Magnetic soft robots offer considerable potential across various scenarios, such as biomedical applications and industrial tasks, because of their shape programmability and reconfigurability, safe interaction and biocompatibility1-4. Despite recent advances, magnetic soft robots are still limited by the difficulties in reprogramming their required magnetization profiles in real time on the spot (in situ), which is essential for performing multiple functions or executing diverse tasks5,6. Here we introduce a method for real-time in situ magnetization reprogramming that enables the rearrangement and recombination of magnetic units to achieve diverse magnetization profiles. We explore the applications of this method in structures of varying dimensions, from one-dimensional tubes to three-dimensional frameworks, showcasing a diverse and expanded range of configurations and their deformations. This method also demonstrates versatility in diverse scenarios, including navigating around objects without undesired contact, reprogramming cilia arrays, managing multiple instruments cooperatively or independently under the same magnetic field, and manipulating objects of various shapes. These abilities extend the range of applications for magnetic actuation technologies. Furthermore, this method frees magnetic soft robots from the sole reliance on external magnetic fields for shape change, facilitating unprecedented modes and varieties of deformation while simultaneously reducing the need for complex magnetic field generation systems, thereby opening avenues for the development of magnetic actuation technologies.

Despite advances in HIV-1 prophylaxis, vertical transmission remains a pressing problem in developing countries1. Given the promise of broadly neutralizing antibodies (bNAbs) for HIV-1 prevention2, we hypothesized that neonatal delivery of bNAbs using adeno-associated virus (AAV) could provide durable HIV-1 immunity during infancy. Here, using infant rhesus macaques (Macaca mulatta) as a model, we show that a one-time administration of an AAV vector encoding bNAb 3BNC117 at birth led to sustained bNAb expression for more than three years without redosing. This approach significantly protected both infant and pre-adolescent rhesus macaques from infection with simian-human immunodeficiency virus in mucosal challenge models that mimic HIV-1 transmission through breastfeeding and sexual intercourse. Age at the time of AAV-3BNC117 administration was a main determinant of success and was inversely correlated with the incidence of host anti-drug antibodies that restricted bNAb expression. Consistent with principles of neonatal tolerance3,4, newborn rhesus macaques exhibited higher levels of bNAb expression than older infants and juveniles following AAV-3BNC117 dosing. Furthermore, in utero exposure to recombinant 3BNC117 suppressed anti-drug antibodies and improved AAV-vectored delivery of this bNAb in older infants. Thus, our results suggest that neonatal and fetal immunological tolerance can be leveraged to improve postnatal AAV delivery of HIV-1 bNAbs in primates. Since years-long HIV-1 immunity can be generated in rhesus macaques from a one-time AAV vector administration at birth, future studies should evaluate the ability of this strategy to prevent perinatal and adolescent HIV-1 infections in humans.

Immunosuppressive tumour microenvironments are common in cancers such as metabolic dysfunction-associated steatohepatitis (MASH)-driven hepatocellular carcinoma (HCC) (MASH-HCC)1-3. Although immune cell metabolism influences effector function, the effect of tumour metabolism on immunogenicity is less understood4. ATP citrate lyase (ACLY) links substrate availability and mitochondrial metabolism with lipid biosynthesis and gene regulation5-7. Although ACLY inhibition shows antiproliferative effects in various tumours, clinical translation has been limited by challenges in inhibitor development and compensatory metabolic pathways8-12. Here, using a mouse model of MASH-HCC that mirrors human disease, genetic inhibition of ACLY in hepatocytes and tumours reduced neoplastic lesions by over 70%. To evaluate the therapeutic potential of this pathway, a novel small-molecule ACLY inhibitor, EVT0185 (6-[4-(5-carboxy-5-methyl-hexyl)-phenyl]-2,2-dimethylhexanoic acid), was identified via phenotypic screening. EVT0185 is converted to a CoA thioester in the liver by SLC27A2 and structural analysis by cryo-electron microscopy reveals that EVT0185-CoA directly interacts with the CoA-binding site of ACLY. Oral delivery of EVT0185 in three mouse models of MASH-HCC dramatically reduces tumour burden as monotherapy and enhances efficacy of current standards of care including tyrosine kinase inhibitors and immunotherapies. Transcriptomic and spatial profiling in mice and humans linked reduced tumour ACLY with increases in the chemokine CXCL13, tumour-infiltrating B cells and tertiary lymphoid structures. The depletion of B cells blocked the antitumour effects of ACLY inhibition. Together, these findings illustrate how targeting tumour metabolism can rewire immune function and suppress cancer progression in MASH-HCC.