Notes

8-Hydroxybriaranes via Octocoral Briareum stechei (Briareidae) (Kükenthal, 1908).
In registered reports (RRs), initial peer review and in-principle acceptance occur before knowing the research outcomes. This combats publication bias and distinguishes planned from unplanned research. How RRs could improve the credibility of research findings is straightforward, but there is little empirical evidence. Mps1-IN-6 MPS1 inhibitor Also, there could be unintended costs such as reducing novelty. Here, 353 researchers peer reviewed a pair of papers from 29 published RRs from psychology and neuroscience and 57 non-RR comparison papers. RRs numerically outperformed comparison papers on all 19 criteria (mean difference 0.46, scale range -4 to +4) with effects ranging from RRs being statistically indistinguishable from comparison papers in novelty (0.13, 95% credible interval [-0.24, 0.49]) and creativity (0.22, [-0.14, 0.58]) to sizeable improvements in rigour of methodology (0.99, [0.62, 1.35]) and analysis (0.97, [0.60, 1.34]) and overall paper quality (0.66, [0.30, 1.02]). RRs could improve research quality while reducing publication bias and ultimately improve the credibility of the published literature.The performance of immune-checkpoint inhibitors, which benefit only a subset of patients and can cause serious immune-related adverse events, underscores the need for strategies that induce T-cell immunity with minimal toxicity. The gut microbiota has been implicated in the outcomes of patients following cancer immunotherapy, yet manipulating the gut microbiome to achieve systemic antitumour immunity is challenging. Here we show in multiple murine tumour models that inulin-a widely consumed dietary fibre-formulated as a 'colon-retentive' orally administered gel can effectively modulate the gut microbiome in situ, induce systemic memory-T-cell responses and amplify the antitumour activity of the checkpoint inhibitor anti-programmed cell death protein-1 (α-PD-1). Orally delivered inulin-gel treatments increased the relative abundances of key commensal microorganisms and their short-chain-fatty-acid metabolites, and led to enhanced recall responses for interferon-γ+CD8+ T cells as well as to the establishment of stem-like T-cell factor-1+PD-1+CD8+ T cells within the tumour microenvironment. Gels for the in situ modulation of the gut microbiome may be applicable more broadly to treat pathologies associated with a dysregulated gut microbiome.RNA-guided CRISPR activation (CRISPRa) systems have been developed in plants. However, the simultaneous activation of multiple genes remains challenging. Here, we develop a highly robust CRISPRa system working in rice, Arabidopsis and tomato, CRISPR-Act3.0, through systematically exploring different effector recruitment strategies and various transcription activators based on deactivated Streptococcus pyogenes Cas9 (dSpCas9). The CRISPR-Act3.0 system results in fourfold to sixfold higher activation than the state-of-the-art CRISPRa systems. We further develop a tRNA-gR2.0 (single guide RNA 2.0) expression system enabling CRISPR-Act3.0-based robust activation of up to seven genes for metabolic engineering in rice. In addition, CRISPR-Act3.0 allows the simultaneous modification of multiple traits in Arabidopsis, which are stably transmitted to the T3 generations. On the basis of CRISPR-Act3.0, we elucidate guide RNA targeting rules for effective transcriptional activation. To target T-rich protospacer adjacent motifs (PAMs), we transfer this activation strategy to CRISPR-dCas12b and further improve the dAaCas12b-based CRISPRa system. Moreover, we develop a potent near-PAM-less CRISPR-Act3.0 system on the basis of the SpRY dCas9 variant, which outperforms the dCas9-NG system in both activation potency and targeting scope. Altogether, our study has substantially improved the CRISPRa technology in plants and provided plant researchers a powerful toolbox for efficient gene activation in foundational and translational research.Resource allocation to reproduction is a critical trait for plant fitness1,2. This trait, called harvest index in the agricultural context3-5, determines how plant biomass is converted to seed yield and consequently financial revenue from numerous major staple crops. While plant diversity has been demonstrated to increase plant biomass6-8, plant diversity effects on seed yield of crops are ambiguous9 and dependent on the production syndrome10. This discrepancy might be explained through changes in the proportion of resources invested in reproduction in response to changes in plant diversity, namely through changes in species interactions and microenvironmental conditions11-14. Here, we show that increasing crop plant diversity from monocultures over two- to four-species mixtures increased annual primary productivity, resulting in overall higher plant biomass and, to a lesser extent, higher seed yield in mixtures compared with monocultures. The difference between the two responses to diversity was due to a reduced harvest index of the eight tested crop species in mixtures, possibly because their common cultivars have been bred for maximum performance in monoculture. While crop diversification provides a sustainable measure of agricultural intensification15, the use of currently available cultivars may compromise larger gains in seed yield. We therefore advocate regional breeding programmes for crop varieties to be used in mixtures that should exploit complementarity16 among crop species.Climate change, increasing populations, competing demands on land for production of biofuels and declining soil quality are challenging global food security. Finding sustainable solutions requires bold new approaches and integration of knowledge from diverse fields, such as materials science and informatics. The convergence of precision agriculture, in which farmers respond in real time to changes in crop growth with nanotechnology and artificial intelligence, offers exciting opportunities for sustainable food production. Coupling existing models for nutrient cycling and crop productivity with nanoinformatics approaches to optimize targeting, uptake, delivery, nutrient capture and long-term impacts on soil microbial communities will enable design of nanoscale agrochemicals that combine optimal safety and functionality profiles.
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