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The autophagic and Hippo pathways are both well characterized contributors to cancer. Here, Tang et al show that LATS1, but not LATS2, negatively regulates autophagy by promoting Beclin1 ubiquitination, which restricts lethal autophagy induced by sorafenib treatment in cancer cells.

Genetic variation in the IFNλ locus has been associated with clearance of hepatitis C virus. Here, the authors show that a single amino-acid variant of IFNλ4 affects its antiviral activity and that patients carrying the impaired variant have better viral clearance rates.

Targeting histone deacetylases (HDACs) alone has shown limited success in solid tumours. Here, authors report that the HDAC1/2 inhibitor romidepsin confers responsiveness to receptor tyrosine kinase inhibitors, with enhanced therapeutic effects in models of hepatocellular carcinoma, leading to tumour regression and an immune-stimulatory profile.

The mechanisms underlying the antiviral activity of type I interferons (IFNs) are still unclear, but IFNα has long been used in the treatment of chronic hepatitis C (CHC). While reviewing the history of IFNα-based CHC treatment, Markus H. Heim highlights the remaining questions and discusses the future challenges of IFN-based therapies.

Femtosecond laser spectroscopy has contributed to our understanding of structure and function of matter. Here, the authors explore the applicability of superfluid helium nanodroplets as a sample preparation method that allows investigation of previously inaccessible classes of tailor-made or fragile molecular systems.

Heim et al. investigate the role of CD8⁺ T cells specific to HBV polymerase in the context of chronic HBV infection. They identify a unique subset of CD8⁺ T cells with an attenuated effector function. The attenuation is driven by TGFβ signaling, offering new insights into the immune landscape of chronic HBV infection and suggesting potential therapeutic avenues for modulating these cells to enhance viral control.

Proteogenomic analyses of hepatocellular carcinomas (HCC) have focused on early-stage, HBV-associated tumours and lacked information about the phosphoproteome. Here, the authors present a comprehensive HCC proteogenomics and phosphoproteomics study in patient samples from multiple etiologies and stages.

A genetic variant in the IFN-lambda 4 gene has been associated with poor hepatitis C virus prognosis but it is not clear how this functions. Here the authors show that IFN-lambda 4 promotes ER stress and inhibits presentation of HCV epitopes to CD8⁺ T cells.

Studies of hepatitis C virus replication in cell culture have suggested that certain microRNAs are required for efficient virus replication and that they may be involved in the antiviral effect of interferon. A study in humans infected with the virus provides a new perspective.

As proof of principle, an analysis using a suite of human-aligned immunocompetent mouse models of hepatocellular carcinoma identifies a promising therapeutic candidate, cladribine, which acts in a highly effective subtype-specific manner in combination with standard-of-care therapy.

RNA-binding proteins (RBP) are an emerging group of post-translational regulators. Here the authors show that the RBP vigilin regulates translation of mRNA encoding for proatherogenic proteins—apoB, apoC-III and fibronectin—representing a potential therapeutic target in cardiovascular diseases.

Laser-assisted electron scattering (LAES) is a commonly observed strong field process in gas phase systems. Here the authors use helium droplets with core atoms and molecules to observe increased electron energy due to multiple LAES events within the droplets.

The contribution of intra-tumour heterogeneity is increasingly associated with resistance to therapy. Here, the authors use genomic analyses to study heterogeneity in colorectal cancer and perform in-depth reconstruction of heterogeneity in one sample.

Ding et al. report a mechanism that allows cells to sense cellular fatty acid levels and adjust lipolysis as needed, which involves peroxisomal degradation of fatty acids, production of reactive oxygen species and post-translational regulation of adipose triglyceride lipase.

Transitional liver progenitor cells (TLPCs), which derive from biliary epithelial cells (BECs), differentiate into hepatocytes after serious liver damage. Notch and WNT/β-catenin signaling regulate BEC-to-TLPC and TLPC-to-hepatocyte conversions, respectively.

3D liver organoids hold great promise for regenerative medicine but the use of ill-defined matrices limits their potential. Here, the authors generate human and mouse liver organoids using a chemically defined matrix, and reveal a link between matrix stiffness and organoid growth that does not require acto-myosin contraction.

Short-term exposure to a high-fat diet reduces colonization resistance to Salmonella Typhimurium infection in mice and is associated with increase bile salts and plasmid transfer; however, E. coli can provide a protective effect under these conditions.

Protein aggregation plays a crucial role in several neurodegenerative diseases. Here the authors demonstrate that phosphorylation of β-amyloid aggregates—the pathological hallmark of Alzheimer's disease—can change the molecular properties of aggregates, suggesting how phosphorylation contributes to disease progression.

Tchorz and colleagues identify a role for the RSPO–LGR4/5–ZNRF3/RNF43 module as master regulator of Wnt/β-catenin-mediated metabolic liver zonation and hepatic growth/size control during development, homeostasis and regeneration.

Probing the photoinduced formation of chemical bonds in aggregates is challenging due to difficulties in reactant preparation under well-defined conditions. Here, the authors use helium droplets to stabilize Mg atoms in a foam-like configuration and track cluster formation using femtosecond time-resolved spectroscopy.

Decreased expression of histidine phosphatase LHPP, a novel tumour suppressor, results in increased global histidine phosphorylation and hepatocellular carcinoma.

Andre Franke and colleagues perform an association study of atopic dermatitis based on high-density genotyping using the Immunochip array. They identify four new susceptibility loci for this common inflammatory skin disease.

Inhibiting virus cell entry by targeting tight junctions cures HCV infection in mice.

The mechanisms by which the cytokine IFN-λ regulates adaptive immune responses are poorly understood. A new study now reveals a novel IFN-λ-mediated signal-transmission system that enhances immunity after infection of the mouse respiratory tract with influenza virus.

Meier, Nuciforo, Coto-Llerena et al. report a rare case of a patient with hepatocellular carcinoma with neuroendocrine differentiation. The authors establish organoids that recapitulate the genetic features of the patient’s tumor and are used for ex vivo drug testing to guide therapy selection in the patient.

Hansmann et al. show that serial intravascular infusions of conditioned media produced by allogenic umbilical cord mesenchymal stem cells markedly improved the clinical features of a young child with severe pulmonary arterial hypertension. The multi-omic approach analyzing the transcriptome and the proteome of these stem cells isolated from four donors provides initial insight into their beneficial paracrine function.

Ercan et al. report clinical, pathological and molecular findings from a patient with focal nodular hyperplasia (FNH) in the liver with concomitant hepatocellular carcinomas (HCC). Genomic analysis performed by the authors suggests that FNH might progress to HCC in very rare cases.

Oral-vaccine-induced IgA cross-links growing bacteria into clonal aggregates, inhibiting pathogenesis, adaption and the spread of antimicrobial resistance genes.