Perovskite solar cells (PSCs) with power-conversion efficiencies comparable to established technologies hold huge promise for becoming the future photovoltaic technology, also given their versatility, low-cost and energy-efficient fabrication processes1. However, PSCs are not stable under moderate reverse bias2-4, an unavoidable situation under real-world operation, for instance, caused by partial shading of a module or installation with PSCs connected in series. Approaches to address this issue have focused on engineering the device architecture to enhance the breakdown voltage and mitigate the detrimental effects of reverse bias2,5,6. Here we present a completely different approach that fully solves the reverse-bias issue. With our Memsol, we developed a new concept of a solar cell with an integrated memristor, which protects the solar cell and simultaneously works as a bypass element. The memristor is realized by area-selective deposition of an additional metal-insulator stack and shares the perovskite and electrodes with the solar-cell part. Reverse-bias and shading tests show that the Memsol remains stable and automatically toggles between a low-resistance bypass state and full-efficiency solar-cell operation, dependent on the illumination and bias conditions. We anticipate that our Memsol concept, which we demonstrated on a nine-cell string in the lab, will be implemented in large-scale modules, accelerating their commercialization and potentially making external bypass diodes unnecessary.

Mammals have evolved a more complex brain, exemplified by the transformation of the single-layer dorsal cortex of excitatory projection neurons (ExNs) in ancestors into a multilayered cerebral neocortex1-4 enriched with diverse intratelencephalic and extratelencephalic ExN subtypes5-7, thereby establishing specialized projection systems that enhance brain connectivity and functionality5-8. This is in contrast to modern reptiles and birds with single-layered or pseudolayered columnar organization of ExNs4,9-12. However, the mechanisms underlying these mammalian-specific adaptations remain elusive. By comparing the landscape of gene expression and putative cis-regulatory elements (CREs) in mouse ExN subtypes and through cross-species examination, we identified mammalian-specific CREs, including a subset bound by the transcription factor ZBTB18 (also RP58, ZFP238 or ZNF238) and associated with genes defining intratelencephalic and extratelencephalic subtypes and connectivity, which have been implicated in intellectual disability and autism. Deletion of Zbtb18 in mouse ExNs dysregulated target gene expression, reduced molecular diversity, diminished cortico-spinal and callosal projections and increased intrahemispheric cortico-cortical association projections to the prefrontal cortex, thereby resembling non-mammalian brain. ZBTB18 binding motifs are highly enriched in callosally projecting intratelencephalic-biased putative CREs and show higher conservation specifically in mammals. This study uncovers critical components and mammalian-specific evolutionary adaptations within a regulatory node essential for neocortical ExN identity and connectivity.

Although immunotherapy has revolutionized cancer treatment, many patients still experience limited benefit, highlighting the urgent need for improved biomarkers1. Although immunotherapy is founded on unleashing T cells2, most existing biomarkers remain tumour-centric and mainly overlook host immune competence. The thymus is a key immune organ that is crucial for T cell maturation, and we hypothesized that thymic functionality is associated with immunotherapy outcomes3. Here we show that thymic health, a radiographic measure of thymic functionality, is strongly associated with immunotherapy outcomes across several cancer types. Using a deep-learning framework applied to routine computed tomography images, we quantified thymic health in a pan-cancer cohort of 3,476 patients receiving immune checkpoint inhibitors. In patients with non-small cell lung cancer, higher thymic health was associated with reduced risks of progression and all-cause mortality. These associations remained significant across clinically relevant levels of programmed death ligand 1 (PD-L1) and tumour mutation burden. In the prospective TRACERx lung cancer study, thymic health was positively associated with T cell receptor diversity and T cell receptor excision circles, and correlated with immune-system signalling pathways, supporting radiographic thymic health as a proxy for thymic activity and adaptive immune competence. Analysis across patients with melanoma, breast cancer or renal cancer demonstrated pan-cancer relevance. Together, these findings identify thymic health as a previously unrecognized, tumour-agnostic determinant of immunotherapy efficacy, with potential implications for patient stratification, treatment timing and the development of immune-rejuvenating strategies in precision immuno-oncology.

The thymus is essential for establishing T cell diversity early in life, but undergoes profound involution with age and has therefore traditionally been regarded as largely nonfunctional in adults1,2. Here we propose that preserving thymic functionality is integral to adult health and longevity. We developed a deep learning framework to quantify thymic health from routine radiographic images and evaluated its association with longevity and risk of major age-associated diseases in two large prospective cohorts of asymptomatic adults: the National Lung Screening Trial (n = 25,031) and the Framingham Heart Study (n = 2,581). In both cohorts, thymic health varied markedly across the population. In the National Lung Screening Trial, higher thymic health was consistently associated with lower all-cause mortality, reduced lung cancer incidence and lower cardiovascular mortality over 12 years of follow-up after adjustment for age, sex, smoking and comorbidities. In the independent Framingham Heart Study cohort, higher thymic health was significantly associated with reduced cardiovascular mortality, independent of age, sex and smoking. Thymic health was further linked to systemic inflammation and metabolic dysregulation, and associated with modifiable lifestyle factors including smoking, obesity and physical activity. Together, these findings reposition the thymus as a central regulator of immune-mediated ageing and disease susceptibility in adulthood, highlighting its potential as a target for preventive and regenerative strategies to promote healthy ageing and longevity.

Radiative forcing from well-mixed greenhouse gases (WMGHGs) is a main driver of Earth's energy imbalance and global surface climate change1,2. It remains difficult to constrain, largely because its longwave (LW) instantaneous radiative forcing (IRF) component depends on atmospheric state and is subject to radiative parameterization error3-7. The IRF measures the immediate change in radiative fluxes at the tropopause8-10 caused by perturbations in WMGHG concentrations. Here we show that increasing WMGHG concentrations have enhanced LW IRF by 3.69 ± 0.07 W m-2 (95% confidence interval) since 1850. We first use global line-by-line radiative transfer simulations to provide a global benchmark of LW IRF for the main WMGHGs under realistic, all-sky conditions. We then identify a robust linear relationship between LW IRF and outgoing longwave radiation (OLR), enabling state-dependent LW IRF to be directly inferred from regressions against satellite-observed OLR. Furthermore, LW IRF explains 91% of the inter-model spread in effective radiative forcing (ERF, which includes rapid atmospheric adjustments beyond the IRF) for CO2 (ref. 11) across Earth system models. Benchmarking model-simulated IRF using the regression technique reveals that most discrepancies originate from radiation parameterizations and correcting LW IRF biases would reduce uncertainty in CO2 ERF by 50%. Our results establish a simple and robust framework for quantifying state-dependent radiative forcing of WMGHGs, providing an observation-informed pathway for future climate assessments.

MicroRNAs (miRNAs) associate with Argonaute (AGO) proteins to form complexes that down-regulate target RNAs, including messenger RNAs from most human genes1-3. Within each complex, the miRNA pairs to target RNAs, and AGO provides effector function while also protecting the miRNA from cellular nucleases2-5. Although much is known about miRNA-directed gene regulation, less is known about how miRNAs themselves are regulated. One pathway that regulates miRNAs involves unusual targets called 'trigger' RNAs, which reverse the canonical regulatory logic and instead down-regulate miRNAs6-9. This target-directed miRNA degradation (TDMD) is thought to require a cullin-RING E3 ligase because it depends on the cullin protein CUL3 and other ubiquitylation components, including the BC-box protein ZSWIM8 (refs. 10,11). ZSWIM8 is required for murine perinatal viability and for destabilization of most short-lived miRNAs, which suggests biological importance of TDMD11-13. Here, biochemical and cellular assays establish AGO binding and polyubiquitylation by the ZSWIM8-CUL3 E3 ligase as the key regulatory steps of TDMD, and thereby define a unique cullin-RING E3 ligase class. Cryogenic electron microscopy analyses show ZSWIM8 recognizing distinct AGO and RNA conformations shaped by pairing of the miRNA to the trigger. Specificity of AGO ubiquitylation is established through generalizable RNA-RNA, RNA-protein and protein-protein interactions. The substrate features recognized by the E3 ligase do not conform to a conventional degron14,15 but instead establish a two-RNA-factor authentication mechanism for specifying a protein ubiquitylation substrate.