Genome sequences of the first Autographiviridae phages infecting marine Roseobacter.

The ubiquitous and abundant marine phages play critical roles in shaping the composition and function of bacterial communities, impacting biogeochemical cycling in marine ecosystems. Autographiviridae is among the most abundant and ubiquitous phage families in the ocean. However, studies on the diversity and ecology of Autographiviridae phages in marine environments are restricted to isolates that infect SAR11 bacteria and cyanobacteria. In this study, ten new roseophages that infect marine Roseobacter strains were isolated from coastal waters. These new roseophages have a genome size ranging from 38 917 to 42 634 bp and G+C content of 44.6-50 %. Comparative genomics showed that they are similar to known Autographiviridae phages regarding gene content and architecture, thus representing the first Autographiviridae roseophages. Phylogenomic analysis based on concatenated conserved genes showed that the ten roseophages form three distinct subgroups within the Autographiviridae, and sequence analysis revealed that they belong to eight new genera. Finally, viromic read-mapping showed that these new Autographiviridae phages are widely distributed in global oceans, mostly inhabiting polar and estuarine locations. This study has expanded the current understanding of the genomic diversity, evolution and ecology of Autographiviridae phages and roseophages. We suggest that Autographiviridae phages play important roles in the mortality and community structure of roseobacters, and have broad ecological applications.

Research progress on mechanism of follicle injury after frozen ovarian tissue transplantation and protective strategies. / 移植冷冻卵巢组织卵泡损伤机制及保护策略.

The iatrogenic ovarian dysfunction caused by cancer treatment have been increasing, along with the age at onset of malignant tumors getting younger, the survival of cancer patients being longer, as well as the delayed childbearing age for females; therefore it becomes a major clinical challenge to preserve the fertility of these patients. Ovarian tissue cryopreservation is the only solution for female cancer patients in prepubertal ages and those who cannot delay gonadotoxic therapy. However, the successful rate of cryopreservation and transplantation of ovarian tissue is still low at present due to the risk of ischemia and hypoxia of grafted tissues. Abnormal activation of primordial follicle and ischemia-reperfusion injury after blood supply recovery also cause massive loss of follicles in grafted ovarian tissues. It has been tried in various studies to reduce the damage of follicles during freezing and transplantation by adding certain drugs, and extend the duration of endocrine and reproductive function in patients with ovarian transplantation. For example, melatonin, N-acetylcysteine, erythropoietin or other antioxidants are used to reduce oxidative stress; mesenchymal stem cells derived from different tissues, basic fibroblast growth factor, vascular endothelial growth factor, angiopoietin 2 and gonadotropin are used to promote revascularization; anti-Müllerian hormone and rapamycin are used to reduce abnormal activation of primordial follicles. This article reviews the research progress on the main mechanisms of follicle loss after ovarian tissue transplantation, including hypoxia, ischemia-reperfusion injury and associated cell death, and abnormal activation of follicles; and explores the methods of reducing graft follicle loss to provide reference for improving the efficiency of ovarian tissue cryopreservation and transplantation.

MUC16 can Predict the Pregnancy Outcomes in Human and Intraperitoneal Administration of MUC16 can Rescue Pregnancy Losses in Mouse Models.

Mucin 16 (MUC16) participates in the process of embryo implantation, but few studies have examined the association between MUC16 and pregnancy loss. To investigate this association, the expression of MUC16 in serum and decidua was compared between women with pregnancy loss and ongoing pregnancies. In vitro experiments and animal models were used to explore the role and underlying mechanisms of MUC16 in pregnancy loss. In human study, the expression of MUC16 in serum and decidua was both consistently lower in the women with pregnancy loss compared with those in women with ongoing pregnancies. In vitro experiments revealed the interaction of MUC16 with peripheral blood natural killer (pNK) cells. MUC16 changed the phenotype and reduced the pro-inflammation ability of pNK cells. MUC16 also inhibited the cytotoxicity of pNK cells through the Src homology region 2 domain-containing phosphatase-1/extracellular signal-regulated kinase (SHP-ERK) pathway. Furthermore, MUC16 promoted the migration, invasion and tube formation of trophoblast cells by co-culturing together with pNK cells. In vivo experiments, the mouse model of abortion was used to further confirm that intraperitoneal administration of MUC16 could rescue the pregnancy loss. This study reveals the still-unknown connection between MUC16 and pNK cells and indicates that MUC16 provides a novel method for future prediction and treatment of unfavorable pregnancy outcomes.

Genomic diversity and biogeographic distributions of a novel lineage of bacteriophages that infect marine OM43 bacteria.

The marine methylotrophic OM43 clade is considered an important bacterial group in coastal microbial communities. OM43 bacteria, which are closely related to phytoplankton blooms, have small cell sizes and streamlined genomes. Bacteriophages profoundly shape the evolutionary trajectories, population dynamics, and physiology of microbes. The prevalence and diversity of several phages that infect OM43 bacteria have been reported. In this study, we isolated and sequenced two novel OM43 phages, MEP401 and MEP402. These phages share 90% of their open reading frames (ORFs) and are distinct from other known phage isolates. Furthermore, a total of 99 metagenomic viral genomes (MVGs) closely related to MEP401 and MEP402 were identified. Phylogenomic analyses suggest that MEP401, MEP402, and these identified MVGs belong to a novel subfamily in the family Zobellviridae and that they can be separated into two groups. Group I MVGs show conserved whole-genome synteny with MEP401, while group II MVGs possess the MEP401-type DNA replication module and a distinct type of morphogenesis and packaging module, suggesting that genomic recombination occurred between phages. Most members in these two groups were predicted to infect OM43 bacteria. Metagenomic read-mapping analysis revealed that the phages in these two groups are globally ubiquitous and display distinct biogeographic distributions, with some phages being predominant in cold regions, some exclusively detected in estuarine stations, and others displaying wider distributions. This study expands our knowledge of the diversity and ecology of a novel phage lineage that infects OM43 bacteria by describing their genomic diversity and global distribution patterns. IMPORTANCE OM43 phages that infect marine OM43 bacteria are important for host mortality, community structure, and physiological functions. In this study, two OM43 phages were isolated and characterized. Metagenomic viral genome (MVG) retrieval using these two OM43 phages as baits led to the identification of two phage groups of a new subfamily in the family Zobellviridae. We found that group I MVGs share similar genomic content and arrangement with MEP401 and MEP402, whereas group II MVGs only possess the MEP401-type DNA replication module. Metagenomic mapping analysis suggests that members in these two groups are globally ubiquitous with distinct distribution patterns. This study provides important insights into the genomic diversity and biogeography of the OM43 phages in the global ocean.

Dysregulation of Histone Deacetylases Inhibits Trophoblast Growth during Early Placental Development Partially through TFEB-Dependent Autophagy-Lysosomal Pathway.

Dysregulated biological behaviors of trophoblast cells can result in recurrent spontaneous abortion (RSA)-whose underlying etiology still remains insufficient. Autophagy, a conserved intracellular physiological process, is precisely monitored throughout whole pregnancy. Although the exact mechanism or role remains elusive, epigenetic modification has emerged as an important process. Herein, we found that a proportion of RSA patients exhibited higher levels of autophagy in villus tissues compared to controls, accompanied with impaired histone deacetylase (HDAC) expression. The purpose of this study is to explore the connection between HDACs and autophagy in the pathological course of RSA. Mechanistically, using human trophoblast cell models, treatment with HDAC inhibitor (HDACI)-trichostatin A (TSA) can induce autophagy by promoting nuclear translocation and transcriptional activity of the central autophagic regulator transcription factor EB (TFEB). Specifically, overactivated autophagy is involved in the TSA-driven growth inhibition of trophoblast, which can be partially reversed by the autophagy inhibitor chloroquine (CQ) or RNA interference of TFEB. In summary, our results reveal that abnormal acetylation and autophagy levels during early gestation may be associated with RSA and suggest the potential novel molecular target TFEB for RSA treatment.

Toxicity from a single injection of human umbilical cord mesenchymal stem cells into rat ovaries.

Intraovarian injection of human umbilical cord mesenchymal stem cells (hUC-MSCs) has been applied and with promising therapeutic effects, but its toxicity and safety remain uncertain. This study evaluated the toxic effects and the affected target organs after a single injection of hUC-MSCs into bilateral rat ovaries. Sixty Sprague-Dawley rats were randomly divided into four groups and intraovarian injected with three different doses of hUC-MSC suspension. Toxicity-related manifestations occurred over the following 14 days postinjection. On day (D)5 and D15, we assessed the clinical pathology; immunotoxicity, including the cytokine IFN-γ, TNF-α, IL-4, and IL-6 levels; the immune organs, and the organ weights. On D5, inflammatory cells mainly infiltrated the ovaries of the low- and medium-dose groups, whereas inflammatory cells infiltrated the oviduct in the medium- and high-dose groups. On D15, inflammatory cells infiltrated the corpus luteal cysts, ovarian sacs and oviducts in each group. Body weights; organ weights; immunotoxicity; clinical pathology and histopathological examinations of the immune organs did not significantly differ among the groups. No obvious hUC-MSC-related clinical symptoms were observed except in the rats that died. The high-dose group exhibited significantly higher mortality than did the control and low-dose groups. Deaths in the high-dose group, who received approximately 50 times the standard clinical dose, were related to the intraovarian hUC-MSC injection. The maximum tolerated dose was approximately ten times the standard clinical dose. The ovary and oviduct may be the target organs for this toxicity. This report provides dosage references and guidance for clinical applications of intraovarian hUC-MSC injections.

Newly identified HMO-2011-type phages reveal genomic diversity and biogeographic distributions of this marine viral group.

Viruses play critical roles in influencing biogeochemical cycles and adjusting host mortality, population structure, physiology, and evolution in the ocean. Marine viral communities are composed of numerous genetically distinct subfamily/genus-level viral groups. Among currently identified viral groups, the HMO-2011-type group is known to be dominant and broadly distributed. However, only four HMO-2011-type cultivated representatives that infect marine SAR116 and Roseobacter strains have been reported to date, and the genetic diversity, potential hosts, and ecology of this group remain poorly elucidated. Here, we present the genomes of seven HMO-2011-type phages that were isolated using four Roseobacter strains and one SAR11 strain, as well as additional 207 HMO-2011-type metagenomic viral genomes (MVGs) identified from various marine viromes. Phylogenomic and shared-gene analyses revealed that the HMO-2011-type group is a subfamily-level group comprising at least 10 discernible genus-level subgroups. Moreover, >2000 HMO-2011-type DNA polymerase sequences were identified, and the DNA polymerase phylogeny also revealed that the HMO-2011-type group contains diverse subgroups and is globally distributed. Metagenomic read-mapping results further showed that most HMO-2011-type phages are prevalent in global oceans and display distinct geographic distributions, with the distribution of most HMO-2011-type phages being associated with temperature. Lastly, we found that members in subgroup IX, represented by pelagiphage HTVC033P, were among the most abundant HMO-2011-type phages, which implies that SAR11 bacteria are crucial hosts for this viral group. In summary, our findings substantially expand current knowledge regarding the phylogenetic diversity, evolution, and distribution of HMO-2011-type phages, highlighting HMO-2011-type phages as major ecological agents that can infect certain key bacterial groups.