]

PEAK pseudokinases regulate cell migration, invasion and proliferation by recruiting key signaling proteins to the cytoskeleton. Despite lacking catalytic activity, alteration in their expression level is associated with several aggressive cancers. Here, we elucidate the molecular details of key PEAK signaling interactions with the adapter proteins CrkII and Grb2 and the scaffold protein 14-3-3. Our findings rationalize why the dimerization of PEAK proteins has a crucial function in signal transduction and provide biophysical and structural data to unravel binding specificity within the PEAK interactome. We identify a conserved high affinity 14-3-3 motif on PEAK3 and demonstrate its role as a molecular switch to regulate CrkII binding and signaling via Grb2. Together, our studies provide a detailed structural snapshot of PEAK interaction networks and further elucidate how PEAK proteins, especially PEAK3, act as dynamic scaffolds that exploit adapter proteins to control signal transduction in cell growth/motility and cancer. The PEAK family of pseudokinases are key hubs in cellular signalling, including cell motility and cancer. Here, the authors characterise how PEAK proteins interact with the adapter proteins CrkII and Grb2 and regulatory scaffold protein 14-3-3, to achieve functional signalling assemblies. [ABSTRACT FROM AUTHOR]

Herein we report the synthesis of nonsymmetrically substituted azobenzene derivatives with meta -alkyl substituents on one side and meta -aryl moieties with electron-donating or electron-withdrawing groups on the other side. The half-lives for the thermal (Z)- to (E)-isomerization of these molecules were measured in n -octane, which allows investigation of the strength of the aryl–alkyl interactions between their substituents. It was found that the London dispersion donor strength of the alkyl substrate is the decisive factor in the observed stabilization, whereas the electronic structure of the aryl fragment does not influence the isomerization in a significant way. [ABSTRACT FROM AUTHOR]

Hydrogels are a type of high-water content and crosslinked polymer networks, which can produce a volumetric expansion or contraction through a water absorption or loss process under external environmental stimulation. Due to their good biocompatibility and adjustable mechanical properties, hydrogels have attracted wide attentions and have been extensively applied in the fields of tissue engineering, biomimetic deformation and intelligent actuation. Light is a noncontact, fast switching and high spatiotemporal resolution stimulus, and therefore is used to regulate the macroscopic structure and properties of hydrogels through photothermal effects, photochemical reactions or photoisomerization. Among them, photoisomerization of molecular switches has a broader application potential because of its advantages of mild irradiation conditions and high reversibility. In this review, we summarize the state-of-the-art of photoresponsive hydrogels based on molecular photoisomerization, emphasizing the principle of molecular design as well as applications in biomimetic actuation, and eventually address their perspectives and challenges in the future development. [ABSTRACT FROM AUTHOR]

Binuclear diaminocarbene complexes, which form as a regioisomer mixture in the reaction between isocyanide–palladium(II) complex cis-[PdCl2(CNXyl)2] and 1,3-thiazol-2-amine, are able to exchange an anionic chloride ligand with other halides, such as Br or I. This process also affords binuclear complexes as mixtures of kinetically and thermodynamically controlled regioisomers. In CDCl3 solutions, we observed interconversion of kinetically and thermodynamically controlled regioisomers. The results of the DFT calculations revealed that in CHCl3 solution, each pair of the isomers exhibited two different types of chalcogen bonding such as S···X or S···N; the presence of CBs for two complexes in the solid state was also proven through X-ray crystallographic study. Based on the combined experimental and theoretical data, it could be concluded that thermodynamic favorability for the formation of thermodynamically controlled regioisomers increases in the Cl < Br ≈ I row and correlate well with the energy difference between S···N and S···X (X = Cl, Br, I) chalcogen bonds in kinetically and thermodynamically controlled products. This means that it is possible to change the structure of metallocycles in binuclear diaminocarbene complexes by simply replacing one halide ligand with another. [ABSTRACT FROM AUTHOR]

Kirsten rat sarcoma (KRAS) is a small GTPase which acts as a molecular switch to regulate several cell biological processes including cell survival, proliferation, and differentiation. Alterations in KRAS have been found in 25% of all human cancers, with pancreatic cancer (90%), colorectal cancer (45%), and lung cancer (35%) being the types of cancer with the highest mutation rates. KRAS oncogenic mutations are not only responsible for malignant cell transformation and tumor development but also related to poor prognosis, low survival rate, and resistance to chemotherapy. Although different strategies have been developed to specifically target this oncoprotein over the last few decades, almost all of them have failed, relying on the current therapeutic solutions to target proteins involved in the KRAS pathway using chemical or gene therapy. Nanomedicine can certainly bring a solution for the lack of specificity and effectiveness of anti-KRAS therapy. Therefore, nanoparticles of different natures are being developed to improve the therapeutic index of drugs, genetic material, and/or biomolecules and to allow their delivery specifically into the cells of interest. The present work aims to summarize the most recent advances related to the use of nanotechnology for the development of new therapeutic strategies against KRAS-mutated cancers. [ABSTRACT FROM AUTHOR]

Owing to the unique chemical structure and photophysical properties of azulene, azulene derivatives show great promise for a wide range of prospective technical applications, such as molecular switching, sensors, solar cells, and biological activities. In addition to functionalization of the existed azulene cores, direct construction of azulenes via condensation with odd‐membered carbocycles such as tropolone, 2‐oxazulanone, cyclopentadiene, and 6‐aminofulvene is another classical method for obtaining azulene derivatives. Although alkynes are widely explored for construction of benzene rings, several unconventional cyclization reactions with alkynes produce azulene, pseudoazulene, or azulenone skeletons. This minireview summarizes these interesting and practical cyclization with a classification based on the function of alkyne in the azulene formation process, aiming at capturing the attention of the scientific community to make efforts in the development of such nonalternant cyclization reactions of alkynes. [ABSTRACT FROM AUTHOR]

In this paper, we investigate a technology to change the method and principle of n+ a‐Si:H etching from conventional dry etch to the innovative wet etch in TFT LCD fabrication. The technology is based on the development of a new wet metal etching solution and the design of the thinnest film thickness of a‐Si:H in the industry, combined with the etching process development, to achieve the etching of two different film layers of metal and N+ a‐Si:H in the back channel of TFT switches in one‐ step(Abbreviated as NW process). The process can effectively improve the capacity of Dry Etch process (Skip N+ Dry Etch); improve the uniformity of back channel a‐Si:H Remain (16.3%‐ >7.6%); improve product characteristics (Dark I on（ TFT working current） 5.5‐>6.0); improve yield (Yield rate↑0.3%).The process has been successfully developed for the first time in Wuhan BOE and has been widely used for batch products, meanwhile, the process has been extended to Hefei BOE and Fuzhou BOE, and other BOE line sites are also actively exploring the experiment. [ABSTRACT FROM AUTHOR]

Some organic ferroelectrics have two possible switching modes: molecular reorientation and proton transfer. Typical examples include 2,5-dihydroxybenzoic acid (DHBA) and Hdabco-ReO 4 (dabco = diazabicyclo[2.2.2]octane). The direction and amplitude of the expected polarization depends on the switching mode. Herein a straightforward method to identify the ferroelectric switching mechanism is demonstrated. First, the relationship between the polarization vectors corresponding to the two modes is illustrated using the Berry phase. Second, the theoretical background for the sign of the piezoelectric coefficient is used to decide which mode occurs. Finally, comparing the theoretically calculated piezoelectric coefficients to the experimental results confirms the switching mode of each compound. [ABSTRACT FROM AUTHOR]

Experimentation under dynamic shocked conditions has attained the status of one of the appealing classes of methods for identifying the functional materials whose degree of long-range order is significantly altered. In the present work, we have systematically investigated the dynamic impact of shock waves on the technologically important single crystal of sulfamic acid at various numbers of shocks exposed and the results have been analyzed by X-ray diffraction and Raman spectroscopic profiles. Based on the obtained results, the shocked phase profile with respect to the number of shock pulses is of the sequential order (Pbca)–disorder–order (Pbca)–disorder–order (Pbca) for the 0, 1, 2, 3 and 4 shocks, respectively. The observed switchable phase transitions of the titled crystal after shocked conditions might be due to the rotational order–disorder transformation that is followed by the molecular symmetry changes of NH3 and SO3 trigonal units for which the possible macroscopic mechanism is provided. The observed switchable phase transitions occurring between order and disorder states may be an interesting asset for molecular electronic devices such as the molecular switches. [ABSTRACT FROM AUTHOR]

In this work, the anion‐responsive conduct of a Ru(II)‐bipyridine complex incorporating pyrazolyl‐bis (benzimidazole) ligand is thoroughly investigated in acetonitrile and water via absorption and emission spectroscopy as well as by square‐wave voltammetry (SWV). Substantial alteration of the photo‐redox behavior of the complex is observed in the presence of the selected anions. The free form of the complex exhibits emission indicating the "on‐state", while inclusion of anions leads to quenching of emission and represents the "off‐state". The restoration of the initial state of the complex is feasible in the presence of acid and the process is reversible and can be recycled. In essence, the complex functions as anion‐ and acid‐responsive molecular switches. Additionally, we applied herein neural network based deep learning methodologies, viz. Artificial Neural Networks (ANNs) and Adaptive Neuro‐Fuzzy Inference System (ANFIS)} for thorough analysis and fully understand the multi‐channel anion sensing behavior of the complex. [ABSTRACT FROM AUTHOR]

Materials with phototunable full-color circularly polarized luminescence (CPL) have a large storage density, high-security level, and enormous prospects in the field of information encryption and decryption. In this work, device-friendly solid films with color tunability are prepared by constructing Förster resonance energy transfer (FRET) platforms with chiral donors and achiral molecular switches in liquid crystal photonic capsules (LCPCs). These LCPCs exhibit photoswitchable CPL from initial blue emission to RGB trichromatic signals under UV irradiation due to the synergistic effect of energy and chirality transfer and show strong time dependence because of the different FRET efficiencies at each time node. Based on these phototunable CPL and time response characteristics, the concept of multilevel data encryption by using LCPC films is demonstrated. Phototunable full-color circularly polarized luminescence (CPL) features large storage density which is important for the field of information encryption and decryption. Here, the authors present a device-friendly solid film with color-tunability by employing Förster resonance energy transfer among a chiral donor and achiral molecular switches in a liquid crystal photonic capsules. [ABSTRACT FROM AUTHOR]

The optical modulation of fluorescence characteristics in molecular aggregates, which mainly involves diverse molecular stacking and the consequent intermolecular interactions, remains a significant challenge for potential applications in optical anticounterfeiting, data storage, and imaging. Here we successfully realize in situ fluorescence switching in molecular aggregates of thianaphthene‐dioxide derivatives by topological [2+2] photocycloaddition, which represents a promising way to regulate the molecular stacking and alter photophysical processes. Notably, 2‐(3,5‐bis‐trifluoromethylphenyl)benzo[b]thiophene‐dioxide (BTO‐TF) in both crystal and powder forms exhibits a unique switching from an initial nonfluorescent state to a highly fluorescent state (ΦPL=0.46) upon UV irradiation, because of the destruction of the [2+2] cycloaddition process by volume expansion of the photodimer. Furthermore, we demonstrate such a [2+2] photocycloaddition can occur when 2‐(4‐carboxypheny)benzo[b]thiophene‐dioxide (BTO‐OH) is doped within selective polymer matrixes, and can be utilized for the visualization of macrophase separation in polymer blends. [ABSTRACT FROM AUTHOR]

Amyloid plaques composed of Aβ fibrils are a hallmark of Alzheimer's disease (AD). However, the molecular architecture of amyloid plaques in the context of fresh mammalian brain tissue is unknown. Here, using cryogenic correlated light and electron tomography we report the in situ molecular architecture of Aβ fibrils in the AppNL-G-F familial AD mouse model containing the Arctic mutation and an atomic model of ex vivo purified Arctic Aβ fibrils. We show that in-tissue Aβ fibrils are arranged in a lattice or parallel bundles, and are interdigitated by subcellular compartments, extracellular vesicles, extracellular droplets and extracellular multilamellar bodies. The Arctic Aβ fibril differs significantly from an earlier AppNL-F fibril structure, indicating a striking effect of the Arctic mutation. These structural data also revealed an ensemble of additional fibrillar species, including thin protofilament-like rods and branched fibrils. Together, these results provide a structural model for the dense network architecture that characterises β-amyloid plaque pathology. In this work the authors reveal in-situ cryoET characterization of β-amyloid plaques in the brain of a mouse model of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

The reversible isomerism of indolinospirobenzopyrans is perhaps among the most studied phenomena in the field of molecular switches. Although they began to gain attention as early as 70 years ago following the seminal work of Hirshberg and Fischer, who were the first to recognize their photochromic behaviours, their implementation as photoacids emerged prominently only in the last decade. In this Review, we contextualize the prerequisites underlying the photo‐triggered proton release that occurs in these molecular switches, highlighting the most recent advances in their characterization and application as "metastable‐state photoacids" in water. [ABSTRACT FROM AUTHOR]

The increasing sodium salts (NaCl, NaHCO3, NaSO4 etc.) in agricultural soil is a serious global concern for sustainable agricultural production and food security. Soybean is an important food crop, and their cultivation is severely challenged by high salt concentration in soils. Classical transgenic and innovative breeding technologies are immediately needed to engineer salt tolerant soybean plants. Additionally, unfolding the molecular switches and the key components of the soybean salt tolerance network are crucial for soybean salt tolerance improvement. Here we review our understandings of the core salt stress response mechanism in soybean. Recent findings described that salt stress sensing, signalling, ionic homeostasis (Na+/K+) and osmotic stress adjustment might be important in regulating the soybean salinity stress response. We also evaluated the importance of antiporters and transporters such as Arabidopsis K+ Transporter 1 (AKT1) potassium channel and the impact of epigenetic modification on soybean salt tolerance. We also review key phytohormones, and osmo-protectants and their role in salt tolerance in soybean. In addition, we discuss the progress of omics technologies for identifying salt stress responsive molecular switches and their targeted engineering for salt tolerance in soybean. This review summarizes recent progress in soybean salt stress functional genomics and way forward for molecular breeding for developing salt-tolerant soybean plant. [ABSTRACT FROM AUTHOR]

G-protein coupled receptors (GPCRs) and ion channels serve as key molecular switches through which extracellular stimuli are transformed into intracellular effects, and it has long been postulated that ion channels are direct effector molecules of the alpha subunit of G-proteins (Gα). However, no complete structural evidence supporting the direct interaction between Gα and ion channels is available. Here, we present the cryo-electron microscopy structures of the human transient receptor potential canonical 5 (TRPC5)-Gαi3 complexes with a 4:4 stoichiometry in lipid nanodiscs. Remarkably, Gαi3 binds to the ankyrin repeat edge of TRPC5 ~ 50 Å away from the cell membrane. Electrophysiological analysis shows that Gαi3 increases the sensitivity of TRPC5 to phosphatidylinositol 4,5-bisphosphate (PIP2), thereby rendering TRPC5 more easily opened in the cell membrane, where the concentration of PIP2 is physiologically regulated. Our results demonstrate that ion channels are one of the direct effector molecules of Gα proteins triggered by GPCR activation–providing a structural framework for unraveling the crosstalk between two major classes of transmembrane proteins: GPCRs and ion channels. Ion channels could be directly regulated by the alpha subunit of heterotrimeric G-proteins. Here, authors present the cryo-EM structure of an ion channel-Gα complex, TRPC5-Gαi3, and present functional insights into their direct interaction. [ABSTRACT FROM AUTHOR]

DNA nanoflowers (DNFs) are topological flower-like nanostructures based on ultralong-strand DNA and inorganic metal-ion frameworks. Because of their programmability, biocompatibility, and controllable assembly size for specific responses to molecular recognition stimuli, DNFs are powerful biosensing tools for detecting biomolecules. Here, we review the current state of DNF-based biosensing strategies for in vivo and in vitro detection, with a view of how the field has evolved towards molecular diagnostics. We also provide a detailed classification of DNF-based biosensing strategies and propose their future utility. Particularly as transduction elements, DNFs can accelerate biosensing engineering by signal amplification. Finally, we discuss the key challenges and further prospects of DNF-based biosensing technologies in developing applications of a broader scope. DNA nanoflower (DNF)-based biosensors can efficiently translate information from targeted biomarkers into physical or chemical signals by the unique programmability and massive repeating copies of flower-like structures. DNF biosensing technologies can be designable platforms for both in vitro detection, applied to cells, proteins, small molecules, and in vivo detection, applied to RNA and ATP. DNF-based biosensing technologies present high specificity, sensitivity, biocompatibility, multiplex detection, and point-of-care testing with fast and equipment-free performance. Theranostic flower-like structures can be used as molecular switches to respond to specific intracellular environment and biomarkers, trigger structure degradation, and controllably release particular loadings. [ABSTRACT FROM AUTHOR]

In this study, fullerene C20 molecule was used and two types of molecular switch structures were designed. Then, using DFT calculations, the effect of electric fields, with powers of 0 to 100 × 10–4 a.u., on their structural and electrical properties was investigated. It was observed that with increasing electric field, the structure of switches 1 and 2 changes and the intensity of changes in dihedral angle is more than other structural parameters. Sudden changes in dihedral angle occur in the electric field, which can indicate that the switch is on. It was shown that as the electric field strength increases, the HLG decreases, which decreases sharply in a given field and then becomes constant. This fast decrease in HLG, which is in correspondence with changing in the dihedral angle, demonstrates the on state of the molecular switch. NBO Charges analysis on the Au, S, N, and O atoms shows that the electric field pushes the electrons toward more positive electric fields. Finally, the evidence shows that switch 1 in the electric field about 0.006 to 0.008 a.u. is switched from off to on, and switch 2 in the electric field is switched from 0.003 to 0.005 a.u. [ABSTRACT FROM AUTHOR]

ortho-Functionalized azobenzenes are much sought after molecular switches, as they may be tuned to absorb in the visible range of light and the (Z)-isomers can have high thermal half-lives. To enable straightforward access to these targets, we have developed a synthetic route via novel ortho-substituted azobenzene-functionalized diaryliodonium salts. Selective transfer of the azobenzene moiety to O-, N-, C- and S-nucleophiles under mild, transition metal-free conditions gives access to an unprecedented range of ortho-substituted azobenzenes. The photoswitching properties of the reagents were investigated and the structure was determined by X-ray crystallography. [ABSTRACT FROM AUTHOR]

The article discusses the cellular and molecular mechanisms underlying tissue regeneration and fibrotic healing in mammals. Topics discussed include egenerative response of spiny mice (Acomys species), which can naturally regenerate complex tissues, to laboratory mouse strains (Mus), which heal with scar tissue, and ERK activation in nonregenerative species.

Solvation of [(CNT)Ln(η8‐COT)] (Ln=La, Ce, Nd, Tb, Er; CNT=cyclononatetraenyl, i.e. C9H9−; COT=cyclooctatetraendiid, i.e. C8H82−) complexes with tetrahydrofuran (THF) gives rise to neutral [(η4‐CNT)Ln(thf)2(η8‐COT)] (Ln=La, Ce) and ionic [Ln(thf)x(η8‐COT)][CNT] (x=4 (Ce, Nd, Tb), 3 (Er)) species in a solid‐to‐solid transformation. Due to the severe distortion of the ligand sphere upon solvation, these species act as switchable luminophores and single‐molecule magnets. The desolvation of the coordinated solvents can be triggered by applying a dynamic vacuum, as well as a temperature gradient stimulus. Raman spectroscopic investigations revealed fast and fully reversible solvation and desolvation processes. Moreover, we also show that a Nd:YAG laser can induce the necessary temperature gradient for a self‐sufficient switching process of the Ce(III) analogue in a spatially resolved manner. [ABSTRACT FROM AUTHOR]

A series of symmetrical and unsymmetrical (indolyl)methanes were synthesized using the Ball milling methodology. The redox switching of the prepared compounds was studied by exploiting their multi‐responsive behavior towards oxidants (light/oxygen), reductants (NaBH4, hydrogen with Pd/C or palladium‐doped magnetic nanoparticles) and electrochemical modulation. Coumarin‐derived (indolyl)methane exhibited distinct color variation and emission On/Off during the redox switching which could be useful in materials/biomaterials applications. Overall, this paper describes the design, synthesis and demonstration of the multi‐responsive behavior of (indolyl)methanes towards redox switching. [ABSTRACT FROM AUTHOR]

Aptamer-based molecular switches that undergo a binding-induced conformational change have proven valuable for a wide range of applications, such as imaging metabolites in cells, targeted drug delivery, and real-time detection of biomolecules. Since conventional aptamer selection methods do not typically produce aptamers with inherent structure-switching functionality, the aptamers must be converted to molecular switches in a post-selection process. Efforts to engineer such aptamer switches often use rational design approaches based on in silico secondary structure predictions. Unfortunately, existing software cannot accurately model three-dimensional oligonucleotide structures or non-canonical base-pairing, limiting the ability to identify appropriate sequence elements for targeted modification. Here, we describe a massively parallel screening-based strategy that enables the conversion of virtually any aptamer into a molecular switch without requiring any prior knowledge of aptamer structure. Using this approach, we generate multiple switches from a previously published ATP aptamer as well as a newly-selected boronic acid base-modified aptamer for glucose, which respectively undergo signal-on and signal-off switching upon binding their molecular targets with second-scale kinetics. Notably, our glucose-responsive switch achieves ~30-fold greater sensitivity than a previously-reported natural DNA-based switch. We believe our approach could offer a generalizable strategy for producing target-specific switches from a wide range of aptamers. Efforts to convert aptamers into molecular switches using rational design are often unsuccessful. Here the authors describe a massively parallel screening-based strategy whereby millions of potential aptamer switches are synthesised, sequenced and screened directly on a flow-cell. [ABSTRACT FROM AUTHOR]

Zn electrodes in aqueous media exhibit an unstable Zn/electrolyte interface due to severe parasitic reactions and dendrite formation. Here, a dynamic Zn interface modulation based on the molecular switch strategy is reported by hiring γ‐butyrolactone (GBL) in ZnCl2/H2O electrolyte. During Zn plating, the increased interfacial alkalinity triggers molecular switch from GBL to γ‐hydroxybutyrate (GHB). GHB strongly anchors on Zn surface via triple Zn−O bonding, leading to suppressive hydrogen evolution and texture‐regulated Zn morphology. Upon Zn stripping, the fluctuant pH turns the molecular switch reaction off through the cyclization of GHB to GBL. This dynamic molecular switch strategy enables high Zn reversibility with Coulombic efficiency of 99.8 % and Zn||iodine batteries with high‐cyclability under high Zn depth of discharge (50 %). This study demonstrates the importance of dynamic modulation for Zn electrode and realizes the reversible molecular switch strategy to enhance its reversibility. [ABSTRACT FROM AUTHOR]

In previous work, we have developed a DNA methylation‐based epigenetic memory system that operates in Escherichia coli to detect environmental signals, trigger a phenotypic switch of the cells and store the information in DNA methylation. The system is based on the CcrM DNA methyltransferase and a synthetic zinc finger (ZnF4), which binds DNA in a CcrM methylation‐dependent manner and functions as a repressor for a ccrM gene expressed together with an egfp reporter gene. Here, we developed a reversible reset for this memory system by adding an increased concentration of ZnSO4 to the bacterial cultivation medium and demonstrate that one bacterial culture could be reversibly switched ON and OFF in several cycles. We show that a previously developed differential equation model of the memory system can also describe the new data. Then, we studied the long‐term stability of the ON‐state of the system over approximately 100 cell divisions showing a gradual loss of ON‐state signal starting after 4 days of cultivation that is caused by individual cells switching from an ON‐ into the OFF‐state. Over time, the methylation of the ZnF4‐binding sites is not fully maintained leading to an increased OFF switching probability of cells, because stronger binding of ZnF4 to partially demethylated operator sites leads to further reductions in the cellular concentrations of CcrM. These data will support future design to further stabilize the ON‐state and enforce the binary switching behaviour of the system. Together with the development of a reversible OFF switch, our new findings strongly increase the capabilities of bacterial epigenetic biosensors. [ABSTRACT FROM AUTHOR]

By employing a mechanically controllable break junction technique, we have realized an ideal single molecular linear actuator based on dithienylethene (DTE) based molecular architecture, which undergoes reversible photothermal isomerization when subjected to UV irradiation under ambient conditions. As a result, open form (compressed, UV OFF) and closed form (elongated, UV ON) of dithienylethene‐based molecular junctions are achieved. Interestingly, the mechanical actuation is achieved without changing the conductance of the molecular junction around the Fermi level over several cycles, which is an essential property required for an ideal single molecular actuator. Our study demonstrates a unique example of achieving a perfect balance between tunneling width and barrier height change upon photothermal isomerization, resulting in no change in conductance but a change in the molecular length, which results in mechanical actuation at the single molecular level. [ABSTRACT FROM AUTHOR]

Protein quality control is a process in which a protein's folding status is constantly monitored. Mislocalized proteins (MLP), are processed by the various quality control pathways, as they are often misfolded due to inappropriate cellular surroundings. Polypeptides that fail to translocate into the ER due to an inefficient signal peptide, mutations or ER stress are recognized by the pre-emptive ER associated quality control (pEQC) pathway and degraded by the 26 S proteasome. In this report we reveal the role of RNF149, a membrane bound E3 ligase in the ubiquitination of known pEQC substrates. We demonstrate its selective binding only to non-translocated proteins and its association with known pEQC components. Impairment in RNF149 function increases translocation flux into the ER and manifests in a myeloproliferative neoplasm (MPN) phenotype, a pathological condition associated with pEQC impairment. Finally, the dynamic localization of RNF149 may provide a molecular switch to regulate pEQC during ER stress. E3 ligase RNF149 contributes to the pre-emptive quality control (pQC) pathway & interacts with AIRAPL in a ubiquitin-dependent manner, with loss of RNF149 function appearing to increase the translocation flux of pQC substrates to the ER. [ABSTRACT FROM AUTHOR]

Adeno-associated virus (AAV)-based gene therapy could be facilitated by the development of molecular switches to control the magnitude and timing of expression of therapeutic transgenes. RNA interference (RNAi)-based approaches hold unique potential as a clinically proven modality to pharmacologically regulate AAV gene dosage in a sequence-specific manner. We present a generalizable RNAi-based rheostat wherein hepatocyte-directed AAV transgene expression is silenced using the clinically validated modality of chemically modified small interfering RNA (siRNA) conjugates or vectorized co-expression of short hairpin RNA (shRNA). For transgene induction, we employ REVERSIR technology, a synthetic high-affinity oligonucleotide complementary to the siRNA or shRNA guide strand to reverse RNAi activity and rapidly recover transgene expression. For potential clinical development, we report potent and specific siRNA sequences that may allow selective regulation of transgenes while minimizing unintended off-target effects. Our results establish a conceptual framework for RNAi-based regulatory switches with potential for infrequent dosing in clinical settings to dynamically modulate expression of virally-delivered gene therapies. Here the authors propose an RNA interference-based switch for dynamic control of AAV transgene expression. In this approach, transgene expression may be silenced by RNAi and subsequently recovered using REVERSIR oligonucleotides. [ABSTRACT FROM AUTHOR]

A bistable [2]rotaxane based on dibenzylammonium (DBA+)/methyl triazolium (MTA+) stations and [23]crown ether (X23C7) wheel component has been obtained in excellent yield. The crown ether X23C7 predominantly occupies the DBA+ station, in the bistable [2]rotaxane. On addition of the base, the crown ether X23C7 shuttles across to the MTA+ station. Acid treatment led to the restoration of X23C7 back to the DBA+ station. Due to this reversibility, a pH‐responsive molecular switch has been obtained. This is the first example of a [23]crown ether, a smaller analogue of [24]crown ether, exhibiting shuttling motion in any crown ether‐based mechanically interlocked molecules. [ABSTRACT FROM AUTHOR]

Extensive use of pesticides in agriculture can lead to environmental pollution and potentially adverse health effects. A fluorescence Turn‐On molecular switch, derived from naturally occurring α‐mangostin (MN), isolated from the pericarp of mangosteen fruit and Graphene Quantum Dots (GQDs) synthesized from honey, was developed for the detection of carbofuran‐an organic toxic carbamate pesticide. GQDs derived from honey shows a strong fluorescence emission centered at 430 nm, which was efficiently quenched by the addition of MN. The quenching of fluorescence of GQDs by the addition of MN (OFF state) and the regaining of quenched fluorescence of GQDs‐MN system (ON state) upon the addition of the pesticide carbofuran was utilized as a detection strategy for the toxic pesticide carbofuran. [ABSTRACT FROM AUTHOR]

Inositol poly- and pyrophosphates (InsPs and PP-InsPs) are central eukaryotic messengers. These very highly phosphorylated molecules can exist in two distinct conformations, a canonical one with five phosphoryl groups in equatorial positions, and a "flipped" conformation with five axial substituents. Using 13C-labeled InsPs/PP-InsPs, the behavior of these molecules was investigated by 2D-NMR under solution conditions reminiscent of a cytosolic environment. Remarkably, the most highly phosphorylated messenger 1,5(PP)2-InsP4 (also termed InsP8) readily adopts both conformations at physiological conditions. Environmental factors—such as pH, metal cation composition, and temperature—strongly influence the conformational equilibrium. Thermodynamic data revealed that the transition of InsP8 from the equatorial to the axial conformation is, in fact, an exothermic process. The speciation of InsPs and PP-InsPs also affects their interaction with protein binding partners; addition of Mg2+ decreased the binding constant Kd of InsP8 to an SPX protein domain. The results illustrate that PP-InsP speciation reacts very sensitively to solution conditions, suggesting it might act as an environment-responsive molecular switch. [ABSTRACT FROM AUTHOR]

The general tool of fluorescent PET (photoinduced electron transfer) sensors/switches – a molecular design principle with engineering features – is outlined, with the aid of frontier orbital energy diagrams. Fluorophores such as anthracene, 1,3‐diaryl‐Δ2‐pyrazolines and 4‐amino‐1,8‐naphthalimides are employed within this system, alongside receptors such as amines, carboxylates, crown ethers and amino acids. This tool appealed to a multinational corporation for building a medical analyzer for electrolytes such as Na+, K+, Ca2+ and gases like CO2, which became a commercially successful application. Finally, the tool was a springboard for chemistry to cross into computer science. The field of molecular logic can elucidate how molecules inside us handle information. Molecular examples of the simplest logic gates such as YES, NOT, OR, AND are described. A case of a human‐level computation – visual edge detection – is also included. [ABSTRACT FROM AUTHOR]

The spindle assembly checkpoint (SAC) is a cellular surveillance mechanism that functions to ensure accurate chromosome segregation during mitosis. Macromolecular complexes known as kinetochores, act as the interface of sister chromatid attachment to spindle microtubules. In response to unattached kinetochores, the SAC activates its effector, the mitotic checkpoint complex (MCC), which delays mitotic exit until all sister chromatid pairs have achieved successful attachment to the bipolar mitotic spindle. Formation of the MCC (composed of Mad2, BubR1, Bub3 and Cdc20) is regulated by an Mps1 kinase‐dependent phosphorylation signaling cascade which assembles and repositions components of the MCC onto a catalytic scaffold. This scaffold functions to catalyze the conversion of the HORMA‐domain protein Mad2 from an "inactive" open‐state (O‐Mad2) into an "active" closed‐Mad2 (C‐Mad2), and simultaneous Cdc20 binding. Here, our current understanding of the molecular mechanisms underlying the kinetic barrier to C‐Mad2:Cdc20 formation will be reviewed. Recent progress in elucidating the precise molecular choreography orchestrated by the catalytic scaffold to rapidly assemble the MCC will be examined, and unresolved questions will be highlighted. Ultimately, understanding how the SAC rapidly activates the checkpoint not only provides insights into how cells maintain genomic integrity during mitosis, but also provides a paradigm for how cells can utilize molecular switches, including other HORMA domain‐containing proteins, to make rapid changes to a cell's physiological state. [ABSTRACT FROM AUTHOR]

In this contribution, we studied the photophysics and photochemistry of an archetypal molecular switch in terms of solar energy storage and release. In detail, we characterized the valence and Rydberg states of norbornadiene (NBD) and quadricyclane (QC) by means of CASPT2//CASSCF theory level, finding a good agreement of the calculated vertical excitation energies with the experimental counterparts. The NBD↔QC thermal and photochemical valence isomerization [2π+2π] reactions have been addressed and investigated. Low energy crossing points between excited states were identified for both the NBD↔QC photochemical reactions, through the calculation of minimum energy paths which revealed that the photochemistry is ruled by the deformation of two coupled reaction coordinates. Such coordinates were also used to build potential energy surfaces through relaxed energy scans with the goal of building a simplified, still accurate, model system able to catch the NBD↔QC photorelaxation. Also, the S1/S0 respective conical intersection were characterized and related to the reaction quantum yield. Interestingly, we found that reverse photoisomerization from QC to the NBD progenitor could in principle occur by direct excitation of σ‐3s and σ‐3p Rydberg excited states in the UV spectral range. In both NBD and QC photoreactivity, the doubly excited valence state has shown to play a crucial role for reaching crossing points leading to nonadiabatic population transfers. [ABSTRACT FROM AUTHOR]

DFT calculations show that a combination of an electric field and electronic excitation is a promising mechanism to force a molecular switch based on amino-imino tautomerisation into one of its two states. By calculating the effect of an electric field in the direction of the moving hydrogen on the shape of the barrier in the ground and low-lying excited states of previously proposed molecular switches consisting of 5- and 7-membered rings with adjacent amino and imino groups, we demonstrate that electric fields and photons in experimentally accessible ranges introduce sufficient asymmetry to push the switch into the desired configuration. Excitation to states with inverted order of the preferred geometry allows reversible switching without reversal of the electric field. [ABSTRACT FROM AUTHOR]

Limited to the structure of traditional light‐emitting devices, electronic devices that can directly convert machine language into human visual information without introducing any back‐end circuit are still not easy to achieve. Based on a specially designed three‐phase co‐planar electrode structure, a new type of three‐phase alternating current driven organic light‐emitting device with the integration of emission and control functions, full‐color tunability and simple device structure is demonstrated in this study. We integrate the light‐emitting function of color‐tunable light‐emitting devices and the switching of three triodes in a single three phase organic light‐emitting device. The state control of luminous color and luminance intensity merely requires the introduction of a kind of machine language, that is an easy‐to‐program 6‐bit binary number coded digital signals. The color adjustable area covers 66% of the color triangle of the National Television System Committee. Such simple and easy‐to‐integrate light‐emitting system has great potential applications in the next‐generation man‐machine interface. [ABSTRACT FROM AUTHOR]

We introduce a new perspective for musical interaction tailored to a specific class of sonic resources: impact sounds. Our work is informed by the field of ubiquitous music (ubimus) and engages with the demands of artistic practices. Through a series of deployments of a low-cost and highly flexible network-based prototype, the Dynamic Drum Collective, we exemplify the limitations and specific contributions of banging interaction. Three components of this new design strategy—adaptive interaction, mid-air techniques and timbre-led design—target the development of creative-action metaphors that make use of resources available in everyday settings. The techniques involving the use of sonic gridworks yielded positive outcomes. The subjects tended to choose sonic materials that—when combined with their actions on the prototype—approached a full rendition of the proposed soundtrack. The results of the study highlighted the subjects' reliance on visual feedback as a non-exclusive strategy to handle both temporal organization and collaboration. The results show a methodological shift from device-centric and instrumental-centric methods to designs that target the dynamic relational properties of ubimus ecosystems. [ABSTRACT FROM AUTHOR]

We use femtosecond optical pump-probe spectroscopy to study the Light Induced Excited Spin State Trapping (LIESST) dynamics in an FeII spin-crossover material. In these systems, LIESST derives from fast molecular switching induced by light from low (LS, S = 0) to high spin (HS, S = 2) states, as reported for molecules in solution as well as in the solid state. Since the direct LS-to-HS conversion is forbidden by selection rules, the switching dynamics involves intermediate electronic states such as metal-to-ligand charge transfer (MLCT) or ligand-field excited states of singlet or triplet nature. In addition, the HS state is structurally trapped by the elongation of the metal-ligand bond, which is accompanied by the coherent activation and damping of the molecular breathing mode. The ultrafast LIESST dynamics was mainly investigated in FeN6 ligand field systems with almost octahedral symmetry, under MLCT excitation. Our recent study on the FeII(pap-5NO2)2 spin-crossover material, with a FeIIN4O2 ligand field of C2 symmetry, has shown that in addition to MLCT bands, optical excitation, through quite intense and low-energy shifted d-d bands, can also drive LIESST. Compared to MLCT, d-d excitation involves shorter-lived intermediates, drives faster LS-to-HS switching, and enhances the coherent structural dynamics. In this paper, we present an ultrafast study of the pump wavelength dependence of LIESST and we evidence a photoselective crossover from the MLCT to the d-d pathways. [ABSTRACT FROM AUTHOR]

Here, we report the development of a molecular rotary switch (a "stator–rotor" consisting of a single oxygen molecule as a stator and a single pyridine molecule as a rotor) on a silver surface. The pyridine molecule was bonded to the oxygen molecule and was found to rotate to enable "ON" or "OFF" vibrational conductance through the oxygen molecule. Four stable sites around the oxygen molecule were observed, and vibration conductance turned on and off depending on the site at which the pyridine molecule bonded. The spatially resolved mapping of the vibrational change revealed two locations of maximal vibration intensity, separated by ∼3 Å. These positions acted as two conducting channels. The two distinct vibrational energy levels were associated with the switching process. Adsorption-induced electron transfer between the silver layers and the molecules enhanced the local interactions between the molecules. The two vibration modes were excited by resonant tunneling despite substantial interactions between the molecules, which resulted in a decrease in tunneling conductance. An independent pathway exists for the vibrational excitation process by tunneling electrons and intermolecular interactions. [ABSTRACT FROM AUTHOR]

Abstract We present the concept of electrostatic field-driven supramolecular translation within electrically connected plasmonic nano-antennas. The antenna serves as an anchoring point for the mechanically interlocked molecules, as an electrode for the electrostatic field, and as an amplifier of the antenna-enhanced fluorescence. The synthesis of a push–pull donor–π–acceptor chromophore with optical properties aligned to the antenna resonance is described and its immobilization on the surface is demonstrated. Photoluminescence experiments of the chromophore on a gold nano-antenna are shown, highlighting the molecule–antenna coupling and resulting emission intensity increase. The successful synthesis of an electrostatic field-sensitive [2]rotaxane in water is described and the tightrope walk between functionality and water solubility is illustrated by unsuccessful designs. In solution, an enhanced fluorescence quantum yield is observed for the chromophore comprising the mechanically interlocked [2]rotaxane in water and DMSO compared to the reference rod, ideal for future experiments in plasmonic nano-antennas.

Abstract A modular access to 2,5-diaryl 6-hydroxyphenalenone derivatives is developed and demonstrated by a small series of 5 molecules. Within this series, the structures 1 and 2 expose terminal methylsulfanyl anchor groups, enabling their integration in a single-molecule junction. The modular synthesis is based on Suzuki cross-coupling of the aryl substituents as boronic acid precursors with 5,8-dibromo-2-(tert-butyl)-4,9-dimethoxy-2,3-dihydro-1H-phenalen-1-one, and the subsequent transformation of the product to the desired 2,5-diaryl 6-hydroxyphenalenone in a reduction/deprotection sequence. The new structures are fully characterized and their optical and electrochemical properties are analysed. For the derivatives 1 and 2 suitable for single-molecule junctions, the corresponding oxophenalenoxyl radicals 1R and 2R were obtained by oxidation and analysed by electron paramagnetic resonance spectroscopy. Preliminary mechanical break junction experiments with 1 display the structureʼs ability to form transient single-molecule junctions. The intention behind the molecular design is to profit from the various redox states of the structure (including the neutral radical) as a molecular switch in an electrochemically triggered single-molecule transport experiment.

Background: Prior drought stress may change plants response patterns and subsequently increase their tolerance to the same condition, which can be referred to as "drought memory" and proved essential for plants well-being. However, the mechanism of transcriptional drought memory in psammophytes remains unclear. Agriophyllum squarrosum, a pioneer species on mobile dunes, is widely spread in Northern China's vast desert areas with outstanding ability of water use efficiency. Here we conducted dehydration-rehydration treatment on A. squarrosum semi-arid land ecotype AEX and arid land ecotype WW to dissect the drought memory mechanism of A. squarrosum, and to determine the discrepancy in drought memory of two contrasting ecotypes that had long adapted to water heterogeneity. Result: Physiological traits monitoring unveiled the stronger ability and longer duration in drought memory of WW than that of AEX. A total of 1,642 and 1,339 drought memory genes (DMGs) were identified in ecotype AEX and WW, respectively. Furthermore, shared DMGs among A. squarrosum and the previously studied species depicted that drought memory commonalities in higher plants embraced pathways like primary and secondary metabolisms; while drought memory characteristics in A. squarrosum were mainly related to response to heat, high light intensity, hydrogen peroxide, and dehydration, which might be due to local adaptation to desert circumstances. Heat shock proteins (HSPs) occupied the center of the protein-protein interaction (PPI) network in drought memory transcription factors (TF), thus playing a key regulatory role in A. squarrosum drought memory. Co-expression analysis of drought memory TFs and DMGs uncovered a novel regulating module, whereby pairs of TFs might function as molecular switches in regulating DMG transforming between high and low expression levels, thus promoting drought memory reset. Conclusion: Based on the co-expression analysis, protein-protein interaction prediction, and drought memory metabolic network construction, a novel regulatory module of transcriptional drought memory in A. squarrosum was hypothesized here, whereby recurrent drought signal is activated by primary TF switches, then amplified by secondary amplifiers, and thus regulates downstream complicated metabolic networks. The present research provided valuable molecular resources on plants' stress-resistance basis and shed light on drought memory in A. squarrosum. [ABSTRACT FROM AUTHOR]

Motile cells have developed a large array of molecular machineries to actively change their direction of movement in response to spatial cues from their environment. In this process, small GTPases act as molecular switches and work in tandem with regulators and sensors of their guanine nucleotide status (GAP, GEF, GDI and effectors) to dynamically polarize the cell and regulate its motility. In this review, we focus on Myxococcus xanthus as a model organism to elucidate the function of an atypical small Ras GTPase system in the control of directed cell motility. M. xanthus cells direct their motility by reversing their direction of movement through a mechanism involving the redirection of the motility apparatus to the opposite cell pole. The reversal frequency of moving M. xanthus cells is controlled by modular and interconnected protein networks linking the chemosensory‐like frizzy (Frz) pathway – that transmits environmental signals – to the downstream Ras‐like Mgl polarity control system – that comprises the Ras‐like MglA GTPase protein and its regulators. Here, we discuss how variations in the GTPase interactome landscape underlie single‐cell decisions and consequently, multicellular patterns. [ABSTRACT FROM AUTHOR]

Small GTPases act as molecular switches and control numerous cellular processes by their binding and hydrolysis of guanosine triphosphate (GTP). The activity of small GTPases is coordinated by guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs). Recent structural and functional studies have characterized a subset of GAPs whose catalytic units consist of longin domains. Longin domain containing GAPs regulate small GTPases that facilitate nutrient signalling, autophagy, vesicular trafficking and lysosome homeostasis. All known examples in this GAP family function as part of larger multiprotein complexes. The three characterized mammalian protein complexes in this class are FLCN:FNIP, GATOR1 and C9orf72:SMCR8. Each complex carries out a unique cellular function by regulating distinct small GTPases. In this article, we explore the roles of longin domain GAPs in nutrient sensing, membrane dynamic, vesicular trafficking and disease. Through a structural lens, we examine the mechanism of each longin domain GAP and highlight potential therapeutic applications. [ABSTRACT FROM AUTHOR]