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Placental trophoblastic cells play important roles in placental development and fetal health. However, the mechanism of trophoblastic cell fusion is still not entirely clear. The level of Tspan5 in the embryo culture medium was detected using enzyme-linked immunosorbent assay (ELISA). Fusion of BeWo cells was observed by immunofluorescence. Cell fusion-related factors and EMT-related factors were identified by qRT-PCR and western blotting. Notch protein repressor DAPT was used to verify the role of Tspan5 in BeWo cells. The expression of Tspan5 was significantly increased in embryo culture medium. The fusion of BeWo cells was observed after treatment with forskolin (FSK). Cell fusion-related factors (i.e. β-hCG and syncytin 1/2) and Tspan5 were significantly increased after FSK treatment. In addition, FSK treatment promoted EMT-related protein expression in BeWo cells. Knockdown of Tspan5 inhibited cell fusion and EMT-related protein levels. Notch-1 and Jagged-1 protein levels were significantly upregulated, and the EMT process was activated by overexpression of Tspan5 in FSK-treated BeWo cells. Interestingly, blocking the Notch pathway by the repressor DAPT had the opposite results. These results indicated that Tspan5 could promote the EMT process by activating the Notch pathway, thereby causing cell fusion. These findings contribute to a better understanding of trophoblast cell syncytialization and embryonic development. Tspan5 may be used as a therapeutic target for normal placental development.
Due to the lack of research between the inner layers in the structure of colonic mucous and the metabolism of fatty acid in the constipation model, we aim to determine the changes in the mucous phenotype of the colonic glycocalyx and the microbial community structure following treatment with Rhubarb extract in our research. The constipation and treatment models are generated using adult male C57BL/6N mice. We perform light microscopy and transmission electron microscopy (TEM) to detect a Muc2-rich inner mucus layer attached to mice colon under different conditions. In addition, 16S rDNA sequencing is performed to examine the intestinal flora. According to TEM images, we demonstrate that Rhubarb can promote mucin secretion and find direct evidence of dendritic structure-linked mucus structures with its assembly into a lamellar network in a pore size distribution in the isolated colon section. Moreover, the diversity of intestinal flora has noticeable changes in constipated mice. The present study characterizes a dendritic structure and persistent cross-links have significant changes accompanied by the alteration of intestinal flora in feces in models of constipation and pretreatment with Rhubarb extract.
For individual cultures, findings on regulating embryo density by changing the microdrop volume are contradictory. The aim of this study was to investigate the relationship between embryo density and the developmental outcome of day 3 embryos after adjusting covariates. In total, 1196 embryos from 206 couples who had undergone in vitro fertilization treatment were analyzed retrospectively. Three embryo densities were used routinely, i.e. one embryo in a drop (30 μl/embryo), two embryos in a drop (15 μl/embryo) and three embryos in a drop (10 μl/embryo). Embryo quality on day 3 was evaluated, both the cell number of day 3 embryos and the proportion of successful implantations served as endpoints. Maternal age, paternal age, antral follicles and level of anti-Müllerian hormone, type of infertility, controlled ovarian stimulation protocol, length of stimulation, number of retrieved oocytes, number of zygotes (two pronuclei) and insemination type were covariates and adjusted. After adjusting fully for all covariates, the cell number of day 3 embryos was significantly increased by 0.40 (95% CI 0.00, 0.79; P = 0.048) and 0.78 (95% CI 0.02, 1.54; P = 0.044) in the 15 μl/embryo and 10 μl/embryo group separately, compared with the 30 μl/embryo group. The proportions of implanted embryos were 42.1%, 48.7% and 0.0% in the 30 μl/embryo, 15 μl/embryo and 10 μl/embryo groups respectively. There was no statistical significance (P = 0.22) between the 30 μl/embryo group and the 15 μl/embryo group. After adjusting for confounders that were significant in univariate analysis, embryo density was still not associated with day 3 embryo implantation potential (P > 0.05). In a 30-μl microdrop, culturing embryos with an embryo density of both 15 and 10 μl/embryo increased the cell number of day 3 embryos, which did not benefit embryo implanting potential, compared with individual culture of 30 μl/embryo.
This survey examined and compared the disaster perception and preparedness of 2421 residents with and without chronic disease in Shenzhen, China.
The participants were recruited and were asked to complete a survey in 2018.
Three types of disasters considered most likely to happen in Shenzhen were: typhoons (73.5% vs 74.9%), major transport accidents (61.5% vs 64.7%), and major fires (60.8% vs 63.0%). Only 5.9% and 5% of them, respectively, considered infectious diseases pandemics to be likely. There were significant differences between those with and without chronic disease in disaster preparedness, only a small percentage could be considered to have prepared for disaster (20.7% vs 14.5%). Logistic regression analyses showed that those aged 65 or older (odds ratio [OR] = 2.76), who had attained a Master’s degree or higher (OR = 2.0), and with chronic disease (OR = 1.38) were more prepared for disasters.
Although participants with chronic disease were better prepared than those without, overall, Shenzhen residents were inadequately prepared for disasters and in need of public education.
The wheat aphid Sitobion miscanthi (CWA) is an important harmful pest in wheat fields. Insecticide application is the main method to effectively control wheat aphids. However, CWA has developed resistance to some insecticides due to its extensive application, and understanding resistance mechanisms is crucial for the management of CWA. In our study, a new P450 gene, CYP4CJ6, was identified from CWA and showed a positive response to imidacloprid and thiamethoxam. Transcription of CYP4CJ6 was significantly induced by both imidacloprid and thiamethoxam, and overexpression of CYP4CJ6 in the imidacloprid-resistant strain was also observed. The sensitivity of CWA to these two insecticides was increased after the knockdown of CYP4CJ6. These results indicated that CYP4CJ6 could be associated with CWA resistance to imidacloprid and thiamethoxam. Subsequently, the posttranscriptional regulatory mechanism was assessed, and miR-316 was confirmed to participate in the posttranscriptional regulation of CYP4CJ6. These results are crucial for clarifying the roles of P450 in the resistance of CWA to insecticides.
Sarcopenic obesity is regarded as a risk factor for the progression and development of non-alcoholic fatty liver disease (NAFLD). Since male sex is a risk factor for NAFLD and skeletal muscle mass markedly varies between the sexes, we examined whether sex influences the association between appendicular skeletal muscle mass to visceral fat area ratio (SVR), that is, an index of skeletal muscle mass combined with abdominal obesity, and the histological severity of NAFLD. The SVR was measured by bioelectrical impedance in a cohort of 613 (M/F = 443/170) Chinese middle-aged individuals with biopsy-proven NAFLD. Multivariable logistic regression and subgroup analyses were used to test the association between SVR and the severity of NAFLD (i.e. non-alcoholic steatohepatitis (NASH) or NASH with the presence of any stage of liver fibrosis). NASH was identified by a NAFLD activity score ≥5, with a minimum score of 1 for each of its categories. The presence of fibrosis was classified as having a histological stage ≥1. The SVR was inversely associated with NASH in men (adjusted OR 0·62; 95 % CI 0·42, 0·92, P = 0·017 for NASH, adjusted OR 0·65; 95 % CI 0·43, 0·99, P = 0·043 for NASH with the presence of fibrosis), but not in women (1·47 (95 % CI 0·76, 2·83), P = 0·25 for NASH, and 1·45 (95 % CI 0·74, 2·83), P = 0·28 for NASH with the presence of fibrosis). There was a significant interaction for sex and SVR (Pinteraction = 0·017 for NASH and Pinteraction = 0·033 for NASH with the presence of fibrosis). Our findings show that lower skeletal muscle mass combined with abdominal obesity is strongly associated with the presence of NASH only in men.
ABSTRACT IMPACT: Triple negative breast cancer (TNBC) affects 10-20% of women with breast cancer and is biologically more aggressive than other subtypes. The novel compound we have developed, DL7076, would give clinicians a vital strategy to improve the commonly used cyclophosphamide (CPA) and doxorubicin (DOX) regimen in the treatment of TNBC. OBJECTIVES/GOALS: The objective of this research project is to develop a novel compound which can activate both 1) the constitutive androstane receptor (CAR) and subsequently enhance the CYP2B6-mediated activation of CPA, and 2) the nuclear factor erythroid- related factor-2 (Nrf2) leading to the cardiomyocyte protection from DOX-associated cardiotoxicity. METHODS/STUDY POPULATION: Following the identification of the compound candidate, DL7076 was evaluated for tissue specific induction of CAR and Nrf2 using qPCR, western blot analysis, and luciferase reporter assays.
Further, we have developed a multicellular coculture model incorporating human primary hepatocytes for metabolism, TNBC spheroids as the target, and cardiomyocytes as a side target of DOX. We have investigated the anticancer effects of CPA/DOX on TNBC cells and the toxic effects on cardiomyocytes with/without a CAR-Nrf2 activator, in a multicellular environment where hepatic metabolism is well-retained. RESULTS/ANTICIPATED RESULTS: We found that our dual activator of CAR and Nrf2, DL7076, exhibits tissue specific induction of CAR and Nrf2. Inclusion of DL7076 in combination with the CPA/DOX regimen improves anticancer efficacy, through the subsequent increase in the formation of the active CPA metabolite. With the addition of DL7076, DOX-mediated off-target cardiotoxicity was markedly reduced.
Lastly, utilizing the novel coculture system with human primary hepatocytes, TNBC spheroids, and cardiomyocytes, the inclusion of DL7076 to the CPA/DOX regimen shows decreased spheroid viability and improved cardiomyocyte viability and function. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our findings suggest that DL7076 can facilitate DOX/CPA containing regimens by increasing CAR-mediated metabolism and subsequent CPA bioactivation while selectively protecting cardiomyocytes from DOX-induced toxicity. This research is expected to translate our basic scientific findings into therapeutic interventions for women with TNBC.
A series of new synthetic armored cables were developed and tested to ensure that they were suitable for use with the RECoverable Autonomous Sonde (RECAS), which is a newly designed freezing-in thermal ice probe. The final version of the cable consists of two concentric conductors that can be used as the power and signal lines. Two polyfluoroalkoxy jackets are used for electrical insulation (one for insulation between conductors, and the other for insulation of the outer conductor). The outer insulation layer is coated by polyurethane jacket to seal the connections between the cable and electrical units. The 0.65 mm thick strength member is made from aramid fibers woven together. To hold these aramid fibers in place, a sheathing layer was produced from a polyamide fabric cover net. The outer diameter of the final version of the cable is ~6.1 mm. The permissible bending radius is as low as 17–20 mm. The maximal breaking force under straight tension is ~12.2 kN. The cable weight is only ~0.061 kg m−1. The mechanical and electrical properties and environmental suitability of the cable were determined through laboratory testing and joint testing with the probe.
For a wide range of insect species, the microbiota has potential roles in determining host developmental programme, immunity and reproductive biology. The tea geometrid moths Ectropis obliqua and E. grisescens are two closely related species that mainly feed on tea leaves. Although they can mate, infertile hybrids are produced. Therefore, these species provide a pair of model species for studying the molecular mechanisms of microbiotal involvement in host reproductive biology. In this study, we first identified and compared the compositions of microbiota between these sibling species, revealing higher microbiotal diversity for E. grisescens. The microbiota of E. obliqua mainly comprised the phyla Firmicutes, Proteobacteria and Cyanobacteria, whereas that of E. grisescens was dominated by Proteobacteria, Actinobacteria and Firmicutes. At the genus level, the dominant microbiota of E. grisescens included Wolbachia, Enterobacter and Pseudomonas and that of E. obliqua included Melissococcus, Staphylococcus and Enterobacter. Furthermore, we verified the rate of Wolbachia to infect 80 samples from eight different geographical populations, and the results supported that only E. grisescens harboured Wolbachia. Taken together, our findings indicate significantly different microbiotal compositions for E. obliqua and E. grisescens, with Wolbachia possibly being a curial factor influencing the reproductive isolation of these species. This study provides new insight into the mechanisms by which endosymbiotic bacteria, particularly Wolbachia, interact with sibling species.
Direct determination of barrier height (ΦBH) value between Ir and single crystal (001) hydrogen-terminated diamond with lightly boron doped has been performed using x-ray photoelectron spectroscopy technique. 70 nm Ir islands were formed on hydrogen-terminated diamond surface using anodic aluminum oxide. The ΦBH value for Ir/hydrogen-terminated diamond was −0.43 ± 0.14 eV, indicating that Ir was a suitable metal for ohmic contact with hydrogen-terminated diamond. The band diagram of Ir/hydrogen-terminated diamond was obtained. The experimental ΦBH was compared with the theoretical ΦBH in this work.
The following paper investigates the prevalence and characteristics of asymptomatic norovirus infection in the population living around oyster farm sites. Two consecutive surveys were conducted from January 2014 to December 2014 and 4549 stool samples were screened during the same time period. The total asymptomatic infection rate was 4.04% (184/4549). Norovirus infection rate was 5.20% in oyster farming population which was significantly higher compared with non-farming population where the infection rate was 3.65% (χ2 = 5.49, P < 0.05). A total of 184 NoV positive samples were identified by real time-quantitative polymerase chain reaction (RT-qPCR) and semi-nested RT-PCR and 136 sequences were obtained. The sequences were clustered into 14 genotypes. GI strains were clustered into six genotypes, including GI.2, GI.3, GI.5, GI.6, GI.8 and GI.9; while GII strains were clustered into GII.2, GII.3, GII.4, GII.5, GII.6, GII.8 and GII.13. GI.9 and GII.17 were the predominant and most prevalent genotypes, respectively. The GII.17 genotype replaced GII.4 becoming the dominant genotype in the oyster farming area in 2014. To sum up, long-term monitoring of asymptomatic infection is crucial for the detection of new variant strains and for identifying outbreaks during the early stage.
A “RE-free” and I-phase-containing Mg–8Sn-based alloy system was developed and successfully fabricated through the equal channel angular pressing (ECAP) process. The influence of the Zn/Al mass ratio on the microstructures and mechanical properties of the as-ECAPed Mg–8Sn–(5,6,7)Zn–2(wt%)Al alloys was investigated using an optical microscope, an X-ray diffractometer, a scanning electron microscope, a transmission electron microscope, and a universal testing machine. Grain size, dynamic recrystallization behavior, and texture were found to be greatly affected by the Zn/Al mass ratio. Furthermore, the ultimate tensile strength (250 MPa) and elongation (14.5%) of the alloy with a Zn/Al mass ratio of 3 were considerably increased compared to those of the as-ECAPed alloys with Zn/Al ratios of 2.5 and 3.5 (ultimate tensile strength and elongation of 215 MPa and 13% and 184 MPa and 10%, respectively). This significant enhancement was attributed to extensive grain boundary strengthening, precipitation strengthening, and higher work hardening capacity as well as texture randomization. The strength and ductility of the as-ECAPed alloys are also discussed in terms of the I-phase and Mg2Sn formation.
Most idiopathic right ventricular tachycardias originate from the outflow tract. We present a case series of idiopathic incessant ventricular tachycardia arising from unusual sites of the right ventricle in children, which were well resolved by catheter ablation.
A retrospective review was performed of all three patients who underwent ablation of idiopathic ventricular tachycardia below the level of the right ventricular outflow tract using three-dimensional mapping in our institute.
All three patients presented with tachycardia-induced cardiomyopathy due to incessant ventricular tachycardia on first admission. The sites of successful ablation were at the proximal right bundle branch, distal right bundle branch, and apex of the right ventricle, respectively. No complications occurred, and there has been no recurrence of ventricular tachycardia after the final ablation at an average follow-up period of 9 months. All three patients have achieved normalisation of left ventricular size and systolic function.
Incessant idiopathic ventricular tachycardia originating from unusual sites of the right ventricle in children, resulting in significant symptoms and impaired ventricular function, can be successfully treated with catheter ablation.
Epidemiological studies have examined associations between dietary patterns and the risk of type 2 diabetes. However, information on dietary patterns and the risk of type 2 diabetes in Chinese populations is scarce. The aim of the present study was to identify dietary patterns and examine their association with incident hyperglycaemia in Nanjing, China.
A community-based prospective cohort study. Dietary assessment was carried out using a validated eighty-seven-item FFQ. Dietary patterns were identified by exploratory factor analysis. Participants were categorized into tertiles of dietary factor score for each dietary pattern. The relationship between dietary patterns and hyperglycaemia risk was analysed using multivariable linear and Cox regression.
Seven communities from two urban districts in Nanjing, China.
A total of 2900 of Chinese local residents aged 30 years or above, free of hyperglycaemia and other serious diseases, who participated in the baseline survey from June to September 2007 were followed up 3 years later from June to September 2010 for the development of hyperglycaemia. Fasting blood samples were collected at both baseline and 3-year follow-up surveys. Hyperglycaemia was defined as fasting plasma glucose concentration of ≥6·1 mmol/l or already taking oral hyperglycaemia agents for treatment of type 2 diabetes.
Five major dietary patterns were identified: (i) the ‘condiments’ pattern; (ii) the ‘animal and plant protein’ pattern; (iii) the ‘healthy traditional’ pattern; (iv) the ‘fruits, eggs and juice’ pattern; and (v) the ‘alcohol, milk and tea’ pattern. A total of 2093 (72·2 %) individuals completed the follow-up survey and the 3-year cumulative incidence of hyperglycaemia was 7·5 % (158/2093). A 1-unit increase in the score for the ‘healthy traditional’ pattern was associated with a decrease of 0·054 mmol/l in fasting plasma glucose (P=0·017), while a 1-unit increase in the ‘fruits, eggs and juice’ pattern score was associated with an increase of 0·050 mmol/l in fasting plasma glucose (P=0·023) by multivariable linear regression. For men, tertile 3 of the ‘fruits, eggs and juice’ pattern was associated with an 88 % greater risk (hazard ratio=1·88; 95 % CI 1·04, 3·54) of hyperglycaemia than tertile 1 of this pattern. Being in tertile 3 of the ‘alcohol, milk and tea’ pattern was associated with a 35 % greater risk (hazard ratio=1·35; 95 % CI 1·04, 2·16) relative to tertile 1 in women, while for the ‘'healthy traditional’ pattern tertile 3 was associated with a 41 % lower risk (hazard ratio=0·59; 95 % CI 0·35, 0·99) compared with tertile 1. The ‘condiments’ and the ‘animal and plant protein’ patterns were not independently associated with hyperglycaemia.
Our findings suggest that modifying dietary patterns could reduce hyperglycaemia incidence in the mainland Chinese adult population.
To assess correlations between cruciferous vegetable intake and urinary isothiocyanate (ITC) level, in addition to glutathione S-transferase (GST) genotypes and other individual factors.
The study included cohort participants whose urinary ITC levels had been previously ascertained. Urinary ITC was assessed using HPLC. Usual dietary intake of cruciferous vegetables was assessed using a validated FFQ and total dietary ITC intake was calculated. Recent cruciferous vegetable intake was determined. GST genotypes were assessed using duplex real-time quantitative PCR assays. Spearman correlations were calculated between the covariates and urinary ITC levels and linear regression analyses were used to calculate the mean urinary ITC excretion according to GST genotype.
Urban city in China.
The study included 3589 women and 1015 men from the Shanghai Women’s and Men’s Health Studies.
Median urinary ITC level was 1·61 nmol/mg creatinine. Self-reported usual cruciferous vegetable intake was weakly correlated with urinary ITC level (rs=0·1149; P<0·0001), while self-reported recent intake was more strongly correlated with urinary ITC (rs=0·2591; P<0·0001). Overall, the GST genotypes were not associated with urinary ITC level, but significant differences according to genotype were observed among current smokers and participants who provided an afternoon urine sample. Other factors, including previous gastrectomy or gastritis, were also related to urinary ITC level.
The study suggests that urinary secretion of ITC may provide additional information on cruciferous vegetable intake and that GST genotypes are related to urinary ITC level only in some subgroups.