Abstract Objective Premature ovarian insufficiency (POI) is a condition characterized by ovarian dysfunction occurring before the age of 40, with a prevalence ranging from 1–4%. The increasing incidence of this disease has a significant impact on women's reproductive health, as well as their metabolic, skeletal, neurological, and cardiovascular systems. The causes of premature ovarian insufficiency are multifactorial, including genetic, immunological, infectious, environmental, and iatrogenic factors, with over half of the cases remaining unexplained. Whether the microbial communities and metabolites in follicular fluid, which is the direct microenvironment for oocyte survival, are related to POI has not been reported. Methods This study included 26 patients with premature ovarian insufficiency and 27 controls with a normal ovarian reserve who underwent in vitro fertilization/embryo transfer. Follicular fluid samples were collected and analyzed using 16S rDNA sequencing and nontargeted metabolomics. Correlations between microbial communities and the metabolic profile of follicular fluid were analyzed to identify key microbial communities and metabolites that might be involved in the development and progression of POI. Results Patients with POI exhibited significant alterations in microbial richness and diversity and metabolic profiles in their follicular fluid. The downregulation of ABC transporters and upregulation of the citrate cycle (TCA cycle) might be critical for the development and progression of POI. G-Rhodopseudomonas and g-Caulobacter were identified as key microbial genera, while L-aspartic acid, citrate, isoleucine, and cytidine were identified as key metabolites. Conclusion This study revealed a distinctive microbial community metabolic profile in the follicular fluid of patients with POI. These findings offer novel insights into the pathogenesis of POI and might pave the way for improved clinical outcomes for individuals suffering from this condition.

Here, we report a new multi-optical maps scaffolder (MOMS) aiming at utilizing complementary information among optical maps labelled by distinct enzymes. This pipeline was designed for data structure organization, scaffolding by path traversal, gap-filling and molecule reuse of optical maps. Our testing showed that this pipeline has uncapped enzyme tolerance in scaffolding. This means that there are no inbuilt limits as to the number of maps generated by different enzymes that can be utilized by MOMS. For the genome assembly of the human GM12878 cell line, MOMS significantly improved the contiguity and completeness with an up to 144-fold increase of scaffold N50 compared with initial assemblies. Benchmarking on the genomes of human and O. sativa showed that MOMS is more effective and robust compared with other optical-map-based scaffolders. We believe this pipeline will contribute to high-fidelity chromosome assembly and chromosome-level evolutionary analysis.

The many-banded krait, Bungarus multicinctus, has been recorded as the animal resource of JinQianBaiHuaShe in the Chinese Pharmacopoeia. Characterization of its venoms classified chief phyla of modern animal neurotoxins. However, the evolutionary origin and diversification of its neurotoxins as well as biosynthesis of its active compounds remain largely unknown due to the lack of its high-quality genome. Here, we present the 1.58 Gbp genome of B. multicinctus assembled into 18 chromosomes with contig/scaffold N50 of 7.53 Mbp/149.8 Mbp. Major bungarotoxin-coding genes were clustered within genome by family and found to be associated with ancient local duplications. The truncation of glycosylphosphatidylinositol anchor in the 3’-terminal of a LY6E paralog released modern three-finger toxins（3FTxs） from membrane tethering before the Colubroidea divergence. Subsequent expansion and mutations diversified and recruited these 3FTxs. After the cobra/krait divergence, the modern unit-B of β-bungarotoxin emerged with an extra cysteine residue. A subsequent point substitution in unit-A enabled theβ-bungarotoxin covalent linkage. The B. multicinctus gene expression, chromatin topological organization, and histone modification characteristics were featured by transcriptome, proteome, chromatin conformation capture sequencing, and ChIP-seq. The results highlighted that venom production was under a sophisticated regulation. Our findings provide new insights into snake neurotoxin research, meanwhile will facilitate antivenom development, toxin-driven drug discovery and the quality control of JinQianBaiHuaShe.

Abstract Problem: To retrospectively observe the abnormally elevated proportion of INF-γ / IL-4 in peripheral blood among patients with recurrent spontaneous abortion, and to evaluate the application value of flow cytometry in detecting peripheral blood INF-γ / IL-4 in early etiological screening of patients with recurrent spontaneous abortion. Method of Study: A total of 77 patients with recurrent spontaneous abortion who were admitted to the Department of Obstetrics and Gynecology of The General Hospital of the People's Liberation Army of China from January 2021 to December 2021 were selected. All patients were women who had experienced two or more consecutive spontaneous abortions before 28 weeks of gestation but had not achieved clinical pregnancy; The peripheral blood of 58 women without recurrent spontaneous abortion history was selected as the control group. The levels of CD3 + CD8-INF-γ and IL-4 in peripheral blood lymphocytes were measured, and the ratio of INF-γ / IL-4 was calculated. Results: The ratio of INF-γ / IL-4 in peripheral blood of patients with rrecurrent spontaneous abortion was significantly higher compared to the control group, and the difference was statistically significant (P=0.000, < 0.001). The difference in the ratio between the two groups was caused by abnormally high INF-γ levels in the recurrent spontaneous abortion group (P=0.000, < 0.001), there was no statistical difference in IL-4 level between the two groups. The cutoff value of INF-γ / IL-4 in peripheral blood was 6.86, and the reference range was 1.28-8.49. The AUC of the detection method was 0.75 (P=0.000, < 0.001), has high clinical diagnostic value. According to the reference range, 33.77% of patients with recurrent spontaneous abortion had abnormally elevated INF-γ / IL-4 ratio. Conclusions: Compared with the control group, INF-γ / IL-4 ratio of peripheral blood in patients with recurrent spontaneous abortion was abnormally higher, and the carrier rate was 33.77%. Flow cytometry has high clinical value in detecting INF-γ / IL-4 ratio in peripheral blood.

Polygonum is a generalized genus of the Polygonaceae family that includes various herbaceous plants. In order to provide aid in understanding the evolutionary and phylogenetic relationship in Polygonum at the chloroplast (cp) genome-scale level, we sequenced and annotated the complete chloroplast genomes of four Polygonum species using next-generation sequencing technology and CpGAVAS. Then, repeat sequences, IR contractions, and expansion and transformation sites of chloroplast genomes of four Polygonum species were studied, and a phylogenetic tree was built using the chloroplast genomes of Polygonum. The results indicated that the chloroplast genome construction of Polygonum also displayed characteristic four types of results, comparable to the published chloroplast genome of recorded angiosperms. The chloroplast genomes of the four Polygonum plants are highly consistent in genome size (159,015 bp–163,461 bp), number of genes (112 genes, including 78 protein-coding genes, 30 tRNA genes, and 4 rRNA genes), gene types, gene order, codon usage, and repeat sequence distribution, which identifies the high preservation among the Polygonum chloroplast genomes. The Polygonum phylogenetic tree was recreated by a full sequence of the chloroplast genome, which illustrates that the P. bistorta, P. orientale, and P. perfoliatum are divided into the same branch, and P. aviculare belongs to Fallopia. The precise system site of lots base parts requires further verification, but the study would provide a basis for developing the available genetic resources and evolutionary relationships of Polygonum.

Oocytes reconstructed by spindle transfer (ST) are prone to chromosome abnormality, which is speculated to be caused by mechanical interference or premature activation, the mechanism is controversial. In this study, C57BL/6N oocytes were used as the model, and electrofusion ST was performed under normal conditions, Ca2+ free, and at room temperature, respectively. The effect of enucleation and electrofusion stimulation on MPF activity, spindle morphology, γ-tubulin localization and chromosome arrangement was compared. We found that electrofusion stimulation could induce premature chromosome separation and abnormal spindle morphology and assembly by decreasing the MPF activity, leading to premature activation, and thus resulting in chromosome abnormality in oocytes reconstructed via ST. Electrofusion stimulation was an independent factor of chromosome abnormality in oocytes reconstructed via ST, and was not related to enucleation, fusion status, temperature, or Ca2+. The electrofusion stimulation number should be minimized, with no more than 2 times being appropriate. As the electrofusion stimulation number increased, several typical abnormalities in chromosome arrangement and spindle assembly occurred. Although blastocyst culture could eliminate embryos with chromosomal abnormalities, it would significantly decrease the number of normal embryos and reduce the availability of embryos. The optimum operating condition for electrofusion ST was the 37°C group without Ca2+.