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The environmental pollutant Benzo(a)pyrene (BaP) has an adverse effect on the reproductive performance of mammals. We previously showed that BaP treatment during early pregnancy damages endometrial morphology and impairs embryo implantation. Endometrial decidualization at the implantation site (IS) after embryo implantation is crucial for pregnancy maintenance and placental development. The balance between proliferation and differentiation in endometrial stromal cells (ESCs) is a crucial event of decidualization, which is regulated by the cell cycle. Here, we report that abnormal decidualization caused by BaP is associated with cell cycle disturbance of stromal cells. The mice in the treatment group were gavaged with 0.2 mg/kg/day BaP from day 1–8 of pregnancy, while those in control were gavaged with corn oil in parallel. BaP damaged the decidualization of ESCs and reduced the number of polyploid cells. Meanwhile, BaP up-regulated the expression of Ki67 and PCNA, affecting the differentiation of stromal cells. The cell cycle progression analysis during decidualization in vivo and in vitro showed that BaP induced polyploid cells deficiency with enhanced expressions of CyclinA(E)/CDK2, CyclinD/CDK4 and CyclinB/CDK1, which promote the transformation of cells from G 1 to S phase and simultaneously activate the G 2 /M phase. The above results indicated that BaP exposure accelerates cell cycle progression, promotes ESC proliferation, inhibits differentiation, and impedes proper decidualization and polyploidy development. Thus, the imbalance of ESC proliferation and differentiation would be an important mechanism for BaP-induced defective decidualization. [Display omitted] • BaP impedes polyploidy development and impacts the decidualization of stromal cells. • BaP promotes proliferation and inhibits differentiation of decidual stromal cells. • BaP accelerates the G 1 /S and G 2 /M phase in mice stromal cells during decidualization. [ABSTRACT FROM AUTHOR]

Low temperature 1H- and 19F-DOSY have been used for analyzing reactive intermediates in glycosylation reactions, where a glycosyl trichloroacetimidate donor has been activated using different catalysts. The DOSY protocols have been optimized for low temperature experiments and provided new insight into acid catalyzed glycosylation chemistry. From the study a new glycosylation intermediate was characterized. [ABSTRACT FROM AUTHOR]

Benzo(a)pyrene (BaP) is a persistent organic pollutant (POP) that is a serious threat to human health. Numerous studies have shown that BaP causes adverse effects in pregnancy, but the mechanism remains unclear. The moderate invasion of trophoblast cells into the endometrium is an important factor during successful embryo implantation. The aim of this study was to investigate the effect and mechanism of BaP on the invasion and migration of trophoblast cells. HTR-8/SVneo cells were treated with different concentrations (1, 5, 10, 25, 50 and 100 μM) of BaP. The invasion and migration of HTR-8/SVneo cells were observed after BaP treatment. The protein levels related to migration and invasion was detected by Western blot. The results confirmed that BaP inhibits the migration and invasion of extravillous trophoblast HTR-8/SVneo cells. Further investigations indicated that the protein levels of MMP-2, MMP-9 and E-cadherin in HTR-8/SVneo cells were changed by BaP treatment. Moreover, the data demonstrated that BaP activated the MAPK signaling pathway. Pretreatment with specific inhibitors of MAPK rescued BaP-induced change in the migration and invasion of HTR-8/SVneo cells. Taken together, our results indicated that BaP inhibits invasion and the migration of HTR-8/SVneo cells, which might cause a failure in early pregnancy. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The dehydration of inulin biomass to the platform chemicals, 5-hydroxymethylfurfural (5-HMF) and levulinic acid (LA), in ZnCl 2 molten salt hydrate medium was investigated. The influence of the Lewis acid catalyst, SnCl 4 , on the product distribution was examined. An in situ 1 H NMR technique was employed to follow the reaction at the molecular level. The experimental results revealed that only 5-HMF was obtained from degradation of inulin biomass in ZnCl 2 molten salt hydrate medium, while the LA was gradually becoming the main product when the reaction temperature was increased in the presence of the Lewis acid catalyst SnCl 4 . In situ NMR spectroscopy could monitor the reaction and give valuable insight. [ABSTRACT FROM AUTHOR]

Objective: This study explored the association between an Alu I polymorphism at position 1,377 of the calcitonin receptor (CTR) gene and endemic fluorosis. Subjects and Methods: A case-control study of 321 participants was conducted in regions with high fluorosis rates (Wushan and Fengjie counties) and those without high fluorosis rates (Yubei Qu county; termed nonfluorosis areas) in Chongqing, China. The participants were divided into three groups: the fluorosis group (FG) from areas with high fluoride exposure (121), the nonfluorosis group (NFG) from areas with high fluoride exposure (130), and a control group (CG) from areas with no excessive fluoride exposure (70). An Alu I polymorphism in the CTR gene was genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis. Results: The genotype distributions within each group were as follows: CC 60.33% (73/121), CT 30.58% (37/121) and TT 9.09% (11/121) for the FG; CC 74.62% (97/130), CT 21.54% (28/130) and TT 3.85% (5/130) for the NFG, and CC 68.57% (48/70), CT 31.43% (22/70) and TT 0% (0/70) for the CG. Significant differences in Alu I genotypes were observed among the groups (χ2 = 12.317, υ = 4, p = 0.015). Allele frequencies of CTR genotypes differed significantly among the groups (χ2 = 8.859, υ = 2, p = 0.012): C 75.62% (183/242) and T 24.38% (59/242) for the FG, C 85.38% (222/260) and T 14.62% (38/260) for the NFG, and C 84.29% (118/140) and T 15.71% (22/140) for the CG. Conclusion: An association between fluorosis and the Alu I polymorphism in the CTR gene was observed in fluoride-exposed populations. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Embryo implantation is a complex process requiring reciprocal interactions between implantation-competent blastocysts and receptive uteri. Accumulating literatures have indicated that T cells are involved in this process. The first signal mediated by T-cell receptor/CD3 complex and the second signal delivered by costimulatory molecules are essential for the differentiation of T cell into an effector cell. Expression and function of CD28, an important costimulatory molecule, during early pregnancy in mice is still unclear. In the present study, we investigated the expression pattern of CD28 in mouse uterus during early pregnancy and pseudopregnancy by real-time quantitative polymerase chain reaction, Western blotting, in situ hybridization, and immunohistochemistry (IHC). We found that injection of the uterine horn with CD28 antisense oligodeoxynucleotides leads to a decreased number of implantation sites. The expression pattern of CD3 protein examined by IHC is similar to that of CD28. These findings suggest that CD28 participates in the process of embryo implantation in mice, which might play its role through delivering the second costimulatory signal. [ABSTRACT FROM AUTHOR]

Highlights: [•] Concentrated ZnCl2 solution can be utilized for chitin biomass conversion to 5-HMF. [•] d-Glucosamine and chitosan polymer can be convert into 5-HMF efficiently. [•] AlCl3 and B(OH)3 can increase 5-HMF yield from d-glucosamine slightly. [•] In situ NMR was applied to monitor the chitin biomass conversion process. [•] Quantitative 1H NMR was utilized for determine 5-HMF yield and substrate conversion. [Copyright &y& Elsevier]

Numerous studies have demonstrated that Bisphenol A ( BPA) can cause reproductive toxicity. Ginseng has wide range of pharmacological actions and, more importantly, has proven its worth with respect to reproductive function in several reports. We have suggested that ginsenosides, the main active components of ginseng, may protect against BPA-induced cell damage. Therefore, an in vitro culture model of 15 P-1 Sertoli cells was employed to investigate whether ginsenosides have protective effects on BPA-stimulated 15 P-1 Sertoli cells. The results revealed that ginsenosides (75 μg/ml) significantly inhibited BPA-induced decreases in cell viability and increases in apoptosis. Immunofluorescence staining showed that BPA exposure-induced collapse of vimentin intermediate filaments was prevented by the application of ginsenosides. Ginsenosides also inhibited extracellular signal-regulated kinase ( ERK1/2) phosphorylation and BPA-induced alterations of Bcl-2 and Bax protein expression in 15 P-1 Sertoli cells. Furthermore, the alterations of T- AOC, superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione and malondialdehyde levels in BPA-stimulated cells were partially prevented with pre-treatment with ginsenosides. Taken together, these results suggest that ginsenosides have protective effects against BPA-induced cell damage and that these effects are mediated by preventing ERK1/2 phosphorylation and through the enhancement of cellular antioxidant capacity. Ginsenosides may therefore be beneficial in the prevention of environmental BPA-induced, reproduction-related toxicity. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) serve as key regulators in tumor immunity, with activated DCs potentiating antitumor responses through the secretion of pro-inflammatory cytokines and the expression of co-stimulatory molecules. Most current studies focus on the relationship between DC subgroups and clear-cell renal-cell carcinoma (ccRCC), but there is limited research on the connection between DCs and ccRCC from the perspective of immune activation. In this study, activated DC genes were identified in both bulk and single-cell RNA-seq data. A prognostic model related to activated DCs was constructed using univariate, multivariate Cox regression and LASSO regression. The prognostic model was validated in three external validation sets: GSE167573, ICGC, and E-MTAB-1980. The prognostic model consists of five genes, PLCB2, XCR1, IFNG, HLA-DQB2, and SMIM24. The expression of these genes was validated in tissue samples using qRT-PCR. Stratified analysis revealed that the prognostic model was able to better predict outcomes in advanced ccRCC patients. The risk scores were associated with tumor progression, tumor mutation burden, immune cell infiltration, and adverse outcomes of immunotherapy. Notably, there was a strong correlation between the expression of the five genes and the sensitivity to JQ1, a BET inhibitor. Molecular docking indicated high-affinity binding of the proteins encoded by these genes with JQ1. In conclusion, our study reveals the crucial role of activated DCs in ccRCC, offering new insights into predicting immune response, targeted therapy effectiveness, and prognosis for ccRCC patients. [ABSTRACT FROM AUTHOR]

Disentanglement is potentially a feasible method to improve the processability of polymers without any additives. But there still lacks the methods to efficiently prepare "in-pellet" disentangled polymers. To realize the large-scale production of disentangled pellets, we firstly designed a novel Polymer Melt Disentanglement Machine (PMDM), which can uniquely impose complex shear field (superposition of rotational shear and oscillatory shear) on polymer melt to induce disentanglement. Then, the disentangled polycarbonate pellets were prepared by PMDM under rotational shear, oscillatory shear and complex shear respectively. Finally, we compared the disentanglement effect of those three shear modes and the results show that the sample disentangled by complex shear field has a lower zero-shear viscosity and a higher melt flow rate compared with the samples disentangled by other two shear modes. Besides, the processing temperature and pressure of the disentangled pellets can be reduced by 20 °C and 25% respectively compared with the raw pellets. Complex shear field can efficiently disentangle polymer melt, which indicates its application prospect to improve the processability of the engineering plastics with high melt viscosity, such as polycarbonate et al., by a large-scale production of "in-pellet" disentangled materials via PMDM prior to processing. Image 1 • A novel "Polymer Melt Disentanglement Machine (PMDM)" was designed. • Disentangling effect of different shear fields on polycarbonate melt was compared by using PDMD. • Disentangled polycarbonate pellets can be processed with lower melt temperature and injection pressure. [ABSTRACT FROM AUTHOR]

Previous studies have shown that shear-induced disentanglement of polyolefins can realize on line. However, it is difficult to realize "in pellet" disentanglement for linear polyolefins. This work tried to retard the recovery of disentanglement of HDPE by adding small amount of UHMWPE. Results showed that shear can induce HDPE/UHMWPE blends disentanglement to a large extent. The total re-entanglement time of blends was as much as twice than HDPE, the half time of re-entanglement of H/U3 and H/U5 climbed up from 140 to 710 and 633s respectively. It is highly possible to realize "in pellet" disentanglement to meet the post processing. Furthermore, it was interestingly found that the viscosity of blend would be lower than that of HDPE at a certain time range under the conditions of this experiment. The reduced entanglement enabled the higher chain mobility, which facilitated the formation of the more perfect crystals. Image 10276 • HDPE/UHMWPE blends with reduced chain entanglements were prepared. • The recovery of HDPE/UHMWPE was retarded significantly in contrast to virgin HDPE. • The viscosity of blends would be lower than that of HDPE at a certain time range under the conditions of this experiment. [ABSTRACT FROM AUTHOR]

Aim: Acetaminophen (APAP) is clinically recommended as analgesic and antipyretic among pregnant women. However, accumulating laboratory evidence shows that the use of APAP during pregnancy may alter fetal development. Since fetal stage is a susceptible window for early oogenesis, we aim to assess the potential effects of maternal administration of APAP on fetal oocytes. Results: Pregnant mice at 14.5 dpc (days post-coitus) were orally administered with APAP (50 and 150mg/kg.bw/day) for 3 days; meanwhile, 14.5 dpc ovaries were collected and cultured with APAP or its metabolite N-acetyl-p-benzoquinone imine (NAPQI; 5 and 15 μM) for 3 days. It showed that APAP caused meiotic aberrations in fetal oocytes through its metabolite NAPQI, including meiotic prophase I (MPI) progression delay and homologous recombination defects. Co-treatment with nicotinamide (NAM) or nicotinamide riboside chloride (NRC), nicotinamide adenine dinucleotide (NAD+) supplements, efficiently restored the MPI arrest, whereas the addition of the inhibitor of sirtuin 7 (SIRT7) invalidated the effect of the NAD+ supplement. In addition, RNA sequencing revealed distorted transcriptomes of fetal ovaries treated with NAPQI. Furthermore, the fecundity of female offspring was affected, exhibiting delayed primordial folliculogenesis and puberty onset, reduced levels of ovarian hormones, and impaired developmental competence of MII oocytes. Innovation: These findings provide the first known demonstration that NAPQI, converted from maternal administration of APAP, disturbs meiotic process of fetal oocytes and further impairs female fecundity in adulthood. The concomitant oral dosing with NAM further supports the benefits of NAD+ supplements on oogenesis. Conclusion: Short-term administration of APAP to pregnant mouse caused meiotic aberrations in fetal oocytes by its metabolite NAPQI, whereas co-treatment with NAD+ supplement efficiently relieves the adverse effects by interacting with SIRT7. [ABSTRACT FROM AUTHOR]

The tumor microenvironment (TME) is crucial in tumor development, metastasis, and response to immunotherapy. DNA methylation can regulate the TME without altering the DNA sequence. However, research on the methylation-driven TME in clear-cell renal cell carcinoma (ccRCC) is still lacking. In this study, integrated DNA methylation and RNA-seq data were used to explore methylation-driven genes (MDGs). Immune scores were calculated using the ESTIMATE, which was employed to identify TME-related genes. A new signature connected with methylation-regulated TME using univariate, multivariate Cox regression and LASSO regression analyses was developed. This signature consists of four TME-MDGs, including AJAP1, HOXB9, MYH14, and SLC6A19, which exhibit high methylation and low expression in tumors. Validation was performed using qRT-PCR which confirmed their downregulation in ccRCC clinical samples. Additionally, the signature demonstrated stable predictive performance in different subtypes of ccRCC. Risk scores are positively correlated with TMN stages, immune cell infiltration, tumor mutation burden, and adverse outcomes of immunotherapy. Interestingly, the expression of four TME-MDGs are highly correlated with the sensitivity of first-line drugs in ccRCC treatment, especially pazopanib. Molecular docking indicates a high affinity binding between the proteins and pazopanib. In summary, our study elucidates the comprehensive role of methylation-driven TME in ccRCC, aiding in identifying patients sensitive to immunotherapy and targeted therapy, and providing new therapeutic targets for ccRCC treatment. [ABSTRACT FROM AUTHOR]

Freeze-drying of dilute polymer solution is a widely accepted method to yield disentangled polymer. By this method, it has been pointed out that samples recovered from dilute solution possess a better crystallization ability than the bulk polymer. Here, the important role of the critical overlap concentration c* in polymer solution is firstly stressed to give a more quantitative understanding in the relation between entanglement state and melt crystallization behavior. Crystallization kinetics of poly (lactic acid) freeze-extracted from dichloromethane solution with various concentration below and above c*, as well as the crystalline structure after isothermal crystallization at 110 °C, were investigated by means of differential scanning calorimetry (DSC) and small-angle X-ray scattering (SAXS). Results indicated that crystallization kinetics and lamellar thickness (L c) show a strong dependence on precursor solution concentration only when the concentration is lower than the critical value (c*), while above c* the crystallization behavior changes a little. Besides, a more rational method to characterize the chain entanglement state in polymer solution and to select concentrations accordingly was suggested, that is, using a dimensionless variable [η]c which is the product of intrinsic viscosity [η] and solution concentration c. Image 1 • Poly (lactic acid) with reduced chain entanglement was prepared by freeze-extraction method. • The product of solution concentration (c) and intrinsic viscosity ([η]) was used to characterize the chain entanglement state. • Melt crystallization kinetics shows a strong dependence on precursor solution concentration only when [η]c < 1. • Above critical overlap concentration ([η]c > 1), the melt crystallization kinetics shows a small change. [ABSTRACT FROM AUTHOR]

In this article, two kinds of isotactic polypropylene (iPP)/high density molecular weight polyethylene (HDPE) blend samples were prepared by an accessible injection-molding method. These two samples contain iPP shish kebab matrix and HDPE dispersed phase (shish kebab and epitaxy crystal, respectively). The variation of microstructures upon annealing was characterized using scanning electron microscopy, differential scanning calorimetry and small-angle X-ray scattering. It was found that the variations of different crystalline structures were changed by varying annealing parameters. Only the rearrangement of partially melted chains into primary lamellae happened for the sample with epitaxy crystalline structure, which was distinguished from the sample with HDPE shish kebab structure. Moreover, the variation of the crystalline structure, crystallinity and melting point were discussed to account for the changes in mechanical properties. These results revealed the relationship among the morphology, annealing parameters and mechanical properties, which provide a practical method to industrial manufacture. [ABSTRACT FROM AUTHOR]

A facile one-pot two-stage photochemical synthesis of aromatic azoxy compounds and imines has been developed by coupling the selective reduction of nitroaromatic compounds with the selective oxidation of amines in an aqueous solution. In the first stage (light illumination, Ar atmosphere), the light excited nitroaromatic molecule abstract H from amine to form ArNO2H and amine radical, which then form nitrosoaromatic, hydroxylamine and imine compounds. Water acts as a green solvent for the dispersion of the reactants and facilitates the formation of nitrosoaromatic and hydroxylamine intermediate compounds. In the second stage (no light, air atmosphere), the condensation of nitrosoaromatic and hydroxylamine compounds yields aromatic azoxy product with the aid of molecular oxygen in air. This photochemical synthesis achieved both high conversion and high product selectivity (>99%) at room temperature. [ABSTRACT FROM AUTHOR]

As a renewable source, fructose is of great significance in biomass conversion and food industries. Currently, most of the chemo-catalysts studied, with glucose as a substrate, are limited by the thermodynamic equilibrium of the reaction, resulting in the maximum yield of fructose of approximately 30–40%. The similar chemical structures and physical properties of monosaccharides bring another challenge for the separation of fructose from the reaction mixture. In this study, the combination of CaCl2 and Et3N was found to alter the thermodynamic equilibrium and promote fructose separation. The reaction parameters were optimized and up to 78% fructose yield could be obtained. The pathways of the isomerization reaction were found to involve both intramolecular hydride shift and an enediol intermediate mechanism, and the former was major. It could be speculated reasonably that Ca2+ played a key role in glucose conversion and interacted with glucose at its C1 and C2 positions, and Et3N interacted with Cl− while providing an alkaline environment. The formation of the α-fructofuranose' complex, from Et3N, CaCl2 and α-fructofuranose, could shift the equilibrium of glucose isomerization towards fructose formation. According to the diffusion-ordered spectroscopy (DOSY) NMR results, the strong complexation slowed down the diffusion rate of the α-fructofuranose' complex, allowing it to gradually precipitate, and hence drove the reaction equilibrium towards the desired fructose. The precipitate was filtered from the reaction mixture and processed further to obtain high-purity fructose in 45% isolated yield. Moreover, the filtrate containing solvent and reagents obtained in the separation process could be recycled. [ABSTRACT FROM AUTHOR]

Background: Two-dimensional ultrathin Ti3C2 nanosheets are increasingly being used in biomedical applications owing to their special physicochemical properties. But, the biological effects of its exposure on the reproductive system is still unclear. This study evaluated the reproductive toxicity of Ti3C2 nanosheets in the testes. Results: Ti3C2 nanosheets at doses of 2.5 mg/kg bw and 5 mg/kg bw in mice caused defects in spermatogenic function, and we also clarified an underlying molecular mechanism of it in vivo and in vitro model. Ti3C2 nanosheets induced an increase of reactive oxygen species (ROS) in testicular and GC-1 cells, which in turn led to the imbalance in oxidative and antioxidant systems (also known as oxidative stress). Additionally, oxidative stress often induces cellular DNA strand damages via the oxidative DNA damages, which triggered cell cycle arrest in the G1/G0 phase, leading to cell proliferation inhibition and irreversible apoptosis. ATM/p53 signaling manifest key role in DNA damage repair (DDR), and we demonstrate that ATM/p53 signaling was activated, and mediated the toxic damage process caused by Ti3C2 nanosheet exposure. Conclusion: Ti3C2 nanosheet-induced disruption of proliferation and apoptosis of spermatogonia perturbed normal spermatogenic function that was mediated by ATM/p53 signaling pathway. Our findings shed more light on the mechanisms of male reproductive toxicity induced by Ti3C2 nanosheets. [ABSTRACT FROM AUTHOR]

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 3-acetyl-1-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, and the optimal molar ratio of 3-acetyl-1-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. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BRCA) is one of the most common cancers in women worldwide and a leading cause of death from malignancy. This study was designed to identify a novel biomarker for prognosticating the survival of BRCA patients. Methods: The prognostic potential of eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) was assessed using RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) as training cohort and validation set, respectively. The functional enrichment analysis of differentially expressed genes (DEGs) was performed. The relationship between EIF4G1 and tumor microenvironment (TME) was analyzed. Immunotherapy responses were explored by the immunophenoscores (IPS) and tumor immune dysfunction and exclusion (TIDE) score. The Connectivity Map (CMap) was used to discover potentially effective therapeutic molecules against BRCA. Immunohistochemistry (IHC) was applied to compare the protein levels of EIF4G1 in normal and cancer tissues and to verify the prognostic value of EIF4G1. Results: BRCA patients with increased expression of EIF4G1 had a shorter overall survival (OS) in all cohorts and results from IHC. EIF4G1-related genes were mainly involved in DNA replication, BRCA metastasis, and the MAPK signaling pathway. Infiltration levels of CD4+-activated memory T cells, macrophages M0, macrophages M1, and neutrophils were higher in the EIF4G1 high-expression group than those in the EIF4G1 low-expression group. EIF4G1 was positively correlated with T cell exhaustion. Lower IPS was revealed in high EIF4G1 expression patients. Five potential groups of drugs against BRCA were identified. Conclusion: EIF4G1 might regulate the TME and affect BRCA metastasis, and it is a potential prognostic biomarker and therapeutic target for BRCA. [ABSTRACT FROM AUTHOR]