Diverse Stimuli Research Articles

Multiple control of azoquinoline based molecular photoswitches.

Multi-addressable molecular switches with high sophistication are creating intensive interest, but are challenging to control. Herein, we incorporated ring-chain dynamic covalent sites into azoquinoline scaffolds for the construction of multi-responsive and multi-state switching systems. The manipulation of ring-chain equilibrium by acid/base and dynamic covalent reactions with primary/secondary amines allowed the regulation of E/Z photoisomerization. Moreover, the carboxyl and quinoline motifs provided recognition handles for the chelation of metal ions and turning off photoswitching, with otherwise inaccessible Z-isomer complexes obtained via the change of stimulation sequence. Particularly, the distinct metal binding behaviors of primary amine and secondary amine products offered a facile way for modulating E/Z switching and dynamic covalent reactivity. As a result, multiple control of azoarene photoswitches was accomplished, including light, pH, metal ions, and amine nucleophiles, with interplay between diverse stimuli further enabling addressable multi-state switching within reaction networks. The underlying structural and mechanistic insights were elucidated, paving the way for the creation of complex switching systems, molecular assemblies, and intelligent materials.

An Overview of the Unfolded Protein Response (UPR) and Autophagy Pathways in Human Viral Oncogenesis.

Autophagy and Unfolded Protein Response (UPR) can be regarded as the safe keepers of cells exposed to intense stress. Autophagy maintains cellular homeostasis, ensuring the removal of foreign particles and misfolded macromolecules from the cytoplasm and facilitating the return of the building blocks into the system. On the other hand, UPR serves as a shock response to prolonged stress, especially Endoplasmic Reticulum Stress (ERS), which also includes the accumulation of misfolded proteins in the ER. Since one of the many effects of viral infection on the host cell machinery is the hijacking of the host translational system, which leaves in its wake a plethora of misfolded proteins in the ER, it is perhaps not surprising that UPR and autophagy are common occurrences in infected cells, tissues, and patient samples. In this book chapter, we try to emphasize how UPR, and autophagy are significant in infections caused by six major oncolytic viruses-Epstein-Barr (EBV), Human Papilloma Virus (HPV), Human Immunodeficiency Virus (HIV), Human Herpesvirus-8 (HHV-8), Human T-cell Lymphotropic Virus (HTLV-1), and Hepatitis B Virus (HBV). Here, we document how whole-virus infection or overexpression of individual viral proteins in vitro and in vivo models can regulate the different branches of UPR and the various stages of macro autophagy. As is true with other viral infections, the relationship is complicated because the same virus (or the viral protein) exerts different effects on UPR and Autophagy. The nature of this response is determined by the cell types, or in some cases, the presence of diverse extracellular stimuli. The vice versa is equally valid, i.e., UPR and autophagy exhibit both anti-tumor and pro-tumor properties based on the cell type and other factors like concentrations of different metabolites. Thus, we have tried to coherently summarize the existing knowledge, the crux of which can hopefully be harnessed to design vaccines and therapies targeted at viral carcinogenesis.

Metabolism and immune memory in invertebrates: are they dissociated?

Since the discovery of specific immune memory in invertebrates, researchers have investigated its immune response to diverse microbial and environmental stimuli. Nevertheless, the extent of the immune system's interaction with metabolism, remains relatively enigmatic. In this mini review, we propose a comprehensive investigation into the intricate interplay between metabolism and specific immune memory. Our hypothesis is that cellular endocycles and epigenetic modifications play pivotal roles in shaping this relationship. Furthermore, we underscore the importance of the crosstalk between metabolism and specific immune memory for understanding the evolutionary costs. By evaluating these costs, we can gain deeper insights into the adaptive strategies employed by invertebrates in response to pathogenic challenges. Lastly, we outline future research directions aimed at unraveling the crosstalk between metabolism and specific immune memory. These avenues of inquiry promise to illuminate fundamental principles governing host-pathogen interactions and evolutionary trade-offs, thus advancing our understanding of invertebrate immunology.

Quantification of Macrophage Cellular Ferrous Iron (Fe2+) Content Using a Highly Specific Fluorescent Probe in a Plate Reader.

Macrophages are at the center of innate immunity and iron metabolism. In the case of an infection, macrophages adapt their cellular iron metabolism to deprive iron from invading bacteria to combat intracellular bacterial proliferation. A concise evaluation of the cellular iron content upon an infection with bacterial pathogens and diverse cellular stimuli is necessary to identify underlying mechanisms concerning iron homeostasis in macrophages. For the characterization of cellular iron levels during infection, we established an in vitro infection model where the murine macrophage cell line J774A.1 is infected with Salmonella enterica serovar Typhimurium (S.tm), the mouse counterpart to S. enterica serovar Typhi, under normal and iron-overload conditions using ferric chloride (FeCl3) treatment. To evaluate the effect of infection and iron stimulation on cellular iron levels, the macrophages are stained with FerroOrange. This fluorescent probe specifically detects Fe2+ ions and its fluorescence can be quantified photometrically in a plate reader. Importantly, FerroOrange fluorescence does not increase with chelated iron or other bivalent metal ions. In this protocol, we present a simple and reliable method to quantify cellular Fe2+ levels in cultured macrophages by applying a highly specific fluorescence probe (FerroOrange) in a TECAN Spark microplate reader. Compared to already established techniques, our protocol allows assessing cellular iron levels in innate immune cells without the use of radioactive iron isotopes or extensive sample preparation, exposing the cells to stress. Key features • Easy quantification of Fe2+ in cultured macrophages with a fluorescent probe. • Analysis of iron in living cells without the need for fixation. • Performed on a plate reader capable of 540 nm excitation and 585 nm emission by trained employees for handling biosafety level 2 bacteria.

Recent advances in tunable solid-state emission based on α-cyanodiarylethenes: from molecular packing regulation to functional development.

The design and development of organic solid-state luminescent materials stand as crucial pillars within the realm of contemporary photofunctional materials. Overcoming challenges such as concentration quenching and achieving tailored luminescent properties necessitates a judicious approach to molecular structure design and the strategic utilization of diverse stimuli to modulate molecular packing patterns. Among the myriad candidates, α-cyanodiarylethenes (CAEs) emerge with distinctive solid-state luminescent attributes, capable of forming self-assembled packing structures with varying degrees of π-π stacking. This characteristic endows them with potential in the field of intelligent molecular responsive materials and optoelectronic devices. This tutorial review embarks on an exploration of design strategies geared towards attaining tunable solid-state emission through customized packing of CAEs. It explores the utilization of stimuli responses, including such as mechanical forces, light irradiation, solvent interactions, thermal influences, as well as the utilization of co-assembly methodologies. The overarching aim of this review is to provide a widely applicable platform fostering the flourishing development of modern organic photofunctional materials through integrating principles of molecular engineering, organic optoelectronics, and materials science.

Mechanical and chemical itch regulated by neuropeptide Y-Y1 signaling.

Itch is a somatosensory sensation to remove potential harmful stimulation with a scratching desire, which could be divided into mechanical and chemical itch according to diverse stimuli, such as wool fiber and insect biting. It has been reported that neuropeptide Y (NPY) neurons, a population of spinal inhibitory interneurons, could gate the transmission of mechanical itch, with no effect on chemical itch. In our study, we verified that chemogenetic activation of NPY neurons could inhibit the mechanical itch as well as the chemical itch, which also attenuated the alloknesis phenomenon in the chronic dry skin model. Afterwards, intrathecal administration of NPY1R agonist, [Leu31, Pro34]-NPY (LP-NPY), showed the similar inhibition effect on mechanical itch, chemical itch and alloknesis as chemo-activation of NPY neurons. Whereas, intrathecal administration of NPY1R antagonist BIBO 3304 enhanced mechanical itch and reversed the alloknesis phenomenon inhibited by LP-NPY treatment. Moreover, selectively knocking down NPY1R by intrathecal injection of Npy1r siRNA enhanced mechanical and chemical itch behavior as well. These results indicate that NPY neurons in spinal cord regulate mechanical and chemical itch, and alloknesis in dry skin model through NPY1 receptors.

Analysis of the Structure and Working Principle of Intelligent Bionic Hand

Intelligent bionic prosthetic hand controlled by intelligent neural networks with perceptual feedback function is a hot topic of research for scientists around the world. This article analyzes the development status of electromyographic prosthetic hands both domestically and internationally over the years, and provides a detailed introduction to the structure of intelligent bionic hands. The intelligent bionic hand consists of three important components: 3D printed bionic hand bone structure, sensors, and intelligent neural network algorithm control system. Among them, the intelligent neural network algorithm control system is its core. The focus is on the working principle of an intelligent bionic hand, where sensors collect electromyography and neural electrical signals generated by human muscle movements. Through the intelligent neural network algorithm control system, the data information obtained is continuously optimized and adjusted to achieve motion control of the prosthetic hand. This article analyzes some problems of intelligent bionic hands and provides development ideas and suggestions. It is pointed out that the reconstruction of the sensing function of the intelligent bionic hand should focus on multimodal feedback, using diverse stimuli and more sensitive sensors for human-machine interaction, so that the intelligent bionic hand can move flexibly and freely, benefiting most disabled patients.

Rhodamine-based Fluorescent Probe With Quick Response and High Selectivity for Imaging Labile Ferrous Iron in Living Cells and Zebrafish.

The transition between its various oxidation states of Iron plays a crucial part in various chemical transformation of cells. Misregulation of iron can give rise to the iron-catalyzed reactive oxygen species disorder which have been linked to a variety of diseases, so it is crucial to monitor the labile iron pool in vivo for clinical diagnosis. According to iron autoxidation and hydrogen abstraction reaction, we reported a novel "off-on" fluorescent probe to response to ferrous (Fe2+) both in solutions and biological systems. The probe responds to Fe2+ with good selectivity toward competing metal ions. What's more, the probe presents significant fluorescent enhancement to Fe2+ in less than 1min, making real-time sensing in biological system possible. The applications of the probe in bioimaging revealed the changes in labile iron pool by iron autoxidation or diverse stimuli.

Sensory input to cortex encoded on low-dimensional periphery-correlated subspaces.

As information about the world is conveyed from the sensory periphery to central neural circuits, it mixes with complex ongoing cortical activity. How do neural populations keep track of sensory signals, separating them from noisy ongoing activity? Here, we show that sensory signals are encoded more reliably in certain low-dimensional subspaces. These coding subspaces are defined by correlations between neural activity in the primary sensory cortex and upstream sensory brain regions; the most correlated dimensions were best for decoding. We analytically show that these correlation-based coding subspaces improve, reaching optimal limits (without an ideal observer), as noise correlations between cortex and upstream regions are reduced. We show that this principle generalizes across diverse sensory stimuli in the olfactory system and the visual system of awake mice. Our results demonstrate an algorithm the cortex may use to multiplex different functions, processing sensory input in low-dimensional subspaces separate from other ongoing functions.

Theoretical perspective for hydrostatic pressure responsive mechanism of room temperature phosphorescence molecules

Stimulus-responsive organic room temperature phosphorescence (RTP) materials are a class of materials that show emission property changes when subjected to diverse environmental stimuli. The change of molecular stacking modes and intermolecular interactions can result in mechanical stimulus-induced emission switching behaviour. The underlying mechanism of mechanoresponsive luminescent material is still unclear. Herein, based on density functional theory and time-dependent density functional theory calculations, the photophysical properties with response to hydrostatic pressure of RTP molecules in crystal are theoretically studied. Excited state dynamic processes are investigated by using quantum mechanics and molecular mechanics method coupled with thermal vibration correlation function method. Results show that the increase of pressure can blue-shift the RTP emissions which is mainly caused by the change of molecular conformation and the increase of bending vibration frequency. Under 2 Gpa, large spin–orbit coupling effect is determined, remarkable radiative and non-radiative decay processes are achieved. At 0.6 Gpa, a small non-radiative decay rate from T 1 to S 0 is obtained, high efficiency and long lifetime (more than 10 times the other pressures) are realised. Through further analysing the staking modes, reorganisation energies and SOC constants, relationships between molecular structures and RTP properties are determined, hydrostatic pressure responsive mechanism is revealed.

Macrophages polarization in renal inflammation and fibrosis animal models (Review)

Macrophages polarization in renal inflammation and fibrosis animal models (Review)

Development and Evaluation of Curcumin-based Transferosomal Gel for Wound Healing

Background: Recently, transferosomes have been discovered to have the potential for transdermal delivery. Curcumin is a bioactive molecule with anti-inflammatory and antioxidant properties, but it has low water solubility and poor skin absorption. The biological response to damage caused by diverse stimuli is known as the inflammatory process. Cyclodextrins are cyclic (-1, 4)-linked oligosaccharides of -D-glucopyranose with a hydrophilic outer surface and a hydrophobic center cavity. Aim: The aim of the study was to develop a curcumin-loaded transferosomal gel to improve the wound healing process. The study has focused on advancing the area of traditional medicine in the field of pharmaceutics by using curcumin in the form of transferosomes to enhance wound healing. Method: Firstly, curcumin was used to synthesize the transferosomes. Secondly, the transferosomes were converted into a transferosomal gel as an alternative for wound healing. Characterization and in vivo investigation were carried out on female Swiss mice. Results: Unpaired Student’s t-test was used to determine the statistical significance at p < 0.5 using UV exposure schedules. All values have been expressed as mean ± SEM calculated by ANOVA with a significant difference among means at P < 0.05. Conclusion: The study has indicated curcumin to be successfully entrapped in transferosomes in order to formulate the gel with powerful wound healing properties.

Stretchable triboelectric sensor array for real-time tactile sensing based on coaxial printing

With the rapid development of flexible and wearable electronics, tactile sensor array has shown great potential to detect diverse external stimuli in human–machine interactions and robotic intelligence. In this study, we developed triboelectric sensor array (TSA) with cross-laminated electrode via low-cost coaxial printing technique with the advantages of high precision, high efficiency and excellent uniformity. The results show that the proposed cross-laminated electrode based TSA possesses the characteristics of easy-fabrication process, high-sensitivity, long-term mechanical endurance and real-time trajectory sensing capacity. It can generate the maximum output voltage of 15.98 V at a frequency 4 Hz and vertical force 5 N in single electrode mode, and the maximum power is about 3.9 μW. Besides, TSA shows excellent stability under harsh mechanical bending, twisting and stretching deformation and even waterproof capability. This work offers a previously unexplored strategy for shortening individual design and fabrication cycle of flexible electronics, and promoting the potential application for stretchable sensor array in electronic skin, tactile detection and human–machine interactions.

Microphase-Separated Elastic and Ultrastretchable Ionogel for Reliable Ionic Skin with Multimodal Sensation.

Bioinspired artificial skins integrated with reliable human-machine interfaces and stretchable electronic systems have attracted considerable attention. However, the current design faces difficulties in simultaneously achieving satisfactory skin-like mechanical compliance and self-powered multimodal sensing. Here, this work reports a microphase-separated bicontinuous ionogel which possesses skin-like mechanical properties and mimics the multimodal sensing ability of biological skin by ion-driven stimuli-electricity conversion. The ionogel exhibits excellent elasticity and ionic conductivity, high toughness, and ultrastretchability, as well as a Young's modulus similar to that of human skin. Leveraging the ion-polymer interactions enabled selective ion transport, the ionogel can output pulsing or continuous electrical signals in response to diverse stimuli such as strain, touch pressure, and temperature sensitively, demonstrating a unique self-powered multimodal sensing. Furthermore, the ionogel-based I-skin can concurrently sense different stimuli and decouple the variations of the stimuli from the voltage signals with the assistance of a machine-learning model. The ease of fabrication, wide tunability, self-powered multimodal sensing, and the excellent environmental tolerance of the ionogels demonstrate a new strategy in the development of next-generation soft smart mechano-transduction devices.

Commentary] Will this novel stimulus be the catalyst for transforming biomedical shape memory polymers?

Shape memory polymers (SMPs) circumscribe materials exhibiting responsive behavior to diverse external stimuli, ranging from heat and light to electric and magnetic fields. Originating in mid-20th-century studies, the realm of SMPs has expanded swiftly, tapping into the domains of biomedical applications, revolutionizing biomaterials, and finding applications from medical devices to regenerative medicine. Evolving beyond biocompatibility, the emphasis shifted to cytocompatible SMPs for cell mechanobiology, paving the way for direct cell-responsive SMPs. Recent breakthroughs in enzymatically triggered SMPs, particularly those influenced by cellular enzymatic activity, signify a transformative leap. This opens avenues for precision drug delivery and biosensors, merging SMPs with biomedical applications. This commentary celebrates the discovery of polymers responding to cells, unfolding the promising future of SMPs in personalized medicine, and seamlessly integrating advanced materials with cellular therapies for groundbreaking medical solutions.

Role of Polymer Concentration on the Release Rates of Proteins from Single- and Double-Network Hydrogels

Controlled delivery of proteins has immense potential for the treatment of various human diseases, but effective strategies for their delivery are required before this potential can be fully realized. Recent research has identified hydrogels as a promising option for the controlled delivery of therapeutic proteins, owing to their ability to respond to diverse chemical and biological stimuli, as well as their customizable properties that allow for desired delivery rates. This study utilized alginate and chitosan as model polymers to investigate the effects of hydrogel properties on protein release rates. The results demonstrated that polymer properties, concentration, and crosslinking density, as well as their responses to pH, can be tailored to regulate protein release rates. The study also revealed that hydrogels may be combined to create double-network hydrogels to provide an additional metric to control protein release rates. Furthermore, the hydrogel scaffolds were also found to preserve the long-term function and structure of encapsulated proteins before their release from the hydrogels. In conclusion, this research demonstrates the significance of integrating porosity and response to stimuli as orthogonal control parameters when designing hydrogel-based scaffolds for therapeutic protein release.

Linear motif specificity in signaling through p38α and ERK2 mitogen-activated protein kinases.

Mitogen-activated protein kinase (MAPK) cascades are essential for eukaryotic cells to integrate and respond to diverse stimuli. Maintaining specificity in signaling through MAPK networks is key to coupling distinct inputs to appropriate cellular responses. Docking sites-short linear motifs found in MAPK substrates, regulators, and scaffolds-can promote signaling specificity through selective interactions, but how they do so remains unresolved. Here, we screened a proteomic library for sequences interacting with the MAPKs extracellular signal-regulated kinase 2 (ERK2) and p38α, identifying selective and promiscuous docking motifs. Sequences specific for p38α had high net charge and lysine content, and selective binding depended on a pair of acidic residues unique to the p38α docking interface. Finally, we validated a set of full-length proteins harboring docking sites selected in our screens to be authentic MAPK interactors and substrates. This study identifies features that help define MAPK signaling networks and explains how specific docking motifs promote signaling integrity.

Modeling gut neuro-epithelial connections in a novel microfluidic device

The intestinal lumen is filled with diverse chemical and physical stimuli. Intestinal epithelial cells sense these stimuli and signal to enteric neurons which coordinate a range of physiologic processes required for normal digestive tract function. Yet, the neuro-epithelial connections remain poorly resolved, in part because the tools for orchestrating interactions between these cellular compartments are lacking. We describe the development of a two-compartment microfluidic device for co-culturing enteric neurons with intestinal epithelial cells. The device contains epithelial and neuronal compartments connected by microgrooves. The epithelial compartment was designed for cell seeding via injection and confinement of intestinal epithelial cells derived from human intestinal organoids. We demonstrated that organoids planarized effectively and retained epithelial phenotype for over a week. In the second chamber we dissociated and cultured intestinal myenteric neurons including intrinsic primary afferent neurons (IPANs) from transgenic mice that expressed the fluorescent protein tdTomato. IPANs extended projections into microgrooves, surrounded and frequently made contacts with epithelial cells. The density and directionality of neuronal projections were enhanced by the presence of epithelial cells in the adjacent compartment. Our microfluidic device represents a platform that may, in the future, be used to dissect structure and function of neuro-epithelial connections in the gut and other organs (skin, lung, bladder, and others) in health and disease.

Metabolic Effects on Mouse Embryonic Stem Cells and the Canonical Mammalian Target of Rapamycin Pathway

Diapause-like features can be extended to naïve mouse embryonic stem cells (mESCs) to induce paused pluripotency by using INK128 (mTi), a mammalian target of rapamycin (mTOR) inhibitor. As a core integrative pathway, mTOR senses diverse stimuli and translates these cues to coordinate several processes. We have previously shown that the withdrawal of leucine and arginine from the culture medium of naïve mESCs can induce features of a paused-pluripotent state, including reduced cell proliferation, cell cycle arrest, and reductions in glycolytic and oxidative metabolism. However, surprisingly, although mTi did indeed provoke a paused-like state, this was distinct from and less pronounced than what resulted from leucine and arginine removal, and, according to our results, these features did not seem to necessarily be mTOR-driven. Therefore, this possibility should be considered in further experiments, and mTOR inhibition when using INK128 should always be confirmed and not merely assumed when INK128 is present in the culture medium.

Characterizing Different Modes of Interplay Between Rap1 and H3 Using Inducible H3-depletion Yeast

Histones and transcription factors (TFs) are two important DNA-binding proteins that interact, compete, and together regulate transcriptional processes in response to diverse internal and external stimuli. Condition-specific depletion of histones in Saccharomyces cerevisiae using a galactose-inducible H3 promoter provides a suitable framework for examining transcriptional alteration resulting from reduced nucleosome content. However, the effect on DNA binding activities of TFs is yet to be fully explored. In this work, we combine ChIP-seq of H3 with RNA-seq to elucidate the genome-scale relationships between H3 occupancy patterns and transcriptional dynamics before and after global H3 depletion. ChIP-seq of Rap1 is also conducted in the H3-depletion and control treatments, to investigate the interplay between this master regulator TF and nucleosomal H3, and to explore the impact on diverse transcriptional responses of different groups of target genes and functions. Ultimately, we propose a working model and testable hypotheses regarding the impact of global and local H3 depletion on transcriptional changes. We also demonstrate different potential modes of interaction between Rap1 and H3, which sheds light on the potential multifunctional regulatory capabilities of Rap1 and potentially other pioneer factors.