In men with NOA, the ICSI outcome is not affected by whether the retrieved testicular sperm is fresh or frozen. Sperm cryopreservation ought to be considered in every surgical sperm retrieval case, which remain feasible even in patients with few testicular sperm retrieved.

Aflatoxin exposure is a crucial factor in promoting the development of primary hepatocellular carcinoma (HCC) in individuals infected with the hepatitis virus. However, the molecular pathways leading to its bioactivation and subsequent toxicity in hepatocytes have not been well-defined. Here, we carried out a genome-wide CRISPR-Cas9 genetic screen to identify aflatoxin B1 (AFB1) targets. Among the most significant hits was the aryl hydrocarbon receptor (AHR), a ligand-binding transcription factor regulating cell metabolism, differentiation, and immunity. AHR-deficient cells tolerated high concentrations of AFB1, in which AFB1 adduct formation was significantly decreased. AFB1 triggered AHR nuclear translocation by directly binding to its N-terminus. Furthermore, AHR mediated the expression of P450 induced by AFB1. AHR expression was also elevated in primary tumor sections obtained from AFB1-HCC patients, which paralleled the upregulation of PD-L1, a clinically relevant immune regulator. Finally, anti-PD-L1 therapy exhibited greater efficacy in HCC xenografts derived from cells with ectopic expression of AHR. These results demonstrated that AHR was required for the AFB1 toxicity associated with HCC, and implicate the immunosuppressive regimen of anti-PD-L1 as a therapeutic option for the treatment of AFB1-associated HCCs.

Background: Alpha-fetoprotein (AFP) expression is closely related to hepatocarcinogenesis, and it is an important prognostic factor for hepatocellular carcinoma (HCC). We aimed to investigate the relationship between serum AFP concentration and tissue AFP status and identify the prognostic value of serum and tissue AFP for HCC.

Importance: The prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) is extremely poor. The clinical outcome of preoperative radiotherapy (RT) is still controversial.