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Introduction: Fetal growth restriction (FGR) is a placenta-mediated pregnancy complication that predisposes fetuses to perinatal complications. Maternal plasma cell-free DNA harbors DNA originating from placental trophoblasts, which is promising for the prenatal diagnosis and prediction of pregnancy complications. Extrachromosomal circular DNA (eccDNA) is emerging as an ideal biomarker and target for several diseases.Methods: We utilized eccDNA sequencing and bioinformatic pipeline to investigate the characteristics and associations of eccDNA in placenta and maternal plasma, the role of placental eccDNA in the pathogenesis of FGR, and potential plasma eccDNA biomarkers of FGR.Results: Using our bioinformatics pipelines, we identified multi-chromosomal-fragment and single-fragment eccDNA in placenta, but almost exclusively single-fragment eccDNA in maternal plasma. Relative to that in plasma, eccDNA in placenta was larger and substantially more abundant in exons, untranslated regions, promoters, repetitive elements [short interspersed nuclear elements (SINEs)/Alu, SINEs/mammalian-wide interspersed repeats, long terminal repeats/endogenous retrovirus-like elements, and single recognition particle RNA], and transcription factor binding motifs. Placental multi-chromosomal-fragment eccDNA was enriched in confident enhancer regions predicted to pertain to genes in apoptosis, energy, cell growth, and autophagy pathways. Placental eccDNA–associated genes whose abundance differed between the FGR and control groups were associated with immunity-related gene ontology (GO) terms. The combined analysis of plasma and placental eccDNA–associated genes in the FGR and control groups led to the identification of potential biomarkers that were assigned to the GO terms of the epigenetic regulation of gene expression and nutrient-related processes, respectively.Conclusion: Together, our results highlight links between placenta functions and multi-chromosomal-fragment and single-fragment eccDNA. The integrative analysis of placental and plasma eccDNA confirmed the potential of these molecules as disease-specific biomarkers of FGR.

Pueraria lobata (Willd) (Pueraria montana var. lobata (Willd.) Maesen & S. M. Almeida ex Sanjappa & Predeep) is an important herbal medicine used in many countries. In P. lobata plants showing symptoms of mosaic, yellow spots, and mottling, mixed infection of new viruses provisionally named Pueraria lobata-associated emaravirus (PloAEV, genus Emaravirus), Pueraria lobata-associated crinivirus (PloACV, genus Crinivirus), and isolate CQ of the previously reported kudzu mosaic virus (KuMV-CQ, genus Begomovirus) was confirmed through high-throughput sequencing. PloAEV has five RNA segments, encoding a putative RNA-dependent RNA polymerase, glycoprotein precursor, nucleocapsid protein, movement protein, and P5, respectively. PloACV has two RNA segments, encoding 11 putative proteins. Only PloAEV could be mechanically transmitted from mixed infected symptomatic kudzu to Nicotiana benthamiana plants. All three viruses were detected in 35 symptomatic samples collected from five different growing areas, whereas no viruses were detected in 21 non-symptomatic plants, suggesting a high association between these three viruses. Thus, this study provides new knowledge on the diversity and molecular characteristics of viruses in P. lobata plants affected by the viral disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused a pandemic of coronavirus disease 2019 (COVID-19) and is threatening global health. SARS-CoV-2 spreads by air with a transmission rate of up to 15%, but the probability of its maternal–fetal transmission through the placenta is reported to be low at around 3.28%. However, it is still unclear that which tissues and developmental periods hold higher risks and what the underlying molecular mechanisms are. We conducted an integrated analysis of large-scale transcriptome and single-cell sequencing data to investigate the key factors that affect SARS-CoV-2 maternal–fetal transmission as well as the characteristics and effects of them. Our results showed that the abundance of cytomegalovirus (CMV) and Zika virus (ZIKV) infection-associated factors in the placenta were higher than their primarily infected tissues, while the expression levels of SARS-CoV-2 binding receptor angiotensin-converting enzyme II (ACE2) were similar between lung and placenta. By contrast, an important SARS-CoV-2 infection-associated factor, type II transmembrane serine protease (TMPRSS2), was poorly expressed in placenta. Further scRNA-Seq analysis revealed that ACE2 and TMPRSS2 were co-expressed in very few trophoblastic cells. Interestingly, during the embryonic development stages, the abundance of ACE2 and TMPRSS2 was much higher in multiple embryonic tissues than in the placenta. Based on our present analysis, the intestine in 20th week of embryonic development was at a high risk of SARS-CoV-2 infection. Additionally, we found that during the fetal development, ACE2 and TMPRSS2 were enriched in pathogen infection-associated pathways and may involve in the biological processes related to T-cell activation. In conclusion, our present study suggests that though the placenta provides a good physical barrier against SARS-CoV-2 infection for healthy fetal development, multiple embryonic tissues are under risks of the virus infection, which may be adversely affected once infected prenatally. Therefore, it is necessary to enhance maternal care to prevent the potential impact and harm of SARS-CoV-2 maternal–fetal transmission.

Our knowledge of citrus viruses is largely skewed toward virus pathology in cultivated orchards. Little is known about the virus diversity in wild citrus species. Here, we used a metatranscriptomics approach to characterize the virus diversity in a wild citrus habitat within the proposed center of the origin of citrus plants. We discovered a total of 44 virus isolates that could be classified into species Citrus tristeza virus and putative species citrus associated ampelovirus 1, citrus associated ampelovirus 2, and citrus virus B within the family Closteroviridae, providing important information to explore the factors facilitating outbreaks of citrus viruses and the evolutionary history of the family Closteroviridae. We found that frequent horizontal gene transfer, gene duplication, and alteration of expression strategy have shaped the genome complexity and diversification of the family Closteroviridae. Recombination frequently occurred among distinct Closteroviridae members, thereby facilitating the evolution of Closteroviridae. Given the potential emergence of similar wild-citrus-originated novel viruses as pathogens, the need for surveillance of their pathogenic and epidemiological characteristics is of utmost priority for global citrus production.