We aim to investigate the spatial experience of patients with chronic scotomas caused by lesion to early visual cortex, including primary visual cortex (V1) and adjacent extrastriate visual areas. These experiments are conducted as part of an adversarial collaboration testing contrasting theories of consciousness: Integrated Information Theory (IIT) and two Predictive Processing accounts, Active Inference (AI) and Neurorepresentationalism (NREP). The central question is whether lesions to early visual cortex alter the experienced extent of visual space itself, or instead primarily disrupt stimulus content within an otherwise preserved visual space. To address this, we use paradigms in which patients estimate distances or spatial extents that either span a scotomatous region or fall entirely within intact visual field locations. Psychometric functions relating perceived and physical extent are modeled to estimate shifts in the point of subjective equality (PSE). According to IIT, lesions to early visual cortex, including V1 and occipital exstrastriate cortex, should lead to systematic reductions in perceived spatial extent across the scotoma (negative PSE shifts), reflecting a contraction of experienced space. In contrast, Predictive Processing accounts posit that higher-level predictive mechanisms preserve spatial structure despite loss of early input, predicting little or no systematic contraction (with NREP allowing limited context-dependent effects). By quantifying distortions in perceived spatial extent, this protocol aims to distinguish between these competing theoretical predictions.

Coastal wetlands are critical blue carbon reservoirs, yet the depth-resolved impacts of warming on belowground carbon dynamics remain poorly understood. Over the course of an 8-year in situ experiment, we investigated plant-derived carbon inputs, soil carbon losses via respiration, and microbially mediated carbon fixation across a 60 cm soil profile under a projected 2°C atmospheric warming scenario. Plant carbon fixation (above- and belowground net primary productivity) and soil respiration exhibited synchronized responses to warming, with an initial increase, followed by a decline in the mid-term, and no significant response in the later stages. Soil and microbial respiration stabilized after prolonged exposure to elevated temperatures, as these processes were constrained by substrate availability. In contrast, phospholipid fatty acid profiling, amino sugar biomarkers, and metagenome-assembled genomes consistently indicated a greater than one-third reduction in microbial carbon fixation within subsoils (40-60 cm). Our fully factorial, depth-stratified warming design reveals the particular vulnerability of deep soil microbial carbon retention to long-term climate warming, independent of shifts in plant input or respiratory carbon loss. This work highlights underappreciated pathways influencing soil blue carbon dynamics in a changing world.

Background The overuse and misuse of antibiotics significantly contributes to antimicrobial resistance (AMR). Adverse reactions to antibiotics are well documented, but their impact on patients’ behaviours requires further exploration. Aim To explore how side effects and allergies influence patients’ behaviours to prescribed antibiotic use. Design & setting A mixed-methods explanatory sequential study in England. Method A survey of 1059 adults with prior experience of antibiotic side effects was conducted. Descriptive statistics identified common side effects and behavioural responses, while chi-squared tests explored demographic differences. Focus groups were held with 21 participants, recruited through a research panel. Thematic analysis captured deeper insight into participants’ personal experiences. Results Many antibiotic side effects were identified, presenting shortly after consumption and affecting several aspects of patients’ lives. One-third of respondents (31%, n =325; 95% CI: 28-34%) were unaware of potential side effects beforehand, citing inaccessible patient information leaflets and limited communication from healthcare professionals as barriers. Almost half (42%, n =440; 95% CI: 37-47%) did not complete their antibiotic course following the side effects, with 32% ( n =142; 95% CI: 28-37%) stopping without medical advice. Many allergy diagnoses were made in childhood without follow-up assessments. Conclusion Antibiotic side effects can significantly disrupt patients’ lives and discourage appropriate use of antibiotics. Providing accessible information before prescribing may help manage expectations and support self-management of side effects. Patients with longstanding allergy labels should be encouraged to undergo reassessment to ensure that they are not contributing to AMR by unnecessarily avoiding the use of first-line antibiotics.

The accurate computation of high-spin/low-spin gaps remains a challenging task in computational chemistry, with significant implications for both theoretical studies and experimental applications. In this work, we present an exchange-dedicated perturbation theory (EDPT2) that allows an efficient calculation of exchange couplings in magnetic systems. Our approach builds on a previously developed second-order perturbative scheme based on de Loth's formalism but refines the treatment of singlet wave functions by explicitly incorporating ionic determinants in the zeroth-order description. The EDPT2 method is derived from a two-electron-two-center model and can be applied to multispin systems using minimal CAS-generated orbitals. A key advantage of EDPT2 lies in its computational efficiency, with a scaling of <i>N</i>⁴, where <i>N</i> is the number of basis functions. Benchmark calculations on diverse test systems demonstrate that EDPT2 achieves high-spin/low-spin gaps with accuracy comparable to the commonly used FIC-NEVPT2 method. Beyond its efficiency, EDPT2 provides valuable information on the mechanisms that govern magnetic exchange. The method allows for a detailed decomposition of second-order contributions, facilitating the identification of dominant exchange pathways. This is exemplified on two bis(nitronyl nitroxide) biradicals, where dynamic spin polarization emerges as the key exchange mechanism. Furthermore, using the example of a trisnitroxide triradical, we demonstrate how the insights from EDPT2 can be used to prepare selective multireference CI approaches. A combined DDCI1 approach with EDPT2-derived corrections is shown to successfully reproduce the experimental doublet-quartet gap.

Dr. Ritchie writes: "The perspective “Structural Nanocomposites” (Y. Dzenis, 25 January, p. 419) describes a quest for improved structural materials and indicates that composites with nanoscale reinforcements would have “exceptional mechanical properties.” Is this true? Why would reinforcements that are small in size or volume offer any particular benefit over larger-scale reinforcements? As the Perspective correctly asserts, if the composite material is to be used for a small-volume structure, clearly the reinforcements must also be small. In addition, small-volume reinforcements are stronger, as has been known since the early days of research on whiskers (1). In this regard, reinforcement by carbon nanotubes, for example, which are thought of as one of the strongest materials in existence (2), would seem ideal. The problem with this notion is that new materials are not limited by strength, but by resistance to fracture (also known as fracture toughness). It is not by accident that most critical structures, such as bridges, ships, and nuclear pressure vessels, are manufactured from materials that are low in strength but high in toughness. Indeed, the majority of toughening mechanisms mentioned by Dzenis—i.e., crack deflection, plastic deformation, and crack bridging—are promoted by increasing, not decreasing, reinforcement dimensions [e.g., (3)]. Is it any surprise that “results obtained so far are disappointing”?... Dr. Dzenis's reply is included.

Body size is a fundamental driver of metabolism, yet it remains unclear whether colonial organisms such as corals conform to the universal ¾-power scaling law. As climate change accelerates metabolic demands, characterizing these scaling relationships is essential to identifying which species are most physiologically vulnerable to environmental shifts. Here, we test whether coral polyp morphological traits can predict aerobic metabolism across a diverse range of reef-building species. We examine relationships between respiration and polyp biovolume, surface area, and corallite width, finding isometric scaling with biovolume and slight positive allometry with surface area, with both exponents close to one. Using median corallite width, we further extrapolate our model to theoretically predict per-polyp respiration for 727 coral species from a publicly available trait database.

Mitochondrial glutathione (mtGSH) supports iron-sulfur cluster (ISC) stability in the electron transport chain (ETC). Here we have investigated the role of the mtGSH transporter SLC25A40 in macrophage activation. SLC25A40 is present in both murine and human macrophages and its expression was increased by LPS treatment. Reducing SLC25A40 expression using siRNA destabilized ISC-rich ETC proteins and elevated mitochondrial and cellular reactive oxygen species (ROS). It also induced expression of the genes Gclc and Gclm, which are involved in GSH biosynthesis. SLC25A40 deficiency also diminished IL-1β and IL-10 production at the transcriptional level in response to LPS. As a result, the production of mature IL-1β was decreased following activation of NLRP3 by nigericin or ATP, with no effect on pyroptosis. Depleting mtGSH with mitochondrially-targeted CDNB phenocopied these defects, whereas supplementation with a cell-permeable GSH ester partially restored pro-IL-1β production. Together, these data identify SLC25A40 as a key regulator that sustains ETC integrity to promote cytokine production, revealing a previously unrecognized role for the SLC25A40-mtGSH axis in coupling mitochondrial redox control to macrophage activation.

Abstract Lipids play crucial roles in immunity and inflammation via controlling immune cell metabolism and function. In particular, phospholipids (PLs), as essential structural elements of biological membranes, critically orchestrate innate and inflammatory responses through coordinating membrane plasticity and cellular signaling. Researches over the past decade have revealed the versatile roles of PL metabolism in innate immunity and inflammation as well as their differential physiological and pathological consequences, highlighting PL metabolites or enzymes as promising potential biomarkers and therapeutic targets. Further unveiling the spatiotemporal characteristics and mechanistic links between phospholipid metabolism, innate immunity, and the development of inflammatory diseases will add new insights into immunometabolism underlying health and diseases, and may suggest new strategies for manipulating PL metabolism toward novel immunotherapy against harmful inflammation and cancer. In this review, we discussed the roles of distinct lipids in innate immunity and inflammation, with particular focus on how phospholipid metabolism and membrane homeostasis are actively reprogrammed during the innate immune response, and how the crosstalk between phospholipids and innate immunity finally orchestrates the outcome of host defense and tissue homeostasis. We also discussed how dysregulation of PL metabolism contributes to pathological processes in inflammatory diseases, such as autoimmune diseases, cardiovascular diseases and cancers, and the potential strategies of restoring PL homeostasis for disease treatment.

ABSTRACT The flexoelectric effect, a polarization phenomenon unrestricted by material symmetry, holds great promise for next‐generation energy harvesting and sensing. However, conventional flexoelectric devices require external mechanical stress, which severely limits their practical applicability. Here, we present a heterojunction‐based dual‐mode flexoelectric nanogenerator that is driven by light and heat, requiring no external mechanical or electrical input. Under illumination (photodetection mode) or temperature variation (thermal response mode), the heterojunction components undergo differential deformation, generating a pronounced interfacial strain gradient that drives strong flexoelectric polarization and flexo‐photovoltaic currents. The photodetection mode demonstrates a broad spectral response from 250 to 600 nm, with a peak responsivity of 2.2 mA W −1 . The thermal response mode exhibits an effective pyroelectric coefficient as high as 7518 µC m −2 K −1 , surpassing conventional pyroelectric materials by over an order of magnitude. By eliminating the need for external stress, this work enables direct coupling among optical, thermal, mechanical, and electrical energies, opening a new avenue for self‐powered photodetectors and thermal sensors based on flexoelectricity.

Protonatable nitroxides are electron paramagnetic resonance (EPR) molecular probes employed for pH measurements in bulk aqueous media. The change in the protonation state of the molecule induces a measurable change in the <i>g</i>- and hyperfine (<i>A</i>) parameters used as pH indicators. The quantitative understanding of the origin of the change of the EPR parameters in terms of electronic structure and different solvation patterns is still lacking. Here, we delve into the origins of the changes in the <i>g</i>- and hyperfine (<i>A</i>) parameters of ¹⁴N upon protonation of the heterocyclic nitrogen of the pH-sensitive nitroxide probe HMI (2,2,3,4,5,5-hexamethylimidazolidin-1-oxyl, C₉H₁₉N₂O) by means of combined experimental and theoretical techniques that have been developed and extensively validated in previous works. To establish a molecular-level understanding of the dependency of EPR parameters on the pH of the medium, we considered two limiting cases of deprotonated (pH ≫ p<i>K</i>_a) and protonated (pH ≪ p<i>K</i>_a) states of HMI. We found that, upon protonation of the heterocyclic nitrogen, the change in the electronic structure dominates the pH dependency of isotropic <i>g</i> and <i>A</i> values. Supporting this prominent role of electronic structure modulation, the average shift of EPR observables between the corresponding hydrogen-bonding states of the protonated and unprotonated forms remains constant. Furthermore, the results establish that the hydrogen bonding network structures around the nucleus of interest only marginally change upon protonation, although the populations of corresponding states with given H-bond numbers strongly do. This feature entails an additional, smaller contribution to the relative pH dependency of <i>g</i>^iso and <i>A</i>^iso values over electronic structure modulation upon protonation in a given H-bond state. The findings of this study pave the way to investigating HMI-based labels in peptides and other pH-sensitive EPR probes in protic polar solvents.

The small gap room temperature semiconductor a-RuCl3 which is known to undergo a Mott-Hubbard transition at low temperatures, is one of the most promising candidates for realisation of an exotic matter form, the quantum spin liquid state, which may have applications in quantum computing. Although being extensively investigated by neutron scattering techniques, electronic study of this system in form of van der Waals heterostructures has been limited to mainly graphene proximity. Here we report a systematic study of planar and tunnelling electronic properties of a -RuCl3 films, where we observe an n-type semiconducting property of a -RuCl3 films at room temperature, with a Mott insulator nature onset below 120K. In constant some of the previous studies, we focus on films of three-layer thickness and below and we find inelastic scattering features, below the Neel temperature of 7-14.5 K, some of which we attribute to single magnon modes. We believe our study electrically confirms preserved low temperature signatures of the bulk zigzag antiferromagnetic order and its single magnon modes within the previously observed continuum in atomically thin film limit. The experimental progress could be a step for future electronic characterisation of quantum spin liquid state in the vicinity of the zigzag antiferromagnetic order as well as the Majorona excitations in a-RuCl3 in tunnelling transistors.