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This article reports the results of a telephone survey (n = 1,015 respondents) that aims to identify the perceived general family functioning and family resources of Hong Kong Chinese families and their linkage to each other in a rapidly transforming society. The perceived general family functioning of the respondents was average, and the five types of family resources--time, income, human capital, psychological capital, and social capital--of the respondents ranged from average to good. The following family resource domains, in descending order, have accounted for significant variance in perceived general family functioning: income, time spent with family, stress coping efficacy, religion, and satisfaction with the living environment. Our findings provide empirical support for policy formulation and social work practice. [ABSTRACT FROM AUTHOR]

Motherhood is subjectively defined and contextually based. This article describes and unfolds the experience of 22 Chinese mothers in Hong Kong in cultivating a sense of perfect motherhood for their children who have mental or behavioural problems that require psychiatric consultation. The mother, the significant others and the general public perceive the latter as a form of imperfection. The mothering experiences were full of frustrations, ambivalence, stresses and tensions, and were crystallized by the repeated theme of mother-blaming and self-blame by the mother. Despite the hardships, these Chinese mothers have gradually developed self-confidence and pride, and have found ways to cope with the burden of care. Implications for practice are highlighted at the end of the paper. [ABSTRACT FROM AUTHOR]

This qualitative study aims to understand the parenting distress and parental investment of Hong Kong Chinese parents with a child having an emotional or behavioural problem. The parents of 24 children and adolescents who sought psychiatric consultation within the study period were interviewed using open-ended questions. The data revealed a vicious reciprocal interaction in which the symptoms affected the parents psychosocial well-being, which in turn impacted unfavourably on the identified patient. With three exceptions, the parents in this study had engaged in different activities prior to the psychiatric consultation, including information search, changes in the methods of parenting, attempts to reduce family stress, reliance on superstitious beliefs, and reaching out for professional help and social services. The parental investment indicated parents resilience in facing the childs problems. Implications for service development and social work intervention are discussed. [ABSTRACT FROM AUTHOR]

Electrophysiological recording of neurons in deep brain regions using optogenetic stimulation is a powerful method for understanding and regulating the role of complex neural activity in biological behavior and cognitive function. Optogenetic techniques have significantly advanced neuroscience research by enabling the optical manipulation of neural activities. Because of the significance of the technique, constant advancements in implantable optrodes that integrate optical stimulation with low-noise, large-scale electrophysiological recording are in demand to improve the spatiotemporal resolution for various experimental designs and future clinical applications. However, robust and easy-to-use neural optrodes that integrate neural recording arrays with high-intensity light emitting diodes (LEDs) are still lacking. Here, we propose a neural optrode based on Gallium Nitride (GaN) on sapphire technology, which integrates a high-intensity blue LED with a 5 × 2 recording array monolithically for simultaneous neural recording and optogenetic manipulation. To reduce the noise interference between the recording electrodes and the LED, which is in close physical proximity, three metal grounding interlayers were incorporated within the optrode, and their ability to reduce LED-induced artifacts during neural recording was confirmed through both electromagnetic simulations and experimental demonstrations. The capability of the sapphire optrode to record action potentials has been demonstrated by recording the firing of mitral/tuft cells in the olfactory bulbs of mice in vivo. Additionally, the elevation of action potential firing due to optogenetic stimulation observed using the sapphire probe in medial superior olive (MSO) neurons of the gerbil auditory brainstem confirms the capability of this sapphire optrode to precisely access neural activities in deep brain regions under complex experimental designs.

CAR T cell therapies often lack specificity, leading to issues ranging from inadequate antigen targeting to off-tumor toxicities. To counter that lack of specificity, we expanded tumor targeting capabilities with universal CAR and spatially defined CAR T cell engagement with targets through a combination of synthetic biology and biomaterial approaches. We developed a novel framework, called " In situ Mobilization: Polymer Activated Cell Therapies" (IMPACT) for polymer-mediated, anatomical control of IF-THEN gated CAR T cells. With IMPACT, a regulated payload such as a BiTE or tumor-targeting CAR will only be expressed after engineered cells engage a tumor-localizing polymer ("IF" condition). In this first demonstration of IMPACT, we engineered CAR T cells to respond to fluorescein that is displayed by an injectable polymer that binds to and is retained in fibrin deposits in tumor microenvironments. This interaction then drives selective and conditional expression of a protein within tumors ("THEN" condition). Here, we develop the polymer and CAR T cell infrastructure of IMPACT and demonstrate tumor-localized CAR T cell activation in a murine tumor model after the intravenous administration of polymer and engineered T cells.

The recent development of modular universal chimeric antigen receptor (CAR) T-cell platforms that use bifunctional adaptor intermediates to redirect engineered T-cell effector function has greatly expanded the capabilities of adoptive T-cell therapy, enabling safer and more comprehensive cancer treatment. However, universal CAR receptor systems rely on unstable transient recognition of tag-coupled intermediates for T-cell activation, and the array of targeting intermediates has been limited to antibodies and small molecules. Addressing these shortcomings, we engineered universal CAR T-cell receptors that can be covalently modified with synthetic biomaterials in vivo by accelerated SpyCatcher003-SpyTag003 chemistry for cancer-cell targeting. SpyCatcher003-modified CARs, nicknamed DB5 CARs, displayed fast, low-nanomolar reaction kinetics with a synthetic αvβ6-binding peptide that incorporates a SpyTag003 peptide via branched peptide synthesis to comprise a bifunctional intermediate. Prearming DB5 CAR T cells or prelabeling target cells with the bifunctional peptide produced selective CD4 + and CD8 + CAR T-cell responses against αvβ6 + cancer cells in vitro . Furthermore, the synthetic targeting intermediate showed robust DB5 CAR T-cell arming in vivo and selectively reduced αvβ6 + tumor progression in a dual flank xenograft model. We demonstrate the versatility and therapeutic potential of "Cyborg" CAR T-cell therapies that utilize synthetic biomaterials to direct CAR T-cell activity via highly selective bioconjugation that occurs in vivo .

Selective therapeutic targeting of T-cell malignancies is difficult due to the shared lineage between healthy and malignant T cells. Current front-line chemotherapy for these cancers is largely nonspecific, resulting in frequent cases of relapsed/refractory disease. The development of targeting approaches for effectively treating T-cell leukemia and lymphoma thus remains a critical goal for the oncology field. Here, we report the discovery of a DNA aptamer, named HR7A1, that displays low nanomolar affinity for the integrin α4β1 (VLA-4), a marker associated with chemoresistance and relapse in leukemia patients. After truncation of HR7A1 to a minimal binding motif, we demonstrate elevated binding of the aptamer to T-lineage cancer cells over healthy immune cells. Using cryo-EM and competition studies, we find that HR7A1 shares an overlapping binding site on α4β1 with fibronectin and VCAM-1, which has implications for sensitizing blood cancers to chemotherapy. We last characterize barriers to in vivo aptamer translation, including serum stability, temperature-sensitive binding, and short circulation half-life, and synthesize an aptamer-polymer conjugate that addresses these challenges. Future work will seek to validate in vivo targeting of α4β1 + tumors with the conjugate, establishing an aptamer-based biomaterial that can be readily adapted for targeted treatment of T-cell malignancies.

Giant dimeric acceptors (GDAs), a sub-type of acceptor materials for organic solar cells (OSCs), have garnered much attention due to the synergistic advantages of their monomeric and polymeric acceptors, forming a well-defined molecular structure with a giant molecular weight for high efficiency and stability. In this study, for the first time, two new GDAs, DYF-V and DY2F-V are designed and synthesized for OSC operation, by connecting one vinylene linker with the mono-/di-fluorinated end group on two Y-series monomers, respectively. After fluorination, both DYF-V and DY2F-V exhibit bathochromic absorption and denser packing modes due to the stronger intramolecular charge transfer effect and torsion-free backbones. Through precise fluorination, the DYF-V-based devices exhibit the highest performance of 18.63% among the GDA-based OSCs, outperforming its non-fluorinated counterpart, DY-V-based ones (16.53%). Theoretical and morphological results demonstrate that proper fluorination in DYF-V-based devices strengthens intra/intermolecular interactions for enhanced crystallinity, superior phase segregation, and less energy disorder, which is beneficial for fast exciton dissociation, rapid carrier transport, and suppressed charge recombination. The work demonstrates that proper fluorination on GDAs with rigid coplanar backbones is effective for broader photon harvesting, stronger packing, and robust stability in GDA-based OSCs., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

This study puts forth a novel terminal group design to develop medium-band gap Y-series acceptors beyond conventional side-chain engineering. We focused on the strategical integration of an electron-donating methoxy group and an electron-withdrawing halogen atom at benzene-fused terminal groups. This combination precisely modulated the dipole moment and electron density of terminal groups, effectively attenuating intramolecular charge transfer effect, and widening the band gap of acceptors. The incorporation of these terminal groups yielded two asymmetric acceptors, named BTP-2FClO and BTP-2FBrO, both of which exhibited open-circuit voltage (V oc ) as high as 0.96 V in binary devices, representing the highest V OC s among the asymmetric Y-series small molecule acceptors. More importantly, both BTP-2FClO and BTP-2FBrO exhibit modest aggregation behaviors and molecular crystallinity, making them suitable as a third component to mitigate excess aggregation of the PM6 : BTP-eC9 blend and optimize the devices' morphology. As a result, the optimized BTP-2FClO-based ternary organic solar cells (OSCs) achieved a remarkable power conversion efficiency (PCE) of 19.34 %, positioning it among the highest-performing OSCs. Our study highlights the molecular design importance on manipulating dipole moments and electron density in developing medium-band gap acceptors, and offers a highly efficient third component for high-performance ternary OSCs., (© 2025 Wiley-VCH GmbH.)

Background : Mental health issues are increasingly prominent worldwide, posing significant threats to patients and deeply affecting their families and social relationships. Traditional diagnostic methods are subjective and delayed, indicating the need for an objective and effective early diagnosis method. Methods : To this end, this paper proposes a lightweight detection method for multi-mental disorders with fewer data sources, aiming to improve diagnostic procedures and enable early patient detection. First, the proposed method takes Electroencephalography (EEG) signals as sources, acquires brain rhythms through Discrete Wavelet Decomposition (DWT), and extracts their approximate entropy, fuzzy entropy, permutation entropy, and sample entropy to establish the entropy-based matrix. Then, six kinds of conventional machine learning classifiers, including Support Vector Machine (SVM), k-Nearest Neighbors (kNN), Naive Bayes (NB), Generalized Additive Model (GAM), Linear Discriminant Analysis (LDA), and Decision Tree (DT), are adopted for the entropy-based matrix to achieve the detection task. Their performances are assessed by accuracy, sensitivity, specificity, and F1-score. Concerning these experiments, three public datasets of schizophrenia, epilepsy, and depression are utilized for method validation. Results : The analysis of the results from these datasets identifies the representative single-channel signals (schizophrenia: O1, epilepsy: F3, depression: O2), satisfying classification accuracies (88.10%, 75.47%, and 89.92%, respectively) with minimal input. Conclusions : Such performances are impressive when considering fewer data sources as a concern, which also improves the interpretability of the entropy features in EEG, providing a reliable detection approach for multi-mental disorders and advancing insights into their underlying mechanisms and pathological states.

Electrophysiological recordings of neurons in deep brain regions using optogenetic stimulation are essential to understanding and regulating the role of complex neural activity in biological behavior and cognitive function. Optogenetic techniques have significantly advanced neuroscience research by enabling the optical manipulation of neural activities. Because of the significance of the technique, constant advancements in implantable optrodes that integrate optical stimulation with low-noise, large-scale electrophysiological recording are in demand to improve the spatiotemporal resolution for various experimental designs and future clinical applications. However, robust and easy-to-use neural optrodes that integrate neural recording arrays with high-intensity light emitting diodes (LEDs) are still lacking. Here, we propose a neural optrode based on Gallium Nitride (GaN) on sapphire technology, which integrates a high-intensity blue LED with a 5x2 recording array monolithically for simultaneous neural recording and optogenetic manipulation. To reduce the noise interference between the recording electrodes and the LED, which is in close physical proximity, three metal grounding interlayers were incorporated within the optrode, and their ability to reduce LED-induced artifacts during neural recording was confirmed through both electromagnetic simulations and experimental demonstrations. The capability of the sapphire optrode to record action potentials has been demonstrated by recording the firing of mitral/tuft cells in the olfactory bulbs of mice in vivo. Additionally, the elevation of action potential firing due to optogenetic stimulation observed using the sapphire probe in medial superior olive (MSO) neurons of the gerbil auditory brainstem confirms the capability of this sapphire optrode to precisely access neural activities in deep brain regions under complex experimental designs.

Multiple helicenes display distinct aromatic cores characterized by highly twisted rings that are shared or fused with constituent helicene moieties. Diversifying these aromatic cores unlocks avenues for creating multiple helicenes with distinct properties and topologies. Herein we report the synthesis of a quadruple[6]helicene featuring pyrene as the aromatic core. The synthesis involved key steps of the annulative π-extension reaction and Scholl reaction. By extending multiple helicenes along the axial direction, the degree of contortion of the aromatic core can be controlled from nearly flat to highly twisted. Notably, quadruple[6]helicene exhibits a significant red-shift of 0.49 eV compared to quadruple[4]helicenes, of which the red-shift arises from both π-extension and augmented effective conjugation due to enhanced twisting. Quantum chemical calculations demonstrate that the degree of contortion in the pyrene core adeptly governs the energy levels of the HOMO and LUMO, which offers an alternative strategy beyond mere enlargement of the π backbone. An intriguing serendipitous finding reveals the formation of one-molecule-thick supramolecular homochiral nanosheets through self-interlocking interactions of enantiomers in single crystals, a rare packing motif for multiple helicenes., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Co-published by University of Science and Technology of China and American Chemical Society.)

Indoor photovoltaics (IPVs) are garnering increasing attention from both the academic and industrial communities due to the pressing demand of the ecosystem of Internet-of-Things. All-polymer solar cells (all-PSCs), emerging as a sub-type of organic photovoltaics, with the merits of great film-forming properties, remarkable morphological and light stability, hold great promise to simultaneously achieve high efficiency and long-term operation in IPV's application. However, the dearth of polymer acceptors with medium-bandgap has impeded the rapid development of indoor all-PSCs. Herein, a highly efficient medium-bandgap polymer acceptor (PYFO-V) is reported through the synergistic effects of side chain engineering and linkage modulation and applied for indoor all-PSCs operation. As a result, the PM6:PYFO-V-based indoor all-PSC yields the highest efficiency of 27.1% under LED light condition, marking the highest value for reported binary indoor all-PSCs to date. More importantly, the blade-coated devices using non-halogenated solvent (o-xylene) maintain an efficiency of over 23%, demonstrating the potential for industry-scale fabrication. This work not only highlights the importance of fine-tuning intramolecular charge transfer effect and intrachain coplanarity in developing high-performance medium-bandgap polymer acceptors but also provides a highly efficient strategy for indoor all-PSC application., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Intracardiac wireless communication is crucial for the development of multi-chamber leadless cardiac pacemakers (LCP). However, the time-varying characteristics of intracardiac channel pose major challenges. As such, mastering the dynamic conduction properties of the intracardiac channel and modeling the equivalent time-varying channel are imperative for realizing LCP multi-chamber pacing. In this article, we present a limiting volume variational approach based on the electrical properties of cardiac tissues and trends in chamber volume variation. This approach was used to establish a quasi-static and a continuous time-varying equivalent circuit model of an intracardiac channel. An equivalence analysis was conducted on the model, and a discrete time-varying equivalent circuit phantom grounded on the cardiac cycle was subsequently established. Moreover, an ex vivo cardiac experimental platform was developed for verification. Results indicate that in the frequency domain, the congruence between phantom and ex vivo experimental outcomes is as high as 94.3%, affirming the reliability of the equivalent circuit model. In the time domain, the correlation is up to 75.3%, corroborating its effectiveness. The proposed time-varying equivalent circuit model exhibits stable and standardized dynamic attributes, serving as a powerful tool for addressing time-varying challenges and simplifying in vivo or ex vivo experiments.

Globally, traumatic injury is a leading cause of suffering and death. The ability to curtail damage and ensure survival after major injury requires a time-sensitive response balancing organ perfusion, blood loss, and portability, underscoring the need for novel therapies for the prehospital environment. Currently, there are few options available for damage control resuscitation (DCR) of trauma victims. We hypothesize that synthetic polymers, which are tunable, portable, and stable under austere conditions, can be developed as effective injectable therapies for trauma medicine. In this work, we design injectable polymers for use as low volume resuscitants (LVRs). Using RAFT polymerization, we evaluate the effect of polymer size, architecture, and chemical composition upon both blood coagulation and resuscitation in a rat hemorrhagic shock model. Our therapy is evaluated against a clinically used colloid resuscitant, Hextend. We demonstrate that a radiant star poly(glycerol monomethacrylate) polymer did not interfere with coagulation while successfully correcting metabolic deficit and resuscitating animals from hemorrhagic shock to the desired mean arterial pressure range for DCR - correcting a 60 % total blood volume (TBV) loss when given at only 10 % TBV. This highly portable and non-coagulopathic resuscitant has profound potential for application in trauma medicine., (© 2024 Wiley-VCH GmbH.)

Optogenetics-based integrated photoelectrodes with high spatiotemporal resolution play an important role in studying complex neural activities. However, the photostimulation artifacts caused by the high level of integration and the high impedance of metal recording electrodes still hinder the application of photoelectrodes for optogenetic studies of neural circuits. In this study, a neural optrode fabricated on sapphire GaN material was proposed, and 4 μLEDs and 14 recording microelectrodes were monolithically integrated on a shank. Poly(3,4-ethylenedioxythiophene)/polystyrenesulfonate and multiwalled carbon nanotubes (PEDOT:PSS-MWCNT) and poly(3,4-ethylenedioxythiophene) and graphene oxide (PEDOT-GO) composite films were deposited on the surface of the recording microelectrode by electrochemical deposition. The results demonstrate that compared with the gold microelectrode, the impedances of both composite films reduced by more than 98%, and the noise amplitudes decreased by 70.73 and 87.15%, respectively, when exposed to light stimulation. Adjusting the high and low levels, we further reduced the noise amplitude by 48.3%. These results indicate that modifying the electrode surface by a polymer composite film can effectively enhance the performance of the microelectrode and further promote the application of the optrode in the field of neuroscience., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

A new armchair carbon nanobelt is successfully synthesized by tuning the regioselectivity of the Scholl reaction of 1,1':2',1'':4'',1''':2''',1''''-quinquephenyl. This nanobelt exhibits a preferential binding affinity towards C 70 over C 60 as found from photoluminescence titration experiments.

With the recent advances in neoantigen identification, peptide-based cancer vaccines offer substantial potential in the field of immunotherapy. However, rapid clearance, low immunogenicity, and insufficient antigen-presenting cell (APC) uptake limit the efficacy of peptide-based cancer vaccines. This review explores the barriers hindering vaccine efficiency, highlights recent advancements in synthetic delivery systems, and features strategies for the key delivery steps of lymph node (LN) drainage, APC delivery, cross-presentation strategies, and adjuvant incorporation. This paper also discusses the design of preclinical studies evaluating vaccine efficiency, including vaccine administration routes and murine tumor models., (Copyright © 2024 Kefan Song and Suzie H. Pun.)

The Stimulator of Interferon Genes (STING) pathway is a promising target for cancer immunotherapy. Despite recent advances, therapies targeting the STING pathway are often limited by routes of administration, suboptimal STING activation, or off-target toxicity. Here, we report a dendritic cell (DC)-targeted polymeric prodrug platform (polySTING) that is designed to optimize intracellular delivery of a diamidobenzimidazole (diABZI) small-molecule STING agonist while minimizing off-target toxicity after parenteral administration. PolySTING incorporates mannose targeting ligands as a comonomer, which facilitates its uptake in CD206 + /mannose receptor + professional antigen-presenting cells (APCs) in the tumor microenvironment (TME). The STING agonist is conjugated through a cathepsin B-cleavable valine-alanine (VA) linker for selective intracellular drug release after receptor-mediated endocytosis. When administered intravenously in tumor-bearing mice, polySTING selectively targeted CD206 + /mannose receptor + APCs in the TME, resulting in increased cross-presenting CD8 + DCs, infiltrating CD8 + T cells in the TME as well as maturation across multiple DC subtypes in the tumor-draining lymph node (TDLN). Systemic administration of polySTING slowed tumor growth in a B16-F10 murine melanoma model as well as a 4T1 murine breast cancer model with an acceptable safety profile. Thus, we demonstrate that polySTING delivers STING agonists to professional APCs after systemic administration, generating efficacious DC-driven antitumor immunity with minimal side effects. This new polymeric prodrug platform may offer new opportunities for combining efficient targeted STING agonist delivery with other selective tumor therapeutic strategies., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

In this article, we proposed a novel fault-tolerant control scheme for quadrotor unmanned aerial vehicles (UAVs) based on spiking neural networks (SNNs), which leverages the inherent features of neural network computing to significantly enhance the reliability and robustness of UAV flight control. Traditional control methods are known to be inadequate in dealing with complex and real-time sensor data, which results in poor performance and reduced robustness in fault-tolerant control. In contrast, the temporal processing, parallelism, and nonlinear capacity of SNNs enable the fault-tolerant control scheme to process vast amounts of sensory data with the ability to accurately identify and respond to faults. Furthermore, SNNs can learn and adjust to new environments and fault conditions, providing effective and adaptive flight control. The proposed SNN-based fault-tolerant control scheme demonstrates significant improvements in control accuracy and robustness compared with conventional methods, indicating its potential applicability and suitability for a range of UAV flight control scenarios.

Controlling the biodistribution of protein- and nanoparticle-based therapeutic formulations remains challenging. In vivo library selection is an effective method for identifying constructs that exhibit desired distribution behavior; library variants can be selected based on their ability to localize to the tissue or compartment of interest despite complex physiological challenges. Here, we describe further development of an in vivo library selection platform based on self-assembling protein nanoparticles encapsulating their own mRNA genomes (synthetic nucleocapsids or synNCs). We tested two distinct libraries: a low-diversity library composed of synNC surface mutations (45 variants) and a high-diversity library composed of synNCs displaying miniproteins with binder-like properties (6.2 million variants). While we did not identify any variants from the low-diversity surface library that yielded therapeutically relevant changes in biodistribution, the high-diversity miniprotein display library yielded variants that shifted accumulation toward lungs or muscles in just two rounds of in vivo selection. Our approach should contribute to achieving specific tissue homing patterns and identifying targeting ligands for diseases of interest.

Ischaemic cardiovascular disease is associated with tissue hypoxia as a significant determinant of angiogenic dysfunction and adverse remodelling. While cord blood-derived endothelial colony-forming cells (CB-ECFCs) hold clear therapeutic potential due to their enhanced angiogenic and proliferative capacity, their impaired functionality within the disease microenvironment represents a major barrier to clinical translation. The aim of this study was to define the specific contribution of NOX4 NADPH oxidase, which we previously reported as a key CB-ECFC regulator, to hypoxia-induced dysfunction and its potential as a therapeutic target. CB-ECFCs exposed to experimental hypoxia demonstrated downregulation of NOX4-mediated reactive oxygen species (ROS) signalling linked with a reduced tube formation, which was partially restored by NOX4 plasmid overexpression. siRNA knockdown of placenta-specific 8 (PLAC8), identified by microarray analysis as an upstream regulator of NOX4 in hypoxic versus normoxic CB-ECFCs, enhanced tube formation, NOX4 expression and hydrogen peroxide generation, and induced several key transcription factors associated with downstream Nrf2 signalling. Taken together, these findings indicated that activation of the PLAC8-NOX4 signalling axis improved CB-ECFC angiogenic functions in experimental hypoxia, highlighting this pathway as a potential target for protecting therapeutic cells against the ischaemic cardiovascular disease microenvironment.

Trauma leading to severe hemorrhage and shock on average kills patients within 3 to 6 hours after injury. With average prehospital transport times reaching 1-6 hours in low- to middle-income countries, stopping the bleeding and reversing hemorrhagic shock is vital. First-generation intravenous hemostats rely on traditional drug delivery platforms, such as self-assembling systems, fabricated nanoparticles, and soluble polymers due to their active targeting, biodistribution, and safety. We discuss some challenges translating these therapies to patients, as very few have successfully made it through preclinical evaluation in large-animals, and none have translated to the clinic. Finally, we discuss the physiology of hemorrhagic shock, highlight a new low volume resuscitant (LVR) PEG-20k, and end with considerations for the rational design of LVRs., Competing Interests: Declaration of competing interest The authors declare no competing financial interests. Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

The manufacturing process of chimeric antigen receptor T cell therapies includes isolation systems that provide pure T cells. Current magnetic-activated cell sorting and immunoaffinity chromatography methods produce desired cells with high purity and yield but require expensive equipment and reagents and involve time-consuming incubation steps. Here, we demonstrate that aptamers can be employed in a continuous-flow resin platform for both depletion of monocytes and selection of CD8 + T cells from peripheral blood mononuclear cells at low cost with high purity and throughput. Aptamer-mediated cell selection could potentially enable fully synthetic, traceless isolations of leukocyte subsets from a single isolation system.

Speech impairment is one of the most serious problems for patients with communication disorders, e.g., stroke survivors. The brain-computer interface (BCI) systems have shown the potential to alternatively control or rehabilitate the neurological damages in speech production. The effects of different cortical regions in speech-based BCI systems are essential to be studied, which are favorable for improving the performance of speech-based BCI systems. This work aimed to explore the impacts of different speech-related cortical regions in the electroencephalogram (EEG) based classification of seventy spoken Mandarin monosyllables carrying four vowels and four lexical tones. Seven audible speech production-related cortical regions were studied, involving Broca's and Wernicke's areas, auditory cortex, motor cortex, prefrontal cortex, sensory cortex, left brain, right brain, and whole brain. Following the previous studies in which EEG signals were collected from ten subjects during Mandarin speech production, the features of EEG signals were extracted by the Riemannian manifold method, and a linear discriminant analysis (LDA) was regarded as a classifier to classify different vowels and lexical tones. The results showed that when using electrodes from whole brain, the classifier reached the best performances, which were 48.5% for lexical tones and 70.0% for vowels, respectively. The vowel classification results under Broca's and Wernicke's areas, auditory cortex, or prefrontal cortex were higher than those under the motor cortex or sensory cortex. No such differences were observed in the lexical tone classification task.

Human alpha oscillation (7-13 Hz) has been extensively studied over the years for its connection with cognition. The individual alpha frequency (IAF), defined as the frequency that provides the highest power in the alpha band, shows a positive correlation with cognitive processes. The modulation of alpha activities has been accomplished through various approaches aimed at improving cognitive performance. However, very few studies focused on the direct modulation of IAF by shifting the peak frequency, and the understanding of IAF modulation remains highly limited. In this study, IAFs of healthy young adults were up-regulated through short-term neurofeedback training using haptic feedback. The results suggest that IAFs have good trainability and are up-regulated, also that IAFs are correlated with the enhanced cognitive performance in mental rotation and n-back tests compared to sham-neurofeedback control. This study demonstrates the feasibility of self-regulating IAF for cognition enhancement and provides potential therapeutic benefits for cognitive-impaired patients.

Aptamers are single-stranded nucleic acids that bind and recognize targets much like antibodies. Recently, aptamers have garnered increased interest due to their unique properties, including inexpensive production, simple chemical modification, and long-term stability. At the same time, aptamers possess similar binding affinity and specificity as their protein counterpart. In this review, we discuss the aptamer discovery process as well as aptamer applications to biosensors and separations. In the discovery section, we describe the major steps of the library selection process for aptamers, called systematic evolution of ligands by exponential enrichment (SELEX). We highlight common approaches and emerging strategies in SELEX, from starting library selection to aptamer-target binding characterization. In the applications section, we first evaluate recently developed aptamer biosensors for SARS-CoV-2 virus detection, including electrochemical aptamer-based sensors and lateral flow assays. Then we discuss aptamer-based separations for partitioning different molecules or cell types, especially for purifying T cell subsets for therapeutic applications. Overall, aptamers are promising biomolecular tools and the aptamer field is primed for expansion in biosensing and cell separation., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Spiking neural networks (SNNs) are more energy- and resource-efficient than artificial neural networks (ANNs). However, supervised SNN learning is a challenging task due to non-differentiability of spikes and computation of complex terms. Moreover, the design of SNN learning engines is not an easy task due to limited hardware resources and tight energy constraints. In this article, a novel hardware-efficient SNN back-propagation scheme that offers fast convergence is proposed. The learning scheme does not require any complex operation such as error normalization and weight-threshold balancing, and can achieve an accuracy of around 97.5% on MNIST dataset using only 158,800 synapses. The multiplier-less inference engine trained using the proposed hard sigmoid SNN training (HaSiST) scheme can operate at a frequency of 135 MHz and consumes only 1.03 slice registers per synapse, 2.8 slice look-up tables, and can infer about 0.03[Formula: see text] features in a second, equivalent to 9.44 giga synaptic operations per second (GSOPS). The article also presents a high-speed, cost-efficient SNN training engine that consumes only 2.63 slice registers per synapse, 37.84 slice look-up tables per synapse, and can operate at a maximum computational frequency of around 50 MHz on a Virtex 6 FPGA., (© 2023. The Author(s).)

Peptide cancer vaccines have had limited clinical success despite their safety, characterization and production advantages. We hypothesize that the poor immunogenicity of peptides can be surmounted by delivery vehicles that overcome the systemic, cellular and intracellular drug delivery barriers faced by peptides. Here, we introduce Man-VIPER, a self-assembling (40-50 nm micelles), pH-sensitive, mannosylated polymeric peptide delivery platform that targets dendritic cells in the lymph nodes, encapsulates peptide antigens at physiological pH, and facilitates endosomal release of antigens at acidic endosomal pH through a conjugated membranolytic peptide melittin. We used d-melittin to improve the safety profile of the formulation without compromising the lytic properties. We evaluated polymers with both releasable (Man-VIPER-R) or non-releasable (Man-VIPER-NR) d-melittin. Both Man-VIPER polymers exhibited superior endosomolysis and antigen cross-presentation compared to non-membranolytic d-melittin-free analogues (Man-AP) in vitro. In vivo, Man-VIPER polymers demonstrated an adjuvanting effect, induced the proliferation of antigen-specific cytotoxic T cells and helper T cells compared to free peptides and Man-AP. Remarkably, antigen delivery with Man-VIPER-NR generated significantly more antigen-specific cytotoxic T cells than Man-VIPER-R in vivo. As our candidate for a therapeutic vaccine, Man-VIPER-NR exerted superior efficacy in a B16F10-OVA tumor model. These results highlight Man-VIPER-NR as a safe and powerful peptide cancer vaccine platform for cancer immunotherapy., (Copyright © 2023. Published by Elsevier B.V.)

Gene therapy approaches that utilize Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) ribonucleases have tremendous potential to treat human disease. However, CRISPR therapies delivered by integrating viral vectors are limited by potential off-target genome editing caused by constitutive activation of ribonuclease functions. Thus, biomaterial formulations are being used for the delivery of purified CRISPR components to increase the efficiency and safety of genome editing approaches. We previously demonstrated that a novel peptide identified by phage display, TAxI-peptide, mediates delivery of recombinant proteins into neurons. In this report we utilized NeutrAvidin protein to formulate neuron-targeted genome-editing nanoparticles. Cas12a ribonucleases was loaded with biotinylated guide RNA and biotinylated TAxI-peptide onto NeutrAvidin protein to coordinate the formation a targeted ribonuclease protein (RNP) complex. TAxI-RNP complexes are polydisperse with a 14.3 nm radius. The nanoparticles are stable after formulation and show good stability in the presence of normal mouse serum. TAxI-RNP nanoparticles increased neuronal delivery of Cas12a in reporter mice, resulting in induced tdTomato expression after direct injection into the dentate gyrus of the hippocampus. TAxI-RNP nanoparticles also increased genome editing efficacy in hippocampal neurons versus glia. These studies demonstrate the ability to assemble RNP nanoformulations with NeutrAvidin by binding biotinylated peptides and gRNA-loaded Cas12a ribonucleases into protein nanoparticles that target CRISPR delivery to specific cell-types in vivo. The potential to deliver CRISPR nanoparticles to specific cell-types and control off-target delivery to further reduce deleterious genome editing is essential for the creation of viable therapies to treat nervous system disease., Competing Interests: Declaration of Competing Interest K Lee is a co-founder and employee of GenEdit Inc. Co-authors N. Murthy, S. H. Pun and D. L. Sellers declare no other competing financial interest., (Copyright © 2022. Published by Elsevier B.V.)

Despite remarkable advances over the past several decades, many therapeutic nanomaterials fail to overcome major in vivo delivery barriers. Controlling immunogenicity, optimizing biodistribution, and engineering environmental responsiveness are key outstanding delivery problems for most nanotherapeutics. However, notable exceptions exist including some lipid and polymeric nanoparticles, some virus-based nanoparticles, and nanoparticle vaccines where immunogenicity is desired. Self-assembling protein nanoparticles offer a powerful blend of modularity and precise designability to the field, and have the potential to solve many of the major barriers to delivery. In this review, we provide a brief overview of key designable features of protein nanoparticles and their implications for therapeutic delivery applications. We anticipate that protein nanoparticles will rapidly grow in their prevalence and impact as clinically relevant delivery platforms.

Optrodes, which are single shaft neural probes integrated with microelectrodes and optical light sources, offer a remarkable opportunity to simultaneously record and modulate neural activities using light within an animal's brain; however, a common problem with optrodes is that stimulation artifacts can be observed in the neural recordings of microelectrodes when the light source on the optrode is activated. These stimulation artifacts are undesirable contaminants, and they cause interpretation complexity when analyzing the recorded neural activities. In this paper, we tried to mitigate the effects of the stimulation artifacts by developing a low-noise, double-sided optrode integrated with multiple Electromagnetic Shielding (EMS) layers. The LED and microelectrodes were constructed separately on the top epitaxial and bottom substrate layers, and EMS layers were used to separate the microelectrodes and LED to reduce signal cross-talks. Compared with conventional single-sided designs, in which the LED and microelectrodes are constructed on the same side, our results indicate that double-sided optrodes can significantly reduce the presence of stimulation artifacts. In addition, the presence of stimulation artifacts can further be reduced by decreasing the voltage difference and increasing the rise/fall time of the driving LED pulsed voltage. With all these strategies, the presence of stimulation artifacts was significantly reduced by ~76%. As well as stimulation suppression, the sapphire substrate also provided strong mechanical stiffness and support to the optrodes, as well as improved electronic stability, thus making the double-sided sapphire optrodes highly suitable for optogenetic neuroscience research on animal models.

We demonstrated a new method for temperature measurement inside a fiber ring laser (FRL) cavity. Different from traditional FRL temperature sensing system which need additional filter working as a sensor, a micro-fiber coupler (MFC) was designed as a beam splitter, filter, and temperature sensor. In addition, isopropanol, a liquid with very high photothermal coefficient, is selectively filled in the MFC in order to improve the sensitivity of the system on temperature. In the dynamic range of 20-40 °C, we obtained a good temperature sensitivity of -1.29 nm/°C, with linear fitting up to 0.998. Benefiting from the advantages of laser sensing, the acquired laser has a 3 - dB bandwidth of less than 0.2 nm and a signal-to-noise ratio (SNR) of up to 40 dB. The proposed sensor has a low cost and high sensitivity, which is expected to be used in biomedical health detection, real-time monitoring of ocean temperature, and other application scenarios.

In both biomedical research and clinical cell therapy manufacturing, there is a need for cell isolation systems that recover purified cells in the absence of any selection agent. Reported traceless cell isolation methods using engineered antigen-binding fragments or aptamers have been limited to processing a single cell type at a time. There remains an unmet need for cell isolation processes that rapidly sort multiple target cell types. Here, we utilized two aptamers along with their designated complementary strands (reversal agents) to tracelessly isolate two cell types from a mixed cell population with one aptamer-labeling step and two sequential cell elution steps with reversal agents. We engineered a CD71-binding aptamer (rvCD71apt) and a reversal agent pair to be used simultaneously with our previously reported traceless purification approach using the CD8 aptamer (rvCD8apt) and its reversal agent. We verified the compatibility of the two aptamer displacement mechanisms by flow cytometry and the feasibility of incorporating rvCD71apt with a magnetic solid state. We then combined rvCD71apt with rvCD8apt to isolate activated CD4 + T cells and resting CD8 + cells by eluting these target cells into separate fractions with orthogonal strand displacements. This is the first demonstration of isolating different cell types using two aptamers and reversal agents at the same time. Potentially, different or more aptamers can be included in this traceless multiplexed isolation system for diverse applications with a shortened operation time and a lower production cost.

The past decade has witnessed remarkable success in the synthesis of curved polycyclic aromatics through Scholl reactions which enable oxidative aryl-aryl coupling even in company with the introduction of significant steric strain. These curved polycyclic aromatics are not only unique objects of structural organic chemistry in relation to the nature of aromaticity but also play an important role in bottom-up approaches to precise synthesis of nanocarbons of unique topology. Moreover, they have received considerable attention in the fields of supramolecular chemistry and organic functional materials because of their interesting properties and promising applications. Despite the great success of Scholl reactions in synthesis of curved polycyclic aromatics, the outcome of a newly designed substrate in the Scholl reaction still cannot be predicted in a generic and precise manner largely due to limited understanding on the reaction mechanism and possible rearrangement processes. This review provides an overview of Scholl reactions with a focus on their applications in synthesis of curved polycyclic aromatics with interesting structures and properties and aims to shed light on the key factors that affect Scholl reactions in synthesizing sterically strained polycyclic aromatics.

During the COVID-19 (coronavirus disease 2019) pandemic, several SARS-CoV-2 variants of concern emerged, including the Omicron variant, which has enhanced infectivity and immune invasion. Many antibodies and aptamers that bind the spike (S) of previous strains of SARS-CoV-2 either do not bind or bind with low affinity to Omicron S. In this study, we report a high-affinity S ARS- C oV-2 O micron R BD-binding aptam e r (SCORe) that binds Omicron BA.1 and BA.2 RBD with nanomolar K D1 . We employ aptamers SCORe.50 and SNAP4.74 in a multiplexed lateral flow assay (LFA) to distinguish between Omicron and wild-type S at concentrations as low as 100 pM. Finally, we show that SCORe.50 and its dimerized form SCOReD can neutralize Omicron S-pseudotyped virus infection of ACE2-overexpressing cells by >70%. SCORe therefore has potential applications in COVID-19 rapid diagnostics as well as in viral neutralization.

Herein, we report robust π-conjugated radical cations resulting from the oxidation of hexabenzoperylene (HBP) derivatives, HBP-B and HBP-H, which have butyl and hexyl groups, respectively, attached to the same twisted double helicene π-backbone. The radical cation of HBP-B was successfully crystallized in the form of hexafluorophosphate, which exhibited conductivity as high as 1.32 ± 0.04 S cm -1 . Photochemical oxidation of HBP-H by molecular oxygen led to the formation of its radical cation in the solid state, as found with different techniques. This allowed the organic field effect transistor of HBP-H to function as a nonvolatile optoelectronic memory, with the memory switching contrast above 10 3 and long-term stability without using a floating gate, an electret layer, or photochromic molecules.

The clinical manufacturing of chimeric antigen receptor (CAR) T cells includes cell selection, activation, gene transduction, and expansion. While the method of T-cell selection varies across companies, current methods do not actively eliminate the cancer cells in the patient's apheresis product from the healthy immune cells. Alarmingly, it has been found that transduction of a single leukemic B cell with the CAR gene can confer resistance to CAR T-cell therapy and lead to treatment failure. In this study, we report the identification of a novel high-affinity DNA aptamer, termed tJBA8.1, that binds transferrin receptor 1 (TfR1), a receptor broadly upregulated by cancer cells. Using competition assays, high resolution cryo-EM, and de novo model building of the aptamer into the resulting electron density, we reveal that tJBA8.1 shares a binding site on TfR1 with holo-transferrin, the natural ligand of TfR1. We use tJBA8.1 to effectively deplete B lymphoma cells spiked into peripheral blood mononuclear cells with minimal impact on the healthy immune cell composition. Lastly, we present opportunities for affinity improvement of tJBA8.1. As TfR1 expression is broadly upregulated in many cancers, including difficult-to-treat T-cell leukemias and lymphomas, our work provides a facile, universal, and inexpensive approach for comprehensively removing cancerous cells from patient apheresis products for safe manufacturing of adoptive T-cell therapies.

Recently, electroencephalography (EEG) signals have shown great potential for emotion recognition. Nevertheless, multichannel EEG recordings lead to redundant data, computational burden, and hardware complexity. Hence, efficient channel selection, especially single-channel selection, is vital. For this purpose, a technique termed brain rhythm sequencing (BRS) that interprets EEG based on a dominant brain rhythm having the maximum instantaneous power at each 0.2 s timestamp has been proposed. Then, dynamic time warping (DTW) is used for rhythm sequence classification through the similarity measure. After evaluating the rhythm sequences for the emotion recognition task, the representative channel that produces impressive accuracy can be found, which realizes single-channel selection accordingly. In addition, the appropriate time segment for emotion recognition is estimated during the assessments. The results from the music emotion recognition (MER) experiment and three emotional datasets (SEED, DEAP, and MAHNOB) indicate that the classification accuracies achieve 70-82% by single-channel data with a 10 s time length. Such performances are remarkable when considering minimum data sources as the primary concerns. Furthermore, the individual characteristics in emotion recognition are investigated based on the channels and times found. Therefore, this study provides a novel method to solve single-channel selection for emotion recognition.

The COVID-19 pandemic is among the greatest health and socioeconomic crises in recent history. Although COVID-19 vaccines are being distributed, there remains a need for rapid testing to limit viral spread from infected individuals. We previously identified the SARS-CoV-2 spike protein N-terminal domain (NTD) binding DNA aptamer 1 (SNAP1) for detection of SARS-CoV-2 virus by aptamer-antibody sandwich enzyme-linked immunoassay (ELISA) and lateral flow assay (LFA). In this work, we identify a new aptamer that also binds at the NTD, named SARS-CoV-2 spike protein NTD-binding DNA aptamer 4 (SNAP4). SNAP4 binds with high affinity (<30 nM) for the SARS-CoV-2 spike protein, a 2-fold improvement over SNAP1. Furthermore, we utilized both SNAP1 and SNAP4 in an aptamer sandwich LFA (AptaFlow), which detected SARS-CoV-2 UV-inactivated virus at concentrations as low as 10 6 copies/mL. AptaFlow costs <$1 per test to produce, provides results in <1 h, and detects SARS-CoV-2 at concentrations that indicate higher viral loads and a high probability of contagious transmission. AptaFlow is a potential approach for a low-cost, convenient antigen test to aid the control of the COVID-19 pandemic.

Peptide-based cancer vaccines offer production and safety advantages but have had limited clinical success due to their intrinsic instability, rapid clearance, and low cellular uptake. Nanoparticle-based delivery vehicles can improve the in vivo stability and cellular uptake of peptide antigens. Here, a well-defined, self-assembling mannosylated polymer is developed for anticancer peptide antigen delivery. The amphiphilic polymer is prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization, and the peptide antigens are conjugated to the pH-sensitive hydrophobic block through the reversible disulfide linkage for selective release after cell entry. The polymer-peptide conjugates self-assemble into sub-100 nm micelles at physiological pH and dissociate at endosomal pH. The mannosylated micellar corona increases the accumulation of vaccine cargoes in the draining inguinal lymph nodes and facilitates nanoparticle uptake by professional antigen presenting cells. In vivo studies demonstrate that the mannosylated micelle formulation improves dendritic cell activation and enhances antigen-specific T cell responses, resulting in higher antitumor immunity in tumor-bearing mice compared to free peptide antigen. The mannosylated polymer is therefore a simple and promising platform for the delivery of peptide cancer vaccines., (© 2021 Wiley-VCH GmbH.)

SARS-CoV-2 has been the cause of a global pandemic since 2019 and remains a medical urgency. siRNA-based therapies are a promising strategy to fight viral infections. By targeting a specific region of the viral genome, siRNAs can efficiently downregulate viral replication and suppress viral infection. However, to achieve the desired therapeutic activity, siRNA requires a suitable delivery system. The VIPER (virus-inspired polymer for endosomal release) block copolymer has been reported as promising delivery system for both plasmid DNA and siRNA in the past years. It is composed of a hydrophilic block for condensation of nucleic acids as well as a hydrophobic, pH-sensitive block that, at acidic pH, exposes the membrane lytic peptide melittin, which enhances endosomal escape. In this study, we aimed at developing a formulation for pulmonary administration of siRNA to suppress SARS-CoV-2 replication in lung epithelial cells. After characterizing siRNA/VIPER polyplexes, the activity and safety profile were confirmed in a lung epithelial cell line. To further investigate the activity of the polyplexes in a more sophisticated cell culture system, an air-liquid interface (ALI) culture was established. siRNA/VIPER polyplexes reached the cell monolayer and penetrated through the mucus layer secreted by the cells. Additionally, the activity against wild-type SARS-CoV-2 in the ALI model was confirmed by qRT-PCR. To investigate translatability of our findings, the activity against SARS-CoV-2 was tested ex vivo in human lung explants. Here, siRNA/VIPER polyplexes efficiently inhibited SARS-CoV-2 replication. Finally, we verified the delivery of siRNA/VIPER polyplexes to lung epithelial cells in vivo, which represent the main cellular target of viral infection in the lung. In conclusion, siRNA/VIPER polyplexes efficiently delivered siRNA to lung epithelial cells and mediated robust downregulation of viral replication both in vitro and ex vivo without toxic or immunogenic side effects in vivo, demonstrating the potential of local siRNA delivery as a promising antiviral therapy in the lung., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Inspired by the biological use of a combination of precision and self-assembly to achieve exquisite control and diversity from 20 natural amino acids, there is considerable scope for the development of synthetic precision materials with complex architecture that can access advanced function for biomedical applications. Single cyclic polymers (SCPs) have been shown to offer different and often better performance compared to their linear analogues. Because multicyclic topology in nature offers enhanced effects relative to single cyclization, we hypothesize that multicyclic polymers (MCPs) would access unique features compared to SCPs. However, there are currently quite limited ways to efficiently synthesize MCPs and to precisely modulate the valency of cyclic units. In this work, we report for the first time a straightforward and robust strategy to synthesize MCPs with controllable valency via facile one-pot statistical reversible addition-fragmentation chain transfer (RAFT) copolymerization. We use this strategy to synthesize biocompatible MCPs based on the most classic and important biocompatible polymers of oligo (ethylene glycol) (OEG) and cyclic poly(ε-caprolactone) (cPCL), which can further self-assemble into well-defined nanostructures. We then apply these MCP-based formulations as drug delivery vehicles and demonstrate greater colloidal stability with a low critical micelle concentration (CMC) of 80.3 nM, larger drug loading capacity, higher cellular uptake efficiency, more tumor accumulation, and increased anti-tumor efficacy in murine tumor models compared to SCP-based analogues. We believe this cumulative work demonstrating facile synthesis of MCPs and demonstration of multicyclic topology-enhanced anti-cancer efficiency in vivo provides key technologies and concepts to the burgeoning field of cyclic topology-derived biomaterials., (Copyright © 2022. Published by Elsevier B.V.)

Despite the rising global incidence of central nervous system (CNS) disorders, CNS drug development remains challenging, with high costs, long pathways to clinical use and high failure rates. The CNS is highly protected by physiological barriers, in particular, the blood-brain barrier and the blood-cerebrospinal fluid barrier, which limit access of most drugs. Biomaterials can be designed to bypass or traverse these barriers, enabling the controlled delivery of drugs into the CNS. In this Review, we first examine the effects of normal and diseased CNS physiology on drug delivery to the brain and spinal cord. We then discuss CNS drug delivery designs and materials that are administered systemically, directly to the CNS, intranasally or peripherally through intramuscular injections. Finally, we highlight important challenges and opportunities for materials design for drug delivery to the CNS and the anticipated clinical impact of CNS drug delivery., Competing Interests: Competing interests The authors declare no competing interests.

The traceless and pH-sensitive properties of boronic esters are attractive for the synthesis of polymer-drug conjugates, but current platforms suffer from both low stability under physiologically relevant conditions and synthetically demanding optimization to tune drug release profiles. We hypothesized that the high catechol affinity and stability of Wulff-type boronic acids could be mimicked by copolymerization of phenyl boronic acid with a tertiary amine and subsequent micellization. This strategy yielded a versatile platform for the preparation of reversible polymer-drug conjugates, which more than doubled the oxidative stability of encapsulated polyphenolic drug cargo at physiologically relevant pH and enabled simple and incremental tuning of drug release kinetics. Moreover, we validated, with 19 F NMR, that these copolymers exhibit uniquely high catechol affinity that could not be replicated by combinations of similarly functionalized small molecules. Overall, this report demonstrates that copolymerization of boronic acid and tertiary amine monomers is a powerful and modular approach to improving boronic ester chemistry for drug delivery applications.

Spatial hearing allows animals to rapidly detect and localize auditory events in the surrounding environment. The auditory brainstem plays a central role in processing and extracting binaural spatial cues through microsecond-precise binaural integration, especially for detecting interaural time differences (ITDs) of low-frequency sounds at the medial superior olive (MSO). A series of mechanisms exist in the underlying neural circuits for preserving accurate action potential timing across multiple fibers, synapses and nuclei along this pathway. One of these is the myelination of afferent fibers that ensures reliable and temporally precise action potential propagation in the axon. There are several reports of fine-tuned myelination patterns in the MSO circuit, but how specifically myelination influences the precision of sound localization remains incompletely understood. Here we present a spiking neural network (SNN) model of the Mongolian gerbil auditory brainstem with myelinated axons to investigate whether different axon myelination thicknesses alter the sound localization process. Our model demonstrates that axon myelin thickness along the contralateral pathways can substantially modulate ITD detection. Furthermore, optimal ITD sensitivity is reached when the MSO receives contralateral inhibition via thicker myelinated axons compared to contralateral excitation, a result that is consistent with previously reported experimental observations. Our results suggest specific roles of axon myelination for extracting temporal dynamics in ITD decoding, especially in the pathway of the contralateral inhibition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Pun, Vai, Lei and Klug.)

Herein, we report the synthesis, structural analysis, optical and chiroptical properties of a novel quadruple helicene, which has two [6] and two [7]helicene moieties fused in a contorted framework of 92 sp 2 carbon atoms. It was synthesized by the Scholl reaction of a perylene-containing substrate with the formation of eight carbon-carbon bonds on the perylene unit in a single synthetic operation. Chemical oxidation of the quadruple helicene with tris(4-bromophenyl)ammoniumyl hexachloroantimonate resulted in an air-stable dication, which exhibits the same helicity in its four helicene moieties as unambiguously identified by single-crystal X-ray crystallography. The quadruple helicene exhibits unusual near-infrared absorption and emission with absorption and emission maxima at 848 nm and 977 nm, respectively, and its isolated enantiomers exhibit electronic circular dichroism in the near-infrared and visible-light regions., (© 2021 Wiley-VCH GmbH.)