A facile DNA coacervate platform for engineering wetting, engulfment, fusion and transient behavior.

Biomolecular coacervates are emerging models to understand biological systems and important building blocks for designer applications. DNA can be used to build up programmable coacervates, but often the processes and building blocks to make those are only available to specialists. Here, we report a simple approach for the formation of dynamic, multivalency-driven coacervates using long single-stranded DNA homopolymer in combination with a series of palindromic binders to serve as a synthetic coacervate droplet. We reveal details on how the length and sequence of the multivalent binders influence coacervate formation, how to introduce switching and autonomous behavior in reaction circuits, as well as how to engineer wetting, engulfment and fusion in multi-coacervate system. Our simple-to-use model DNA coacervates enhance the understanding of coacervate dynamics, fusion, phase transition mechanisms, and wetting behavior between coacervates, forming a solid foundation for the development of innovative synthetic and programmable coacervates for fundamental studies and applications.

DNA-empowered synthetic cells as minimalistic life forms.

Cells, the fundamental units of life, orchestrate intricate functions - motility, adaptation, replication, communication, and self-organization within tissues. Originating from spatiotemporally organized structures and machinery, coupled with information processing in signalling networks, cells embody the 'sensor-processor-actuator' paradigm. Can we glean insights from these processes to construct primitive artificial systems with life-like properties? Using de novo design approaches, what can we uncover about the evolutionary path of life? This Review discusses the strides made in crafting synthetic cells, utilizing the powerful toolbox of structural and dynamic DNA nanoscience. We describe how DNA can serve as a versatile tool for engineering entire synthetic cells or subcellular entities, and how DNA enables complex behaviour, including motility and information processing for adaptive and interactive processes. We chart future directions for DNA-empowered synthetic cells, envisioning interactive systems wherein synthetic cells communicate within communities and with living cells.

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.

Scalable Approach to Molecular Motor-Polymer Conjugates for Light-Driven Artificial Muscles.

The integration of molecular machines and motors into materials represents a promising avenue for creating dynamic and functional molecular systems, with potential applications in soft robotics or reconfigurable biomaterials. However, the development of truly scalable and controllable approaches for incorporating molecular motors into polymeric matrices has remained a challenge. Here, it is shown that light-driven molecular motors with sensitive photo-isomerizable double bonds can be converted into initiators for Cu-mediated controlled/living radical polymerization enabling the synthesis of star-shaped motor-polymer conjugates. This approach enables scalability, precise control over the molecular structure, block copolymer structures, and high-end group fidelity. Moreover, it is demonstrated that these materials can be crosslinked to form gels with quasi-ideal network topology, exhibiting light-triggered contraction. The influence of arm length and polymer structure is investigated, and the first molecular dynamics simulation framework to gain deeper insights into the contraction processes is developed. Leveraging this scalable methodology, the creation of bilayer soft robotic devices and cargo-lifting artificial muscles is showcased, highlighting the versatility and potential applications of this advanced polymer chemistry approach. It is anticipated that the integrated experimental and simulation framework will accelerate scalable approaches for active polymer materials based on molecular machines, opening up new horizons in materials science and bioscience.

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.

Hierarchical Mechanical Transduction of Precision-Engineered DNA Hydrogels with Sacrificial Bonds.

Engineering the response to external signals in mechanically switchable hydrogels is important to promote smart materials applications. However, comparably little attention has focused on embedded precision mechanisms for autonomous nonlinear response in mechanical profiles in hydrogels, and we lack understanding of how the behavior from the molecular scale transduces to the macroscale. Here, we design a nonlinear stress-strain response into hydrogels by engineering sacrificial DNA hairpin loops into model network hydrogels formed from star-shaped building blocks. We characterize the force-extension response of single DNA hairpins and are able to describe how the specific topology influences the nonlinear mechanical behavior at different length scales. For this purpose, we utilize force spectroscopy as well as microscopic and macroscopic deformation tests. This study contributes to a better understanding of designing nonlinear strain-adaptive features into hydrogel materials.

Transient co-assemblies of micron-scale colloids regulated by ATP-fueled reaction networks.

Self-assembly of colloidal particles offers an attractive bottom-up approach to functional materials. Current design strategies for colloidal assemblies are mostly based on thermodynamically controlled principles and lack autonomous behavior. The next advance in the properties of colloidal assemblies will come from coupling these structures to out-of-equilibrium chemical reaction networks furnishing them with autonomous and dynamic behavior. This, however, constitutes a major challenge of carefully modulating the interparticle potentials on a temporal circuit program and avoiding kinetic trapping and irreversible aggregation. Herein, we report the coupling of a fuel-driven DNA-based enzymatic reaction network (ERN) to micron-sized colloidal particles to achieve their transient co-assembly. The ERN operating on the molecular level transiently releases an Output strand which links two DNA functionalized microgel particles together into co-assemblies with a programmable assembly lifetime. The system generates minimal waste and recovers all components of the ERN after the consumption of the ATP fuel. The system can be reactivated by addition of new fuel as shown for up to three cycles. The design can be applied to organize other building blocks into hierarchical structures and materials with advanced biomimetic properties.

Exhaustion and cardiovascular risk factors: the role of vagally-mediated heart rate variability.

PURPOSE: Exhaustion symptoms are known to be associated with cardiovascular disease (CVD) risk; however, the underlying mechanisms remain unclear. Autonomic imbalance, as indicated by reductions in vagally-mediated heart rate variability (vmHRV), appears to be a valid candidate for such a biological link, as it has been associated with both exhaustion symptoms and CVD risk and mortality. METHODS: The present study examined a potential mediation of vmHRV on the association between exhaustion symptoms and self-reported CVD risk factors as well as the age dependency of this mediation in a large, heterogeneous sample of the Dresden Burnout Study (N = 388; 72.9% females; Mage = 42.61, SD = 11.67). RESULTS: Results indicate that exhaustion symptoms were indirectly associated with CVD risk factors through vmHRV even after adjusting for well-known confounders (i.e., sex, body mass index, depressive symptoms). Moreover, this pattern was significant only among middle-aged (i.e., 54.27 years) and older individuals. CONCLUSIONS: Our findings add to growing evidence that autonomic imbalance may be a key biological link between exhaustion symptoms and CVD risk in middle-aged and older individuals. Implications for public health are discussed.

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.

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.

Evaluation of a male-specific psychotherapeutic program for major depressive disorder compared to cognitive behavioral therapy and waitlist: study protocol for a six-arm randomized clinical superiority trial examining depressed eugonadal and hypogonadal men receiving testosterone.

Background: Treatment of major depressive disorder (MDD) in men is complicated by the endorsement of traditional masculinity ideologies (TMI) often leading to reluctance toward psychotherapy, therapy interfering processes, or premature termination. In addition, it has been shown that men with MDD have a significantly increased risk of being hypogonadal (e.g., total testosterone levels <12.1 nmoL/L). Therefore, it is recommended to examine depressed men with regard to their testosterone status and if hypogonadism is present to combine psychotherapy with testosterone treatment (TT). Aim: This project aims to evaluate a male-specific psychotherapeutic program (MSPP) for MDD in depressed eugonadal and hypogonadal men receiving testosterone in comparison to a standard cognitive behavioral therapy (CBT) for MDD and a Waitlist. Methods: The study presents a 2×3 factorial study design. In total, 144 men aged between 25 and 50 will be stratified by testosterone status (eugonadal/hypogonadal) and then randomized into one of the three conditions (MSPP, CBT, or Waitlist). Additionally, a healthy control group of 100 men will be recruited, which will undergo only baseline assessments. Both standardized psychotherapy programs will encompass 18 sessions delivered in a weekly manner. Aligned with the TT-related medical visits of the 72 hypogonadal men, all participants will be followed up with clinical assessments and bio sampling at weeks 0, 6, 15, 24, and 36. Expected results: Compared to Waitlist control groups, treatment groups are expected to be more effective and efficacious (depression score reduction of ≥50%) at week 24 and at the follow-up at week 36. The MSPP is expected to show higher effectiveness and efficacy for depressive symptoms and higher acceptability (lower dropout rate) as compared to CBT. Discussion: This study represents the first attempt to test a male-specific psychotherapy for MDD in a single-setting compared to standard CBT and a Waitlist control condition using randomized clinical trial methodology. In addition, the potential positive adjunct effect of psychotherapy to TT in reducing depressive burden and improving quality of life in hypogonadal depressed men represents a neglected research area and might introduce new hypogonadism screening procedures in depressed men and combined treatment approaches for depressed men suffering from hypogonadism. Limitations are the rigorous inclusion and exclusion criteria, which limit the generalizability of the study results to first episode treatment naïve depressed men. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05435222.

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.

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.

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.

[Prehospital emergency anesthesia in adults : Current recommendations for performing prehospital emergency anesthesia based on the recommendations for prehospital emergency anesthesia in adults]. / Präklinische Notfallnarkose beim Erwachsenen : Aktuelle Empfehlungen zur Durchführung einer prähospitalen Notfallnarkose basierend auf den Handlungsempfehlungen zur prähospitalen Notfallnarkose beim Erwachsenen.

The frequency of prehospital emergency anesthesia in Germany is around 2-3% of all emergency medical missions. The Association of the Scientific Medical Societies of Germany (AWMF) has published guidelines for the implementation of a prehospital emergency anesthesia. The purpose of this article is to highlight important aspects from these guidelines and to present the implementation and special features for specific patient groups. A case study is intended to illustrate that the preclinical setting can provide various facets that make a certain amount of experience and expertise indispensable. The article emphasizes that clear standard situations are not always present and that there are some challenges in the preclinical setting. Therefore, mastering the content of prehospital emergency anesthesia and the manual skills of induction of anesthesia are essential and obligatory for the emergency team.

[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.

New directions in male-tailored psychotherapy for depression.

Purpose of review: Societal, cultural, and contextual norms about how men should be and behave (so called traditional masculinity ideologies; TMI) affect men's presentation of depressive disorders, psychotherapy use, and treatment engagement. Only recently, however, male-tailored psychotherapy approaches for depressive disorders have been developed, which aim to systematically soften dysfunctional TMI. In this review, we outline the necessary groundwork as well as recent advances in research on TMI, men's help-seeking, male depression, and their interrelatedness. Subsequently, we discuss the potential value of these findings for male-tailored psychotherapy for depressive disorders. Recent findings: A preliminary evaluation of a male-specific psychoeducation program found that a male-specific psychoeducation text could reduce negative affect as well as state shame and potentially elicit a shift from externalizing depression symptoms toward more prototypical depression symptoms. The James' Place program, a male-tailored community-based service, improved suicidal men's overall well-being, problems, functioning, and suicide risk. The Heads Up Guys! program, an eHealth resource aimed at depressed men, reported a high and increasing global interest in their website, with considerable visitor engagement. The Man Therapy online resource improved depressive symptoms, suicidal ideation, and help-seeking behavior. Finally, the Men in Mind program, an online training program for clinical practitioners, increased practitioners' capacity to engage and support men in therapy. Summary: Male-tailored psychotherapy programs for depressive disorders, which are informed by recent advances in TMI research, may potentially increase therapeutic effectiveness, engagement, and adherence. While recent preliminary analyses of individual male-tailored treatment programs show promising results, extensive and systematic primary studies evaluating these programs are pending but greatly needed.

Not Always a "Buffer": Self-Compassion as Moderator of the Link Between Masculinity Ideologies and Help-Seeking Intentions After Experiences of Intimate Partner Violence.

Many women and men experience intimate partner violence (IPV) during their lifetime. However, only relatively few people actually seek formal help after such an experience. The current study applied the mediated-moderation model of self-compassion and stigma that has previously been used to explain men's help-seeking behavior for depressive symptoms. The current study analyzed whether conformity to masculinity ideologies (CMI), self-stigma, and self-compassion were related to women's and men's intention to seek formal help after IPV experiences. A cross-sectional online questionnaire study was conducted with 491 German-speaking participants (65.8% women/34.2% men; age: M = 36.1 years; SD = 14.2). Participants read three vignettes about experienced IPV and then indicated how likely they would be to seek medical or psychological help if they were in the main character's situation. Additionally, the Conformity to Masculine Norms Inventory, Self-Stigma of Seeking Help Scale, and Self-Compassion Scale were used. Separate manifest path models for women and men revealed that strong CMI was linked to strong self-stigma in women and men. In turn, strong self-stigma was linked to weak intentions to seek formal help after IPV experiences. In men, strong self-compassion weakened (i.e., "buffered") the link between CMI and self-stigma. However, direct associations between strong CMI and weak intentions to seek formal help remained, especially for those participants with strong self-compassion. The current study adds to the existing literature on associations between CMI, self-compassion, and self-stigma by showing that those links are also relevant in women. However, self-compassion might not always act as a "buffer" and mediators that explain links between strong CMI and weak intentions to seek formal help in people with strong self-compassion need to be found in future studies.

How do traditional masculinity ideologies and emotional competence relate to aggression and physical domestic violence in cisgender men?

Background: Men are disproportionately often perpetrators of physical domestic violence (DV). Gender role constructs, such as traditional masculinity ideologies (TMI), are broadly accepted as an explanation for this effect. Emotional competence further constitutes an important role in TMI and the prevention of DV. However, the interactions between these constructs remains unclear. Objective: The present study aims to investigate associations of TMI with aggression, DV perpetration, and emotional competence, while also examining emotional competence as a potential moderator. Method: A sample of 428 cisgender men (M age = 43.9 ± 15.3) from German-speaking countries in Europe completed an anonymous online survey that assessed TMI, aggression, and DV perpetration as well as alexithymia, emotion regulation, and self-compassion as indicators of emotional competence. Results: Strong TMI were associated with high levels of aggression and overall reduced emotional competence, as reflected by high levels of alexithymia, frequent use of expressive suppression, and low levels of self-compassion. Strong conformity to TMI was associated with a higher likelihood for DV perpetration when considering relevant sociodemographic covariates. Moderation analyses revealed that expressive suppression buffered the association between TMI and DV perpetration. Conclusion: Men with strong TMI report high levels of aggression and impaired emotional competence. While strong conformity to TMI was associated with more frequent perpetration of DV, higher expressive suppression seems to buffer the association between TMI and DV perpetration. The present study highlights the importance of addressing gender ideologies when working on aggression, DV perpetration and emotional competence in men.