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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.

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.

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.

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.

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.

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.

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.

The mitochondrial unfolded protein response is shown to inhibit pluripotency during somatic cell reprogramming and to inhibit the mesenchymal-to-epithelial transition through c-Jun-mediated histone acetylation.

Socioeconomic status is multidimensional and can change over time. Xu, Lui, Ji et al. found dimension-specific, late-stage-specific and change-specific socioeconomic effects on brain, cognition, personality and emotion.

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.

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.

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.

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

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

A high-quality genome assembly of pea cultivar ZW6 and pan-genome analyses provide insights into pea genome evolution and domestication as well as genomic resources for pea improvement.

Genome-wide association meta-analyses in populations of East Asian and European ancestries identify variant–trait associations for 44 hippocampal traits and provide insight into the genetic architectures of hippocampal and subfield volumes.

Acquired radioresistance is a challenge for the cure of glioblastoma. Here, the authors show that radioresistant glioblastoma boosts mitochondrial fatty acid oxidation that fuels cell proliferation and induces immunosuppression via CD47 mediated anti-phagocytosis. Inhibition of FAO by etomoxir combined with anti-CD47 antibodies sensitizes glioblastoma to radiotherapy.

An mRNA vaccine platform to prevent HIV-1 infection generated broadly neutralizing antibodies in non-human primates and protected some animals from infection, raising hope that optimization of this approach might lead to an effective HIV vaccine.

At Li-garnet interface, the poor interfacial wettability due to Li₂CO₃ passivation causes large resistance and unstable contact. Here the authors propose a Li₂CO₃-affiliative mechanism for air-accessible interface engineering of garnet electrolyte with superior wettability via facile liquid metal painting.

Broadly neutralizing antibodies (bNAbs) are being evaluated for HIV post-exposure prophylaxis (PEP) in the setting of vertical transmission. Here, using a macaque model of perinatal SHIV infection, the authors show that PEP for infant macaques within 30–48 h of SHIV exposure is highly effective using either bNAbs or ART.