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With growing propensity towards personalised medication, the application and impact of molecular theragnostic (or, theranostic) is expected to increase dramatically. Molecular theragnostic is the combination of diagnostics and therapeutics in single targeted molecule. If successful, molecular theragnostic will determine the treatment strategy and therapeutic outcome apart from favourably influencing the time of treatment and comfort of the patient. Recent developments such as [64Cu]Cu‐ATSM for imaging tumor‐hypoxia, 99Y silicate for arthritis, 1⁷⁷Lu‐PSMA‐617 for prostate cancer etc has been discussed in detail in the literature.[1,2] This sectioned review deals in particular with the development of nuclear molecular theragnostic agents. The genesis and design strategies are presented after compiling recent reports. [ABSTRACT FROM AUTHOR]

Compared with aggregate spin behavior, single‐molecule spin behavior can be accurately understood, controlled, and applied at the level of basic building blocks. The potential of single‐molecule electronic and nuclear spins for monitoring and control represents a beacon of promise for the advancement of molecular spin devices, which are fabricated by connecting a single molecule between two electrodes. Metal complexes, celebrated for their superior magnetic attributes, are widely used in the devices to explore spin effects. Moreover, single‐molecule electrical techniques with high signal‐to‐noise ratio, temporal resolution, and reliability help to understand the spin characteristics. In this review, the focus is on the devices with metal complexes, especially single‐molecule magnets, and systematically present experimental and theoretical state of the art of this field at the single‐molecule level, including the fundamental concepts of the electronic and nuclear spin and their basic spin effects. Then, several experimental methods developed to regulate the spin characteristics of metal complexes at single‐molecule level are introduced, as well as the corresponding intrinsic mechanisms. A brief discussion is provided on the comprehensive applications and the considerable challenges of single‐molecule spin devices in detail, along with a prospect on the potential future directions of this field. [ABSTRACT FROM AUTHOR]

Infrared (IR) spectroscopy stands as a workhorse for exploring bond vibrations, offering a wealth of chemical insights across diverse frontiers. With increasing focus on the regime of single molecules, obtaining IR‐sensitive information from individual molecules at room temperature would provide essential information about unknown molecular properties. Here, we leverage bond‐selective fluorescence microscopy, facilitated by narrowband picosecond mid‐IR and near‐IR double‐resonance excitation, for high‐throughput mid‐IR structural probing of single molecules. We robustly capture single‐molecule images and analyze the combined polarization dependence, vibrational peaks, linewidths, and lifetimes of probe molecules with representative scaffolds. From bulk to single molecules, we find that vibrational lifetimes remain consistent, while linewidths are narrowed by approximately twofold and anisotropy becomes more pronounced. Additionally, unexpected peak shifts from single molecules were observed, attributed to the generation of new modes due to previously unexplored dimerization, supported by quantum chemistry calculations. These findings underscore the importance of infrared analysis on individual single molecules in ambient environments, offering molecular information crucial for functional imaging and the investigation of the fundamental properties and utilities of luminescent molecules. [ABSTRACT FROM AUTHOR]

High‐mobility emissive n‐type polymer semiconductors (HMEN‐CPs) are essential for organic optoelectronic devices. However, due to the lack of highly electron‐deficient building blocks with excellent physicochemical properties and the molecular design trade‐offs, the development of HMEN‐CPs has significantly lagged behind that of p‐type counterparts. Here, a new electron‐deficient acceptor, TFBVDPP is developed, by integrating the efficient carrier‐transporting diketopyrrolopyrrole and intense light‐emitting phenylene‐vinylene into a single molecule system. A series of all‐acceptor‐type polymers are synthesized by Pd‐catalyzed Suzuki polycondensation. The introduction of a vinyl bridge induces intra‐/intermolecular non‐covalent interactions, significantly narrowing the optical bandgap while enhancing coplanarity and crystallinity of the conjugated backbone, thus one of the polymers P1 exhibits ideal ambipolar transports with hole and electron mobilities reaching 4.6 and 3.7 cm2 V−1 s−1, respectively. Additionally, by directly homopolymerizing TFBVDPP, the non‐radiative transition is effectively suppressed, maintaining high electron transport while enhancing emission. This system shows excellent unipolar electron mobility (µe) and high quantum yield (Φ), achieving a record Φ · µe value exceeding 10−2 cm2 V−1 s−1, which is at least three orders of magnitude higher than the reported values. This study provides a new approach for developing HMEN‐CPs, and demonstrates their great potential in advancing organic optoelectronic technologies. [ABSTRACT FROM AUTHOR]

After the recent double revolutions in structural biology, which include the use of direct detectors for cryo‐electron microscopy resulting in a significant improvement in the expected resolution of large macromolecule structures, and the advent of AlphaFold which allows for near‐accurate prediction of any protein structures, the field of structural biology is now pursuing more ambitious targets, including several MDa assemblies. But complex target systems cannot be tackled using a single biophysical technique. The field of integrative structural biology has emerged as a global solution. The aim is to integrate data from multiple complementary techniques to produce a final three‐dimensional model that cannot be obtained from any single technique. The absence of atomic force microscopy data from integrative structural biology platforms is not necessarily due to its nm resolution, as opposed to Å resolution for x‐ray crystallography, nuclear magnetic resonance, or electron microscopy. Rather a significant issue was that the AFM topographic data lacked interpretability. Fortunately, with the introduction of the AFM‐Assembly pipeline and other similar tools, it is now possible to integrate AFM topographic data into integrative modeling platforms. The advantages of single molecule techniques, such as AFM, include the ability to confirm experimentally any assembled molecular models or to produce alternative conformations that mimic the inherent flexibility of large proteins or complexes. The review begins with a brief overview of the historical developments of AFM data in structural biology, followed by an examination of the strengths and limitations of AFM imaging, which have hindered its integration into modern modeling platforms. This review discusses the correction and improvement of AFM topographic images, as well as the principles behind the AFM‐Assembly pipeline. It also presents and discusses a series of challenges that need to be addressed in order to improve the incorporation of AFM data into integrative modeling platform. [ABSTRACT FROM AUTHOR]

In single‐molecule microscopy, a big question is how precisely we can estimate the location of a single molecule. Our research shows that by using iterative localisation microscopy and factoring in the prior information, we can boost precision and reduce the number of photons needed. Leveraging the Van Trees inequality aids in determining the optimal precision achievable. Our approach holds promise for wider application in discerning the optimal precision across diverse imaging scenarios, encompassing various illumination strategies, point spread functions and overarching control methodologies. [ABSTRACT FROM AUTHOR]

Correlative super‐resolution microscopy has the potential to accurately visualize and validate new biological structures past the diffraction limit. However, combining different super‐resolution modalities, such as deterministic stimulated emission depletion (STED) and stochastic single‐molecule localization microscopy (SMLM), is a challenging endeavour. For correlative STED and SMLM, the following poses a significant challenge: (1) the photobleaching of the fluorophores in STED; (2) the subsequent reactivation of the fluorophores for SMLM and (3) finding the right fluorochrome and imaging buffer for both imaging modalities. Here, we highlight how the deep ultraviolet (DBUE) wavelengths of the Mercury (Hg) arc lamp can help recover STED bleaching and allow for the reactivation of single molecules for SMLM imaging. We also show that Alexa Fluor 594 and the commercially available Prolong Diamond to be excellent fluorophores and imaging media for correlative STED and SMLM. [ABSTRACT FROM AUTHOR]

Human parainfluenza viruses (hPIVs) are causative agents of upper and lower respiratory tract infections and they have four serotypes. The virion surface displays hemagglutinin‐neuraminidase (HN), having hemagglutinating (HA) and neuraminidase (NA) activities in a single molecule. The HA activity binds the virion to sialic acid on the viral receptor on host cells and the NA releases the progeny viruses from the cell surface. There are several methods for assaying viral NA activity, such as the thiobarbituric acid assay, 4‐methylumbelliferyl‐N‐acetyl‐α‐d‐neuraminic acid assay, NA‐Star assay, and enzyme‐linked lectin assay (ELLA). However, these are mainly used for influenza viruses and not for hPIVs. A fluorescent‐based cytochemical NA assay using BTP3‐Neu5Ac as the substrate was recently developed and used for orthomyxo‐ and paramyxoviruses, including types 1 and 3 hPIVs. In this study, we used the ELLA, and BTP‐Neu5Ac assay for 14 field isolate strains of hPIVs including all four serotypes. The reaction in ELLA at pH 6.5 using peanut agglutinin (PNA) as a lectin was very low for all tested viruses except a type 3 virus strain with the maximum reaction at pH 6.5 and the acidic conditions did not enhance the reaction. ELLA with another lectin, Erythrina cristagalli agglutinin exhibited significant and stronger reactions than with PNA in some strains of types 1 and 3 viruses. The BTP3‐Neu5Ac assay showed a fluorescent signal on cells infected with all the viruses except the hPIV1/Sendai/713/2018 strain in LLC‐MK2 and/or MNT‐1. The signal was detected in cell‐free virus, as well, in all the viruses except the hPIV4a/Sendai/3935/2003 strain. The strength of the signal varied among viral strains but it was stronger in the reaction at pH 4.0 than pH 7.0 and strongest in type 2 hPIVs. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) pathogenesis involves dysregulation in diverse biochemical processes. Nevertheless, plasma tau phosphorylated at threonine 181 (P‐tau181), a recognised AD biomarker, has been described to reflect early‐stage cortical amyloid‐β (Aβ) deposition in cognitively normal (CN) adults. Therefore, identifying changes in plasma metabolites associated with plasma P‐tau181 at the pre‐clinical stage may provide insights into underlying biochemical mechanisms to better understand initial AD pathogenesis. In the current study, plasma P‐tau181, quantified via single molecule array (Simoa) technology, and plasma metabolites, quantified via targeted‐mass spectrometry, were investigated for associations in CN older adults and upon stratification by positron emission tomography (PET)‐Aβ load. In addition, the P‐tau181‐linked metabolites were evaluated for cognitive performance and neuroimaging markers of AD and the potential to distinguish between CN Aβ− and CN Aβ+ individuals. Significant positive associations of medium‐ and long‐chain acylcarnitines (ACs) were observed with P‐tau181 in the entire cohort, CN Aβ− and CN Aβ+, suggesting a link between initial Aβ pathology and fatty acid oxidation‐mediated energy metabolism pathways. However, in CN Aβ−, additional linear associations of P‐tau181 were observed with muscle metabolism and nitric oxide homeostasis‐associated metabolites. Upon investigating the P‐tau181‐linked metabolites for cognitive performance, significant inverse correlations of the verbal and visual episodic memory and the global composite score were noted in CN Aβ+ with medium‐ and long‐chain ACs, suggesting prognostic value of ACs accompanying weaker cognitive performance. While investigating neuroimaging markers, ACs had positive associations with PET‐Aβ load and inverse associations with hippocampal volume in CN Aβ+, indicating connections of ACs with initial AD pathogenesis. Furthermore, based on receiver operating characteristics analysis, the associated ACs potentially classified PET‐Aβ status in older adults. Therefore, plasma P‐tau181‐linked circulating ACs may serve as potential prognostic markers for initial AD pathogenesis in CN older adults. However, further cross‐sectional and longitudinal research in highly characterised AD cohorts is needed to validate current findings. [ABSTRACT FROM AUTHOR]

Understanding the mechanisms underlying amyloid‐β (Aβ) aggregation is pivotal in the context of Alzheimer's disease. This study aims to elucidate the secondary nucleation process of Aβ42 peptides by combining experimental and computational methods. Using a newly developed nanopipette‐based amyloid seeding and translocation assay, confocal fluorescence spectroscopy, and molecular dynamics simulations, the influence of the seed properties on Aβ aggregation is investigated. Both fragmented and unfragmented seeds played distinct roles in the formation of oligomers, with fragmented seeds facilitating the formation of larger aggregates early in the incubation phase. The results show that secondary nucleation leads to the formation of oligomers of various sizes and structures as well as larger fibrils structured in β‐sheets. From these findings a mechanism of secondary nucleation involving two types of aggregate populations, one released and one growing on the mother fiber is proposed. [ABSTRACT FROM AUTHOR]

Double phosphorescence components from a single organic molecule is rarely reported before because most organic molecules must follow Kasha's rule and merely emit phosphorescence from T1 state. We discover a unique phenomenon of conformation‐controlled expression of double phosphorescence components. The green phosphorescence component and the red phosphorescence component are assigned to the dinaphthylamine moiety and the pyrene unit of N,N‐di(naphthalen‐2‐yl)pyren‐1‐amine (NaPy), respectively. NaPy shows time‐dependent and excitation‐dependent afterglow color change in copolymerized MMA film at room temperature due to simultaneous expression of the double phosphorescence components. However, in PMMA film and copolymerized MA film, NaPy just expresses the red phosphorescence component, suggesting that matrix rigidity greatly affects expression of the double phosphorescence components via altering conformation of NaPy. In low‐rigidity matrix, the NaPy conformation is dyanmic due to free rotation and triplet excitons relax to T1 state via inner conversion or vibration relaxation, leading to the sole expression of the red phosphorescence component. In high‐rigidity matrix, the highly twisted conformation of NaPy is stabilized due to limitation of rotation and triplet excitons at T1 state and T2 state return to S0 state separately, resulting in simultaneous expression of the double phosphorescence components. Thus, NaPy follows Kasha's rule in low‐rigidity matrix but disobeys Kasha's rule in high‐rigidity matrix. In high‐rigidity matrix, the dinaphthylamine moiety and the pyrene unit can function relatively independently, resulting in time‐dependent and excitation‐dependent wide‐range afterglow color change. [ABSTRACT FROM AUTHOR]

Organic photovoltaics (OPVs) have made significant strides with efficiencies now exceeding 20%, positioning them as potential competitors to inorganic solar technologies. One of the most critical challenges toward this goal is the severe open‐circuit voltage (Voc) loss caused by the nonradiative charge recombination (NRCR). Herein, this review comprehensively summarizes the NRCR mechanisms and suppression techniques of OPVs across various scales from molecule to device. Specifically, the origins of NRCR in a single molecule are first summarized, and molecular design principles toward high photoluminescence quantum yield are reviewed following the Marcus theory. Next, the effect of aggregation on NRCR is reviewed, as well as the molecular and processing strategies to modulate the film packing for NRCR suppression. Furthermore, the progresses in the avoidance of nonradiative loss pathways mediated by charge transfer states and triplet states in donor:acceptor bulk heterojunctions are tracked. Besides, the interfacial optimization and device structure design to maximize the electroluminescent quantum efficiency are presented. Finally, several potential pathways toward curtailing NRCR for high‐performance OPVs are outlined. Therefore, this review shows an insightful perspective to understand and mitigate the NRCR at multi‐scales, and is poised to provide a clear roadmap for the next breakthrough of OPVs. [ABSTRACT FROM AUTHOR]

Generative models, such as diffusion models, have made significant advancements in recent years, enabling the synthesis of high‐quality realistic data across various domains. Here, the adaptation and training of a diffusion model on super‐resolution microscopy images are explored. It is shown that the generated images resemble experimental images, and that the generation process does not exhibit a large degree of memorization from existing images in the training set. To demonstrate the usefulness of the generative model for data augmentation, the performance of a deep learning‐based single‐image super‐resolution (SISR) method trained using generated high‐resolution data is compared against training using experimental images alone, or images generated by mathematical modeling. Using a few experimental images, the reconstruction quality and the spatial resolution of the reconstructed images are improved, showcasing the potential of diffusion model image generation for overcoming the limitations accompanying the collection and annotation of microscopy images. Finally, the pipeline is made publicly available, runnable online, and user‐friendly to enable researchers to generate their own synthetic microscopy data. This work demonstrates the potential contribution of generative diffusion models for microscopy tasks and paves the way for their future application in this field. [ABSTRACT FROM AUTHOR]

Stable open‐shell luminescent radicals have recently attracted much attention due to their unique luminescence properties. However, a radical molecule with both Kasha and anti‐Kasha doublet emission properties has not been reported. Herein, we have successfully synthesized a stable chlorine‐substituted Chichibabin's hydrocarbon, TTM‐TTM, along with its mono‐radical counterpart, TTM‐HTTM. The emission of TTM‐TTM follows Kasha's rule in the near infrared region. However, TTM‐HTTM shows dual channel doublet emissions of Kasha and anti‐Kasha. Remarkably, these two types of emission compete dynamically in both solution and condensed states. Our findings provide valuable insights into the rational design and discovery of stable radicals that possess distinctive luminescent properties, thus broadening the horizons of luminescent materials research. [ABSTRACT FROM AUTHOR]

Photoactivatable fluorescent probes are valuable tools in bioimaging for tracking cells down to single molecules and for single molecule localization microscopy. For the latter application, green emitting dyes are in demand. We herein developed an efficient green‐emitting photoactivatable furanyl‐BODIPY (PFB) and we established a new mechanism of photoactivation called Directed Photooxidation Induced Activation (DPIA) where the furan is photo‐oxidized in a directed manner by the singlet oxygen produced by the probe. The efficient photoconverter (93‐fold fluorescence enhancement at 510 nm, 49 % yield conversion) is functionalizable and allowed targeting of several subcellular structures and organelles, which were photoactivated in live cells. Finally, we demonstrated the potential of PFB in super‐resolution imaging by performing PhotoActivated Localization Microscopy (PALM) in live cells. [ABSTRACT FROM AUTHOR]

The advent of third‐generation sequencing (TGS) represents a significant shift in the field of genetic sequencing, enabling single‐molecule sequencing to overcome limitations of short‐read NGS platforms. Several studies have assessed the utilisation of TGS in HLA genotyping, though many of these studies have described the high error rate as an obstacle to achieving a robust and highly accurate HLA typing assay. In 2021, Oxford Nanopore Technologies (ONT) released the high‐accuracy sequencing Kit 14 and the MinION flow cell model R10.4.1, which were reported to achieve sequencing accuracies up to 99%. The aim of this study was to validate this novel high‐accuracy sequencing kit for HLA genotyping coupled with a full‐gene HLA PCR assay. Comparison with historical data obtained using legacy flow cell models such as R9.4, R10.3 and R10.4 was also done to assess progressive improvement in sequencing performance with each sequential release. The workflow was validated based on data throughput, sequence quality and accuracy, and HLA genotyping resolution. An initial validation was performed using an internal reference panel of 42 samples representing common HLA allele groups, followed by an analysis of data obtained from 111 sequencing batch runs since the implementation, to assess assay performance and define quality control metrics to assess inter‐run variability and monitor quality. Furthermore, challenges arising from MinION flow cell stability and use, and assessment of barcode contamination are discussed. The findings of this study highlight advantages of ONT sequencing kit 14/R10.4.1 for HLA genotyping and the implementation considerations for the routine diagnostic HLA laboratory. [ABSTRACT FROM AUTHOR]

Proteins play a vital role in different biological processes by forming complexes through precise folding with exclusive inter‐ and intra‐molecular interactions. Understanding the structural and regulatory mechanisms underlying protein complex formation provides insights into biophysical processes. Furthermore, the principle of protein assembly gives guidelines for new biomimetic materials with potential applications in medicine, energy, and nanotechnology. Atomic force microscopy (AFM) is a powerful tool for investigating protein assembly and interactions across spatial scales (single molecules to cells) and temporal scales (milliseconds to days). It has significantly contributed to understanding nanoscale architectures, inter‐ and intra‐molecular interactions, and regulatory elements that determine protein structures, assemblies, and functions. This review describes recent advancements in elucidating protein assemblies with in situ AFM. We discuss the structures, diffusions, interactions, and assembly dynamics of proteins captured by conventional and high‐speed AFM in near‐native environments and recent AFM developments in the multimodal high‐resolution imaging, bimodal imaging, live cell imaging, and machine‐learning‐enhanced data analysis. These approaches show the significance of broadening the horizons of AFM and enable unprecedented explorations of protein assembly for biomaterial design and biomedical research. [ABSTRACT FROM AUTHOR]

Metalated covalent organic frameworks (COFs) for 2D and 3D topologies are continuously being developed, whereas metalated COFs with 1D topologies are still in their infancy. Here, a novel 1D phenanthroline‐based COF containing 4,4‐(1,10‐phenanthroline‐2,9‐diyl)bis[benzaldehyde] (PBA) is reported (PAD‐COF). Subsequently, a metalated 1D COF, Co SAS/PAD‐COF, is constructed using the bidentate ligand properties of PBA and anchoring the single Co atoms in PAD‐COF through a post‐synthetic modification strategy. This complex significantly improved the photocatalytic performance of PAD‐COF, and the CO yield of the optimized Co SAS/PAD‐COF was stable at 3091 µmol g−1 h−1 with a selectivity of 93%, which is approximately 43.7 times that of the original PAD‐COF. Experimental and theoretical results demonstrate the excellent CO2 photoreduction activity of Co SAS/PAD‐COF owing to the synergistic effect of single Co catalytic sites and PAD‐COF. Among them, PAD‐COF, as the host, adsorbs CO2 molecules and loads single Co atoms. Meanwhile, Co atoms function as catalytic sites and promote the adsorption and activation of CO2, while reducing the reaction energy barrier formed by the *COOH intermediates. Therefore, this unique metalated 1D COF provides a fresh approach to photocatalytic CO2 reduction. [ABSTRACT FROM AUTHOR]

Here we report the synthesis and luminescent properties of the modified polyhedral oligomeric silsesquioxane (POSS) that possesses two types of luminophores, cyanobenzene and N,N‐diethylaniline for inducing significant emission not only from each dye but also from molecular interactions on the POSS core. From the optical measurements in the diluted solution, we observed both locally‐excited emission and excimer emission originating from intramolecular interactions assisted by POSS. Moreover, highly‐efficient exciplex emission was observed from the thin film, indicating that the interaction between luminophores easily occurs in the solid state by accumulating two kinds of molecules in the single POSS molecule. Finally, we also found that the modified POSS showed a unique acid responsiveness which can be caused by protonation at two types of amino moieties. In this manuscript, it is shown that POSS is able to play various roles at the same time: recruiting excited molecules to form exciplexes, suppressing concentration quenching in the solid state, and imparting stimulus responsiveness to exciplexes. [ABSTRACT FROM AUTHOR]

ABSTRACT Venturello‐structured polyoxometalates (POMs) are effective homogeneous catalysts and confining POMs to size‐matched metal‐organic frameworks (MOFs) as heterogeneous catalyst is an effective way to improve their practical application. The appropriate pore and narrow window of pristine UiO‐67 can not only enclose POMs in single molecule but also limit their leaching and can provide a suitable platform for the oxidation of most sulfur‐containing organic compound. The composite (CTA)3PW4@UiO‐67 was prepared by a facile in situ synthesis method, characterized by a variety of means and tested for desulfurization of multicomponent simulated diesel. The results prove that the active component (CTA)3PW4 is effectively encapsulated, and the composite (CTA)3PW4@UiO‐67 show remarkable desulfurization activity and excellent reusability. In addition, the kinetics and possible mechanism of the reaction were investigated. This work opens up a new idea for the design of “host‐guest adapted” catalyst suitable for fuel desulfurization technology. [ABSTRACT FROM AUTHOR]

A synergetic interaction between two or more photochromic chromophores has a potential to achieve advanced photochemical properties beyond conventional photochromic molecules and to realize photochemical control of complex systems using only a single molecule. Herein, we report a hybrid photochromic molecule consisting of hexaarylbiimidazole (HABI) and terarylene that exhibits multi‐state photochromism. The biphotochrome hybrid shows four‐state photochromic reaction involving sequentially proceeding photoreactions. The UV or visible light irradiation to the biphotochrome leads to the C−N bond breaking reaction of the HABI in preference to the ring‐closing reaction of the 6π‐electron system in the terarylene unit, leading to two terarylene radical molecules. The photogenerated terarylene radical further exhibits the 6π‐electrocyclization reaction by UV irradiation. The delocalized π‐radical on the closed‐ring form of the terarylene is efficient to enhance the photosensitivity to the NIR−I and ‐II region. Furthermore, a recombination reaction of radicals between the open‐ and closed‐ring isomers of terarylene affords an unprecedented photochromic dimer as a structural isomer of the initial molecule. This is a consequence of the sequential hybrid photochromic system involving the HABI and terarylene units. [ABSTRACT FROM AUTHOR]

Optical microcavities, particularly whispering gallery mode (WGM) microcavities enhanced by plasmonic nanorods, are emerging as powerful platforms for single‐molecule sensing. However, the impact of optical forces from the plasmonic near field on analyte molecules is inadequately understood. Using a standard optoplasmonic WGM single‐molecule sensor to monitor two enzymes, both of which undergo an open‐to‐closed‐to‐open conformational transition, the work done on an enzyme by the WGM sensor as atoms of the enzyme move through the electric field gradient of the plasmonic hotspot during conformational change has been quantified. As the work done by the sensor on analyte enzymes can be modulated by varying WGM intensity, the WGM microcavity system can be used to apply free energy penalties to regulate enzyme activity at the single‐molecule level. The findings advance the understanding of optical forces in WGM single‐molecule sensing, potentially leading to the capability to precisely manipulate enzyme activity at the single‐molecule level through tailored optical modulation. [ABSTRACT FROM AUTHOR]

Donor–acceptor (D–A) structure with charge transfer (CT) effect is widely utilized in the construction of organic luminescent materials. The adjustment of their CT effect and related luminescent property usually relies on the changes of molecular structure with different D or A moieties, which will lead to some uncertainties in structure‐property relationship. With the aim to explore the clear inherent luminescent mechanism for D–A molecule with CT effect, it is ideal that the regulation of intramolecular charge transfer in one same D–A molecule can be realized. Accordingly, three D–A type organic phosphorescence luminogens are designed and synthesized. Once being doped into different polymer matrixes, disparate charge transfer effects and related room temperature phosphorescence (RTP) properties can be achieved for a single molecule. Subsequent experiments confirm that different distributions of molecules with locally excited (LE) state and CT state are mainly responsible for their distinct RTP behaviors, exhibiting the well‐clarified structure‐property relationship of D–A type phosphorescence luminogens. Furthermore, the transition from CT to LE state can even be realized through chemical reaction, leading to the activated RTP effect for practical applications. [ABSTRACT FROM AUTHOR]

Single Molecule Localisation Microscopy (SMLM) is becoming a widely used technique in cell biology. After processing the images, the molecular localisations are typically stored in a table as xy (or xyz) coordinates, with additional information, such as number of photons, etc. This set of coordinates can be used to generate an image to visualise the molecular distribution, for example, a 2D or 3D histogram of localisations. Many different methods have been devised to analyse SMLM data, among which cluster analysis of the localisations is popular. However, it can be useful to first segment the data, to extract the localisations in a specific region of a cell or in individual cells, prior to downstream analysis. Here we describe a pipeline for annotating localisations in an SMLM dataset in which we compared membrane segmentation approaches, including Otsu thresholding and machine learning models, and subsequent cell segmentation. We used an SMLM dataset derived from dSTORM images of sectioned cell pellets, stained for the membrane proteins EGFR (epidermal growth factor receptor) and EREG (epiregulin) as a test dataset. We found that a Cellpose model retrained on our data performed the best in the membrane segmentation task, allowing us to perform downstream cluster analysis of membrane versus cell interior localisations. We anticipate this will be generally useful for SMLM analysis. LAY DESCRIPTION: A form of microscopy called single‐molecule localisation microscopy (SMLM) allows researchers to locate the positions of proteins with very high precision inside cells. The organisation of these proteins is typically important for their function. Once the imaging data is acquired, it is useful to segment (select areas) regions of the cells to find out how proteins are organised in these specific regions. Here we have developed an approach that can select localisations of proteins within the plasma membrane as well as localisations within the cell, for downstream analysis. We used this data to determine how clusters of molecules varied between the plasma membrane and the interior of the cell. This approach could be generally useful for segmenting SMLM datasets. [ABSTRACT FROM AUTHOR]

Light‐emitting organic small molecules require high internal and external quantum efficiencies with excellent radiative characteristics for their potential application in next‐generation optoelectronics. Nonetheless, achieving high efficiency in solid states remains a formidable challenge, primarily owing to the non‐radiative processes. Therefore, conformational modulation in solid states is pivotal in influencing emission properties to mitigate non‐radiative decay. Notably, modifying intra‐ and intermolecular non‐covalent interactions (NCIs) is a promising strategy that can simultaneously realize rigidity and stabilization of flexible single bonds, thus suppressing reorganization energy associated with non‐radiative decay. Consequently, considerable emission enhancement is attainable through adept manipulation of NCIs, corresponding to systems ranging from single molecules to multimolecular networks in solid states. This review systematically summarizes and analyzes the influence of diverse NCIs in efficient light‐emitting organic small molecules. The effects of NCIs on single‐and multimolecular‐systems are discussed, based on the fundamentals of light emission mechanism and the correlation between molecular design strategy and photophysical properties. Additionally, strategic perspectives are provided for the advancement of future light‐emitting organic small molecules. Therefore, this review serves as a comprehensive molecular design library, providing an up‐to‐date overview of molecular design leveraging NCIs for efficient light‐emitting organic small molecules. [ABSTRACT FROM AUTHOR]

With the development of metalloimmunology, the potential of platinum drugs in cancer immunotherapy has attracted extensive attention. Although immunochemotherapy combining PD‐1/PD−L1 antibodies with platinum drugs has achieved great success in the clinic, combination therapy commonly brings new problems. Herein, we have developed a platinum‐metformin conjugate as a promising alternative to antibody‐based PD−L1 inhibitors, not only disrupting PD‐1/PD−L1 axis on cell surface but also down‐regulating the total PD−L1 levels in non‐small cell lung cancer (NSCLC) cells comprehensively, thus achieving highly efficient immunochemotherapy by a single small molecule. Mechanism studies demonstrate that Pt‐metformin conjugate can selectively accumulate in lysosomes, promote lysosomal‐dependent PD−L1 degradation via the AMPK‐TFEB pathway, and modulate the upstream regulatory proteins related to PD−L1 expression (e.g. HIF‐1α and NF‐κB), eventually decreasing the total abundance of PD−L1 in NSCLC, overcoming tumor hypoxia, and activating anti‐tumor immunity in vivo. This work suggests an AMPK‐mediated lysosomal degradation pathway of PD−L1 for the first time and provides a unique design perspective for the development of novel platinum drugs for immunochemotherapy. [ABSTRACT FROM AUTHOR]

Bipolar‐type electrode materials are capable of improving the specific power and reducing the manufacturing costs for rechargeable symmetric batteries, while their development is plagued by the lack of reliable and affordable bipolar‐type materials. Here, a bipolar‐type indanthrene (IDT) with synergetic coupling effects of two redox centers of p‐type dihydrophenazines and n‐type anthraquinone in a single molecule is proposed to construct a symmetric battery. Due to the mutually affecting of n‐type and p‐type redox couples, the conjugated "p–n fusion" in the IDT material facilitates mutual electron cloud donation and withdrawal between two redox centers, thus a considerable output voltage of 0.62 V is realized in symmetric aqueous battery. Benefiting from its enriched redox centers and extended π‐conjugated structure, the symmetric battery also delivers a specific capacity of 139 mAh g−1 at 0.1 A g−1 and a long cycling stability with a capacity retention of 79% after 600 cycles at 2 A g−1. Comprehensive ex‐situ characterizations paired with density functional theroy calculations reveal both reversible HSO4− and H+ uptake/removal behavior during charging/discharging process. Additionally, a symmetric cell with quasi‐solid electrolyte is established, which exhibits superior practical application capability with a capacity retention of 78% at 2 A g−1 over 1000 cycles. [ABSTRACT FROM AUTHOR]

Nanoelectromechanical systems (NEMS)‐based mass spectrometry (MS) is an emerging technique that enables determination of the mass of individual adsorbed particles by driving nanomechanical devices at resonance and monitoring the real‐time changes in their resonance frequencies induced by each single molecule adsorption event. We incorporate NEMS into an Orbitrap mass spectrometer and report our progress towards leveraging the single‐molecule capabilities of the NEMS to enhance the dynamic range of conventional MS instrumentation and to offer new capabilities for performing deep proteomic analysis of clinically relevant samples. We use the hybrid instrument to deliver E. coli GroEL molecules (801 kDa) to the NEMS devices in their native, intact state. Custom ion optics are used to focus the beam down to 40 μm diameter with a maximum flux of 25 molecules/second. The mass spectrum obtained with NEMS‐MS shows good agreement with the known mass of GroEL. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs), crucial mediators of cell‐to‐cell communication, hold significant diagnostic potential due to their ability to concentrate protein biomarkers in bodily fluids. However, challenges in isolating EVs from biological specimens hinder their widespread use. The preferred strategy involves direct analysis, integrating isolation and analysis solutions, with immunoaffinity methods currently dominating. Yet, the heterogeneous nature of EVs poses challenges, as proposed markers may not be as universally present as thought, raising concerns about biomarker screening reliability. This issue extends to EV‐mimics, where conventional methods may lack applicability. Addressing these challenges, the study reports on Membrane Sensing Peptides (MSP) as pan‐vesicular affinity ligands for both EVs and their non‐canonical analogs, streamlining capture and phenotyping through Single Molecule Array (SiMoA). MSP ligands enable direct analysis of circulating EVs, eliminating the need for prior isolation. Demonstrating clinical translation, MSP technology detects an EV‐associated epitope signature in serum and plasma, distinguishing myocardial infarction from stable angina. Additionally, MSP allow analysis of tetraspanin‐lacking Red Blood Cell‐derived EVs, overcoming limitations associated with antibody‐based methods. Overall, the work underlines the value of MSP as complementary tools to antibodies, advancing EV analysis for clinical diagnostics and beyond, and marking the first‐ever peptide‐based application in SiMoA technology. [ABSTRACT FROM AUTHOR]

A total of 43 novel HLA alleles detected in haematopoietic cell donors using single molecule real‐time DNA sequencing. [ABSTRACT FROM AUTHOR]

Complex materials exhibit fascinating features especially in situations far from equilibrium. Thus, methods for investigating structural dynamics with sub‐second time resolution are becoming a question of interest at varying spatial scales. With novel microscopy techniques steadily improving, the temporal and spatial limits of multiple imaging methods are investigated with an emphasis on the important role of correlative imaging and cryo‐fixation. A deep‐dive is taken into cryo‐correlative light and electron microscopy (CLEM) as a starting point for multimodal investigations of ultrastructural dynamics at high spatiotemporal resolution. The focus is on highlighting the different microscopy methods that capture the following key aspects: 1) samples are as close to native state as possible 2) dynamic process information is captured, 3) high structural resolution is enabled. Additionally, the size of samples that can be imaged under these conditions is looked at and approaches not only focusing on single molecules, but larger structures are highlighted. [ABSTRACT FROM AUTHOR]

Electrochemiluminescence (ECL) is rapidly evolving from an analytical method into an optical microscopy. The orthogonality of the electrochemical trigger and the optical readout distinguishes it from classic microscopy and electrochemical techniques, owing to its near‐zero background, remarkable sensitivity, and absence of photobleaching and phototoxicity. In this minireview, we summarize the recent advances in ECL imaging technology, emphasizing original configurations which enable the imaging of biological entities and the improvement of the analytical properties by increasing the complexity and multiplexing of bioassays. Additionally, mapping the (electro)chemical reactivity in space provides valuable information on nanomaterials and facilitates deciphering ECL mechanisms for improving their performances in diagnostics and (electro)catalysis. Finally, we highlight the recent achievements in imaging at the ultimate limits of single molecules, single photons or single chemical reactions, and the current challenges to translate the ECL imaging advances to other fields such as material science, catalysis and biology. [ABSTRACT FROM AUTHOR]

Pancreatic cancer, ranking as the third factor in cancer‐related deaths, necessitates enhanced diagnostic measures through early detection. In response, SiMoT‐Single‐molecule with a large Transistor multiplexing array, achieving a Technology Readiness Level of 5, is proposed for a timely identification of pancreatic cancer precursor cysts and is benchmarked against the commercially available chemiluminescent immunoassay SIMOA (Single molecule array) SP‐X System. A cohort of 39 samples, comprising 33 cyst fluids and 6 blood plasma specimens, undergoes detailed examination with both technologies. The SiMoT array targets oncoproteins MUC1 and CD55, and oncogene KRAS, while the SIMOA SP‐X planar technology exclusively focuses on MUC1 and CD55. Employing Principal Component Analysis (PCA) for multivariate data processing, the SiMoT array demonstrates effective discrimination of malignant/pre‐invasive high‐grade or potentially malignant low‐grade pancreatic cysts from benign non‐mucinous cysts. Conversely, PCA analysis applied to SIMOA assay reveals less effective differentiation ability among the three cyst classes. Notably, SiMoT unique capability of concurrently analyzing protein and genetic markers with the threshold of one single molecule in 0.1 mL positions it as a comprehensive and reliable diagnostic tool. The electronic response generated by the SiMoT array facilitates direct digital data communication, suggesting potential applications in the development of field‐deployable liquid biopsy. [ABSTRACT FROM AUTHOR]

The complement is a conserved cascade that plays a central role in the innate immune system. To maintain a delicate equilibrium preventing excessive complement activation, complement inhibitors are essential. One of the major fluid-phase complement inhibitors is C4b-binding protein (C4BP). Human C4BP is a macromolecular glycoprotein composed of two distinct subunits, C4BPα and C4BPβ. These associate with vitamin K-dependent protein S (ProS) forming an ensemble of co-occurring higher-order structures. Here, we characterize these C4BP assemblies. We resolve and quantify isoforms of purified human serum C4BP using distinct single-particle detection techniques: charge detection mass spectrometry, and mass photometry accompanied by high-speed atomic force microscopy. Combining cross-linking mass spectrometry, glycoproteomics, and structural modeling, we report comprehensive glycoproteoform profiles and full-length structural models of the endogenous C4BP assemblies, expanding knowledge of this key complement inhibitor's structure and composition. Finally, we reveal that an increased C4BPα to C4BPβ ratio coincides with elevated C-reactive protein levels in patient plasma samples. This observation highlights C4BP isoform variation and affirms a distinct role of co-occurring C4BP assemblies upon acute phase inflammation. Synopsis: C4b-binding protein complement inhibitor forms co-occurring assemblies in human serum. Here, by using an integrative structural biology approach, structural and compositional details of C4BP are exposed, resulting in structural models of full-length glycosylated C4BP assemblies. Integrating high-speed atomic force microscopy and cross-linking mass spectrometry we present full-length structural models of C4BP, a spider-like assembly of C4BPα and C4BPβ, non-covalently interacting with vitamin K-dependent protein S. Dominant C4BP variants in healthy human serum are C4BP(β+) captured and analyzed by single molecule mass photometry and charge detection mass spectrometry. Quantitative serum proteomics reveals that C4BP variant composition changes during acute phase inflammation, with an increase in α7 variant abundance. Structual analysis of complement inhibitor C4BP uncovers full-length spider-like assemblies of C4BPα and C4BPβ subunits and composition changes during acute phase inflammation. [ABSTRACT FROM AUTHOR]

The success of a nanopore experiment relies not only on the quality of the experimental design but also on the performance of the analysis program utilized to decipher the ionic perturbations necessary for understanding the fundamental molecular intricacies. An event extraction framework is developed that leverages parallel computing, efficient memory management, and vectorization, yielding significant performance enhancement. The newly developed abf‐ultra‐simple function extracts key parameters from the header critical for the operation of open‐seek‐read‐close data loading architecture running on multiple cores. This underpins the swift analysis of large files where an ≈ × 18 improvement is found for a 100 min‐long file (≈4.5 GB) compared to the more traditional single (cell) array data loading method. The application is benchmarked against five other analysis platforms showcasing significant performance enhancement (>2 ×–1120 ×). The integrated provisions for batch analysis enable concurrently analyzing multiple files (vital for high‐bandwidth experiments). Furthermore, the application is equipped with multi‐level data fitting based on abrupt changes in the event waveform. The application condenses the extracted events to a single binary file improving data portability (e.g., 16 GB file with 28 182 events reduces to 47.9 MB–343 × size reduction) and enables a multitude of post‐analysis extractions to be done efficiently. [ABSTRACT FROM AUTHOR]

The structural diversity of biological macromolecules in different environments contributes complexity to enzymological processes vital for cellular functions. Fluorescence resonance energy transfer and electron microscopy are used to investigate the enzymatic reaction of T4 DNA ligase catalyzing the ligation of nicked DNA. The data show that both the ligase–AMP complex and the ligase–AMP–DNA complex can have four conformations. This finding suggests the parallel occurrence of four ligation reaction pathways, each characterized by specific conformations of the ligase–AMP complex that persist in the ligase–AMP–DNA complex. Notably, these complexes have DNA bending angles of ≈0°, 20°, 60°, or 100°. The mechanism of parallel reactions challenges the conventional notion of simple sequential reaction steps occurring among multiple conformations. The results provide insights into the dynamic conformational changes and the versatile attributes of T4 DNA ligase and suggest that the parallel multiple reaction pathways may correspond to diverse T4 DNA ligase functions. This mechanism may potentially have evolved as an adaptive strategy across evolutionary history to navigate complex environments. [ABSTRACT FROM AUTHOR]

Gaseous signaling molecules (GSMs) including nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) have presented excellent therapeutic efficacy such as anti‐inflammatory, anti‐microbial and anti‐cancer effects and multiple biomedical applications in recent years. As the three most vital signaling molecules in human physiology, these three GSMs show so intertwined and orchestrated interactions that the synergy of multiple gases may demonstrate a more complex therapeutic potential than single gas delivery. Consequently, researchers have been devoted to developing codelivery systems of GSMs by synthesizing a single molecule as a dual donor to maximize the gaseous therapeutic efficacy. In this minireview, we summarize the recent developments of molecules or materials enabling codelivery of GSMs for biomedical applications. It appears that compared with the abundant cases of codelivery of NO and H2S, research on codelivery of CO and the other two GSMs separately remains to be explored. [ABSTRACT FROM AUTHOR]

In modern cancer therapy, blockage of more than one target is a standard approach, and there are already many dual‐target drugs that can achieve multiple inhibition through a single molecule. Herein, we designed and synthesized a series of novel derivatives with signal transducer and activator of transcription 3 (STAT3) and histone deacetylase (HDAC) inhibitory activity through strategy of combining pharmacophore based on the STAT3 inhibitor E28 and HDAC inhibitor MS‐275. Among them, compound 24 (IC50 = 8.22 ± 0.27 μM) showed better anti‐tumor activity than the clinical Class I HDAC inhibitor MS‐275 (IC50 = 14.65 ± 0.24 μM) in MCF‐7 breast cancer cells. Furthermore, the dual inhibition to HDAC and STAT3 of compound 24 was validated by western blot analysis. The study provides new tool compounds for further exploration of STAT3–HDAC pathway inhibitor achieved with a single molecule. [ABSTRACT FROM AUTHOR]

Nonlinear photochromic reactions that work with weak incoherent light are important for molecular operations with high spatial resolution and multiple photofunctions based on single molecules. However, nonlinear photochromic compounds generally require complex molecular design, restricting accessibility in various fields. Herein, we report nonlinear photochromic properties in a perylene‐substituted rhodamine spirolactam derivative (Rh−Pe), which is synthesized from rhodamine B in facile procedures. Direct excitation of Rh−Pe produces the triplet excited state via the charge‐transfer (CT) state. The triplet excited state causes triplet–triplet annihilation to bring the generation of the intensely colored ring‐open form with nonlinear behavior. Furthermore, green‐ and red‐light‐induced photochromism was achieved in Rh−Pe using triplet sensitizers, although Rh−Pe can be directly excited only by ultraviolet and blue light. Our findings are expected to contribute to the development of photofunctional materials showing nonlinear behavior and low‐energy light responsivity. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Investigating the quantum interference effect in single molecules is essential to comprehensively understand the underlying mechanism of single‐molecule charge transport. In this study, we employed the mother molecule m‐OPE and introduced a series of side groups with various electronic effects at the 2‐position of the central phenyl ring, creating four daughter m‐OPE derivatives. The single molecular conductivities of these molecule wires were measured using the scanning tunneling microscope breaking junction technique. Our findings demonstrate that the substitutions regularly modulate the destructive quantum interference occurring within the m‐OPE molecules. By combining optical and electrochemical investigations, along with density functional theory computations, we discover that the conductivity of the molecules corresponds to the electron‐donating/withdrawing ability of the substituents. Specifically, by adjusting the electron structures of the molecular backbone, we can systematically tailor the destructive quantum interference in the m‐OPE molecules. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Investigating the quantum interference effect in single molecules is essential to comprehensively understand the underlying mechanism of single‐molecule charge transport. In this study, we employed the mother molecule m‐OPE and introduced a series of side groups with various electronic effects at the 2‐position of the central phenyl ring, creating four daughter m‐OPE derivatives. The single molecular conductivities of these molecule wires were measured using the scanning tunneling microscope breaking junction technique. Our findings demonstrate that the substitutions regularly modulate the destructive quantum interference occurring within the m‐OPE molecules. By combining optical and electrochemical investigations, along with density functional theory computations, we discover that the conductivity of the molecules corresponds to the electron‐donating/withdrawing ability of the substituents. Specifically, by adjusting the electron structures of the molecular backbone, we can systematically tailor the destructive quantum interference in the m‐OPE molecules. [ABSTRACT FROM AUTHOR]

The article explores SMARCAL1's role as a dual regulator of tumor immune evasion by modulating innate immune signaling and PD-L1 expression. Topics include: the dual functionality of SMARCAL1 in regulating the cGAS–STING pathway and PD-L1 expression; the implications of SMARCAL1 deficiency on tumor immunity; and the potential for combining SMARCAL1-targeted therapies with immune checkpoint inhibitors for enhanced cancer treatment.

Zn metal as a promising anode of aqueous batteries faces severe challenges from dendrite growth and side reactions. Here, tetraphenylporphyrin tetrasulfonic acid (TPPS) is explored as an electrolyte additive for advanced Zn anodes. It is interesting to note that TPPS spontaneously assembles into unique aggregates. As they adsorb on the Zn anode, the aggregates enhance the resistance to electrolyte percolation and dendrite growth compared to single molecules. Meanwhile, TPPS facilitates anion association in the solvation sheath of Zn2+, and boosts the transference number of Zn2+ up to 0.95. Therefore, anion‐related side reactions and anion‐induced electrode overpotentials are reduced accordingly. In this context, the electrolyte containing TPPS exhibits excellent electrochemical performance. Even under a high loading of MnO2 (25 mg cm−2), a limited Zn supply (N/P ratio=1.7), and a lean electrolyte (15 μL mAh−1), the full cells still represent a higher cumulative capacity compared to the reported data. The advantages of this electrolyte are also adapted to other cathode materials. The pouch cells of Zn||NaV3O8 ⋅ 1.5H2O realize a capacity of ~0.35 Ah at 0.4 C under harsh conditions. [ABSTRACT FROM AUTHOR]

Surface‐enhanced Raman spectroscopy (SERS) is a powerful optical technique with high sensitivity to identify analytes down to a single molecule by fingerprinting vibrational information. The strong coupling in microcavities for supermodes with promoted quality factors demonstrates the capability to boost the interaction between photons and molecules for nonlinear effects. Here a strong‐coupling cascade microsphere‐cavity (MC) achieving spontaneous Raman enhancement is reported, for the first time. The cascade MC is composed of two size‐mismatched microspheres, both of which support optical whispering‐gallery modes (WGMs) with significantly different free‐space ranges. The strong coupling between the supported WGMs in the microspheres can be achieved when the quasi‐vernier effect of resonant modes occurs, by which the energy splitting is up to 4 meV. The fast energy transfer between the size‐mismatched MCs therefore increases the quality factor up to 2.1 × 103 for the upper supermode branch. The strong‐coupling cascade MC structure provides an extra enhancement channel for the Au‐based SERS substrate, demonstrating an enhancement factor of Raman intensity (EFRI) up to 2.6 × 1010 for the limit of detection (LoD) down to 10−12 M of 4‐aminothiophenol (4‐ATP). The strong‐coupling cascade MC substrates also exhibit the versatility for identification of multiple analytes for high‐performance Raman trace‐detection applications. [ABSTRACT FROM AUTHOR]

In contrast to its behavior in solution, the adduct [(LiBr)(tBu)(Ph)Bpin]− (pin=pinacol) transfers its phenyl anion from boron to lithium upon fragmentation in the gas phase. Quantum chemical calculations predict this exceptional transmetalation to be exothermic relative to the separated reactants, [(tBu)(Ph)Bpin]− and LiBr, which we attribute to the high phenyl‐anion affinity of the coordinatively unsaturated LiBr unit. The addition of a single molecule of tetrahydrofuran drastically reduces the phenyl‐anion affinity of LiBr and thereby renders the transmetalation from boron to lithium endothermic. Thus, the probed system highlights the importance of solvation and ligation effects in transmetalations. For correctly predicting the direction, in which these reactions proceed, it is not sufficient to consider the electronegativities or partial charges of the involved metals or metalloids. Instead, the individual coordination states and their changes over the course of the reaction must be taken into account. [ABSTRACT FROM AUTHOR]

Left–right (LR) asymmetry is crucial for animal development, particularly in Drosophila where LR‐asymmetric morphogenesis of organs hinges on cellular‐level chirality, termed cell chirality. In this species, two class I myosins, Myosin1D (Myo1D), and Myosin1C (Myo1C), respectively determine dextral (wild type) and sinistral (mirror image) cell chirality. Previous studies demonstrated Myo1D's ability to propel F‐actin in leftward circles during in vitro gliding assays, suggesting its mechanochemical role in defining dextral chirality. Conversely, Myo1C propels F‐actin without exhibiting LR‐directional preference in this assay, suggesting at other properties governing sinistral chirality. Given the interaction of Myo1D and Myo1C with the membrane, we hypothesized that differences in their membrane behaviors might be critical in dictating their dextral or sinistral activities. In this study, employing single‐molecule imaging analyses, we investigated the dynamic behaviors of Myo1D and Myo1C on the plasma membrane. Our findings revealed that Myo1C exhibits a significantly greater proportion of slow‐diffusing population compared to Myo1D. Importantly, this characteristic was contingent upon both head and tail domains of Myo1C. The distinct diffusion patterns of Myo1D and Myo1C did not exert mutual influence on each other. This divergence in membrane diffusion between Myo1D and Myo1C may be crucial for dictating cell and organ chirality. [ABSTRACT FROM AUTHOR]

This work aims to develop a method for analyzing the dynamic flow of single DNA molecules through nanochannels in fluidic chip which work passively. For this purpose, a two‐laser system was used, which is coupled into a fluorescence microscope and can detect labeled DNA molecules using a single photon counter for signal read‐out in real‐time. The two laser spots are focused at different points of the nanochannel, and can be used to obtain the speed and molecular extension of the DNA. For example, a velocity of 1.82 μm/ms and a spatial extension of 0.9 μm were determined for pUC18/19 DNA (2686 bp) in a nanochannel with a width and depth of 200 nm × 100 nm and a length of 10 μm. © 2024 Institute of Electrical Engineer of Japan and Wiley Periodicals LLC. [ABSTRACT FROM AUTHOR]

Electronic conductance through a single molecule is sensitive to its structural orientation between two electrodes, owing to the distribution of molecular orbitals and their coupling to the electrode levels, that are governed by quantum confinement effects. Herein, the contact geometry of the porphine molecule is varied by attaching two Au tip electrodes that resemble the mechanical break junction, via thiol anchoring groups, is varied. The current–voltage characteristics of all the contact geometries are investigated using nonequilibrium Green's function formalism along with density functional theory and tight‐binding framework. Varying current responses are observed with changing contact sites, originating from varied wave‐function delocalization and quantum interference effect. The calculations show asymmetric current–voltage characteristics under forward and reverse biases due to structural asymmetry of the tip electrodes on either side of the molecule. This phenomenon is established as a universal feature for any molecular electronic device, irrespective of the inherent structural symmetry of a molecule. These findings provide fundamental insights into electronic transport through single molecules in the real experimental setup. Furthermore, the observations of varying current response can further motivate the fabrication of sensor devices with porphine‐based biomolecules that control important physiological activities, in view of their applications in advanced diagnostics. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) genotyping is widely used, particularly in combination with high‐risk (HR) HPV tests for cervical cancer screening. We developed a genotyping method using sequences of approximately 800 bp in the E6/E7 region obtained by PacBio single molecule real‐time sequencing (SMRT) and evaluated its performance against MY09‐11 L1 sequencing and after the APTIMA HPV genotyping assay. The levels of concordance of PacBio E6/E7 SMRT sequencing with MY09‐11 L1 sequencing and APTIMA HPV genotyping were 100% and 90.8%, respectively. The sensitivity of PacBio E6/EA7 SMRT was slightly greater than that of L1 sequencing and, as expected, lower than that of HR‐HPV tests. In the context of cervical cancer screening, PacBio E6/E7 SMRT is then best used after a positive HPV test. PacBio E6/E7 SMRT genotyping is an attractive alternative for HR and LR‐HPV genotyping of clinical samples. PacBio SMRT sequencing provides unbiased genotyping and can detect multiple HPV infections and haplotypes within a genotype. [ABSTRACT FROM AUTHOR]

Single‐molecule white‐light and near‐infrared circularly polarized luminescent materials are effective complements to the demonstrated enhancements of visible emission in the high contrast 3D images or organic light‐emitting diodes. In this contribution, two binaphthalene‐containing luminogenic enantiomers (BIT or BITM) with aggregation‐induced emission are synthesized which exhibit circularly polarized luminescence in solution with dissymmetry factors of ±5.0 × 10−3 and ±4.8 × 10−3, respectively. Additionally, the dual‐fluorescence spectra of single‐molecule white emission (CIE: 0.33, 0.34) in toluene solution are observed with (R)/(S)‐BIT in low polarity solvent originating from locally excited and twisted intramolecular charge‐transfer emission. While (R)/(S)‐BITM only shows single NIR luminescence with peaks at 720 nm in powder state. The nondoped OLEDs exhibit high maximum external quantum efficiencies of up to 4.2% with small efficiency roll‐off and NIR electroluminescence peak at 709 nm. [ABSTRACT FROM AUTHOR]