Unbiased metastatic niche-labeling identifies estrogen receptor-positive macrophages as a barrier of T cell infiltration during bone colonization.

Microenvironment niches determine cellular fates of metastatic cancer cells. However, robust and unbiased approaches to identify niche components and their molecular profiles are lacking. We established Sortase A-Based Microenvironment Niche Tagging (SAMENT), which selectively labels cells encountered by cancer cells during metastatic colonization. SAMENT was applied to multiple cancer models colonizing the same organ and the same cancer to different organs. Common metastatic niche features include macrophage enrichment and T cell depletion. Macrophage niches are phenotypically diverse between different organs. In bone, macrophages express the estrogen receptor alpha (ERα) and exhibit active ERα signaling in male and female hosts. Conditional knockout of Esr1 in macrophages significantly retarded bone colonization by allowing T cell infiltration. ERα expression was also discovered in human bone metastases of both genders. Collectively, we identified a unique population of ERα+ macrophages in the metastatic niche and functionally tied ERα signaling in macrophages to T cell exclusion during metastatic colonization. HIGHLIGHTS: SAMENT is a robust metastatic niche-labeling approach amenable to single-cell omics.Metastatic niches are typically enriched with macrophages and depleted of T cells.Direct interaction with cancer cells induces ERα expression in niche macrophages. Knockout of Esr1 in macrophages allows T cell infiltration and retards bone colonization.

Laparoscopic surgery for ectopic pregnancy: A comparative study on the clinical benefits and impact on tubal patency and reproductive outcomes.

BACKGROUND: Ectopic pregnancy is a major contributor to maternal morbidity and mortality across the globe. OBJECTIVE: This study aims to investigate the clinical benefits of laparoscopic surgery in treating ectopic pregnancy, and its impact on tubal patency and reproductive outcomes. METHODS: A clinical study was conducted to compare laparoscopic and medical conservative treatment for ectopic pregnancy. A total of 206 patients were treated for ectopic pregnancy at our hospital from January 2018 to June 2020. Among them, 46 underwent laparoscopic ipsilateral salpingectomy, 54 underwent laparoscopic ipsilateral salpingostomy with lesion removal, and 106 were treated conservatively with medication. RESULTS: The age range and average age of each group are provided, with no significant differences in these general demographic characteristics (p> 0.05). Both the salpingostomy and medication groups had higher rates of ectopic pregnancy compared to the salpingectomy group, with statistically significant differences (p< 0.05). The comparison of ectopic pregnancy rates between the salpingostomy and medication groups showed no significant difference. Within three years, the salpingostomy group had 10 cases of recurrent ectopic pregnancy, with 2 cases on the same side, while the medication group had 18 cases, with 8 cases on the same side. At 3 months after the normalization of blood ß-HCG, the salpingostomy group showed 43 cases of tubal patency (patency rate: 79.63%), while the medication group showed 57 cases (patency rate: 53.77%), with a statistically significant difference between the two groups (p= 0.01). CONCLUSION: Laparoscopic surgery for ectopic pregnancy offers significant clinical benefits over conservative medical treatment, including higher rates of tubal patency and improved reproductive outcomes. These findings support laparoscopic surgery as an effective approach for the management of ectopic pregnancy.

Surfactant-assisted preparation of all-gel-state flexible supercapacitor with remarkable electrochemical performance based on polyaniline-polyacrylamide/sodium alginate hydrogels.

The electrochemical performance of polyaniline-based all-gel-state supercapacitor (AGSSC) is significantly depended on the dispersity and mass loaded of polyaniline (PANI). In this manuscript, inspired by the properties of surfactant, sodium dodecylbenzene sulfonate (SDBS) was introduced to prepare various PANI-polyacrylamide/sodium alginate/SDBS (PANIy-PSSx) AGSSCs. With presence of SDBS, the electrochemical performance of PANIy-PSSx AGSSCs was greatly improved, displaying a trend of initial rise and then decrease with increasing concentration of SDBS from 0 to 0.75 wt%. As the content of SDBS was 0.5 wt%, the resulting PANI1.0-PSS0.5 AGSSC displayed the optimum electrochemical properties with area capacitance and energy density of 913.79 mF/cm2 and 81.23 µWh/cm2, respectively. The capacitance rate of PANI1.0-PSS0.5 AGSSC was still more than 93 % after 2000 cycles of sequential CV scans at the scan rate of 200 mV/s. These data were greatly higher than many reported PANI-based AGSSCs. Moreover, the resultant PANI1.0-PSS0.5 AGSSC could maintain high electrochemical performance even after various operations, such as compression, puncture, fluctuating temperature, bending situations and various voltage windows and series-parallel connections. The resultant PANI1.0-PSS0.5 AGSSC had the wide potentials to satisfy the real application requirements. This study offered a facile strategy for design and preparation of flexible supercapacitor with excellent electrochemical performance.

Siglec-15/sialic acid axis as a central glyco-immune checkpoint in breast cancer bone metastasis.

Immunotherapy is a promising approach for treating metastatic breast cancer (MBC), offering new possibilities for therapy. While checkpoint inhibitors have shown great progress in the treatment of metastatic breast cancer, their effectiveness in patients with bone metastases has been disappointing. This lack of efficacy seems to be specific to the bone environment, which exhibits immunosuppressive features. In this study, we elucidate the multiple roles of the sialic acid-binding Ig-like lectin (Siglec)-15/sialic acid glyco-immune checkpoint axis in the bone metastatic niche and explore potential therapeutic strategies targeting this glyco-immune checkpoint. Our research reveals that elevated levels of Siglec-15 in the bone metastatic niche can promote tumor-induced osteoclastogenesis as well as suppress antigen-specific T cell responses. Next, we demonstrate that antibody blockade of the Siglec-15/sialic acid glyco-immune checkpoint axis can act as a potential treatment for breast cancer bone metastasis. By targeting this pathway, we not only aim to treat bone metastasis but also inhibit the spread of metastatic cancer cells from bone lesions to other organs.

Evaluation of altered starch mutants and identification of candidate genes responsible for starch variation in wheat.

BACKGROUND: Induction of mutation through chemical mutagenesis is a novel approach for preparing diverse germplasm. Introduction of functional alleles in the starch biosynthetic genes help in the improvement of the quality and yield of cereals. RESULTS: In the present study, a set of 350 stable mutant lines were used to evaluate dynamic variation of the total starch contents. A megazyme kits were used for measuring the total starch content, resistant starch, amylose, and amylopectin content. Analysis of variance showed significant variation (p < 0.05) in starch content within the population. Furthermore, two high starch mutants (JE0173 and JE0218) and two low starch mutants (JE0089 and JE0418) were selected for studying different traits. A multiple comparison test showed that significant variation in all physiological and morphological traits, with respect to the parent variety (J411) in 2019-2020 and 2020-2021. The quantitative expression of starch metabolic genes revealed that eleven genes of JE0173 and twelve genes of JE0218 had consistent expression in high starch mutant lines. Similarly, in low starch mutant lines, eleven genes of JE0089 and thirteen genes of JE0418 had consistent expression in all stages of seed development. An additional two candidate genes showed over-expression (PHO1, PUL) in the high starch mutant lines, indicating that other starch metabolic genes may also contribute to the starch biosynthesis. The overexpression of SSII, SSIII and SBEI in JE0173 may be due to presence of missense mutations in these genes and SSI also showed overexpression which may be due to 3-primer_UTR variant. These mutations can affect the other starch related genes and help to increase the starch content in this mutant line (JE0173). CONCLUSIONS: This study screened a large scale of mutant population and identified mutants, could provide useful genetic resources for the study of starch biosynthesis and genetic improvement of wheat in the future. Further study will help to understand new genes which are responsible for the fluctuation of total starch.

EVs-mediated delivery of CB2 receptor agonist for Alzheimer's disease therapy.

Alzheimer's disease (AD) is a typical neurodegenerative disease that leads to irreversible neuronal degeneration, and effective treatment remains elusive due to the unclear mechanism. We utilized biocompatible mesenchymal stem cell-derived extracellular vesicles as carriers loaded with the CB2 target medicine AM1241 (EVs-AM1241) to protect against neurodegenerative progression and neuronal function in AD model mice. According to the results, EVs-AM1241 were successfully constructed and exhibited better bioavailability and therapeutic effects than bare AM1241. The Morris water maze (MWM) and fear conditioning tests revealed that the learning and memory of EVs-AM1241-treated model mice were significantly improved. In vivo electrophysiological recording of CA1 neurons indicated enhanced response to an auditory conditioned stimulus following fear learning. Immunostaining and Western blot analysis showed that amyloid plaque deposition and amyloid ß (Aß)-induced neuronal apoptosis were significantly suppressed by EVs-AM1241. Moreover, EVs-AM1241 increased the number of neurons and restored the neuronal cytoskeleton, indicating that they enhanced neuronal regeneration. RNA sequencing revealed that EVs-AM1241 facilitated Aß phagocytosis, promoted neurogenesis and ultimately improved learning and memory through the calcium-Erk signaling pathway. Our study showed that EVs-AM1241 efficiently reversed neurodegenerative pathology and enhanced neurogenesis in model mice, indicating that they are very promising particles for treating AD.

Identification of New Prognostic Genes and Construction of a Prognostic Model for Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is a rapidly progressive malignancy, and its mortality rate is very high. In this study, we aimed at finding novel prognosis-related genes and constructing a credible prognostic model to improve the prediction for LUAD patients. Differential gene expression, mutant subtype, and univariate Cox regression analyses were conducted with the dataset from the Cancer Genome Atlas (TCGA) database to screen for prognostic features. These features were employed in the following multivariate Cox regression analysis and the produced prognostic model included the stage and expression of SMCO2, SATB2, HAVCR1, GRIA1, and GALNT4, as well as mutation subtypes of TP53. The exactness of the model was confirmed by an overall survival (OS) analysis and disease-free survival (DFS) analysis, which indicated that patients in the high-risk group had a poorer prognosis compared to those in the low-risk group. The area under the receiver operating characteristic curve (AUC) was 0.793 in the training group and 0.779 in the testing group. The AUC of tumor recurrence was 0.778 in the training group and 0.815 in the testing group. In addition, the number of deceased patients increased as the risk scores raised. Furthermore, the knockdown of prognostic gene HAVCR1 suppressed the proliferation of A549 cells, which supports our prognostic model that the high expression of HAVCR1 predicts poor prognosis. Our work created a reliable prognostic risk score model for LUAD and provided potential prognostic biomarkers.

Osteoprogenitor-GMP crosstalk underpins solid tumor-induced systemic immunosuppression and persists after tumor removal.

Remote tumors disrupt the bone marrow (BM) ecosystem (BME), eliciting the overproduction of BM-derived immunosuppressive cells. However, the underlying mechanisms remain poorly understood. Herein, we characterized breast and lung cancer-induced BME shifts pre- and post-tumor removal. Remote tumors progressively lead to osteoprogenitor (OP) expansion, hematopoietic stem cell dislocation, and CD41- granulocyte-monocyte progenitor (GMP) aggregation. The tumor-entrained BME is characterized by co-localization between CD41- GMPs and OPs. OP ablation abolishes this effect and diminishes abnormal myeloid overproduction. Mechanistically, HTRA1 carried by tumor-derived small extracellular vesicles upregulates MMP-13 in OPs, which in turn induces the alterations in the hematopoietic program. Importantly, these effects persist post-surgery and continue to impair anti-tumor immunity. Conditional knockout or inhibition of MMP-13 accelerates immune reinstatement and restores the efficacies of immunotherapies. Therefore, tumor-induced systemic effects are initiated by OP-GMP crosstalk that outlasts tumor burden, and additional treatment is required to reverse these effects for optimal therapeutic efficacy.

Identification of RNA-Binding Protein Targets with HyperTRIBE in Saccharomyces cerevisiae.

As a master regulator in cells, RNA-binding protein (RBP) plays critical roles in organismal development, metabolism and various diseases. It regulates gene expression at various levels mostly by specific recognition of target RNA. The traditional CLIP-seq method to detect transcriptome-wide RNA targets of RBP is less efficient in yeast due to the low UV transmissivity of their cell walls. Here, we established an efficient HyperTRIBE (Targets of RNA-binding proteins Identified By Editing) in yeast, by fusing an RBP to the hyper-active catalytic domain of human RNA editing enzyme ADAR2 and expressing the fusion protein in yeast cells. The target transcripts of RBP were marked with new RNA editing events and identified by high-throughput sequencing. We successfully applied HyperTRIBE to identifying the RNA targets of two yeast RBPs, KHD1 and BFR1. The antibody-free HyperTRIBE has competitive advantages including a low background, high sensitivity and reproducibility, as well as a simple library preparation procedure, providing a reliable strategy for RBP target identification in Saccharomyces cerevisiae.

The enhanced generation of motor neurons from mESCs by MgAl layered double hydroxide nanoparticles.

The committed differentiation of stem cells into neurons is a promising therapeutic strategy for neurological diseases. Predifferentiation of transplanted stem cells into neural precursors could enhance their utilization and control the direction of differentiation. Embryonic stem cells with totipotency can differentiate into specific nerve cells under appropriate external induction conditions. Layered double hydroxide (LDH) nanoparticles have been proven to regulate the pluripotency of mouse ESCs (mESCs), and LDH could be used as carrier in neural stem cells for nerve regeneration. Hence, we sought to study the effects of LDH without loaded factors on mESCs neurogenesis in this work. A series of characteristics analyses indicated the successful construction of LDH nanoparticles. LDH nanoparticles that may adhere to the cell membranes had insignificant effect on cell proliferation and apoptosis. The enhanced differentiation of mESCs into motor neurons by LDH was systematically validated by immunofluorescent staining, quantitative real-time PCR analysis and western blot analysis. In addition, transcriptome sequencing analysis and mechanism verification elucidated the significant regulatory roles of focal adhesion signaling pathway in the enhanced mESCs neurogenesis by LDH. Taken together, the functional validation of inorganic LDH nanoparticles promoting motor neurons differentiation provide a novel strategy and therapeutic prospect for the clinical transition of neural regeneration.

Transcriptomics and Selection Pressure Analysis Reveals the Influence Mechanism of PLIN1 Protein on the Development of Small Size in Min Pigs.

Body size is an important biological phenotypic trait that has attracted substantial attention. Small domestic pigs can serve as excellent animal models for biomedicine and also help meet sacrificial culture needs in human societies. Although the mechanisms underlying vertebral development regulating body size variation in domestic pigs during the embryonic period have been well described, few studies have examined the genetic basis of body size variation in post embryonic developmental stages. In this study, seven candidate genes-PLIN1, LIPE, PNPLA1, SCD, FABP5, KRT10 and IVL-significantly associated with body size were identified in Min pigs, on the basis of weighted gene co-expression network analysis (WGCNA), and most of their functions were found to be associated with lipid deposition. Six candidate genes except for IVL were found to have been subjected to purifying selection. PLIN1 had the lowest ω value (0.139) and showed heterogeneous selective pressure among domestic pig lineages with different body sizes (p < 0.05). These results suggested that PLIN1 is an important genetic factor regulating lipid deposition and consequently affecting body size variation in pigs. The culture of whole pig sacrifice in Manchu during the Qing Dynasty in China might have contributed to the strong artificial domestication and selection of Hebao pigs.

Bone Metastasis Initiation Is Coupled with Bone Remodeling through Osteogenic Differentiation of NG2+ Cells.

The bone microenvironment is dynamic and undergoes remodeling in normal and pathologic conditions. Whether such remodeling affects disseminated tumor cells (DTC) and bone metastasis remains poorly understood. Here, we demonstrated that pathologic fractures increase metastatic colonization around the injury. NG2+ cells are a common participant in bone metastasis initiation and bone remodeling in both homeostatic and fractured conditions. NG2+ bone mesenchymal stem/stromal cells (BMSC) often colocalize with DTCs in the perivascular niche. Both DTCs and NG2+ BMSCs are recruited to remodeling sites. Ablation of NG2+ lineage impaired bone remodeling and concurrently diminished metastatic colonization. In cocultures, NG2+ BMSCs, especially when undergoing osteodifferentiation, enhanced cancer cell proliferation and migration. Knockout of N-cadherin in NG2+ cells abolished these effects in vitro and phenocopied NG2+ lineage depletion in vivo. These findings uncover dual roles of NG2+ cells in metastasis and remodeling and indicate that osteodifferentiation of BMSCs promotes metastasis initiation via N-cadherin-mediated cell-cell interaction. SIGNIFICANCE: The bone colonization of cancer cells occurs in an environment that undergoes constant remodeling. Our study provides mechanistic insights into how bone homeostasis and pathologic repair lead to the outgrowth of disseminated cancer cells, thereby opening new directions for further etiologic and epidemiologic studies of tumor recurrences. This article is highlighted in the In This Issue feature, p. 247.

Vaginal Microbiota Changes Caused by HPV Infection in Chinese Women.

Human papillomavirus (HPV) infection is one of the most common sexually transmitted diseases. After studying 602 unvaccinated Chinese women using 16S rRNA to detect cervical-vaginal microecology, we analyzed the relationship between HPV infection and vaginal microecology including 20 HPV types. In Chinese women, L. gasseri-dominated and L. jensenii-dominated clusters were significantly absence. Microbial alpha diversity was significantly higher in HPV-infected and cervical intraepithelial neoplasia (CIN)-diagnosed groups than in healthy control group. Certain bacteria were associated with HPV infection and CIN, including Streptococcus, Prevotella, Chlamydia, Bifidobacterium, Ralstonia, and Aerococcus. With the development of disease, the proportions of community state type III (CST-III) and CST-IV-B gradually increased, whereas the proportions of CST-I and CST-IV-A gradually decreased. In addition, age was an influential factor for HPV infection. With aging, the probability of HPV infection and the proportion of CST-IV-B increase. In conclusion, our study was a large cross-sectional study that evaluated the relationship between vaginal microbiota and HPV infection, and brought essential comparable data.

A cross-sectional analysis about bacterial vaginosis, high-risk human papillomavirus infection, and cervical intraepithelial neoplasia in Chinese women.

Bacterial vaginosis (BV) is a genital infection that frequently presents in women infected with human papillomavirus (HPV), but the correlation between BV, HPV and cervical intraepithelial neoplasia (CIN) development is still elusive. We organized a cross-sectional analysis which enrolled 624 participants and obtained 423 samples of vaginal secretions from them, including 193 HPV-negative samples and 230 HR-HPV-positive samples. We used 16S rRNA sequencing to measure the vaginal microbiota diversity in women with different BV, HPV and CIN status, and then calculated risk factors for CIN by logistic regression. We found that the diversity of vaginal microbiota was significantly increased after BV, HPV and BV-infected CIN group. The Observed species and Chao1 index of H.C group showed little difference with normal group, while its Shannon index was considerable higher than normal group. L. iners enriched in HPV infection group compared with others significantly. BV (OR = 0.358; 95% CI = 0.195-0.656; P < .05) and HR-HPV infection (OR = 0.016; 95% CI = 0.004-0.072; P < .001) were risk factors for CIN. In conclusion, we consider BV as a risk factor for CIN. The enrichment of L. iners under HPV infection state may contribute to maintenance of vaginal dysbiosis, and BV infection could facilitate the disturb.

Complement 4 Aids in the Prediction of Newly Diagnosed Multiple Myeloma Outcome in Patients.

BACKGROUND: A cure for the heterogeneous hematological malignancy multiple myeloma (MM) is yet to be developed. To date, the early risk factors associated with poor outcomes in MM have not been fully elucidated. Studies have shown an aberrant complement system in patients with MM, but the precise association necessitates elucidation. Therefore, this study scrutinizes the correlation between serum complement level and the disease outcome of patients with MM. METHODS: A retrospective analysis of 72 patients with MM (new diagnosis) with complement C4 and C3 along with common laboratory indicators was done. The Pearson χ2 test and the Mann-Whitney U-test were done to evaluate categorical or binary variables and intergroup variance, respectively. Kaplan-Meier test and Cox proportional hazards regression were used for quantification of overall survival (OS) and univariate or multivariate analyses, respectively. RESULTS: The Cox proportional hazard model analysis unveiled the following: platelet ⩽115.5 × 109/L (hazard ratio [HR] = 5.82, 95% confidence interval [CI] = 2.522-13.436, P < .001), complement C4 ⩽0.095 g/L(HR = 3.642, 95% CI = 1.486-8.924, P = .005), age ⩾67 years (HR = 0.191, 95% CI = 0.078-0.47, P < .001), and bone marrow plasma cell percentage ⩾30.75% (HR = 0.171, 95% CI = 0.06-0.482, P = .001) can be used as independent predictors of OS. Of these, advanced age, low platelet level, and a high proportion of bone marrow plasma cells have been implicated in poor outcomes in patients with MM. Interestingly, a low complement 4 level can function as a new indicator of poor prognosis in patients with MM. CONCLUSION: Low levels of C4 are indicative of a poor outcome in newly diagnosed patients with MM.

Neurogenesis potential of oligodendrocyte precursor cells from oligospheres and injured spinal cord.

Severe traumatic spinal cord injury (SCI) leads to long-lasting oligodendrocyte death and extensive demyelination in the lesion area. Oligodendrocyte progenitor cells (OPCs) are the reservoir of new mature oligodendrocytes during damaged myelin regeneration, which also have latent potential for neurogenic regeneration and oligospheres formation. Whether oligospheres derived OPCs can differentiate into neurons and the neurogenesis potential of OPCs after SCI remains unclear. In this study, primary OPCs cultures were used to generate oligospheres and detect the differentiation and neurogenesis potential of oligospheres. In vivo, SCI models of juvenile and adult mice were constructed. Combining the single-cell RNA sequencing (scRNA-seq), bulk RNA sequencing (RNA-seq), bioinformatics analysis, immunofluorescence staining, and molecular experiment, we investigated the neurogenesis potential and mechanisms of OPCs in vitro and vivo. We found that OPCs differentiation and oligodendrocyte morphology were significantly different between brain and spinal cord. Intriguingly, we identify a previously undescribed findings that OPCs were involved in oligospheres formation which could further differentiate into neuron-like cells. We also firstly detected the intermediate states of oligodendrocytes and neurons during oligospheres differentiation. Furthermore, we found that OPCs were significantly activated after SCI. Combining scRNA-seq and bulk RNA-seq data from injured spinal cord, we confirmed the neurogenesis potential of OPCs and the activation of endoplasmic reticulum stress after SCI. Inhibition of endoplasmic reticulum stress could effectively attenuate OPCs death. Additionally, we also found that endoplasmic reticulum may regulate the stemness and differentiation of oligospheres. These findings revealed the neurogenesis potential of OPCs from oligospheres and injured spinal cord, which may provide a new source and a potential target for spinal cord repair.

Acute carbohydrate overfeeding: a redox model of insulin action and its impact on metabolic dysfunction in humans.

A role for fat overfeeding in metabolic dysfunction in humans is commonly implied in the literature. Comparatively less is known about acute carbohydrate overfeeding (COF). We tested the hypothesis that COF predisposes to oxidative stress by channeling electrons away from antioxidants to support energy storage. In a study of 24 healthy human subjects with and without obesity, COF was simulated by oral administration of excess carbohydrates; a two-step hyperinsulinemic clamp was used to evaluate insulin action. The distribution of electrons between oxidative and reductive pathways was evaluated by the changes in the reduction potentials (Eh) of cytoplasmic (lactate, pyruvate) and mitochondrial (ß-hydroxybutyrate, acetoacetate) redox couples. Antioxidant redox was measured by the ratio of reduced to oxidized glutathione. We used cross-correlation analysis to evaluate the relationships between the trajectories of Eh, insulin, glucose, and respiratory exchange during COF. DDIT3 and XBP1s/u mRNA were measured as markers of endoplasmic reticulum stress (ER stress) in adipose tissue before and after COF. Here, we show that acute COF is characterized by net transfer of electrons from mitochondria to cytoplasm. Circulating glutathione is oxidized in a manner that significantly cross-correlates with increasing insulin levels and precedes the decrease in cytoplasmic Eh. This effect is more pronounced in overweight individuals (OW). Markers of ER stress in subcutaneous fat are detectable in OW within 4 h. We conclude that acute COF contributes to metabolic dysfunction through insulin-dependent pathways that promote electron transfer to the cytoplasm and decrease antioxidant capacity. Characterization of redox during overfeeding is important for understanding the pathophysiology of obesity and type 2 diabetes.NEW & NOTEWORTHY Current principles assume that conversion of thermic energy to metabolically useful energy follows fixed rules. These principles ignore the possibility of variable proton uncoupling in mitochondria. Our study shows that the net balance of electron distribution between mitochondria and cytoplasm is influenced by insulin in a manner that reduces proton leakage during overfeeding. Characterization of the effects of insulin on redox balance is important for understanding obesity and insulin resistance.

Translocation of vaginal microbiota is involved in impairment and protection of uterine health.

The vaginal and uterine microbiota play important roles in the health of the female reproductive system. However, the interactions among the microbes in these two niches and their effects on uterine health remain unclear. Here we profile the vaginal and uterine microbial samples of 145 women, and combine with deep mining of public data and animal experiments to characterize the microbial translocation in the female reproductive tract and its role in modulating uterine health. Synchronous variation and increasing convergence of the uterine and vaginal microbiome with advancing age are shown. We also find that transplanting certain strains of vaginal bacteria into the vagina of rats induces or reduces endometritis-like symptoms, and verify the damaging or protective effects of certain vaginal bacteria on endometrium. This study clarifies the interdependent relationship of vaginal bacterial translocation with uterine microecology and endometrial health, which will undoubtedly increase our understanding of female reproductive health.

Dispersal and mating patterns determine the fate of naturally dispersed populations: evidence from Bombina orientalis.

BACKGROUND: In contrast to the explosive increase of a population following biological invasion, natural dispersal, i.e., when a population disperses from its original range into a new range, is a passive process that is affected by resources, the environment, and other factors. Natural dispersal is also negatively impacted by genetic drift and the founder effect. Although the fates of naturally dispersed populations are unknown, they can adapt evolutionarily over time to the new environment. Can naturally dispersed populations evolve beneficial adaptive strategies to offset these negative effects to maintain their population in a stable state? RESULTS: The current study addressed this question by focusing on the toad Bombina orientalis, the population of which underwent natural dispersal following the Last Glacial Maximum in Northeast Asia. Population genetic approaches were used to determine the genetic structure, dispersal pattern, and mating system of the population of B. orientalis in northeast China (Northern population). The results showed that this northern population of B. orientalis is a typical naturally dispersed population, in which the stable genetic structure and high level of genetic diversity of the population have been maintained through the long-distance biased dispersal behavior of males and the pattern of promiscuity within the population. CONCLUSIONS: Our findings suggest that naturally dispersed populations can evolve effective adaptive strategies to maintain a stable population. Different species may have different strategies. The relevance of these maintenance mechanisms for naturally dispersed populations provide a new perspective for further understanding the processes of speciation and evolution.

Evolutionary history of the oriental fire-bellied toad (Bombina orientalis) in Northeast China.

The evolutionary history of a species is generally affected by the combination of geological events and climate fluctuations. By analyzing the population features, genetic structure and the effective population historical dynamics of existing species, the population evolutionary history can be reestablished. In recent years, geological evidence shows that the Yilan-Yitong fault zone located in Northeast Asia experienced strong and frequent geological changes in the late Quaternary period. Species population history has been shaped by the combination of the complex climatic conditions of the Quaternary and Pleistocene glacial interglacial cycles and palaeogeological events in Northeast Asia and it has become a research focus for evolutionary biology researchers. In this study, mitochondrial and microsatellite molecular markers were used to reveal the population features, genetic structure, and the effective population historical dynamics of the Oriental fire-bellied toad (Bombina orientalis). The results showed that the strong seismic activity of the Yilan-Yitong fault zone in the late Quaternary period was the main reason for the population differentiation of Oriental fire-bellied toad in northeast China. The Quaternary Pleistocene glacial interglacial cycles led to the significant bottleneck effect of the western population located in the Maoer mountain area. As a result, the western population has low genetic diversity. Recent gene flow between eastern and western populations and historical evidence of population expansion proved that the dispersal behavior of the western populations was the main cause of the low genetic diversity and mitochondrial and nuclear discordance. Human economic activity may be the mainly driving factor. These evidences showed that the comprehensive influence of geology, climate, human activities and other factors should be considered in the process of exploring the evolutionary history of species.