Explore the vast range of titles available.

The past decade has seen the materialization of immune checkpoint blockade as an emerging approach to cancer treatment. However, the overall response and patient survival are still modest. Various efforts to study the “cancer immunogram” have highlighted complex biology that necessitates a multipronged approach. This includes increasing the antigenicity of the tumor, strengthening the immune infiltration in the tumor microenvironment, removing the immunosuppressive mechanisms, and reducing immune cell exhaustion. The coordination of these approaches, as well as the ability to enhance them through delivery, is evaluated. Due to their success in multiple preclinical models, external‐stimuli‐responsive nanoparticles have received tremendous attention. Several studies report success in distantly located tumor regression, metastases, and reoccurrence in preclinical mouse models. However, clinical translation in this space remains low. Herein, the recent advancement in external‐stimuli‐responsive nanoconstruct‐synergized immune checkpoint blockade is summarized, offering an industry perspective on the limitations of current academic innovations and discussing challenges in translation from a technical, manufacturing, and regulatory perspective. These limitations and challenges will need to be addressed to establish external‐stimuli‐based therapeutic strategies for patients. Herein, the recent advancement in external‐stimuli‐responsive nanoconstruct‐synergized immune checkpoint blockade is summarized, offering an industry perspective on the limitations of current academic innovations and discussing challenges in translation from a technical, manufacturing, and regulatory perspective. These limitations and challenges will need to be addressed to establish external‐stimuli‐based therapeutic strategies for patients.

Scientific evidence suggests that emotions affect actual human decision-making, particularly in highly emotionally situations such as human-wildlife interactions. In this study we assess the role of fear on preferences for wildlife conservation, using a discrete choice experiment. The sample was split into two treatment groups and a control. In the treatment groups the emotion of fear towards wildlife was manipulated using two different pictures of a wolf, one fearful and one reassuring, which were presented to respondents during the experiment. Results were different for the two treatments. The assurance treatment lead to higher preferences and willingness to pay for the wolf, compared to the fear treatment and the control, for several population sizes. On the other hand, the impact of the fear treatment was lower than expected and only significant for large populations of wolves, in excess of 50 specimen. Overall, the study suggests that emotional choices may represent a source of concern for the assessment of stable preferences. The impact of emotional choices is likely to be greater in situations where a wildlife-related topic is highly emphasized, positively or negatively, by social networks, mass media, and opinion leaders. When stated preferences towards wildlife are affected by the emotional state of fear due to contextual external stimuli, welfare analysis does not reflect stable individual preferences and may lead to sub-optimal conservation policies. Therefore, while more research is recommended for a more accurate assessment, it is advised to control the decision context during surveys for potential emotional choices.

How is it that groups of neurons dispersed through the brain interact to generate complex behaviors? Three papers in this issue present brain-scale studies of neuronal activity and dynamics (see the Perspective by Huk and Hart). Allen et al. found that in thirsty mice, there is widespread neural activity related to stimuli that elicit licking and drinking. Individual neurons encoded task-specific responses, but every brain area contained neurons with different types of response. Optogenetic stimulation of thirst-sensing neurons in one area of the brain reinstated drinking and neuronal activity across the brain that previously signaled thirst. Gründemann et al. investigated the activity of mouse basal amygdala neurons in relation to behavior during different tasks. Two ensembles of neurons showed orthogonal activity during exploratory and nonexploratory behaviors, possibly reflecting different levels of anxiety experienced in these areas. Stringer et al. analyzed spontaneous neuronal firing, finding that neurons in the primary visual cortex encoded both visual information and motor activity related to facial movements. The variability of neuronal responses to visual stimuli in the primary visual area is mainly related to arousal and reflects the encoding of latent behavioral states. Science , this issue p. eaav3932 , p. eaav8736 , p. eaav7893 ; see also p. 236 Neurons in the primary visual cortex encode both visual information and motor activity. Neuronal populations in sensory cortex produce variable responses to sensory stimuli and exhibit intricate spontaneous activity even without external sensory input. Cortical variability and spontaneous activity have been variously proposed to represent random noise, recall of prior experience, or encoding of ongoing behavioral and cognitive variables. Recording more than 10,000 neurons in mouse visual cortex, we observed that spontaneous activity reliably encoded a high-dimensional latent state, which was partially related to the mouse’s ongoing behavior and was represented not just in visual cortex but also across the forebrain. Sensory inputs did not interrupt this ongoing signal but added onto it a representation of external stimuli in orthogonal dimensions. Thus, visual cortical population activity, despite its apparently noisy structure, reliably encodes an orthogonal fusion of sensory and multidimensional behavioral information.

Low power electronics endowed with artificial intelligence and biological afferent characters are beneficial to neuromorphic sensory network. Highly distributed synaptic sensory neurons are more readily driven by portable, distributed, and ubiquitous power sources. Here, we report a contact-electrification-activated artificial afferent at femtojoule energy. Upon the contact-electrification effect, the induced triboelectric signals activate the ion-gel-gated MoS 2 postsynaptic transistor, endowing the artificial afferent with the adaptive capacity to carry out spatiotemporal recognition/sensation on external stimuli (e.g., displacements, pressures and touch patterns). The decay time of the synaptic device is in the range of sensory memory stage. The energy dissipation of the artificial afferents is significantly reduced to 11.9 fJ per spike. Furthermore, the artificial afferents are demonstrated to be capable of recognizing the spatiotemporal information of touch patterns. This work is of great significance for the construction of next-generation neuromorphic sensory network, self-powered biomimetic electronics and intelligent interactive equipment. Low power electronics endowed with artificial intelligence and biological afferent characters are beneficial to neuromorphic sensory network. Here, the authors report contact-electrification-activated artificial afferent at femtojoule energy, which is able to carry out spatiotemporal recognition on external stimuli.

Shape-changing hydrogels that can bend, twist, or actuate in response to external stimuli are critical to soft robots, programmable matter, and smart medicine. Shape change in hydrogels has been induced by global cues, including temperature, light, or pH. Here we demonstrate that specific DNA molecules can induce 100-fold volumetric hydrogel expansion by successive extension of cross-links. We photopattern up to centimeter-sized gels containing multiple domains that undergo different shape changes in response to different DNA sequences. Experiments and simulations suggest a simple design rule for controlled shape change. Because DNA molecules can be coupled to molecular sensors, amplifiers, and logic circuits, this strategy introduces the possibility of building soft devices that respond to diverse biochemical inputs and autonomously implement chemical control programs.

Numerous dynamic molecular crystals whose physical properties can be switched by external stimuli have recently been developed. This Review discusses how the precise control of the electron, proton and molecular movement within the crystals through the application of external stimuli can lead to considerable changes in their properties. The development of molecular materials whose physical properties can be controlled by external stimuli — such as light, electric field, temperature, and pressure — has recently attracted much attention owing to their potential applications in molecular devices. There are a number of ways to alter the physical properties of crystalline materials. These include the modulation of the spin and redox states of the crystal's components, or the incorporation within the crystalline lattice of tunable molecules that exhibit stimuli-induced changes in their molecular structure. A switching behaviour can also be induced by changing the molecular orientation of the crystal's components, even in cases where the overall molecular structure is not affected. Controlling intermolecular interactions within a molecular material is also an effective tool to modulate its physical properties. This Review discusses recent advances in the development of such stimuli-responsive, switchable crystalline compounds — referred to here as dynamic molecular crystals — and suggests how different approaches can serve to prepare functional materials.

Bionic electronic skin (E-skin) that could convert external physical or mechanical stimuli into output signals has a wide range of applications including wearable devices, artificial prostheses, software robots, etc. Here, we present a chameleon-inspired multifunctional E-skin based on hydroxypropyl cellulose (HPC), Poly(Acrylamide--co-Acrylic acid) (PACA), and carbon nanotubes (CNTs) composited liquid-crystal hydrogel. We found that the HPC could still form cholesteric liquid-crystal photonic structures with the CNTs additive for enhancing their color saturation and PACA polymerization for locating their assembled periodic structures. As the composite hydrogel containing HPC elements and the PACA scaffold responds to different stimuli, such as temperature variations, mechanical pressure, and tension, it could correspondingly change its volume or internal nanostructure and report these as visible color switches. In addition, due to the additive of CNTs, the composite hydrogel could also output these stimuli as electrical resistance signals. Thus, the hydrogel E-skins had the ability of quantitatively feeding back external stimuli through electrical resistance as well as visually mapping the stimulating sites by color variation. This dual-signal sensing provides the ability of visible-user interaction as well as antiinterference, endowing the multifunctional E-skin with great application prospects.

Traditional hydrogels are strong candidates for biomedical applications; however, they may suffer from drawbacks such as weak mechanics, static properties, and an inability to fully replicate aspects of the cellular microenvironment. These challenges can be addressed through the incorporation of second networks to form interpenetrating polymer network (IPN) hydrogels. The objective of this review is to establish clear trends on the enhanced functionality achieved by incorporating secondary networks into traditional, biopolymer-based hydrogels. These include mechanical reinforcement, ‘smart’ systems that respond to external stimuli, and the ability to tune cell–material interactions. Through attention to network structure and chemistry, IPN hydrogels may advance to meet challenging criteria for a wide range of biomedical fields. The extracellular matrix (ECM) is a complex assembly of biopolymers, the organization and composition of which combine to provide structural, mechanical, and biochemical signals to cells. Although single network hydrogels recapitulate features of the ECM, further advancements are needed to expand their functionality for many applications.Incorporation of secondary networks into biopolymer hydrogels imparts mechanical reinforcement, the ability to respond to stimuli, and increased mimicry of the ECM. These interpenetrating polymer network hydrogels are promising for tissue engineering, drug delivery, and in vitro disease models for drug discovery and screening.Addition of a second network makes conventional hydrogels amenable to many emerging biofabrication techniques geared towards achieving hierarchical architectures and personalized medicine.

Key Points The immunology of pregnancy has been considered as a host–graft response characterized by immune suppression and consequently a period of increased risk of bacterial and viral infection. However, accumulating evidence suggests that pregnancy is a more complex immunological condition, and thus a reassessment of many the immunological processes evaluated during pregnancy is required. Whereas a successful organ transplant requires constant immunosuppression, a successful pregnancy requires a robust, dynamic and responsive immune system. Embryo implantation and trophoblast invasion require a local inflammatory environment that promotes cell clearance, angiogenesis, cell growth and tolerance. Pregnancy complications, such as preterm birth, are often polymicrobial in nature and can involve viral infections that sensitize the pregnant mother to subsequent bacterial infections. Interferon-β is a crucial immune modulator during pregnancy; it protects the fetus against viral infections and contributes to the process of immune regulation at the maternal–fetal interface. The immune response associated with placental viral infections can affect maternal and fetal survival. Maternal inflammation due to viral or bacterial infections has detrimental consequences for fetal development. Although healthy pregnancies were traditionally considered to require an anti-inflammatory state, emerging evidence suggests that inflammation is important for a healthy pregnancy. Here, the authors discuss how the immune response varies throughout the main stages of pregnancy, and they consider how bacterial and viral infections can affect immune responses at the maternal–fetal interface. The comparison of the immunological state of pregnancy to an immunosuppressed host–graft model continues to lead research and clinical practice to ill-defined approaches. This Review discusses recent evidence that supports the idea that immunological responses at the receptive maternal–fetal interface are not simply suppressed but are instead highly dynamic. We discuss the crucial role of trophoblast cells in shaping not only the way in which immune cells respond to the invading blastocyst but also how they collectively react to external stimuli. We also discuss the role of the microbiota in promoting a tolerogenic maternal immune system and highlight how subclinical viral infections can disrupt this status quo, leading to pregnancy complications.

In this Review we survey the molecular sieving behaviour of metal–organic framework (MOF) and covalent organic framework (COF) membranes, which is different from that of classical zeolite membranes. The nature of MOFs as inorganic–organic hybrid materials and COFs as purely organic materials is powerful and disruptive for the field of gas separation membranes. The possibility of growing neat MOFs and COFs on membrane supports, while also allowing successful blending into polymer–filler composites, has a huge advantage over classical zeolite molecular sieves. MOFs and COFs allow synthetic access to more than 100,000 different structures and tailor-made molecular gates. Additionally, soft evacuation below 100 °C is often enough to achieve pore activation. Therefore, a huge number of synthetic methods for supported MOF and COF membrane thin films, such as solvothermal synthesis, seed-mediated growth and counterdiffusion, exist. Among them, methods with high scale-up potential, for example, layer-by-layer dip- and spray-coating, chemical and physical vapour deposition, and electrochemical methods. Additionally, physical methods have been developed that involve external stimuli, such as electric fields and light. A particularly important point is their ability to react to stimuli, which has allowed the ‘drawbacks’ of the non-ideality of the molecular sieving properties to be exploited in a completely novel research direction. Controllable gas transport through membrane films is a next-level property of MOFs and COFs, leading towards adaptive process deviation. MOF and COF particles are highly compatible with polymers, which allows for mixed-matrix membranes. However, these membranes are not simple MOF–polymer blends, as they require improved polymer–filler interactions, such as cross-linking or surface functionalization. This critical Review discusses the molecular sieving behaviour of metal–organic framework and covalent organic framework membranes as thin supported layers and mixed-matrix membranes. This behaviour is different from that of classical zeolite membranes.