ALKBH5 modulates macrophages polarization in tumor microenvironment of ovarian cancer.

BACKGROUND: Macrophages play an essential role in regulating ovarian cancer immune microenvironment. Studies have shown that m6A methylation could influence immune microenvironment in cancer. In this study, we investigated the roles of m6A demethylase ALKBH5 and m6A recognition protein IGF2BP2 played in regulating macrophages polarization in ovarian cancer. METHODS: In this study, we first explored the differentially expressed m6A methylation enzymes in M0 and M2 macrophages according to two independent GEO datasets. TIMER2.0 and GSCA database were used to explore the immune analysis of ALKBH5 and IGF2BP2 in ovarian cancer. K-M plotter and TIMER2.0 databases were used to evaluate the prognostic role of ALKBH5 and IGF2BP2 in ovarian cancer. For CNV mutation analysis of ALKBH5 and IGF2BP2, cBioPortal and GSCA databases were used. For single-cell analysis, sc-TIME and HPA softwares were used to analyze the roles of ALKBH5 and IGF2BP2 played in immune cells in ovarian cancer. To identify the role of ALKBH5 played in macrophage polarization, RT-PCR was used to verify the macrophage polarization related markers in vitro study. The function of ALKBH5 played in ovarian cancer was further analyzed through GO and KEGG analysis. FINDINGS: In this study, we found that ALKBH5 and IGF2BP2 were up-regulated in M2 macrophages, which showed closely correlation with immune cells expressions in ovarian cancer, especially with macrophages. Ovarian cancer patients with higher expression of ALKBH5 and IGF2BP2 showed worse prognosis, possibly because of their close correlation with immune response. ALKBH5 also correlated with macrophage phenotypes in single-cell levels analysis. However, the expression level of IGF2BP2 in ovarian cancer immune microenvironment was very low. The results of RT-PCR indicated the potential role of ALKBH5 in M2 polarization of macrophages. INTERPRETATION: ALKBH5 participated in regulating macrophage M2 polarization in ovarian cancer immune microenvironment.

Artificial intelligence-driven prognostic system for conception prediction and management in intrauterine adhesions following hysteroscopic adhesiolysis: a diagnostic study using hysteroscopic images.

Introduction: Intrauterine adhesions (IUAs) caused by endometrial injury, commonly occurring in developing countries, can lead to subfertility. This study aimed to develop and evaluate a DeepSurv architecture-based artificial intelligence (AI) system for predicting fertility outcomes after hysteroscopic adhesiolysis. Methods: This diagnostic study included 555 intrauterine adhesions (IUAs) treated with hysteroscopic adhesiolysis with 4,922 second-look hysteroscopic images from a prospective clinical database (IUADB, NCT05381376) with a minimum of 2 years of follow-up. These patients were randomly divided into training, validation, and test groups for model development, tuning, and external validation. Four transfer learning models were built using the DeepSurv architecture and a code-free AI application for pregnancy prediction was also developed. The primary outcome was the model's ability to predict pregnancy within a year after adhesiolysis. Secondary outcomes were model performance which evaluated using time-dependent area under the curves (AUCs) and C-index, and ART benefits evaluated by hazard ratio (HR) among different risk groups. Results: External validation revealed that using the DeepSurv architecture, InceptionV3+ DeepSurv, InceptionResNetV2+ DeepSurv, and ResNet50+ DeepSurv achieved AUCs of 0.94, 0.95, and 0.93, respectively, for one-year pregnancy prediction, outperforming other models and clinical score systems. A code-free AI application was developed to identify candidates for ART. Patients with lower natural conception probability indicated by the application had a higher ART benefit hazard ratio (HR) of 3.13 (95% CI: 1.22-8.02, p = 0.017). Conclusion: InceptionV3+ DeepSurv, InceptionResNetV2+ DeepSurv, and ResNet50+ DeepSurv show potential in predicting the fertility outcomes of IUAs after hysteroscopic adhesiolysis. The code-free AI application based on the DeepSurv architecture facilitates personalized therapy following hysteroscopic adhesiolysis.

Research on Inter-Frame Feature Mismatch Removal Method of VSLAM in Dynamic Scenes.

Visual Simultaneous Localization and Mapping (VSLAM) estimates the robot's pose in three-dimensional space by analyzing the depth variations of inter-frame feature points. Inter-frame feature point mismatches can lead to tracking failure, impacting the accuracy of the mobile robot's self-localization and mapping. This paper proposes a method for removing mismatches of image features in dynamic scenes in visual SLAM. First, the Grid-based Motion Statistics (GMS) method was introduced for fast coarse screening of mismatched image features. Second, an Adaptive Error Threshold RANSAC (ATRANSAC) method, determined by the internal matching rate, was proposed to improve the accuracy of removing mismatched image features in dynamic and static scenes. Third, the GMS-ATRANSAC method was tested for removing mismatched image features, and experimental results showed that GMS-ATRANSAC can remove mismatches of image features on moving objects. It achieved an average error reduction of 29.4% and 32.9% compared to RANSAC and GMS-RANSAC, with a corresponding reduction in error variance of 63.9% and 58.0%, respectively. The processing time was reduced by 78.3% and 38%, respectively. Finally, the effectiveness of inter-frame feature mismatch removal in the initialization thread of ORB-SLAM2 and the tracking thread of ORB-SLAM3 was verified for the proposed algorithm.

miR-141-3p Regulates the Proliferation and Apoptosis of Endometrial-Myometrial Interface Smooth Muscle Cells in Adenomyosis Via JAK2/STAT3 Pathway.

Adenomyosis (ADS) is a common benign gynecological disease. Abnormal proliferation at the endometrial-myometrial interface (EMI) plays a crucial role in the occurrence and progression of ADS. miR-141-3p is associated with cell proliferation and apoptosis. However, the specific mechanism of miR-141-3p in the etiology of ADS is still unknown. In this study, we explored the effects of miR-141-3p on the proliferation and apoptosis of ADS EMI smooth muscle cells (SMCs). We collected EMI tissues for the primary culture of SMCs from 25 patients diagnosed with ADS and 20 without ADS. Real-time quantitative polymerase chain reaction and western blot were used to measure the mRNA and protein expression levels of miR-141-3p, JAK2, STAT3, phospho-JAK2, and phospho-STAT3 in ADS EMI SMCs. The cell counting kit 8 assay and flow cytometry analysis were used to evaluate the proliferation and apoptosis of EMI SMCs. The miR-141-3p mimic/inhibitor was used to increase or decrease the expression level of miR-141-3p. We added WP1066 to block the phosphorylation of JAK2/STAT3 pathway components. The miR-141-3p levels were decreased, while JAK2 and STAT3 levels were increased in ADS EMI SMCs. miR-141-3p overexpression significantly inhibited the proliferation and enhanced the apoptosis of EMI SMCs, whereas a decrease in miR-141-3p expression level was connected to the opposite results. Meanwhile, inactivated JAK2/STAT3 pathway decreased proliferation and enhanced apoptosis of EMI SMCs after WP1066 treatment. Furthermore, rescue experiments confirmed that the JAK2/STAT3 pathway was the downstream pathway of miR-141-3p and reduced the effect of miR-141-3p on the proliferation and apoptosis of EMI SMCs. These results demonstrate that miR-141-3p regulates the proliferation and apoptosis of ADS EMI SMCs by modulating the JAK2/STAT3 pathway.

The role of the junctional zone in the management of adenomyosis with infertility.

The junctional zone (JZ) is an important structure in the myometrium that maintains uterine fertility. Changes in the junctional zone are closely related to infertility and adenomyosis (ADS). As an increasing number of young women are affected by ADS, the disease is no longer considered typical of women over 40. With these changes, an increasing number of patients refuse hysterectomy and desire fertility preservation treatment. At the same time, ADS is a crucial factor causing female infertility. Therefore, the treatment of ADS-related infertility and preservation of reproductive function is one of the other major challenges facing clinicians. For these young patients, preserving fertility and even promoting reproduction has become a new challenge. Therefore, we searched and summarized these studies on PubMed and Google Scholar using keywords such as "adenomyosis", "junctional zone", and "infertility" to explore infertility causes, diagnosis, and treatment of ADS patients who wish to preserve their uterus or fertility and become pregnant, focusing on the junctional zone, to obtain a full appreciation of the new perspective on this disease.

Low-intensity pulsed ultrasound in obstetrics and gynecology: advances in clinical application and research progress.

In the past decade, research on ultrasound therapy in obstetrics and gynecology has rapidly developed. Currently, high-intensity ultrasound has been widely used in clinical practice, while low-intensity ultrasound has gradually emerged as a new trend of transitioning from pre-clinical research to clinical applications. Low-intensity pulsed ultrasound (LIPUS), characterized by a non-invasive low-intensity pulse wave stimulation method, employs its non-thermal effects to achieve safe, economical, and convenient therapeutic outcomes. LIPUS converts into biochemical signals within cells through pathways such as cavitation, acoustic flow, and mechanical stimulation, regulating molecular biological mechanisms and exerting various biological effects. The molecular biology mechanisms underlying the application of LIPUS in obstetrics and gynecology mainly include signaling pathways, key gene expression, angiogenesis, inflammation inhibition, and stem cell differentiation. LIPUS plays a positive role in promoting soft tissue regeneration, bone regeneration, nerve regulation, and changes in cell membrane permeability. LIPUS can improve the treatment benefit of premature ovarian failure, pelvic floor dysfunction, nerve damage caused by intrauterine growth restriction, ovariectomized osteoporosis, and incomplete uterine involution through the above biological effects, and it also has application value in the adjuvant treatment of malignant tumors such as ovarian cancer and cervical cancer. This study outlines the biological mechanisms and applications of LIPUS in treating various obstetric and gynecologic diseases, aiming to promote its precise application and provide a theoretical basis for its use in the field.

Reproductive outcomes and risk factors of women with septate uterus after hysteroscopic metroplasty.

Background: Hysteroscopic metroplasty of the uterine septum has been the standard treatment strategy to improve reproductive outcomes, but there are still controversies about the appropriateness of metroplasty. In addition, there have been few studies of the factors related to reproductive outcomes of women after surgery. The study aimed to evaluate the reproductive outcomes and the associated risk factors that influence reproductive outcomes after hysteroscopic metroplasty of women with septate uterus and the desire to conceive. Methods: This study was an observational study. Cases were screened by searching electronic patient files, and demographic factors were collected. We conducted telephone follow-ups to collect the postoperative reproductive outcomes. The primary outcome of this study was live birth, and secondary outcomes were ongoing pregnancy, clinical pregnancy, early miscarriage, and preterm birth. Demographic variables included patients' age, body mass index (BMI), the type of septum, infertility and miscarriage history, and complications including intrauterine adhesions, endometrial polyps, endometriosis, and adenomyosis were collected to perform univariate and multivariate analyses to predict the risk factors of reproductive outcomes after surgery treatment. Results: In total, 348 women were evaluated and followed up. There were 95 cases (27.3%, 95/348) with combined infertility, 195 cases (56.0%, 195/348) with miscarriage history, and cases combined with intrauterine adhesions, endometrial polyps, endometriosis, and adenomyosis were 107 (30.7%, 107/348), 53 (15.2%, 53/348), 28 (8.0%, 28/348), and 5 (1.4%), respectively. Following surgery, the live birth rate and clinical pregnancy rate were significantly higher than prior to surgery (84.6% vs 3.7%, p= 0.000; and 78.2% vs 69.5%, p= 0.01, respectively), early miscarriage rate and preterm delivery rate were significantly lower (8.8% vs 80.6%, p= 0.000; and 7.0% vs 66.7%, p=0.000, respectively). After adjusting for body mass index, miscarriage history, and complications, multivariable logistic regression analysis revealed age ≥ 35 years and primary infertility as independent factors that affected postoperative clinical pregnancy (OR 4.025, 95% CI 2.063-7.851, p= 0.000; and OR 3.603, 95% CI 1.903-6.820, p= 0.000; respectively) and ongoing pregnancy (OR 3.420, 95% CI 1.812-6.455, p= 0.000; and OR 2.586, 95% CI 1.419-4.712, p= 0.002; respectively). Conclusions: Hysteroscopic metroplasty could lead to improved reproductive outcomes of women with septate uterus. Both age and primary infertility were independent factors for postoperative reproductive outcomes. Trial registration: Chi ECRCT20210343.

An XGBoost predictive model of ongoing pregnancy in patients following hysteroscopic adhesiolysis.

RESEARCH QUESTION: What are the factors influencing the fertility of patients with intrauterine adhesions (IUA) after hysteroscopic adhesiolysis and which assessment system is more efficient in predicting post-operative ongoing pregnancy? DESIGN: The clinical information of 369 individuals diagnosed with and treated for IUA were obtained from the Multicentre Prospective Clinical Database for the Construction of Predictive Models on Risk of Intrauterine Adhesion (NCT05381376) and randomly divided into the training and validation cohorts. A univariate analysis was performed to identify relevant clinical indicators, followed by a least absolute shrinkage and selection operator (LASSO) regression for regularization and SHapley Additive exPlanation (SHAP) for extreme gradient boosting (XGBoost) predictive model visualization. Finally, receiver operating characteristic (ROC) curves were constructed to assess the model's efficiency. RESULTS: Univariate analysis and LASSO regression demonstrated that 12 clinical indicators were significantly associated with post-operative ongoing pregnancy in IUA patients. SHAP visualization indicated that post-operative Fallopian tube ostia, blood supply, uterine cavity shape and age had the highest significance. The area under the ROC curve (AUC) of the XGBoost model in the training and validation cohorts was 0.987 (95% CI 0.979-0.996) and 0.985 (95% CI 0.967-1), respectively. These values were significantly higher than those of the American Fertility Society (AFS) classification, the Chinese Society for Gynecological Endoscopy (CSGE) classification and endometrial thickness (all P < 0.001). CONCLUSIONS: The XGBoost model had higher accuracy in predicting post-operative reproductive outcomes in IUA patients. Clinically, the model may be useful for managing and categorizing IUA and determining optimal action to aid in pregnancy.

Endometrial microbiota in women with and without adenomyosis: A pilot study.

Introduction: The endometrial microbiota plays an essential role in the health of the female reproductive system. However, the interactions between the microbes in the endometrium and their effects on adenomyosis remain obscure. Materials and methods: We profile endometrial samples from 38 women with (n=21) or without (n=17) adenomyosis to characterize the composition of the microbial community and its potential function in adenomyosis using 5R 16S rRNA gene sequencing. Results: The microbiota profiles of patients with adenomyosis were different from the control group without adenomyosis. Furthermore, analysis identified Lactobacillus zeae, Burkholderia cepacia, Weissella confusa, Prevotella copri, and Citrobacter freundii as potential biomarkers for adenomyosis. In addition, Citrobacter freundii, Prevotella copri, and Burkholderia cepacia had the most significant diagnostic value for adenomyosis. PICRUSt results identified 30 differentially regulated pathways between the two groups of patients. In particular, we found that protein export, glycolysis/gluconeogenesis, alanine, aspartate, and glutamate metabolism were upregulated in adenomyosis. Our results clarify the relationship between the endometrial microbiota and adenomyosis. Discussion: The endometrial microbiota of adenomyosis exhibits a unique structure and Citrobacter freundii, Prevotella copri, and Burkholderia cepacia were identified as potential pathogenic microorganisms associated with adenomyosis. Our findings suggest that changes in the endometrial microbiota of patients with adenomyosis are of potential value for determining the occurrence, progression, early of diagnosis, and treatment oadenomyosis.

Pharmacokinetics, mass balance, and metabolism of [14C]TPN171, a novel PDE5 inhibitor, in humans for the treatment of pulmonary arterial hypertension.

TPN171 is a novel phosphodiesterase-5 (PDE5) inhibitor used to treat pulmonary arterial hypertension (PAH) and erectile dysfunction (ED), which currently is undergoing phase II clinical trials in China. In this single-center, single-dose, nonrandomized, and open design study, radiolabeled [14C]TPN171 was used to investigate the metabolic mechanism, pharmacokinetic characteristics, and clearance pathways of TPN171 in 6 healthy Chinese male volunteers. Each volunteer was administered a single oral suspension of 10 mg (100 µCi) of [14C]TPN171. We found that TPN171 was absorbed rapidly in humans with a peak time (Tmax) of 0.667 h and a half-life (t1/2) of approximately 9.89 h in plasma. Excretion of radiopharmaceutical-related components was collected 216 h after administration, accounting for 95.21% of the dose (46.61% in urine and 48.60% in feces). TPN171 underwent extensive metabolism in humans. Twenty-two metabolites were detected in human plasma, urine, and feces using a radioactive detector combined with a high-resolution mass spectrometer. According to radiochromatograms, a glucuronide metabolite of O-dealkylated TPN171 exceeded 10% of the total drug-related components in human plasma. However, according to the Food and Drug Administration (FDA) guidelines, no further tests are needed to evaluate the safety of this metabolite because it is a phase II metabolite, but the compound is still worthy of attention. The main metabolic biotransformation of TPN171 was mono-oxidation (hydroxylation and N-oxidation), dehydrogenation, N-dealkylation, O-dealkylation, amide hydrolysis, glucuronidation, and acetylation. Cytochrome P450 3A4 (CYP3A4) mainly catalyzed the formation of metabolites, and CYP2E1 and CYP2D6 were involved in the oxidative metabolism of TPN171 to a lesser extent. According to the incubation data, M1 was mainly metabolized to M1G by UDP-glucuronosyltransferase 1A9 (UGT1A9), followed by UGT1A7 and UGT1A10.

Umbilical cord mesenchymal stem cell-derived exosomes reverse endometrial fibrosis by the miR-145-5p/ZEB2 axis in intrauterine adhesions.

RESEARCH QUESTION: What is the specific mechanism of umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-exos) in regulating endometrial repair and regeneration? DESIGN: In this study, UCMSC-exos were harvested by differential ultracentrifugation from umbilical cord mesenchymal stem cell culture supernatant and identified with western blotting, transmission electron microscopy and nanoparticle tracking analysis. Transforming growth factor-ß1 (TGFß1) at different concentrations was used to construct the intrauterine adhesions cell model. The fibrotic markers were assessed by quantitative reverse transcription-polymerase chain reaction and western blotting. The effects of miR-145-5p over-expression on endometrial fibrosis were assessed. Dual luciferase assay was performed to verify the relationship between miR-145-5p and zinc finger E-box binding homeobox 2 (ZEB2). RESULTS: The isolated UCMSC-exos had a typical cup-shaped morphology, expressed the specific exosomal markers Alix, CD63 and TSG101, and were approximately 50-150 nm in diameter. TGFß1 at 10 ng/ml significantly promoted endometrial fibrosis, which was reversed by 20 µg/ml UCMSC-exos. Exosomal miR-145-5p ameliorated TGFß1-induced endometrial fibrosis. ZEB2 was inversely regulated by exosomal miR-145-5p as a direct target. CONCLUSIONS: UCMSC-exos might reverse endometrial stromal cell fibrosis by regulating the miR-145-5p/ZEB2 axis, representing a potential novel strategy to promote endometrial repair.

Customized synthesis of phosphoprotein bearing phosphoserine or its nonhydrolyzable analog.

Studies on the mechanism of protein phosphorylation and therapeutic interventions of its related molecular processes are limited by the difficulty in the production of purpose-built phosphoproteins harboring site-specific phosphorylated amino acids or their nonhydrolyzable analogs. Here we address this limitation by customizing the cell-free protein synthesis (CFPS) machinery via chassis strain selection and orthogonal translation system (OTS) reconfiguration screening. The suited chassis strains and reconfigured OTS combinations with high orthogonality were consequently picked out for individualized phosphoprotein synthesis. Specifically, we synthesized the sfGFP protein and MEK1 protein with site-specific phosphoserine (O-pSer) or its nonhydrolyzable analog, 2-amino-4-phosphonobutyric acid (C-pSer). This study successfully realized building cell-free systems for site-specific incorporation of phosphonate mimics into the target protein. Our work lays the foundation for developing a highly expansible CFPS platform and the streamlined production of user-defined phosphoproteins, which can facilitate research on the physiological mechanism and potential interference tools toward protein phosphorylation.

Genetically Encoded Phosphine Ligand for Metalloprotein Design.

Phosphine ligands are the most important class of ligands for cross-coupling reactions due to their unique electronic and steric properties. However, metalloproteins generally rely on nitrogen, sulfur, or oxygen ligands. Here, we report the genetic incorporation of P3BF, which contains a biocompatible borane-protected phosphine, into proteins. This step is followed by a straightforward one-pot strategy to perform deboronation and palladium coordination in aqueous and aerobic conditions. The genetically encoded phosphine ligand P3BF should significantly expand our ability to design functional metalloproteins.

Efficacy of autologous platelet-rich plasma in preventing adhesion reformation following hysteroscopic adhesiolysis: a randomized controlled trial.

RESEARCH QUESTION: What is the efficacy of platelet-rich plasma (PRP) in reducing adhesion reformation in women with moderate to severe intrauterine adhesions (IUA)? DESIGN: In this randomized controlled trial, women with moderate-to-severe IUA were recruited between November 2019 and June 2021 from a university hospital and randomized into the PRP or control group. The PRP group was treated using an intrauterine-suitable balloon combined with PRP infusion following hysteroscopic adhesiolysis, whereas the control group received only the former intervention. The reductions in adhesion scores from before to after surgery and the adhesion reformation rate were analysed. RESULTS: A total of 123 participants successfully completed the study (PRP group, 63; control group, 60). Age, pregnancy history, menstrual score and American Fertility Society score before surgery were not significantly different between the two groups. At the second-look hysteroscopy, the PRP group had a significantly greater reduction in adhesion score than the control group (7 versus 6, respectively; P = 0.027). The postoperative adhesion reformation rates in the PRP group and the control group were 20.6% and 30.0%, respectively (risk ratio 0.69, 95% confidence interval 0.27-1.38, P = 0.232; number needed to treat 10.6). CONCLUSIONS: Intrauterine PRP infusion seems to be beneficial in reducing postoperative adhesion reformation following hysteroscopic adhesiolysis.

Hysteroscopy Combined with Laser Vaporesection for Endometrial Polyps.

OBJECTIVE: To compare the safety and efficiency of hysteroscopic laser vaporesection and hysteroscopic resection in the treatment of endometrial polyps.Methods: The literatures in databases were searched comprehensively, the literatures that met the inclusion criteria were screened out and the data were extracted. The data were combined with Stata12.0 statistical software. RESULTS: 4 literatures were included with a total sample size of 334. Meta-analysis showed that intraoperative blood loss in laser group was less than that in electrosurgical group [-3.043, 95% CI (-4.09, -2.00), P < 0.001]. Length of stay in the laser group was shorter than that in the electrotomy group [-1.013, 95% CI (-1.37, -0.65), P < 0.001]. The recurrence rate [0.275, 95%CI (0.135,0.563), P < 0.001] and complication rate [0.148, 95%CI (0.07,0.32), P < 0.001] in the laser group were lower than those in the electrotomy group. There was no significant difference in operative time between hysteroscopy combined with 2 µm laser and hysteroscopic electrotomy for endometrial polyps [-0.38, 95% CI (-1.34, 0.58), P = 0.441 > 0.05]. CONCLUSION: Hysteroscopic 2 µm laser vaporesection for the treatment of endometrial polyps has better safety and clinical efficacy. Compared with hysteroscopic electroresection, hysteroscopic laser vaporesection in the treatment of endometrial polyps may be safer and more effective. Given the potential limitations, we need larger, well-designed randomized controlled trials to verify our findings.

RNA-seq reveals co-dysregulated circular RNAs in the adenomyosis eutopic endometrium and endometrial-myometrial interface.

BACKGROUND: Uterine adenomyosis is associated with chronic pelvic pain, abnormal uterine bleeding, and infertility. The pathogenesis of adenomyosis is still unclear. Circular RNAs (circRNAs) have been implicated in several benign diseases and malignant tumors. We aimed to explore the co-dysregulated circular RNA profile in the eutopic endometrium and endometrial-myometrial interface (EMI) of adenomyosis. METHODS: Total RNA was extracted from the eutopic endometrium and EMI of 5 patients with adenomyosis and 3 patients without adenomyosis. Next-generation sequencing was performed to identify the circRNA expression profile of the two tissue types. Bioinformatics analysis was performed to predict circRNA-binding miRNAs and miRNA-binding mRNAs and construct ceRNA networks, and functional enrichment analysis was performed to predict the biological functions of circRNAs. RESULTS: Among the adenomyosis patients, 760 circRNAs were significantly upregulated and 119 circRNAs were significantly downregulated in the EMI of adenomyosis, while 47 circRNAs were significantly upregulated and 17 circRNAs were significantly downregulated in the eutopic endometrium of adenomyosis. We identified hsa_circ_0002144 and hsa_circ_0005806 as co-upregulated and hsa_circ_0079536 and hsa_circ_0024766 as co-downregulated in the eutopic endometrium and EMI. Bioinformatics analysis was performed to construct a ceRNA network of codifferentially expressed circRNAs. The MAPK signaling pathway is the most important signaling pathway involved in the function of the ceRNA network. CONCLUSIONS: Co-dysregulated circRNAs were present in the eutopic endometrium and EMI of adenomyosis. MiRNA binding sites were observed for all of these circRNAs and found to regulate gene expression. Co-dysregulated circRNAs may induce the eutopic endometrial invagination process through the MAPK signaling pathway and promote the progression of adenomyosis.

The Comprehensive Analysis of Interferon-Related Prognostic Signature with regard to Immune Features in Ovarian Cancer.

Interferon plays an important role in immune response of ovarian cancer. However, the expression pattern of interferon in ovarian cancer remains unclear. This study is aimed at exploring the expression profile of interferon-relate genes and constructing an interferon-based prognostic signature in ovarian cancer. The ovarian cancer samples collected from TCGA database were viewed as the training set, and ovarian cancer samples collected from GEO datasets were used as the independent validation sets. Univariate Cox regression analysis and multivariate Cox regression analysis were used to construct interferon-related signature, which worked as independent prognostic factor. Bioinformatics based on David software, GSEA, and R software were used to investigate the relationship between immune status and the signature in ovarian cancer. The signature showed close correlation with the status for ovarian cancer immune microenvironment, which might provide the possibility for clinical targeted therapy.

Intrinsically Disordered Protein Condensate-Modified Surface for Mitigation of Biofouling and Foreign Body Response.

Mitigation of biofouling and the host's foreign body response (FBR) is a critical challenge with biomedical implants. The surface coating with various anti-fouling materials provides a solution to overcome it, but limited options in clinic and their potential immunogenicity drive the development of more alternative coating materials. Herein, inspired by liquid-liquid phase separation of intrinsically disordered proteins (IDPs) to form separated condensates in physiological conditions, we develop a new type of low-fouling biomaterial based on flexible IDP of FUS protein containing rich hydrophilic residues. A chemical structure-defined FUS IDP sequence tagged with a tetra-cysteine motif (IDPFUS) was engineered and applied for covalent immobilization on various surfaces to form a uniform layer of protein tangles, which boosted strong hydration on surfaces, as revealed by molecular dynamics simulation. The IDPFUS-coated surfaces displayed excellent performance in resisting adsorption of various proteins and adhesion of different cells, platelets, and bacteria. Moreover, the IDPFUS-coated implants largely mitigated the host's FBR compared with bare implants and particularly outperformed PEG-coated implants in reducing collagen encapsulation. Thus, this novel low-fouling and anti-FBR strategy provides a potential surface coating material for biomedical implants, which will also shed light on exploring similar applications of other IDP proteins.