Influence of l-NAME -induced hypertension on spermatogenesis and sperm tsRNA profile in mice.

Sperm is the key media between the father's aberrant exposure and the offspring's phenotype. Whether paternal hypertension affects offspring through sperm epigenetics remains to be explored. To investigate the underlying mechanisms, we constructed a hypertensive mice model induced by drinking l-NAME and found that spermatocytes and spermatids in the testis were increased significantly after l-NAME treatment. The sequencing of sperm showed that tsRNA profiles changed with 315 tsRNAs (195 up-regulated and 120 down-regulated) altered. Meanwhile, KEGG pathway analysis showed that the target genes of these altered tsRNAs were involved in influencing some important signaling pathways, such as the cAMP signaling path, the mTOR signaling path, the Hippo signaling path, and the Ras signaling path. Bioinformatics of tsRNA-miRNA-mRNA pathway interactions revealed several ceRNA mechanisms, such as tsRNA-00051, the ceRNA of miR-128-1-5p, co-targeting Agap1. This study provides evidence for enriching and further understanding the pathophysiology and paternal epigenetic mechanisms of testicular reproduction, as well as contributing to a rethinking of the transgenerational reprogramming mechanisms of paternal exposure in hypertension.

The potential contributions to organic carbon utilization in a stable acetate-fed Anammox process under low nitrogen-loading rates.

The unique ability of Anammox bacteria to metabolize short-chain fatty acids have been demonstrated. However, the potential contributions of active Anammox species to carbon utilization in a mixotrophic Anammox-denitrification process are less well understood. In this study, we combined genome-resolved metagenomics and DNA stable isotope probing (DNA-SIP) to characterize an Anammox process fed with acetate under COD/TN ratios of around 0.30-0.40 and low nitrogen-loading rates. A draft genome of "Candidatus Jettenia caeni" and a novel species that was phylogenetically close to "Candidatus Brocadia sinica" were recovered. Essential genes encoding the key enzymes for acetate metabolism and dissimilatory nitrate reduction to ammonium were identified in the two Anammox draft genomes. The DNA-SIP revealed that Ignavibacterium, "Candidatus Jettenia caeni," Thauera, Denitratisoma, and Calorithrix predominantly contributed to organic carbon utilization in the acetate-fed Anammox process. In particular, the "Candidatus Jettenia caeni" accounted for a higher proportion of 13C-DNA communities than "Candidatus Brocadia sinica." This result well confirmed the theory of maintenance energy between the interspecies competition of the two Anammox species under low nitrogen-loading rates. Our study revealed its potential important role of the Anammox genus "Candidatus Jettenia" in the treatment of wastewater containing low organic matter and ammonia.

Terminating the renewal of tumor-associated macrophages: A sialic acid-based targeted delivery strategy for cancer immunotherapy.

Mononuclear phagocytes are efficient drug delivery targets for cancers owing to their cancerous tissue-accumulating nature. As receptors of sialic acid, Siglecs (sialic acid-binding immunoglobulin-type lectins) are noticeably found on peripheral blood monocytes (PBMs) and tumor-associated macrophages (TAMs), which renew by the differentiation of recruited PBMs at the tumor site and positively correlate with tumor growth. Given this, a sialic acid-octadecylamine conjugate (SA-ODA) was synthesized and then modified on the surface of liposomal epirubicin (EPI-SAL) as a potent tumor-targeting delivery strategy. A cellular uptake assay indicated that SA-modified liposomes provided improved distribution of the drug in both PBMs and TAMs. Pharmacodynamic tests demonstrated that the antitumor efficacy of the EPI-SAL group was better than that of the other groups, owing to both inhibition of TAMs by EPI-SAL, and high-efficiency targeting of PBMs by EPI-SAL, after which PBMs containing EPI-SAL were recruited to the tumor site and then killed by EPI. Thus, an SA-based targeted delivery strategy effectively interdicted the generation of TAMs. Our research provides the feasibility of the SA-ODA decorated liposome as an active carrier for cancer immunotherapy.