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Although two-dimensional (2D) layered double hydroxides (LDHs) have been widely used as efficient nanoagents for biological diagnosis and treatment, they have been found to be inert as photosensitizers (PSs) for photodynamic therapy (PDT). Herein, we report the defect engineering of ultrathin 2D CoMo-LDH and NiMo-LDH nanosheets as highly active inorganic PSs for PDT in the third near-infrared (NIR-III) window. Hydrothermal-synthesized 2D CoMo-LDH and NiMo-LDH nanosheets are etched via a simple acid treatment to obtain defect-rich CoMo-LDH and NiMo-LDH nanosheets. Importantly, the defect-rich CoMo-LDH nanosheets exhibit much higher activity (~97 times) for generation of reactive oxygen species than that of the pristine CoMo-LDH nanosheets under a NIR-III 1567 nm laser irradiation. Therefore, after modification with polyethylene glycol, the defect-rich CoMo-LDH nanosheets can be used as an efficient inorganic PS for PDT to efficiently induce cancer cells apoptosis in vitro and eradicate tumors in vivo under 1567 nm laser irradiation. Defect engineering of 2 dimensional layered double hydroxide sheets improves their photocatalytic activity. Here, the authors etch sheets in acid and show that the etched sheets generate substantially more reactive oxygen species that untreated sheets and the treated sheets can be used to kill cancer cells in vitro and in vivo.

Multifunctional hydrogel with asymmetric and reversible adhesion characteristics is essential to handle the obstructions towards bioapplications of trauma removal and postoperative tissue synechia. Herein, we developed a responsively reversible and asymmetrically adhesive Janus hydrogel that enables on-demand stimuli-triggered detachment for efficient myocardial infarction (MI) repair, and synchronously prevents tissue synechia and inflammatory intrusion after surgery. In contrast with most irreversibly and hard-to-removable adhesives, this Janus hydrogel exhibited a reversible adhesion capability and can be noninvasively detached on-demand just by slight biologics. It is interesting that the adhesion behaves exhibited a molecularly encoded adhesion-adaptive stiffening feature similar to the self-protective stress–strain effect of biological tissues. In vitro and in vivo experiments demonstrated that Janus hydrogel can promote the maturation and functions of cardiomyocytes, and facilitate MI repair by reducing oxidative damage and inflammatory response, reconstructing electrical conduction and blood supply in infarcted area. Furthermore, no secondary injury and tissue synechia were triggered after transplantation of Janus hydrogel. This smart Janus hydrogel reported herein offers a potential strategy for clinically transformable cardiac patch and anti-postoperative tissue synechia barrier. Reversible and asymmetric adhesion is needed in removable post-operative patches to reduce trauma and prevent tissue adhesions. Here, the authors report on a conductive musselinspired adhesive Janus hydrogel with an anti-adhesive top for cardiac repair which can be removed using glutathione solutions.

The discovery of natural adhesion phenomena and mechanisms has advanced the development of a new generation of tissue adhesives in recent decades. In this study, we develop a natural biological adhesive from snail mucus gel, which consists a network of positively charged protein and polyanionic glycosaminoglycan. The malleable bulk adhesive matrix can adhere to wet tissue through multiple interactions. The biomaterial exhibits excellent haemostatic activity, biocompatibility and biodegradability, and it is effective in accelerating the healing of full-thickness skin wounds in both normal and diabetic male rats. Further mechanistic study shows it effectively promotes the polarization of macrophages towards the anti-inflammatory phenotype, alleviates inflammation in chronic wounds, and significantly improves epithelial regeneration and angiogenesis. Its abundant heparin-like glycosaminoglycan component is the main active ingredient. These findings provide theoretical and material insights into bio-inspired tissue adhesives and bioengineered scaffold designs. Natural adhesives have received a lot of attention recently. Here, the authors develop a natural biological adhesive from snail mucus that can adhere to wet tissue and be used to accelerate healing of skin wounds.

Key Points Newly developed technologies enable us to gain novel insights into how the brain generates fear and anxiety states, based on the identification and manipulation of neuronal circuits within and among individual brain regions. Fear is mediated by a brain-wide distributed network involving long-range projection pathways and local connectivity. The disinhibitory microcircuit is a common motif in the basolateral amygdala (BLA), central amygdala and the prelimbic region of the medial prefrontal cortex, and is instrumental in fear acquisition and expression. Encoding of fear extinction involves many of the same brain areas that are involved in fear acquisition and expression; however, different circuits within the amygdala and prefrontal cortex are involved. Indeed, fear extinction circuits may in fact inhibit fear circuits to dampen fearful responding. As with fear and fear extinction, a brain-wide neuronal network underlies anxiety, with identified local microcircuits within the bed nucleus of the stria terminalis, the lateral septum, the ventral tegmental area (VTA) and the BLA. Importantly, there is potential overlap between fear and anxiety circuits. There is overlap of neuronal circuits that mediate negative and positive valence in areas such as the VTA. Understanding the interplay between these circuits is of vital importance for understanding adaptive behavioural states. Recent methodological progress has greatly facilitated the determination of the connectivity and functional characterization of complex neural circuits. In this Review, Tovote, Fadok and Lüthi examine studies that have adopted circuit-based approaches to gain insight into how the brain governs fear and anxiety. Decades of research has identified the brain areas that are involved in fear, fear extinction, anxiety and related defensive behaviours. Newly developed genetic and viral tools, optogenetics and advanced in vivo imaging techniques have now made it possible to characterize the activity, connectivity and function of specific cell types within complex neuronal circuits. Recent findings that have been made using these tools and techniques have provided mechanistic insights into the exquisite organization of the circuitry underlying internal defensive states. This Review focuses on studies that have used circuit-based approaches to gain a more detailed, and also more comprehensive and integrated, view on how the brain governs fear and anxiety and how it orchestrates adaptive defensive behaviours.

Key Points Observational and experimental studies dating back to the 1950s demonstrate that mammals spontaneously help distressed conspecifics. Research emphasizes the untrained, unrewarded nature of this behaviour, which is also biased towards familiar individuals, thus arguing against explanations that are exclusively based on associative learning or conditioning. The perception–action model extends an existing motor theory on overlapping representations to emotional phenomena; it states that observers who attend to a target's state understand and 'feel into' it through personal distributed representations of the target, the state and the situation. Easily observed manifestations of this mechanism are emotional contagion and motor mimicry, which have been demonstrated in many animals. In cognitive forms of empathy, the same representations are accessed from the top-down. Experiments on two common mammalian expressions of empathy — the consolation of distressed individuals and spontaneous assistance to those in need — support the crucial role of caught distress and arousal because these behaviours are suppressed by anti-anxiety medication and engage the same neuropeptide system that supports social attachment. The Russian-doll model seeks to arrange forms of empathy into layers that are built on top of each other — with the layers ranging from emotional contagion to more cognitive forms of empathy — in a functionally integrated whole based on perception–action processes. Perspective-taking is well developed in some non-human species, as manifested by theory-of-mind and targeted helping. One can segregate emotional and cognitive empathy (as well as felt and observed states) in the brains of observers, but all forms require some initial access to the observer's distributed, shared, personal representations of the target's state. At least in the initial phase of processing, this access helps to decode the target's state and provide subsequent processing with content and meaning, even if the shared state is not experienced, or is incomplete or inaccurate. Empathic pain does not usually include the peripheral sensation of the target's injury, but it can include sensory information when the stimuli and task instructions emphasize the specific nature of the feeling at the location of the injury. Empathy is a characteristic of all mammals that ranges from being sensitive to another's emotions to adopting their perspective. In this Review, de Waal and Preston discuss current hypotheses concerning how the emotional states of others are understood in a variety of species. Recent research on empathy in humans and other mammals seeks to dissociate emotional and cognitive empathy. These forms, however, remain interconnected in evolution, across species and at the level of neural mechanisms. New data have facilitated the development of empathy models such as the perception–action model (PAM) and mirror-neuron theories. According to the PAM, the emotional states of others are understood through personal, embodied representations that allow empathy and accuracy to increase based on the observer's past experiences. In this Review, we discuss the latest evidence from studies carried out across a wide range of species, including studies on yawn contagion, consolation, aid-giving and contagious physiological affect, and we summarize neuroscientific data on representations related to another's state.

Adhesive hydrogels have gained popularity in biomedical applications, however, traditional adhesive hydrogels often exhibit short-term adhesiveness, poor mechanical properties and lack of antibacterial ability. Here, a plant-inspired adhesive hydrogel has been developed based on Ag-Lignin nanoparticles (NPs)triggered dynamic redox catechol chemistry. Ag-Lignin NPs construct the dynamic catechol redox system, which creates long-lasting reductive-oxidative environment inner hydrogel networks. This redox system, generating catechol groups continuously, endows the hydrogel with long-term and repeatable adhesiveness. Furthermore, Ag-Lignin NPs generate free radicals and trigger self-gelation of the hydrogel under ambient environment. This hydrogel presents high toughness for the existence of covalent and non-covalent interaction in the hydrogel networks. The hydrogel also possesses good cell affinity and high antibacterial activity due to the catechol groups and bactericidal ability of Ag-Lignin NPs. This study proposes a strategy to design tough and adhesive hydrogels based on dynamic plant catechol chemistry. Biomimetic catechol-based adhesives have attracted significant interest but can lose adhesion due to excessive oxidation. Here, the authors report on the addition of silver-Lignin nanoparticles as a dynamic catechol redox system to maintain catechol/quinone balance, making a reusable, antibacterial bioadhesive.

Transcranial electric stimulation is a non-invasive tool that can influence brain activity; however, the parameters necessary to affect local circuits in vivo remain to be explored. Here, we report that in rodents and human cadaver brains, ~75% of scalp-applied currents are attenuated by soft tissue and skull. Using intracellular and extracellular recordings in rats, we find that at least 1 mV/mm voltage gradient is necessary to affect neuronal spiking and subthreshold currents. We designed an ‘intersectional short pulse’ stimulation method to inject sufficiently high current intensities into the brain, while keeping the charge density and sensation on the scalp surface relatively low. We verify the regional specificity of this novel method in rodents; in humans, we demonstrate how it affects the amplitude of simultaneously recorded EEG alpha waves. Our combined results establish that neuronal circuits are instantaneously affected by intensity currents that are higher than those used in conventional protocols. Though transcranial electric stimulation has been used to influence brain activity, it is debated whether neuronal spiking activity is directly affected by commonly-used protocols. Here, the authors quantify the voltage gradients necessary to instantaneously affect neuronal spiking and show that they are higher than commonly-used protocols.

Key Points The prefrontal cortex (PFC) and hippocampus support complementary functions in episodic memory. Connections between the PFC and the hippocampus are particularly important for episodic memory. In addition, these areas interact bidirectionally through oscillatory synchrony. Distinct types of interactions between the PFC and hippocampus are supported by a direct hippocampus–PFC connection and by bidirectional pathways via intermediaries in the thalamus and perirhinal and lateral entorhinal cortices. This Review outlines a model of how the PFC and hippocampus interact during episodic memory tasks. The prefrontal cortex and the hippocampus have distinct and complementary roles in episodic memory, and their interactions are also crucial for memory. Eichenbaum describes the pathways and mechanisms mediating these interactions and suggests a model of how these regions communicate to retrieve cued memories. The roles of the hippocampus and prefrontal cortex (PFC) in memory processing — individually or in concert — are a major topic of interest in memory research. These brain areas have distinct and complementary roles in episodic memory, and their interactions are crucial for learning and remembering events. Considerable evidence indicates that the PFC and hippocampus become coupled via oscillatory synchrony that reflects bidirectional flow of information. Furthermore, newer studies have revealed specific mechanisms whereby neural representations in the PFC and hippocampus are mediated through direct connections or through intermediary regions. These findings suggest a model of how the hippocampus and PFC, along with their intermediaries, operate as a system that uses the current context of experience to retrieve relevant memories.

Implant-associated infections due to the formation of bacterial biofilms pose a serious threat in medical healthcare, which needs effective therapeutic methods. Here, we propose a multifunctional nanoreactor by spatiotemporal ultrasound-driven tandem catalysis to amplify the efficacy of sonodynamic and chemodynamic therapy. By combining piezoelectric barium titanate with polydopamine and copper, the ultrasound-activated piezo-hot carriers transfer easily to copper by polydopamine. It boosts reactive oxygen species production by piezoelectrics, and facilitates the interconversion between Cu2 + and Cu + to promote hydroxyl radical generation via Cu +  -catalyzed chemodynamic reactions. Finally, the elevated reactive oxygen species cause bacterial membrane structure loosening and DNA damage. Transcriptomics and metabolomics analysis reveal that intracellular copper overload restricts the tricarboxylic acid cycle, promoting bacterial cuproptosis-like death. Therefore, the polyetherketoneketone scaffold engineered with the designed nanoreactor shows excellent antibacterial performance with ultrasound stimulation and promotes angiogenesis and osteogenesis on-demand in vivo. Implantation-associated infections often lead to infections. Here, the authors propose a piezo-based nanoreactor to achieve US-excited tandem catalysis, endowing the polyetherketoneketone bone scaffold with on-demand antibacterial and osteogenic capacities.

The dopamine system has been implicated in a number of psychiatric disorders, including depression and schizophrenia. Here, Grace describes evidence for disrupted afferent regulation of dopamine neuron firing in these disorders and considers the role of stress in driving this pathology. The dopamine system is unique among the brain's modulatory systems in that it has discrete projections to specific brain regions involved in motor behaviour, cognition and emotion. Dopamine neurons exhibit several activity patterns — including tonic and phasic firing — that are determined by a combination of endogenous pacemaker conductances and regulation by multiple afferent systems. Emerging evidence suggests that disruptions in these regulatory systems may underlie the pathophysiology of several psychiatric disorders, including schizophrenia and depression.