Embryonic miscarriage severely affects the life quality and physical and mental state of pregnant women. However, the detailed mechanism underlying embryonic miscarriage is not fully understood. This study is aimed at analyzing embryonic miscarriage. We collected samples from 25 normal pregnant women and 25 embryonic miscarriage patients of similar age to analyze microbiota isolated from the vagina. Crude examination of the vagina isolates showed that compared with the control group, 80% of the embryonic miscarriage group contained a significantly lower number of Lactobacillus, the major healthy microbe in the vagina. Furthermore, the levels of Th1 and Th2 secreted cytokine interleukin 2 (IL-2) and interleukin10 (IL-10), respectively, were examined. Results showed that the IL2 level was higher, and IL10 level was lower in the embryonic miscarriage group than in the control group, whereas the IL2/IL10 level was higher in the embryonic miscarriage group than in the control group. This finding suggested that the immune response was suppressed in the embryonic miscarriage group. To further dissect the microbiota of the vagina in the two groups, 16S rDNA sequencing was performed. Bioinformatics analysis showed that 1096 and 998 overlapped operational taxonomic units were identified from the embryonic miscarriage and control groups, respectively. At the genus level, the relative abundance of Fam_Finegoldia, Lac_Coprococcus_3, and Lac_Roseburia significantly differed in the embryonic miscarriage group. Overall, our analyses provided potential biomarkers for embryonic miscarriage and elucidated the causative relationship between microbiota and immune responses and may enable the possible diagnosis and therapeutics of early pregnancy loss.

A novel water-stable metal-organic framework based on In(III), namely, [In 3 (btta) 2 -(OH) 3 (H 2 O)]⋅(DMA) 2 (1, DMA = N,, constructed from a novel ligand (2E,2 ′ E,2 ″ E)-3,3 ′ ,3 ″ -(benzene-1,3,5-triyl)triacrylic acid (H 3 btta), was obtained by a solvothermal reaction and structurally characterized by X-ray diffraction of single crystal along with elemental analysis. Owing to its high porosity and insensitive luminescent emission at room temperature, it was studied as a light-emitting sensor for detecting toxic Cr 2 O 7 2− anion in water, which shows high selectivity and sensitivity. To solve the bacterial problem, the protective effect of the compound against bacterial infection after missed abortion was evaluated. In the in vivo model, after the treatment with the compound, the clonal formation unit (CFU) in the uterine tissue was evaluated, and the animal weight was measured and recorded. In addition to this, the level of IL-18, C-reactive protein, TNF-, as well as IL-1 within the infectious tissues was detected by the ELISA method. Pose scoring software and molecular docking showed that the compound might bind to the NF-B protein, and this might offer a latent regulatory mechanism for the compound. K E Y W O R D S bacterial infection, Cr 2 O 7 2sensing, In(III)-complex, inflammatory response, missed abortion, molecular docking, porous framework, thermal shift 178

Aim: Intrauterine device (IUD) is a commonly used contraceptive method worldwide. Abnormal uterine bleeding (AUB) is one of the most common side effects of Cu-IUDs. Since AUB varies among Cu-IUD users, changes in the bleeding-related genetic factors may contribute to AUB. This study aimed to determine the genetic risk factors of AUB after Cu-IUD insertion. Methods: We conducted a case-control study on women who experienced AUB after Cu-IUD insertion (case:control = 62:59). Six candidate variants were genotyped using the Sequenom MassARRAY. Genotype and allele frequencies were analyzed using SHEsisPlus. We performed Pearson's Chi-squared test to analyze categorical data, and ESEfinder to predict the impact on splicing regulation. Results: MCM8 coding sequence variants: rs3761873-A>C was in Exon 7 and rs16991617 A>G was in Exon 12 of all 19 exons, both of which were significantly different between cases and controls (p allele = 0.039 and p genotype = 0.092). rs6022 and rs6029 in F5 gene and rs3761873 and rs16991617 in the MCM8 gene showed strong linkage disequilibrium (R 2 > 0.8). ESEfinder indicated that the variants of MCM8 may affect the splicing regulation. Conclusions: MCM8 rs376187 and rs16991617 were associated with AUB in Cu-IUDs users. MCM8 may play a role in AUB by regulating functions of reproductive organs and primary ovarian insufficiency. Our findings may improve the understanding of the genetic basis of AUB caused by Cu-IUDs.

Objective To investigate changes in the level of protein in serum and uncover the underlying pathogenesis of abnormal uterine bleeding (AUB) associated with copper intrauterine devices (Cu IUD). Methods Protein profiles were investigated via tandem mass tag (TMT)‐based quantitative proteomics and bioinformatics technology. Quantification and characterization of candidate proteins were further performed in 33 controls and 45 cases by Luminex assay and enzyme‐linked immunosorbent assay. Results In total, 842 proteins were identified via TMT coupled with liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) in the serum of individuals with IUDs. Among them, 25 differentially expressed proteins (p < 0.05) were observed, including eight upregulated proteins and 17 downregulated proteins. Ten proteins were verified, and Alpha‐1‐Antitrypsin (a1AT) had a significantly elevated expression in women with AUB associated with the Cu IUD compared with healthy controls (p = 0.026) and a high area under the curve value (0.656), as well as sensitivity (64.9%) and specificity (71.9%). Conclusion This is the first study to explore changes in serum protein and the underlying mechanisms of AUB associated with the Cu IUD via TMT technology. a1AT with biomarker potential was validated. These findings might provide an experimental basis for the early diagnosis or treatment of AUB associated with the Cu IUD.

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