Fuel-Driven Enzymatic Reaction Networks to Program Autonomous Thiol/Disulfide Redox Systems.

Fuel-driven dissipative formation of disulfide bonds using competing oxidative activation and reductive deactivation presents a possibly very versatile avenue for autonomous materials design. However, this is challenging to realize because of the direct annihilation of oxidizing fuel and a deactivating reducing agent. We overcome this challenge by introducing a redox-based enzymatic reaction network (ERN), enabling the dissipative disulfide formation for molecularly dissolved thiols in a fully autonomous manner. Moreover, the ERN allows for programming hydrogel lifetimes by utilizing thiol-terminated star polymers (sPEG-SH). The ERN can be customized to operate with aliphatic and aromatic thiols and should thus be broadly applicable to functional thiols.

Cyclodextrin 'Chaperones' Enable Quasi-Ideal Supramolecular Network Formation and Enhanced Photodimerization of Hydrophobic, Red-shifted Photoswitches in Water.

Precision-engineered light-triggered hydrogels are important for a diversity of applications. However, fields such as biomaterials require wavelength outside the harsh UV regime to prevent photodamage, typically requiring chromophores with extended π-conjugation that suffer from poor water solubility. Herein, we demonstrate how cyclodextrins can be used as auxiliary agents to not only solubilize such chromophores, but even to preorganize them in a 2 : 2 host-guest inclusion complex to facilitate photodimerization. We apply our concept to styrylpyrene-end-functionalized star-shaped polyethylene glycols (sPEGs). We initially unravel details of the host-guest inclusion complex using spectroscopy and mass spectrometry to give clear evidence of a 2 : 2 complex formation. Subsequently, we show that the resultant supramolecularly linked hydrogels conform to theories of supramolecular quasi-ideal model networks, and derive details on their association dynamics using in-depth rheological measurements and kinetic models. By comparing sPEGs of different arm length, we further elucidate the model network topology and the accessible mechanical property space. The photo-mediated dimerization proceeds smoothly, allowing to transform the supramolecular model networks into covalent ones. We submit that our strategy opens avenues for executing hydrophobic photochemistry in aqueous environments with enhanced control over reactivity, hydrogel topology or programmable mechanical properties.

Switchable Hydrophobic Pockets in DNA Protocells Enhance Chemical Conversion.

Synthetic cell models help us understand living cells and the origin of life. Key aspects of living cells are crowded interiors where secondary structures, such as the cytoskeleton and membraneless organelles/condensates, can form. These can form dynamically and serve structural or functional purposes, such as protection from heat shock or as crucibles for various biochemical reactions. Inspired by these phenomena, we introduce a crowded all-DNA protocell and encapsulate a temperature-switchable DNA-b-polymer block copolymer, in which the synthetic polymer phase-segregates at elevated temperatures. We find that thermoreversible phase segregation of the synthetic polymer occurs via bicontinuous phase separation, resulting in artificial organelle structures that can reorient into larger domains depending on the viscoelastic properties of the protocell interior. Fluorescent sensors confirm the formation of hydrophobic compartments, which enhance the reactivity of bimolecular reactions. This study leverages the strengths of biological and synthetic polymers to construct advanced biohybrid artificial cells that provide insights into phase segregation under crowded conditions and the formation of organelles and microreactors in response to environmental stress.

DNA-Based Signaling Networks for Transient Colloidal Co-Assemblies.

Programmable chemical circuits inspired by signaling networks in living cells are a promising approach for the development of adaptive and autonomous self-assembling molecular systems and material functions. Progress has been made at the molecular level, but connecting molecular control circuits to self-assembling larger elements such as colloids that enable real-space studies and access to functional materials is sparse and can suffer from kinetic traps, flocculation, or difficult system integration protocols. Herein, we report a toehold-mediated DNA strand displacement reaction network capable of autonomously directing two different microgels into transient and self-regulating co-assemblies. The microgels are functionalized with DNA and become elemental components of the network. The flexibility of the circuit design allows the installation of delay phases or accelerators by chaining additional circuit modules upstream or downstream of the core circuit. The design provides an adaptable and robust route to regulate other building blocks for advanced biomimetic functions.

Precarious Manhood Beliefs Are Positively Associated with Erectile Dysfunction in Cisgender Men.

The notions that manhood is hard to attain, easy to lose, and needs to be proven via public action constitute precarious manhood beliefs (PMB). PMB is a new concept and it remains unclear whether and how PMB relate to erectile dysfunction (ED) in cisgender men. The ability to achieve an erection remains considered as a cornerstone of masculinity and sexual performance can be conceived as a proof of one's masculinity. In this context, ED can be received as sexual failure and a threat to a man's masculinity and sense of adequacy. For these reasons, the hypothesis that PMB are associated with ED warranted empirical testing. In an anonymous online survey focusing on men's mental health conducted in German-speaking countries of Europe, 507 cisgender men (Mage = 44.2, SDage = 15.2) completed measures on PMB, sexual function, self-stigma, social desirability, and conformity to traditional masculinity ideology (TMI). Multilinear regression analysis with stepwise introduction of relevant covariates evaluated potential associations between PMB and ED. Of a 507 cisgendered male sample, 63.1% reported an increased risk for ED based on previously established cutoff points. Elevated levels of PMB endorsement among the men predicted reduced sexual and erectile function in all models, even when accounting for relevant control variables such as age, education, self-stigma, social desirability, or conformity to TMI. Group comparisons revealed that the men suffering from ED showed higher levels of PMB endorsement but not self-stigma nor TMI relative to men without ED. PMB are significantly associated with ED. While determining causality will require further study, our results may support the hypothesis that higher levels of PMB endorsement may lead to increased tension to perform sexually, resulting in increased psychological pressure and a higher risk to develop ED.

Psychic Pain Among Men: Factor Structure, Psychosocial Correlates, and Mediation of Social Connectedness and Suicidal Ideation.

ABSTRACT: The Psychic Pain Scale (PPS) measures a form of mental pain involving overwhelming negative affect and loss of self-control. Understanding psychic pain among men is needed to advance efforts for preventing male suicide. The present study examined the factor structure and psychosocial correlates of the PPS among 621 online help-seeking men. Confirmatory factor analysis indicated a higher-order factor comprising affect deluge and loss of control factors. Psychic pain evinced significant associations with general psychological distress, r = 0.64; perceived social support, r = -0.43; social connectedness, r = -0.55; and suicidal ideation, r = 0.65 (all p 's < 0.001)-the latter three remained significant after controlling for general distress. Psychic pain also mediated the association between social disconnection and suicidal ideation (standardized indirect effect = -0.14 [-0.21, -0.09]), after controlling for social support and distress. Findings support the PPS as a promising measure for investigating psychic pain among men and indicate psychic pain as a link between social disconnection and suicidal ideation.

Cognitive function in older patients and their stress challenge using different anesthesia regimes: a single center observational study.

BACKGROUND: With increasing age older patients are at higher risk for cognitive decline after surgery. Even tailored anesthesia procedures in older patients remain a high risk for postoperative cognitive disorder. Additional stress derived from anxiety and anesthesia itself can negatively impact postoperative cognitive outcomes. The objective of this study was to evaluate the impact of general versus regional anesthesia on postoperative cognitive disorder and indicators of perioperative stress in elderly undergoing surgery. METHODS: In this single center prospective study between December 2014 and November 2015, 46 patients aged 50 to 85 years undergoing dermatology surgery were enrolled. Patients were stratified by receiving general versus regional nerve anesthesia. On three consecutive days, saliva cortisol levels were analyzed three times per day. Cognitive function was assessed on the day before and the day after surgery using comprehensive neuropsychological testing of multiple cognitive functions including memory, executive function, attention and processing speed. RESULTS: Comparing the regional anesthesia group (RAG, n = 28) with the general anesthesia group (GAG, n = 18) no significant difference in the postoperative cognitive function was observed. However, patients in the GAG had significantly higher postoperative cortisol levels when compared to patients in the RAG. In both groups, a peak of cortisol value was detected on the day of surgery, which was higher in the GAG in comparison to the RAG. CONCLUSIONS: We did not observe a difference in postoperative cognitive function between patients undergoing regional or general anesthesia for dermatology surgery. However, we found lower cortisol level in the RAG. Based on these findings, future studies should investigate alternatives to reduce stress in a general anesthesia setting. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02505815.

Online reverberation time and clarity estimation in dynamic acoustic conditions.

Previously proposed methods for estimating acoustic parameters from reverberant, noisy speech signals exhibit insufficient performance under changing acoustic conditions. A data-centric approach is proposed to overcome the limiting assumption of fixed source-receiver transmission paths. The obtained solution significantly enlarges the scope of potential applications for such estimators. The joint estimation of reverberation time RT60 and clarity index C50 in multiple frequency bands is studied with a focus on dynamic acoustic environments. Three different convolutional recurrent neural network architectures are considered to solve the tasks of single-band, multi-band, and multi-task parameter estimation. A comprehensive performance evaluation is provided that highlights the benefits of the proposed approach.

1D Colloidal chains: recent progress from formation to emergent properties and applications.

Integrating nanoscale building blocks of low dimensionality (0D; i.e., spheres) into higher dimensional structures endows them and their corresponding materials with emergent properties non-existent or only weakly existent in the individual building blocks. Constructing 1D chains, 2D arrays and 3D superlattices using nanoparticles and colloids therefore continues to be one of the grand goals in colloid and nanomaterial science. Amongst these higher order structures, 1D colloidal chains are of particular interest, as they possess unique anisotropic properties. In recent years, the most relevant advances in 1D colloidal chain research have been made in novel synthetic methodologies and applications. In this review, we first address a comprehensive description of the research progress concerning various synthetic strategies developed to construct 1D colloidal chains. Following this, we highlight the amplified and emergent properties of the resulting materials, originating from the assembly of the individual building blocks and their collective behavior, and discuss relevant applications in advanced materials. In the discussion of synthetic strategies, properties, and applications, particular attention will be paid to overarching concepts, fresh trends, and potential areas of future research. We believe that this comprehensive review will be a driver to guide the interdisciplinary field of 1D colloidal chains, where nanomaterial synthesis, self-assembly, physical property studies, and material applications meet, to a higher level, and open up new research opportunities at the interface of classical disciplines.

[Psilocybin-Assisted Treatment of Depression, Anxiety and Substance use Disorders: Neurobiological Basis and Clinical Application]. / Psilocybin-gestützte Therapie von Depression, Angst und Suchtstörungen: Neurobiologische Grundlagen und klinische Anwendung.

Successful therapy of mental disorders is very important in view of the high level of suffering of those affected. Since established pharmaceutical and psychotherapeutic approaches do not lead to the desired improvement in all cases, complementary or alternative treatment methods are intensively researched. Psilocybin-assisted psychotherapy seems particularly promising, and has been approved in the USA for larger clinical trials. Psilocybin belongs to the group of psychedelics and influences psychological experiences. In assisted therapy, psilocybin is administered in controlled doses under medical supervision to patients with different mental disorders. In the studies conducted so far, longer-term positive effects could be shown after just one or a few doses. In order to provide a better understanding of the potential therapeutic mechanisms, this article will first describe neurobiological and psychological effects of psilocybin. To better assess the potential of psilocybin-assisted psychotherapy for various disorders, clinical studies conducted so far with patients administered psilocybin are reviewed.

Communication and Cross-Regulation between Chemically Fueled Sender and Receiver Reaction Networks.

Nature connects multiple fuel-driven chemical/enzymatic reaction networks (CRNs/ERNs) via cross-regulation to hierarchically control biofunctions for a tailored adaption in complex sensory landscapes. Herein, we introduce a facile example of communication and cross-regulation among two fuel-driven DNA-based ERNs regulated by a concatenated RNA transcription regulator. ERN1 ("sender") is designed for the fuel-driven promoter formation for T7 RNA polymerase, which activates RNA transcription. The produced RNA can deactivate or activate DNA in ERN2 ("receiver") by toehold-mediated strand displacement, leading to a communication between two ERNs. The RNA from ERN1 can repress or promote the fuel-driven state of ERN2; ERN2 in turn feedbacks to regulate the lifetime of ERN1. Furthermore, the incorporation of RNase H allows for RNA degradation and enables the autonomous recovery of ERN2. We believe that concatenation of multiple CRNs/ERNs provides a basis for the design of more elaborate autonomous regulatory mechanisms in systems chemistry and synthetic biology.

Mechano-Activated Self-Immolation of Hydrogels via Signal Amplification.

Cellular organisms possess intricate mechano-adaptive systems that enable them to sense forces and process them with (bio)chemical circuits for functional adaptation. Inspired by such processes, this study introduces a hydrogel system capable of mechanically activated and chemically transduced self-destruction. Our judiciously designed hydrogels can mechanically generate radicals that are processed and amplified in a self-propagating radical de-crosslinking reaction, ultimately leading to mechanically triggered self-immolation. We put such systems to work in mechano-induced debonding, and in a bilayer actuator, where swelling-induced bending generates sufficient force for selective degradation of one layer, leading to autonomous self-regulation associated with unbending. Our work helps define design criteria for molecularly controlled adaptive and self-regulating materials with embodied mechano-chemical information processing, and showcases their potential for adhesives and soft robotics.

An Opto- and Thermal-Rewrite PCM/CNF-IR 780 Energy Storage Nanopaper with Mechanical Regulated Performance.

In spite of efforts to fabricate self-assembled energy storage nanopaper with potential applications in displays, greenhouses, and sensors, few studies have investigated their multiple stimuli-sensitivities. Here, an opto- and thermal-rewrite phase change material/cellulose nanofibril (PCM/CNF) energy storage nanopaper with mechanical regulated performance is facilely fabricated, through 5 min sonication of PCMs and CNFs in an aqueous system. The combination of PCM and CNF not only guarantees the recyclability of PCM without leakage, but also offers nanopaper adaptive properties by leveraging the mobility and optical variation accompanying solid-to-liquid transition of PCM. Besides, trace near-infrared (NIR) dye (IR 780) in it imparts a PCM-embedded nanopaper photothermal effect to modulate the local transparency via time- and position-controlled laser exposure, leading to a reusable opto-writing nanopaper. Furthermore, since the synergistic effect of stick-and-slip function attributes from PCMs and pore structures are produced by calcium ions, the PCM/CNF energy storage nanopaper exhibits excellent mechanically regulated performance from rigid to flexible, which greatly enriches their application in energy-efficient smart buildings and displays.

Efficient Softening and Toughening Strategies of Cellulose Nanofibril Nanocomposites Using Comb Polyurethane.

Cellulose nanofibrils (CNFs) have attracted attention as building blocks for sustainable materials owing to their high performance and the advantages of their abundant natural resources. Bioinspired CNF/polymer nanocomposites, consisting of a soft polymer phase and a high fraction (>50 wt %) of CNF reinforcement, have been focused on excellent mechanical properties, including Young's modulus, mechanical strength, and toughness, mimicking the energy dissipation system in nature. However, efficient softening and toughening with a small amount of the soft phase is still a challenge because a large amount of the polymer phase (nearly 50%) is still required to provide ductility and toughness. Here, we describe a topological strategy in the polymer phase for efficient toughening of bioinspired CNF nanocomposites with a water-soluble comb polyurethane (PU). The comb PU provided higher elongation at break and more efficient flexibility for the nanocomposite than the linear PU, even at a small content. Moreover, CNF nanocomposites with 30 wt % of PU content and tetrabutylammonium as bulky counterions showed enhanced toughness (180% higher) and strain at break (250% higher) when compared to pure CNF due to the promotion of slippage between nanofibrils. Scanning electron microscopy (SEM) images of the fracture surface for CNF/comb PU nanocomposites displayed the pull-out of mesoscale layers and nanofibrils, supporting that the comb topology promotes the slippage between fibrils. Furthermore, the rheological study revealed that the comb PU has an entanglement plateau modulus lower than linear PU by 1 order of magnitude, related to the loosened entanglements. Our study establishes an efficient softening and toughening strategy while using small amounts of polymer phase addition, promoting interfibrillar slippage with the loosely entangled comb PU phase.

Data-driven local average room transfer function estimation for multi-point equalization.

Multi-point room equalization (EQ) aims to achieve a desired sound quality within a wider listening area than single-point EQ. However, multi-point EQ necessitates the measurement of multiple room impulse responses at a listener position, which may be a laborious task for an end-user. This article presents a data-driven method that estimates a spatially averaged room transfer function (RTF) from a single-point RTF in the low-frequency region. A deep neural network (DNN) is trained using only simulated RTFs and tested with both simulated and measured RTFs. It is demonstrated that the DNN learns a spatial smoothing operation: notches across the spectrum are smoothed out while the peaks of the single-point RTF are preserved. An EQ framework based on a finite impulse response filter is used to evaluate the room EQ performance. The results show that while not fully reaching the level of multi-point EQ performance, the proposed data-driven local average RTF estimation method generally brings improvement over single-point EQ.

Self-Regulating Colloidal Co-Assemblies That Accelerate Their Own Destruction via Chemo-Structural Feedback.

Biological self-assemblies self- and cross-regulate each other via chemical reaction networks (CRNs) and feedback. Although artificial transient self-assemblies have been realized via activation/deactivation CRNs, the transient structures themselves do mostly not engage in the CRN. We introduce a rational design approach for chemo-structural feedback, and present a transient colloidal co-assembly system, where the formed co-assemblies accelerate their destruction autonomously. We achieve this by immobilizing enzymes of a deactivating acid-producing enzymatic cascade on pH-switchable microgels that can form co-assemblies at high pH. Since the enzyme partners are immobilized on individual microgels, the co-assembled state brings them close enough for enhanced acid generation. The amplified deactivator production (acid) leads to an almost two-fold reduction in the lifetime of the transiently formed pH-state. Our study thus introduces versatile mechanisms for chemo-structural feedback.

Dissipative Organization of DNA Oligomers for Transient Catalytic Function.

The development of synthetic non-equilibrium systems opens doors for man-made life-like materials. Yet, creating distinct transient functions from artificial fuel-driven structures remains a challenge. Building on our ATP-driven dynamic covalent DNA assembly in an enzymatic reaction network of concurrent ATP-powered ligation and restriction, we introduce ATP-fueled transient organization of functional subunits for various functions. The programmability of the ligation/restriction site allows to precisely organize multiple sticky-end-encoded oligo segments into double-stranded (ds) DNA complexes. We demonstrate principles of ATP-driven organization into sequence-defined oligomers by sensing barcode-embedded targets with different defects. Furthermore, ATP-fueled DNAzymes for substrate cleavage are achieved by transiently ligating two DNAzyme subunits into a dsDNA complex, rendering ATP-fueled transient catalytic function.

Mechanistic Insights into the Phase Separation Behavior and Pathway-Directed Information Exchange in all-DNA Droplets.

Liquid-liquid phase separation provides a versatile approach to fabricating cell-mimicking coacervates. Recently, it was discovered that phase separation of single-stranded DNA (ssDNA) allows for forming protocells and microgels in multicomponent systems. However, the mechanism of the ssDNA phase separation is not comprehensively understood. Here, we present mechanistic insights into the metal-dependent phase separation of ssDNA and leverage this understanding for a straightforward formation of all-DNA droplets. Two phase separation temperatures are found that correspond to the formation of primary nuclei and a growth process. Ca2+ allows for irreversible, whereas Mg2+ leads to reversible phase separation. Capitalizing on these differences makes it possible to control the information transfer of one-component DNA droplets and two-component core-shell protocells. This study introduces new kinetic traps of phase separating ssDNA that lead to new phenomena in cell-mimicking systems.

Optogenetic and chemogenetic insights into the neurocircuitry of depression-like behaviour: A systematic review.

Major depressive disorder (MDD) and its treatment are challenges for global health. Optogenetics and chemogenetics are driving MDD research forward by unveiling causal relations between cell-type-specific control of neurons and depressive-like behaviour in rodents. Using a systematic search process, in this review, a set of 43 original studies applying optogenetic or chemogenetic techniques in rodent models of depression was identified. Our aim was to provide an examination of all available studies elucidating central neuronal mechanisms leading to depressive-like behaviour in rodents and thereby unveiling the most promising routes for future research. A complex interacting network of relevant structures, in which central circuitries causally related to depressive-like behaviour are implicated, has been identified. As most relevant structures emerge: medial prefrontal cortex, anterior cingulate cortex, amygdala, nucleus accumbens, ventral tegmental area, hippocampus and raphe nuclei. Further evidence, though examined by only few studies, emerges for structures like the lateral habenula, or medial dorsal thalamus. Most of the identified brain areas have previously been associated with MDD neuropathology, but now evidence can be provided for causal pathological mechanisms within a complex cortico-limbic reward circuitry. However, the studies also show conflicting results concerning the mechanisms underlying the causal involvement of specific circuitries. Comparability of studies is partly limited since even small deviations in methodological approaches lead to different outcomes. Factors influencing study outcomes were identified and need to be considered in future studies (e.g. frequency used for stimulation, time and duration of stimulation, limitations of applied animal models of MDD).

Multivalency Pattern Recognition to Sort Colloidal Assemblies.

Multivalent interaction is an important principle for self-assembly and has been widely used to assemble colloids. However, surface binding partners are statistically distributed, which falls short of the interaction possibilities arising from geometrically controlled multivalency patterns as seen in viruses. Herein, the precision provided by 3D DNA origami is exploited to introduce multivalency pattern recognition via designing geometrically precise interaction patterns at patches of patchy nanocylinders. This gives rise to self-sorting of colloidal assemblies despite having the same type and number of supramolecular binding motifs-solely based on the pattern located on a 20 × 20 nm2 cross-section. The degree of sorting can be modulated by the geometric overlap of patterns and homo; mixed and alternating supracolloidal polymerizations are demonstrated. Multivalency patterns are able to provide an additional information layer to organize soft matter, important towards engineering of biological responses and functional materials design.