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Perovskite solar cells (PSCs) have rapidly evolved into next-generation photovoltaic devices because of their fascinating power conversion efficiencies and low manufacturing costs. However, achieving peak performance requires precise engineering of the electron transport layer (ETL) to optimise charge extraction and suppress recombination. Doping rare-earth (RE) into SnO2 is one potential way to enhance ETL properties and has been extensively studied1. In this study, we utilize SCAPS-1D simulations to investigate the impact of rare-earth (RE) doping (La, Ce, and Eu) in SnO2 ETLs within a FAPbI3-based PSC architecture. While variations in thickness and donor density of the perovskite layer were examined, our results reveal that device performance is primarily governed by bandgap engineering induced by the Burstein-Moss effect. This doping-induced bandgap widening shifts the conduction band edge, facilitating a quasi-ohmic contact and superior band alignment with the FAPbI3 absorber. At high defect densities and thicker absorber layer, however, a performance crossover was observed, highlighting the sensitivity of optimized interfaces to severe Fermi-level pinning. Motivated by this findings, we systematically optimized the perovskite absorber thickness and defect density (Nt), identifying a critical sweet spot at 0.6 μm and 1014 cm-3, respectively, where photon harvesting and bulk recombination are balanced. Notably, La-doped SnO2 exhibited the highest tolerance to bulk defects, maintaining superior Voc and FF through enhanced extraction kinetics that outrun trap-assisted recombination. Under optimized conditions, the La-doped device emerged as the champion configuration, significantly outperforming pristine device and marginally better than Ce-, and Eu-doped variants. These findings provide a fundamental framework for leveraging RE-doping to engineer interfacial energy levels, offering a clear pathway for the development of high-efficiency, defect-tolerant perovskite photovoltaics.

Concrete Outdoor Runs (OUTRUNs) are a characteristic part of organic pig housing. They must allow species-specific behaviours such as rooting and elimination, as explicitly required by organic legislation of the European Union (EU). However, OUTRUN design often fails to fulfil behavioural needs, and excreta can cover large parts of the OUTRUN leading to poor pen hygiene and associated ammonia (NH3) emissions. This review integrates legislative, ethological and environmental requirements for OUTRUNs for organic growing-finishing pigs. While EU regulations specify some welfare-related standards for OUTRUNs (e.g. minimal space allowance), national and private standards interpret some aspects differently, e.g. the proportion of roofed and slatted floor area. Furthermore, reducing NH3 emissions is equally a challenge for organic systems, even though EU legislation does not explicitly refer to OUTRUNs. Depending on the actual use of the OUTRUN for elimination, higher space allowance compared to conventional production norms increases the potential for a large NH3-emitting surface. The design of pen features (e.g. roof, floor, enrichment) can encourage pigs to separate functional areas and consequently reduce the elimination area and associated NH3 emissions. While providing the main lying area indoors, resting outdoors should be possible for sub-groups during the day. A roof protects pigs and resources (e.g. bedding) from adverse weather, but the effect on pig welfare and NH3 emissions is site-specific. A floor design that ensures practicable manure removal and drainage is most important to reduce emissions. Providing opportunities for exploring and rooting in the OUTRUN has particular relevance for pigs' behavioural needs and can improve pen hygiene by reducing the elimination area. Cooling facilities are increasingly important to prevent heat stress and its detrimental effects on welfare and pen hygiene. Finally, practicability for farmers needs to be ensured for all resources provided in OUTRUNs, as good management is crucial. Research gaps emerge regarding the association between soiling and NH3 and the influence of certain pen features (shape, roof, feeder location, pen partitions and wet areas) on pig behaviour and soiling.

Bacteriophages ("phage") are viruses that prey on bacteria in diverse environments, from biological tissues to soils. In many of these environments, bacterial hosts are constantly migrating, yet how bacterial migration is influenced by phage predation remains poorly understood. Using transparent granular hydrogels that mimic natural habitats, we directly visualize populations of motile Escherichia coli encountering lytic T4 phage. Unexpectedly, we find that even in phage-rich environments, bacteria successfully form chemotactic fronts that enable them to migrate over large distances without needing to develop phage resistance. Higher phage concentrations delay front formation but not steady-state front speed or shape. By combining our experiments with biophysical modeling, we demonstrate that this phenomenon arises from the ability of cells to collectively outrun trailing phage bursts-as quantified by a dimensionless "escape parameter" comparing chemotactic and predation rates. This work thus reveals and provides mechanistic insight into the role of cell motility in shaping phage-bacteria interactions in spatially-extended environments.

Methylglyoxal is a reactive aldehyde produced by macrophages as part of their antimicrobial innate immune arsenal. Our prior work showed that Listeria monocytogenes relies on glyoxalase A (GloA) and bacterial glutathione to detoxify methylglyoxal and that loss of GloA severely impairs bacterial virulence in mice and results in a 100 to 1,000 increase in bacterial mutation frequency. Glutathione is required for both methylglyoxal detoxification and for allosteric activation of the master virulence regulator PrfA, underscoring its central, yet complicated role in pathogenesis. We previously demonstrated that mutations that lock PrfA in its active conformation (PrfA*) rescue the virulence of gloA mutants. Here, we show that PrfA* not only restores virulence but also rescues the elevated mutation frequency of gloA mutants independently of canonical DNA repair pathways. We hypothesized that a PrfA-regulated gene mediates a GloA-independent mechanism to avoid the toxic effects of methylglyoxal and found that the absence of ActA abolished the PrfA*-mediated rescue of gloA mutations. In addition, loss of ActA in a wild-type background also increased the in vivo mutation frequency of L. monocytogenes. Since the primary role of ActA is to mediate bacterial cell-to-cell spread, we hypothesized that ActA allows L. monocytogenes to migrate away from MG-rich inflammatory foci populated by activated macrophages. Indeed, antibody depletion of elicited macrophages and neutrophils rescued the virulence defect and reduced mutation frequency of gloA mutants. We propose a model in which ActA-mediated actin-based motility allows L. monocytogenes to spatially evade localized methylglyoxal production and hence outrun host defenses.

Head and neck cancers represent a diverse group of malignancies with substantial heterogeneity in biology and prognosis for which management of advanced-stage disease remains a formidable challenge. Although the incorporation of immune checkpoint inhibitors has led the way to a new era of treatment possibilities, the current state of the science calls for further innovation and a nuanced approach to clinical trial design to address several unmet needs. This article from the NRG Oncology Recurrent/Metastatic Head and Neck Working Group aimed to critically identify gaps in clinical practice and the scientific literature and to propose actionable recommendations for future research in the framework of recurrent or metastatic squamous cell carcinoma of the head and neck.

The MINDY family of deubiquitinases (DUBs) are exemplified by their preference for cleaving K48-linked polyubiquitin. MINDY3 is architecturally distinct from other MINDY DUBs as its catalytic domain spans the entire length of the protein except for an atypical EF-hand insertion. We uncover this EF-hand (MINDY3EF-hand) to be a ubiquitin-binding domain with three distinct binding sites, enabling MINDY3 to bind and effectively cleave long polyubiquitin chains. Furthermore, the MINDY3EF-hand domain binds not only to polyubiquitin but also to the UBL domain of the proteasome shuttling and DNA repair factors RAD23A and RAD23B. The MINDY3EF-hand facilitates this interaction with RAD23s in cells and mediates MINDY3 recruitment to DNA damage sites, establishing this unique DUB as a potential regulator of cellular DNA damage responses. MINDY3 binds specifically to the UBL domain of RAD23s, and none of the other UBLs tested. The crystal structure of the MINDY3EF-hand:RAD23AUBL domain complex reveals the molecular basis for specificity. We find that MINDY3 can form a ternary complex with RAD23A/B and polyubiquitin, and our findings suggest a model wherein MINDY3 can deubiquitylate RAD23A/B-bound clients.

E3 ligases partner with E2 enzymes to regulate vast eukaryotic biology. The hierarchical nature of these pairings, with >600 E3s and ~40 E2s in humans, necessitates that E2s cofunction with numerous different E3s. Here, focusing on E3s in the RING-between-RING (RBR) family and their partner UBE2L3 and UBE2D-family E2s, we report an approach to interrogate selected pathways. We screened phage-displayed libraries of structure-based E2 variants (E2Vs) to discover enzymes with enhanced affinity and specificity toward half of all RBR E3 ligases (ARIH1, ARIH2, ANKIB1, CUL9, HOIL1, HOIP, and RNF14). Collectively, these E2Vs allowed distinguishing actions of different cofunctioning E3s, obtaining high-resolution cryogenic Electron Microscopy (cryo-EM) structures of an RBR E3 in the context of a substrate-bound multiprotein complex, and profiling an endogenous RBR E3 response to an extracellular stimulus. Overall, we anticipate that E2V technology will be a generalizable tool to enable in-depth mechanistic and structural analysis of E3 ligase functions, and mapping their activity states and protein partners in cellular signaling cascades.

The detection of viral RNA inside cells triggers a diverse range of antiviral responses, including global translation inhibition, interferon secretion, and RNA sequestration. Mutations in the gene zinc-finger NFX1-type containing 1 (ZNFX1) cause severe pediatric immunodeficiencies, including chronic viral infection and autoinflammation. Here, we show that ZNFX1 is an RNA helicase with cryptic and unusual bifurcating E3 ubiquitin ligase activity. Nucleotide-dependent RNA binding stimulates ZNFX1 to generate complex ubiquitin chains via a two-component ubiquitin circuit wired in parallel, with ubiquitin flux occurring via two competing paths. One route produces K63-linked polyubiquitin that drives RNA entrapment within self-propagating ZNFX1 aggregates, and the other route produces K48-linked polyubiquitin that drives ZNFX1 turnover. RNA entrapment restricts RNA virus replication and is reversible by deubiquitination. Pathogenic ZNFX1 variants are defective for viral restriction, linking RNA entrapment to antiviral immunity in vivo.

In 2022, consecutive sweeps of highly transmissible SARS-CoV-2 Omicron-derived lineages (B.1.1.529*) maintained viral transmission despite extensive antigen exposure from both vaccinations and infections. To better understand Omicron variant emergence in the context of the dynamic fitness landscape of 2022, we aimed to explore putative drivers behind SARS-CoV-2 lineage replacements. Variant fitness is determined through its ability to either outrun previously dominant lineages or more efficiently circumvent host immune responses to previous infections and vaccinations. By analyzing data collected through our local genomic surveillance program from Connecticut, USA, we compared emerging Omicron lineages' growth rates, estimated infections, effective reproductive rates, average viral copy numbers, and likelihood for causing infections in recently vaccinated individuals. We find that newly emerging Omicron lineages outcompeted dominant lineages through a combination of enhanced viral shedding or advanced immune escape depending on the population-level exposure state. This analysis integrates individual-level sequencing data with demographic, vaccination, laboratory, and epidemiological data and provides further insights into host-pathogen dynamics beyond public aggregate data.

As worldwide ecological difficulties become more profound, Quality High Green Development (HGD) is crucial to sustainable economic growth and prosperity. The use of new quality productivity (NQP) is a required driving force of firms' high-quality green transformation. This involves high-tech change, which has an impact here on ways of production and a higher quality production process, and included efficiency in process, related growth in this innovation and efficiency. This characteristic of NQP causes the way of sustainable development to improve, while giving the essential way in which enterprises practice permanent ecological responsibility in the future. This research uses a database that spans a decade (from 2012 to 2022) of Chinese enterprises listed on A-shares to explore the influence of NQP on the enterprise's HGD pursuit strategy in an empirical study. The results show that NQP can be regarded as a motivation factor for the ecological transition, in this case in enterprise-based development, and the results obtained prove significant even when subjected to a series robustness test. The thesis also examines the channels of transmission to indicate two main factors, the increase of the quality of labor used in industry, and the increase in potential outrun posed by financial restrictions. Such changes induce swifter change in enterprise vitality because productivity is considerably appropriately enhanced. The heterogeneity testing demonstrates that the positive impact is more pronounced in state-owned enterprises, large firms, firms located in advanced economic regions, and firms with isolated positions between the board of directors and chief executive officer. In light of this finding, policy suggestions are presented as follows: to put emphasis on environmental technology advancement as a foundation for improving NQP, to establish the markets for promoting corporate HGD, and to program specific strategies for this evolution. This contributes to the implications of companies' HGD, environmental quality, and sustainable development.

Induced proximity using small molecules, exemplified by targeted protein degradation (TPD), represents a highly promising therapeutic strategy with significant untapped potential. However, evaluating an induced proximity event that accurately reflects drug binding typically requires the challenging and costly development of specific ligands, which limits the advancement of medicines based on this modality. To overcome this bottleneck, we combine genetic code expansion with ultra-fast bioorthogonal chemistry to sensitize specific protein sites at single-residue resolution to a generic bioorthogonal proximity inducer (BPI) molecule. Mammalian cells expressing sensitized mutants of the ubiquitin E3 ligases VHL and CRBN exhibit neosubstrate degradation in the presence of a BPI equipped with a ligand targeting bromodomain and extraterminal (BET) proteins. Furthermore, we demonstrate E3-independent degradation through recruitment of an upstream E2 conjugating enzyme. We anticipate that this approach will have broad applicability, enabling comprehensive assessment of the scope of induced proximity.