Xin Hu

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and has been acknowledged as a leading cause of death among cirrhosis patients. Difficulties in early diagnosis and heterogeneity are obstacles to effective treatment, especially for advanced HCC. Liver transplantation (LT) is considered the best therapy for HCC. Although many biomarkers are being proposed, alpha-fetoprotein (AFP), which was identified over 60 years ago, remains the most utilized. Recently, much hope has been placed in the immunogenicity of AFP to develop novel therapies, such as AFP vaccines and AFP-specific adoptive T-cell transfer (ACT). This review summarizes the performance of AFP as a biomarker for HCC diagnosis and prognosis, as well as its correlation with molecular classes. In addition, the role of AFP in LT is also described. Finally, we highlight the mechanism and application prospects of two immune therapies (AFP vaccine and ACT) for HCC. In general, our review points out the prevalence of AFP in HCC, accompanied by some controversies and novel directions for future research.

Using a predistortion linearizer is an important way to improve traveling-wave tube amplifier (TWTA) linearity. However, predistortion linearizers cannot usually control amplitude modulation (AM)/AM and AM/phase modulation (PM) conversion separately, so it is difficult to satisfy linearization requirements for AM/AM and AM/PM conversion simultaneously. This paper proposes a predistortion linearizer with a relatively simple circuit structure, which provides good control of gain expansion over the input power dynamic range while keeping the amount of phase expansion small. Good linearity improvement has been obtained for a 45-W X-band TWTA with this predistortion linearizer.

Despite the extensive interest in solid-state lithium batteries (SSLBs), the voids/gaps inside the solid-state electrolyte (SSE) and between the SSE-electrode interfaces significantly limit the performance of the SSLBs. In this work, we developed a void-free design combining an inorganic-gel hybrid electrolyte with in-situ polymeric interlayers for SSLBs. The designed inorganic-gel hybrid SSE enables facile Li+ ion conduction, and the in-situ fabricated solid polymer electrolyte between the electrodes and the hybrid electrolyte improves interfacial compatibility. We found that, during the Li plating-stripping, the interfacial property between Li and SSE dictates critical current density, while bulk electrolyte properties affect cycling stability. Ascribed to its layered structure, our hybrid electrolyte efficiently mitigated dendritic Li deposition as revealed by a high specific capacity of 154 mAh g-1 at 0.3 C and extended cycling stability in LiFePO4-based SSLB. Moreover, in the solid-state Li-S batteries, the ionic liquid in the inorganic-gel hybrid electrolyte and the polymeric interlayer successfully regulates polysulfide dissolution at only cathode side and completely block its migration to the Li anode. The as-prepared solid-state Li-S cells delivers a high specific capacity of 845.6 mAh g-1 at 0.2 C with 81.2% capacity retention and a high Coulombic efficiency of 95.7% after 100 cycles under room temperature. Our void-free design for SSLBs could widen SSE compatibility in different Li+ ion-based battery systems.

Recent studies suggest that circular RNA (circRNA)-mediated post-translational modification of RNA-binding proteins (RBP) plays a pivotal role in metastasis of hepatocellular carcinoma (HCC). However, the specific mechanism and potential clinical therapeutic significance remain vague. This study attempts to profile the regulatory networks of circRNA and RBP using a multi-omics approach. Has_circ_0006646 (circ0006646) is an unreported circRNA in HCC and is associated with a poor prognosis. Silencing of circ0006646 significantly hinders metastasis in vivo. Mechanistically, circ0006646 prevents the interaction between nucleolin (NCL) and the E3 ligase tripartite motif-containing 21 to reduce the proteasome-mediated degradation of NCL via K48-linked polyubiquitylation. Furthermore, the change of NCL expression is proven to affect the phosphorylation levels of multiple proteins and inhibit p53 translation. Moreover, patient-derived tumor xenograft and lentivirus injection, which is conducted to simulate clinical treatment confirmed the potential therapeutic value. Overall, this study describes the integrated multi-omics landscape of circRNA-mediated NCL ubiquitination degradation in HCC metastasis and provides a novel therapeutic target.