Abstract Bougainvillea is a popular ornamental plant. Although Bougainvillea is abundant in germplasm resources, cultivars and flower colors, there is no rare blue colour varieties, due to the absence of delphinidin-based anthocyanins. This study analyzed the Bougainvillea leaf and bract transcriptome to select hosts of genetic transformation that would be suitable for the accumulation of delphinidin. A total of 36 gigabyte (GB) of raw data was obtained by transcriptome sequencing, with 4,058 significantly differentially expressed genes, including 1,854 upregulated and 2,204 downregulated genes. Annotation of these genes was performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. Through annotation, two CHS genes, one F3H gene, one DFR gene, and one F3'H gene involved in the delphinidin biosynthesis pathway were identified. The expression levels of these genes and total flavonoid content in the bracts of six Bougainvillea varieties were examined through quantitative real-time PCR and spectrophotometry, respectively. Through the comprehensive evaluation based on membership function method, the suitable host order for a blue-hued Bougainvillea transgene is Singapore White>Elizabeth Angus>Ratana Yellow>China Beauty>Orange King>Brilliant Variegata. Thus, Singapore White variety was the most appropriate transgene host for blue-hued Bougainvillea. The results of this study provide a reference for the directed breeding of blue-hued Bougainvillea. plant resources colors delphinidinbased anthocyanins 3 GB (GB sequencing 4058 4 058 4,05 1854 1 854 1,85 2204 2 204 2,20 databases annotation FH F H F3 identified realtime real time spectrophotometry respectively method bluehued hued WhiteElizabeth Elizabeth AngusRatana Angus Ratana YellowChina Yellow China BeautyOrange Beauty Orange KingBrilliant King Brilliant Variegata Thus 405 05 4,0 185 85 1,8 220 20 2,2 40 0 4, 18 8 1, 22 2,

Ulcerative colitis (UC) is a difficult intestinal disease characterized by inflammation, and its mechanism is complex and diverse. Angiopoietin-like protein 2 (ANGPT2) plays an important regulatory role in inflammatory diseases. However, the role of ANGPT2 in UC has not been reported so far. After exploring the expression level of ANGPT2 in serum of UC patients, the reaction mechanism of ANGPT2 was investigated in dextran sodium sulfate (DSS)-induced UC mice. After ANGPT2 expression was suppressed, the clinical symptoms and pathological changes of UC mice were detected. Colonic infiltration, oxidative stress, and colonic mucosal barrier in UC mice were evaluated utilizing immunohistochemistry, immunofluorescence, and related kits. Finally, western blot was applied for the estimation of mTOR signaling pathway and NLRP3 inflammasome-related proteins. ANGPT2 silencing improved clinical symptoms and pathological changes, alleviated colonic inflammatory infiltration and oxidative stress, and maintained the colonic mucosal barrier in DSS-induced UC mice. The regulatory effect of ANGPT2 on UC disease might occur by regulating the mTOR signaling pathway and thus affecting autophagy-mediated NLRP3 inflammasome inactivation. ANGPT2 silencing alleviated UC by regulating autophagy-mediated NLRP3 inflammasome inactivation via the mTOR signaling pathway. (UC inflammation diverse Angiopoietinlike Angiopoietin like ANGPT (ANGPT2 diseases However far patients DSSinduced DSS induced suppressed detected stress immunohistochemistry immunofluorescence kits Finally NLRP inflammasomerelated proteins autophagymediated autophagy mediated (ANGPT

ABSTRACT Introduction: This study aimed to investigate the predictive value of the vasoactive-inotropic score (VIS) at different time points for postoperative prolonged mechanical ventilation (PMV) in adult congenital heart disease patients undergoing surgical treatment combined with coronary artery bypass grafting. Methods: Patients were divided into two groups that developed PMV or not. The propensity score matching method was applied to reduce the effects of confounding factors between the two groups. VIS at different time points (VIS at the end of surgery, VIS6h, VIS12h, and VIS12h max) after surgery were recorded and calculated. The value of VIS in predicting PMV was analyzed by the receiver operating characteristic (ROC) curve, and multivariate logistic regression was used to analyze independent risk factors. Results: Among 250 patients, 52 were in the PMV group, and 198 were in the non-PMV group. PMV rate was 20.8%. After propensity score matching, 94 patients were matched in pairs. At each time point, the area under the ROC curve predicted by VIS for PMV was > 0.500, among which VIS at the end of surgery was the largest (0.805). The optimal cutoff point for VIS of 6.5 could predict PMV with 78.7% sensitivity and 72.3% specificity. VIS at the end of surgery was an independent risk factor for PMV (odds ratio=1.301, 95% confidence interval 1.091~1.551, P<0.01). Conclusion: VIS at the end of surgery is an independent predictor for PMV in patients with adult congenital heart disease surgical treatment combined with coronary artery bypass grafting. Introduction vasoactiveinotropic vasoactive inotropic (PMV grafting Methods not VIS6h VISh h max calculated (ROC Results 25 5 group 19 nonPMV non 208 20 8 20.8% 9 pairs 0500 0 500 0.500 0.805. 0805 0.805 . 805 (0.805) 65 6 6. 787 78 7 78.7 723 72 3 72.3 specificity odds ratio1301 ratio 1 301 ratio=1.301 95 10911551 091 551 1.091~1.551 P<0.01. P001 P P<0.01 01 P<0.01) Conclusion 2 20.8 050 50 0.50 080 0.80 80 (0.805 78. 72. ratio130 30 ratio=1.30 1091155 09 55 1.091~1.55 P00 P<0.0 20. 05 0.5 08 0.8 (0.80 ratio13 ratio=1.3 109115 1.091~1.5 P0 P<0. 0. (0.8 ratio1 ratio=1. 10911 1.091~1. P<0 (0. ratio=1 1091 1.091~1 P< (0 ratio= 109 1.091~ ( 10 1.091 1.09 1.0 1.

Abstract Objective Kawasaki Disease (KD) may mimic Parapharyngeal (PPI) and Retropharyngeal Infections (RPI), leading to misdiagnosis as Deep Neck Infections (DNIs). The treatment plans for the two diseases are different, and delayed treatment can lead to serious complications. Therefore, prompt diagnosis and management are necessary. This study was performed to evaluate the clinical features of KD mimicking DNIs and explore the treatment options. Methods Children with cellulitis or abscess in parapharyngeal or retropharyngeal space in neck CT were included in this study. The medical records of enrolled children were retrospectively reviewed. Results In total, 56 children were diagnosed with PPI or/and RPI. Twenty-two (39.3%) participants were eventually diagnosed with KD, and 34 (60.7%) were diagnosed with DNIs. Compared with the DNIs group, the KD group had a higher body temperature (p = 0.007), and higher levels of AST (p = 0.040), ALT (p = 0.027), and ESR (p = 0.030). Deep cervical cellulitis (p = 0.005) were more common in the KD group. However, deep neck abscess often occurred in the DNIs group (p = 0.002), with parapharyngeal abscess being the most common type of abscess (p = 0.004). The KD mimicking DNIs cases did not respond to antibiotic treatment, but symptoms significantly improved after the use of Immunoglobulin (IVIG) and aspirin. Conclusion Children with KD may exhibit retropharyngeal or parapharyngeal inflammation in the early stages. KD should be considered a differential diagnosis for children with DNIs, high fever, and no response to antibiotic therapy. Surgery in KD mimicking deep neck abscess requires caution. Level of Evidence I. (KD (PPI RPI, RPI , (RPI) . (DNIs) different complications Therefore necessary options reviewed total 5 orand Twentytwo Twenty 39.3% 393 39 3 (39.3% 60.7% 607 60 7 (60.7% p 0.007, 0007 0.007 0 007 0.007) 0.040, 0040 0.040 040 0.040) 0.027, 0027 0.027 027 0.027) 0.030. 0030 0.030 030 0.030) 0.005 0005 005 However 0.002, 0002 0.002 002 0.002) 0.004. 0004 0.004 004 0.004) IVIG (IVIG aspirin stages fever therapy caution I (RPI (DNIs 39.3 (39.3 60.7 6 (60.7 000 0.00 00 0.04 04 0.02 02 003 0.03 03 39. (39. 60. (60. 0.0 (39 (60 0. (3 (6 (

The clinical application of 5-fluorouracil (5-Fu), a potent chemotherapeutic agent, is often hindered by its well-documented cardiotoxic effects. Nevertheless, natural polyphenolic compounds like resveratrol (RES), known for their dual anti-tumor and cardioprotective properties, are potential adjunct therapeutic agents. In this investigation, we examined the combined utilization of RES and 5-Fu for the inhibition of gastric cancer using both in vitro and in vivo models, as well as their combined impact on cardiac cytotoxicity. Our study revealed that the co-administration of RES and 5-Fu effectively suppressed MFC cell viability, migration, and invasion, while also reducing tumor weight and volume. Mechanistically, the combined treatment prompted p53-mediated apoptosis and autophagy, leading to a considerable anti-tumor effect. Notably, RES mitigated the heightened oxidative stress induced by 5-Fu in cardiomyocytes, suppressed p53 and Bax expression, and elevated Bcl-2 levels. This favorable influence enhanced primary cardiomyocyte viability, decreased apoptosis and autophagy, and mitigated 5-Fu-induced cardiotoxicity. In summary, our findings suggested that RES holds promise as an adjunct therapy to enhance the efficacy of gastric cancer treatment in combination with 5-Fu, while simultaneously mitigating cardiotoxicity. 5fluorouracil fluorouracil 5 5Fu, 5Fu Fu , (5-Fu) agent welldocumented documented effects Nevertheless RES, (RES) antitumor anti properties agents investigation models cytotoxicity coadministration co administration viability migration invasion volume Mechanistically p53mediated pmediated mediated p autophagy effect Notably cardiomyocytes p5 expression Bcl2 Bcl 2 Bcl- levels 5Fuinduced Fuinduced cardiotoxicity summary Fu, (5-Fu (RES

ABSTRACT Purpose: To investigate the impact of the Chinese medicine compound Ento-PB on oxazolone (OXZ)-induced ulcerative colitis (UC) in rats. Methods: UC rats induced by OXZ were treated with Ento-PB. The damage to the colon was assessed using several measures, including the disease activity index (DAI), colon length, colon weight/length ratio, colonic mucosal damage index, and histological score. The levels of interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-13 (IL-13), epidermal growth factor (EGF), inducible nitric oxide synthase, and total nitric oxide synthase (tNOS) in rat serum, as well as the levels of tumor necrosis factor-α (TNF-α) and myeloperoxidase (MPO) in rat colon tissue, were determined using enzyme-linked immunosorbent assay and conventional kits. Results: After being treated with Ento-PB, the DAI score and macroscopic lesion score of OXZ-induced UC rats were significantly reduced. Ento-PB prevented the shortening of rat colons, reduced the ratio of colon weight to length, and improved colon tissue lesions. Meanwhile, Ento-PB could significantly inhibit the activities of proinflammatory cytokines TNF-α, IL-13, and MPO, as well as tNOS and iNOS, while upregulating the expression of anti-inflammatory cytokines IL-4 and IL-10. Moreover, a significant increase in the expression level of EGF was observed in UC rats treated with Ento-PB, indicating that Ento-PB could enhance the repair of damaged intestinal epithelial tissue. Conclusions: Ento-PB demonstrates significant anti-UC activities in OXZ-induced UC rats by regulating the expression levels of inflammatory factors and promoting the repair of colon tissue. This study provides scientific evidence to support the further development of Ento-PB. Purpose EntoPB Ento PB OXZinduced (UC Methods EntoPB. PB. measures DAI, , (DAI) length weightlength interleukin4 interleukin 4 interleukin- IL4, IL4 IL (IL-4) interleukin10 10 interleukin-1 IL10, IL10 (IL-10) interleukin13 13 IL13, IL13 (IL-13) EGF, (EGF) (tNOS serum factorα α TNFα TNF (TNF-α MPO (MPO enzymelinked enzyme linked kits Results EntoPB, PB, colons lesions Meanwhile TNFα, α, TNF-α 13, IL-13 iNOS antiinflammatory anti IL- IL10. 10. IL-10 Moreover Conclusions antiUC (DAI (IL-4 interleukin1 1 IL1 (IL-10 (IL-13 (EGF IL-1 (IL- (IL-1 (IL

Abstract Backgroud Homocitrulline (Hcit), is involved in the pathological processes of some diseases. However, the role and function of Hcit (CBL) in human skin remains largely obscure. Objective To investigate the correlation of the level of Hcit in seborrheic keratosis, skin aging, and its clinical significance. Methods Immunohistochemistry was used to analyze the level of Hcit in skin lesions of seborrheic keratosis (SK), unaffected skin (distant 0.5 centimeters from SK lesion), and normal skin of healthy subjects in the control group. ELISA test was used to detect the serum level of CBL in SK patients and healthy subjects of different ages. Results Hcit was mainly localized in the nucleus of epidermal cells. In healthy control skin, the expression of Hcit increased with age and showed a positive correlation with age (the correlation coefficient was 0.806, p = 0.0002). The expressional level of Hcit in SK lesions was higher than that in healthy control skin (Z = −3.703, p = 0.0002). The serum level of CBL in healthy subjects and in SK patients increased with age (the correlation coefficient were 0.5763, p = 0.0032; 0.682, p = 0.004. respectively). The serum level of CBL in SK patients was higher than that in healthy subjects (Z = −2.19, p = 0.030). Study limitations The small serum sample size in the study. Conclusion The high expressional level of Hcit is correlated with seborrheic keratosis and skin aging. HCit may be one of the potential biomarkers of skin aging. Hcit, , (Hcit) diseases However (CBL obscure aging significance SK, (SK) distant 05 0 5 0. lesion, lesion lesion) group ages cells 0806 806 0.806 0.0002. 00002 0.0002 . 0002 0.0002) Z 3703 3 703 −3.703 05763 5763 0.5763 0.0032 00032 0032 0682 682 0.682 0004 004 0.004 respectively. respectively respectively) 219 2 19 −2.19 0.030. 0030 0.030 030 0.030) study (Hcit (SK 080 80 0.80 0000 0.000 000 370 70 −3.70 0576 576 0.576 0.003 0003 003 068 68 0.68 00 0.00 21 1 −2.1 0.03 03 08 8 0.8 37 7 −3.7 057 57 0.57 06 6 0.6 0.0 −2. −3. −2 −3 −

ABSTRACT BACKGROUND: Primary thyroid tuberculosis (PTT) is an uncommon type of extrapulmonary tuberculosis, which is caused by Mycobacterium tuberculosis. It does not have specific clinical manifestations, and most cases are diagnosed through postoperative histopathological examination. OBJECTIVE: To evaluate the diagnostic pattern and management strategy among patients with primary thyroid tuberculosis. DESIGN AND SETTING: Retrospective study on patients with primary thyroid tuberculosis in the First Hospital of Jilin University (Changchun, China). METHODS: Between March 2015 and June 2020, nine cases of PTT were diagnosed and treated in the Department of Thyroid Surgery of the First Hospital of Jilin University. Age at diagnosis, primary symptoms, preoperative biopsy, operation method, pathological classification, acid-fast staining test, anti-TB therapy and prognosis were registered in order to explore the appropriate protocol for diagnosis and treatment of this disease. RESULTS: None of the patients was diagnosed with thyroid tuberculosis before surgery. All the patients underwent surgery. Granulomatous changes or caseous necrosis in thyroid tissue were found through postoperative histopathological evaluation. Polymerase chain reaction (PCR) results for Mycobacterium tuberculosis were positive in all patients. Most patients had a good prognosis after surgery and anti-tuberculosis drug therapy. CONCLUSION: PTT is a rare disease. It is important to improve the preoperative diagnosis. Preoperative diagnostic accuracy relies on increased awareness of the disease and appropriate use of preoperative diagnostic methods, such as PCR detection, fine-needle aspiration cytology, acid-fast bacillus culture, ultrasound and blood sedimentation. PCR detection of M. tuberculosis is recommended as the gold standard for diagnosis.

Abstract Our aim was to investigate molecular features of thalassemia for proper clinical consultation and prevention in Heyuan. In our research, a total of 25,437 positive screening subjects were further subjected to a genetic analysis of α-thalassemia (α-thal) and β-thalassemia (β-thal). The deletion of α-thal mutation was tested by Gap-PCR, while the non-deletion of α-thal and β-thal mutation were identified by the PCR-reverse dot blot (PCR-RDB) technique. Nested PCR detected Hkαα/-- SEA and Hkαα/αα. Among the 25,437 positive screening subjects, 44.09% (11216/25437) subjects were bearers of thalassemia variations, and 30.85% (7847/25437) subjects showed α-thal changes alone. Among the 23 genotypes with α-thal mutation alone, the three common genotypes were --SEA/αα(68.34%), -α3.7/αα(16.44%), and -α4.2/αα(6.38%). Of the 11.50% (2924/25437) subjects and 29 genotypes with β-thal mutation alone, the three common genotypes were βCD41-42/βN(36.22%), βIVS-II-654/βN(30.88%), and β-28/βN(13.47%). Additionally, of the 1.75% (445/25437) subjects and 55 genotypes showed both α- and β-thal mutations. We also identified 269 cases of Hb H and six patients of Hkαα. Furthermore, the common genotypes of α-thal and β-thal mutations were consistent with allele frequencies of mutations. Our study establishes molecular features of thalassemia among Hakka people in Heyuan. It will be useful for developing strategies to prevent thalassemia.

Abstract Background: Unsubstantiated concerns have been raised on the potential correlation between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and infertility, leading to vaccine hesitancy in reproductive-aged population. Herein, we aim to evaluate the impact of inactivated SARS-CoV-2 vaccination on embryo ploidy, which is a critical indicator for embryo quality and pregnancy chance. Methods: This was a retrospective cohort study of 133 patients who underwent preimplantation genetic testing for aneuploidy (PGT-A) cycles with next-generation sequencing technology from June 1st 2021 to March 17th 2022 at a tertiary-care medical center in China. Women fully vaccinated with two doses of Sinopharm or Sinovac inactivated vaccines (n = 66) were compared with unvaccinated women (n = 67). The primary outcome was the euploidy rate per cycle. Multivariate linear and logistic regression analyses were performed to adjust for potential confounders. Results: The euploidy rate was similar between vaccinated and unvaccinated groups (23.2 ± 24.6% vs. 22.6 ± 25.9%, P = 0.768), with an adjusted β of 0.01 (95% confidence interval [CI]: -0.08–0.10). After frozen-thawed single euploid blastocyst transfer, the two groups were also comparable in clinical pregnancy rate (75.0% vs. 60.0%, P = 0.289), with an adjusted odds ratio of 6.21 (95% CI: 0.76–50.88). No significant associations were observed between vaccination and cycle characteristics or other laboratory and pregnancy outcomes. Conclusions: Inactivated SARS-CoV-2 vaccination had no detrimental impact on embryo ploidy during in vitro fertilization treatment. Our finding provides further reassurance for vaccinated women who are planning to conceive. Future prospective cohort studies with larger datasets and longer follow-up are needed to confirm the conclusion.

Abstract The paper investigated the effects of Allicin on the changes of activities of PPARα and PPARγ signaling pathways, and the relations with the subsequent myocardial cell hypertrophy, apoptosis, myocardial interstitial remodeling, RAAS activation and heart failure. The heart obtained from the 1-day-old Wistar suckling rats was isolated and cultured in an ordinary medium. After adding AngII and AngII+ of different concentrations respectively, the conditions of cardiomyocyte hypertrophy, apoptosis and interstitial remodeling were observed. AngII activated the re-expression of β-MHC in cardiomyocytes, which increased the area of cardiomyocytes, indicating that myocardial hypertrophy had occurred, and the model of cardiomyocyte hypertrophy was successfully established. Compared with the control group, after being treated with different concentrations of Allicin for 24 h, the AngII-induced cardiomyocyte hypertrophy was significantly reversed, α-MHC expression increased, β-MHC expression decreased, and α/β-MHC ratio obviously increased. Allicin inhibited AngII-induced cardiomyocyte apoptosis, decreased Fas/FasL protein expression, increased Bcl-2 protein expression, and decreased Bax protein expression. The Bcl-2/Bax ratio increased significantly. PPARα and PPARγ signaling pathways are involved in the inhibition of cardiomyocyte hypertrophy. Allicin-activated PPARα and PPARγ pathways can reverse cardiomyocyte hypertrophy, inhibit cardiomyocyte apoptosis, and alter expressions of Bcl-2/Bax and Fas/Fas-L in apoptosis-related gene.

Abstract Objective This study aimed to explore the precise temporospatial distributions of bone morphogenetic protein (BMP) and Wnt signaling pathways during postnatal development of mammalian tooth roots after the termination of crown morphogenesis. Methodology A total of two transgenic mouse lines, BRE-LacZ mice and BAT-gal mice, were undertaken. The mice were sacrificed on every postnatal (PN) day from PN 3d up to PN 21d. Then, the first lower molars were extracted, and the dissected mandibles were stained with 5-bromo-4-chloro-3-indolyl-β-d-galactopyranoside (X-gal) and fixed. Serial sections at 10 µm were prepared after decalcification, dehydration, and embedding in paraffin. Results We observed BMP/Smads and Wnt/β-catenin signaling activities in the dental sac, dental pulp, and apical papilla with a certain degree of variation. The position of activation of the BMP/Smad signaling pathway was located more coronally in the early stage, which then gradually expanded as root elongation proceeded and was associated with blood vessels in the pulp and developing complex apical tissues in the later stage. However, Wnt/β-catenin signaling was highly concentrated in the mesenchyme below the cusps in the early stage, gradually expanded to regions around the root in the transition/root stage, and then disappeared entirely in the later stage. Conclusions These results further confirmed the participation of both BMP and Wnt canonical signaling pathways in tooth root development, as well as formed the basis for future studies on how precisely integrated signaling pathways regulate root morphogenesis and regeneration.

ABSTRACT Purpose: To make a further evaluation of perioperative outcomes between the robot-assisted radical prostatectomy (RARP) and open radical prostatectomy (ORP), we conducted a comparison and trend analysis by using the Nationwide Inpatient Sample (NIS) from 2009 to 2014. Materials and Methods: Adult prostate cancer patients with radical prostatectomy were abstracted from the NIS. RARP and ORP were identified according to the International Classification of Diseases, 9th Revision, Clinical Modification procedure codes. The perioperative outcomes included blood transfusion, intraoperative and postoperative complications, prolonged length of stay (pLOS), and in-hospital mortality. Propensity score matching method and multivariable logistic regression model were performed to adjust for the pre-defined covariates. The annual percent change (APC) was used to detect the change trend of rates for outcomes. Results: A total of 77.054 patients were included in our study. According to the results of propensity score matching analyses, RARP outperformed ORP in blood transfusion (1.96% vs. 9.40%), intraoperative complication (0.73% vs. 1.25%), overall postoperative complications (8.87% vs. 11.97%), and pLOS (13.39% vs. 36.70%). We also found that there was a significant decreasing tendency of incidence in blood transfusion (APC=-9.81), intraoperative complication (APC=-12.84), and miscellaneous surgical complications (APC=-14.09) for the RARP group. The results of multivariable analyses were almost consistent with those of propensity score matching analyses. Conclusions: The RARP approach has lower incidence rates of perioperative complications than the ORP approach, and there is a potential decreasing tendency of complication incidence rates for the RARP.

Macrophages play pivotal roles in host defense and immune homeostasis, which have two major functional polarization states, the classically activated M1 and the alternatively activated M2. Interleukin (IL)-17A is an immune modulator able to shape macrophage phenotypes. Wnt/β-catenin is a developmental signaling pathway that plays crucial roles in morphogenesis and tissue homeostasis, which has also been recently demonstrated playing roles in immune regulation. A growing amount of evidence suggests that both Wnt and IL-17A signaling are involved in macrophage polarization. However, their interaction in macrophage polarization remains elusive. The aim of present study was to explore impacts of Wnt/β-catenin on IL-17A-mediated macrophage M1/M2 polarization in murine monocyte/macrophage-like cell line RAW264.7. Results revealed that IL-17A activated Wnt/β-catenin signaling and induced macrophage M1 polarization, but inhibited M2 polarization. In contrast, the activation of Wnt/β-catenin signaling led to the inhibition of M1 macrophage polarization but the promotion of M2 polarization. Importantly, the activation of Wnt/β-catenin also showed abilities to inhibit the IL-17A-induced M1 macrophage polarization while diminishing the IL-17A-inhibited M2 polarization. Molecular analysis further uncovered that the JAK/STAT signaling pathway was involved in the interaction of Wnt/β-catenin and IL-17A in the modulation of macrophage polarization. These results suggested that the Wnt/β-catenin signaling modulated IL-17A-altered macrophage polarization in part by regulating the JAK/STAT signaling pathway. This study thus revealed a novel function of Wnt/β-catenin signaling in regulating IL-17A-altered macrophage polarization.

Although estrogen has crucial functions for endometrium growth, the specific dose and underlying molecular mechanism in intrauterine adhesion (IUA) remain unclear. In this study, we aimed to investigate the effects of estrogen on epithelial-mesenchymal transition (EMT) in normal and fibrotic endometrium, and the role of estrogen and Wnt/β-catenin signaling in the formation of endometrial fibrosis. CCK-8 and immunofluorescence assay were performed to access the proliferation of different concentrations of estrogen on normal human endometrial epithelial cells (hEECs). qRT-PCR and western blot assay were utilized to explore the effect of estrogen on EMT in normal and fibrotic endometrium, and main components of Wnt/β-catenin signaling pathway in vitro. Hematoxylin and eosin and Masson staining were used to evaluate the effect of estrogen on endometrial morphology and fibrosis in vivo. Our results indicated that the proliferation of normal hEECs was inhibited by estrogen at a concentration of 30 nM accompanied by upregulation of mesenchymal markers and downregulation of epithelial markers. Interestingly, in the model of transforming growth factor β1 (TGF-β1)-induced endometrial fibrosis, the same concentration of estrogen inhibited the process of EMT, which might be partially mediated by regulation of the Wnt/β-catenin pathway. In addition, relatively high doses of estrogen efficiently increased the number of endometrial glands and reduced the area of fibrosis as determined by the reduction of EMT in IUA animal models. Taken together, our results demonstrated that an appropriate concentration of estrogen may prevent the occurrence and development of IUA by inhibiting the TGF-β1-induced EMT and activating the Wnt/β-catenin pathway.