: As the predominant lymphocyte subset in the liver, natural killer (NK) cells have been shown to be highly associated with the outcomes of patients with chronic hepatitis B virus infection (CHB) and hepatocellular carcinoma (HCC). Previously, we reported that NKG2A, a checkpoint candidate, mediates human and murine NK cell dysfunction in CHB. However, NK cell exhaustion and, particularly, the level of NKG2A expression within liver tumors have not been reported. : In this study, we analyzed NKG2A expression and the related dysfunction of NK cells located in intra- or peritumor regions of liver tissue samples from 207 HCC patients, in addition to analyzing disease outcomes.: The expression of NKG2A in NK cells and the NKG2A ligand, HLA-E, in intratumor HCC tissues was observed to be increased. These NK cells, and particularly CD56 NK cells, with higher NKG2A expression showed features of functional exhaustion and were associated with a poor prognosis. The increase in NKG2A expression might be induced by IL-10, which was present at a high level in the plasma of HCC patients. Blocking IL-10 could specifically inhibit NKG2A expression in NK cells. : These findings indicate that NKG2A expression is influenced by factors from cancer nests and contributes to NK cell exhaustion, suggesting that NKG2A blockade has the potential to restore immunity against liver tumors by reversing NK cell exhaustion.

A dual-targeting biomimetic codelivery and treatment strategy was developed for anti-glioma activity.

The activation of the Ras/p38 MAPK/CREB pathway is required for AngII-induced periostin expression. ERK1/2 also participates in AngII-induced periostin expression by regulating TGF-β1/Smad signalling.

Hierarchical cobalt assemblies such as spheres, flowers with dendritic petals, and flowers with sharp petals are successfully synthesized via a facile liquid-phase reduction method by simply adjusting the reaction conditions. The morphology evolution process and transformation mechanism from spheres to dendrites and finally to flowers have been systematically investigated. It is determined that coercivity H c depends more on sample size than on shape anisotropy, while saturation magnetization M s is greatly affected by pinned surface magnetic moment. Even at a thinner thickness, as-synthesized cobalt samples exhibit stronger microwave absorbing ability compared with reported cobalt in the same frequency band. Especially, the cobalt flowers with dendritic petals exhibit the strongest absorption in middle frequency because incident wave and reflected wave are totally canceled at matching thickness. The architectural design of material morphologies is critical for improving properties toward future application.

The persistence of hepatitis B virus (HBV) infection is maintained by the nuclear viral covalently closed circular DNA (cccDNA), which serves as transcription template for viral mRNAs. Previous studies suggested that cccDNA contains methylation-prone CpG islands, and that the minichromosome structure of cccDNA is epigenetically regulated by DNA methylation. However, the regulatory effect of each CpG island methylation on cccDNA activity remains elusive. In the present study, we analyzed the distribution of CpG methylation within cccDNA in patient samples and investigated the impact of CpG island methylation on cccDNA-driven virus replication. Our study revealed the following observations: 1) Bisulfite sequencing of cccDNA from chronic hepatitis B patients indicated that CpG island I was seldom methylated, 2) CpG island II methylation was correlated to the low level of serum HBV DNA in patients, and in vitro methylation studies confirmed that CpG island II methylation markedly reduced cccDNA transcription and subsequent viral core DNA replication, 3) CpG island III methylation was associated with low serum HBsAg titers, and 4) Furthermore, we found that HBV genotype, HBeAg positivity, and patient age and liver fibrosis stage were also relevant to cccDNA CpG methylation status. Therefore, we clearly demonstrated that the status of cccDNA methylation is connected to the biological behavior of HBV. Taken together, our study provides a complete profile of CpG island methylation within HBV cccDNA and new insights for the function of CpG methylation in regulating HBV cccDNA transcription.

CTRP3 alleviates cardiac fibrosis in a rat post-MI model and in cardiac fibroblasts. CTRP3 inhibits fibroblast-to-myofibroblast differentiation. CTRP3 exerts anti-fibrotic effect through targeting Smad3 activation. AMPK mediates the anti-fibrotic effect of CTRP3 by inhibition of Smad3 activation.

Multidrug resistance (MDR) is an issue that is not only related to cancer cells but also associated with the tumor microenvironments. MDR involves the complicated cancer cellular events and the crosstalk between cancer cells and their surroundings. Ideally, an effective system against MDR cancer should take dual action on both cancer cells and tumor microenvironments. The authors find that both the drug‐resistant colon cancer cells and the protumor M2 macrophages highly express two nutrient transporters, i.e., secreted protein acidic and rich in cysteine (SPARC) and mannose receptors (MR). By targeting SPARC and MR, a system can act on both cancer cells and M2 macrophages. Herein the authors develop a mannosylated albumin nanoparticles with coencapsulation of different drugs, i.e., disulfiram/copper complex (DSF/Cu) and regorafenib (Rego). The results show that combination therapy of DSF/Cu and Rego efficiently inhibits the growth of drug‐resistant colon tumor, and the combination has not been reported yet for use in anticancer treatment. The system significantly improves the treatment outcomes in the animal model bearing drug‐resistant tumors. The therapeutic mechanisms involve enhanced apoptosis, upregulation of intracellular ROS, anti‐angiogenesis, and tumor‐associated macrophage “re‐education.” This strategy is characterized by dual targeting to and the simultaneous action on cancer cells and M2 macrophages, with biomimetic codelivery of a novel drug combination.

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) play their essential roles in regulating biological events. Their aberrant behaviors are mostly associated with pathophysiological processes. A better understanding of these processes can assuredly help us in examining the pathogenesis and progression of diseases and is beneficial for the ultimate clinical therapy. Numerous fluorescent probes have been developed in the last 5 years for detecting ROS and RNS involved in diverse pathophysiological processes, and these are summarized in this review. Optical properties of the fluorescent probes will be described, and their applications in ROS and RNS detection in pathophysiological models, including in chemical-and bacteria-triggered inflammation, druginduced organ toxicity, specific diseases, injury of different tissues and organs, and other pathophysiological processes, will be elaborated. Finally, we judiciously highlight the achievement, limitations, and future perspectives in this field.