Hepatitis B surface antigen (HBsAg) loss or functional cure (FC), is considered the desirable therapeutic outcome for chronic hepatitis B (CHB) patients. However, the immune-pathological biomarkers and underlying mechanisms remain unclear. In this study we comprehensively interrogate disease-associated cell states (DACS) identified within intra-hepatic tissue and matched PBMCs from either CHB or FC patients, at the resolution of single cells, to provide novel insights into putative mechanisms underlying FC. We combined single cell transcriptomics (scRNA-seq) with multiparametric flow cytometry-based immune phenotyping, and multiplexed immunofluorescence to elucidate the immunopathological cell states associated with CHB vs FC. We find that the intra-hepatic environment of CHB and FC patients displays specific cell identities and molecular signatures that are distinct from those found in matched PBMCs. FC is associated with emergence of an altered adaptive immune response marked by CD4 cytotoxic T lymphocytes (CD4-CTLs), and an activated innate response represented by liver-resident natural killer (LR-NK) cells, specific Kupffer cell (KC) subtypes and marginated neutrophils. Surprisingly, we find that FC patients are also characterized by the presence of MHC class II-expressing hepatocytes and low but persistent levels of cccDNA and pgRNA, which may play an important role in achieving functional cure in HBV patients. Our study provides conceptually novel insights into the immuno-pathological control of HBV cure, and opens exciting new avenues for clinical management, biomarker discovery and therapeutic interventions. We believe that the discoveries from this study, as it relates to the activation of an innate and altered immune response that may facilitate sustained, low-grade inflammation, may have broader implications in the resolution of chronic viral hepatitis.

Promising results in clinical studies have been demonstrated by the utilization of electrothermal agents (ETAs) in cancer therapy. However, a difficulty arises from the balance between facilitating the degradation of ETAs, and at the same time, increasing the electrothermal performance/stability required for highly efficient treatment. In this study, we controlled the thermal signature of the MoS₂ by harnessing MoS₂ nanostructures with M13 phage (MNM) via the structural assembling (hydrophobic interaction) phenomena and developed a combined PANC-1 cancer cell–MNM alternating current (AC)-stimulus framework for cancer cell ablation and electrothermal therapy. A percentage decrease in the cell viability of ~23% was achieved, as well as a degradation time of 2 weeks; a stimulus length of 100 μs was also achieved. Molecular dynamics (MD) simulations revealed the assembling kinetics in integrated M13 phage–cancer cell protein systems and the structural origin of the hydrophobic interaction-enabled increase in thermal conduction. This study not only introduced an ‘ideal’ agent that avoided the limitations of ETAs but also provided a proof-of-concept application of MoS₂-based materials in efficacious cancer therapy.

A few-volt nanosecond alternating-current stimulation method with an increased number of pulses exploiting orientational-disordering processes.

The development of combined 2D-material-polymer-phage frameworks that can enhance cancer cell detection via the enhancement of electrical conductivity.