Stimulus-responsive and task-dependent activations in occipital regions during pitch perception by early blind listeners.

Although it has been established that cross-modal activations occur in the occipital cortex during auditory processing among congenitally and early blind listeners, it remains uncertain whether these activations in various occipital regions reflect sensory analysis of specific sound properties, non-perceptual cognitive operations associated with active tasks, or the interplay between sensory analysis and cognitive operations. This fMRI study aimed to investigate cross-modal responses in occipital regions, specifically V5/MT and V1, during passive and active pitch perception by early blind individuals compared to sighted individuals. The data showed that V5/MT was responsive to pitch during passive perception, and its activations increased with task complexity. By contrast, widespread occipital regions, including V1, were only recruited during two active perception tasks, and their activations were also modulated by task complexity. These fMRI results from blind individuals suggest that while V5/MT activations are both stimulus-responsive and task-modulated, activations in other occipital regions, including V1, are dependent on the task, indicating similarities and differences between various visual areas during auditory processing.

Interfacing Lanthanide Metal-Organic Frameworks with ZnO Nanowires for Alternating Current Electroluminescence.

Alternating current electroluminescence (ACEL) devices are attractive candidates in cost-effective lighting, sensing, and flexible displays due to their uniform luminescence, stable performance, and outstanding deformability. However, ACEL devices have suffered from limited options for the light-emitting layer, which presents a significant constraint in the progress of utilizing ACEL. Herein, a new class of ACEL phosphors based on lanthanide metal-organic frameworks (Ln-MOFs) is devised. A synthesis of lanthanide-benzenetricarboxylate (Ln-BTC) thin film on a brass grid substrate seeded with ZnO nanowires (NWs) as anchors is developed. The as-synthesized Ln-BTC thin film is employed as the emissive layer and shows visible electroluminescence driven by alternating current (2.9 V µm-1 , 1 kHz) for the first time. Mechanistic investigations reveal that the Ln-based ACEL stems from impact excitation by accelerated electrons from ZnO NWs. Fine-tuning of the ACEL color is also demonstrated by controlling the Ln-MOF compositions and introducing an extra ZnS emitting layer. The advances in these optical materials expand the application of ACEL devices in anti-counterfeiting.

Artificial Multi-Stimulus-Responsive E-Skin Based on an Ionic Film with a Counter-Ion Exchange Reagent.

Sensing pressure and temperature are two important functions of human skin that integrate different types of tactile receptors. In this paper, a deformable artificial flexible multi-stimulus-responsive sensor is demonstrated that can distinguish mechanical pressure from temperature by measuring the impedance and the electrical phase at the same frequency without signal interference. The electrical phase, which is used for measuring the temperature, is totally independent of the pressure by controlling the surface micro-shapes and the ion content of the ionic film. By doping the counter-ion exchange reagent into the ionic liquid before pouring, the upper temperature measuring limit increases from 35 to 50 °C, which is higher than the human body temperature and the ambient temperature on Earth. The sensor shows high sensitivity to pressure (up to 0.495 kPa-1) and a wide temperature sensing range (-10 to 50 °C). A multimodal ion-electronic skin (IEM-skin) with an 8 × 8 multi-stimulus-responsive sensor array is fabricated and can successfully sense the distribution of temperature and pressure at the same time. Finally, the sensors are used for monitoring the touching motions of a robot-arm finger controlled by a remote interactive glove and successfully detect the touching states and the temperature changes of different objects.

Progress in Fabrication and Applications of Cholesteric Liquid Crystal Microcapsules.

Liquid crystals (LCs) are well known for inherent responsiveness to external stimuli, such as light, thermal, magnetic, and electric fields. Cholesteric LCs are among the most fascinating, since they possess distinctive optical properties due to the helical molecular orientation. However, the good flow, easy contamination, and poor stability of small-molecule LCs limit their further applications, and microencapsulation as one of the most effective tools can evade these disadvantages. Microencapsulation can offer shell-core structure with LCs in the core can strengthen their stability, avoiding interference with the environment while maintaining the stimuli-responsiveness and optical properties. Here, we report recent progress in the fabrication and applications of cholesteric LC microcapsules (CLCMCs). We summarize general properties and basic principles, fabrication methods including interfacial polymerization, in-situ polymerization, complex coacervation, solvent evaporation, microfluidic and polymerization of reactive mesogens, and then give a comprehensive overview of their applications in various popular domains, including smart fabrics, smart sensor, smart displays, anti-counterfeiting, information encryption, biomedicine and actuators. Finally, we discuss the currently facing challenges and the potential development directions in this field.

Atomistic Molecular Dynamics Simulations of ABA-Type Polymer Peptide Conjugates: Insights into Supramolecular Structures and their Circular Dichroism Spectra.

A combination of atomistic molecular dynamics (aMD) simulations and circular dichroism (CD) analysis is used to explore supramolecular structures of amphiphilic ABA-type triblock polymer peptide conjugates (PPC). Using the example of a recently introduced PPC with pH- and temperature responsive self-assembling behavior [Otter et al., Macromolecular Rapid Communications 2018, 39, 1800459], this study shows how molecular dynamics simulations of simplified fragment molecules can add crucial information to CD data, which helps to correctly identify the self-assembled structures and monitor the folding/unfolding pathways of the molecules. The findings offer insights into the nature of structural transitions induced by external stimuli, thus contributing to the understanding of the connection of microscopic structures with macroscopic properties.

On-Demand Opioid Effect Reversal with an Injectable Light-Triggered Polymer-Naloxone Conjugate.

Misuse of opioids can lead to a potential lethal overdose. Timely administration of naloxone is critical for survival. Here, we designed a polymer-naloxone conjugate that can provide on-demand phototriggered opioid reversal. Naloxone was attached to the polymer poly(lactic-co-glycolic acid) via a photocleavable coumarin linkage and formulated as injectable nanoparticles. In the absence of irradiation, the formulation did not release naloxone. Upon irradiation with blue (400 nm) light, the nanoparticles released free naloxone, reversing the effect of morphine in mice. Such triggered events could be performed days and weeks after the initial administration of the nanoparticles and could be performed repeatedly.

Photo-induced Ultrafast Charge Transfer and Air-Stable Radical Formation in Tetraphenylpyrene Derivatives.

Stable organic radicals generated by photo-excitation hold applications in molecular switching devices and information storage. It remains challenging to develop photo-generated radical materials with rapid response and air stability in the solid state. Here, we report a structure based on 1,3,6,8-tetraphenylpyrene derivative (Py-TTAc) displaying photo-induced radicals with air stability in the solid state. Photo-induced electron transfer, exposed to a 365 nm ultraviolet lamp for 1 minute, affords radicals in Py-TTAc powder as confirmed by electron paramagnetic resonance (EPR) spectroscopy. The maximum radical concentration reaches 2.21% after continuous irradiation for 1 hour and recurs more than 10 times without any chemical degradation. The mechanistic study according to the femtosecond transient absorption (fsTA) and X-ray technology suggests that the radicals are derived from photo-induced symmetry-breaking charge separation (SB-CS) and stabilized through non-covalent interactions. The photo-generated stable radical system is employed in anti-counterfeiting paper and optoelectronic device applications. This study will provide insights into the development of photoactive organic radical materials.

Förster Resonance Energy Transfer: Stimulus-Responsive Purely Organic Room Temperature Phosphorescence through Dynamic B-N bond.

Recently, stimulus-responsive organic materials with room-temperature phosphorescence (RTP) properties have attracted significant attention owing to their potential applications in chemical sensing, anticounterfeiting, and displays. However, molecular design currently lacks systematicity and effectiveness. Herein, we report a capture-release strategy for the construction of reversible RTP via B/N Lewis pairs. Specifically, the RTP of the Lewis acid of 7-bromo-5,9-dioxa-13b-boranaphtho[3,2,1-de]anthracene (BrBA) can be deactivated through capturing by the Lewis base, N,N-diphenyl-4-(pyridin-4-yl)aniline (TPAPy), and reactivated by dissociation of B-N bonds to release BrBA. Reversible RTP is attributed to the exceptional self-assembly capability of BrBA, whereas the tunable RTP colors are derived from distinct Förster resonance energy transfer (FRET) processes. The potential applications of RTP materials in information storage and anti-counterfeiting were also experimentally validated. The capture-release approach proposed in this study offers an effective strategy for designing stimulus-responsive materials.

Polysaccharide-Based Stimulus-Responsive Nanomedicines for Combination Cancer Immunotherapy.

Cancer immunotherapy is a promising antitumor approach, whereas nontherapeutic side effects, tumor microenvironment (TME) intricacy, and low tumor immunogenicity limit its therapeutic efficacy. In recent years, combination immunotherapy with other therapies has been proven to considerably increase antitumor efficacy. However, achieving codelivery of the drugs to the tumor site remains a major challenge. Stimulus-responsive nanodelivery systems show controlled drug delivery and precise drug release. Polysaccharides, a family of potential biomaterials, are widely used in the development of stimulus-responsive nanomedicines due to their unique physicochemical properties, biocompatibility, and modifiability. Here, the antitumor activity of polysaccharides and several combined immunotherapy strategies (e.g., immunotherapy combined with chemotherapy, photodynamic therapy, or photothermal therapy) are summarized. More importantly, the recent progress of polysaccharide-based stimulus-responsive nanomedicines for combination cancer immunotherapy is discussed, with the focus on construction of nanomedicine, targeted delivery, drug release, and enhanced antitumor effects. Finally, the limitations and application prospects of this new field are discussed.

A Bone-Penetrating Precise Controllable Drug Release System Enables Localized Treatment of Osteoporotic Fracture Prevention via Modulating Osteoblast-Osteoclast Communication.

Improving local bone mineral density (BMD) at fracture-prone sites of bone is a clinical concern for osteoporotic fracture prevention. In this study, a featured radial extracorporeal shock wave (rESW) responsive nano-drug delivery system (NDDS) is developed for local treatment. Based on a mechanic simulation, a sequence of hollow zoledronic acid (ZOL)-contained nanoparticles (HZNs) with controllable shell thickness that predicts various mechanical responsive properties is constructed by controlling the deposition time of ZOL and Ca2+ on liposome templates. Attributed to the controllable shell thickness, the fragmentation of HZNs and the release of ZOL and Ca2+ can be precisely controlled with the intervention of rESW. Furthermore, the distinct effect of HZNs with different shell thicknesses on bone metabolism after fragmentation is verified. In vitro co-culture experiments demonstrate that although HZN2 does not have the strongest osteoclasts inhibitory effect, the best pro-osteoblasts mineralization results are achieved via maintaining osteoblast-osteoclast (OB-OC) communication. In vivo, the HZN2 group also shows the strongest local BMD enhancement after rESW intervention and significantly improves bone-related parameters and mechanical properties in the ovariectomy (OVX)-induced osteoporosis (OP) rats. These findings suggest that an adjustable and precise rESW-responsive NDDS can effectively improve local BMD in OP therapy.

Single Pulse Nanosecond Laser-Stimulated Targeted Delivery of Anti-Cancer Drugs from Hybrid Lipid Nanoparticles Containing 5 nm Gold Nanoparticles.

Encapsulating chemotherapeutic drugs like doxorubicin (DOX) inside lipid nanoparticles (LNPs) can overcome their acute, systematic toxicity. However, a precise drug release at the tumor microenvironment for improving the maximum tolerated dose and reducing side effects has yet to be well-established by implementing a safe stimuli-responsive strategy. This study proposes an integrated nanoscale perforation to trigger DOX release from hybrid plasmonic multilamellar LNPs composed of 5 nm gold (Au) NPs clustered at the internal lamellae interfaces. To promote site-specific DOX release, a single pulse irradiation strategy is developed by taking advantage of the resonant interaction between nanosecond pulsed laser radiation (527 nm) and the plasmon mode of the hybrid nanocarriers. This approach enlarges the amount of DOX in the target cells up to 11-fold compared to conventional DOX-loaded LNPs, leading to significant cancer cell death. The simulation of the pulsed laser interactions of the hybrid nanocarriers suggests a release mechanism mediated by either explosive vaporization of thin water layers adjacent to AuNP clusters or thermo-mechanical decomposition of overheated lipid layers. This simulation indicates an intact DOX integrity following irradiation since the temperature distribution is highly localized around AuNP clusters and highlights a controlled light-triggered drug delivery system.

Respiration-Responsive Colorful Room-Temperature Phosphorescent Materials and Assembly-Induced Phosphorescence Enhancement Strategies.

It is still very challenging to obtain colorful and long-afterglow room-temperature phosphorescent (RTP) materials from pure organic polymers. Herein, it is found that chitosan (CS), a natural polymer, not only has its own RTP, but also reacts with different phosphorescent molecules to obtain a multicolor, long-afterglow RTP material. CS can emit RTP with a lifetime of 48 ms. In addition, CS is rich in amino groups, and grafting different phosphorescent molecules onto CS by an amidation reaction can modulate it to emit different colors of phosphorescence and obtain a series of colorful CS derivatives. The obtained polymer films also have ultra-long RTP due to the good film-forming ability. In addition, one of the CS derivatives selected with α-cyclodextrin is used to construct RTP materials with lifetimes of up to seconds. The host-guest interactions are used to suppress nonradiative relaxation and build crystalline domains, thus synergistically enhancing the RTP. Interestingly, the RTP properties of the CS derivative films are extremely sensitive to water and heat stimuli, because water broke the hydrogen bonds between adjacent CS molecules and thus altered the rigid environment in the material. Finally, they can be used as a stimuli-responsive ink and for monitoring environmental humidity.

Clusterization-Triggered Room Temperature Phosphorescence Supramolecular Assembly with Extraordinary Stimulus-responsive Features from Nonaromatic Amino Acids.

Achieving stimulus-responsive performance in room-temperature phosphorescence (RTP) materials especially systems without classic conjugated groups is attractive and important but remains a great challenge. Herein we propose a universal approach to construct colors-tunable RTP supramolecular co-assemblies (AC@amino acid) with excitation wavelength-dependent properties through co-assembly of functional aminoclay (AC) and nonconjugated amino acid using environmentally friendly strategy. Experimental and theoretical results successfully disclose that the RTP feature is attributable to space conjugation through effective space electronic communications among different π and n (lone pair) electrons of amino acid molecules and the effective stabilization of their triplet state by AC. Meanwhile, their colors-tunable performances are mainly owing to the co-existence of clusters with different aggregates degree through recrystallization of amino acid taking AC as a template. Importantly, AC@amino acid exhibit sensitive stimulus response features towards water, yet their RTP performance can be maintained in other solvents, such as ethanol (EtOH). By virtue of this unique feature, multilevel information encryption application were demonstrated. This work provides a unique insight and more deep understanding on designing novel RTP systems without classic conjugated groups. Importantly, their extraordinary stimulus-responsive performances endow these RTP systems with a highly promising potential for intelligent information encryption applications.

Advances in preparation, interaction and stimulus responsiveness of protein-based nanodelivery systems.

The improved understanding of the connection between diet and health has led to growing interest in the development of functional foods designed to improve health and wellbeing. Many of the potentially health-promoting bioactive ingredients that food manufacturers would like to incorporate into these products are difficult to utilize because of their chemical instability, poor solubility, or low bioavailability. For this reason, nano-based delivery systems are being developed to overcome these problems. Food proteins possess many functional attributes that make them suitable for formulating various kinds of nanocarriers, including their surface activity, water binding, structuring, emulsification, gelation, and foaming, as well as their nutritional aspects. Proteins-based nanocarriers are therefore useful for introducing bioactive ingredients into functional foods, especially for their targeted delivery in specific applications.This review focusses on the preparation, properties, and applications of protein-based nanocarriers, such as nanoparticles, micelles, nanocages, nanoemulsions, and nanogels. In particular, we focus on the development and application of stimulus-responsive protein-based nanocarriers, which can be used to release bioactive ingredients in response to specific environmental triggers. Finally, we discuss the potential and future challenges in the design and application of these protein-based nanocarriers in the food industry.

Lighting Up Fluorescence: Precise Recognition of Halogenated Solvents Through Effective Fluorescence Detection Using Chalcone Derivatives as a D-A-D-A-type Fluorescent Chemosensor.

In this paper, we report a D-A-D-A-type fluorescence sensor, FX, composed of triphenylamine and pyrazine units as electron donors, pyridine units, and α-ß unsaturated carbon-based structures as electron acceptors. FX exhibits typical ICT characteristics. As a dual-emission material, FX undergoes acid-base-induced color changes and displays mechanofluorochromic properties in the solid state. In solution, FX, as an AIE material, shows significant fluorescence enhancement behavior in most halogenated solvents. Notably, it achieves a high quantum yield of 0.672 in a chloroform solution. We utilized this phenomenon to quantitatively detect chloroform through fluorescence titration analysis, with a detection limit of 0.061%. Additionally, we developed a test paper to verify the practical applicability of the sensor for detecting halogenated solvents. The fluorescence enhancement behavior was confirmed through DFT calculations. The results indicate that FX is not only a multifunctional dual-state emission material but also provides valuable references for the fluorescence detection of halogenated solvents.

Synthesis of Self-healing and Light-, Thermal-, and Humidity-induced Deformative Polyurethane Actuator.

Intelligent actuating materials have drawn enormous attention because of their potential applications in soft robots, smart sensors, bionics, etc. Aiming to integrate light, thermal, and humidity stimuli deformations and self-healing function into a single polymer, a smart actuating polyurethane material CPPU-50 is designed and successfully synthesized through co-polymerization of azobenzene-containing Azo-C12 , polyethylene glycol 200 (PEG200), and 4,4'-diphenylmethane diisocyanate (MDI) at a ratio of 1:1:2. The obtained polyurethane CPPU-50 exhibits good photoinduced bending, thermal responsive shape memory effect, humidity triggered deflections and self-healing properties. Furthermore, an actuator combining light and thermal stimuli is created and the self-healing CPPU-50 film can withstand the object of 1800 times without tearing. This work can pave a way for further development of long-lived multi-stimuli-responsive actuating devices and intelligent materials.

A multi-functional hypoxia/esterase dual stimulus responsive and hyaluronic acid-based nanomicelle for targeting delivery of chloroethylnitrosouea.

Carmustine (BCNU), a vital type of chloroethylnitrosourea (CENU), inhibits tumor cells growth by inducing DNA damage at O6 position of guanine and eventually forming dG-dC interstrand cross-links (ICLs). However, the clinical application of BCNU is hindered to some extent by the absence of tumor selectivity, poor stability and O6-alkylguanine-DNA alkyltransferase (AGT) mediated drug resistance. In recent years, tumor microenvironment has been widely utilized for advanced drug delivery. In the light of the features of tumor microenvironment, we constructed a multifunctional hypoxia/esterase-degradable nanomicelle with AGT inhibitory activity named HACB NPs for tumor-targeting BCNU delivery and tumor sensitization. HACB NPs was self-assembled from hyaluronic acid azobenzene AGT inhibitor conjugates, in which O6-BG analog acted as an AGT inhibitor, azobenzene acted as a hypoxia-responsive linker and carboxylate ester bond acted as both an esterase-sensitive switch and a connector with hyaluronic acid (HA). The obtained HACB NPs possessed good stability, favorable biosafety and hypoxia/esterase-responsive drug-releasing ability. BCNU-loaded HACB/BCNU NPs exhibited superior cytotoxicity and apoptosis-inducing ability toward the human uterine cervix carcinoma HeLa cells compared with traditional combined medication of BCNU plus O6-BG. In vivo studies further demonstrated that after a selective accumulation in the tumor site, the micelles could respond to hypoxic tumor tissue for rapid drug release to an effective therapeutic dosage. Thus, this multifunctional stimulus-responsive nanocarrier could be a new promising strategy to enhance the anticancer efficacy and reduce the side effects of BCNU and other CENUs.

Visualizing stimulus-responsive dual-ligand fluorescent probes for hypochlorite: A novel strategy for real application in tap water.

As an effective ingredient of disinfectants, ClO- inevitably remains in water, which induces potential health hazards such as lung damage and kidney disease. In this study, we synthesized stimulus-responsive dual-ligand luminol-Tb-GMP coordination polymer nanoparticles (luminol-Tb-GMP CPNPs) as highly selective fluorescent probes for the real-time and visual detection of ClO- . CPNPs consist of Tb3+ , a nuclear metal, that coordinates with GMP and luminol, an auxiliary ligand. GMP can be oxidized by ClO- and damage its structure, resulting in fluorescence quenching of CPNPs. The two-ligand CPNPs sensor has a rapid fluorescent response, significant fluorescent color change, and high sensitivity, with a linear range of 2-18 µM and a detection limit of 0.14 µM. It has been successfully used to detect ClO- in tap water, fountain water, and drinking water. Simultaneously, the portable filter paper strip was prepared to expand the range of applications outside the laboratory, which will provide a promising application for the real-time and semiquantitative analysis of ClO- .

Stimulus-Responsive Ultrathin Films for Bioapplications: A Concise Review.

The term "nanosheets" has been coined recently to describe supported and free-standing "ultrathin film" materials, with thicknesses ranging from a single atomic layer to a few tens of nanometers. Owing to their physicochemical properties and their large surface area with abundant accessible active sites, nanosheets (NSHs) of inorganic materials such as Au, amorphous carbon, graphene, and boron nitride (BN) are considered ideal building blocks or scaffolds for a wide range of applications encompassing electronic and optical devices, membranes, drug delivery systems, and multimodal contrast agents, among others. A wide variety of synthetic methods are employed for the manufacturing of these NSHs, and they can be categorized into (1) top-down approaches involving exfoliation of layered materials, or (2) bottom-up approaches where crystal growth of nanocomposites takes place in a liquid or gas phase. Of note, polymer template liquid exfoliation (PTLE) methods are the most suitable as they lead to the fabrication of high-performance and stable hybrid NSHs and NSH composites with the appropriate quality, solubility, and properties. Moreover, PTLE methods allow for the production of stimulus-responsive NSHs, whose response is commonly driven by a favorable growth in the appropriate polymer chains onto one side of the NSHs, resulting in the ability of the NSHs to roll up to form nanoscrolls (NSCs), i.e., open tubular structures with tunable interlayer gaps between their walls. On the other hand, this review gives insight into the potential of the stimulus-responsive nanostructures for biosensing and controlled drug release systems, illustrating the last advances in the PTLE methods of synthesis of these nanostructures and their applications.

Strong, Healable, Stimulus-Responsive Fluorescent Elastomers Based on Assembled Borate Dynamic Nanostructures.

Self-healing materials integrated with robust mechanical property and fascinating functions synchronously hold great prospects in many applications, but it still remains a grand challenge. Here, a bottom-up assembly method of preparing borate dynamic nanostructures (BDN) with controllable morphologies and interfacial crosslinks is proposed, from which a robust self-healing elastomer is fabricated. The BDN is optimized to construct dense and strong interfacial boronic easter crosslinks, endowing the elastomer with outstanding stretchability (2050%), high strength (17.9 MPa) as well as healing efficiency (77.1%). Moreover, the elastomer also exhibits pH stimulus-responsive fluorescence property and excellent functional repairability, enabling its potential application in intelligent material fields such as information encoding and encryption. This study demonstrates a general approach to produce self-healable functional materials with robust mechanical properties, and defines a rich platform for exploring various functional nanostructured materials.