Low-grade systemic inflammation links heavy metal exposures to mortality: A multi-metal inflammatory index approach.

Certain heavy metals have been correlated to an elevated risk of inflammation-related diseases and mortality. Nevertheless, the intricate relationships between metal exposure, inflammation and mortality remain unknown. We included 3741 adults with measurements of ten urinary heavy metals in the National Health and Nutritional Examination Survey (NHANES) 2005-2010, followed up to December 31, 2019. Low-grade systemic inflammation was evaluated by various markers, including C-reactive protein (CRP) and ratios derived from regular blood tests. We assessed associations between heavy metal and all-cause mortality using multivariate COX regressions. Then we assessed the mediation effect of low-grade systemic inflammation on the associations via Sobel Test. To gauge the systemic inflammatory potential of the multi-metal mixture and its correlation with all-cause mortality, a Metal Mixture Inflammatory Index (MMII) was developed using reduced rank regression (RRR) models. The association between MMII and all-cause mortality was explored via multivariate COX regressions. Cadmium, antimony and uranium displayed positive associations with mortality, with hazard ratios (HR) ranging from 1.18 to 1.46 (all P-FDR < 0.05). Mediation analyses revealed that the associations between specific heavy metals (cadmium and antimony) and mortality risk were slightly mediated by the low-grade systemic inflammation markers, with mediation proportions ranging from 3.11 % to 5.38 % (all P < 0.05). MMII, the weighted sum of 9 heavy metals, significantly predicted platelet-to-lymphocyte ratio (PLR) and CRP (ß = 0.10 and 1.16, all P < 0.05), was positively associated with mortality risk (HR 1.28, 95 % CI 1.14 to 1.43). Exposure to heavy metals might increase all-cause mortality, partly mediated by low-grade systemic inflammation. MMII, designed to assess the potential systemic inflammatory effects of exposure to multiple heavy metals, was closely related to the all-cause mortality risk. This study introduces MMII as an approach to evaluating co-exposure and its potential health effects comprehensively.

Preparation of ethyl cellulose bimodal nanofibrous membrane by green electrospinning based on molecular weight regulation for high-performance air filtration.

Preparing bio-based air filtration membrane through green electrospinning strategy is a vital approach to alleviating environmental and energy crises. However, the development of related biomaterials and method for regulating membrane structure are still lacking. In this study, ethyl cellulose (EC) bimodal nanofibrous membrane was prepared by electrospinning using ethanol and water as solvents to achieve high-performance air filtration. A new strategy for bimodal fiber molding based on molecular weight modulation was proposed. The EC polymer chains with medium molecular weights were subject to the highest degree of inhomogeneity of solvent intrusion, and there were significant differences in viscous forces "microscopically", leading to the formation of bimodal structure by inhomogeneous stretching of the jet. The well-defined bimodal structure endowed EC membrane with excellent air filtration performance. The filtration efficiency for PM0.3, pressure drop, quality factor were 99.11 %, 42.2 Pa, and 0.112 Pa-1, respectively. Compared to the commonly used zein, EC cost just 12.77 %, and its solution had a 50 % longer shelf life, making it a more desirable biomaterial. This work will facilitate the application of more biomaterials in air filtration, promote the green fabrication of high-performance air filtration membranes, and realize sustainable development.

Identification of circRNA Expression Profile and Potential Systemic Immune Imbalance Modulation in Premature Rupture of Membranes.

Premature rupture of membrane (PROM) refers to the rupture of membranes before the onset of labor which increases the risk of perinatal morbidity and mortality. Recently, circular RNAs (circRNAs) have emerged as promising regulators of diverse diseases. However, the circRNA expression profiles and potential circRNA-miRNA-mRNA regulatory mechanisms in PROM remain enigmatic. In this study, we displayed the expression profiles of circRNAs and mRNAs in plasma and fetal membranes of PROM and normal control (NC) groups based on circRNA microarray, the Gene Expression Omnibus database, and NCBI's Sequence Read Archive. A total of 1,459 differentially expressed circRNAs (DECs) in PROM were identified, with 406 upregulated and 1,053 downregulated. Then, we constructed the circRNA-miRNA-mRNA network in PROM, encompassing 22 circRNA-miRNA pairs and 128 miRNA-mRNA pairs. Based on the analysis of gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene set enrichment analysis (GSEA), DECs were implicated in immune-related pathways, with certain alterations persisting even postpartum. Notably, 11 host genes shared by DECs of fetal membrane tissue and prenatal plasma in PROM were significantly implicated in inflammatory processes and extracellular matrix regulation. Our results suggest that structurally stable circRNAs may predispose to PROM by mediating systemic immune imbalances, including peripheral leukocyte disorganization, local immune imbalance at the maternal-fetal interface, and local collagen disruption. This is the first time to decipher a landscape on circRNAs of PROM, reveals the pathogenic cause of PROM from the perspective of circRNA, and opens up a new direction for the diagnosis and treatment of PROM.

Research waste among randomized controlled trials in ovarian cancer: A cross-sectional study.

OBJECTIVE: To examine the association between trial characteristics and research waste in randomized controlled trials (RCTs) on ovarian cancer over the past two decades. METHODS: ClinicalTrials.gov was searched for RCTs registered between 2000 and 2020 using the keyword ovarian cancer. Publication status of RCTs was determined through systematic searches of the PubMed and Google Scholar databases. Reporting adequacy was evaluated using the CONSORT checklist. Design limitations were assessed based on the risk of bias and whether a relevant systematic review was cited in the manuscript. The primary outcome was research waste, defined as an RCT that was unpublished, inadequately reported, or had avoidable design limitations. RESULTS: Among the 117 RCTs evaluated, 89 (76.1 %) were published as of February 14, 2024. Published RCTs were more likely to be pharmacological, conducted in North America or Europe, have a multicenter or multinational design, have a larger sample size (over 200 participants), and receive external funding (P < 0.05). Among the published RCTs, 73 (82.0 %) and 24 (27.0 %) were considered adequately reported and free from design limitations, respectively. Overall, 96 of the 117 RCTs (82.1 %) were associated with research waste. Factors independently associated with research waste were an open-label design and smaller sample size (P < 0.05). CONCLUSION: Over 80 % of the RCTs on ovarian cancer demonstrated at least one feature of research waste. Future efforts should focus on minimizing the potential waste in unblinded small-scale RCTs.

High level 27-HC impairs trophoblast cell invasion and migration via LXR in pre-eclampsia.

INTRODUCTION: To explore the potential impact of 27-hydroxycholesterol (27-HC) on trophoblast cell function in pre-eclampsia. RESULTS: The levels of 27-HC and the expression of CYP27A1 are upregulated in clinical samples of PE. Furthermore, high concentrations of 27-HC can inhibit the invasion and migration ability of trophoblast cells in vitro, and this inhibitory effect is weakened after LXR silencing. In HTR8/SVneo cells treated with 27-HC, the expression of ABCA1/ABCG1 are increased. Finally, we established a mouse model of PE using l-NAME (N-Nitro-l-Arginine Methyl Ester). We found an increase in the levels of 27-HC in the peripheral blood serum of the PE mouse model, and an upregulation of CYP27A1 and LXR expressions in the placenta of the PE mouse model. CONCLUSION: 27-HC inhibits the invasion and migration ability of trophoblast cells by activating the LXR signaling pathway, which is involved in the pathogenesis of Pre-eclampsia(PE).

An innovative Z-type Sb2S3/In2S3/TiO2 heterostructure: superior performance in the photocatalytic removal of levofloxacin and mechanistic insight.

In this study, Sb2S3/In2S3/TiO2 (SIT) heterojunction photocatalysts were prepared by a simple two-step hydrothermal method and applied to the photocatalytic degradation of levofloxacin (LEV). After 160 min of reaction under visible light, the SIT heterojunction photocatalyst degraded 10 mg L-1 LEV at a rate of 86.7%. The degradation of LEV follows pseudo-first-order kinetics with a rate constant 1.16 × 10-2 min-1, which is 1.42, 1.22 and 1.05 times higher than that of TiO2, SI and IT, respectively. Meanwhile, the SIT photocatalysts also showed high photocatalytic activity for other antibiotics. The enhanced photocatalytic activity of the ternary heterostructures was attributed to the full-spectrum response and the synergistic effect of the dual Z-type heterojunctions, which improved the visible light absorption and facilitated the charge separation. In addition, ˙OH and ˙O2- play a dominant role in the photodegradation process. This work contributes to the design of novel photocatalytic materials with dual Z-type heterojunctions and efficient photocatalysts for the degradation of antibiotics.

Synthesis of Bis-Heterocycles Bearing Methyleneindole Motifs by Pd-Catalyzed Domino Reaction.

A highly robust, general, and practically simple palladium-catalyzed domino bicyclization strategy is presented to synthesize nitrogen-containing bis-heterocycles bearing methylene indole motifs from alkyne-tethered carbamoyl chlorides and ß,γ- or γ,δ-unsaturated hydrazones. The salient features of this transformation include broad substrate scope, good functional group tolerance, ease for scale-up, and convenient conversion.

Au nanoparticle sensitized blue TiO2 nanorod arrays for efficient Gatifloxacin photodegradation.

TiO2 nanorod arrays have been widely used in photocatalytic processes, but their poor visible light absorption and rapid carrier recombination limit their application. Both introducing oxygen vacancies and using precious metals as surface plasmon resonance (SPR) stimulators are effective strategies to enhance their photocatalytic performance. Herein, Au nanoparticle sensitized blue TiO2 nanorod arrays (Au/B-TiO2) were successfully fabricated for efficient Gatifloxacin photodegradation. The degradation efficiency of Gatifloxacin was up to 95.0%. Moreover, the corresponding reaction rate constant (Ka) was up to 0.02007 min-1. Additionally, it was suggested that Gatifloxacin could be subject to three different degradation pathways. The superior catalytic activity of Au/B-TiO2 is a result of the combined effect of the two components. Firstly, TiO2 nanorod arrays provide a larger surface area for Au deposition and act as efficient transfer channels. Secondly, the presence of oxygen vacancies in blue TiO2 nanorod arrays enhances the catalytic activity. Thirdly, Au acts as a SPR activator, providing a large number of high-energy electrons in the photocatalysis process. Lastly, the improved light capture capabilities are essential for efficient removal of Gatifloxacin. This work provides a new approach for the construction of a high-performance heterojunction photocatalyst in advanced oxidation processes.

The genetic variation in drought resistance in eighteen perennial ryegrass varieties and the underlying adaptation mechanisms.

BACKGROUND: Drought resistance is a complex characteristic closely related to the severity and duration of stress. Perennial ryegrass (Lolium perenne L.) has no distinct drought tolerance but often encounters drought stress seasonally. Although the response of perennial ryegrass to either extreme or moderate drought stress has been investigated, a comprehensive understanding of perennial ryegrass response to both conditions of drought stress is currently lacking. RESULTS: In this study, we investigated the genetic variation in drought resistance in 18 perennial ryegrass varieties under both extreme and moderate drought conditions. The performance of these varieties exhibited obvious diversity, and the survival of perennial ryegrass under severe stress was not equal to good growth under moderate drought stress. 'Sopin', with superior performance under both stress conditions, was the best-performing variety. Transcriptome, physiological, and molecular analyses revealed that 'Sopin' adapted to drought stress through multiple sophisticated mechanisms. Under stress conditions, starch and sugar metabolic enzymes were highly expressed, while CslA was expressed at low levels in 'Sopin', promoting starch degradation and soluble sugar accumulation. The expression and activity of superoxide dismutase were significantly higher in 'Sopin', while the activity of peroxidase was lower, allowing for 'Sopin' to maintain a better balance between maintaining ROS signal transduction and alleviating oxidative damage. Furthermore, drought stress-related transcriptional and posttranscriptional regulatory mechanisms, including the upregulation of transcription factors, kinases, and E3 ubiquitin ligases, facilitate abscisic acid and stress signal transduction. CONCLUSION: Our study provides insights into the resistance of perennial ryegrass to both extreme and moderate droughts and the underlying mechanisms by which perennial ryegrass adapts to drought conditions.

Developments in small-angle X-ray scattering (SAXS) for characterizing the structure of surfactant-macromolecule interactions and their complex.

The surfactant-macromolecule interactions (SMI) are one of the most critical topics for scientific research and industrial application. Small-angle X-ray scattering (SAXS) is a powerful tool for comprehensively studying the structural and conformational features of macromolecules at a size ranging from Angstroms to hundreds of nanometers with a time-resolve in milliseconds scale. The SAXS integrative techniques have emerged for comprehensively analyzing the SMI and the structure of their complex in solution. Here, the various types of emerging interactions of surfactant with macromolecules, such as protein, lipid, nuclear acid, polysaccharide and virus, etc. have been systematically reviewed. Additionally, the principle of SAXS and theoretical models of SAXS for describing the structure of SMI as well as their complex has been summarized. Moreover, the recent developments in the applications of SAXS for charactering the structure of SMI have been also highlighted. Prospectively, the capacity to complement artificial intelligence (AI) in the structure prediction of biological macromolecules and the high-throughput bioinformatics sequencing data make SAXS integrative structural techniques expected to be the primary methodology for illuminating the self-assembling dynamics and nanoscale structure of SMI. As advances in the field continue, we look forward to proliferating uses of SAXS based upon its abilities to robustly produce mechanistic insights for biology and medicine.

Exploring the pharmacological mechanisms and key active ingredients of total flavonoids from Lamiophlomis rotata (Benth.) Kudo against rheumatoid arthritis based on multi-technology integrated network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Lamiophlomis rotata (Benth.) Kudo (LR, Lamiaceae) is a traditional Tibetan medicinal material in China. Tibetan medicine classic and research report suggested that LR could be used to cure rheumatoid arthritis (RA). However, the anti-RA active ingredients and pharmacological mechanisms of LR have not been elucidated. AIM OF THE STUDY: To explore the mechanisms and key active ingredients of total flavonoids from LR (TFLR) against RA. MATERIALS AND METHODS: First, the mechanisms of TFLR against RA were investigated on collagen-induced arthritis (CIA) rat model by analyzing paw appearance, paw swelling, arthritis score, spleen index, thymus index, inflammatory cytokine (TNF-α, IL-1ß, IL-6 and IL-17) levels in serum, histopathology of ankle joint and synovium from knee joint (hematoxylin-eosin, safranin O-fast green and DAB-TUNEL staining), and apoptosis-related protein (PI3K, Akt1, p-Akt, Bad, p-Bad, Bcl-xL and Bcl-2) levels in the synovium of ankle joints (Western blot). Then, the crucially active ingredients of TFLR against RA were explored by network pharmacology, ingredient analysis, in vitro metabolism and TNF-α-induced human RA synovial fibroblast MH7A proliferation assays. Network pharmacology was applied to predict the key active ingredients of TFLR against RA. The ingredient analysis and in vitro metabolism of TFLR were performed on HPLC, and MH7A proliferation assay were applied to evaluate the predicted results of network pharmacology. RESULTS: TFLR shown excellently anti-RA effect by reducing paw swelling, arthritis score, spleen index, thymus index and inflammatory cytokine (IL-1ß, IL-6 and IL-17) levels, and improving the histopathological changes of ankle joint and synovium from knee joint in CIA rats. Results of Western blot indicated that TFLR reversed the changes of PI3K, p-Akt, p-Bad, Bcl-xL and Bcl-2 levels in the ankle joint synovium of CIA rats. Results of network pharmacology exhibited that luteolin was identified as the pivotal active ingredient of TFLR against RA. The ingredient analysis of TFLR indicated that the main ingredient in TFLR was luteoloside. The in vitro metabolism study of TFLR suggested that luteoloside could be converted to luteolin in artificial gastric juice and intestinal juice. Results of MH7A proliferation assay showed that there was no significant difference between TFLR and equal luteoloside on the viability of MH7A cells, indicating that luteoloside was the key active ingredient of TFLR against RA. Additionally, the luteolin (same mol as luteoloside) showed better inhibitory effect on the viability of MH7A cells than luteoloside. CONCLUSION: TFLR showed anti-RA effect, and the mechanism was related to promoting synovial cell apoptosis mediated by PI3K/Akt/Bad pathway. Meanwhile, this work indicated that luteoloside was the key active ingredient of TFLR against RA. This work lays a foundation for providing TFLR product with clear mechanism and stable quality to treat RA.

The performance of temperature and acid-modified sludge in removing lead and cadmium.

In the present study, the aluminum-containing wastewater treatment residue was modified at 400 °C and 2.5 mol/L HCl and used in the removal of Pb and Cd from an aqueous solution for the first time. The modified sludge was characterized by SEM, XRD, FTIR, and BET. Under the optimized conditions, including pH 6, adsorbent dose 3 g/L, Pb/Cd reaction time 120 and 180 min, and Pb/Cd concentration 400 and 100 mg/L, Pb/Cd adsorption capacity was obtained as 90.72 and 21.39 mg/g, respectively. The adsorption process of sludge before and after modification is more consistent with the quasi-second-order kinetics, and the correlation coefficients R2 are all above 0.99. The fitting of data with the Langmuir isotherm and pseudo-second-order kinetics showed that the adsorption process is monolayer and chemical in nature. The adsorption reaction included ion exchange, electrostatic interaction, surface complexation, cation-π interaction, co-precipitation, and physical adsorption. This work implies that the modified sludge has greater potential in the removal of Pb and Cd from wastewater relative to raw sludge.

LINC01589 serves as a potential tumor-suppressor and immune-related biomarker in endometrial cancer: A review.

Currently, increasing attention is being paid to biomarkers in endometrial cancer. Immune infiltration of the tumor microenvironment has been shown to significantly affect the overall survival (OS) of uterine corpus endometrial carcinoma (UCEC) patients. LINC01589 is a long non-coding RNA (lncRNA) that is rarely reported in cancer and is assumed to play a role in immune regulation. We therefore evaluated the role of LINC01589 in UCEC using the Cancer Genome Atlas (TCGA) database. We analyzed the expression of LINC01589 using the gene expression profiles of LINC01589 in the UCEC projects in TCGA. Comparisons between the differentially expressed genes (DEGs) of the cancer and adjacent normal tissues of the UCEC projects revealed that LINC01589 expression was decreased in UCEC tissues. A multivariate cox regression analysis indicated that LINC01589 upregulation could serve as an independent prognostic factor for survival. Furthermore, there was a positive correlation between LINC01589 expression and B cell, T cell, NK cell, monocytic lineage, and myeloid dendritic cell infiltration in UCEC patients. In addition, 5 clusters of hub genes were detected by comparison of different expression levels of LINC01589 in the UCEC groups. The analysis of the reactome pathway using gene set enrichment analysis (GSEA) revealed immune-related pathways, including CD22-mediated B cell receptor (BCR) regulation and antigen-activated BCRs, leading to the generation of second messengers and complement cascade pathways that were significantly enriched in the high LINC01589 expression group. Thus, LINC01589 may serve as a prognostic biomarker, as it is associated with immune infiltration in UCEC.

Detection of multiple types of cancer driver mutations using targeted RNA sequencing in non-small cell lung cancer.

BACKGROUND: DNA-based next-generation sequencing has been widely used in the selection of target therapies for patients with nonsmall cell lung cancer (NSCLC). RNA-based next-generation sequencing has been proven to be valuable in detecting fusion and exon-skipping mutations and is recommended by National Comprehensive Cancer Network guidelines for these mutation types. METHODS: The authors developed an RNA-based hybridization panel targeting actionable driver oncogenes in solid tumors. Experimental and bioinformatics pipelines were optimized for the detection of fusions, single-nucleotide variants (SNVs), and insertion/deletion (indels). In total, 1253 formalin-fixed, paraffin-embedded samples from patients with NSCLC were analyzed by DNA and RNA panel sequencing in parallel to assess the performance of the RNA panel in detecting multiple types of mutations. RESULTS: In analytical validation, the RNA panel achieved a limit of detection of 1.45-3.15 copies per nanogram for SNVs and 0.21-6.48 copies per nanogram for fusions. In 1253 formalin-fixed, paraffin-embedded NSCLC samples, the RNA panel identified a total of 124 fusion events and 26 MET exon 14-skipping events, in which 14 fusions and six MET exon 14-skipping mutations were missed by DNA panel sequencing. By using the DNA panel as the reference, the positive percent agreement and the positive predictive value of the RNA panel were 98.08% and 98.62%, respectively, for detecting targetable SNVs and 98.15% and 99.38%, respectively, for detecting targetable indels. CONCLUSIONS: Parallel DNA and RNA sequencing analyses demonstrated the accuracy and robustness of the RNA sequencing panel in detecting multiple types of clinically actionable mutations. The simplified experimental workflow and low sample consumption will make RNA panel sequencing a potentially effective method in clinical testing.

Recent advances in structural characterization of biomacromolecules in foods via small-angle X-ray scattering.

Small-angle X-ray scattering (SAXS) is a method for examining the solution structure, oligomeric state, conformational changes, and flexibility of biomacromolecules at a scale ranging from a few Angstroms to hundreds of nanometers. Wide time scales ranging from real time (milliseconds) to minutes can be also covered by SAXS. With many advantages, SAXS has been extensively used, it is widely used in the structural characterization of biomacromolecules in food science and technology. However, the application of SAXS in charactering the structure of food biomacromolecules has not been reviewed so far. In the current review, the principle, theoretical calculations and modeling programs are summarized, technical advances in the experimental setups and corresponding applications of in situ capabilities: combination of chromatography, time-resolved, temperature, pressure, flow-through are elaborated. Recent applications of SAXS for monitoring structural properties of biomacromolecules in food including protein, carbohydrate and lipid are also highlighted, and limitations and prospects for developing SAXS based on facility upgraded and artificial intelligence to study the structural properties of biomacromolecules are finally discussed. Future research should focus on extending machine time, simplifying SAXS data treatment, optimizing modeling methods in order to achieve an integrated structural biology based on SAXS as a practical tool for investigating the structure-function relationship of biomacromolecules in food industry.

Michael acceptor molecules in natural products and their mechanism of action.

Purpose: Michael receptor molecules derived from plants are biologically active due to electrophilic groups in their structure. They can target nucleophilic residues on disease-related proteins, with significant therapeutic effects and low toxicity for many diseases. They provide a good option for relevant disease treatment. The aim of this study is to summarize the existing MAMs and their applications, and lay a foundation for the application of Michael receptor molecules in life science in the future. Methods: This review summarizes the published studies on Michael receptor molecules isolated from plants in literature databases such as CNKI, Wanfang Data, PubMed, Web of Science, ScienceDirect, and Wiley. Latin names of plants were verified through https://www.iplant.cn/. All relevant compound structures were verified through PubChem and literature, and illustrated with ChemDraw 20.0. Result: A total of 50 Michael receptor molecules derived from various plants were discussed. It was found that these compounds have similar pharmacological potential, most of them play a role through the Keap1-Nrf2-ARE pathway and the NF-κB pathway, and have biological activities such as antioxidant and anti-inflammatory. They can be used to treat inflammatory diseases and tumors. Conclusion: The Michael receptor molecule has electrophilicity due to its unsaturated aldehyde ketone structure, which can combine with nucleophilic residues on the protein to form complexes and activate or inhibit the protein pathway to play a physiological role. Michael receptor molecules can regulate the Keap1-Nrf2-ARE pathway and the NF-κB pathway. Michael receptor molecules can be used to treat diseases such as inflammation, cancer, oxidative stress, etc.

Predictor assessment of complete miscarriage after medical treatment for early pregnancy loss in women with previous cesarean section.

This study aimed to evaluate clinical predictors associated with complete miscarriage after medical treatment for early pregnancy loss (EPL) in women with previous cesarean section. Patients with retained uterine content after expulsion followed by administration of mifepristone and misoprostol were included if they chose continued medical treatment rather than surgical intervention. Clinical characteristics including maternal age, gravidity, parity, history of previous cesarean section and ultrasound findings regarding average diameter of the gestational sac, uterine position, width, and blood flow signal of the residual uterine content after expulsion of the gestational sac were included in the analysis to determine predictors of complete miscarriage. A recursive partitioning analysis (RPA) was used to divide the patients into probability groups and assess their probability of complete miscarriage. A total of 89 patients were analyzed. The complete miscarriage rate was 58.43% overall. Multivariable logistic regression analysis showed that the width and blood flow signal of the residual after expulsion were both independent predictors for complete miscarriage (all P < .05). Patients were divided into high-probability (no blood flow signal, width of residual <1 cm), intermediate-probability (no blood flow signal, width of residual ≥1 cm; blood flow signal, width of residual <1 cm), and low-probability (blood flow signal, width of residual ≥ 1 cm) groups by RPA according to these 2 factors. The incidences of complete miscarriage were 88.24%, 67.57%, and 34.29%, respectively, P < .001). Surgical evacuation may be avoided in patients without ultrasonic blood flow of the uterine residual and width of the residual <1 cm. More active treatment could be recommended for patients with ultrasonic blood flow of the uterine residual and width of the residual ≥ 1 cm. Clinicians and patients should be aware of these differences when proceeding with medical treatment for EPL patients with previous cesarean section.

The landscape of circular RNA in preterm birth.

Background: Preterm birth (PTB) is a multifactorial syndrome that seriously threatens the health of pregnant women and babies worldwide. Recently, circular RNAs (circRNAs) have been understood as important regulators of various physiological and pathological processes. However, the expression pattern and potential roles of circRNAs in PTB are largely unclear. Methods: In this study, we extracted and analyzed the circRNA expression profiles in maternal and fetal samples of preterm and term pregnancies, including maternal plasma, maternal monocytes, myometrium, chorion, placenta, and cord blood. We identified the circRNAs which is associated with PTB in different tissues and explored their relationships from the perspective of the overall maternal-fetal system. Furthermore, co-expression analysis of circRNAs and mRNAs, target microRNAs (miRNAs), and RNA-binding proteins (RBPs), provided new clues about possible mechanisms of circRNA function in PTB. In the end, we investigated the potential special biofunctions of circRNAs in different tissues and their common features and communication in PTB. Results: Significant differences in circRNA types and expression levels between preterm and term groups have been proved, as well as between tissues. Nevertheless, there were still some PTB-related differentially expressed circRNAs (DECs) shared by these tissues. The functional enrichment analysis showed that the DECs putatively have important tissue-specific biofunctions through their target miRNA and co-expressed mRNAs, which contribute to the signature pathologic changes of each tissue within the maternal-fetal system in PTB (e.g., the contraction of the myometrium). Moreover, DECs in different tissues might have some common biological activities, which are mainly the activation of immune-inflammatory processes (e.g., interleukin1/6/8/17, chemokine, TLRs, and complement). Conclusions: In summary, our data provide a preliminary blueprint for the expression and possible roles of circRNAs in PTB, which lays the foundation for future research on the mechanisms of circRNAs in PTB.

Investigation and Validation of Molecular Characteristics of Endometrium in Recurrent Miscarriage and Unexplained Infertility from a Transcriptomic Perspective.

Recurrent miscarriage (RM) and unexplained infertility (UI) are gordian knots in reproductive medicine, which are troubling many patients, doctors, and researchers. Although these two diseases of early pregnancy have a significant impact on human reproductive health, little is known about the specific mechanisms, which caused treatment difficulties. This study focused on the molecular signatures underlying the pathological phenotypes of two diseases, with the hope of using statistical methods to identify the significant core genes. An unbiased Weighted Correlation Network Analysis (WGCNA) algorithm was used for endometrial transcriptome data analysis and the disease-related gene modules were screened out. Through enrichment analysis of the candidate genes, we found similarities between both diseases and shared enrichment of immune-related pathways. Therefore, we used immune algorithms to assess the infiltration of immune cells and found abnormal increases of CD8+T cells and neutrophils. In order to explore the molecular profile behind the immunophenotypic changes, we used the SVM algorithm and LASSO regression to identify the core genes with diagnostic capacity in both diseases and discussed their significance of immune disorders in the endometrium. In the end, the satisfactory diagnostic ability of these core genes was verified in the broader group. Our results demonstrated the presence of immune disorders in non-pregnancy tissues of RM and UI, and identified the core molecules of this phenotype, and discuss mechanisms. This provides exploratory evidence for the in-depth understanding of the mechanism of RM and UI and may provide potential targets for their future treatment.

Presence of cell-free fetal circRNA in maternal plasma.

Introduction: There is an urgent need to find novel stable cell-free fetal (cff-) RNA in the maternal circulation to facilitate the advance of non-invasive prenatal testing (NIPT) to more effectively avoid birth defects. Methods: CircRNA microarray was used to detect the cff-circRNA in plasma. Results: There were cff-circRNAs from the fetus in the peripheral blood of pregnant women and they persisted even until at least 24 h after delivery. In addition, we found that cff-circRNA might have a specific expression pattern in gestational disease. Conclusions: We demonstrated the presence of cff-circRNA in the maternal circulation, which may shed new light on the development of NIPT.