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Polaritonic states, which are formed by resonances between a molecular excitation and the photonic mode of a cavity, have a number of useful properties that offer new routes to control molecular photochemistry using electric fields. To provide a theoretical description of how polaritonic states affect the real-time electron dynamics in molecules, a new method is described where the effects of strong light–molecule coupling are implemented using real-time electronic structure theory. The coupling between the molecular electronic states and the cavity is described by the Pauli–Fierz Hamiltonian, and transitions between polaritonic states are induced via an external time-dependent electric field using time-dependent configuration interaction (TDCI) theory, producing quantum electrodynamics TDCI (QED-TDCI). This method is used to study laser-induced ultrafast charge transfer and dipole-switching dynamics of the LiCN molecule inside a cavity. The increase in cavity coupling strength is found to have a significant impact on the energies and transition dipole moments of the molecule–cavity system. The convergence of the polaritonic state energies as a function of the number of included electronic and photonic basis states is discussed. [ABSTRACT FROM AUTHOR]

Collective cell migration (CCM) is involved in multiple biological processes, including embryonic morphogenesis, angiogenesis, and cancer invasion. However, the molecular mechanisms underlying CCM, especially leader cell formation, are poorly understood. Here, we show that a signaling pathway regulating angiomotin (AMOT) cleavage plays a role in CCM, using mammalian epithelial cells and mouse models. In a confluent epithelial monolayer, full-length AMOT localizes at cell-cell junctions and limits cell motility. After cleavage, the C-terminal fragment of AMOT (AMOT-CT) translocates to the cell-matrix interface to promote the maturation of focal adhesions (FAs), generate traction force, and induce leader cell formation. Meanwhile, decreased full-length AMOT at cell-cell junctions leads to tissue fluidization and coherent migration of cell collectives. Hence, the cleavage of AMOT serves as a molecular switch to generate polarized contraction, promoting leader cell formation and CCM. [Display omitted] • The AMOT cleavage signaling pathway is indispensable for collective cell migration • Cleavage product AMOT-CT induces focal adhesion maturation and leader cell formation • AMOT cleavage leads to cell monolayer fluidization and collective migration • AMOT-CT expression promotes cancer cell invasion and metastasis Wang et al. demonstrate that the cleavage of AMOT is essential for collective cell migration (CCM) and tumor metastasis. The cleavage of AMOT results in its spatial redistribution from apical junctions to focal adhesions (FAs), promoting leader cell formation, cell fluidization, and coherent cell migration. [ABSTRACT FROM AUTHOR]

Heterotrimeric G-proteins, comprising Gα, Gβ, and Gγ subunits, act as crucial molecular switches for signaling transduction in all eukaryotic organisms. Through precise modulation of specific receptors or effectors coupled with heterotrimeric G-proteins in signaling cascades, plants have the capability to activate or suppress unique signaling pathways necessary for plant growth, development, and stress responses. This review provides an overview of the heterotrimeric G-proteins signaling pathway obtained to date, and highlights novel areas for future exploration and agricultural application based on the emerging significance and potential of heterotrimeric G proteins in regulating plant development and responses to abiotic stress. [ABSTRACT FROM AUTHOR]

A pyrido‐pyrimidinone heterocycle derived pH‐activated, hydrazone based molecular switch and its switching mechanism are reported here. The introduction of a new conjugated π electronic framework (enone part in the molecule) allowed the system to undergo hydrazone‐azo tautomerization, followed by E‐Z isomerization through rotation around the partial C−N single bond. Under acidic pH, protonation took place selectively on pyrimidinone nitrogen, and that turned the molecule to the corresponding ZH+ configuration. On the other hand, addition of triethylamine in the same solution reverted the molecule back to its original E‐configuration. Extensive proton‐NMR, and detailed X‐ray crystallography coupled with UV‐vis spectroscopy were carried out to establish the switching phenomena. Theoretical DFT calculations leading to free energy diagrams, transition states, and intermediates shed light on the mechanism behind the switching phenomenon. [ABSTRACT FROM AUTHOR]

Filopodia, microspikes and cytonemes are implicated in sensing the environment and in dissemination of morphogens, organelles and pathogens across tissues. Their major structural component is parallel bundles of actin filaments that assemble from the cell membrane. Whilst the length of filopodia is central to their function, it is not known how their lengths are determined by actin bundle dynamics. Here, we identified a set of monoclonal antibodies that lengthen filopodia-like structures formed in a cell-free reconstitution system, and used them to uncover a key molecular switch governing length regulation. Using immunolabelling, enzyme-linked immunosorbent assays, immunoprecipitation and immunoblock experiments, we identified four antibodies that lengthen actin bundles by selectively binding the open DNase 1-binding loop (D-loop) of actin filaments. The antibodies inhibit actin disassembly and their effects can be alleviated by providing additional actin or cofilin. This work indicates that maintaining an open state of the actin filament D-loop is a mechanism of generating long filopodia-like actin bundles. [ABSTRACT FROM AUTHOR]

Orphan nuclear estrogen‐related receptor γ (ERRγ) has been recognized as a potential therapeutic target for cancer, inflammation and metabolic disorder. The ERRγ contains a regulatory AF2 helical tail linked C‐terminally to its ligand‐binding domain (LBD), which is a self‐binding peptide (SBP) and serves as molecular switch to dynamically regulate the receptor alternation between active and inactive states by binding to and unbinding from the AF2‐binding site on ERRγ LBD surface, respectively. Traditional ERRγ modulators are all small‐molecule chemical ligands that can be classified into agonists and inverse agonists in terms of their action mechanism; the agonists stabilize the AF2 in ABS site with an agonist conformation, while the inverse agonists lock the AF2 out of the site to largely abolish ERRγ transcriptional activity. Here, a class of ERRγ peptidic antagonists was described to compete with native AF2 for the ABS site, thus blocking the active state of AF2 binding to ERRγ LBD domain. Self‐inhibitory peptide was derived from the SBP‐covering AF2 region and we expected it can rebind potently to the ABS site by reducing its intrinsic disorder and entropy cost upon the rebinding. Hydrocarbon stapling was employed to do so, which employed an all‐hydrocarbon bridge across the [i, i + 4]‐anchor residue pair in the N‐terminal, middle or C‐terminal region of the self‐inhibitory peptide. As might be expected, it is revealed that the stapled peptides are good binders of ERRγ LBD domain and can effectively compete with the native AF2 helical tail for ERRγ ABS site, which exhibit a basically similar binding mode with AF2 to the site and form diverse noncovalent interactions with the site, thus conferring stability and specificity to the domain–peptide complexes. [ABSTRACT FROM AUTHOR]

Acute liver failure (ALF) is a hepatology emergency with rapid hepatic destruction, multiple organ failures, and high mortality. Despite decades of research, established ALF has minimal therapeutic options. Here, we report that the small bioactive compound SCM-198 increases the survival of male ALF mice to 100%, even administered 24 hours after ALF establishment. We identify adiponectin receptor 2 (AdipoR2) as a selective target of SCM-198, with the AdipoR2 R335 residue being critical for the binding and signaling of SCM-198-AdipoR2 and AdipoR2 Y274 residue serving as a molecular switch for Ca2+ influx. SCM-198-AdipoR2 binding causes Ca2+ influx and elevates the phosphorylation levels of CaMKII and NOS3 in the AdipoR2-CaM-CaMKII-NOS3 complex identified in this study, rapidly inducing nitric oxide production for liver protection in murine ALF. SCM-198 also protects human ESC-derived liver organoids from APAP/TAA injuries. Thus, selectively targeting the AdipoR2-CaM-CaMKII-NOS3 axis by SCM-198 is a rapid-acting therapeutic strategy for advanced ALF. Late-stage acute liver failure (ALF) has limited therapies. The authors show that the bioactive compound SCM-198 extends the ALF treatment window from 3 to 24 hours in mice by selectively targeting the identified AdipoR2-CaM-CaMKII-NOS3-NO axis. [ABSTRACT FROM AUTHOR]

The phenomenon which is called spin crossover is known to occur in some coordination compounds with an octahedral ligand field and electron configurations from 3d4 to 3d7. Thereby, a reversible transition between spin states (high spin and low spin state) is possible, through several external stimuli. Iron(II) triazole complexes exhibit this phenomenon at a wide range of temperatures depending on the ligands and anions used. For this reason, they are often considered for several possible practical applications. It is also possible to combine ligands or anions to modify the transition temperature. The latter of which was rarely discussed in the past. In this study we synthesized a series of iron(II)‐4‐Aminotriazole complexes, with different ratios of chloride‐ and tetrafluoroborate‐anions, of the formula [Fe(Atrz)3]Cl2−X(BF4)X. We show that the combination of these anions leads to transition temperatures between those of their corresponding pure anion complexes. We furthermore present that a simple modification of the synthesis leads to a possible easy way of fine‐tuning transitions temperatures. [ABSTRACT FROM AUTHOR]

The development of molecular switches with tunable properties has garnered considerable interest over several decades. A novel spin‐crossover (SCO) material based on iron(II) complexes incorporating 4‐acetylpyridine (4‐acpy) and [Hg(SCN)4]2− anions was synthesized and formulated as [Fe(4‐acpy)2][Hg(μ‐SCN)4] (1). Compound 1 is crystallized in a three‐dimensional network in the non‐centrosymmetric orthorhombic space group Pna21 with two octahedral [Fe(4‐acpy)2(NCS)4] entities featuring two distinct Fe centers (Fe1 and Fe2). Crystallographic, magnetic, and Mössbauer measurements reveal an incomplete SCO exclusively at Fe2, with transition temperature T1/2≈102 K. Photomagnetic studies conducted at 10 K with lasers ranging from 405 to 1310 nm evidence light‐induced excited spin‐state trapping (LIESST) and reverse‐LIESST effects, with a unique near‐infrared‐responsive LIESST phenomenon at 1064 and 1310 nm. Advanced photocrystallographic studies at 40 K provide precise structural evidence for these metastable states. The optical and vibrational properties consistently corroborate with magnetic and photomagnetic studies. Additionally, temperature‐ and light‐dependent terahertz (THz) absorptions are associated with phonon vibrations around Fe2 centers, through SCO behavior, as supported by ab initio calculation. The Fe(II)−Hg(II) systems can be promising benchmarks for exploring synergistic switching effects in structural, magnetic, and spectroscopic properties. [ABSTRACT FROM AUTHOR]

The mobility of proteins in the bilayer membrane is affected by (local) changes in lipid environment, which is important to their biological functioning. Artificial molecular systems that—to some extent—imitate tasks of membrane‐embedded proteins are increasingly developed, however, they are usually controlled through responsive units in their core structure. Here we present an alternative approach based on an amphiphilic stiff‐stilbene derivative that enables control of membrane fluidity by light. The fluidity increase upon E‐to‐Z isomerization is shown to enhance the activity of known synthetic anion transporters as a result of a higher mobility. The photoisomerization process is studied by UV/Vis and 1H NMR spectroscopy in solution and in POPC vesicles, where the light‐induced changes in fluidity and hence, activity of anion transporters, are monitored by fluorescence spectroscopy. Dynamic light‐scattering (DLS) and cryo‐EM studies show that vesicle integrity is not impaired by photoswitching. Our work introduces a versatile approach to control solute transport by carrier molecules. Moreover, the photocontrol over membrane fluidity and, with that, mobility could eventually be used for directed motion, which we expect to be key in achieving active transport in the future. [ABSTRACT FROM AUTHOR]

In this study, a novel multi‐stimulus responsive RGB fluorescent organic molecule, RTPE‐NH2, was designed and synthesized based on the combination of aggregation‐induced emission tetraphenylethylene (TPE) luminophore and acid‐responsive fluorescent molecular switch Rhodamine B. RTPE‐NH2 exhibits aggregation‐induced emission behavior, as well as UV irradiation‐stimulus and acid‐stimulus responsive fluorescence properties. It could emit orange‐red (R), green(G), and blue(B) light in both solution and PMMA film under 365 nm excitation. The dark through‐bond energy transfer (DTBET) mechanism was proposed and supported by control experiments and TD‐DFT calculations. The synthesis and application of RTPE‐NH2 could accelerate the development of organic smart materials with high sensitivity and excellent optical properties. [ABSTRACT FROM AUTHOR]

One key aspect for the development of functional molecular electronic devices is the ability to precisely tune and reversibly switch the conductance of individual molecules in electrode‐molecule‐electrode junctions in response to external stimuli. In this work, we present a new approach to access molecular switches by deliberately controlling the flexibility in the molecular backbone. We here describe two new conductance switches based on bis(triarylamines) that rely on the reversible toggling between two conformers, each associated with vastly different conductances. By molecular design, we were able to realize an on/off ratio Ghigh/Glow of ~103, which is one of the largest values reported to date. Flicker noise analysis and molecular transport calculations indicate that on/off switching relies on a change of the conduction pathway and vast differences in molecule‐electrode coupling. We thereby provide a new scaffold for further development of molecular conductance switches that are both efficient and easily refined. [ABSTRACT FROM AUTHOR]

Long-range proton transfer in several conjugated proton cranes, originating from 7-hydroxy quinoline as a proton transfer platform, has been investigated theoretically by means of DFT and TD-DFT methodology. Major emphasis was given to their applicability to provide clean switching upon irradiation. The border conditions require the existence of a single enol tautomer in the ground state, which under excitation through a series of consecutive exited and ground state intramolecular proton transfer steps is transferred to the keto tautomer. It was shown that the most suitable candidates are based on using iso-quinoline, pyrimidine and 4-nitropyridine as proton crane units. Their suitability is a function of aromaticity changes, the basicity of the nitrogen atom from the proton crane unit and the structural effects originating from their conjugation with 7-hydroxy quinoline. [ABSTRACT FROM AUTHOR]

Molecular aggregation or supramolecular aggregation‐induced emission is one of the research hotspots in chemistry, biology, and materials. Herein, we report negatively charged sulfato‐β‐cyclodextrin (SCD) induced cyanovinylene derivatives (DPy‐6C) directional aggregation to form regular nanorods (DPy‐6C@SCD) through supramolecular multivalent interactions, not only achieves ultraviolet‐visible absorption redshifted from 453 to 521 nm but also displays near‐infrared (NIR) aggregation‐induced emission with a large spectral redshift of 135 nm. The DPy‐6C monomer presents random nanosheets with weak fluorescence but obtains regular aggregates after assembly with SCD through electrostatic interactions. In the presence of H+, the DPy‐6C@SCD can further aggregate into elliptical nanosheets without fluorescence changes due to the protonation of secondary amines. In contrast, the morphology of DPy‐6C@SCD becomes flexible and sticks together upon the addition of OH− with an emission blue shift of 72 nm and a 90‐fold intensity increase because of disrupting the stacking mode of aggregates, thereby achieving acid‐base regulated reversible fluorescence behaviors that cannot be realized by DPy‐6C monomer. The DPy‐6C@SCD can efficiently select the detection of volatile organic amines both in liquid and gas phases within 5 s at the nanomolar level. Taking advantage of RGB analysis and calculation formula application, the DPy‐6C@SCD has been successfully used to monitor various organic amines on a smartphone, accompanied by naked‐eye visible photoluminescence. Therefore, the present research provides an efficient directional aggregation method through supramolecular multivalent interactions, which not only realizes topological morphology transformation but also achieves reversible NIR luminescent molecular switch and high sensitivity organic amines fluorescent sensing devices. [ABSTRACT FROM AUTHOR]

Allergen-specific immunotherapy (AIT) induces immune tolerance, showing the highest success rate (>95%) for insect venom while a much lower chance for pollen allergy. However, the molecular switches leading to successful durable tolerance restoration remain elusive. The primary outcome of this observational study is the comprehensive immunological cellular characterization during the AIT initiation phase, whereas the secondary outcomes are the serological and Th2-cell-type-specific transcriptomic analyses. Here we apply a multilayer-omics approach to reveal dynamic peripheral immune landscapes during the AIT-initiation phase in venom allergy patients (VAP) versus pollen-allergic and healthy controls. Already at baseline, VAP exhibit altered abundances of several cell types, including classical monocytes (cMono), CD4+ hybrid type 1-type 17 cells (Th1-Th17 or Th1/17) and CD8+ counterparts (Tc1-Tc17 or Tc1/17). At 8-24 h following AIT launch in VAP, we identify a uniform AIT-elicited pulse of late-transitional/IL-10-producing B cells, IL-6 signaling within Th2 cells and non-inflammatory serum-IL-6 levels. Sequential induction of activation and survival protein markers also immediately occur. A disequilibrium between serum IL-6 and cMono in VAP baseline is restored at day seven following AIT launch. Our longitudinal analysis discovers molecular switches during initiation-phase insect-venom AIT that secure long-term outcomes. Trial number: NCT02931955. Allergen specific immunotherapy (AIT) is both, safe and effective in reducing systemic symptoms of venom allergy in individuals. Here the authors examine the underlying immune cell changes after venom specific AIT in early time points after therapy initiation showing indicative changes in specific immune cell populations. [ABSTRACT FROM AUTHOR]

Although the intrinsic electronic properties of polyoxometalates (POMs) can be greatly influenced by modifying them with organic substituents, their resistive switching behavior on surfaces dependent on the organic substituents remains largely unexplored. In this work, we assessed the importance of electron‐withdrawing and electron‐donating ligand substituents on the material properties of a series of hybrid Lindqvist‐type hexavanadates TBA2[V6O13((OCH2)3CCH2OH)2] (TBA2V6‐OH), TBA2[V6O13((OCH2)3CMe)2] (TBA2V6‐Me), TBA2[V6O13((OCH2)3CNHCOCH2Cl)2] (TBA2V6‐Cl), and TBA2[V6O13((OCH2)3CNHCOCH2‐OOCC10H15)2] (TBA2V6‐Ad) as potential resistive random‐access memory (ReRAM) components. Compared to their redox behavior in solution, changing the ligand substituents on surfaces results in no significant effect on the potential and, thus, no effect on the resistance steps in the current‐voltage profiles. However, while the current‐voltage characteristics do not change, the peripheral metal‐free substituents in the trisalkoxide framework of Lindqvist‐type hexavanadate molecules influence the adsorption and switching stability of these POMs on gold. This work highlights the noticeable differences between hexavanadate's redox properties in solution (which follow the trend observed in the gas phase) and hexavanadate's resistive switching properties on conducting surfaces. Importantly, their multi‐state switching behavior is not significantly altered by the different type of substituent at the periphery of the trisalkoxo ligands. [ABSTRACT FROM AUTHOR]

The lateral wall of the mouse subventricular zone harbors neural stem cells (NSC, B cells) which generate proliferating transient-amplifying progenitors (TAP, C cells) that ultimately give rise to neuroblasts (NB, A cells). Molecular profiling at the single-cell level struggles to distinguish these different cell types. Here, we combined transcriptome analyses of FACS-sorted cells and single-cell RNAseq to demonstrate the existence of an abundant, clonogenic and multipotent population of immature neuroblasts (iNB cells) at the transition between TAP and migrating NB (mNB). iNB are reversibly engaged in neuronal differentiation. Indeed, they keep molecular features of both undifferentiated progenitors, plasticity and unexpected regenerative properties. Strikingly, they undergo important progressive molecular switches, including changes in the expression of splicing regulators leading to their differentiation in mNB subdividing them into two subtypes, iNB1 and iNB2. Due to their plastic properties, iNB could represent a new target for regenerative therapy of brain damage. [ABSTRACT FROM AUTHOR]

For over 60 years, cyclophanes have inspired the design of novel molecular architectures of different sizes and geometries, unleashing significant advances in supramolecular chemistry and also in biomedical and materials sciences. Reported cyclophanes are countless and more complex molecular structures continue to be spawned. Herein, the study classifies cyclophanes into different families to emphasize and feature their structure‐properties relationships. While neutral cyclophanes have attracted more attention owing to their solid‐state physical properties, water‐soluble anionic cyclophanes have been explored predominantly in drug delivery. In the broad family of cationic cyclophanes, viologen‐based cyclophanes (VBCs) are widely investigated for designing molecular interlocked molecules (MIMs), molecular switches, and machines owing to their unique electrochemical properties. Despite decades of ground‐breaking research in academia, controlling the cationic cyclophanes and MIMs solid‐state structures is still a limiting factor when it comes to introducing them into functional materials. Here, the study draws attention to some current challenges in cyclophane chemistry from a materials sciences perspective and highlights processes that, if overcome, would lead to cyclophanes producing transformational materials. It is envisioned that zwitterionic VBCs can have a seminal impact on host–guest chemistry, MIMs, molecular machines, and supramolecular tessellations, which can pave the way toward next‐generation technologies. [ABSTRACT FROM AUTHOR]

This review highlights important research on anion coordination chemistry for materials applications over the last decade. This field has numerous applications in various areas, such as the environment, industry, and medicine. Despite its enormous potential, real‐world applicability is still pending. However, there has been a new trajectory in the field recently, with rapid advancement in designing sophisticated molecular systems for various materials applications. To keep track of this dynamic advancement, we have discussed some outstanding research work with enormous potential for materials applications soon. [ABSTRACT FROM AUTHOR]

This paper reports the development of a highly crosslinked hyper-branched polyglycerol (HPG) polymer bound to elastin-like proteins (ELPs) to create a membrane that undergoes a distinct closed-to-open permeation transition at 32 °C. The crosslinked HPG forms a robust, mesoporous structure (150–300 nm pores), suitable for selective filtration. The membranes were characterized by FTIR, UV–visible spectroscopy, SEM, and AFM, revealing their structural and morphological properties. Incorporating a synthetic polypeptide introduced thermo-responsive behavior, with the membrane transitioning from impermeable to permeable above the lower critical solution temperature (LCST) of 32 °C. Permeation studies using crystal violet (CV) demonstrated selective transport, where CV permeated only above 32 °C, while water permeated at all temperatures. This hybrid HPG-ELP membrane system, acting as a molecular switch, offers potential for applications in drug delivery, bioseparations, and smart filtration systems, where permeability can be controlled by temperature. [ABSTRACT FROM AUTHOR]

Immune system regulation is a key indicator of the gut microbiota (GM) influencing disease development. The causal role of the GM in Guillain-Barré syndrome (GBS) and whether it can be mediated by immune cells is unknown. Genome-wide association study (GWAS) summary statistics for the GM were obtained from the Dutch Microbiota Project (n = 7,738) and the FINRISK 2002 (FR02) cohort (n = 5,959). Inverse variance weighting method (IVW) were used as the main method to evaluate the causal relationship between GM and GBS. Subsequently, the mediating effects of 731 immune traits were evaluated. Additionally, we also executed the Bayesian Weighting algorithm for verification. Mendelian randomization (MR) analysis determined the protective effect of the pyrimidine deoxyribonucleoside degradation superpathway on GBS (IVW: P = 0.0019, OR = 0.4508). It is worth noting that in the causal effects of pyrimidine deoxyribonucleoside degradation superpathway on GBS, the mediated proportions of herpesvirus entry mediator (HVEM) (HVEM on CM CD4 + , HVEM on naive CD4 + , HVEM on CD45RA − CD4 + , HVEM on CM CD8br) in the T cell maturation stage on GBS were -0.0398, -0.0452, -0.0414, -0.0425, accounting for 5.00%, 5.67%, 5.19% and 5.34% of the total effect. 11 types of intestinal bacteria might be involved in the pyrimidine deoxyriboside degradation superpathway, including Staphylococcus A fleurettii, AR31,CAG-274 sp000432155, Photobacterium, Acetobacteraceae, Dysgonomonadaceae, NK4A144,Leptospirae, CAG-81 sp000435795, Leptospirales and CAG-873 sp001701165. This study suggests that there is a causal relationship between pyrimidine deoxyribonucleoside degradation superpathway and GBS, which may be mediated by HVEM on CD4 + and CD8 + T cells. As a bidirectional molecular switch, HVEM plays an important role in T cell regulation. 11 intestinal flora were found to be involved in pyrimidine deoxyribonucleoside degradation superpathway, and their changes may be related to the occurrence of GBS. However, extensive research is still warranted before microbiome sequencing can be used for prevention and targeted treatment of GBS. [ABSTRACT FROM AUTHOR]

Introduction: Cancer is still a major challenge of human health. The abnormality of intracellular cancer-related signal pathways is an important mechanism for the occurrence of cancer. Methods: We used a molecular-senor to act on the endogenous signal molecules within the cell to redirect the abnormal signal flows in the cell to treat cancer. Based on CRISPR-dCas12f procedures, we combined aptamers and ribozymes to construct riboswitches, which served as molecular switches to reprogram sgRNAs, so that CRISPR-dCas12f redirected the intracellular anti-cancer signal flows after sensing specific input signal molecules. In addition, the activated molecular sensors and the inhibitory molecular sensors were constructed by combining transcription factors (VP64) and transcription inhibitors (KRAB) to specifically activate and inhibit target genes of interest. Results: Our experimental results showed that the molecular sensors that we designed and constructed specifically sensed the endogenous signal molecules and then redirect the cancer related signal networks of cancer cells. In addition, corresponding logic gates were constructed to distinguish cancer cells from normal cells and redirect anticancer signal flows to trigger specific cancer immunotherapy. Conclusion: The constructed molecular sensors constructed specifically recognized the signal molecules within the cell and redirected the endogenous signal pathway to reprogram the fate of cancer cells. [ABSTRACT FROM AUTHOR]

Oligo‐adenine (polyA) is primarily known for its critical role in mRNA stability, translational status, and gene regulation. Beyond its biological functions, extensive research has unveiled the diverse applications of polyA. In response to environmental stimuli, single polyA strands undergo distinctive structural transitions into diverse secondary configurations, which are reversible upon the introduction of appropriate counter‐triggers. In this review, we systematically summarize recent advances of noncanonical structures derived from polyA, including A‐motif duplex, A‐cyanuric acid triplex, A‐coralyne‐A duplex, and T ⋅ A‐T triplex. The structural characteristics and mechanisms underlying these conformations under specific external stimuli are addressed, followed by examples of their applications in stimuli‐responsive DNA hydrogels, supramolecular fibre assembly, molecular electronics and switches, biosensing and bioengineering, payloads encapsulation and release, and others. A detailed comparison of these polyA‐derived noncanonical structures is provided, highlighting their distinctive features. Furthermore, by integrating their stimuli‐responsiveness and conformational characteristics, advanced material development, such as pH‐cascaded DNA hydrogels and supramolecular fibres exhibiting dynamic structural transitions adapting environmental cues, are introduced. An outlook for future developments is also discussed. These polyA derived, stimuli‐responsive, noncanonical structures enrich the arsenal of DNA "toolbox", offering dynamic DNA frameworks for diverse future applications. [ABSTRACT FROM AUTHOR]

Temperature is an omnipresent factor impacting on many aspects of life. In bacteria and ectothermic eukaryotes, various thermosensors and temperature-controlled switches have been described, ranging from RNA thermometers controlling the heat shock response in prokaryotes to temperature-dependent sex determination in reptiles, likely controlled through protein phosphorylation. However, the impact of subtle changes of human core body temperature are only beginning to be acknowledged. In this review, we will discuss thermosensing mechanisms and their functional implications with a focus on mammalian cells, also in the context of disease conditions. We will point out open questions and possible future directions for this emerging research field, which, in addition to molecularmechanistic insights, holds the potential for the development of new therapeutic approaches. [ABSTRACT FROM AUTHOR]

Designing proteins with tunable activities from easily accessible external cues remains a biotechnological challenge. Here, we set out to create a small antibody-binding domain equipped with a molecular switch inspired by the allosteric response to calcium seen in naturally derived proteins like calmodulin. We have focused on one of the three domains of Protein G that show inherent affinity to antibodies. By combining a semi-rational protein design with directed evolution, we engineered novel variants containing a calciumbinding loop rendering the inherent antibody affinity calcium-dependent. The evolved variants resulted from a designed selection strategy subjecting them to negative and positive selection pressures focused on conditional antibody binding. Hence, these variants contains molecular "on/off" switches, controlling the target affinity towards antibody fragments simply by the presence or absence of calcium. From NMR spectroscopy we found that the molecular mechanism underlying the evolved switching behavior was a coupled calcium-binding and folding event where the target binding surface was intact and functional only in the presence of bound calcium. Notably, it was observed that the response to the employed selection pressures gave rise to the evolution of a cooperative folding mechanism. This observation illustrates why the cooperative folding reaction is an effective solution seen repeatedly in the natural evolution of fine-tuned macromolecular recognition. Engineering binding moieties to confer conditional target interaction has great potential due to the exquisite interaction control that is tunable to application requirements. Improved understanding of the molecular mechanisms behind regulated interactions is crucial to unlock how to engineer switchable proteins useful in a variety of biotechnological applications. [ABSTRACT FROM AUTHOR]

The study investigates the impact of thionation on N,N'‐di(dodecyl)‐4,5,8,9‐naphthalene diimide (NDI) through computational methods such as density functional theory (DFT/TD‐DFT), quantum theory of atoms in molecules (QTAIM), and Landauer theory (LT). Thionation, involving the replacement of diamide oxygens with sulfurs in NDI, significantly enhances quantum‐electronic/thermoelectric properties. Computational analyzes of energy of frontier orbitals HOMO/LUMO, dipole moment, polarizability, first superpolarizability, UV spectrum, and cohesive energy show the superior performance of the thione structure (M2) compared to the pristine structure (M1). Thionation decreased the energy gap from 01.3 eV (in M1 structure) to 1.87 eV (in M2 structure). The absorption wavelength in the pristine structure (M1) is calculated to be 507 nm, which increased to 1067 nm after thionation (M2). Cohesive energy values for each of M1 and M2 structures are calculated as 12.76 and 12.89 Kcal mol−1, respectively, which indicates the improvement of stability after thionation. After connecting M1 and M2 to gold electrodes (Au‐M1‐Au and Au‐M2‐Au) and applying electric fields, the Au‐M2‐Au structure shows a lower energy gap, lower thermoelectric activity and higher conductivity at field intensities with higher than 140 × 10−4 (a.u.), indicating its use as a field‐effect molecular device (such as molecular wire or molecular switch). [ABSTRACT FROM AUTHOR]

G protein-coupled receptors (GPCRs) are sensors for the G protein complex to sense changes in environmental factors and molecular switches for G protein complex signal transduction. In this study, the homologous gene of GPCR-like proteins was identified from maize and named as ZmCOLD1. Subcellular analysis showed that the ZmCOLD1 protein is localized to the cell membrane and endoplasmic reticulum. A CRISPR/Cas9 knock-out line of ZmCOLD1 was further created and its plant height was significantly lower than the wild-type maize at both the seedling and adult stages. Histological analysis showed that the increased cell number but significantly smaller cell size may result in dwarfing of zmcold1, indicating that the ZmCOLD1 gene could regulate plant height development by affecting the cell division process. Additionally, ZmCOLD1 was verified to interact with the maize Gα subunit, ZmCT2, though the central hydrophilic loop domain by in vivo and in vitro methods. Abscisic acid (ABA) sensitivity analysis by seed germination assays exhibited that zmcold1 were hypersensitive to ABA, indicating its important roles in ABA signaling. Finally, transcriptome analysis was performed to investigate the transcriptional change in zmcold1 mutant. Overall, ZmCOLD1 functions as a GPCR-like protein and an important regulator to plant height. [ABSTRACT FROM AUTHOR]

Multifunctional molecular switches have attracted much attention because of their unique stimulus response behavior and advanced applications. However, precise regulation of the structure for property enrichment is still a great challenge. Herein, the first case of a single‐molecule switch BN‐S with multiple structurally tunable and full‐color fluorescent properties is reported. Interestingly, BN‐S exhibits a butterfly‐like "metamorphosis" crystal growth process accompanied by full‐color fluorescence emission (including white light, CIE = 0.33, 0.33; 456 nm → 610 nm). It is shown that this is related to the reversible B←N bonding and the tunability of the spatial structure of the BN‐S. Thus, BN‐S exhibits superior multicolor tunability in different states (solid, liquid, and film), and its applications in white‐light optical light emitting diodes (OLEDs) and multicolor fluorescent inks also show great promise. This will provide a new strategy for designing and synthesizing the development of multifunctional molecular switching materials and enriching the variety of organoboron luminescent materials. [ABSTRACT FROM AUTHOR]

The phosphoproteome is vast and intricate, with many aspects of its extent and site-specific functional roles still largely unexplored. While traditional studies have primarily focused on Ser/Thr and Tyr phosphorylation, new methodologies are emerging to study non-canonical phosphorylation events. Protein phosphatases play critical roles in cellular signaling, with recent studies highlighting their complexity and involvement in various biological processes. A significant portion of the kinome, referred to as the 'dark' kinome, remains understudied and holds great potential for novel discoveries. Pseudokinases and pseudophosphatases, despite lacking catalytic activity, play crucial roles in cell signaling. Recent advances in experimental and computational analyses have improved the understanding of kinase–substrate and phosphatase–substrate interactions. Protein phosphorylation is a crucial regulatory mechanism in cell signaling, acting as a molecular switch that modulates protein function. Catalyzed by protein kinases and reversed by phosphoprotein phosphatases, it is essential in both normal physiological and pathological states. Recent advances have uncovered a vast and intricate landscape of protein phosphorylation that include histidine phosphorylation and more unconventional events, such as pyrophosphorylation and polyphosphorylation. Many questions remain about the true size of the phosphoproteome and, more importantly, its site-specific functional relevance. The involvement of unconventional actors such as pseudokinases and pseudophosphatases adds further complexity to be resolved. This review explores recent discoveries and ongoing challenges, highlighting the need for continued research to fully elucidate the roles and regulation of protein phosphorylation. [ABSTRACT FROM AUTHOR]

Long-range proton transfer in several conjugated proton cranes, originating from 7-hydroxy quinoline as a proton transfer platform, has been investigated theoretically by means of DFT and TD-DFT methodology. Major emphasis was given to their applicability to provide clean switching upon irradiation. The border conditions require the existence of a single enol tautomer in the ground state, which under excitation through a series of consecutive exited and ground state intramolecular proton transfer steps is transferred to the keto tautomer. It was shown that the most suitable candidates are based on using iso-quinoline, pyrimidine and 4-nitropyridine as proton crane units. Their suitability is a function of aromaticity changes, the basicity of the nitrogen atom from the proton crane unit and the structural effects originating from their conjugation with 7-hydroxy quinoline.

[Display omitted] Strong molecule-electrode coupling originating from orbit hybridization between gold and the delocalized molecular wires in single-molecule junctions facilitates facile transport towards smart molecular devices. In this paper, we report ultra-highly conductive single-molecule circuits based on highly delocalized nickel bis(dithiolene) (NiS 4) molecular junctions using scanning tunneling microscope break junction technique. Single-molecule charge transport measurement of both NiS 4 reveals they exhibits high conductance of 10−1.49 G 0 and 10−1.51 G 0 , respectively. Moreover, under intervention of high bias voltage the molecular conductance could be further improved to approximately 10−1.00 G 0 , the highest value reported to date with similar molecular lengths. Theoretical calculations suggest that the strong hybridization of the π-channels and the gold electrodes in both junctions exists and it further extends from molecule-electrode interfaces to metal electrodes as visualized by the isosurface plots of the transmitting eigenstate, which lead to not only a distinct energy shift of the dominated LUMO peaks toward Fermi level, but also broad peaks in the LUMO resonance in the transmission functions. In addition, the both molecular junctions show remarkable photoconductance of approximately 10−1.00 G 0 under resonant light excitation, due to possible exciton binding in these junctions. Interestingly, the conductance switching of both molecular junctions under optoelectronic modulation is highly reversible, forming a multi-stimulus responsive molecular switch. This work not only provides a building block for fabricating highly conducting molecular wires with strong molecule-electrode coupling, but also lays a foundation for designing optoelectronic modulated functional molecule-scale devices. [ABSTRACT FROM AUTHOR]

Multifunctional magnetic materials have broad application prospects in molecular switches and information storage. In this study, four mononuclear Fe(II) complexes are synthesized using a series of pyrenylhydrazone ligands HL1–4. Two deprotonated ligands are coordinated to the iron(II) ions in an enolic form, leading to neutral complexes FeII(Lx)2·xsol with a FeIIN4O2 octahedral coordination environment. Magnetic measurements suggest that complex Fe(L1)2·2ACE (1·2ACE, ACE = acetone) is mainly low spin below 300 K and complex Fe(L3)2·ACE (3·ACE) is high spin, whereas complexes Fe(L2)2 (2) and Fe(L4)2·6H2O (4·6H2O) exhibit gradual spin crossover behavior. The spin states of complexes 1–4 are confirmed by single-crystal X-ray diffraction analysis. The substituent effect on the magnetic properties of the complexes is significant in this system. Temperature-dependent fluorescence emission spectra show the coexistence but no coupling effect of spin crossover and fluorescence for complexes 2 and 4·6H2O. [ABSTRACT FROM AUTHOR]

Synthetic molecular photoswitches have taken center stage as high‐precision tools to introduce light‐responsiveness at the smallest scales. Today they are found in all areas of applied chemistry, covering materials research, chemical biology, catalysis, or nanotechnology. For a next step of applicability truly orthogonal photoswitching is highly desirable but to date such independent addressability of different photoswitches remains highly challenging. Herein we present the first example of all‐visible, all‐light responsive, and path‐ independent orthogonal photoswitching. By combining two recently developed indigoid photoswitches ‐ peri‐anthracenethioindigo and a rhodanine‐based chromophore ‐ a four‐state system is established and each state can be accessed in high yields completely independently and also with visible light irradiation only. The four states give rise to four different colors, which can be transferred to a solid polymer matrix to yield a versatile multi‐state photochromic material. Further, combination with a fluorescent dye as a third component is possible, demonstrating the applicability of this orthogonal photoswitching system in all‐photonic molecular logic behavior and information processing. [ABSTRACT FROM AUTHOR]

Electron‐rich symmetric pull‐push‐pull molecules can act as efficient two‐photon absorbing units. When these chromophores are bonded directly to photo‐switchable molecules they can function as antenna systems to indirectly induce photochemical transformations in isomerizable groups after energy transfer. Recently, we developed an antenna–molecular switch system based on a pyrrolo–pyrrole two‐photon active chromophore. When this antenna section is functionalized with symmetrically situated azo‐sections as N,N’‐pyrrolic‐substituents, these azo molecular switches can be efficiently transformed from their E to their Z isomers after non‐linear light absorption by the antenna, followed by indirect excitation of the azo‐sections. In this contribution we present a case‐study of one of these systems through femtosecond‐resolved fluorescence to observe the dynamics involved in the excitation and relaxation steps within the antenna section, as well as the energy transfer pathways. By time‐resolving the emission signals we observed that the energy transfer can occur in parallel with the relaxation within the first singlet vibronic states localized at the pyrrolo–pyrrole antenna. In fact, the antenna‐to‐azo section energy transfer shows a biphasic nature. At early times, during the relaxation within the antenna, there is an initial population of azo‐section excited molecules. In addition, after the system has evolved to the fully relaxed S1 state at the antenna section, the energy transfer has components related to thermal fluctuations which increase the couplings with the receiver states at the azo‐switches giving transfer rates of the order of 1010 s−1 at room temperature. The characterization of these relaxation and energy transfer steps, as well as the role of the solvent in these processes, gives insights for the development of future molecules with indirect two‐photon isomerization properties using this kind of pull‐push‐pull two‐photon active antenna. Due to their two‐photon reactive properties, these systems can have applications in schemes where highly localized photo‐isomerization is required. [ABSTRACT FROM AUTHOR]

Rho/Rac of plant (ROP) GTPases are plant-specific proteins that function as molecular switches, activated by guanine nucleotide exchange factors (GEFs) and inactivated by GTPase-activating proteins (GAPs). The bryophyte Marchantia polymorpha contains single copies of ROP (MpROP), GEFs [ROPGEF and SPIKE (SPK)] and GAPs [ROPGAP and ROP ENHANCER (REN)]. MpROP regulates the development of various tissues and organs, such as rhizoids, gemmae and air chambers. The ROPGEF KARAPPO (MpKAR) is essential for gemma initiation, but the functions of other ROP regulatory factors are less understood. This study focused on two GAPs: MpROPGAP and MpREN. Mpren single mutants showed defects in thallus growth, rhizoid tip growth, gemma development, and air-chamber formation, whereas Mpropgap mutants showed no visible abnormalities. However, Mpropgap Mpren double mutants had more severe phenotypes than the Mpren single mutants, suggesting backup roles of MpROPGAP in processes involving MpREN. Overexpression of MpROPGAP and MpREN resulted in similar gametophyte defects, highlighting the importance of MpROP activation/inactivation cycling (or balancing). Thus, MpREN predominantly, and MpROPGAP as a backup, regulate gametophyte development, likely by controlling MpROP activation in M. polymorpha. [ABSTRACT FROM AUTHOR]

The reversible photo-induced conformation transition of a single molecule with a [5]helicene backbone has garnered considerable interest in recent studies. Based on such a switching process, one can build molecular photo-driven switches for potential applications of nanoelectronics. But the achievement of high-performance reversible single-molecule photoswitches is still rare. Here, we theoretically propose a 13,14-dimethylcethrene switch whose photoisomerization between the ring-closed and ring-open forms can be triggered by ultraviolet (UV) and visible light irradiation. The electronic structure transitions and charge transport characteristics, concurrent with the photo-driven electrocyclization of the molecule, are calculated by the non-equilibrium Green's function (NEGF) in combination with density functional theory (DFT). The electrical conductivity bears great diversity between the closed and open configurations, certifying the switching behavior and leading to a maximum on–off ratio of up to 103, which is considerable in organic junctions. Further analysis confirms the evident switching behaviors affected by the molecule–electrode interfaces in molecular junctions. Our findings are helpful for the rational design of organic photoswitches at the single-molecule level based on cethrene and analogous organic molecules. [ABSTRACT FROM AUTHOR]

Background: Normal cells express functional tumor suppressor WW domain-containing oxidoreductase (WWOX), designated WWOXf. UV irradiation induces WWOXf cells to undergo bubbling cell death (BCD) — an event due to the accumulation of nuclear nitric oxide (NO) gas that forcefully pushes the nuclear and cell membranes to form one or two bubbles at room temperature (22 °C) and below. In contrast, when WWOX-deficient or -dysfunctional (WWOXd) cells are exposed to UV and/or cold shock, the cells undergo nuclear pop-out explosion death (POD). We aimed to determine the morphological and biochemical changes in WWOXf cells during BCD versus apoptosis. Methods: WWOXf and WWOXd cells were exposed to UV followed by measuring BCD or POD by time-lapse microscopy and/or time-lapse holographic microscopy at 4, 22, or 37 °C to visualize morphological changes. Live cell stains were used to measure the kinetics of nitric oxide (NO) production and Ca2+ influx. Extent of cell death was measured by uptake of propidium iodide and by internucleosomal DNA fragmentation using agarose gel electrophoresis. Results: WWOXf cells were exposed to UV and then cold shock, or cold shock and then UV, and cultured at 4, 10, and 22 °C, respectively. Initially, UV induced calcium influx and NO production, which led to nuclear bubbling and final death. Cold shock pretreatment completely suppressed UV-mediated bubbling at 37 °C, so the UV/cold shock-treated cells underwent apoptosis. Without cold shock, UV only induced bubbling at all temperatures, whereas the efficiency of bubbling at 37 °C was reduced by greater than 50%. Morphologically, the WWOXf cell height or thickness was significantly increased during cell division or apoptosis, but the event did not occur in BCD. In comparison, when WWOXd cancer cells received UV or UV/cold shock, these cells underwent NO-independent POD. UV/cold shock effectively downregulated the expression of many proteins such as the housekeeping α-tubulin (> 70%) and β-actin (< 50%), and cortactin (> 70%) in WWOXf COS7 cells. UV/cold shock induced relocation of α-tubulin to the nucleus and nuclear bubbles in damaged cells. UV induced co-translocation of the WWOX/TRAF2 complex to the nuclei, in which the prosurvival TRAF2 blocked the proapoptotic WWOX via its zinc finger domain. Without WWOX, TRAF2 did not relocate to the nuclei. Cold shock caused the dissociation of the WWOX/TRAF2 complex in the nucleus needed for BCD. In contrast, the formation of the WWOX/TRAF2 complex, plus p53, was strengthened at 37 °C required for apoptosis. Conclusions: The temperature-sensitive nuclear WWOX/TRAF2 complex acts as a molecular switch, whose dissociation favors BCD at low temperatures, and the association supports apoptosis at 37 °C in UV-treated WWOXf cells. [ABSTRACT FROM AUTHOR]

The evaluation of the Z/E photoisomerization efficiency is an essential task to design photoactive molecular devices. Nevertheless, this photoreactivity can be correctly described only by applying extensive and expensive computational methods. In this study, a predictive tool to screen the photoinduced Z/E isomerization efficiency of molecular switches is presented, based on three key properties: the structure of the ground state minimum, the nature of the electronic transition populating the optically bright state, and the presence of crossings between the optically bright state and the one lower in energy. Our methodology allows evaluating these properties by few and affordable calculations, potentially enabling the screening of large sets of photoswitches. After presenting the formal aspects, the tool is applied to model systems of paradigmatic classes of photoswitches (retinal, green fluorescent protein, hemithioindigo, chiroptical, and stilbene compounds) including derivatives. A comparison with the available experimental data is performed to validate our approach. Cis-trans photoisomerization is a key process for many processes in biology and materials science, but only careful and time-consuming quantum chemistry methods can describe such reaction in detail. Here, a predictive tool is presented requiring few and affordable calculations, evaluating the efficiency of paradigmatic and modified photoswitches. [ABSTRACT FROM AUTHOR]

Many researchers have focused on molecular electronics, and this field can progress faster by applying semiconductors to molecular modeling. In this work, two middle rings of a bipyridine–biborinine molecular diode are rotated from 25∘ to 90∘ such that the current along the molecule is reduced. The current is minimum and almost zero at 90∘, while it is maximum at 25∘. Accordingly, considering these two angles, the molecule can act as a switching device when the two middle rings are rotated. The bipyridine–biborinine molecular diode is modeled considering the effect of rotation by including two resistors in the model. Two parallel diodes are used in this modeling for pyridine and borinine rings. The ideality factors of these diodes are varied based on the electronegativity of pyridine and borinine rings. This model is then applied to consider different molecular logic gates such as NAND, NOR, NOT, OR and AND gates, as well as molecular logic circuits (half adder and full adder), using the unique capabilities of the LTspice software. [ABSTRACT FROM AUTHOR]

Crystallization of organic materials can lead to different assembly structure with different reactivity, but this phenomenon is rarely observed for delocalized hydrocarbon radicals. This report introduces a crystallization‐induced radical–radical coupling reaction, which employs a series of stable nonplanar organic π‐radicals as reactants. Six stable radical congeners are synthesized, resulting in radical–radical coupling at the allenyl radical site during crystallization to produce close‐shell dimers. This coupling reaction is absent in the solution phase, which highlights the importance of preorganization in the lattice. Remarkably, the attempts of cocrystallization of different congeners yielded homocoupling products instead of cross‐coupling products. In specific cases, two distinct polymorphs are observed and their reactivity is different according to the distance of the reaction sites. Theoretical calculations indicate that the transition from a metastable preorganized monomer to a dimer is barrierless and spontaneous. The dimer could regenerate free radicals by heating or photoirradiation in the solution phase. This discovery may lead to controllable molecular switches. [ABSTRACT FROM AUTHOR]

The BCL (B-cell lymphoma) protein family is a diverse group of regulators critically involved in apoptosis, a tightly controlled process crucial for maintaining tissue homeostasis. Dysregulation of apoptosis is a common feature in cancer, emphasizing the need to comprehend the intricate mechanisms underlying the function of the BCL family. This literature review offers a comprehensive exploration of the structural domain organization of the BCL family, shedding light on how these proteins orchestrate apoptosis. The family comprises anti-apoptotic proteins, pro-apoptotic effectors, and BH3(BCL-2 homology 3)-only proteins, each with distinct structural features and functional roles in apoptotic signaling pathways. Anti-apoptotic proteins like BCL-2 serve as guardians against cell death by preserving mitochondrial integrity. Pro-apoptotic effectors, on the other hand, actively promote apoptosis by inducing mitochondrial outer membrane permeabilization. BH3-only proteins act as molecular switches, mediating the delicate balance between proand anti-apoptotic signals. This review delves into the specific role of BCL-2, a prominent family member, in various cancers such as lung, breast, and prostate cancers. Highlighting its significance as a potential therapeutic target, the article underscores the importance of understanding the molecular nuances of BCL-2 in cancer progression. Moreover, recent advancements in BCL-2 inhibitor development are discussed, showcasing their potential as targeted therapies for cancer treatment. These inhibitors represent a promising avenue for personalized cancer therapy, aiming to selectively induce apoptosis in cancer cells while sparing normal cells. The review emphasizes the importance of these inhibitors in addressing the specific challenges posed by BCL-2 dysregulation in diverse cancer types. By elucidating the structural and functional aspects of the BCL protein family, this literature review provides valuable insights into apoptotic signaling pathways. It not only deepens our understanding of the molecular intricacies governing cell death but also presents novel strategies to modulate apoptosis in cancer cells. Ultimately, the article highlights the significance of BCL proteins as promising therapeutic targets and the potential of BCL-2 inhibitors for personalized cancer therapy, paving the way for advancements in cancer treatment. [ABSTRACT FROM AUTHOR]

Summary: At present, many DNA logic circuits have been successfully constructed. However, advanced complex DNA computing tasks with simple structure, fast response, and modularization still remain a huge challenge. In this paper, molecular switch circuits (MSCs) are constructed based on DNA strand displacement to improve above problems. At first, molecular switch is constructed, which is the basic element for building logic circuits. Next, the functions of AND, OR, Fan‐in, and Fan‐out are realized through switches cascading in series or parallel. Furthermore, switch canvas strategy is explored to obtain the shortest reaction path and highest output concentration for circuits. Finally, a novel strategy of integrating computing module using molecular switches is proposed. Here, we construct a half‐adder, half‐subtractor, and a 9‐bit parity checking circuits to verify its feasibility. Compared with the classical monorail and dual‐track logic circuits, the structure scale is reduced by more than two times, and the DNA strands are decreased by more than four times, which effectively reduces the circuit complexity and raises the reaction speed. The above results show that MSC strategy has a great potential to construct large‐scale DNA circuits and provides a development model for the scalability and modularity of biological computing. [ABSTRACT FROM AUTHOR]

Toxin–antitoxin (TA) systems in bacteria are key regulators of the cell cycle and can activate a death response under stress conditions. Like other bacterial elements, TA modules have been widely exploited for biotechnological purposes in diverse applications, such as molecular cloning and anti-cancer therapies. However, their use in plants has been limited, leaving room for the development of new approaches. In this study, we examined two TA systems previously tested in plants, MazEF and YefM-YoeB, and identified interesting differences between them, likely related to their modes of action. We engineered modifications to these specific modules to transform them into molecular switches that can be activated by a protease, inducing necrosis in the plant cells where they are expressed. Finally, we demonstrated the antiviral potential of the modified TA modules by using, as a proof-of-concept, the potyvirus plum pox virus as an activator of the death phenotype. [ABSTRACT FROM AUTHOR]

The incorporation of molecular switches into polymer networks has been a powerful approach for the development of functional polymer materials that display macroscopic actuation and function enabled directly by molecular changes. However, such materials sometimes require harsh conditions to perform their functions, and the design of new molecular photoswitches that can function under physiological conditions is highly needed. Here, we report the design and synthesis of a spiropyridine-based photoswitchable hydrogel that exhibits light-driven actuation at physiological pH. Owing to its high pKa, spiropyridine maintains its ring-open protonated form at neutral pH, and the resulting hydrogel remains in a swollen state. Upon irradiation with visible light, the ring closure of spiropyridine leads to a decrease in the charge and a reduction in the volume of the hydrogel. The contracted gel could spontaneously recover to its expanding state in the dark, and this process is highly dynamic and reversible when the light is switched on and off. Furthermore, the hydrogel shows switchable fluorescence in response to visible light. Bending deformation is observed in the hydrogel thin films upon irradiation from one side. Importantly, the independence of this spiropyridine hydrogel from the acidic environment makes it biotolerant and shows excellent biocompatibility. This biocompatible spiropyridine hydrogel might have important biorelated applications in the future. [ABSTRACT FROM AUTHOR]

Biradicals are important intermediates in the formation and breaking of a chemical bond. Their use as molecular switches is of particular interest. Much less is known about tetraradicals, which can, for example, consist of two biradical(oid) units. Here we report the synthesis of the first persistent phosphorus‐centred tetraradical bound to a transition metal fragment. Starting from a zirconocene complex, rac‐(ebthi)ZrCl2 (rac‐(ebthi)=1,2‐ethylene‐1,10‐bis(η5‐tetrahydroindenyl), two cyclo‐1,3‐diphospha‐pentane‐1,3‐diyls were successfully introduced, which finally led to the isolation of a deep green zirconcene‐bridged bis(biradicaloid) complex (5) that can act as a double molecular switch. Under the influence of light (570 nm), this tetraradical forms a transannular bond in each of the two five‐membered biradical units, leading to the formation of housane 5 h. Upon irradiation at 415 nm, the reverse reaction is observed, fully recovering tetraradical 5. Through single‐crystal‐to‐single‐crystal transformation, both stable species of the molecular switch could be structurally characterised using SCXRD. The switching under the influence of light and the activation of molecular hydrogen were analysed in solution using NMR and UV spectroscopy. It was found that the addition of one or two equivalents of molecular hydrogen can be switched on and off by light. [ABSTRACT FROM AUTHOR]

Bioorthogonal reactions that enable switching molecular functions by breaking chemical bonds have gained prominence, with the tetrazine‐mediated cleavage of trans‐cyclooctene caged compounds (click‐to‐release) being particularly noteworthy for its high versatility, biocompatibility, and fast reaction rates. Despite several recent advances, the development of highly reactive tetrazines enabling quantitative elimination from trans‐cyclooctene linkers remains challenging. In this study, we present the synthesis and application of sulfo‐tetrazines, a class of derivatives featuring phenolic hydroxyl groups with increased acidity constants (pKa). This unique property leads to accelerated elimination and complete release of the caged molecules within minutes. Moreover, the inclusion of sulfonate groups provides a valuable synthetic handle, enabling further derivatization into sulfonamides, modified with diverse substituents. Significantly, we demonstrate the utility of sulfo‐tetrazines in efficiently activating fluorogenic compounds and prodrugs in living cells, offering exciting prospects for their application in bioorthogonal chemistry. [ABSTRACT FROM AUTHOR]

The booming demand on data security has aroused great interest for developing smart materials with temporal display feature and dynamic multicolor fluorescence. However, it remains challenging to implement both features on most responsive molecules. Herein, we construct a polymer free volume‐controlled "molecular clock and emitter" via covalently embedding a multi‐stimuli responsive molecular switch (i.e. spiropyran) into a polymer network (i.e. poly(pentafluorophenyl acrylate)) with programmable crosslink density and free volume. By the aminolysis of pentafluorophenyl ester with different amount of diamine crosslinkers, pPFPA‐co‐SP networks with controllable crosslink densities are generated, which have different confinement effects on the rate constant of SP/MC isomerization, thus leading to time‐dependent photochromism. In addition, PTF1, a fluorescent probe that is sensitive to polymer rigidity, is introduced to further endow pPFPA‐co‐SP system with phototunable dynamic full‐color emission. Therefore, relying on their synergistical responses to the rigidity of the polymer network, we have successfully developed a versatile molecular clock and emitter via an "one stone two birds" manner, which shows time‐dependent data display along with dynamic multicolor fluorescence switching, providing great potential for advanced encryption and anticounterfeiting with a high security level. [ABSTRACT FROM AUTHOR]

The single‐molecule localization concept MINFLUX has triggered a reevaluation of the features of fluorophores for attaining nanometer‐scale resolution. MINFLUX nanoscopy benefits from temporally controlled fluorescence ("on"/"off") photoswitching. Combined with an irreversible switching behavior, the localization process is expected to turn highly efficient and quantitative data analysis simple. The potential in the recently reported photoactivable xanthone (PaX) dyes is recognized to extend the list of molecular switches used for MINFLUX with 561 nm excitation beyond the fluorescent protein mMaple. The MINFLUX localization success rates of PaX560, PaX+560, and mMaple are quantitatively compared by analyzing the effective labeling efficiency of endogenously tagged nuclear pore complexes. The PaX dyes prove to be superior to mMaple and on par with the best reversible molecular switches routinely used in single‐molecule localization microscopy. Moreover, the rationally designed PaX595 is introduced for complementing PaX560 in dual color 561 nm MINFLUX imaging based on spectral classification and the deterministic, irreversible, and additive‐independent nature of PaX photoactivation is showcased in fast live‐cell MINFLUX imaging. The PaX dyes meet the demands of MINFLUX for a robust readout of each label position and fill the void of reliable fluorophores dedicated to 561 nm MINFLUX imaging. [ABSTRACT FROM AUTHOR]