SummaryDevelopment of spermatogonia and spermatocytes are the critical steps of spermatogenesis, impacting on male fertility. Investigation of the related regulators benefits the understanding of male reproduction. The proteasome system has been reported to regulate spermatogenesis, but the mechanisms and key contributing factors in vivo are poorly explored. Here we found that ablation of REGγ, a proteasome activator, resulted in male subfertility. Analysis of the mouse testes after birth showed there was a decreased number of PLZF+ spermatogonia and spermatocytes. Molecular analysis found that REGγ loss significantly increased the abundance of p53 protein in the testis, and directly repressed PLZF transcription in cell lines. Of note, allelic p53 haplodeficiency partially rescued the defects in spermatogenesis observed in REGγ-deficient mice. In summary, our results identify REGγ-p53-PLZF to be a critical pathway that regulates spermatogenesis and establishes a new molecular link between the proteasome system and male reproduction.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, with high rates of recurrence and death. Surgical resection and ablation therapy have limited efficacy for patients with advanced HCC and poor liver function, so pharmacotherapy is the first-line option for those patients. Traditional antitumor drugs have the disadvantages of poor biological distribution and pharmacokinetics, poor target selectivity, high resistance, and high toxicity to nontargeted tissues. Recently, the development of nanotechnology has significantly improved drug delivery to tumor sites by changing the physical and biological characteristics of drugs and nanocarriers to improve their pharmacokinetics and biological distribution and to selectively accumulate cytotoxic agents at tumor sites. Here, we systematically review the tumor microenvironment of HCC and the recent application of nanotechnology in HCC.

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Atopic dermatitis (AD), also referred to as atopic eczema, is a long-term inflammatory condition that is characterized by itchy, red, swollen and cracked skin. Accumulating evidence suggests that AD is caused by genetic factors, environmental exposure and immune system dysfunction; however, its underlying molecular mechanism remains unclear. Current treatment strategies aim to decrease the severity and frequency of flares. Heme oxygenase-1 (HO-1) is a nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated gene that plays crucial roles against stress, inflammation and oxidation, and exerts cytoprotective effects. Previous studies have reported that treatment of AD induces high expression levels of HO-1 and Nrf2, indicating that HO-1 may play an important role in the treatment of AD. The present study constructed the recombinant protein, cell-penetrating peptide-HO-1 (CPP-HO-1), which was expressed in Escherichia coli and isolated with a 6xHis-tag using HiTrap His column (1 ml). AD was established using 4-dinitrochlorobenzene (DNCB) in mice. It was observed that the CPP-HO-1 fusion protein decreased the severity of AD, inhibited scratching in mice and decreased skin inflammation. Taken together, the results of the present study suggested that the CPP-HO-1 fusion protein may play a protective role against DNCB-induced AD in mice.