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.

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.

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.

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.

Ru@N/S/TiO2/rGO: a high performance HER electrocatalyst prepared by dye-sensitization.

Hydrogen production from water-splitting is one of the most promising hydrogen production methods, and the preparation of the hydrogen evolution reaction (HER) catalyst is very important. Although Pt-based materials have the best catalytic activity for HER, their high price and scarcity greatly limit their large-scale industrial application prospects. Herein, a new method to prepare HER catalyst is described, where dyes used in dye-sensitized solar cells (DSSCs) were used as precursors. A high performance HER catalyst (Ru@N/S/TiO2/rGO, Ru nanoparticles (NPs) supported on N/S-doped TiO2/rGO hybrids) was prepared, and the stereoscopic molecular structure of the porphyrin dye, JR1, not only provides a prerequisite for the preparation of the hyperdispersed Ru NPs, but also successfully realizes N/S co-doping. The Ru@N/S/TiO2/rGO shows an excellent catalytic performance for the HER, which is almost the same as that with Pt/C. In 0.5 M H2SO4, the overpotential is 60 mV at 10 mA cm-2, and the Tafel slope is only 51 mV dec-1. In 1 M KOH, the overpotential is only 5 mV at 10 mA cm-2, and the Tafel slope is only 45 mV dec-1, and this performance is much better than most of the HER catalysts that have been reported. When Ru@N/S/TiO2/rGO is utilized as a catalyst in an alkaline water electrolyzer, a bias of only 1.52 V is able to complement overall water-splitting at 10 mA cm-2 (1.78 V, 100 mA cm-2). The molecular structure and coordination metal species of the dyes are easy to adjust, and the the stereoscopic structure is very helpful for inhibiting the aggregation of the metal NPs, and the strong anchoring effect with TiO2 or other carbon materials is also very helpful to achieve heteroatom doping. In addition, the process of dye-sensitization is simple and repeatable, and is a novel and efficient method to prepare the electrocatalyst.

DNN-DTIs: Improved drug-target interactions prediction using XGBoost feature selection and deep neural network.

Analysis and prediction of drug-target interactions (DTIs) play an important role in understanding drug mechanisms, as well as drug repositioning and design. Machine learning (ML)-based methods for DTIs prediction can mitigate the shortcomings of time-consuming and labor-intensive experimental approaches, while providing new ideas and insights for drug design. We propose a novel pipeline for predicting drug-target interactions, called DNN-DTIs. First, the target information is characterized by a number of features, namely, pseudo-amino acid composition, pseudo position-specific scoring matrix, conjoint triad composition, transition and distribution, Moreau-Broto autocorrelation, and structural features. The drug compounds are subsequently encoded using substructure fingerprints. Next, eXtreme gradient boosting (XGBoost) is used to determine the subset of non-redundant features of importance. The optimal balanced set of sample vectors is obtained by applying the synthetic minority oversampling technique (SMOTE). Finally, a DTIs predictor, DNN-DTIs, is developed based on a deep neural network (DNN) via a layer-by-layer learning scheme. Experimental results indicate that DNN-DTIs achieves better performance than other state-of-the-art predictors with ACC values of 98.78%, 98.60%, 97.98%, 98.24% and 98.00% on Enzyme, Ion Channels (IC), GPCR, Nuclear Receptors (NR) and Kuang's datasets. Therefore, the accurate prediction performance of DNN-DTIs makes it a favored choice for contributing to the study of DTIs, especially drug repositioning.

Temporary Ligation of the Bilateral Uterine Arteries During Laparoscopy Combined with Hysteroscopy in the Treatment of Caesarean Scar Pregnancy: Experience at a Chinese Teaching Hospital.

PURPOSE: This study aimed to investigate the clinical efficacy of temporary ligation of the bilateral uterine arteries during laparoscopy combined with hysteroscopy in the treatment of caesarean scar pregnancy (CSP). PATIENTS AND METHODS: This study was a retrospective analysis of 83 patients who had initially undergone laparoscopy combined with hysteroscopy for CSP between 2012 and 2018 at Xiamen Women and Children's Hospital. Patients were assigned to the ligation group or the no ligation group according to whether they underwent temporary ligation of the bilateral uterine arteries. Factors extracted from the database included general preoperative information, surgical indicators (intraoperative blood loss, operation time, and blood transfusion), postoperative recovery indicators (ß-hCG on day 3 after surgery, time to ß-hCG normalization), and postoperative complications (decrease in menstrual bleeding, alteration in the menstrual cycle) and were compared between the two groups. RESULTS: The intraoperative blood loss of patients in the ligation group was significantly less than that of patients in the no ligation group (P=0.027), especially in patients with higher serum ß-hCG level (P=0.030). No significant differences in the operation time, blood transfusion, decline ratio of hCG on day 3 after surgery, reduction in haemoglobin and haematocrit value, decrease in menstrual bleeding, or alteration in the menstrual cycle were observed between the two groups (P>0.05). CONCLUSION: For CSP patients, temporary ligation of the bilateral uterine arteries during laparoscopy combined with hysteroscopy achieved better clinical outcomes than laparoscopy combined with hysteroscopy without ligation with respect to intraoperative blood loss. This approach offers effective and safe surgical management for CSP in clinical practice.

Prediction of protein-protein interaction sites through eXtreme gradient boosting with kernel principal component analysis.

Predicting protein-protein interaction sites (PPI sites) can provide important clues for understanding biological activity. Using machine learning to predict PPI sites can mitigate the cost of running expensive and time-consuming biological experiments. Here we propose PPISP-XGBoost, a novel PPI sites prediction method based on eXtreme gradient boosting (XGBoost). First, the characteristic information of protein is extracted through the pseudo-position specific scoring matrix (PsePSSM), pseudo-amino acid composition (PseAAC), hydropathy index and solvent accessible surface area (ASA) under the sliding window. Next, these raw features are preprocessed to obtain more optimal representations in order to achieve better prediction. In particular, the synthetic minority oversampling technique (SMOTE) is used to circumvent class imbalance, and the kernel principal component analysis (KPCA) is applied to remove redundant characteristics. Finally, these optimal features are fed to the XGBoost classifier to identify PPI sites. Using PPISP-XGBoost, the prediction accuracy on the training dataset Dset186 reaches 85.4%, and the accuracy on the independent validation datasets Dtestset72, PDBtestset164, Dset_448 and Dset_355 reaches 85.3%, 83.9%, 85.8% and 85.4%, respectively, which all show an increase in accuracy against existing PPI sites prediction methods. These results demonstrate that the PPISP-XGBoost method can further enhance the prediction of PPI sites.