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Ni-based CO₂ reduction electrocatalysts have been reported to produce multicarbon products up to C₆ but with limited selectivity. Here the reaction mechanism of the process is elucidated. Consequently, pulsed potential electrolysis and electrolyte deuteration are respectively employed to enhance the selectivity of branched hydrocarbons and increase the total hydrocarbon Faradaic efficiency to 22%.

Artemisinin-resistantPlasmodium is an increasing problem. Here, using a medicinal chemistry programme, the authors identify a tetraoxane-based drug candidate that shows no cross-resistance with an artemisinin-resistant strain (PfK13-C580Y) and is efficient in Plasmodiummouse models.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

Over the past year there have been major advances in the rapidly evolving field of atherothrombosis study, in both basic and experimental research, and in clinical studies. In this Review, Javier Sanz, Pedro Moreno and Valentin Fuster provide an update of such advances for physicians and scientists with an interest in the study of atherothrombotic disease.

The restructuring of carbon-based supports under reaction conditions limits catalyst stability for vinyl chloride synthesis. Here, the authors report that hydrogen chloride generates defect sites on carbon nitride supports, promoting acetylene polymerization and accelerating catalyst deactivation.

It is unknown whether capsulized fecal microbiota transplantation (FMT) can modify the microbiota of people with HIV. Here, the authors report the results of a pilot double-blind study, where 30 HIV-infected subjects on ART were randomized to either weekly oral FMT capsules or placebo for 8 weeks, and show that transplanted microbiota successfully engrafts and is able to attenuate HIV-associated dysbiosis.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

Liu et al. demonstrate that human-driven soil contamination in natural areas mirrors that in nearby urban greenspaces globally, and highlight the potential influence that soil contaminants have on ecosystem functions.

The results of EMPATROPISM-FE, a post hoc analysis of the EMPA-TROPISM trial performed by Angermann et al., suggest that the beneficial effects of empagliflozin treatment in heart failure populations may be related to changes in iron metabolism.

The liver is segregated into spatially organized areas that serve distinct functions, though how these zones are patterned remains unclear. Here they show that mTORC1 controls spatial segregation of liver metabolic functions via modulation of Wnt signaling, and find that impaired zonation is also observed in pigs given total parenteral nutrition.

Crh proteins catalyze crosslinking of chitin and glucan polymers in fungal cell walls. Here, Bi et al. show that a Crh protein from the phytopathogenic fungus Botrytis cinerea acts as a cytoplasmic effector and elicitor of plant defense, and plants expressing this gene exhibit reduced sensitivity to the pathogen.

Sul-2 is a steroid sulfatase in c.elegans. Here the authors show that, in the absence of sul-2 enzymatic activity, worm lifespan is increased, and that chemical inhibition ameliorates symptoms of neurodegenerative disorders in worms and mice.

Transglycosylases strengthen the fungal cell wall by forming a rigid network of crosslinks. Here, Fang et al. show that the five Crh transglycosylases of Aspergillus fumigatus are dispensable for cell wall integrity in vitro, and solve the crystal structure of Crh5 in complex with chitooligosaccharides.

Authors propose their splenic mimetic filtration method, microsphiltration, and utilise this approach in a drug-screen, to identify compounds that induce a stiffening effect on Plasmodium falciparum-infected erythrocytes. They proceed to assess safety and tolerability of one identified compound in a phase I clinical trial.

Small proteins encoded by previously assumed non-coding RNAs can have cell regulatory functions. Here the authors report that TINCR lncRNA encodes pTINCR, a ubiquitin-like protein (UBL) that promotes epithelial differentiation through the SUMOylation and activation of CDC42, and it has tumour suppressor activity in epithelial cancers.

AMPK modulates idiopathic and hypoxic pulmonary hypertension in adults, largely via unknown mechanisms. Here, the authors show that AMPK deficiency in smooth muscles causes persistent pulmonary hypertension of the new born and premature death in mice, due to increased muscularisation and remodeling of pulmonary arteries, reduced alveolar numbers and alveolar membrane thickening

CDK4/6 inhibitor resistance is common in breast cancer. Here, the authors show that p16 overexpression may be linked to reduced efficacy of CDK4/6 inhibition, and show that the combination with PI3K inhibitors may increase anti-tumour effects.

Here, de Vries et al. perform a pre-clinical characterization of the antimalarial compound MMV693183: the compound targets acetyl-CoA synthetase, has efficacy in humanized mice against Plasmodium falciparum infection, blocks transmission to mosquito vectors, is safe in rats, and pharmacokinetic-pharmacodynamic modeling informs about a potential oral human dosing regimen.

Thirteen pharmaceutical companies have shared and integrated preclinical and clinical data for creating computational resources that enhance translational drug safety assessment.

Analysis of 2,170 SARS-CoV-2 sequences from the first wave of the COVID-19 epidemic in Spain provides insights into transmission patterns and the effects of lockdown on the emergence of new variants.

Benzoxaboroles have been shown to be active against different pathogens. Here, the authors show that the benzoxaborole AN3661 inhibitsPlasmodium falciparum in vitroand in mouse models, and identify a homologue of a mammalian cleavage and polyadenylation specificity factor as a drug target.

The description of a compound (DDD107498) with antimalarial activity against multiple life-cycle stages of Plasmodium falciparum and good pharmacokinetic and safety properties, with potential for single-dose treatment, chemoprotection and prevention of transmission.

Here, nearly 2 million compounds from GlaxoSmithKline's chemical library were screened for inhibitors of the malaria parasite Plasmodium falciparum, grown in red blood cells. Of these compounds, some 13,500 inhibited parasite growth, and more than 8,000 also showed potent activity against a multidrug resistant strain. The targets of these compounds were inferred through bioinformatic analysis, revealing several new mechanisms of antimalarial action.

Protein kinases are promising drug targets for treatment of malaria. Here, starting with a medicinal chemistry approach, Baker et al. generate an imidazopyridine that selectively targets Plasmodium falciparum PKG, inhibits blood stage parasite growth in vitro and in mice and blocks transmission to mosquitoes.

FlyWire presents a neuronal wiring diagram of the whole fly brain with annotations for cell types, classes, nerves, hemilineages and predicted neurotransmitters, with data products and an open ecosystem to facilitate exploration and browsing.

The genomes of two long-lived giant tortoises, including Lonesome George, reveal candidate genes and pathways associated with their development, gigantism and longevity.