Circular RNAs (circRNAs) have emerged as novel molecules of interest in gene regulation as other noncoding RNAs. Though they have been explored in some species and tissues, the expression and functions of circRNAs in human reproductive systems remain unknown. Here we revealed the expression profiles of circRNAs in human testis tissue using high-throughput sequencing. The conformation of these testis-derived circRNAs in seminal plasma was also investigated, aiming to provide a non-invasive liquid biopsy surrogate for testicular biopsy. We predicted >15,000 circRNAs in human testis, with most of them (10,792; 67%) new. In all the 5,928 circRNA forming genes, 1,017 are first reported by us to generate circRNAs. Interestingly, these genes are mostly related to spermatogenesis, sperm motility, fertilization, etc. The sequence feature, chromosome location, alternative splicing and other characteristics of the circRNAs in human testis were also explored. Moreover, we found that these testis-derived circRNAs could be stably detected in seminal plasma. Most of them were probably bound with proteins in seminal plasma and were very stable at room temperature. Our work has laid the foundations to decipher regulation mechanisms of circRNAs in spermatogenesis and to develop circRNAs as novel noninvasive biomarkers for male infertile diseases.

BackgroundIn 2005, the FDA cautioned that exposure to paroxetine, a selective serotonin reuptake inhibitor (SSRI), during the first trimester of pregnancy may increase the risk of cardiac malformations. Since then, the association between maternal use of SSRIs during pregnancy and congenital malformations in infants has been the subject of much discussion and controversy. The aim of this study is to systematically review the associations between SSRIs use during early pregnancy and the risk of congenital malformations, with particular attention to the potential confounding by indication.MethodsThe study protocol was registered with PROSPERO (CRD42018088358). Cohort studies on congenital malformations in infants born to mothers with first-trimester exposure to SSRIs were identified via PubMed, Embase, Web of Science, and the Cochrane Library databases through 17 January 2018. Random-effects models were used to calculate summary relative risks (RRs).ResultsTwenty-nine cohort studies including 9,085,954 births were identified. Overall, use of SSRIs was associated with an increased risk of overall major congenital anomalies (MCAs, RR 1.11, 95% CI 1.03 to 1.19) and congenital heart defects (CHD, RR 1.24, 95% CI 1.11 to 1.37). No significantly increased risk was observed when restricted to women with a psychiatric diagnosis (MCAs, RR 1.04, 95% CI 0.95 to 1.13; CHD, RR 1.06, 95% CI 0.90 to 1.26). Similar significant associations were observed using maternal citalopram exposure (MCAs, RR 1.20, 95% CI 1.09 to 1.31; CHD, RR 1.24, 95% CI 1.02 to 1.51), fluoxetine (MCAs, RR 1.17, 95% CI 1.07 to 1.28; CHD, 1.30, 95% CI 1.12 to 1.53), and paroxetine (MCAs, RR 1.18, 95% CI 1.05 to 1.32; CHD, RR 1.17, 95% CI 0.97 to 1.41) and analyses restricted to using women with a psychiatric diagnosis were not statistically significant. Sertraline was associated with septal defects (RR 2.69, 95% CI 1.76 to 4.10), atrial septal defects (RR 2.07, 95% CI 1.26 to 3.39), and respiratory system defects (RR 2.65, 95% CI 1.32 to 5.32).ConclusionsThe evidence suggests a generally small risk of congenital malformations and argues against a substantial teratogenic effect of SSRIs. Caution is advisable in making decisions about whether to continue or stop treatment with SSRIs during pregnancy.Electronic supplementary materialThe online version of this article (10.1186/s12916-018-1193-5) contains supplementary material, which is available to authorized users.

This paper describes an experimental investigation into the pore structure of cement mortar using mercury porosimeter. Ordinary Portland cement, manufactured sand, and natural sand were used. The porosity of the manufactured sand mortar is higher than that of natural sand at the same mix proportion; on the contrary, the probable pore size and threshold radius of manufactured sand mortar are finer. Besides, the probable pore size and threshold radius increased with increasing water to cement ratio and sand to cement ratio. In addition, the existing models of pore size distribution of cement-based materials have been reviewed and compared with test results in this paper. Finally, the extended Bhattacharjee model was built to examine the relationship between compressive strength and pore structure.

A successful pregnancy depends on not only the tolerance of the fetal immune system by the mother but also resistance against the threat of hazardous microorganisms. Infection with pathogenic microorganisms during pregnancy may lead to premature delivery, miscarriage, growth restriction, neonatal morbidity, and other adverse outcomes. Moreover, the host also has an intact immune system to avoid these adverse outcomes. It is important to note the presence of normal bacteria in the maternal reproductive tract and the principal role of the maternal-placental-fetal interaction in antimicrobial immunity. Previous studies mainly focused on maternal infection during pregnancy. However, this review summarizes the new views on the study of the maternal microbiome and expounds the innate immune defense mechanism of the maternal vagina and decidua as well as how cytotrophoblasts and syncytiotrophoblasts recognize and kill bacteria in the placenta. Fetal immune systems, thought to be weak, also exhibit an immune defense function that is indispensable for maintaining the safety of the fetus. The skin, lungs, and intestines of the fetus during pregnancy constitute the main immune barriers. These findings will provide a new understanding of the effects of normal microbial flora and how the host resists harmful microbes during pregnancy. We believe that it may also contribute to the reference on the clinical prevention and treatment of gestational infection to avoid adverse pregnancy outcomes.

Background Chinese herbal medicine (CHM) is thought to be a potential intervention in the treatment of coronavirus disease (COVID-19). Purpose This study aimed to investigate the efficacy and safety of CHM or CHM combination therapy for COVID-19. Study design Systematic review and meta-analysis Methods We searched for relevant studies in the CNKI, CBM, Wanfang Data, PubMed, Cochrane Library, Embase, and other resources from their inception to April 15, 2020. Randomized controlled trials, cohort studies, and case-control studies on CHM or CHM combination therapy for COVID-19 were included. Meta-analysis was performed according to the Cochrane Handbook. Results Overall, 19 studies with 1474 patients were included. Meta-analysis showed that the overall clinical effectiveness (OR = 2.67, 95% CI 1.83-3.89, I 2 = 0%), improvement in the CT scan (OR = 2.43, 95% CI 1.80-3.29, I 2 = 0%), percentage of cases turning to severe/critical (OR = 0.40, 95% CI 0.24-0.67, I 2 = 17.1%), reverse transcription-polymerase chain reaction (RT-PCR) negativity rate (OR = 2.55, 95% CI 1.06-6.17, I 2 = 56.4%) and disappearance rate of symptoms (fever, cough, and fatigue) were superior by combined CHM treatment of COVID-19. However, there was no statistical difference between the two groups in terms of length of hospital stay (WMD = -0.46, 95% CI -3.87 - 2.95, I 2 = 99.5%), and rate of adverse effects (OR = 1.21, 95% CI 0.48-3.07, I 2 = 43.5%). The quality of evidence was very low to low. Conclusion The combined treatment of COVID-19 with Chinese and Western medicine may be effective in controlling symptoms and reducing the rate of disease progression due to low quality evidence.

Lactic acid (LA) metabolism in the tumor microenvironment contributes to the establishment and maintenance of immune tolerance. This pathway is characterized in tumor associated macrophages. However, the role and pathway of LA metabolism at maternal-fetal interface during early pregnancy, especially in decidual macrophage differentiation, are still unclear. Herein, for the first time, we discovered that LA can trigger either M2 or M1 macrophage polarization via oxidative phosphorylation and glycolysis regulation under normoxia or hypoxia, respectively. Also, LA metabolism played a vital role in decidual macrophages-mediated recurrent pregnancy loss (RPL), through HIF-1α/SRC/LDHA pathway. Moreover, blockade of LA intake with AZD3965 (MCT-1 inhibitor) could rescue pregnancy in an abortion-prone mouse model, suggesting a potential therapeutic target in RPL. Collectively, the present study identifies the previously unknown functions of LA metabolism in the differentiation of decidual macrophages in early normal pregnancy and RPL, and provides a potential therapeutic strategy in RPL by manipulating decidual macrophages' functions through LA metabolic pathway.

Successful pregnancy is a unique situation requires the maternal immune system to recognize and tolerate a semi‐identical fetus and allow normal invasion of trophoblast cells. Although efforts have been made, the deep mechanisms of the maternal‐fetal crosstalk have not yet been fully deciphered. Immune checkpoint molecules (ICMs) are a group of negative modulators of the immune response that avoid immune damage. They have been extensively studied in the fields of oncology and transplantation, while the latest evidence suggests that they are closely associated with pregnancy outcomes via multiple inhibitory mechanisms. Although studies have mostly demonstrated the regulatory role of the well‐known PD‐1, CTLA‐4 at the maternal‐fetal interface, what is unique about the newly discovered multiple ICMs remains a mystery. Here, we review the latest knowledge on ICMs, focusing on the first generation of checkpoints (PD‐1, CTLA‐4) and the next generation (Tim‐3, Tigit, Lag‐3, VISTA) highlighting their immunoregulatory roles in maternal‐fetal tolerance and decidual vascular remodeling, and their involvement in pathological pregnancies. The content covers three aspects: the characteristics they possess, the dynamic expression profile of their expression at the maternal‐fetal interface, and their involvement in pathological pregnancy. In immunotherapy strategies for pregnancy complications, upregulation of immune checkpoints may play a role. Meanwhile, the impact on pregnancy outcomes when using ICMs in clinical cancer treatment during pregnancy is a topic worth exploring. These may serve as a guide for future basic research and clinical applications of maternal‐fetal immunity.

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