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A foundation model validated in a prospective multi-centre cohort of 21,601 patients undergoing low-dose computed tomography screening for breast and lung cancer showed comparable performance to existing screening by radiologists.

Several in vitro synthetic enzymatic biosystems (ivSEBs) to produce poly-3-hydroxybutyrate (PHB) via acetyl-coenzyme A (acetyl-CoA) have been reported, but suffer from complicated operation procedures, low yields, and/or dependence on costly ATP. Here, the authors report the design of an ATP-free ivSEB for one-pot, high-yield PHB biosynthesis via acetyl-CoA utilizing starch-derived maltodextrin as the sole substrate.

A new type of device, the band-to-band tunnel transistor, which has atomically thin molybdenum disulfide as the active channel, operates in a fundamentally different way from a conventional silicon (MOSFET) transistor; it has turn-on characteristics and low-power operation that are better than those of state-of-the-art MOSFETs or any tunnelling transistor reported so far.

A multimodal model for the stratification of breast cancer risk based on clinical metadata, mammography and trimodal ultrasound images performed as well as or better than radiologists at tumour classification and at differential diagnosis.

Nuclear architecture depends on proper regulation of lamin A/C modifications. Here, the authors show that TAF4A and NF-Y control Kansl2 expression in muscle stem cells, preserving genome stability and supporting muscle regeneration.

Xuejun Zhang, Jun Wang, Liangdan Sun, Lennart Hammarström and colleagues sequence the MHC region in 20,635 Han Chinese individuals. Their Han-MHC database allows identification of new susceptibility loci for psoriasis and could serve as a tool for investigating the role of the MHC region in other complex diseases.

By regulating the level of accessible cholesterol on endothelial cells via OSBP/ORP-mediated transport, tetraspanin tunes the balance of Cdc42 and RhoA activities to affect vascular inflammation. Reducing accessible cholesterol by statin treatment or blocking its non-vesicular transport by OSBP/ORP inhibition can limit vascular inflammation.

Tumor suppressor PTEN negatively regulates PI3K-AKT signaling by dephosphorylating PIP3. PTEN can also dephosphorylate peptide substrates in vitro, but the physiological relevance of this activity was unclear. Jiang and colleagues show that PTEN is a protein tyrosine phosphatase that selectively dephosphorylates insulin receptor substrate-1 and thus regulates cell metabolism and growth.

A comprehensive phylogeny and taxonomy for the medically and ecologically important genus Artemisia remain unavailable. Here, the authors combine genomic data with morphological analyses to reconstruct the most comprehensive phylogeny and taxonomy of global Artemisia.

Hyperuricemia, a major cause of gout, results from impaired urate excretion. Here, the authors reveal how key anti-gout drugs block URAT1, providing structural insights for designing better hyperuricemia treatments.

In this work, the authors study the immunological and virological effects of administering either wild-type anti-HIV-1 broadly neutralizing antibodies (bNAbs) or bNAbs with a mutation that increases binding to Fc-gamma receptors (FcγRs) to rhesus macaques in the acute phase of SHIV_AD8-EO infection.

DUR3 absorbs low-concentration urea from soil and recycles urea from senescent leaves. Here, authors resolve the DUR3 structure, clarify how urea is specifically recognized, and elucidate the proton-driven urea transport mechanisms of DUR3.

Seafood methylmercury contamination is a global food safety issue. A model is developed to explore the impact of China’s municipal wastewater policies on seafood safety and reductions in methylmercury exposure.

Bacterial lipoproteins have important biological functions, and the lipoprotien biogenesis enzyme Lgt is essential in most gram-negative bacteria. Here, the authors use structural and biochemical techniques to shed light on the function of Lgt in post-translational transacylation modification.

It is unclear how early-life urbanicity influences adult neurobehavioral traits. This study reveals that earlier menarche mediates the relationship between early-life urbanicity and adult neurobehavioral traits associated with mental disorders.

Utrophin is a dystrophin-related protein stabilizing the sarcolemma in absence of dystrophin. Here the authors report that inactivation of the protein deacetylase SIRT6, involved in the deacetylation of the epigenetic mark H3K56ac in muscle cells, increases expression of utrophin and ameliorates dystrophic muscle pathology in mice.

A cross-ancestry GWAS meta-analyses of brainstem structures identify 713 associations. It reveals shared/distinct genetic architectures across ancestries/substructures and overlaps with neuropsychiatric disorders and physiological functions.

Elucidation of broadly neutralizing antibodies (bnAb) is a goal in HIV vaccine development. Here, Bradley et al. show that administration of CTLA-4 blocking antibody with vaccine antigens increases HIV-1 envelope antibody responses in macaques and a bnAb precursor mouse model.

Gorman et al. designed a Lassa virus prefusion-stabilized soluble glycoprotein complex trimer (GPC), with which they identified a Lassa virus-neutralizing nanobody that bound the GPC apex and elicited neutralizing antibody responses in guinea pigs.

Wei et al. identify the HDL receptor SR-B1 as a host factor that enhances infection of cultured cells with SARS-CoV-2 in the presence of ACE2, thus providing a possible molecular connection between lipoprotein metabolism and COVID-19.

Inhibition of the fatty acid oxidation metabolic pathway through inactivation of Cpt1b enhances cardiomyocyte survival and proliferation and allows heart regeneration in adult mice.

Cryo-EM structures of the human pentameric glycosylphosphatidylinositol transamidase (GPIT) complex reveal its subunit assembly and its catalytic and GPI-binding sites.

Smooth muscle cell-specific knockout of Tet3 in mice leads to loss of intragenic 5-hydroxymethylcytosine, accumulation of spurious transcripts and TLR7/8-mediated lung inflammation resembling asthma in human lung samples.

Suppression of transcription in S-phase is crucial to prevent genome instability. Zhang et al demonstrate that increase of H4K20me1 due to loss of Kmt5b cause genome instability in muscle stem cells, resulting in stem cell senescence but rhabdomyosarcoma formation when p53 is inactivated.

CaV1.2 is crucial in cardiac, vascular and neuronal function, serving as a target for many drugs. Here, authors identify the binding site of herb-derived drug tetrandrine, and explore inhibitory mechanism of L/T-type selective DHP drug benidipine.

Na_V1.3 is involved in neuronal development, hormone secretion and pain perception. Here, the authors elucidate the molecular mechanism for modulation of Na_V1.3 by a site-2 neurotoxin bulleyaconitine A and a subtype selective antagonist ICA121431.

The presentation of systemic lupus erythematosus has been known to differ by ancestry, but the underlying genetic factors remain unclear. Here, the authors report ancestry-specific susceptibility loci and better risk prediction when using data from matched ancestral groups.

Apolipoprotein N-acyl transferase (Lnt) catalyses the final step in the protein lipidation pathway of Gram-negative bacteria. Here, the authors present the crystal structure ofE. coliLnt, which consists of a transmembrane domain and a nitrilase domain localised at the periplasmic side of the membrane.

The elimination of latently infected cells is a sought after goal in the treatment of HIV-1 infections. Here the authors develop an approach to eliminate latently HIV-1 infected cells by using an immunomodulatory protein, which can activate viral gene expression in these cells and direct T lymphocytes to lyse them in vitro.

Quaternary contacts mediated by an extended heavy-chain framework region 3 (FR3) have been shown to improve binding to HIV envelope and virus neutralization for a few antibodies. Here, Liu et al. engraft such an FR3 loop onto several potent broadly neutralizing antibodies, resulting in improved neutralization activity and pharmacokinetics.

Lipopolysaccharide, an essential component of the Gram-negative bacteria outer membrane, is inserted by LptD–LptE, a protein complex with a unique ‘barrel and plug’ architecture; the structure of the LptD–LptE complex of Shigella flexneri determined here shows LptD forming a 26-stranded β-barrel with LptE located inside the barrel of LptD, the first two β-strands are distorted by two proline residues, creating a potential portal in the barrel wall that might allow lateral diffusion of lipopolysaccharide into the outer membrane.

N6-methyladenosine (m6A) methylation of RNA is a common type of RNA modification that regulates gene expression. Here, the authors report m6A methylation of serpin 2 A negatively regulates inflammation and reduces heart dysfunction in the setting of sepsis.

An alternative HIV vaccine design facilitates generation of HIV-1-antibodies, with promising neutralization breadth in rodents and nonhuman primates.

Bispecific antibodies can have advantages compared to antibody cocktails. Here, the authors engineer and characterize two different approaches for generating bispecific SARS-CoV-2 specific antibodies and find that only one design increases antigen-binding and virus neutralizing activities.

The Ca_V2.3 channel is involved in synaptic plasticity and neurological disorders. Here, authors resolve the human Ca_V2.3 structure to explore functional heterogeneity of VSDs and elucidated the closed- and open-state inactivation mechanisms of the channel.

Hydroxyl-carboxylic acid receptor 2 (HCA2) functions as a high-affinity receptor for nicotinic acid (vitamin B3). Here, authors report the cryo-EM structure of the HCA2-G_i complex with the agonist MK-6892 and inactive state crystal structures of mutation stabilized HCA2, to describe the mechanism of HCA2 signaling.

Results from a phase 1 clinical trial show that a broadly neutralizing, HIV-specific antibody is durably expressed in vivo from a viral vector, highlighting an alternate approach for the delivery of antibodies in humans.

Sodium/proton exchanger 1 (NHE1) and its obligate binding partner Calcineurin B-homologous protein 1 (CHP1) regulate intracellular pH and volume homeostasis. Structures of the human NHE1-CHP1 complex offer insight into the regulation of NHE1 pH-sensitivity by CHP1 and into the interactions with NHE1 inhibitors.

In a prespecified interim analysis of the multicenter, randomized, phase 3 FLAMES trial, maintenance therapy with a PARP inhibitor in patients with ovarian cancer showed prolonged progression-free survival compared with placebo in all subgroups defined by BRCA or homologous recombination status.

Utilization of the entire lignocellulose is essential for sustainable and cost-effective biorefineries, but it is hindered by a trade-off between efficient carbohydrate utilization and lignin-to-chemical conversion yield. Here, the authors report a mild lignocellulosic fractionation process using aqueous diethylamine which produces a carbohydrate fraction susceptible to enzymatic hydrolysis and a high-quality lignin that delivers high monomer yields upon catalytic amination and depolymerization.

The E2-like enzyme human Atg3 catalyses the transfer of ubiquitin-like mammalian LC3 to the lipid phosphatidylethanolamine during autophagosome formation. Here, the authors combine NMR measurements with in vitro biochemical and in vivo cellular assays and show that the N-terminal conserved region of human Atg3 communicates information from the curvature-sensing domain to its active site.

Unmet need exists for a vaccine against Middle East respiratory syndrome coronavirus (MERS-CoV). Here the authors report the establishment and evaluation, in mice and primates, of a series of MERS-CoV immunogens and show that they can serve as promising leads for vaccine development.

Huang and colleagues identify that EAG2 and Kvβ2 physically interact to form a potassium channel complex in glioblastoma and develop a designer peptide that disrupts their interaction and induces tumor regression.

Crystal structures of PAFR in complex with the antagonist SR 27417 and the inverse agonist ABT-491, together with accompanying experiments, provide insight into recognition of PAF and reveal an unusual ligand-dependent conformation of helical bundle.

Cross-ancestry genome-wide association studies of 3,414 brain imaging phenotypes in Chinese Han and white British participants identify autosomal and X-chromosomal associations in more diverse populations.

The authors report the structures of glutamate-gated kainate receptors in complex with NETO2 in both the resting and the desensitized states and reveal how kainate receptors in the brain are regulated by NETO2.

Worldwide, the number of only-child families is increasing. This research examines how growing up without siblings affects adult brain structure, function and connectivity, cognition, personality and mental health.