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Many sporadic cases of hypertrophic cardiomyopathy have unknown genetic basis. Here, the authors identify a mutation in the gene NAP1L1 to be associated with cases of hypertrophic cardiomyopathy, linking it to cGAS-STING-IFN signaling.

Broad and potent neutralizing antibodies to SARS-CoV-2 variants can be efficiently identified via accurate deep-mutational-scanning-based prediction of viral evolution and delivered to mice using mRNA–lipid nanoparticles.

A millimetre-scale bioresorbable optoelectronic system with an onboard power supply and a wireless, optical control mechanism is developed for general applications in electrotherapy and specific uses in temporary cardiac pacing.

The balance between apoptosis and autophagy is critical for normal development, proper tissue function, and disease pathogenesis. Here, the authors show previously unannotated BIRC6 domains, including a ubiquitin-like ___domain, and how it utilizes its ubiquitylation function to regulate both apoptosis and autophagy.

Tubulointerstitial inflammation occurs frequently in acute kidney injury (AKI), and Mφ autophagy is a known contributor to inflammation-related diseases. Here, Yuan et al. show that Mφ autophagy deficiency induces systemic inflammation, impairs mitochondria, and worsens kidney injury in AKI mice.

In patients with advanced cancer, the development of brain metastasis (BM) often signals a worsening prognosis with limited therapeutic options. Here, the authors assemble a large, open-source neuroimaging dataset of BM and perform spatial and morphological analysis which they use to develop a framework for function-sparing brain radiotherapy design.

Nitric oxide (NO) is an important gaseous signaling molecule with multiple physiological roles in cardiovascular system. Here the authors develop a cardiac patch with NO releasing function that favors heart repair after myocardial infarction.

How interhemispheric connections are organized and how interhemispheric communication are regulated are not fully understood. Here authors delineate the diverse single-neuron projection patterns of interhemispheric connections in mice and uncover their influence on functional dynamics, highlighting the importance of heterotopic projections in interhemispheric communication.

This study shows how auditory cortex activation and cognitive function develop during a six-month follow-up after gene therapy in children with congenital deafness.

Brain injury after stroke requires glutamate receptor activation of neuronal nitric oxide synthase (nNOS), but inhibiting either of these proteins can cause side effects. Now, Dong-Ya Zhu and colleagues show that a drug that blocks the interaction between nNOS and a glutamate receptor docking protein can reduce stroke damage in vivo, with no observed side effects.

Sun and colleagues identify lnc-CTHCC, a cancer-testis lncRNA that binds to hnRNP K, activates YAP1 transcription and promotes hepatocellular carcinogenesis.

A prophylactic cancer vaccine consisting of commercial adjuvants wrapped by membranes from pluripotent stem cells inhibited tumour progression in mice, owing to shared antigens between tumour membranes and the pluripotent stem cell membranes.

Water dissociation has proven power in tuning the behaviors of electrochemical CO₂ reduction. Here, the authors report the spontaneous water dissociation capability of the intermetallic electride LaCu_0.67Si_1.33 material that enables high rate electrosynthesis of methane from CO₂.

The miR-17-92 cluster has been shown to regulate cardiomyocyte proliferation in vitro and in genetic mutation and overexpression models. Here the authors show that the cluster member miR-19a/19b regulates cardiomyocyte proliferation in vivo, and that delivery of miR-19a/19b to the heart leads to both short-term and long-term protective responses to myocardial infarction.

Hepatic fibrosis causes blood ammonia accumulation, which leads to hepatic encephalopathy. Here, a biocompatible water-powered Zn micromotor is developed for chemotactic migration towards and targeted clearance of ammonia for the treatment of hepatic encephalopathy.

Pan-genome analysis of 24 alfalfa accessions identifies key structural variations associated with salt tolerance and quality traits and provides resources for genomics-assisted breeding in alfalfa.

The transcription factor interferon regulatory factor 8 (IRF8) is known to regulate differentiation and function of immune cells. Here the authors show that IRF8 is upregulated in the hypertrophic heart in humans and mice, where it suppresses cardiac remodelling by inhibiting calcineurin signalling.

Structures of ketamine bound to human NMDA receptors show how ketamine inhibits receptor activity.

The human papillomavirus (HPV) E6 oncoprotein hijacks the ligase activity of the host E6AP to ubiquitinate the tumor suppressor p53. Here, the authors show how the presence of the HPV E6 oncoprotein transforms the inactive E6AP monomer into an active dimer, providing a structural understanding of the physiological and pathophysiological mechanisms of E6AP function.

Yuan et al. show that the MBNL3 splicing factor promotes alternative splicing of the lncRNA-PXN-AS1 antisense transcript of PXN, leading to the stabilization of PXN mRNA and increasing its protein levels to promote liver cancer growth.

In this report, Skokowa et al. delineate a new molecular pathway by which synthesis of the metabolite NAD⁺ through the action of the enzyme NAMPT promotes myeloid cell differentiation. The potential clinical relevance of this pathway was demonstrated by showing that administration of vitamin B3, a precursor to NAD⁺, increases neutrophil counts in healthy individuals, and that defective myeloid cell differentiation in individuals with congenital neutropenia can be rescued in vitro by administration of NAMPT.

Using single-cell and spatial molecular profiling of infarcted mouse and human hearts, Li, Ni, Wang and colleagues identify a subset of cardiac fibroblasts expressing CD248 that plays a critical role in fibroblast–T cell interaction, and show that disrupting this interaction with monoclonal antibodies or anti-CD248 chimeric antigen receptor T cells results in reduced cardiac fibrosis and improved function.

Infection with SARS-CoV-2 causes interstitial pneumonia and viral replication in the lungs of transgenic mice that express a human version of ACE2, confirming the pathogenicity of the virus in this model.

Traditional approaches for transition-metal catalyzed oxidative cross-coupling reactions rely on sp²-hybridized starting materials. Here the authors report a heterogeneous Pd-catalyzed radical relay method for the conversion of a heteroarene C(sp³)–H bond into ethers.

Tackling obesity from different angles might result in better therapeutic outcomes. Here the authors present a virus-like particle targeted to adipose tissues that combines photodynamic therapy and adipose browning induction to induce weight loss in animal models, and use photoacoustic imaging to monitor the treatment progress.

Malik, Guo et al. show that Ntrk2/Trkb-mediated neurotrophic signalling regulates dopamine levels by controlling glutathione–ascorbate metabolism, thus impacting striatal dopaminergic circuits and motor function