Copper (Cu) is a necessary micronutrient at lower concentration, while excessive Cu exposure or Cu homeostasis disorders can lead to toxicity. The mechanism of male reproductive toxicity induced by Cu is still unknown. This study aims to investigate whether autophagy plays an important role in copper-induced spermatogenesis disorder in vivo and vitro. The present study showed that copper sulfate (CuSO₄) might significantly promote autophagy level in the testis and mouse-derived spermatogonia cell line GC-1 spg cells. Concurrently, CuSO₄ could induce autophagy via AMPK-mTOR pathway that downregulated p-mTOR/mTOR and subsequently upregulated p-AMPKα/AMPKα as well as p-ULK1/ULK1. In the meanwhile, CuSO₄ treatment could also increase expression levels of the autophagy-related proteins. Then, the role of oxidative stress in CuSO₄-induced autophagy was investigated. The findings demonstrated that oxidative stress inhibitor (NAC) attenuated CuSO₄-induced autophagy in vivo and vitro, reversing the activation for AMPK-mTOR pathway. Additionally, the study also investigated how autophagy worked under the spermatogenesis disorder induced by CuSO₄. Inhibition of autophagy could decrease cell viability, and enhance the ROS accumulation and apoptosis in the GC-1 cells, meanwhile, the spermatogenesis disorder, oxidative stress and histopathological changes were increased in the testis. Furthermore, co-treatment with the apoptosis inhibitor (Z-VAD-FMK) could decrease the spermatogenesis disorder but not influence autophagy. Besides, the crosslink between autophagy and ferroptosis were also measured, the data showed that inhibition of autophagy could suppress CuSO₄-induced ferroptosis in in vivo and vitro. Altogether, abovementioned results indicated that CuSO₄ induced autophagy via oxidative stress-dependent AMPK-mTOR pathway in the GC-1 cells and testis, and autophagy activation possibly led to the generation of protection mechanism through oxidative damage and apoptosis inhibition, however, autophagy also aggravate CuSO₄ toxicology through promoting ferroptosis. Overall, autophagy plays a positive role for attenuating CuSO₄-induced testicular damage and spermatogenesis disorder. Our study provides a possible targeted therapy for Cu overload-induced reproduction toxicology.

Macrophages are crucial components of the immune system and play a critical role in the initial defense against pathogens. They are highly heterogeneous and plastic and can be polarized into classically activated macrophages (M1) or selectively activated macrophages (M2) in response to local microenvironments. Macrophage polarization involves the regulation of multiple signaling pathways and transcription factors. Here, we focused on the origin of macrophages, the phenotype and polarization of macrophages, as well as the signaling pathways associated with macrophage polarization. We also highlighted the role of macrophage polarization in lung diseases. We intend to enhance the understanding of the functions and immunomodulatory features of macrophages. Based on our review, we believe that targeting macrophage phenotypes is a viable and promising strategy for treating lung diseases.

Porcine reproductive and respiratory syndrome virus (PRRSV) is an important pathogen that poses a serious threat to the global pig industry. Sichuan Province is one of the largest pig breeding provinces in China. There is a lack of reports on the continuous surveillance and systematic analysis of prevalent strains of PRRSV in Sichuan Province in recent years. To fill this gap, a total of 539 samples were collected from 13 breeding regions in Sichuan during 2012–2020. The detection result showed that the positive rate of PRRSV was 52.32% (282/539). The ORF5s and Nsp2 were obtained and further analyzed, with Chinese reference strains downloaded from the GenBank. Phylogenetic analysis showed that the PRRSV strains sequenced in this study belonged to PRRSV-1 and PRRSV-2 (lineage 1, 3, 5 and 8). In total, 168 PRRSV-2 strains were selected for ORF5 analyses, and these strains were classified into sub-lineage 8.7 (HP-PRRSV), sub-lineage 5.1 (classical PRRSV), sub-lineage 1.8 (NADC30-like), sub-lineage 1.5 (NADC34-like) and sub-lineage 3.5 (QYYZ-like), accounting for 60.71% (102/168), 11.31% (19/168), 18.45% (31/168), 2.97% (5/168) and 6.55% (11/168) of the total analyzed strains, respectively. The Nsp2 of identified PRRSV strains exhibited a nucleotide identity of 44.5–100%, and an amino acid identity of 46.82–100%. The ORF5 of the identified PRRSV strains exhibited a nucleotide identity of 81.3–100%, and an amino acid identity of 78.5–100%. A sequence analysis of ORF5 revealed that the mutation sites of GP5 were mainly concentrated in HVR1 and HVR2 and the virulence sites. In summary, the HP-PRRSV, NADC30-like PRRSV, Classic-PRRSV, QYYZ-like PRRSV, NADC34-like PRRSV and PRRSV-1 strains exist simultaneously in pigs in Sichuan. NADC30-like PRRSV was gradually becoming the most prevalent genotype currently in Sichuan province. This study suggested that PRRSV strains in Sichuan were undergoing genomic divergence.