Regulating effects of low salt dry-curing pre-treatment on microbiota, biochemical changes and flavour precursors of grass carp (Ctenopharyngodon idella) fillets during storage at 4 °C.

Low salt dry-curing (LSD), as a healthier pre-treatment for the preservation of fishery products, is a potential technique substitute for excessively salty curing. The regulatory effects of 2 % and 3 % LSD on the quality evolution through an intrinsic correlation between microbiota succession and flavour precursors of refrigerated grass carp fillets were investigated in this study. The results showed that the LSD pre-treatment was effective in promoting proteolysis, free amino acid and fatty acid metabolism with the microbiota succession and quality evolution. Compared with unpre-treated samples, the 3 % LSD pre-treatment effectively extended the shelf life by 10 days within the acceptable quality attributes. Not only did the LSD pre-treatment lead to catalytic microbiota succession and inhibitive spoilage substance production but it also improved the flavour precursors, which are taste-active amino acids and polyunsaturated fatty acids (PUFAs). Moreover, considerable correlations between quality attributes, taste-active amino acids, PUFAs and microbiota were obtained.

The improvement of tyrosol bioavailability by encapsulation into liposomes using pH-driven method.

To improve the poor water solubility and oral bioavailability of tyrosol, novel tyrosol liposomes (Tyr-LPs) were prepared by pH-driven method. Fourier transform infrared (FTIR) absorption spectra and X-ray diffraction (XRD) analysis indicated that Tyr-LPs were successfully encapsulated and tyrosol was in an amorphous state in liposomes. When tyrosol content in Tyr-LP was 1.33 mg/ml and the Tyr:LP (mass ratio) = 1:2, favorable dispersibility of Tyr-LP was exhibited, with an instability index of 0.049 ± 0.004, PDI of 0.274 ± 0.003, and the EE of 94.8 ± 2.5 %. In vivo pharmacokinetic studies showed that after oral administration of tyrosol or Tyr-LP (Tyr:LP = 1:2), concentration-versus-time curve (AUC0-720mins) and maximum concentration (Cmax) values of Tyr-LP was respectively 1.5-fold (P < 0.01) and 2.25-fold (P < 0.01) higher than tyrosol, which indicated that the oral bioavailability of tyrosol was effectively improved in Tyr-LPs. Our study thereby provides theoretical support for the application of Tyr-LP for optimal delivery of tryosol.

Effects of steam explosion on raspberry leaf structure and the release of water-soluble nutrients and phenolics.

Raspberry leaves were subjected to steam explosion at 0.5 and 1.0 MPa for 60-120 s, aiming to disrupt their physical and chemical structure and, consequently, promote the release of phenolic compounds into the leaf aqueous infusion. Under optimal condition of 1.0 MPa for 60 s, steam explosion led to a notable 23 % increase in total phenolic content, a 29 % elevation in ABTS radical scavenging capacity, and a 13 % rise in DPPH radical scavenging capacity of the aqueous infusion. Utilizing UHPLC-Q-TOF-MS/MS and UHPLC-QE-MS/MS techniques, respectively, a total of 39 phenolic compounds were identified from raspberry leaves, and the changes in the contents of the most important 11 species were analyzed following steam explosion. Through correlation analysis and considering the content of each phenolic compound, it was inferred that the heightened antioxidant capacity of the aqueous infusion primarily stemmed from a substantial increase in the release of ellagic acid after steam explosion.

Non-alcoholic fatty liver disease associated with greater herpes zoster risk than alcoholic fatty liver disease.

BACKGROUND: Disease-related stress can trigger the occurrence of herpes zoster (HZ). Fatty liver disease (FLD) can have adverse effects on the human body and may induce stress in affected individuals. In this study, we investigated whether FLD is associated with an elevated risk of HZ. METHODS: For this study, we utilized data from the National Health Insurance Research Database, patients with FLD from 2000 to 2017 were observed (follow-up until 2018). Patients were considered to have FLD if they had at least two outpatient visits or at least one admission record with a diagnostic code of FLD. Patients with FLD were matched 1:1 by age, sex, comorbidities, and index year with control patients. Additionally, the FLD was further categorized into non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) groups. Multivariable Cox proportional hazards model was used to calculate the incidence rate and adjusted hazard ratio (aHR) of HZ for FLD and AFLD and for various age groups, sex and comorbidities. Cumulative incidence curve for HZ was plotted through the Kaplan-Meier method, and p-value was calculated using the log-rank test. RESULTS: After 1:1 propensity-score matching, each cohort comprised 62,418 patients. The FLD cohort was further divided into NAFLD and AFLD groups, which respectively comprised 55,709 and 6709 patients. The FLD cohort had a risk of HZ significantly higher than that of the control cohort (aHR = 1.06; p < 0.001). Additionally, the NAFLD group exhibited a significantly higher risk of HZ than did the AFLD group (aHR = 1.22; p < 0.001). Among patients without any comorbidities, those with FLD had a higher risk of HZ than did those without FLD (aHR = 1.14; p < 0.001). CONCLUSION: Patients with FLD are at an increased risk of HZ development. Additionally, NAFLD is associated with a higher risk of HZ than AFLD. Therefore, patients with NAFLD should be informed of their increased risk of HZ.

Highly Dispersed FeAg-MCM41 Catalyst for Medium-Temperature Hydrogen Sulfide Oxidation in Coke Oven Gas.

The traditional hydrolysis-cooling-adsorption process for coke oven gas (COG) desulfurization urgently needs to be improved because of its complex nature and high energy consumption. One promising alternative for replacing the last two steps is selective catalytic oxidation. However, most catalysts used in selective catalytic oxidation require a high temperature to achieve effective desulfurization. Herein, a robust 30Fe-MCM41 catalyst is developed for direct desulfurization at medium temperatures after hydrolysis. This catalyst exhibits excellent stability for over 300 h and a high breakthrough sulfur capacity (2327.6 mgS gcat-1). Introducing Ag into the 30Fe-MCM41 (30Fe5Ag-MCM41) catalyst further enhances the H2S removal efficiency and sulfur selectivity at 120 °C. Its outstanding performance can be attributed to the synergistic effect of Fe-Ag clusters. During H2S selective oxidation, Fe serves as the active site for H2S adsorption and dissociation, while Ag functions as the catalyst promoter, increasing Fe dispersion, reducing the oxidation capacity of the catalyst, improving the desorption capacity of sulfur, and facilitating the reaction between active oxygen species and [HS]. This process provides a potential route for enhancing COG desulfurization.

Impact of maternal body mass index on outcomes of singleton pregnancies after assisted reproductive technology: a 14-year analysis of the US Nationwide Inpatient Sample.

BACKGROUND: Obesity is increasing globally, which affects multiple human functions, including reproductive health. Many women with overweight and obesity of child-bearing years are treated with assisted reproductive technology (ART). However, the clinical impact of body mass index (BMI) on pregnancy outcomes after ART remains to be determined. Therefore, this population-based retrospective cohort study aimed to assess whether and how higher BMI affects singleton pregnancy outcomes. METHODS: This study used the large nationally representative database of the US National Inpatient Sample (NIS), extracting data of women with singleton pregnancies who had received ART from 2005 to 2018. Diagnostic codes of the International Classification of Diseases, Ninth and Tenth edition (ICD-9 and ICD-10) were used to identify females admitted to US hospitals with delivery-related discharge diagnoses or procedures and secondary diagnostic codes for ART, including in vitro fertilization. The included women were further categorized into three groups based on BMI values < 30, 30-39, and ≥ 40 kg/m2. Univariate and multivariable regression analysis were conducted to assess the associations between study variables and maternal and fetal outcomes. RESULTS: Data of totally 17,048 women were included in the analysis, which represented a population of 84,851 women in the US. Number of women in the three BMI groups were 15, 878 (BMI < 30 kg/m2), 653 (BMI 30-39 kg/m2), and 517 (BMI ≥ 40 kg/m2), respectively. The multivariable regression analysis revealed that, compared to BMI < 30 kg/m2, BMI 30-39 kg/m2 was significantly associated with increased odds for pre-eclampsia and eclampsia (adjusted OR = 1.76, 95% CI = 1.35, 2.29), gestational diabetes (adjusted OR = 2.25, 95% CI = 1.70, 2.98), and Cesarean delivery (adjusted OR = 1.36, 95% CI = 1.15, 1.60). Further, BMI ≥ 40 kg/m2 was associated with greater odds for pre-eclampsia and eclampsia (adjusted OR = 2.25, 95% CI = 1.73, 2.94), gestational diabetes (adjusted OR = 3.64, 95% CI = 2.80, 4.72), disseminated intravascular coagulation (DIC) (adjusted OR = 3.79, 95% CI = 1.47, 9.78), Cesarean delivery (adjusted OR = 1.85, 95% CI = 1.54, 2.23), and hospital stay ≥ 6 days (adjusted OR = 1.60, 95% CI = 1.19, 2.14). However, higher BMI was not significantly associated with greater risk of the fetal outcomes assessed. CONCLUSIONS: Among US pregnant women who received ART, having a higher BMI level independently increases the risk for adverse maternal outcomes such as pre-eclampsia and eclampsia, gestational diabetes, DIC, longer hospital stays, and higher rates of Cesarean delivery, while risk is not increased for fetal outcomes.

Poor Karnofsky performance status is not a contraindication for neurosurgical resection in patients with lung cancer brain metastases: a multicenter, retrospective PSM-IPTW cohort study.

BACKGOUND: Neurosurgical resection is a standard local treatment for lung cancer brain metastases (BMs). This study aims to investigate whether neurosurgical resection provides survival benefit in lung cancer BMs with poor KPS. MATERIALS AND METHODS: This multicenter retrospective study included 386 lung cancer BMs with pretreatment KPS ≤ 70 among a total of 1177 lung cancer BMs treated at three centers from August 2010 to July 2021. Data analysis was performed from July to September 2022. Inverse probability of treatment weighting (IPTW) and propensity scores matching (PSM) based on propensity scoring were used to minimize bias. The main outcome was overall survival (OS) after diagnosis of BMs. Risk factors of OS were estimated using Cox proportional hazards regression models. All Characteristics were included in the multivariate Cox regression. RESULTS: 386 patients with pretreatment KPS ≤ 70 were included (age mean [SD], 57.85 [10.36] years; KPS mean [SD], 60.91 [10.11]). Among them, 111 patients received neurosurgical resection, while 275 patients did not. Baseline characteristics were balanced between groups after IPTW or PSM. Neurosurgical resection was associated with significantly better prognosis in unadjusted multivariate COX analysis (hazard ratio [HR]: 0.68, 95% confidence interval [CI]: 0.51-0.91, P = 0.01), and PSM-adjusted multivariate COX analysis (HR: 0.61, 95%CI: 0.39-0.94, P = 0.03), IPTW-adjusted multivariate COX analysis (HR: 0.58, 95%CI: 0.40-0.84, P = 0.004). OS was significantly longer in neurosurgical resection group compared with non-surgical resection group according to unadjusted data (Median OS, surgery vs non-surgery, 14.7 vs 12.5 months, P = 0.01), PSM-adjusted data (median OS, 17.7 vs 12.3 months, P < 0.01) and IPTW-adjusted data (median OS, 17.7 vs 12.5 months, P < 0.01). CONCLUSIONS: Neurosurgical resection was associated with improved survival in patients with lung cancer BMs with poor KPS, suggesting that poor KPS is not a contraindication for neurosurgical resection in these patients.

Single-cell chromatin accessibility and transcriptome atlas of mouse embryos.

Cis-regulatory elements regulate gene expression and lineage specification. However, the potential regulation of cis-elements on mammalian embryogenesis remains largely unexplored. To address this question, we perform single-cell assay for transposase-accessible chromatin using sequencing (ATAC-seq) and RNA-seq in embryonic day 7.5 (E7.5) and E13.5 mouse embryos. We construct the chromatin accessibility landscapes with cell spatial information in E7.5 embryos, showing the spatial patterns of cis-elements and the spatial distribution of potentially functional transcription factors (TFs). We further show that many germ-layer-specific cis-elements and TFs in E7.5 embryos are maintained in the cell types derived from the corresponding germ layers at later stages, suggesting that these cis-elements and TFs are important during cell differentiation. We also find a potential progenitor for Sertoli and granulosa cells in gonads. Interestingly, both Sertoli and granulosa cells exist in male gonads and female gonads during gonad development. Collectively, we provide a valuable resource to understand organogenesis in mammals.

Comparing the effects of two different progesterone vaginal gels, Progeson™ and Crinone™, from pharmacokinetics study to clinical applications in patients undergone fresh embryo transfer and frozen-thawed embryo transfer via natural cycle endometrial preparation protocol.

OBJECTIVE: The pharmacokinetics performance and clinical pregnancy rate of two vaginal progesterone gel, Progeson™ and Crinone™, were compared in this study. MATERIALS AND METHODS: In the pharmacokinetics performance, Progeson showed similar long-term dissolution rate as Crinone. In the clinical study, 141 subjects undergone in vitro fertilization (IVF) treatments were included to compare serum progesterone level and clinical pregnancy rates. RESULTS: Among the subjects, 78 subjects received fresh embryo transfer and 63 subjects received frozen embryo transfer via natural cycle endometrial preparation protocol. In each group, subjects were given either Crinone™ or Progeson™ for luteal phase support without combination with other progesterone products. The study showed that Crinone™ group led to higher estrogen level at mid-luteal phase in the fresh embryo transfer group, and Progeson™ group led to higher progesterone level at mid-luteal phase and pregnancy test day in the frozen-thawed embryo transfer group. CONCLUSION: Subjects received Crinone™ or Progeson™ had similar rate of pregnancy, live birth, and stillbirth in both fresh embryo transfer and frozen-thawed embryo transfer group. Thus, Progeson™ might be a suitable substitute for Crinone™ in assisted reproductive therapy.

Survival Benefits of Radiotherapy and Surgery in Lung Cancer Brain Metastases with Poor Prognosis Factors.

BACKGROUND: Radiotherapy and surgery are the standard local treatments for lung cancer brain metastases (BMs). However, limited studies focused on the effects of radiotherapy and surgery in lung cancer BMs with poor prognosis factors. METHODS: We retrospectively analyzed 714 patients with lung cancer BMs. Analyses of overall survival (OS) and risk factors for OS were assessed by the log-rank test and Cox proportional hazard model. RESULTS: Age ≥ 65 years, a Karnofsky Performance Scale (KPS) score ≤ 70, anaplastic large-cell lymphoma kinase (ALK)/epidermal growth factor receptor (EGFR) wild type, and extracranial metastases were related to poor prognosis. Patients were stratified according to these poor prognosis factors. In patients with the ALK/EGFR wild type, whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), and surgery improved the OS of patients. WBRT and SRS were the independent protective factors for OS. In patients with extracranial metastases, patients who received WBRT plus SRS or WBRT alone had longer OS than those who did not receive radiotherapy. WBRT plus SRS and WBRT were the independent protective factors for OS. CONCLUSIONS: Radiotherapy and surgery are associated with improved survival for lung cancer BMs with the ALK/EGFR wild type. Radiotherapy is associated with improved survival in lung cancer BMs with extracranial metastases.

Integrated metabolomics analysis of Lactobacillus in fermented milk with fish gelatin hydrolysate in different degrees of hydrolysis.

Dual-platform metabolomics combined with multivariate data analysis was used to investigate the effects of adding fish gelatin (FGH) at different degrees of hydrolysis (DH) on the growth and metabolic pathways of different species of Lactobacillus in fermented milk. The results showed that the promotion effect of FGH on Lactobacillus was related to the species of probiotics. The corresponding metabolic pathways also changed, with the promotion of Lactobacillus by FGH mainly regulated through amino acid metabolism, lipid metabolism, and nucleotide metabolism pathways. The excess DH inhibited the growth of L. paracasei by adjusting its metabolic state through reducing nucleotide requirements, allocating protein resources, and adopting a stress response. In conclusion, this study revealed the effectiveness of dual-platform metabolomics in explaining the metabolic mechanisms of probiotics, providing theoretical support and a scientific basis for the development of functional fermented foods.

Modulation of PPARα-thermogenesis gut microbiota interactions in obese mice administrated with zingerone.

BACKGROUND: This study aimed to uncover the potential effects of zingerone (ZIN), one of the bioactive compounds in ginger, on the development of obesity as well as the mechanisms responsible for these effects in C57BL/6J mice fed with a high-fat diet (HFD). RESULTS: Supplementation with 0.2% (wt/wt) zingerone for 16 weeks significantly reduced the final body weight, liver weight, and epididymal white adipose tissue (eWAT) weight without changing the food intake of the mice when compared with the HFD group. The hyperlipidemia of HFD-fed mice was ameliorated after zingerone administration, including decreased plasma triacylglycerol (TG) and total cholesterol (TC) level. The lipid content in liver was lower and the adipocyte size in eWAT and inguinal white adipose tissue (iWAT) was smaller in HFD + ZIN-fed mice compared with HFD group. Zingerone also binds with nuclear hormone receptor peroxisome proliferator-activated receptor alpha (PPARα) with an optimal docking energy of -7.31 kJ/mol. Uncoupling protein 1 (UCP1), PPAR-γ coactivator-1α (PGC-1α), and PR domain containing 16 (PRDM16), the downstream genes of PPAR which are related to thermogenic function of adipocytes, were significantly increased in both brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT) after zingerone administration, in comparison with HFD fed mice. Zingerone intake also restructured the community composition of gut microbiota. The ratio of Firmicutes to Bacteroidetes was decreased, and the relative abundance of Akkermansia_mucinphila was increased. CONCLUSION: Zingerone can attenuate obesity and related symptoms in HFD-fed mice, probably through the modulation of PPARα-thermogenesis-gut microbiota interactions. © 2022 Society of Chemical Industry.

The signatures of liver metabolomics and gut microbiota in high-fat diet fed mice supplemented with rhododendrol.

As aromatic compounds found within red fruits and berries, raspberry ketones (RK) have the potential for nonalcoholic fatty liver disease (NAFLD) amelioration. However, the mechanism of RK on NAFLD is unclear, and their bioactive metabolite is unknown. As the major metabolites of RK that are mainly distributed in the liver, rhododendrol (RHO) is used in our current study to test whether RHO accounts for the beneficial effect of RK on NAFLD and the underlying mechanism. In a 16-week trial, RHO significantly decreased final body weight, improved serum lipid profile and ameliorated liver inflammation. Moreover, RHO changed the gut microbiota composition, including lean phenotype-related genera, such as Bacteroides, Bilophila, Oscillibacter, Lachnospiraceae_bacterium_28_4 and Bacteroides sartorii. Liver metabolomics analysis indicated that RHO enhanced the abundance of metabolites related to alanine, aspartate, and glutamate metabolism, as well as arginine and proline metabolism. Spearman correlation analysis revealed that these metabolites were positively correlated with the gut genera enriched by RHO. Here, our findings suggested that the metabolic effects of RK might be partially attributed to its metabolite-RHO, and mice supplemented with RHO have dramatically altered hepatic metabolisms concurrent with shifts in specific gut bacteria.

Predicting glioblastoma molecular subtypes and prognosis with a multimodal model integrating convolutional neural network, radiomics, and semantics.

OBJECTIVE: The aim of this study was to build a convolutional neural network (CNN)-based prediction model of glioblastoma (GBM) molecular subtype diagnosis and prognosis with multimodal features. METHODS: In total, 222 GBM patients were included in the training set from Sun Yat-sen University Cancer Center (SYSUCC) and 107 GBM patients were included in the validation set from SYSUCC, Xuanwu Hospital Capital Medical University, and the First Hospital of Jilin University. The multimodal model was trained with MR images (pre- and postcontrast T1-weighted images and T2-weighted images), corresponding MRI impression, and clinical patient information. First, the original images were segmented using the Multimodal Brain Tumor Image Segmentation Benchmark toolkit. Convolutional features were extracted using 3D residual deep neural network (ResNet50) and convolutional 3D (C3D). Radiomic features were extracted using pyradiomics. Report texts were converted to word embedding using word2vec. These three types of features were then integrated to train neural networks. Accuracy, precision, recall, and F1-score were used to evaluate the model performance. RESULTS: The C3D-based model yielded the highest accuracy of 91.11% in the prediction of IDH1 mutation status. Importantly, the addition of semantics improved precision by 11.21% and recall in MGMT promoter methylation status prediction by 14.28%. The areas under the receiver operating characteristic curves of the C3D-based model in the IDH1, ATRX, MGMT, and 1-year prognosis groups were 0.976, 0.953, 0.955, and 0.976, respectively. In external validation, the C3D-based model showed significant improvement in accuracy in the IDH1, ATRX, MGMT, and 1-year prognosis groups, which were 88.30%, 76.67%, 85.71%, and 85.71%, respectively (compared with 3D ResNet50: 83.51%, 66.67%, 82.14%, and 70.79%, respectively). CONCLUSIONS: The authors propose a novel multimodal model integrating C3D, radiomics, and semantics, which had a great performance in predicting IDH1, ATRX, and MGMT molecular subtypes and the 1-year prognosis of GBM.

Potential therapeutic strategies for quercetin targeting critical pathological mechanisms associated with colon adenocarcinoma and COVID-19.

Patients with colon adenocarcinoma (COAD) are at a higher probability of infection with COVID-19 than healthy individuals. However, there is no globally accepted treatment protocol for patients with COAD/COVID-19. Quercetin has been found to have significant antitumor, antiviral and anti-inflammatory effects in several studies. Therefore, this study sought to evaluate the potential of quercetin as the agent for COAD/COVID-19 and to explore its mechanisms. We used bioinformatics algorithms to obtain COAD/COVID-19-related genes (CCRG) from COAD-related transcriptome data and COVID-related transcriptome sequencing data, and used these genes to construct a COAD prognostic model. We intersected the CCRG with the therapeutic target genes of quercetin and obtained a total of 105 genes (potential target genes of quercetin for the treatment of COAD/COVID-19). By constructing a protein-protein interaction (PPI) network, we ascertained FOS, NFKB1, NFKB1A, JUNB, and JUN as possible core target genes of quercetin for the treatment of COAD/COVID-19. Bioinformatic analysis of these 105 genes revealed that the mechanisms for quercetin the treatment of COAD/COVID-19 may be associated with oxidative stress, apoptosis, anti-inflammatory, immune, anti-viral and multiple pathways containing IL-17, TNF, HIF-1. In this study, we constructed a prognostic model of COAD/COVID19 patients by using CCRG and elucidated for the first time the potential target genes and molecular mechanisms of quercetin for the treatment of COAD/COVID-19, which may benefit the clinical treatment of COAD/COVID-19 patients. However, no clinical trials have yet been conducted to further validate the findings, but this will be the future direction of our research.

Gene editing monkeys: Retrospect and outlook.

Animal models play a key role in life science research, especially in the study of human disease pathogenesis and drug screening. Because of the closer proximity to humans in terms of genetic evolution, physiology, immunology, biochemistry, and pathology, nonhuman primates (NHPs) have outstanding advantages in model construction for disease mechanism study and drug development. In terms of animal model construction, gene editing technology has been widely applied to this area in recent years. This review summarizes the current progress in the establishment of NHPs using gene editing technology, which mainly focuses on rhesus and cynomolgus monkeys. In addition, we discuss the limiting factors in the applications of genetically modified NHP models as well as the possible solutions and improvements. Furthermore, we highlight the prospects and challenges of the gene-edited NHP models.

Analysis of the potential role of photocurable hydrogel in patient-derived glioblastoma organoid culture through RNA sequencing.

Patient-derived glioblastoma organoid (GBO) growth in hydrogels recapitulates key features of parental tumors, making GBOs a useful tool for fundamental research on cancer biology and offer deeper insight into the development of innovative therapeutic strategies for cancer treatment. Matrigel as a natural hydrogel has been widely used for 3D culture in most tumor organoid studies, but the volatility in its biochemical and biophysical properties makes it difficult to be further applied in GBO cultures. Thus, several kinds of biomimetic hydrogels from synthetic or biological polymers have been developed for tumor organoid growth. Here, we innovatively utilize a photocurable hydrogel-based biomimetic instructive system containing gelatin methacryloyl (GelMA) mixed with a hyaluronic acid (HA) hydrogel as a scaffold for generating GBOs. Furthermore, we evaluated the GBO biological properties at the transcriptome level, which showed that GBOs cultured with this hydrogel retain the expression profile of key neurodevelopmental markers, driving mutations and alternative splicing of parental tumors. Notably, GBOs cultured with the photocurable hydrogel may provide a platform for precision cancer medicine, bridging the gap between basic research and clinical application. Although significant challenges remain, biomimetic hydrogels can provide an exceptional window for the construction of tumor organoids to ensure the accuracy of the research and clinical data.

Exploration of the Shared Gene and Molecular Mechanisms Between Endometriosis and Recurrent Pregnancy Loss.

Endometriosis (EMs) is a common benign gynecological disease in women of childbearing age, which usually causes pelvic pain, secondary dysmenorrhea, and infertility. EMs has been linked to recurrent pregnancy loss (RPL) in epidemiological data. The relationship of both, however, remains unknown. The purpose of this study is to explore the underlying pathological mechanisms between EMs and RPL. We searched Gene Expression Omnibus (GEO) database to obtain omics data of EMs and RPL. Co-expression modules for EMs and RPL were investigated by using weighted gene co-expression network analysis (WGCNA). The intersections of gene modules with the strong correlation to EMs or RPL obtained by WGCNA analysis were considered as shared genes. MicroRNAs (miRNAs) and their corresponding target genes linked to EMs and RPL were found though the Human MicroRNA Disease Database (HMDD) and the miRTarbase database. Finally, we constructed miRNAs-mRNAs regulatory networks associated with the two disorders by using the intersection of previously obtained target genes and shared genes. We discovered as significant modules for EMs and RPL, respectively, by WGCNA. The energy metabolism might be the common pathogenic mechanism of EMs and RPL, according to the findings of a Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. We discovered several target genes that might be linked to these two disorders, as well as the potential mechanisms. RAB8B, GNAQ, H2AFZ, SUGT1, and LEO1 could be therapeutic candidates for RPL and EMs. The PI3K-Akt signaling pathway and platelet activation were potentially involved in the mechanisms of EM-induced RPL. Our findings for the first time revealed the underlying pathological mechanisms of EM-induced RPL and identified several useful biomarkers and potential therapeutic targets.

Identification of Potential Molecular Mechanism Related to Infertile Endometriosis.

Objectives: In this research, we aim to explore the bioinformatic mechanism of infertile endometriosis in order to identify new treatment targets and molecular mechanism. Methods: The Gene Expression Omnibus (GEO) database was used to download MRNA sequencing data from infertile endometriosis patients. The "limma" package in R software was used to find differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) was used to classify genes into modules, further obtained the correlation coefficient between the modules and infertility endometriosis. The intersection genes of the most disease-related modular genes and DEGs are called gene set 1. To clarify the molecular mechanisms and potential therapeutic targets for infertile endometriosis, we used Gene Ontology (GO), Kyoto Gene and Genome Encyclopedia (KEGG) enrichment, Protein-Protein Interaction (PPI) networks, and Gene Set Enrichment Analysis (GSEA) on these intersecting genes. We identified lncRNAs and miRNAs linked with infertility and created competing endogenous RNAs (ceRNA) regulation networks using the Human MicroRNA Disease Database (HMDD), mirTarBase database, and LncRNA Disease database. Results: Firstly, WGCNA enrichment analysis was used to examine the infertile endometriosis dataset GSE120103, and we discovered that the Meorangered1 module was the most significantly related with infertile endometriosis. The intersection genes were mostly enriched in the metabolism of different amino acids, the cGMP-PKG signaling pathway, and the cAMP signaling pathway according to KEGG enrichment analysis. The Meorangered1 module genes and DEGs were then subjected to bioinformatic analysis. The hub genes in the PPI network were performed KEGG enrichment analysis, and the results were consistent with the intersection gene analysis. Finally, we used the database to identify 13 miRNAs and two lncRNAs linked to infertility in order to create the ceRNA regulatory network linked to infertile endometriosis. Conclusion: In this study, we used a bioinformatics approach for the first time to identify amino acid metabolism as a possible major cause of infertility in patients with endometriosis and to provide potential targets for the diagnosis and treatment of these patients.