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Background Endometriosis is well known as a chronic inflammatory disease. The development of endometriosis is heavily influenced by the estrogen receptor β (ERβ), while NOD-like receptors (NLRs) family CARD domain-containing 5 (NLRC5) exhibits anti-inflammatory properties during endometriosis. However, whether NLRC5-mediated anti-inflammation is involved in the ERβ-mediated endometriosis is still uncertain. This study aimed to assess that relation. Methods Nine cases of eutopic endometrial tissue and ten cases of ectopic endometrial tissue were collected from patients with endometriosis, and endometrial samples from ten healthy fertile women were analyzed, and the expression levels of ERβ were quantified using immunohistochemistry (IHC). Subsequently, we constructed mouse model of endometriosis by intraperitoneal injection. We detected the expression of ERβ, NLRC5, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-10 and measured the volume of ectopic lesions in mice with endometriosis. In vitro, human endometrial stromal cells (hESCs) were transfected respectively with ERβ-overexpressing and NLRC5-overexpressing plasmids. We then assessed the expression of ERβ and NLRC5 using quantitative real-time PCR (qRT-PCR) and western blot analysis. Furthermore, we measured the concentrations of TNF-α, IL-6, and IL-10 in the cell culture supernatant through enzyme-linked immunosorbent assay (ELISA). Additionally, we evaluated the migration and invasion ability of hESCs using transwell and wound healing assays. Results Inhibition of NLRC5 expression promotes the development of ectopic lesions in mice with endometriosis, upregulates the expression of pro-inflammatory factors TNF-α and IL-6, and downregulates the expression of anti-inflammatory factor IL-10. The high expression of NLRC5 in endometriosis depended on the ERβ overexpression. And ERβ promoted the migration of hESCs partially depend on inflammatory microenvironment. Lastly, NLRC5 overexpression inhibited ERβ-mediated development and inflammatory response of endometriosis. Conclusions Our results suggest that the innate immune molecule NLRC5-mediated anti-inflammation participates in ERβ-mediated endometriosis development, and partly clarifies the pathological mechanism of endometriosis, expanding our knowledge of the specific molecules related to the inflammatory response involved in endometriosis and potentially providing a new therapeutic target for endometriosis.

Interspecific differences in functional traits are a key factor for explaining the positive diversity–productivity relationship in plant communities. However, the role of intraspecific variation attributable to phenotypic plasticity in diversity–productivity relationships has largely been overlooked. By taking a wheat (Triticum aestivum)–maize (Zea mays) intercrop as an elementary example of mixed vegetation, we show that plasticity in plant traits is an important factor contributing to complementary light capture in species mixtures. We conceptually separated net biodiversity effect into the effect attributable to interspecific trait differences and species distribution (community structure effect), and the effect attributable to phenotypic plasticity. Using a novel plant architectural modelling approach, wholevegetation light capture was simulated for scenarios with and without plasticity based on empirical plant trait data. Light capture was 23% higher in the intercrop with plasticity than the expected value from monocultures, of which 36% was attributable to community structure and 64% was attributable to plasticity. For wheat, plasticity in tillering was the main reason for increased light capture, whereas for intercropped maize, plasticity induced a major reduction in light capture. The results illustrate the potential of plasticity for enhancing resource acquisition in mixed stands, and indicate the importance of plasticity in the performance of species-diverse plant communities.

Difficulties in scaling up theoretical and experimental results have raised controversy over the consequences of biodiversity loss for the functioning of natural ecosystems. Using a global survey of reef fish assemblages, we show that in contrast to previous theoretical and experimental studies, ecosystem functioning (as measured by standing biomass) scales in a non-saturating manner with biodiversity (as measured by species and functional richness) in this ecosystem. Our field study also shows a significant and negative interaction between human population density and biodiversity on ecosystem functioning (i.e., for the same human density there were larger reductions in standing biomass at more diverse reefs). Human effects were found to be related to fishing, coastal development, and land use stressors, and currently affect over 75% of the world's coral reefs. Our results indicate that the consequences of biodiversity loss in coral reefs have been considerably underestimated based on existing knowledge and that reef fish assemblages, particularly the most diverse, are greatly vulnerable to the expansion and intensity of anthropogenic stressors in coastal areas.

Summary Hundreds of experiments have now manipulated species richness (SR) of various groups of organisms and examined how this aspect of biological diversity influences ecosystem functioning. Ecologists have recently expanded this field to look at whether phylogenetic diversity (PD) among species, often quantified as the sum of branch lengths on a molecular phylogeny leading to all species in a community, also predicts ecological function. Some have hypothesized that phylogenetic divergence should be a superior predictor of ecological function than SR because evolutionary relatedness represents the degree of ecological and functional differentiation among species. But studies to date have provided mixed support for this hypothesis. Here, we reanalyse data from 16 experiments that have manipulated plant SR in grassland ecosystems and examined the impact on above‐ground biomass production over multiple time points. Using a new molecular phylogeny of the plant species used in these experiments, we quantified how the PD of plants impacts average community biomass production as well as the stability of community biomass production through time. Using four complementary analyses, we show that, after statistically controlling for variation in SR, PD (the sum of branches in a molecular phylogenetic tree connecting all species in a community) is neither related to mean community biomass nor to the temporal stability of biomass. These results run counter to past claims. However, after controlling for SR, PD was positively related to variation in community biomass over time due to an increase in the variances of individual species, but this relationship was not strong enough to influence community stability. In contrast to the non‐significant relationships between PD, biomass and stability, our analyses show that SR per se tends to increase the mean biomass production of plant communities, after controlling for PD. The relationship between SR and temporal variation in community biomass was either positive, non‐significant or negative depending on which analysis was used. However, the increases in community biomass with SR, independently of PD, always led to increased stability. These results suggest that PD is no better as a predictor of ecosystem functioning than SR. Synthesis. Our study on grasslands offers a cautionary tale when trying to relate PD to ecosystem functioning suggesting that there may be ecologically important trait and functional variation among species that is not explained by phylogenetic relatedness. Our results fail to support the hypothesis that the conservation of evolutionarily distinct species would be more effective than the conservation of SR as a way to maintain productive and stable communities under changing environmental conditions. Lay Summary

Despite empirical support for an increase in ecosystem productivity with species diversity in synthetic systems, there is ample evidence that this relationship is dependent on environmental characteristics, especially in structurally more complex natural systems. Empirical support for this relationship in forests is urgently needed, as these ecosystems play an important role in carbon sequestration. We tested whether tree wood production is positively related to tree species richness while controlling for climatic factors, by analyzing 55265 forest inventory plots in 11 forest types across five European countries. On average, wood production was 24% higher in mixed than in monospecific forests. Taken alone, wood production was enhanced with increasing tree species richness in almost all forest types. In some forests, wood production was also greater with increasing numbers of tree types. Structural Equation Modeling indicated that the increase in wood production with tree species richness was largely mediated by a positive association between stand basal area and tree species richness. Mean annual temperature and mean annual precipitation affected wood production and species richness directly. However, the direction and magnitude of the influence of climatic variables on wood production and species richness was not consistent, and vary dependent on forest type. Our analysis is the first to find a local scale positive relationship between tree species richness and tree wood production occurring across a continent. Our results strongly support incorporating the role of biodiversity in management and policy plans for forest carbon sequestration.

To predict the ecological consequences of biodiversity loss, researchers have spent much time and effort quantifying how biological variation affects the magnitude and stability of ecological processes that underlie the functioning of ecosystems. Here we add to this work by looking at how biodiversity jointly impacts two aspects of ecosystem functioning at once: (1) the production of biomass at any single point in time (biomass/area or biomass/volume), and (2) the stability of biomass production through time (the CV of changes in total community biomass through time). While it is often assumed that biodiversity simultaneously enhances both of these aspects of ecosystem functioning, the joint distribution of data describing how species richness regulates productivity and stability has yet to be quantified. Furthermore, analyses have yet to examine how diversity effects on production covary with diversity effects on stability. To overcome these two gaps, we reanalyzed the data from 34 experiments that have manipulated the richness of terrestrial plants or aquatic algae and measured how this aspect of biodiversity affects community biomass at multiple time points. Our reanalysis confirms that biodiversity does indeed simultaneously enhance both the production and stability of biomass in experimental systems, and this is broadly true for terrestrial and aquatic primary producers. However, the strength of diversity effects on biomass production is independent of diversity effects on temporal stability. The independence of effect sizes leads to two important conclusions. First, while it may be generally true that biodiversity enhances both productivity and stability, it is also true that the highest levels of productivity in a diverse community are not associated with the highest levels of stability. Thus, on average, diversity does not maximize the various aspects of ecosystem functioning we might wish to achieve in conservation and management. Second, knowing how biodiversity affects productivity gives no information about how diversity affects stability (or vice versa). Therefore, to predict the ecological changes that occur in ecosystems after extinction, we will need to develop separate mechanistic models for each independent aspect of ecosystem functioning.

Background Transcervical resection of adhesions (TCRA) is the standard treatment for intrauterine adhesion (IUA). Previous studies have shown that postoperative oral estrogen or an intrauterine physical barrier could reduce the recurrence of IUA by promoting the proliferation of the endometrium or inhibiting the reformation of adhesions. Our team designed an intrauterine stent that can release estrogen within the uterine cavity slowly. In this study, we aimed to investigate the efficacy and safety of the estrogen-releasing intrauterine system in preventing the recurrence of moderate to severe IUA. Methods This was a multicenter prospective randomized controlled 2-arm parallel trial that included patients who were diagnosed with moderate to severe IUA and who received TCRA. A total of 250 patients were randomly assigned, at a 1:1 ratio, to receive the intrauterine estrogen-releasing system or a Foley catheter balloon combined with oral estrogen therapy after surgery. The primary outcome was the rate of adhesion reduction in the two groups. The secondary outcomes included endometrial thickness at the ovulation period, menstrual improvement rates, and other reported adverse events during follow-up. Results The average daily drug release amount for all the tested stents was 0.21 mg/day. At 60 days postoperatively, the rate of adhesion reduction was significantly greater in the experimental group than in the control group (93.33% vs. 58.56%, p  < 0.001). The endometrium of the experimental group was thicker than that of the control group ( p  < 0.001). Consistently, the rate of improvement in menstruation was greater in the experimental group than in the control group ( p  = 0.010). No grade 3–4 adverse events were found in the two groups during the 1-year follow-up. Conclusions In the cohort of patients with moderate to severe IUA, the intrauterine estrogen-releasing system was more effective at reducing adhesion than traditional oral estrogen combined with an intrauterine Foley catheter after TCRA. This novel intrauterine system provides a new option for the management of IUA after surgery. Trial registration The registration number is NCT04972032. Date of registration: August 15, 2021.

Background Chronic pelvic pain (CPP) is a multifactorial syndrome that can substantially affect a patient’s quality of life. Endometriosis is one cause of CPP, and alterations of the immune and microbiome profiles have been observed in patients with endometriosis. The objective of this pilot study was to investigate differences in the vaginal and gastrointestinal microbiomes and cervicovaginal immune microenvironment in patients with CPP and endometriosis diagnosis compared to those with CPP without endometriosis and no CPP. Methods Vaginal swabs, rectal swabs, and cervicovaginal lavages (CVL) were collected among individuals undergoing gynecologic laparoscopy. Participants were grouped based on patients seeking care for chronic pain and/or pathology results: CPP and endometriosis (CPP-Endo) ( n  = 35), CPP without endometriosis ( n  = 23), or patients without CPP or endometriosis (controls) ( n  = 15). Sensitivity analyses were performed on CPP with endometriosis location, stage, and co-occurring gynecologic conditions (abnormal uterine bleeding, fibroids). 16S rRNA sequencing was performed to profile the microbiome, and a panel of soluble immune mediators was quantified using a multiplex assay. Statistical analysis was conducted with SAS, R, MicrobiomeAnalyst, MetaboAnalyst, and QIIME 2. Results Significant differences were observed between participants with CPP alone, CPP-Endo, and surgical controls for body mass index, ethnicity, diagnosis of ovarian cysts, and diagnosis of fibroids. In rectal microbiome analysis, both CPP alone and CPP-Endo exhibited lower alpha diversity than controls, and both CPP groups revealed enrichment of irritable bowel syndrome-associated bacteria. CPP-Endo exhibited an increased abundance of vaginal Streptococcus anginosus and rectal Ruminococcus . Patients with CPP and endometrioma (s) demonstrated increased vaginal Streptococcus , Lactobacillus, and Prevotella compared to other endometriosis sites. Further, abnormal uterine bleeding was associated with an increased abundance of bacterial vaginosis-associated bacteria. Immunoproteomic profiles were distinctly clustered by CPP alone and CPP-Endo compared to controls. CPP-Endo was enriched in TNF⍺, MDC, and IL-1⍺. Conclusions Vaginal and rectal microbiomes were observed to differ between patients with CPP alone and CPP with endometriosis, which may be useful in personalized treatment for individuals with CPP and endometriosis from those with other causes of CPP. Further investigation is warranted in patients with additional co-occurring conditions, such as AUB/fibroids, which add additional complexity to these conditions and reveal the enrichment of distinct pathogenic bacteria in both mucosal sites. This study provides foundational microbiome-immunoproteomic knowledge related to chronic pelvic pain, endometriosis, and co-occurring gynecologic conditions that can help improve the treatment of patients seeking care for pain.

Background Despite surgical and pharmacological interventions, endometriosis can recur. Reliable information regarding risk of recurrence following a first diagnosis is scant. The aim of this study was to examine clinical and survey data in the setting of disease recurrence to identify predictors of risk of endometriosis recurrence. Methods This observational study reviewed data from 794 patients having surgery for pelvic pain or endometriosis. Patients were stratified into two analytic groups based on self-reported or surgically confirmed recurrent endometriosis. Statistical analyses included univariate, followed by multivariate logistic regression to identify risk factors of recurrence, with least absolute shrinkage and selection operator (Lasso) regularisation. Risk-calibrated Supersparse Linear Integer Models (RiskSLIM) and survival analyses (with Lasso) were undertaken to identify predictive features of recurrence. Results Several significant features were repeatedly identified in association with recurrence, including adhesions, high rASRM score, deep disease, bowel lesions, adenomyosis, emergency room attendance for pelvic pain, younger age at menarche, higher gravidity, high blood pressure and older age. In the surgically confirmed group, with a score of 5, the RiskSLIM method was able to predict the risk of recurrence (compared to a single diagnosis) at 95.3% and included adenomyosis and adhesions in the model. Survival analysis further highlighted bowel lesions, adhesions and adenomyosis. Conclusions Following an initial diagnosis of endometriosis, clinical decision-making regarding disease management should take into consideration the presence of bowel lesions, adhesions and adenomyosis, which increase the risk of endometriosis recurrence.

Background Endometriosis is a chronic, estrogen-dependent, benign condition, affecting 10–15% of women of reproductive age. It is associated with a prevalence of sexual dysfunction that is nearly twice as high as that seen in women with other benign gynecological conditions. Our study aimed to assess the effect of surgical intervention on sexual function, as measured by the FSFI (Female Sexual Function Index) score, in women with endometriosis compared to those with other benign gynecological conditions, both before and after surgery. Methods A comparative analysis was conducted at the Medical University of Vienna from 2015 to 2020. The study included patients suspected of having endometriosis, fibroids, adnexal cysts, and/or infertility. Based on findings during surgery, patients were categorized into two groups: those with endometriosis ( n  = 64) and control patients ( n  = 38). All participants completed the FSFI questionnaire before surgery and again 8 to 18 weeks after the operation. Results No significant differences were observed in the preoperative FSFI scores between the endometriosis patients and the control group. Similarly, no significant differences were found between the two groups in postoperative scores. However, in women diagnosed with endometriosis, surgical removal of endometriotic lesions significantly increased their full-scale FSFI score, and resulted in a significant improvement in the areas “desire” and “satisfaction”. Improvements were noted in all other areas as well, though they were not statistically significant. Conclusions Our research indicates that the surgical removal of endometriotic lesions can lead to an improvement in sexual function, as measured by the FSFI, within 8 to 18 weeks post-surgery. This improvement was not observed in the control group, which underwent surgery for other benign gynecological issues.