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Sustainable development based on the value-added utilization of furfural residues (FRs) is an effective way to achieve a profitable circular economy. This comprehensive work highlights the potential of FRs as precursor to prepare porous carbons for high performance supercapacitors (SCs). To improve the electrochemical performance of FR-based carbon materials, a facile route based on methanol pretreatment coupled with pre-carbonization and followed KOH activation is proposed. More defects could be obtained after methanol treatment, which is incline to optimize textural structure. The activated methanol treated FR-based carbon materials (AFRMs) possess high specific surface area (1753.5 m2 g−1), large pore volume (0.85 cm3 g−1), interconnected micro/mesoporous structure, which endow the AFRMs with good electrochemical performance in half-cell (326.1 F g−1 at 0.1 A g−1, 189.4 F g−1 at 50 A g−1 in 6 M KOH). The constructed symmetric SCs based on KOH, KOH–K3Fe(CN)6 and KOH-KI electrolyte deliver energy density up to 8.9, 9.9 and 10.6 Wh kg−1 with a capacitance retention of over 86% after 10,000 cycles. Furthermore, the self-discharge can be restrained by the addition of K3Fe(CN)6 and KI in KOH electrolyte. This study provides an effective approach for high-valued utilization of FR waste.

Pretreatment is the initial stage of lignocellulosic biorefinery process, but is limited by the time-consuming processes, harsh conditions and/or undesirable products. Herein, a mild (60 °C) and highly efficient pretreatment strategy is developed. The novel mechanocatalytical reaction system driven by fluid shear force helps to exfoliate cellulose from lignocellulose, and the heat generated by the shear process can be used to precipitate and recover the dissolved cellulose from the precooled NaOH/urea solution. The regenerated cellulose shows satisfying crystal structure (cellulose II), significantly decreased crystallinity and nearly tripled enzymolysis glucose yield. Almost 90% of lignin and hemicellulose could be rapidly separated. The separated lignin shows a nearly native structure with 64% β-O-4 linkage, which is even higher than the ball-milling lignin (60%). This research provides a theoretical guidance for the mild pretreatment of lignocellulosic biomass, which will push the application of mechanocatalytical reaction system in biorefinery processes on a large scale.

Smart artificial viruses have been successfully developed by co-assembly of de novo designed peptides with DNA, which achieved stimuli-responsibility and efficient gene transfection in cancer cells. The peptides were designed to incorporate several functional segments, including a hydrophobic aromatic segment to drive self-assembly, two or more cysteines to regulate the assemblage shape and stabilize the assembled nanostructures via forming disulfide bonds, several lysines to facilitate co-assembly with DNA and binding to cell membranes, and an enzyme-cleavable segment to introduce cancer sensitivity. The rationally designed peptides self-assembled into stable nanospheres with a uniform diameter of 10 nm, which worked as capsid-like subunits to further interact with DNA to produce hierarchical virus-mimicking structures by encapsulating DNA in the interior. Such artificial viruses can effectively protect DNA from nuclease digestion and achieve efficient genome release by enzyme-triggered structure disassembly, which ensured a high level of gene transfection in tumor cells. The system emulates very well the structural and functional properties of natural viruses from the aspects of capsid formation, genome package and gene transfection, which is highly promising for application as efficient gene vectors.

Research question : What is the expression pattern of inflammatory mRNA profiles of dehydroepiandrosterone (DHEA) plus high-fat diet (HFD)-induced polycystic ovary syndrome (PCOS) mouse model? Design : In this study, RNA sequencing was performed to investigate the mRNA expression profiles in the ovarian tissues of a DHEA plus HFD-induced PCOS mouse model. Six samples were divided into two groups (control and PCOS), with three biological replicates in each group. This was followed by hierarchical clustering, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The relative expression levels of nine inflammatory genes were validated via quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Results : A total of 436 genes were differentially expressed between the control and PCOS mice. Out of these, 137 genes were up-regulated while 299 genes were down-regulated. Gene ontology analysis indicated that differentially expressed mRNAs were associated with T cell-mediated cytotoxicity and homocysteine metabolic processes. Pathway analysis further showed that these abnormally expressed mRNAs were associated with signaling pathways, such as NF-kB signaling, tyrosine metabolism, and phenylalanine metabolism. All these pathways are involved in chronic inflammation and PCOS. Conclusion : The differentially expressed genes are potentially involved in the inflammation that is evident in PCOS, and so could serve as therapeutic options against the disease. Nevertheless, prospective studies are needed to test this hypothesis.

Coal chemical wastewater (CCW) with the features of high toxicity and poor biodegradability is a big issue in environmental remediation, posing a great threat to aquatic ecosystems and to human beings. Such complex molecular mixtures are notoriously difficult to characterize without initial physical separation. Herein, we present the 3D diffusion ordered spectroscopy (DOSY) analysis for CCW using DOSY-COSY and DOSY-HSQC methods, the advantages of this strategy have been demonstrated in the analysis of mixtures of aliphatic oxygenates and aromatic compounds, before being implemented on a genuine CCW sample in this study. The results showed that 3D DOSY is a robust and reliable tool for providing superior resolution and virtual separation of complex pollutants, and can be used as a general approach for structural elucidation.

Altered fructose tautomeric equilibria and following reverse-isomerization from fructose to glucose enabled a high lactic acid yield of 68.3 wt% over the “monolithic” Sn-beta catalyst, which is attributed to the non-thermal effect of microwave.

Poly-p-phenylene terephthamide (PPTA) is widely applied in bulletproof products and composite materials because of its high strength, high modulus, high temperature resistance and creep resistance. The PPTA molecule with highly symmetrical and regular structure is linear structure formed by the alternating connection of benzene ring and amide bond, and the amide bonds between the molecular chains form strong hydrogen bonds. Therefore, the dissolution and depolymerization of PPTA is very challenging. In this work, an efficient catalytic system was developed for the controllable degradation of waste PPTA, and the high-value added monomers terephthalic acid (TPA) and p-phenylenediamine (PPD) were recovered. The results show that the amide bonds of PPTA can be selectively cleaved by the strong Bronsted base catalysts in alcohols, especially in the NaOH/n-butanol system. Under the optimal degradation conditions (5 wt% NaOH in n-butanol, 180 °C, 6 h), the percentage degradation of PPTA is 100%, and the yields of TPA and PPD are 92.0% and 91.5%, respectively. In addition, it is found that the wettability of n-alcohols on PPTA monofilament and the addition of a small amount of water have important influences on the degradation of PPTA. The work elucidates the degradation mechanism of PPTA, and reveals the important factors affecting the depolymerization of PPTA.

Graphical abstract, The long non‐coding RNAs (lncRNAs) play critical roles in various biological processes and are associated with many diseases. Functional annotation of lncRNAs in diseases attracts great attention in understanding their etiology. However, the traditional co-expression-based analysis usually produces a significant number of false positive function assignments. It is thus crucial to develop a new approach to obtain lower false discovery rate for functional annotation of lncRNAs. Here, a novel strategy termed DAnet which combining disease associations with cis-regulatory network between lncRNAs and neighboring protein-coding genes was developed, and the performance of DAnet was systematically compared with that of the traditional differential expression-based approach. Based on a gold standard analysis of the experimentally validated lncRNAs, the proposed strategy was found to perform better in identifying the experimentally validated lncRNAs compared with the other method. Moreover, the majority of biological pathways (40%∼100%) identified by DAnet were reported to be associated with the studied diseases. In sum, the DAnet is expected to be used to identify the function of specific lncRNAs in a particular disease or multiple diseases.

Background: Two-dimensional ultrathin Ti3C2 nanosheets are increasingly being used in biomedical applications owing to their special physicochemical properties. Meanwhile, the biological effects of its exposure, especially on the reproductive system, deserve attention. However, this effect on the reproductive system has not been studied yet. Results: In the present study, we established an in vivo Ti3C2 nanosheet exposure model in mice and an in vitro Ti3C2 nanosheet exposure model in GC-1 cells. In vivo, Ti3C2 nanosheets accumulated in the testes of mice, leading to male reproductive dysfunction, including diminished sperm quantity and quality. Furthermore, they also induced elevated reactive oxygen species (ROS) and DNA damage in testis tissues and activated the DNA damage response signaling pathway (ATM/p53). In vitro, they entered the GC-1 cytoplasm and reduced cell viability. Ti3C2 nanosheets also induced elevated ROS levels and DNA double-strand breaks, activated the ATM/p53 signaling pathway, caused cell cycle arrest in the G1/G0 phase, inhibited proliferation, and increased apoptosis in GC-1 cells. Conclusions: Ti3C2 nanosheet-induced suppression of spermatogonia proliferation disrupted normal spermatogenic function, which was mediated by the ATM/p53 signaling pathway. Thus, our findings shed more lights on the mechanisms of male reproductive toxicity induced by Ti3C2 nanosheets.

BackgroundOvarian cancer (OC) is the most lethal gynecologic malignancy, yet the clinical results for OC patients are still variable. Therefore, we examined how elafin expression affects the patients’ prognoses and immunotherapy responses in OC, which may facilitate treatment selection and improve prognosis.MethodsThe elafin mRNA expression profile was downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus. Elafin’s prognostic potential and its relationship with clinical variables were investigated using Kaplan–Meier survival curves, time-dependent receiver operating characteristic curves as well as univariate and multivariate Cox regression models. As validation, protein expression in the tumor and adjacent tissues of OC patients was investigated by using immunohistochemistry (IHC). Comprehensive analyses were then conducted to explore the correlation between immune infiltration and elafin expression.ResultsA higher mRNA expression of elafin was associated with an unfavorable prognosis in TCGA cohort and was validated in GSE31245 and IHC. Moreover, elafin was indicated as an independent risk factor for OC. A significantly higher protein expression of elafin was detected in the adjacent tissues of OC patients with shorter overall survival (OS). The immune-related pathways were mainly enriched in the high-elafin-mRNA-expression group. However, the mRNA expression of elafin was favorably correlated with indicators of the immune filtration and immunotherapy response, which also proved better immunotherapy outcomes.ConclusionThe high elafin expression was associated with an unfavorable OS, while it also indicated better immunotherapy responses. Thus, the detection of elafin is beneficial to diagnosis and treatment selection.

Numerous studies have suggested the possibility of explaining the etiology of metabolic syndrome through DNA methylation. DNA methyltransferase 3B (DNMT3B) plays an important role in de novo DNA methylation. There was an alteration in maternal (F0) endometrial function, which might lead to growth and developmental disorder in offspring (F1). In this study, we investigated the effect of maternal endometrial DNMT3B deficiency on the metabolism in offspring. We constructed endometrial DNMT3B conditional knockout female mice (cKO) which were mated with normal C57BL/6 male mice to obtain the F1 generation. Further, to study the development of these offspring, we observed them at three different life stages which included the 6-week-old juvenile, 9-week-old sub-adult and 12-week-old adult. Follow the detection of a range of metabolism-related indicators, we found that in the cKO F1 generation, liver triglyceride level was significantly elevated in 9-week-old female mice, lipid droplet deposition was significantly increased in 9-week-old and 12-week-old mice, and the expression of lipid metabolism key factors in the liver was markedly decreased except of 6-week-old male mice. These results indicate that maternal endometrial DNMT3B conditional knockout leads to imbalance in hepatic metabolism in F1 generation, the mechanism of which requires further discussion.

As the frontier in heterogeneous catalyst, a monomer and positively charged active sites in the single-atom catalyst (SAC), anchored by high electronegative N, O, S, P, etc., atoms, may not be active for the multispecies (O2, substrates, intermediates, solvent etc.) involved liquid-phase aerobic oxidation. Here, with catalytic, aerobic oxidation of 5-hydroxymethylfurfural as an example, Pt SAC (Pt1-N4) was synthesized and tested first. With commercial Pt/C (Pt loading of 5 wt %) as a benchmark, 2,5-furandicarboxylic acid (FDCA) yield of 97.6% was obtained. Pt SAC (0.56 wt %) gave a much lower FDCA yield (28.8%). By changing the coordination atoms from highly electronegative N to low electronegative Co atoms, the prepared Pt single-atom alloy (SAA, Pt1-Co3) catalyst with ultralow Pt loading (0.06 wt %) gave a much high FDCA yield (99.6%). Density functional theory (DFT) calculations indicated that positively charged Pt sites (+0.712e) in Pt1-N4 almost lost the capability for oxygen adsorption and activation, as well as the adsorption for the key intermediate. In Pt1-Co3 SAA, the central negatively charged Pt atom (-0.446e) facilitated the adsorption of the key intermediate; meanwhile, the nearby Co atoms around the Pt atom constituted the O2-preferred adsorption/activation sites. This work shows the difference between the SAC with NPs and the SAA during liquid-phase oxidation of HMF and gives a useful guide in the future single-atom catalyst design in other related reactions.

Introduction Trophoblast development is a crucial event in placentation and pregnancy complications but its underlying mechanisms remain unclear. Thus, we aimed at investigating the role of DiO2 in trophoblast cell line decisions and assessing its placental villous expression in early recurrent miscarriage (ERM) patients. Methods The placental villous expression of DiO2 was determined with immunofluorescence. Cell proliferation was measured with the CCK8 kit while cell-cycle and apoptosis were studied with flow-cytometry. Cell migration and invasion were measured with wound-healing and transwell assays, respectively. Gene expression was then assessed with RT-qPCR and western blotting. Results DiO2 is expressed in the CTB, PCT, DCT and STB of the placenta. Its overexpression arrested trophoblast cell line proliferation at the G1 phase of the cell-cycle by downregulating cyclin-D1 and PCNA, while promoting apoptosis via increased caspase-3 activity and inhibition of the AKT and ERK1/2 signaling pathways. Also, it augmented trophoblast cell line migration and invasion via the upregulation of N-cadherin, vimentin, fascin-1, twist-1 and other epithelial-mesenchymal transition genes. DiO2 knockdown elicited the opposite effects. Surprisingly, each of these effects of DiO2 manipulation was not mediated by thyroid hormone metabolism. Assessment of the ERM placental villi revealed a downregulation of DiO2, N-cadherin, vimentin, fascin-1 and twist-1. The expression of E-cadherin remained unchanged in these placentae. Discussion During placentation, DiO2 may inhibit trophoblast proliferation while facilitating their differentiation into an invasive phenotype; and that its downregulation may contribute to the shallow trophoblast invasion that precedes ERM. Hence, DiO2 is a potential therapeutic target against ERM.

The acidity and basicity of the solvents can influence the reaction outcome notably, and hence the precise measurement of pH is important for reaction. However, not all the pH values of organic solvents can be determined with a classic pH meter straightly. In this research, the acidity and basicity of environmentally friendly green solvents, such as ZnCl2 molten salt hydrate, ionic liquids (ILs) and deep eutectic solvents (DESs), were characterized by 31P and 1H NMR spectroscopy using trimethylphosphine oxide (TMPO) and pyrrole as probe molecules at 298 K. For the ZnCl2 molten salt hydrate, the acidic strength of the ZnCl2 molten salt hydrate increased with the concentration of ZnCl2. By using the 1H-pyrrole NMR approach, it was found that the base strength of amino acid-based ILs follows the order: [Ch][Lys] > [Ch][His].

Numerous studies have suggested the possibility of explaining the etiology of metabolic syndrome through DNA methylation. DNA methyltransferase 3B (DNMT3B) plays an important role in

5-Chloro-2-pentanone (5C2P) and its derivatives are widely utilized in the pharmaceutical and agrochemical industry. A new catalytic approach was proposed to convert acetyl-n-propanol to 5C2P using bis(trichloromethyl)carbonate (triphosgene, BTC) as the efficient chlorine source. Various qualitative and quantitative nuclear magnetic resonance techniques (1H, 13C NMR) especially 1D selective gradient total correlation spectroscopy (Sel-TOCSY) and 2D heteronuclear single quantum correlation (1H-13C HSQC) were used in the process. The reaction conditions, such as temperature, time, mole ratio, solvent as well as initiator were optimized. Experiment results showed that the yield of 5C2P reached a maximum of 97.93% in 1,2-dichloroethane at 80°C after 2 h under the initiation of N,N-dimethylacetamide (DMAC), and the optimal molar ratio of acetyl-n-propanol to BTC was 1:0.4. The reaction mechanism was proposed and confirmed accordingly. Interestingly, an intermediate product of 1-(dimethylamino)ethyl carbonochloridate was observed and its chemical structure was characterized by both Sel-TOCSY and 1H-13C HSQC. This study enriched the catalytic reaction ways for the preparation of 5C2P.

Existing evidence suggests that adverse pregnancy outcomes are closely related to dietary factors. Folate plays an important role in neural tube formation and fetal growth, folate deficiency is a major risk factor of birth defects. Our early studies showed that folate deficiency could impair enddecidualization, however, the mechanism is still unclear. Dysfunctional autophagy is associated with many diseases. Here, we aimed to evaluate the adverse effect of folate deficiency on endometrial decidualization, with a particular focus on endometrial cell autophagy. Mice were fed with no folate diet in vivo and the mouse endometrial stromal cell was cultured in a folate-free medium in vitro. The decrease of the number of endometrial autophagosomes and the protein expressions of autophagy in the folate-deficient group indicated that autophagosome formation, autophagosome-lysosome fusion, and lysosomal degradation were inhibited. Autophagic flux examination using mCherry-GFP-LC3 transfection showed that the fusion of autophagosomes with lysosomes was inhibited by folate deficiency. Autophagy inducer rapamycin could reverse the impairment of folate deficiency on endometrial decidualization. Moreover, folate deficiency could reduce autophagy by disrupting AMPK/mTOR signaling, resulting in aberrant endometrial decidualization and adverse pregnancy outcomes. Further co-immunoprecipitation examination showed that decidual marker protein Hoxa10 could interact with autophagic marker protein Cathepsin L, and the interaction was notably reduced by folate deficiency. In conclusion, AMPK/mTOR downregulated autophagy was essential for aberrant endometrial decidualization in early pregnant mice, which could result in adverse pregnancy outcomes. This provided some new clues for understanding the causal mechanisms of birth defects induced by folate deficiency.

Ternary deep eutectic solvents (TDESs) comprising choline chloride (ChCl), glycerol and l -arginine were synthesized as catalysts and solvents for the conversion of d -glucosamine (GlcNH2) into deoxyfructosazine (DOF). The interactions between these three components in the prepared TDESs were studied by 1H-, 35Cl-NMR spectra and 1H diffusion-ordered spectroscopy (DOSY) measurements. The chemical shift changes of active hydrogen in the 1H-NMR spectra of TDES system and widening of signals in the 35Cl-NMR spectra confirmed the hydrogen bonding interaction between the components, which was further supported by the decrease of diffusion coefficients (D) of the TDES components according to 1H DOSY measurements. The influences of reaction temperature and l -arginine content in the TDESs on the yield of DOF were also studied. The experimental results have shown that when the molar ratio of ChCl, glycerol, and l -arginine was 1:2:0.1, DOF was the major product with a yield of 22.6% at 90 °C for 120 min. The chemical shift titration indicated that the carboxyl group of l -arginine in the TDES is the catalytical active site, so the mechanism of the catalytic reaction between GlcNH2 and the TDES was proposed. Moreover, a reaction intermediate, dihydrofructosazine, was identified in the self-condensation reaction of GlcNH2 by an in situ 1H NMR technique.

Decidualization of endometrial stromal cells (ESCs) accompanied with embryo implantation is a key process in mammalian reproduction. Evidence suggests that maintenance of decidual cells function is essential. As a critical part in post-transcriptional gene regulation, microRNAs (miRNAs/miR) have been confirmed to be involved in decidualization. However, whether microRNAs regulate decidual cells function has not been reported. Aiming to clarify the role and potential mechanism of miRNAs in decidual cells, artificial induced decidualization model in mice was established. There are 94 differentially expressed miRNAs (≥two-fold change) between decidualized and non-decidualized tissues, including 60 upregulated and 34 downregulated miRNAs. Of the differentially expressed miRNAs, mmu-miR-21a is up-regulated. RT-qPCR also confirmed the up-regulation of mmu-miR-21a following decidualization in vivo and in vitro, and bioinformatic analysis and luciferase activity assay revealed Pdcd4 to be the target gene of mmu-miR-21a. Inhibition of mmu-miR-21a restrained secretory function of decidual cells induced by mESCs, accompanied with increase of Pdcd4 expression and resulted in the increase of cell apoptosis. In addition, we also determined the expression of hsa-miR-21 and Pdcd4 in human proliferative endometrial tissues and decidua tissues. hsa-miR-21 showed higher expression in human decidua tissues compared with proliferative endometrial tissues, while expression of Pdcd4 was contrary to that of hsa-miR-21. Similarly, cell apoptosis increased significantly in human endometrial stromal cell line in response to inhibition of hsa-miR-21. Collectively, we conclude that mmu-miR-21a/hsa-miR-21 may play a key role in regulating the function of decidual cells by inhibiting cell apoptosis through targeting Pdcd4.

Acidic deep eutectic solvents (ADESs) have been utilized in various applications. Clearly, it is crucial to obtain acidity information that could reveal the relationship with performance. However, appropriate methods for measuring acidity are limited. Herein, we developed two promising approaches (without additional solvents) to identify and characterize both Lewis and Brønsted acidities by applying acetonitrile as an infrared probe and trimethylphosphine oxide (TMPO) as a nuclear magnetic resonance (NMR) probe. The acetonitrile IR approach is suitable for measuring the acidity of Lewis ADESs by monitoring the peak of

Polycystic ovary syndrome (PCOS) exerts negative effects on females of childbearing age. It is important to identify more suitable models for fundamental research on PCOS. We evaluated animal models from a novel perspective with the aim of helping researchers select the best model for PCOS. RNA sequencing was performed to investigate the mRNA expression profiles in the ovarian tissues of mice with dehydroepiandrosterone (DHEA) plus high-fat diet (HFD)-induced PCOS. Meanwhile, 14 datasets were obtained from the Gene Expression Omnibus (GEO), including eight studies on humans, three on rats and three on mice, and genes associated with PCOS were obtained from the PCOSKB website. We compared the consistency of each animal model and human PCOS in terms of DEGs and pathway enrichment analysis results. There were 239 DEGs shared between prenatally androgenized (PNA) mice and PCOS patients. Moreover, 1113 genes associated with PCOS from the PCOSKB website were identified among the DEGs of PNA mice. A total of 134 GO and KEGG pathways were shared between PNA mice and PCOS patients. These findings suggest that the PNA mouse model is the best animal model to simulate PCOS.

The wide application of melamine–formaldehyde resins (MFRs) in the food industry aggravates plastic pollution problems. Recycling of the waste MFRs remains a big challenge due to its compact structure. Herein, a high MFR degradation ratio of ca. 84 wt% was achieved under mild conditions (180 °C) in a methanesulfonic acid (MSA)–tetrahydrofuran (THF)–H2O system with cyanuric acid as the main degradation product. The SEM results showed that the degradation of MFRs followed different reaction mechanisms when H2O and THF were applied as solvents, respectively. The combination of the two solvents showed an obvious synergistic effect for the degradation of MFRs. The degradation experimental results with melamine as the model intermediate indicated that the degradation of MFRs proceeded via the selective cleavage of the sp2C–sp3N and sp3C–sp3N bonds to recover valuable C and N alternated-aromatic ring (CNAR) units, followed by their transformation into a valuable chemical of cyanuric acid.

A series of poly(ionic liquid)s (PILs) based on 1-vinyl-3-(3-sulfopropyl)imidazolium (VSpIm) and sodium p-styrenesulfonate (NaSS) have been successfully synthesized and fully characterized. The swelling behaviours of the PILs in 18 solvents with a wide range of Hansen solubility parameters (δT) were investigated. The PILs exhibited distinct swelling properties in solvents with δT > 24.5 MPa1/2, such as water, formamide and methanol. The molar swelling ratio (QM), which represented the swelling ability of the PILs in solvent, was linearly positively correlated with the δT value. Moreover, the enrichment behaviours of the PILs in various mixed solvents were also studied. In water/solvent and formamide/solvent monophasic mixed solvents, the enrichment factors of the PILs to water and formamide were up to 39.82 (water/THF) and 17.69 (formamide/THF), respectively. The enrichment factor of the PILs to water (or formamide) was linearly positively correlated with the difference between δT (water) (or δT (formamide)) and δT (solvent). The excellent swelling and enrichment properties of the PILs in solvents were attributed to the strong interactions between the PILs and solvent molecules, especially the hydrogen-bonding interactions, which was supported by nuclear magnetic resonance (NMR) spectroscopy. Furthermore, a PIL was used as a catalyst for the hydration of alkyne and found that it had higher catalytic activity than those of both heterogeneous and homogeneous catalysts.

Background: Recent studies have demonstrated that endometrial DNA methylation is essential for embryo implantation during early pregnancy. Dnmt3a is one of the key enzymes for DNA methylation and could be expressed in the endometrium regularly at this stage. Objective and Methods: In this study, we conditionally ablated uterine Dnmt3a using progesterone receptor-cre (Pgrcre) to define the physiological roles of Dnmt3a in female reproduction. Results: We found that ovarian function was not apparently altered and the number of embryo implantation sites in Dnmt3aloxP/loxP Pgrcre/+ (cKO) was not significantly varied during early pregnancy. Western blotting and immunohistochemistry results showed no difference in expression or location of the estrogen receptor α (ERα) and mucin 1 (Muc1), the marker of uterine receptivity. Although the expression of decidual markers, matrix metalloproteinase-2 (Mmp2), matrix metalloproteinase-9(Mmp9), and bone morphogenetic protein-2 (Bmp2), was slightly decreased in Dnmt3a cKO females, the gross morphology of mice uteri during decidualization was not significantly influenced. In the artificial induction of the decidualization model, there was also no remarkable difference in visually observed morphology or uterine weight in Dnmt3a cKO. Lastly, a continuous breeding study showed that the fertility of Dnmt3a cKO female mice was not strikingly altered. Conclusion: Overall, these results demonstrated that although some decidual markers are expressed abnormally, conditional knockout of Dnmt3a in the uterus did not significantly affect the endometrial function during embryo implantation; the embryo could implant into the endometrium normally.

Placentation is a major determinant of the success of pregnancy. It is regulated by several factors such as cell adhesion molecules, tight junctions, and gap junctions. The cell adhesion molecules are integrins, cadherins, immunoglobulins, nectins, and selectins. The tight junctions are composed of claudins, occludin, and junction adhesion molecule proteins while the gap junctions are composed of connexins of varying molecular weights. During placentation, some of these molecules regulate trophoblast proliferation, trophoblast fusion, trophoblast migration, trophoblast invasion, trophoblast-endothelium adhesion, glandular remodeling, and spiral artery remodeling. There is a dysregulated placental expression of some of these molecules during obstetric complications. We have, hereby, indicated the expression patterns of the subunits of each of these molecules in the various trophoblast subtypes and in the decidua, and have highlighted their involvement in physiological and pathological placentation. The available evidence points to the relevance of these molecules as distinguishing markers of the various trophoblast lineages and as potential therapeutic targets in the management of malplacentation-mediated diseases.

Besides the environmental factors having tremendous impacts on the composition of microbial community, the host factors have recently gained extensive attentions on their roles in shaping human microbiota. There are two major types of host factors: host genetic factors (HGFs) and host immune factors (HIFs). These factors of each type are essential for defining the chemical and physical landscapes inhabited by microbiota, and the collective consideration of both types have great implication to serve comprehensive health management. However, no database was available to provide the comprehensive factors of both types. Herein, a database entitled ‘Host Genetic and Immune Factors Shaping Human Microbiota (GIMICA)’ was constructed. Based on the 4257 microbes confirmed to inhabit nine sites of human body, 2851 HGFs (1368 single nucleotide polymorphisms (SNPs), 186 copy number variations (CNVs), and 1297 non-coding ribonucleic acids (RNAs)) modulating the expression of 370 microbes were collected, and 549 HIFs (126 lymphocytes and phagocytes, 387 immune proteins, and 36 immune pathways) regulating the abundance of 455 microbes were also provided. All in all, GIMICA enabled the collective consideration not only between different types of host factor but also between the host and environmental ones, which is freely accessible without login requirement at: https://idrblab.org/gimica/, Graphical Abstract Graphical AbstractGIMICA is unique in: (i) providing both host genetic and immune factors shaping human microbiota and (ii) enabling collective consideration not only among various host factors but also between the host and environmental ones.

Ephrins are ligands of Eph receptors (Ephs); both of which are sorted into two classes, A and B. There are five types of ephrin-As (ephrin-A1–5) and three types of ephrin-Bs (ephrin-B1–3). Also, there are 10 types of EphAs (EphA1–10) and six types of EphBs (EphB1–6). Binding of ephrins to the Eph receptors activates signaling cascades that regulate several biological processes such as cellular proliferation, differentiation, migration, angiogenesis, and vascular remodeling. Clarification of their roles in the female reproductive system is crucial to understanding the physiology and pathology of this system. Such knowledge will also create awareness regarding the importance of these molecules in diagnostic, prognostic, and therapeutic medicine. Hence, we have discussed the involvement of these molecules in the physiological and pathological events that occur within the female reproductive system. The evidence so far suggests that the ephrins and the Eph receptors modulate folliculogenesis, ovulation, embryo transport, implantation, and placentation. Abnormal expression of some of these molecules is associated with polycystic ovarian syndrome, ovarian cancer, tubal pregnancy, endometrial cancer, uterine leiomyoma (fibroids), cervical cancer, and preeclampsia, suggesting the need to utilize these molecules in the clinical setting. To enhance a quick development of this gradually emerging field in female reproductive medicine, we have highlighted some “gaps in knowledge” that need prospective investigation.

Circular RNAs (circRNAs) are a novel class of endogenous noncoding RNAs that play important roles in gene expression regulation. This study aimed to evaluate the potential role of circRNAs in decidual tissue of patients with early recurrent miscarriage (RM). We constructed circRNA expression profiles in decidual tissue using microarray data. A total of 123 differentially expressed circRNAs, including 78 upregulated and 45 downregulated circRNAs were detected in the early RM group compared with the control group (P

Autophagy has been reported to play a dual "double-edged sword" role in the occurrence and development of Alzheimer’s disease (AD). To assess the relationship between AD and autophagy, the dynamic changes of autophagic flux in the brain of postmortem AD patients, animal models and cell models were studied. The results showed that autophagosomes (APs) accumulation and expression of lysosomal markers were decreased in the brains of AD patients. In the brain of APP/PS1 double transgenic mice, APs did not accumulate before the formation of SPs but accumulated along with the deposition of SPs, as well as the level of lysosomal markers cathepsin B and Lamp1 protein decreased significantly. In the brains of APP/PS1/LC3 triple - transgenic mice, the number of APs increased with age, but the number of ALs did not increase accordingly. The activation of autophagy is mainly due to the increase in Aβ rather than the overexpression of mutated APP gene. However, both the treatment with exogenous Aβ25-35 and the mutation of the endogenous APP gene blocked the fusion of APs with lysosomes and decreased lysosomal functioning in AD model cells, which may be the main mechanism of autophagy dysregulation in AD.

Embryo implantation is essential for normal pregnancy. Decidualization is known to facilitate embryo implantation and maintain pregnancy. Uterine stromal cells undergo transformation into decidual cells after embryo attachment to the endometrium. Pyruvate kinase M2 (PKM2) is a rate limiting enzyme in the glycolysis process which catalyzes phosphoenolpyruvic acid into pyruvate. However, little is known regarding the role of PKM2 during endometrial decidualization. In this study, PKM2 was found to be mainly located in the uterine glandular epithelium and luminal epithelium on day 1 and day 4 of pregnancy and strongly expressed in the decidual zone after embryo implantation. PKM2 was dramatically increased with the onset of decidualization. Upon further exploration, PKM2 was found to be more highly expressed at the implantation sites than at the inter-implantation sites on days 5 to 7 of pregnancy. PKM2 expression was also significantly increased after artificial decidualization both in vivo and in vitro. After PKM2 expression was knocked down by siRNA, the number of embryo implantation sites in mice on day 7 of pregnancy was significantly reduced, and the decidualization markers BMP2 and Hoxa10 were also obviously downregulated in vivo and in vitro. Downregulated PKM2 could also compromise cell proliferation in primary endometrial stromal cells and in Ishikawa cells. The migration rate of Ishikawa cells was also obviously suppressed by si-PKM2 according to the wound healing assay. In conclusion, PKM2 might play an important role in decidualization during early pregnancy, and cell proliferation might be one pathway for PKM2 regulated decidualization.

Fischer-Tropsch (F-T) process is an important synthesis route to acquire clean liquid fuels through modern coal chemical industry, which converts syngas (CO and H2) into hydrocarbon, and also generates oxygenates discharged as the F-T waste-water. These oxygen-containing compounds in F-T waste-water have the similar molecular weight and some are even isomers of each other. Hence, it is necessary to develop rapid and efficient analysis tools to obtain identification and quantitative information of the F-T waste-water. The pure shift NMR techniques provided only chemical shift information in one-dimension 1H NMR spectra, without homonuclear JH-H coupling. In this work, we tested and compared three pure shift NMR techniques (including Zangger-Sterk, PSYCHE and TSE-PSYCHE methods) in the analysis of two F-T waste-water model mixtures, genuine waste-water and two alcohol isomer mixtures. The results show that JH-H coupling multiplicities are collapsed into singlets corresponding to individual chemically distinct protons of the compound. For some severely overlapped signals in the pure shift NMR spectra, the chemical shift selective filters with TOCSY (CSSF-TOCSY) experiments were conducted to assist the signal assignment. Thus, pure shift NMR approaches can identify most signals of components, and CSSF-TOCSY can extract the signal of a specific compound. The combination of these two NMR techniques offers a powerful tool to analyze the F-T waste-water or other complex mixtures including isomer mixtures.

The actin cytoskeleton is extremely dynamic and supports diverse cellular functions in many physiological and pathological processes, including tumorigenesis. However, the mechanisms that regulate the actin-related protein 2/3 (ARP2/3) complex and thereby promote actin polymerization and organization in cancer cells are not well-understood. We previously implicated the proline-rich 11 (PRR11) protein in lung cancer development. In this study, using immunofluorescence staining, actin polymerization assays, and siRNA-mediated gene silencing, we uncovered that cytoplasmic PRR11 is involved in F-actin polymerization and organization. We found that dysregulation of PRR11 expression results in F-actin rearrangement and nuclear instability in non-small cell lung cancer cells. Results from molecular mechanistic experiments indicated that PRR11 associates with and recruits the ARP2/3 complex, facilitates F-actin polymerization, and thereby disrupts the F-actin cytoskeleton, leading to abnormal nuclear lamina assembly and chromatin reorganization. Inhibition of the ARP2/3 complex activity abolished irregular F-actin polymerization, lamina assembly, and chromatin reorganization due to PRR11 overexpression. Notably, experiments with truncated PRR11 variants revealed that PRR11 regulates F-actin through different regions. We found that deletion of either the N or C terminus of PRR11 abrogates its effects on F-actin polymerization and nuclear instability and that deletion of amino acid residues 100–184 or 100–200 strongly induces an F-actin structure called the actin comet tail, not observed with WT PRR11. Our findings indicate that cytoplasmic PRR11 plays an essential role in regulating F-actin assembly and nuclear stability by recruiting the ARP2/3 complex in human non-small cell lung carcinoma cells.

Cigarette smoke significantly induces oxidative stress, resulting in cardiovascular disease. NRF2, a well-known antioxidative stress response factor, is generally considered to play protective roles in cardiovascular dysfunction triggered by oxidative stress. Interestingly, recent studies reported adverse effects of NRF2 on the cardiovascular system. These unfavourable pathogenic effects of NRF2 need to be further investigated. Our work shows that cigarette smoke extract (CSE)-induced oxidative stress disturbs fibronectin (FN) assembly during angiogenesis. Furthermore, this effect largely depends on hyperactive NRF2-STAT3 signalling, which consequently promotes abnormal FN deposition. Consistently, disruption of this pathway by inhibiting NRF2 or STAT3 prevents CSE-induced FN disorganization and vasculature disruption in human umbilical vein endothelial cells or zebrafish. Taken together, these findings demonstrate the cardiovascular dysfunction caused by CSE from a novel perspective that NRF2-dependent signalling engages in FN disorganization.

Background Breast cancer is the most common malignancy in women worldwide, which seriously threatens women's physical and mental health, but currently, there is no classification method for tumor samples based on gene expression profiles for faster breast cancer diagnosis. The study aimed to establish a novel genetic model to distinguish breast cancer patients from the normal population.Results We utilized published expression profiles of breast cancer patients (GSE15852, GSE70905) to identify potential predictive gene panels. A total of 7 differentially expressed genes were identified as predictors. Random forest algorithm and artificial neural network were applied to screen the predictive features and build a model to predict breast cancer. In parallel, we validated this prediction model using expression profiling of a completely independent set of breast cancer patients(GSE70947). The new model was successfully built based on the molecular prognostic scoring system and showed significant predictive value in the training group (AUC = 0.991), which was simultaneously validated in an independent dataset (AUC = 0.817).Conclusions Random forest algorithm combined with artificial neural network successfully constructed a prediction model for breast cancer. The new model can predict breast cancer patients, which is helpful for the diagnosis of breast cancer in the clinic.

Benzo(a)pyrene (BaP) is a well-known environmental endocrine pollutant, which has ovarian toxicity in mammals. Ovarian corpus luteum (CL), as the main source of progesterone synthesis in early pregnant female, requires a large number of mitochondria for energy supply. We previously demonstrated that BaP and its metabolite benzo(a)pyren-7, 8-dihydrodiol-9, 10-epoxide (BPDE) inhibited the ovarian melatonin receptors (MTRs) expression and decreased the levels of estrogen and progesterone during early pregnancy in mice. Emerging researches show that MTRs also exist on mitochondrial membrane and participate in the regulation of mitochondrial function. However, the relationship between BaP, MTRs on mitochondrial membrane and mitochondrial function remains unknown. Consequently, this study focuses on the effect and potential mechanism of BaP on ovarian luteal mitochondrial function during early pregnancy. We found that BaP and its metabolite BPDE decreased MTRs in early pregnant CL and luteinized KGN cells, especially in mitochondria. Furthermore, BaP or BPDE up-regulated the expression of SIRT3, Mfn2 and Drp-1, damaged mitochondrial morphology and decreased the MMP and the ATP levels, thereby causing mitochondrial dysfunction. Notably, activation of the MTRs on mitochondrial membrane by MTRs agonist ramelteon partially alleviated BPDE-induced up-regulation of SIRT3, Mfn2 and Drp-1, reduced mitochondrial fragmentation and enhanced the MMP and the ATP levels, thus restoring the expression of steroid rate-limiting enzymes. Together, these findings firstly proved that BaP and BPDE down-regulate MTRs on mitochondrial membrane, and further injure mitochondrial function in early pregnant rats' CL, which provides a new insight for understanding the exact mechanism of the BaP-induced ovarian toxicity.

AimRecurrent miscarriage (RM) is associated with numerous clinical factors. However, some RM occurred without specific factors. It has been revealed that some molecules such as hormones, miRNAs, and transcription factors are involved in RM by regulating proliferation, apoptosis, etc. However, the mechanism of RM has yet to be identified clearly. Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs that often act as sponges for miRNAs or binds to proteins involved in biological processes. However, the functional role of circRNAs in the uterine decidua of patients with early RM is still unclear. In this study, we aimed to investigate the mechanisms of circ-CYP24A1 in RM.MethodsThe Dual-Luciferase Activity Assay was designed to analyze the bonding between circ-CYP24A1 and miR-224, and miR-224 and prolactin receptor (PRLR) mRNA 3′UTR. In situ hybridization (ISH) and immunohistochemistry (IHC) were used to observe the expression of circ-CYP24A1 and PRLR in the decidua. Rescue experiments were performed to investigate the regulating effects of circ-CYP24A1, miR-224, and PRLR. Western blotting was conducted to test the expression level of PRLR. The proliferation and apoptosis-related markers in Ishikawa cells were analyzed using CCK8, immunofluorescence staining, and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay.ResultsIn this study, based on the microarray analysis data, we identified a high level of circ-CYP24A1 and PRLR in the decidua of patients with early RM. Based on the bioinformatics prediction, the binding relationship between circ-CYP24A1 and miR-224, as well as miR-224 and PRLR, were verified. Functional experiments demonstrated that circ-CYP24A1 regulated proliferation and apoptosis by binding to and inhibiting miR-224, resulting in increased PRLR expression. Taken together, this study provides new insights into the mechanism of RM.ConclusionIn this study, we found that circ-CYP24A1 plays a role in RM by impairing the balance of cell proliferation and apoptosis by sponging miR-224, thereby regulating PRLR.